Bench-to-bedside review: Rapid molecular diagnostics for bloodstream infection - a new frontier?

PubMed Central

2012-01-01

Among critically ill patients, the diagnosis of bloodstream infection poses a major challenge. Current standard bacterial identification based on blood culture platforms is intrinsically time-consuming and slow. The continuous evolvement of molecular techniques has the potential of providing a faster, more sensitive and direct identification of causative pathogens without prior need for cultivation. This may ultimately impact clinical decision-making and antimicrobial treatment. This review summarises the currently available technologies, their strengths and limitations and the obstacles that have to be overcome in order to develop a satisfactory bedside point-of-care diagnostic tool for detection of bloodstream infection. PMID:22647543

Roadmap to risk evaluation and mitigation strategies (REMS) success

PubMed Central

Balian, John D.; Malhotra, Rachpal; Perentesis, Valerie

2010-01-01

Medical safety-related risk management is a rapidly evolving and increasingly important aspect of drug approval and market longevity. To effectively meet the challenges of this new era, we describe a risk management roadmap that proactively yet practically anticipates risk-management requirements, provides the foundation for enduring yet appropriately flexible risk-management practices, and leverages these techniques to efficiently and effectively utilize risk evaluation and mitigation strategies (REMS)/risk minimization programs as market access enablers. This fully integrated risk-management paradigm creates exciting opportunities for newer tools, techniques, and approaches to more successfully optimize product development, approval, and commercialization, with patients as the ultimate beneficiaries. PMID:25083193

The role of ecological theory in microbial ecology.

PubMed

Prosser, James I; Bohannan, Brendan J M; Curtis, Tom P; Ellis, Richard J; Firestone, Mary K; Freckleton, Rob P; Green, Jessica L; Green, Laura E; Killham, Ken; Lennon, Jack J; Osborn, A Mark; Solan, Martin; van der Gast, Christopher J; Young, J Peter W

2007-05-01

Microbial ecology is currently undergoing a revolution, with repercussions spreading throughout microbiology, ecology and ecosystem science. The rapid accumulation of molecular data is uncovering vast diversity, abundant uncultivated microbial groups and novel microbial functions. This accumulation of data requires the application of theory to provide organization, structure, mechanistic insight and, ultimately, predictive power that is of practical value, but the application of theory in microbial ecology is currently very limited. Here we argue that the full potential of the ongoing revolution will not be realized if research is not directed and driven by theory, and that the generality of established ecological theory must be tested using microbial systems.

Laser Capture Microdissection in the Genomic and Proteomic Era: Targeting the Genetic Basis of Cancer

PubMed Central

Domazet, Barbara; MacLennan, Gregory T.; Lopez-Beltran, Antonio; Montironi, Rodolfo; Cheng, Liang

2008-01-01

The advent of new technologies has enabled deeper insight into processes atsubcellular levels, which will ultimately improve diagnostic procedures and patient outcome. Thanks to cell enrichment methods, it is now possible to study cells in their native environment. This has greatly contributed to a rapid growth in several areas, such as gene expression analysis, proteomics, and metabolonomics. Laser capture microdissection (LCM) as a method of procuring subpopulations of cells under direct visual inspection is playing an important role in these areas. This review provides an overview of existing LCM technology and its downstream applications in genomics, proteomics, diagnostics and therapy. PMID:18787684

Laser capture microdissection in the genomic and proteomic era: targeting the genetic basis of cancer.

PubMed

Domazet, Barbara; Maclennan, Gregory T; Lopez-Beltran, Antonio; Montironi, Rodolfo; Cheng, Liang

2008-03-15

The advent of new technologies has enabled deeper insight into processes at subcellular levels, which will ultimately improve diagnostic procedures and patient outcome. Thanks to cell enrichment methods, it is now possible to study cells in their native environment. This has greatly contributed to a rapid growth in several areas, such as gene expression analysis, proteomics, and metabolonomics. Laser capture microdissection (LCM) as a method of procuring subpopulations of cells under direct visual inspection is playing an important role in these areas. This review provides an overview of existing LCM technology and its downstream applications in genomics, proteomics, diagnostics and therapy.

Pervasive Home Environments

NASA Astrophysics Data System (ADS)

Bull, P.; Limb, R.; Payne, R.

An increasing number of computers and other equipment, such as games consoles and multimedia appliances for the home, have networking capability. The rapid growth of broadband in the home is also fuelling the demand for people to network their homes. In the near future we will see a number of market sectors trying to 'own' the home by providing gateways either from the traditional ISP or from games and other service providers. The consumer is bombarded with attractive advertising to acquire the latest technological advances, but is left with a plethora of different appliances, which have a bewildering range of requirements and features in terms of networking, user interface, and higher-level communications protocols. In many cases, these are proprietary, preventing interworking. Such technical and usability anarchy confuses the consumer and could ultimately suppress market adoption.

Robotics in urologic surgery: an evolving new technology.

PubMed

Atug, Fatih; Castle, Erik P; Woods, Michael; Davis, Rodney; Thomas, Raju

2006-07-01

Rapid technological developments in the past two decades have produced new inventions such as robots and incorporated them into our daily lives. Today, robots perform vital functions in homes, outer space, hospitals and on military instillations. The development of robotic surgery has given hospitals and health care providers a valuable tool that is making a profound impact on highly technical surgical procedures. The field of urology is one area of medicine that has adopted and incorporated robotic surgery into its armamentarium. Innovative robotic urologic surgical applications and techniques are being developed and reported everyday. Increased utilization and development will ultimately fuel the discovery of newer applications of robotic systems in urologic surgery. Herein we provide an overview of the history, development, and applications of robotics in surgery with a focus on urologic surgery.

Large-deflection-theory Analysis of the Effect of Web Initial Curvature on the Ultimate Strength of Steel Plate Girder

NASA Astrophysics Data System (ADS)

Kala, Jiří; Kala, Zdeněk

2011-09-01

The objective of the paper is to analyze the influence of initial imperfections on the behaviour of thin-walled girders welded of slender plate elements. In parallel with experiments, one of the ultimate load tests was computer modelled. In so doing, the girder was modelled, using the geometrically and materially non-linear variant of the shell finite element method, by the ANSYS program. The shape changing during loading process is often accompanying with sudden "snap-through" i. e. rapid curvature change.

Microbial contributions to the persistence of coral reefs.

PubMed

Webster, Nicole S; Reusch, Thorsten B H

2017-10-01

On contemplating the adaptive capacity of reef organisms to a rapidly changing environment, the microbiome offers significant and greatly unrecognised potential. Microbial symbionts contribute to the physiology, development, immunity and behaviour of their hosts, and can respond very rapidly to changing environmental conditions, providing a powerful mechanism for acclimatisation and also possibly rapid evolution of coral reef holobionts. Environmentally acquired fluctuations in the microbiome can have significant functional consequences for the holobiont phenotype upon which selection can act. Environmentally induced changes in microbial abundance may be analogous to host gene duplication, symbiont switching / shuffling as a result of environmental change can either remove or introduce raw genetic material into the holobiont; and horizontal gene transfer can facilitate rapid evolution within microbial strains. Vertical transmission of symbionts is a key feature of many reef holobionts and this would enable environmentally acquired microbial traits to be faithfully passed to future generations, ultimately facilitating microbiome-mediated transgenerational acclimatisation (MMTA) and potentially even adaptation of reef species in a rapidly changing climate. In this commentary, we highlight the capacity and mechanisms for MMTA in reef species, propose a modified Price equation as a framework for assessing MMTA and recommend future areas of research to better understand how microorganisms contribute to the transgenerational acclimatisation of reef organisms, which is essential if we are to reliably predict the consequences of global change for reef ecosystems.

The genesis of neurosurgery and the evolution of the neurosurgical operative environment: part II--concepts for future development, 2003 and beyond.

PubMed

Liu, Charles Y; Spicer, Mark; Apuzzo, Michael L J

2003-01-01

The future development of the neurosurgical operative environment is driven principally by concurrent development in science and technology. In the new millennium, these developments are taking on a Jules Verne quality, with the ability to construct and manipulate the human organism and its surroundings at the level of atoms and molecules seemingly at hand. Thus, an examination of currents in technology advancement from the neurosurgical perspective can provide insight into the evolution of the neurosurgical operative environment. In the future, the optimal design solution for the operative environment requirements of specialized neurosurgery may take the form of composites of venues that are currently mutually distinct. Advances in microfabrication technology and laser optical manipulators are expanding the scope and role of robotics, with novel opportunities for bionic integration. Assimilation of biosensor technology into the operative environment promises to provide neurosurgeons of the future with a vastly expanded set of physiological data, which will require concurrent simplification and optimization of analysis and presentation schemes to facilitate practical usefulness. Nanotechnology derivatives are shattering the maximum limits of resolution and magnification allowed by conventional microscopes. Furthermore, quantum computing and molecular electronics promise to greatly enhance computational power, allowing the emerging reality of simulation and virtual neurosurgery for rehearsal and training purposes. Progressive minimalism is evident throughout, leading ultimately to a paradigm shift as the nanoscale is approached. At the interface between the old and new technological paradigms, issues related to integration may dictate the ultimate emergence of the products of the new paradigm. Once initiated, however, history suggests that the process of change will proceed rapidly and dramatically, with the ultimate neurosurgical operative environment of the future being far more complex in functional capacity but strikingly simple in apparent form.

Optical detection of special nuclear materials: an alternative approach for standoff and remote sensing

NASA Astrophysics Data System (ADS)

Johnson, J. Bruce; Reeve, S. W.; Burns, W. A.; Allen, Susan D.

2010-04-01

Termed Special Nuclear Material (SNM) by the Atomic Energy Act of 1954, fissile materials, such as 235U and 239Pu, are the primary components used to construct modern nuclear weapons. Detecting the clandestine presence of SNM represents an important capability for Homeland Security. An ideal SNM sensor must be able to detect fissile materials present at ppb levels, be able to distinguish between the source of the detected fissile material, i.e., 235U, 239Pu, 233U or other fission source, and be able to perform the discrimination in near real time. A sensor with such capabilities would provide not only rapid identification of a threat but, ultimately, information on the potential source of the threat. For example, current detection schemes for monitoring clandestine nuclear testing and nuclear fuel reprocessing to provide weapons grade fissile material rely largely on passive air sampling combined with a subsequent instrumental analysis or some type of wet chemical analysis of the collected material. It would be highly useful to have a noncontact method of measuring isotopes capable of providing forensic information rapidly at ppb levels of detection. Here we compare the use of Kr, Xe and I as "canary" species for distinguishing between 235U and 239Pu fission sources by spectroscopic methods.

Characterisation and identification of bacteria using SERS.

PubMed

Jarvis, Roger M; Goodacre, Royston

2008-05-01

Within microbiology Raman spectroscopy is considered as a very important whole-organism fingerprinting technique, which is used to characterise, discriminate and identify microorganisms and assess how they respond to abiotic or biotic stress. Enhancing the sensitivity of Raman spectroscopy is very beneficial for the rapid analysis of bacteria (and indeed biological systems in general), where the ultimate goal is to achieve this without the need for lengthy cell culture. Bypassing this step would provide significant benefits in many areas such as medical, environmental and industrial microbiology, microbial systems biology, biological warfare countermeasures and bioprocess monitoring. In this tutorial review we will report on the advances made in bacterial studies, a relatively new and exciting application area for SERS.

Ozone Therapy in Dentistry

PubMed Central

Domb, William C

2014-01-01

Summary The 21st century dental practice is quite dynamic. New treatment protocols and new materials are being developed at a rapid pace. Ozone dental therapy falls into the category of new treatment protocols in dentistry, yet ozone is not new at all. Ozone therapy is already a major treatment modality in Europe, South America and a number of other countries. What is provided here will not be an exhaustive scientific treatise so much as a brief general introduction into what dentists are now doing with ozone therapies and the numerous oral/systemic links that make this subject so important for physicians so that, ultimately, they may serve their patients more effectively and productively. PMID:25363268

Ozone therapy in dentistry. A brief review for physicians.

PubMed

Domb, William C

2014-10-31

The 21(st) century dental practice is quite dynamic. New treatment protocols and new materials are being developed at a rapid pace. Ozone dental therapy falls into the category of new treatment protocols in dentistry, yet ozone is not new at all. Ozone therapy is already a major treatment modality in Europe, South America and a number of other countries. What is provided here will not be an exhaustive scientific treatise so much as a brief general introduction into what dentists are now doing with ozone therapies and the numerous oral/systemic links that make this subject so important for physicians so that, ultimately, they may serve their patients more effectively and productively.

Rodent-repellent studies. III. Advanced studies in the evaluation of chemical repellents

USGS Publications Warehouse

Bellack, E.; DeWitt, J.B.

1949-01-01

In order to bridge the gap between preliminary screening of chemicals for potential rodent repellency and the application ofthese compounds to paper cartons, more advanced studies in the evaluation ofpromising materials have been carried out. These studies have resulted in: (1) a modification of the food acceptance technique which eliminates doubtful compounds and also provides a closer analogy to the ultimate goal, and (2) a method for rapidly testing chemicals incorporated in paper. When the results of these latter tests are expressed as a function of time, it can be shown that a distinct correlation exists between the deterrency exhibited by treated paper and the repellency of treated food.

Autonomous Metabolomics for Rapid Metabolite Identification in Global Profiling

DOE PAGES

Benton, H. Paul; Ivanisevic, Julijana; Mahieu, Nathaniel G.; ...

2014-12-12

An autonomous metabolomic workflow combining mass spectrometry analysis with tandem mass spectrometry data acquisition was designed to allow for simultaneous data processing and metabolite characterization. Although previously tandem mass spectrometry data have been generated on the fly, the experiments described herein combine this technology with the bioinformatic resources of XCMS and METLIN. We can analyze large profiling datasets and simultaneously obtain structural identifications, as a result of this unique integration. Furthermore, validation of the workflow on bacterial samples allowed the profiling on the order of a thousand metabolite features with simultaneous tandem mass spectra data acquisition. The tandem mass spectrometrymore » data acquisition enabled automatic search and matching against the METLIN tandem mass spectrometry database, shortening the current workflow from days to hours. Overall, the autonomous approach to untargeted metabolomics provides an efficient means of metabolomic profiling, and will ultimately allow the more rapid integration of comparative analyses, metabolite identification, and data analysis at a systems biology level.« less

Optical coherence elastography in ophthalmology

NASA Astrophysics Data System (ADS)

Kirby, Mitchell A.; Pelivanov, Ivan; Song, Shaozhen; Ambrozinski, Łukasz; Yoon, Soon Joon; Gao, Liang; Li, David; Shen, Tueng T.; Wang, Ruikang K.; O'Donnell, Matthew

2017-12-01

Optical coherence elastography (OCE) can provide clinically valuable information based on local measurements of tissue stiffness. Improved light sources and scanning methods in optical coherence tomography (OCT) have led to rapid growth in systems for high-resolution, quantitative elastography using imaged displacements and strains within soft tissue to infer local mechanical properties. We describe in some detail the physical processes underlying tissue mechanical response based on static and dynamic displacement methods. Namely, the assumptions commonly used to interpret displacement and strain measurements in terms of tissue elasticity for static OCE and propagating wave modes in dynamic OCE are discussed with the ultimate focus on OCT system design for ophthalmic applications. Practical OCT motion-tracking methods used to map tissue elasticity are also presented to fully describe technical developments in OCE, particularly noting those focused on the anterior segment of the eye. Clinical issues and future directions are discussed in the hope that OCE techniques will rapidly move forward to translational studies and clinical applications.

Achieving Hand Hygiene Success With a Partnership Between Graduate Medical Education, Hospital Leadership, and Physicians.

PubMed

Rosenbluth, Glenn; Garritson, Susan; Green, Adrienne L; Milev, Dimiter; Vidyarthi, Arpana R; Auerbach, Andrew D; Baron, Robert B

2016-11-01

Engaging physicians in hand hygiene programs is a challenge faced by many academic medical centers. Partnerships between education and academic leaders present opportunities for effective collaboration and improvement. The authors developed a robust hand hygiene quality improvement program, with attention to rapid-cycle improvements, including all levels of staff and health care providers. The program included a defined governance structure, clear data collection process, educational interventions, rapid-cycle improvements, and financial incentive for staff and physicians (including residents and fellows). Outcomes were measured on patients in all clinical areas. Run charts were used to document compliance in aggregate and by subgroups throughout the project duration. Institutional targets were achieved and then exceeded, with sustained hand hygiene compliance >90%. Physician compliance lagged behind aggregate compliance but ultimately was sustained at a level exceeding the target. Successfully achieving the institutional goal required collaboration among all stakeholders. Physician-specific data and physician champions were essential to drive improvement. © The Author(s) 2015.

On-site bundled rapid HIV/HCV testing in substance use disorder treatment programs: study protocol for a hybrid design randomized controlled trial.

PubMed

Frimpong, Jemima A; D'Aunno, Thomas; Perlman, David C; Strauss, Shiela M; Mallow, Alissa; Hernandez, Diana; Schackman, Bruce R; Feaster, Daniel J; Metsch, Lisa R

2016-03-03

More than 1.2 million people in the United States are living with human immunodeficiency virus (HIV), and 3.2 million are living with hepatitis C virus (HCV). An estimated 25 % of persons living with HIV also have HCV. It is therefore of great public health importance to ensure the prompt diagnosis of both HIV and HCV in populations that have the highest prevalence of both infections, including individuals with substance use disorders (SUD). In this theory-driven, efficacy-effectiveness-implementation hybrid study, we will develop and test an on-site bundled rapid HIV/HCV testing intervention for SUD treatment programs. Its aim is to increase the receipt of HIV and HCV test results among SUD treatment patients. Using a rigorous process involving patients, providers, and program managers, we will incorporate rapid HCV testing into evidence-based HIV testing and linkage to care interventions. We will then test, in a randomized controlled trial, the extent to which this bundled rapid HIV/HCV testing approach increases receipt of HIV and HCV test results. Lastly, we will conduct formative research to understand the barriers to, and facilitators of, the adoption, implementation, and sustainability of the bundled rapid testing strategy in SUD treatment programs. Novel approaches that effectively integrate on-site rapid HIV and rapid HCV testing are needed to address both the HIV and HCV epidemics. If feasible and efficacious, bundled rapid HIV/HCV testing may offer a scalable, potentially cost-effective approach to testing high-risk populations, such as patients of SUD treatment programs. It may ultimately lead to improved linkage to care and progress through the HIV and HCV care and treatment cascades. ClinicalTrials.gov: NCT02355080 . (30 January 2015).

Revisiting perceptions of quality of hospice care: managing for the ultimate referral.

PubMed

Churchman, Richard; York, Grady S; Woodard, Beth; Wainright, Charles; Rau-Foster, Mary

2014-08-01

Hospice services provided in the final months of life are delivered through complex interpersonal relationships between caregivers, patients, and families. Often, service value and quality are defined by these interpersonal interactions. This understanding provides hospice leaders with an enormous opportunity to create processes that provide the optimal level of care during the last months of life. The authors argue that the ultimate referral is attained when a family member observes the care of a loved one, and the family member conveys a desire to receive the same quality of services their loved one received at that facility. The point of this article is to provide evidence that supports the methods to ultimately enhance the patient's and family's experience and increase the potential for the ultimate referral. © The Author(s) 2013.

Healthcare providers' knowledge and attitudes about rapid tissue donation (RTD): phase one of establishing a rapid tissue donation programme in thoracic oncology.

PubMed

Schabath, Matthew B; McIntyre, Jessica; Pratt, Christie; Gonzalez, Luis E; Munoz-Antonia, Teresita; Haura, Eric B; Quinn, Gwendolyn P

2014-02-01

In preparation for the development of a rapid tissue donation (RTD) programme, we surveyed healthcare providers (HCPs) in our institution about knowledge and attitudes related to RTD with lung cancer patients. A 31-item web based survey was developed collecting data on demographics, knowledge and attitudes about RTD. The survey contained three items measuring participants' knowledge about RTD, five items assessing attitudes towards RTD recruitment and six items assessing HCPs' level of agreement with factors influencing decisions to discuss RTD. Response options were presented on a 5-point Likert scale. Ninety-one HCPs participated in the study. 66% indicated they had never heard of RTD prior to the survey, 78% rated knowledge of RTD as none or limited and 95.6% reported not having ethical or religious concerns about discussing RTD with patients. The majority were either not comfortable (17.8%) or not sure if they felt comfortable discussing RTD with cancer patients (42.2%). 56.1% indicated their knowledge of RTD would play an integral role in their decision to discuss RTD with patients. 71.4% reported concerns with RTD discussion and the emotional state of the patient. Physicians and nurses play an important role in initiating conversations about recruitment and donation to research that can ultimately influence uptake. Increasing HCP knowledge about RTD is a necessary step towards building an RTD programme. Our study provides important information about characteristics associated with low levels of knowledge and practice related to RTD where additional education and training may be warranted.

26 CFR 48.6427-8 - Diesel fuel and kerosene; claims by ultimate purchasers.

Code of Federal Regulations, 2010 CFR

2010-04-01

... 26 Internal Revenue 16 2010-04-01 2010-04-01 true Diesel fuel and kerosene; claims by ultimate... kerosene; claims by ultimate purchasers. (a) Overview. This section provides rules under which ultimate purchasers of taxed diesel fuel and kerosene may claim the income tax credits or payments allowed by section...

26 CFR 48.6427-8 - Diesel fuel and kerosene; claims by ultimate purchasers.

Code of Federal Regulations, 2013 CFR

2013-04-01

... 26 Internal Revenue 16 2013-04-01 2013-04-01 false Diesel fuel and kerosene; claims by ultimate... kerosene; claims by ultimate purchasers. (a) Overview. This section provides rules under which ultimate purchasers of taxed diesel fuel and kerosene may claim the income tax credits or payments allowed by section...

26 CFR 48.6427-8 - Diesel fuel and kerosene; claims by ultimate purchasers.

Code of Federal Regulations, 2011 CFR

2011-04-01

... 26 Internal Revenue 16 2011-04-01 2011-04-01 false Diesel fuel and kerosene; claims by ultimate... kerosene; claims by ultimate purchasers. (a) Overview. This section provides rules under which ultimate purchasers of taxed diesel fuel and kerosene may claim the income tax credits or payments allowed by section...

26 CFR 48.6427-8 - Diesel fuel and kerosene; claims by ultimate purchasers.

Code of Federal Regulations, 2012 CFR

2012-04-01

... 26 Internal Revenue 16 2012-04-01 2012-04-01 false Diesel fuel and kerosene; claims by ultimate... kerosene; claims by ultimate purchasers. (a) Overview. This section provides rules under which ultimate purchasers of taxed diesel fuel and kerosene may claim the income tax credits or payments allowed by section...

Degassing procedure for ultrahigh vacuum

NASA Technical Reports Server (NTRS)

Moore, B. C.

1979-01-01

Calculations based on diffusion coefficients and degassing rates for stainless-steel vacuum chambers indicate that baking at lower temperatures for longer periods give lower ultimate pressures than rapid baking at high temperatures. Process could reduce pressures in chambers for particle accelerators, fusion reactors, material research, and other applications.

Exposure Space: Integrating Exposure Data and Modeling with Toxicity Information

EPA Science Inventory

Recent advances have been made in high-throughput (HTP) toxicity testing, e.g. from ToxCast, which will ultimately be combined with HTP predictions of exposure potential to support next-generation chemical safety assessment. Rapid exposure methods are essential in selecting chemi...

When dementia progresses quickly: a practical approach to the diagnosis and management of rapidly progressive dementia.

PubMed

Day, Gregory S; Tang-Wai, David F

2014-01-01

Making a diagnosis of rapidly progressive dementia requires practical adaptation of the skills used to assess patients with chronic causes of cognitive impairment. An expedited assessment, commensurate with the accelerated pace of the disease, is required to identify the cause of symptoms amidst a myriad of possibilities. Features upon history, physical examination and cognitive assessment that support specific diagnoses are reviewed, and a stratified approach to testing is presented. The use of readily-accessible investigations is prioritized, acknowledging the implications and applications of novel diagnostic tests. The coordinated use of clinical and laboratory measures are promoted as a means of facilitating rapid evaluation, with the ultimate goal of identifying patients with potentially reversible causes of rapidly progressive dementia.

Tensile properties of HK31XA-H24 magnesium-alloy sheet under rapid-heating conditions and constant elevated temperatures

NASA Technical Reports Server (NTRS)

Gibbs, Thomas W

1956-01-01

Specimens of HK31XA-H24 magnesium-alloy sheet from an experimental batch were heated to failure at nominal temperature rates from 0.2 F to 100 F per second under constant-load conditions. Rapid-heating yield and rupture stresses are presented and compared with the yield and ultimate stresses from elevated-temperature tensile stress-strain tests for 1/2-hour exposure. Linear temperature-rate parameters were used to correlate rapid-heating results by constructing master curves which can be used for predicting yield stresses and temperatures and for estimating rupture stresses and temperatures.

Overview of Space Transportation and Propulsion at NASA

NASA Technical Reports Server (NTRS)

Sackheim, Robert L.

2003-01-01

Topics considered include: 1. Scientific discovery: The search for the life beyond Earth. Understanding our Planet. Understanding our Universe. Exploration of the Planets and beyond. 2. The ultimate high ground for national security: Intelligence, communications, rapid response, GPS. 3. Space-based commerce: Communications and Earth observing.

Q-Switched Raman laser system

DOEpatents

George, E. Victor

1985-01-01

Method and apparatus for use of a Raman or Brillouin switch together with a conventional laser and a saturable absorber that is rapidly bleached at a predetermined frequency .nu.=.nu..sub.0, to ultimately produce a Raman or Brillouin pulse at frequency .nu.=.nu..sub.0 .+-..nu..sub.Stokes.

Q-switched Raman laser system

DOEpatents

George, E.V.

Method and apparatus for use of a Raman or Brillouin switch together with a conventional laser and a saturable absorber that is rapidly bleached at a predeterimined frequency nu = nu/sub O/, to ultimately produce a Raman or Brillouin pulse at frequency nu = nu/sub O/ +- nu /sub Stokes/.

COMPARISON OF MICROBIAL POPULATIONS IN A CONVENTIONAL AND BIOREACTING MUNICIPAL SOLID WASTE LANDFILLS

EPA Science Inventory

Landfills are the ultimate reactors for biodegradation as they contain nutrients, bacteria, and various redox conditions which, then, change over time. Enhancement of the landill environment to optimize the rates of biodegradation and to ensure more rapid stabilization of the was...

Cancer: a reproductive strategy of "ultra-selfish" genes?

PubMed

Schuiling, G A

2004-01-01

A hypothesis is presented in which the process of "malignant transformation" which ultimately results in the rapidly dividing tumor(s)(cells) causing "cancer", is regarded as an evolved reproductive strategy of "ultra-selfish" (proto-)(onco-) genes, already present in the genome, or introduced by a virus.

Culture and Ethics in First Nations Educational Research

ERIC Educational Resources Information Center

Taylor, Josiah; Plaice, Evie; Perley, Imelda

2010-01-01

In this paper, we share phenomena experienced by a multi-cultural research team working collaboratively with Wolastoq (Maliseet) First Nations Elders to document rapidly disappearing Wolastoq language, culture, and knowledge. This knowledge will ultimately be stored in databanks for future educational, community, and heritage use. Embedded within…

Disease management: old wine in new bottles?

PubMed

Ritterband, D R

2000-01-01

Disease management is a holistic, patient-focused approach to the treatment of disease across the spectrum of healthcare delivery. In its current form, disease management was created in response to the societal and economic burden that chronic illness contributes. There has recently been rapid growth in the development of disease management programs and sponsors are widespread within the industry, with the largest increase in independent vendors. Although growth has been substantial, the hurdles these programs have encountered have kept them from reaching their full potential. The challenges that exist include clinical, financial, and regulatory issues, and these challenges have significant meaning to healthcare managers. In deciding whether to develop or enhance programs, executives must consider their capability of outcomes measurement, their provider relationships, and the arrangements for program implementation. Ultimately, if programs provide improved health and quality of life for participants, cost savings will follow.

A Toolset for Supporting Iterative Human Automation: Interaction in Design

NASA Technical Reports Server (NTRS)

Feary, Michael S.

2010-01-01

The addition of automation has greatly extended humans' capability to accomplish tasks, including those that are difficult, complex and safety critical. The majority of Human - Automation Interacton (HAl) results in more efficient and safe operations, ho,,:,ever ertain unpected atomatlon behaviors or "automation surprises" can be frustrating and, In certain safety critical operations (e.g. transporttion, manufacturing control, medicine), may result in injuries or. the loss of life.. (Mellor, 1994; Leveson, 1995; FAA, 1995; BASI, 1998; Sheridan, 2002). This papr describes he development of a design tool that enables on the rapid development and evaluation. of automaton prototypes. The ultimate goal of the work is to provide a design platform upon which automation surprise vulnerability analyses can be integrated.

Rapid ordering of block copolymer thin films

NASA Astrophysics Data System (ADS)

Majewski, Pawel W.; Yager, Kevin G.

2016-10-01

Block-copolymers self-assemble into diverse morphologies, where nanoscale order can be finely tuned via block architecture and processing conditions. However, the ultimate usage of these materials in real-world applications may be hampered by the extremely long thermal annealing times—hours or days—required to achieve good order. Here, we provide an overview of the fundamentals of block-copolymer self-assembly kinetics, and review the techniques that have been demonstrated to influence, and enhance, these ordering kinetics. We discuss the inherent tradeoffs between oven annealing, solvent annealing, microwave annealing, zone annealing, and other directed self-assembly methods; including an assessment of spatial and temporal characteristics. We also review both real-space and reciprocal-space analysis techniques for quantifying order in these systems.

Rapid O serogroup identification of the ten most clinically relevant STECs by Luminex microbead-based suspension array

USDA-ARS?s Scientific Manuscript database

Identification and serotyping of Shiga toxin-producing Escherichia coli during foodborne outbreaks can aid in matching clinical, food, and environmental isolates when trying to identify the sources of illness and ultimately food contamination. Herein we describe a Luminex microbead-based suspension ...

Importance of Rootstock and Scion Tomato Mosaic Virus Resistance for Grafting Heirloom Tomatoes

USDA-ARS?s Scientific Manuscript database

During the 2011-2012 tomato production season at a Florida organic farm, heirloom tomato scions grafted onto Tomato yellow leaf curl virus (TYLCV)-resistant tomato rootstocks were observed to undergo a rapid and severe wilt, and ultimately die. The soilborne fungus, Sclerotium rolfsii, was isolated...

Enhancing Student Learning with Brain-Based Research

ERIC Educational Resources Information Center

Bonnema, Ted R.

2009-01-01

This paper discusses brain-based learning and its relation to classroom instruction. A rapidly growing quantity of research currently exists regarding how the brain perceives, processes, and ultimately learns new information. In order to maximize their teaching efficacy, educators should have a basic understanding of key memory functions in the…

Interactive internet-based clinical education: an efficient and cost-savings approach to point-of-care test training.

PubMed

Knapp, Herschel; Chan, Kee; Anaya, Henry D; Goetz, Matthew B

2011-06-01

We successfully created and implemented an effective HIV rapid testing training and certification curriculum using traditional in-person training at multiple sites within the U.S. Department of Veterans Affairs (VA) Healthcare System. Considering the multitude of geographically remote facilities in the nationwide VA system, coupled with the expansion of HIV diagnostics, we developed an alternate training method that is affordable, efficient, and effective. Using materials initially developed for in-person HIV rapid test in-services, we used a distance learning model to offer this training via live audiovisual online technology to educate clinicians at a remote outpatient primary care VA facility. Participants' evaluation metrics showed that this form of remote education is equivalent to in-person training; additionally, HIV testing rates increased considerably in the months following this intervention. Although there is a one-time setup cost associated with this remote training protocol, there is potential cost savings associated with the point-of-care nurse manager's time productivity by using the Internet in-service learning module for teaching HIV rapid testing. If additional in-service training modules are developed into Internet-based format, there is the potential for additional cost savings. Our cost analysis demonstrates that the remote in-service method provides a more affordable and efficient alternative compared with in-person training. The online in-service provided training that was equivalent to in-person sessions based on first-hand supervisor observation, participant satisfaction surveys, and follow-up results. This method saves time and money, requires fewer personnel, and affords access to expert trainers regardless of geographic location. Further, it is generalizable to training beyond HIV rapid testing. Based on these consistent implementation successes, we plan to expand use of online training to include remote VA satellite facilities spanning several states for a variety of diagnostic devices. Ultimately, Internet-based training has the potential to provide "big city" quality of care to patients at remote (rural) clinics.

11. Chernobyl's radioactive impact on microbial biota.

PubMed

Yablokov, Alexey V

2009-11-01

Of the few microorganisms that have been studied, all underwent rapid changes in the areas heavily contaminated by Chernobyl. Organisms such as tuberculosis bacilli; hepatitis, herpes, and tobacco mosaic viruses; cytomegalovirus; and soil micromycetes and bacteria were activated in various ways. The ultimate long-term consequences for the Chernobyl microbiologic biota may be worse than what we know today. Compared to humans and other mammals, the profound changes that take place among these small live organisms with rapid reproductive turnover do not bode well for the health and survival of other species.

A novel rapid access testicular cancer clinic: prospective evaluation after one year.

PubMed

Carey, K; Davis, N F; Elamin, S; Ahern, P; Brady, C M; Sweeney, P

2016-02-01

Our institution has recently developed a rapid access outpatient clinic to investigate men with testicular lumps and/or pain suspicious for testicular cancer (TCa). To present our experience after 12 months. All referrals to the rapid access testicular clinic (RATC) clinic were prospectively analysed from 01/01/2013 to 01/01/2014. The primary outcome variable was incidence of TCa in the referred patient cohort. Secondary outcome variables were waiting times prior to clinical review and waiting times prior to radical orchidectomy in patients diagnosed with TCa. Seventy-four new patients were referred to the RATC during the 1-year period and the mean age was 34 (range 15-81 years). TCa was the most common diagnosis and was found in 18 (25 %) patients. Patients diagnosed with TCa underwent radical orchidectomy, a median of 3 (range 1-5) days after their initial GP referral. Patients requiring surgical intervention for benign scrotal pathology underwent their procedure a median of 32 (range 3-61) days after their initial referral. Of the 18 patients diagnosed with TCa, 9 (50 %) were diagnosed with a seminomatous germ cell tumour on histopathology. The RATC is a new initiative in Ireland that provides expedient and definitive treatment of patients with newly diagnosed TCa. Early treatment will ultimately improve long-term prognosis in this patient cohort.

Rapid emergence and mechanisms of resistance by U87 glioblastoma cells to doxorubicin in an in vitro tumor microfluidic ecology

NASA Astrophysics Data System (ADS)

Austin, Robert; Lee, Sanghyuk; Park, Sungsu

We have developed a microfluidic device consisting of approximately 500 hexagonal micro-compartments which provides a complex ecology with wide ranges of drug and nutrient gradients and local populations. This ecology of a fragmented metapopulation induced the drug resistance in stage IV U87 glioblastoma cells to doxorubicin in seven days. Exome and transcriptome sequencing of the resistant cells identified mutations and differentially expressed genes. Gene ontology and pathway analyses of the genes identified showed that they were functionally relevant with the established mechanisms of doxorubicin action. Functional experiments support the in silico analyses and together demonstrate the effects of these genetic changes. Our findings suggest that given the rapid evolution of resistance and the focused response, this technology could act as a rapid screening modality for genetic aberrations leading to resistance to chemotherapy as well as counter-selection of drugs unlikely to be successful ultimately. Technology Innovation Program of the Ministry of Trade, Industry and Energy, Republic of Korea (10050154 to S.L. and S.P.), the National Research Foundation of Korea (NRF-2014M3C9A3065221 to S.L., NRF-2015K1A4A3047851 to J.K. and S.L.) funded by the Minis.

Multi-layered epigenetic mechanisms contribute to transcriptional memory in T lymphocytes.

PubMed

Dunn, Jennifer; McCuaig, Robert; Tu, Wen Juan; Hardy, Kristine; Rao, Sudha

2015-05-06

Immunological memory is the ability of the immune system to respond more rapidly and effectively to previously encountered pathogens, a key feature of adaptive immunity. The capacity of memory T cells to "remember" previous cellular responses to specific antigens ultimately resides in their unique patterns of gene expression. Following re-exposure to an antigen, previously activated genes are transcribed more rapidly and robustly in memory T cells compared to their naïve counterparts. The ability for cells to remember past transcriptional responses is termed "adaptive transcriptional memory". Recent global epigenome studies suggest that epigenetic mechanisms are central to establishing and maintaining transcriptional memory, with elegant studies in model organisms providing tantalizing insights into the epigenetic programs that contribute to adaptive immunity. These epigenetic mechanisms are diverse, and include not only classical acetylation and methylation events, but also exciting and less well-known mechanisms involving histone structure, upstream signalling pathways, and nuclear localisation of genomic regions. Current global health challenges in areas such as tuberculosis and influenza demand not only more effective and safer vaccines, but also vaccines for a wider range of health priorities, including HIV, cancer, and emerging pathogens such as Ebola. Understanding the multi-layered epigenetic mechanisms that underpin the rapid recall responses of memory T cells following reactivation is a critical component of this development pathway.

Superconducting Detectors Come of Age, or Ready to Leave the Lab

NASA Technical Reports Server (NTRS)

Moseley, Samuel H.

2008-01-01

Cryogenically cooled superconducting detectors have become essential tools for a wide range of measurement applications, ranging from quantum limited heterodyne detection in the millimeter range to direct searches for dark matter with superconducting phonon detectors operating at 20 mK. Superconducting detectors have several fundamental and practical advantages which have resulted in their rapid adoption by experimenters. Their excellent performance arises in part from reductions in noise resulting from their low operating temperatures, but unique superconducting properties provide a wide range of mechanisms for detection. For example, the steep dependence of resistance with temperature on the superconductor normal transition provides a sensitive thermometer for calorimetric and bolometric applications. Parametric changes in the properties of superconducting resonators provide a mechanism for high sensitivity detection of submillil.neter photons. From a practical point of view, the use of superconducting detectors has grown rapidly because many of these devices couple well to SQUID amplifiers, which are easily integrated with the detectors. These SQUID-based amplifiers and multiplexers have matured with the detectors; they are convenient to use, and have excellent noise performance. The first generation of fully integrated large-scale superconducting detection systems is now being deployed. Improved understanding of the operation of these detectors, combined with rapidly improving fabrication techniques, is quickly expanding the capability of these detectors. I will review the development and application of superconductor-based detectors, the ultimate limits to their performance, and consider prospects for their future applications. Continued advances promise to enable important new measurements in physics, and with appropriate advances in cryogenic infrastncturem, ay result in the use of these detectors in everyday monitoring applications.

Plasmonic Nanobubbles as Tunable Cellular Probes for Cancer Theranostics

PubMed Central

Lapotko, Dmitri

2011-01-01

This review is focused on a novel cellular probe, the plasmonic nanobubble (PNB), which has the dynamically tunable and multiple functions of imaging, diagnosis, delivery, therapy and, ultimately, theranostics. The concept of theranostics was recently introduced in order to unite the clinically important stages of treatment, namely diagnosis, therapy and therapy guidance, into one single, rapid and highly accurate procedure. Cell level theranostics will have far-reaching implications for the treatment of cancer and other diseases at their earliest stages. PNBs were developed to support cell level theranostics as a new generation of on-demand tunable cellular probes. A PNB is a transient vapor nanobubble that is generated within nanoseconds around an overheated plasmonic nanoparticle with a short laser pulse. In the short term, we expect that PNB technology will be rapidly adaptable to clinical medicine, where the single cell resolution it provides will be critical for diagnosing incipient or residual disease and eliminating cancer cells, while leaving healthy cells intact. This review discusses mechanisms of plasmonic nanobubbles and their biomedical applications with the focus on cancer cell theranostics. PMID:21442036

Cell Surface and Membrane Engineering: Emerging Technologies and Applications

PubMed Central

Saeui, Christopher T.; Mathew, Mohit P.; Liu, Lingshui; Urias, Esteban; Yarema, Kevin J.

2015-01-01

Membranes constitute the interface between the basic unit of life—a single cell—and the outside environment and thus in many ways comprise the ultimate “functional biomaterial”. To perform the many and often conflicting functions required in this role, for example to partition intracellular contents from the outside environment while maintaining rapid intake of nutrients and efflux of waste products, biological membranes have evolved tremendous complexity and versatility. This article describes how membranes, mainly in the context of living cells, are increasingly being manipulated for practical purposes with drug discovery, biofuels, and biosensors providing specific, illustrative examples. Attention is also given to biology-inspired, but completely synthetic, membrane-based technologies that are being enabled by emerging methods such as bio-3D printers. The diverse set of applications covered in this article are intended to illustrate how these versatile technologies—as they rapidly mature—hold tremendous promise to benefit human health in numerous ways ranging from the development of new medicines to sensitive and cost-effective environmental monitoring for pathogens and pollutants to replacing hydrocarbon-based fossil fuels. PMID:26096148

15 CFR 748.11 - Statement by Ultimate Consignee and Purchaser.

Code of Federal Regulations, 2011 CFR

2011-01-01

... ultimate consignee, provided the required statements are contained in Block 24 on the license application... copy submitted by the applicant must be of sufficient quality to ensure all assertions made on the...) Form or letter. The ultimate consignee and purchaser must complete either a statement on company...

15 CFR 748.11 - Statement by Ultimate Consignee and Purchaser.

Code of Federal Regulations, 2010 CFR

2010-01-01

... ultimate consignee, provided the required statements are contained in Block 24 on the license application... copy submitted by the applicant must be of sufficient quality to ensure all assertions made on the...) Form or letter. The ultimate consignee and purchaser must complete either a statement on company...

Cholinergic aspects of cyanide intoxication

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

Von Bredow, J.D.; Vick, J.A.

1993-05-13

The acute exposure of pentobarbital anesthetized dogs to cyanide leads to a rapid increase and sudden halt in respiration accompanied by cardiovascular irregularities and extreme bradycardia which ultimately lead to cardiac arrest and death. Cardiac irregularities and cardiac arrest in the presence of cyanide induced respiratory arrest are assumed to be due to anoxia and therefore unresponsive to cardiotonic agents. Pretreatment or treatment with atropine sulfate or methyl atropine nitrate provides a marked reduction in the cardiovascular irregularities, bradycardia and hypotension. The cyanide induced cardiovascular effect can also be prevented by bilateral vagotomy. An intramuscularly injected combination of 20 mg/kgmore » sodium nitrite and 1 mg/kg of atropine sulfate ensured recovery of pentobarbital anesthetized dogs exposed to lethal concentrations (2.5 mg/kg i.v.) of sodium cyanide.« less

Rapid ordering of block copolymer thin films

DOE PAGES

Majewski, Pawel W.; Yager, Kevin G.

2016-08-18

Block-copolymers self-assemble into diverse morphologies, where nanoscale order can be finely tuned via block architecture and processing conditions. However, the ultimate usage of these materials in real-world applications may be hampered by the extremely long thermal annealing times—hours or days—required to achieve good order. Here, we provide an overview of the fundamentals of block-copolymer self-assembly kinetics, and review the techniques that have been demonstrated to influence, and enhance, these ordering kinetics. We discuss the inherent tradeoffs between oven annealing, solvent annealing, microwave annealing, zone annealing, and other directed self-assembly methods; including an assessment of spatial and temporal characteristics. Here, wemore » also review both real-space and reciprocal-space analysis techniques for quantifying order in these systems.« less

Strategies for clinical approach to neurodegeneration in Amyotrophic lateral sclerosis.

PubMed

Carlesi, Cecilia; Pasquali, Livia; Piazza, Selina; Lo Gerfo, Annalisa; Caldarazzo Ienco, Elena; Alessi, Rosaria; Fornai, Francesco; Siciliano, Gabriele

2011-03-01

Amyotrophic lateral sclerosis (ALS) is a rapidly progressive and ultimately fatal neurodegenerative disorder of unknown aetiology that involves the loss of upper and lower motor neurons in the cerebral cortex, brainstem and spinal cord. Significant progress in understanding the cellular mechanisms of motor neuron degeneration in ALS has not been matched with the development of therapeutic strategies to prevent disease progression, and riluzole remains the only available therapy, with only marginal effects on disease survival. More recently alterations of mRNA processing in genetically defined forms of ALS, as those related to TDP-43 and FUS-TLS gene mutations have provided important insights into the molecular networks implicated in the disease pathogenesis. Here we review some of the recent progress in promoting therapeutic strategies for neurodegeneration.

The neurobiology of climate change

NASA Astrophysics Data System (ADS)

O'Donnell, Sean

2018-02-01

Directional climate change (global warming) is causing rapid alterations in animals' environments. Because the nervous system is at the forefront of animals' interactions with the environment, the neurobiological implications of climate change are central to understanding how individuals, and ultimately populations, will respond to global warming. Evidence is accumulating for individual level, mechanistic effects of climate change on nervous system development and performance. Climate change can also alter sensory stimuli, changing the effectiveness of sensory and cognitive systems for achieving biological fitness. At the population level, natural selection forces stemming from directional climate change may drive rapid evolutionary change in nervous system structure and function.

The neurobiology of climate change.

PubMed

O'Donnell, Sean

2018-01-06

Directional climate change (global warming) is causing rapid alterations in animals' environments. Because the nervous system is at the forefront of animals' interactions with the environment, the neurobiological implications of climate change are central to understanding how individuals, and ultimately populations, will respond to global warming. Evidence is accumulating for individual level, mechanistic effects of climate change on nervous system development and performance. Climate change can also alter sensory stimuli, changing the effectiveness of sensory and cognitive systems for achieving biological fitness. At the population level, natural selection forces stemming from directional climate change may drive rapid evolutionary change in nervous system structure and function.

Genes encoding a callose synthase and phytochrome A are adjacent to a MAP3Ka-like gene in Beta vulgaris USH20

USDA-ARS?s Scientific Manuscript database

MAP3Ka encodes a key conserved protein kinase responsible for orchestrating a rapid cascade of cellular events ultimately leading to localized cell death. Hypersensitive response, as it is termed, enables genetically-resistant plants to limit microbial invasion under the right environmental conditio...

Digital Marketing: The Time for a New "Academic Major" Has Arrived

ERIC Educational Resources Information Center

Wymbs, Cliff

2011-01-01

The rapidly emerging digital economy is challenging the relevance of existing marketing practices, and a radical redesign of the marketing curriculum consistent with the emerging student and business needs of the 21st century is required. To remain relevant to our students and to the ultimate consumers of our output, businesses, the marketing…

Acute brain herniation from lead toxicity.

PubMed

Berkowitz, Sheldon; Tarrago, Rod

2006-12-01

A 4-year-old black boy was admitted to the hospital with vomiting, low-grade fever, and dehydration that were thought to be caused by viral gastroenteritis. He proceeded over the next 12 hours to rapidly deteriorate with brain herniation leading to brain death. The ultimate cause of death was found to be acute lead intoxication from a swallowed foreign body.

Organizational Culture, Values, and Routines in Iranian Medical Schools

ERIC Educational Resources Information Center

Bikmoradi, Ali; Brommels, Mats; Shoghli, Alireza; Zavareh, Davoud Khorasani; Masiello, Italo

2009-01-01

In Iran, restructuring of medical education and the health care delivery system in 1985 resulted in a rapid shift from elite to mass education, ultimately leading to an increase in the number of medical schools, faculties, and programs and as well as some complications. This study aimed to investigate views on academic culture, values, and…

Medical informatics--an Australian perspective.

PubMed

Hannan, T

1991-06-01

Computers, like the X-ray and stethoscope can be seen as clinical tools, that provide physicians with improved expertise in solving patient management problems. As tools they enable us to extend our clinical information base, and they also provide facilities that improve the delivery of the health care we provide. Automation (computerisation) in the health domain will cause the computer to become a more integral part of health care management and delivery before the start of the next century. To understand how the computer assists those who deliver and manage health care, it is important to be aware of its functional capabilities and how we can use them in medical practice. The rapid technological advances in computers over the last two decades has had both beneficial and counterproductive effects on the implementation of effective computer applications in the delivery of health care. For example, in the 1990s the computer hobbyist is able to make an investment of less than $10,000 on computer hardware that will match or exceed the technological capacities of machines of the 1960s. These rapid technological advances, which have produced a quantum leap in our ability to store and process information, have tended to make us overlook the need for effective computer programmes which will meet the needs of patient care. As the 1990s begin, those delivering health care (eg, physicians, nurses, pharmacists, administrators ...) need to become more involved in directing the effective implementation of computer applications that will provide the tools for improved information management, knowledge processing, and ultimately better patient care.

Symptomatic Cushing's syndrome and hyperandrogenemia in a steroid cell ovarian neoplasm: a case report.

PubMed

Sedhom, Ramy; Hu, Sophia; Ohri, Anupam; Infantino, Dorian; Lubitz, Sara

2016-10-12

Malignant steroid cell tumors of the ovary are rare and frequently associated with hormonal abnormalities. There are no guidelines on how to treat rapidly progressive Cushing's syndrome, a medical emergency. A 67-year-old white woman presented to our hospital with rapidly developing signs and symptoms of Cushing's syndrome secondary to a steroid-secreting tumor. Her physical and biochemical manifestations of Cushing's syndrome progressed, and she was not amenable to undergoing conventional chemotherapy secondary to the debilitating effects of high cortisol. Her rapidly progressive Cushing's syndrome ultimately led to her death, despite aggressive medical management with spironolactone, ketoconazole, mitotane, and mifepristone. We report an unusual and rare case of Cushing's syndrome secondary to a malignant steroid cell tumor of the ovary. The case is highlighted to discuss the complications of rapidly progressive Cushing's syndrome, an underreported and often unrecognized endocrine emergency, and the best available evidence for treatment.

An enhanced cluster analysis program with bootstrap significance testing for ecological community analysis

USGS Publications Warehouse

McKenna, J.E.

2003-01-01

The biosphere is filled with complex living patterns and important questions about biodiversity and community and ecosystem ecology are concerned with structure and function of multispecies systems that are responsible for those patterns. Cluster analysis identifies discrete groups within multivariate data and is an effective method of coping with these complexities, but often suffers from subjective identification of groups. The bootstrap testing method greatly improves objective significance determination for cluster analysis. The BOOTCLUS program makes cluster analysis that reliably identifies real patterns within a data set more accessible and easier to use than previously available programs. A variety of analysis options and rapid re-analysis provide a means to quickly evaluate several aspects of a data set. Interpretation is influenced by sampling design and a priori designation of samples into replicate groups, and ultimately relies on the researcher's knowledge of the organisms and their environment. However, the BOOTCLUS program provides reliable, objectively determined groupings of multivariate data.

PLUMED 2: New feathers for an old bird

NASA Astrophysics Data System (ADS)

Tribello, Gareth A.; Bonomi, Massimiliano; Branduardi, Davide; Camilloni, Carlo; Bussi, Giovanni

2014-02-01

Enhancing sampling and analyzing simulations are central issues in molecular simulation. Recently, we introduced PLUMED, an open-source plug-in that provides some of the most popular molecular dynamics (MD) codes with implementations of a variety of different enhanced sampling algorithms and collective variables (CVs). The rapid changes in this field, in particular new directions in enhanced sampling and dimensionality reduction together with new hardware, require a code that is more flexible and more efficient. We therefore present PLUMED 2 here—a complete rewrite of the code in an object-oriented programming language (C++). This new version introduces greater flexibility and greater modularity, which both extends its core capabilities and makes it far easier to add new methods and CVs. It also has a simpler interface with the MD engines and provides a single software library containing both tools and core facilities. Ultimately, the new code better serves the ever-growing community of users and contributors in coping with the new challenges arising in the field.

Silk-based blood stabilization for diagnostics.

PubMed

Kluge, Jonathan A; Li, Adrian B; Kahn, Brooke T; Michaud, Dominique S; Omenetto, Fiorenzo G; Kaplan, David L

2016-05-24

Advanced personalized medical diagnostics depend on the availability of high-quality biological samples. These are typically biofluids, such as blood, saliva, or urine; and their collection and storage is critical to obtain reliable results. Without proper temperature regulation, protein biomarkers in particular can degrade rapidly in blood samples, an effect that ultimately compromises the quality and reliability of laboratory tests. Here, we present the use of silk fibroin as a solid matrix to encapsulate blood analytes, protecting them from thermally induced damage that could be encountered during nonrefrigerated transportation or freeze-thaw cycles. Blood samples are recovered by simple dissolution of the silk matrix in water. This process is demonstrated to be compatible with a number of immunoassays and provides enhanced sample preservation in comparison with traditional air-drying paper approaches. Additional processing can remediate interactions with conformational structures of the silk protein to further enhance blood stabilization and recovery. This approach can provide expanded utility for remote collection of blood and other biospecimens empowering new modalities of temperature-independent remote diagnostics.

Opportunities for the Cardiovascular Community in the Precision Medicine Initiative.

PubMed

Shah, Svati H; Arnett, Donna; Houser, Steven R; Ginsburg, Geoffrey S; MacRae, Calum; Mital, Seema; Loscalzo, Joseph; Hall, Jennifer L

2016-01-12

The Precision Medicine Initiative recently announced by President Barack Obama seeks to move the field of precision medicine more rapidly into clinical care. Precision medicine revolves around the concept of integrating individual-level data including genomics, biomarkers, lifestyle and other environmental factors, wearable device physiological data, and information from electronic health records to ultimately provide better clinical care to individual patients. The Precision Medicine Initiative as currently structured will primarily fund efforts in cancer genomics with longer-term goals of advancing precision medicine to all areas of health, and will be supported through creation of a 1 million person cohort study across the United States. This focused effort on precision medicine provides scientists, clinicians, and patients within the cardiovascular community an opportunity to work together boldly to advance clinical care; the community needs to be aware and engaged in the process as it progresses. This article provides a framework for potential involvement of the cardiovascular community in the Precision Medicine Initiative, while highlighting significant challenges for its successful implementation. © 2016 American Heart Association, Inc.

Imaging CD4 T Cell Interstitial Migration in the Inflamed Dermis

PubMed Central

Gaylo, Alison; Overstreet, Michael G.; Fowell, Deborah J.

2016-01-01

The ability of CD4 T cells to carry out effector functions is dependent upon the rapid and efficient migration of these cells in inflamed peripheral tissues through an as-yet undefined mechanism. The application of multiphoton microscopy to the study of the immune system provides a tool to measure the dynamics of immune responses within intact tissues. Here we present a protocol for non-invasive intravital multiphoton imaging of CD4 T cells in the inflamed mouse ear dermis. Use of a custom imaging platform and a venous catheter allows for the visualization of CD4 T cell dynamics in the dermal interstitium, with the ability to interrogate these cells in real-time via the addition of blocking antibodies to key molecular components involved in motility. This system provides advantages over both in vitro models and surgically invasive imaging procedures. Understanding the pathways used by CD4 T cells for motility may ultimately provide insight into the basic function of CD4 T cells as well as the pathogenesis of both autoimmune diseases and pathology from chronic infections. PMID:27078264

Marjolin's Ulcer Complicating a Pressure Sore: The Clock is Ticking.

PubMed

Khan, Kamran; Giannone, Anna Lucia; Mehrabi, Erfan; Khan, Ayda; Giannone, Roberto E

2016-02-22

Malignant degeneration in any chronic wound is termed a Marjolin's ulcer (MU). The overall metastatic rate of MU is approximately 27.5%. However, the prognosis of MU specific to pressure sores is poor, with a reported metastatic rate of 61%. This is due to insidious, asymptomatic malignant degeneration, a lack of healthcare provider awareness, and, ultimately, delayed management. An 85-year-old white male was noted by his wound-care nurse to have a rapidly developing growth on his lower back over a period of 4 months. There was history of a non-healing, progressive pressure ulcer of the lower back for the past 10 years. On examination, there was a 4 × 4 cm pressure ulcer of the lower back, with a superimposed 1.5 × 2 cm growth in the superior region. There was an absence of palpable regional lymphadenopathy. Punch biopsy revealed squamous cell carcinoma consistent with Marjolin's ulcer. The ulcer underwent excision with wide margins, and a skin graft was placed. Due to the prompt recognition of an abnormality by the patient's wound-care nurse, metastasis was not evident on imaging. There are no signs of recurrence at 1-year follow-up. Marjolin's ulcer has a rapid progression from local disease to widespread metastasis. Therefore, it is essential that wound-care providers are aware of the clinical signs and symptoms of malignant degeneration in chronic wounds.

Data fusion algorithm for rapid multi-mode dust concentration measurement system based on MEMS

NASA Astrophysics Data System (ADS)

Liao, Maohao; Lou, Wenzhong; Wang, Jinkui; Zhang, Yan

2018-03-01

As single measurement method cannot fully meet the technical requirements of dust concentration measurement, the multi-mode detection method is put forward, as well as the new requirements for data processing. This paper presents a new dust concentration measurement system which contains MEMS ultrasonic sensor and MEMS capacitance sensor, and presents a new data fusion algorithm for this multi-mode dust concentration measurement system. After analyzing the relation between the data of the composite measurement method, the data fusion algorithm based on Kalman filtering is established, which effectively improve the measurement accuracy, and ultimately forms a rapid data fusion model of dust concentration measurement. Test results show that the data fusion algorithm is able to realize the rapid and exact concentration detection.

Fuels planning: science synthesis and integration; economic uses fact sheet 04: My Fuel Treatment Planner

Treesearch

Rocky Mountain Research Station USDA Forest Service

2004-01-01

In the face of rapidly changing public and political attitudes toward fire and fuel planning, one thing remains constant: the fuel planner is ultimately responsible for making decisions on the land. This fact sheet discusses the options for fuel treatments, and the need, development, and use of the MS Excel-based tool, My Fuel Treatment Planner.

Infectious pancreatic necrosis: its detection and identification

USGS Publications Warehouse

Wolf, K.

1965-01-01

Ultimate control of infectious pancreatic necrosis (IPN) in hatcheries depends largely upon learning where the virus occurs. To detect the presence of virus either susceptible fish or susceptible fish cell cultures may be used as test systems. In modern virology, it is generally agreed that cell cultures are more convenient, are usually a much more sensitive test system, and allow more rapid determinations.

Reform Doesn't Work: Grassroots Efforts Can Provide Answers to School Improvement

ERIC Educational Resources Information Center

Babbage, Keen

2012-01-01

Where does education happen? In classrooms. Teachers can provide the ultimate reform of education and teachers can be the ultimate reformers of education. Still, teachers cannot create all of the needed improvements in education alone. Input from, involvement from, ideas from, and participation from many other people can combine with what only…

Reliability and precision of stress sonography of the ulnar collateral ligament.

PubMed

Bica, David; Armen, Joseph; Kulas, Anthony S; Youngs, Kevin; Womack, Zachary

2015-03-01

Musculoskeletal sonography has emerged as an additional diagnostic tool that can be used to assess medial elbow pain and laxity in overhead throwers. It provides a dynamic, rapid, and noninvasive modality in the evaluation of ligamentous structural integrity. Many studies have demonstrated the utility of dynamic sonography for medial elbow and ulnar collateral ligament (UCL) integrity. However, evaluating the reliabilityand precision of these measurements is critical if sonography is ultimately used as a clinical diagnostic tool. The purpose of this study was to evaluate the reliability and precision of stress sonography applied to the medial elbow. We conducted a cross-sectional study during the 2011 baseball off-season. Eighteen National Collegiate Athletic Association Division I pitchers were enrolled, and 36 elbows were studied. Using sonography, the medial elbow was assessed, and measurements of the UCL length and ulnohumeral joint gapping were performed twice under two conditions (unloaded and loaded) and bilaterally. Intraclass correlation coefficients (0.72-0.94) and standard errors of measurements (0.3-0.9 mm) for UCL length and ulnohumeral joint gapping were good to excellent. Mean differences between unloaded and loaded conditions for the dominant arms were 1.3 mm (gapping; P < .001) and 1.4 mm (UCL length; P < .001). Medial elbow stress sonography is a reliable and precise method for detecting changes in ulnohumeral joint gapping and UCL lengthening. Ultimately, this method may provide clinicians valuable information regarding the medial elbow's response to valgus loading and may help guide treatment options. © 2015 by the American Institute of Ultrasound in Medicine.

Rapidly progressive Scheuermann's disease in an adolescent after pectus bar placement treated with posterior vertebral-column resection: case report and review of the literature.

PubMed

Sugrue, Patrick A; OʼShaughnessy, Brian A; Blanke, Kathy M; Lenke, Lawrence G

2013-02-15

Case report and review of the literature. This case illustrates the importance of the costosternal complex in maintaining the stability and alignment of the thoracic spine. The patient was iatrogenically destabilized by placement of a pectus bar leading to rapid symptomatic progression of his Scheuermann's kyphosis, ultimately requiring surgical correction. Scheuermann's kyphosis is a disease process defined by strict radiographical and clinical criteria. Surgical treatment is generally recommended for curves greater than 75°. This case demonstrates the critical role of the costosternal complex in maintaining the stability of the thoracic spine. The patient described in this report underwent placement of a pectus bar for correction of symptomatic pectus excavatum. He subsequently developed a progressive symptomatic Scheuermann's kyphosis as a result of the destabilization of his costosternal complex. This patient ultimately required removal of the pectus bar and posterior instrumented kyphosis correction. Progressive symptomatic Scheuermann's kyphosis (105°) corrected by removal of the pectus bar, T11 posterior vertebral-column resection and T4-L3 instrumented posterior spinal fusion. The patient had an uneventful immediate postoperative course. He was discharged neurologically intact with dramatic kyphosis correction and significant symptomatic improvement. Radiographs obtained 3 years postoperatively reveal stable thoracolumbar correction. The costosternal complex plays a critically important role in the intrinsic stability of the thoracic spine. Iatrogenic disruption of the costosternal complex can result in rapid progression of thoracic/thoracolumbar kyphosis in the setting of Scheuermann's disease.

Perspectives on rapid elimination and ultimate global eradication of paralytic poliomyelitis caused by polioviruses.

PubMed

Sabin, A B

1991-03-01

Poliomyelitis caused by polioviruses has already been eradicated from industrialized countries of North America, Europe, Asia and Oceania, but the procedures by which this eradication was achieved are not adequate for the poor tropical and subtropical countries. The major challenge now is first to eliminate it rapidly from Asia and Africa where an estimated 250,000 cases and 25,000 deaths currently occur annually. The great progress toward eradication of "wild" polioviruses from poor tropical and subtropical countries in Latin America was achieved not by the procedures still recommended by the WHO Expanded Program on Immunization (EPI) but by the independently organized annual, national days of antipolio vaccination - all based on the use of large armies of well-trained non-professional, community volunteers - first used in Cuba (1962), Brazil (1980), Nicaragua (1981), Dominican Republic (1983), Paraguay (1985), and Mexico (1986). This novel approach, described in some detail in this communication, is recommended for the rapid elimination of wild polioviruses from Asia and Africa, and for ultimate global eradication with the help of a special cadre within the EPI of WHO. The extensive use by the Pan American Health Organization (PAHO) of highly sophisticated regional virus laboratories has led to the recognition that, in areas from which poliomyelitis caused by polioviruses has been largely eliminated, there are thousands of cases of acute flaccid paralysis, previously clinically diagnosed as "probable poliomyelitis", that have no viral etiology, a phenomenon previously reported by Dr. Manuel Ramos Alvarez in Mexico City in 1967.

Unravelling biology and shifting paradigms in cancer with single-cell sequencing.

PubMed

Baslan, Timour; Hicks, James

2017-08-24

The fundamental operative unit of a cancer is the genetically and epigenetically innovative single cell. Whether proliferating or quiescent, in the primary tumour mass or disseminated elsewhere, single cells govern the parameters that dictate all facets of the biology of cancer. Thus, single-cell analyses provide the ultimate level of resolution in our quest for a fundamental understanding of this disease. Historically, this quest has been hampered by technological shortcomings. In this Opinion article, we argue that the rapidly evolving field of single-cell sequencing has unshackled the cancer research community of these shortcomings. From furthering an elemental understanding of intra-tumoural genetic heterogeneity and cancer genome evolution to illuminating the governing principles of disease relapse and metastasis, we posit that single-cell sequencing promises to unravel the biology of all facets of this disease.

Global Change Data Center: Mission, Organization, Major Activities, and 2003 Highlights

NASA Technical Reports Server (NTRS)

2004-01-01

Rapid, efficient access to Earth sciences data from satellites and ground validation stations is fundamental to the nation's efforts to understand the effects of global environmental changes and their implications for public policy. It becomes a bigger challenge in the future when data volumes increase from current levels to terabytes per day. Demands on data storage, data access, network throughput, processing power, and database and information management are increased by orders of magnitude, while budgets remain constant and even shrink.The Global Change Data Center's (GCDC) mission is to develop and operate data systems, generate science products, and provide archival and distribution services for Earth science data in support of the U.S. Global Change Program and NASA's Earth Sciences Enterprise. The ultimate product of the GCDC activities is access to data to support research, education, and public policy.

Mechanics of dual-mode dilative failure in subaqueous sediment deposits

NASA Astrophysics Data System (ADS)

You, Yao; Flemings, Peter; Mohrig, David

2014-07-01

We introduce dual-mode dilative failure with flume experiments. Dual-mode dilative failure combines slow and steady release of sediments by breaching with periodic sliding, which rapidly releases an internally coherent wedge of sediments. It occurs in dilative sandy deposits. This periodic slope failure results from cyclic evolution of the excess pore pressure in the deposit. Sliding generates large, transient, negative excess pore pressure that strengthens the deposit and allows breaching to occur. During breaching, negative excess pore pressure dissipates, the deposit weakens, and ultimately sliding occurs once again. We show that the sliding frequency is proportional to the coefficient of consolidation. We find that thicker deposits are more susceptible to dual-mode dilative failure. Discovery of dual-mode dilative failure provides a new mechanism to consider when interpreting the sedimentary deposits linked to submarine slope failures.

Adjudicating pathological criminal incapacity within a climate of ultimate issue barriers: a comparative perspective.

PubMed

Stevens, Geert Philip

2015-01-01

Mental health experts are increasingly being utilised by the criminal justice system to provide assistance to courts during the assessment of issues falling beyond the knowledge and/or experience of the courts. A particular domain where the assistance of qualified psychiatrists and psychologists is becoming essential is where the defence of pathological criminal incapacity falls to be assessed. Mental health professionals testifying during trials where the defence of pathological criminal incapacity is raised will present opinion evidence which is one of the exceptions to the rule of inadmissibility of opinion evidence. Mental health professionals providing their opinion evidence are, however, prohibited from expressing opinions on so-called "ultimate issues" upon which only the court may ultimately rule upon. The latter rule is also commonly known in practice as the "ultimate issue" rule which presents multifaceted challenges in respect of the application of the defence of pathological criminal incapacity. In this article, the author assesses the application of the ultimate issue rule with reference to the defence of pathological criminal incapacity as it operates within the South African criminal law context. A comparative analysis is also provided with reference to the rule as it operates in the United States of America and more specifically Federal Rule 704. It is concluded that the ultimate issue rule unnecessarily restricts testimony provided by mental health professionals as such placing a barrier on such evidence. As such, it is argued that the rule is superfluous as it remains within the discretion of the trier of fact to decide as to what weight to attach to such evidence. Copyright © 2015. Published by Elsevier Ltd.

Rapid Turn Around BRIC-PDFU Payload: A New Paradigm for Spaceflight Experiments

NASA Technical Reports Server (NTRS)

Levine, Howard G.; Slater, K. A.; Cox, D. R.

2010-01-01

In 2009, NASA's Fundamental Space Biology program provided an opportunity for investigators to propose for a quick-turn-around multi-user spaceflight experiment that focused on the model plant species Arabidopsis thaliana. This was a passive payload with no on-orbit power or communications available. An NRA was rapidly written (8/09), released (NNH09ZTT004N; 9/09), proposals were received (11/09) and peer reviewed with 3 PI groups selected for flight (1/10): (1) A-L Paul, University of Florida, (2) E. Blancaflor, Noble Foundation, (3) J. Kiss, Miami University. The investigators flew Arabidopsis seeds or callus cultures of their choosing (plated onto 60 mm diameter Petri dishes containing agarsolidified media) on the STS-131 Space Shuttle mission (launched 4/5/10) and the resulting plant tissues returned to earth on 4/20/10. Each petri dish was placed inside its own Petri Dish Fixation Unit (PDFU), which was assembled and loaded with either formaldehyde, glutaraldehyde or RNAlater for crew-facilitated on-orbit fixation. Five PDFUs plus a temperature data logger were loaded into each of 8 BRIC-PDFUs (Biological Research In Canisters PDFU). All eight BRIC-PDFUs were loaded into a half tray along with actuator equipment that the crew used for the fixations. Pre-flight turn-over was 28 hours prior to launch. The BRIC-PDFU assemblies were removed from the orbiter and handed over to the investigator teams for processing 5-6 hours after landing. This payload demonstrated a rapid response turnaround for flying multiple peer-reviewed science investigations using previously flown hardware and minimal ISS-resources. The approach used reduced both hardware/certification and PI costs. The time waiting for a flight opportunity for the selected Pls was minimal. This new paradigm for spaceflight experiments may provide a model for future flight research opportunities. The ultimate goal is to fly as many investigators as rapidly as possible and reinvigorate the space biology community while obtaining high-quality, peer-reviewed science.

Management of Resistance to Crizotinib in Anaplastic Lymphoma Kinase-Positive Non-Small-cell Lung Cancer.

PubMed

Matikas, Alexios; Kentepozidis, Nikolaos; Georgoulias, Vassilis; Kotsakis, Athanasios

2016-11-01

During the past decade, the recognition of an ever-expanding list of driver oncogenic mutations in non-small-cell lung cancer has resulted in rapid therapeutic advances. Since the first description of the echinoderm microtubule-associated protein-like 4 anaplastic lymphoma kinase (EML4-ALK) rearrangement in 4% of cases of non-small-cell lung cancer in 2007, a highly potent and selective ALK inhibitor, crizotinib, was developed and approved in record time. However, it soon became apparent that although the responses can be dramatic and durable and primary intrinsic resistance to crizotinib is uncommon, the emergence of secondary resistance is inevitable. Efforts to elucidate the specific mechanisms that confer acquired resistance to crizotinib are underway. These have led to the recognition of the role of secondary resistance mutations, of ALK amplification, and of activation of bypass signaling, all of which contribute to resistance to crizotinib. Moreover, the rapid preclinical and clinical development of multiple second-generation ALK inhibitors that exhibit significant clinical activity against crizotinib-resistant disease has provided multiple options to treating physicians, with the ultimate goal the delivery of tailored medicine. Copyright © 2016 Elsevier Inc. All rights reserved.

Rapid Generation of Optimal Asteroid Powered Descent Trajectories Via Convex Optimization

NASA Technical Reports Server (NTRS)

Pinson, Robin; Lu, Ping

2015-01-01

This paper investigates a convex optimization based method that can rapidly generate the fuel optimal asteroid powered descent trajectory. The ultimate goal is to autonomously design the optimal powered descent trajectory on-board the spacecraft immediately prior to the descent burn. Compared to a planetary powered landing problem, the major difficulty is the complex gravity field near the surface of an asteroid that cannot be approximated by a constant gravity field. This paper uses relaxation techniques and a successive solution process that seeks the solution to the original nonlinear, nonconvex problem through the solutions to a sequence of convex optimal control problems.

Sharing the Sky: The Role of Family and Consumer Sciences in Sustainability.

ERIC Educational Resources Information Center

Makela, Carole J.

2003-01-01

Explains why sustainability is integral to family and consumer sciences. Presents a framework depicting the relationship of ultimate means, intermediate means, intermediate ends, and ultimate ends. Provides classroom activities. (SK)

Innovating aging: promises and pitfalls on the road to life extension

PubMed Central

Vijg, Jan; de Grey, Aubrey D.N.J.

2014-01-01

One of the main benefits from the dramatic technological progress over the last two centuries is the enormous increase in human life expectancy, which has now reached record highs. After conquering most childhood diseases and a fair fraction of the diseases that plague adulthood, medical technology is now mainly pre-occupied by age-related disorders. Further progress is dependent on circumventing the traditional medical focus on individual diseases and instead targeting aging as a whole as the ultimate cause of the health problems that affect humankind at old age. In principle, a major effort to control the gradual accumulation of molecular and cellular damage – considered by many as the ultimate cause of intrinsic aging – may rapidly lead to interventions for regenerating aged and worn-out tissues and organs. While considered impossible by many, there really is no reason to reject this as scientifically implausible. However, as we discuss, it is not only scientific progress that is currently a limiting factor, but societal factors that hinder and may ultimately prevent further progress in testing and adopting the many possible interventions to cure aging. PMID:24732067

Portable Body Temperature Conditioner

DTIC Science & Technology

2013-12-01

thermal manikin. This research will identify specific design improvements to be implemented in a reiterative process , ultimately leading to an...activity in hot environmental conditions. Studies have shown that lowering the patient’s core body temperature rapidly to 38oC improves complications and...further attempts to hire a second technician, during the past year (Year 2) UNSOM began the process of hiring a bio-heat transfer engineering expert to

Analytical modeling of mercury injection in high-rank coalbed methane reservoirs based on pores and microfractures: a case study of the upper carboniferous Taiyuan Formation in the Heshun block of the Qinshui Basin, central China

NASA Astrophysics Data System (ADS)

Gu, Yang; Ding, Wenlong; Yin, Shuai; Wang, Ruyue; Mei, Yonggui; Liu, Jianjun

2017-03-01

The coalbed gas reservoirs in the Qinshui Basin in central China are highly heterogeneous; thus, the reservoir characteristics are difficult to assess. Research on the pore structure of a reservoir can provide a basis for understanding the occurrence and seepage mechanisms of coal reservoirs, rock physics modeling and the formulation of rational development plans. Therefore, the pore structure characteristics of the coalbed gas reservoirs in the high rank bituminous coal in the No. 15 coal seam of the Carboniferous Taiyuan Group in the Heshun coalbed methane (CBM) blocks in the northeastern Qinshui Basin were analyzed based on pressure mercury and scanning electron microscopy data. The results showed that the effective porosity system of the coal reservoir was mainly composed of pores and microfractures and that the pore throat configuration of the coal reservoir was composed of pores and microthroats. A model was developed based on the porosity and microfractures of the high rank coal rock and the mercury injection and drainage curves. The mercury injection curve model and the coal permeability are well correlated and were more reliable for the analysis of coal and rock pore system connectivity than the mercury drainage curve model. Coal rocks with developed microfractures are highly permeable; the production levels are often high during the initial drainage stages, but they decrease rapidly. A significant portion of the natural gas remains in the strata and cannot be exploited; therefore, the ultimate recovery is rather low. Coal samples with underdeveloped microfractures have lower permeabilities. While the initial production levels are lower, the production cycle is longer, and the ultimate recovery is higher. Therefore, the initial production levels of coal reservoirs with poorly developed microfractures in some regions of China may be low. However, over the long term, due to their higher ultimate recoveries and longer production cycles, the total gas production levels will increase. This understanding can provide an important reference for developing appropriate CBM development plans.

Design variables for mechanical properties of bone tissue scaffolds.

PubMed

Howk, Daniel; Chu, Tien-Min G

2006-01-01

The reconstruction of segmental defect in long bone is a clinical challenge. Multiple surgeries are typically required to restore the structure and function of the affected defect site. In order to overcome this defect a biodegradable bone tissue engineering scaffold is used. This scaffold acts as a carrier of proteins and growth factors, while also supporting the load that the bone would normally sustain, until the natural bone can regenerate in its place. Work was done to optimize an existing solid free-form scaffold design. The goal of the optimization was to increase the porosity of the scaffold while maintaining the strength of a previously-tested prototype design. With this in mind, eight new designs were created. These designs were drawn using CAD software and then through the use of finite element analysis the theoretical ultimate compressive strength of each design was obtained. Each scaffold design was constructed by casting a thermal-curable poly(propylene fumarate)/tricalcium phosphate (PPF/TCP) suspension into wax molds fabricated on inkjet printing rapid prototyping machine. The constructs were then experimentally tested by applying a uniaxial compressive load. The theoretical and experimental values of ultimate compressive strength and specific strength of each design were compared. Theoretically, the best scaffold design produced from this work improved upon the current design by increasing the porosity by 46% and also increasing the ultimate compressive strength by 27%. The experimental data was found to match the theoretical strength in four designs, but deviate from the theoretical strength in five designs. The reasons for the deviations and their relation to the rapid prototyping manufacturing technique were discussed. The results of this work show that it is possible to increase the porosity and strength of a bone tissue engineering scaffold through simple iterations in architectural design.

The Role of Moist Processes in the Intrinsic Predictability of Indian Ocean Cyclones

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

Taraphdar, Sourav; Mukhopadhyay, P.; Leung, Lai-Yung R.

The role of moist processes and the possibility of error cascade from cloud scale processes affecting the intrinsic predictable time scale of a high resolution convection permitting model within the environment of tropical cyclones (TCs) over the Indian region are investigated. Consistent with past studies of extra-tropical cyclones, it is demonstrated that moist processes play a major role in forecast error growth which may ultimately limit the intrinsic predictability of the TCs. Small errors in the initial conditions may grow rapidly and cascades from smaller scales to the larger scales through strong diabatic heating and nonlinearities associated with moist convection.more » Results from a suite of twin perturbation experiments for four tropical cyclones suggest that the error growth is significantly higher in cloud permitting simulation at 3.3 km resolutions compared to simulations at 3.3 km and 10 km resolution with parameterized convection. Convective parameterizations with prescribed convective time scales typically longer than the model time step allows the effects of microphysical tendencies to average out so convection responds to a smoother dynamical forcing. Without convective parameterizations, the finer-scale instabilities resolved at 3.3 km resolution and stronger vertical motion that results from the cloud microphysical parameterizations removing super-saturation at each model time step can ultimately feed the error growth in convection permitting simulations. This implies that careful considerations and/or improvements in cloud parameterizations are needed if numerical predictions are to be improved through increased model resolution. Rapid upscale error growth from convective scales may ultimately limit the intrinsic mesoscale predictability of the TCs, which further supports the needs for probabilistic forecasts of these events, even at the mesoscales.« less

Risk assessment, cross-resistance potential, and biochemical mechanism of resistance to emamectin benzoate in a field strain of house fly (Musca domestica Linnaeus).

PubMed

Khan, Hafiz Azhar Ali; Akram, Waseem; Khan, Tiyyabah; Haider, Muhammad Saleem; Iqbal, Naeem; Zubair, Muhammad

2016-05-01

Reduced sensitivity to insecticides in insect pests often results in control failures and increases in the dose and frequency of applications, ultimately polluting the environment. Reduced sensitivity to emamectin benzoate, a broad-spectrum agrochemical belonging to the avermectin group of pesticides, was reported in house flies (Musca domestica L.) collected from Punjab, Pakistan, in 2013. The aim of the present study was to investigate the risk for resistance development, biochemical mechanism, and cross-resistance potential to other insecticides in an emamectin benzoate selected (EB-SEL) strain of house flies. A field-collected strain showing reduced sensitivity to emamectin was re-selected in the laboratory for five consecutive generations and compared with a laboratory susceptible (Lab-Susceptible) reference strain, using bioassays. The field strain showed rapid development of resistance to emamectin (resistance ratio (RR) increased from 35.15 to 149.26-fold) as a result of selection experiments; however, resistance declined when the selection pressure uplifted. The EB-SEL strain showed reduction in resistance to abamectin, indoxacarb, and thiamethoxam. The results of synergism experiments using piperonyl butoxide (PBO) and S,S,S-tributylphosphorotrithioate (DEF) enzyme inhibitors and biochemical analyses revealed that the metabolic resistance mechanism was not responsible in developing emamectin resistance in the EB-SEL strain. In conclusion, the risk for the rapid development of emamectin resistance under continuous selection pressure suggests using a multifaceted integrated pest management approach for house flies. Moreover, the instable nature of emamectin resistance in the EB-SEL strain and lack of cross-resistance to other insecticides provide windows for the rotational use of insecticides with different modes of action. This will ultimately reduce emamectin selection pressure and help improving management programs for house flies without polluting the environment. Copyright © 2016 Elsevier Ltd. All rights reserved.

Is the Bakken Formation the Answer to our Energy Independence?

NASA Astrophysics Data System (ADS)

Waggoner, E. G.; Hall, C.

2012-12-01

The Bakken Formation has garnered substantial attention due to an unprecedented surge in US domestic oil production, much of it from shale oil from the Bakken. The sheer size of the formation coupled with technological advances in horizontal drilling and hydraulic fracking have led many, including the former head of BP, to speculate that domestic shale oil will free the US from its dependence upon foreign oil entirely. Shale oil is indeed likely to provide a significant contribution to our domestic energy portfolio, but real problems exist in the form of physical limitations. Our preliminary analysis indicates that the most important fields in the Bakken Formation are depleting rapidly. Mckenzie and Mountrail Counties, the two largest oil producing counties in North Dakota, account for over 50% of North Dakota's total oil production. However, Mountrail County appears to have hit peak production between the months of March and April 2012. The decline is especially apparent in the Mountrail County's two largest producing fields, suggesting that much of production occurs in concentrated areas and many of these fields with high profitability are undergoing rapid production declines. In order to maintain a consistent level of production and offset these growing declines, an increasing number of wells must be drilled throughout the lifetime of a field. Energy Return on Investment (EROI), the ratio of energy outputs over energy inputs, can be utilized to determine the profitability of resource base. Preliminary EROI analysis indicates that newly developed fields in the Bakken are less profitable and yield far less energy than the larger producing predecessors such as those in Mountrail County. Will the smaller fields ultimately compensate for the steep declines witnessed in the larger fields? If current trends continue, ultimate production from the Bakken will be far less than predicted. This poses significant financial implications for the future of shale oil and US energy independence.

Application of the SHOALS survey system to fisheries investigations in the Columbia River

USGS Publications Warehouse

Tiffan, Kenneth F.; Wagner, Paul G.; Wolf, Keith S.; Hoffarth , Paul A.

2009-01-01

We used a Scanning Hydrographic Operational Airborne LiDAR (Light Detection and Ranging) Survey (SHOALS) system to collect high-resolution bathymetry for 33 km of the Hanford Reach. Data were used in conjunction with hydrodynamic and predictive habitat models within a GIS (Geographical Information System) framework to evaluate the effects of a varying hydrograph on juvenile fall Chinook salmon rearing habitat and risk from stranding and entrapment. Furthermore, we were able to estimate the number of juvenile fish that were stranded and entrapped in pools when operations at Priest Rapids Dam caused rapid decreases in river flows. Our findings were ultimately used to estimate impacts of power generation operations at Priest Rapids Dam and develop long-term policy and operational guidelines to protect juvenile fall Chinook salmon during the spring rearing period.

K-Channel: A Multifunctional Architecture for Dynamically Reconfigurable Sample Processing in Droplet Microfluidics.

PubMed

Doonan, Steven R; Bailey, Ryan C

2017-04-04

By rapidly creating libraries of thousands of unique, miniaturized reactors, droplet microfluidics provides a powerful method for automating high-throughput chemical analysis. In order to engineer in-droplet assays, microfluidic devices must add reagents into droplets, remove fluid from droplets, and perform other necessary operations, each typically provided by a unique, specialized geometry. Unfortunately, modifying device performance or changing operations usually requires re-engineering the device among these specialized geometries, a time-consuming and costly process when optimizing in-droplet assays. To address this challenge in implementing droplet chemistry, we have developed the "K-channel," which couples a cross-channel flow to the segmented droplet flow to enable a range of operations on passing droplets. K-channels perform reagent injection (0-100% of droplet volume), fluid extraction (0-50% of droplet volume), and droplet splitting (1:1-1:5 daughter droplet ratio). Instead of modifying device dimensions or channel configuration, adjusting external conditions, such as applied pressure and electric field, selects the K-channel process and tunes its magnitude. Finally, interfacing a device-embedded magnet allows selective capture of 96% of droplet-encapsulated superparamagnetic beads during 1:1 droplet splitting events at ∼400 Hz. Addition of a second K-channel for injection (after the droplet splitting K-channel) enables integrated washing of magnetic beads within rapidly moving droplets. Ultimately, the K-channel provides an exciting opportunity to perform many useful droplet operations across a range of magnitudes without requiring architectural modifications. Therefore, we envision the K-channel as a versatile, easy to use microfluidic component enabling diverse, in-droplet (bio)chemical manipulations.

A SAFE PROTOCOL FOR RAPID DESENSITIZATION IN PATIENTS WITH CYSTIC FIBROSIS AND ANTIBIOTIC HYPERSENSITIVITY

PubMed Central

Legere, Henry J.; Palis, Ross I.; Bouza, Tito Rodriguez; Uluer, Ahmet Z.; Castells, Mariana C.

2009-01-01

Background CF patients often demonstrate hypersensitivity to one or multiple antibiotics due to frequent and repeated exposures. Attempts at antibiotic desensitization in this population are historically complicated by higher reaction rates, failure to complete the procedure and consequent withholding of first-line therapy. This study evaluates the outcomes of a rapid desensitization protocol developed at our institution. Methods We retrospectively reviewed the medical records of 15 patients undergoing 52 rapid antibiotic desensitizations at Brigham and Women’s Hospital and Children’s Hospital Boston utilizing our protocol. Results Mean FEV1 % predicted was 44.1 (SD 16.5), with two patients at <30% and one patient desensitized during bilateral lung transplantation. Adverse reactions during desensitization occurred in 13.4%, and most were mild. 100% of patients completed the protocol and ultimately tolerated subsequent full-strength antibiotic courses. Conclusions CF patients with antibiotic hypersensitivity can safely receive first-line antibiotics via our rapid desensitization protocol, including those with severe obstructive lung disease. PMID:19740711

Spin-up of a rapidly rotating star by angular momentum loss - Effects of general relativity

NASA Technical Reports Server (NTRS)

Cook, Gregory B.; Shapiro, Stuart L.; Teukolsky, Saul A.

1992-01-01

It has recently been shown that a rapidly rotating Newtonian star can spin up by radiating angular momentum. Extremely fast pulsars losing energy and angular momentum by magnetic dipole radiation or gravitational radiation may exhibit this behavior. Here, we show that this phenomenon is more widespread for rapidly rotating stars in general relativity. We construct and tabulate polytropic sequences of fully relativistic rotating stars of constant rest mass and entropy. We find that the range of adiabatic indices allowing spin-up extends somewhat above 4/3 because of the nonlinear effects of relativistic gravity. In addition, there is a new class of 'supramassive' stars which will inevitably spin up by losing angular momentum regardless of their equation of state. A supramassive star, spinning up via angular momentum loss, will ultimately evolve until it becomes unstable to catastrophic collapse to a black hole. Spin-up in a rapidly rotating star may thus be an observational precursor to such collapse.

Update on modern neuraxial analgesia in labour: a review of the literature of the last 5 years.

PubMed

Loubert, C; Hinova, A; Fernando, R

2011-03-01

Several strategies and alternative therapies have been used to provide analgesia for labour pain. Over the last few years, a number of improvements have enhanced the efficacy and safety of neuraxial analgesia and ultimately have improved mothers' satisfaction with their birth experience. As labour analgesia is a field of obstetric anaesthesia that is rapidly evolving, this review is an update, from a clinical point of view, of developments over the last 5-7 years. We discuss advantages and controversies related to combined spinal-epidural analgesia, patient controlled epidural analgesia and the integration of computer systems into analgesic modalities. We also review the recent literature on future clinical and research perspectives including ultrasound guided neuraxial block placement, epidural adjuvants and pharmacogenetics. We finally look at the latest work with regards to epidural analgesia and breastfeeding. © 2011 The Authors. Anaesthesia © 2011 The Association of Anaesthetists of Great Britain and Ireland.

Intelligent Vision Systems Independent Research and Development (IR&D) 2006

NASA Technical Reports Server (NTRS)

Patrick, Clinton; Chavis, Katherine

2006-01-01

This report summarizes results in conduct of research sponsored by the 2006 Independent Research and Development (IR&D) program at Marshall Space Flight Center (MSFC) at Redstone Arsenal, Alabama. The focus of this IR&D is neural network (NN) technology provided by Imagination Engines, Incorporated (IEI) of St. Louis, Missouri. The technology already has many commercial, military, and governmental applications, and a rapidly growing list of other potential spin-offs. The goal for this IR&D is implementation and demonstration of the technology for autonomous robotic operations, first in software and ultimately in one or more hardware realizations. Testing is targeted specifically to the MSFC Flat Floor, but may also include other robotic platforms at MSFC, as time and funds permit. For the purpose of this report, the NN technology will be referred to by IEI's designation for a subset configuration of its patented technology suite: Self-Training Autonomous Neural Network Object (STANNO).

Sex as a Biological Variable in Emergency Medicine Research and Clinical Practice: A Brief Narrative Review

PubMed Central

McGregor, Alyson J.; Beauchamp, Gillian A.; Wira, Charles R.; Perman, Sarah M.; Safdar, Basmah

2017-01-01

The National Institutes of Health recently highlighted the significant role of sex as a biological variable (SABV) in research design, outcome and reproducibility, mandating that this variable be accounted for in all its funded research studies. This move has resulted in a rapidly increasing body of literature on SABV with important implications for changing the clinical practice of emergency medicine (EM). Translation of this new knowledge to the bedside requires an understanding of how sex-based research will ultimately impact patient care. We use three case-based scenarios in acute myocardial infarction, acute ischemic stroke and important considerations in pharmacologic therapy administration to highlight available data on SABV in evidence-based research to provide the EM community with an important foundation for future integration of patient sex in the delivery of emergency care as gaps in research are filled. PMID:29085541

[Doctor, may I travel in space? Aeromedical considerations regarding commercial suborbital space flights].

PubMed

Haerkens, Marck H T M; Simons, Ries; Kuipers, André

2011-01-01

Within a few years, the first commercial operators will start flying passengers on suborbital flights to the verge of space. Medical data on the effects of space journeys on humans have mainly been provided by professional astronauts. There is very little research into the aeromedical consequences of suborbital flights for the health of untrained passengers. Low air pressure and oxygen tension can be compensated for by pressurising the spacecraft or pressure suit. Rapid changes in gravitational (G-)force pose ultimate challenges to cardiovascular adaptation mechanisms. Zero-gravity and G-force may cause motion sickness. Vibrations and noise during the flight may disturb communication between passengers and crew. In addition, the psychological impact of a suborbital flight should not be underestimated. There are currently no legal requirements available for medical examinations for commercial suborbital flights, but it seems justifiable to establish conditions for potential passengers' states of health.

Autism spectrum disorder causes, mechanisms, and treatments: focus on neuronal synapses

PubMed Central

Won, Hyejung; Mah, Won; Kim, Eunjoon

2013-01-01

Autism spectrum disorder (ASD) is a group of developmental disabilities characterized by impairments in social interaction and communication and restricted and repetitive interests/behaviors. Advances in human genomics have identified a large number of genetic variations associated with ASD. These associations are being rapidly verified by a growing number of studies using a variety of approaches, including mouse genetics. These studies have also identified key mechanisms underlying the pathogenesis of ASD, many of which involve synaptic dysfunctions, and have investigated novel, mechanism-based therapeutic strategies. This review will try to integrate these three key aspects of ASD research: human genetics, animal models, and potential treatments. Continued efforts in this direction should ultimately reveal core mechanisms that account for a larger fraction of ASD cases and identify neural mechanisms associated with specific ASD symptoms, providing important clues to efficient ASD treatment. PMID:23935565

A human-centered framework for innovation in conservation incentive programs.

PubMed

Sorice, Michael G; Donlan, C Josh

2015-12-01

The promise of environmental conservation incentive programs that provide direct payments in exchange for conservation outcomes is that they enhance the value of engaging in stewardship behaviors. An insidious but important concern is that a narrow focus on optimizing payment levels can ultimately suppress program participation and subvert participants' internal motivation to engage in long-term conservation behaviors. Increasing participation and engendering stewardship can be achieved by recognizing that participation is not simply a function of the payment; it is a function of the overall structure and administration of the program. Key to creating innovative and more sustainable programs is fitting them within the existing needs and values of target participants. By focusing on empathy for participants, co-designing program approaches, and learning from the rapid prototyping of program concepts, a human-centered approach to conservation incentive program design enhances the propensity for discovery of novel and innovative solutions to pressing conservation issues.

Sonography of pediatric superficial lumps and bumps: illustrative examples from head to toe.

PubMed

Bansal, Anmol Gupta; Rosenberg, Henrietta Kotlus

2017-08-01

Superficial lumps and bumps are extremely common in children, and the vast majority ultimately prove to be benign. Duplex/color Doppler ultrasound (US) has emerged as the first-line imaging modality for the evaluation of these superficial pediatric masses because it provides a means for rapid acquisition of information including size, shape, location, internal content and vascularity. More important, it does so without utilizing radiation, iodinated contrast material or sedation/anesthesia. In this review, we present the sonographic findings of a variety of cases ranging from head to toe that are either uncommonly seen or were diagnosed in an atypical fashion (i.e. ultrasound). In situations where the lesion is too deep, hyperechoic or large to be fully assessed within the field of view or if malignancy is suspected, then additional cross-sectional imaging is warranted for further evaluation.

Microbes Should Be Central to Ecological Education and Outreach

PubMed Central

Barberán, Albert; Hammer, Tobin J.; Madden, Anne A.; Fierer, Noah

2016-01-01

Our planet is changing rapidly, and responding to the ensuing environmental challenges will require an informed citizenry that can understand the inherent complexity of ecological systems. However, microorganisms are usually neglected in the narratives that we use to understand nature. Here, we advocate for the inclusion of microbial ecology across education levels and delineate the often neglected benefits of incorporating microbes into ecology curricula. We provide examples across education levels, from secondary school (by considering one’s self as a microbial ecosystem), to higher education (by incorporating our knowledge of the global ecological role and medical application of microbes), to the general public (by engagement through citizen-science projects). The greater inclusion of microbes in ecological education and outreach will not only help us appreciate the natural world we are part of, but will ultimately aid in building a citizenry better prepared to make informed decisions on health and environmental policies. PMID:27047584

Software Certification and Software Certificate Management Systems

NASA Technical Reports Server (NTRS)

Denney, Ewen; Fischer, Bernd

2005-01-01

Incremental certification and re-certification of code as it is developed and modified is a prerequisite for applying modem, evolutionary development processes, which are especially relevant for NASA. For example, the Columbia Accident Investigation Board (CAIB) report 121 concluded there is "the need for improved and uniform statistical sampling, audit, and certification processes". Also, re-certification time has been a limiting factor in making changes to Space Shuttle code close to launch time. This is likely to be an even bigger problem with the rapid turnaround required in developing NASA s replacement for the Space Shuttle, the Crew Exploration Vehicle (CEV). Hence, intelligent development processes are needed which place certification at the center of development. If certification tools provide useful information, such as estimated time and effort, they are more likely to be adopted. The ultimate impact of such a tool will be reduced effort and increased reliability.

Improving confidence in environmental DNA species detection.

PubMed

Jerde, Christopher L; Mahon, Andrew R

2015-05-01

Will we catch fish today? Our grandfathers' responses were usually something along the lines of, 'Probably. I've caught them here before'. One of the foundations of ecology is identifying which species are present, and where. This informs our understanding of species richness patterns, spread of invasive species, and loss of threatened and endangered species due to environmental change. However, our understanding is often lacking, particularly in aquatic environments where biodiversity remains hidden below the water's surface. The emerging field of metagenetic species surveillance is aiding our ability to rapidly determine which aquatic species are present, and where. In this issue of Molecular Ecology Resources, Ficetola et al. () provide a framework for metagenetic environmental DNA surveillance to foster the confidence of our grandfathers' fishing prowess by more rigorously evaluating the replication levels necessary to quantify detection errors and ultimately improving our confidence in aquatic species presence. © 2015 John Wiley & Sons Ltd.

Project of Near-Real-Time Generation of ShakeMaps and a New Hazard Map in Austria

NASA Astrophysics Data System (ADS)

Jia, Yan; Weginger, Stefan; Horn, Nikolaus; Hausmann, Helmut; Lenhardt, Wolfgang

2016-04-01

Target-orientated prevention and effective crisis management can reduce or avoid damage and save lives in case of a strong earthquake. To achieve this goal, a project for automatic generated ShakeMaps (maps of ground motion and shaking intensity) and updating the Austrian hazard map was started at ZAMG (Zentralanstalt für Meteorologie und Geodynamik) in 2015. The first goal of the project is set for a near-real-time generation of ShakeMaps following strong earthquakes in Austria to provide rapid, accurate and official information to support the governmental crisis management. Using newly developed methods and software by SHARE (Seismic Hazard Harmonization in Europe) and GEM (Global Earthquake Model), which allows a transnational analysis at European level, a new generation of Austrian hazard maps will be ultimately calculated. More information and a status of our project will be given by this presentation.

[Monolithic column-gold composite substrate preparation and application to SERS detection of pigment].

PubMed

Xie, Yun-Fei; Li, Yan; Yu, Hui; Qian, He; Yao, Wei-Rong

2014-03-01

In the present study, we developed a novel SERS substrate with the porous monolith material combined with classic gold nanoparticles, and erythrosine as the research object, by adjusting the different experimental conditions for optimal SERS enhancements, including system pH and mixing time, and ultimately selected the optimum pH value 5.06 and mixing time 25 min. Compared with the traditional gold plastic substrate enhancement effect, the experimental conditions were applied to the monolith substrate SERS detection of dye erythrosine, different concentrations of samples were used for erythrosine SERS detection, and the detection limit reached 0.1 g x mL(-1). The method uses the payload of gold nanoparticles in mesoporous materials to effectively enhance the SERS signal. And this method has the advantages of simpleness and good stability, which provides a favorable theoretical basis for the rapid prohibited colorings screening.

The MetSkill Program — Rapidly Developing Effective Young Engineers in the Workplace

NASA Astrophysics Data System (ADS)

Drinkwater, Diana; Bianco, Nina

MetSkill is a professional development program for metallurgical engineers that integrates with normal duties in their first one or two years of service. Graduates work together on a structured technical project, facilitated by specialists and supported by formal learning, and ultimately reported to their technical managers. The program enables graduates to "fill the gaps" in their undergraduate education, which is increasingly pertinent as engineering degrees become more general. Participants report that they enjoy the focus on more challenging (rewarding) aspects of their jobs and feel more confident about problem solving. Sponsor companies add that the relationships developed with external technical specialists enhances opportunities for innovation and development. MetSkill was delivered to two major resource companies in Australia in 2012. This paper provides an outline of the program and the reasons for its success, and demonstrates how the learning model could be applied to groups of graduates in other engineering disciplines.

SYTO probes: markers of apoptotic cell demise.

PubMed

Wlodkowic, Donald; Skommer, Joanna

2007-10-01

As mechanistic studies on tumor cell death advance towards their ultimate translational goal, there is a need for specific, rapid, and high-throughput analytical tools to detect diverse cell demise modes. Patented DNA-binding SYTO probes, for example, are gaining increasing interest as easy-to-use markers of caspase-dependent apoptotic cell death. They are proving convenient for tracking apoptosis in diverse hematopoietic cell lines and primary tumor samples, and, due to their spectral characteristics, appear to be useful for the development of multiparameter flow cytometry assays. Herein, several protocols for multiparametric assessment of apoptotic events using SYTO probes are provided. There are protocols describing the use of green fluorescent SYTO 16 and red fluorescent SYTO 17 dyes in combination with plasma membrane permeability markers. Another protocol highlights the multiparametric use of SYTO 16 dye in conjunction with the mitochondrial membrane potential sensitive probe, tetramethylrhodamine methyl ester (TMRM), and the plasma membrane permeability marker, 7-aminoactinomycin D (7-AAD).

Current understanding of the human microbiome.

PubMed

Gilbert, Jack A; Blaser, Martin J; Caporaso, J Gregory; Jansson, Janet K; Lynch, Susan V; Knight, Rob

2018-04-10

Our understanding of the link between the human microbiome and disease, including obesity, inflammatory bowel disease, arthritis and autism, is rapidly expanding. Improvements in the throughput and accuracy of DNA sequencing of the genomes of microbial communities that are associated with human samples, complemented by analysis of transcriptomes, proteomes, metabolomes and immunomes and by mechanistic experiments in model systems, have vastly improved our ability to understand the structure and function of the microbiome in both diseased and healthy states. However, many challenges remain. In this review, we focus on studies in humans to describe these challenges and propose strategies that leverage existing knowledge to move rapidly from correlation to causation and ultimately to translation into therapies.

Current understanding of the human microbiome

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

Gilbert, Jack A.; Blaser, Martin J.; Caporaso, J. Gregory

Our understanding of the link between the human microbiome and disease, including obesity, inflammatory bowel disease, arthritis and autism, is rapidly expanding. Improvements in the throughput and accuracy of DNA sequencing of the genomes of microbial communities associated with human samples, complemented by analysis of transcriptomes, proteomes, metabolomes and immunomes, and mechanistic experiments in model systems, have vastly improved our ability to understand the structure and function of the microbiome in both diseased and healthy states. However, many challenges remain. In this Review we focus on studies in humans to describe these challenges, and propose strategies that leverage existing knowledgemore » to move rapidly from correlation to causation, and ultimately to translation.« less

Zika virus: a previously slow pandemic spreads rapidly through the Americas.

PubMed

Gatherer, Derek; Kohl, Alain

2016-02-01

Zika virus (family Flaviviridae) is an emerging arbovirus. Spread by Aedes mosquitoes, it was first discovered in Uganda in 1947, and later in humans elsewhere in sub-Saharan Africa, arriving in south-east Asia at latest by the mid-twentieth century. In the twenty-first century, it spread across the Pacific islands reaching South America around 2014. Since then it has spread rapidly northwards reaching Mexico in November 2015. Its clinical profile is that of a dengue-like febrile illness, but associations with Guillain-Barré syndrome and microcephaly have appeared recently. The final geographical range and ultimate clinical impact of Zika virus are still a matter for speculation.

RAPID RESCUE: BREAKING THE MOLD OF ROUTINE CONTINGENCY RESPONSE FOR PERSONNEL RECOVERY

DTIC Science & Technology

2016-10-23

ultimately lead to timelier response and greater economy of force for an already critically strained Air Force core function. 1 INTRODUCTION...achieve economy of force. When an OPLAN calls for PR, a capability is requested rather than individual unit. The existing UTCs are too rigid and...the combatant commander and operational planners to achieve unity and economy of force without exceeding PR capacity.61 Tactical Employment

Update on Simulating Ice-Cliff Failure

NASA Astrophysics Data System (ADS)

Parizek, B. R.; Christianson, K. A.; Alley, R. B.; Voytenko, D.; Vankova, I.; Dixon, T. H.; Walker, R. T.; Holland, D.

2017-12-01

Using a 2D full-Stokes diagnostic ice-flow model and engineering and glaciological failure criteria, we simulate the limiting physical conditions for rapid structural failure of subaerial ice cliffs. Previously, using a higher-order flowline model, we reported that the threshold height, in crevassed ice and/or under favorable conditions for hydrofracture or crack lubrication, may be only slightly above the 100-m maximum observed today and that under well-drained or low-melt conditions, mechanically-competent ice supports cliff heights up to 220 m (with a likely range of 180-275 m) before ultimately succumbing to tensional and compressive failure along a listric surface. However, proximal to calving fronts, bridging effects lead to variations in vertical normal stress from the background glaciostatic stress state that give rise to the along-flow gradients in vertical shear stress that are included within a full-Stokes momentum balance. When including all flowline stresses within the physics core, diagnostic solutions continue to support our earlier findings that slumping failure ultimately limits the upper bound for cliff heights. Shear failure still requires low cohesive strength, tensile failure leads to deeper dry-crevasse propagation (albeit, less than halfway through the cliff), and compressive failure drops the threshold height for triggering rapid ice-front retreat via slumping to 200 m (145-280 m).

Reduced Design Load Basis for Ultimate Blade Loads Estimation in Multidisciplinary Design Optimization Frameworks

NASA Astrophysics Data System (ADS)

Pavese, Christian; Tibaldi, Carlo; Larsen, Torben J.; Kim, Taeseong; Thomsen, Kenneth

2016-09-01

The aim is to provide a fast and reliable approach to estimate ultimate blade loads for a multidisciplinary design optimization (MDO) framework. For blade design purposes, the standards require a large amount of computationally expensive simulations, which cannot be efficiently run each cost function evaluation of an MDO process. This work describes a method that allows integrating the calculation of the blade load envelopes inside an MDO loop. Ultimate blade load envelopes are calculated for a baseline design and a design obtained after an iteration of an MDO. These envelopes are computed for a full standard design load basis (DLB) and a deterministic reduced DLB. Ultimate loads extracted from the two DLBs with the two blade designs each are compared and analyzed. Although the reduced DLB supplies ultimate loads of different magnitude, the shape of the estimated envelopes are similar to the one computed using the full DLB. This observation is used to propose a scheme that is computationally cheap, and that can be integrated inside an MDO framework, providing a sufficiently reliable estimation of the blade ultimate loading. The latter aspect is of key importance when design variables implementing passive control methodologies are included in the formulation of the optimization problem. An MDO of a 10 MW wind turbine blade is presented as an applied case study to show the efficacy of the reduced DLB concept.

The changing epitome of species identification – DNA barcoding

PubMed Central

Ajmal Ali, M.; Gyulai, Gábor; Hidvégi, Norbert; Kerti, Balázs; Al Hemaid, Fahad M.A.; Pandey, Arun K.; Lee, Joongku

2014-01-01

The discipline taxonomy (the science of naming and classifying organisms, the original bioinformatics and a basis for all biology) is fundamentally important in ensuring the quality of life of future human generation on the earth; yet over the past few decades, the teaching and research funding in taxonomy have declined because of its classical way of practice which lead the discipline many a times to a subject of opinion, and this ultimately gave birth to several problems and challenges, and therefore the taxonomist became an endangered race in the era of genomics. Now taxonomy suddenly became fashionable again due to revolutionary approaches in taxonomy called DNA barcoding (a novel technology to provide rapid, accurate, and automated species identifications using short orthologous DNA sequences). In DNA barcoding, complete data set can be obtained from a single specimen irrespective to morphological or life stage characters. The core idea of DNA barcoding is based on the fact that the highly conserved stretches of DNA, either coding or non coding regions, vary at very minor degree during the evolution within the species. Sequences suggested to be useful in DNA barcoding include cytoplasmic mitochondrial DNA (e.g. cox1) and chloroplast DNA (e.g. rbcL, trnL-F, matK, ndhF, and atpB rbcL), and nuclear DNA (ITS, and house keeping genes e.g. gapdh). The plant DNA barcoding is now transitioning the epitome of species identification; and thus, ultimately helping in the molecularization of taxonomy, a need of the hour. The ‘DNA barcodes’ show promise in providing a practical, standardized, species-level identification tool that can be used for biodiversity assessment, life history and ecological studies, forensic analysis, and many more. PMID:24955007

Retinal Prosthetics, Optogenetics, and Chemical Photoswitches

PubMed Central

2015-01-01

Three technologies have emerged as therapies to restore light sensing to profoundly blind patients suffering from late-stage retinal degenerations: (1) retinal prosthetics, (2) optogenetics, and (3) chemical photoswitches. Prosthetics are the most mature and the only approach in clinical practice. Prosthetic implants require complex surgical intervention and provide only limited visual resolution but can potentially restore navigational ability to many blind patients. Optogenetics uses viral delivery of type 1 opsin genes from prokaryotes or eukaryote algae to restore light responses in survivor neurons. Targeting and expression remain major problems, but are potentially soluble. Importantly, optogenetics could provide the ultimate in high-resolution vision due to the long persistence of gene expression achieved in animal models. Nevertheless, optogenetics remains challenging to implement in human eyes with large volumes, complex disease progression, and physical barriers to viral penetration. Now, a new generation of photochromic ligands or chemical photoswitches (azobenzene-quaternary ammonium derivatives) can be injected into a degenerated mouse eye and, in minutes to hours, activate light responses in neurons. These photoswitches offer the potential for rapidly and reversibly screening the vision restoration expected in an individual patient. Chemical photoswitch variants that persist in the cell membrane could make them a simple therapy of choice, with resolution and sensitivity equivalent to optogenetics approaches. A major complexity in treating retinal degenerations is retinal remodeling: pathologic network rewiring, molecular reprogramming, and cell death that compromise signaling in the surviving retina. Remodeling forces a choice between upstream and downstream targeting, each engaging different benefits and defects. Prosthetics and optogenetics can be implemented in either mode, but the use of chemical photoswitches is currently limited to downstream implementations. Even so, given the high density of human foveal ganglion cells, the ultimate chemical photoswitch treatment could deliver cost-effective, high-resolution vision for the blind. PMID:25089879

Countdown to Drawdown: an initial overview of exponential scaling of potential societal tipping points for deep decarbonization of global energy infrastructure by 2050

NASA Astrophysics Data System (ADS)

McCaffrey, Mark; Bhowmik, Avit

2017-04-01

The 194 signatories to the Paris Agreement range in size from small island nations (Tuvalu, less than 10,000 people) to massive states (India and China, which between them have 2.6 billion people). Their cultural backgrounds, political, economic and social systems vary widely. What they all share is an agreement for climate stabilisation at 1.5-2˚ C. A roadmap outlining potential exponential transitions towards a carbon-free economy may benefit from a logarithmic "powers of ten" framework that sets aside backgrounds and systems to examine the relative population concentration scales-from the individual (100) to local/neighborhood (103) to the national/transnational scales (108) and ultimately the global population of around 10 billion anticipated in 2050 (1010). What are the related targets and indicators for successful engagement at each level for rapid and radical reductions of carbon emissions and concentrations? What are the possible interventions and barriers that may be applied at different levels of population concentration? What "drawdown" strategies are most appropriate for different scales? Could focusing demonstrations of clean energy and sustainable practices on the local/neighborhood to urban scale (103-104) provide a leverage that has not been achieved at more complex national and transnational scales? Ultimately, backgrounds and systems are important factors in the equation, but the "powers of 10" scaling framework may provide a compass to assist in identifying the challenges, opportunities and related thresholds and tipping points for achieving deep decarbonization and transformation of the global energy infrastructure at every level of society over the next thirty-three years.

Educational Projects in Unmanned Aerial Systems at the NASA Ames Research Center

NASA Technical Reports Server (NTRS)

Dahlgren, Robert P.

2017-01-01

Unmanned aerial systems (UAS), autonomy and robotics technology have been fertile ground for developing a wide variety of interdisciplinary student learning opportunities. In this talk, several projects will be described that leverage small fixed-wing UAS that have been modified to carry science payloads. These aircraft provide a unique hands-on experience for a wide range of students from college juniors to graduate students pursuing degrees in electrical engineering, aeronautical engineering, mechanical engineering, applied mathematics, physics, structural engineering and other majors. By combining rapid prototyping, design reuse and open-source philosophies, a sustainable educational program has been organized structured as full-time internships during the summer, part-time internships during the school year, short details for military cadets, and paid positions. As part of this program, every summer one or more UAS is developed from concept through design, build and test phases using the tools and facilities at the NASA Ames Research Center, ultimately obtaining statements of airworthiness and flight release from the Agency before test flights are performed. In 2016 and 2017 student projects focused on the theme of 3D printed modular airframes that may be optimized for a given mission and payload. Now in its fifth year this program has served over 35 students, and has provided a rich learning experience as they learn to rapidly develop new aircraft concepts in a highly regulated environment, on systems that will support principal investigators at university, NASA, and other US federal agencies.

Crowdsourcing Precision Cerebrovascular Health: Imaging and Cloud Seeding A Million Brains Initiative™.

PubMed

Liebeskind, David S

2016-01-01

Crowdsourcing, an unorthodox approach in medicine, creates an unusual paradigm to study precision cerebrovascular health, eliminating the relative isolation and non-standardized nature of current imaging data infrastructure, while shifting emphasis to the astounding capacity of big data in the cloud. This perspective envisions the use of imaging data of the brain and vessels to orient and seed A Million Brains Initiative™ that may leapfrog incremental advances in stroke and rapidly provide useful data to the sizable population around the globe prone to the devastating effects of stroke and vascular substrates of dementia. Despite such variability in the type of data available and other limitations, the data hierarchy logically starts with imaging and can be enriched with almost endless types and amounts of other clinical and biological data. Crowdsourcing allows an individual to contribute to aggregated data on a population, while preserving their right to specific information about their own brain health. The cloud now offers endless storage, computing prowess, and neuroimaging applications for postprocessing that is searchable and scalable. Collective expertise is a windfall of the crowd in the cloud and particularly valuable in an area such as cerebrovascular health. The rise of precision medicine, rapidly evolving technological capabilities of cloud computing and the global imperative to limit the public health impact of cerebrovascular disease converge in the imaging of A Million Brains Initiative™. Crowdsourcing secure data on brain health may provide ultimate generalizability, enable focused analyses, facilitate clinical practice, and accelerate research efforts.

Rapidly Progressive Quadriplegia and Encephalopathy.

PubMed

Wynn, DonRaphael; McCorquodale, Donald; Peters, Angela; Juster-Switlyk, Kelsey; Smith, Gordon; Ansari, Safdar

2016-11-01

A woman aged 77 years was transferred to our neurocritical care unit for evaluation and treatment of rapidly progressive motor weakness and encephalopathy. Examination revealed an ability to follow simple commands only and abnormal movements, including myoclonus, tongue and orofacial dyskinesias, and opsoclonus. Imaging study findings were initially unremarkable, but when repeated, they demonstrated enhancement of the cauda equina nerve roots, trigeminal nerve, and pachymeninges. Cerebrospinal fluid examination revealed mildly elevated white blood cell count and protein levels. Serial electrodiagnostic testing demonstrated a rapidly progressive diffuse sensory motor axonopathy, and electroencephalogram findings progressed from generalized slowing to bilateral periodic lateralized epileptiform discharges. Critical details of her recent history prompted a diagnostic biopsy. Over time, the patient became completely unresponsive with no further abnormal movements and ultimately died. The differential diagnosis, pathological findings, and diagnosis are discussed with a brief review of a well-known yet rare diagnosis.

Imaging Atherosclerosis

PubMed Central

Tarkin, Jason M.; Dweck, Marc R.; Evans, Nicholas R.; Takx, Richard A.P.; Brown, Adam J.; Tawakol, Ahmed; Fayad, Zahi A.

2016-01-01

Advances in atherosclerosis imaging technology and research have provided a range of diagnostic tools to characterize high-risk plaque in vivo; however, these important vascular imaging methods additionally promise great scientific and translational applications beyond this quest. When combined with conventional anatomic- and hemodynamic-based assessments of disease severity, cross-sectional multimodal imaging incorporating molecular probes and other novel noninvasive techniques can add detailed interrogation of plaque composition, activity, and overall disease burden. In the catheterization laboratory, intravascular imaging provides unparalleled access to the world beneath the plaque surface, allowing tissue characterization and measurement of cap thickness with micrometer spatial resolution. Atherosclerosis imaging captures key data that reveal snapshots into underlying biology, which can test our understanding of fundamental research questions and shape our approach toward patient management. Imaging can also be used to quantify response to therapeutic interventions and ultimately help predict cardiovascular risk. Although there are undeniable barriers to clinical translation, many of these hold-ups might soon be surpassed by rapidly evolving innovations to improve image acquisition, coregistration, motion correction, and reduce radiation exposure. This article provides a comprehensive review of current and experimental atherosclerosis imaging methods and their uses in research and potential for translation to the clinic. PMID:26892971

Silicon wafer-based tandem cells: The ultimate photovoltaic solution?

NASA Astrophysics Data System (ADS)

Green, Martin A.

2014-03-01

Recent large price reductions with wafer-based cells have increased the difficulty of dislodging silicon solar cell technology from its dominant market position. With market leaders expected to be manufacturing modules above 16% efficiency at 0.36/Watt by 2017, even the cost per unit area (60-70/m2) will be difficult for any thin-film photovoltaic technology to significantly undercut. This may make dislodgement likely only by appreciably higher energy conversion efficiency approaches. A silicon wafer-based cell able to capitalize on on-going cost reductions within the mainstream industry, but with an appreciably higher than present efficiency, might therefore provide the ultimate PV solution. With average selling prices of 156 mm quasi-square monocrystalline Si photovoltaic wafers recently approaching 1 (per wafer), wafers now provide clean, low cost templates for overgrowth of thin, wider bandgap high performance cells, nearly doubling silicon's ultimate efficiency potential. The range of possible Si-based tandem approaches is reviewed together with recent results and ultimate prospects.

Doping evolution of spin and charge excitations in the Hubbard model

DOE PAGES

Kung, Y. F.; Nowadnick, E. A.; Jia, C. J.; ...

2015-11-05

We shed light on how electronic correlations vary across the phase diagram of the cuprate superconductors, examining the doping evolution of spin and charge excitations in the single-band Hubbard model using determinant quantum Monte Carlo (DQMC). In the single-particle response, we observe that the effects of correlations weaken rapidly with doping, such that one may expect the random phase approximation (RPA) to provide an adequate description of the two-particle response. In contrast, when compared to RPA, we find that significant residual correlations in the two-particle excitations persist up to 40% hole and 15% electron doping (the range of dopings achievedmore » in the cuprates). Ultimately, these fundamental differences between the doping evolution of single- and multi-particle renormalizations show that conclusions drawn from single-particle processes cannot necessarily be applied to multi-particle excitations. Eventually, the system smoothly transitions via a momentum-dependent crossover into a weakly correlated metallic state where the spin and charge excitation spectra exhibit similar behavior and where RPA provides an adequate description.« less

Endorepellin causes endothelial cell disassembly of actin cytoskeleton and focal adhesions through α2β1 integrin

PubMed Central

Bix, Gregory; Fu, Jian; Gonzalez, Eva M.; Macro, Laura; Barker, Amy; Campbell, Shelly; Zutter, Mary M.; Santoro, Samuel A.; Kim, Jiyeun K.; Höök, Magnus; Reed, Charles C.; Iozzo, Renato V.

2004-01-01

Endorepellin, the COOH-terminal domain of the heparan sulfate proteoglycan perlecan, inhibits several aspects of angiogenesis. We provide evidence for a novel biological axis that links a soluble fragment of perlecan protein core to the major cell surface receptor for collagen I, α2β1 integrin, and provide an initial investigation of the intracellular signaling events that lead to endorepellin antiangiogenic activity. The interaction between endorepellin and α2β1 integrin triggers a unique signaling pathway that causes an increase in the second messenger cAMP; activation of two proximal kinases, protein kinase A and focal adhesion kinase; transient activation of p38 mitogen-activated protein kinase and heat shock protein 27, followed by a rapid down-regulation of the latter two proteins; and ultimately disassembly of actin stress fibers and focal adhesions. The end result is a profound block of endothelial cell migration and angiogenesis. Because perlecan is present in both endothelial and smooth muscle cell basement membranes, proteolytic activity during the initial stages of angiogenesis could liberate antiangiogenic fragments from blood vessels' walls, including endorepellin. PMID:15240572

A modular wireless in vivo surgical robot with multiple surgical applications.

PubMed

Hawks, Jeff A; Rentschler, Mark E; Farritor, Shane; Oleynikov, Dmitry; Platt, Stephen R

2009-01-01

The use of miniature in vivo robots that fit entirely inside the peritoneal cavity represents a novel approach to laparoscopic surgery. Previous work demonstrates that both mobile and fixed-based robots can successfully operate inside the abdominal cavity. A modular wireless mobile platform has also been developed to provide surgical vision and task assistance. This paper presents an overview of recent test results of several possible surgical applications that can be accommodated by this modular platform. Applications such as a biopsy grasper, stapler and clamp, video camera, and physiological sensors have been integrated into the wireless platform and tested in vivo in a porcine model. The modular platform facilitates rapid development and conversion from one type of surgical task assistance to another. These self-contained surgical devices are much more transportable and much lower in cost than current robotic surgical assistants. These devices could ultimately be carried and deployed by non-medical personnel at the site of an injury. A remotely located surgeon could use these robots to provide critical first response medical intervention.

The regulatory mechanism of fungal elicitor-induced secondary metabolite biosynthesis in medical plants.

PubMed

Zhai, Xin; Jia, Min; Chen, Ling; Zheng, Cheng-Jian; Rahman, Khalid; Han, Ting; Qin, Lu-Ping

2017-03-01

A wide range of external stress stimuli trigger plant cells to undergo complex network of reactions that ultimately lead to the synthesis and accumulation of secondary metabolites. Accumulation of such metabolites often occurs in plants subjected to stresses including various elicitors or signal molecules. Throughout evolution, endophytic fungi, an important constituent in the environment of medicinal plants, have known to form long-term stable and mutually beneficial symbiosis with medicinal plants. The endophytic fungal elicitor can rapidly and specifically induce the expression of specific genes in medicinal plants which can result in the activation of a series of specific secondary metabolic pathways resulting in the significant accumulation of active ingredients. Here we summarize the progress made on the mechanisms of fungal elicitor including elicitor signal recognition, signal transduction, gene expression and activation of the key enzymes and its application. This review provides guidance on studies which may be conducted to promote the efficient synthesis and accumulation of active ingredients by the endogenous fungal elicitor in medicinal plant cells, and provides new ideas and methods of studying the regulation of secondary metabolism in medicinal plants.

Dynamics of a New 5D Hyperchaotic System of Lorenz Type

NASA Astrophysics Data System (ADS)

Zhang, Fuchen; Chen, Rui; Wang, Xingyuan; Chen, Xiusu; Mu, Chunlai; Liao, Xiaofeng

Ultimate boundedness of chaotic dynamical systems is one of the fundamental concepts in dynamical systems, which plays an important role in investigating the stability of the equilibrium, estimating the Lyapunov dimension of attractors and the Hausdorff dimension of attractors, the existence of periodic solutions, chaos control, chaos synchronization. However, it is often difficult to obtain the bounds of the hyperchaotic systems due to the complex algebraic structure of the hyperchaotic systems. This paper has investigated the boundedness of solutions of a nonlinear hyperchaotic system. We have obtained the global exponential attractive set and the ultimate bound set for this system. To obtain the ellipsoidal ultimate bound, the ultimate bound of the proposed system is theoretically estimated using Lagrange multiplier method, Lyapunov stability theory and optimization theory. To show the ultimate bound region, numerical simulations are provided.

Rapid Isolation of Viable Circulating Tumor Cells from Patient Blood Samples

PubMed Central

Hughes, Andrew D.; Mattison, Jeff; Powderly, John D.; Greene, Bryan T.; King, Michael R.

2012-01-01

Circulating tumor cells (CTC) are cells that disseminate from a primary tumor throughout the circulatory system and that can ultimately form secondary tumors at distant sites. CTC count can be used to follow disease progression based on the correlation between CTC concentration in blood and disease severity1. As a treatment tool, CTC could be studied in the laboratory to develop personalized therapies. To this end, CTC isolation must cause no cellular damage, and contamination by other cell types, particularly leukocytes, must be avoided as much as possible2. Many of the current techniques, including the sole FDA-approved device for CTC enumeration, destroy CTC as part of the isolation process (for more information see Ref. 2). A microfluidic device to capture viable CTC is described, consisting of a surface functionalized with E-selectin glycoprotein in addition to antibodies against epithelial markers3. To enhance device performance a nanoparticle coating was applied consisting of halloysite nanotubes, an aluminosilicate nanoparticle harvested from clay4. The E-selectin molecules provide a means to capture fast moving CTC that are pumped through the device, lending an advantage over alternative microfluidic devices wherein longer processing times are necessary to provide target cells with sufficient time to interact with a surface. The antibodies to epithelial targets provide CTC-specificity to the device, as well as provide a readily adjustable parameter to tune isolation. Finally, the halloysite nanotube coating allows significantly enhanced isolation compared to other techniques by helping to capture fast moving cells, providing increased surface area for protein adsorption, and repelling contaminating leukocytes3,4. This device is produced by a straightforward technique using off-the-shelf materials, and has been successfully used to capture cancer cells from the blood of metastatic cancer patients. Captured cells are maintained for up to 15 days in culture following isolation, and these samples typically consist of >50% viable primary cancer cells from each patient. This device has been used to capture viable CTC from both diluted whole blood and buffy coat samples. Ultimately, we present a technique with functionality in a clinical setting to develop personalized cancer therapies. PMID:22733259

40 CFR 86.128-79 - Transmissions.

Code of Federal Regulations, 2010 CFR

2010-07-01

..., shall be run according to the manufacturer's recommendations to the ultimate purchaser, Provided, That... recommendations to the ultimate purchaser. (c) Idle modes less than one minute in length shall be run with automatic transmissions in “Drive” and the wheels braked; manual transmissions shall be in gear with the...

Implications of the U.S. War on Terrorism for U.S.-China Policy: A Strategic Window

DTIC Science & Technology

2002-04-12

network of supporting ministerial forums: including trade ministers, foreign ministers, finance ministers, ministers of the environment, and...especially the banks, so it can finance efficiently a rapidly growing economy.113 The pace of reform is ultimately constrained by the economy�s...Thailand’s beaches and California’s Disneyland . Over one million Chinese traveled abroad on pleasure trips in 1998, a record number despite the

Defeating the Islamic State at Three Levels of War

DTIC Science & Technology

2016-05-13

Middle East, Northern Africa , and Southeast Asia while using terrorism to attack the West. In order to fulfill the President’s end state of “ultimately...war. IS is expanding throughout the Middle East, Northern Africa , and Southeast Asia while using terrorism to attack the West. In order to...N-S) and theater-strategic (T-S) levels of war (See Figure 1). The insurgency is rapidly expanding throughout the Middle East, Northern Africa , and

Tailored Systems Architecture for Design of Space Science and Technology Missions Using DoDAF V2.0

DTIC Science & Technology

2009-12-01

programs do exist. Given the focus on rapid development and transition, if a system architecture framework could be developed and used to increase ...and scope are still being developed and refined at all levels within the DoD. As organizations have attempted to develop system architectures that...to produce architecture descriptions during the early-stages of system development. (3 p. 19) conformance, organizations ultimately using the

Wilderness education: The ultimate commitment to quality wilderness stewardship

Treesearch

Gregory F. Hansen; Tom Carlson

2007-01-01

The effective planning, implementation, and monitoring of a wilderness education program will ultimately produce measurable results that can be instrumental in achieving wilderness management goals and objectives. This paper will provide a simple step-by-step overview of how to develop and maintain a successful wilderness education program through planning,...

Upgrading short-read animal genome assemblies to chromosome level using comparative genomics and a universal probe set.

PubMed

Damas, Joana; O'Connor, Rebecca; Farré, Marta; Lenis, Vasileios Panagiotis E; Martell, Henry J; Mandawala, Anjali; Fowler, Katie; Joseph, Sunitha; Swain, Martin T; Griffin, Darren K; Larkin, Denis M

2017-05-01

Most recent initiatives to sequence and assemble new species' genomes de novo fail to achieve the ultimate endpoint to produce contigs, each representing one whole chromosome. Even the best-assembled genomes (using contemporary technologies) consist of subchromosomal-sized scaffolds. To circumvent this problem, we developed a novel approach that combines computational algorithms to merge scaffolds into chromosomal fragments, PCR-based scaffold verification, and physical mapping to chromosomes. Multigenome-alignment-guided probe selection led to the development of a set of universal avian BAC clones that permit rapid anchoring of multiple scaffolds to chromosomes on all avian genomes. As proof of principle, we assembled genomes of the pigeon ( Columbia livia ) and peregrine falcon ( Falco peregrinus ) to chromosome levels comparable, in continuity, to avian reference genomes. Both species are of interest for breeding, cultural, food, and/or environmental reasons. Pigeon has a typical avian karyotype (2n = 80), while falcon (2n = 50) is highly rearranged compared to the avian ancestor. By using chromosome breakpoint data, we established that avian interchromosomal breakpoints appear in the regions of low density of conserved noncoding elements (CNEs) and that the chromosomal fission sites are further limited to long CNE "deserts." This corresponds with fission being the rarest type of rearrangement in avian genome evolution. High-throughput multiple hybridization and rapid capture strategies using the current BAC set provide the basis for assembling numerous avian (and possibly other reptilian) species, while the overall strategy for scaffold assembly and mapping provides the basis for an approach that (provided metaphases can be generated) could be applied to any animal genome. © 2017 Damas et al.; Published by Cold Spring Harbor Laboratory Press.

Upgrading short-read animal genome assemblies to chromosome level using comparative genomics and a universal probe set

PubMed Central

O'Connor, Rebecca; Lenis, Vasileios Panagiotis E.; Martell, Henry J.; Mandawala, Anjali; Fowler, Katie; Joseph, Sunitha; Swain, Martin T.; Griffin, Darren K.; Larkin, Denis M.

2017-01-01

Most recent initiatives to sequence and assemble new species’ genomes de novo fail to achieve the ultimate endpoint to produce contigs, each representing one whole chromosome. Even the best-assembled genomes (using contemporary technologies) consist of subchromosomal-sized scaffolds. To circumvent this problem, we developed a novel approach that combines computational algorithms to merge scaffolds into chromosomal fragments, PCR-based scaffold verification, and physical mapping to chromosomes. Multigenome-alignment-guided probe selection led to the development of a set of universal avian BAC clones that permit rapid anchoring of multiple scaffolds to chromosomes on all avian genomes. As proof of principle, we assembled genomes of the pigeon (Columbia livia) and peregrine falcon (Falco peregrinus) to chromosome levels comparable, in continuity, to avian reference genomes. Both species are of interest for breeding, cultural, food, and/or environmental reasons. Pigeon has a typical avian karyotype (2n = 80), while falcon (2n = 50) is highly rearranged compared to the avian ancestor. By using chromosome breakpoint data, we established that avian interchromosomal breakpoints appear in the regions of low density of conserved noncoding elements (CNEs) and that the chromosomal fission sites are further limited to long CNE “deserts.” This corresponds with fission being the rarest type of rearrangement in avian genome evolution. High-throughput multiple hybridization and rapid capture strategies using the current BAC set provide the basis for assembling numerous avian (and possibly other reptilian) species, while the overall strategy for scaffold assembly and mapping provides the basis for an approach that (provided metaphases can be generated) could be applied to any animal genome. PMID:27903645

Blocking lactate export by inhibiting the Myc target MCT1 Disables glycolysis and glutathione synthesis.

PubMed

Doherty, Joanne R; Yang, Chunying; Scott, Kristen E N; Cameron, Michael D; Fallahi, Mohammad; Li, Weimin; Hall, Mark A; Amelio, Antonio L; Mishra, Jitendra K; Li, Fangzheng; Tortosa, Mariola; Genau, Heide Marika; Rounbehler, Robert J; Lu, Yunqi; Dang, Chi V; Kumar, K Ganesh; Butler, Andrew A; Bannister, Thomas D; Hooper, Andrea T; Unsal-Kacmaz, Keziban; Roush, William R; Cleveland, John L

2014-02-01

Myc oncoproteins induce genes driving aerobic glycolysis, including lactate dehydrogenase-A that generates lactate. Here, we report that Myc controls transcription of the lactate transporter SLC16A1/MCT1 and that elevated MCT1 levels are manifest in premalignant and neoplastic Eμ-Myc transgenic B cells and in human malignancies with MYC or MYCN involvement. Notably, disrupting MCT1 function leads to an accumulation of intracellular lactate that rapidly disables tumor cell growth and glycolysis, provoking marked alterations in glycolytic intermediates, reductions in glucose transport, and in levels of ATP, NADPH, and ultimately, glutathione (GSH). Reductions in GSH then lead to increases in hydrogen peroxide, mitochondrial damage, and ultimately, cell death. Finally, forcing glycolysis by metformin treatment augments this response and the efficacy of MCT1 inhibitors, suggesting an attractive combination therapy for MYC/MCT1-expressing malignancies.

Optogenetics in preclinical neuroscience and psychiatry research: recent insights and potential applications.

PubMed

McDevitt, Ross A; Reed, Sean J; Britt, Jonathan P

2014-01-01

There have been significant advances in the treatment of psychiatric disease in the last half century, but it is still unclear which neural circuits are ultimately responsible for specific disease states. Fortunately, technical limitations that have constrained this research have recently been mitigated by advances in research tools that facilitate circuit-based analyses. The most prominent of these tools is optogenetics, which refers to the use of genetically encoded, light-sensitive proteins that can be used to manipulate discrete neural circuits with temporal precision. Optogenetics has recently been used to examine the neural underpinnings of both psychiatric disease and symptom relief, and this research has rapidly identified novel therapeutic targets for what could be a new generation of rational drug development. As these and related methodologies for controlling neurons ultimately make their way into the clinic, circuit-based strategies for alleviating psychiatric symptoms could become a remarkably refined approach to disease treatment.

Constraining the Spatial Extent of Marine Oil Snow Sedimentation and Flocculent Accumulation Following the Deepwater Horizon Event Using an Excess 210Pb Flux Approach.

PubMed

Schwing, P T; Brooks, G R; Larson, R A; Holmes, C W; O'Malley, B J; Hollander, D J

2017-06-06

Following the Deepwater Horizon (DWH) event in 2010, there were several lines of evidence indicating the presence of marine oil snow sedimentation and flocculent accumulation (MOSSFA). A significant amount of marine oil snow formed in the water column of the northern Gulf of Mexico (nGoM), settled rapidly, and ultimately accumulated in the sediments of the nGoM. This study utilized a commonly used radioisotope tracer (excess 210 Pb, 210 Pb xs ) from 32 sediment cores collected from 2010 to 2013 to characterize the spatial extent of MOSSFA on the seafloor. Relative to pre-DWH conditions, an increase in 210 Pb xs flux occurred in two distinct regions: (1) in the western portion of the study area on an east-northeast to west-southwest axis, stretching 230 km southwest and 140 km northeast of the DWH wellhead, and (2) in the eastern portion of the study area on a 70 km northeast to southwest axis near the DeSoto Canyon. The total sedimentary spatial extent of MOSSFA, as calculated by increased 210 Pb xs flux after 2010, ranged from 12 805 to 35 425 km 2 . 210 Pb xs flux provides a valuable tool for documenting the spatial extent of MOSSFA following DWH and will continue to aid in the determination of advective transport and ultimate depocenters of MOSSFA material.

Influence of loading and unloading velocity of confining pressure on strength and permeability characteristics of crystalline sandstone

NASA Astrophysics Data System (ADS)

Zhang, Dong-ming; Yang, Yu-shun; Chu, Ya-pei; Zhang, Xiang; Xue, Yan-guang

2018-06-01

The triaxial compression test of crystalline sandstone under different loading and unloading velocity of confining pressure is carried out by using the self-made "THM coupled with servo-controlled seepage apparatus for containing-gas coal", analyzed the strength, deformation and permeability characteristics of the sample, the results show that: with the increase of confining pressures loading-unloading velocity, Mohr's stress circle center of the specimen shift to the right, and the ultimate intensity, peak strain and residual stress of the specimens increase gradually. With the decrease of unloading velocity of confining pressure, the axial strain, the radial strain and the volumetric strain of the sample decrease first and then increases, but the radial strain decreases more greatly. The loading and unloading of confining pressure has greater influence on axial strain of specimens. The deformation modulus decreases rapidly with the increase of axial strain and the Poisson's ratio decreases gradually at the initial stage of loading. When the confining pressure is loaded, the deformation modulus decrease gradually, and the Poisson's ratio increases gradually. When the confining pressure is unloaded, the deformation modulus increase gradually, and the Poisson's ratio decreases gradually. When the specimen reaches the ultimate intensity, the deformation modulus decreases rapidly, while the Poisson's ratio increases rapidly. The fitting curve of the confining pressure and the deformation modulus and the Poisson's ratio in accordance with the distribution of quadratic polynomial function in the loading-unloading confining pressure. There is a corresponding relationship between the evolution of rock permeability and damage deformation during the process of loading and unloading. In the late stage of yielding, the permeability increases slowly, and the permeability increases sharply after the rock sample is destroyed. Fitting the permeability and confining pressure conform to the variation law of the exponential function.

Dorsomedial prefrontal cortex mediates rapid evaluations predicting the outcome of romantic interactions

PubMed Central

Cooper, Jeffrey C.; Dunne, Simon; Furey, Teresa; O’Doherty, John P.

2012-01-01

Humans frequently make real-world decisions based on rapid evaluations of minimal information – for example, should we talk to an attractive stranger at a party? Little is known, however, about how the brain makes rapid evaluations with real and immediate social consequences. To address this question, we scanned participants with FMRI while they viewed photos of individuals that they subsequently met at real-life “speed-dating” events. Neural activity in two areas of dorsomedial prefrontal cortex, paracingulate cortex and rostromedial prefrontal cortex (RMPFC), was predictive of whether each individual would be ultimately pursued for a romantic relationship or rejected. Activity in these areas was attributable to two distinct components of romantic evaluation: either consensus judgments about physical beauty (paracingulate cortex) or individualized preferences based on a partner’s perceived personality (RMPFC). These data identify novel computational roles for these regions of the dorsomedial prefrontal cortex in even very rapid social evaluations. Even a first glance, then, can accurately predict romantic desire, but that glance involves a mix of physical and psychological judgments that depend on specific regions of dorsomedial prefrontal cortex. PMID:23136406

Sensory, physical and chemical characteristics of cooked ham manufactured from rapidly chilled and earlier deboned M. semimembranosus.

PubMed

Tomović, Vladimir M; Jokanović, Marija R; Petrović, Ljiljana S; Tomović, Mila S; Tasić, Tatjana A; Ikonić, Predrag M; Sumić, Zdravko M; Sojić, Branislav V; Skaljac, Snežana B; Sošo, Milena M

2013-01-01

Effects of rapid chilling of carcasses (at -31°C in the first 3h of chilling, and then at 2-4°C) and earlier deboning (8h post-mortem), compared to rapid (till 24h post-mortem) and conventional chilling (at 2-4°C, till 24h post-mortem), on quality characteristics of pork M. semimebranosus and cooked ham were investigated. Quality measurements included pH value, colour (CIEL a b values) and total aerobic count of M. semimebranosus, as well as sensory (colour, juiciness, texture, and flavour), physical (pH value, colour - CIEL a b values and texture - Warner-Bratzler shear and penetration forces) and chemical (protein, total fat, and moisture content) characteristics of cooked ham. The cooked ham was manufactured from pieces of M. semimebranosus with ultimate lightness (CIEL value) lower than 50. Rapid chilling and earlier deboning significantly increased quantity of M. semimebranosus desirable for cooked ham manufacturing. Earlier start of pork fabrication did not affect important quality characteristics of cooked ham. Copyright © 2012 Elsevier Ltd. All rights reserved.

The Ultimate Sampling Dilemma in Experience-Based Decision Making

ERIC Educational Resources Information Center

Fiedler, Klaus

2008-01-01

Computer simulations and 2 experiments demonstrate the ultimate sampling dilemma, which constitutes a serious obstacle to inductive inferences in a probabilistic world. Participants were asked to take the role of a manager who is to make purchasing decisions based on positive versus negative feedback about 3 providers in 2 different product…

β1-adrenergic receptors activate two distinct signaling pathways in striatal neurons

PubMed Central

Meitzen, John; Luoma, Jessie I.; Stern, Christopher M.; Mermelstein, Paul G.

2010-01-01

Monoamine action in the dorsal striatum and nucleus accumbens plays essential roles in striatal physiology. Although research often focuses on dopamine and its receptors, norepinephrine and adrenergic receptors are also crucial in regulating striatal function. While noradrenergic neurotransmission has been identified in the striatum, little is known regarding the signaling pathways activated by β-adrenergic receptors in this brain region. Using cultured striatal neurons, we characterized a novel signaling pathway by which activation of β1-adrenergic receptors leads to the rapid phosphorylation of cAMP Response Element Binding Protein (CREB), a transcription-factor implicated as a molecular switch underlying long-term changes in brain function. Norepinephrine-mediated CREB phosphorylation requires β1-adrenergic receptor stimulation of a receptor tyrosine kinase, ultimately leading to the activation of a Ras/Raf/MEK/MAPK/MSK signaling pathway. Activation of β1-adrenergic receptors also induces CRE-dependent transcription and increased c-fos expression. In addition, stimulation of β1-adrenergic receptors produces cAMP production, but surprisingly, β1-adrenergic receptor activation of adenylyl cyclase was not functionally linked to rapid CREB phosphorylation. These findings demonstrate that activation of β1-adrenergic receptors on striatal neurons can stimulate two distinct signaling pathways. These adrenergic actions can produce long-term changes in gene expression, as well as rapidly modulate cellular physiology. By elucidating the mechanisms by which norepinephrine and β1-adrenergic receptor activation affects striatal physiology, we provide the means to more fully understand the role of monoamines in modulating striatal function, specifically how norepinephrine and β1-adrenergic receptors may affect striatal physiology. PMID:21143600

Reconfigurable virtual electrowetting channels.

PubMed

Banerjee, Ananda; Kreit, Eric; Liu, Yuguang; Heikenfeld, Jason; Papautsky, Ian

2012-02-21

Lab-on-a-chip systems rely on several microfluidic paradigms. The first uses a fixed layout of continuous microfluidic channels. Such lab-on-a-chip systems are almost always application specific and far from a true "laboratory." The second involves electrowetting droplet movement (digital microfluidics), and allows two-dimensional computer control of fluidic transport and mixing. The merging of the two paradigms in the form of programmable electrowetting channels takes advantage of both the "continuous" functionality of rigid channels based on which a large number of applications have been developed to date and the "programmable" functionality of digital microfluidics that permits electrical control of on-chip functions. In this work, we demonstrate for the first time programmable formation of virtual microfluidic channels and their continuous operation with pressure driven flows using an electrowetting platform. Experimental, theoretical, and numerical analyses of virtual channel formation with biologically relevant electrolyte solutions and electrically-programmable reconfiguration are presented. We demonstrate that the "wall-less" virtual channels can be formed reliably and rapidly, with propagation rates of 3.5-3.8 mm s(-1). Pressure driven transport in these virtual channels at flow rates up to 100 μL min(-1) is achievable without distortion of the channel shape. We further demonstrate that these virtual channels can be switched on-demand between multiple inputs and outputs. Ultimately, we envision a platform that would provide rapid prototyping of microfluidic concepts and would be capable of a vast library of functions and benefitting applications from clinical diagnostics in resource-limited environments to rapid system prototyping to high throughput pharmaceutical applications.

Simulation in shoulder surgery.

PubMed

Colaço, Henry B; Tennent, Duncan

2016-10-01

Simulation is a rapidly developing field in medical education. There is a growing need for trainee surgeons to acquire surgical skills in a cost-effective learning environment to improve patient safety and compensate for a reduction in training time and operative experience. Although simulation is not a replacement for traditional models of surgical training, and robust assessment metrics need to be validated before widespread use for accreditation, it is a useful adjunct that may ultimately lead to improving surgical outcomes for our patients.

Exertional heat illness: a review of the syndrome affecting racing Thoroughbreds in hot and humid climates.

PubMed

Brownlow, M A; Dart, A J; Jeffcott, L B

2016-07-01

Metabolic heat produced by Thoroughbred racehorses during racing can rapidly elevate core body temperature (1°C/min). When environmental conditions are hot and humid, the normal physiological cooling mechanisms become ineffective. The heat accumulated may exceed a critical thermal maximum (estimated to be 42°C), which may trigger a complex pathophysiological cascade with potentially lethal consequences. This syndrome has been labelled exertional heat illness (EHI). EHI is described in humans, but has not been well documented in Thoroughbred racehorses. The clinical signs described in racehorses would suggest that the pathophysiological events affecting the central nervous (CNS) and gastrointestinal systems are similar to those described in humans. Clinical signs are progressive and include signs of endotoxaemia and increasing levels of CNS dysfunction. Initially, horses that may be mildly irritable (agitated, randomly kicking out) may progress to unmanageable (disorientation, severe ataxia, falling) and ultimately convulsions, coma and death. Currently, the approach to treatment is largely empirical and involves rapid and effective cooling, administration of drugs to provide sedation, administration of non-steroidal anti-inflammatory drugs to ameliorate the effects of endotoxaemia and glucocorticoids to stabilise cell membranes and reduce the effects of inflammation on the CNS. This review provides an overview of the current knowledge about EHI in Thoroughbred racehorses, suggests a likely pathophysiology of the syndrome in horses based on the current literature on heat illness in humans and horses, and outlines current treatment strategies being used to treat racehorses with clinical signs of EHI. © 2016 Australian Veterinary Association.

New computer and communications environments for light armored vehicles

NASA Astrophysics Data System (ADS)

Rapanotti, John L.; Palmarini, Marc; Dumont, Marc

2002-08-01

Light Armoured Vehicles (LAVs) are being developed to meet the modern requirements of rapid deployment and operations other than war. To achieve these requirements, passive armour is minimized and survivability depends more on sensors, computers and countermeasures to detect and avoid threats. The performance, reliability, and ultimately the cost of these components, will be determined by the trends in computing and communications. These trends and the potential impact on DAS (Defensive Aids Suite) development were investigated and are reported in this paper. Vehicle performance is affected by communication with other vehicles and other ISTAR (Intelligence, Surveillance, Target Acquisition and Reconnaissance) battlefield assets. This investigation includes the networking technology Jini developed by SUN Microsystems, which can be used to interface the vehicle to the ISTAR network. VxWorks by Wind River Systems, is a real time operating system designed for military systems and compatible with Jini. Other technologies affecting computer hardware development include, dynamic reconfiguration, hot swap, alternate pathing, CompactPCI, and Fiber Channel serial communication. To achieve the necessary performance at reasonable cost, and over the long service life of the vehicle, a DAS should have two essential features. A fitted for, but not fitted with approach will provide the necessary rapid deployment without a need to equip the entire fleet. With an expected vehicle service life of 50 years, 5-year technology upgrades can be used to maintain vehicle performance over the entire service life. A federation of modules instead of integrated fused sensors will provide the capability for incremental upgrades and mission configurability. A plug and play capability can be used for both hardware and expendables.

Platelet “First Responders” in Wound Response, Cancer, and Metastasis

PubMed Central

Menter, David G.; Kopetz, Scott; Hawk, Ernest; Sood, Anil K.; Loree, Jonathan M; Gresele, Paolo; Honn, Kenneth V.

2017-01-01

Platelets serve as “First Responders” during normal wounding and homeostasis. Arising from bone marrow stem cell lineage megakaryocytes, anucleate platelets can influence inflammation and immune regulation. Biophysically, platelets are optimized due to size and discoid morphology to distribute near vessel walls, monitor vascular integrity and initiate quick responses to vascular lesions. Adhesion receptors linked to a highly reactive filopodia-generating cytoskeleton maximizes their vascular surface contact allowing rapid response capabilities. Functionally, platelets normally initiate rapid clotting, vasoconstriction, inflammation and wound biology that leads to sterilization, tissue repair and resolution. Platelets also are among the first to sense, phagocytize, decorate, or react to pathogens in the circulation. These platelet first responder properties are commandeered during chronic inflammation, cancer progression and metastasis. Leaky or inflammatory reaction blood vessel genesis during carcinogenesis provides opportunities for platelet invasion into tumors. Cancer is thought of as a non-healing or chronic wound that can be actively aided by platelet mitogenic properties to stimulate tumor growth. This growth ultimately outstrips circulatory support leads to angiogenesis and intravasation of tumor cells into the blood stream. Circulating tumor cells reengage additional platelets, which facilitates tumor cell adhesion, arrest and extravasation and metastasis. This process, along with the hypercoagulable states associated with malignancy is amplified by IL6 production in tumors that stimulate liver thrombopoietin production and elevates circulating platelet numbers by thrombopoiesis in the bone marrow. These complex interactions and the “First Responder” role of platelets during diverse physiologic stresses provides a useful therapeutic target that deserves further exploration. PMID:28730545

Commentary: Why Pharmaceutical Scientists in Early Drug Discovery Are Critical for Influencing the Design and Selection of Optimal Drug Candidates.

PubMed

Landis, Margaret S; Bhattachar, Shobha; Yazdanian, Mehran; Morrison, John

2018-01-01

This commentary reflects the collective view of pharmaceutical scientists from four different organizations with extensive experience in the field of drug discovery support. Herein, engaging discussion is presented on the current and future approaches for the selection of the most optimal and developable drug candidates. Over the past two decades, developability assessment programs have been implemented with the intention of improving physicochemical and metabolic properties. However, the complexity of both new drug targets and non-traditional drug candidates provides continuing challenges for developing formulations for optimal drug delivery. The need for more enabled technologies to deliver drug candidates has necessitated an even more active role for pharmaceutical scientists to influence many key molecular parameters during compound optimization and selection. This enhanced role begins at the early in vitro screening stages, where key learnings regarding the interplay of molecular structure and pharmaceutical property relationships can be derived. Performance of the drug candidates in formulations intended to support key in vivo studies provides important information on chemotype-formulation compatibility relationships. Structure modifications to support the selection of the solid form are also important to consider, and predictive in silico models are being rapidly developed in this area. Ultimately, the role of pharmaceutical scientists in drug discovery now extends beyond rapid solubility screening, early form assessment, and data delivery. This multidisciplinary role has evolved to include the practice of proactively taking part in the molecular design to better align solid form and formulation requirements to enhance developability potential.

Does the public deserve free access to climate system science?

NASA Astrophysics Data System (ADS)

Grigorov, Ivo

2010-05-01

Some time ago it was the lack of public access to medical research data that really stirred the issue and gave inertia for legislation and a new publishing model that puts tax payer-funded medical research in the hands of those who fund it. In today's age global climate change has become the biggest socio-economic challenge, and the same argument resonates: climate affects us all and the publicly-funded science quantifying it should be freely accessible to all stakeholders beyond academic research. Over the last few years the ‘Open Access' movement to remove as much as possible subscription, and other on-campus barriers to academic research has rapidly gathered pace, but despite significant progress, the climate system sciences are not among the leaders in providing full access to their publications and data. Beyond the ethical argument, there are proven and tangible benefits for the next generation of climate researchers to adapt the way their output is published. Through the means provided by ‘open access', both data and ideas can gain more visibility, use and citations for the authors, but also result in a more rapid exchange of knowledge and ideas, and ultimately progress towards a sought solution. The presentation will aim to stimulate discussion and seek progress on the following questions: Should free access to climate research (& data) be mandatory? What are the career benefits of using ‘open access' for young scientists? What means and methods should, or could, be incorporated into current European graduate training programmes in climate research, and possible ways forward?

The Radius and Entropy of a Magnetized, Rotating, Fully Convective Star: Analysis with Depth-dependent Mixing Length Theories

NASA Astrophysics Data System (ADS)

Ireland, Lewis G.; Browning, Matthew K.

2018-04-01

Some low-mass stars appear to have larger radii than predicted by standard 1D structure models; prior work has suggested that inefficient convective heat transport, due to rotation and/or magnetism, may ultimately be responsible. We examine this issue using 1D stellar models constructed using Modules for Experiments in Stellar Astrophysics (MESA). First, we consider standard models that do not explicitly include rotational/magnetic effects, with convective inhibition modeled by decreasing a depth-independent mixing length theory (MLT) parameter α MLT. We provide formulae linking changes in α MLT to changes in the interior specific entropy, and hence to the stellar radius. Next, we modify the MLT formulation in MESA to mimic explicitly the influence of rotation and magnetism, using formulations suggested by Stevenson and MacDonald & Mullan, respectively. We find rapid rotation in these models has a negligible impact on stellar structure, primarily because a star’s adiabat, and hence its radius, is predominantly affected by layers near the surface; convection is rapid and largely uninfluenced by rotation there. Magnetic fields, if they influenced convective transport in the manner described by MacDonald & Mullan, could lead to more noticeable radius inflation. Finally, we show that these non-standard effects on stellar structure can be fabricated using a depth-dependent α MLT: a non-magnetic, non-rotating model can be produced that is virtually indistinguishable from one that explicitly parameterizes rotation and/or magnetism using the two formulations above. We provide formulae linking the radially variable α MLT to these putative MLT reformulations.

An introduction to UGRS: the ultimate grading and remanufacturing system

Treesearch

John Moody; Charles J. Gatchell; Elizabeth S. Walker; Powsiri Klinkhachorn

1998-01-01

The Ultimate Grading and Remanufactming System (UGRS) is an advanced computer program for grading and remanufacturing lumber. It is an interactive program that will both grade lumber according to NHLA rules and remanufacture it for maximum value. UGRS is written to run under Microsoft Windows 3.0 or later updates and provides a sophisticated graphical user interface....

Ultimate Limit State Assessment of Timber Bolt Connection Subjected to Double Unequal Shears

NASA Astrophysics Data System (ADS)

Musilek, Josef; Plachy, Jan

2017-10-01

Nowadays the problems occur when a structure engineer need to assess the ultimate limit state of timber bolt connection which is subjected to double unequal shears. This assessment of ultimate limit state shows the reliability of these connections. In assessing the reliability of this connection in ultimate limit state is a problem, because the formulas and equations that are currently available in design standards and available literature, describing only connections loaded symmetrically - this mean that they describe the timber bolt connection subjected to double equal shears. This fact causes problems because structural engineers have no available support, according to which they could assess reliability of the connection in terms of the ultimate limit state. They must therefore often report following an asymmetrically loaded connections carry about using formulas, which are primarily designed for checking connections loaded symmetrically. This leads logically to the fact that it is not respected by the actual behaviour of the connection in the ultimate limit state. Formulas derived in this paper provide the possibility to assess the ultimate limit state for such connection. The formulas derived in this article allow to carry out a reliability assessment of the ultimate limit state of timber bolt connection subjected to double shear. The using of the formulas derived in this paper leads to better description of the behaviour of this type of connection and also to the more economic design. An example of using these derived formulas is shown. There is shown in this example, how to assess the reliability of timber bolt connection subjected to double unequal shears in terms of ultimate limit states.

Ultimate pier and contraction scour prediction in cohesive soils at selected bridges in Illinois

USGS Publications Warehouse

Straub, Timothy D.; Over, Thomas M.; Domanski, Marian M.

2013-01-01

The Scour Rate In COhesive Soils-Erosion Function Apparatus (SRICOS-EFA) method includes an ultimate scour prediction that is the equilibrium maximum pier and contraction scour of cohesive soils over time. The purpose of this report is to present the results of testing the ultimate pier and contraction scour methods for cohesive soils on 30 bridge sites in Illinois. Comparison of the ultimate cohesive and noncohesive methods, along with the Illinois Department of Transportation (IDOT) cohesive soil reduction-factor method and measured scour are presented. Also, results of the comparison of historic IDOT laboratory and field values of unconfined compressive strength of soils (Qu) are presented. The unconfined compressive strength is used in both ultimate cohesive and reduction-factor methods, and knowing how the values from field methods compare to the laboratory methods is critical to the informed application of the methods. On average, the non-cohesive method results predict the highest amount of scour, followed by the reduction-factor method results; and the ultimate cohesive method results predict the lowest amount of scour. The 100-year scour predicted for the ultimate cohesive, noncohesive, and reduction-factor methods for each bridge site and soil are always larger than observed scour in this study, except 12% of predicted values that are all within 0.4 ft of the observed scour. The ultimate cohesive scour prediction is smaller than the non-cohesive scour prediction method for 78% of bridge sites and soils. Seventy-six percent of the ultimate cohesive predictions show a 45% or greater reduction from the non-cohesive predictions that are over 10 ft. Comparing the ultimate cohesive and reduction-factor 100-year scour predictions methods for each bridge site and soil, the scour predicted by the ultimate cohesive scour prediction method is less than the reduction-factor 100-year scour prediction method for 51% of bridge sites and soils. Critical shear stress remains a needed parameter in the ultimate scour prediction for cohesive soils. The unconfined soil compressive strength measured by IDOT in the laboratory was found to provide a good prediction of critical shear stress, as measured by using the erosion function apparatus in a previous study. Because laboratory Qu analyses are time-consuming and expensive, the ability of field-measured Rimac data to estimate unconfined soil strength in the critical shear–soil strength relation was tested. A regression analysis was completed using a historic IDOT dataset containing 366 data pairs of laboratory Qu and field Rimac measurements from common sites with cohesive soils. The resulting equations provide a point prediction of Qu, given any Rimac value with the 90% confidence interval. The prediction equations are not significantly different from the identity Qu = Rimac. The alternative predictions of ultimate cohesive scour presented in this study assume Qu will be estimated using Rimac measurements that include computed uncertainty. In particular, the ultimate cohesive predicted scour is greater than observed scour for the entire 90% confidence interval range for predicting Qu at the bridges and soils used in this study, with the exception of the six predicted values that are all within 0.6 ft of the observed scour.

Emerging trends in the outsourcing of medical and surgical care.

PubMed

Boyd, Jennifer B; McGrath, Mary H; Maa, John

2011-01-01

As total health care expenditures are expected to constitute an increasing portion of the US gross domestic product during the coming years, the US health care system is anticipating a historic spike in the need for care. Outsourcing medical and surgical care to other nations has expanded rapidly, and several ethical, legal, and financial considerations require careful evaluation. Ultimately, the balance between cost savings, quality, and patient satisfaction will be the key determinant in the future of medical outsourcing.

The Introduction and Clinical Use of Cardiac-Specific Troponin Assays.

PubMed

Antman, Elliott M

2018-01-01

The earliest biomarkers introduced to diagnose myocardial infarction (MI) such as aspartate aminotransferase (AST) and lactic dehydrogenase (LDH) lacked cardiac specificity and were replaced by creatine kinase (CK), the CK-MB isoenzyme, and ultimately the cardiac-specific troponins (cTnT and cTnI). This has opened up the possibilities of ruling out MI more rapidly and also identifying patients with a chronic elevation of cTn and a poor prognosis in a range of cardiac conditions. © 2017 ASCPT.

Clam Shell Dredging in Lakes Pontchartrain and Maurepas, Louisiana. Volume 1. Final Environmental Impact Statement and Appendixes.

DTIC Science & Technology

1987-11-01

SHELL DREDGING IN. LAKES PONTCHARTRAIN AND’ MAUREPAS, LOUISIANAD lc . - . . - ~ K’. .. E.LEC .-- *- pas .- K - E ---.Ms---- g * ~ ,~VAUREPAS ~ ~ K...cause significant impacts due to the gradual decline and ultimate cessation of the shell dredging industry (see Sections 3.6 and 3.7). g . Long-term...process and the lakes i.1 the area expanded rapidly to their general present configurit ion. .IS - O .,* g Lake Pontchartrain is the focal point of the

Rapidly Deployable Security System Final Report CRADA No. TC-2030-01

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

Kohlhepp, V.; Whiteman, B.; McKibben, M. T.

The ultimate objective of the LEADER and LLNL strategic partnership was to develop and commercialize_a security-based system product and platform for the use in protecting the substantial physical and economic assets of the government and commerce of the United States. The primary goal of this project was to integrate video surveillance hardware developed by LLNL with a security software backbone developed by LEADER. Upon completion of the project, a prototype hardware/software security system that is highly scalable was to be demonstrated.

Evaluating markers for the early detection of cancer: overview of study designs and methods.

PubMed

Baker, Stuart G; Kramer, Barnett S; McIntosh, Martin; Patterson, Blossom H; Shyr, Yu; Skates, Steven

2006-01-01

The field of cancer biomarker development has been evolving rapidly. New developments both in the biologic and statistical realms are providing increasing opportunities for evaluation of markers for both early detection and diagnosis of cancer. To review the major conceptual and methodological issues in cancer biomarker evaluation, with an emphasis on recent developments in statistical methods together with practical recommendations. We organized this review by type of study: preliminary performance, retrospective performance, prospective performance and cancer screening evaluation. For each type of study, we discuss methodologic issues, provide examples and discuss strengths and limitations. Preliminary performance studies are useful for quickly winnowing down the number of candidate markers; however their results may not apply to the ultimate target population, asymptomatic subjects. If stored specimens from cohort studies with clinical cancer endpoints are available, retrospective studies provide a quick and valid way to evaluate performance of the markers or changes in the markers prior to the onset of clinical symptoms. Prospective studies have a restricted role because they require large sample sizes, and, if the endpoint is cancer on biopsy, there may be bias due to overdiagnosis. Cancer screening studies require very large sample sizes and long follow-up, but are necessary for evaluating the marker as a trigger of early intervention.

NEON's Mobile Deployment Platform: A research tool for integrating ecological processes across scales

NASA Astrophysics Data System (ADS)

Sanclements, M.

2016-12-01

Here we provide an update on construction of the five NEON Mobile Deployment Platforms (MDPs) as well as a description of the infrastructure and sensors available to researchers in the near future. Additionally, we include information (i.e. timelines and procedures) on requesting MDPs for PI led projects. The MDPs will provide the means to observe stochastic or spatially important events, gradients, or quantities that cannot be reliably observed using fixed location sampling (e.g. fires and floods). Due to the transient temporal and spatial nature of such events, the MDPs are designed to accommodate rapid deployment for time periods up to 1 year. Broadly, the MDPs are comprised of infrastructure and instrumentation capable of functioning individually or in conjunction with one another to support observations of ecological change, as well as education, training and outreach. More specifically, the MDPs include the capability to make tower based measures of ecosystem exchange, radiation, and precipitation in conjunction with baseline soils data such as CO2 flux, and soil temperature and moisture. An aquatics module is also available with the MDP to facilitate research integrating terrestrial and aquatic processes. Ultimately, the NEON MDPs provides a tool for linking PI led research to the continental scale data sets collected by NEON.

NEON's Mobile Deployment Platform: A Resource for Community Research

NASA Astrophysics Data System (ADS)

Sanclements, M.

2017-12-01

Here we provide an update on construction of the five NEON Mobile Deployment Platforms (MDPs) as well as a description of the infrastructure and sensors available to researchers in the near future. Additionally, we include information (i.e. timelines and procedures) on requesting MDPs for PI led projects. The MDPs will provide the means to observe stochastic or spatially important events, gradients, or quantities that cannot be reliably observed using fixed location sampling (e.g. fires and floods). Due to the transient temporal and spatial nature of such events, the MDPs are designed to accommodate rapid deployment for time periods up to 1 year. Broadly, the MDPs are comprised of infrastructure and instrumentation capable of functioning individually or in conjunction with one another to support observations of ecological change, as well as education, training and outreach. More specifically, the MDPs include the capability to make tower based measures of ecosystem exchange, radiation, and precipitation in conjunction with baseline soils data such as CO2 flux, and soil temperature and moisture. An aquatics module is also available with the MDP to facilitate research integrating terrestrial and aquatic processes. Ultimately, the NEON MDPs provide a tool for linking PI led research to the continental scale data sets collected by NEON.

The Netherlands Brain Bank for Psychiatry.

PubMed

Rademaker, Marleen C; de Lange, Geertje M; Palmen, Saskia J M C

2018-01-01

The Netherlands Brain Bank (NBB) performs rapid autopsies of donors who gave written informed consent during life for the use of their brain tissue and medical files for research. The NBB initiated the Netherlands Brain Bank for Psychiatry (NBB-Psy), a prospective donor program for psychiatric diseases. NBB-Psy wants to expand the tissue collections in order to provide a strong incentive to increase research in psychiatry. The ultimate goal of NBB-Psy is to reduce the burden of psychiatric disorders for patients, their families, and for society as a whole. NBB-Psy consists of an antemortem and postmortem donor program. This chapter focuses on the design of NBB-Psy and the antemortem donor program, where patients and relatives are actively informed on the possibility to become a brain donor. Since the initiation of NBB-Psy, the number of registered donors with a psychiatric diagnosis has increased from 149 in 2010 to 1018 in May 2016. Copyright © 2018 Elsevier B.V. All rights reserved.

In silico models for the prediction of dose-dependent human hepatotoxicity

NASA Astrophysics Data System (ADS)

Cheng, Ailan; Dixon, Steven L.

2003-12-01

The liver is extremely vulnerable to the effects of xenobiotics due to its critical role in metabolism. Drug-induced hepatotoxicity may involve any number of different liver injuries, some of which lead to organ failure and, ultimately, patient death. Understandably, liver toxicity is one of the most important dose-limiting considerations in the drug development cycle, yet there remains a serious shortage of methods to predict hepatotoxicity from chemical structure. We discuss our latest findings in this area and present a new, fully general in silico model which is able to predict the occurrence of dose-dependent human hepatotoxicity with greater than 80% accuracy. Utilizing an ensemble recursive partitioning approach, the model classifies compounds as toxic or non-toxic and provides a confidence level to indicate which predictions are most likely to be correct. Only 2D structural information is required and predictions can be made quite rapidly, so this approach is entirely appropriate for data mining applications and for profiling large synthetic and/or virtual libraries.

Granulomatosis with polyangiitis mimicking infective endocarditis in an adolescent male.

PubMed

Varnier, Giulia Camilla; Sebire, Neil; Christov, Georgi; Eleftheriou, Despina; Brogan, Paul A

2016-09-01

Granulomatosis with polyangiitis (GPA) is a rare but serious small vessel vasculitis with heterogeneous clinical presentation ranging from mainly localised disease with a chronic course, to a florid, acute small vessel vasculitic form characterised by severe pulmonary haemorrhage and/or rapidly progressive vasculitis or other severe systemic vasculitic manifestations. Cardiac involvement is, however, uncommon in the paediatric population. We report a case of a 16-year-old male who presented with peripheral gangrene and vegetation with unusual location on the supporting apparatus of the tricuspid valve, initially considered to have infective endocarditis but ultimately diagnosed with GPA. We provide an overview of the limited literature relating to cardiac involvement in GPA, and the diagnostic challenge relating to infective endocarditis in this context, especially focusing on the interpretation of the antineutrophil cytoplasmic antibody (ANCA) and the characteristic clinical features to identify in order to promptly recognise GPA, since timely diagnosis and treatment are essential for this potentially life-threatening condition.

Hydrogel-Forming Microneedle Arrays for Enhanced Transdermal Drug Delivery

PubMed Central

Donnelly, Ryan F; Singh, Thakur Raghu Raj; Garland, Martin J; Migalska, Katarzyna; Majithiya, Rita; McCrudden, Cian M; Kole, Prashant Laxman; Mahmood, Tuan Mazlelaa Tuan; McCarthy, Helen O; Woolfson, A David

2012-01-01

Unique microneedle arrays prepared from crosslinked polymers, which contain no drug themselves, are described. They rapidly take up skin interstitial fluid upon skin insertion to form continuous, unblockable, hydrogel conduits from attached patch-type drug reservoirs to the dermal microcirculation. Importantly, such microneedles, which can be fabricated in a wide range of patch sizes and microneedle geometries, can be easily sterilized, resist hole closure while in place, and are removed completely intact from the skin. Delivery of macromolecules is no longer limited to what can be loaded into the microneedles themselves and transdermal drug delivery is now controlled by the crosslink density of the hydrogel system rather than the stratum corneum, while electrically modulated delivery is also a unique feature. This technology has the potential to overcome the limitations of conventional microneedle designs and greatly increase the range of the type of drug that is deliverable transdermally, with ensuing benefits for industry, healthcare providers and, ultimately, patients. PMID:23606824

Prospects for use of the ELA test in control of trichinellosis in swine

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

Clinard, E.H.; Saunders, G.C.; Leighty, J.C.

1976-01-01

A practicable system for examining food animals at the time of slaughter to detect the presence of humoral antibodies against diseases of significance to human or animal health would be a valuable adjunct to meat inspection. Trichinosis, which has the characteristics of many of the disease problems that are of interest to the Meat and Poultry Inspection Program, was selected as a model for this purpose. Preliminary work indicated that the enzyme-labeled antibody test (ELA) could be used for detection of antibodies to Trichinella spiralis in swine. Other characteristics of the ELA test, such as its low cost, sensitivity, specificity,more » and potential for automation, supported its further development. The ultimate goal of this work is to provide a rapid, economical, automated test which will identify all swine constituting a human health hazard due to presence of infective T. spiralis larvae at the time of slaughter and identify all animals which have been infected by this parasite.« less

Ultrabroadband infrared nanospectroscopic imaging

PubMed Central

Bechtel, Hans A.; Muller, Eric A.; Olmon, Robert L.; Martin, Michael C.; Raschke, Markus B.

2014-01-01

Characterizing and ultimately controlling the heterogeneity underlying biomolecular functions, quantum behavior of complex matter, photonic materials, or catalysis requires large-scale spectroscopic imaging with simultaneous specificity to structure, phase, and chemical composition at nanometer spatial resolution. However, as with any ultrahigh spatial resolution microscopy technique, the associated demand for an increase in both spatial and spectral bandwidth often leads to a decrease in desired sensitivity. We overcome this limitation in infrared vibrational scattering-scanning probe near-field optical microscopy using synchrotron midinfrared radiation. Tip-enhanced localized light–matter interaction is induced by low-noise, broadband, and spatially coherent synchrotron light of high spectral irradiance, and the near-field signal is sensitively detected using heterodyne interferometric amplification. We achieve sub-40-nm spatially resolved, molecular, and phonon vibrational spectroscopic imaging, with rapid spectral acquisition, spanning the full midinfrared (700–5,000 cm−1) with few cm−1 spectral resolution. We demonstrate the performance of synchrotron infrared nanospectroscopy on semiconductor, biomineral, and protein nanostructures, providing vibrational chemical imaging with subzeptomole sensitivity. PMID:24803431

GLIMPSE: a rapid decision framework for energy and environmental policy.

PubMed

Akhtar, Farhan H; Pinder, Robert W; Loughlin, Daniel H; Henze, Daven K

2013-01-01

Over the coming decades, new energy production technologies and the policies that oversee them will affect human health, the vitality of our ecosystems, and the stability of the global climate. The GLIMPSE decision model framework provides insights about the implications of technology and policy decisions on these outcomes. Using GLIMPSE, decision makers can identify alternative techno-policy futures, examining their air quality, health, and short- and long-term climate impacts. Ultimately, GLIMPSE will support the identification of cost-effective strategies for simultaneously achieving performance goals for these metrics. Here, we demonstrate the utility of GLIMPSE by analyzing several future energy scenarios under existing air quality regulations and potential CO2 emission reduction policies. We find opportunities for substantial cobenefits in setting both climate change mitigation and health-benefit based air quality improvement targets. Though current policies which prioritize public health protection increase near-term warming, establishing policies that also reduce greenhouse gas emissions may offset warming in the near-term and lead to significant reductions in long-term warming.

Metavisitor, a Suite of Galaxy Tools for Simple and Rapid Detection and Discovery of Viruses in Deep Sequence Data

PubMed Central

Vernick, Kenneth D.

2017-01-01

Metavisitor is a software package that allows biologists and clinicians without specialized bioinformatics expertise to detect and assemble viral genomes from deep sequence datasets. The package is composed of a set of modular bioinformatic tools and workflows that are implemented in the Galaxy framework. Using the graphical Galaxy workflow editor, users with minimal computational skills can use existing Metavisitor workflows or adapt them to suit specific needs by adding or modifying analysis modules. Metavisitor works with DNA, RNA or small RNA sequencing data over a range of read lengths and can use a combination of de novo and guided approaches to assemble genomes from sequencing reads. We show that the software has the potential for quick diagnosis as well as discovery of viruses from a vast array of organisms. Importantly, we provide here executable Metavisitor use cases, which increase the accessibility and transparency of the software, ultimately enabling biologists or clinicians to focus on biological or medical questions. PMID:28045932

Health care in China: improvement, challenges, and reform.

PubMed

Wang, Chen; Rao, Keqin; Wu, Sinan; Liu, Qian

2013-02-01

Over the past 2 decades, significant progress has been made in improving the health-care system and people's health conditions in China. Following rapid economic growth and social development, China's health-care system is facing new challenges, such as increased health-care demands and expenditure, inefficient use of health-care resources, unsatisfying implementation of disease management guidelines, and inadequate health-care insurance. Facing these challenges, the Chinese government carried out a national health-care reform in 2009. A series of policies were developed and implemented to improve the health-care insurance system, the medical care system, the public health service system, the pharmaceutical supply system, and the health-care institution management system in China. Although these measures have shown promising results, further efforts are needed to achieve the ultimate goal of providing affordable and high-quality care for both urban and rural residents in China. This article not only covers the improvement, challenges, and reform of health care in general in China, but also highlights the status of respiratory medicine-related issues.

Plant iTRAQ-based proteomics

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

Handakumbura, Pubudu; Hixson, Kim K.; Purvine, Samuel O.

We present a simple one-­pot extraction protocol, which rapidly isolates hydrophyllic metabolites, lipids, and proteins from the same pulverized plant sample. Also detailed is a global plant proteomics sample preparation method utilizing iTRAQ multiplexing reagents that enables deep proteome coverage due to the use of HPLC fractionation of the peptides prior to mass spectrometric analysis. We have successfully used this protocol on several different plant tissues (e.g., roots, stems, leaves) from different plants (e.g., sorghum, poplar, Arabidopsis, soybean), and have been able to successfully detect and quantify thousands of proteins. Multiplexing strategies such as iTRAQ and the bioinformatics strategy outlinedmore » here, ultimately provide insight into which proteins are significantly changed in abundance between two or more groups (e.g., control, perturbation). Our bioinformatics strategy yields z-­score values, which normalize the expression data into a format that can easily be cross-­compared with other expression data (i.e., metabolomics, transcriptomics) obtained from different analytical methods and instrumentation.« less

Observation of optomechanical buckling transitions

PubMed Central

Xu, H.; Kemiktarak, U.; Fan, J.; Ragole, S.; Lawall, J.; Taylor, J. M.

2017-01-01

Correlated phases of matter provide long-term stability for systems as diverse as solids, magnets and potential exotic quantum materials. Mechanical systems, such as buckling transition spring switches, can have engineered, stable configurations whose dependence on a control variable is reminiscent of non-equilibrium phase transitions. In hybrid optomechanical systems, light and matter are strongly coupled, allowing engineering of rapid changes in the force landscape, storing and processing information, and ultimately probing and controlling behaviour at the quantum level. Here we report the observation of first- and second-order buckling transitions between stable mechanical states in an optomechanical system, in which full control of the nature of the transition is obtained by means of the laser power and detuning. The underlying multiwell confining potential we create is highly tunable, with a sub-nanometre distance between potential wells. Our results enable new applications in photonics and information technology, and may enable explorations of quantum phase transitions and macroscopic quantum tunnelling in mechanical systems. PMID:28248293

Choice and maintenance of equipment for electron crystallography.

PubMed

Mills, Deryck J; Vonck, Janet

2013-01-01

The choice of equipment for an electron crystallography laboratory will ultimately be determined by the available budget; nevertheless, the ideal lab will have two electron microscopes: a dedicated 300 kV cryo-EM with a field emission gun and a smaller LaB(6) machine for screening. The high-end machine should be equipped with photographic film or a very large CCD or CMOS camera for 2D crystal data collection; the screening microscope needs a mid-size CCD for rapid evaluation of crystal samples. The microscope room installations should provide adequate space and a special environment that puts no restrictions on the collection of high-resolution data. Equipment for specimen preparation includes a carbon coater, glow discharge unit, light microscope, plunge freezer, and liquid nitrogen containers and storage dewars. When photographic film is to be used, additional requirements are a film desiccator, dark room, optical diffractometer, and a film scanner. Having the electron microscopes and ancillary equipment well maintained and always in optimum condition facilitates the production of high-quality data.

The thyroid hormone receptor β induces DNA damage and premature senescence.

PubMed

Zambrano, Alberto; García-Carpizo, Verónica; Gallardo, María Esther; Villamuera, Raquel; Gómez-Ferrería, Maria Ana; Pascual, Angel; Buisine, Nicolas; Sachs, Laurent M; Garesse, Rafael; Aranda, Ana

2014-01-06

There is increasing evidence that the thyroid hormone (TH) receptors (THRs) can play a role in aging, cancer and degenerative diseases. In this paper, we demonstrate that binding of TH T3 (triiodothyronine) to THRB induces senescence and deoxyribonucleic acid (DNA) damage in cultured cells and in tissues of young hyperthyroid mice. T3 induces a rapid activation of ATM (ataxia telangiectasia mutated)/PRKAA (adenosine monophosphate-activated protein kinase) signal transduction and recruitment of the NRF1 (nuclear respiratory factor 1) and THRB to the promoters of genes with a key role on mitochondrial respiration. Increased respiration leads to production of mitochondrial reactive oxygen species, which in turn causes oxidative stress and DNA double-strand breaks and triggers a DNA damage response that ultimately leads to premature senescence of susceptible cells. Our findings provide a mechanism for integrating metabolic effects of THs with the tumor suppressor activity of THRB, the effect of thyroidal status on longevity, and the occurrence of tissue damage in hyperthyroidism.

One-way membrane trafficking of SOS in receptor-triggered Ras activation.

PubMed

Christensen, Sune M; Tu, Hsiung-Lin; Jun, Jesse E; Alvarez, Steven; Triplet, Meredith G; Iwig, Jeffrey S; Yadav, Kamlesh K; Bar-Sagi, Dafna; Roose, Jeroen P; Groves, Jay T

2016-09-01

SOS is a key activator of the small GTPase Ras. In cells, SOS-Ras signaling is thought to be initiated predominantly by membrane recruitment of SOS via the adaptor Grb2 and balanced by rapidly reversible Grb2-SOS binding kinetics. However, SOS has multiple protein and lipid interactions that provide linkage to the membrane. In reconstituted-membrane experiments, these Grb2-independent interactions were sufficient to retain human SOS on the membrane for many minutes, during which a single SOS molecule could processively activate thousands of Ras molecules. These observations raised questions concerning how receptors maintain control of SOS in cells and how membrane-recruited SOS is ultimately released. We addressed these questions in quantitative assays of reconstituted SOS-deficient chicken B-cell signaling systems combined with single-molecule measurements in supported membranes. These studies revealed an essentially one-way trafficking process in which membrane-recruited SOS remains trapped on the membrane and continuously activates Ras until being actively removed via endocytosis.

One-way membrane trafficking of SOS in receptor-triggered Ras activation

PubMed Central

Christensen, Sune M.; Tu, Hsiung-Lin; Jun, Jesse E.; Alvarez, Steven; Triplet, Meredith G.; Iwig, Jeffrey S.; Yadav, Kamlesh K.; Bar-Sagi, Dafna; Roose, Jeroen P.; Groves, Jay T.

2016-01-01

SOS is a key activator of the small GTPase Ras. In cells, SOS-Ras signaling is thought to be initiated predominantly by membrane-recruitment of SOS via the adaptor Grb2 and balanced by rapidly reversible Grb2:SOS binding kinetics. However, SOS has multiple protein and lipid interactions that provide linkage to the membrane. In reconstituted membrane experiments, these Grb2-independent interactions are sufficient to retain SOS on the membrane for many minutes, during which a single SOS molecule can processively activate thousands of Ras molecules. These observations raise questions concerning how receptors maintain control of SOS in cells and how membrane-recruited SOS is ultimately released. We addressed these questions in quantitative reconstituted SOS-deficient chicken B cell signaling systems combined with single molecule measurements in supported membranes. These studies reveal an essentially one-way trafficking process in which membrane-recruited SOS remains trapped on the membrane and continuously activates Ras until it is actively removed via endocytosis. PMID:27501536

Camouflage, communication and thermoregulation: lessons from colour changing organisms.

PubMed

Stuart-Fox, Devi; Moussalli, Adnan

2009-02-27

Organisms capable of rapid physiological colour change have become model taxa in the study of camouflage because they are able to respond dynamically to the changes in their visual environment. Here, we briefly review the ways in which studies of colour changing organisms have contributed to our understanding of camouflage and highlight some unique opportunities they present. First, from a proximate perspective, comparison of visual cues triggering camouflage responses and the visual perception mechanisms involved can provide insight into general visual processing rules. Second, colour changing animals can potentially tailor their camouflage response not only to different backgrounds but also to multiple predators with different visual capabilities. We present new data showing that such facultative crypsis may be widespread in at least one group, the dwarf chameleons. From an ultimate perspective, we argue that colour changing organisms are ideally suited to experimental and comparative studies of evolutionary interactions between the three primary functions of animal colour patterns: camouflage; communication; and thermoregulation.

Camouflage, communication and thermoregulation: lessons from colour changing organisms

PubMed Central

Stuart-Fox, Devi; Moussalli, Adnan

2008-01-01

Organisms capable of rapid physiological colour change have become model taxa in the study of camouflage because they are able to respond dynamically to the changes in their visual environment. Here, we briefly review the ways in which studies of colour changing organisms have contributed to our understanding of camouflage and highlight some unique opportunities they present. First, from a proximate perspective, comparison of visual cues triggering camouflage responses and the visual perception mechanisms involved can provide insight into general visual processing rules. Second, colour changing animals can potentially tailor their camouflage response not only to different backgrounds but also to multiple predators with different visual capabilities. We present new data showing that such facultative crypsis may be widespread in at least one group, the dwarf chameleons. From an ultimate perspective, we argue that colour changing organisms are ideally suited to experimental and comparative studies of evolutionary interactions between the three primary functions of animal colour patterns: camouflage; communication; and thermoregulation. PMID:19000973

Assessing Juvenile Salmonid Passage Through Culverts: Field Research in Support of Protocol Development

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

Williams, Greg D.; Evans, Nathan R.; Pearson, Walter H.

2001-10-30

The primary goal of our research this spring/ summer was to refine techniques and examine scenarios under which a standardized protocol could be applied to assess juvenile coho salmon (O. kisutch) passage through road culverts. Field evaluations focused on capture-mark- recapture methods that allowed analysis of fish movement patterns, estimates of culvert passability, and potential identification of cues inducing these movements. At this stage, 0+ age coho salmon fry 30 mm to 65 mm long (fork length) were the species and age class of interest. Ultimately, the protocol will provide rapid, statistically rigorous methods for trained personnel to perform standardizedmore » biological assessments of culvert passability to a number of juvenile salmon species. Questions to be addressed by the research include the following: ? Do hydraulic structures such as culverts restrict habitat for juvenile salmonids? ? How do existing culverts and retrofits perform relative to juvenile salmonid passage? ? Do some culvert characteristics and hydraulic conditions provide better passage than others? ? Does the culvert represent a barrier to certain size classes of fish? Recommendations addressed issues of study site selection, initial capture, marking, recapture/observations, and estimating movement.« less

Expanding the horizons of microRNA bioinformatics.

PubMed

Huntley, Rachael P; Kramarz, Barbara; Sawford, Tony; Umrao, Zara; Kalea, Anastasia Z; Acquaah, Vanessa; Martin, Maria-Jesus; Mayr, Manuel; Lovering, Ruth C

2018-06-05

MicroRNA regulation of key biological and developmental pathways is a rapidly expanding area of research, accompanied by vast amounts of experimental data. This data, however, is not widely available in bioinformatic resources, making it difficult for researchers to find and analyse microRNA-related experimental data and define further research projects. We are addressing this problem by providing two new bioinformatics datasets that contain experimentally verified functional information for mammalian microRNAs involved in cardiovascular-relevant, and other, processes. To date, our resource provides over 3,900 Gene Ontology annotations associated with almost 500 miRNAs from human, mouse and rat and over 2,200 experimentally validated miRNA:target interactions. We illustrate how this resource can be used to create miRNA-focused interaction networks with a biological context using the known biological role of miRNAs and the mRNAs they regulate, enabling discovery of associations between gene products, biological pathways and, ultimately, diseases. This data will be crucial in advancing the field of microRNA bioinformatics and will establish consistent datasets for reproducible functional analysis of microRNAs across all biological research areas. Published by Cold Spring Harbor Laboratory Press for the RNA Society.

Sleep in vertebrate and invertebrate animals, and insights into the function and evolution of sleep.

PubMed

Miyazaki, Shinichi; Liu, Chih-Yao; Hayashi, Yu

2017-05-01

Many mammalian species, including humans, spend a substantial fraction of their life sleeping. Sleep deprivation in rats ultimately leads to death, indicating the essential role of sleep. Exactly why sleep is so essential, however, remains largely unknown. From an evolutionary point of view, almost all animal species that have been investigated exhibit sleep or sleep-like states, suggesting that sleep may benefit survival. In certain mammalian and avian species, sleep can be further divided into at least two stages, rapid eye movement (REM) sleep and non-REM sleep. In addition to a widely conserved role for sleep, these individual sleep stages may have roles unique to these animals. The recent use of state-of-the-art techniques, including optogenetics and chemogenetics, has greatly broadened our understanding of the neural mechanisms of sleep regulation, allowing us to address the function of sleep. Studies focusing on non-mammalian animals species have also provided novel insights into the evolution of sleep. This review provides a comprehensive overview regarding the current knowledge of the function and evolution of sleep. Copyright © 2017 Elsevier Ireland Ltd and Japan Neuroscience Society. All rights reserved.

Air travel and vector-borne disease movement.

PubMed

Tatem, A J; Huang, Z; Das, A; Qi, Q; Roth, J; Qiu, Y

2012-12-01

Recent decades have seen substantial expansions in the global air travel network and rapid increases in traffic volumes. The effects of this are well studied in terms of the spread of directly transmitted infections, but the role of air travel in the movement of vector-borne diseases is less well understood. Increasingly however, wider reaching surveillance for vector-borne diseases and our improving abilities to map the distributions of vectors and the diseases they carry, are providing opportunities to better our understanding of the impact of increasing air travel. Here we examine global trends in the continued expansion of air transport and its impact upon epidemiology. Novel malaria and chikungunya examples are presented, detailing how geospatial data in combination with information on air traffic can be used to predict the risks of vector-borne disease importation and establishment. Finally, we describe the development of an online tool, the Vector-Borne Disease Airline Importation Risk (VBD-Air) tool, which brings together spatial data on air traffic and vector-borne disease distributions to quantify the seasonally changing risks for importation to non-endemic regions. Such a framework provides the first steps towards an ultimate goal of adaptive management based on near real time flight data and vector-borne disease surveillance.

Efficacy of NH3 as a secondary barrier treatment for inactivation of Salmonella Typhimurium and methicillin-resistant Staphylococcus aureus in digestate of animal carcasses: Proof-of-concept

PubMed Central

2017-01-01

Managing the disposal of infectious animal carcasses from routine and catastrophic disease outbreaks is a global concern. Recent research suggests that burial in lined and aerated trenches provides the rapid pathogen containment provided by burial, while reducing air and water pollution potential and the length of time that land is taken out of agricultural production. Survival of pathogens in the digestate remains a concern, however. A potential answer is a ‘dual’-barrier approach in which ammonia is used as a secondary barrier treatment to reduce the risk of pathogen contamination when trench liners ultimately leak. Results of this study showed that the minimum inhibitory concentration (MIC) of NH3 is 0.1 M (~1,468 NH3-N mg/L), and 0.5 M NH3 (~7,340 NH3-N mg/L) for ST4232 & MRSA43300, respectively at 24 h and pH = 9±0.1 and inactivation was increased by increasing NH3 concentration and/or treatment time. Results for digestate treated with NH3 were consistent with the MICs, and both pathogens were completely inactivated within 24 h. PMID:28475586

Design and implementation of an automated compound management system in support of lead optimization.

PubMed

Quintero, Catherine; Kariv, Ilona

2009-06-01

To meet the needs of the increasingly rapid and parallelized lead optimization process, a fully integrated local compound storage and liquid handling system was designed and implemented to automate the generation of assay-ready plates directly from newly submitted and cherry-picked compounds. A key feature of the system is the ability to create project- or assay-specific compound-handling methods, which provide flexibility for any combination of plate types, layouts, and plate bar-codes. Project-specific workflows can be created by linking methods for processing new and cherry-picked compounds and control additions to produce a complete compound set for both biological testing and local storage in one uninterrupted workflow. A flexible cherry-pick approach allows for multiple, user-defined strategies to select the most appropriate replicate of a compound for retesting. Examples of custom selection parameters include available volume, compound batch, and number of freeze/thaw cycles. This adaptable and integrated combination of software and hardware provides a basis for reducing cycle time, fully automating compound processing, and ultimately increasing the rate at which accurate, biologically relevant results can be produced for compounds of interest in the lead optimization process.

Standard operating procedure for calculating genome-to-genome distances based on high-scoring segment pairs.

PubMed

Auch, Alexander F; Klenk, Hans-Peter; Göker, Markus

2010-01-28

DNA-DNA hybridization (DDH) is a widely applied wet-lab technique to obtain an estimate of the overall similarity between the genomes of two organisms. To base the species concept for prokaryotes ultimately on DDH was chosen by microbiologists as a pragmatic approach for deciding about the recognition of novel species, but also allowed a relatively high degree of standardization compared to other areas of taxonomy. However, DDH is tedious and error-prone and first and foremost cannot be used to incrementally establish a comparative database. Recent studies have shown that in-silico methods for the comparison of genome sequences can be used to replace DDH. Considering the ongoing rapid technological progress of sequencing methods, genome-based prokaryote taxonomy is coming into reach. However, calculating distances between genomes is dependent on multiple choices for software and program settings. We here provide an overview over the modifications that can be applied to distance methods based in high-scoring segment pairs (HSPs) or maximally unique matches (MUMs) and that need to be documented. General recommendations on determining HSPs using BLAST or other algorithms are also provided. As a reference implementation, we introduce the GGDC web server (http://ggdc.gbdp.org).

Protecting workers and the environment: An environmental NGO's perspective on nanotechnology

NASA Astrophysics Data System (ADS)

Balbus, John M.; Florini, Karen; Denison, Richard A.; Walsh, Scott A.

2007-01-01

Nanotechnology, the design and manipulation of materials at the atomic scale, may well revolutionize many of the ways our society manufactures products, produces energy, and treats diseases. New materials based on nanotechnology are already reaching the market in a wide variety of consumer products. Some of the observed properties of nanomaterials call into question the adequacy of current methods for determining hazard and exposure and for controlling resulting risks. Given the limitations of existing regulatory tools and policies, we believe two distinct kinds of initiatives are needed: first, a major increase in the federal investment in nanomaterial risk research; second, rapid development and implementation of voluntary standards of care pending development of adequate regulatory safeguards in the longer term. Several voluntary programs are currently at various stages of evolution, though the eventual outputs of each of these are still far from clear. Ultimately, effective regulatory safeguards are necessary to provide a level playing field for industry while adequately protecting human health and the environment. This paper reviews the existing toxicological literature on nanomaterials, outlines and analyzes the current regulatory framework, and provides our recommendations, as an environmental non-profit organization, for safe nanotechnology development.

Complex networks with scale-free nature and hierarchical modularity

NASA Astrophysics Data System (ADS)

Shekatkar, Snehal M.; Ambika, G.

2015-09-01

Generative mechanisms which lead to empirically observed structure of networked systems from diverse fields like biology, technology and social sciences form a very important part of study of complex networks. The structure of many networked systems like biological cell, human society and World Wide Web markedly deviate from that of completely random networks indicating the presence of underlying processes. Often the main process involved in their evolution is the addition of links between existing nodes having a common neighbor. In this context we introduce an important property of the nodes, which we call mediating capacity, that is generic to many networks. This capacity decreases rapidly with increase in degree, making hubs weak mediators of the process. We show that this property of nodes provides an explanation for the simultaneous occurrence of the observed scale-free structure and hierarchical modularity in many networked systems. This also explains the high clustering and small-path length seen in real networks as well as non-zero degree-correlations. Our study also provides insight into the local process which ultimately leads to emergence of preferential attachment and hence is also important in understanding robustness and control of real networks as well as processes happening on real networks.

Hybrid surgical guidance based on the integration of radionuclear and optical technologies

PubMed Central

Valdés-Olmos, Renato; Buckle, Tessa; Vidal-Sicart, Sergi

2016-01-01

With the evolution of imaging technologies and tracers, the applications for nuclear molecular imaging are growing rapidly. For example, nuclear medicine is increasingly being used to guide surgical resections in complex anatomical locations. Here, a future workflow is envisioned that uses a combination of pre-operative diagnostics, navigation and intraoperative guidance. Radioguidance can provide means for pre-operative and intraoperative identification of “hot” lesions, forming the basis of a virtual data set that can be used for navigation. Luminescence guidance has shown great potential in the intraoperative setting by providing optical feedback, in some cases even in real time. Both of these techniques have distinct drawbacks, which include inaccuracy in areas that contain a background signal (radioactivity) or a limited degree of signal penetration (luminescence). We, and others, have reasoned that hybrid/multimodal approaches that integrate the use of these complementary modalities may help overcome their individual weaknesses. Ultimately, this will lead to advancement of the field of interventional molecular imaging/image-guided surgery. In this review, an overview of clinically applied hybrid surgical guidance technologies is given, whereby the focus is placed on tracers and hardware. PMID:26943463

An adaptive toolkit for image quality evaluation in system performance test of digital breast tomosynthesis

NASA Astrophysics Data System (ADS)

Zhang, Guozhi; Petrov, Dimitar; Marshall, Nicholas; Bosmans, Hilde

2017-03-01

Digital breast tomosynthesis (DBT) is a relatively new diagnostic imaging modality for women. Currently, various models of DBT systems are available on the market and the number of installations is rapidly increasing. EUREF, the European Reference Organization for Quality Assured Breast Screening and Diagnostic Services, has proposed a preliminary Guideline - protocol for the quality control of the physical and technical aspects of digital breast tomosynthesis systems, with an ultimate aim of providing limiting values guaranteeing proper performance for different applications of DBT. In this work, we introduce an adaptive toolkit developed in accordance with this guideline to facilitate the process of image quality evaluation in DBT performance test. This toolkit implements robust algorithms to quantify various technical parameters of DBT images and provides a convenient user interface in practice. Each test is built into a separate module with configurations set corresponding to the European guideline, which can be easily adapted to different settings and extended with additional tests. This toolkit largely improves the efficiency for image quality evaluation of DBT. It is also going to evolve with the development of protocols in quality control of DBT systems.

Harnessing person-generated health data to accelerate patient-centered outcomes research: the Crohn’s and Colitis Foundation of America PCORnet Patient Powered Research Network (CCFA Partners)

PubMed Central

Sandler, Robert S; Long, Millie D; Ahrens, Sean; Burris, Jessica L; Martin, Christopher F; Anton, Kristen; Robb, Amber; Caruso, Thomas P; Jaeger, Elizabeth L; Chen, Wenli; Clark, Marshall; Myers, Kelly; Dobes, Angela; Kappelman, Michael D

2016-01-01

The Crohn’s and Colitis Foundation of America Partners Patient-Powered Research Network (PPRN) seeks to advance and accelerate comparative effectiveness and translational research in inflammatory bowel diseases (IBDs). Our IBD-focused PCORnet PPRN has been designed to overcome the major obstacles that have limited patient-centered outcomes research in IBD by providing the technical infrastructure, patient governance, and patient-driven functionality needed to: 1) identify, prioritize, and undertake a patient-centered research agenda through sharing person-generated health data; 2) develop and test patient and provider-focused tools that utilize individual patient data to improve health behaviors and inform health care decisions and, ultimately, outcomes; and 3) rapidly disseminate new knowledge to patients, enabling them to improve their health. The Crohn’s and Colitis Foundation of America Partners PPRN has fostered the development of a community of citizen scientists in IBD; created a portal that will recruit, retain, and engage members and encourage partnerships with external scientists; and produced an efficient infrastructure for identifying, screening, and contacting network members for participation in research. PMID:26911821

AMP-Activated Kinase Regulates Lipid Droplet Localization and Stability of Adipose Triglyceride Lipase in C. elegans Dauer Larvae.

PubMed

Xie, Meng; Roy, Richard

2015-01-01

Animals have developed diverse mechanisms to adapt to their changing environment. Like many organisms the free-living nematode C. elegans can alternate between a reproductive mode or a diapause-like "dauer" stage during larval development to circumvent harsh environmental conditions. The master metabolic regulator AMP-activated protein kinase (AMPK) is critical for survival during the dauer stage, where it phosphorylates adipose triglyceride lipase (ATGL-1) at multiple sites to block lipid hydrolysis and ultimately protect the cellular triglyceride-based energy depot from rapid depletion. However, how the AMPK-mediated phosphorylation affects the function of ATGL-1 has not been characterised at the molecular level. Here we show that AMPK phosphorylation leads to the generation of 14-3-3 binding sites on ATGL-1, which are recognized by the C. elegans 14-3-3 protein orthologue PAR-5. Physical interaction of ATGL-1 with PAR-5 results in sequestration of ATGL-1 away from the lipid droplets and eventual proteasome-mediated degradation. In addition, we also show that the major AMPK phosphorylation site on ATGL-1, Ser 303, is required for both modification of its lipid droplet localization and its degradation. Our data provide mechanistic insight as to how AMPK functions to enhance survival through its ability to protect the accumulated triglyceride deposits from rapid hydrolysis to preserve the energy stores during periods of extended environmental duress.

Contamination of drinking-water by arsenic in Bangladesh: a public health emergency.

PubMed Central

Smith, A. H.; Lingas, E. O.; Rahman, M.

2000-01-01

The contamination of groundwater by arsenic in Bangladesh is the largest poisoning of a population in history, with millions of people exposed. This paper describes the history of the discovery of arsenic in drinking-water in Bangladesh and recommends intervention strategies. Tube-wells were installed to provide "pure water" to prevent morbidity and mortality from gastrointestinal disease. The water from the millions of tube-wells that were installed was not tested for arsenic contamination. Studies in other countries where the population has had long-term exposure to arsenic in groundwater indicate that 1 in 10 people who drink water containing 500 micrograms of arsenic per litre may ultimately die from cancers caused by arsenic, including lung, bladder and skin cancers. The rapid allocation of funding and prompt expansion of current interventions to address this contamination should be facilitated. The fundamental intervention is the identification and provision of arsenic-free drinking water. Arsenic is rapidly excreted in urine, and for early or mild cases, no specific treatment is required. Community education and participation are essential to ensure that interventions are successful; these should be coupled with follow-up monitoring to confirm that exposure has ended. Taken together with the discovery of arsenic in groundwater in other countries, the experience in Bangladesh shows that groundwater sources throughout the world that are used for drinking-water should be tested for arsenic. PMID:11019458

Nanoscale detection of bacteriophage triggered ion cascade (Invited Paper)

NASA Astrophysics Data System (ADS)

Dobozi-King, Maria; Seo, Sungkyu; Kim, Jong U.; Cheng, Mosong; Kish, Laszlo B.; Young, Ryland

2005-05-01

In an era of potential bioterrorism and pandemics of antibiotic-resistant microbes, bacterial contaminations of food and water supplies is a major concern. There is an urgent need for the rapid, inexpensive and specific identification of bacteria under field conditions. Here we describe a method that combines the specificity and avidity of bacteriophages with fluctuation analysis of electrical noise. The method is based on the massive, transitory ion leakage that occurs at the moment of phage DNA injection into the host cell. The ion fluxes require only that the cells be physiologically viable (i.e., have energized membranes) and can occur within seconds after mixing the cells with sufficient concentrations of phage particles. To detect these fluxes, we have constructed a nano-well, a lateral, micron-size capacitor of titanium electrodes with gap size of 150 nm, and used it to measure the electrical field fluctuations in microliter (mm3) samples containing phage and bacteria. In mixtures where the analyte bacteria were sensitive to the phage, large stochastic waves with various time and amplitude scales were observed, with power spectra of approximately 1/f2 shape over at 1 - 10 Hz. Development of this SEPTIC (SEnsing of Phage-Triggered Ion Cascades) technology could provide rapid detection and identification of live, pathogenic bacteria on the scale of minutes, with unparalleled specificity. The method has a potential ultimate sensitivity of 1 bacterium/microliter (1 bacterium/mm3).

Queerspawn Speak out: A Review of "Let's Get This Straight: The Ultimate Handbook for Youth with LGBTQ Parents"

ERIC Educational Resources Information Center

Ryan, Caitlin L.

2012-01-01

"Let's Get This Straight: The Ultimate Handbook for Youth With LGBTQ Parents" provides an engaging and accessible set of tools for youth from LGBTQ-headed families. The stories and resources shared encourage these youth to take pride in their families, value their diverse experiences, and work against homophobia, transphobia, and other forms of…

Redistributive land and tenancy reform in Bangladesh agriculture.

PubMed

Taslim, M A

1993-04-01

Land is scarce and population dense in Bangladesh. Accordingly, there is great need to maximize agricultural production with intensive cultivation and the diffusion of modern technology. The realization of this goal, however, is impeded by the prevailing inequitable and inefficient structure of agricultural land tenure in which a few rural households hold the bulk of cultivatable land. Cropsharing and the system of land tenancy perpetuates low productivity and stagnation throughout the country. Development professionals, ruling politicians, and general populations in many countries under similar circumstances often suggest that share tenancy be abolished and tenants given ownership of tenanted plots, with large farms broken into smaller ones with an ultimate ceiling on farm size. The political and undertaken by new governments coming to power after violent social upheavals. Careful review reveals that such reform has hardly ever led to the establishment of prosperous and independent peasantries. Small family farms have instead become more dependent on the state and on off-farm employment. The rural elite is destroyed and a small peasant proprietorship dependent on the state is established which is ultimately controlled by the urban elite of the country; control over rural populations is reinforced. The dubious historical motivation for and results of land reform suggest that Bangladesh abandon its consideration in favor of promoting vocational training and education; providing research and extension services to agriculture for more rapid diffusion of high-yield innovations; mobilizing domestic resources to build up the infrastructure; fostering the development of private initiatives; and informing and advising about sustainable development practices to encourage their adoption so that an ecological balance may be maintained.

Dual enhancement of electroluminescence efficiency and operational stability by rapid upconversion of triplet excitons in OLEDs

PubMed Central

Furukawa, Taro; Nakanotani, Hajime; Inoue, Munetomo; Adachi, Chihaya

2015-01-01

Recently, triplet harvesting via a thermally activated delayed fluorescence (TADF) process has been established as a realistic route for obtaining ultimate internal electroluminescence (EL) quantum efficiency in organic light-emitting diodes (OLEDs). However, the possibility that the rather long transient lifetime of the triplet excited states would reduce operational stability due to an increased chance for unwarranted chemical reactions has been a concern. Herein, we demonstrate dual enhancement of EL efficiency and operational stability in OLEDs by employing a TADF molecule as an assistant dopant and a fluorescent molecule as an end emitter. The proper combination of assistant dopant and emitter molecules realized a “one-way” rapid Förster energy transfer of singlet excitons from TADF molecules to fluorescent emitters, reducing the number of cycles of intersystem crossing (ISC) and reverse ISC in the TADF molecules and resulting in a significant enhancement of operational stability compared to OLEDs with a TADF molecule as the end emitter. In addition, we found that the presence of this rapid energy transfer significantly suppresses singlet-triplet annihilation. Using this finely-tuned rapid triplet-exciton upconversion scheme, OLED performance and lifetime was greatly improved. PMID:25673259

Understanding and preventing contrast-induced acute kidney injury.

PubMed

Fähling, Michael; Seeliger, Erdmann; Patzak, Andreas; Persson, Pontus B

2017-03-01

Contrast-induced acute kidney injury (CIAKI) occurs in up to 30% of patients who receive iodinated contrast media and is generally considered to be the third most common cause of hospital-acquired AKI. Accurate assessment of the incidence of CIAKI is obscured, however, by the use of various definitions for diagnosis, the different populations studied and the prophylactic measures put in place. A deeper understanding of the mechanisms that underlie CIAKI is required to enable reliable risk assessment for individual patients, as their medical histories will determine the specific pathways by which contrast media administration might lead to kidney damage. Here, we highlight common triggers that prompt the development of CIAKI and the subsequent mechanisms that ultimately cause kidney damage. We also discuss effective protective measures, such as rapidly acting oral hydration schemes and loop diuretics, in the context of CIAKI pathophysiology. Understanding of how CIAKI arises in different patient groups could enable a marked reduction in incidence and improved outcomes. The ultimate goal is to shape CIAKI prevention strategies for individual patients.

Persistent bacteraemia caused by Staphylococcus aureus in the gall bladder.

PubMed

Yu, Alexander Tin Han; Cun, Tony; Benamu, Esther; Renault, Cybele

2017-11-08

Staphylococcus aureus bacteraemia (SAB) remains a complex disease with a high associated morbidity and mortality, especially when it is able to establish an occult nidus safe from antimicrobial eradication. Without rapid identification and intervention, the nidus can cause persistent relapse of disease, morbidity and mortality. Having a high clinical suspicion for the foci of occult S. aureus is important, and awareness of potential sites of infection is critical and can be life-saving.We present a unique case of a 65-year-old man with end-stage renal disease receiving haemodialysis who developed septic shock from SAB. Despite 18 days of appropriate antibiotics, the patient had persistent high-grade bacteraemia until his gall bladder was ultimately percutaneously drained. The day after drainage, he cleared his blood cultures, although he ultimately passed away as he decided to transition his care to focus on comfort measures. © BMJ Publishing Group Ltd (unless otherwise stated in the text of the article) 2017. All rights reserved. No commercial use is permitted unless otherwise expressly granted.

Mectizan(®) procurement and delivery for onchocerciasis mass drug administration programmes.

PubMed

Ogoussan, Kisito T; Hopkins, Adrian

2011-09-01

The discovery of Mectizan has engendered a safe onchocerciasis chemoprevention tool. To make the drug available promptly to people at risk of onchocerciasis, a procurement and delivery mechanism has been put in place around the Mectizan Donation Program, which oversees the Merck donation of Mectizan. The number of yearly approved treatment doses has increased rapidly since 1988 from 255,000 to more than 80 million in 2007 and 2008. Cumulatively, from 1987 to 2008 more than 697 million treatment doses have been approved corresponding to 1.5 billion Mectizan tablets shipped. Although the current demand for treatment is met, the ultimate goal is to cover all people at risk. A comprehensive drug policy from recipient countries is still needed to back up the current efficient procurement and delivery mechanism in order to attain the ultimate to goal, and is equally important for scaling up mass drug administration as part of national neglected tropical disease control/elimination strategies. Copyright © 2010 Elsevier B.V. All rights reserved.

Rapid determination of sugar level in snack products using infrared spectroscopy.

PubMed

Wang, Ting; Rodriguez-Saona, Luis E

2012-08-01

Real-time spectroscopic methods can provide a valuable window into food manufacturing to permit optimization of production rate, quality and safety. There is a need for cutting edge sensor technology directed at improving efficiency, throughput and reliability of critical processes. The aim of the research was to evaluate the feasibility of infrared systems combined with chemometric analysis to develop rapid methods for determination of sugars in cereal products. Samples were ground and spectra were collected using a mid-infrared (MIR) spectrometer equipped with a triple-bounce ZnSe MIRacle attenuated total reflectance accessory or Fourier transform near infrared (NIR) system equipped with a diffuse reflection-integrating sphere. Sugar contents were determined using a reference HPLC method. Partial least squares regression (PLSR) was used to create cross-validated calibration models. The predictability of the models was evaluated on an independent set of samples and compared with reference techniques. MIR and NIR spectra showed characteristic absorption bands for sugars, and generated excellent PLSR models (sucrose: SEP < 1.7% and r > 0.96). Multivariate models accurately and precisely predicted sugar level in snacks allowing for rapid analysis. This simple technique allows for reliable prediction of quality parameters, and automation enabling food manufacturers for early corrective actions that will ultimately save time and money while establishing a uniform quality. The U.S. snack food industry generates billions of dollars in revenue each year and vibrational spectroscopic methods combined with pattern recognition analysis could permit optimization of production rate, quality, and safety of many food products. This research showed that infrared spectroscopy is a powerful technique for near real-time (approximately 1 min) assessment of sugar content in various cereal products. © 2012 Institute of Food Technologists®

Stratigraphic, sedimentologic, and dendrogeomorphic analyses of rapid floodplain formation along the Rio Grande in Big Bend National Park, Texas

USGS Publications Warehouse

Dean, D.J.; Scott, M.L.; Shafroth, P.B.; Schmidt, J.C.

2011-01-01

The channel of the lower Rio Grande in the Big Bend region rapidly narrows during years of low mean and peak flow. We conducted stratigraphic, sedimentologic, and dendrogeomorphic analyses within two long floodplain trenches to precisely reconstruct the timing and processes of recent floodplain formation. We show that the channel of the Rio Grande narrowed through the oblique and vertical accretion of inset floodplains following channel-widening floods in 1978 and 1990-1991. Vertical accretion occurred at high rates, ranging from 16 to 35 cm/yr. Dendrogeomorphic analyses show that the onset of channel narrowing occurred during low-flow years when channel bars obliquely and vertically accreted fine sediment. This initial stage of accretion occurred by both bedload and suspended-load deposition within the active channel. Vegetation became established on top of these fine-grained deposits during years of low peak flow and stabilized these developing surfaces. Subsequent deposition by moderate floods (between 1.5 and 7 yr recurrence intervals) caused additional accretion at rapid rates. Suspended-sediment deposition was dominant in the upper deposits, resulting in the formation of natural levees at the channel margins and the deposition of horizontally bedded, fining-upward deposits in the floodplain trough. Overall, channel narrowing and floodplain formation occurred through an evolution from active-channel to floodplain depositional processes. High-resolution dendrogeomorphic analyses provide the ability to specifically correlate the flow record to the onset of narrowing, the establishment of riparian vegetation, the formation of natural levees, and ultimately, the conversion of portions of the active channel to floodplains. ?? 2011 Geological Society of America.

Ultimate Attainment in Late Second Language Acquisition: Phonetic and Grammatical Challenges in Advanced Dutch-English Bilingualism

ERIC Educational Resources Information Center

Schmid, Monika S.; Gilbers, Steven; Nota, Amber

2014-01-01

The present article provides an exploration of ultimate attainment in second language (L2) and its limitations. It is argued that the question of maturational constraints can best be investigated when the reference population is bilingual and exposed on a regular basis to varieties of their first language (L1) that show cross-linguistic influence.…

HIV single staging algorithm: integration and maximization of resources by reducing time between HIV diagnosis and treatment.

PubMed

Bennett, Berry; Hardy, Bonnie; Fordan, Sally; Haddock-Morilla, Lizzette; Rowlinson, Marie-Claire; Crowe, Susanne

2013-12-01

Early HIV diagnosis, linkage and engagement into care are vital to improved personal health outcomes. The initiation of antiretroviral therapy, with retention in care and drug adherence leads to viral load suppression, a significant decrease in HIV transmission rates and ultimately a reduction in HIV incidence rates. In the U.S only 51% of those diagnosed with HIV infection are retained in care and 28% have a suppressed viral load. Reducing the time and number of visits from HIV diagnosis to entry into care, has the potential to engage and treat an increased number of infected individuals. (1) Evaluate the feasibility of conducting HIV-1 supplemental testing concurrently with baseline clinical management testing; (2) to evaluate whether all tests could be completed and reported prior to the traditional posttest counseling appointment; (3) to monitor the return activity for posttest and medical provider appointments. Baseline CD4 and HIV-1 viral load tests were performed concurrently with an HIV-1/2 antibody immunoassay (IA) and HIV-1 Western blot (WB) on 105 individuals with preliminary positive rapid test results. Participating study-sites were located in high-risk, high-morbidity locations: a county jail, a county mobile unit and a county hospital emergency department. Based on the individual's self-reporting statement of "No" to a previous HIV diagnosis and the POC preliminary positive rapid test result, blood specimens were processed via the Single Staging Algorithm. Study site data and medical record review established time intervals between the rapid test and subsequent visits. Of the 105 individuals with HIV-1 preliminary positive rapid test results, 102 were confirmed positive with HIV-1 WB (plus 3rd generation IA repeatedly reactive) and one was confirmed by an HIV-1 WB indeterminate (gp160), HIV-1 Nucleic Acid Amplification Test (NAAT) reactive (an algorithm-defined early infection). The concordance between POC preliminary positive rapid tests and the confirmatory test of the single staging algorithm was 98%. Ninety-six (91%) HIV-1 baseline viral load test results and 82 (78%) CD4/CD8 absolute counts were performed and made available to the provider prior to posttest counseling. The average number of visits for posttest counseling at 14 days was 44.7% (range 37.9-56.5%) with an additional 31.1% (range 22.7-37.9%) returning within 30 days. The average number of clients that returned for the medical provider appointment was 55.4%. A high percentage of HIV-1 clinical management baseline results (78-91%) and 100% confirmatory diagnostic results were completed and reported prior to the traditional posttest counseling appointment. Additional data and analysis is needed to determine the impact of the Single Staging Algorithm on medical provider appointments if the posttest appointment is more than 30 days after the preliminary HIV diagnosis. Copyright © 2013 Elsevier B.V. All rights reserved.

Properties of the subglacial till inferred from supraglacial lake drainage

NASA Astrophysics Data System (ADS)

Neufeld, J. A.; Hewitt, D.

2017-12-01

The buildup and drainage of supraglacial lakes along the margins of the Greenland ice sheet has been previously observed using detailed GPS campaigns which show that rapid drainage events are often preceded by localised, transient uplift followed by rapid, and much broader scale, uplift and flexure associated with the main drainage event [1,2]. Previous models of these events have focused on fracturing during rapid lake drainage from an impermeable bedrock [3] or a thin subglacial film [4]. We present a new model of supraglacial drainage that couples the water flux from rapid lake drainage events to a simplified model of the pore-pressure in a porous, subglacial till along with a simplified model of the flexure of glacial ice. Using a hybrid mathematical model we explore the internal transitions between turbulent and laminar flow throughout the evolving subglacial cavity and porous till. The model predicts that an initially small water flux may locally increase pore-pressure in the till leading to uplift and a local divergence in the ice velocity that may ultimately be responsible for large hydro-fracturing and full-scale drainage events. Furthermore, we find that during rapid drainage while the presence of a porous, subglacial till is crucial for propagation, the manner of spreading is remarkably insensitive to the properties of the subglacial till. This is in stark contrast to the post-drainage relaxation of the pore pressure, and hence sliding velocity, which is highly sensitive to the permeability, compressibility and thickness of subglacial till. We use our model, and the inferred sensitivity to the properties of the subglacial till after the main drainage event, to infer the properties of the subglacial till. The results suggest that a detailed interpretation of supraglacial lake drainage may provide important insights into the hydrology of the subglacial till along the margins of the Greenland ice sheet, and the coupling of pore pressure in subglacial till with the observed ice velocity. 1 Das et al. Science 320, 778-781 (2008) 2 Stevens et al. Nature 522, 73-76 (2015) 3 Tsai & Rice J. Geophys. Res. 115, 1-18 (2010) 4 Adhikari & Tsai J. Geophys. Res. 120, 580-603 (2015)

Feedstock powder processing research needs for additive manufacturing development

DOE PAGES

Anderson, Iver E.; White, Emma M. H.; Dehoff, Ryan

2018-02-01

Additive manufacturing (AM) promises to redesign traditional manufacturing by enabling the ultimate in agility for rapid component design changes in commercial products and for fabricating complex integrated parts. Here, by significantly increasing quality and yield of metallic alloy powders, the pace for design, development, and deployment of the most promising AM approaches can be greatly accelerated, resulting in rapid commercialization of these advanced manufacturing methods. By successful completion of a critical suite of processing research tasks that are intended to greatly enhance gas atomized powder quality and the precision and efficiency of powder production, researchers can help promote continued rapidmore » growth of AM. Finally, other powder-based or spray-based advanced manufacturing methods could also benefit from these research outcomes, promoting the next wave of sustainable manufacturing technologies for conventional and advanced materials.« less

Advances in synthetic peptides reagent discovery

NASA Astrophysics Data System (ADS)

Adams, Bryn L.; Sarkes, Deborah A.; Finch, Amethist S.; Stratis-Cullum, Dimitra N.

2013-05-01

Bacterial display technology offers a number of advantages over competing display technologies (e.g, phage) for the rapid discovery and development of peptides with interaction targeted to materials ranging from biological hazards through inorganic metals. We have previously shown that discovery of synthetic peptide reagents utilizing bacterial display technology is relatively simple and rapid to make laboratory automation possible. This included extensive study of the protective antigen system of Bacillus anthracis, including development of discovery, characterization, and computational biology capabilities for in-silico optimization. Although the benefits towards CBD goals are evident, the impact is far-reaching due to our ability to understand and harness peptide interactions that are ultimately extendable to the hybrid biomaterials of the future. In this paper, we describe advances in peptide discovery including, new target systems (e.g. non-biological materials), advanced library development and clone analysis including integrated reporting.

Degradation of Teflon(trademark) FEP Following Charged Particle Radiation and Rapid Thermal Cycling

NASA Technical Reports Server (NTRS)

Townsend, Jacqueline; Powers, Charles; Viens, Michael; Ayres-Treusdell, Mary; Munoz, Bruno

1999-01-01

During the Second Servicing Mission (SM2) of the Hubble Space Telescope (HST) severe degradation was observed on the outer layer of the thermal control blankets. Astronaut observations and photographs revealed large cracks in the metallized Teflon(trademark) FEP (fluorinated ethylene propylene), the outer layer of the multi-layer insulation (MLI), in many locations around the telescope. In an effort to understand what elements of the space environment might cause such damage, pristine Teflon(trademark) FEP was tested for durability to radiation and thermal cycling. Specimens were subjected to electron and proton fluences comparable to those experienced by HST and were subsequently thermal cycled in a custom-built rapid thermal cycle chamber. Tensile tests of the specimens showed that radiation followed by thermal cycling significantly reduced the ultimate strength and elongation of Teflon(trademark) FEP.

Degradation of Teflon(tm) FEP Following Charged Particle Radiation and Rapid Thermal Cycling

NASA Technical Reports Server (NTRS)

Townsend, Jacqueline A.; Powers, Charles E.; Viens, Michael J.; Ayres-Treusdell, Mary T.; Munoz, Bruno

1998-01-01

During the Second Servicing Mission (SM2) of the Hubble Space Telescope (HST) severe degradation was observed on the outer layer of the thermal control blankets. Astronaut observations and photographs revealed large cracks in the metallized Teflon FEP (fluorinated ethylene propylene), the outer layer of the multi-layer insulation (MLI), in many locations around the telescope. In an effort to understand what elements of the space environment might cause such damage, pristine Teflon' FEP was tested for durability to radiation and thermal cycling. Specimens were subjected to electron and proton fluences comparable to those experienced by HST and were subsequently thermal cycled in a custom-built rapid thermal cycle chamber. Tensile tests of the specimens showed that radiation followed by thermal cycling significantly reduced the ultimate strength and elongation of Teflon FEP.

Degradation of Teflon(tm) FEP Following Charged Particle Radiation and Rapid Thermal Cycling

NASA Technical Reports Server (NTRS)

Townsend, Jacqueline A.; Powers, Charles E.; Viens, Michael J.; Ayres-Treusdell, Mary T.; Munoz, Bruno F.

1998-01-01

During the Second Servicing Mission (SM2) of the Hubble Space Telescope (HST) severe degradation was observed on the outer layer of the thermal control blankets. Astronaut observations and photographs revealed large cracks in the metallized Teflon' FEP (fluorinated ethylene propylene), the outer layer of the multi-layer insulation (MLI), in many locations around the telescope. In an effort to understand what elements of the space environment might cause such damage, pristine Teflon(registered trademark) FEP was tested for durability to radiation and thermal cycling. Specimens were subjected to electron and proton fluences comparable to those experienced by HST and were subsequently thermal cycled in a custom-built rapid thermal cycle chamber. Tensile tests of the specimens showed that radiation followed by thermal cycling significantly reduced the ultimate strength and elongation of Teflon(registered trademark) FEP.

Degradation of Teflon(tm) FEP Following Charged Particle Radiation and Rapid Thermal Cycling

NASA Technical Reports Server (NTRS)

Townsend, Jacqueline; Powers, Charles; Viens, Michael; Ayres-Treusdell, Mary; Munoz, Bruno

1998-01-01

During the Second Servicing Mission (SM2) of the Hubble Space Telescope (HST) severe degradation was observed on the outer layer of the thermal control blankets. Astronaut observations and photographs revealed large cracks in the metallized Teflon(R) FEP (fluorinated ethylene propylene), the outer layer of the multi-layer insulation (MLI), in many locations around the telescope. In an effort to understand what elements of the space environment might cause such damage, pristine Teflon(R) FEP was tested for durability to radiation and thermal cycling. Specimens were subjected to electron and proton fluences comparable to those experienced by HST and were subsequently thermal cycled in a custom-built rapid thermal cycle chamber. Tensile tests of the specimens showed that radiation followed by thermal cycling significantly reduced the ultimate strength and elongation of Teflon(R) FEP.

Feedstock powder processing research needs for additive manufacturing development

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

Anderson, Iver E.; White, Emma M. H.; Dehoff, Ryan

Additive manufacturing (AM) promises to redesign traditional manufacturing by enabling the ultimate in agility for rapid component design changes in commercial products and for fabricating complex integrated parts. Here, by significantly increasing quality and yield of metallic alloy powders, the pace for design, development, and deployment of the most promising AM approaches can be greatly accelerated, resulting in rapid commercialization of these advanced manufacturing methods. By successful completion of a critical suite of processing research tasks that are intended to greatly enhance gas atomized powder quality and the precision and efficiency of powder production, researchers can help promote continued rapidmore » growth of AM. Finally, other powder-based or spray-based advanced manufacturing methods could also benefit from these research outcomes, promoting the next wave of sustainable manufacturing technologies for conventional and advanced materials.« less

Assessing Concentrations and Health Impacts of Air Quality Management Strategies: Framework for Rapid Emissions Scenario and Health impact ESTimation (FRESH-EST)

PubMed Central

Milando, Chad W.; Martenies, Sheena E.; Batterman, Stuart A.

2017-01-01

In air quality management, reducing emissions from pollutant sources often forms the primary response to attaining air quality standards and guidelines. Despite the broad success of air quality management in the US, challenges remain. As examples: allocating emissions reductions among multiple sources is complex and can require many rounds of negotiation; health impacts associated with emissions, the ultimate driver for the standards, are not explicitly assessed; and long dispersion model run-times, which result from the increasing size and complexity of model inputs, limit the number of scenarios that can be evaluated, thus increasing the likelihood of missing an optimal strategy. A new modeling framework, called the "Framework for Rapid Emissions Scenario and Health impact ESTimation" (FRESH-EST), is presented to respond to these challenges. FRESH-EST estimates concentrations and health impacts of alternative emissions scenarios at the urban scale, providing efficient computations from emissions to health impacts at the Census block or other desired spatial scale. In addition, FRESH-EST can optimize emission reductions to meet specified environmental and health constraints, and a convenient user interface and graphical displays are provided to facilitate scenario evaluation. The new framework is demonstrated in an SO2 non-attainment area in southeast Michigan with two optimization strategies: the first minimizes emission reductions needed to achieve a target concentration; the second minimizes concentrations while holding constant the cumulative emissions across local sources (e.g., an emissions floor). The optimized strategies match outcomes in the proposed SO2 State Implementation Plan without the proposed stack parameter modifications or shutdowns. In addition, the lower health impacts estimated for these strategies suggest the potential for FRESH-EST to identify pollution control alternatives for air quality management planning. PMID:27318620

Combination of magnetic dispersive micro solid-phase extraction and supramolecular solvent-based microextraction followed by high-performance liquid chromatography for determination of trace amounts of cholesterol-lowering drugs in complicated matrices.

PubMed

Arghavani-Beydokhti, Somayeh; Rajabi, Maryam; Asghari, Alireza

2017-07-01

A novel, efficient, rapid, simple, sensitive, selective, and environmentally friendly method termed magnetic dispersive micro solid-phase extraction combined with supramolecular solvent-based microextraction (Mdμ-SPE-SSME) followed by high-performance liquid chromatography (HPLC) with UV detection is introduced for the simultaneous microextraction of cholesterol-lowering drugs in complicated matrices. In the first microextraction procedure, using layered double hydroxide (LDH)-coated Fe 3 O 4 magnetic nanoparticles, an efficient sample cleanup is simply and rapidly provided without the need for time-consuming centrifugation and elution steps. In the first step, desorption of the target analytes is easily performed through dissolution of the LDH-coated magnetic nanoparticles containing the target analytes in an acidic solution. In the next step, an emulsification microextraction method based on a supramolecular solvent is used for excellent preconcentration, ultimately resulting in an appropriate determination of the target analytes in real samples. Under the optimal experimental conditions, the Mdμ-SPE-SSME-HPLC-UV detection procedure provides good linearity in the ranges of 1.0-1500 ng mL -1 , 1.5-2000 ng mL -1 , and 2.0-2000 ng mL -1 with coefficients of determination of 0.995 or less, low limits of detection (0.3, 0.5, and 0.5 ng mL -1 ), and good extraction repeatabilities (relative standard deviations below 7.8%, n = 5) in deionized water for rosuvastatin, atorvastatin, and gemfibrozil, respectively. Finally, the proposed method is successfully applied for the determination of the target analytes in complicated matrices. Graphical Abstract Mdμ-SPE-SSME procedure.

Decorin evokes rapid secretion of thrombospondin-1 in basal breast carcinoma cells via inhibition of RhoA/ROCK1

PubMed Central

Neill, Thomas; Jones, Holly R.; Crane-Smith, Zoe; Owens, Rick T.; Schaefer, Liliana; Iozzo, Renato V.

2013-01-01

Pathological neovascularization relies on an imbalance between potent pro-angiogenic agents and equally effective anti-angiogenic cues. Collectively, these factors contribute to an angiogenic niche within the tumor microenvironment. Oncogenic events and hypoxia contribute to augmented levels of angiokines and thereby activate the so-called angiogenic switch to promote aggressive tumorigenic and metastatic growth. Soluble decorin functions as a paracrine pan-inhibitor of receptor tyrosine kinases (RTK), such as Met and EGFR, and thus is capable of suppressing angiogenesis under normoxia. This leads to a non-canonical repression of HIF1-α and VEGFA and a concurrent induction of thrombospondin-1. The substantial induction of endogenous tumor cell-derived thrombospondin-1, a potent anti-angiogenic effector, led us to the discovery of an unexpected secretory phenotype occurring very rapidly (within 5 min) after decorin treatment of the triple-negative basal breast carcinoma cell line, MDA-MB-231. Surprisingly, the effect was not mediated by Met receptor antagonism, as initially hypothesized, but required EGFR signaling to achieve swift and robust thrombospondin-1 release. Furthermore, this effect was ultimately dependent on the prompt degradation of RhoA, via the 26S proteasome, leading to direct inactivation of ROCK1. The latter led to a derepression of thrombospondin-1 secretion. Collectively, these data provide a novel mechanistic role for the ROCK1 kinase in addition of providing the first conclusive evidence of decorin exclusively targeting a RTK to achieve a specific effect. The overall effects of soluble decorin on the tumor microenvironment would cause an immediately-early as well as sustained anti-angiogenic response in vivo. PMID:23350987

Lactase persistence and augmented salivary alpha-amylase gene copy numbers might have been selected by the combined toxic effects of gluten and (food born) pathogens.

PubMed

Pruimboom, Leo; Fox, Tom; Muskiet, Frits A J

2014-03-01

Various positively selected adaptations to new nutrients have been identified. Lactase persistence is among the best known, conferring the ability for drinking milk at post weaning age. An augmented number of amylase gene (AMY1) copies, giving rise to higher salivary amylase activity, has been implicated in the consumption of starch-rich foods. Higher AMY1 copy numbers have been demonstrated in populations with recent histories of starchy-rich diets. It is however questionable whether the resulting polymorphisms have exerted positive selection only by providing easily available sources of macro and micronutrients. Humans have explored new environments more than any other animal. Novel environments challenge the host, but especially its immune system with new climatic conditions, food and especially pathogens. With the advent of the agricultural revolution and the concurrent domestication of cattle came new pathogens. We contend that specific new food ingredients (e.g., gluten) and novel pathogens drove selection for lactase persistence and higher AMY gene copy numbers. Both adaptations provide ample glucose for activating the sodium glucose-dependent co-transporter 1 (SGLT1), which is the principal glucose, sodium and water transporter in the gastro-intestinal tract. Their rapid uptake confers protection against potentially lethal dehydration, hyponatremia and ultimately multiple organ failure. Oral rehydration therapy aims at SGLT1 activity and is the current treatment of choice for chronic diarrhoea and vomiting. We hypothesize that lifelong lactase activity and rapid starch digestion should be looked at as the evolutionary covalent of oral rehydration therapy. Copyright © 2014 Elsevier Ltd. All rights reserved.

Ocean observing systems support operational forecasts for the timing of Maine's lobster fishery

NASA Astrophysics Data System (ADS)

Mills, K.; Hernandez, C.; Pershing, A. J.

2016-02-01

American lobster supports one of the most valuable fisheries in the United States, with a landed value in 2013 exceeding $460M. Although US lobstermen are free to fish throughout the year, the New England climate, lobster biology and fleet dynamics lead to a strong annual cycle with catch rates rising rapidly in early summer and landings peaking in late summer. When this annual cycle is disrupted, it can impact the supply and ultimately the price of lobsters. During the record warm conditions in 2012, the rise in catch rates occurred three weeks ahead of normal. Combined with higher than normal landings from the spring Canadian fishery, the early and high volume landings in 2012 led to a collapse in price that severely stressed the U. S. fishery, especially in Maine where over 85% of the landings occur. Based on this experience, we have been developing seasonal forecasts of the phenology of Maine lobster landings. Using temperatures at 50m from four NERACOOS buoys in the Gulf of Maine, we can reliably forecast the date when the Maine lobster fishery will `turn on' for the year, with prediction accuracy peaking in April. The high-landings period normally starts in July, and the 2-3 month lead-time provides some advance warning to dealers and processors of when their capacity needs to be ready and to fishermen of potential supply chain and market impacts such as we observed in 2012. We are currently working towards finer-scale regional forecasts along the Maine coast that may include other features that will provide information to help the lobster industry adapt to the rapid changes that are underway in the Gulf of Maine.

Characterizing of tissue microstructure with single-detector polarization-sensitive optical coherence tomography

NASA Astrophysics Data System (ADS)

Liu, Bin; Harman, Michelle; Giattina, Susanne; Stamper, Debra L.; Demakis, Charles; Chilek, Mark; Raby, Stephanie; Brezinski, Mark E.

2006-06-01

Assessing tissue birefringence with imaging modality polarization-sensitive optical coherence tomography (PS-OCT) could improve the characterization of in vivo tissue pathology. Among the birefringent components, collagen may provide invaluable clinical information because of its alteration in disorders ranging from myocardial infarction to arthritis. But the features required of clinical imaging modality in these areas usually include the ability to assess the parameter of interest rapidly and without extensive data analysis, the characteristics that single-detector PS-OCT demonstrates. But beyond detecting organized collagen, which has been previously demonstrated and confirmed with the appropriate histological techniques, additional information can potentially be gained with PS-OCT, including collagen type, form versus intrinsic birefringence, the collagen angle, and the presence of multiple birefringence materials. In part I, we apply the simple but powerful fast-Fourier transform (FFT) to both PS-OCT mathematical modeling and in vitro bovine meniscus for improved PS-OCT data analysis. The FFT analysis yields, in a rapid, straightforward, and easily interpreted manner, information on the presence of multiple birefringent materials, distinguishing the true anatomical structure from patterns in image resulting from alterations in the polarization state and identifying the tissue/phantom optical axes. Therefore the use of the FFT analysis of PS-OCT data provides information on tissue composition beyond identifying the presence of organized collagen in real time and directly from the image without extensive mathematical manipulation or data analysis. In part II, Helistat phantoms (collagen type I) are analyzed with the ultimate goal of improved tissue characterization. This study, along with the data in part I, advance the insights gained from PS-OCT images beyond simply determining the presence or absence of birefringence.

Research Technology

NASA Image and Video Library

2004-04-15

Pictured is an artist's concept of the Rocket Based Combined Cycle (RBCC) launch. The RBCC's overall objective is to provide a technology test bed to investigate critical technologies associated with opperational usage of these engines. The program will focus on near term technologies that can be leveraged to ultimately serve as the near term basis for Two Stage to Orbit (TSTO) air breathing propulsions systems and ultimately a Single Stage To Orbit (SSTO) air breathing propulsion system.

Discussion of the Method to Determine the Ultimate Bearing Capacity of Soil Foundation

NASA Astrophysics Data System (ADS)

Du, Peng; Liu, Xiaoling; Zhang, Yangfu

2017-12-01

Combining literature examples, this paper has carried out Contrastive analysis of the theoretical formula method and finite element method about the ultimate bearing capacity of foundation, To verify rationality and superiority of the incremental load method in finite element ABAQUS in solving the bearing capacity of foundation soil. The study can provide certain reference for practical engineering calculation and analysis of foundation bearing capacity.

Phantom energy: dark energy with w <--1 causes a cosmic doomsday.

PubMed

Caldwell, Robert R; Kamionkowski, Marc; Weinberg, Nevin N

2003-08-15

We explore the consequences that follow if the dark energy is phantom energy, in which the sum of the pressure and energy density is negative. The positive phantom-energy density becomes infinite in finite time, overcoming all other forms of matter, such that the gravitational repulsion rapidly brings our brief epoch of cosmic structure to a close. The phantom energy rips apart the Milky Way, solar system, Earth, and ultimately the molecules, atoms, nuclei, and nucleons of which we are composed, before the death of the Universe in a "big rip."

Systems-Level Analysis of Innate Immunity

PubMed Central

Zak, Daniel E.; Tam, Vincent C.; Aderem, Alan

2014-01-01

Systems-level analysis of biological processes strives to comprehensively and quantitatively evaluate the interactions between the relevant molecular components over time, thereby enabling development of models that can be employed to ultimately predict behavior. Rapid development in measurement technologies (omics), when combined with the accessible nature of the cellular constituents themselves, is allowing the field of innate immunity to take significant strides toward this lofty goal. In this review, we survey exciting results derived from systems biology analyses of the immune system, ranging from gene regulatory networks to influenza pathogenesis and systems vaccinology. PMID:24655298

Spontaneous Massive Adrenal Hemorrhage: A Management Dilemma

PubMed Central

Agarwal, Anshuman

2015-01-01

Abstract Adrenal hemorrhage (AH) is a rare but life-threatening condition. Small focal hemorrhage may present subclinically, but massive hemorrhage may lead to rapid cardiovascular collapse and ultimately death if not diagnosed appropriately and treated quickly. Most cases reported in the literature have been treated conservatively. In an event of increasing hemorrhage during conservative management, it may be tricky to intervene surgically because of the hematoma around the gland. Here we describe a case where we managed a large spontaneous AH by a combination of angioembolization and laparoscopic adrenalectomy. PMID:27579389

A world without bacterial meningitis: how genomic epidemiology can inform vaccination strategy.

PubMed

Rodrigues, Charlene M C; Maiden, Martin C J

2018-01-01

Bacterial meningitis remains an important cause of global morbidity and mortality. Although effective vaccinations exist and are being increasingly used worldwide, bacterial diversity threatens their impact and the ultimate goal of eliminating the disease. Through genomic epidemiology, we can appreciate bacterial population structure and its consequences for transmission dynamics, virulence, antimicrobial resistance, and development of new vaccines. Here, we review what we have learned through genomic epidemiological studies, following the rapid implementation of whole genome sequencing that can help to optimise preventative strategies for bacterial meningitis.

Profibrogenic chemokines and viral evolution predict rapid progression of hepatitis C to cirrhosis

PubMed Central

Farci, Patrizia; Wollenberg, Kurt; Diaz, Giacomo; Engle, Ronald E.; Lai, Maria Eliana; Klenerman, Paul; Purcell, Robert H.; Pybus, Oliver G.; Alter, Harvey J.

2012-01-01

Chronic hepatitis C may follow a mild and stable disease course or progress rapidly to cirrhosis and liver-related death. The mechanisms underlying the different rates of disease progression are unknown. Using serial, prospectively collected samples from cases of transfusion-associated hepatitis C, we identified outcome-specific features that predict long-term disease severity. Slowly progressing disease correlated with an early alanine aminotransferase peak and antibody seroconversion, transient control of viremia, and significant induction of IFN-γ and MIP-1β, all indicative of an effective, albeit insufficient, adaptive immune response. By contrast, rapidly progressive disease correlated with persistent and significant elevations of alanine aminotransferase and the profibrogenic chemokine MCP-1 (CCL-2), greater viral diversity and divergence, and a higher rate of synonymous substitution. This study suggests that the long-term course of chronic hepatitis C is determined early in infection and that disease severity is predicted by the evolutionary dynamics of hepatitis C virus and the level of MCP-1, a chemokine that appears critical to the induction of progressive fibrogenesis and, ultimately, the ominous complications of cirrhosis. PMID:22829669

Rapid enhancement of chemical weathering recorded by extremely light seawater lithium isotopes at the Permian–Triassic boundary

PubMed Central

Sun, He; Xiao, Yilin; Zhang, Guijie; Casey, John F.; Shen, Yanan

2018-01-01

Lithium (Li) isotope analyses of sedimentary rocks from the Meishan section in South China reveal extremely light seawater Li isotopic signatures at the Permian–Triassic boundary (PTB), which coincide with the most severe mass extinction in the history of animal life. Using a dynamic seawater lithium box model, we show that the light seawater Li isotopic signatures can be best explained by a significant influx of riverine [Li] with light δ7Li to the ocean realm. The seawater Li isotope excursion started ≥300 Ky before and persisted up to the main extinction event, which is consistent with the eruption time of the Siberian Traps. The eruption of the Siberian Traps exposed an enormous amount of fresh basalt and triggered CO2 release, rapid global warming, and acid rains, which in turn led to a rapid enhancement of continental weathering. The enhanced continental weathering delivered excessive nutrients to the oceans that could lead to marine eutrophication, anoxia, acidification, and ecological perturbation, ultimately resulting in the end-Permian mass extinction. PMID:29581278

Profibrogenic chemokines and viral evolution predict rapid progression of hepatitis C to cirrhosis.

PubMed

Farci, Patrizia; Wollenberg, Kurt; Diaz, Giacomo; Engle, Ronald E; Lai, Maria Eliana; Klenerman, Paul; Purcell, Robert H; Pybus, Oliver G; Alter, Harvey J

2012-09-04

Chronic hepatitis C may follow a mild and stable disease course or progress rapidly to cirrhosis and liver-related death. The mechanisms underlying the different rates of disease progression are unknown. Using serial, prospectively collected samples from cases of transfusion-associated hepatitis C, we identified outcome-specific features that predict long-term disease severity. Slowly progressing disease correlated with an early alanine aminotransferase peak and antibody seroconversion, transient control of viremia, and significant induction of IFN-γ and MIP-1β, all indicative of an effective, albeit insufficient, adaptive immune response. By contrast, rapidly progressive disease correlated with persistent and significant elevations of alanine aminotransferase and the profibrogenic chemokine MCP-1 (CCL-2), greater viral diversity and divergence, and a higher rate of synonymous substitution. This study suggests that the long-term course of chronic hepatitis C is determined early in infection and that disease severity is predicted by the evolutionary dynamics of hepatitis C virus and the level of MCP-1, a chemokine that appears critical to the induction of progressive fibrogenesis and, ultimately, the ominous complications of cirrhosis.

Cannabinoid-induced actomyosin contractility shapes neuronal morphology and growth

PubMed Central

Roland, Alexandre B; Ricobaraza, Ana; Carrel, Damien; Jordan, Benjamin M; Rico, Felix; Simon, Anne; Humbert-Claude, Marie; Ferrier, Jeremy; McFadden, Maureen H; Scheuring, Simon; Lenkei, Zsolt

2014-01-01

Endocannabinoids are recently recognized regulators of brain development, but molecular effectors downstream of type-1 cannabinoid receptor (CB1R)-activation remain incompletely understood. We report atypical coupling of neuronal CB1Rs, after activation by endo- or exocannabinoids such as the marijuana component ∆9-tetrahydrocannabinol, to heterotrimeric G12/G13 proteins that triggers rapid and reversible non-muscle myosin II (NM II) dependent contraction of the actomyosin cytoskeleton, through a Rho-GTPase and Rho-associated kinase (ROCK). This induces rapid neuronal remodeling, such as retraction of neurites and axonal growth cones, elevated neuronal rigidity, and reshaping of somatodendritic morphology. Chronic pharmacological inhibition of NM II prevents cannabinoid-induced reduction of dendritic development in vitro and leads, similarly to blockade of endocannabinoid action, to excessive growth of corticofugal axons into the sub-ventricular zone in vivo. Our results suggest that CB1R can rapidly transform the neuronal cytoskeleton through actomyosin contractility, resulting in cellular remodeling events ultimately able to affect the brain architecture and wiring. DOI: http://dx.doi.org/10.7554/eLife.03159.001 PMID:25225054

Rapid enhancement of chemical weathering recorded by extremely light seawater lithium isotopes at the Permian-Triassic boundary

NASA Astrophysics Data System (ADS)

Sun, He; Xiao, Yilin; Gao, Yongjun; Zhang, Guijie; Casey, John F.; Shen, Yanan

2018-04-01

Lithium (Li) isotope analyses of sedimentary rocks from the Meishan section in South China reveal extremely light seawater Li isotopic signatures at the Permian–Triassic boundary (PTB), which coincide with the most severe mass extinction in the history of animal life. Using a dynamic seawater lithium box model, we show that the light seawater Li isotopic signatures can be best explained by a significant influx of riverine [Li] with light δ7Li to the ocean realm. The seawater Li isotope excursion started ≥300 Ky before and persisted up to the main extinction event, which is consistent with the eruption time of the Siberian Traps. The eruption of the Siberian Traps exposed an enormous amount of fresh basalt and triggered CO2 release, rapid global warming, and acid rains, which in turn led to a rapid enhancement of continental weathering. The enhanced continental weathering delivered excessive nutrients to the oceans that could lead to marine eutrophication, anoxia, acidification, and ecological perturbation, ultimately resulting in the end-Permian mass extinction.

Increases in the amounts of Vibrio spp. in oysters upon addition of exogenous bacteria.

PubMed

Froelich, Brett; Oliver, James

2013-09-01

The bacterial pathogen Vibrio vulnificus is found naturally in brackish coastal waters but can be greatly concentrated by filter-feeding organisms such as shellfish. Numerous experiments in which exogenous V. vulnificus cells are added to oysters in an attempt to measure uptake and depuration have been performed. In nearly all cases, results have shown that laboratory-grown bacteria are rapidly taken up by the oysters but ultimately eliminated, while naturally present Vibrio populations in oysters are resistant to depuration. In this study, oysters harvested during winter months, with low culturable Vibrio concentrations, were incubated in aquaria supplemented with strains of V. vulnificus that were either genotypically or phenotypically distinct from the background bacteria. These exogenous cells were eliminated from the oysters, as previously seen, but other vibrios already inhabiting the oysters responded to the V. vulnificus inoculum by rapidly increasing in number and maintaining a large stable population. The presence of such an oyster-adapted Vibrio population would be expected to prevent colonization by exogenous V. vulnificus cells, thus explaining the rapid depuration of these added bacteria.

The roles of government in improving health care quality and safety.

PubMed

Tang, Ning; Eisenberg, John M; Meyer, Gregg S

2004-01-01

Discussions surrounding the role of government have been and continue to be a favorite American pastime. A framework is provided for understanding the 10 roles that government plays in improving health care quality and safety in the United States. Examples of proposed federal actions to reduce medical errors and enhance patient safety are provided to illustrate the 10 roles: (1) purchase health care, (2) provide health care, (3) ensure access to quality care for vulnerable populations, (4) regulate health care markets, (5) support acquisition of new knowledge, (6) develop and evaluate health technologies and practices, (7) monitor health care quality, (8) inform health care decision makers, (9) develop the health care workforce, and (10) convene stakeholders from across the health care system. Government's responsibility to protect and advance the interests of society includes the delivery of high-quality health care. Because the market alone cannot ensure all Americans access to quality health care, the government must preserve the interests of its citizens by supplementing the market where there are gaps and regulating the market where there is inefficiency or unfairness. The ultimate goal of achieving high quality of care will require strong partnerships among federal, state, and local governments and the private sector. Translating general principles regarding the appropriate role of government into specific actions within a rapidly changing, decentralized delivery system will require the combined efforts of the public and private sectors.

Driving CT developments the last mile: case examples of successful and somewhat less successful translations into clinical practice

NASA Astrophysics Data System (ADS)

Sodickson, Aaron D.

2017-03-01

CT technology has advanced rapidly in recent years, yet not all innovations translate readily into clinical practice. Technology advances must meet certain key requirements to make it into routine use: They must provide a well-defined clinical benefit. They must be easy to use and integrate readily into existing workflows, or better still, further streamline these workflows. These requirements heavily favor fully integrated or automated solutions that remove the human factor and provide a reproducible output independent of operator skill level. Further, to achieve these aims, collaboration with the ultimate end users is needed as early as possible in the development cycle, not just at the point of product testing. Technology innovators are encouraged to engage such collaborators even at early stages of feature or product definition. This manuscript highlights these concepts through exploration of challenging areas in CT imaging in an Emergency Department setting. Technique optimization for pulmonary embolus CT is described as an example of successful integration of multiple advances in radiation dose reduction and imaging speed. The typical workflow of a trauma "pan-scan" (incorporating scans from head through pelvis) is described to highlight workflow challenges and opportunities for improvement. Finally, Dual Energy CT is discussed to highlight the undeniable clinical value of the material characterization it provides, yet also its surprisingly slow integration into routine use beyond early adopters.

Rocket Based Combined Cycle (RBCC) Engine

NASA Technical Reports Server (NTRS)

2004-01-01

Pictured is an artist's concept of the Rocket Based Combined Cycle (RBCC) launch. The RBCC's overall objective is to provide a technology test bed to investigate critical technologies associated with opperational usage of these engines. The program will focus on near term technologies that can be leveraged to ultimately serve as the near term basis for Two Stage to Orbit (TSTO) air breathing propulsions systems and ultimately a Single Stage To Orbit (SSTO) air breathing propulsion system.

Ultimate Gradient Limitation in Niobium Superconducting Accelerating Cavities

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

Checchin, Mattia; Grassellino, Anna; Martinello, Martina

2016-06-01

The present study is addressed to the theoretical description of the ultimate gradient limitation in SRF cavities. Our intent is to exploit experimental data to confirm models which provide feed-backs on how to improve the current state-of-art. New theoretical insight on the cavities limiting factor can be suitable to improve the quench field of N-doped cavities, and therefore to take advantage of high Q 0 at high gradients.

Synthesis of the first radiolabeled 188Re N-heterocyclic carbene complex and initial studies on its potential use in radiopharmaceutical applications

PubMed Central

Wagner, Thomas; Zeglis, Brian M.; Groveman, Sam; Hille, Claudia; Pöthig, Alexander; Francesconi, Lynn C.; Herrmann, Wolfgang A.; Kühn, Fritz E.; Reiner, Thomas

2015-01-01

A novel approach towards the synthesis of radiolabeled organometallic rhenium complexes is presented. We successfully synthesized and analyzed the first 188Re-labeled N-heterocyclic biscarbene complex, trans-dioxobis(1,1′-methylene-bis(3,3′-diisopropylimidazolium-2-ylidene))188rhenium(V) hexafluorophosphate (188Re-4) via transmetalation using an air-stable and moisture-stable silver(I) biscarbene complex. In order to assess the viability of this complex as a potential lead structure for in vivo applications, the stability of the 188Re-NHC complex was tested in physiologically relevant media. Ultimately, our studies illustrate that the complex we synthesized dissociates rapidly and is therefore unsuitable for use in radiopharmaceuticals. However, it is clear that the transmetalation approach we have developed is a rapid, robust, and mild method for the synthesis of new 188Re-labeled carbene complexes. PMID:24889257

Rapid Detection and Identification of a Pathogen's DNA Using Phi29 DNA Polymerase

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

Xu, Y.; Dunn, J.; Gao, S.

2008-10-31

Zoonotic pathogens including those transmitted by insect vectors are some of the most deadly of all infectious diseases known to mankind. A number of these agents have been further weaponized and are widely recognized as being potentially significant biothreat agents. We describe a novel method based on multiply-primed rolling circle in vitro amplification for profiling genomic DNAs to permit rapid, cultivation-free differential detection and identification of circular plasmids in infectious agents. Using Phi29 DNA polymerase and a two-step priming reaction we could reproducibly detect and characterize by DNA sequencing circular DNA from Borrelia burgdorferi B31 in DNA samples containing asmore » little as 25 pg of Borrelia DNA amongst a vast excess of human DNA. This simple technology can ultimately be adapted as a sensitive method to detect specific DNA from both known and unknown pathogens in a wide variety of complex environments.« less

Dysfunction of Rapid Neural Adaptation in Dyslexia.

PubMed

Perrachione, Tyler K; Del Tufo, Stephanie N; Winter, Rebecca; Murtagh, Jack; Cyr, Abigail; Chang, Patricia; Halverson, Kelly; Ghosh, Satrajit S; Christodoulou, Joanna A; Gabrieli, John D E

2016-12-21

Identification of specific neurophysiological dysfunctions resulting in selective reading difficulty (dyslexia) has remained elusive. In addition to impaired reading development, individuals with dyslexia frequently exhibit behavioral deficits in perceptual adaptation. Here, we assessed neurophysiological adaptation to stimulus repetition in adults and children with dyslexia for a wide variety of stimuli, spoken words, written words, visual objects, and faces. For every stimulus type, individuals with dyslexia exhibited significantly diminished neural adaptation compared to controls in stimulus-specific cortical areas. Better reading skills in adults and children with dyslexia were associated with greater repetition-induced neural adaptation. These results highlight a dysfunction of rapid neural adaptation as a core neurophysiological difference in dyslexia that may underlie impaired reading development. Reduced neurophysiological adaptation may relate to prior reports of reduced behavioral adaptation in dyslexia and may reveal a difference in brain functions that ultimately results in a specific reading impairment. Copyright © 2016 Elsevier Inc. All rights reserved.

Rapid Resolution of Grief with IV Infusion of Ketamine: A Unique Phenomenological Experience

PubMed Central

Gowda, Mahesh Ramanna; Srinivasa, Preethi; Kumbar, Prabha S.; Ramalingaiah, Vinay Hosagavi; Muthyalappa, Chandrashekar; Durgoji, Sumit

2016-01-01

Ketamine, a primarily FDA-approved anaesthetic agent is also used as recreational drug. Based on preclinical findings and later the clinical observations it is noted to have rapid antidepressant effect due to its mechanisms related to NMDA antagonism. In spite of established evidence of ketamine being effective in depression with significant role in treatment resistant cases as well, there was absolute dearth of literature regarding its utility in grief-related disorders. In this context we present a case of 28-year-old graduate male who presented to us in complicated grief following death of his wife due to obstetric complications. With the patient and immediate family members consenting for use of ketamine as off-label use, patient had single IV infusion of ketamine following which he had unique phenomenological experience ultimately resolving his grief in few minutes. Through this case we highlight the enormous therapeutic promise of ketamine in complicated grief. PMID:27011405

Recce mission planning

NASA Astrophysics Data System (ADS)

York, Andrew M.

2000-11-01

The ever increasing sophistication of reconnaissance sensors reinforces the importance of timely, accurate, and equally sophisticated mission planning capabilities. Precision targeting and zero-tolerance for collateral damage and civilian casualties, stress the need for accuracy and timeliness. Recent events have highlighted the need for improvement in current planning procedures and systems. Annotating printed maps takes time and does not allow flexibility for rapid changes required in today's conflicts. We must give aircrew the ability to accurately navigate their aircraft to an area of interest, correctly position the sensor to obtain the required sensor coverage, adapt missions as required, and ensure mission success. The growth in automated mission planning system capability and the expansion of those systems to include dedicated and integrated reconnaissance modules, helps to overcome current limitations. Mission planning systems, coupled with extensive integrated visualization capabilities, allow aircrew to not only plan accurately and quickly, but know precisely when they will locate the target and visualize what the sensor will see during its operation. This paper will provide a broad overview of the current capabilities and describe how automated mission planning and visualization systems can improve and enhance the reconnaissance planning process and contribute to mission success. Think about the ultimate objective of the reconnaissance mission as we consider areas that technology can offer improvement. As we briefly review the fundamentals, remember where and how TAC RECCE systems will be used. Try to put yourself in the mindset of those who are on the front lines, working long hours at increasingly demanding tasks, trying to become familiar with new operating areas and equipment, while striving to minimize risk and optimize mission success. Technical advancements that can reduce the TAC RECCE timeline, simplify operations and instill Warfighter confidence, ultimately improve the desired outcome.

Drivers and Dynamics of Global Environmental Change in Southern Africa

NASA Astrophysics Data System (ADS)

Jewitt, Graham; Munishi, Subira; Kunz, Richard; Viola, Paula

2010-05-01

Africa's potential to provide food, fuel, fibre and fodder for future global food and energy security has made it a target for a myriad investors from developed and developing countries alike. In many places, land grants and purchases have led to the establishment of huge monoculture production areas for food, fuel, fibre (maize, sugar cane, jatropha, plantation forestry etc) often preceded by deforestation and large scale utilisation and modification of available water resources. This coupled with the likelihood of rapid urbanisation in Africa over the next forty years and associated impacts linked to the high concentrations of inhabitants utilising and ultimately degrading available natural resources (e.g. wood for charcoal; water quality) have made Africa's ecosystems and people amongst the most vulnerable to global environmental change. Key questions that arise are how available scientific knowledge can best be utilized to reduce this vulnerability, where key gaps in knowledge in understanding the inter-linkages between societal needs and Food- Fibre-Energy-Water supply exist and how to best address the necessary complexity of considering these at different spatial and temporal scales. Drawing on the Ecosystem Goods and Services approach, we present key messages from ongoing research activities in South Africa, Swaziland, Mozambique and Tanzania and report on progress in applying management tools and systems to support decision making in these areas where development needs are critical. We also highlight lessons drawn from situations where unintended consequences have resulted from well meaning or politically expedient initiatives linked to large donor or foreign investment schemes, such as "outgrower" programmes, and where major environmental damage and ultimately the permanent loss of productivity of some landscapes has occurred.

Development Of A Data Assimilation Capability For RAPID

NASA Astrophysics Data System (ADS)

Emery, C. M.; David, C. H.; Turmon, M.; Hobbs, J.; Allen, G. H.; Famiglietti, J. S.

2017-12-01

The global decline of in situ observations associated with the increasing ability to monitor surface water from space motivates the creation of data assimilation algorithms that merge computer models and space-based observations to produce consistent estimates of terrestrial hydrology that fill the spatiotemporal gaps in observations. RAPID is a routing model based on the Muskingum method that is capable of estimating river streamflow over large scales with a relatively short computing time. This model only requires limited inputs: a reach-based river network, and lateral surface and subsurface flow into the rivers. The relatively simple model physics imply that RAPID simulations could be significantly improved by including a data assimilation capability. Here we present the early developments of such data assimilation approach into RAPID. Given the linear and matrix-based structure of the model, we chose to apply a direct Kalman filter, hence allowing for the preservation of high computational speed. We correct the simulated streamflows by assimilating streamflow observations and our early results demonstrate the feasibility of the approach. Additionally, the use of in situ gauges at continental scales motivates the application of our new data assimilation scheme to altimetry measurements from existing (e.g. EnviSat, Jason 2) and upcoming satellite missions (e.g. SWOT), and ultimately apply the scheme globally.

Recent progress on thin-film encapsulation technologies for organic electronic devices

NASA Astrophysics Data System (ADS)

Yu, Duan; Yang, Yong-Qiang; Chen, Zheng; Tao, Ye; Liu, Yun-Fei

2016-03-01

Among the advanced electronic devices, flexible organic electronic devices with rapid development are the most promising technologies to customers and industries. Organic thin films accommodate low-cost fabrication and can exploit diverse molecules in inexpensive plastic light emitting diodes, plastic solar cells, and even plastic lasers. These properties may ultimately enable organic materials for practical applications in industry. However, the stability of organic electronic devices still remains a big challenge, because of the difficulty in fabricating commercial products with flexibility. These organic materials can be protected using substrates and barriers such as glass and metal; however, this results in a rigid device and does not satisfy the applications demanding flexible devices. Plastic substrates and transparent flexible encapsulation barriers are other possible alternatives; however, these offer little protection to oxygen and water, thus rapidly degrading the devices. Thin-film encapsulation (TFE) technology is most effective in preventing water vapor and oxygen permeation into the flexible devices. Because of these (and other) reasons, there has been an intense interest in developing transparent barrier materials with much lower permeabilities, and their market is expected to reach over 550 million by 2025. In this study, the degradation mechanism of organic electronic devices is reviewed. To increase the stability of devices in air, several TFE technologies were applied to provide efficient barrier performance. In this review, the degradation mechanism of organic electronic devices, permeation rate measurement, traditional encapsulation technologies, and TFE technologies are presented.

Bioengineered Systems and Designer Matrices That Recapitulate the Intestinal Stem Cell Niche.

PubMed

Wang, Yuli; Kim, Raehyun; Hinman, Samuel S; Zwarycz, Bailey; Magness, Scott T; Allbritton, Nancy L

2018-03-01

The relationship between intestinal stem cells (ISCs) and the surrounding niche environment is complex and dynamic. Key factors localized at the base of the crypt are necessary to promote ISC self-renewal and proliferation, to ultimately provide a constant stream of differentiated cells to maintain the epithelial barrier. These factors diminish as epithelial cells divide, migrate away from the crypt base, differentiate into the postmitotic lineages, and end their life span in approximately 7 days when they are sloughed into the intestinal lumen. To facilitate the rapid and complex physiology of ISC-driven epithelial renewal, in vivo gradients of growth factors, extracellular matrix, bacterial products, gases, and stiffness are formed along the crypt-villus axis. New bioengineered tools and platforms are available to recapitulate various gradients and support the stereotypical cellular responses associated with these gradients. Many of these technologies have been paired with primary small intestinal and colonic epithelial cells to re-create select aspects of normal physiology or disease states. These biomimetic platforms are becoming increasingly sophisticated with the rapid discovery of new niche factors and gradients. These advancements are contributing to the development of high-fidelity tissue constructs for basic science applications, drug screening, and personalized medicine applications. Here, we discuss the direct and indirect evidence for many of the important gradients found in vivo and their successful application to date in bioengineered in vitro models, including organ-on-chip and microfluidic culture devices.

Combination of neurofilament heavy chain and complement c3 as CSF biomarkers for ALS

PubMed Central

Ganesalingam, Jeban; An, Jiyan; Shaw, Christopher E; Shaw, Gerry; Lacomis, David; Bowser, Robert

2011-01-01

Amyotrophic lateral sclerosis (ALS) is a rapidly progressive and ultimately fatal neurodegenerative disease with an average survival of 3 years from symptom onset. Rapid and conclusive early diagnosis is essential if interventions with disease-modifying therapies are to be successful. Cytoskeletal modification and inflammation are known to occur during the pathogenesis of ALS. We measured levels of cytoskeletal proteins and inflammatory markers in the cerebrospinal fluid (CSF) of ALS, disease controls and healthy subjects. We determined threshold values for each protein that provided the optimal sensitivity and specificity for ALS within a training set, as determined by receiver operating characteristic (ROC) analysis. Interestingly, the optimal assay was a ratio of the levels for phosphorylated neurofilament heavy chain and complement C3 (pNFH/C3). We next applied this assay to a separate test set of CSF samples to verify our results. Overall, the predictive pNFH/C3 ratio identified ALS with 87.3% sensitivity and 94.6% specificity in a total of 71 ALS subjects, 52 disease control subjects and 40 healthy subjects. In addition, the level of CSF pNFH correlated with survival of ALS patients. We also detected increased pNFH in the plasma of ALS patients and observed a correlation between CSF and plasma pNFH levels within the same subjects. These findings support large-scale prospective biomarker studies to determine the clinical utility of diagnostic and prognostic signatures in ALS. PMID:21418221

Ex situ remediation of polluted soils by absorptive polymers, and a comparison of slurry and two-phase partitioning bioreactors for ultimate contaminant degradation.

PubMed

Tomei, M Concetta; Mosca Angelucci, Domenica; Annesini, M Cristina; Daugulis, Andrew J

2013-11-15

The present study has provided a comparison between a conventional ex situ method for the treatment of contaminated soil, a soil slurry bioreactor, with a novel technology in which a contaminant is rapidly and effectively removed from the soil by means of absorptive polymer beads, which are then added to a two-phase partitioning bioreactor (TPPB) for biodegradation of the target molecule. 4-nitrophenol (4NP) was selected as a model contaminant, being representative of a large class of xenobiotics, and the DuPont thermoplastic Hytrel™ 8206 was utilized for its extraction from soil over ranges of soil contamination level, soil moisture content, and polymer:soil ratios. Since the polymers were able to rapidly (up to 77% and 85% in 4 and 24h respectively) and selectively remove the contaminant, the soil retained its nutrient and microflora content, which is in contrast to soil washing which can remove these valuable soil resources. After 4h of reaction time, the TPPB system demonstrated removal efficiency four times higher (77% vs 20%) than the slurry system, with expected concomitant savings in time and energy. A volumetric removal rate of 75 mg4NPh(-1) L(-1) was obtained in the TPPB, significantly greater than the value of 1.7 obtained in the slurry bioreactor. The polymers were readily regenerated for subsequent reuse, demonstrating the versatility of the polymer-based soil treatment technology. Copyright © 2013 Elsevier B.V. All rights reserved.

Reconsidering plant memory: Intersections between stress recovery, RNA turnover, and epigenetics

PubMed Central

Crisp, Peter A.; Ganguly, Diep; Eichten, Steven R.; Borevitz, Justin O.; Pogson, Barry J.

2016-01-01

Plants grow in dynamic environments where they can be exposed to a multitude of stressful factors, all of which affect their development, yield, and, ultimately, reproductive success. Plants are adept at rapidly acclimating to stressful conditions and are able to further fortify their defenses by retaining memories of stress to enable stronger or more rapid responses should an environmental perturbation recur. Indeed, one mechanism that is often evoked regarding environmental memories is epigenetics. Yet, there are relatively few examples of such memories; neither is there a clear understanding of their duration, considering the plethora of stresses in nature. We propose that this field would benefit from investigations into the processes and mechanisms enabling recovery from stress. An understanding of stress recovery could provide fresh insights into when, how, and why environmental memories are created and regulated. Stress memories may be maladaptive, hindering recovery and affecting development and potential yield. In some circumstances, it may be advantageous for plants to learn to forget. Accordingly, the recovery process entails a balancing act between resetting and memory formation. During recovery, RNA metabolism, posttranscriptional gene silencing, and RNA-directed DNA methylation have the potential to play key roles in resetting the epigenome and transcriptome and in altering memory. Exploration of this emerging area of research is becoming ever more tractable with advances in genomics, phenomics, and high-throughput sequencing methodology that will enable unprecedented profiling of high-resolution stress recovery time series experiments and sampling of large natural populations. PMID:26989783

Therapeutic and prevention strategies against human enterovirus 71 infection

PubMed Central

Kok, Chee Choy

2015-01-01

Human enterovirus 71 (HEV71) is the cause of hand, foot and mouth disease and associated neurological complications in children under five years of age. There has been an increase in HEV71 epidemic activity throughout the Asia-Pacific region in the past decade, and it is predicted to replace poliovirus as the extant neurotropic enterovirus of highest global public health significance. To date there is no effective antiviral treatment and no vaccine is available to prevent HEV71 infection. The increase in prevalence, virulence and geographic spread of HEV71 infection over the past decade provides increasing incentive for the development of new therapeutic and prevention strategies against this emerging viral infection. The current review focuses on the potential, advantages and disadvantages of these strategies. Since the explosion of outbreaks leading to large epidemics in China, research in natural therapeutic products has identified several groups of compounds with anti-HEV71 activities. Concurrently, the search for effective synthetic antivirals has produced promising results. Other therapeutic strategies including immunotherapy and the use of oligonucleotides have also been explored. A sound prevention strategy is crucial in order to control the spread of HEV71. To this end the ultimate goal is the rapid development, regulatory approval and widespread implementation of a safe and effective vaccine. The various forms of HEV71 vaccine designs are highlighted in this review. Given the rapid progress of research in this area, eradication of the virus is likely to be achieved. PMID:25964873

Immediate propagation of deglacial environmental change to turbidite systems along the Chilean continental slope

NASA Astrophysics Data System (ADS)

Bernhardt, Anne; Schwanghart, Wolfgang; Hebbeln, Dierk; Stuut, Jan-Berend; Strecker, Manfred

2017-04-01

Understanding how Earth-surface processes respond to past climatic perturbations is crucial for making informed predictions about future impacts of climate change on sediment fluxes. Sedimentary records provide the archives for inferring these processes but their interpretation is compromised by our incomplete understanding of how sediment-routing systems respond to millennial-scale climate cycles. We analyzed seven sediment cores recovered from turbidite depositional sites along the continental slope of the Chile convergent margin. These depositional systems represent the ultimate sedimentary archives before sediment gets recycled during subduction processes and provide relatively continuous and well-dated records. The study sites span a pronounced arid-to-humid gradient with variable topographic gradients and related connectivity of terrestrial and marine landscapes on the continental slope. This setting allowed us to study event-related depositional processes from the Last Glacial Maximum to present in different climatic and geomorphic settings. The turbidite record was quantified in terms of turbidite thickness and frequency. The three studied sites show a steep decline of turbidite deposition during deglaciation. High rates of sea-level rise significantly lag the decline in turbidite deposition by 3-6.5 kyrs. However, comparison to paleoclimate proxies shows that this spatio-temporal sedimentary pattern mirrors the deglacial humidity decrease and concomitant warming with little to no lag times. Our results suggest that the deglacial humidity decrease resulted in a decrease of fluvial sediment supply, which propagated rapidly through the highly connected systems into the marine sink in north-central Chile. In contrast, in south-central Chilean systems, connectivity between the Andean erosional zone and the fluvial transfer zone probably decreased abruptly by the deglaciation of piedmont lakes, resulting in a significant and rapid decrease of sediment supply to the ocean. Additionally, reduced moisture supply may have also contributed to the rapid decline of turbidite deposition. These different causes result in similar depositional patterns in the marine sinks. We conclude that turbiditic strata can act as reliable recorders of climate change across a wide range of climatic zones and geomorphic conditions. However, the underlying causes for similar signal manifestations in the sinks may differ, ranging from maintained high system connectivity to abrupt connectivity loss.

Antimicrobial stewardship – can we afford to do without it?

PubMed Central

Aryee, Anna; Price, Nicholas

2015-01-01

Antimicrobial resistance (AMR) is a rapidly developing and alarming global threat which has been highlighted by national governments and public health bodies including the World Health Organization. The spectre of a ‘post-antibiotic era’ is a real possibility unless curtailing the development and spread of these organisms is given high priority. Numerous studies have shown that AMR is associated with worse outcomes for patients and higher healthcare costs. While clinical data from low and middle income countries is lacking, there is increasing evidence that the problem in these areas is as great, or even greater, than in high income nations. Of the many drivers behind the development of AMR, the most significant is selection pressure caused by antibiotic use. Antimicrobial stewardship programmes are a set of interventions that aim to ensure the judicious use of antimicrobials by preventing their unnecessary use, and by providing targeted and limited therapy in situations where they are warranted. The ultimate goal of these programmes is to provide effective antimicrobial therapy whilst safeguarding their effectiveness for future generations. Whilst they do require an initial investment, they have been shown to be an effective way of controlling antimicrobial use, and have been associated with improved patient outcomes and reduced healthcare costs. PMID:24803175

Using Automatic Control Approach In Detention Storages For Storm Water Management In An Urban Watershed

NASA Astrophysics Data System (ADS)

Goyal, A.; Yadav, H.; Tyagi, H.; Gosain, A. K.; Khosa, R.

2017-12-01

Increased imperviousness due to rapid urbanization have changed the urban hydrological cycle. As watersheds are urbanized, infiltration and groundwater recharge have decreased, surface runoff hydrograph shows higher peak indicating large volumes of surface runoff in lesser time durations. The ultimate panacea is to reduce the peak of hydrograph or increase the retention time of surface flow. SWMM is widely used hydrologic and hydraulic software which helps to simulate the urban storm water management with the provision to apply different techniques to prevent flooding. A model was setup to simulate the surface runoff and channel flow in a small urban catchment. It provides the temporal and spatial information of flooding in a catchment. Incorporating the detention storages in the drainage network helps achieve reduced flooding. Detention storages provided with predefined algorithms were for controlling the pluvial flooding in urban watersheds. The algorithm based on control theory, automated the functioning of detention storages ensuring that the storages become active on occurrence of flood in the storm water drains and shuts down when flooding is over. Detention storages can be implemented either at source or at several downstream control points. The proposed piece of work helps to mitigate the wastage of rainfall water, achieve desirable groundwater and attain a controlled urban storm water management system.

Optimization of genome editing through CRISPR-Cas9 engineering.

PubMed

Zhang, Jian-Hua; Adikaram, Poorni; Pandey, Mritunjay; Genis, Allison; Simonds, William F

2016-04-01

CRISPR (Clustered Regularly-Interspaced Short Palindromic Repeats)-Cas9 (CRISPR associated protein 9) has rapidly become the most promising genome editing tool with great potential to revolutionize medicine. Through guidance of a 20 nucleotide RNA (gRNA), CRISPR-Cas9 finds and cuts target protospacer DNA precisely 3 base pairs upstream of a PAM (Protospacer Adjacent Motif). The broken DNA ends are repaired by either NHEJ (Non-Homologous End Joining) resulting in small indels, or by HDR (Homology Directed Repair) for precise gene or nucleotide replacement. Theoretically, CRISPR-Cas9 could be used to modify any genomic sequences, thereby providing a simple, easy, and cost effective means of genome wide gene editing. However, the off-target activity of CRISPR-Cas9 that cuts DNA sites with imperfect matches with gRNA have been of significant concern because clinical applications require 100% accuracy. Additionally, CRISPR-Cas9 has unpredictable efficiency among different DNA target sites and the PAM requirements greatly restrict its genome editing frequency. A large number of efforts have been made to address these impeding issues, but much more is needed to fully realize the medical potential of CRISPR-Cas9. In this article, we summarize the existing problems and current advances of the CRISPR-Cas9 technology and provide perspectives for the ultimate perfection of Cas9-mediated genome editing.

Traversing the mountaintop: world fossil fuel production to 2050.

PubMed

Nehring, Richard

2009-10-27

During the past century, fossil fuels--petroleum liquids, natural gas and coal--were the dominant source of world energy production. From 1950 to 2005, fossil fuels provided 85-93% of all energy production. All fossil fuels grew substantially during this period, their combined growth exceeding the increase in world population. This growth, however, was irregular, providing for rapidly growing per capita production from 1950 to 1980, stable per capita production from 1980 to 2000 and rising per capita production again after 2000. During the past half century, growth in fossil fuel production was essentially limited by energy demand. During the next half century, fossil fuel production will be limited primarily by the amount and characteristics of remaining fossil fuel resources. Three possible scenarios--low, medium and high--are developed for the production of each of the fossil fuels to 2050. These scenarios differ primarily by the amount of ultimate resources estimated for each fossil fuel. Total fossil fuel production will continue to grow, but only slowly for the next 15-30 years. The subsequent peak plateau will last for 10-15 years. These production peaks are robust; none of the fossil fuels, even with highly optimistic resource estimates, is projected to keep growing beyond 2050. World fossil fuel production per capita will thus begin an irreversible decline between 2020 and 2030.

Harnessing person-generated health data to accelerate patient-centered outcomes research: the Crohn's and Colitis Foundation of America PCORnet Patient Powered Research Network (CCFA Partners).

PubMed

Chung, Arlene E; Sandler, Robert S; Long, Millie D; Ahrens, Sean; Burris, Jessica L; Martin, Christopher F; Anton, Kristen; Robb, Amber; Caruso, Thomas P; Jaeger, Elizabeth L; Chen, Wenli; Clark, Marshall; Myers, Kelly; Dobes, Angela; Kappelman, Michael D

2016-05-01

The Crohn's and Colitis Foundation of America Partners Patient-Powered Research Network (PPRN) seeks to advance and accelerate comparative effectiveness and translational research in inflammatory bowel diseases (IBDs). Our IBD-focused PCORnet PPRN has been designed to overcome the major obstacles that have limited patient-centered outcomes research in IBD by providing the technical infrastructure, patient governance, and patient-driven functionality needed to: 1) identify, prioritize, and undertake a patient-centered research agenda through sharing person-generated health data; 2) develop and test patient and provider-focused tools that utilize individual patient data to improve health behaviors and inform health care decisions and, ultimately, outcomes; and 3) rapidly disseminate new knowledge to patients, enabling them to improve their health. The Crohn's and Colitis Foundation of America Partners PPRN has fostered the development of a community of citizen scientists in IBD; created a portal that will recruit, retain, and engage members and encourage partnerships with external scientists; and produced an efficient infrastructure for identifying, screening, and contacting network members for participation in research. © The Author 2016. Published by Oxford University Press on behalf of the American Medical Informatics Association. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

Repurposing the Saccharomyces cerevisiae peroxisome for compartmentalizing multi-enzyme pathways

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

DeLoache, William; Russ, Zachary; Samson, Jennifer

The peroxisome of Saccharomyces cerevisiae was targeted for repurposing in order to create a synthetic organelle that provides a generalizable compartment for engineered metabolic pathways. Compartmentalization of enzymes into organelles is a promising strategy for limiting metabolic crosstalk, improving pathway efficiency, and ultimately modifying the chemical environment to be distinct from that of the cytoplasm. We focused on the Saccharomyces cerevisiae peroxisome, as this organelle is not required for viability when grown on conventional media. We identified an enhanced peroxisomal targeting signal type 1 (PTS1) for rapidly importing non-native cargo proteins. Additionally, we performed the first systematic in vivo measurementsmore » of nonspecific metabolite permeability across the peroxisomal membrane using a polymer exclusion assay and characterized the size dependency of metabolite trafficking. Finally, we applied these new insights to compartmentalize a two-enzyme pathway in the peroxisome and characterize the expression regimes where compartmentalization leads to improved product titer. This work builds a foundation for using the peroxisome as a synthetic organelle, highlighting both promise and future challenges on the way to realizing this goal.« less

Raman fiberoptic probe for monitoring human tissue engineered oral mucosa constructs

NASA Astrophysics Data System (ADS)

Khmaladze, Alexander; Kuo, Shiuhyang; Okagbare, Paul; Marcelo, Cynthia L.; Feinberg, Stephen E.; Morris, Michael D.

2013-02-01

In oral and maxillofacial surgery, there is a need for tissue engineered constructs for dental implants, reconstructions due to trauma, oral cancer or congenital defects. A non-invasive quality monitoring of the fabrication of tissue engineered constructs during their production and implantation is a required component of any successful tissue engineering technique. We demonstrate the design and application of a Raman spectroscopic probe for rapid and noninvasive monitoring of Ex Vivo Produced Oral Mucosa Equivalent constructs (EVPOMEs). We conducted in vivo studies to identify Raman spectroscopic failure indicators for EVPOMEs (already developed in vitro), and found that Raman spectra of EVPOMEs exposed to thermal stress showed correlation of the band height ratio of CH2 deformation to phenylalanine ring breathing modes, providing a Raman metric to distinguish between viable and nonviable constructs. This is the first step towards the ultimate goal to design a stand-alone system, which will be usable in a clinical setting, as the data processing and analysis will be performed with minimal user intervention, based on already established and tested Raman spectroscopic indicators for EVPOMEs.

Flight Testing of a Low Cost De-Orbiting Device for Small Satellites

NASA Technical Reports Server (NTRS)

Turse, Dana; Keller, Phil; Taylor, Robert; Reavis, Mark; Tupper, Mike; Koehler, Chris

2014-01-01

Use of small and very small spacecraft is rapidly becoming more common. Methods to intentionally deorbit these spacecraft at the end of useful satellite life are required. A family of mass efficient Roll-Out De- Orbiting devices (RODEO"TM") was developed by Composite Technology Development, Inc. (CTD). RODEO"TM" consists of lightweight film attached to a simple, ultra-lightweight, roll-out composite boom structure. This system is rolled to stow within a lightweight launch canister, allowing easy integration to the small satellite bus. The device is released at the end of useful lifetime and the RODEO"TM" composite boom unrolls the drag sail in a matter of seconds. This dramatically increases the deployed surface area, resulting in the higher aerodynamic drag that significantly reduces the time until reentry. A RODEO"TM" flight demonstration was recently conducted as part of the Colorado Space Grant Consortium's (COSGC) RocketSat-8 program, a program to provide students hands-on experience in developing experiments for space flight. The experiment was ultimately a success and RODEO (trademark) is now ready for future CubeSat missions.

Galaxy Interactions and AGN-triggering to z~1: an unprecedented new view from the Hyper Suprime-Cam Survey

NASA Astrophysics Data System (ADS)

Goulding, Andy D.; Greene, Jenny E.; Bezanson, Rachel; Greco, Johnny; Johnson, Sean; Medezinski, Elinor; Strauss, Michael A.; HSC Collaboration

2017-01-01

Collisions and interactions between galaxies are thought to be pivotal stages in their formation and evolution, causing the rapid production of new stars, and may also serve as a mechanism for fueling supermassive black holes (BH). Harnessing the exquisite spatial resolution (0.3—0.7 arcsec) afforded by the new 1400 deg2 Hyper Suprime-Cam (HSC) Survey, we present our new constraints on the importance of major and minor mergers in growing BHs throughout the last ~7 Gyrs. Utilizing the first ~170 deg2 of the HSC Survey, and mid-infrared observations in the WISE All-Sky survey, we have robustly selected active galactic nuclei (AGN), starburst, and mass-matched control galaxy samples, totaling ~120,000 spectroscopically confirmed systems at i<22 mag. We identify galaxy interactions using a novel machine-learning technique, and use these data to map the growth of BHs as a function of interaction-stage, redshift and AGN luminosity, ultimately providing the necessary large-number statistics required to investigate merger—AGN triggering in the context of galaxy evolution out to z~1.

Global Change Data Center: Mission, Organization, Major Activities, and 2001 Highlights

NASA Technical Reports Server (NTRS)

Wharton, Stephen W. (Technical Monitor)

2002-01-01

Rapid efficient access to Earth sciences data is fundamental to the Nation's efforts to understand the effects of global environmental changes and their implications for public policy. It becomes a bigger challenge in the future when data volumes increase further and missions with constellations of satellites start to appear. Demands on data storage, data access, network throughput, processing power, and database and information management are increased by orders of magnitude, while budgets remain constant and even shrink. The Global Change Data Center's (GCDC) mission is to provide systems, data products, and information management services to maximize the availability and utility of NASA's Earth science data. The specific objectives are (1) support Earth science missions be developing and operating systems to generate, archive, and distribute data products and information; (2) develop innovative information systems for processing, archiving, accessing, visualizing, and communicating Earth science data; and (3) develop value-added products and services to promote broader utilization of NASA Earth Sciences Enterprise (ESE) data and information. The ultimate product of GCDC activities is access to data and information to support research, education, and public policy.

International standards in mitigating trade risks.

PubMed

Thiermann, A B

2011-04-01

This paper describes the role of the World Organisation for Animal Health (OIE), as a science-based and democratic standard-setting organisation that provides guidance on preventing the spread of animal diseases, including zoonoses, in international trade. The World Trade Organization is identified as the international institution with the legal power to encourage adherence to international standards and mediate trade disputes. The importance of assuring good governance and the credibility of national Veterinary Services through a process of official certification is identified as an essential component in the safety of trade. Private-public partnerships and the evolution of responsibilities are also identified as essential for the implementation of health guarantees such as compartmentalisation. The rapid emergence of private standards is described as a potential complement to the implementation of sanitary standards, as long as they are applied globally and in support of the OIE standards. Ultimately, the biggest challenge is for the international community to create the incentives and generate the political will for fair trade and for the universal recognition and application of the established international sanitary standards.

Advanced Neuroimaging in Traumatic Brain Injury

PubMed Central

Edlow, Brian L.; Wu, Ona

2013-01-01

Advances in structural and functional neuroimaging have occurred at a rapid pace over the past two decades. Novel techniques for measuring cerebral blood flow, metabolism, white matter connectivity, and neural network activation have great potential to improve the accuracy of diagnosis and prognosis for patients with traumatic brain injury (TBI), while also providing biomarkers to guide the development of new therapies. Several of these advanced imaging modalities are currently being implemented into clinical practice, whereas others require further development and validation. Ultimately, for advanced neuroimaging techniques to reach their full potential and improve clinical care for the many civilians and military personnel affected by TBI, it is critical for clinicians to understand the applications and methodological limitations of each technique. In this review, we examine recent advances in structural and functional neuroimaging and the potential applications of these techniques to the clinical care of patients with TBI. We also discuss pitfalls and confounders that should be considered when interpreting data from each technique. Finally, given the vast amounts of advanced imaging data that will soon be available to clinicians, we discuss strategies for optimizing data integration, visualization and interpretation. PMID:23361483

The Apache OODT Project: An Introduction

NASA Astrophysics Data System (ADS)

Mattmann, C. A.; Crichton, D. J.; Hughes, J. S.; Ramirez, P.; Goodale, C. E.; Hart, A. F.

2012-12-01

Apache OODT is a science data system framework, borne over the past decade, with 100s of FTEs of investment, tens of sponsoring agencies (NASA, NIH/NCI, DoD, NSF, universities, etc.), and hundreds of projects and science missions that it powers everyday to their success. At its core, Apache OODT carries with it two fundamental classes of software services and components: those that deal with information integration from existing science data repositories and archives, that themselves have already-in-use business processes and models for populating those archives. Information integration allows search, retrieval, and dissemination across these heterogeneous systems, and ultimately rapid, interactive data access, and retrieval. The other suite of services and components within Apache OODT handle population and processing of those data repositories and archives. Workflows, resource management, crawling, remote data retrieval, curation and ingestion, along with science data algorithm integration all are part of these Apache OODT software elements. In this talk, I will provide an overview of the use of Apache OODT to unlock and populate information from science data repositories and archives. We'll cover the basics, along with some advanced use cases and success stories.

Turbulent Kinetic Energy in the Energy Balance of a Solar Flare

NASA Astrophysics Data System (ADS)

Kontar, E. P.; Perez, J. E.; Harra, L. K.; Kuznetsov, A. A.; Emslie, A. G.; Jeffrey, N. L. S.; Bian, N. H.; Dennis, B. R.

2017-04-01

The energy released in solar flares derives from a reconfiguration of magnetic fields to a lower energy state, and is manifested in several forms, including bulk kinetic energy of the coronal mass ejection, acceleration of electrons and ions, and enhanced thermal energy that is ultimately radiated away across the electromagnetic spectrum from optical to x rays. Using an unprecedented set of coordinated observations, from a suite of instruments, we here report on a hitherto largely overlooked energy component—the kinetic energy associated with small-scale turbulent mass motions. We show that the spatial location of, and timing of the peak in, turbulent kinetic energy together provide persuasive evidence that turbulent energy may play a key role in the transfer of energy in solar flares. Although the kinetic energy of turbulent motions accounts, at any given time, for only ˜(0.5 - 1 )% of the energy released, its relatively rapid (˜1 - 10 s ) energization and dissipation causes the associated throughput of energy (i.e., power) to rival that of major components of the released energy in solar flares, and thus presumably in other astrophysical acceleration sites.

Turbulent Kinetic Energy in the Energy Balance of a Solar Flare.

PubMed

Kontar, E P; Perez, J E; Harra, L K; Kuznetsov, A A; Emslie, A G; Jeffrey, N L S; Bian, N H; Dennis, B R

2017-04-14

The energy released in solar flares derives from a reconfiguration of magnetic fields to a lower energy state, and is manifested in several forms, including bulk kinetic energy of the coronal mass ejection, acceleration of electrons and ions, and enhanced thermal energy that is ultimately radiated away across the electromagnetic spectrum from optical to x rays. Using an unprecedented set of coordinated observations, from a suite of instruments, we here report on a hitherto largely overlooked energy component-the kinetic energy associated with small-scale turbulent mass motions. We show that the spatial location of, and timing of the peak in, turbulent kinetic energy together provide persuasive evidence that turbulent energy may play a key role in the transfer of energy in solar flares. Although the kinetic energy of turbulent motions accounts, at any given time, for only ∼(0.5-1)% of the energy released, its relatively rapid (∼1-10  s) energization and dissipation causes the associated throughput of energy (i.e., power) to rival that of major components of the released energy in solar flares, and thus presumably in other astrophysical acceleration sites.

Nuclear Forensics and Attribution: A National Laboratory Perspective

NASA Astrophysics Data System (ADS)

Hall, Howard L.

2008-04-01

Current capabilities in technical nuclear forensics - the extraction of information from nuclear and/or radiological materials to support the attribution of a nuclear incident to material sources, transit routes, and ultimately perpetrator identity - derive largely from three sources: nuclear weapons testing and surveillance programs of the Cold War, advances in analytical chemistry and materials characterization techniques, and abilities to perform ``conventional'' forensics (e.g., fingerprints) on radiologically contaminated items. Leveraging that scientific infrastructure has provided a baseline capability to the nation, but we are only beginning to explore the scientific challenges that stand between today's capabilities and tomorrow's requirements. These scientific challenges include radically rethinking radioanalytical chemistry approaches, developing rapidly deployable sampling and analysis systems for field applications, and improving analytical instrumentation. Coupled with the ability to measure a signature faster or more exquisitely, we must also develop the ability to interpret those signatures for meaning. This requires understanding of the physics and chemistry of nuclear materials processes well beyond our current level - especially since we are unlikely to ever have direct access to all potential sources of nuclear threat materials.

Identification of Abiotic Stress Protein Biomarkers by Proteomic Screening of Crop Cultivar Diversity

PubMed Central

Barkla, Bronwyn J.

2016-01-01

Modern day agriculture practice is narrowing the genetic diversity in our food supply. This may compromise the ability to obtain high yield under extreme climactic conditions, threatening food security for a rapidly growing world population. To identify genetic diversity, tolerance mechanisms of cultivars, landraces and wild relatives of major crops can be identified and ultimately exploited for yield improvement. Quantitative proteomics allows for the identification of proteins that may contribute to tolerance mechanisms by directly comparing protein abundance under stress conditions between genotypes differing in their stress responses. In this review, a summary is provided of the data accumulated from quantitative proteomic comparisons of crop genotypes/cultivars which present different stress tolerance responses when exposed to various abiotic stress conditions, including drought, salinity, high/low temperature, nutrient deficiency and UV-B irradiation. This field of research aims to identify molecular features that can be developed as biomarkers for crop improvement, however without accurate phenotyping, careful experimental design, statistical robustness and appropriate biomarker validation and verification it will be challenging to deliver what is promised. PMID:28248236

Identification of Abiotic Stress Protein Biomarkers by Proteomic Screening of Crop Cultivar Diversity.

PubMed

Barkla, Bronwyn J

2016-09-08

Modern day agriculture practice is narrowing the genetic diversity in our food supply. This may compromise the ability to obtain high yield under extreme climactic conditions, threatening food security for a rapidly growing world population. To identify genetic diversity, tolerance mechanisms of cultivars, landraces and wild relatives of major crops can be identified and ultimately exploited for yield improvement. Quantitative proteomics allows for the identification of proteins that may contribute to tolerance mechanisms by directly comparing protein abundance under stress conditions between genotypes differing in their stress responses. In this review, a summary is provided of the data accumulated from quantitative proteomic comparisons of crop genotypes/cultivars which present different stress tolerance responses when exposed to various abiotic stress conditions, including drought, salinity, high/low temperature, nutrient deficiency and UV-B irradiation. This field of research aims to identify molecular features that can be developed as biomarkers for crop improvement, however without accurate phenotyping, careful experimental design, statistical robustness and appropriate biomarker validation and verification it will be challenging to deliver what is promised.

Health conditions and health-policy innovations in Brazil: the way forward.

PubMed

Victora, Cesar G; Barreto, Mauricio L; do Carmo Leal, Maria; Monteiro, Carlos A; Schmidt, Maria Ines; Paim, Jairnilson; Bastos, Francisco I; Almeida, Celia; Bahia, Ligia; Travassos, Claudia; Reichenheim, Michael; Barros, Fernando C

2011-06-11

Brazil is a large complex country that is undergoing rapid economic, social, and environmental change. In this Series of six articles, we have reported important improvements in health status and life expectancy, which can be ascribed largely to progress in social determinants of health and to implementation of a comprehensive national health system with strong social participation. Many challenges remain, however. Socioeconomic and regional disparities are still unacceptably large, reflecting the fact that much progress is still needed to improve basic living conditions for a large proportion of the population. New health problems arise as a result of urbanisation and social and environmental change, and some old health issues remain unabated. Administration of a complex, decentralised public-health system, in which a large share of services is contracted out to the private sector, together with many private insurance providers, inevitably causes conflict and contradiction. The challenge is ultimately political, and we conclude with a call for action that requires continuous engagement by Brazilian society as a whole in securing the right to health for all Brazilian people. Copyright © 2011 Elsevier Ltd. All rights reserved.

Guidelines and recommendations on yeast cell death nomenclature

PubMed Central

Carmona-Gutierrez, Didac; Bauer, Maria Anna; Zimmermann, Andreas; Aguilera, Andrés; Austriaco, Nicanor; Ayscough, Kathryn; Balzan, Rena; Bar-Nun, Shoshana; Barrientos, Antonio; Belenky, Peter; Blondel, Marc; Braun, Ralf J.; Breitenbach, Michael; Burhans, William C.; Büttner, Sabrina; Cavalieri, Duccio; Chang, Michael; Cooper, Katrina F.; Côrte-Real, Manuela; Costa, Vítor; Cullin, Christophe; Dawes, Ian; Dengjel, Jörn; Dickman, Martin B.; Eisenberg, Tobias; Fahrenkrog, Birthe; Fasel, Nicolas; Fröhlich, Kai-Uwe; Gargouri, Ali; Giannattasio, Sergio; Goffrini, Paola; Gourlay, Campbell W.; Grant, Chris M.; Greenwood, Michael T.; Guaragnella, Nicoletta; Heger, Thomas; Heinisch, Jürgen; Herker, Eva; Herrmann, Johannes M.; Hofer, Sebastian; Jiménez-Ruiz, Antonio; Jungwirth, Helmut; Kainz, Katharina; Kontoyiannis, Dimitrios P.; Ludovico, Paula; Manon, Stéphen; Martegani, Enzo; Mazzoni, Cristina; Megeney, Lynn A.; Meisinger, Chris; Nielsen, Jens; Nyström, Thomas; Osiewacz, Heinz D.; Outeiro, Tiago F.; Park, Hay-Oak; Pendl, Tobias; Petranovic, Dina; Picot, Stephane; Polčic, Peter; Powers, Ted; Ramsdale, Mark; Rinnerthaler, Mark; Rockenfeller, Patrick; Ruckenstuhl, Christoph; Schaffrath, Raffael; Segovia, Maria; Severin, Fedor F.; Sharon, Amir; Sigrist, Stephan J.; Sommer-Ruck, Cornelia; Sousa, Maria João; Thevelein, Johan M.; Thevissen, Karin; Titorenko, Vladimir; Toledano, Michel B.; Tuite, Mick; Vögtle, F.-Nora; Westermann, Benedikt; Winderickx, Joris; Wissing, Silke; Wölfl, Stefan; Zhang, Zhaojie J.; Zhao, Richard Y.; Zhou, Bing; Galluzzi, Lorenzo; Kroemer, Guido; Madeo, Frank

2018-01-01

Elucidating the biology of yeast in its full complexity has major implications for science, medicine and industry. One of the most critical processes determining yeast life and physiology is cellular demise. However, the investigation of yeast cell death is a relatively young field, and a widely accepted set of concepts and terms is still missing. Here, we propose unified criteria for the definition of accidental, regulated, and programmed forms of cell death in yeast based on a series of morphological and biochemical criteria. Specifically, we provide consensus guidelines on the differential definition of terms including apoptosis, regulated necrosis, and autophagic cell death, as we refer to additional cell death routines that are relevant for the biology of (at least some species of) yeast. As this area of investigation advances rapidly, changes and extensions to this set of recommendations will be implemented in the years to come. Nonetheless, we strongly encourage the authors, reviewers and editors of scientific articles to adopt these collective standards in order to establish an accurate framework for yeast cell death research and, ultimately, to accelerate the progress of this vibrant field of research. PMID:29354647

Research Technology (ASTP) Rocket Based Combined Cycle (RBCC) Engine

NASA Technical Reports Server (NTRS)

2004-01-01

Pictured is an artist's concept of the Rocket Based Combined Cycle (RBCC) launch. The RBCC's overall objective is to provide a technology test bed to investigate critical technologies associated with opperational usage of these engines. The program will focus on near term technologies that can be leveraged to ultimately serve as the near term basis for Two Stage to Orbit (TSTO) air breathing propulsions systems and ultimately a Single Stage To Orbit (SSTO) air breathing propulsion system.

Vaccine production, distribution, access and uptake

PubMed Central

Smith, Jon; Lipsitch, Marc; Almond, Jeffrey W.

2011-01-01

Making human vaccines available on a global scale requires the use of complex production methods, meticulous quality control and reliable distribution channels that ensure the products are potent and effective at their point of use. The technologies involved in manufacturing different types of vaccines may strongly influence vaccine cost, ease of industrial scale-up, stability and ultimately world-wide availability. Manufacturing complexity is compounded by the need for different formulations for different countries and age groups. Reliable vaccine production in appropriate quantities and at affordable prices is the cornerstone of developing global vaccination policies. However, ensuring optimal access and uptake also requires strong partnerships between private manufacturers, regulatory authorities and national and international public health services. For vaccines whose supplies are limited, either due to rapidly emerging diseases or longer-term mismatch of supply and demand, prioritizing target groups can increase vaccine impact. Focusing on influenza vaccines as an example that well illustrates many of the relevant points, this article considers current production, distribution, access and other factors that ultimately impact on vaccine uptake and population-level effectiveness. PMID:21664680

Engineering microbial chemical factories to produce renewable "biomonomers".

PubMed

Adkins, Jake; Pugh, Shawn; McKenna, Rebekah; Nielsen, David R

2012-01-01

By applying metabolic engineering tools and strategies to engineer synthetic enzyme pathways, the number and diversity of commodity and specialty chemicals that can be derived directly from renewable feedstocks is rapidly and continually expanding. This of course includes a number of monomer building-block chemicals that can be used to produce replacements to many conventional plastic materials. This review aims to highlight numerous recent and important advancements in the microbial production of these so-called "biomonomers." Relative to naturally-occurring renewable bioplastics, biomonomers offer several important advantages, including improved control over the final polymer structure and purity, the ability to synthesize non-natural copolymers, and allowing products to be excreted from cells which ultimately streamlines downstream recovery and purification. To highlight these features, a handful of biomonomers have been selected as illustrative examples of recent works, including polyamide monomers, styrenic vinyls, hydroxyacids, and diols. Where appropriate, examples of their industrial penetration to date and end-product uses are also highlighted. Novel biomonomers such as these are ultimately paving the way toward new classes of renewable bioplastics that possess a broader diversity of properties than ever before possible.

Predictive Models of Cognitive Outcomes of Developmental Insults

NASA Astrophysics Data System (ADS)

Chan, Yupo; Bouaynaya, Nidhal; Chowdhury, Parimal; Leszczynska, Danuta; Patterson, Tucker A.; Tarasenko, Olga

2010-04-01

Representatives of Arkansas medical, research and educational institutions have gathered over the past four years to discuss the relationship between functional developmental perturbations and their neurological consequences. We wish to track the effect on the nervous system by developmental perturbations over time and across species. Except for perturbations, the sequence of events that occur during neural development was found to be remarkably conserved across mammalian species. The tracking includes consequences on anatomical regions and behavioral changes. The ultimate goal is to develop a predictive model of long-term genotypic and phenotypic outcomes that includes developmental insults. Such a model can subsequently be fostered into an educated intervention for therapeutic purposes. Several datasets were identified to test plausible hypotheses, ranging from evoked potential datasets to sleep-disorder datasets. An initial model may be mathematical and conceptual. However, we expect to see rapid progress as large-scale gene expression studies in the mammalian brain permit genome-wide searches to discover genes that are uniquely expressed in brain circuits and regions. These genes ultimately control behavior. By using a validated model we endeavor to make useful predictions.

GTA (ground test accelerator) Phase 1: Baseline design report

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

Not Available

1986-08-01

The national Neutral Particle Beam (NPB) program has two objectives: to provide the necessary basis for a discriminator/weapon decision by 1992, and to develop the technology in stages that lead ultimately to a neutral particle beam weapon. The ground test accelerator (GTA) is the test bed that permits the advancement of the state-of-the-art under experimental conditions in an integrated automated system mode. An intermediate goal of the GTA program is to support the Integrated Space Experiments, while the ultimate goal is to support the 1992 decision. The GTA system and each of its major subsystems are described, and project schedulesmore » and resource requirements are provided. (LEW)« less

Core formation in the early solar system through percolation: 4-D in-situ visualization of melt migration

NASA Astrophysics Data System (ADS)

Bromiley, G.; Berg, M.; Le Godec, Y.; Mezouar, N.; Atwood, R. C.; Phillipe, J.

2015-12-01

Although core formation was a key stage in the evolution of terrestrial planets, the physical processes which resulted in segregation of iron and silicate remain poorly understood. Formation of a silicate magma oceans provides an obvious mechanism for segregation of core-forming liquids, although recent work has strengthened arguments for a complex, multi-stage model of core formation. Extreme pressure1 and the effects of deformation2 have both been shown to promote percolation of Fe-rich melts in a solid silicate matrix, providing mechanisms for early, low temperature core-formation. However, the efficiency of these processes remains untested and we lack meaningful experimental data on resulting melt segregation velocities. Arguments regarding the efficiency of core formation through percolation of Fe-rich melts in solid silicate are based on simple, empirical models. Here, we review textural evidence from recent experiments which supports early core formation driven by deformation-aided percolation of Fe-rich melts. We then present results of novel in-situ synchrotron studies designed to provide time-resolved 3-D microimaging of percolating melt in model systems under extreme conditions. Under low strain rates characteristic of deformation-aided core formation, segregation of metallic (core-forming) melts by percolation is driven by stress gradients. This is expected to ultimately result in channelization and efficient segregation of melts noted in high-strain, low pressure experiments3. In-situ visualization also demonstrates that percolation of viscous metallic melts is surprisingly rapid. A combination of melt channelization and hydraulic fracture results in rapid, episodic melt migration, even over the limited time scale of experiments. The efficiency of this process depends strongly on the geometry of the melt network and is scaled to grain size in the matrix. We use both in-situ visualization and high-resolution ex-situ analysis to provide accurate constraints on melt migration velocities via this combined mechanism and will propose a model by which results can be scaled to core formation in the early solar system. References[1] Shi et al. Nature GeoSc. 6, 971 (2013).[2] Bruhn et al. Nature 403, 883 (2000).[3] Kohlstedt & Holtzman Ann. Rev. Earth. Planet. Sci. 37, 561 (2009).

Merging paleobiology with conservation biology to guide the future of terrestrial ecosystems

USGS Publications Warehouse

Barnosky, Anthony D.; Hadly, Elizabeth A.; Head, Jason; Gonzalez, Patrick; Polly, P. David; Lawing, A. Michelle; Eronen, Jussi T.; Ackerly, David D.; Alex, Ken; Biber, Eric; Blois, Jessica L.; Brashares, Justin; Ceballos, Gerardo; Davis, Edward; Dietl, Gregory P.; Dirzo, Rodolfo; Doremus, Holly; Fortelius, Mikael; Greene, Harry W.; Hellmann, Jessica; Hickler, Thomas; Jackson, Stephen T.; Kemp, Melissa; Koch, Paul L.; Kremen, Claire; Lindsey, Emily L.; Looy, Cindy; Marshall, Charles R.; Mendenhall, Chase; Mulch, Andreas; Mychajliw, Alexis M.; Nowak, Carsten; Ramakrishnan, Uma; Schnitzler, Jan; Das Shrestha, Kashish; Solari, Katherine; Stegner, Lynn; Stegner, M. Allison; Stenseth, Nils Chr.; Wake, Marvalee H.; Zhang, Zhibin

2017-01-01

The current impacts of humanity on nature are rapid and destructive, but species turnover and change have occurred throughout the history of life. Although there is much debate about the best approaches to take in conservation, ultimately, we need to permit or enhance the resilience of natural systems so that they can continue to adapt and function into the future. In a Review, Barnosky et al. argue that the best way to do this is to look back at paleontological history as a way to understand how ecological resilience is maintained, even in the face of change.

Manufacturing of Smart Structures Using Fiber Placement Manufacturing Processes

NASA Technical Reports Server (NTRS)

Thomas, Matthew M.; Glowasky, Robert A.; McIlroy, Bruce E.; Story, Todd A.

1996-01-01

Smart structures research and development, with the ultimate aim of rapid commercial and military production of these structures, are at the forefront of the Synthesis and Processing of Intelligent Cost-Effective Structures (SPICES) program. As part of this ARPA-sponsored program, MDA-E is using fiber placement processes to manufacture integrated smart structure systems. These systems comprise advanced composite structures with embedded fiber optic sensors, shape memory alloys, piezoelectric actuators, and miniature accelerometers. Cost-effective approaches and solutions to smart material synthesis in the fiber-placement process, based upon integrated product development, are discussed herein.

Integrating surgery and genetic testing for the modern surgeon.

PubMed

Caso, Raul; Beamer, Matthew; Lofthus, Alexander D; Sosin, Michael

2017-10-01

The field of cancer genetics is rapidly evolving and several genetic mutations have been identified in hereditary cancer syndromes. These mutations can be diagnosed via routine genetic testing allowing prompt intervention. This is especially true for certain variants of colorectal, breast, and thyroid cancers where genetic testing may guide surgical therapy. Ultimately, surgical intervention may drastically diminish disease manifestation or progression in individuals deemed as high-risk based on their genetic makeup. Understanding the concepts of gene-based testing and integrating into current surgical practice is crucial. This review addresses common genetic syndromes, tests, and interventions salient to the current surgeon.

From the journal archives: cyclopropane: induction and recovery with a bang!

PubMed

Bokoch, Michael P; Gelb, Adrian W

2014-08-01

To review the history of the early development of cyclopropane Cyclopropane was initially investigated because it was thought to be the toxic element in ethylene. Instead, it turned out to be an excellent anesthetic with very rapid onset and recovery while maintaining stable hemodynamics. Its use was ultimately limited because it was highly explosive. Development required collaboration among laboratory scientists and clinicians in Toronto, Canada, clinicians in Madison, USA, and industry in both countries. The phenomenal success of cyclopropane in over 40 years of clinical use resulted from a lucky, but incorrect, hypothesis that it was a toxic contaminant.

Search for Life Beyond the Solar System. Exoplanets, Biosignatures & Instruments

NASA Astrophysics Data System (ADS)

Apai, Daniel; Gabor, Pavel

2014-03-01

Motivated by the rapidly increasing number of known Earth-sized planets, the increasing range of extreme conditions in which life on Earth can persist, and the progress toward a technology that will ultimately enable the search for life on exoplanets, the Vatican Observatory and the Steward Observatory announce a major conference entitled The Search for Life Beyond the Solar System: Exoplanets, Biosignatures & Instruments. The goal of the conference is to bring together the interdisciplinary community required to address this multi-faceted challenge: experts on exoplanet observations, early and extreme life on Earth, atmospheric biosignatures, and planet-finding telescopes.

A rare case of duodenal ulcer perforation accompanied by Boerhaave syndrome

PubMed Central

Rokicki, Wojciech; Rokicki, Marek

2015-01-01

Esophageal perforation is the fastest progressing and the most life-threatening disruption of gastrointestinal tract continuity. It must be regarded as an emergency condition that requires early diagnosis as well as very aggressive and rapid implementation of treatment in order to avoid serious complications and death. Methods of treatment for spontaneous esophageal perforation continue to be a matter of controversy. However, all authors emphasize that ultimate success depends largely on the time taken to establish the diagnosis. The authors of this study describe a rare case of duodenal ulcer perforation accompanied by Boerhaave syndrome. PMID:26702287

Dual Causality and the Autonomy of Biology.

PubMed

Bock, Walter J

2017-03-01

Ernst Mayr's concept of dual causality in biology with the two forms of causes (proximate and ultimate) continues to provide an essential foundation for the philosophy of biology. They are equivalent to functional (=proximate) and evolutionary (=ultimate) causes with both required for full biological explanations. The natural sciences can be classified into nomological, historical nomological and historical dual causality, the last including only biology. Because evolutionary causality is unique to biology and must be included for all complete biological explanations, biology is autonomous from the physical sciences.

Rapid population growth and environmental degradation: ultimate versus proximate factors.

PubMed

Shaw, R P

1989-01-01

This philosophical review of 2 arguments about responsibility for and solutions to environmental degradation concludes that both sides are correct: the ultimate and the proximal causes. Ultimate causes of pollution are defined as the technology responsible for a given type of pollution, such as burning fossil fuel; proximate causes are defined as situation-specific factors confounding the problem, such as population density or rate of growth. Commoner and others argue that developed countries with low or negative population growth rates are responsible for 80% of world pollution, primarily in polluting technologies such as automobiles, power generation, plastics, pesticides, toxic wastes, garbage, warfaring, and nuclear weapons wastes. Distortionary policies also contribute; examples are agricultural trade protection, land mismanagement, urban bias in expenditures, and institutional rigidity., Poor nations are responsible for very little pollution because poverty allows little waste or expenditures for polluting, synthetic technologies. The proximal causes of pollution include numbers and rate of growth of populations responsible for the pollution. Since change in the ultimate cause of pollution remains out of reach, altering the numbers of polluters can make a difference. Predictions are made for proportions of the world's total waste production, assuming current 1.6 tons/capita for developed countries and 0.17 tons/capita for developing countries. If developing countries grow at current rates and become more wealthy, they will be emitting half the world's waste by 2025. ON the other hand, unsustainable population growth goes along with inadequate investment in human capital: education, health, employment, infrastructure. The solution is to improve farming technologies in the 117 non-self-sufficient countries, fund development in the most unsustainable enclaves of growing countries, break institutionalized socio-political rigidity in these enclaves, and focus on educating and empowering women in these enclaves. Women are in charge of birth spacing and all aspects of management of energy, food, water and the local environment, more so than men, in most countries.

Ecosystem goods and services at the neighborhood scale

EPA Science Inventory

Mapping ecosystem functions and articulating the ecosystem goods and services (EGS) they provide to human beneficiaries are important aspects that: link human actions to human costs and benefits from ecosystem, and ultimately provide this information to the general public, public...

Physiology and pathology of saccades and gaze holding.

PubMed

Shaikh, Aasef G; Ghasia, Fatema F

2013-01-01

Foveation is the fundamental requirement for clear vision. Saccades rapidly shift the gaze to the interesting target while gaze holding ensures foveation of the desired object. We will review the pertinent physiology of saccades and gaze holding and their pathophysiology leading to saccadic oscillations, slow saccades, saccadic dysmetria, and nystagmus. Motor commands for saccades are generated at multiple levels of the neuraxis. The frontal and parietal eye field send saccadic commands to the superior colliculus. Latter then projects to the brain-stem saccadic burst generator. The brain-stem burst generators guarantee optimum signal to ensure rapid saccadic velocity, while the neural integrator, by mathematically integrating the saccadic pulse, facilitates stable gaze holding. Reciprocal innervations that ensure rapid saccadic velocity are prone to inherent instability leading to saccadic oscillations. In contrast, suboptimal function of the burst generators causes slow saccades. Impaired error correction, either at the cerebellum or the inferior olive, leads to impaired saccade adaptation and ultimately saccadic dysmetria and oculopalatal tremor. Impairment in the function of neural integrator causes nystagmus. Neurophysiology of saccades, gaze holding, and their deficits are well recognized. These principles can be implemented to define novel therapeutic and rehabilitation approaches.

Accelerators: Sparking Innovation and Transdisciplinary Team Science in Disparities Research

PubMed Central

Horowitz, Carol R.; Shameer, Khader; Gabrilove, Janice; Atreja, Ashish; Shepard, Peggy; Goytia, Crispin N.; Smith, Geoffrey W.; Dudley, Joel; Manning, Rachel; Bickell, Nina A.; Galvez, Maida P.

2017-01-01

Development and implementation of effective, sustainable, and scalable interventions that advance equity could be propelled by innovative and inclusive partnerships. Readied catalytic frameworks that foster communication, collaboration, a shared vision, and transformative translational research across scientific and non-scientific divides are needed to foster rapid generation of novel solutions to address and ultimately eliminate disparities. To achieve this, we transformed and expanded a community-academic board into a translational science board with members from public, academic and private sectors. Rooted in team science, diverse board experts formed topic-specific “accelerators”, tasked with collaborating to rapidly generate new ideas, questions, approaches, and projects comprising patients, advocates, clinicians, researchers, funders, public health and industry leaders. We began with four accelerators—digital health, big data, genomics and environmental health—and were rapidly able to respond to funding opportunities, transform new ideas into clinical and community programs, generate new, accessible, actionable data, and more efficiently and effectively conduct research. This innovative model has the power to maximize research quality and efficiency, improve patient care and engagement, optimize data democratization and dissemination among target populations, contribute to policy, and lead to systems changes needed to address the root causes of disparities. PMID:28241508

Accelerators: Sparking Innovation and Transdisciplinary Team Science in Disparities Research.

PubMed

Horowitz, Carol R; Shameer, Khader; Gabrilove, Janice; Atreja, Ashish; Shepard, Peggy; Goytia, Crispin N; Smith, Geoffrey W; Dudley, Joel; Manning, Rachel; Bickell, Nina A; Galvez, Maida P

2017-02-23

Development and implementation of effective, sustainable, and scalable interventions that advance equity could be propelled by innovative and inclusive partnerships. Readied catalytic frameworks that foster communication, collaboration, a shared vision, and transformative translational research across scientific and non-scientific divides are needed to foster rapid generation of novel solutions to address and ultimately eliminate disparities. To achieve this, we transformed and expanded a community-academic board into a translational science board with members from public, academic and private sectors. Rooted in team science, diverse board experts formed topic-specific "accelerators", tasked with collaborating to rapidly generate new ideas, questions, approaches, and projects comprising patients, advocates, clinicians, researchers, funders, public health and industry leaders. We began with four accelerators-digital health, big data, genomics and environmental health-and were rapidly able to respond to funding opportunities, transform new ideas into clinical and community programs, generate new, accessible, actionable data, and more efficiently and effectively conduct research. This innovative model has the power to maximize research quality and efficiency, improve patient care and engagement, optimize data democratization and dissemination among target populations, contribute to policy, and lead to systems changes needed to address the root causes of disparities.

The ultimate legs of Chilopoda (Myriapoda): a review on their morphological disparity and functional variability

PubMed Central

Kenning, Matthes; Müller, Carsten H.G.

2017-01-01

The arthropodium is the key innovation of arthropods. Its various modifications are the outcome of multiple evolutionary transformations, and the foundation of nearly endless functional possibilities. In contrast to hexapods, crustaceans, and even chelicerates, the spectrum of evolutionary transformations of myriapod arthropodia is insufficiently documented and rarely scrutinized. Among Myriapoda, Chilopoda (centipedes) are characterized by their venomous forcipules—evolutionarily transformed walking legs of the first trunk segment. In addition, the posterior end of the centipedes’ body, in particular the ultimate legs, exhibits a remarkable morphological heterogeneity. Not participating in locomotion, they hold a vast functional diversity. In many centipede species, elongation and annulation in combination with an augmentation of sensory structures indicates a functional shift towards a sensory appendage. In other species, thickening, widening and reinforcement with a multitude of cuticular protuberances and glandular systems suggests a role in both attack and defense. Moreover, sexual dimorphic characteristics indicate that centipede ultimate legs play a pivotal role in intraspecific communication, mate finding and courtship behavior. We address ambiguous identifications and designations of podomeres in order to point out controversial aspects of homology and homonymy. We provide a broad summary of descriptions, illustrations, ideas and observations published in past 160 years, and propose that studying centipede ultimate legs is not only essential in itself for filling gaps of knowledge in descriptive morphology, but also provides an opportunity to explore diverse pathways of leg transformations within Myriapoda. PMID:29158971

14 CFR 23.301 - Loads.

Code of Federal Regulations, 2010 CFR

2010-01-01

... load would significantly change the distribution of external or internal loads, this redistribution...) and ultimate loads (limit loads multiplied by prescribed factors of safety). Unless otherwise provided...

Do animacy effects persist in memory for context?

PubMed

Gelin, Margaux; Bonin, Patrick; Méot, Alain; Bugaiska, Aurélia

2018-04-01

The adaptive view of human memory assumes that animates (e.g, rabbit) are remembered better than inanimates (e.g. glass) because animates are ultimately more important for fitness than inanimates. Previous studies provided evidence for this view by showing that animates were recalled or recognized better than inanimates, but they did not assess memory for contextual details (e.g., where animates vs inanimates occurred). In this study, we tested recollection of spatial information (Study 1) and temporal information (Study 2) associated with animate versus inanimate words. The findings showed that the two types of contextual information were remembered better when they were related to animates than to inanimates. These findings provide further evidence for an ultimate explanation of animacy effects.

Interdisciplinary Approach: A Lever to Business Innovation

ERIC Educational Resources Information Center

Razmak, Jamil; Bélanger, Charles H.

2016-01-01

The advances in interdisciplinary studies are driving universities to utilize their available resources to efficiently enable development processes and provide increasing examples of research while gradually allocating the disciplines' resources. Ultimately, this trend asks universities to provide a platform of integrated disciplines, along with…

Further insights into the oxidation chemistry and biochemistry of the serotonergic neurotoxin 5,6-dihydroxytryptamine.

PubMed

Singh, S; Dryhurst, G

1990-11-01

The neurodegenerative properties of the serotonergic neurotoxin 5,6-dihydroxytryptamine (5,6-DHT) are widely believed to result from its autoxidation in the central nervous system. The autoxidation chemistry of 5,6-DHT has been studied in aqueous solution at pH 7.2. The reaction is initiated by direct oxidation of the indolamine by molecular oxygen with resultant formation of the corresponding o-quinone 1 and H2O2. A rapid nucleophilic attack by 5,6-DHT on 1 leads to 2,7'-bis(5,6-dihydroxytryptamine) (6) which is more rapidly autoxidized than 5,6-DHT to give the corresponding diquinone 7 along with 2 mol of H2O2. The accumulation of 6 in the reaction solution during the autoxidation of 5,6-DHT despite its more rapid autoxidation indicates that diquinone 7 chemically oxidizes 5,6-DHT (2 mol) to quinone 1 so that an autocatalytic cycle is established. The H2O2 formed as a byproduct of these autoxidation reactions can undergo Fenton chemistry catalyzed by trace transition metal ion contaminants with resultant formation of the hydroxyl radical, HO., which directly oxidizes 5,6-DHT to a radical intermediate (9a/9b). This radical is directly attacked by O2 to yield quinone 1 and superoxide radical anion, O2.-, which further facilitates Fenton chemistry by reducing, inter alia, Fe3+ to Fe2+. A minor side reaction of 1 with water leads to formation of at least two trihydroxytryptamines. Diquinone 7 ultimately reacts with 6, 5,6-DHT, and perhaps trihydroxytryptamines, leading via a sequence of coupling and oxidation reactions to a black indolic melanin polymer. Enzymes such as tyrosinase, ceruloplasmin, and peroxidase and rat brain mitochondria catalyze the oxidation of 5,6-DHT to form dimer 7 and, ultimately, indolic melanin. The role of the autoxidation and the enzyme-mediated and mitochondria-promoted oxidations of 5,6-DHT in expressing the neurodegenerative properties of the indolamine are discussed.

The geohydrologic setting of Yucca Mountain, Nevada

USGS Publications Warehouse

Stuckless, J.S.; Dudley, W.W.

2002-01-01

This paper provides a geologic and hydrologic framework of the Yucca Mountain region for the geochemical papers in this volume. The regional geologic units, which range in age from late Precambrian through Holocene, are briefly described. Yucca Mountain is composed of dominantly pyroclastic units that range in age from 11.4 to 15.2 Ma. The principal focus of study has been on the Paintbrush Group, which includes two major zoned and welded ash-flow tuffs separated by an important hydrogeologic unit referred to as the Paintbrush non-welded (PTn). The regional structural setting is currently one of extension, and the major local tectonic domains are presented together with a tectonic model that is consistent with the known structures at Yucca Mountain. Streamflow in this arid to semi-arid region occurs principally in intermittent or ephemeral channels. Near Yucca Mountain, the channels of Fortymile Wash and Amargosa River collect infrequent runoff from tributary basins, ultimately draining to Death Valley. Beneath the surface, large-scale interbasin flow of groundwater from one valley to another occurs commonly in the region. Regional groundwater flow beneath Yucca Mountain originates in the high mesas to the north and returns to the surface either in southern Amargosa Desert or in Death Valley, where it is consumed by evapotranspiration. The water table is very deep beneath the upland areas such as Yucca Mountain, where it is 500-750 m below the land surface, providing a large thickness of unsaturated rocks that are potentially suitable to host a nuclear-waste repository. The nature of unsaturated flow processes, which are important for assessing radionuclide migration, are inferred mainly from hydrochemical or isotopic evidence, from pneumatic tests of the fracture systems, and from the results of in situ experiments. Water seeping down through the unsaturated zone flows rapidly through fractures and more slowly through the pores of the rock matrix. Although capillary forces are expected to divert much of the flow around repository openings, some may drip onto waste packages, ultimately causing release of radionuclides, followed by transport down to the water table. ?? 2002 Elsevier Science Ltd. All rights reserved.

High Temperature Mechanical Characterization of Ceramic Matrix Composites

NASA Technical Reports Server (NTRS)

Gyekenyesi, John Z.

1998-01-01

A high temperature mechanical characterization laboratory has been assembled at NASA Lewis Research Center. One contribution of this work is to test ceramic matrix composite specimens in tension in environmental extremes. Two high temperature tensile testing systems were assembled. The systems were assembled based on the performance and experience of other laboratories and meeting projected service conditions for the materials in question. The systems use frames with an electric actuator and a center screw. A PC based data acquisition and analysis system is used to collect and analyze the data. Mechanical extensometers are used to measure specimen strain. Thermocouples, placed near the specimen, are used to measure the specimen gage section temperature. The system for testing in air has a resistance element furnace with molybdenum disilicide elements and pneumatic grips with water cooling attached to hydraulic alignment devices. The system for testing in an inert gas has a graphite resistance element furnace in a chamber with rigidly mounted, water cooled, hydraulically actuated grips. Unidirectional SiC fiber reinforced reaction bonded Si3N4 and triaxially woven, two dimensional, SiC fiber reinforced enhanced SiC composites were tested in unidirectional tension. Theories for predicting the Young's modulus, modulus near the ultimate strength, first matrix cracking stress, and ultimate strength were applied and evaluated for suitability in predicting the mechanical behavior of SiC/RBSN and enhanced SiC/SiC composites. The SiC/RBSN composite exhibited pseudo tough behavior (increased area under the stress/strain curve) from 22 C to 1500 C. The rule of mixtures provides a good estimate of the Young's modulus of the SiC/RBSN composite using the constituent properties from room temperature to 1440 C for short term static tensile tests in air or nitrogen. The rule of mixtures significantly overestimates the secondary modulus near the ultimate strength. The ACK theory provides the best approximation of the first matrix cracking stress when residual stresses are ignored. The theory of Cao and Thouless, based on Weibull statistics, gave the best prediction for the composite ultimate strength. The enhanced SiC/SiC composite exhibited nonlinear stress/strain behavior from 24 C to 1370 C in air with increased ultimate strain when compared to monolithic SiC. The theory of Yang and Chou with the assumption of a frictional fiber/matrix interface provided the best estimate of the Young's modulus. The theory of Cao and Thouless gave the best estimate for the ultimate strength.

Constructing diabatic representations using adiabatic and approximate diabatic data--Coping with diabolical singularities.

PubMed

Zhu, Xiaolei; Yarkony, David R

2016-01-28

We have recently introduced a diabatization scheme, which simultaneously fits and diabatizes adiabatic ab initio electronic wave functions, Zhu and Yarkony J. Chem. Phys. 140, 024112 (2014). The algorithm uses derivative couplings in the defining equations for the diabatic Hamiltonian, H(d), and fits all its matrix elements simultaneously to adiabatic state data. This procedure ultimately provides an accurate, quantifiably diabatic, representation of the adiabatic electronic structure data. However, optimizing the large number of nonlinear parameters in the basis functions and adjusting the number and kind of basis functions from which the fit is built, which provide the essential flexibility, has proved challenging. In this work, we introduce a procedure that combines adiabatic state and diabatic state data to efficiently optimize the nonlinear parameters and basis function expansion. Further, we consider using direct properties based diabatizations to initialize the fitting procedure. To address this issue, we introduce a systematic method for eliminating the debilitating (diabolical) singularities in the defining equations of properties based diabatizations. We exploit the observation that if approximate diabatic data are available, the commonly used approach of fitting each matrix element of H(d) individually provides a starting point (seed) from which convergence of the full H(d) construction algorithm is rapid. The optimization of nonlinear parameters and basis functions and the elimination of debilitating singularities are, respectively, illustrated using the 1,2,3,4(1)A states of phenol and the 1,2(1)A states of NH3, states which are coupled by conical intersections.

Infection-control basics. A common sense review for EMS personnel.

PubMed

West, Katherine

2002-05-01

Infection-control principles and practices based on science and common sense have been around for thousands of years. They've proven effective. If you know how a disease is transmitted, then you'll know what PPE to use to block transmission. Viruses don't multiply or survive for long outside a living host, so they may be present on a given surface, but in low numbers--and most often not numbers large enough to cause infection. However, hepatitis B virus can survive up to seven days in the presence of dried blood; that's why contaminated equipment must be cleaned as soon as possible after use. If it's not possible to use PPE in a given situation or it fails, then post-exposure medical follow-up and treatment can protect you. Ensuring there's an effective communication network in place for reporting an exposure to your DO is essential. Your agency should verify that hospitals are aware of their responsibilities under the Ryan White Law to share patient testing information if an exposure event occurs. The DO's role includes working with hospitals to provide proper medical follow-up, rapid patient testing and counseling for the exposed provider. Your DO is your advocate. Each and every component of your department's exposure control plan assists in reducing the risk for acquiring an infection on the job. Risk reduction and risk management are both vital. Ultimately, the responsibility lies with you--the provider--to know infection-control principles and practice good habits.

Canine Cytogenetics - From band to basepair

PubMed Central

Breen, Matthew

2008-01-01

Humans and dogs have coexisted for thousands of years, during which time we have developed a unique bond, centered on companionship. Along the way, we have developed purebred dog breeds in a manner that has resulted unfortunately in many of them being affected by serious genetic disorders, including cancers. With serendipity and irony the unique genetic architecture of the 21st Century genome of Man's best friend may ultimately provide many of the keys to unlock some of nature's most intriguing biological puzzles. Canine cytogenetics has advanced significantly over the past 10 years, spurred on largely by the surge of interest in the dog as a biomedical model for genetic disease and the availability of advanced genomics resources. As such the role of canine cytogenetics has moved rapidly from one that served initially to define the gross genomic organization of the canine genome and provide a reliable means to determine the chromosomal location of individual genes, to one that enabled the assembled sequence of the canine genome to be anchored to the karyotype. Canine cytogenetics now presents the biomedical research community with a means to assist in our search for a greater understanding of how genome architectures altered during speciation and in our search for genes associated with cancers that affect both dogs and humans. The cytogenetics ‘toolbox’ for the dog is now loaded. This review aims to provide a summary of some of the recent advancements in canine cytogenetics. PMID:18467825

Dried haematic microsamples and LC-MS/MS for the analysis of natural and synthetic cannabinoids.

PubMed

Protti, Michele; Rudge, James; Sberna, Angelo Eliseo; Gerra, Gilberto; Mercolini, Laura

2017-02-15

Synthetic cannabinoids are new psychoactive substances (NPS) with similar effects when compared to natural ones found in Cannabis derivatives. They have rapidly integrated into the illicit market, often sold as alternatives under international control. The need to identify and quantify an unprecedented and growing number of new compounds represents a unique challenge for toxicological, forensic and anti-doping analysis. Dried blood spots have been used within the bioanalytical framework in place of plasma or serum, in order to reduce invasiveness, lower sample size, simplify handling, storage and shipping of samples and to facilitate home-based and on-field applications. However, DBS implementation has been limited mainly by concerns related to haematocrit effect on method accuracy. Volumetric absorptive microsampling (VAMS™), a second generation dried miniaturized sampling technology, has been developed just in order to eliminate haematocrit effect, thus providing accurate sampling but still granting feasible sample processing. An original LC-MS/MS method was herein developed and validated for the analysis of THC and its 2 main metabolites, together with 10 representative synthetic cannabinoids in both DBS and VAMS dried microsamples. The ultimate goal of this work is to provide highly innovative DBS and VAMS analytical protocols, whose performances were extensively optimized and compared, in order to provide effective and alternative tools that can be applied for natural and synthetic cannabinoid determination, in place of classical analytical strategies. Copyright © 2016 Elsevier B.V. All rights reserved.

Temperature tolerance of young-of-the-year cisco, Coregonus artedii

USGS Publications Warehouse

Edsall, Thomas A.; Colby, Peter J.

1970-01-01

Young-of-the-year ciscoes (Coregonus artedii) acclimated to 2, 5, 10, 20 and 25 C and tested for tolerance to high and low temperatures provide the first detailed description of the thermal tolerance of coregonids in North America. The upper ultimate lethal temperature of the young ciscoes was 26 C (6 C higher than the maximum sustained temperature tolerated by adult ciscoes in nature) and the ultimate lower lethal temperature approached 0 C (near that commonly tolerated in nature by adult ciscoes). The temperature of 26 C is slightly higher than the lowest ultimate upper lethal temperature recorded for North American freshwater fishes; however, published information on the depth distributions of fishes in the Great Lakes suggests that some of the other coregonids may be less tolerant of high temperatures than the cisco.

Telemedicine-Assisted Intubation in Rural Emergency Departments: A National Emergency Airway Registry Study.

PubMed

Van Oeveren, Lucas; Donner, Julie; Fantegrossi, Andrea; Mohr, Nicholas M; Brown, Calvin A

2017-04-01

Intubation in rural emergency departments (EDs) is a high-risk procedure, often with little or no specialty support. Rural EDs are utilizing real-time telemedicine links, connecting providers to an ED physician who may provide clinical guidance. We endeavored to describe telemedicine-assisted intubation in rural EDs that are served by an ED telemedicine network. Prospective data were collected on all patients who had an intubation attempt while on the video telemedicine link from May 1, 2014 to April 30, 2015. We report demographic information, indication, methods, number of attempts, operator characteristics, telemedicine involvement/intervention, adverse events, and clinical outcome by using descriptive statistics. Included were 206 intubations. The most common indication for intubation was respiratory failure. First-pass success rate (postactivation) was 71%, and 96% were eventually intubated. Most attempts (66%) used rapid-sequence intubation. Fifty-four percent of first attempts used video laryngoscopy (VL). Telemedicine providers intervened in 24%, 43%, and 55% of first-third attempts, respectively. First-pass success with VL and direct laryngoscopy was equivalent (70% vs. 71%, p = 0.802). Adverse events were reported in 49 cases (24%), which were most frequently hypoxemia. The impact of telemedicine during emergency intubation is not defined. We showed a 71% first-pass rate post-telemedicine linkage (70% of cases had a previous attempt). Our ultimate success rate was 96%, similar to that in large-center studies. Telemedicine support may contribute to success. Telemedicine-supported endotracheal intubation performed in rural hospitals is feasible, with good success rates. Future research is required to better define the impact of telemedicine providers on emergency airway management.

Designer Dual Therapy Nanolayered Implant Coatings Eradicate Biofilms and Accelerate Bone Tissue Repair.

PubMed

Min, Jouha; Choi, Ki Young; Dreaden, Erik C; Padera, Robert F; Braatz, Richard D; Spector, Myron; Hammond, Paula T

2016-04-26

Infections associated with orthopedic implants cause increased morbidity and significant healthcare cost. A prolonged and expensive two-stage procedure requiring two surgical steps and a 6-8 week period of joint immobilization exists as today's gold standard for the revision arthroplasty of an infected prosthesis. Because infection is much more common in implant replacement surgeries, these issues greatly impact long-term patient care for a continually growing part of the population. Here, we demonstrate that a single-stage revision using prostheses coated with self-assembled, hydrolytically degradable multilayers that sequentially deliver the antibiotic (gentamicin) and the osteoinductive growth factor (BMP-2) in a time-staggered manner enables both eradication of established biofilms and complete and rapid bone tissue repair around the implant in rats with induced osteomyelitis. The nanolayered construct allows precise independent control of release kinetics and loading for each therapeutic agent in an infected implant environment. Antibiotics contained in top layers can be tuned to provide a rapid release at early times sufficient to eliminate infection, followed by sustained release for several weeks, and the underlying BMP-2 component enables a long-term sustained release of BMP-2, which induced more significant and mechanically competent bone formation than a short-term burst release. The successful growth factor-mediated osteointegration of the multilayered implants with the host tissue improved bone-implant interfacial strength 15-fold when compared with the uncoated one. These findings demonstrate the potential of this layered release strategy to introduce a durable next-generation implant solution, ultimately an important step forward to future large animal models toward the clinic.

Juvenile pumice and pyroclastic obsidian reveal the eruptive conditions necessary for the stability of Plinian eruption of rhyolitic magma

NASA Astrophysics Data System (ADS)

Giachetti, T.; Shea, T.; Gonnermann, H. M.; McCann, K. A.; Hoxsie, E. C.

2016-12-01

Significant explosive activity generally precedes or coexists with the large effusion of rhyolitic lava (e.g., Mono Craters; Medicine Lake Volcano; Newberry; Chaitén; Cordón Caulle). Such explosive-to-effusive transitions and, ultimately, cessation of activity are commonly explained by the overall waning magma chamber pressure accompanying magma withdrawal, albeit modulated by magma outgassing. The tephra deposits of such explosive-to-effusive eruptions record the character of the transition - abrupt or gradual - as well as potential changes in eruptive conditions, such as magma composition, volatiles content, mass discharge rate, conduit size, magma outgassing. Results will be presented from a detailed study of both the gas-rich (pumice) and gas-poor (obsidian) juvenile pyroclasts produced during the Plinian phase of the 1060 CE Glass Mountain eruption of Medicine Lake Volcano, California. In the proximal deposits, a multitude of pumice-rich sections separated by layers rich in dense clasts suggests a pulsatory behavior of the explosive phase. Density measurements on 2,600 pumices show that the intermediate, most voluminous deposits have a near constant median porosity of 65%. However, rapid increase in porosity to 75-80% is observed at both the bottom and the top of the fallout deposits, suggestive of rapid variations in magma degassing. In contrast, a water content of pyroclastic obsidians of approximately 0.6 wt% does remain constant throughout the eruption, suggesting that the pyroclastic obsidians degassed up to a constant pressure of a few megapascals. Numerical modeling of eruptive magma ascent and degassing is used to provide constraints on eruption conditions.

The Goal of Adequate Nutrition: Can It Be Made Affordable, Sustainable, and Universal?

PubMed

McFarlane, Ian

2016-11-30

Until about 1900, large proportions of the world population endured hunger and poverty. The 20th century saw world population increase from 1.6 to 6.1 billion, accompanied and to some extent made possible by rapid improvements in health standards and food supply, with associated advances in agricultural and nutrition sciences. In this paper, I use the application of linear programming (LP) in preparation of rations for farm animals to illustrate a method of calculating the lowest cost of a human diet selected from locally available food items, constrained to provide recommended levels of food energy and nutrients; then, to find a realistic minimum cost, I apply the further constraint that the main sources of food energy in the costed diet are weighted in proportion to the actual reported consumption of food items in that area. Worldwide variations in dietary preferences raise the issue as to the sustainability of popular dietary regimes, and the paper reviews the factors associated with satisfying requirements for adequate nutrition within those regimes. The ultimate physical constraints on food supply are described, together with the ways in which climate change may affect those constraints. During the 20th century, food supply increased sufficiently in most areas to keep pace with the rapid increase in world population. Many challenges will need to be overcome if food supply is to continue to meet demand, and those challenges are made more severe by rising expectations of quality of life in the developing world, as well as by the impacts of climate change on agriculture and aquaculture.

HIV-1 Tat reduces nephrin in human podocytes: a potential mechanism for enhanced glomerular permeability in HIV-associated nephropathy.

PubMed

Doublier, Sophie; Zennaro, Cristina; Spatola, Tiziana; Lupia, Enrico; Bottelli, Antonella; Deregibus, Maria Chiara; Carraro, Michele; Conaldi, Pier Giulio; Camussi, Giovanni

2007-02-19

To determine whether HIV-1 Tat may directly alter glomerular permeability in HIV-associated nephropathy (HIVAN). Heavy proteinuria is a hallmark of HIVAN. The slit diaphragm is the ultimate glomerular filtration barrier critical for maintaining the efficiency of the ultrafiltration unit of the kidney. In this study, we evaluated the direct effect of Tat protein on the permeability of isolated glomeruli and on the expression of nephrin, the main slit diaphragm component, by human cultured podocytes. Permeability was studied by measuring the permeability to albumin in isolated rat glomeruli. We also evaluated the expression of nephrin in human cultured podocytes by using immunofluorescence and Western blot. We found that Tat increased albumin permeability in isolated glomeruli, and rapidly induced the redistribution and loss of nephrin in cultured podocytes. Pretreatment of glomeruli and podocytes with blocking antibodies showed that Tat reduced nephrin expression by engaging vascular endothelial growth factor receptors types 2 and 3 and the integrin alphavbeta3. Pre-incubation of podocytes with two platelet-activating factor (PAF) receptor antagonists prevented the loss and redistribution of nephrin induced by Tat, suggesting that PAF is an intracellular mediator of Tat action. Tat induced a rapid PAF synthesis by podocytes. When podocytes transfected to overexpress PAF-acetylhydrolase, the main catabolic enzyme of PAF, were stimulated with Tat, the redistribution and loss of nephrin was abrogated. The present results define a mechanism by which Tat may reduce nephrin expression in podocytes, thus increasing glomerular permeability. This provides new insights in the understanding of HIVAN pathogenesis.

Rapid finite-fault inversions in Southern California using Cybershake Green's functions

NASA Astrophysics Data System (ADS)

Thio, H. K.; Polet, J.

2017-12-01

We have developed a system for rapid finite fault inversion for intermediate and large Southern California earthquakes using local, regional and teleseismic seismic waveforms as well as geodetic data. For modeling the local seismic data, we use 3D Green's functions from the Cybershake project, which were made available to us courtesy of the Southern California Earthquake Center (SCEC). The use of 3D Green's functions allows us to extend the inversion to higher frequency waveform data and smaller magnitude earthquakes, in addition to achieving improved solutions in general. The ultimate aim of this work is to develop the ability to provide high quality finite fault models within a few hours after any damaging earthquake in Southern California, so that they may be used as input to various post-earthquake assessment tools such as ShakeMap, as well as by the scientific community and other interested parties. Additionally, a systematic determination of finite fault models has value as a resource for scientific studies on detailed earthquake processes, such as rupture dynamics and scaling relations. We are using an established least-squares finite fault inversion method that has been applied extensively both on large as well as smaller regional earthquakes, in conjunction with the 3D Green's functions, where available, as well as 1D Green's functions for areas for which the Cybershake library has not yet been developed. We are carrying out validation and calibration of this system using significant earthquakes that have occurred in the region over the last two decades, spanning a range of locations and magnitudes (5.4 and higher).

Rapid Detection of Thrombin and Other Protease Activity Directly in Whole Blood

NASA Astrophysics Data System (ADS)

Yu, Johnson Chung Sing

Thrombin is a serine protease that plays a key role in the clotting cascade to promote hemostasis following injury to the endothelium. From a clinical diagnostic perspective, in-vivo thrombin activity is linked to various blood clotting disorders, as well as cardiovascular disease (DVT, arteriosclerosis, etc). Thus, the ability to rapidly measure protease activity directly in whole blood will provide important new diagnostics, and clinical researchers with a powerful tool to further elucidate the relationship between circulating protease levels and disease. The ultimate goal is to design novel point of care (POC) diagnostic devices that are capable of monitoring protease activities directly in whole blood and biological sample. A charge-changing substrate specific to the thrombin enzyme was engineered and its functionality was confirmed by a series of experiments. This led to the preliminary design, construction, and testing of two device platforms deemed fully functional for the electrophoretic separation and focusing of charged peptide fragments. The concept of using the existing charge-changing substrate platform for bacterial protease detection was also investigated. Certain strains of E coli are associated with severe symptoms such as abdominal cramps, bloody diarrhea, and vomiting. The OmpT protease is expressed on the outer membrane of E coli and plays a role in the cleavage of antimicrobial peptides, the degradation of recombinant heterologous proteins, and the activation of plasminogen in the host. Thus, a synthetic peptide substrate specific to the OmpT protease was designed and modeled for the purpose of detecting E coli in biological sample.

Outplanting [Chapter 17

Treesearch

Diane L. Haase; Thomas D. Landis; R. Kasten Dumroese

2014-01-01

Survival and growth after outplanting are the ultimate tests of nursery plant quality. After the nursery plants are established in the field, they will provide many benefits to the environment by improving soil quality, enhancing biodiversity, inhibiting establishment of invasive plants, sequestering carbon, restoring native plant populations, providing windbreaks,...

7 CFR 4280.21 - Eligible REDG Ultimate Recipients and Projects.

Code of Federal Regulations, 2010 CFR

2010-01-01

... eligible entities to provide medical training and related professional health care skills to rural health... facilitate medical or educational services or job training; or (6) Project feasibility studies and Technical Assistance. A qualified Independent Provider must perform feasibility studies or Technical Assistance. (b...

Toward a better guard of coastal water safety-Microbial distribution in coastal water and their facile detection.

PubMed

Xie, Yunxuan; Qiu, Ning; Wang, Guangyi

2017-05-15

Prosperous development in marine-based tourism has raised increasing concerns over the sanitary quality of coastal waters with potential microbial contamination. The World Health Organization has set stringent standards over a list of pathogenic microorganisms posing potential threats to people with frequent coastal water exposure and has asked for efficient detection procedures for pathogen facile identification. Inspection of survey events regarding the occurrence of marine pathogens in recreational beaches in recent years has reinforced the need for the development of a rapid identification procedure. In this review, we examine the possibility of recruiting uniform molecular assays to identify different marine pathogens and the feasibility of appropriate biomarkers, including enterochelin biosynthetic genes, for general toxicity assays. The focus is not only on bacterial pathogens but also on other groups of infectious pathogens. The ultimate goal is the development of a handy method to more efficiently and rapidly detect marine pathogens. Copyright © 2017 Elsevier Ltd. All rights reserved.

Rapid measurement and compensation method of eccentricity in automatic profile measurement of the ICF capsule.

PubMed

Li, Shaobai; Wang, Yun; Wang, Qi; Ma, Xianxian; Wang, Longxiao; Zhao, Weiqian; Zhang, Xusheng

2018-05-10

In this paper, we propose a new measurement and compensation method for the eccentricity of the inertial confinement fusion (ICF) capsule, which combines computer vision and the laser differential confocal method to align the capsule in rotation measurement. This technique measures the eccentricity of the capsule by obtaining the sub-pixel profile with a moment-based algorithm, then performs the preliminary alignment by the two-dimensional adjustment. Next, we use the laser differential confocal sensor to measure the height data of the equatorial surface of the capsule by turning it around, then obtain and compensate the remaining eccentricity ultimately. This method is a non-contact, automatic, rapid, high-precision measurement and compensation technique of eccentricity for the capsule. Theoretical analyses and preliminary experiments indicate that the maximum measurement range of eccentricity of this proposed method is 1.8 mm for the capsule with a diameter of 1 mm, and it could eliminate the eccentricity to less than 0.5 μm in 30 s.

Rapid non-invasive tests for diagnostics of infectious diseases

NASA Astrophysics Data System (ADS)

Malamud, Daniel

2014-06-01

A rapid test for an infectious disease that can be used at point-of-care at a physician's office, a pharmacy, or in the field is critical for the prompt and appropriate therapeutic intervention. Ultimately by treating infections early on will decrease transmission of the pathogen. In contrast to metabolic diseases or cancer where multiple biomarkers are required, infectious disease targets (e.g. antigen, antibody, nucleic acid) are simple and specific for the pathogen causing the disease. Our laboratory has focused on three major infectious disease; HIV, Tuberculosis, and Malaria. These diseases are pandemic in much of the world thus putting natives, tourists and military personnel at risk for becoming infected, and upon returning to the U.S., transmitting these diseases to their contacts. Our devices are designed to detect antigens, antibodies or nucleic acids in blood or saliva samples in less than 30 minutes. An overview describing the current status of each of the three diagnostic platforms is presented. These microfluidic point-of-care devices will be relatively inexpensive, disposable, and user friendly.

A facile alternative technique for large-area graphene transfer via sacrificial polymer

DOE PAGES

Auchter, Eric; Marquez, Justin; Yarbro, Stephen L.; ...

2017-12-07

A novel method of transferring large-area graphene sheets onto a variety of substrates using Formvar (polyvinyl formal) is presented. Due to the ease at which formvar can be dissolved in chloroform this method allows for a consistent, a clean, and a more rapid transfer than other techniques including the PMMA assisted one. This novel transfer method is demonstrated by transferring large-area graphene onto a range of substrates including commercial TEM grids, silicon dioxide and glass. Raman spectroscopy was used to confirm the presence of graphene and characterize the morphological properties of the large-area sheets. SEM and AFM analyses demonstrated themore » effectiveness of our rapid transfer technique for clean crystalline large-area graphene sheets. The removal of the sacrificial polymer was found to be one to two orders of magnitude faster than PMMA methods. Ultimately this facile transfer technique offers new opportunities for a wide range of applications for large-area graphene through the utilization of a new sacrificial polymer.« less

The genetics of Leigh syndrome and its implications for clinical practice and risk management.

PubMed

Ruhoy, Ilene S; Saneto, Russell P

2014-01-01

Leigh syndrome, also referred to as subacute necrotizing encephalomyelopathy, is a severe, early-onset neurodegenerative disorder that is relentlessly progressive and devastating to both the patient and the patient's family. Attributed to the ultimate failure of the mitochondrial respiratory chain, once it starts, the disease often results in the regression of both mental and motor skills, leading to disability and rapid progression to death. It is a mitochondrial disorder with both phenotypic and genetic heterogeneity. The cause of death is most often respiratory failure, but there are a whole host of complications, including refractory seizures, that may further complicate morbidity and mortality. The symptoms may develop slowly or with rapid progression, usually associated with age of onset. Although the disease is usually diagnosed within the first year of life, it is important to note that recent studies reveal phenotypic heterogeneity, with some patients having evidence of in utero presentation and others having adult-onset symptoms.

Microbial invasion of the Caribbean by an Indo-Pacific coral zooxanthella.

PubMed

Pettay, D Tye; Wham, Drew C; Smith, Robin T; Iglesias-Prieto, Roberto; LaJeunesse, Todd C

2015-06-16

Human-induced environmental changes have ushered in the rapid decline of coral reef ecosystems, particularly by disrupting the symbioses between reef-building corals and their photosymbionts. However, escalating stressful conditions enable some symbionts to thrive as opportunists. We present evidence that a stress-tolerant "zooxanthella" from the Indo-Pacific Ocean, Symbiodinium trenchii, has rapidly spread to coral communities across the Greater Caribbean. In marked contrast to populations from the Indo-Pacific, Atlantic populations of S. trenchii contained exceptionally low genetic diversity, including several widespread and genetically similar clones. Colonies with this symbiont tolerate temperatures 1-2 °C higher than other host-symbiont combinations; however, calcification by hosts harboring S. trenchii is reduced by nearly half, compared with those harboring natives, and suggests that these new symbioses are maladapted. Unforeseen opportunism and geographical expansion by invasive mutualistic microbes could profoundly influence the response of reef coral symbioses to major environmental perturbations but may ultimately compromise ecosystem stability and function.

Microbial invasion of the Caribbean by an Indo-Pacific coral zooxanthella

PubMed Central

Pettay, D. Tye; Wham, Drew C.; Smith, Robin T.; Iglesias-Prieto, Roberto; LaJeunesse, Todd C.

2015-01-01

Human-induced environmental changes have ushered in the rapid decline of coral reef ecosystems, particularly by disrupting the symbioses between reef-building corals and their photosymbionts. However, escalating stressful conditions enable some symbionts to thrive as opportunists. We present evidence that a stress-tolerant “zooxanthella” from the Indo-Pacific Ocean, Symbiodinium trenchii, has rapidly spread to coral communities across the Greater Caribbean. In marked contrast to populations from the Indo-Pacific, Atlantic populations of S. trenchii contained exceptionally low genetic diversity, including several widespread and genetically similar clones. Colonies with this symbiont tolerate temperatures 1–2 °C higher than other host–symbiont combinations; however, calcification by hosts harboring S. trenchii is reduced by nearly half, compared with those harboring natives, and suggests that these new symbioses are maladapted. Unforeseen opportunism and geographical expansion by invasive mutualistic microbes could profoundly influence the response of reef coral symbioses to major environmental perturbations but may ultimately compromise ecosystem stability and function. PMID:26034268

Fabrication of phonon-based metamaterial structures using focused ion beam patterning

NASA Astrophysics Data System (ADS)

Bassim, Nabil D.; Giles, Alexander J.; Ocola, Leonidas E.; Caldwell, Joshua D.

2018-02-01

The focused ion beam (FIB) is a powerful tool for rapid prototyping and machining of functional nanodevices. It is employed regularly to fabricate test metamaterial structures but, to date, has been unsuccessful in fabricating metamaterial structures with features at the nanoscale that rely on surface phonons as opposed to surface plasmons because of the crystalline damage that occurs with the collision cascade associated with ion sputtering. In this study, we employ a simple technique of protecting the crystalline substrate in single-crystal 4H-SiC to design surface phonon polariton-based optical resonance structures. By coating the material surface with a thin film of chromium, we have placed a material of high sputter resistance on the surface, which essentially absorbs the energy in the beam tails. When the beam ultimately punches through the Cr film, the hard walls in the film have the effect of channeling the beam to create smooth sidewalls. This demonstration opens the possibility of further rapid-prototyping of metamaterials using FIB.

The genetics of Leigh syndrome and its implications for clinical practice and risk management

PubMed Central

Ruhoy, Ilene S; Saneto, Russell P

2014-01-01

Leigh syndrome, also referred to as subacute necrotizing encephalomyelopathy, is a severe, early-onset neurodegenerative disorder that is relentlessly progressive and devastating to both the patient and the patient’s family. Attributed to the ultimate failure of the mitochondrial respiratory chain, once it starts, the disease often results in the regression of both mental and motor skills, leading to disability and rapid progression to death. It is a mitochondrial disorder with both phenotypic and genetic heterogeneity. The cause of death is most often respiratory failure, but there are a whole host of complications, including refractory seizures, that may further complicate morbidity and mortality. The symptoms may develop slowly or with rapid progression, usually associated with age of onset. Although the disease is usually diagnosed within the first year of life, it is important to note that recent studies reveal phenotypic heterogeneity, with some patients having evidence of in utero presentation and others having adult-onset symptoms. PMID:25419155

Chinese perceptions of the interface between school and museum education

NASA Astrophysics Data System (ADS)

Kang, Changyun; Anderson, David; Wu, Xinchun

2010-09-01

The current political and social backdrop in China that is characterized by rapid educational reforms to the K-12 education system, rapid growth in the number of science museum institutions, and Central Government policy which encourages collaboration between museums and school has the potential to be fertile ground for meaningful engagement between museums and schools. Notwithstanding, the Chinese K-12 education system generally does not utilize museum resources to support the curriculum, as is common in Western countries. This hermeneutic phenomenographic study elucidates the current Chinese views and perceptions among three stakeholders—school teachers, museum staffs and science educators—around this collaborative concept. The outcomes demonstrate that strongly entrenched cultural views and long-standing practices among stakeholder groups are obstacles to meaningful collaboration despite Central Government policy which encourages such engagement. The cultural values and perceptual views of stakeholder groups were discerned with the purpose of promoting mutual understandings and ultimately enabling meaningful collaboration in support of K-12 education in China.

A facile alternative technique for large-area graphene transfer via sacrificial polymer

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

Auchter, Eric; Marquez, Justin; Yarbro, Stephen L.

A novel method of transferring large-area graphene sheets onto a variety of substrates using Formvar (polyvinyl formal) is presented. Due to the ease at which formvar can be dissolved in chloroform this method allows for a consistent, a clean, and a more rapid transfer than other techniques including the PMMA assisted one. This novel transfer method is demonstrated by transferring large-area graphene onto a range of substrates including commercial TEM grids, silicon dioxide and glass. Raman spectroscopy was used to confirm the presence of graphene and characterize the morphological properties of the large-area sheets. SEM and AFM analyses demonstrated themore » effectiveness of our rapid transfer technique for clean crystalline large-area graphene sheets. The removal of the sacrificial polymer was found to be one to two orders of magnitude faster than PMMA methods. Ultimately this facile transfer technique offers new opportunities for a wide range of applications for large-area graphene through the utilization of a new sacrificial polymer.« less

Femtosecond pump-probe photoionization-photofragmentation spectroscopy: photoionization-induced twisting and coherent vibrational motion of azobenzene cation.

PubMed

Ho, Jr-Wei; Chen, Wei-Kan; Cheng, Po-Yuan

2009-10-07

We report studies of ultrafast dynamics of azobenzene cation using femtosecond photoionization-photofragmentation spectroscopy. In our experiments, a femtosecond pump pulse first produces an ensemble of azobenzene cations via photoionization of the neutrals. A delayed probe pulse then brings the evolving ionic system to excited states that ultimately undergo ion fragmentation. The dynamics is followed by monitoring either the parent-ion depletion or fragment-ion formation as a function of the pump-probe delay time. The observed transients for azobenzene cation are characterized by a constant ion depletion modulated by a rapidly damped oscillatory signal with a period of about 1 ps. Theoretical calculations suggest that the oscillation arises from a vibration motion along the twisting inversion coordinate involving displacements in CNNC and phenyl-ring torsions. The oscillation is damped rapidly with a time constant of about 1.2 ps, suggesting that energy dissipation from the active mode to bath modes takes place in this time scale.

PROTEINS IN NUCLEOCYTOPLASMIC INTERACTIONS

PubMed Central

Goldstein, Lester; Prescott, David M.

1967-01-01

By the transplantation of amino acid-3H-labeled nuclei between cells and the subsequent isolation of nuclei for quantitative assay, we have confirmed that all the nuclear proteins of Amoeba proteus are divisible into two classes that are sharply defined by their physiological behavior. About 40% of the proteins in the nucleus rapidly migrates back and forth between the nucleus and the cytoplasm. These rapidly migrating proteins (RMP) are 25–50 times more concentrated in the nucleus than in the cytoplasm, and migration into the nucleus therefore occurs against a high concentration differential. The remaining 60% of nuclear proteins has been classified as slow turnover proteins (STP) since (as reported in a following paper) virtually all of them ultimately undergo turnover. Turnover in this context means loss of label from the nucleus, by either protein breakdown or protein migration to the cytoplasm. Isolation of nuclei in the detergent Triton X-100 results in a 20% loss of nuclear proteins but conclusions about RMP and STP were not found to be significantly affected by this loss. PMID:6036526

Application of Design of Experiments and Surrogate Modeling within the NASA Advanced Concepts Office, Earth-to-Orbit Design Process

NASA Technical Reports Server (NTRS)

Zwack, Mathew R.; Dees, Patrick D.; Holt, James B.

2016-01-01

Decisions made during early conceptual design have a large impact upon the expected life-cycle cost (LCC) of a new program. It is widely accepted that up to 80% of such cost is committed during these early design phases. Therefore, to help minimize LCC, decisions made during conceptual design must be based upon as much information as possible. To aid in the decision making for new launch vehicle programs, the Advanced Concepts Office (ACO) at NASA Marshall Space Flight Center (MSFC) provides rapid turnaround pre-phase A and phase A concept definition studies. The ACO team utilizes a proven set of tools to provide customers with a full vehicle mass breakdown to tertiary subsystems, preliminary structural sizing based upon worst-case flight loads, and trajectory optimization to quantify integrated vehicle performance for a given mission. Although the team provides rapid turnaround for single vehicle concepts, the scope of the trade space can be limited due to analyst availability and the manpower requirements for manual execution of the analysis tools. In order to enable exploration of a broader design space, the ACO team has implemented an advanced design methods (ADM) based approach. This approach applies the concepts of design of experiments (DOE) and surrogate modeling to more exhaustively explore the trade space and provide the customer with additional design information to inform decision making. This paper will first discuss the automation of the ACO tool set, which represents a majority of the development effort. In order to fit a surrogate model within tolerable error bounds a number of DOE cases are needed. This number will scale with the number of variable parameters desired and the complexity of the system's response to those variables. For all but the smallest design spaces, the number of cases required cannot be produced within an acceptable timeframe using a manual process. Therefore, automation of the tools was a key enabler for the successful application of an ADM approach to an ACO design study. Following the overview of the tool set automation, an example problem will be given to illustrate the implementation of the ADM approach. The example problem will first cover the inclusion of ground rules and assumptions (GR&A) for a study. The GR&A are very important to the study as they determine the constraints within which a trade study can be conducted. These trades must ultimately reconcile with the customer's desired output and any anticipated "what if" questions. The example problem will then illustrate the setup and execution of a DOE through the automated ACO tools. This process is accomplished more efficiently in this work by splitting the tools into two separate environments. The first environment encompasses the structural optimization and mass estimation tools, while the second is focused on trajectory optimization. Surrogate models are fit to the outputs of each environment and are "integrated" via connection of the surrogate equations. Throughout this process, checks are implemented to compare the output of the surrogates to the output of manually run cases to ensure that the error of the final surrogates is at an acceptable level. The conclusion of the example problem demonstrates the utility of the ADM based approach. Using surrogate models gives the ACO team the ability to visualize vehicle sensitivities to various design parameters and identify regions of interest within the design space. The ADM approach can thus be used to inform concept down selection and isolate promising vehicle configurations to be explored in more detail through the manual design process. In addition it provides the customer with an almost instantaneous turnaround on any ''what if" questions that may arise within the bounds of the surrogate model. This approach ultimately expands the ability of the ACO team to provide its customer with broad and rapid turnaround trade studies for launch vehicle conceptual design. The ability to identify a selection of designs which can meet the customer requirements will help ensure lower LCC of launch vehicle designs originating from ACO.

Application of Design of Experiments and Surrogate Modeling within the NASA Advanced Concepts Office, Earth-to-Orbit Design Process

NASA Technical Reports Server (NTRS)

Zwack, Mathew R.; Dees, Patrick D.; Holt, James B.

2016-01-01

Decisions made during early conceptual design have a large impact upon the expected life-cycle cost (LCC) of a new program. It is widely accepted that up to 80% of such cost is committed during these early design phases.1 Therefore, to help minimize LCC, decisions made during conceptual design must be based upon as much information as possible. To aid in the decision making for new launch vehicle programs, the Advanced Concepts Office (ACO) at NASA Marshall Space Flight Center (MSFC) provides rapid turnaround pre-phase A and phase A concept definition studies. The ACO team utilizes a proven set of tools to provide customers with a full vehicle mass breakdown to tertiary subsystems, preliminary structural sizing based upon worst-case flight loads, and trajectory optimization to quantify integrated vehicle performance for a given mission.2 Although the team provides rapid turnaround for single vehicle concepts, the scope of the trade space can be limited due to analyst availability and the manpower requirements for manual execution of the analysis tools. In order to enable exploration of a broader design space, the ACO team has implemented an Advanced Design Methods (ADM) based approach. This approach applies the concepts of Design of Experiments (DOE) and surrogate modeling to more exhaustively explore the trade space and provide the customer with additional design information to inform decision making. This paper will first discuss the automation of the ACO tool set, which represents a majority of the development e ort. In order to t a surrogate model within tolerable error bounds a number of DOE cases are needed. This number will scale with the number of variable parameters desired and the complexity of the system's response to those variables. For all but the smallest design spaces, the number of cases required cannot be produced within an acceptable timeframe using a manual process. Therefore, automation of the tools was a key enabler for the successful application of an ADM approach to an ACO design study. Following the overview of the tool set automation, an example problem will be given to illustrate the implementation of the ADM approach. The example problem will first cover the inclusion of Ground Rules and Assumptions (GR&A) for a study. The GR&A are very important to the study as they determine the constraints within which a trade study can be conducted. These trades must ultimately reconcile with the customer's desired output and any anticipated \\what if" questions. The example problem will then illustrate the setup and execution of a DOE through the automated ACO tools. This process is accomplished more efficiently in this work by splitting the tools into two separate environments. The first environment encompasses the structural optimization and mass estimation tools, while the second is focused on trajectory optimization. Surrogate models are t to the outputs of each environment and are integrated via connection of the surrogate equations. Throughout this process, checks are implemented to compare the output of the surrogates to the output of manually run cases to ensure that the error of the final surrogates is at an acceptable level. The conclusion of the example problem demonstrates the utility of the ADM based approach. Using surrogate models gives the ACO team the ability to visualize vehicle sensitivities to various design parameters and identify regions of interest within the design space. The ADM approach can thus be used to inform concept down selection and isolate promising vehicle configurations to be explored in more detail through the manual design process. In addition it provides the customer with an almost instantaneous turnaround on any \\what if" questions that may arise within the bounds of the surrogate model. This approach ultimately expands the ability of the ACO team to provide its customer with broad and rapid turnaround trade studies for launch vehicle conceptual design. The ability to identify a selection of designs which can meet the customer requirements will have the potential to lower LCC of launch vehicle designs originating from ACO.

Editorial Commentary: "Virtual Reality" Simulation in Orthopaedic Surgery: Realistically Helpful, or Virtually Useless?

PubMed

Camp, Christopher L

2018-05-01

Although we have come a long way, the rapidly expanding field of virtual reality simulation for arthroscopic surgical skills acquisition is supported by only a limited amount of evidence. That said, the good news is that the evidence suggests that simulator experience translates into improved performance in the operating room. If proving this relation is our ultimate goal, more work is certainly needed. In this commentary, a "Task List" is proposed for surgeons and educators interested in using simulators and better defining their role in resident education. Copyright © 2018 Arthroscopy Association of North America. Published by Elsevier Inc. All rights reserved.

The Genomics of Microbial Domestication in the Fermented Food Environment

PubMed Central

Gibbons, John G; Rinker, David C

2015-01-01

Shortly after the agricultural revolution, the domestication of bacteria, yeasts, and molds, played an essential role in enhancing the stability, quality, flavor, and texture of food products. These domestication events were likely the result of human food production practices that entailed the continual recycling of isolated microbial communities in the presence of abundant agricultural food sources. We suggest that within these novel agrarian food niches the metabolic requirements of those microbes became regular and predictable resulting in rapid genomic specialization through such mechanisms as pseudogenization, genome decay, interspecific hybridization, gene duplication, and horizontal gene transfer. The ultimate result was domesticated strains of microorganisms with enhanced fermentative capacities. PMID:26338497

Perspectives and advances of biological H2 production in microorganisms.

PubMed

Rupprecht, Jens; Hankamer, Ben; Mussgnug, Jan H; Ananyev, Gennady; Dismukes, Charles; Kruse, Olaf

2006-09-01

The rapid development of clean fuels for the future is a critically important global challenge for two main reasons. First, new fuels are needed to supplement and ultimately replace depleting oil reserves. Second, fuels capable of zero CO2 emissions are needed to slow the impact of global warming. This review summarizes the development of solar powered bio-H2 production processes based on the conversion of photosynthetic products by fermentative bacteria, as well as using photoheterotrophic and photoautrophic organisms. The use of advanced bioreactor systems and their potential and limitations in terms of process design, efficiency, and cost are also briefly reviewed.

Advances in bioartificial liver assist devices.

PubMed

Patzer, J F

2001-11-01

Rapid advances in development of bioartificial liver assist devices (BLADs) are exciting clinical interest in the application of BLAD technology for support of patients with acute liver failure. Four devices (Circe Biomedical HepatAssist, Vitagen ELAD, Gerlach BELS, and Excorp Medical BLSS) that rely on hepatocytes cultured in hollow-fiber membrane technology are currently in various stages of clinical evaluation. Several alternative approaches for culture and perfusion of hepatocytes have been evaluated in preclinical, large animal models of liver failure, or at a laboratory scale. Engineering design issues with respect to xenotransplantation, BLAD perfusion, hepatocyte functionality and culture maintenance, and ultimate distribution of a BLAD to a clinical site are delineated.

Leadership styles in nursing.

PubMed

Cope, Vicki; Murray, Melanie

2017-06-21

Nurses are often asked to think about leadership, particularly in times of rapid change in healthcare, and where questions have been raised about whether leaders and managers have adequate insight into the requirements of care. This article discusses several leadership styles relevant to contemporary healthcare and nursing practice. Nurses who are aware of leadership styles may find this knowledge useful in maintaining a cohesive working environment. Leadership knowledge and skills can be improved through training, where, rather than having to undertake formal leadership roles without adequate preparation, nurses are able to learn, nurture, model and develop effective leadership behaviours, ultimately improving nursing staff retention and enhancing the delivery of safe and effective care.

Livers, guts and gills: mapping the decay profiles of soft tissues to understand authigenic mineral replacement.

NASA Astrophysics Data System (ADS)

Clements, Thomas; Purnell, Mark; Gabbott, Sarah

2016-04-01

The hard mineralised parts of organisms such as shells, teeth and bones dominate the fossil record. There are, however, sites around the world where soft-tissues are preserved often through rapid replacement of original tissue by rapidly-precipitating authigenic minerals. These exceptionally well-preserved soft-bodied fossils are much more informative about the anatomy, physiology, ecology and behaviour of ancient organisms as well as providing a more inclusive picture of ecosystems and evolution throughout geological time. However, despite the wealth of information that soft-bodied fossils can provide they must first be correctly interpreted as the processes of both decay and preservation act to modify the carcass from its in vivo condition. Decay leads to alteration of the appearance and topology of anatomy, and ultimately to loss. Preservation is selective with some anatomical features being more likely to be captured than others. These problems are especially germane to the interpretation of deep-time and/or enigmatic fossils where no modern analogue exist for comparative anatomical analysis. It is therefore of vital importance to understand the processes carcasses undergo during the fossilisation process, , in order to interpret the anatomical remains of fossils and thus extract true evolutionary presence or absence of anatomy from absence due to taphonomic biases. We have designed a series of novel experiments to investigate, in real time, how decay processes affect the fossilisation potential of soft-tissues - especially of internal anatomy. Our data allow us to unravel both the timing and sequence of anatomical decay of different organs. At the same time through measuring Eh and pH in selected organs we can predict when anatomical features will fall in to the window of authigenic mineralization and thus potentially become preserved. We can also place constraints on which minerals will operate to capture tissues. Our findings are applied to the fossil record allowing greater accuracy in reading the record of exceptionally preserved organisms.

Assessing concentrations and health impacts of air quality management strategies: Framework for Rapid Emissions Scenario and Health impact ESTimation (FRESH-EST).

PubMed

Milando, Chad W; Martenies, Sheena E; Batterman, Stuart A

2016-09-01

In air quality management, reducing emissions from pollutant sources often forms the primary response to attaining air quality standards and guidelines. Despite the broad success of air quality management in the US, challenges remain. As examples: allocating emissions reductions among multiple sources is complex and can require many rounds of negotiation; health impacts associated with emissions, the ultimate driver for the standards, are not explicitly assessed; and long dispersion model run-times, which result from the increasing size and complexity of model inputs, limit the number of scenarios that can be evaluated, thus increasing the likelihood of missing an optimal strategy. A new modeling framework, called the "Framework for Rapid Emissions Scenario and Health impact ESTimation" (FRESH-EST), is presented to respond to these challenges. FRESH-EST estimates concentrations and health impacts of alternative emissions scenarios at the urban scale, providing efficient computations from emissions to health impacts at the Census block or other desired spatial scale. In addition, FRESH-EST can optimize emission reductions to meet specified environmental and health constraints, and a convenient user interface and graphical displays are provided to facilitate scenario evaluation. The new framework is demonstrated in an SO2 non-attainment area in southeast Michigan with two optimization strategies: the first minimizes emission reductions needed to achieve a target concentration; the second minimizes concentrations while holding constant the cumulative emissions across local sources (e.g., an emissions floor). The optimized strategies match outcomes in the proposed SO2 State Implementation Plan without the proposed stack parameter modifications or shutdowns. In addition, the lower health impacts estimated for these strategies suggest that FRESH-EST could be used to identify potentially more desirable pollution control alternatives in air quality management planning. Copyright © 2016 Elsevier Ltd. All rights reserved.

The GSK3/Shaggy-Like Kinase ASKα Contributes to Pattern-Triggered Immunity1[OPEN

PubMed Central

Fritz, Marion

2016-01-01

The first layer of immunity against pathogenic microbes relies on the detection of conserved pathogen-associated molecular patterns (PAMPs) that are recognized by pattern recognition receptors (PRRs) to activate pattern-triggered immunity (PTI). Despite the increasing knowledge of early PTI signaling mediated by PRRs and their associated proteins, many downstream signaling components remain elusive. Here, we identify the Arabidopsis (Arabidopsis thaliana) GLYCOGEN SYNTHASE KINASE3 (GSK3)/Shaggy-like kinase ASKα as a positive regulator of plant immune signaling. The perception of several unrelated PAMPs rapidly induced ASKα kinase activity. Loss of ASKα attenuated, whereas its overexpression enhanced, diverse PTI responses, ultimately affecting susceptibility to the bacterial pathogen Pseudomonas syringae. Glucose-6-phosphate dehydrogenase (G6PD), the key enzyme of the oxidative pentose phosphate pathway, provides reducing equivalents important for defense responses and is a direct target of ASKα. ASKα phosphorylates cytosolic G6PD6 on an evolutionarily conserved threonine residue, thereby stimulating its activity. Plants deficient for or overexpressing G6PD6 showed a modified immune response, and the insensitivity of g6pd6 mutant plants to PAMP-induced growth inhibition was complemented by a phosphomimetic but not by a phosphonegative G6PD6 version. Overall, our data provide evidence that ASKα and G6PD6 constitute an immune signaling module downstream of PRRs, linking protein phosphorylation cascades to metabolic regulation. PMID:27208232

Traversing the mountaintop: world fossil fuel production to 2050

PubMed Central

Nehring, Richard

2009-01-01

During the past century, fossil fuels—petroleum liquids, natural gas and coal—were the dominant source of world energy production. From 1950 to 2005, fossil fuels provided 85–93% of all energy production. All fossil fuels grew substantially during this period, their combined growth exceeding the increase in world population. This growth, however, was irregular, providing for rapidly growing per capita production from 1950 to 1980, stable per capita production from 1980 to 2000 and rising per capita production again after 2000. During the past half century, growth in fossil fuel production was essentially limited by energy demand. During the next half century, fossil fuel production will be limited primarily by the amount and characteristics of remaining fossil fuel resources. Three possible scenarios—low, medium and high—are developed for the production of each of the fossil fuels to 2050. These scenarios differ primarily by the amount of ultimate resources estimated for each fossil fuel. Total fossil fuel production will continue to grow, but only slowly for the next 15–30 years. The subsequent peak plateau will last for 10–15 years. These production peaks are robust; none of the fossil fuels, even with highly optimistic resource estimates, is projected to keep growing beyond 2050. World fossil fuel production per capita will thus begin an irreversible decline between 2020 and 2030. PMID:19770156

High-efficiency removal of NOx using dielectric barrier discharge nonthermal plasma with water as an outer electrode

NASA Astrophysics Data System (ADS)

Dan, ZHAO; Feng, YU; Amin, ZHOU; Cunhua, MA; Bin, DAI

2018-01-01

With the rapid increase in the number of cars and the development of industry, nitrogen oxide (NOx) emissions have become a serious and pressing problem. This work reports on the development of a water-cooled dielectric barrier discharge reactor for gaseous NOx removal at low temperature. The characteristics of the reactor are evaluated with and without packing of the reaction tube with 2 mm diameter dielectric beads composed of glass, ZnO, MnO2, ZrO2, or Fe2O3. It is found that the use of a water-cooled tube reduces the temperature, which stabilizes the reaction, and provides a much greater NO conversion efficiency (28.8%) than that obtained using quartz tube (14.1%) at a frequency of 8 kHz with an input voltage of 6.8 kV. Furthermore, under equivalent conditions, packing the reactor tube with glass beads greatly increases the NO conversion efficiency to 95.85%. This is because the dielectric beads alter the distribution of the electric field due to the influence of polarization at the glass bead surfaces, which ultimately enhances the plasma discharge intensity. The presence of the dielectric beads increases the gas residence time within the reactor. Experimental verification and a theoretical basis are provided for the industrial application of the proposed plasma NO removal process employing dielectric bead packing.

Biomarkers of susceptibility: State of the art and implications for occupational exposure to engineered nanomaterials

PubMed Central

Iavicoli, Ivo; Leso, Veruscka; Schulte, Paul A.

2016-01-01

Rapid advances and applications in nanotechnology are expected to result in increasing occupational exposure to nano-sized materials whose health impacts are still not completely understood. Scientific efforts are required to identify hazards from nanomaterials and define risks and precautionary management strategies for exposed workers. In this scenario, the definition of susceptible populations, which may be at increased risk of adverse effects may be important for risk assessment and management. The aim of this review is to critically examine available literature to provide a comprehensive overview on susceptibility aspects potentially affecting heterogeneous responses to nanomaterials workplace exposure. Genetic, genotoxic and epigenetic alterations induced by nanomaterials in experimental studies were assessed with respect to their possible function as determinants of susceptibility. Additionally, the role of host factors, i.e. age, gender, and pathological conditions, potentially affecting nanomaterial toxicokinetic and health impacts, were also analysed. Overall, this review provides useful information to obtain insights into the nanomaterial mode of action in order to identify potentially sensitive, specific susceptibility biomarkers to be validated in occupational settings and addressed in risk assessment processes. The findings of this review are also important to guide future research into a deeper characterization of nanomaterial susceptibility in order to define adequate risk communication strategies. Ultimately, identification and use of susceptibility factors in workplace settings has both scientific and ethical issues that need addressing. PMID:26724381

Why did Nature choose manganese to make oxygen?

PubMed Central

Armstrong, Fraser A

2007-01-01

This paper discusses the suitability of manganese for its function in catalysing the formation of molecular oxygen from water. Manganese is an abundant element. In terms of its inherent properties, Mn has a particularly rich redox chemistry compared with other d-block elements, with several oxidizing states accessible. The most stable-state Mn2+ behaves like a Group 2 element—it is mobile, weakly complexing, easily taken up by cells and redox-inactive in simple aqueous media. Only in the presence of suitable ligands does Mn2+ become oxidized, so it provides an uncomplicated building unit for the oxygen-evolving centre (OEC). The intermediate oxidation states Mn(III) and Mn(IV) are strongly complexed by O2− and form robust mixed-valence poly-oxo clusters in which the Mn(IV)/Mn(III) ratio can be elevated, one electron at a time, accumulating oxidizing potential and capacity. The OEC is a Mn4CaOx cluster that undergoes sequential oxidations by P680+ at potentials above 1 V, ultimately to a super-oxidized level that includes one Mn(V) or a Mn(IV)-oxyl radical. The latter is powerfully oxidizing and provides the crucial ‘power stroke’ necessary to generate an O–O bond. This leaves a centre still rich in Mn(IV), ensuring a rapid follow-through to O2. PMID:17971329

Air fluorescence detection of large air showers below the horizon

NASA Technical Reports Server (NTRS)

Halverson, P.; Bowen, T.

1985-01-01

In the interest of exploring the cosmic ray spectrum at energies greater than 10 to the 18th power eV, where flux rates at the Earth's surface drop below 100 yr(-1) km(-2) sr(-1), cosmic ray physicists have been forced to construct ever larger detectors in order to collect useful amounts of data in reasonable lengths of time. At present, the ultimate example of this trend is the Fly's Eye system in Utah, which uses the atmosphere around an array of skyward-looking photomultiplier tubes. The air acts as a scintillator to give detecting areas as large as 5000 square kilometers sr (for highest energy events). This experiment has revealed structure (and a possible cutoff) in the ultra-high energy region above 10 o the 19th power eV. The success of the Fly's Eye experiment provides impetus for continuing the development of larger detectors to make accessible even higher energies. However, due to the rapidly falling flux, a tenfold increase in observable energy would call for a hundredfold increase in the detecting area. But, the cost of expanding the Fly's Eye detecting area will approximately scale linearly with area. It is for these reasons that the authors have proposed a new approach to using the atmosphere as a scintillator; one which will require fewer photomultipliers, less hardware (thus being less extensive), yet will provide position and shower size information.

Optimization of genome editing through CRISPR-Cas9 engineering

PubMed Central

Zhang, Jian-Hua; Adikaram, Poorni; Pandey, Mritunjay; Genis, Allison; Simonds, William F.

2016-01-01

ABSTRACT CRISPR (Clustered Regularly-Interspaced Short Palindromic Repeats)-Cas9 (CRISPR associated protein 9) has rapidly become the most promising genome editing tool with great potential to revolutionize medicine. Through guidance of a 20 nucleotide RNA (gRNA), CRISPR-Cas9 finds and cuts target protospacer DNA precisely 3 base pairs upstream of a PAM (Protospacer Adjacent Motif). The broken DNA ends are repaired by either NHEJ (Non-Homologous End Joining) resulting in small indels, or by HDR (Homology Directed Repair) for precise gene or nucleotide replacement. Theoretically, CRISPR-Cas9 could be used to modify any genomic sequences, thereby providing a simple, easy, and cost effective means of genome wide gene editing. However, the off-target activity of CRISPR-Cas9 that cuts DNA sites with imperfect matches with gRNA have been of significant concern because clinical applications require 100% accuracy. Additionally, CRISPR-Cas9 has unpredictable efficiency among different DNA target sites and the PAM requirements greatly restrict its genome editing frequency. A large number of efforts have been made to address these impeding issues, but much more is needed to fully realize the medical potential of CRISPR-Cas9. In this article, we summarize the existing problems and current advances of the CRISPR-Cas9 technology and provide perspectives for the ultimate perfection of Cas9-mediated genome editing. PMID:27340770

Systems of mechanized and reactive droplets powered by multi-responsive surfactants

NASA Astrophysics Data System (ADS)

Yang, Zhijie; Wei, Jingjing; Sobolev, Yaroslav I.; Grzybowski, Bartosz A.

2018-01-01

Although ‘active’ surfactants, which are responsive to individual external stimuli such as temperature, electric or magnetic fields, light, redox processes or chemical agents, are well known, it would be interesting to combine several of these properties within one surfactant species. Such multi-responsive surfactants could provide ways of manipulating individual droplets and possibly assembling them into larger systems of dynamic reactors. Here we describe surfactants based on functionalized nanoparticle dimers that combine all of these and several other characteristics. These surfactants and therefore the droplets that they cover are simultaneously addressable by magnetic, optical and electric fields. As a result, the surfactant-covered droplets can be assembled into various hierarchical structures, including dynamic ones, in which light powers the rapid rotation of the droplets. Such rotating droplets can transfer mechanical torques to their non-nearest neighbours, thus acting like systems of mechanical gears. Furthermore, droplets of different types can be merged by applying electric fields and, owing to interfacial jamming, can form complex, non-spherical, ‘patchy’ structures with different surface regions covered with different surfactants. In systems of droplets that carry different chemicals, combinations of multiple stimuli can be used to control the orientations of the droplets, inter-droplet transport, mixing of contents and, ultimately, sequences of chemical reactions. Overall, the multi-responsive active surfactants that we describe provide an unprecedented level of flexibility with which liquid droplets can be manipulated, assembled and reacted.

Human perception testing methodology for evaluating EO/IR imaging systems

NASA Astrophysics Data System (ADS)

Graybeal, John J.; Monfort, Samuel S.; Du Bosq, Todd W.; Familoni, Babajide O.

2018-04-01

The U.S. Army's RDECOM CERDEC Night Vision and Electronic Sensors Directorate (NVESD) Perception Lab is tasked with supporting the development of sensor systems for the U.S. Army by evaluating human performance of emerging technologies. Typical research questions involve detection, recognition and identification as a function of range, blur, noise, spectral band, image processing techniques, image characteristics, and human factors. NVESD's Perception Lab provides an essential bridge between the physics of the imaging systems and the performance of the human operator. In addition to quantifying sensor performance, perception test results can also be used to generate models of human performance and to drive future sensor requirements. The Perception Lab seeks to develop and employ scientifically valid and efficient perception testing procedures within the practical constraints of Army research, including rapid development timelines for critical technologies, unique guidelines for ethical testing of Army personnel, and limited resources. The purpose of this paper is to describe NVESD Perception Lab capabilities, recent methodological improvements designed to align our methodology more closely with scientific best practice, and to discuss goals for future improvements and expanded capabilities. Specifically, we discuss modifying our methodology to improve training, to account for human fatigue, to improve assessments of human performance, and to increase experimental design consultation provided by research psychologists. Ultimately, this paper outlines a template for assessing human perception and overall system performance related to EO/IR imaging systems.

A Probablistic Diagram to Guide Chemical Design with ...

EPA Pesticide Factsheets

Toxicity is a concern with many chemicals currently in commerce, and with new chemicals that are introduced each year. The standard approach to testing chemicals is to run studies in laboratory animals (e.g. rats, mice, dogs), but because of the expense of these studies and concerns for animal welfare, few chemicals besides pharmaceuticals and pesticides are fully tested. Over the last decade there have been significant developments in the field of computational toxicology which combines in vitro tests and computational models. The ultimate goal of this ?field is to test all chemicals in a rapid, cost effective manner with minimal use of animals. One of the simplest measures of toxicity is provided by high-throughput in vitro cytotoxicity assays, which measure the concentration of a chemical that kills particular types of cells. Chemicals that are cytotoxic at low concentrations tend to be more toxic to animals than chemicals that are less cytotoxic. We employed molecular characteristics derived from density functional theory (DFT) and predicted values of log(octanol-water partition coe?fficient) (logP)to construct a design variable space, and built a predictive model for cytotoxicity using a Naive Bayesian algorithm. External evaluation showed that the area under the curve (AUC) for the receiver operating characteristic (ROC) of the model to be 0.81. Using this model, we provide design rules to help synthetic chemists minimize the chance that a newly synthesize

Breath biomarkers in toxicology.

PubMed

Pleil, Joachim D

2016-11-01

Exhaled breath has joined blood and urine as a valuable resource for sampling and analyzing biomarkers in human media for assessing exposure, uptake metabolism, and elimination of toxic chemicals. This article focuses current use of exhaled gas, aerosols, and vapor in human breath, the methods for collection, and ultimately the use of the resulting data. Some advantages of breath are the noninvasive and self-administered nature of collection, the essentially inexhaustible supply, and that breath sampling does not produce potentially infectious waste such as needles, wipes, bandages, and glassware. In contrast to blood and urine, breath samples can be collected on demand in rapid succession and so allow toxicokinetic observations of uptake and elimination in any time frame. Furthermore, new technologies now allow capturing condensed breath vapor directly, or just the aerosol fraction alone, to gain access to inorganic species, lung pH, proteins and protein fragments, cellular DNA, and whole microorganisms from the pulmonary microbiome. Future applications are discussed, especially the use of isotopically labeled probes, non-targeted (discovery) analysis, cellular level toxicity testing, and ultimately assessing "crowd breath" of groups of people and the relation to dose of airborne and other environmental chemicals at the population level.

Options and limits of quantitative and qualitative online-monitoring of industrial discharges into municipal sewage systems.

PubMed

Hoppe, H; Messmann, S; Giga, A; Grüning, H

2009-01-01

In some cities, industrial enterprises' discharges into municipal sewage systems have a major impact on the quantity and quality of inflows to the municipal treatment plants. In many cases, industrial discharges stand out on account of the great fluctuations in their volumetric rates of flow, pollution loads and temperatures. As a result, these discharges put a great strain on the sewage system, the treatment plant, and ultimately the receiving waters. The enterprises concerned have to pay the treatment plant operators fees based on the load and/or volume discharged. In most cases, qualitative monitoring operations merely consist of spot checks. This means that continuously surveillance is not possible and infringements of the permissible limit values are only discovered by accident. If impermissible discharges are carried out that may be susceptible to causing a treatment plant failure, the rapid initiation of countermeasures is not possible. Hence, spectrometer probes and mobile flowmeters were used in order to determine volumetric rates of flow, COD concentrations, and ultimately the loads discharged. The possibilities for, and limits to, online monitoring as well as shortcomings of spot-checks are discussed in the course of this paper, which also includes an uncertainty analysis.

Ultimate Longitudinal Strength of Composite Ship Hulls

NASA Astrophysics Data System (ADS)

Zhang, Xiangming; Huang, Lingkai; Zhu, Libao; Tang, Yuhang; Wang, Anwen

2017-01-01

A simple analytical model to estimate the longitudinal strength of ship hulls in composite materials under buckling, material failure and ultimate collapse is presented in this paper. Ship hulls are regarded as assemblies of stiffened panels which idealized as group of plate-stiffener combinations. Ultimate strain of the plate-stiffener combination is predicted under buckling or material failure with composite beam-column theory. The effects of initial imperfection of ship hull and eccentricity of load are included. Corresponding longitudinal strengths of ship hull are derived in a straightforward method. A longitudinally framed ship hull made of symmetrically stacked unidirectional plies under sagging is analyzed. The results indicate that present analytical results have a good agreement with FEM method. The initial deflection of ship hull and eccentricity of load can dramatically reduce the bending capacity of ship hull. The proposed formulations provide a simple but useful tool for the longitudinal strength estimation in practical design.

Stormwater TMDL Implementation Support Manual

EPA Pesticide Factsheets

The objective of this document is to provide support to stakeholders, who will be implementing the TMDLs, in identifying and taking actions to reduce, and ultimately fix, stormwater impairments in water bodies.

PDS4 Bundle Creation Governance Using BPMN

NASA Astrophysics Data System (ADS)

Radulescu, C.; Levoe, S. R.; Algermissen, S. S.; Rye, E. D.; Hardman, S. H.

2015-06-01

The AMMOS-PDS Pipeline Service (APPS) provides a Bundle Builder tool, which governs the process of creating, and ultimately generates, PDS4 bundles incrementally, as science products are being generated.

Design of ERIC Usage Studies. Volume I.

ERIC Educational Resources Information Center

ERIC Clearinghouse on Information Resources, Syracuse, NY.

Tables showing the types of Educational Resources Information Center (ERIC) products and their dispersion provide background information for the executive summaries of usage study design reports focusing on three levels: (1) system operations; (2) subscribers to the services provided; and (3) the ultimate "end-users" of the service. The…

Nucleotide diversity and linkage disequilibrium in wild avocado (Persea americana Mill.).

PubMed

Chen, Haofeng; Morrell, Peter L; de la Cruz, Marlene; Clegg, Michael T

2008-01-01

Resequencing studies provide the ultimate resolution of genetic diversity because they identify all mutations in a gene that are present within the sampled individuals. We report a resequencing study of Persea americana, a subtropical tree species native to Meso- and Central America and the progenitor of cultivated avocado. The sample includes 21 wild accessions from Mexico, Costa Rica, Ecuador, and the Dominican Republic. Estimated levels of nucleotide polymorphism and linkage disequilibrium (LD) are obtained from fully resolved haplotype data from 4 nuclear loci that span 5960 nucleotide sites. Results show that, although avocado is a subtropical tree crop and a predominantly outcrossing plant, the overall level of genetic variation is not exceptionally high (nucleotide diversity at silent sites, pi(sil) = 0.0102) compared with available estimates from temperate plant species. Intralocus LD decays rapidly to half the initial value within about 1 kb. Estimates of recombination rate (based on the sequence data) show that the rate is not exceptionally high when compared with annual plants such as wild barley or maize. Interlocus LD is significant owing to substantial population structure induced by mixing of the 3 botanical races of avocado.

Standardization of the experimental autoimmune myasthenia gravis (EAMG) model by immunization of rats with Torpedo californica acetylcholine receptors — Recommendations for methods and experimental designs

PubMed Central

Losen, Mario; Martinez-Martinez, Pilar; Molenaar, Peter C.; Lazaridis, Konstantinos; Tzartos, Socrates; Brenner, Talma; Duan, Rui-Sheng; Luo, Jie; Lindstrom, Jon; Kusner, Linda

2015-01-01

Myasthenia gravis (MG) with antibodies against the acetylcholine receptor (AChR) is characterized by a chronic, fatigable weakness of voluntary muscles. The production of autoantibodies involves the dysregulation of T cells which provide the environment for the development of autoreactive B cells. The symptoms are caused by destruction of the postsynaptic membrane and degradation of the AChR by IgG autoantibodies, predominantly of the G1 and G3 subclasses. Active immunization of animals with AChR from mammalian muscles, AChR from Torpedo or Electrophorus electric organs, and recombinant or synthetic AChR fragments generates a chronic model of MG, termed experimental autoimmune myasthenia gravis (EAMG). This model covers cellular mechanisms involved in the immune response against the AChR, e.g. antigen presentation, T cell-help and regulation, B cell selection and differentiation into plasma cells. Our aim is to define standard operation procedures and recommendations for the rat EAMG model using purified AChR from the Torpedo californica electric organ, in order to facilitate more rapid translation of preclinical proof of concept or efficacy studies into clinical trials and, ultimately, clinical practice. PMID:25796590

Biomarkers in mood disorders research: developing new and improved therapeutics

PubMed Central

Niciu, Mark J.; Mathews, Daniel C.; Ionescu, Dawn F.; Richards, Erica M.; Furey, Maura L.; Yuan, Peixiong; Nugent, Allison C.; Henter, Ioline D.; Machado-Vieira, Rodrigo; Zarate, Carlos A.

2015-01-01

Background Recently, surrogate neurobiological biomarkers that correlate with target engagement and therapeutic response have been developed and tested in early phase studies of mood disorders. Objective The identification of biomarkers could help develop personalized psychiatric treatments that may impact public health. Methods These biomarkers, which are associated with clinical response post-treatment, can be directly validated using multimodal approaches including genetic tools, proteomics/metabolomics, peripheral measures, neuroimaging, biostatistical predictors, and clinical predictors. Results To date, early phase biomarker studies have sought to identify measures that can serve as “biosignatures”, or biological patterns of clinical response. These studies have also sought to identify clinical predictors and surrogate outcomes associated with pathophysiological domains consistently described in the National Institute of Mental Health’s (NIMH) new Research Domain Criteria (RDoC). Using the N-methyl-D-aspartate (NMDA) antagonist ketamine as an example, we identified changes in several domains (clinical, cognitive, and neurophysiological) that predicted ketamine’s rapid and sustained antidepressant effects in individuals with treatment-resistant major depressive disorder (MDD) or bipolar depression. Discussion These approaches may ultimately provide clues into the neurobiology of psychiatric disorders and may have enormous impact Backon the development of novel therapeutics. PMID:26082563

Tissue Engineering in Osteoarthritis: Current Status and Prospect of Mesenchymal Stem Cell Therapy.

PubMed

Im, Gun-Il

2018-04-27

Osteoarthritis (OA) is the most common form of arthritis. Over the last 20 years, attempts have been made to regenerate articular cartilage to overcome the limitations of conventional treatments. As OA is generally associated with larger and diffuse involvement of articular surfaces and alteration of joint homeostasis, a tissue engineering approach for cartilage regeneration is more difficult than in simple chondral defects. Autologous and allogeneic mesenchymal stem cells (MSCs) have rapidly emerged as investigational products for cartilage regeneration. This review outlines points to consider in MSC-based approaches for OA treatment, including allogeneic MSCs, sources of MSCs, dosages, feasibility of multiple injections, indication according to severity of OA lesion and patient age, and issues regarding implantation versus injection. We introduce possible mechanisms of action of implanted or injected MSCs as well as the immunological aspects of MSC therapy and provide a summary of clinical trials of MSCs in the treatment of OA. Given current knowledge, it is too early to draw conclusions on the ultimate effectiveness of intra-articular application of MSCs in terms of regenerative effects. Further radiological and histological data will be needed, with a larger pool of patients, before this question can be answered.

Toxicologic pathology in a multicultural world--India.

PubMed

Schultze, A Eric; Reddy, Vijayapal R; Donnelly, Kevin B; Berridge, Brian R

2011-10-01

The global practice of drug development is expanding into many different continents and countries. India, in particular, is rapidly emerging as an economic force in this arena by offering ever-expanding opportunities for pharmaceutical market expansion as well as productive drug development partnerships. The key to the country's current socioeconomic success appears to be education, particularly the development of higher and professional education. Also, recent modifications to India's patent laws offer greater protections and incentives for international investment. Increasing numbers of competent contract research organizations create attractive opportunities for large Western pharmaceutical companies with a desire to gain access to burgeoning markets as well as mitigate the rising cost of drug development with less costly services. Well-trained veterinary pathologists are available, appropriate facilities are being constructed, and laboratory capabilities are expanding. Developing a productive partnership with a credible laboratory service in India, as with any new provider, requires due diligence and knowledgeable scrutiny of key elements of the work stream, such as facilities, education and training of laboratory personnel, Good Laboratory Practices, animal care, timelines, and data management. Ultimately and with appropriate management, mutually beneficial drug development partnerships are available in India.

Scorecard cardiovascular medicine. Its impact and future directions.

PubMed

Topol, E J; Califf, R M

1994-01-01

Public release of operator-specific data for cardiovascular procedures has set a new precedent, introducing the "scorecard" era. Justification exists for public disclosure, but the mechanics of appropriate data release are complex from a clinical, statistical, and logistic standpoint. Scorecard medicine may appropriately promote regionalization of medical centers and consolidation of services, but unless the process is directed effectively, it may impair the development of new treatments because of a more restrictive clinical practice environment. We propose revamping our current system to facilitate rapid and accurate access to outcome data in the local practice environment so that improvement in practice occurs on a voluntary basis rather than in response to punitive restrictions. A rational plan needs to be developed for dealing with high-risk patients, perhaps through compensation in regression models used to calculate expected outcomes, and for the start-up of novice physicians. Special provisions are needed to promote clinical research. Before procedures are done, it would be ideal to provide a full disclosure informed consent, whereby the physician reports operator-specific data and the patient's decision-making process is facilitated. Overall, appropriate implementation of scorecards could ultimately lead to a substantial improvement in the quality of U.S. cardiovascular medicine.

Nucleic acid-based approaches to investigate microbial-related cheese quality defects

PubMed Central

O'Sullivan, Daniel J.; Giblin, Linda; McSweeney, Paul L. H.; Sheehan, Jeremiah J.; Cotter, Paul D.

2012-01-01

The microbial profile of cheese is a primary determinant of cheese quality. Microorganisms can contribute to aroma and taste defects, form biogenic amines, cause gas and secondary fermentation defects, and can contribute to cheese pinking and mineral deposition issues. These defects may be as a result of seasonality and the variability in the composition of the milk supplied, variations in cheese processing parameters, as well as the nature and number of the non-starter microorganisms which come from the milk or other environmental sources. Such defects can be responsible for production and product recall costs and thus represent a significant economic burden for the dairy industry worldwide. Traditional non-molecular approaches are often considered biased and have inherently slow turnaround times. Molecular techniques can provide early and rapid detection of defects that result from the presence of specific spoilage microbes and, ultimately, assist in enhancing cheese quality and reducing costs. Here we review the DNA-based methods that are available to detect/quantify spoilage bacteria, and relevant metabolic pathways in cheeses and, in the process, highlight how these strategies can be employed to improve cheese quality and reduce the associated economic burden on cheese processors. PMID:23346082

2nd Congress on applied synthetic biology in Europe (Málaga, Spain, November 2013).

PubMed

Vetter, Beatrice V; Pantidos, Nikolaos; Edmundson, Matthew

2014-05-25

The second meeting organised by the EFB on the advances of applied synthetic biology in Europe was held in Málaga, Spain in November 2013. The potential for the broad application of synthetic biology was reflected in the five sessions of this meeting: synthetic biology for healthcare applications, tools and technologies for synthetic biology, production of recombinant proteins, synthetic plant biology, and biofuels and other small molecules. Outcomes from the meeting were that synthetic biology offers methods for rapid development of new strains that will result in decreased production costs, sustainable chemical production and new medical applications. Additionally, it also introduced novel ways to produce sustainable energy and biofuels, to find new alternatives for bioremediation and resource recovery, and environmentally friendly foodstuff production. All the above-mentioned advances could enable biotechnology to solve some of the major problems of Society. However, while there are still limitations in terms of lacking tools, standardisation and suitable host organisms, this meeting has laid a foundation providing cutting-edge concepts and techniques to ultimately convert the potential of synthetic biology into practice. Copyright © 2014. Published by Elsevier B.V. All rights reserved.

Foudroyant Course of an Extensive Clostridium septicum Gas Gangrene in a Diabetic Patient with Occult Carcinoma of the Colon

PubMed Central

Kutup, Asad; Gehl, Axel; Zustin, Jozef; Grossterlinden, Lars G.; Rueger, Johannes M.; Lehmann, Wolfgang

2013-01-01

Background. Spontaneous gas gangrene is a rare disease in which Clostridium septicum frequently can be detected. After an incubation period of 5–48 hours, a very painful swelling is accompanied by a rapidly spreading toxic-infectious clinical picture ultimately leading to septic shock and multiple organ failure. We present a case of a completely documented rare infectious disease with triage findings including initial vital signs, initial medical findings, and the emergency lab., radiological, intraoperative, histopathological, microbiological, and postmortem results. After initial diagnosis of the underlying disease, the patient has been immediately transferred to the operating theatre. The laboratory findings reflect the devastating effect of toxin α which is a toxin typically produced by C. septicum. The patient presented both an anaemia and a manifest coagulopathy as well as an onset of multiple organ failure. Despite the aggressive medical and surgical measures that have been taken, this patient could not be saved. Discussion. The case presented vividly emphasises the difficulty to identify these cases early enough to save a patient. This documentation may help health care providers to identify this life threatening disease as early as possible in future cases. PMID:23864974

Driving forces: Slab subduction and mantle convection

NASA Technical Reports Server (NTRS)

Hager, Bradford H.

1988-01-01

Mantle convection is the mechanism ultimately responsible for most geological activity at Earth's surface. To zeroth order, the lithosphere is the cold outer thermal boundary layer of the convecting mantle. Subduction of cold dense lithosphere provides tha major source of negative buoyancy driving mantle convection and, hence, surface tectonics. There are, however, importnat differences between plate tectonics and the more familiar convecting systems observed in the laboratory. Most important, the temperature dependence of the effective viscosity of mantle rocks makes the thermal boundary layer mechanically strong, leading to nearly rigid plates. This strength stabilizes the cold boundary layer against small amplitude perturbations and allows it to store substantial gravitational potential energy. Paradoxically, through going faults at subduction zones make the lithosphere there locally weak, allowing rapid convergence, unlike what is observed in laboratory experiments using fluids with temperature dependent viscosities. This bimodal strength distribution of the lithosphere distinguishes plate tectonics from simple convection experiments. In addition, Earth has a buoyant, relatively weak layer (the crust) occupying the upper part of the thermal boundary layer. Phase changes lead to extra sources of heat and bouyancy. These phenomena lead to observed richness of behavior of the plate tectonic style of mantle convection.

Isolation of circulating tumor cells using photoacoustic flowmetry and two phase flow

NASA Astrophysics Data System (ADS)

O'Brien, Christine M.; Rood, Kyle D.; Gupta, Sagar K.; Mosley, Jeffrey D.; Goldschmidt, Benjamin S.; Sharma, Nikhilesh; Sengupta, Shramik; Viator, John A.

2011-03-01

Melanoma is the deadliest form of skin cancer, yet current diagnostic methods are inadequately sensitive. Patients must wait until secondary tumors form before malignancy can be diagnosed and treatment prescribed. Detection of cells that have broken off the original tumor and flow through the blood or lymph system can provide data for diagnosing and monitoring cancer. Our group utilizes the photoacoustic effect to detect metastatic melanoma cells, which contain the pigmented granule melanin. As a rapid laser pulse irradiates melanoma, the melanin undergoes thermo-elastic expansion and ultimately creates a photoacoustic wave. Thus, melanoma patient's blood samples can be enriched, leaving the melanoma in a white blood cell (WBC) suspension. Irradiated melanoma cells produce photoacoustic waves, which are detected with a piezoelectric transducer, while the optically transparent WBCs create no signals. Here we report an isolation scheme utilizing two-phase flow to separate detected melanoma from the suspension. By introducing two immiscible fluids through a t-junction into one flow path, the analytes are compartmentalized. Therefore, the slug in which the melanoma cell is located can be identified and extracted from the system. Two-phase immiscible flow is a label free technique, and could be used for other types of pathological analytes.

Epidemiology of urban water distribution systems

NASA Astrophysics Data System (ADS)

Bardet, Jean-Pierre; Little, Richard

2014-08-01

Urban water distribution systems worldwide contain numerous old and fragile pipes that inevitably break, flood streets and damage property, and disrupt economic and social activities. Such breaks often present dramatically in temporal clusters as occurred in Los Angeles during 2009. These clustered pipe breaks share many characteristics with human mortality observed during extreme climatological events such as heat waves or air pollution. Drawing from research and empirical studies in human epidemiology, a framework is introduced to analyze the time variations of disruptive pipe breaks that can help water agencies better understand clustered pipe failures and institute measures to minimize the disruptions caused by them. It is posited that at any time, a cohort of the pipes comprising the water distribution system will be in a weakened state due to fatigue and corrosion. This frail cohort becomes vulnerable during normal operations and ultimately breaks due to rapid increase in crack lengths induced by abnormal stressors. The epidemiological harvesting model developed in this paper simulates an observed time series of monthly pipe breaks and has both explanatory and predictive power. It also demonstrates that models from nonengineering disciplines such as medicine can provide improved insights into the performance of infrastructure systems.

Detection of lipopolysaccharides in serum using a waveguide-based optical biosensor

NASA Astrophysics Data System (ADS)

Noormohamed, Aneesa; Stromberg, Loreen R.; Anderson, Aaron S.; Karim, Zachary; Dighe, Priya; Kempaiah, Prakasha; Ong'echa, John M.; Perkins, Douglas J.; Doggett, Norman; McMahon, Benjamin; Mukundan, Harshini

2017-02-01

Direct ultra-sensitive detection of pathogen biomarkers in blood could provide a universal strategy for diagnosis of bacterial infections, which remain a leading cause of morbidity and mortality in many areas of the world. Many factors complicate diagnosis, including the presence of multiple co-infections in a given patient, and lack of infrastructure in rural settings. In some pediatric patients, such as those in areas with poor resources, an additional challenge exists with low sample volumes due to age and other health factors such as anemia and dehydration. Our team is working on developing novel diagnostic assays, with a waveguide-based biosensor platform, to rapidly and specifically identify pathogen biomarkers from small samples of serum or plasma, allowing for the timely and sensitive diagnosis of infection at the point of care. In addition to the platform, we have developed novel membrane insertion and lipoprotein capture assay methods, to capture lipidated pathogen biomarkers in aqueous blood, by virtue of their interactions with host lipoprotein carriers. Herein, we demonstrate our efforts to adapt the lipoprotein capture assay for the detection of small concentrations of pathogen-secreted lipopolysaccharides in aqueous blood, with the ultimate aim of diagnosing Gram-negative infections effectively.

A WebGIS-based system for analyzing and visualizing air quality data for Shanghai Municipality

NASA Astrophysics Data System (ADS)

Wang, Manyi; Liu, Chaoshun; Gao, Wei

2014-10-01

An online visual analytical system based on Java Web and WebGIS for air quality data for Shanghai Municipality was designed and implemented to quantitatively analyze and qualitatively visualize air quality data. By analyzing the architecture of WebGIS and Java Web, we firstly designed the overall scheme for system architecture, then put forward the software and hardware environment and also determined the main function modules for the system. The visual system was ultimately established with the DIV + CSS layout method combined with JSP, JavaScript, and some other computer programming languages based on the Java programming environment. Moreover, Struts, Spring, and Hibernate frameworks (SSH) were integrated in the system for the purpose of easy maintenance and expansion. To provide mapping service and spatial analysis functions, we selected ArcGIS for Server as the GIS server. We also used Oracle database and ESRI file geodatabase to store spatial data and non-spatial data in order to ensure the data security. In addition, the response data from the Web server are resampled to implement rapid visualization through the browser. The experimental successes indicate that this system can quickly respond to user's requests, and efficiently return the accurate processing results.

Accurate, rapid identification of dislocation lines in coherent diffractive imaging via a min-max optimization formulation

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

Ulvestad, A.; Menickelly, M.; Wild, S. M.

Defects such as dislocations impact materials properties and their response during external stimuli. Imaging these defects in their native operating conditions to establish the structure-function relationship and, ultimately, to improve performance via defect engineering has remained a considerable challenge for both electron-based and x-ray-based imaging techniques. While Bragg coherent x-ray diffractive imaging (BCDI) is successful in many cases, nuances in identifying the dislocations has left manual identification as the preferred method. Derivative-based methods are also used, but they can be inaccurate and are computationally inefficient. Here we demonstrate a derivative-free method that is both more accurate and more computationally efficientmore » than either derivative-or human-based methods for identifying 3D dislocation lines in nanocrystal images produced by BCDI. We formulate the problem as a min-max optimization problem and show exceptional accuracy for experimental images. We demonstrate a 227x speedup for a typical experimental dataset with higher accuracy over current methods. We discuss the possibility of using this algorithm as part of a sparsity-based phase retrieval process. We also provide MATLAB code for use by other researchers.« less

Structural Sizing of a Horizontal Take-Off Launch Vehicle with an Air Collection and Enrichment System

NASA Technical Reports Server (NTRS)

McCurdy, David R.; Roche, Joseph M.

2004-01-01

In support of NASA's Next Generation Launch Technology (NGLT) program, the Andrews Gryphon booster was studied. The Andrews Gryphon concept is a horizontal lift-off, two-stage-to-orbit, reusable launch vehicle that uses an air collection and enrichment system (ACES). The purpose of the ACES is to collect atmospheric oxygen during a subsonic flight loiter phase and cool it to cryogenic temperature, ultimately resulting in a reduced initial take-off weight To study the performance and size of an air-collection based booster, an initial airplane like shape was established as a baseline and modeled in a vehicle sizing code. The code, SIZER, contains a general series of volume, surface area, and fuel fraction relationships that tie engine and ACES performance with propellant requirements and volumetric constraints in order to establish vehicle closure for the given mission. A key element of system level weight optimization is the use of the SIZER program that provides rapid convergence and a great deal of flexibility for different tank architectures and material suites in order to study their impact on gross lift-off weight. This paper discusses important elements of the sizing code architecture followed by highlights of the baseline booster study.

Next generation sequencing applications for breast cancer research

PubMed Central

PETRIC, ROXANA COJOCNEANU; POP, LAURA-ANCUTA; JURJ, ANCUTA; RADULY, LAJOS; DUMITRASCU, DAN; DRAGOS, NICOLAE; NEAGOE, IOANA BERINDAN

2015-01-01

For some time, cancer has not been thought of as a disease, but as a multifaceted, heterogeneous complex of genotypic and phenotypic manifestations leading to tumorigenesis. Due to recent technological progress, the outcome of cancer patients can be greatly improved by introducing in clinical practice the advantages brought about by the development of next generation sequencing techniques. Biomedical suppliers have come up with various applications which medical researchers can use to characterize a patient’s disease from molecular and genetic point of view in order to provide caregivers with rapid and relevant information to guide them in choosing the most appropriate course of treatment, with maximum efficiency and minimal side effects. Breast cancer, whose incidence has risen dramatically, is a good candidate for these novel diagnosis and therapeutic approaches, particularly when referring to specific sequencing panels which are designed to detect germline or somatic mutations in genes that are involved in breast cancer tumorigenesis and progression. Benchtop next generation sequencing machines are becoming a more common presence in the clinical setting, empowering physicians to better treat their patients, by offering early diagnosis alternatives, targeted remedies, and bringing medicine a step closer to achieving its ultimate goal, personalized therapy. PMID:26609257

Development of Advanced Verification and Validation Procedures and Tools for the Certification of Learning Systems in Aerospace Applications

NASA Technical Reports Server (NTRS)

Jacklin, Stephen; Schumann, Johann; Gupta, Pramod; Richard, Michael; Guenther, Kurt; Soares, Fola

2005-01-01

Adaptive control technologies that incorporate learning algorithms have been proposed to enable automatic flight control and vehicle recovery, autonomous flight, and to maintain vehicle performance in the face of unknown, changing, or poorly defined operating environments. In order for adaptive control systems to be used in safety-critical aerospace applications, they must be proven to be highly safe and reliable. Rigorous methods for adaptive software verification and validation must be developed to ensure that control system software failures will not occur. Of central importance in this regard is the need to establish reliable methods that guarantee convergent learning, rapid convergence (learning) rate, and algorithm stability. This paper presents the major problems of adaptive control systems that use learning to improve performance. The paper then presents the major procedures and tools presently developed or currently being developed to enable the verification, validation, and ultimate certification of these adaptive control systems. These technologies include the application of automated program analysis methods, techniques to improve the learning process, analytical methods to verify stability, methods to automatically synthesize code, simulation and test methods, and tools to provide on-line software assurance.

Changing perceptions of United States natural-gas resources as shown by successive U. S. Department of the Interior assessments

USGS Publications Warehouse

Schmoker, James W.; Dyman, Thaddeus S.

2001-01-01

Trends in four successive estimates of United States technically recoverable natural gas resources are examined in this report. The effective dates of these assessments were January 1 of 1975, 1980, 1987, and 1994. The 1994 estimate of the U.S. total gas endowment increased significantly over the previous three estimates, indicating that the technically recoverable endowment of gas is not an absolute volume, but rather is a quantity that can increase through time in response to advances in technology and in geologic understanding. Much of this increase was in the category of reserve growth. Reserve growth refers to additions to the estimated ultimate recovery of fields that typically occur as discovered fields are developed and produced. The potential for U.S. reserve growth, rather than being rapidly used up, appears to be sustainable for many years by intensive engineering efforts coupled with improving technology. Potential additions to reserves in continuous (unconventional) accumulations also represent a type of reserve growth, and were estimated (for the first time) in the 1994 assessment at 358 trillion cubic feet of gas. This resource category provides a significant new contribution to the estimated U.S. total gas endowment.

Hepatitis C virus resistance to the new direct-acting antivirals.

PubMed

Esposito, Isabella; Trinks, Julieta; Soriano, Vicente

2016-10-01

The treatment of hepatitis C virus (HCV) infection has dramatically improved in recent years with the widespread use of interferon-free combination regimens. Despite the high sustained virological response (SVR) rates (over 90%) obtained with direct-acting antivirals (DAAs), drug resistance has emerged as a potential challenge. The high replication rate of HCV and the low fidelity of its RNA polymerase result in a high degree of genetic variability in the HCV population, which ultimately explains the rapid selection of drug resistance associated variants (RAVs). Results from clinical trials and real-world experience have both provided important information on the rate and clinical significance of RAVs. They can be present in treatment-naive patients as natural polymorphisms although more frequently they are selected upon treatment failure. In patients engaged in high-risk behaviors, RAVs can be transmitted. Although DAA failures generally occur in less than 10% of treated chronic hepatitis C patients, selection of drug resistance is the rule in most cases. HCV re-treatment options are available, but first-line therapeutic strategies should be optimized to efficiently prevent DAA failure due to baseline HCV resistance. Considerable progress is being made and next-generation DAAs are coming with pangenotypic activity and higher resistance barrier.

On rate-dependent polycrystal deformation: the temperature sensitivity of cold dwell fatigue

PubMed Central

Zhang, Zhen; Cuddihy, M. A.; Dunne, F. P. E.

2015-01-01

A temperature and rate-dependent crystal plasticity framework has been used to examine the temperature sensitivity of stress relaxation, creep and load shedding in model Ti-6Al polycrystal behaviour under dwell fatigue conditions. A temperature close to 120°C is found to lead to the strongest stress redistribution and load shedding, resulting from the coupling between crystallographic slip rate and slip system dislocation hardening. For temperatures in excess of about 230°C, grain-level load shedding from soft to hard grains diminishes because of the more rapid stress relaxation, leading ultimately to the diminution of the load shedding and hence, it is argued, the elimination of the dwell debit. Under conditions of cyclic stress dwell, at temperatures between 20°C and 230°C for which load shedding occurs, the rate-dependent accumulation of local slip by ratcheting is shown to lead to the progressive cycle-by-cycle redistribution of stress from soft to hard grains. This phenomenon is termed cyclic load shedding since it also depends on the material's creep response, but develops over and above the well-known dwell load shedding, thus providing an additional rationale for the incubation of facet nucleation. PMID:26528078

Accurate, rapid identification of dislocation lines in coherent diffractive imaging via a min-max optimization formulation

NASA Astrophysics Data System (ADS)

Ulvestad, A.; Menickelly, M.; Wild, S. M.

2018-01-01

Defects such as dislocations impact materials properties and their response during external stimuli. Imaging these defects in their native operating conditions to establish the structure-function relationship and, ultimately, to improve performance via defect engineering has remained a considerable challenge for both electron-based and x-ray-based imaging techniques. While Bragg coherent x-ray diffractive imaging (BCDI) is successful in many cases, nuances in identifying the dislocations has left manual identification as the preferred method. Derivative-based methods are also used, but they can be inaccurate and are computationally inefficient. Here we demonstrate a derivative-free method that is both more accurate and more computationally efficient than either derivative- or human-based methods for identifying 3D dislocation lines in nanocrystal images produced by BCDI. We formulate the problem as a min-max optimization problem and show exceptional accuracy for experimental images. We demonstrate a 227x speedup for a typical experimental dataset with higher accuracy over current methods. We discuss the possibility of using this algorithm as part of a sparsity-based phase retrieval process. We also provide MATLAB code for use by other researchers.

Thick layered semiconductor devices with water top-gates: High on-off ratio field-effect transistors and aqueous sensors.

PubMed

Huang, Yuan; Sutter, Eli; Wu, Liangmei; Xu, Hong; Bao, Lihong; Gao, Hong-Jun; Zhou, Xingjiang; Sutter, Peter

2018-06-21

Layered semiconductors show promise as channel materials for field-effect transistors (FETs). Usually, such devices incorporate solid back or top gate dielectrics. Here, we explore de-ionized (DI) water as a solution top gate for field-effect switching of layered semiconductors including SnS2, MoS2, and black phosphorus. The DI water gate is easily fabricated, can sustain rapid bias changes, and its efficient coupling to layered materials provides high on-off current ratios, near-ideal sub-threshold swing, and enhanced short-channel behavior even for FETs with thick, bulk-like channels where such control is difficult to realize with conventional back-gating. Screening by the high-k solution gate eliminates hysteresis due to surface and interface trap states and substantially enhances the field-effect mobility. The onset of water electrolysis sets the ultimate limit to DI water gating at large negative gate bias. Measurements in this regime show promise for aqueous sensing, demonstrated here by the amperometric detection of glucose in aqueous solution. DI water gating of layered semiconductors can be harnessed in research on novel materials and devices, and it may with further development find broad applications in microelectronics and sensing.

Quantitative surface topography assessment of directly compressed and roller compacted tablet cores using photometric stereo image analysis.

PubMed

Allesø, Morten; Holm, Per; Carstensen, Jens Michael; Holm, René

2016-05-25

Surface topography, in the context of surface smoothness/roughness, was investigated by the use of an image analysis technique, MultiRay™, related to photometric stereo, on different tablet batches manufactured either by direct compression or roller compaction. In the present study, oblique illumination of the tablet (darkfield) was considered and the area of cracks and pores in the surface was used as a measure of tablet surface topography; the higher a value, the rougher the surface. The investigations demonstrated a high precision of the proposed technique, which was able to rapidly (within milliseconds) and quantitatively measure the obtained surface topography of the produced tablets. Compaction history, in the form of applied roll force and tablet punch pressure, was also reflected in the measured smoothness of the tablet surfaces. Generally it was found that a higher degree of plastic deformation of the microcrystalline cellulose resulted in a smoother tablet surface. This altogether demonstrated that the technique provides the pharmaceutical developer with a reliable, quantitative response parameter for visual appearance of solid dosage forms, which may be used for process and ultimately product optimization. Copyright © 2015 Elsevier B.V. All rights reserved.

Identification of pulmonary edema in forensic autopsy cases of fatal anaphylactic shock using Fourier transform infrared microspectroscopy.

PubMed

Lin, Hancheng; Luo, Yiwen; Wang, Lei; Deng, Kaifei; Sun, Qiran; Fang, Ruoxi; Wei, Xin; Zha, Shuai; Wang, Zhenyuan; Huang, Ping

2018-03-01

Anaphylaxis is a rapid allergic reaction that may cause sudden death. Currently, postmortem diagnosis of anaphylactic shock is sometimes difficult and often achieved through exclusion. The aim of our study was to investigate whether Fourier transform infrared (FTIR) microspectroscopy combined with pattern recognition methods would be complementary to traditional methods and provide a more accurate postmortem diagnosis of fatal anaphylactic shock. First, the results of spectral peak area analysis showed that the pulmonary edema fluid of the fatal anaphylactic shock group was richer in protein components than the control group, which included mechanical asphyxia, brain injury, and acute cardiac death. Subsequently, principle component analysis (PCA) was performed and showed that the anaphylactic shock group contained more turn and α-helix protein structures as well as less tyrosine-rich proteins than the control group. Ultimately, a partial least-square discriminant analysis (PLS-DA) model combined with a variables selection method called the genetic algorithm (GA) was built and demonstrated good separation between these two groups. This pilot study demonstrates that FTIR microspectroscopy has the potential to be an effective aid for postmortem diagnosis of fatal anaphylactic shock.

Investigation of large transit vehicle accidents and establishing appropriate protection for wheelchair riders.

PubMed

Shaw, Greg

2008-01-01

Securing wheelchairs and restraining wheelchair riders on buses is difficult for many wheelchair riders and transit providers. This study examined injury-producing events aboard large transit buses in general in an attempt to better understand the potential risks and required protection for wheelchair users. The study found that few injuries and fatalities occur on large transit buses. Examination of the relatively few injury-producing events advanced the understanding of these events in terms of acceleration/deceleration magnitude and direction. Low acceleration/deceleration, or low-g, events such as those involving abrupt braking or turning occur frequently and are associated with approximately half of onboard passenger injuries. Unfortunately, the actual frequency of high-g events was not determined. Most of the injurious events involved the bus rapidly decelerating because of frontal impacts with another vehicle or roadside object. Further study is needed to determine the magnitude and frequency of high-g events. This information is necessary to determine the level of protection commensurate with real-world risk necessary for wheelchair riders in the transit bus environment and may ultimately facilitate the development of easier-to-use safety systems that secure and restrain wheelchairs and their riders.

The delineation and interpretation of the earth's gravity field

NASA Technical Reports Server (NTRS)

Marsh, Bruce D.

1988-01-01

A series of fluid dynamical experiments in variable viscosity fluid have been made and are in progress to study: (1) the onset of small scale convection relative to lithosphere growth rate; (2) the influence of paired fracture zones in modulating the horizontal scale of small scale convection; (3) the influence of the mantle vertical viscosity structure on determing the mode of small scale convection; and (4) the 3-D and temporal evolution of flows beneath a high viscosity lid. These experiments extend and amplify the present experimental work that has produced small scale convection beneath a downward-moving solidification front. Rapid growth of a high viscosity lid stifles the early onset of convection such that convection only begins once the lithosphere is older than a certain minimum age. The interplay of this convection with both the structure of the lithosphere and mantle provide a fertile field of investigation into the origin of geoid, gravity, and topographic anomalies in the central Pacific. These highly correlated fields of intermediate wavelength (approximately 200 to 2000 km), but not the larger wavelengths. It is the ultimate, dynamic origin of this class of anomalies that is sought in this investigation.

Guidelines and recommendations on yeast cell death nomenclature.

PubMed

Carmona-Gutierrez, Didac; Bauer, Maria Anna; Zimmermann, Andreas; Aguilera, Andrés; Austriaco, Nicanor; Ayscough, Kathryn; Balzan, Rena; Bar-Nun, Shoshana; Barrientos, Antonio; Belenky, Peter; Blondel, Marc; Braun, Ralf J; Breitenbach, Michael; Burhans, William C; Büttner, Sabrina; Cavalieri, Duccio; Chang, Michael; Cooper, Katrina F; Côrte-Real, Manuela; Costa, Vítor; Cullin, Christophe; Dawes, Ian; Dengjel, Jörn; Dickman, Martin B; Eisenberg, Tobias; Fahrenkrog, Birthe; Fasel, Nicolas; Fröhlich, Kai-Uwe; Gargouri, Ali; Giannattasio, Sergio; Goffrini, Paola; Gourlay, Campbell W; Grant, Chris M; Greenwood, Michael T; Guaragnella, Nicoletta; Heger, Thomas; Heinisch, Jürgen; Herker, Eva; Herrmann, Johannes M; Hofer, Sebastian; Jiménez-Ruiz, Antonio; Jungwirth, Helmut; Kainz, Katharina; Kontoyiannis, Dimitrios P; Ludovico, Paula; Manon, Stéphen; Martegani, Enzo; Mazzoni, Cristina; Megeney, Lynn A; Meisinger, Chris; Nielsen, Jens; Nyström, Thomas; Osiewacz, Heinz D; Outeiro, Tiago F; Park, Hay-Oak; Pendl, Tobias; Petranovic, Dina; Picot, Stephane; Polčic, Peter; Powers, Ted; Ramsdale, Mark; Rinnerthaler, Mark; Rockenfeller, Patrick; Ruckenstuhl, Christoph; Schaffrath, Raffael; Segovia, Maria; Severin, Fedor F; Sharon, Amir; Sigrist, Stephan J; Sommer-Ruck, Cornelia; Sousa, Maria João; Thevelein, Johan M; Thevissen, Karin; Titorenko, Vladimir; Toledano, Michel B; Tuite, Mick; Vögtle, F-Nora; Westermann, Benedikt; Winderickx, Joris; Wissing, Silke; Wölfl, Stefan; Zhang, Zhaojie J; Zhao, Richard Y; Zhou, Bing; Galluzzi, Lorenzo; Kroemer, Guido; Madeo, Frank

2018-01-01

Elucidating the biology of yeast in its full complexity has major implications for science, medicine and industry. One of the most critical processes determining yeast life and physiology is cel-lular demise. However, the investigation of yeast cell death is a relatively young field, and a widely accepted set of concepts and terms is still missing. Here, we propose unified criteria for the defi-nition of accidental, regulated, and programmed forms of cell death in yeast based on a series of morphological and biochemical criteria. Specifically, we provide consensus guidelines on the differ-ential definition of terms including apoptosis, regulated necrosis, and autophagic cell death, as we refer to additional cell death rou-tines that are relevant for the biology of (at least some species of) yeast. As this area of investigation advances rapidly, changes and extensions to this set of recommendations will be implemented in the years to come. Nonetheless, we strongly encourage the au-thors, reviewers and editors of scientific articles to adopt these collective standards in order to establish an accurate framework for yeast cell death research and, ultimately, to accelerate the pro-gress of this vibrant field of research.

Cysteine proteases and wheat (Triticum aestivum L) under drought: A still greatly unexplored association.

PubMed

Botha, Anna-Maria; Kunert, Karl J; Cullis, Christopher A

2017-09-01

Bread wheat (Triticum aestivum L.) provides about 19% of global dietary energy. Environmental stress, such as drought, affects wheat growth causing premature plant senescence and ultimately plant death. A plant response to drought is an increase in protease-mediated proteolysis with rapid degradation of proteins required for metabolic processes. Among the plant proteases that are increased in their activity following stress, cysteine proteases are the best characterized. Very little is known about particular wheat cysteine protease sequences, their expression and also localization. The current knowledge on wheat cysteine proteases belonging to the five clans (CA, CD, CE, CF and CP) is outlined, in particular their expression and possible function under drought. The first successes in establishing an annotated wheat genome database are further highlighted which has allowed more detailed mining of cysteine proteases. We also share our thoughts on future research directions considering the growing availability of genomic resources of this very important food crop. Finally, we also outline future application of developed knowledge in transgenic wheat plants for environmental stress protection and also as senescence markers to monitor wheat growth under environmental stress conditions. © 2017 John Wiley & Sons Ltd.

The Convergence of Virtual Reality and Social Networks: Threats to Privacy and Autonomy.

PubMed

O'Brolcháin, Fiachra; Jacquemard, Tim; Monaghan, David; O'Connor, Noel; Novitzky, Peter; Gordijn, Bert

2016-02-01

The rapid evolution of information, communication and entertainment technologies will transform the lives of citizens and ultimately transform society. This paper focuses on ethical issues associated with the likely convergence of virtual realities (VR) and social networks (SNs), hereafter VRSNs. We examine a scenario in which a significant segment of the world's population has a presence in a VRSN. Given the pace of technological development and the popularity of these new forms of social interaction, this scenario is plausible. However, it brings with it ethical problems. Two central ethical issues are addressed: those of privacy and those of autonomy. VRSNs pose threats to both privacy and autonomy. The threats to privacy can be broadly categorized as threats to informational privacy, threats to physical privacy, and threats to associational privacy. Each of these threats is further subdivided. The threats to autonomy can be broadly categorized as threats to freedom, to knowledge and to authenticity. Again, these three threats are divided into subcategories. Having categorized the main threats posed by VRSNs, a number of recommendations are provided so that policy-makers, developers, and users can make the best possible use of VRSNs.

Co-extinction in a host-parasite network: identifying key hosts for network stability.

PubMed

Dallas, Tad; Cornelius, Emily

2015-08-17

Parasites comprise a substantial portion of total biodiversity. Ultimately, this means that host extinction could result in many secondary extinctions of obligate parasites and potentially alter host-parasite network structure. Here, we examined a highly resolved fish-parasite network to determine key hosts responsible for maintaining parasite diversity and network structure (quantified here as nestedness and modularity). We evaluated four possible host extinction orders and compared the resulting co-extinction dynamics to random extinction simulations; including host removal based on estimated extinction risk, parasite species richness and host level contributions to nestedness and modularity. We found that all extinction orders, except the one based on realistic extinction risk, resulted in faster declines in parasite diversity and network structure relative to random biodiversity loss. Further, we determined species-level contributions to network structure were best predicted by parasite species richness and host family. Taken together, we demonstrate that a small proportion of hosts contribute substantially to network structure and that removal of these hosts results in rapid declines in parasite diversity and network structure. As network stability can potentially be inferred through measures of network structure, our findings may provide insight into species traits that confer stability.

One electron oxidation of 3-methylcholanthrene: A chemical model for its mechanism of carcinogenesis

NASA Astrophysics Data System (ADS)

Lehner, Andreas F.; Horn, Jamie; Flesher, James W.

2017-06-01

One electron transfer oxidation has long been proposed as a route to the ultimate electrophilic and carcinogenic metabolites of both methylated and non-methylated polycyclic aromatic hydrocarbons (PAH). The carcinogenic hydrocarbon 3-methylcholanthrene (3-MC) has a methyl-analogous function at its meso-anthracenic center in the form of a dimethylene bridge, and treatment of this compound with the one electron transfer oxidizing reagent ferric ferricyanide, FeIII(FeIII(CN)6), in mixed aqueous-organic media generated multiple oxygenated species, many of which duplicate those found in mammalian metabolism including known carcinogens 1-hydroxy-3MC and 1-keto-3MC. These results are in agreement with a Unified Theory for PAH Carcinogenicity which predicts in vivo generation of a proximate benzylic alcohol metabolite from the 3-MC procarcinogen and conjugation with a moiety such as sulfate intended for rapid urinary excretion. The sulfate instead acts as a leaving group and generates an electrophilic carbocation capable of reacting with sensitive nucleophiles such as DNA in cellular nuclei. The products of one electron transfer oxidation align well with predictions of the Unified Theory since in many cases these products provide substrates or precursors for conjugation reactions.

7 CFR 4280.21 - Eligible REDG Ultimate Recipients and Projects.

Code of Federal Regulations, 2011 CFR

2011-01-01

... facilitate medical or educational services or job training; or (6) Project feasibility studies and Technical Assistance. A qualified Independent Provider must perform feasibility studies or Technical Assistance. (b...

Coal Quality and Major, Minor, and Trace Elements in the Powder River, Green River, and Williston Basins, Wyoming and North Dakota

USGS Publications Warehouse

Stricker, Gary D.; Flores, Romeo M.; Trippi, Michael H.; Ellis, Margaret S.; Olson, Carol M.; Sullivan, Jonah E.; Takahashi, Kenneth I.

2007-01-01

The U.S. Geological Survey (USGS), in cooperation with the Wyoming Reservoir Management Group (RMG) of the Bureau of Land Management (BLM) and nineteen independent coalbed methane (CBM) gas operators in the Powder River and Green River Basins in Wyoming and the Williston Basin in North Dakota, collected 963 coal samples from 37 core holes (fig. 1; table 1) between 1999 and 2005. The drilling and coring program was in response to the rapid development of CBM, particularly in the Powder River Basin (PRB), and the needs of the RMG BLM for new and more reliable data for CBM resource estimates and reservoir characterization. The USGS and BLM entered into agreements with the gas operators to drill and core Fort Union coal beds, thus supplying core samples for the USGS to analyze and provide the RMG with rapid, real-time results of total gas desorbed, coal quality, and high pressure methane adsorption isotherm data (Stricker and others, 2006). The USGS determined the ultimate composition of all coal core samples; for selected samples analyses also included proximate analysis, calorific value, equilibrium moisture, apparent specific gravity, and forms of sulfur. Analytical procedures followed those of the American Society of Testing Materials (ASTM; 1998). In addition, samples from three wells (129 samples) were analyzed for major, minor, and trace element contents. Ultimate and proximate compositions, calorific value, and forms of sulfur are fundamental parameters in evaluating the economic value of a coal. Determining trace element concentrations, along with total sulfur and ash yield, is also essential to assess the environmental effects of coal use, as is the suitability of the coal for cleaning, gasification, liquefaction, and other treatments. Determination of coal quality in the deeper part (depths greater than 1,000 to 1,200 ft) of the PRB (Rohrbacher and others, 2006; Luppens and others, 2006) is especially important, because these coals are targeted for future mining and development. This report contains summary tables, histograms, and isopleth maps of coal analyses. Details of the compositional internal variability of the coal beds are based on the continuous vertical sampling of coal sequences, including beds in the deeper part of the PRB. Such sampling allows for close comparisons of the compositions of different parts of coal beds as well as within the same coal beds at different core hole locations within short distances of each other.

Sequestration of Sr-90 Subsurface Contamination in the Hanford 100-N Area by Surface Infiltration of a Ca-Citrate-Phosphate Solution

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

Szecsody, James E.; Rockhold, Mark L.; Oostrom, Martinus

The objective of this project is to develop a method to emplace apatite precipitate in the 100N vadose zone, which results in sorption and ultimately incorporation of Sr-90 into the apatite structure. The Ca-citrate-PO4 solution can be infiltrated into unsaturated sediments to result in apatite precipitate to provide effective treatment of Sr-90 contamination. Microbial redistribution during solution infiltration and a high rate of citrate biodegradation for river water microbes (water used for solution infiltration) results in a relatively even spatial distribution of the citrate biodegradation rate and ultimately apatite precipitate in the sediment. Manipulation of the Ca-citrate-PO4 solution infiltration strategymore » can be used to result in apatite precipitate in the lower half of the vadose zone (where most of the Sr-90 is located) and within low-K layers (which are hypothesized to have higher Sr-90 concentrations). The most effective infiltration strategy to precipitate apatite at depth (and with sufficient lateral spread) was to infiltrate a high concentration solution (6 mM Ca, 15 mM citrate, 60 mM PO4) at a rapid rate (near ponded conditions), followed by rapid, then slow water infiltration. Repeated infiltration events, with sufficient time between events to allow water drainage in the sediment profile can be used to buildup the mass of apatite precipitate at greater depth. Low-K heterogeneities were effectively treated, as the higher residual water content maintained in these zones resulted in higher apatite precipitate concentration. High-K zones did not receive sufficient treatment by infiltration, although an alternative strategy of air/surfactant (foam) was demonstrated effective for targeting high-K zones. The flow rate manipulation used in this study to treat specific depths and heterogeneities are not as easy to implement at field scale due to the lack of characterization of heterogeneities and difficulty tracking the wetting front over a large subsurface area. However, the use of real-time surface and cross-borehole geophysics can be used to track the infiltrating Ca-citrate-PO4 front so some adjustments can be made in the infiltration rate to precipitate apatite in desired zones. In addition, the reactive transport code used in this study with field scale physical parameters for sediments can be used to evaluate infiltration strategies along with preliminary water infiltration tests at field scale.« less

Ultrasonic Micro-Blades for the Rapid Extraction of Impact Tracks from Aerogel

NASA Technical Reports Server (NTRS)

Ishii, H. A.; Graham, G. A.; Kearsley, A. T.; Grant, P. G.; Snead, C. J.; Bradley, J. P.

2005-01-01

The science return of NASA's Stardust Mission with its valuable cargo of cometary debris hinges on the ability to efficiently extract particles from silica aerogel collectors. The current method for extracting cosmic dust impact tracks is a mature procedure involving sequential perforation of the aerogel with glass needles on computer controlled micromanipulators. This method is highly successful at removing well-defined aerogel fragments of reasonable optical clarity while causing minimal damage to the surrounding aerogel collector tile. Such a system will be adopted by the JSC Astromaterials Curation Facility in anticipation of Stardust s arrival in early 2006. In addition to Stardust, aerogel is a possible collector for future sample return missions and is used for capture of hypervelocity ejecta in high power laser experiments of interest to LLNL. Researchers will be eager to obtain Stardust samples for study as quickly as possible, and rapid extraction tools requiring little construction, training, or investment would be an attractive asset. To this end, we have experimented with micro-blades for the Stardust impact track extraction process. Our ultimate goal is a rapid extraction system in a clean electron beam environment, such as an SEM or dual-beam FIB, for in situ sample preparation, mounting and analysis.

The global decline of cheetah Acinonyx jubatus and what it means for conservation.

PubMed

Durant, Sarah M; Mitchell, Nicholas; Groom, Rosemary; Pettorelli, Nathalie; Ipavec, Audrey; Jacobson, Andrew P; Woodroffe, Rosie; Böhm, Monika; Hunter, Luke T B; Becker, Matthew S; Broekhuis, Femke; Bashir, Sultana; Andresen, Leah; Aschenborn, Ortwin; Beddiaf, Mohammed; Belbachir, Farid; Belbachir-Bazi, Amel; Berbash, Ali; Brandao de Matos Machado, Iracelma; Breitenmoser, Christine; Chege, Monica; Cilliers, Deon; Davies-Mostert, Harriet; Dickman, Amy J; Ezekiel, Fabiano; Farhadinia, Mohammad S; Funston, Paul; Henschel, Philipp; Horgan, Jane; de Iongh, Hans H; Jowkar, Houman; Klein, Rebecca; Lindsey, Peter Andrew; Marker, Laurie; Marnewick, Kelly; Melzheimer, Joerg; Merkle, Johnathan; M'soka, Jassiel; Msuha, Maurus; O'Neill, Helen; Parker, Megan; Purchase, Gianetta; Sahailou, Samaila; Saidu, Yohanna; Samna, Abdoulkarim; Schmidt-Küntzel, Anne; Selebatso, Eda; Sogbohossou, Etotépé A; Soultan, Alaaeldin; Stone, Emma; van der Meer, Esther; van Vuuren, Rudie; Wykstra, Mary; Young-Overton, Kim

2017-01-17

Establishing and maintaining protected areas (PAs) are key tools for biodiversity conservation. However, this approach is insufficient for many species, particularly those that are wide-ranging and sparse. The cheetah Acinonyx jubatus exemplifies such a species and faces extreme challenges to its survival. Here, we show that the global population is estimated at ∼7,100 individuals and confined to 9% of its historical distributional range. However, the majority of current range (77%) occurs outside of PAs, where the species faces multiple threats. Scenario modeling shows that, where growth rates are suppressed outside PAs, extinction rates increase rapidly as the proportion of population protected declines. Sensitivity analysis shows that growth rates within PAs have to be high if they are to compensate for declines outside. Susceptibility of cheetah to rapid decline is evidenced by recent rapid contraction in range, supporting an uplisting of the International Union for the Conservation of Nature (IUCN) Red List threat assessment to endangered. Our results are applicable to other protection-reliant species, which may be subject to systematic underestimation of threat when there is insufficient information outside PAs. Ultimately, conserving many of these species necessitates a paradigm shift in conservation toward a holistic approach that incentivizes protection and promotes sustainable human-wildlife coexistence across large multiple-use landscapes.

The global decline of cheetah Acinonyx jubatus and what it means for conservation

PubMed Central

Mitchell, Nicholas; Groom, Rosemary; Pettorelli, Nathalie; Ipavec, Audrey; Jacobson, Andrew P.; Woodroffe, Rosie; Böhm, Monika; Becker, Matthew S.; Broekhuis, Femke; Bashir, Sultana; Andresen, Leah; Aschenborn, Ortwin; Beddiaf, Mohammed; Berbash, Ali; Brandao de Matos Machado, Iracelma; Breitenmoser, Christine; Chege, Monica; Cilliers, Deon; Davies-Mostert, Harriet; Dickman, Amy J.; Ezekiel, Fabiano; Farhadinia, Mohammad S.; Funston, Paul; Henschel, Philipp; Horgan, Jane; de Iongh, Hans H.; Jowkar, Houman; Klein, Rebecca; Lindsey, Peter Andrew; Marker, Laurie; Marnewick, Kelly; Melzheimer, Joerg; Merkle, Johnathan; M'soka, Jassiel; Msuha, Maurus; O'Neill, Helen; Parker, Megan; Purchase, Gianetta; Sahailou, Samaila; Saidu, Yohanna; Samna, Abdoulkarim; Schmidt-Küntzel, Anne; Selebatso, Eda; Sogbohossou, Etotépé A.; Stone, Emma; van der Meer, Esther; van Vuuren, Rudie; Wykstra, Mary; Young-Overton, Kim

2017-01-01

Establishing and maintaining protected areas (PAs) are key tools for biodiversity conservation. However, this approach is insufficient for many species, particularly those that are wide-ranging and sparse. The cheetah Acinonyx jubatus exemplifies such a species and faces extreme challenges to its survival. Here, we show that the global population is estimated at ∼7,100 individuals and confined to 9% of its historical distributional range. However, the majority of current range (77%) occurs outside of PAs, where the species faces multiple threats. Scenario modeling shows that, where growth rates are suppressed outside PAs, extinction rates increase rapidly as the proportion of population protected declines. Sensitivity analysis shows that growth rates within PAs have to be high if they are to compensate for declines outside. Susceptibility of cheetah to rapid decline is evidenced by recent rapid contraction in range, supporting an uplisting of the International Union for the Conservation of Nature (IUCN) Red List threat assessment to endangered. Our results are applicable to other protection-reliant species, which may be subject to systematic underestimation of threat when there is insufficient information outside PAs. Ultimately, conserving many of these species necessitates a paradigm shift in conservation toward a holistic approach that incentivizes protection and promotes sustainable human–wildlife coexistence across large multiple-use landscapes. PMID:28028225

Registry Assessment of Peripheral Interventional Devices (RAPID)　- Registry Assessment of Peripheral Interventional Devices Core Data Elements.

PubMed

Jones, W Schuyler; Krucoff, Mitchell W; Morales, Pablo; Wilgus, Rebecca W; Heath, Anne H; Williams, Mary F; Tcheng, James E; Marinac-Dabic, J Danica; Malone, Misti L; Reed, Terrie L; Fukaya, Rie; Lookstein, Robert; Handa, Nobuhiro; Aronow, Herbert D; Bertges, Daniel J; Jaff, Michael R; Tsai, Thomas T; Smale, Joshua A; Zaugg, Margo J; Thatcher, Robert J; Cronenwett, Jack L; Nc, Durham; Md, Silver Spring; Japan, Tokyo; Ny, New York; Ri, Providence; Vt, Burlington; Mass, Newton; Colo, Denver; Ariz, Tempe; Calif, Santa Clara; Minn, Minneapolis; Nh, Lebanon

2018-01-25

The current state of evaluating patients with peripheral artery disease and more specifically of evaluating medical devices used for peripheral vascular intervention (PVI) remains challenging because of the heterogeneity of the disease process, the multiple physician specialties that perform PVI, the multitude of devices available to treat peripheral artery disease, and the lack of consensus about the best treatment approaches. Because PVI core data elements are not standardized across clinical care, clinical trials, and registries, aggregation of data across different data sources and physician specialties is currently not feasible.Methods and Results:Under the auspices of the U.S. Food and Drug Administration's Medical Device Epidemiology Network initiative-and its PASSION (Predictable and Sustainable Implementation of the National Registries) program, in conjunction with other efforts to align clinical data standards-the Registry Assessment of Peripheral Interventional Devices (RAPID) workgroup was convened. RAPID is a collaborative, multidisciplinary effort to develop a consensus lexicon and to promote interoperability across clinical care, clinical trials, and national and international registries of PVI. The current manuscript presents the initial work from RAPID to standardize clinical data elements and definitions, to establish a framework within electronic health records and health information technology procedural reporting systems, and to implement an informatics-based approach to promote the conduct of pragmatic clinical trials and registry efforts in PVI. Ultimately, we hope this work will facilitate and improve device evaluation and surveillance for patients, clinicians, health outcomes researchers, industry, policymakers, and regulators.

Relativistic Tsiolkovsky equation -- a case study in special relativity

NASA Astrophysics Data System (ADS)

Redd, Jeremy; Panin, Alexander

2011-10-01

A possibility of using antimatter in future space propulsion systems is seriously discussed in scientific literature. Annihilation of matter and antimatter is not only the energy source of ultimate density 9x10^16 J/kg (provided that antimatter fuel is available on board or can be collected along the journey) but also potentially allows to reach ultimate exhaust speed -- speed of light c. Using relativistic rocket equation we discuss the feasibility of achieving relativistic velocities with annihilation powered photon engine, as well as the advantages and disadvantages of interstellar travel with relativistic and ultrarelativistic velocities.

Trials and Tribulations of Fluorescent Dissolved Organic Matter Chemical Interpretations: A case study of polar ice cores

NASA Astrophysics Data System (ADS)

D'Andrilli, J.

2017-12-01

Excitation emission matrix fluorescence spectroscopy is widely applied for rapid dissolved organic matter (DOM) characterization in aquatic systems. Fluorescent DOM surveys are booming, not only as a central focus in aquatic environments, but also as an important addition to interdisciplinary research (e.g., DOM analysis in concert with ice core paleoclimate reconstructions, stream metabolism, hydrologic regimes, agricultural developments, and biological activity), opening new doors, not just for novelty, but also for more challenges with chemical interpretations. Recently, the commonly used protein- versus humic-like classifications of DOM have been ineffective at describing DOM chemistry in various systems (e.g., ice cores, wastewaters, incubations/engineered). Moreover, the oversimplification of such classifications used to describe fluorescing components, without further scrutiny, has become commonplace, ultimately producing vague reporting. For example, West Antarctic ice core DOM was shown to contain fluorescence in the low excitation/emission wavelength region, however resolved fluorophores depicting tyrosine- and tryptophan-like DOM were not observed. At first, as literature suggested, we reported this result as protein-like, and concluded that microbial contributions were dominant in deep ice. That initial interpretation would disintegrate the conservation paradigm of atmospheric composition during deposition, the crux of ice core research, and contradict other lines of evidence. This begged the question, "How can we describe DOM chemistry without distinct fluorophores?" Antarctic ice core DOM was dominated by neither tyrosine- nor tryptophan-like fluorescence, causing "unusual" looking fluorescent components. After further examination, deep ice DOM was reported to contain fluorescent species most similar to monolignols and tannin-like phenols, describing the precursors of lignin from low carbon producing environments, consistent with marine sediment records. Currently, we are working towards more detailed descriptions of fluorescence, thus accepting variation in and around protein- and humic-like regions, and achieving robust chemical interpretations of DOM chemistry, ultimately providing insight to its interwoven nature in the environment.

Metabolic Mapping: Quantitative Enzyme Cytochemistry and Histochemistry to Determine the Activity of Dehydrogenases in Cells and Tissues.

PubMed

Molenaar, Remco J; Khurshed, Mohammed; Hira, Vashendriya V V; Van Noorden, Cornelis J F

2018-05-26

Altered cellular metabolism is a hallmark of many diseases, including cancer, cardiovascular diseases and infection. The metabolic motor units of cells are enzymes and their activity is heavily regulated at many levels, including the transcriptional, mRNA stability, translational, post-translational and functional level. This complex regulation means that conventional quantitative or imaging assays, such as quantitative mRNA experiments, Western Blots and immunohistochemistry, yield incomplete information regarding the ultimate activity of enzymes, their function and/or their subcellular localization. Quantitative enzyme cytochemistry and histochemistry (i.e., metabolic mapping) show in-depth information on in situ enzymatic activity and its kinetics, function and subcellular localization in an almost true-to-nature situation. We describe a protocol to detect the activity of dehydrogenases, which are enzymes that perform redox reactions to reduce cofactors such as NAD(P) + and FAD. Cells and tissue sections are incubated in a medium that is specific for the enzymatic activity of one dehydrogenase. Subsequently, the dehydrogenase that is the subject of investigation performs its enzymatic activity in its subcellular site. In a chemical reaction with the reaction medium, this ultimately generates blue-colored formazan at the site of the dehydrogenase's activity. The formazan's absorbance is therefore a direct measure of the dehydrogenase's activity and can be quantified using monochromatic light microscopy and image analysis. The quantitative aspect of this protocol enables researchers to draw statistical conclusions from these assays. Besides observational studies, this technique can be used for inhibition studies of specific enzymes. In this context, studies benefit from the true-to-nature advantages of metabolic mapping, giving in situ results that may be physiologically more relevant than in vitro enzyme inhibition studies. In all, metabolic mapping is an indispensable technique to study metabolism at the cellular or tissue level. The technique is easy to adopt, provides in-depth, comprehensive and integrated metabolic information and enables rapid quantitative analysis.

Modification of a Pollen Trap Design To Capture Airborne Conidia of Entomophaga maimaiga and Detection of Conidia by Quantitative PCR.

PubMed

Bittner, Tonya D; Hajek, Ann E; Liebhold, Andrew M; Thistle, Harold

2017-09-01

The goal of this study was to develop effective and practical field sampling methods for quantification of aerial deposition of airborne conidia of Entomophaga maimaiga over space and time. This important fungal pathogen is a major cause of larval death in invasive gypsy moth ( Lymantria dispar ) populations in the United States. Airborne conidia of this pathogen are relatively large (similar in size to pollen), with unusual characteristics, and require specialized methods for collection and quantification. Initially, dry sampling (settling of spores from the air onto a dry surface) was used to confirm the detectability of E. maimaiga at field sites with L. dispar deaths caused by E. maimaiga , using quantitative PCR (qPCR) methods. We then measured the signal degradation of conidial DNA on dry surfaces under field conditions, ultimately rejecting dry sampling as a reliable method due to rapid DNA degradation. We modified a chamber-style trap commonly used in palynology to capture settling spores in buffer. We tested this wet-trapping method in a large-scale (137-km) spore-trapping survey across gypsy moth outbreak regions in Pennsylvania undergoing epizootics, in the summer of 2016. Using 4-day collection periods during the period of late instar and pupal development, we detected variable amounts of target DNA settling from the air. The amounts declined over the season and with distance from the nearest defoliated area, indicating airborne spore dispersal from outbreak areas. IMPORTANCE We report on a method for trapping and quantifying airborne spores of Entomophaga maimaiga , an important fungal pathogen affecting gypsy moth ( Lymantria dispar ) populations. This method can be used to track dispersal of E. maimaiga from epizootic areas and ultimately to provide critical understanding of the spatial dynamics of gypsy moth-pathogen interactions. Copyright © 2017 American Society for Microbiology.

Selection of pipe repair methods.

DOT National Transportation Integrated Search

2013-06-01

The objective of this research is to provide pipeline operators with testing procedures and : results of the performance of composite pipe repair methods and ultimately, improve their : selection and installation, and reduce the risks associated with...

Disinfection and Stabilization Processes

EPA Science Inventory

Municipal wastewater sludges are composed of organic and inorganic contaminants from domestic, commercial and industrial wastewaters entering collection systems. Many options are available for ultimate disposal of residual solids, however few of these options provide for benefic...

Final analysis of cost, value, and risk.

DOT National Transportation Integrated Search

2009-03-05

USDOT understands that access to emergency services provided by 9-1-1 in todays world of evolving : technology will ultimately occur within a broader array of interconnected networks comprehensively : supporting emergency servicesfrom public ac...

Evolving T-cell vaccine strategies for HIV, the virus with a thousand faces

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

Korber, Bette

HIV's rapid global spread and the human suffering it has left in its wake have made AIDS a global heath priority for the 25 years since its discovery. Yet its capacity to rapidly evolve has made combating this virus a tremendous challenge. The obstacles to creating an effective HIV vaccine are formidable, but there are advances in the field on many fronts, in terms of novel vectors, adjuvants, and antigen design strategies. SIV live attenuated vaccine models are able to confer protection against heterologous challenge, and this continues to provide opportunities to explore the biological underpinnings of a protective effectmore » (9). More indirect, but equally important, is new understanding regarding the biology of acute infection (43), the role of immune response in long-term non-progression (6,62, 81), and defining characteristics of broadly neutralizing antibodies (4). In this review we will focus on summarizing strategies directed towards a single issue, that of contending with HIV variation in terms of designing aT-cell vaccine. The strategies that prove most effective in this area can ultimately be combined with the best strategies under development in other areas, with the hope of ultimately converging on a viable vaccine candidate. Only two large HIV vaccine efficacy trials have been completed and both have failed to prevent infection or confer a benefit to infected individual (23,34), but there is ample reason to continue our efforts. A historic breakthrough came in 1996, when it was realized that although the virus could escape from a single antiretroviral (ARV) therapy, it could be thwarted by a combination of medications that simultaneously targeted different parts of the virus (HAART) (38). This revelation came after 15 years of research, thought, and clinical testing; to enable that vital progress the research and clinical communities had to first define and understand, then develop a strategy to counter, the remarkable evolutionary potential of the virus. HAART, for the first time, provided an effective treatment to help those with living with HIV stay healthy. Nonetheless, the treatment has limitations. People with HIV face a lifetime of expensive daily multi-drug regimens, often with side effects; drug resistance at the individual and population level are issues (56); and universal access, despite substantial progress, is a dream not yet realized for many of the millions of the world's poor who are living with HIV (68). These issues, combined with the growing numbers of people infected globally and impact of HIV on society, make the development of an HIV vaccine or a prophylactic prevention strategy a crucial if elusive goal. In some ways, the history of HIV vaccine deVelopment has paralleled the early stages of designing effective therapy. We had to test the simple strategies first, but meanwhile the story of the impact of diversity from an immunological perspective is still unfolding, and novel ideas countermeasures are being explored.« less

Meningitis in a College Student in Connecticut, 2007

ERIC Educational Resources Information Center

Sosa, Lynn E.; Gupta, Shaili; Juthani-Mehta, Manisha; Hadler, James L.

2009-01-01

The authors describe a case of aseptic meningitis in a college student that was ultimately attributed to infection with lymphocytic choriomeningitis virus (LCMV). The authors also provide a review of LCMV infection, epidemiology, and public health implications. Providers should be aware of LCMV as a cause of meningitis in college students,…

Whatever It Takes: A Mixed Methods Study Evaluating the Implementation of Professional Learning Communities across a District

ERIC Educational Resources Information Center

French, N. Shalene

2013-01-01

Professional Learning Communities (PLCs) provide the basis for meeting the challenges and expectations in today's educational environment. Effective PLCs provide the framework for school improvement and ultimately impact student academic success. School leadership is fundamental in this process (Bennis, 2009; Buffum, Mattos, & Weber, 2009;…

Importance of Rapid Eye Movement Sleep Behavior Disorder to the Primary Care Physician.

PubMed

McCarter, Stuart J; Howell, Michael J

2016-10-01

Sleep disorders and neurodegenerative diseases are commonly encountered in primary care. A common, but underdiagnosed sleep disorder, rapid eye movement sleep behavior disorder (RBD), is highly associated with Parkinson disease and related disorders. Rapid eye movement sleep behavior disorder is common. It is estimated to affect 0.5% of the general population and more than 7% of individuals older than 60 years; however, most cases go unrecognized. Rapid eye movement sleep behavior disorder presents as dream enactment, often with patients thrashing, punching, and kicking while they are sleeping. Physicians can quickly assess for the presence of RBD with high sensitivity and specificity by asking patients the question "Have you ever been told that you act out your dreams, for example by punching or flailing your arms in the air or screaming and shouting in your sleep?" Patients with RBD exhibit subtle signs of neurodegenerative disease, such as mild motor slowing, constipation, or changes in sense of smell. These signs and symptoms may predict development of a neurodegenerative disease within 3 years. Ultimately, most patients with RBD develop a neurodegenerative disease, highlighting the importance of serial neurological examinations to assess for the presence of parkinsonism and/or cognitive impairment and prognostic counseling for these patients. Rapid eye movement sleep behavior disorder is treatable with melatonin (3-6 mg before bed) or clonazepam (0.5-1 mg before bed) and may be the most common, reversible cause of sleep-related injury. Thus, it is important to identify patients at risk of RBD in a primary care setting so that bedroom safety can be addressed and treatment may be initiated. Copyright © 2016 Mayo Foundation for Medical Education and Research. Published by Elsevier Inc. All rights reserved.

The Baltic Sea as a time machine for the future coastal ocean.

PubMed

Reusch, Thorsten B H; Dierking, Jan; Andersson, Helen C; Bonsdorff, Erik; Carstensen, Jacob; Casini, Michele; Czajkowski, Mikolaj; Hasler, Berit; Hinsby, Klaus; Hyytiäinen, Kari; Johannesson, Kerstin; Jomaa, Seifeddine; Jormalainen, Veijo; Kuosa, Harri; Kurland, Sara; Laikre, Linda; MacKenzie, Brian R; Margonski, Piotr; Melzner, Frank; Oesterwind, Daniel; Ojaveer, Henn; Refsgaard, Jens Christian; Sandström, Annica; Schwarz, Gerald; Tonderski, Karin; Winder, Monika; Zandersen, Marianne

2018-05-01

Coastal global oceans are expected to undergo drastic changes driven by climate change and increasing anthropogenic pressures in coming decades. Predicting specific future conditions and assessing the best management strategies to maintain ecosystem integrity and sustainable resource use are difficult, because of multiple interacting pressures, uncertain projections, and a lack of test cases for management. We argue that the Baltic Sea can serve as a time machine to study consequences and mitigation of future coastal perturbations, due to its unique combination of an early history of multistressor disturbance and ecosystem deterioration and early implementation of cross-border environmental management to address these problems. The Baltic Sea also stands out in providing a strong scientific foundation and accessibility to long-term data series that provide a unique opportunity to assess the efficacy of management actions to address the breakdown of ecosystem functions. Trend reversals such as the return of top predators, recovering fish stocks, and reduced input of nutrient and harmful substances could be achieved only by implementing an international, cooperative governance structure transcending its complex multistate policy setting, with integrated management of watershed and sea. The Baltic Sea also demonstrates how rapidly progressing global pressures, particularly warming of Baltic waters and the surrounding catchment area, can offset the efficacy of current management approaches. This situation calls for management that is (i) conservative to provide a buffer against regionally unmanageable global perturbations, (ii) adaptive to react to new management challenges, and, ultimately, (iii) multisectorial and integrative to address conflicts associated with economic trade-offs.

Constructing diabatic representations using adiabatic and approximate diabatic data – Coping with diabolical singularities

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

Zhu, Xiaolei, E-mail: virtualzx@gmail.com; Yarkony, David R., E-mail: yarkony@jhu.edu

2016-01-28

We have recently introduced a diabatization scheme, which simultaneously fits and diabatizes adiabatic ab initio electronic wave functions, Zhu and Yarkony J. Chem. Phys. 140, 024112 (2014). The algorithm uses derivative couplings in the defining equations for the diabatic Hamiltonian, H{sup d}, and fits all its matrix elements simultaneously to adiabatic state data. This procedure ultimately provides an accurate, quantifiably diabatic, representation of the adiabatic electronic structure data. However, optimizing the large number of nonlinear parameters in the basis functions and adjusting the number and kind of basis functions from which the fit is built, which provide the essential flexibility,more » has proved challenging. In this work, we introduce a procedure that combines adiabatic state and diabatic state data to efficiently optimize the nonlinear parameters and basis function expansion. Further, we consider using direct properties based diabatizations to initialize the fitting procedure. To address this issue, we introduce a systematic method for eliminating the debilitating (diabolical) singularities in the defining equations of properties based diabatizations. We exploit the observation that if approximate diabatic data are available, the commonly used approach of fitting each matrix element of H{sup d} individually provides a starting point (seed) from which convergence of the full H{sup d} construction algorithm is rapid. The optimization of nonlinear parameters and basis functions and the elimination of debilitating singularities are, respectively, illustrated using the 1,2,3,4{sup 1}A states of phenol and the 1,2{sup 1}A states of NH{sub 3}, states which are coupled by conical intersections.« less

4D display of the outflow track of embryonic-chick hearts (HH 14-19) using a high speed streak mode OCT

NASA Astrophysics Data System (ADS)

Ma, Siyu; Wang, Rui; Goodwin, Richard L.; Markwald, Roger R.; Borg, Thomas K.; Runyan, Raymond B.; Gao, Zhi

2013-02-01

Congenital Heart Disease (CHD) is the most common congenital malformation in newborns in the US. Although knowledge of CHD is limited, altered hemodynamic conditions are suspected as the factor that stimulates cardiovascular cell response, resulting in the heart morphology remodeling that ultimately causes CHDs. Therefore, one of recent efforts in CHD study is to develop high-speed imaging tools to correlate the rapidly changing hemodynamic condition and the morphological adaptations of an embryonic heart in vivo. We have developed a high-speed streak mode OCT that works at the center wavelength of 830 nm and is capable of providing images (292x220 μm2) of the outflow tract of an embryonic chick heart at the rate of 1000 Hz. The modality can provide a voxel resolution in the range of 10 μm3, and the spectral resolution allows a depth range of 1.63 mm. In the study reported here, each of the 4D images of an outflow tract was recorded for 2 seconds. The recording was conducted every 2 hours (HH17 to HH18), 3 hours (HH14 to HH17), and 4 hours (HH18 to HH19). Because of the fast scan speed, there is no need for postacquisition processing such as use of gating techniques to provide a fine 3D structure. In addition, more details of the outflow tract are preserved in the recorded images. The 4D images can be used in the future to determine the role of blood flow in CHD development.

The Baltic Sea as a time machine for the future coastal ocean

PubMed Central

Reusch, Thorsten B. H.; Andersson, Helen C.; Bonsdorff, Erik; Carstensen, Jacob; Kuosa, Harri; Laikre, Linda; Melzner, Frank; Oesterwind, Daniel; Sandström, Annica; Schwarz, Gerald; Winder, Monika; Zandersen, Marianne

2018-01-01

Coastal global oceans are expected to undergo drastic changes driven by climate change and increasing anthropogenic pressures in coming decades. Predicting specific future conditions and assessing the best management strategies to maintain ecosystem integrity and sustainable resource use are difficult, because of multiple interacting pressures, uncertain projections, and a lack of test cases for management. We argue that the Baltic Sea can serve as a time machine to study consequences and mitigation of future coastal perturbations, due to its unique combination of an early history of multistressor disturbance and ecosystem deterioration and early implementation of cross-border environmental management to address these problems. The Baltic Sea also stands out in providing a strong scientific foundation and accessibility to long-term data series that provide a unique opportunity to assess the efficacy of management actions to address the breakdown of ecosystem functions. Trend reversals such as the return of top predators, recovering fish stocks, and reduced input of nutrient and harmful substances could be achieved only by implementing an international, cooperative governance structure transcending its complex multistate policy setting, with integrated management of watershed and sea. The Baltic Sea also demonstrates how rapidly progressing global pressures, particularly warming of Baltic waters and the surrounding catchment area, can offset the efficacy of current management approaches. This situation calls for management that is (i) conservative to provide a buffer against regionally unmanageable global perturbations, (ii) adaptive to react to new management challenges, and, ultimately, (iii) multisectorial and integrative to address conflicts associated with economic trade-offs. PMID:29750199

The prospects of cellulase-producing bacteria for the bioconversion of lignocellulosic biomass.

PubMed

Maki, Miranda; Leung, Kam Tin; Qin, Wensheng

2009-07-29

Lignocellulosic biomass is a renewable and abundant resource with great potential for bioconversion to value-added bioproducts. However, the biorefining process remains economically unfeasible due to a lack of biocatalysts that can overcome costly hurdles such as cooling from high temperature, pumping of oxygen/stirring, and, neutralization from acidic or basic pH. The extreme environmental resistance of bacteria permits screening and isolation of novel cellulases to help overcome these challenges. Rapid, efficient cellulase screening techniques, using cellulase assays and metagenomic libraries, are a must. Rare cellulases with activities on soluble and crystalline cellulose have been isolated from strains of Paenibacillus and Bacillus and shown to have high thermostability and/or activity over a wide pH spectrum. While novel cellulases from strains like Cellulomonas flavigena and Terendinibacter turnerae, produce multifunctional cellulases with broader substrate utilization. These enzymes offer a framework for enhancement of cellulases including: specific activity, thermalstability, or end-product inhibition. In addition, anaerobic bacteria like the clostridia offer potential due to species capable of producing compound multienzyme complexes called cellulosomes. Cellulosomes provide synergy and close proximity of enzymes to substrate, increasing activity towards crystalline cellulose. This has lead to the construction of designer cellulosomes enhanced for specific substrate activity. Furthermore, cellulosome-producing Clostridium thermocellum and its ability to ferment sugars to ethanol; its amenability to co-culture and, recent advances in genetic engineering, offer a promising future in biofuels. The exploitation of bacteria in the search for improved enzymes or strategies provides a means to upgrade feasibility for lignocellulosic biomass conversion, ultimately providing means to a 'greener' technology.

The prospects of cellulase-producing bacteria for the bioconversion of lignocellulosic biomass

PubMed Central

Maki, Miranda; Leung, Kam Tin; Qin, Wensheng

2009-01-01

Lignocellulosic biomass is a renewable and abundant resource with great potential for bioconversion to value-added bioproducts. However, the biorefining process remains economically unfeasible due to a lack of biocatalysts that can overcome costly hurdles such as cooling from high temperature, pumping of oxygen/stirring, and, neutralization from acidic or basic pH. The extreme environmental resistance of bacteria permits screening and isolation of novel cellulases to help overcome these challenges. Rapid, efficient cellulase screening techniques, using cellulase assays and metagenomic libraries, are a must. Rare cellulases with activities on soluble and crystalline cellulose have been isolated from strains of Paenibacillus and Bacillus and shown to have high thermostability and/or activity over a wide pH spectrum. While novel cellulases from strains like Cellulomonas flavigena and Terendinibacter turnerae, produce multifunctional cellulases with broader substrate utilization. These enzymes offer a framework for enhancement of cellulases including: specific activity, thermalstability, or end-product inhibition. In addition, anaerobic bacteria like the clostridia offer potential due to species capable of producing compound multienzyme complexes called cellulosomes. Cellulosomes provide synergy and close proximity of enzymes to substrate, increasing activity towards crystalline cellulose. This has lead to the construction of designer cellulosomes enhanced for specific substrate activity. Furthermore, cellulosome-producing Clostridium thermocellum and its ability to ferment sugars to ethanol; its amenability to co-culture and, recent advances in genetic engineering, offer a promising future in biofuels. The exploitation of bacteria in the search for improved enzymes or strategies provides a means to upgrade feasibility for lignocellulosic biomass conversion, ultimately providing means to a 'greener' technology. PMID:19680472

Fossil Energy: Drivers and Challenges.

NASA Astrophysics Data System (ADS)

Friedmann, Julio

2007-04-01

Concerns about rapid economic growth, energy security, and global climate change have created a new landscape for fossil energy exploration, production, and utilization. Since 85% of primary energy supply comes from fossil fuels, and 85% of greenhouse gas emissions come from fossil fuel consumption, new and difficult technical and political challenges confront commercial, governmental, and public stakeholders. As such, concerns over climate change are explicitly weighed against security of international and domestic energy supplies, with economic premiums paid for either or both. Efficiency improvements, fuel conservation, and deployment of nuclear and renewable supplies will help both concerns, but are unlikely to offset growth in the coming decades. As such, new technologies and undertakings must both provide high quality fossil energy with minimal environmental impacts. The largest and most difficult of these undertakings is carbon management, wherein CO2 emissions are sequestered indefinitely at substantial incremental cost. Geological formations provide both high confidence and high capacity for CO2 storage, but present scientific and technical challenges. Oil and gas supply can be partially sustained and replaced through exploitation of unconventional fossil fuels such as tar-sands, methane hydrates, coal-to-liquids, and oil shales. These fuels provide enormous reserves that can be exploited at current costs, but generally require substantial energy to process. In most cases, the energy return on investment (EROI) is dropping, and unconventional fuels are generally more carbon intensive than conventional, presenting additional carbon management challenges. Ultimately, a large and sustained science and technology program akin to the Apollo project will be needed to address these concerns. Unfortunately, real funding in energy research has dropped dramatically (75%) in the past three decades, and novel designs in fission and fusion are not likely to provide any substantial offset in the next 30 years when they are most needed internationally.

Status of molten carbonate fuel cell technology development

NASA Astrophysics Data System (ADS)

Parsons, E. L., Jr.; Williams, M. C.; George, T. J.

The MCFC technology has been identified by the DOE as a promising product for commercialization. Development of the MCFC technology supports the National Energy Strategy. Review of the status of the MCFC technology indicates that the MCFC technology developers are making rapid and significant progress. Manufacturing facility development and extensive testing is occurring. Improvements in performance (power density), lower costs, improved packaging, and scale up to full height are planned. MCFC developers need to continue to be responsive to end-users in potential markets. It will be market demands for the correct product definition which will ultimately determine the character of MCFC power plants. There is a need for continued MCFC product improvement and multiple product development tests.

Penile necrosis secondary to purpura fulminans: a case report and review of literature.

PubMed

Hogarth, David B; Cheon, Paul M; Kassam, Javeed; Seal, Alexander E; Kavanagh, Alexander G

2017-02-01

We report the case of a 60-year-old Hispanic male with widespread necrotic purpuric lesions involving the penile, suprapubic, inguinal and hip dermis due to purpura fulminans. Purpura fulminans describes a rare syndrome involving intravascular thrombosis and hemorrhagic infarction of the skin; this rapidly progressing syndrome features vascular collapse and disseminated intravascular coagulation. This patient's penile necrosis involved the majority of the penile shaft and glans penis, and ultimately required partial glansectomy and repeated debridement for treatment. Subsequently, full thickness skin grafting was completed for reconstruction with good effect. While reports of penile necrosis secondary to various causes are documented in the literature, no prior reports describe penile necrosis secondary to purpura fulminans.

Activation of olefins via asymmetric Bronsted acid catalysis

DOE PAGES

Tsuji, Nobuya; Kennemur, Jennifer L.; Buyck, Thomas; ...

2018-03-30

The activation of olefins for asymmetric chemical synthesis traditionally relies on transition metal catalysts. In contrast, biological enzymes with Bronsted acidic sites of appropriate strength can protonate olefins and thereby generate carbocations that ultimately react to form natural products. Although chemists have recently designed chiral Bronsted acid catalysts to activate imines and carbonyl compounds, mimicking these enzymes to protonate simple olefins that then engage in asymmetric catalytic reactions has remained a substantial synthetic challenge. Here, we show that a class of confined and strong chiral Bronsted acids enables the catalytic asymmetric intramolecular hydroalkoxylation of unbiased olefins. In conclusion, the methodologymore » gives rapid access to biologically active 1,1-disubstituted tetrahydrofurans, including (–)-Boivinianin A.« less

The linac coherent light source single particle imaging road map

PubMed Central

Aquila, A.; Barty, A.; Bostedt, C.; Boutet, S.; Carini, G.; dePonte, D.; Drell, P.; Doniach, S.; Downing, K. H.; Earnest, T.; Elmlund, H.; Elser, V.; Gühr, M.; Hajdu, J.; Hastings, J.; Hau-Riege, S. P.; Huang, Z.; Lattman, E. E.; Maia, F. R. N. C.; Marchesini, S.; Ourmazd, A.; Pellegrini, C.; Santra, R.; Schlichting, I.; Schroer, C.; Spence, J. C. H.; Vartanyants, I. A.; Wakatsuki, S.; Weis, W. I.; Williams, G. J.

2015-01-01

Intense femtosecond x-ray pulses from free-electron laser sources allow the imaging of individual particles in a single shot. Early experiments at the Linac Coherent Light Source (LCLS) have led to rapid progress in the field and, so far, coherent diffractive images have been recorded from biological specimens, aerosols, and quantum systems with a few-tens-of-nanometers resolution. In March 2014, LCLS held a workshop to discuss the scientific and technical challenges for reaching the ultimate goal of atomic resolution with single-shot coherent diffractive imaging. This paper summarizes the workshop findings and presents the roadmap toward reaching atomic resolution, 3D imaging at free-electron laser sources. PMID:26798801

The linac coherent light source single particle imaging road map

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

Aquila, A.; Barty, A.; Bostedt, C.

Intense femtosecond x-ray pulses from free-electron laser sources allow the imaging of individual particles in a single shot. Early experiments at the Linac Coherent Light Source (LCLS) have led to rapid progress in the field and, so far, coherent diffractive images have been recorded from biological specimens, aerosols, and quantum systems with a few-tens-of-nanometers resolution. In March 2014, LCLS held a workshop to discuss the scientific and technical challenges for reaching the ultimate goal of atomic resolution with single-shot coherent diffractive imaging. This paper summarizes the workshop findings and presents the roadmap toward reaching atomic resolution, 3D imaging at free-electronmore » laser sources.« less

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

Greenberg, S.D.; Smith, S.; Swank, P.R.

Visual cell profiles were used to analyze the distribution of atypical bronchial cells in sputum specimens from cigarette-smoking volunteers, cigarette-smoking asbestos workers and cigarette-smoking uranium miners. The preliminary results of these sputum visual cell profile studies have demonstrated distinctive distributions of bronchial cell atypias in progressive patterns of squamous metaplasia, mild, moderate and severe atypias and carcinoma, similar to those the authors have previously reported using cell image analysis techniques to determine an atypia status index (ASI). The information gained from this study will be helpful in further validating this ASI and subsequently achieving the ultimate goal of employing cellmore » image analysis for the rapid and precise identification of premalignant atypias in sputum.« less

Activation of olefins via asymmetric Bronsted acid catalysis

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

Tsuji, Nobuya; Kennemur, Jennifer L.; Buyck, Thomas

The activation of olefins for asymmetric chemical synthesis traditionally relies on transition metal catalysts. In contrast, biological enzymes with Bronsted acidic sites of appropriate strength can protonate olefins and thereby generate carbocations that ultimately react to form natural products. Although chemists have recently designed chiral Bronsted acid catalysts to activate imines and carbonyl compounds, mimicking these enzymes to protonate simple olefins that then engage in asymmetric catalytic reactions has remained a substantial synthetic challenge. Here, we show that a class of confined and strong chiral Bronsted acids enables the catalytic asymmetric intramolecular hydroalkoxylation of unbiased olefins. In conclusion, the methodologymore » gives rapid access to biologically active 1,1-disubstituted tetrahydrofurans, including (–)-Boivinianin A.« less

Urey prize lecture: On the diversity of plausible planetary systems

NASA Technical Reports Server (NTRS)

Lissauer, J. J.

1995-01-01

Models of planet formation and of the orbital stability of planetary systems are used to predict the variety of planetary and satellite systems that may be present within our galaxy. A new approximate global criterion for orbital stability of planetary systems based on an extension of the local resonance overlap criterion is proposed. This criterion implies that at least some of Uranus' small inner moons are significantly less massive than predicted by estimates based on Voyager volumes and densities assumed to equal that of Miranda. Simple calculations (neglecting planetary gravity) suggest that giant planets which acrete substantial amounts of gas while their envelopes are extremely distended ultimately rotate rapidly in the prgrade direction.

Stereotactic ablative body radiotherapy combined with immunotherapy: present status and future perspectives.

PubMed

Rekers, N H; Troost, E G C; Zegers, C M L; Germeraad, W T V; Dubois, L J; Lambin, P

2014-10-01

Radiotherapy is along with surgery and chemotherapy one of the prime treatment modalities in cancer. It is applied in the primary, neoadjuvant as well as the adjuvant setting. Radiation techniques have rapidly evolved during the past decade enabling the delivery of high radiation doses, reducing side-effects in tumour-adjacent normal tissues. While increasing local tumour control, current and future efforts ought to deal with microscopic disease at a distance of the primary tumour, ultimately responsible for disease-progression. This review explores the possibility of bimodal treatment combining radiotherapy with immunotherapy. Copyright © 2014 Société française de radiothérapie oncologique (SFRO). Published by Elsevier SAS. All rights reserved.

Supervised Machine Learning for Population Genetics: A New Paradigm

PubMed Central

Schrider, Daniel R.; Kern, Andrew D.

2018-01-01

As population genomic datasets grow in size, researchers are faced with the daunting task of making sense of a flood of information. To keep pace with this explosion of data, computational methodologies for population genetic inference are rapidly being developed to best utilize genomic sequence data. In this review we discuss a new paradigm that has emerged in computational population genomics: that of supervised machine learning (ML). We review the fundamentals of ML, discuss recent applications of supervised ML to population genetics that outperform competing methods, and describe promising future directions in this area. Ultimately, we argue that supervised ML is an important and underutilized tool that has considerable potential for the world of evolutionary genomics. PMID:29331490

Water Intelligence and the Cyber-Infrastructure Revolution

NASA Astrophysics Data System (ADS)

Cline, D. W.

2015-12-01

As an intrinsic factor in national security, the global economy, food and energy production, and human and ecological health, fresh water resources are increasingly being considered by an ever-widening array of stakeholders. The U.S. intelligence community has identified water as a key factor in the Nation's security risk profile. Water industries are growing rapidly, and seek to revolutionize the role of water in the global economy, making water an economic value rather than a limitation on operations. Recent increased focus on the complex interrelationships and interdependencies between water, food, and energy signal a renewed effort to move towards integrated water resource management. Throughout all of this, hydrologic extremes continue to wreak havoc on communities and regions around the world, in some cases threatening long-term economic stability. This increased attention on water coincides with the "second IT revolution" of cyber-infrastructure (CI). The CI concept is a convergence of technology, data, applications and human resources, all coalescing into a tightly integrated global grid of computing, information, networking and sensor resources, and ultimately serving as an engine of change for collaboration, education and scientific discovery and innovation. In the water arena, we have unprecedented opportunities to apply the CI concept to help address complex water challenges and shape the future world of water resources - on both science and socio-economic application fronts. Providing actionable local "water intelligence" nationally or globally is now becoming feasible through high-performance computing, data technologies, and advanced hydrologic modeling. Further development on all of these fronts appears likely and will help advance this much-needed capability. Lagging behind are water observation systems, especially in situ networks, which need significant innovation to keep pace with and help fuel rapid advancements in water intelligence.

Plenario: An Open Data Discovery and Exploration Platform for Urban Science

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

Catlett, Charlie; Malik, Tanu; Goldstein, Brett J.

2014-12-01

The past decade has seen the widespread release of open data concerning city services, conditions, and activities by government bodies and public institutions of all sizes. Hundreds of open data portals now host thousands of datasets of many different types. These new data sources represent enormous po- tential for improved understanding of urban dynamics and processes—and, ultimately, for more livable, efficient, and prosperous communities. However, those who seek to realize this potential quickly discover that discovering and applying those data relevant to any particular question can be extraordinarily dif- ficult, due to decentralized storage, heterogeneous formats, and poor documentation. Inmore » this context, we introduce Plenario, a platform designed to automating time-consuming tasks associated with the discovery, exploration, and application of open city data—and, in so doing, reduce barriers to data use for researchers, policymakers, service providers, journalists, and members of the general public. Key innovations include a geospatial data warehouse that allows data from many sources to be registered into a common spatial and temporal frame; simple and intuitive interfaces that permit rapid discovery and exploration of data subsets pertaining to a particular area and time, regardless of type and source; easy export of such data subsets for further analysis; a user-configurable data ingest framework for automated importing and periodic updating of new datasets into the data warehouse; cloud hosting for elastic scaling and rapid creation of new Plenario instances; and an open source implementation to enable community contributions. We describe here the architecture and implementation of the Plenario platform, discuss lessons learned from its use by several communities, and outline plans for future work.« less

Testing of a Helium Loop Heat Pipe for Large Area Cryocooling

NASA Technical Reports Server (NTRS)

Ku, Jentung; Robinson, Franklin

2016-01-01

Future NASA space telescopes and exploration missions require cryocooling of large areas such as optics, detector arrays, and cryogenic propellant tanks. One device that can potentially be used to provide closed-loop cryocooling is the cryogenic loop heat pipe (CLHP). A CLHP has many advantages over other devices in terms of reduced mass, reduced vibration, high reliability, and long life. A helium CLHP has been tested extensively in a thermal vacuum chamber using a cryocooler as the heat sink to characterize its transient and steady performance and verify its ability to cool large areas or components in the 3K temperature range. A copper plate with attached electrical heaters was used to simulate the heat source, and heat was collected by the CLHP evaporator and transferred to the cryocooler for ultimate heat rejection. The helium CLHP thermal performance test included cool-down from the ambient temperature, startup, capillary limit, heat removal capability, rapid power changes, and long duration steady state operation. The helium CLHP demonstrated robust operation under steady state and transient conditions. The loop could be cooled from the ambient temperature to subcritical temperatures very effectively, and could start successfully without pre-conditioning by simply applying power to both the capillary pump and the evaporator plate. It could adapt to rapid changes in the heat load, and reach a new steady state very quickly. Heat removal between 10mW and 140mW was demonstrated, yielding a power turn down ratio of 14. When the CLHP capillary limit was exceeded, the loop could resume its normal function by reducing the power to the capillary pump. Steady state operations up to 17 hours at several heat loads were demonstrated. The ability of the helium CLHP to cool large areas was therefore successfully verified.

Testing of a Helium Loop Heat Pipe for Large Area Cryocooling

NASA Technical Reports Server (NTRS)

Ku, Jentung; Robinson, Franklin Lee

2015-01-01

Future NASA space telescopes and exploration missions require cryocooling of large areas such as optics, detector arrays, and cryogenic propellant tanks. One device that can potentially be used to provide closed-loop cryocooling is the cryogenic loop heat pipe (CLHP). A CLHP has many advantages over other devices in terms of reduced mass, reduced vibration, high reliability, and long life. A helium CLHP has been tested extensively in a thermal vacuum chamber using a cryocooler as the heat sink to characterize its transient and steady performance and verify its ability to cool large areas or components in the 3K temperature range. A copper plate with attached electrical heters was used to simulate the heat source, and heat was collected by the CLHP evaporator and transferred to the cryocooler for ultimate heat rejection. The helium CLHP thermal performance test included cool-down from the ambient temperature, startup, capillary limit, heat removal capability, rapid power changes, and long duration steady state operation. The helium CLHP demonstrated robust operation under steady state and transient conditions. The loop could be cooled from the ambient temperature to subcritical temperatures very effectively, and could start successfully without pre-conditioning by simply applying power to both the capillary pump and the evaporator plate. It could adapt to rapid changes in the heat load, and reach a new steady state very quickly. Heat removal between 10mW and 140mW was demonstrated, yielding a power turn down ratio of 14. When the CLHP capillary limit was exceeded, the loop could resume its normal function by reducing the power to the capillary pump. Steady state operations up to 17 hours at several heat loads were demonstrated. The ability of the helium CLHP to cool large areas was therefore successfully verified.

Assessing the Utility of a Satellite-Based Flood Inundation and Socio-Economic Impact Tool for the Lower Mekong River Basin

NASA Astrophysics Data System (ADS)

Ahamed, A.; Bolten, J. D.

2016-12-01

Flood disaster events in Southeast Asia result in significant loss of life and economic damage. Remote sensing information systems designed to monitor floods and assess their severity can help governments and international agencies formulate an effective response before and during flood events, and ultimately alleviate impacts to population, infrastructure, and agriculture. Recent examples of destructive flood events in the Lower Mekong River Basin occurred in 2000, 2011, and 2013. Floods can be particularly costly in the developing countries of Southeast Asia where large portions of the population live on or near the floodplain (Jonkman, 2005; Kirsch et al., 2012; Long and Trong, 2001; Stromberg. 2007). Regional studies (Knox, 1993; Mirza, 2002; Schiermeier, 2011; Västilä et al, 2010) and Intergovernmental Panel on Climate Change (IPCC, 2007) projections suggest that precipitation extremes and flood frequency are increasing. Thus, improved systems to rapidly monitor flooding in vulnerable areas are needed. This study determines surface water extent for current and historic flood events by using stacks of historic multispectral Moderate-resolution Imaging Spectroradiometer (MODIS) 250-meter imagery and the spectral Normalized Difference Vegetation Index (NDVI) signatures of permanent water bodies (MOD44W). Supporting software tools automatically assess flood impacts to population and infrastructure to provide a rapid first set of impact numbers generated hours after the onset of an event. The near real-time component uses twice daily imagery acquired at 3-hour latency, and performs image compositing routines to minimize cloud cover. Case studies for historic flood events are presented. Results suggest that near real-time remote sensing-based observation and impact assessment systems can serve as effective regional decision support tools for governments, international agencies, and disaster responders.

Management of Risks From Water and Ice From Ice Machines for the Very Immunocompromised Host: A Process Improvement Project Prompted by an Outbreak of Rapidly Growing Mycobacteria on a Pediatric Hematopoietic Stem Cell Transplant (Hsct) Unit.

PubMed

Guspiel, Amanda; Menk, Jeremiah; Streifel, Andrew; Messinger, Keith; Wagner, John; Ferrieri, Patricia; Kline, Susan

2017-07-01

BACKGROUND In 2011, pediatric hematopoietic stem cell transplant (HSCT) patients were moved from an older hospital to a new children's hospital. To minimize bacterial growth in the new hospital's water during construction, the plumbing system was flushed and disinfected before occupancy. However, 6 months after occupancy, an increased incidence of rapidly growing mycobacteria (RGM) was detected in clinical cultures. Over 10 months, 15 pediatric HSCT patients were infected, while no pediatric HSCT patients had been infected in the preceding 12 months. OBJECTIVE To determine the cause of the outbreak and to interrupt patient acquisition of RGM. METHODS Water samples were collected from water entering the hospital and from drinking water and ice machines (DWIMs) from the old and new hospitals. Total heterotrophic plate counts (HPCs, CFU/mL) of water were undertaken, and select isolates were identified as RGM. RESULTS The cause of the outbreak was increased bacterial levels in the water (including RGM) in the DWIMs in the new (2011) hospital. Tests revealed higher HPCs in drinking water and ice from the DWIMs in the new hospital than in the DWIMs in the old hospital. Ultimately, HPCs were reduced by several different interventions. CONCLUSION In response to an RGM outbreak, HSCT patients were banned from ingesting DWIM ice and water and bottled water was provided. Since this interverntion 4 years ago, no additional RGM isolates have been identified in HSCT patient cultures. Our measures to reduce HPCs to goal levels in drinking water from DWIMs were successful, but the HPCs for ice have not consistently reached the goal of <500 CFU/mL. Infect Control Hosp Epidemiol 2017;38:792-800.

Probing electron transfer mechanisms in Shewanella oneidensis MR-1 using a nanoelectrode platform and single-cell imaging

PubMed Central

Jiang, Xiaocheng; Hu, Jinsong; Fitzgerald, Lisa A.; Biffinger, Justin C.; Xie, Ping; Ringeisen, Bradley R.; Lieber, Charles M.

2010-01-01

Microbial fuel cells (MFCs) represent a promising approach for sustainable energy production as they generate electricity directly from metabolism of organic substrates without the need for catalysts. However, the mechanisms of electron transfer between microbes and electrodes, which could ultimately limit power extraction, remain controversial. Here we demonstrate optically transparent nanoelectrodes as a platform to investigate extracellular electron transfer in Shewanella oneidensis MR-1, where an array of nanoholes precludes or single window allows for direct microbe-electrode contacts. Following addition of cells, short-circuit current measurements showed similar amplitude and temporal response for both electrode configurations, while in situ optical imaging demonstrates that the measured currents were uncorrelated with the cell number on the electrodes. High-resolution imaging showed the presence of thin, 4- to 5-nm diameter filaments emanating from cell bodies, although these filaments do not appear correlated with current generation. Both types of electrodes yielded similar currents at longer times in dense cell layers and exhibited a rapid drop in current upon removal of diffusible mediators. Reintroduction of the original cell-free media yielded a rapid increase in current to ∼80% of original level, whereas imaging showed that the positions of > 70% of cells remained unchanged during solution exchange. Together, these measurements show that electron transfer occurs predominantly by mediated mechanism in this model system. Last, simultaneous measurements of current and cell positions showed that cell motility and electron transfer were inversely correlated. The ability to control and image cell/electrode interactions down to the single-cell level provide a powerful approach for advancing our fundamental understanding of MFCs. PMID:20837546

Plenario: A Spatio-Temporal Platform for Discovery and Exploration of Urban Science Data

NASA Astrophysics Data System (ADS)

Engler, W. H.; Malik, T.; Catlett, C.; Foster, I.; Goldstein, B.

2015-12-01

The past decade has seen the widespread release of open data concerning city services, conditions, and activities by government bodies and public institutions of all sizes. Hundreds of open data portals now host thousands of datasets of many different types. These new data sources represent enormous potential for improved understanding of urban dynamics and processes—and, ultimately, for more livable, efficient, and prosperous communities. However, those who seek to realize this potential quickly discover that discovering and applying those data relevant to any particular question can be extraordinarily difficult, due to decentralized storage, heterogeneous formats, and poor documentation. In this context, we introduce Plenario, a platform designed to automating time-consuming tasks associated with the discovery, exploration, and application of open city data—and, in so doing, reduce barriers to data use for researchers, policymakers, service providers, journalists, and members of the general public. Key innovations include a geospatial data warehouse that allows data from many sources to be registered into a common spatial and temporal frame; simple and intuitive interfaces that permit rapid discovery and exploration of data subsets pertaining to a particular area and time, regardless of type and source; easy export of such data subsets for further analysis; a user-configurable data ingest framework for automated importing and periodic updating of new datasets into the data warehouse; cloud hosting for elastic scaling and rapid creation of new Plenario instances; and an open source implementation to enable community contributions. We describe here the architecture and implementation of the Plenario platform, discuss lessons learned from its use by several communities, and outline plans for future work.

Cross-species pharmacokinetic comparison from mouse to man of a second-generation antisense oligonucleotide, ISIS 301012, targeting human apolipoprotein B-100.

PubMed

Yu, Rosie Z; Kim, Tae-Won; Hong, An; Watanabe, Tanya A; Gaus, Hans J; Geary, Richard S

2007-03-01

The pharmacokinetics of a 2'-O-(2-methoxyethyl)-modified oligonucleotide, ISIS 301012 [targeting human apolipoprotein B-100 (apoB-100)], was characterized in mouse, rat, monkey, and human. Plasma pharmacokinetics following parental administration was similar across species, exhibiting a rapid distribution phase with t(1/2alpha) of several hours and a prolonged elimination phase with t(1/2beta) of days. The prolonged elimination phase represents equilibrium between tissues and circulating drug due to slow elimination from tissues. Absorption was nearly complete following s.c. injection, with bioavailability ranging from 80 to 100% in monkeys. Plasma clearance scaled well across species as a function of body weight alone, and this correlation was improved when corrected for plasma protein binding. In all of the animal models studied, the highest tissue concentrations of ISIS 301012 were observed in kidney and liver. Urinary excretion was less than 3% in monkeys and human in the first 24 h. ISIS 301012 is highly bound to plasma proteins, probably preventing rapid removal by renal filtration. However, following 25 mg/kg s.c. administration in mouse and 5-mg/kg i.v. bolus administration in rat, plasma concentrations of ISIS 301012 exceeded their respective protein binding capacity. Thus, urinary excretion increased to 16% or greater within the first 24 h. Albeit slow, urinary excretion of ISIS 301012 and its shortened metabolites is the ultimate elimination pathway of this compound, as demonstrated by 32% of dose recovered in total excreta by 14 days in a rat mass balance study. The pharmacokinetics of ISIS 301012 in human is predictable from the pharmacokinetics measured in animals. The pharmacokinetic properties of ISIS 301012 provide guidance for clinical development and support infrequent dose administration.

Carbamoyl phosphate synthetase-1 is a rapid turnover biomarker in mouse and human acute liver injury.

PubMed

Weerasinghe, Sujith V W; Jang, You-Jin; Fontana, Robert J; Omary, M Bishr

2014-08-01

Several serum markers are used to assess hepatocyte damage, but they have limitations related to etiology specificity and prognostication. Identification of novel hepatocyte-specific biomarkers could provide important prognostic information and better pathogenesis classification. We tested the hypothesis that hepatocyte-selective biomarkers are released after subjecting isolated mouse hepatocytes to Fas-ligand-mediated apoptosis. Proteomic analysis of hepatocyte culture medium identified the mitochondrial matrix protein carbamoyl phosphate synthetase-1 (CPS1) among the most readily detected proteins that are released by apoptotic hepatocytes. CPS1 was also detected in mouse serum upon acute challenge with Fas-ligand or acetaminophen and in hepatocytes upon hypoosmotic stress, independent of hepatocyte caspase activation. Furthermore, CPS1 was observed in sera of mice chronically fed the hepatotoxin 3,5-diethoxycarbonyl-1,4-dihydrocollidine. Mouse CPS1 detectability was similar in serum and plasma, and its half-life was 126 ± 9 min. Immune staining showed that CPS1 localized to mouse hepatocytes but not ductal cells. Analysis of a few serum samples from patients with acute liver failure (ALF) due to acetaminophen, Wilson disease, or ischemia showed readily detectable CPS1 that was not observed in several patients with chronic viral hepatitis or in control donors. Notably, CPS1 rapidly decreased to undetectable levels in sera of patients with acetaminophen-related ALF who ultimately recovered, while alanine aminotransferase levels remained elevated. Therefore, CPS1 becomes readily detectable upon hepatocyte apoptotic and necrotic death in culture or in vivo. Its abundance and short serum half-life, compared with alanine aminotransferase, suggest that it may be a useful prognostic biomarker in human and mouse liver injury. Copyright © 2014 the American Physiological Society.

Interganglionic segregation of distinct vagal afferent fibre phenotypes in guinea-pig airways.

PubMed Central

Ricco, M M; Kummer, W; Biglari, B; Myers, A C; Undem, B J

1996-01-01

1. The present study addressed the hypothesis that jugular and nodose vagal ganglia contain the somata of functionally and anatomically distinct airway afferent fibres. 2. Anatomical investigations were performed by injecting guinea-pig airways with the neuronal tracer Fast Blue. The animals were killed 7 days later, and the ganglia were removed and immunostained with antisera against substance P (SP) and neurofilament protein (NF). In the nodose ganglion, NF-immunoreactive neurones accounted for about 98% of the Fast Blue-labelled cells while in the jugular ganglion they accounted for approximately 48%. SP and NF immunoreactivity was never (n = 100) observed in the same cell suggesting that the antisera labelled distinct populations. 3. Electrophysiological investigations were performed using an in vitro guinea-pig tracheal and bronchial preparation with intact afferent vagal pathways, including nodose and jugular ganglia. Action potentials arriving from single airway afferent nerve endings were monitored extracellularly using a glass microelectrode positioned near neuronal cell bodies in either ganglion. 4. The nodose ganglion contained the somata of mainly fast-conducting tracheal A delta fibres whereas the jugular ganglion contained equal numbers of C fibre and A delta fibre tracheal afferent somata. The nodose A delta neurones adapted rapidly to mechanical stimulation, had relatively low mechanical thresholds, were not activated by capsaicin and adapted rapidly to a hyperosmotic stimulus. By contrast, jugular A delta and C fibres adapted slowly to mechanical stimulation, were often activated by capsaicin, had higher mechanical thresholds and displayed a slow adaptation to a hyperosmotic stimulus. 5. The anatomical, physiological and pharmacological data provide evidence to support the contention that the vagal ganglionic source of the fibre supplying the airways ultimately dictates its neurochemical and physiological phenotype. Images Figure 1 PMID:8910234

Designer biomaterials for mechanobiology

NASA Astrophysics Data System (ADS)

Li, Linqing; Eyckmans, Jeroen; Chen, Christopher S.

2017-12-01

Biomaterials engineered with specific bioactive ligands, tunable mechanical properties and complex architecture have emerged as powerful tools to probe cell sensing and response to physical properties of their material surroundings, and ultimately provide designer approaches to control cell function.

Solar thermal aerosol flow reaction process

DOEpatents

Weimer, Alan W.; Dahl, Jaimee K.; Pitts, J. Roland; Lewandowski, Allan A.; Bingham, Carl; Tamburini, Joseph R.

2005-03-29

The present invention provides an environmentally beneficial process using concentrated sunlight to heat radiation absorbing particles to carry out highly endothermic gas phase chemical reactions ultimately resulting in the production of hydrogen or hydrogen synthesis gases.

76 FR 64327 - Office of Oceanic and Atmospheric Research Draft Strategic Plan

Federal Register 2010, 2011, 2012, 2013, 2014

2011-10-18

... science integrity. Ultimately, this plan provides the framework that OAR will use to deliver significant benefits to society while working to advance NOAA's mission of science, service, and stewardship. Dated...

Preliminary analysis of cost, value, and risk.

DOT National Transportation Integrated Search

2008-02-12

The U.S. Department of Transportation (USDOT) understands that access to emergency services provided by 9-1-1 in todays world of evolving technology will ultimately occur within a broader array of interconnected networks comprehensively supporting...

Risk manager formula for success: Influencing decision making.

PubMed

Midgley, Mike

2017-10-01

Providing the ultimate decision makers with a quantitative risk analysis based on thoughtful assessment by the organization's experts enables an efficient decision. © 2017 American Society for Healthcare Risk Management of the American Hospital Association.

Annual verifications--a tick-box exercise?

PubMed

Walker, Gwen; Williams, David

2014-09-01

With the onus on healthcare providers and their staff to protect patients against all elements of 'avoidable harm' perhaps never greater, Gwen Walker, a highly experienced infection prevention control nurse specialist, and David Williams, MD of Approved Air, who has 30 years' experience in validation and verification of ventilation and ultraclean ventilation systems, examine changing requirements for, and trends in, operating theatre ventilation. Validation and verification reporting on such vital HVAC equipment should not, they argue, merely be viewed as a 'tick-box exercise'; it should instead 'comprehensively inform key stakeholders, and ultimately form part of clinical governance, thus protecting those ultimately named responsible for organisation-wide safety at Trust board level'.

Approaches to resource recovery in controlled ecological life support systems

NASA Technical Reports Server (NTRS)

Bubenheim, D. L.; Wydeven, T.

1994-01-01

Recovery of resources from waste streams in a space habitat is essential to minimize the resupply burden and achieve self sufficiency. The ultimate goal of a Controlled Ecological Life Support System (CELSS) is to achieve the greatest practical level of mass recycle and provide self sufficiency and safety for humans. Several mission scenarios leading to the ultimate application could employ CELSS component technologies or subsystems with initial emphasis on recycle of the largest mass components of the waste stream. Candidate physical/chemical and biological processes for resource recovery from liquid and solid waste streams are discussed and the current fundamental recovery potentials are estimated.

Plastic and evolutionary responses to climate change in fish

PubMed Central

Crozier, Lisa G; Hutchings, Jeffrey A

2014-01-01

The physical and ecological ‘fingerprints’ of anthropogenic climate change over the past century are now well documented in many environments and taxa. We reviewed the evidence for phenotypic responses to recent climate change in fish. Changes in the timing of migration and reproduction, age at maturity, age at juvenile migration, growth, survival and fecundity were associated primarily with changes in temperature. Although these traits can evolve rapidly, only two studies attributed phenotypic changes formally to evolutionary mechanisms. The correlation-based methods most frequently employed point largely to ‘fine-grained’ population responses to environmental variability (i.e. rapid phenotypic changes relative to generation time), consistent with plastic mechanisms. Ultimately, many species will likely adapt to long-term warming trends overlaid on natural climate oscillations. Considering the strong plasticity in all traits studied, we recommend development and expanded use of methods capable of detecting evolutionary change, such as the long term study of selection coefficients and temporal shifts in reaction norms, and increased attention to forecasting adaptive change in response to the synergistic interactions of the multiple selection pressures likely to be associated with climate change. PMID:24454549

Transient lattice contraction in the solid to plasma transition of x-ray heated xenon clusters

NASA Astrophysics Data System (ADS)

Bostedt, C.; Ferguson, K.; Gorkhover, T.; Bucksbaum, P. H.; Boutet, S.; Koglin, J. E.; Lutman, A.; Marinelli, A.; Turner, J.; Bucher, M.; Ho, P.; Knight, C.; Young, L.; Fukuzawa, H.; Kumagai, Y.; Ueda, K.; Nagaya, K.; Messerschmidt, M.; Williams, G.

2016-05-01

Any sample in the focus of intense x-ray pulses will be transformed into a nanoplasma within femtoseconds. We have employed the novel two-color two-pulse mode available at the Linac Coherent Light Source free-electron laser to investigate the structural dynamics in nanoparticles upon x-ray exposure. We find that the nanoparticle transiently contracts within the first 80 fs following x-ray irradiation before ultimately disintegrating in a rapid hydrodynamic expansion. The contraction can be attributed to the massive x-ray induced electronic excitation that induces a collective change in the bond character of the nanoparticles. Alternative explanations for the contraction include a compression wave stemming from a rapid surface explosion of the nanoparticle. Computer simulations under way can elucidate the dominant contraction mechanism and yield further insight into the complex x-ray induced dynamics in nanoscale samples. This work is funded by the U.S. Department of Energy, Office of Science, Office of Basic Energy Sciences, Division of Chemical Sciences, Geosciences, and Biosciences, under Contract No. DE-AC02-06CH11357.

Strontium administration in young chickens improves bone volume and architecture but does not enhance bone structural and material strength.

PubMed

Shahnazari, M; Lang, D H; Fosmire, G J; Sharkey, N A; Mitchell, A D; Leach, R M

2007-03-01

Genetic selection for rapid body growth in broiler chickens has resulted in adverse effects on the skeletal system exemplified by a higher rate of cortical fractures in leg bones. Strontium (Sr) has been reported to have beneficial effects on bone formation and strength. We supplemented the diet of 300-day-old chicks with increasing dosages of Sr (0%, 0.12%, or 0.24%) to study the capacity of the element to improve bone quality and mechanical integrity. Treatment with Sr increased cortical bone volume and reduced bone porosity as measured by micro-computed tomography. The higher level of Sr significantly reduced bone Ca content (34.7%) relative to controls (37.2%), suggesting that Sr replaced some of the Ca in bone. Material properties determined by the three-point bending test showed that bone in the Sr-treated groups withstood greater deformation prior to fracture. Load to failure and ultimate stress were similar across groups. Our results indicate that Sr treatment in rapidly growing chickens induced positive effects on bone volume but did not improve the breaking strength of long bones.

Effect of rigor temperature, ageing and display time on the meat quality and lipid oxidative stability of hot boned beef Semimembranosus muscle.

PubMed

Mungure, Tanyaradzwa E; Bekhit, Alaa El-Din A; Birch, E John; Stewart, Ian

2016-04-01

The effects of rigor temperature (5, 15, 20 and 25°C), ageing (3, 7, 14, and 21 days) and display time on meat quality and lipid oxidative stability of hot boned beef M. Semimembranosus (SM) muscle were investigated. Ultimate pH (pH(u)) was rapidly attained at higher rigor temperatures. Electrical conductivity increased with rigor temperature (p<0.001). Tenderness, purge and cooking losses were not affected by rigor temperature; however purge loss and tenderness increased with ageing (p<0.01). Lightness (L*) and redness (a*) of the SM increased as rigor temperature increased (p<0.01). Lipid oxidation was assessed using (1)H NMR where changes in aliphatic to olefinic (R(ao)) and diallylmethylene (R(ad)) proton ratios can be rapidly monitored. R(ad), R(ao), PUFA and TBARS were not affected by rigor temperature, however ageing and display increased lipid oxidation (p<0.05). This study shows that rigor temperature manipulation of hot boned beef SM muscle does not have adverse effects on lipid oxidation. Copyright © 2016 Elsevier Ltd. All rights reserved.

Plastic and evolutionary responses to climate change in fish.

PubMed

Crozier, Lisa G; Hutchings, Jeffrey A

2014-01-01

The physical and ecological 'fingerprints' of anthropogenic climate change over the past century are now well documented in many environments and taxa. We reviewed the evidence for phenotypic responses to recent climate change in fish. Changes in the timing of migration and reproduction, age at maturity, age at juvenile migration, growth, survival and fecundity were associated primarily with changes in temperature. Although these traits can evolve rapidly, only two studies attributed phenotypic changes formally to evolutionary mechanisms. The correlation-based methods most frequently employed point largely to 'fine-grained' population responses to environmental variability (i.e. rapid phenotypic changes relative to generation time), consistent with plastic mechanisms. Ultimately, many species will likely adapt to long-term warming trends overlaid on natural climate oscillations. Considering the strong plasticity in all traits studied, we recommend development and expanded use of methods capable of detecting evolutionary change, such as the long term study of selection coefficients and temporal shifts in reaction norms, and increased attention to forecasting adaptive change in response to the synergistic interactions of the multiple selection pressures likely to be associated with climate change.

Engineered nanoconstructs for the multiplexed and sensitive detection of high-risk pathogens

NASA Astrophysics Data System (ADS)

Seo, Youngmin; Kim, Ji-Eun; Jeong, Yoon; Lee, Kwan Hong; Hwang, Jangsun; Hong, Jongwook; Park, Hansoo; Choi, Jonghoon

2016-01-01

Many countries categorize the causative agents of severe infectious diseases as high-risk pathogens. Given their extreme infectivity and potential to be used as biological weapons, a rapid and sensitive method for detection of high-risk pathogens (e.g., Bacillus anthracis, Francisella tularensis, Yersinia pestis, and Vaccinia virus) is highly desirable. Here, we report the construction of a novel detection platform comprising two units: (1) magnetic beads separately conjugated with multiple capturing antibodies against four different high-risk pathogens for simple and rapid isolation, and (2) genetically engineered apoferritin nanoparticles conjugated with multiple quantum dots and detection antibodies against four different high-risk pathogens for signal amplification. For each high-risk pathogen, we demonstrated at least 10-fold increase in sensitivity compared to traditional lateral flow devices that utilize enzyme-based detection methods. Multiplexed detection of high-risk pathogens in a sample was also successful by using the nanoconstructs harboring the dye molecules with fluorescence at different wavelengths. We ultimately envision the use of this novel nanoprobe detection platform in future applications that require highly sensitive on-site detection of high-risk pathogens.

Rapid trench initiated recrystallization and stagnation in narrow Cu interconnect lines

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

O'Brien, Brendan B.; Rizzolo, Michael; Prestowitz, Luke C.

2015-10-26

Understanding and ultimately controlling the self-annealing of Cu in narrow interconnect lines has remained a top priority in order to continue down-scaling of back-end of the line interconnects. Recently, it was hypothesized that a bottom-up microstructural transformation process in narrow interconnect features competes with the surface-initiated overburden transformation. Here, a set of transmission electron microscopy images which captures the grain coarsening process in 48 nm lines in a time resolved manner is presented, supporting such a process. Grain size measurements taken from these images have demonstrated that the Cu microstructural transformation in 48 nm interconnect lines stagnates after only 1.5 h atmore » room temperature. This stubborn metastable structure remains stagnant, even after aggressive elevated temperature anneals, suggesting that a limited internal energy source such as dislocation content is driving the transformation. As indicated by the extremely low defect density found in 48 nm trenches, a rapid recrystallization process driven by annihilation of defects in the trenches appears to give way to a metastable microstructure in the trenches.« less

At-Risk Preschool Children: Establishing Developmental Ranges That Suggest At-Promise

ERIC Educational Resources Information Center

McGee, Lea M.; Dail, Alanna Rochelle

2013-01-01

The Early Reading First (ERF) program provided grants to transform preschools into centers of education excellence with the ultimate goal of preventing later reading difficulties (No Child Left Behind Act of 2001). The intent of ERF grants was to provide preschoolers with the necessary cognitive, early language, and literacy skills for success in…

The carrot genome provides insights into crop origins and a foundation for future crop improvement

USDA-ARS?s Scientific Manuscript database

The sequencing of the carrot genome was an effort that formally began in 2012 and culminated with the publication and release of the genome in 2016. A full genome sequence provides the ultimate foundation to study genetics, gene function, and evolution of a species. The primary goal of the carrot ge...

The effect of rapid and sustained decompression on barotrauma in juvenile brook lamprey and Pacific lamprey: implications for passage at hydroelectric facilities

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

Colotelo, Alison HA; Pflugrath, Brett D.; Brown, Richard S.

Fish passing downstream through hydroelectric facilities may pass through hydroturbines where they experience a rapid decrease in barometric pressure as they pass by turbine blades, which can lead to barotraumas including swim bladder rupture, exopthalmia, emboli, and hemorrhaging. In juvenile Chinook salmon, the main mechanism for injury is thought to be expansion of existing gases (particularly those present in the swim bladder) and the rupture of the swim bladder ultimately leading to exopthalmia, emboli and hemorrhaging. In fish that lack a swim bladder, such as lamprey, the rate and severity of barotraumas due to rapid decompression may be reduced however;more » this has yet to be extensively studied. Another mechanism for barotrauma can be gases coming out of solution and the rate of this occurrence may vary among species. In this study, juvenile brook and Pacific lamprey acclimated to 146.2 kPa (equivalent to a depth of 4.6 m) were subjected to rapid (<1 sec; brook lamprey only) or sustained decompression (17 minutes) to a very low pressure (13.8 kPa) using a protocol previously applied to juvenile Chinook salmon. No mortality or evidence of barotraumas, as indicated by the presence of hemorrhages, emboli or exopthalmia, were observed during rapid or sustained decompression, nor following recovery for up to 120 h following sustained decompression. In contrast, mortality or injury would be expected for 97.5% of juvenile Chinook salmon exposed to a similar rapid decompression to these very low pressures. Additionally, juvenile Chinook salmon experiencing sustained decompression died within 7 minutes, accompanied by emboli in the fins and gills and hemorrhaging in the tissues. Thus, juvenile lamprey may not be susceptible to barotraumas associated with hydroturbine passage to the same degree as juvenile salmonids, and management of these species should be tailored to their specific morphological and physiological characteristics.« less

New ORNL Method Could Unleash Solar Power Potential

ScienceCinema

Simpson, Mary Jane

2018-01-16

Measurement and data analysis techniques developed at the Department of Energy’s Oak Ridge National Laboratory could provide new insight into performance-robbing flaws in crystalline structures, ultimately improving the performance of solar cells.

Halaven® - eribulin mesylate (analog of halichondrin B) | NCI Technology Transfer Center | TTC

Cancer.gov

Under a CRADA with NCI, Eisai Co. provided eribulin for NCI's preclinical development activities and to support NCI's Phase I clinical trials. Eisai ultimately took the product, Halaven®, to licensure.

ASTM METHODS

EPA Science Inventory

ASTM is a not-for-profit organization that provides a forum for producers, users, ultimate consumers, and those having a general interest (representatives of government and academia) to meet on common ground and write standards for materials, products, systems, and services. From...

Leadership Criteria under Maximum Performance Conditions

DTIC Science & Technology

2011-03-01

other a priori psychological constructs investigated across the maximum and typical performance continuum (Scholtz & Schuler, 1993). While many...reviewed by three trained subject matter experts to ultimately determine a psychological dimension that appropriately captured each input provided. The

The Economic Burden of Malnutrition in Pregnant Women and Children under 5 Years of Age in Cambodia

PubMed Central

Moench-Pfanner, Regina; Silo, Sok; Laillou, Arnaud; Wieringa, Frank; Hong, Rathamony; Hong, Rathavuth; Poirot, Etienne; Bagriansky, Jack

2016-01-01

Malnutrition is locked in a vicious cycle of increased mortality, poor health, impaired cognitive development, slow physical growth, reduced learning capacity, inferior performance, and ultimately lower adult work performance and productivity. The consensus of global scientific evidence indicates that lowering the rates of malnutrition will be an indispensable component of any successful program to raise the quality of human capital and resources. This study used a “consequence model” to apply the coefficient risk-deficit on economic losses, established in the global scientific literature, to Cambodian health, demographic, and economic data to develop a national estimate of the value of economic losses due to malnutrition. The impact of the indicators of malnutrition analyzed represent a burden to the national economy of Cambodia estimated at 266 million USD annually (1.7% of GDP). Stunting is reducing the Cambodian economic output by more than 120 million USD, and iodine deficiency disorders alone by 57 million USD. This economic burden is too high in view of Cambodia’s efforts to drive economic development. The government should rapidly expand a range of low-cost effective nutrition interventions to break the current cycle of increased mortality, poor health and ultimately lower work performance, productivity, and earnings. PMID:27187462

Importance of the rate of hydration of pharmaceutical preparations of guar gum; a new in vitro monitoring method.

PubMed

Ellis, P R; Morris, E R

1991-05-01

Dietary supplements of guar gum are known to improve blood glucose control in diabetic patients. The efficacy of guar is probably dependent mainly upon its capacity to hydrate rapidly and thus to increase viscosity in the small intestine post-prandially. Measurement of the rate of hydration in vitro might therefore be a useful index of the effectiveness of guar formulations. A simple method for monitoring the hydration rate of guar gum has been developed, which involves measuring the changes in viscosity at discrete time intervals over a period of 5 h using a Brookfield RVT rotoviscometer. Six different samples of guar gum (four pharmaceutical preparations and two food grades of guar flour) were hydrated in sealed glass jars rotated at 6 rev min-1 in order to prevent particle aggregation. Marked differences in hydration rate and ultimate (maximum) viscosity between the different guar samples were observed. Three of the four pharmaceutical preparations were lower in viscosity than the food grades of guar flour during the first 60 min of hydration. Two of the preparations hydrated so slowly that even after 5 h they attained viscosity levels of only 60% of their ultimate viscosity. These results may explain why some guar gum preparations are clinically ineffective.

Monitoring the effect of poplar trees on petroleum-hydrocarbon and chlorinated-solvent contaminated ground water

USGS Publications Warehouse

Landmeyer, James E.

2001-01-01

At contaminated groundwater sites, poplar trees can be used to affect ground-water levels, flow directions, and ultimately total groundwater and contaminant flux to areas downgradient of the trees. The magnitude of the hydrologic changes can be monitored using fundamental concepts of groundwater hydrology, in addition to plant physiology-based approaches, and can be viewed as being almost independent of the contaminant released. The affect of poplar trees on the fate of groundwater contaminants, however, is contaminant dependent. Some petroleum hydrocarbons or chlorinated solvents may be mineralized or transformed to innocuous compounds by rhizospheric bacteria associated with the tree roots, mineralized or transformed by plant tissues in the transpiration stream or leaves after uptake, or passively volatilized and rapidly dispersed or oxidized in the atmosphere. These processes also can be monitored using a combination of physiological- or geochemical-based field or laboratory approaches. When combined, such hydrologic and contaminant monitoring approaches can result in a more accurate assessment of the use of poplar trees to meet regulatory goals at contaminated groundwater sites, verify that these goals continue to be met in the future, and ultimately lead to a consensus on how the performance of plant-based remedial strategies (phytoremediation) is to be assessed.

Coarse-grained molecular dynamics simulations of the tensile behavior of a thermosetting polymer.

PubMed

Yang, Shaorui; Qu, Jianmin

2014-07-01

Using a previously developed coarse-grained model, we conducted large-scale (∼ 85 × 85 × 85 nm(3)) molecular dynamics simulations of uniaxial-strain deformation to study the tensile behavior of an epoxy molding compound, epoxy phenol novolacs (EPN) bisphenol A (BPA). Under the uniaxial-strain deformation, the material is found to exhibit cavity nucleation and growth, followed by stretching of the ligaments separated by the cavities, until the ultimate failure through ligament scissions. The nucleation sites of cavities are rather random and the subsequent cavity growth accounts for much (87%) of the volumetric change during the uniaxial-strain deformation. Ultimate failure of the materials occurs when the cavity volume fraction reaches ∼ 60%. During the entire deformation process, polymer strands in the network are continuously extended to their linear states and broken in the postyielding strain hardening stage. When most of the strands are stretched to their taut configurations, rapid scission of a large number of strands occurs within a small strain increment, which eventually leads to fracture. Finally, through extensive numerical simulations of various loading conditions in addition to uniaxial strain, we find that yielding of the EPN-BPA can be described by the pressure-modified von Mises yield criterion.

The Economic Burden of Malnutrition in Pregnant Women and Children under 5 Years of Age in Cambodia.

PubMed

Moench-Pfanner, Regina; Silo, Sok; Laillou, Arnaud; Wieringa, Frank; Hong, Rathamony; Hong, Rathavuth; Poirot, Etienne; Bagriansky, Jack

2016-05-14

Malnutrition is locked in a vicious cycle of increased mortality, poor health, impaired cognitive development, slow physical growth, reduced learning capacity, inferior performance, and ultimately lower adult work performance and productivity. The consensus of global scientific evidence indicates that lowering the rates of malnutrition will be an indispensable component of any successful program to raise the quality of human capital and resources. This study used a "consequence model" to apply the coefficient risk-deficit on economic losses, established in the global scientific literature, to Cambodian health, demographic, and economic data to develop a national estimate of the value of economic losses due to malnutrition. The impact of the indicators of malnutrition analyzed represent a burden to the national economy of Cambodia estimated at 266 million USD annually (1.7% of GDP). Stunting is reducing the Cambodian economic output by more than 120 million USD, and iodine deficiency disorders alone by 57 million USD. This economic burden is too high in view of Cambodia's efforts to drive economic development. The government should rapidly expand a range of low-cost effective nutrition interventions to break the current cycle of increased mortality, poor health and ultimately lower work performance, productivity, and earnings.

Coarse-grained molecular dynamics simulations of the tensile behavior of a thermosetting polymer

NASA Astrophysics Data System (ADS)

Yang, Shaorui; Qu, Jianmin

2014-07-01

Using a previously developed coarse-grained model, we conducted large-scale (˜85×85×85nm3) molecular dynamics simulations of uniaxial-strain deformation to study the tensile behavior of an epoxy molding compound, epoxy phenol novolacs (EPN) bisphenol A (BPA). Under the uniaxial-strain deformation, the material is found to exhibit cavity nucleation and growth, followed by stretching of the ligaments separated by the cavities, until the ultimate failure through ligament scissions. The nucleation sites of cavities are rather random and the subsequent cavity growth accounts for much (87%) of the volumetric change during the uniaxial-strain deformation. Ultimate failure of the materials occurs when the cavity volume fraction reaches ˜60%. During the entire deformation process, polymer strands in the network are continuously extended to their linear states and broken in the postyielding strain hardening stage. When most of the strands are stretched to their taut configurations, rapid scission of a large number of strands occurs within a small strain increment, which eventually leads to fracture. Finally, through extensive numerical simulations of various loading conditions in addition to uniaxial strain, we find that yielding of the EPN-BPA can be described by the pressure-modified von Mises yield criterion.

Directional reversals enable Myxococcus xanthus cells to produce collective one-dimensional streams during fruiting-body formation

PubMed Central

Thutupalli, Shashi; Sun, Mingzhai; Bunyak, Filiz; Palaniappan, Kannappan; Shaevitz, Joshua W.

2015-01-01

The formation of a collectively moving group benefits individuals within a population in a variety of ways. The surface-dwelling bacterium Myxococcus xanthus forms dynamic collective groups both to feed on prey and to aggregate during times of starvation. The latter behaviour, termed fruiting-body formation, involves a complex, coordinated series of density changes that ultimately lead to three-dimensional aggregates comprising hundreds of thousands of cells and spores. How a loose, two-dimensional sheet of motile cells produces a fixed aggregate has remained a mystery as current models of aggregation are either inconsistent with experimental data or ultimately predict unstable structures that do not remain fixed in space. Here, we use high-resolution microscopy and computer vision software to spatio-temporally track the motion of thousands of individuals during the initial stages of fruiting-body formation. We find that cells undergo a phase transition from exploratory flocking, in which unstable cell groups move rapidly and coherently over long distances, to a reversal-mediated localization into one-dimensional growing streams that are inherently stable in space. These observations identify a new phase of active collective behaviour and answer a long-standing open question in Myxococcus development by describing how motile cell groups can remain statistically fixed in a spatial location. PMID:26246416

In vivo MRI-based simulation of fatigue process: a possible trigger for human carotid atherosclerotic plaque rupture.

PubMed

Huang, Yuan; Teng, Zhongzhao; Sadat, Umar; He, Jing; Graves, Martin J; Gillard, Jonathan H

2013-04-23

Atherosclerotic plaque is subjected to a repetitive deformation due to arterial pulsatility during each cardiac cycle and damage may be accumulated over a time period causing fibrous cap (FC) fatigue, which may ultimately lead to rupture. In this study, we investigate the fatigue process in human carotid plaques using in vivo carotid magnetic resonance (MR) imaging. Twenty seven patients with atherosclerotic carotid artery disease were included in this study. Multi-sequence, high-resolution MR imaging was performed to depict the plaque structure. Twenty patients were found with ruptured FC or ulceration and 7 without. Modified Paris law was used to govern crack propagation and the propagation direction was perpendicular to the maximum principal stress at the element node located at the vulnerable site. The predicted crack initiations from 20 patients with FC defect all matched with the locations of the in vivo observed FC defect. Crack length increased rapidly with numerical steps. The natural logarithm of fatigue life decreased linearly with the local FC thickness (R(2) = 0.67). Plaques (n=7) without FC defect had a longer fatigue life compared with those with FC defect (p = 0.03). Fatigue process seems to explain the development of cracks in FC, which ultimately lead to plaque rupture.

Tentative civil airworthiness flight criteria for powered-lift transports

NASA Technical Reports Server (NTRS)

Hynes, C. S.; Scott, B. C.

1976-01-01

Representatives of the U.S., British, French, and Canadian airworthiness authorities participated in a NASA/FAA program to formulate tentative civil airworthiness flight criteria for powered-lift transports. The ultimate limits of the flight envelope are defined by boundaries in the airspeed/path-angle plane. Angle of attack and airspeed margins applied to these ultimate limits provide protection against both atmospheric disturbances and disturbances resulting from pilot actions or system variability, but do not ensure maneuvering capability directly, as the 30% speed margin does for conventional transports. Separate criteria provide for direct demonstration of adequate capability for approach path control, flare and landing, and for go-around. Demonstration maneuvers are proposed, and appropriate abuses and failures are suggested. Taken together, these criteria should permit selection of appropriate operating points within the flight envelopes for the approach, landing, and go-around flight phases which are likely to be most critical for powered-lift aircraft.

Modeling small cell lung cancer (SCLC) biology through deterministic and stochastic mathematical models.

PubMed

Salgia, Ravi; Mambetsariev, Isa; Hewelt, Blake; Achuthan, Srisairam; Li, Haiqing; Poroyko, Valeriy; Wang, Yingyu; Sattler, Martin

2018-05-25

Mathematical cancer models are immensely powerful tools that are based in part on the fractal nature of biological structures, such as the geometry of the lung. Cancers of the lung provide an opportune model to develop and apply algorithms that capture changes and disease phenotypes. We reviewed mathematical models that have been developed for biological sciences and applied them in the context of small cell lung cancer (SCLC) growth, mutational heterogeneity, and mechanisms of metastasis. The ultimate goal is to develop the stochastic and deterministic nature of this disease, to link this comprehensive set of tools back to its fractalness and to provide a platform for accurate biomarker development. These techniques may be particularly useful in the context of drug development research, such as combination with existing omics approaches. The integration of these tools will be important to further understand the biology of SCLC and ultimately develop novel therapeutics.

Continuum modelling of silicon diffusion in indium gallium arsenide

NASA Astrophysics Data System (ADS)

Aldridge, Henry Lee, Jr.

A possible method to overcome the physical limitations experienced by continued transistor scaling and continue improvements in performance and power consumption is integration of III-V semiconductors as alternative channel materials for logic devices. Indium Gallium Arsenide (InGaAs) is such a material from the III-V semiconductor family, which exhibit superior electron mobilities and injection velocities than that of silicon. In order for InGaAs integration to be realized, contact resistances must be minimized through maximizing activation of dopants in this material. Additionally, redistribution of dopants during processing must be clearly understood and ultimately controlled at the nanometer-scale. In this work, the activation and diffusion behavior of silicon, a prominent n-type dopant in InGaAs, has been characterized and subsequently modelled using the Florida Object Oriented Process and Device Simulator (FLOOPS). In contrast to previous reports, silicon exhibits non-negligible diffusion in InGaAs, even for smaller thermal budget rapid thermal anneals (RTAs). Its diffusion is heavily concentration-dependent, with broadening "shoulder-like" profiles when doping levels exceed 1-3x1019cm -3, for both ion-implanted and Molecular Beam Epitaxy (MBE)-grown cases. Likewise a max net-activation value of ˜1.7x1019cm -3 is consistently reached with enough thermal processing, regardless of doping method. In line with experimental results and several ab-initio calculation results, rapid concentration-dependent diffusion of Si in InGaAs and the upper limits of its activation is believed to be governed by cation vacancies that serve as compensating defects in heavily n-type regions of InGaAs. These results are ultimately in line with an amphoteric defect model, where the activation limits of dopants are an intrinsic limitation of the material, rather than governed by individual dopant species or their methods of incorporation. As a result a Fermi level dependent point defect diffusion model and activation limit model were subsequently developed in FLOOPS with outputs in good agreement with experimental results.

Biomarkers of susceptibility: State of the art and implications for occupational exposure to engineered nanomaterials.

PubMed

Iavicoli, Ivo; Leso, Veruscka; Schulte, Paul A

2016-05-15

Rapid advances and applications in nanotechnology are expected to result in increasing occupational exposure to nano-sized materials whose health impacts are still not completely understood. Scientific efforts are required to identify hazards from nanomaterials and define risks and precautionary management strategies for exposed workers. In this scenario, the definition of susceptible populations, which may be at increased risk of adverse effects may be important for risk assessment and management. The aim of this review is to critically examine available literature to provide a comprehensive overview on susceptibility aspects potentially affecting heterogeneous responses to nanomaterials workplace exposure. Genetic, genotoxic and epigenetic alterations induced by nanomaterials in experimental studies were assessed with respect to their possible function as determinants of susceptibility. Additionally, the role of host factors, i.e. age, gender, and pathological conditions, potentially affecting nanomaterial toxicokinetic and health impacts, were also analysed. Overall, this review provides useful information to obtain insights into the nanomaterial mode of action in order to identify potentially sensitive, specific susceptibility biomarkers to be validated in occupational settings and addressed in risk assessment processes. The findings of this review are also important to guide future research into a deeper characterization of nanomaterial susceptibility in order to define adequate risk communication strategies. Ultimately, identification and use of susceptibility factors in workplace settings has both scientific and ethical issues that need addressing. Copyright © 2015 Elsevier Inc. All rights reserved.

Identifying Corridors among Large Protected Areas in the United States

PubMed Central

Belote, R. Travis; Dietz, Matthew S.; McRae, Brad H.; Theobald, David M.; McClure, Meredith L.; Irwin, G. Hugh; McKinley, Peter S.; Gage, Josh A.; Aplet, Gregory H.

2016-01-01

Conservation scientists emphasize the importance of maintaining a connected network of protected areas to prevent ecosystems and populations from becoming isolated, reduce the risk of extinction, and ultimately sustain biodiversity. Keeping protected areas connected in a network is increasingly recognized as a conservation priority in the current era of rapid climate change. Models that identify suitable linkages between core areas have been used to prioritize potentially important corridors for maintaining functional connectivity. Here, we identify the most “natural” (i.e., least human-modified) corridors between large protected areas in the contiguous Unites States. We aggregated results from multiple connectivity models to develop a composite map of corridors reflecting agreement of models run under different assumptions about how human modification of land may influence connectivity. To identify which land units are most important for sustaining structural connectivity, we used the composite map of corridors to evaluate connectivity priorities in two ways: (1) among land units outside of our pool of large core protected areas and (2) among units administratively protected as Inventoried Roadless (IRAs) or Wilderness Study Areas (WSAs). Corridor values varied substantially among classes of “unprotected” non-core land units, and land units of high connectivity value and priority represent diverse ownerships and existing levels of protections. We provide a ranking of IRAs and WSAs that should be prioritized for additional protection to maintain minimal human modification. Our results provide a coarse-scale assessment of connectivity priorities for maintaining a connected network of protected areas. PMID:27104683

Biological pathways, candidate genes and molecular markers associated with quality-of-life domains: an update

PubMed Central

Sprangers, Mirjam A.G.; Thong, Melissa S.Y.; Bartels, Meike; Barsevick, Andrea; Ordoñana, Juan; Shi, Qiuling; Wang, Xin Shelley; Klepstad, Pål; Wierenga, Eddy A.; Singh, Jasvinder A.; Sloan, Jeff A.

2014-01-01

Background There is compelling evidence of a genetic foundation of patient-reported QOL. Given the rapid development of substantial scientific advances in this area of research, the current paper updates and extends reviews published in 2010. Objectives The objective is to provide an updated overview of the biological pathways, candidate genes and molecular markers involved in fatigue, pain, negative (depressed mood) and positive (well-being/happiness) emotional functioning, social functioning, and overall QOL. Methods We followed a purposeful search algorithm of existing literature to capture empirical papers investigating the relationship between biological pathways and molecular markers and the identified QOL domains. Results Multiple major pathways are involved in each QOL domain. The inflammatory pathway has the strongest evidence as a controlling mechanism underlying fatigue. Inflammation and neurotransmission are key processes involved in pain perception and the COMT gene is associated with multiple sorts of pain. The neurotransmitter and neuroplasticity theories have the strongest evidence for their relationship with depression. Oxytocin-related genes and genes involved in the serotonergic and dopaminergic pathways play a role in social functioning. Inflammatory pathways, via cytokines, also play an important role in overall QOL. Conclusions Whereas the current findings need future experiments and replication efforts, they will provide researchers supportive background information when embarking on studies relating candidate genes and/or molecular markers to QOL domains. The ultimate goal of this area of research is to enhance patients’ QOL. PMID:24604075

Identifying Corridors among Large Protected Areas in the United States.

PubMed

Belote, R Travis; Dietz, Matthew S; McRae, Brad H; Theobald, David M; McClure, Meredith L; Irwin, G Hugh; McKinley, Peter S; Gage, Josh A; Aplet, Gregory H

2016-01-01

Conservation scientists emphasize the importance of maintaining a connected network of protected areas to prevent ecosystems and populations from becoming isolated, reduce the risk of extinction, and ultimately sustain biodiversity. Keeping protected areas connected in a network is increasingly recognized as a conservation priority in the current era of rapid climate change. Models that identify suitable linkages between core areas have been used to prioritize potentially important corridors for maintaining functional connectivity. Here, we identify the most "natural" (i.e., least human-modified) corridors between large protected areas in the contiguous Unites States. We aggregated results from multiple connectivity models to develop a composite map of corridors reflecting agreement of models run under different assumptions about how human modification of land may influence connectivity. To identify which land units are most important for sustaining structural connectivity, we used the composite map of corridors to evaluate connectivity priorities in two ways: (1) among land units outside of our pool of large core protected areas and (2) among units administratively protected as Inventoried Roadless (IRAs) or Wilderness Study Areas (WSAs). Corridor values varied substantially among classes of "unprotected" non-core land units, and land units of high connectivity value and priority represent diverse ownerships and existing levels of protections. We provide a ranking of IRAs and WSAs that should be prioritized for additional protection to maintain minimal human modification. Our results provide a coarse-scale assessment of connectivity priorities for maintaining a connected network of protected areas.

Molecular typing of Sarcocystis neurona: current status and future trends.

PubMed

Elsheikha, Hany M; Mansfield, Linda S

2007-10-21

Sarcocystis neurona is an important protozoal pathogen because it causes the serious neurological disease equine protozoal myeloencephalitis (EPM). The capacity of this organism to cause a wide spectrum of neurological signs in horses and the broad geographic distribution of observed cases in the Americas drive the need for sensitive, reliable and rapid typing methods to characterize strains. Various molecular methods have been developed and used to diagnose EPM due to S. neurona, to identify S. neurona isolates and to determine the heterogeneity and evolutionary relatedness within this species and related Sarcocystis spp. These methods included sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE), immuno-fluorescent assay (IFA), slide agglutination test (SAT), SnSAG-specific ELISA, random amplified polymorphic DNA (RAPD), PCR-based restriction fragment length polymorphism (RFLP), amplified fragment length polymorphism (AFLP) fingerprinting, and sequence analysis of surface protein genes, ribosomal genes, microsatellite alleles and other molecular markers. Here, the utility of these molecular methods is reviewed and evaluated with respect to the need for molecular approaches that utilize well-characterized polymorphic, simple, independent, and stable genetic markers. These tools have the potential to add to knowledge of the genetic population structure of S. neurona and to provide new insights into the pathogenesis of EPM and S. neurona epidemiology. In particular, these methods provide new tools to address the hypothesis that particular genetic variants are associated with adverse clinical outcomes (severe pathotypes). The ultimate goal is to utilize them in future studies to improve treatment and prevention strategies.

Genome-wide characterization of differentially expressed genes provides insights into regulatory network of heat stress response in radish (Raphanus sativus L.).

PubMed

Wang, Ronghua; Mei, Yi; Xu, Liang; Zhu, Xianwen; Wang, Yan; Guo, Jun; Liu, Liwang

2018-03-01

Heat stress (HS) causes detrimental effects on plant morphology, physiology, and biochemistry that lead to drastic reduction in plant biomass production and economic yield worldwide. To date, little is known about HS-responsive genes involved in thermotolerance mechanism in radish. In this study, a total of 6600 differentially expressed genes (DEGs) from the control and Heat24 cDNA libraries of radish were isolated by high-throughput sequencing. With Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis, some genes including MAPK, DREB, ERF, AP2, GST, Hsf, and Hsp were predominantly assigned in signal transductions, metabolic pathways, and biosynthesis and abiotic stress-responsive pathways. These pathways played significant roles in reducing stress-induced damages and enhancing heat tolerance in radish. Expression patterns of 24 candidate genes were validated by reverse-transcription quantitative PCR (RT-qPCR). Based mainly on the analysis of DEGs combining with the previous miRNAs analysis, the schematic model of HS-responsive regulatory network was proposed. To counter the effects of HS, a rapid response of the plasma membrane leads to the opening of specific calcium channels and cytoskeletal reorganization, after which HS-responsive genes are activated to repair damaged proteins and ultimately facilitate further enhancement of thermotolerance in radish. These results could provide fundamental insight into the regulatory network underlying heat tolerance in radish and facilitate further genetic manipulation of thermotolerance in root vegetable crops.

Local Data Integration in East Central Florida

NASA Technical Reports Server (NTRS)

Case, Jonathan L.; Manobianco, John T.

1999-01-01

The Applied Meteorology Unit has configured a Local Data Integration System (LDIS) for east central Florida which assimilates in-situ and remotely-sensed observational data into a series of high-resolution gridded analyses. The ultimate goal for running LDIS is to generate products that may enhance weather nowcasts and short-range (less than 6 h) forecasts issued in support of the 45th Weather Squadron (45 WS), Spaceflight Meteorology Group (SMG), and the Melbourne National Weather Service (NWS MLB) operational requirements. LDIS has the potential to provide added value for nowcasts and short-ten-n forecasts for two reasons. First, it incorporates all data operationally available in east central Florida. Second, it is run at finer spatial and temporal resolutions than current national-scale operational models such as the Rapid Update Cycle and Eta models. LDIS combines all available data to produce grid analyses of primary variables (wind, temperature, etc.) at specified temporal and spatial resolutions. These analyses of primary variables can be used to compute diagnostic quantities such as vorticity and divergence. This paper demonstrates the utility of LDIS over east central Florida for a warm season case study. The evolution of a significant thunderstorm outflow boundary is depicted through horizontal and vertical cross section plots of wind speed, divergence, and circulation. In combination with a suitable visualization too], LDIS may provide users with a more complete and comprehensive understanding of evolving mesoscale weather than could be developed by individually examining the disparate data sets over the same area and time.

Engineering 3D bicontinuous hierarchically macro-mesoporous LiFePO4/C nanocomposite for lithium storage with high rate capability and long cycle stability

PubMed Central

Zhang, Qian; Huang, Shao-Zhuan; Jin, Jun; Liu, Jing; Li, Yu; Wang, Hong-En; Chen, Li-Hua; Wang, Bin-Jie; Su, Bao-Lian

2016-01-01

A highly crystalline three dimensional (3D) bicontinuous hierarchically macro-mesoporous LiFePO4/C nanocomposite constructed by nanoparticles in the range of 50~100 nm via a rapid microwave assisted solvothermal process followed by carbon coating have been synthesized as cathode material for high performance lithium-ion batteries. The abundant 3D macropores allow better penetration of electrolyte to promote Li+ diffusion, the mesopores provide more electrochemical reaction sites and the carbon layers outside LiFePO4 nanoparticles increase the electrical conductivity, thus ultimately facilitating reverse reaction of Fe3+ to Fe2+ and alleviating electrode polarization. In addition, the particle size in nanoscale can provide short diffusion lengths for the Li+ intercalation-deintercalation. As a result, the 3D macro-mesoporous nanosized LiFePO4/C electrode exhibits excellent rate capability (129.1 mA h/g at 2 C; 110.9 mA h/g at 10 C) and cycling stability (87.2% capacity retention at 2 C after 1000 cycles, 76.3% at 5 C after 500 cycles and 87.8% at 10 C after 500 cycles, respectively), which are much better than many reported LiFePO4/C structures. Our demonstration here offers the opportunity to develop nanoscaled hierarchically porous LiFePO4/C structures for high performance lithium-ion batteries through microwave assisted solvothermal method. PMID:27181195

Engineering 3D bicontinuous hierarchically macro-mesoporous LiFePO4/C nanocomposite for lithium storage with high rate capability and long cycle stability.

PubMed

Zhang, Qian; Huang, Shao-Zhuan; Jin, Jun; Liu, Jing; Li, Yu; Wang, Hong-En; Chen, Li-Hua; Wang, Bin-Jie; Su, Bao-Lian

2016-05-16

A highly crystalline three dimensional (3D) bicontinuous hierarchically macro-mesoporous LiFePO4/C nanocomposite constructed by nanoparticles in the range of 50~100 nm via a rapid microwave assisted solvothermal process followed by carbon coating have been synthesized as cathode material for high performance lithium-ion batteries. The abundant 3D macropores allow better penetration of electrolyte to promote Li(+) diffusion, the mesopores provide more electrochemical reaction sites and the carbon layers outside LiFePO4 nanoparticles increase the electrical conductivity, thus ultimately facilitating reverse reaction of Fe(3+) to Fe(2+) and alleviating electrode polarization. In addition, the particle size in nanoscale can provide short diffusion lengths for the Li(+) intercalation-deintercalation. As a result, the 3D macro-mesoporous nanosized LiFePO4/C electrode exhibits excellent rate capability (129.1 mA h/g at 2 C; 110.9 mA h/g at 10 C) and cycling stability (87.2% capacity retention at 2 C after 1000 cycles, 76.3% at 5 C after 500 cycles and 87.8% at 10 C after 500 cycles, respectively), which are much better than many reported LiFePO4/C structures. Our demonstration here offers the opportunity to develop nanoscaled hierarchically porous LiFePO4/C structures for high performance lithium-ion batteries through microwave assisted solvothermal method.

Bookshelf: a simple curation system for the storage of biomolecular simulation data.

PubMed

Vohra, Shabana; Hall, Benjamin A; Holdbrook, Daniel A; Khalid, Syma; Biggin, Philip C

2010-01-01

Molecular dynamics simulations can now routinely generate data sets of several hundreds of gigabytes in size. The ability to generate this data has become easier over recent years and the rate of data production is likely to increase rapidly in the near future. One major problem associated with this vast amount of data is how to store it in a way that it can be easily retrieved at a later date. The obvious answer to this problem is a database. However, a key issue in the development and maintenance of such a database is its sustainability, which in turn depends on the ease of the deposition and retrieval process. Encouraging users to care about meta-data is difficult and thus the success of any storage system will ultimately depend on how well used by end-users the system is. In this respect we suggest that even a minimal amount of metadata if stored in a sensible fashion is useful, if only at the level of individual research groups. We discuss here, a simple database system which we call 'Bookshelf', that uses python in conjunction with a mysql database to provide an extremely simple system for curating and keeping track of molecular simulation data. It provides a user-friendly, scriptable solution to the common problem amongst biomolecular simulation laboratories; the storage, logging and subsequent retrieval of large numbers of simulations. Download URL: http://sbcb.bioch.ox.ac.uk/bookshelf/

Bookshelf: a simple curation system for the storage of biomolecular simulation data

PubMed Central

Vohra, Shabana; Hall, Benjamin A.; Holdbrook, Daniel A.; Khalid, Syma; Biggin, Philip C.

2010-01-01

Molecular dynamics simulations can now routinely generate data sets of several hundreds of gigabytes in size. The ability to generate this data has become easier over recent years and the rate of data production is likely to increase rapidly in the near future. One major problem associated with this vast amount of data is how to store it in a way that it can be easily retrieved at a later date. The obvious answer to this problem is a database. However, a key issue in the development and maintenance of such a database is its sustainability, which in turn depends on the ease of the deposition and retrieval process. Encouraging users to care about meta-data is difficult and thus the success of any storage system will ultimately depend on how well used by end-users the system is. In this respect we suggest that even a minimal amount of metadata if stored in a sensible fashion is useful, if only at the level of individual research groups. We discuss here, a simple database system which we call ‘Bookshelf’, that uses python in conjunction with a mysql database to provide an extremely simple system for curating and keeping track of molecular simulation data. It provides a user-friendly, scriptable solution to the common problem amongst biomolecular simulation laboratories; the storage, logging and subsequent retrieval of large numbers of simulations. Download URL: http://sbcb.bioch.ox.ac.uk/bookshelf/ PMID:21169341

Unsteady boundary layer development on a wind turbine blade: an experimental study of a surrogate problem

NASA Astrophysics Data System (ADS)

Cadel, Daniel R.; Zhang, Di; Lowe, K. Todd; Paterson, Eric G.

2018-04-01

Wind turbines with thick blade profiles experience turbulent, periodic approach flow, leading to unsteady blade loading and large torque fluctuations on the turbine drive shaft. Presented here is an experimental study of a surrogate problem representing some key aspects of the wind turbine unsteady fluid mechanics. This experiment has been designed through joint consideration by experiment and computation, with the ultimate goal of numerical model development for aerodynamics in unsteady and turbulent flows. A cylinder at diameter Reynolds number of 65,000 and Strouhal number of 0.184 is placed 10.67 diameters upstream of a NACA 63215b airfoil with chord Reynolds number of 170,000 and chord-reduced frequency of k=2π fc/2/V=1.5. Extensive flow field measurements using particle image velocimetry provide a number of insights about this flow, as well as data for model validation and development. Velocity contours on the airfoil suction side in the presence of the upstream cylinder indicate a redistribution of turbulent normal stresses from transverse to streamwise, consistent with rapid distortion theory predictions. A study of the boundary layer over the suction side of the airfoil reveals very low Reynolds number turbulent mean streamwise velocity profiles. The dominance of the high amplitude large eddy passages results in a phase lag in streamwise velocity as a function of distance from the wall. The results and accompanying description provide a new test case incorporating moderate-reduced frequency inflow for computational model validation and development.

Liquid crystal waveguides: new devices enabled by >1000 waves of optical phase control

NASA Astrophysics Data System (ADS)

Davis, Scott R.; Farca, George; Rommel, Scott D.; Johnson, Seth; Anderson, Michael H.

2010-02-01

A new electro-optic waveguide platform, which provides unprecedented voltage control over optical phase delays (> 2mm), with very low loss (< 0.5 dB/cm) and rapid response time (sub millisecond), will be presented. This technology, developed by Vescent Photonics, is based upon a unique liquid-crystal waveguide geometry, which exploits the tremendous electro-optic response of liquid crystals while circumventing their historic limitations. The waveguide geometry provides nematic relaxation speeds in the 10's of microseconds and LC scattering losses that are reduced by orders of magnitude from bulk transmissive LC optics. The exceedingly large optical phase delays accessible with this technology enable the design and construction of a new class of previously unrealizable photonic devices. Examples include: 2-D analog non-mechanical beamsteerers, chip-scale widely tunable lasers, chip-scale Fourier transform spectrometer (< 5 nm resolution demonstrated), widely tunable micro-ring resonators, tunable lenses, ultra-low power (< 5 microWatts) optical switches, true optical time delay devices for phased array antennas, and many more. All of these devices may benefit from established manufacturing technologies and ultimately may be as inexpensive as a calculator display. Furthermore, this new integrated photonic architecture has applications in a wide array of commercial and defense markets including: remote sensing, micro-LADAR, OCT, FSO, laser illumination, phased array radar, etc. Performance attributes of several example devices and application data will be presented. In particular, we will present a non-mechanical beamsteerer that steers light in both the horizontal and vertical dimensions.

Biological pathways, candidate genes, and molecular markers associated with quality-of-life domains: an update.

PubMed

Sprangers, Mirjam A G; Thong, Melissa S Y; Bartels, Meike; Barsevick, Andrea; Ordoñana, Juan; Shi, Qiuling; Wang, Xin Shelley; Klepstad, Pål; Wierenga, Eddy A; Singh, Jasvinder A; Sloan, Jeff A

2014-09-01

There is compelling evidence of a genetic foundation of patient-reported quality of life (QOL). Given the rapid development of substantial scientific advances in this area of research, the current paper updates and extends reviews published in 2010. The objective was to provide an updated overview of the biological pathways, candidate genes, and molecular markers involved in fatigue, pain, negative (depressed mood) and positive (well-being/happiness) emotional functioning, social functioning, and overall QOL. We followed a purposeful search algorithm of existing literature to capture empirical papers investigating the relationship between biological pathways and molecular markers and the identified QOL domains. Multiple major pathways are involved in each QOL domain. The inflammatory pathway has the strongest evidence as a controlling mechanism underlying fatigue. Inflammation and neurotransmission are key processes involved in pain perception, and the catechol-O-methyltransferase (COMT) gene is associated with multiple sorts of pain. The neurotransmitter and neuroplasticity theories have the strongest evidence for their relationship with depression. Oxytocin-related genes and genes involved in the serotonergic and dopaminergic pathways play a role in social functioning. Inflammatory pathways, via cytokines, also play an important role in overall QOL. Whereas the current findings need future experiments and replication efforts, they will provide researchers supportive background information when embarking on studies relating candidate genes and/or molecular markers to QOL domains. The ultimate goal of this area of research is to enhance patients' QOL.

Rapidly Learned Identification of Epileptic Seizures from Sonified EEG

PubMed Central

Loui, Psyche; Koplin-Green, Matan; Frick, Mark; Massone, Michael

2014-01-01

Sonification refers to a process by which data are converted into sound, providing an auditory alternative to visual display. Currently, the prevalent method for diagnosing seizures in epilepsy is by visually reading a patient’s electroencephalogram (EEG). However, sonification of the EEG data provides certain advantages due to the nature of human auditory perception. We hypothesized that human listeners will be able to identify seizures from EEGs using the auditory modality alone, and that accuracy of seizure identification will increase after a short training session. Here, we describe an algorithm that we have used to sonify EEGs of both seizure and non-seizure activity, followed by a training study in which subjects listened to short clips of sonified EEGs and determined whether each clip was of seizure or normal activity, both before and after a short training session. Results show that before training subjects performed at chance level in differentiating seizures from non-seizures, but there was a significant improvement of accuracy after the training session. After training, subjects successfully distinguished seizures from non-seizures using the auditory modality alone. Further analyses using signal detection theory demonstrated improvement in sensitivity and reduction in response bias as a result of training. This study demonstrates the potential of sonified EEGs to be used for the detection of seizures. Future studies will attempt to increase accuracy using novel training and sonification modifications, with the goals of managing, predicting, and ultimately controlling seizures using sonification as a possible biofeedback-based intervention for epilepsy. PMID:25352802

The distribution, fate, and effects of propylene glycol substances in the environment.

PubMed

West, Robert; Banton, Marcy; Hu, Jing; Klapacz, Joanna

2014-01-01

The propylene glycol substances comprise a homologous family of synthetic organic molecules that have widespread use and very high production volumes across the globe. The information presented and summarized here is intended to provide an overview of the most current and reliable information available for assessing the potential environmental exposures and impacts of these substances across the manufacture, use, and disposal phases of their product life cycles.The PG substances are characterized as being miscible in water, having very low octanol-water partition coefficients (log Pow) and exhibiting low potential to volatilize from water or soil in both pure and dissolved forms. The combination of these properties dictates that, almost regardless of the mode of their initial emission, they will ultimately associate with surface water, soil, and the related groundwater compartments in the environment. These substances have low affinity for soil and sediment particles, and thus will remain mobile and bio-available within these media.In the atmosphere, the PG substances are demonstrated to have short lifetimes(I. 7-11 h), due to rapid reaction with photochemically-generated hydroxyl radicals.This reactivity, combined with efficient wet deposition of their vapor and aerosol forms, lends to their very low potential for long-range transport via the atmosphere.In the aquatic and terrestrial compartments of the environment, the PG substances are rapidly and ultimately biodegraded under both aerobic and anaerobic conditions by a wide variety of microorganisms, regardless of prior adaptation to the substances.Except for the TePG substance, the propylene glycol substances meet the OECD definition of "readily biodegradable", and according to this definition are not expected to persist in either aquatic or terrestrial environments. The TePG exhibits inherent biodegradability, is not regarded to be persistent, and is expected to ultimately biodegrade in the environment, albeit at a somewhat slower rate. The apparent ease with which microorganisms and higher organisms can metabolize the PG substances, along with their low log Pow and very high water solubility values, portends them to have very low potential for bioaccumulation and/or biomagnification in aquatic and terrestrial organisms. These same properties, along with their neutral structures and lack of biological reactivity, are the reasons for which the PG substances exhibit a base-line, non-polar narcosis mode of toxicity.The PG substances have been shown here to be practically non-toxic to essentially every aquatic and terrestrial animal and plant species tested. Collectively, the available wealth of information relating to persistence, bioaccumulation, and eco-toxicity of these substances allows a definitive conclusion of their categorization as not being PBT (i.e., persistently bioaccumulative/toxic). The PBT screening and categorization of substances on the Canadian Domestic Substances List (DSL) by Environment Canada has formally concluded that each member of this substance family is "not P", "not B", and "not T' according to their associated PBT criteria.Similarly, the preceding evaluations of these high production volume substances within the OECD SIDS program concluded that MPG, DPG, and TPG are low priorities for further examination of potential impacts to humans and the environment.More extensive evaluations of potential risks to human health and the environment were recently completed by industry, as required for their registration under the European Union REACh legislation; each evaluation demonstrated that current uses, associated exposures, and controls thereof, will not result in exposures that exceed predicted no effect concentrations in the environment.

The biomechanical strength of a hardware-free femoral press-fit method for ACL bone-tendon-bone graft fixation.

PubMed

Arnold, M P; Burger, L D; Wirz, D; Goepfert, B; Hirschmann, M T

2017-04-01

The purpose was to investigate graft slippage and ultimate load to failure of a femoral press-fit fixation technique for anterior cruciate ligament (ACL) reconstruction. Nine fresh-frozen knees were used. Standardized harvesting of the B-PT-B graft was performed. The femora were cemented into steel rods, and a tunnel was drilled outside-in into the native ACL footprint and expanded using a manual mill bit. The femoral bone block was fixed press-fit. To pull the free end of the graft, it was fixed to a mechanical testing machine using a deep-freezing technique. A motion capture system was used to assess three-dimensional micro-motion. After preconditioning of the graft, 1000 cycles of tensile loading were applied. Finally, an ultimate load to failure test was performed. Graft slippage in mm ultimate load to failure as well as type of failure was noted. In six of the nine measured specimens, a typical pattern of graft slippage was observed during cyclic loading. For technical reasons, the results of three knees had to be discarded. 78.6 % of total graft slippage occurred in the first 100 cycles. Once the block had settled, graft slippage converged to zero, highlighting the importance of initial preconditioning of the graft in the clinical setting. Graft slippage after 1000 cycles varied around 3.4 ± 3.2 mm (R = 1.3-9.8 mm) between the specimens. Ultimate loading (n = 9) revealed two characteristic patterns of failure. In four knees, the tendon ruptured, while in five knees the bone block was pulled out of the femoral tunnel. The median ultimate load to failure was 852 N (R = 448-1349 N). The implant-free femoral press-fit fixation provided adequate primary stability with ultimate load to failure pull forces at least equal to published results for interference screws; hence, its clinical application is shown to be safe.

Biomechanical characteristics of the horizontal mattress stitch: implication for double-row and suture-bridge rotator cuff repair.

PubMed

Tamboli, Mallika; Mihata, Teruhisa; Hwang, James; McGarry, Michelle H; Kang, Yangmi; Lee, Thay Q

2014-03-01

We investigated the effects of bite-size horizontal mattress stitch (distance between the limbs passed through the tendon) on the biomechanical properties of the repaired tendon. We anchored 20 bovine Achilles tendons to bone using no. 2 high-strength suture and 5-mm titanium suture anchors in a mattress-suture technique. Tendons were allocated randomly into two groups of ten each to receive stitches with a 4- or 10-mm bite. Specimens underwent cyclic loading from 5 to 30 N at 1 mm/s for 30 cycles, followed by tensile testing to failure. Gap formation, tendon strain, hysteresis, stiffness, yield load, ultimate load, energy to yield load, and energy to ultimate load were compared between groups using unpaired t tests. The 4-mm group had less (p < 0.05) gap formation and less (p < 0.05) longitudinal strain than did the 10-mm group. Ultimate load (293.6 vs. 148.9 N) and energy to ultimate load (2,563 vs. 1,472 N-mm) were greater (p < 0.001) for the 10-mm group than the 4-mm group. All tendons repaired with 4-mm suturing failed at the suture-tendon interface, with sutures pulling through the tendon, whereas the suture itself failed before the tendon did in seven of the ten specimens in the 10-mm group. Whereas a 4-mm bite fixed the tendon more tightly but at the cost of decreased ultimate strength, a 10-mm bite conveyed greater ultimate strength but with increased gap and strain. These results suggest that for the conventional double-row repair, small mattress stitches provide a tighter repair, whereas large stitches are beneficial to prevent sutures from pulling through the tendon after surgery. For suture-bridge rotator cuff repair, large stitches are beneficial because the repaired tendon has a higher strength, and the slightly mobile medial knot can be tightened by lateral fixation.

Registry Assessment of Peripheral Interventional Devices (RAPID): Registry assessment of peripheral interventional devices core data elements.

PubMed

Jones, W Schuyler; Krucoff, Mitchell W; Morales, Pablo; Wilgus, Rebecca W; Heath, Anne H; Williams, Mary F; Tcheng, James E; Marinac-Dabic, J Danica; Malone, Misti L; Reed, Terrie L; Fukaya, Rie; Lookstein, Robert A; Handa, Nobuhiro; Aronow, Herbert D; Bertges, Daniel J; Jaff, Michael R; Tsai, Thomas T; Smale, Joshua A; Zaugg, Margo J; Thatcher, Robert J; Cronenwett, Jack L

2018-02-01

The current state of evaluating patients with peripheral artery disease and more specifically of evaluating medical devices used for peripheral vascular intervention (PVI) remains challenging because of the heterogeneity of the disease process, the multiple physician specialties that perform PVI, the multitude of devices available to treat peripheral artery disease, and the lack of consensus about the best treatment approaches. Because PVI core data elements are not standardized across clinical care, clinical trials, and registries, aggregation of data across different data sources and physician specialties is currently not feasible. Under the auspices of the U.S. Food and Drug Administration's Medical Device Epidemiology Network initiative-and its PASSION (Predictable and Sustainable Implementation of the National Registries) program, in conjunction with other efforts to align clinical data standards-the Registry Assessment of Peripheral Interventional Devices (RAPID) workgroup was convened. RAPID is a collaborative, multidisciplinary effort to develop a consensus lexicon and to promote interoperability across clinical care, clinical trials, and national and international registries of PVI. The current manuscript presents the initial work from RAPID to standardize clinical data elements and definitions, to establish a framework within electronic health records and health information technology procedural reporting systems, and to implement an informatics-based approach to promote the conduct of pragmatic clinical trials and registry efforts in PVI. Ultimately, we hope this work will facilitate and improve device evaluation and surveillance for patients, clinicians, health outcomes researchers, industry, policymakers, and regulators. Copyright © 2017 Society for Vascular Surgery. All rights reserved.

Response of microbial community of organic-matter-impoverished arable soil to long-term application of soil conditioner derived from dynamic rapid fermentation of food waste

PubMed Central

Hou, Jiaqi; Li, Mingxiao; Mao, Xuhui; Hao, Yan; Ding, Jie; Liu, Dongming; Liu, Hongliang

2017-01-01

Rapid fermentation of food waste can be used to prepare soil conditioner. This process consumes less time and is more cost-effective than traditional preparation technology. However, the succession of the soil microbial community structure after long-term application of rapid fermentation-derived soil conditioners remains unclear. Herein, dynamic rapid fermentation (DRF) of food waste was performed to develop a soil conditioner and the successions and diversity of bacterial communities in an organic-matter-impoverished arable soil after six years of application of DRF-derived soil conditioner were investigated. Results showed that the treatment increased soil organic matter (SOM) accumulation and strawberry yield by 5.3 g/kg and 555.91 kg/ha, respectively. Proteobacteria, Actinobacteria, Acidobacteria, and Firmicutes became the dominant phyla, occupying 65.95%–77.52% of the bacterial sequences. Principal component analysis (PCA) results showed that the soil bacterial communities were largely influenced by the treatment. Redundancy analysis (RDA) results showed that the relative abundances of Gemmatimonadetes, Chloroflexi, Verrucomicrobia, Nitrospirae, and Firmicutes were significantly correlated with soil TC, TN, TP, NH4+-N, NO3−-N, OM, and moisture. These communities were all distributed in the soil samples collected in the sixth year of application. Long-term treatment did not enhance the diversity of bacterial species but significantly altered the distribution of major functional bacterial communities in the soils. Application of DRF-derived soil conditioner could improve the soil quality and optimize the microbial community, ultimately enhancing fruit yields. PMID:28419163

Startup of RAPID-L Lunar Base Reactor by Lithium Release Module

NASA Astrophysics Data System (ADS)

Kambe, Mitsuru

The 200 kWe uranium-nitride fueled lithium cooled fast reactor concept RAPID-L to be combined with thermoelectric power conversion system for lunar base power system is demonstrated. Unique challenges in reactivity control systems design have been attempted in RAPID-L concept. The reactor involves the following innovative reactivity control systems: Lithium Expansion Modules (LEM) for inherent reactivity feedback, Lithium Injection Modules (LIM) for inherent ultimate shutdown, and Lithium Release Modules (LRM) for automated reactor startup. All these systems adopt lithium-6 as a liquid poison instead of conventional B4C rods or Be reflectors. These systems are effective independent of the magnitude and direction of the gravity force. In 2006, however, the following design amendment has been made. 1) B4C poison rods were added to ensure criticality safety in unintended positive reactivity insertion by LRMs due to fire in the launch phase accident; because LRM freeze seal melts at 800°C which result in positive reactivity insertion. 2) Lower hot standby temperature of 200°C was adopted instead of conventional 800°C to reduce the external power at the startup. In this paper, development of the LRM orifice which dominates the startup transient of RAPID-L is discussed. An attention was focused how to achieve sufficiently small flow rate of 6Li in the orifice because it enables moderate positive reactivity insertion rate. The LRM orifice performance has been confirmed using 0.5 mm diameter SUS316 orifice/lithium flow test setup in the glove box.

Evolution of the rodent eosinophil-associated RNase gene family by rapid gene sorting and positive selection

PubMed Central

Zhang, Jianzhi; Dyer, Kimberly D.; Rosenberg, Helene F.

2000-01-01

The mammalian RNase A superfamily comprises a diverse array of ribonucleolytic proteins that have a variety of biochemical activities and physiological functions. Two rapidly evolving RNases of higher primates are of particular interest as they are major secretory proteins of eosinophilic leukocytes and have been found to possess anti-pathogen activities in vitro. To understand how these RNases acquired this function during evolution and to develop animal models for the study of their functions in vivo, it is necessary to investigate these genes in many species. Here, we report the sequences of 38 functional genes and 23 pseudogenes of the eosinophil-associated RNase (EAR) family from 5 rodent species. Our phylogenetic analysis of these genes showed a clear pattern of evolution by a rapid birth-and-death process and gene sorting, a process characterized by rapid gene duplication and deactivation occurring differentially among lineages. This process ultimately generates distinct or only partially overlapping inventories of the genes, even in closely related species. Positive Darwinian selection also contributed to the diversification of these EAR genes. The striking similarity between the evolutionary patterns of the EAR genes and those of the major histocompatibility complex, immunoglobulin, and T cell receptor genes stands in strong support of the hypothesis that host-defense and generation of diversity are among the primary physiological function of the rodent EARs. The discovery of a large number of divergent EARs suggests the intriguing possibility that these proteins have been specifically tailored to fight against distinct rodent pathogens. PMID:10758160

Response of microbial community of organic-matter-impoverished arable soil to long-term application of soil conditioner derived from dynamic rapid fermentation of food waste.

PubMed

Hou, Jiaqi; Li, Mingxiao; Mao, Xuhui; Hao, Yan; Ding, Jie; Liu, Dongming; Xi, Beidou; Liu, Hongliang

2017-01-01

Rapid fermentation of food waste can be used to prepare soil conditioner. This process consumes less time and is more cost-effective than traditional preparation technology. However, the succession of the soil microbial community structure after long-term application of rapid fermentation-derived soil conditioners remains unclear. Herein, dynamic rapid fermentation (DRF) of food waste was performed to develop a soil conditioner and the successions and diversity of bacterial communities in an organic-matter-impoverished arable soil after six years of application of DRF-derived soil conditioner were investigated. Results showed that the treatment increased soil organic matter (SOM) accumulation and strawberry yield by 5.3 g/kg and 555.91 kg/ha, respectively. Proteobacteria, Actinobacteria, Acidobacteria, and Firmicutes became the dominant phyla, occupying 65.95%-77.52% of the bacterial sequences. Principal component analysis (PCA) results showed that the soil bacterial communities were largely influenced by the treatment. Redundancy analysis (RDA) results showed that the relative abundances of Gemmatimonadetes, Chloroflexi, Verrucomicrobia, Nitrospirae, and Firmicutes were significantly correlated with soil TC, TN, TP, NH4+-N, NO3--N, OM, and moisture. These communities were all distributed in the soil samples collected in the sixth year of application. Long-term treatment did not enhance the diversity of bacterial species but significantly altered the distribution of major functional bacterial communities in the soils. Application of DRF-derived soil conditioner could improve the soil quality and optimize the microbial community, ultimately enhancing fruit yields.

Cardiac parasympathetic reactivation following exercise: implications for training prescription.

PubMed

Stanley, Jamie; Peake, Jonathan M; Buchheit, Martin

2013-12-01

The objective of exercise training is to initiate desirable physiological adaptations that ultimately enhance physical work capacity. Optimal training prescription requires an individualized approach, with an appropriate balance of training stimulus and recovery and optimal periodization. Recovery from exercise involves integrated physiological responses. The cardiovascular system plays a fundamental role in facilitating many of these responses, including thermoregulation and delivery/removal of nutrients and waste products. As a marker of cardiovascular recovery, cardiac parasympathetic reactivation following a training session is highly individualized. It appears to parallel the acute/intermediate recovery of the thermoregulatory and vascular systems, as described by the supercompensation theory. The physiological mechanisms underlying cardiac parasympathetic reactivation are not completely understood. However, changes in cardiac autonomic activity may provide a proxy measure of the changes in autonomic input into organs and (by default) the blood flow requirements to restore homeostasis. Metaboreflex stimulation (e.g. muscle and blood acidosis) is likely a key determinant of parasympathetic reactivation in the short term (0-90 min post-exercise), whereas baroreflex stimulation (e.g. exercise-induced changes in plasma volume) probably mediates parasympathetic reactivation in the intermediate term (1-48 h post-exercise). Cardiac parasympathetic reactivation does not appear to coincide with the recovery of all physiological systems (e.g. energy stores or the neuromuscular system). However, this may reflect the limited data currently available on parasympathetic reactivation following strength/resistance-based exercise of variable intensity. In this review, we quantitatively analyse post-exercise cardiac parasympathetic reactivation in athletes and healthy individuals following aerobic exercise, with respect to exercise intensity and duration, and fitness/training status. Our results demonstrate that the time required for complete cardiac autonomic recovery after a single aerobic-based training session is up to 24 h following low-intensity exercise, 24-48 h following threshold-intensity exercise and at least 48 h following high-intensity exercise. Based on limited data, exercise duration is unlikely to be the greatest determinant of cardiac parasympathetic reactivation. Cardiac autonomic recovery occurs more rapidly in individuals with greater aerobic fitness. Our data lend support to the concept that in conjunction with daily training logs, data on cardiac parasympathetic activity are useful for individualizing training programmes. In the final sections of this review, we provide recommendations for structuring training microcycles with reference to cardiac parasympathetic recovery kinetics. Ultimately, coaches should structure training programmes tailored to the unique recovery kinetics of each individual.

42 CFR 68c.2 - Definitions.

Code of Federal Regulations, 2011 CFR

2011-10-01

... Secretary, wherein the applicant agrees to participate in research on infertility or contraceptive... as required. Contraceptive development means research whose ultimate goal is to provide new or... determined by the Secretary. Research on infertility or contraceptive development means activities which...

42 CFR 68c.2 - Definitions.

Code of Federal Regulations, 2012 CFR

2012-10-01

... Secretary, wherein the applicant agrees to participate in research on infertility or contraceptive... as required. Contraceptive development means research whose ultimate goal is to provide new or... determined by the Secretary. Research on infertility or contraceptive development means activities which...