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Sample records for accelerated biological function

  1. Avoidance of accelerated aging in schizophrenia?: Clinical and biological characterization of an exceptionally high functioning individual.

    PubMed

    Palmer, Barton W; Moore, Raeanne C; Eyler, Lisa T; Pinto, Luz L; Saks, Elyn R; Jeste, Dilip V

    2017-08-08

    To determine the clinical and biological characteristics of an exceptionally high functioning index person (IP) with schizophrenia in her mid-50s, which may represent compensatory mechanisms, and potentially, avoidance of the accelerated aging typically associated with schizophrenia. IP, 11 other women with schizophrenia, and 11 non-psychiatric comparison (NC) women were assessed with standard ratings of psychopathology, neurocognitive function, decisional capacity, and functional brain imaging. IP was also compared to a sample of demographically similar NCs (N=45) and persons with schizophrenia (N=42) on a set of blood-based biomarkers of aging related to metabolic function, oxidative stress, and inflammation. IP's scores on working memory, and levels of brain activation during an affective face matching task in the left fusiform, right lingual, and left precentral gyri, exceeded NCs. IP was similar to NCs in severity of negative symptoms, most neurocognitive functions, decisional capacity, and brain activation in the left inferior occipital gyrus during a selective stopping task. IP's levels on 11 of 14 metabolic and inflammatory biomarkers of aging were better than NCs and the schizophrenia group. Although speculative, results suggest a possible model in which superior working memory permits a person to be aware of the potentially psychotic nature of a thought or perception, and adjust response accordingly. Compensatory overactivity of brain regions during affective processing may also reflect heightened meta-awareness in emotional situations. Biomarker levels raise the possibility that IP partially avoided the accelerated biological aging associated with schizophrenia. Published by Elsevier B.V.

  2. Menopause accelerates biological aging

    PubMed Central

    Levine, Morgan E.; Lu, Ake T.; Chen, Brian H.; Hernandez, Dena G.; Singleton, Andrew B.; Ferrucci, Luigi; Bandinelli, Stefania; Salfati, Elias; Manson, JoAnn E.; Quach, Austin; Kusters, Cynthia D. J.; Kuh, Diana; Wong, Andrew; Teschendorff, Andrew E.; Widschwendter, Martin; Ritz, Beate R.; Absher, Devin; Assimes, Themistocles L.; Horvath, Steve

    2016-01-01

    Although epigenetic processes have been linked to aging and disease in other systems, it is not yet known whether they relate to reproductive aging. Recently, we developed a highly accurate epigenetic biomarker of age (known as the “epigenetic clock”), which is based on DNA methylation levels. Here we carry out an epigenetic clock analysis of blood, saliva, and buccal epithelium using data from four large studies: the Women's Health Initiative (n = 1,864); Invecchiare nel Chianti (n = 200); Parkinson's disease, Environment, and Genes (n = 256); and the United Kingdom Medical Research Council National Survey of Health and Development (n = 790). We find that increased epigenetic age acceleration in blood is significantly associated with earlier menopause (P = 0.00091), bilateral oophorectomy (P = 0.0018), and a longer time since menopause (P = 0.017). Conversely, epigenetic age acceleration in buccal epithelium and saliva do not relate to age at menopause; however, a higher epigenetic age in saliva is exhibited in women who undergo bilateral oophorectomy (P = 0.0079), while a lower epigenetic age in buccal epithelium was found for women who underwent menopausal hormone therapy (P = 0.00078). Using genetic data, we find evidence of coheritability between age at menopause and epigenetic age acceleration in blood. Using Mendelian randomization analysis, we find that two SNPs that are highly associated with age at menopause exhibit a significant association with epigenetic age acceleration. Overall, our Mendelian randomization approach and other lines of evidence suggest that menopause accelerates epigenetic aging of blood, but mechanistic studies will be needed to dissect cause-and-effect relationships further. PMID:27457926

  3. Acceleration of cardiovascular-biological age by amphetamine exposure is a power function of chronological age

    PubMed Central

    Norman, Amanda; Hulse, Gary Kenneth

    2017-01-01

    Background Amphetamine abuse is becoming more widespread internationally. The possibility that its many cardiovascular complications are associated with a prematurely aged cardiovascular system, and indeed biological organism systemically, has not been addressed. Methods Radial arterial pulse tonometry was performed using the SphygmoCor system (Sydney). 55 amphetamine exposed patients were compared with 107 tobacco smokers, 483 non-smokers and 68 methadone patients (total=713 patients) from 2006 to 2011. A cardiovascular-biological age (VA) was determined. Results The age of the patient groups was 30.03±0.51–40.45±1.15 years. This was controlled for with linear regression. The sex ratio was the same in all groups. 94% of amphetamine exposed patients had used amphetamine in the previous week. When the (log) VA was regressed against the chronological age (CA) and a substance-type group in both cross-sectional and longitudinal models, models quadratic in CA were superior to linear models (both p<0.02). When log VA/CA was regressed in a mixed effects model against time, body mass index, CA and drug type, the cubic model was superior to the linear model (p=0.001). Interactions between CA, (CA)2 and (CA)3 on the one hand and exposure type were significant from p=0.0120. The effects of amphetamine exposure persisted after adjustment for all known cardiovascular risk factors (p<0.0001). Conclusions These results show that subacute exposure to amphetamines is associated with an advancement of cardiovascular-organismal age both over age and over time, and is robust to adjustment. That this is associated with power functions of age implies a feed-forward positively reinforcing exacerbation of the underlying ageing process. PMID:28243315

  4. Effects and biological limitations of +Gz acceleration on the autonomic functions-related circulation in rats.

    PubMed

    Nishida, Yasuhiro; Maruyama, Satoshi; Shouji, Ichiro; Kemuriyama, Takehito; Tashiro, Akimasa; Ohta, Hiroyuki; Hagisawa, Kohsue; Hiruma, Megumi; Yokoe, Hidetake

    2016-11-01

    The effects of gravitational loading (G load) on humans have been studied ever since the early 20th century. After the dangers of G load in the vertical head-to-leg direction (+Gz load) became evident, many animal experiments were performed between 1920 and 1945 in an effort to identify the origins of high G-force-induced loss of consciousness (G-LOC), which led to development of the anti-G suit. The establishment of norms and training for G-LOC prevention resulted in a gradual decline in reports of animal experiments on G load, a decline that steepened with the establishment of anti-G techniques in humans, such as special breathing methods and skeletal muscle contraction, called an anti-G straining maneuver, which are voluntary physiological functions. Because the issue involves humans during flight, the effects on humans themselves are clearly of great importance, but ethical considerations largely preclude any research on the human body that probes to any depth the endogenous physiological states and functions. The decline in reports on animal experiments may therefore signify a general decline in research into the changes seen in the various involuntary, autonomic functions. The declining number of related reports on investigations of physiological autonomic systems other than the circulatory system seems to bear this out. In this review, we therefore describe our findings on the effects of G load on the autonomic nervous system, cardiac function, cerebral blood flow, tissue oxygen level, and other physiological autonomic functions as measured in animal experiments, including denervation or pharmacological blocking, in an effort to present the limits and the mechanisms of G-load response extending physiologically. We demonstrate previously unrecognized risks due to G load, and also describe fundamental research aimed at countering these effects and development of a scientific training measure devised for actively enhancing +Gz tolerance in involuntary

  5. Accelerating scientific publication in biology

    PubMed Central

    Vale, Ronald D.

    2015-01-01

    Scientific publications enable results and ideas to be transmitted throughout the scientific community. The number and type of journal publications also have become the primary criteria used in evaluating career advancement. Our analysis suggests that publication practices have changed considerably in the life sciences over the past 30 years. More experimental data are now required for publication, and the average time required for graduate students to publish their first paper has increased and is approaching the desirable duration of PhD training. Because publication is generally a requirement for career progression, schemes to reduce the time of graduate student and postdoctoral training may be difficult to implement without also considering new mechanisms for accelerating communication of their work. The increasing time to publication also delays potential catalytic effects that ensue when many scientists have access to new information. The time has come for life scientists, funding agencies, and publishers to discuss how to communicate new findings in a way that best serves the interests of the public and the scientific community. PMID:26508643

  6. Accelerating scientific publication in biology.

    PubMed

    Vale, Ronald D

    2015-11-03

    Scientific publications enable results and ideas to be transmitted throughout the scientific community. The number and type of journal publications also have become the primary criteria used in evaluating career advancement. Our analysis suggests that publication practices have changed considerably in the life sciences over the past 30 years. More experimental data are now required for publication, and the average time required for graduate students to publish their first paper has increased and is approaching the desirable duration of PhD training. Because publication is generally a requirement for career progression, schemes to reduce the time of graduate student and postdoctoral training may be difficult to implement without also considering new mechanisms for accelerating communication of their work. The increasing time to publication also delays potential catalytic effects that ensue when many scientists have access to new information. The time has come for life scientists, funding agencies, and publishers to discuss how to communicate new findings in a way that best serves the interests of the public and the scientific community.

  7. Biological accelerator mass spectrometry at Uppsala University.

    PubMed

    Salehpour, Mehran; Possnert, Göran; Bryhni, Helge; Palminger-Hallén, Ira; Ståhle, Lars

    2009-03-01

    A new research programme for the biological applications of accelerator mass spectrometry has been initiated at Uppsala University and the first results are presented. A (14)C-labelled pharmaceutical substance has been dissolved in human blood, plasma and urine and diluted over 3 orders of magnitude. The measured drug concentrations were found to be in good agreement with the predicted values. Furthermore, the effect of the sample preparation background contribution has been studied as the sample amount was varied down to sub-microl sizes.

  8. Accelerator mass spectrometry of small biological samples.

    PubMed

    Salehpour, Mehran; Forsgard, Niklas; Possnert, Göran

    2008-12-01

    Accelerator mass spectrometry (AMS) is an ultra-sensitive technique for isotopic ratio measurements. In the biomedical field, AMS can be used to measure femtomolar concentrations of labeled drugs in body fluids, with direct applications in early drug development such as Microdosing. Likewise, the regenerative properties of cells which are of fundamental significance in stem-cell research can be determined with an accuracy of a few years by AMS analysis of human DNA. However, AMS nominally requires about 1 mg of carbon per sample which is not always available when dealing with specific body substances such as localized, organ-specific DNA samples. Consequently, it is of analytical interest to develop methods for the routine analysis of small samples in the range of a few tens of microg. We have used a 5 MV Pelletron tandem accelerator to study small biological samples using AMS. Different methods are presented and compared. A (12)C-carrier sample preparation method is described which is potentially more sensitive and less susceptible to contamination than the standard procedures.

  9. Is biological aging accelerated in drug addiction?

    PubMed

    Bachi, Keren; Sierra, Salvador; Volkow, Nora D; Goldstein, Rita Z; Alia-Klein, Nelly

    2017-02-01

    Drug-addiction may trigger early onset of age-related disease, due to drug-induced multi-system toxicity and perilous lifestyle, which remains mostly undetected and untreated. We present the literature on pathophysiological processes that may hasten aging and its relevance to addiction, including: oxidative stress and cellular aging, inflammation in periphery and brain, decline in brain volume and function, and early onset of cardiac, cerebrovascular, kidney, and liver disease. Timely detection of accelerated aging in addiction is crucial for the prevention of premature morbidity and mortality.

  10. Biological assessments for the low energy demonstration accelerator, 1996

    SciTech Connect

    Cross, S.

    1997-03-01

    This report discusses the biological impact to the area around the Los Alamos National Laboratory of the Low Energy Demonstration Accelerator. In particular the impact to the soils, water quality, vegetation, and wildlife are discussed.

  11. Accelerating Yeast Prion Biology using Droplet Microfluidics

    NASA Astrophysics Data System (ADS)

    Ung, Lloyd; Rotem, Assaf; Jarosz, Daniel; Datta, Manoshi; Lindquist, Susan; Weitz, David

    2012-02-01

    Prions are infectious proteins in a misfolded form, that can induce normal proteins to take the misfolded state. Yeast prions are relevant, as a model of human prion diseases, and interesting from an evolutionary standpoint. Prions may also be a form of epigenetic inheritance, which allow yeast to adapt to stressful conditions at rates exceeding those of random mutations and propagate that adaptation to their offspring. Encapsulation of yeast in droplet microfluidic devices enables high-throughput measurements with single cell resolution, which would not be feasible using bulk methods. Millions of populations of yeast can be screened to obtain reliable measurements of prion induction and loss rates. The population dynamics of clonal yeast, when a fraction of the cells are prion expressing, can be elucidated. Furthermore, the mechanism by which certain strains of bacteria induce yeast to express prions in the wild can be deduced. Integrating the disparate fields of prion biology and droplet microfluidics reveals a more complete picture of how prions may be more than just diseases and play a functional role in yeast.

  12. Functions in Biological Kind Classification

    ERIC Educational Resources Information Center

    Lombrozo, Tania; Rehder, Bob

    2012-01-01

    Biological traits that serve functions, such as a zebra's coloration (for camouflage) or a kangaroo's tail (for balance), seem to have a special role in conceptual representations for biological kinds. In five experiments, we investigate whether and why functional features are privileged in biological kind classification. Experiment 1…

  13. Functions in Biological Kind Classification

    ERIC Educational Resources Information Center

    Lombrozo, Tania; Rehder, Bob

    2012-01-01

    Biological traits that serve functions, such as a zebra's coloration (for camouflage) or a kangaroo's tail (for balance), seem to have a special role in conceptual representations for biological kinds. In five experiments, we investigate whether and why functional features are privileged in biological kind classification. Experiment 1…

  14. The relativity of biological function.

    PubMed

    Laubichler, Manfred D; Stadler, Peter F; Prohaska, Sonja J; Nowick, Katja

    2015-12-01

    Function is a central concept in biological theories and explanations. Yet discussions about function are often based on a narrow understanding of biological systems and processes, such as idealized molecular systems or simple evolutionary, i.e., selective, dynamics. Conflicting conceptions of function continue to be used in the scientific literature to support certain claims, for instance about the fraction of "functional DNA" in the human genome. Here we argue that all biologically meaningful interpretations of function are necessarily context dependent. This implies that they derive their meaning as well as their range of applicability only within a specific theoretical and measurement context. We use this framework to shed light on the current debate about functional DNA and argue that without considering explicitly the theoretical and measurement contexts all attempts to integrate biological theories are prone to fail.

  15. Accelerators for America's Future Workshop: Medicine and Biology.

    PubMed

    Alonso, Jose R

    2012-11-01

    "Medicine and Biology" was one of five working groups of the "Accelerators for America's Future" Workshop held October 2009. The recently-released workshop report stresses that the leadership position of the United States in fields where accelerators play an important part is being seriously eroded because of lack of coordinated agency support for accelerator research and development. This is particularly true for biology and medicine. Radiation therapy with beams of protons and light ions was pioneered in the United States and has proven successful in the treatment of several different tumor sites in the body. Proton therapy is available in the United States in a number of centers; however, all but one contain accelerator and beam-delivery components manufactured abroad. Light-ion therapy is only available overseas. Why has the United States lost its lead in this field? The Working Group noted that in other countries, central governments are subsidizing construction and technology development by their industries, whereas in the United States funding for purchasing and building clinical facilities must be raised from private sources. As a result, most proton facilities in the United States, by virtue of having to recover investment costs, favor reimbursable treatments, detracting from the development of research protocols. The financial hurdle for starting a light-ion facility in the United States has been totally prohibitive for the private-equity market. While technological advances are being made that will provide some reduction in capital costs, the field will not flourish in the United States until effective funding means are developed that do not put the full burden on the private sector.

  16. Accelerating functional verification of an integrated circuit

    SciTech Connect

    Deindl, Michael; Ruedinger, Jeffrey Joseph; Zoellin, Christian G.

    2015-10-27

    Illustrative embodiments include a method, system, and computer program product for accelerating functional verification in simulation testing of an integrated circuit (IC). Using a processor and a memory, a serial operation is replaced with a direct register access operation, wherein the serial operation is configured to perform bit shifting operation using a register in a simulation of the IC. The serial operation is blocked from manipulating the register in the simulation of the IC. Using the register in the simulation of the IC, the direct register access operation is performed in place of the serial operation.

  17. Determination of higher order accelerations by a functional method

    NASA Astrophysics Data System (ADS)

    Tudosie, C.

    A functional method is developed for the simultaneous determination of all the linear accelerations which exist in the differential equation of a material system dynamics. The method introduces variable angular accelerations of different orders, called direct connection functions, which allow the passing from a linear acceleration of a certain order to that of a higher order. Feedback functions are also introduced which allow the passing from a linear acceleration of a certain order to that of lower orders. This method is applicable to accelerations which occur when passenger trains move rapidly around a curve and at the vertical vibrations of trucks and tractors.

  18. The biological function of consciousness

    PubMed Central

    Earl, Brian

    2014-01-01

    This research is an investigation of whether consciousness—one's ongoing experience—influences one's behavior and, if so, how. Analysis of the components, structure, properties, and temporal sequences of consciousness has established that, (1) contrary to one's intuitive understanding, consciousness does not have an active, executive role in determining behavior; (2) consciousness does have a biological function; and (3) consciousness is solely information in various forms. Consciousness is associated with a flexible response mechanism (FRM) for decision-making, planning, and generally responding in nonautomatic ways. The FRM generates responses by manipulating information and, to function effectively, its data input must be restricted to task-relevant information. The properties of consciousness correspond to the various input requirements of the FRM; and when important information is missing from consciousness, functions of the FRM are adversely affected; both of which indicate that consciousness is the input data to the FRM. Qualitative and quantitative information (shape, size, location, etc.) are incorporated into the input data by a qualia array of colors, sounds, and so on, which makes the input conscious. This view of the biological function of consciousness provides an explanation why we have experiences; why we have emotional and other feelings, and why their loss is associated with poor decision-making; why blindsight patients do not spontaneously initiate responses to events in their blind field; why counter-habitual actions are only possible when the intended action is in mind; and the reason for inattentional blindness. PMID:25140159

  19. Functional morphology and evolutionary biology.

    PubMed

    Dullemeijer, P

    1980-01-01

    In this study the relationship between functional morpholoy and evolutionary biology is analysed by confronting the main concepts in both disciplines. Rather than only discussing this connection theoretically, the analysis is carried out by introducing important practical and experimental studies, which use aspects from both disciplines. The mentioned investigations are methodologically analysed and the consequences for extensions of the relationship are worked out. It can be shown that both disciplines have a large domain of their own and also share a large common ground. Many disagreements among evolutionary biologists can be reduced to differences in general philosophy (idealism vs. realism), selection of phenomenona (structure vs. function), definition of concepts (natural selection) and the position of the concept theory as an explaining factor (neutralists vs selectionist, random variation, determinate selection, etc.). The significance of functional morphology for evolutionary biology, and vice versa depends on these differences. For a neo-Darwinian evolutionary theory, contributions from functional and ecological morphology are indispensable. Of ultimate importance are the notions of internal selection and constraints in the constructions determining further development. In this context the concepts of random variation and natural selection need more detailed definition. The study ends with a recommendation for future research founded in a system-theoretical or structuralistic conception.

  20. The biological function of consciousness.

    PubMed

    Earl, Brian

    2014-01-01

    This research is an investigation of whether consciousness-one's ongoing experience-influences one's behavior and, if so, how. Analysis of the components, structure, properties, and temporal sequences of consciousness has established that, (1) contrary to one's intuitive understanding, consciousness does not have an active, executive role in determining behavior; (2) consciousness does have a biological function; and (3) consciousness is solely information in various forms. Consciousness is associated with a flexible response mechanism (FRM) for decision-making, planning, and generally responding in nonautomatic ways. The FRM generates responses by manipulating information and, to function effectively, its data input must be restricted to task-relevant information. The properties of consciousness correspond to the various input requirements of the FRM; and when important information is missing from consciousness, functions of the FRM are adversely affected; both of which indicate that consciousness is the input data to the FRM. Qualitative and quantitative information (shape, size, location, etc.) are incorporated into the input data by a qualia array of colors, sounds, and so on, which makes the input conscious. This view of the biological function of consciousness provides an explanation why we have experiences; why we have emotional and other feelings, and why their loss is associated with poor decision-making; why blindsight patients do not spontaneously initiate responses to events in their blind field; why counter-habitual actions are only possible when the intended action is in mind; and the reason for inattentional blindness.

  1. Functional Aspects of Biological Networks

    NASA Astrophysics Data System (ADS)

    Sneppen, Kim

    2007-03-01

    We discuss biological networks with respect to 1) relative positioning and importance of high degree nodes, 2) function and signaling, 3) logic and dynamics of regulation. Visually the soft modularity of many real world networks can be characterized in terms of number of high and low degrees nodes positioned relative to each other in a landscape analogue with mountains (high-degree nodes) and valleys (low-degree nodes). In these terms biological networks looks like rugged landscapes with separated peaks, hub proteins, which each are roughly as essential as any of the individual proteins on the periphery of the hub. Within each sup-domain of a molecular network one can often identify dynamical feedback mechanisms that falls into combinations of positive and negative feedback circuits. We will illustrate this with examples taken from phage regulation and bacterial uptake and regulation of small molecules. In particular we find that a double negative regulation often are replaced by a single positive link in unrelated organisms with same functional requirements. Overall we argue that network topology primarily reflects functional constraints. References: S. Maslov and K. Sneppen. ``Computational architecture of the yeast regulatory network." Phys. Biol. 2:94 (2005) A. Trusina et al. ``Functional alignment of regulatory networks: A study of temerate phages". Plos Computational Biology 1:7 (2005). J.B. Axelsen et al. ``Degree Landscapes in Scale-Free Networks" physics/0512075 (2005). A. Trusina et al. ``Hierarchy and Anti-Hierarchy in Real and Scale Free networks." PRL 92:178702 (2004) S. Semsey et al. ``Genetic Regulation of Fluxes: Iron Homeostasis of Escherichia coli". (2006) q-bio.MN/0609042

  2. Biocellion: accelerating computer simulation of multicellular biological system models

    PubMed Central

    Kang, Seunghwa; Kahan, Simon; McDermott, Jason; Flann, Nicholas; Shmulevich, Ilya

    2014-01-01

    Motivation: Biological system behaviors are often the outcome of complex interactions among a large number of cells and their biotic and abiotic environment. Computational biologists attempt to understand, predict and manipulate biological system behavior through mathematical modeling and computer simulation. Discrete agent-based modeling (in combination with high-resolution grids to model the extracellular environment) is a popular approach for building biological system models. However, the computational complexity of this approach forces computational biologists to resort to coarser resolution approaches to simulate large biological systems. High-performance parallel computers have the potential to address the computing challenge, but writing efficient software for parallel computers is difficult and time-consuming. Results: We have developed Biocellion, a high-performance software framework, to solve this computing challenge using parallel computers. To support a wide range of multicellular biological system models, Biocellion asks users to provide their model specifics by filling the function body of pre-defined model routines. Using Biocellion, modelers without parallel computing expertise can efficiently exploit parallel computers with less effort than writing sequential programs from scratch. We simulate cell sorting, microbial patterning and a bacterial system in soil aggregate as case studies. Availability and implementation: Biocellion runs on x86 compatible systems with the 64 bit Linux operating system and is freely available for academic use. Visit http://biocellion.com for additional information. Contact: seunghwa.kang@pnnl.gov PMID:25064572

  3. GPU accelerated dynamic functional connectivity analysis for functional MRI data.

    PubMed

    Akgün, Devrim; Sakoğlu, Ünal; Esquivel, Johnny; Adinoff, Bryon; Mete, Mutlu

    2015-07-01

    Recent advances in multi-core processors and graphics card based computational technologies have paved the way for an improved and dynamic utilization of parallel computing techniques. Numerous applications have been implemented for the acceleration of computationally-intensive problems in various computational science fields including bioinformatics, in which big data problems are prevalent. In neuroimaging, dynamic functional connectivity (DFC) analysis is a computationally demanding method used to investigate dynamic functional interactions among different brain regions or networks identified with functional magnetic resonance imaging (fMRI) data. In this study, we implemented and analyzed a parallel DFC algorithm based on thread-based and block-based approaches. The thread-based approach was designed to parallelize DFC computations and was implemented in both Open Multi-Processing (OpenMP) and Compute Unified Device Architecture (CUDA) programming platforms. Another approach developed in this study to better utilize CUDA architecture is the block-based approach, where parallelization involves smaller parts of fMRI time-courses obtained by sliding-windows. Experimental results showed that the proposed parallel design solutions enabled by the GPUs significantly reduce the computation time for DFC analysis. Multicore implementation using OpenMP on 8-core processor provides up to 7.7× speed-up. GPU implementation using CUDA yielded substantial accelerations ranging from 18.5× to 157× speed-up once thread-based and block-based approaches were combined in the analysis. Proposed parallel programming solutions showed that multi-core processor and CUDA-supported GPU implementations accelerated the DFC analyses significantly. Developed algorithms make the DFC analyses more practical for multi-subject studies with more dynamic analyses. Copyright © 2015 Elsevier Ltd. All rights reserved.

  4. Integrating functional genomics to accelerate mechanistic personalized medicine

    PubMed Central

    Tyner, Jeffrey W.

    2017-01-01

    The advent of deep sequencing technologies has resulted in the deciphering of tremendous amounts of genetic information. These data have led to major discoveries, and many anecdotes now exist of individual patients whose clinical outcomes have benefited from novel, genetically guided therapeutic strategies. However, the majority of genetic events in cancer are currently undrugged, leading to a biological gap between understanding of tumor genetic etiology and translation to improved clinical approaches. Functional screening has made tremendous strides in recent years with the development of new experimental approaches to studying ex vivo and in vivo drug sensitivity. Numerous discoveries and anecdotes also exist for translation of functional screening into novel clinical strategies; however, the current clinical application of functional screening remains largely confined to small clinical trials at specific academic centers. The intersection between genomic and functional approaches represents an ideal modality to accelerate our understanding of drug sensitivities as they relate to specific genetic events and further understand the full mechanisms underlying drug sensitivity patterns. PMID:28299357

  5. Integrating functional genomics to accelerate mechanistic personalized medicine.

    PubMed

    Tyner, Jeffrey W

    2017-03-01

    The advent of deep sequencing technologies has resulted in the deciphering of tremendous amounts of genetic information. These data have led to major discoveries, and many anecdotes now exist of individual patients whose clinical outcomes have benefited from novel, genetically guided therapeutic strategies. However, the majority of genetic events in cancer are currently undrugged, leading to a biological gap between understanding of tumor genetic etiology and translation to improved clinical approaches. Functional screening has made tremendous strides in recent years with the development of new experimental approaches to studying ex vivo and in vivo drug sensitivity. Numerous discoveries and anecdotes also exist for translation of functional screening into novel clinical strategies; however, the current clinical application of functional screening remains largely confined to small clinical trials at specific academic centers. The intersection between genomic and functional approaches represents an ideal modality to accelerate our understanding of drug sensitivities as they relate to specific genetic events and further understand the full mechanisms underlying drug sensitivity patterns.

  6. [The use of biological age on mental work capacity model in accelerated aging assessment of professional lorry-drivers].

    PubMed

    Bashkireva, A S

    2012-01-01

    The studies of biological age, aging rate, mental work capacity in professional drivers were conducted. The examination revealed peculiarities of system organization of functions determining the mental work capacity levels. Dynamics of the aging process of professional driver's organism in relation with calendar age and driving experience were shown using the biological age model. The results point at the premature decrease of the mental work capacity in professional drivers. It was proved, that premature age-related changes of physiologic and psychophysiologic indices in drivers are just "risk indicators", while long driving experience is a real risk factor, accelerating the aging process. The "risk group" with manifestations of accelerating aging was observed in 40-49-year old drivers with 15-19 years of professional experience. The expediency of using the following methods for the age rate estimation according to biologic age indices and necessity of prophylactic measures for premature and accelerated aging prevention among working population was demonstrated.

  7. [Biological function of vitamin A].

    PubMed

    Dusheiko, A A

    1980-01-01

    The paper deals with the generalized results of complex studies in the biological function of vitamin A conducted on the chicken glandular stomach. It is found out that at a certain diet the glandular stomach of chickens manifests a specific response to vitamin A deficiency: the amount of cells in the organ increases, their differentiation changes, the tissues relation is disturbed, hyperfunction is observed. The content of acid glycosaminglycanes varies, their biosynthesis is inhibited, the concentration of cations in the intercellular space increases. On the basis of these facts a conclusion is drawn that disturbances in the structure and function of glycocalyx are decisive in development of A-avitaminosis. It is established that the stomach intermediate zone mucosa secretion contains vitamin A which is strongly bound with a specific water-insoluble glycolipoprotein. The absence of vitamin A causes a disturbance in lipidation, glycosylation sulphatation and hydration of the secretion. A hypothesis is put forward according to which, vitamin A, joining the specific protein synthetized on ribosomes, initiates organization of the lipid phase. The latter might determine the direction and rate of protein transport in the system of smooth membranes where it is glycosidated. Formation of the lipid phase is disturbed when vitamin A is absent. This leads to changes in the protein migration pathways in the Golgi apparatus, which results in glycosidation disturbance as well. According to the same principle vitamin A may articipate in formation of glycolipoproteins not only of secretion but also of the intercellular substance, plasmatic membranes nuclei, lysosomes and other organelles.

  8. Three-directional acceleration phase mapping of myocardial function.

    PubMed

    Staehle, Felix; Jung, Bernd A; Bauer, Simon; Leupold, Jochen; Bock, Jelena; Lorenz, Ramona; Föll, Daniela; Markl, Michael

    2011-05-01

    An optimized acceleration encoded phase contrast method termed "acceleration phase mapping" for the assessment of regional myocardial function is presented. Based on an efficient gradient waveform design using two-sided encoding for in vivo three-directional acceleration mapping, echo and repetition times TE = 12-14 ms and TR = 15-17 ms for low accelerations sensitivity aenc = 5-8 m/s(2) were achieved. In addition to phantom validation, the technique was applied in a study with 10 healthy volunteers at 1.5T and 3T to evaluate its feasibility to assess regional myocardial acceleration at 1.5T and 3T. Results of the acceleration measurements were compared with the temporal derivative of myocardial velocities from three-directional velocity encoded standard phase contrast MRI in the same volunteers. The feasibility to assess myocardial acceleration along the radial, circumferential, and longitudinal direction of the left ventricle was demonstrated. Despite improved signal-to-noise-ratio at 3T (34% increase compared with 1.5T), image quality with respect to susceptibility artifacts was better 1.5T compared with 3T. Analysis of global and regional left ventricular acceleration showed characteristic patterns of systolic and diastolic acceleration and deceleration. Comparisons of directly measured and derived myocardial acceleration dynamics over the cardiac cycle revealed good correlation (r = 0.45-0.68, P < 0.01) between both methods. Copyright © 2010 Wiley-Liss, Inc.

  9. DNASU plasmid and PSI:Biology-Materials repositories: resources to accelerate biological research.

    PubMed

    Seiler, Catherine Y; Park, Jin G; Sharma, Amit; Hunter, Preston; Surapaneni, Padmini; Sedillo, Casey; Field, James; Algar, Rhys; Price, Andrea; Steel, Jason; Throop, Andrea; Fiacco, Michael; LaBaer, Joshua

    2014-01-01

    The mission of the DNASU Plasmid Repository is to accelerate research by providing high-quality, annotated plasmid samples and online plasmid resources to the research community through the curated DNASU database, website and repository (http://dnasu.asu.edu or http://dnasu.org). The collection includes plasmids from grant-funded, high-throughput cloning projects performed in our laboratory, plasmids from external researchers, and large collections from consortia such as the ORFeome Collaboration and the NIGMS-funded Protein Structure Initiative: Biology (PSI:Biology). Through DNASU, researchers can search for and access detailed information about each plasmid such as the full length gene insert sequence, vector information, associated publications, and links to external resources that provide additional protein annotations and experimental protocols. Plasmids can be requested directly through the DNASU website. DNASU and the PSI:Biology-Materials Repositories were previously described in the 2010 NAR Database Issue (Cormier, C.Y., Mohr, S.E., Zuo, D., Hu, Y., Rolfs, A., Kramer, J., Taycher, E., Kelley, F., Fiacco, M., Turnbull, G. et al. (2010) Protein Structure Initiative Material Repository: an open shared public resource of structural genomics plasmids for the biological community. Nucleic Acids Res., 38, D743-D749.). In this update we will describe the plasmid collection and highlight the new features in the website redesign, including new browse/search options, plasmid annotations and a dynamic vector mapping feature that was developed in collaboration with LabGenius. Overall, these plasmid resources continue to enable research with the goal of elucidating the role of proteins in both normal biological processes and disease.

  10. Accelerated soil carbon loss by biological changes under warming in Alaskan tundra

    NASA Astrophysics Data System (ADS)

    Liang, J.; Schuur, E.; Luo, Y.; Cole, J. R.; Jiang, L.; Konstantinidis, K.; Mauritz, M.; Natali, S.; Pegoraro, E.; Penton, C. R.; Plaza, C.; Salmon, V. G.; Shi, Z.; Tiedje, J. M.; Wu, L.; Xia, J.; Zhou, J.

    2016-12-01

    Permafrost regions, which contain a large amount of temperature-protected organic carbon (C), could be a significant C source as climate gets warmer. Climate warming can result in physical (e.g., temperature rise and permafrost thaw) and biological (e.g., microbial community composition) changes in the permafrost regions. While it is well agreed that physical changes can accelerate C releases to the atmosphere by increasing thermodynamic reaction rates and the accessibility of soil organic C (SOC) to decomposers, how biological changes impact permafrost soil C loss is still unclear. In this study, we quantified the impact of the biological changes on soil C loss in an Alaskan tundra through combining a process-based model and a unique field experiment. Our results showed that warming reduced the allocation of gross primary production to plants. In addition, warming significantly changed soil microbial functional community structure and consequently, stimulated the turnover rate of SOC, but decreased the C use efficiency. The altered biological properties significantly intensified soil C loss. Our study suggests that the predicted C loss in the permafrost regions may be underestimated due to the absence of the biological changes in Earth system models.

  11. Impaired lymphatic function accelerates cancer growth

    PubMed Central

    Steinskog, Eli Sihn Samdal; Sagstad, Solfrid Johanne; Wagner, Marek; Karlsen, Tine Veronica; Yang, Ning; Markhus, Carl Erik; Yndestad, Synnøve; Wiig, Helge; Eikesdal, Hans Petter

    2016-01-01

    Increased lymphangiogenesis is a common feature of cancer development and progression, yet the influence of impaired lymphangiogenesis on tumor growth is elusive. C3HBA breast cancer and KHT-1 sarcoma cell lines were implanted orthotopically in Chy mice, harboring a heterozygous inactivating mutation of vascular endothelial growth factor receptor-3, resulting in impaired dermal lymphangiogenesis. Accelerated tumor growth was observed in both cancer models in Chy mice, coinciding with reduced peritumoral lymphangiogenesis. An impaired lymphatic washout was observed from the peritumoral area in Chy mice with C3HBA tumors, and the number of macrophages was significantly reduced. While fewer macrophages were detected, the fraction of CD163+ M2 macrophages remained constant, causing a shift towards a higher M2/M1 ratio in Chy mice. No difference in adaptive immune cells was observed between wt and Chy mice. Interestingly, levels of pro- and anti-inflammatory macrophage-associated cytokines were reduced in C3HBA tumors, pointing to an impaired innate immune response. However, IL-6 was profoundly elevated in the C3HBA tumor interstitial fluid, and treatment with the anti-IL-6 receptor antibody tocilizumab inhibited breast cancer growth. Collectively, our data indicate that impaired lymphangiogenesis weakens anti-tumor immunity and favors tumor growth at an early stage of cancer development. PMID:27329584

  12. Dispatching function calls across accelerator devices

    DOEpatents

    Jacob, Arpith C.; Sallenave, Olivier H.

    2017-01-10

    In one embodiment, a computer-implemented method for dispatching a function call includes receiving, at a supervisor processing element (PE) and from an origin PE, an identifier of a target device, a stack frame of the origin PE, and an address of a function called from the origin PE. The supervisor PE allocates a target PE of the target device. The supervisor PE copies the stack frame of the origin PE to a new stack frame on a call stack of the target PE. The supervisor PE instructs the target PE to execute the function. The supervisor PE receives a notification that execution of the function is complete. The supervisor PE copies the stack frame of the target PE to the stack frame of the origin PE. The supervisor PE releases the target PE of the target device. The supervisor PE instructs the origin PE to resume execution of the program.

  13. Dispatching function calls across accelerator devices

    DOEpatents

    Jacob, Arpith C.; Sallenave, Olivier H.

    2017-01-17

    In one embodiment, a computer-implemented method for dispatching a function call includes receiving, at a supervisor processing element (PE) and from an origin PE, an identifier of a target device, a stack frame of the origin PE, and an address of a function called from the origin PE. The supervisor PE allocates a target PE of the target device. The supervisor PE copies the stack frame of the origin PE to a new stack frame on a call stack of the target PE. The supervisor PE instructs the target PE to execute the function. The supervisor PE receives a notification that execution of the function is complete. The supervisor PE copies the stack frame of the target PE to the stack frame of the origin PE. The supervisor PE releases the target PE of the target device. The supervisor PE instructs the origin PE to resume execution of the program.

  14. Integrating Functional, Developmental and Evolutionary Biology into Biology Curricula

    ERIC Educational Resources Information Center

    Haave, Neil

    2012-01-01

    A complete understanding of life involves how organisms are able to function in their environment and how they arise. Understanding how organisms arise involves both their evolution and development. Thus to completely comprehend living things, biology must study their function, development and evolution. Previous proposals for standardized…

  15. Functional Error Models to Accelerate Nested Sampling

    NASA Astrophysics Data System (ADS)

    Josset, L.; Elsheikh, A. H.; Demyanov, V.; Lunati, I.

    2014-12-01

    The main challenge in groundwater problems is the reliance on large numbers of unknown parameters with wide rage of associated uncertainties. To translate this uncertainty to quantities of interest (for instance the concentration of pollutant in a drinking well), a large number of forward flow simulations is required. To make the problem computationally tractable, Josset et al. (2013, 2014) introduced the concept of functional error models. It consists in two elements: a proxy model that is cheaper to evaluate than the full physics flow solver and an error model to account for the missing physics. The coupling of the proxy model and the error models provides reliable predictions that approximate the full physics model's responses. The error model is tailored to the problem at hand by building it for the question of interest. It follows a typical approach in machine learning where both the full physics and proxy models are evaluated for a training set (subset of realizations) and the set of responses is used to construct the error model using functional data analysis. Once the error model is devised, a prediction of the full physics response for a new geostatistical realization can be obtained by computing the proxy response and applying the error model. We propose the use of functional error models in a Bayesian inference context by combining it to the Nested Sampling (Skilling 2006; El Sheikh et al. 2013, 2014). Nested Sampling offers a mean to compute the Bayesian Evidence by transforming the multidimensional integral into a 1D integral. The algorithm is simple: starting with an active set of samples, at each iteration, the sample with the lowest likelihood is kept aside and replaced by a sample of higher likelihood. The main challenge is to find this sample of higher likelihood. We suggest a new approach: first the active set is sampled, both proxy and full physics models are run and the functional error model is build. Then, at each iteration of the Nested

  16. Fast economic development accelerates biological invasions in China.

    PubMed

    Lin, Wen; Zhou, Guofa; Cheng, Xinyue; Xu, Rumei

    2007-11-21

    Increasing levels of global trade and intercontinental travel have been cited as the major causes of biological invasion. However, indirect factors such as economic development that affect the intensity of invasion have not been quantitatively explored. Herein, using principal factor analysis, we investigated the relationship between biological invasion and economic development together with climatic information for China from the 1970s to present. We demonstrate that the increase in biological invasion is coincident with the rapid economic development that has occurred in China over the past three decades. The results indicate that the geographic prevalence of invasive species varies substantially on the provincial scale, but can be surprisingly well predicted using the combination of economic development (R(2) = 0.378) and climatic factors (R(2) = 0.347). Economic factors are proven to be at least equal to if not more determinant of the occurrence of invasive species than climatic factors. International travel and trade are shown to have played a less significant role in accounting for the intensity of biological invasion in China. Our results demonstrate that more attention should be paid to economic factors to improve the understanding, prediction and management of biological invasions.

  17. Fast Economic Development Accelerates Biological Invasions in China

    PubMed Central

    Lin, Wen; Zhou, Guofa; Cheng, Xinyue; Xu, Rumei

    2007-01-01

    Increasing levels of global trade and intercontinental travel have been cited as the major causes of biological invasion. However, indirect factors such as economic development that affect the intensity of invasion have not been quantitatively explored. Herein, using principal factor analysis, we investigated the relationship between biological invasion and economic development together with climatic information for China from the 1970s to present. We demonstrate that the increase in biological invasion is coincident with the rapid economic development that has occurred in China over the past three decades. The results indicate that the geographic prevalence of invasive species varies substantially on the provincial scale, but can be surprisingly well predicted using the combination of economic development (R2 = 0.378) and climatic factors (R2 = 0.347). Economic factors are proven to be at least equal to if not more determinant of the occurrence of invasive species than climatic factors. International travel and trade are shown to have played a less significant role in accounting for the intensity of biological invasion in China. Our results demonstrate that more attention should be paid to economic factors to improve the understanding, prediction and management of biological invasions. PMID:18030342

  18. Functional Translational Readthrough: A Systems Biology Perspective

    PubMed Central

    Schueren, Fabian

    2016-01-01

    Translational readthrough (TR) has come into renewed focus because systems biology approaches have identified the first human genes undergoing functional translational readthrough (FTR). FTR creates functional extensions to proteins by continuing translation of the mRNA downstream of the stop codon. Here we review recent developments in TR research with a focus on the identification of FTR in humans and the systems biology methods that have spurred these discoveries. PMID:27490485

  19. Functional Translational Readthrough: A Systems Biology Perspective.

    PubMed

    Schueren, Fabian; Thoms, Sven

    2016-08-01

    Translational readthrough (TR) has come into renewed focus because systems biology approaches have identified the first human genes undergoing functional translational readthrough (FTR). FTR creates functional extensions to proteins by continuing translation of the mRNA downstream of the stop codon. Here we review recent developments in TR research with a focus on the identification of FTR in humans and the systems biology methods that have spurred these discoveries.

  20. Metacognition: computation, biology and function.

    PubMed

    Fleming, Stephen M; Dolan, Raymond J; Frith, Christopher D

    2012-05-19

    Many complex systems maintain a self-referential check and balance. In animals, such reflective monitoring and control processes have been grouped under the rubric of metacognition. In this introductory article to a Theme Issue on metacognition, we review recent and rapidly progressing developments from neuroscience, cognitive psychology, computer science and philosophy of mind. While each of these areas is represented in detail by individual contributions to the volume, we take this opportunity to draw links between disciplines, and highlight areas where further integration is needed. Specifically, we cover the definition, measurement, neurobiology and possible functions of metacognition, and assess the relationship between metacognition and consciousness. We propose a framework in which level of representation, order of behaviour and access consciousness are orthogonal dimensions of the conceptual landscape.

  1. Metacognition: computation, biology and function

    PubMed Central

    Fleming, Stephen M.; Dolan, Raymond J.; Frith, Christopher D.

    2012-01-01

    Many complex systems maintain a self-referential check and balance. In animals, such reflective monitoring and control processes have been grouped under the rubric of metacognition. In this introductory article to a Theme Issue on metacognition, we review recent and rapidly progressing developments from neuroscience, cognitive psychology, computer science and philosophy of mind. While each of these areas is represented in detail by individual contributions to the volume, we take this opportunity to draw links between disciplines, and highlight areas where further integration is needed. Specifically, we cover the definition, measurement, neurobiology and possible functions of metacognition, and assess the relationship between metacognition and consciousness. We propose a framework in which level of representation, order of behaviour and access consciousness are orthogonal dimensions of the conceptual landscape. PMID:22492746

  2. Biological dose volume histograms during conformal hypofractionated accelerated radiotherapy for prostate cancer

    SciTech Connect

    Koukourakis, Michael I.; Abatzoglou, Ioannis; Touloupidis, Stavros; Manavis, Ioannis

    2007-01-15

    Radiobiological data suggest that prostate cancer has a low {alpha}/{beta} ratio. Large radiotherapy fractions may, therefore, prove more efficacious than standard radiotherapy, while radiotherapy acceleration should further improve control rates. This study describes the radiobiology of a conformal hypofractionated accelerated radiotherapy scheme for the treatment of high risk prostate cancer. Anteroposterior fields to the pelvis deliver a daily dose of 2.7 Gy, while lateral fields confined to the prostate and seminal vesicles deliver an additional daily dose of 0.7 Gy. Radiotherapy is accomplished within 19 days (15 fractions). Dose volume histograms, calculated for tissue specific {alpha}/{beta} ratios and time factors, predict a high biological dose to the prostate and seminal vesicles (77-93 Gy). The biological dose to normal pelvic tissues is maintained at standard levels. Radiobiological dosimetry suggests that, using hypofractionated and accelerated radiotherapy, high biological radiation dose can be given to the prostate without overdosing normal tissues.

  3. Aluminum-26 as a biological tracer using accelerator mass spectrometry

    NASA Astrophysics Data System (ADS)

    Flarend, Richard Edward

    1997-06-01

    The development of accelerator mass spectrometry (AMS) has provided a practical method of detection for the only isotope of aluminum suitable as a tracer, 26Al. The use of 26Al as a tracer for aluminum has made possible the study of aluminum metabolism and the pharmacokinetics of aluminum-containing drugs at physiological levels. An overview of the various advantages of using 26Al as a tracer for aluminum and a general description of the AMS technique as applied to bio-medical applications is given. To illustrate the versatility of 26Al as a tracer for aluminum, 26Al studies of the past several years are discussed briefly. In addition, Two novel investigations dealing with 26Al-labeled drugs will be presented in more detail. In one of these studies, it was found that 26Al from aluminum hydroxide and aluminum phosphate vaccine adjuvants appeared in the blood just one hour after intramuscular injection. This is a surprising result since the currently held theory of how adjuvants work assumes that adjuvants remain insoluble and hold the antigen at the injection site for a long period of time. In another project, 26Al-labeled antiperspirants are being characterized by combining AMS with traditional analytical and chromatographic techniques. Future directions for this and other possible studies are discussed.

  4. Leg joint function during walking acceleration and deceleration.

    PubMed

    Qiao, Mu; Jindrich, Devin L

    2016-01-04

    Although constant-average-velocity walking has been extensively studied, less is known about walking maneuvers that change speed. We investigated the function of individual leg joints when humans walked at a constant speed, accelerated or decelerated. We hypothesized that leg joints make different functional contributions to maneuvers. Specifically, we hypothesized that the hip generates positive mechanical work (acting like a "motor"), the knee generates little mechanical work (acting like a "strut"), and the ankle absorbs energy during the first half of stance and generates energy during the second half (consistent with "spring"-like function). We recorded full body kinematics and kinetics, used inverse dynamics to estimate net joint moments, and decomposed joint function into strut-, motor-, damper-, and spring-like components using indices based on net joint work. Although overall leg mechanics were primarily strut-like, individual joints did not act as struts during stance. The hip functioned as a power generating "motor," and ankle function was consistent with spring-like behavior. Even though net knee work was small, the knee did not behave solely as a strut but also showed motor-, and damper-like function. Acceleration involved increased motor-like function of the hip and ankle. Deceleration involved decreased hip motor-like function and ankle spring-like function and increased damping at the knee and ankle. Changes to joint mechanical work were primarily due to changes in joint angular displacements and not net moments. Overall, joints maintain different functional roles during unsteady locomotion.

  5. Determination of acceptance criteria and sample sizes for accelerated stability comparability studies for biologics.

    PubMed

    Yu, Binbing; Zeng, Lingmin; Yang, Harry

    2017-07-22

    Changes of manufacturing processes are common. It is required by the regulatory agencies that manufacturers establish adequate and appropriate comparability between pre-change and post-change products. The goals of comparability assessments are to demonstrate the comparability and consistency of product quality before and after change and to demonstrate that the changes do not have an adverse effect on safety and efficacy of the drug products. Accelerated or stressed stability studies may shed light on drug quality under stressed environmental conditions and on product differences in the degradation pathways. Comparability of accelerated stability data may provide further evidence on the impact of process change. Equivalence test has been recommended to demonstrate the comparability of stability profiles for accelerated stability studies. Selection of appropriate acceptance criteria for determining comparability is one of the most challenging steps in the comparability studies. Because of the inherent heterogeneity of biologics, the stability profiles may vary considerably from batch to batch. It is more challenging to set the acceptance criteria for comparing the accelerated stability data for biologics. In this article, we present an approach for determining the acceptance criteria and necessary sample sizes for accelerated comparability studies for biologics. Copyright © 2017 International Alliance for Biological Standardization. Published by Elsevier Ltd. All rights reserved.

  6. Accelerating cancer systems biology research through Semantic Web technology.

    PubMed

    Wang, Zhihui; Sagotsky, Jonathan; Taylor, Thomas; Shironoshita, Patrick; Deisboeck, Thomas S

    2013-01-01

    Cancer systems biology is an interdisciplinary, rapidly expanding research field in which collaborations are a critical means to advance the field. Yet the prevalent database technologies often isolate data rather than making it easily accessible. The Semantic Web has the potential to help facilitate web-based collaborative cancer research by presenting data in a manner that is self-descriptive, human and machine readable, and easily sharable. We have created a semantically linked online Digital Model Repository (DMR) for storing, managing, executing, annotating, and sharing computational cancer models. Within the DMR, distributed, multidisciplinary, and inter-organizational teams can collaborate on projects, without forfeiting intellectual property. This is achieved by the introduction of a new stakeholder to the collaboration workflow, the institutional licensing officer, part of the Technology Transfer Office. Furthermore, the DMR has achieved silver level compatibility with the National Cancer Institute's caBIG, so users can interact with the DMR not only through a web browser but also through a semantically annotated and secure web service. We also discuss the technology behind the DMR leveraging the Semantic Web, ontologies, and grid computing to provide secure inter-institutional collaboration on cancer modeling projects, online grid-based execution of shared models, and the collaboration workflow protecting researchers' intellectual property.

  7. Accelerating Cancer Systems Biology Research through Semantic Web Technology

    PubMed Central

    Wang, Zhihui; Sagotsky, Jonathan; Taylor, Thomas; Shironoshita, Patrick; Deisboeck, Thomas S.

    2012-01-01

    Cancer systems biology is an interdisciplinary, rapidly expanding research field in which collaborations are a critical means to advance the field. Yet the prevalent database technologies often isolate data rather than making it easily accessible. The Semantic Web has the potential to help facilitate web-based collaborative cancer research by presenting data in a manner that is self-descriptive, human and machine readable, and easily sharable. We have created a semantically linked online Digital Model Repository (DMR) for storing, managing, executing, annotating, and sharing computational cancer models. Within the DMR, distributed, multidisciplinary, and inter-organizational teams can collaborate on projects, without forfeiting intellectual property. This is achieved by the introduction of a new stakeholder to the collaboration workflow, the institutional licensing officer, part of the Technology Transfer Office. Furthermore, the DMR has achieved silver level compatibility with the National Cancer Institute’s caBIG®, so users can not only interact with the DMR through a web browser but also through a semantically annotated and secure web service. We also discuss the technology behind the DMR leveraging the Semantic Web, ontologies, and grid computing to provide secure inter-institutional collaboration on cancer modeling projects, online grid-based execution of shared models, and the collaboration workflow protecting researchers’ intellectual property. PMID:23188758

  8. Discrete Variables Function Optimization Using Accelerated Biogeography-Based Optimization

    NASA Astrophysics Data System (ADS)

    Lohokare, M. R.; Pattnaik, S. S.; Devi, S.; Panigrahi, B. K.; Das, S.; Jadhav, D. G.

    Biogeography-Based Optimization (BBO) is a bio-inspired and population based optimization algorithm. This is mainly formulated to optimize functions of discrete variables. But the convergence of BBO to the optimum value is slow as it lacks in exploration ability. The proposed Accelerated Biogeography-Based Optimization (ABBO) technique is an improved version of BBO. In this paper, authors accelerated the original BBO to enhance the exploitation and exploration ability by modified mutation operator and clear duplicate operator. This significantly improves the convergence characteristics of the original algorithm. To validate the performance of ABBO, experiments have been conducted on unimodal and multimodal benchmark functions of discrete variables. The results shows excellent performance when compared with other modified BBOs and other optimization techniques like stud genetic algorithm (SGA) and ant colony optimization (ACO). The results are also analyzed by using two paired t- test.

  9. Accelerating Computation of Large Biological Datasets using MapReduce Framework.

    PubMed

    Wang, Chao; Dai, Dong; Li, Xi; Wang, Aili; Zhou, Xuehai

    2016-04-05

    The maximal information coefficient (MIC) has been proposed to discover relationships and associations between pairs of variables. It poses significant challenges for bioinformatics scientists to accelerate the MIC calculation, especially in genome sequencing and biological annotations. In this paper we explore a parallel approach which uses MapReduce framework to improve the computing efficiency and throughput of the MIC computation. The acceleration system includes biological data storage on HDFS, preprocessing algorithms, distributed memory cache mechanism, and the partition of MapReduce jobs. Based on the acceleration approach, we extend the traditional two-variable algorithm to multiple variables algorithm. The experimental results show that our parallel solution provides a linear speedup comparing with original algorithm without affecting the correctness and sensitivity.

  10. Biological and medical research with accelerated heavy ions at the Bevalac, 1977-1980. [Lead abstract

    SciTech Connect

    Pirruccello, M.C.; Tobias, C.A.

    1980-11-01

    Separate abstracts were prepared for the 46 papers presented in this progress report. This report is a major review of studies with accelerated heavy ions carried out by the Biology and Medicine Division of Lawrence Berkeley Laboratory from 1977 to 1980. (KRM)

  11. Network biology: a direct approach to study biological function.

    PubMed

    Emmert-Streib, Frank; Glazko, Galina V

    2011-01-01

    In this paper we discuss the dualism of gene networks and their role in systems biology. We argue that gene networks (1) can serve as a conceptual framework, forming a fundamental level of a phenomenological description, and (2) are a means to represent and analyze data. The latter point does not only allow a systems analysis but is even amenable for a direct approach to study biological function. Here we focus on the clarity of our main arguments and conceptual meaning of gene networks, rather than the causal inference of gene networks from data. WIREs Syst Biol Med 2011 3 379-391 DOI: 10.1002/wsbm.134 For further resources related to this article, please visit the WIREs website. Copyright © 2010 John Wiley & Sons, Inc.

  12. Functional model of biological neural networks

    PubMed Central

    2010-01-01

    A functional model of biological neural networks, called temporal hierarchical probabilistic associative memory (THPAM), is proposed in this paper. THPAM comprises functional models of dendritic trees for encoding inputs to neurons, a first type of neuron for generating spike trains, a second type of neuron for generating graded signals to modulate neurons of the first type, supervised and unsupervised Hebbian learning mechanisms for easy learning and retrieving, an arrangement of dendritic trees for maximizing generalization, hardwiring for rotation-translation-scaling invariance, and feedback connections with different delay durations for neurons to make full use of present and past informations generated by neurons in the same and higher layers. These functional models and their processing operations have many functions of biological neural networks that have not been achieved by other models in the open literature and provide logically coherent answers to many long-standing neuroscientific questions. However, biological justifications of these functional models and their processing operations are required for THPAM to qualify as a macroscopic model (or low-order approximate) of biological neural networks. PMID:22132040

  13. Particle Accelerator Applications: Ion and Electron Irradiation in Materials Science, Biology and Medicine

    SciTech Connect

    Rodriguez-Fernandez, Luis

    2010-09-10

    Although the developments of particle accelerators are devoted to basic study of matter constituents, since the beginning these machines have been applied with different purposes in many areas also. Today particle accelerators are essential instruments for science and technology. This work presents an overview of the main application for direct particle irradiation with accelerator in material science, biology and medicine. They are used for material synthesis by ion implantation and charged particle irradiation; to make coatings and micromachining; to characterize broad kind of samples by ion beam analysis techniques; as mass spectrometers for atomic isotopes determination. In biomedicine the accelerators are applied for the study of effects by charged particles on cells. In medicine the radiotherapy by electron irradiation is widely used, while hadrontherapy is still under development. Also, they are necessary for short life radioisotopes production required in radiodiagnostic.

  14. Particle Accelerator Applications: Ion and Electron Irradiation in Materials Science, Biology and Medicine

    NASA Astrophysics Data System (ADS)

    Rodríguez-Fernández, Luis

    2010-09-01

    Although the developments of particle accelerators are devoted to basic study of matter constituents, since the beginning these machines have been applied with different purposes in many areas also. Today particle accelerators are essential instruments for science and technology. This work presents an overview of the main application for direct particle irradiation with accelerator in material science, biology and medicine. They are used for material synthesis by ion implantation and charged particle irradiation; to make coatings and micromachining; to characterize broad kind of samples by ion beam analysis techniques; as mass spectrometers for atomic isotopes determination. In biomedicine the accelerators are applied for the study of effects by charged particles on cells. In medicine the radiotherapy by electron irradiation is widely used, while hadrontherapy is still under development. Also, they are necessary for short life radioisotopes production required in radiodiagnostic.

  15. Measurement of acceleration: a new method of monitoring neuromuscular function.

    PubMed

    Viby-Mogensen, J; Jensen, E; Werner, M; Nielsen, H K

    1988-01-01

    A new method for monitoring neuromuscular function based on measurement of acceleration is presented. The rationale behind the method is Newton's second law, stating that the acceleration is directly proportional to the force. For measurement of acceleration, a piezo-electric ceramic wafer was used. When this piezo electrode was fixed to the thumb, an electrical signal proportional to the acceleration was produced whenever the thumb moved in response to nerve stimulation. The electrical signal was registered and analysed in a Myograph 2000 neuromuscular transmission monitor. In 35 patients anaesthetized with halothane, train-of-four ratios measured with the accelerometer (ACT-TOF) were compared with simultaneous mechanical train-of-four ratios (FDT-TOF). Control ACT-TOF ratios were significantly higher than control FDT-TOF ratios: 116 +/- 12 and 98 +/- 4 (mean +/- s.d.), respectively. In five patients not given any relaxant during the anaesthetic procedure (20-60 min), both responses were remarkably constant. In 30 patients given vecuronium, a close linear relationship was found during recovery between ACT-TOF and FDT-TOF ratios. It is concluded that the method fulfils the basic requirements for a simple and reliable clinical monitoring tool.

  16. Phenological response of a key ecosystem function to biological invasion.

    PubMed

    Alp, Maria; Cucherousset, Julien; Buoro, Mathieu; Lecerf, Antoine

    2016-05-01

    Although climate warming has been widely demonstrated to induce shifts in the timing of many biological events, the phenological consequences of other prominent global change drivers remain largely unknown. Here, we investigated the effects of biological invasions on the seasonality of leaf litter decomposition, a crucial freshwater ecosystem function. Decomposition rates were quantified in 18 temperate shallow lakes distributed along a gradient of crayfish invasion and a temperature-based model was constructed to predict yearly patterns of decomposition. We found that, through direct detritus consumption, omnivorous invasive crayfish accelerated decomposition rates up to fivefold in spring, enhancing temperature dependence of the process and shortening the period of major detritus availability in the ecosystem by up to 39 days (95% CI: 15-61). The fact that our estimates are an order of magnitude higher than any previously reported climate-driven phenological shifts indicates that some powerful drivers of phenological change have been largely overlooked.

  17. [Biological functions of tin and disease].

    PubMed

    Arakawa, Yasuaki; Tomiyama, Kenichi

    2016-07-01

    Tin generates a wide variety of biological functions due to its chemical character. In this article, the modes of the biological functions of tin(especially organotin compounds) are reviewed, with special emphasis on the connection with the immune system, brain nervous system and endocrine system, on the basis of our data. To sum up this article, the biological functions of organotin compounds appear to be due to the following several processes: (1) their incorporation into the cells in vesicle form through fusion or in a similar manner to their incorporation in cationic form; (2) transport to and accumulation in the regions of the Golgi apparatus and endoplasmic reticulum (ER), but not to or in the plasma membrane or nucleus because of their hydrophobicity; (3) inhibition of intracellular phospholipid transport between organelles due to impairment of the structures and functions of the Golgi apparatus and ER; (4) inhibition of the membrane-mediated signal transduction system leading to DNA synthesis via phospholipid turnover and Ca2+ mobilization, as in cell proliferation systems; (5) disturbance of the trace element balance and the localization of certain elements; (6) disorders of membrane-mediated Ca2+ homeostasis via various channel functions including Zn modulation on the plasma and organelle membranes, and protein phosphorylation, as in the signal transduction systems of memory and olfaction; (7) necrosis or apoptosis in vivo or toxic cell death in vitro.

  18. Engineering functionality gradients by dip coating process in acceleration mode.

    PubMed

    Faustini, Marco; Ceratti, Davide R; Louis, Benjamin; Boudot, Mickael; Albouy, Pierre-Antoine; Boissière, Cédric; Grosso, David

    2014-10-08

    In this work, unique functional devices exhibiting controlled gradients of properties are fabricated by dip-coating process in acceleration mode. Through this new approach, thin films with "on-demand" thickness graded profiles at the submillimeter scale are prepared in an easy and versatile way, compatible for large-scale production. The technique is adapted to several relevant materials, including sol-gel dense and mesoporous metal oxides, block copolymers, metal-organic framework colloids, and commercial photoresists. In the first part of the Article, an investigation on the effect of the dip coating speed variation on the thickness profiles is reported together with the critical roles played by the evaporation rate and by the viscosity on the fluid draining-induced film formation. In the second part, dip-coating in acceleration mode is used to induce controlled variation of functionalities by playing on structural, chemical, or dimensional variations in nano- and microsystems. In order to demonstrate the full potentiality and versatility of the technique, original graded functional devices are made including optical interferometry mirrors with bidirectional gradients, one-dimensional photonic crystals with a stop-band gradient, graded microfluidic channels, and wetting gradient to induce droplet motion.

  19. Menopause Is Associated with Accelerated Lung Function Decline.

    PubMed

    Triebner, Kai; Matulonga, Bobette; Johannessen, Ane; Suske, Sandra; Benediktsdóttir, Bryndís; Demoly, Pascal; Dharmage, Shyamali C; Franklin, Karl A; Garcia-Aymerich, Judith; Gullón Blanco, José Antonio; Heinrich, Joachim; Holm, Mathias; Jarvis, Debbie; Jõgi, Rain; Lindberg, Eva; Moratalla Rovira, Jesús Martínez; Muniozguren Agirre, Nerea; Pin, Isabelle; Probst-Hensch, Nicole; Puggini, Luca; Raherison, Chantal; Sánchez-Ramos, José Luis; Schlünssen, Vivi; Sunyer, Jordi; Svanes, Cecilie; Hustad, Steinar; Leynaert, Bénédicte; Gómez Real, Francisco

    2017-04-15

    Menopause is associated with changes in sex hormones, which affect immunity, inflammation, and osteoporosis and may impair lung function. Lung function decline has not previously been investigated in relation to menopause. To study whether lung function decline, assessed by FVC and FEV1, is accelerated in women who undergo menopause. The population-based longitudinal European Community Respiratory Health Survey provided serum samples, spirometry, and questionnaire data about respiratory and reproductive health from three study waves (n = 1,438). We measured follicle-stimulating hormone and luteinizing hormone and added information on menstrual patterns to determine menopausal status using latent class analysis. Associations with lung function decline were investigated using linear mixed effects models, adjusting for age, height, weight, pack-years, current smoking, age at completed full-time education, spirometer, and including study center as random effect. Menopausal status was associated with accelerated lung function decline. The adjusted mean FVC decline was increased by -10.2 ml/yr (95% confidence interval [CI], -13.1 to -7.2) in transitional women and -12.5 ml/yr (95% CI, -16.2 to -8.9) in post-menopausal women, compared with women menstruating regularly. The adjusted mean FEV1 decline increased by -3.8 ml/yr (95% CI, -6.3 to -2.9) in transitional women and -5.2 ml/yr (95% CI, -8.3 to -2.0) in post-menopausal women. Lung function declined more rapidly among transitional and post-menopausal women, in particular for FVC, beyond the expected age change. Clinicians should be aware that respiratory health often deteriorates during reproductive aging.

  20. Functionalizing Electrospun Fibers with Biologically Relevant Macromolecules

    PubMed Central

    Casper, Cheryl L.; Yamaguchi, Nori; Kiick, Kristi L.; Rabolt, John F.

    2008-01-01

    The development of functionalized polymers that can elicit specific biological responses is of great interest in the biomedical community, as well as the development of methods to fabricate these biologically functionalized polymers. For example, the generation of fibrous matrices with biological properties and fiber diameters commensurate with those of the natural extracellular matrix (ECM) may permit the development of novel materials for use in wound healing or tissue engineering. The goal of this work is, therefore, to create a biologically active functionalized electrospun matrix to permit immobilization and long-term delivery of growth factors. In this work, poly(ethylene glycol) functionalized with low molecular weight heparin (PEG-LMWH) was fabricated into fibers for possible use in drug delivery, tissue engineering, or wound repair applications. Electrospinning was chosen to process the LMWH into fiber form due to the small fiber diameters and high degree of porosity that can be obtained relatively quickly and using small amounts of starting material. Both free LMWH and PEG-LMWH were investigated for their ability to be incorporated into electrospun fibers. Each of the samples were mixed with a carrier polymer consisting of either a 10 wt % poly(ethylene oxide) (PEO) or 45 wt % poly(lactide-co-glycolide) (PLGA). Field emission scanning electron microscopy (FESEM), energy-dispersive X-ray analysis (EDX), UV–vis spectroscopy, and multiphoton microscopy were used to characterize the electrospun matrices. The incorporation of heparin into the electrospun PEO and PLGA fibers did not affect the surface morphology or fiber diameters. The fibers produced had diameters ranging from approximately 100 to 400 nm. Toluidine blue assays of heparin suggest that it can be incorporated into an electrospun matrix at concentrations ranging from 3.5 to 85 μg per milligram of electrospun fibers. Multiphoton microscopy confirmed that incorporation of PEG-LMWH into the matrix

  1. Accelerating Density Functional Calculations with Graphics Processing Unit.

    PubMed

    Yasuda, Koji

    2008-08-01

    An algorithm is presented for graphics processing units (GPUs), which execute single-precision arithmetic much faster than commodity microprocessors (CPUs), to calculate the exchange-correlation term in ab initio density functional calculations. The algorithm was implemented and applied to two molecules, taxol and valinomycin. The errors in the total energies were about 10(-5) a.u., which is accurate enough for practical usage. If the exchange-correlation term is split into a simple analytic model potential and the correction to it, and only the latter is calculated with the GPU, the energy error is decreased by an order of magnitude. The resulting time to compute the exchange-correlation term is smaller than it is on the latest CPU by a factor of 10, indicating that a GPU running the proposed algorithm accelerates the density functional calculation considerably.

  2. Marine Carotenoids: Biological Functions and Commercial Applications

    PubMed Central

    Vílchez, Carlos; Forján, Eduardo; Cuaresma, María; Bédmar, Francisco; Garbayo, Inés; Vega, José M.

    2011-01-01

    Carotenoids are the most common pigments in nature and are synthesized by all photosynthetic organisms and fungi. Carotenoids are considered key molecules for life. Light capture, photosynthesis photoprotection, excess light dissipation and quenching of singlet oxygen are among key biological functions of carotenoids relevant for life on earth. Biological properties of carotenoids allow for a wide range of commercial applications. Indeed, recent interest in the carotenoids has been mainly for their nutraceutical properties. A large number of scientific studies have confirmed the benefits of carotenoids to health and their use for this purpose is growing rapidly. In addition, carotenoids have traditionally been used in food and animal feed for their color properties. Carotenoids are also known to improve consumer perception of quality; an example is the addition of carotenoids to fish feed to impart color to farmed salmon. PMID:21556162

  3. Marine carotenoids: biological functions and commercial applications.

    PubMed

    Vílchez, Carlos; Forján, Eduardo; Cuaresma, María; Bédmar, Francisco; Garbayo, Inés; Vega, José M

    2011-03-03

    Carotenoids are the most common pigments in nature and are synthesized by all photosynthetic organisms and fungi. Carotenoids are considered key molecules for life. Light capture, photosynthesis photoprotection, excess light dissipation and quenching of singlet oxygen are among key biological functions of carotenoids relevant for life on earth. Biological properties of carotenoids allow for a wide range of commercial applications. Indeed, recent interest in the carotenoids has been mainly for their nutraceutical properties. A large number of scientific studies have confirmed the benefits of carotenoids to health and their use for this purpose is growing rapidly. In addition, carotenoids have traditionally been used in food and animal feed for their color properties. Carotenoids are also known to improve consumer perception of quality; an example is the addition of carotenoids to fish feed to impart color to farmed salmon.

  4. Aegerolysins: Structure, function, and putative biological role

    PubMed Central

    Berne, Sabina; Lah, Ljerka; Sepčić, Kristina

    2009-01-01

    Aegerolysins, discovered in fungi, bacteria and plants, are highly similar proteins with interesting biological properties. Certain aegerolysins possess antitumoral, antiproliferative, and antibacterial activities. Further possible medicinal applications include their use in the prevention of atherosclerosis, or as vaccines. Additional biotechnological value of fungal aegerolysins lies in their involvement in development, which could improve cultivation of commercially important edible mushrooms. Besides, new insights on microheterogeneity of raft-like membrane domains could be gained by using aegerolysins as specific markers in cell and molecular biology. Although the exact function of aegerolysins in their producing organisms remains to be explained, they are biochemically well characterized all-β structured proteins sharing the following common features: low isoelectric points, similar molecular weights (15–17 kDa), and stability in a wide pH range. PMID:19309687

  5. Anti-Muscarinic Adjunct Therapy Accelerates Functional Human Oligodendrocyte Repair

    PubMed Central

    Abiraman, Kavitha; Pol, Suyog U.; O'Bara, Melanie A.; Chen, Guang-Di; Khaku, Zainab M.; Wang, Jing; Thorn, David; Vedia, Bansi H.; Ekwegbalu, Ezinne C.; Li, Jun-Xu; Salvi, Richard J.

    2015-01-01

    Therapeutic repair of myelin disorders may be limited by the relatively slow rate of human oligodendrocyte differentiation. To identify appropriate pharmacological targets with which to accelerate differentiation of human oligodendrocyte progenitors (hOPCs) directly, we used CD140a/O4-based FACS of human forebrain and microarray to hOPC-specific receptors. Among these, we identified CHRM3, a M3R muscarinic acetylcholine receptor, as being restricted to oligodendrocyte-biased CD140a+O4+ cells. Muscarinic agonist treatment of hOPCs resulted in a specific and dose-dependent blockade of oligodendrocyte commitment. Conversely, when hOPCs were cocultured with human neurons, M3R antagonist treatment stimulated oligodendrocytic differentiation. Systemic treatment with solifenacin, an FDA-approved muscarinic receptor antagonist, increased oligodendrocyte differentiation of transplanted hOPCs in hypomyelinated shiverer/rag2 brain. Importantly, solifenacin treatment of engrafted animals reduced auditory brainstem response interpeak latency, indicative of increased conduction velocity and thereby enhanced functional repair. Therefore, solifenacin and other selective muscarinic antagonists represent new adjunct approaches to accelerate repair by engrafted human progenitors. PMID:25716865

  6. [Structure and biologic function of IFNgamma].

    PubMed

    Nammous, Abdul Halim; Pietruczuk, Małgorzata; Zubacki, Dymitr; Dobrzycki, Ignacy

    2005-01-01

    IFNgamma is a pro-inflammatory, pleiotropic cytokine mainly produced by the CD4+, CD8+ lymphocytes and NK cells, that play an important role in macrophage activation, antigen presentation enhance and induce innate, and acquired immune responses. IFNgamma by interaction with they cell-surface receptors (IFNgammaR) activates cellular effects including stimulation of antiviral and antimicrobial mechanisms, inhibition of cellular proliferation, regulates cells apoptosis and leukocyte trafficing to sites of inflammation. The purpose of this article is to present the current understending of structure and biological function of IFNgamma in the light of current opinions regarding this matter.

  7. Wet Lab Accelerator: A Web-Based Application Democratizing Laboratory Automation for Synthetic Biology.

    PubMed

    Bates, Maxwell; Berliner, Aaron J; Lachoff, Joe; Jaschke, Paul R; Groban, Eli S

    2017-01-20

    Wet Lab Accelerator (WLA) is a cloud-based tool that allows a scientist to conduct biology via robotic control without the need for any programming knowledge. A drag and drop interface provides a convenient and user-friendly method of generating biological protocols. Graphically developed protocols are turned into programmatic instruction lists required to conduct experiments at the cloud laboratory Transcriptic. Prior to the development of WLA, biologists were required to write in a programming language called "Autoprotocol" in order to work with Transcriptic. WLA relies on a new abstraction layer we call "Omniprotocol" to convert the graphical experimental description into lower level Autoprotocol language, which then directs robots at Transcriptic. While WLA has only been tested at Transcriptic, the conversion of graphically laid out experimental steps into Autoprotocol is generic, allowing extension of WLA into other cloud laboratories in the future. WLA hopes to democratize biology by bringing automation to general biologists.

  8. Flavonoids: biosynthesis, biological functions, and biotechnological applications

    PubMed Central

    Falcone Ferreyra, María L.; Rius, Sebastián P.; Casati, Paula

    2012-01-01

    Flavonoids are widely distributed secondary metabolites with different metabolic functions in plants. The elucidation of the biosynthetic pathways, as well as their regulation by MYB, basic helix-loop-helix (bHLH), and WD40-type transcription factors, has allowed metabolic engineering of plants through the manipulation of the different final products with valuable applications. The present review describes the regulation of flavonoid biosynthesis, as well as the biological functions of flavonoids in plants, such as in defense against UV-B radiation and pathogen infection, nodulation, and pollen fertility. In addition, we discuss different strategies and achievements through the genetic engineering of flavonoid biosynthesis with implication in the industry and the combinatorial biosynthesis in microorganisms by the reconstruction of the pathway to obtain high amounts of specific compounds. PMID:23060891

  9. Transcription factor binding energy vs. biological function

    NASA Astrophysics Data System (ADS)

    Djordjevic, M.; Grotewold, E.

    2007-03-01

    Transcription factors (TFs) are proteins that bind to DNA and regulate expression of genes. Identification of transcription factor binding sites within the regulatory segments of genomic DNA is an important step towards understanding of gene regulatory networks. Recent theoretical advances that we developed [1,2], allow us to infer TF-DNA interaction parameters from in-vitro selection experiments [3]. We use more than 6000 binding sequences [3], assembled under controlled conditions, to obtain protein-DNA interaction parameters for a mammalian TF with up to now unprecedented accuracy. Can one accurately identify biologically functional TF binding sites (i.e. the binding sites that regulate gene expression), even with the best possible protein-DNA interaction parameters? To address this issue we i) compare our prediction of protein binding with gene expression data, ii) use evolutionary comparison between related mammalian genomes. Our results strongly suggest that in a genome there exists a large number of randomly occurring high energy binding sites that are not biologically functional. [1] M Djordjevic, submitted to Biomol. Eng. [2] M. Djordjevic and A. M. Sengupta, Phys. Biol. 3: 13, 2006. [3] E. Roulet et al., Nature Biotech. 20: 831, 2002.

  10. Do US Black Women Experience Stress-Related Accelerated Biological Aging?

    PubMed Central

    Hicken, Margaret T.; Pearson, Jay A.; Seashols, Sarah J.; Brown, Kelly L.; Cruz, Tracey Dawson

    2010-01-01

    We hypothesize that black women experience accelerated biological aging in response to repeated or prolonged adaptation to subjective and objective stressors. Drawing on stress physiology and ethnographic, social science, and public health literature, we lay out the rationale for this hypothesis. We also perform a first population-based test of its plausibility, focusing on telomere length, a biomeasure of aging that may be shortened by stressors. Analyzing data from the Study of Women's Health Across the Nation (SWAN), we estimate that at ages 49–55, black women are 7.5 years biologically “older” than white women. Indicators of perceived stress and poverty account for 27% of this difference. Data limitations preclude assessing objective stressors and also result in imprecise estimates, limiting our ability to draw firm inferences. Further investigation of black-white differences in telomere length using large-population-based samples of broad age range and with detailed measures of environmental stressors is merited. PMID:20436780

  11. The functional biology of human milk oligosaccharides.

    PubMed

    Bode, Lars

    2015-11-01

    Human milk oligosaccharides (HMOs) are a group of complex sugars that are highly abundant in human milk, but currently not present in infant formula. More than a hundred different HMOs have been identified so far. The amount and composition of HMOs are highly variable between women, and each structurally defined HMO might have a distinct functionality. HMOs are not digested by the infant and serve as metabolic substrates for select microbes, contributing to shape the infant gut microbiome. HMOs act as soluble decoy receptors that block the attachment of viral, bacterial or protozoan parasite pathogens to epithelial cell surface sugars, which may help prevent infectious diseases in the gut and also the respiratory and urinary tracts. HMOs are also antimicrobials that act as bacteriostatic or bacteriocidal agents. In addition, HMOs alter host epithelial and immune cell responses with potential benefits for the neonate. The article reviews current knowledge as well as future challenges and opportunities related to the functional biology of HMOs. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

  12. Frameworks for programming biological function through RNA parts and devices

    PubMed Central

    Win, Maung Nyan; Liang, Joe C.; Smolke, Christina D.

    2009-01-01

    One of the long-term goals of synthetic biology is to reliably engineer biological systems that perform human-defined functions. Currently, researchers face several scientific and technical challenges in designing and building biological systems, one of which is associated with our limited ability to access, transmit, and control molecular information through the design of functional biomolecules exhibiting novel properties. The fields of RNA biology and nucleic acid engineering, along with the tremendous interdisciplinary growth of synthetic biology, are fueling advances in the emerging field of RNA programming in living systems. Researchers are designing functional RNA molecules that exhibit increasingly complex functions and integrating these molecules into cellular circuits to program higher-level biological functions. The continued integration and growth of RNA design and synthetic biology presents exciting potential to transform how we interact with and program biology. PMID:19318211

  13. Dispersion function and closed orbit distortion in accelerator rings

    SciTech Connect

    Liu, R.Z.

    1984-02-01

    Dispersion Function Distortion (DFD) affects accelerator operation and thus deserves attention, somehow as Closed Orbit Distortion (COD) does. Consequently, DFD correction schemes under computer control have been successfully developed and adopted in many rings such as PEP. It was realized during the author's study on the problem, however, that the existing DFD correction schemes ignore those terms that arise from bending magnets and their edges. Being of first order of correcting strength, the terms are significant in small rings, though really not important in big machines. This reminds of what has been noticed in the chromaticity calculation. A comparison between this note and the existing schemes shows a difference in DFD sensitivity matrix that is significant for sub-GeV machines and appears not negligible even for SPEAR. Many storage rings at energy around 0.7 to 3 GeV are being proposed, constructed or operated everywhere as synchrotron radiation generators. Vertical DFD correction should be an important part of their operation, because vertical DFD enlarges beam height and hence reduces light source brightness. This is the purpose the author had in mind when beginning to study the problem. In addition, a correct DFD analysis along with COD analysis can hopefully help spot magnet misalignments and remove them.

  14. Biological assessments for the low energy demonstration accelerator, 1996 and 1997

    SciTech Connect

    Cross, S.

    1998-12-31

    The Department of Energy (DOE) plans to build, install, and operate a Low Energy Demonstration Accelerator (LMA) in Technical Area 53 of the Los Alamos National Laboratory (LANL). LEDA will demonstrate the accelerator technology necessary to produce tritium, but is not designed to produce tritium at LANL. USFWS reviewers of the Biological Assessment prepared for LEDA insisted that the main drainage be monitored to measure and document changes to vegetation, soils, wildlife, and habitats due to LEDA effluent discharges. The Biology Team of ESH-20 (LANL`s Ecology Group) has performed these monitoring activities during 1996 and 1997 to document baseline conditions before LEDA released significant effluent discharges. Quarterly monitoring of the outfall which will discharge LEDA blowdown effluent had one exceedance of permitted parameters, a high chlorine discharge that was quickly remedied. Samples from 12 soil pits in the drainage area contained no hydric indicators, such as organic matter in the upper layers, streaking, organic pans, and oxidized rhizospheres. Vegetation transacts in the meadows that LEDA discharges will flow through contained 44 species of herbaceous plants, all upland taxa. Surveys of resident birds, reptiles, and amphibians documented a fauna typical of local dry canyons. No threatened or endangered species inhabit the project area, but increased effluent releases may make the area more attractive to many wildlife species, an endangered raptor, and several other species of concern. Biological best management practices especially designed for LEDA are discussed, including protection of floodplains, erosion control measures, hazards posed by increased usage of the area by deer and elk and revegetation of disturbed areas.

  15. Healthy obesity and risk of accelerated functional decline and disability.

    PubMed

    Bell, J A; Sabia, S; Singh-Manoux, A; Hamer, M; Kivimäki, M

    2017-06-01

    obesity, even if metabolically healthy, accelerates age-related declines in functional ability and poses a threat to independence in older age.

  16. An interdisciplinary approach to study individuality in biological and physical systems functioning

    PubMed Central

    Mygal, V. P.; But, A. V.; Mygal, G. V.; Klimenko, I. A.

    2016-01-01

    Signals of system functioning of different nature are presented in the parameter space (state-velocity-acceleration) as a trajectory of dynamic events. Such signals geometrization allows to reveal the hidden spatio-temporal correlation in dynamics of systems functioning. It is shown that the nature of relationship between the dynamic parameters of signal determines the natural cycle of sensor functioning. Its restructuring displays the inherited features of systems functioning in signature package. The universal differential-geometry parameters and new integrative indexes of system functioning are used to analyze the signatures of biological and physical signals. PMID:27412253

  17. Subspace accelerated inexact Newton method for large scale wave functions calculations in Density Functional Theory

    SciTech Connect

    Fattebert, J

    2008-07-29

    We describe an iterative algorithm to solve electronic structure problems in Density Functional Theory. The approach is presented as a Subspace Accelerated Inexact Newton (SAIN) solver for the non-linear Kohn-Sham equations. It is related to a class of iterative algorithms known as RMM-DIIS in the electronic structure community. The method is illustrated with examples of real applications using a finite difference discretization and multigrid preconditioning.

  18. The Structure and Function of Biological Networks

    ERIC Educational Resources Information Center

    Wu, Daniel Duanqing

    2010-01-01

    Biology has been revolutionized in recent years by an explosion in the availability of data. Transforming this new wealth of data into meaningful biological insights and clinical breakthroughs requires a complete overhaul both in the questions being asked and the methodologies used to answer them. A major challenge in organizing and understanding…

  19. The Structure and Function of Biological Networks

    ERIC Educational Resources Information Center

    Wu, Daniel Duanqing

    2010-01-01

    Biology has been revolutionized in recent years by an explosion in the availability of data. Transforming this new wealth of data into meaningful biological insights and clinical breakthroughs requires a complete overhaul both in the questions being asked and the methodologies used to answer them. A major challenge in organizing and understanding…

  20. Industrialization of Biology. A Roadmap to Accelerate the Advanced Manufacturing of Chemicals

    SciTech Connect

    Friedman, Douglas C.

    2015-09-01

    The report stresses the need for efforts to inform the public of the nature of industrial biotechnology and of its societal benefits, and to make sure that concerns are communicated effectively between the public and other stakeholders. In addition to scientific advances, a number of governance and societal factors will influence the industrialization of biology. Industry norms and standards need to be established in areas such as read/write accuracy for DNA, data and machine technology specifications, and organism performance in terms of production rates and yields. An updated regulatory regime is also needed to accelerate the safe commercialization of new host organisms, metabolic pathways, and chemical products, and regulations should be coordinated across nations to enable rapid, safe, and global access to new technologies and products.

  1. Experimental stand for studying the impact of laser-accelerated protons on biological objects

    NASA Astrophysics Data System (ADS)

    Burdonov, K. F.; Eremeev, A. A.; Ignatova, N. I.; Osmanov, R. R.; Sladkov, A. D.; Soloviev, A. A.; Starodubtsev, M. V.; Ginzburg, V. N.; Kuz'min, A. A.; Maslennikova, A. V.; Revet, G.; Sergeev, A. M.; Fuchs, J.; Khazanov, E. A.; Chen, S.; Shaykin, A. A.; Shaikin, I. A.; Yakovlev, I. V.

    2016-04-01

    An original experimental stand is presented, aimed at studying the impact of high-energy protons, produced by the laser-plasma interaction at a petawatt power level, on biological objects. In the course of pilot experiments with the energy of laser-accelerated protons up to 25 MeV, the possibility is demonstrated of transferring doses up to 10 Gy to the object of study in a single shot with the magnetic separation of protons from parasitic X-ray radiation and fast electrons. The technique of irradiating the cell culture HeLa Kyoto and measuring the fraction of survived cells is developed. The ways of optimising the parameters of proton beams and the suitable methods of their separation with respect to energy and transporting to the studied living objects are discussed. The construction of the stand is intended for the improvement of laser technologies for hadron therapy of malignant neoplasms.

  2. Dynamics of biomolecules, ligand binding & biological functions

    NASA Astrophysics Data System (ADS)

    Yi, Myunggi

    Proteins are flexible and dynamic. One static structure alone does not often completely explain biological functions of the protein, and some proteins do not even have high resolution structures. In order to provide better understanding to the biological functions of nicotinic acetylcholine receptor, Diphtheria toxin repressor and M2 proton channel, the dynamics of these proteins are investigated using molecular modeling and molecular dynamics (MD) simulations. With absence of high resolution structure of alpha7 receptor, the homology models of apo and cobra toxin bound forms have been built. From the MD simulations of these model structures, we observed one subunit of apo simulation moved away from other four subunits. With local movement of flexible loop regions, the whole subunit tilted clockwise. These conformational changes occurred spontaneously, and were strongly correlated with the conformational change when the channel is activated by agonists. Unlike other computational studies, we directly compared our model of open conformation with the experimental data. However, the subunits of toxin bound form were stable, and conformational change is restricted by the bound cobra toxin. These results provide activation and inhibition mechanisms of alpha7 receptors and a possible explanation for intermediate conductance of the channel. Intramolecular complex of SH3-like domain with a proline-rich (Pr) peptide segment in Diphtheria toxin repressor (DtxR) is stabilized in inactive state. Upon activation of DtxR by transition metal binding, this intramolecular complex should be dissociated. The dynamics of this intramolecular complex is investigated using MD simulations and NMR spectroscopy. We observed spontaneous opening and closing motions of the Pr segment binding pockets in both Pr-SH3 and SH3 simulations. The MD simulation results and NMR relaxation data suggest that the Pr segment exhibits a binding ↔ unbinding equilibrium. Despite a wealth of experimental

  3. The biological research programme of the nuclear microprobe at the National Accelerator Centre, Faure

    NASA Astrophysics Data System (ADS)

    Prozesky, V. M.; Pineda, C. A.; Mesjasz-Przybylowicz, J.; Przybylowicz, W. J.; Churms, C. L.; Springhorn, K. A.; Moretto, Ph; Michelet, C.; Chikte, U.; Wenzl, P.

    2000-03-01

    The nuclear microprobe (NMP) unit of the National Accelerator Centre (NAC) has initiated a focused research programme on studies of biological material, ranging from applications in medicine to agriculture and botany. During this period a state-of-the-art cryo-preparation laboratory was also developed. This research programme has resulted in a wide range of projects, and has shown how well suited the NMP is for studies of biological material in general. This paper reports on some of the problems and demands in this field, as well as some of the results obtained using particle induced X-ray spectroscopy (PIXE) and Rutherford backscattering (RBS). True elemental imaging is routinely performed using the dynamic analysis (DA) method, which forms part of the GeoPIXE suite of programmes. A collaborative project, together with the CENBG group of Bordeaux-Gradignan in France, on the development of a facility with the aim of studying effects of single-events of radiation in living cells was recently established and is discussed.

  4. Applying accelerator mass spectrometry for low-level detection of complex engineered nanoparticles in biological media.

    PubMed

    Wang, Binghui; Jackson, George S; Yokel, Robert A; Grulke, Eric A

    2014-08-01

    Complex engineered nanoparticles (CENPs), which have different core and surface components, are being developed for medicinal, pharmaceutical and industrial applications. One of the key challenges for environmental health and safety assessments of CENPs is to identify and quantity their transformations in biological environments. This study reports the effects of in vivo exposure of citrate-coated nanoalumina with different rare isotope labels on each component. This CENP was dosed to the rat and accelerator mass spectrometry (AMS) was used to quantify (26)Al, (14)C, and their ratio in the dosing material and tissue samples. For CENPs detected in the liver, the rare isotope ratio, (14)C/(26)Al, was 87% of the dosing material's ratio. The citrate coating on the nanoalumina in the liver was stable or, if it degraded, its metabolites were incorporated with nearby tissues. However, in brain and bone where little alumina was detected, the rare isotope ratio greatly exceeded that of the dosing material. Therefore, in the animal, citrate dissociated from CENPs and redistributed to brain and bone. Tracking both the core and surface components by AMS presents a new approach for characterizing transformations of CENPs components in biological milieu or environments.

  5. Track Structure and the Biological Effectiveness of Accelerated Particles for the Induction of Chromosome Damage

    NASA Technical Reports Server (NTRS)

    George, K.; Hada, M.; Chappell, L.; Cucinotta, F. A.

    2011-01-01

    Track structure models predict that at a fixed value of LET, particles with lower charge number, Z will have a higher biological effectiveness compared to particles with a higher Z. In this report we investigated how track structure effects induction of chromosomal aberration in human cells. Human lymphocytes were irradiated in vitro with various energies of accelerated iron, silicon, neon, or titanium ions and chromosome damage was assessed in using three color FISH chromosome painting in chemically induced PCC samples collected a first cell division post irradiation. The LET values for these ions ranged from 30 to195 keV/micron. Of the particles studied, Neon ions have the highest biological effectiveness for induction of total chromosome damage, which is consistent with track structure model predictions. For complex-type exchanges 64 MeV/ u Neon and 450 MeV/u Iron were equally effective and induced the most complex damage. In addition we present data on chromosomes exchanges induced by six different energies of protons (5 MeV/u to 2.5 GeV/u). The linear dose response term was similar for all energies of protons suggesting that the effect of the higher LET at low proton energies is balanced by the production of nuclear secondaries from the high energy protons.

  6. Measurement of Beryllium in Biological Samples by Accelerator Mass Spectrometry: Applications for Studying Chronic Beryllium Disease

    SciTech Connect

    Chiarappa-Zucca, M L; Finkel, R C; Martinelli, R E; McAninch, J E; Nelson, D O; Turtletaub, K W

    2004-04-15

    A method using accelerator mass spectrometry (AMS) has been developed for quantifying attomoles of beryllium (Be) in biological samples. This method provides the sensitivity to trace Be in biological samples at very low doses with the purpose of identifying the molecular targets involved in chronic beryllium disease. Proof of the method was tested by administering 0.001, 0.05, 0.5 and 5.0 {micro}g {sup 9}Be and {sup 10}Be by intraperitoneal injection to male mice and removing spleen, liver, femurs, blood, lung, and kidneys after 24 h exposure. These samples were prepared for AMS analysis by tissue digestion in nitric acid, followed by further organic oxidation with hydrogen peroxide and ammonium persulfate and lastly, precipitation of Be with ammonium hydroxide, and conversion to beryllium oxide at 800 C. The {sup 10}Be/{sup 9}Be ratio of the extracted beryllium oxide was measured by AMS and Be in the original sample was calculated. Results indicate that Be levels were dose-dependent in all tissues and the highest levels were measured in the spleen and liver. The measured {sup 10}Be/{sup 9}Be ratios spanned 4 orders of magnitude, from 10{sup -10} to 10{sup -14}, with a detection limit of 3.0 x 10{sup -14}, which is equivalent to 0.8 attomoles of {sup 10}Be. These results show that routine quantification of nanogram levels of Be in tissues is possible and that AMS is a sensitive method that can be used in biological studies to understand the molecular dosimetry of Be and mechanisms of toxicity.

  7. Function-Based Algorithms for Biological Sequences

    ERIC Educational Resources Information Center

    Mohanty, Pragyan Sheela P.

    2015-01-01

    Two problems at two different abstraction levels of computational biology are studied. At the molecular level, efficient pattern matching algorithms in DNA sequences are presented. For gene order data, an efficient data structure is presented capable of storing all gene re-orderings in a systematic manner. A common characteristic of presented…

  8. Function-Based Algorithms for Biological Sequences

    ERIC Educational Resources Information Center

    Mohanty, Pragyan Sheela P.

    2015-01-01

    Two problems at two different abstraction levels of computational biology are studied. At the molecular level, efficient pattern matching algorithms in DNA sequences are presented. For gene order data, an efficient data structure is presented capable of storing all gene re-orderings in a systematic manner. A common characteristic of presented…

  9. Biological Structures, Interactions, Function and Behavior: Research Opportunities for Physicists

    NASA Astrophysics Data System (ADS)

    Concepcion, Gisela P.

    2008-06-01

    Studies on marine biomolecules at the Marine Natural Products Laboratory (MNPL) and studies on biomedically relevant proteins at the Virtual Laboratory of Biomolecular Structures (VIRLS) of the University of the Philippines Marine Science Institute (UPMSI) are presented. These serve to illustrate some underlying principles of biological structures, interactions, function and behavior, and also to draw out some unresolved questions in biology of possible interest to non-biologists. The Biological Structures course offered at UPMSI, which aims to introduce underlying biological principles to non-biology majors and to promote trans-disciplinary research efforts, is also presented.

  10. Acceleration of peripheral nerve regeneration through asymmetrically porous nerve guide conduit applied with biological/physical stimulation.

    PubMed

    Kim, Jin Rae; Oh, Se Heang; Kwon, Gu Birm; Namgung, Uk; Song, Kyu Sang; Jeon, Byeong Hwa; Lee, Jin Ho

    2013-12-01

    Sufficient functional restoration of damaged peripheral nerves is a big clinical challenge. In this study, a nerve guide conduit (NGC) with selective permeability was prepared by rolling an asymmetrically porous polycaprolactone/Pluronic F127 membrane fabricated using a novel immersion precipitation method. Dual stimulation (nerve growth factor [NGF] as a biological stimulus and low-intensity pulse ultrasound [US] as a physical stimulus) was adapted to enhance nerve regeneration through an NGC. The animal study revealed that each stimulation (NGF or US) has a positive effect to promote the peripheral nerve regeneration through the NGC, however, the US-stimulated NGC group allowed more accelerated nerve regeneration compared with the NGF-stimulated group. The NGC group that received dual stimulation (NGF and US) showed more effective nerve regeneration behavior than the groups that received a single stimulation (NGF or US). The asymmetrically porous NGC with dual NGF and US stimulation may be a promising strategy for the clinical treatment of delayed and insufficient functional recovery of a peripheral nerve.

  11. Functionalized apertures for the detection of chemical and biological materials

    DOEpatents

    Letant, Sonia E.; van Buuren, Anthony W.; Terminello, Louis J.; Thelen, Michael P.; Hope-Weeks, Louisa J.; Hart, Bradley R.

    2010-12-14

    Disclosed are nanometer to micron scale functionalized apertures constructed on a substrate made of glass, carbon, semiconductors or polymeric materials that allow for the real time detection of biological materials or chemical moieties. Many apertures can exist on one substrate allowing for the simultaneous detection of numerous chemical and biological molecules. One embodiment features a macrocyclic ring attached to cross-linkers, wherein the macrocyclic ring has a biological or chemical probe extending through the aperture. Another embodiment achieves functionalization by attaching chemical or biological anchors directly to the walls of the apertures via cross-linkers.

  12. From functional genomics to systems biology: concepts and practices.

    PubMed

    Auffray, Charles; Imbeaud, Sandrine; Roux-Rouquié, Magali; Hood, Leroy

    2003-01-01

    Systems biology is the iterative and integrative study of biological systems as systems in response to perturbations. It is founded on hypotheses formalized in models built from the results of global functional genomics analyses of the complexity of the genome, transcriptome, proteome, metabolome, etc. Its implementation by cross-disciplinary teams in a standardized mode under quality assurance should allow accessing the small variations of the large number of elements determining functioning of biological systems. Galactose utilization in yeast, and sea urchin development are two examples of emerging systems biology.

  13. Microwave-accelerated bioassay technique for rapid and quantitative detection of biological and environmental samples.

    PubMed

    Mohammed, Muzaffer; Syed, Maleeha F; Aslan, Kadir

    2016-01-15

    Quantitative detection of molecules of interest from biological and environmental samples in a rapid manner, particularly with a relevant concentration range, is imperative to the timely assessment of human diseases and environmental issues. In this work, we employed the microwave-accelerated bioassay (MAB) technique, which is based on the combined use of circular bioassay platforms and microwave heating, for rapid and quantitative detection of Glial Fibrillary Acidic Protein (GFAP) and Shiga like toxin (STX 1). The proof-of-principle use of the MAB technique with the circular bioassay platforms for the rapid detection of GFAP in buffer based on colorimetric and fluorescence readouts was demonstrated with a 900W kitchen microwave. We also employed the MAB technique with a new microwave system (called the iCrystal system) for the detection of GFAP from mice with brain injuries and STX 1 from a city water stream. Control bioassays included the commercially available gold standard bioassay kits run at room temperature. Our results show that the lower limit of detection (LLOD) of the colorimetric and fluorescence based bioassays for GFAP was decreased by ~1000 times using the MAB technique and our circular bioassay platforms as compared to the commercially available bioassay kits. The overall bioassay time for GFAP and STX 1 was reduced from 4h using commercially available bioassay kits to 10min using the MAB technique.

  14. Graphics processing unit parallel accelerated solution of the discrete ordinates for photon transport in biological tissues.

    PubMed

    Peng, Kuan; Gao, Xinbo; Qu, Xiaochao; Ren, Nunu; Chen, Xueli; He, Xiaowei; Wang, Xiaorei; Liang, Jimin; Tian, Jie

    2011-07-20

    As a widely used numerical solution for the radiation transport equation (RTE), the discrete ordinates can predict the propagation of photons through biological tissues more accurately relative to the diffusion equation. The discrete ordinates reduce the RTE to a serial of differential equations that can be solved by source iteration (SI). However, the tremendous time consumption of SI, which is partly caused by the expensive computation of each SI step, limits its applications. In this paper, we present a graphics processing unit (GPU) parallel accelerated SI method for discrete ordinates. Utilizing the calculation independence on the levels of the discrete ordinate equation and spatial element, the proposed method reduces the time cost of each SI step by parallel calculation. The photon reflection at the boundary was calculated based on the results of the last SI step to ensure the calculation independence on the level of the discrete ordinate equation. An element sweeping strategy was proposed to detect the calculation independence on the level of the spatial element. A GPU parallel frame called the compute unified device architecture was employed to carry out the parallel computation. The simulation experiments, which were carried out with a cylindrical phantom and numerical mouse, indicated that the time cost of each SI step can be reduced up to a factor of 228 by the proposed method with a GTX 260 graphics card. © 2011 Optical Society of America

  15. Biological and biomedical (14)C-accelerator mass spectrometry and graphitization of carbonaceous samples.

    PubMed

    Chung, Ill-Min; Kim, Seung-Hyun

    2013-06-21

    Accelerator mass spectrometry (AMS) is the ultimate technique for measuring rare isotopes in small samples. Biological and biomedical applications of (14)C-AMS (bio-(14)C-AMS) commenced in the early 1990s and are now widely used in many research fields including pharmacology, toxicology, food, and nutrition. For accurate, precise, and reproducible bio-(14)C-AMS analysis, the graphitization step in sample preparation is the most critical step. So, various sample preparation methods for a process called graphitization have been reported for specific applications. Catalytic graphitization using either a flame-sealed borosilicate tube or a septa-sealed vial is a popular sample preparation method for bio-(14)C-AMS. In this review, we introduce the AMS system, especially for bio-(14)C-AMS. In addition, we also review the graphitization method for bio-(14)C-AMS to promote further understanding and improvement of sample preparation for this technique. Examples of catalytic graphitization methods over the past two decades are described.

  16. Microwave-Accelerated Bioassay Technique for Rapid and Quantitative Detection of Biological and Environmental Samples

    PubMed Central

    Mohammed, Muzaffer; Syed, Maleeha F.; Aslan, Kadir

    2015-01-01

    Quantitative detection of molecules of interest from biological and environmental samples in a rapid manner, particularly with a relevant concentration range, is imperative to the timely assessment of human diseases and environmental issues. In this work, we employed the microwave-accelerated bioassay (MAB) technique, which is based on the combined use of circular bioassay platforms and microwave heating, for rapid and quantitative detection of Glial Fibrillary Acidic Protein (GFAP) and Shiga like toxin (STX 1). The proof-of-principle use of the MAB technique with the circular bioassay platforms for the rapid detection of GFAP in buffer based on colorimetric and fluorescence readouts was demonstrated with a 900 W kitchen microwave. We also employed the MAB technique with a new microwave system (called the iCrystal system) for the detection of GFAP from mice with brain injuries and STX 1 from a city water stream. Control bioassays included the commercially available gold standard bioassay kits run at room temperature. Our results show that the lower limit of detection (LLOD) of the colorimetric and fluorescence based bioassays for GFAP was decreased by ~1,000 times using the MAB technique and our circular bioassay platforms as compared to the commercially available bioassay kits. The overall bioassay time for GFAP and STX 1 was reduced from 4 hours using commercially available bioassay kits to 10 minutes using the MAB technique. PMID:26356762

  17. Deficient high-acceleration vestibular function in patients with polyneuropathy.

    PubMed

    Palla, A; Schmid-Priscoveanu, A; Studer, A; Hess, K; Straumann, D

    2009-06-09

    Unsteadiness during standing and walking is a frequent complaint of patients with polyneuropathy (PNP). To determine whether balance disorders in patients with PNP may be caused by reduced proprioceptive input from the feet alone or whether impaired vestibular input, resulting from involvement of the vestibular nerve, can be an additional factor. A total of 37 patients (mean age 65 years +/- 12 SD; 12 women) with electrodiagnostically confirmed PNP (predominantly axonal: 18; predominantly demyelinating: 19) underwent horizontal search-coil head-impulse testing, which assesses the high-acceleration vestibulo-ocular reflex (VOR). Relative to a healthy comparison group, the gains (eye velocity divided by head velocity) of the horizontal VOR were reduced in 27 of 37 patients (unilateral: 13; bilateral: 14). The percentages of patients with unilateral or bilateral VOR deficits were not significantly different between patients with axonal or demyelinating PNP. Two thirds of patients with axonal or demyelinating polyneuropathy (PNP) showed unilateral (approximately 50%) or bilateral (approximately 50%) gain reductions of the horizontal high-acceleration vestibulo-ocular reflex. This finding suggests that, in many patients with PNP, the neuropathic process includes the vestibular nerve. Such information is highly relevant for subsequent physical therapy, since vestibular exercise improves balance control and reduces disability.

  18. Functionalized Nanodiamonds for Biological and Medical Applications.

    PubMed

    Lai, Lin; Barnard, Amanda S

    2015-02-01

    Nanodiamond is a promising material for biological and medical applications, owning to its relatively inexpensive and large-scale synthesis, unique structure, and superior optical properties. However, most biomedical applications, such as drug delivery and bio-imaging, are dependent upon the precise control of the surfaces, and can be significantly affected by the type, distribution and stability of chemical funtionalisations of the nanodiamond surface. In this paper, recent studies on nanodiamonds and their biomedical applications by conjugating with different chemicals are reviewed, while highlighting the critical importance of surface chemical states for various applications.

  19. Tunable ultrasensitivity: functional decoupling and biological insights

    PubMed Central

    Wang, Guanyu; Zhang, Mengshi

    2016-01-01

    Sensitivity has become a basic concept in biology, but much less is known about its tuning, probably because allosteric cooperativity, the best known mechanism of sensitivity, is determined by rigid conformations of interacting molecules and is thus difficult to tune. Reversible covalent modification (RCM), owing to its systems-level ingenuity, can generate concentration based, tunable sensitivity. Using a mathematical model of regulated RCM, we find sensitivity tuning can be decomposed into two orthogonal modes, which provide great insights into vital biological processes such as tissue development and cell cycle progression. We find that decoupling of the two modes of sensitivity tuning is critical to fidelity of cell fate decision; the decoupling is thus important in development. The decomposition also allows us to solve the ‘wasteful degradation conundrum’ in budding yeast cell cycle checkpoint, which further leads to discovery of a subtle but essential difference between positive feedback and double negative feedback. The latter guarantees revocability of stress-induced cell cycle arrest; while the former does not. By studying concentration conditions in the system, we extend applicability of ultrasensitivity and explain the ubiquity of reversible covalent modification. PMID:26847155

  20. Angular velocities, angular accelerations, and coriolis accelerations

    NASA Technical Reports Server (NTRS)

    Graybiel, A.

    1975-01-01

    Weightlessness, rotating environment, and mathematical analysis of Coriolis acceleration is described for man's biological effective force environments. Effects on the vestibular system are summarized, including the end organs, functional neurology, and input-output relations. Ground-based studies in preparation for space missions are examined, including functional tests, provocative tests, adaptive capacity tests, simulation studies, and antimotion sickness.

  1. Angular velocities, angular accelerations, and coriolis accelerations

    NASA Technical Reports Server (NTRS)

    Graybiel, A.

    1975-01-01

    Weightlessness, rotating environment, and mathematical analysis of Coriolis acceleration is described for man's biological effective force environments. Effects on the vestibular system are summarized, including the end organs, functional neurology, and input-output relations. Ground-based studies in preparation for space missions are examined, including functional tests, provocative tests, adaptive capacity tests, simulation studies, and antimotion sickness.

  2. Detachment of captured cancer cells under flow acceleration in a bio-functionalized microchannel.

    PubMed

    Cheung, Luthur Siu Lun; Zheng, Xiangjun; Stopa, Ashley; Baygents, James C; Guzman, Roberto; Schroeder, Joyce A; Heimark, Ronald L; Zohar, Yitshak

    2009-06-21

    Attachment, deformation and detachment of N-cadherin expressing prostate and breast cancer cell lines in a functionalized microchannel under hydrodynamic loading have been studied. N-cadherin antibodies are immobilized on the microchannel surface to capture the target cancer cells, PC3N and MDA-MB-231-N, from a homogeneous cell suspension. Although difficult, a significant fraction of moving cells can be captured under a low flow rate. More than 90% of the target cells are captured after a certain incubation time under no flow condition. The mechanical response of a captured cancer cell to hydrodynamic flow field is investigated and, in particular, the effect of flow acceleration is examined. The observed cell deformation is dramatic under low acceleration, but is negligible under high acceleration. Consequently, the detachment of captured cells depends on both flow rate and flow acceleration. The flow rate required for cell detachment is a random variable that can be described by a log-normal distribution. Two flow acceleration limits have been identified for proper scaling of the flow rate required to detach captured cells. A time constant for the mechanical response of a captured cell, on the order of 1 min, has been identified for scaling the flow acceleration. Based on these acceleration limits and time constant, an exponential-like empirical model is proposed to predict the flow rate required for cell detachment as a function of flow acceleration.

  3. Printable Bioelectronics To Investigate Functional Biological Interfaces.

    PubMed

    Manoli, Kyriaki; Magliulo, Maria; Mulla, Mohammad Yusuf; Singh, Mandeep; Sabbatini, Luigia; Palazzo, Gerardo; Torsi, Luisa

    2015-10-19

    Thin-film transistors can be used as high-performance bioelectronic devices to accomplish tasks such as sensing or controlling the release of biological species as well as transducing the electrical activity of cells or even organs, such as the brain. Organic, graphene, or zinc oxide are used as convenient printable semiconducting layers and can lead to high-performance low-cost bioelectronic sensing devices that are potentially very useful for point-of-care applications. Among others, electrolyte-gated transistors are of interest as they can be operated as capacitance-modulated devices, because of the high capacitance of their charge double layers. Specifically, it is the capacitance of the biolayer, being lowest in a series of capacitors, which controls the output current of the device. Such an occurrence allows for extremely high sensitivity towards very weak interactions. All the aspects governing these processes are reviewed here.

  4. Chemical Biology for Understanding Matrix Metalloproteinase Function

    PubMed Central

    Knapinska, Anna; Fields, Gregg B.

    2013-01-01

    The matrix metalloproteinase (MMP) family has long been associated with normal physiological processes such as embryonic implantation, tissue remodeling, organ development, and wound healing, as well as multiple aspects of cancer initiation and progression, osteoarthritis, inflammatory and vascular diseases, and neurodegenerative diseases. The development of chemically designed MMP probes has advanced our understanding of the roles of MMPs in disease in addition to shedding considerable light on the mechanisms of MMP action. The first generation of protease-activated agents has demonstrated proof of principle as well as providing impetus for in vivo applications. One common problem has been a lack of agent stability at nontargeted tissues and organs due to activation by multiple proteases. The present review considers how chemical biology has impacted the progress made in understanding the roles of MMPs in disease and the basic mechanisms of MMP action. PMID:22933318

  5. Chemical biology for understanding matrix metalloproteinase function.

    PubMed

    Knapinska, Anna; Fields, Gregg B

    2012-09-24

    The matrix metalloproteinase (MMP) family has long been associated with normal physiological processes such as embryonic implantation, tissue remodeling, organ development, and wound healing, as well as multiple aspects of cancer initiation and progression, osteoarthritis, inflammatory and vascular diseases, and neurodegenerative diseases. The development of chemically designed MMP probes has advanced our understanding of the roles of MMPs in disease in addition to shedding considerable light on the mechanisms of MMP action. The first generation of protease-activated agents has demonstrated proof of principle as well as providing impetus for in vivo applications. One common problem has been a lack of agent stability at nontargeted tissues and organs due to activation by multiple proteases. The present review considers how chemical biology has impacted the progress made in understanding the roles of MMPs in disease and the basic mechanisms of MMP action. Copyright © 2012 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  6. Gels as functional nanomaterials for biology and medicine.

    PubMed

    Xu, Bing

    2009-08-04

    This perspective focuses on the potential uses of gels as materials in biological and medical applications. It describes how molecular self-assembly can confer well-defined secondary structures (e.g., nanofibers, nanotubes, and nanospheres) in a liquid that initiates functions within biological systems. Some prospects for future development and the challenges for achieving them are discussed.

  7. High performance hybrid functional Petri net simulations of biological pathway models on CUDA.

    PubMed

    Chalkidis, Georgios; Nagasaki, Masao; Miyano, Satoru

    2011-01-01

    Hybrid functional Petri nets are a wide-spread tool for representing and simulating biological models. Due to their potential of providing virtual drug testing environments, biological simulations have a growing impact on pharmaceutical research. Continuous research advancements in biology and medicine lead to exponentially increasing simulation times, thus raising the demand for performance accelerations by efficient and inexpensive parallel computation solutions. Recent developments in the field of general-purpose computation on graphics processing units (GPGPU) enabled the scientific community to port a variety of compute intensive algorithms onto the graphics processing unit (GPU). This work presents the first scheme for mapping biological hybrid functional Petri net models, which can handle both discrete and continuous entities, onto compute unified device architecture (CUDA) enabled GPUs. GPU accelerated simulations are observed to run up to 18 times faster than sequential implementations. Simulating the cell boundary formation by Delta-Notch signaling on a CUDA enabled GPU results in a speedup of approximately 7x for a model containing 1,600 cells.

  8. Normal form from biological motion despite impaired ventral stream function.

    PubMed

    Gilaie-Dotan, S; Bentin, S; Harel, M; Rees, G; Saygin, A P

    2011-04-01

    We explored the extent to which biological motion perception depends on ventral stream integration by studying LG, an unusual case of developmental visual agnosia. LG has significant ventral stream processing deficits but no discernable structural cortical abnormality. LG's intermediate visual areas and object-sensitive regions exhibit abnormal activation during visual object perception, in contrast to area V5/MT+ which responds normally to visual motion (Gilaie-Dotan, Perry, Bonneh, Malach, & Bentin, 2009). Here, in three studies we used point light displays, which require visual integration, in adaptive threshold experiments to examine LG's ability to detect form from biological and non-biological motion cues. LG's ability to detect and discriminate form from biological motion was similar to healthy controls. In contrast, he was significantly deficient in processing form from non-biological motion. Thus, LG can rely on biological motion cues to perceive human forms, but is considerably impaired in extracting form from non-biological motion. Finally, we found that while LG viewed biological motion, activity in a network of brain regions associated with processing biological motion was functionally correlated with his V5/MT+ activity, indicating that normal inputs from V5/MT+ might suffice to activate his action perception system. These results indicate that processing of biologically moving form can dissociate from other form processing in the ventral pathway. Furthermore, the present results indicate that integrative ventral stream processing is necessary for uncompromised processing of non-biological form from motion. Copyright © 2011 Elsevier Ltd. All rights reserved.

  9. Functionally dissimilar neighbors accelerate litter decomposition in two grass species.

    PubMed

    Barbe, Lou; Jung, Vincent; Prinzing, Andreas; Bittebiere, Anne-Kristel; Butenschoen, Olaf; Mony, Cendrine

    2017-02-16

    Plant litter decomposition is a key regulator of nutrient recycling. In a given environment, decomposition of litter from a focal species depends on its litter quality and on the efficiency of local decomposers. Both may be strongly modified by functional traits of neighboring species, but the consequences for decomposition of litter from the focal species remain unknown. We tested whether decomposition of a focal plant's litter is influenced by the functional-trait dissimilarity to the neighboring plants. We cultivated two grass species (Brachypodium pinnatum and Elytrigia repens) in experimental mesocosms with functionally similar and dissimilar neighborhoods, and reciprocally transplanted litter. For both species, litter quality increased in functionally dissimilar neighborhoods, partly as a result of changes in functional traits involved in plant-plant interactions. Furthermore, functional dissimilarity increased overall decomposer efficiency in one species, probably via complementarity effects. Our results suggest a novel mechanism of biodiversity effects on ecosystem functioning in grasslands: interspecific functional diversity within plant communities can enhance intraspecific contributions to litter decomposition. Thus, plant species might better perform in diverse communities by benefiting from higher remineralization rates of their own litter.

  10. Biological functions and metabolism of oleoylethanolamide.

    PubMed

    Thabuis, Clémentine; Tissot-Favre, Delphine; Bezelgues, Jean-Baptiste; Martin, Jean-Charles; Cruz-Hernandez, Cristina; Dionisi, Fabiola; Destaillats, Frédéric

    2008-10-01

    The present review is focused on the metabolism and the emerging roles of oleoylethanolamide (OEA) with emphasis on its effects on food intake control and lipid metabolism. The biological mechanism of action, including a non-genomic effect mediated through peroxisome proliferator-activated receptor alpha (PPAR-alpha) and transient receptor potential vanilloid type 1 (TRPV1) receptor, is discussed. The research related to fatty acid ethanolamides has been focused until recently on anandamide and its interaction with cannabinoid receptor subtype 1. The roles of other N-acyl ethanolamine fatty acid derivatives have been neglected until it was demonstrated that OEA can modulate food intake control through interaction with PPAR-alpha. Further investigations demonstrated that OEA modulates lipid and glucose metabolism, and recent study confirmed that OEA is an antagonist of TRVP1. It has been demonstrated that OEA has beneficial effects on health by inducing food intake control, lipid beta-oxidation, body weight loss and analgesic effects. The investigation of the mechanism of action revealed that OEA activates PPAR-alpha and stimulates the vagal nerve through the capsaicin receptor TRPV1. Pre-clinical studies showed that OEA remains active when administered orally.

  11. Autofluorescence: Biological functions and technical applications.

    PubMed

    García-Plazaola, José Ignacio; Fernández-Marín, Beatriz; Duke, Stephen O; Hernández, Antonio; López-Arbeloa, Fernando; Becerril, José María

    2015-07-01

    Chlorophylls are the most remarkable examples of fluorophores, and their fluorescence has been intensively studied as a non-invasive tool for assessment of photosynthesis. Many other fluorophores occur in plants, such as alkaloids, phenolic compounds and porphyrins. Fluorescence could be more than just a physicochemical curiosity in the plant kingdom, as several functional roles in biocommunication occur or have been proposed. Besides, fluorescence emitted by secondary metabolites can convert damaging blue and UV into wavelengths potentially useful for photosynthesis. Detection of the fluorescence of some secondary phytochemicals may be a cue for some pollinators and/or seed dispersal organisms. Independently of their functions, plant fluorophores provide researchers with a tool that allows the visualization of some metabolites in plants and cells, complementing and overcoming some of the limitations of the use of fluorescent proteins and dyes to probe plant physiology and biochemistry. Some fluorophores are influenced by environmental interactions, allowing fluorescence to be also used as a specific stress indicator.

  12. Genomic Functionalization: The Next Revolution In Biology

    SciTech Connect

    Anderson, Peter; Schoeniger, Joseph S.; Imbro, Paula M.

    2014-07-01

    We have implemented a ligand-alignment algorithm into our developed computational pipeline for identifying specificity-determining features (SDFs) in protein-ligand complexes. Given a set of protein-ligand complex structures, the algorithm aligns the complexes by ligand rather than by the C -RMSD or standard approach, providing a single reference frame for extracting SDFs. We anticipate that this ligand-alignment capability will be highly useful for protein function prediction. We already have a database containing > 20 K ligand-protein complex crystal structures taken from the Protein Data Bank. By aligning these proteins to single reference frames using ligand alignment, we can submit the complexes to our pipeline for SDF extraction. The SDFs derived from this training procedure can be used as thumbprints that are hallmarks of individual enzyme classes. These SDF thumbprints may then serve as guides to the prediction of function of new unknown proteins.

  13. Chemical synthesis and biological function of lipidated proteins.

    PubMed

    Yang, Aimin; Zhao, Lei; Wu, Yao-Wen

    2015-01-01

    Lipidated proteins play a key role in many essential biological processes in eukaryotic cells, including signal transduction, membrane trafficking, immune response and pathology. The investigation of the function of lipidated proteins requires access to a reasonable amount of homogenous lipid-modified proteins with defined structures and functional groups. Chemical approaches have provided useful tools to perform such studies. In this review we summarize synthetic methods of lipidated peptides and developments in the chemoselective ligation for the production of lipidated proteins. We introduce the biology of lipidated proteins and highlight the application of synthetic lipidated proteins to tackle important biological questions.

  14. Labeling and Functionalizing Amphipols for Biological Applications

    PubMed Central

    Bon, Christel Le; Popot, Jean-Luc; Giusti, Fabrice

    2014-01-01

    Amphipols (APols) are short amphipathic polymers developed as an alternative to detergents for handling membrane proteins (MPs) in aqueous solution. MPs are, as a rule, much more stable following trapping with APols than they are in detergent solutions. The best-characterized APol to date, called A8-35, is a mixture of short-chain sodium polyacrylates randomly derivatized with octylamine and isopropylamine. Its solution properties have been studied in detail, and it has been used extensively for biochemical and biophysical studies of MPs. One of the attractive characteristics of APols is that it is relatively easy to label them, isotopically or otherwise, without affecting their physical-chemical properties. Furthermore, several variously modified APols can be mixed, achieving multiple functionalization of MP/APol complexes in the easiest possible manner. Labeled or tagged APols are being used to study the solution properties of APols, their miscibility, their biodistribution upon injection into living organisms, their association with MPs and the composition, structure and dynamics of MP/APol complexes, examining the exchange of surfactants at the surface of MPs, labeling MPs to follow their distribution in fractionation experiments or to immobilize them, increasing the contrast between APols and solvent or MPs in biophysical experiments, improving NMR spectra, etc. Labeling or functionalization of APols can take various courses, each of which has its specific constraints and advantages regarding both synthesis and purification. The present review offers an overview of the various derivatives of A8-35 and its congeners that have been developed in our laboratory and discusses the pros and cons of various synthetic routes. PMID:24696186

  15. Labeling and functionalizing amphipols for biological applications.

    PubMed

    Le Bon, Christel; Popot, Jean-Luc; Giusti, Fabrice

    2014-10-01

    Amphipols (APols) are short amphipathic polymers developed as an alternative to detergents for handling membrane proteins (MPs) in aqueous solution. MPs are, as a rule, much more stable following trapping with APols than they are in detergent solutions. The best-characterized APol to date, called A8-35, is a mixture of short-chain sodium polyacrylates randomly derivatized with octylamine and isopropylamine. Its solution properties have been studied in detail, and it has been used extensively for biochemical and biophysical studies of MPs. One of the attractive characteristics of APols is that it is relatively easy to label them, isotopically or otherwise, without affecting their physical-chemical properties. Furthermore, several variously modified APols can be mixed, achieving multiple functionalization of MP/APol complexes in the easiest possible manner. Labeled or tagged APols are being used to study the solution properties of APols, their miscibility, their biodistribution upon injection into living organisms, their association with MPs and the composition, structure and dynamics of MP/APol complexes, examining the exchange of surfactants at the surface of MPs, labeling MPs to follow their distribution in fractionation experiments or to immobilize them, increasing the contrast between APols and solvent or MPs in biophysical experiments, improving NMR spectra, etc. Labeling or functionalization of APols can take various courses, each of which has its specific constraints and advantages regarding both synthesis and purification. The present review offers an overview of the various derivatives of A8-35 and its congeners that have been developed in our laboratory and discusses the pros and cons of various synthetic routes.

  16. Accelerating expansion or inhomogeneity? II. Mimicking acceleration with the energy function in the Lemaître-Tolman model

    NASA Astrophysics Data System (ADS)

    Krasiński, Andrzej

    2014-07-01

    This is a continuation of the paper published in Phys. Rev. D 89, 023520 (2014). Here we investigate how the luminosity distance-redshift relation DL(z) of the ΛCDM model is duplicated in the Lemaître-Tolman (L-T) model with Λ =0, constant bang-time function tB and the energy function E(r) mimicking accelerated expansion on the observer's past light cone (r is a uniquely defined comoving radial coordinate). Numerical experiments show that E>0 necessarily. The functions z(r) and E(r) are numerically calculated from the initial point at the observer's position, then backward from the initial point at the apparent horizon (AH). Reconciling the results of the two calculations allows one to determine the values of E/r2 at r=0 and at the AH. The problems connected with continuing the calculation through the AH are discussed in detail and solved. Then z(r) and E(r) are continued beyond the AH, up to the numerical crash that signals the contact of the light cone with the big bang. Similarly, the light cone of the L-T model is calculated by proceeding from the two initial points, and compared with the ΛCDM light cone. The model constructed here contains shell crossings, but they can be removed by matching the L-T region to a Friedmann background, without causing any conflict with the type Ia supernovae observations. The mechanism of imitating the accelerated expansion by the E(r) function is explained in a descriptive way.

  17. Functional changes in systemic and regional (intracranial) circulation accompanying low accelerations

    NASA Technical Reports Server (NTRS)

    Usachev, V. V.; Shinkarevskaya, I. P.

    1973-01-01

    Functional changes in systemic and cerebral hemodynamics were studied with respect to vestibular stresses. The main types of responses, differing qualitatively with respect to the tolerance of test subjects to low accelerations (particularly to Coriolis accelerations), were established. This is of practical importance in the selection of aircraft and space pilots. The data presented sheds light on the physiological mechanisms of adaptation and disturbed compensation during vestibular stimulation. Further studies in this important field of aerospace medicine are outlined.

  18. Functional changes in systemic and regional (intracranial) circulation accompanying low accelerations

    NASA Technical Reports Server (NTRS)

    Usachev, V. V.; Shinkarevskaya, I. P.

    1973-01-01

    Functional changes in systemic and cerebral hemodynamics were studied with respect to vestibular stresses. The main types of responses, differing qualitatively with respect to the tolerance of test subjects to low accelerations (particularly to Coriolis accelerations), were established. This is of practical importance in the selection of aircraft and space pilots. The data presented sheds light on the physiological mechanisms of adaptation and disturbed compensation during vestibular stimulation. Further studies in this important field of aerospace medicine are outlined.

  19. [Biological experiments in microgravity: equilibrium function].

    PubMed

    Gorgiladze, G I; Shipov, A A; Horn, E

    2012-01-01

    The review deals with the investigations of structural and functional modifications in the equilibrium organ (EO) in invertebrates (coelenterates, shells, crustaceans and insects) and vertebrates (fishes, amphibians, rats, primates) on different ontogenetic stages in the condition of microgravity and during readaptation to the Earth's gravity. Results of the investigations detail the adaptive strategy of terrestrial organism in the environment lacking the gravitational components that leads to the discrepancy of an inner model of the body-environment schema constructed by the central nervous system at 1 g and the novel reality. It is manifested by ataxic behavior and increased graviceptors' afferentation against efferent system inactivation. The new condition is defined as a sensibilization phase ensued by the eluding phase: behavior obeys the innate motion strategy, whereas graviceptors' afferentation decreases due to activation of the efferent system. Readaptation to 1 G takes several to 50 days and proceeds as a sequence of slow in motion behavior, ataxia and vestibular sensitization. Reactivity of the gravitosensory system to microgravity was found to be age-dependent. Gain in the EO inertial mass in microgravity and reduction with return to 1 g indicates gravity relevance to EO genesis.

  20. ACCELERATORS: A GUI tool for beta function measurement using MATLAB

    NASA Astrophysics Data System (ADS)

    Chen, Guang-Ling; Tian, Shun-Qiang; Jiang, Bo-Cheng; Liu, Gui-Min

    2009-04-01

    The beta function measurement is used to detect the shift in the betatron tune as the strength of an individual quadrupole magnet is varied. A GUI (graphic user interface) tool for the beta function measurement is developed using the MATLAB program language in the Linux environment, which facilitates the commissioning of the Shanghai Synchrotron Radiation Facility (SSRF) storage ring. In this paper, we describe the design of the application and give some measuring results and discussions about the definition of the measurement. The program has been optimized to solve some restrictions of the AT tracking code. After the correction with LOCO (linear optics from closed orbits), the horizontal and the vertical root mean square values (rms values) can be reduced to 0.12 and 0.10.

  1. Hamiltonian Monte Carlo acceleration using surrogate functions with random bases.

    PubMed

    Zhang, Cheng; Shahbaba, Babak; Zhao, Hongkai

    2017-11-01

    For big data analysis, high computational cost for Bayesian methods often limits their applications in practice. In recent years, there have been many attempts to improve computational efficiency of Bayesian inference. Here we propose an efficient and scalable computational technique for a state-of-the-art Markov chain Monte Carlo methods, namely, Hamiltonian Monte Carlo. The key idea is to explore and exploit the structure and regularity in parameter space for the underlying probabilistic model to construct an effective approximation of its geometric properties. To this end, we build a surrogate function to approximate the target distribution using properly chosen random bases and an efficient optimization process. The resulting method provides a flexible, scalable, and efficient sampling algorithm, which converges to the correct target distribution. We show that by choosing the basis functions and optimization process differently, our method can be related to other approaches for the construction of surrogate functions such as generalized additive models or Gaussian process models. Experiments based on simulated and real data show that our approach leads to substantially more efficient sampling algorithms compared to existing state-of-the-art methods.

  2. Evidence for a Role of Executive Functions in Learning Biology

    ERIC Educational Resources Information Center

    Rhodes, Sinéad M.; Booth, Josephine N.; Campbell, Lorna Elise; Blythe, Richard A.; Wheate, Nial J.; Delibegovic, Mirela

    2014-01-01

    Research examining cognition and science learning has focused on working memory, but evidence implicates a broader set of executive functions. The current study examined executive functions and learning of biology in young adolescents. Fifty-six participants, aged 12-13?years, completed tasks of working memory (Spatial Working Memory), inhibition…

  3. Chemical biology approaches to membrane homeostasis and function.

    PubMed

    Takahashi-Umebayashi, Miwa; Pineau, Ludovic; Hannich, Thomas; Zumbuehl, Andreas; Doval, David Alonso; Matile, Stefan; Heinis, Christian; Turcatti, Gerardo; Loewith, Robbie; Roux, Aurélien; Reymond, Luc; Johnsson, Kai; Riezman, Howard

    2011-01-01

    The study of membranes is at a turning point. New theories about membrane structure and function have recently been proposed, however, new technologies, combining chemical, physical, and biochemical approaches are necessary to test these hypotheses. In particular, the NCCR in chemical biology aims to visualize and characterize membrane microdomains and determine their function during hormone signaling.

  4. Evidence for a Role of Executive Functions in Learning Biology

    ERIC Educational Resources Information Center

    Rhodes, Sinéad M.; Booth, Josephine N.; Campbell, Lorna Elise; Blythe, Richard A.; Wheate, Nial J.; Delibegovic, Mirela

    2014-01-01

    Research examining cognition and science learning has focused on working memory, but evidence implicates a broader set of executive functions. The current study examined executive functions and learning of biology in young adolescents. Fifty-six participants, aged 12-13?years, completed tasks of working memory (Spatial Working Memory), inhibition…

  5. Functional toxicology: a new approach to detect biologically active xenobiotics.

    PubMed Central

    McLachlan, J A

    1993-01-01

    The pervasiveness of chemicals in the environment with estrogenic activity and other biological functions recommends the development of new approaches to monitor and study them. Chemicals can be screened for activity in vitro using a panel of human or animal cells that have been transfected with a specific receptor and reporter gene; for example, the estrogen receptor. By using a variety of different receptors, the screening of xenobiotics for biological functions can be broad. Chemicals could then be classified by their function in vitro which, in some cases, may be a useful guide for toxicological studies. Images Figure 1. PMID:8119246

  6. Mimicking biological functionality with polymers for biomedical applications

    NASA Astrophysics Data System (ADS)

    Green, Jordan J.; Elisseeff, Jennifer H.

    2016-12-01

    The vast opportunities for biomaterials design and functionality enabled by mimicking nature continue to stretch the limits of imagination. As both biological understanding and engineering capabilities develop, more sophisticated biomedical materials can be synthesized that have multifaceted chemical, biological and physical characteristics designed to achieve specific therapeutic goals. Mimicry is being used in the design of polymers for biomedical applications that are required locally in tissues, systemically throughout the body, and at the interface with tissues.

  7. Principles for modeling and functional simulation of biological microstructures

    NASA Astrophysics Data System (ADS)

    Kriete, Andres

    1997-04-01

    This paper discusses some aspects of computer based modeling of biological microstructures. The workflow tom model and simulate a biological structure is described as a feedback- loop. Beside the system definition by structural and dynamical properties, the simulation is discussed as a mathematical representation coupled with a computer visualization. As an example, the investigation of the functional behavior of lung structures is described with special emphasis to the modeling of respiratory units.

  8. A Chemical Biology Approach to Developing STAT Inhibitors: Molecular Strategies for Accelerating Clinical Translation

    PubMed Central

    Nelson, Erik A.; Sharma, Sreenath V.; Settleman, Jeffrey; Frank, David A.

    2011-01-01

    STAT transcription factors transduce signals from the cell surface to the nucleus, where they regulate the expression of genes that control proliferation, survival, self-renewal, and other critical cellular functions. Under normal physiological conditions, the activation of STATs is tightly regulated. In cancer, by contrast, STAT proteins, particularly STAT3 and STAT5, become activated constitutively, thereby driving the malignant phenotype of cancer cells. Since these proteins are largely dispensable in the function of normal adult cells, STATs represent a potentially important target for cancer therapy. Although transcription factors have traditionally been viewed as suboptimal targets for pharmacological inhibition, chemical biology approaches have been particularly fruitful in identifying compounds that can modulate this pathway through a variety of mechanisms. STAT inhibitors have notable anti-cancer effects in many tumor systems, show synergy with other therapeutic modalities, and have the potential to eradicate tumor stem cells. Furthermore, STAT inhibitors identified through the screening of chemical libraries can then be employed in large scale analyses such as gene expression profiling, RNA interference screens, or large-scale tumor cell line profiling. Data derived from these studies can then provide key insights into mechanisms of STAT signal transduction, as well as inform the rational design of targeted therapeutic strategies for cancer patients. PMID:21680956

  9. Head and Tibial Acceleration as a Function of Stride Frequency and Visual Feedback during Running

    PubMed Central

    Busa, Michael A.; Lim, Jongil; van Emmerik, Richard E. A.; Hamill, Joseph

    2016-01-01

    Individuals regulate the transmission of shock to the head during running at different stride frequencies although the consequences of this on head-gaze stability remain unclear. The purpose of this study was to examine if providing individuals with visual feedback of their head-gaze orientation impacts tibial and head accelerations, shock attenuation and head-gaze motion during preferred speed running at different stride frequencies. Fifteen strides from twelve recreational runners running on a treadmill at their preferred speed were collected during five stride frequencies (preferred, ±10% and ±20% of preferred) in two visual task conditions (with and without real-time visual feedback of head-gaze orientation). The main outcome measures were tibial and head peak accelerations assessed in the time and frequency domains, shock attenuation from tibia to head, and the magnitude and velocity of head-gaze motion. Decreasing stride frequency resulted in greater vertical accelerations of the tibia (p<0.01) during early stance and at the head (p<0.01) during early and late stance; however, for the impact portion the increase in head acceleration was only observed for the slowest stride frequency condition. Visual feedback resulted in reduced head acceleration magnitude (p<0.01) and integrated power spectral density in the frequency domain (p<0.01) in late stance, as well as overall of head-gaze motion (p<0.01). When running at preferred speed individuals were able to stabilize head acceleration within a wide range of stride frequencies; only at a stride frequency 20% below preferred did head acceleration increase. Furthermore, impact accelerations of the head and tibia appear to be solely a function of stride frequency as no differences were observed between feedback conditions. Increased visual task demands through head gaze feedback resulted in reductions in head accelerations in the active portion of stance and increased head-gaze stability. PMID:27271850

  10. Head and Tibial Acceleration as a Function of Stride Frequency and Visual Feedback during Running.

    PubMed

    Busa, Michael A; Lim, Jongil; van Emmerik, Richard E A; Hamill, Joseph

    2016-01-01

    Individuals regulate the transmission of shock to the head during running at different stride frequencies although the consequences of this on head-gaze stability remain unclear. The purpose of this study was to examine if providing individuals with visual feedback of their head-gaze orientation impacts tibial and head accelerations, shock attenuation and head-gaze motion during preferred speed running at different stride frequencies. Fifteen strides from twelve recreational runners running on a treadmill at their preferred speed were collected during five stride frequencies (preferred, ±10% and ±20% of preferred) in two visual task conditions (with and without real-time visual feedback of head-gaze orientation). The main outcome measures were tibial and head peak accelerations assessed in the time and frequency domains, shock attenuation from tibia to head, and the magnitude and velocity of head-gaze motion. Decreasing stride frequency resulted in greater vertical accelerations of the tibia (p<0.01) during early stance and at the head (p<0.01) during early and late stance; however, for the impact portion the increase in head acceleration was only observed for the slowest stride frequency condition. Visual feedback resulted in reduced head acceleration magnitude (p<0.01) and integrated power spectral density in the frequency domain (p<0.01) in late stance, as well as overall of head-gaze motion (p<0.01). When running at preferred speed individuals were able to stabilize head acceleration within a wide range of stride frequencies; only at a stride frequency 20% below preferred did head acceleration increase. Furthermore, impact accelerations of the head and tibia appear to be solely a function of stride frequency as no differences were observed between feedback conditions. Increased visual task demands through head gaze feedback resulted in reductions in head accelerations in the active portion of stance and increased head-gaze stability.

  11. Infrared Structural Biology: Detect Functionally Important Structural Motions of Proteins

    NASA Astrophysics Data System (ADS)

    Xie, Aihua

    Proteins are dynamic. Lack of dynamic structures of proteins hampers our understanding of protein functions. Infrared structural biology (IRSB) is an emerging technology. There are several advantages of IRSB for mechanistic studies of proteins: (1) its excellent dynamic range (detecting structural motions from picoseconds to >= seconds); (2) its high structural sensitivity (detect tiny but functionally important structural motions such as proton transfer and changes in hydrogen bonding interaction); (3) its ability to detect different structural motions simultaneously. Successful development of infrared structural biology demands not only new experimental techniques (from infrared technologies to chemical synthesis and cell biology), but also new data processing (how to translate infrared signals into quantitative structural information of proteins). These topics will be discussed as well as examples of how to use IRSB to study structure-function relationship of proteins. This work was supported by NSF DBI1338097 and OCAST HR10-078.

  12. Can Simple Biophysical Principles Yield Complicated Biological Functions?

    NASA Astrophysics Data System (ADS)

    Liphardt, Jan

    2011-03-01

    About once a year, a new regulatory paradigm is discovered in cell biology. As of last count, eukaryotic cells have more than 40 distinct ways of regulating protein concentration and function. Regulatory possibilities include site-specific phosphorylation, epigenetics, alternative splicing, mRNA (re)localization, and modulation of nucleo-cytoplasmic transport. This raises a simple question. Do all the remarkable things cells do, require an intricately choreographed supporting cast of hundreds of molecular machines and associated signaling networks? Alternatively, are there a few simple biophysical principles that can generate apparently very complicated cellular behaviors and functions? I'll discuss two problems, spatial organization of the bacterial chemotaxis system and nucleo-cytoplasmic transport, where the latter might be true. In both cases, the ability to precisely quantify biological organization and function, at the single-molecule level, helped to find signatures of basic biological organizing principles.

  13. The physical characteristics of human proteins in different biological functions.

    PubMed

    Wang, Tengjiao; Tang, Hailin

    2017-01-01

    The physical properties of gene products are the foundation of their biological functions. In this study, we systematically explored relationships between physical properties and biological functions. The physical properties including origin time, evolution pressure, mRNA and protein stability, molecular weight, hydrophobicity, acidity/alkaline, amino acid compositions, and chromosome location. The biological functions are defined from 4 aspects: biological process, molecular function, cellular component and cell/tissue/organ expression. We found that the proteins associated with basic material and energy metabolism process originated earlier, while the proteins associated with immune, neurological system process etc. originated later. Tissues may have a strong influence on evolution pressure. The proteins associated with energy metabolism are double-stable. Immune and peripheral cell proteins tend to be mRNA stable/protein unstable. There are very few function items with double-unstable of mRNA and protein. The proteins involved in the cell adhesion tend to consist of large proteins with high proportion of small amino acids. The proteins of organic acid transport, neurological system process and amine transport have significantly high hydrophobicity. Interestingly, the proteins involved in olfactory receptor activity tend to have high frequency of aromatic, sulfuric and hydroxyl amino acids.

  14. Relative biological effectiveness of accelerated heavy ions for induction of morphological transformation in Syrian hamster embryo cells.

    PubMed

    Han, Z B; Suzuki, H; Suzuki, F; Suzuki, M; Furusawa, Y; Kato, T; Ikenaga, M

    1998-09-01

    Syrian hamster embryo cells were used to study the morphological transformation induced by accelerated heavy ions with different linear energy transfer (LET) ranging from 13 to 400 keV/micron. Exponentially growing cells were irradiated with 12C or 28Si ion beams generated by the Heavy Ion Medical Accelerator in Chiba (HIMAC), then inoculated to culture dishes. Morphologically altered colonies were scored as transformants. Over the LET range examined, the frequency of transformation induced by the heavy ions increased sharply at very low doses no greater than 5 cGy. The relative biological effectiveness (RBE) of the heavy ions relative to X-rays first increased with LET, reached a maximum value of about 7 at 100 keV/micron, then decreased with the further increase of LET. Our findings confirmed that high LET heavy ions are much more effective than X-rays for the induction of in vitro cell transformation.

  15. Diffusive Particle Acceleration in Shocked, Viscous Accretion Disks: Green's Function Energy Distribution

    NASA Astrophysics Data System (ADS)

    Becker, Peter A.; Das, Santabrata; Le, Truong

    2011-12-01

    The acceleration of relativistic particles in a viscous accretion disk containing a standing shock is investigated as a possible explanation for the energetic outflows observed around radio-loud black holes. The energy/space distribution of the accelerated particles is computed by solving a transport equation that includes the effects of first-order Fermi acceleration, bulk advection, spatial diffusion, and particle escape. The velocity profile of the accreting gas is described using a model for shocked viscous disks recently developed by the authors, and the corresponding Green's function distribution for the accelerated particles in the disk and the outflow is obtained using a classical method based on eigenfunction analysis. The accretion-driven, diffusive shock acceleration scenario explored here is conceptually similar to the standard model for the acceleration of cosmic rays at supernova-driven shocks. However, in the disk application, the distribution of the accelerated particles is much harder than would be expected for a plane-parallel shock with the same compression ratio. Hence the disk environment plays a key role in enhancing the efficiency of the shock acceleration process. The presence of the shock helps to stabilize the disk by reducing the Bernoulli parameter, while channeling the excess binding energy into the escaping relativistic particles. In applications to M87 and Sgr A*, we find that the kinetic power in the jet is {\\sim}0.01\\,\\dot{M} c^2, and the outflowing relativistic particles have a mean energy ~300 times larger than that of the thermal gas in the disk at the shock radius. Our results suggest that a standing shock may be an essential ingredient in accretion onto underfed black holes, helping to resolve the long-standing problem of the stability of advection-dominated accretion disks.

  16. Metabolism and biological functions of human milk oligosaccharides.

    PubMed

    Bertino, E; Peila, C; Giuliani, F; Martano, C; Cresi, F; Di Nicola, P; Occhi, L; Sabatino, G; Fabris, C

    2012-01-01

    It is well known that breastfeeding is beneficial both for its nutritional properties and for the presence of biologically active compounds. Among these, human milk oligosaccharides (HMOs), representing the third largest fraction of human milk, have been assigned important biological functions, such as prebiotic and immunomodulatory and antimicrobial effects. HMOs are synthesized in the mammary gland by glycosyltransferase enzymes and can be divided in core-oligosaccharides, sialo-oligosaccharides, fucosyl-oligosaccharides and sialo-fucosyl-oligosaccharides on the basis of their chemical structure. Glycosyltransferases enzymes are partially regulated by genetic mechanisms; according to the expression of secretory and Lewis' genes, it is possible to classify human milk in 4 different secretory groups. We hereby present a review of the current knowledge concerning HMOs, their metabolism and main biological functions.

  17. Shortening tobacco life cycle accelerates functional gene identification in genomic research.

    PubMed

    Ning, G; Xiao, X; Lv, H; Li, X; Zuo, Y; Bao, M

    2012-11-01

    Definitive allocation of function requires the introduction of genetic mutations and analysis of their phenotypic consequences. Novel, rapid and convenient techniques or materials are very important and useful to accelerate gene identification in functional genomics research. Here, over-expression of PmFT (Prunus mume), a novel FT orthologue, and PtFT (Populus tremula) lead to shortening of the tobacco life cycle. A series of novel short life cycle stable tobacco lines (30-50 days) were developed through repeated self-crossing selection breeding. Based on the second transformation via a gusA reporter gene, the promoter from BpFULL1 in silver birch (Betula pendula) and the gene (CPC) from Arabidopsis thaliana were effectively tested using short life cycle tobacco lines. Comparative analysis among wild type, short life cycle tobacco and Arabidopsis transformation system verified that it is optional to accelerate functional gene studies by shortening host plant material life cycle, at least in these short life cycle tobacco lines. The results verified that the novel short life cycle transgenic tobacco lines not only combine the advantages of economic nursery requirements and a simple transformation system, but also provide a robust, effective and stable host system to accelerate gene analysis. Thus, shortening tobacco life cycle strategy is feasible to accelerate heterologous or homologous functional gene identification in genomic research.

  18. Students' Perceptions of Long-Functioning Cooperative Teams in Accelerated Adult Degree Programs

    ERIC Educational Resources Information Center

    Favor, Judy

    2012-01-01

    This study examined 718 adult students' perceptions of long-functioning cooperative study teams in accelerated associate's, bachelor's, and master's business degree programs. Six factors were examined: attraction toward team, alignment of performance expectations, intrateam conflict, workload sharing, preference for teamwork, and impact on…

  19. Students' Perceptions of Long-Functioning Cooperative Teams in Accelerated Adult Degree Programs

    ERIC Educational Resources Information Center

    Favor, Judy

    2012-01-01

    This study examined 718 adult students' perceptions of long-functioning cooperative study teams in accelerated associate's, bachelor's, and master's business degree programs. Six factors were examined: attraction toward team, alignment of performance expectations, intrateam conflict, workload sharing, preference for teamwork, and impact on…

  20. Upper limit for the accelerating gradient in the collinear wakefield accelerator as a function of the transformer ratio

    NASA Astrophysics Data System (ADS)

    Baturin, S. S.; Zholents, A.

    2017-06-01

    The interrelation between the accelerating gradient and the transformer ratio in the collinear wakefield accelerator has been analyzed. It has been shown that the high transformer ratio and the high efficiency of the energy transfer from the drive bunch to the witness bunch can only be achieved at the expense of the accelerating gradient. Rigorous proof is given that in best cases of meticulously shaped charge density distributions in the drive bunch, the maximum accelerating gradient falls proportionally to the gain in the transformer ratio. Conclusions are verified using several representative examples.

  1. Upper limit for the acceleration gradient in the collinear wake field accelerator as a function of the transformer ratio

    DOE PAGES

    Baturin, Stanislav; Zholents, A.

    2017-06-19

    Here, the interrelation between the accelerating gradient and the transformer ratio in the collinear wake field accelerator has been analyzed. It has been shown that the high transformer ratio and the high efficiency of the energy transfer from the drive bunch to the witness bunch can only be achieved at the expense of the accelerating gradient. Rigorous proof is given that in best cases of meticulously shaped charge density distributions in the drive bunch, the maximum accelerating gradient falls proportionally to the gain in the transformer ratio. Conclusions are verified using several representative examples.

  2. Evolutionary cell biology: functional insight from "endless forms most beautiful".

    PubMed

    Richardson, Elisabeth; Zerr, Kelly; Tsaousis, Anastasios; Dorrell, Richard G; Dacks, Joel B

    2015-12-15

    In animal and fungal model organisms, the complexities of cell biology have been analyzed in exquisite detail and much is known about how these organisms function at the cellular level. However, the model organisms cell biologists generally use include only a tiny fraction of the true diversity of eukaryotic cellular forms. The divergent cellular processes observed in these more distant lineages are still largely unknown in the general scientific community. Despite the relative obscurity of these organisms, comparative studies of them across eukaryotic diversity have had profound implications for our understanding of fundamental cell biology in all species and have revealed the evolution and origins of previously observed cellular processes. In this Perspective, we will discuss the complexity of cell biology found across the eukaryotic tree, and three specific examples of where studies of divergent cell biology have altered our understanding of key functional aspects of mitochondria, plastids, and membrane trafficking. © 2015 Richardson et al. This article is distributed by The American Society for Cell Biology under license from the author(s). Two months after publication it is available to the public under an Attribution–Noncommercial–Share Alike 3.0 Unported Creative Commons License (http://creativecommons.org/licenses/by-nc-sa/3.0).

  3. Exploring the mechanical basis for acceleration: pelvic limb locomotor function during accelerations in racing greyhounds (Canis familiaris).

    PubMed

    Williams, S B; Usherwood, J R; Jespers, K; Channon, A J; Wilson, A M

    2009-02-01

    Animals in their natural environments are confronted with a regular need to perform rapid accelerations (for example when escaping from predators or chasing prey). Such acceleration requires net positive mechanical work to be performed on the centre of mass by skeletal muscle. Here we determined how pelvic limb joints contribute to the mechanical work and power that are required for acceleration in galloping quadrupeds. In addition, we considered what, if any, biomechanical strategies exist to enable effective acceleration to be achieved. Simultaneous kinematic and kinetic data were collected for racing greyhounds undergoing a range of low to high accelerations. From these data, joint moments and joint powers were calculated for individual hindlimb joints. In addition, the mean effective mechanical advantage (EMA) of the limb and the ;gear ratio' of each joint throughout stance were calculated. Greatest increases in joint work and power with acceleration appeared at the hip and hock joints, particularly in the lead limb. Largest increases in absolute positive joint work occurred at the hip, consistent with the hypothesis that quadrupeds power locomotion by torque about the hip. In addition, hindlimb EMA decreased substantially with increased acceleration - a potential strategy to increase stance time and thus ground impulses for a given peak force. This mechanism may also increase the mechanical advantage for applying the horizontal forces necessary for acceleration.

  4. Linking structural features of protein complexes and biological function

    PubMed Central

    Sowmya, Gopichandran; Breen, Edmond J; Ranganathan, Shoba

    2015-01-01

    Protein–protein interaction (PPI) establishes the central basis for complex cellular networks in a biological cell. Association of proteins with other proteins occurs at varying affinities, yet with a high degree of specificity. PPIs lead to diverse functionality such as catalysis, regulation, signaling, immunity, and inhibition, playing a crucial role in functional genomics. The molecular principle of such interactions is often elusive in nature. Therefore, a comprehensive analysis of known protein complexes from the Protein Data Bank (PDB) is essential for the characterization of structural interface features to determine structure–function relationship. Thus, we analyzed a nonredundant dataset of 278 heterodimer protein complexes, categorized into major functional classes, for distinguishing features. Interestingly, our analysis has identified five key features (interface area, interface polar residue abundance, hydrogen bonds, solvation free energy gain from interface formation, and binding energy) that are discriminatory among the functional classes using Kruskal-Wallis rank sum test. Significant correlations between these PPI interface features amongst functional categories are also documented. Salt bridges correlate with interface area in regulator-inhibitors (r = 0.75). These representative features have implications for the prediction of potential function of novel protein complexes. The results provide molecular insights for better understanding of PPIs and their relation to biological functions. PMID:26131659

  5. Applications of large-scale density functional theory in biology

    NASA Astrophysics Data System (ADS)

    Cole, Daniel J.; Hine, Nicholas D. M.

    2016-10-01

    Density functional theory (DFT) has become a routine tool for the computation of electronic structure in the physics, materials and chemistry fields. Yet the application of traditional DFT to problems in the biological sciences is hindered, to a large extent, by the unfavourable scaling of the computational effort with system size. Here, we review some of the major software and functionality advances that enable insightful electronic structure calculations to be performed on systems comprising many thousands of atoms. We describe some of the early applications of large-scale DFT to the computation of the electronic properties and structure of biomolecules, as well as to paradigmatic problems in enzymology, metalloproteins, photosynthesis and computer-aided drug design. With this review, we hope to demonstrate that first principles modelling of biological structure-function relationships are approaching a reality.

  6. Modeling Functional Motions of Biological Systems by Customized Natural Moves.

    PubMed

    Demharter, Samuel; Knapp, Bernhard; Deane, Charlotte M; Minary, Peter

    2016-08-23

    Simulating the functional motions of biomolecular systems requires large computational resources. We introduce a computationally inexpensive protocol for the systematic testing of hypotheses regarding the dynamic behavior of proteins and nucleic acids. The protocol is based on natural move Monte Carlo, a highly efficient conformational sampling method with built-in customization capabilities that allows researchers to design and perform a large number of simulations to investigate functional motions in biological systems. We demonstrate the use of this protocol on both a protein and a DNA case study. Firstly, we investigate the plasticity of a class II major histocompatibility complex in the absence of a bound peptide. Secondly, we study the effects of the epigenetic mark 5-hydroxymethyl on cytosine on the structure of the Dickerson-Drew dodecamer. We show how our customized natural moves protocol can be used to investigate causal relationships of functional motions in biological systems.

  7. Venom Proteins from Parasitoid Wasps and Their Biological Functions.

    PubMed

    Moreau, Sébastien J M; Asgari, Sassan

    2015-06-26

    Parasitoid wasps are valuable biological control agents that suppress their host populations. Factors introduced by the female wasp at parasitization play significant roles in facilitating successful development of the parasitoid larva either inside (endoparasitoid) or outside (ectoparasitoid) the host. Wasp venoms consist of a complex cocktail of proteinacious and non-proteinacious components that may offer agrichemicals as well as pharmaceutical components to improve pest management or health related disorders. Undesirably, the constituents of only a small number of wasp venoms are known. In this article, we review the latest research on venom from parasitoid wasps with an emphasis on their biological function, applications and new approaches used in venom studies.

  8. Venom Proteins from Parasitoid Wasps and Their Biological Functions

    PubMed Central

    Moreau, Sébastien J. M.; Asgari, Sassan

    2015-01-01

    Parasitoid wasps are valuable biological control agents that suppress their host populations. Factors introduced by the female wasp at parasitization play significant roles in facilitating successful development of the parasitoid larva either inside (endoparasitoid) or outside (ectoparasitoid) the host. Wasp venoms consist of a complex cocktail of proteinacious and non-proteinacious components that may offer agrichemicals as well as pharmaceutical components to improve pest management or health related disorders. Undesirably, the constituents of only a small number of wasp venoms are known. In this article, we review the latest research on venom from parasitoid wasps with an emphasis on their biological function, applications and new approaches used in venom studies. PMID:26131769

  9. Neuroscience in the era of functional genomics and systems biology.

    PubMed

    Geschwind, Daniel H; Konopka, Genevieve

    2009-10-15

    Advances in genetics and genomics have fuelled a revolution in discovery-based, or hypothesis-generating, research that provides a powerful complement to the more directly hypothesis-driven molecular, cellular and systems neuroscience. Genetic and functional genomic studies have already yielded important insights into neuronal diversity and function, as well as disease. One of the most exciting and challenging frontiers in neuroscience involves harnessing the power of large-scale genetic, genomic and phenotypic data sets, and the development of tools for data integration and mining. Methods for network analysis and systems biology offer the promise of integrating these multiple levels of data, connecting molecular pathways to nervous system function.

  10. Electron distribution function behavior during localized transverse ion acceleration events in the topside auroral zone

    NASA Technical Reports Server (NTRS)

    Lynch, K. A.; Arnoldy, R. L.; Kintner, P. M.; Vago, J. L.

    1994-01-01

    The Topaz3 auroral sounding rocket made the following observations concerning the transfer of precipitating auroral electron energy to transverse ion acceleration in the topside auroral zone. During the course of the flight, the precipitating electron beam was modified to varying degrees by interaction with VLF hiss, at times changing the beam into a field-aligned plateau. The electron distribution functions throughout the flight are classified according to the extent of this modification, and correspondences with ion acceleration events are sought. The hiss power during most of this rocket flight apparently exceeded the threshold for collapse into solitary structures. At the times of plateaued electron distributions, the collapse of these structures was limited by Landau damping through the ambient ions, resulting in a velocity-dependent acceleration of both protons and oxygen. This initial acceleration is sufficient to supply the number flux of upflowing ions observed at satellite altitudes. The bursty ion acceleration was anticorrelated, on 1-s or smaller timescales, with dispersive bursts of precipitating field-aligned electrons, although on longer timescales the bursty ions and the bursty electrons are correlated.

  11. Electron distribution function behavior during localized transverse ion acceleration events in the topside auroral zone

    NASA Technical Reports Server (NTRS)

    Lynch, K. A.; Arnoldy, R. L.; Kintner, P. M.; Vago, J. L.

    1994-01-01

    The Topaz3 auroral sounding rocket made the following observations concerning the transfer of precipitating auroral electron energy to transverse ion acceleration in the topside auroral zone. During the course of the flight, the precipitating electron beam was modified to varying degrees by interaction with VLF hiss, at times changing the beam into a field-aligned plateau. The electron distribution functions throughout the flight are classified according to the extent of this modification, and correspondences with ion acceleration events are sought. The hiss power during most of this rocket flight apparently exceeded the threshold for collapse into solitary structures. At the times of plateaued electron distributions, the collapse of these structures was limited by Landau damping through the ambient ions, resulting in a velocity-dependent acceleration of both protons and oxygen. This initial acceleration is sufficient to supply the number flux of upflowing ions observed at satellite altitudes. The bursty ion acceleration was anticorrelated, on 1-s or smaller timescales, with dispersive bursts of precipitating field-aligned electrons, although on longer timescales the bursty ions and the bursty electrons are correlated.

  12. Morpho-chemistry and functionality of diseased biological tissues

    NASA Astrophysics Data System (ADS)

    Lange, Marta; Cicchi, Riccardo; Pavone, Francesco

    2014-09-01

    Heart and cardiovascular diseases are one of the most common in the world, in particular - arthrosclerosis. The aim of the research is to distinguish pathological and healthy tissue regions in biological samples, in this case - to distinguish collagen and lipid rich regions within the arterial wall. In the work a specific combination of such methods are used: FLIM and SHG in order to evaluate the biological tissue morphology and functionality, so that this research could give a contribution for creating a new biological tissue imaging standard in the closest future. During the study the most appropriate parameter for fluorescence lifetime decay was chosen in order to evaluate lifetime decay parameters and the isotropy of the arterial wall and deposition, using statistical methods FFT and GLCM. The research gives a contribution or the future investigations for evaluating lipid properties when it can de-attach from the arterial wall and cause clotting in the blood vessel or even a stroke.

  13. Carbon-Oxygen Hydrogen Bonding in Biological Structure and Function

    PubMed Central

    Horowitz, Scott; Trievel, Raymond C.

    2012-01-01

    Carbon-oxygen (CH···O) hydrogen bonding represents an unusual category of molecular interactions first documented in biological structures over 4 decades ago. Although CH···O hydrogen bonding has remained generally underappreciated in the biochemical literature, studies over the last 15 years have begun to yield direct evidence of these interactions in biological systems. In this minireview, we provide a historical context of biological CH···O hydrogen bonding and summarize some major advancements from experimental studies over the past several years that have elucidated the importance, prevalence, and functions of these interactions. In particular, we examine the impact of CH···O bonds on protein and nucleic acid structure, molecular recognition, and enzyme catalysis and conclude by exploring overarching themes and unresolved questions regarding unconventional interactions in biomolecular structure. PMID:23048026

  14. From Structure and Function of Proteins Toward in Silico Biology

    NASA Astrophysics Data System (ADS)

    Yamato, Ichiro

    2013-01-01

    Researches of biology are targeted on three major flows, materials (or chemicals), energy, and information. I have been mainly concerned with the studies on bioenergy transducing mechanisms. I have studied the mechanism of secondary active transport systems and proposed an affinity change mechanism as a general hypothesis, then tried to confirm that it is applicable to other kinds of bioenergy transducing systems. Choosing Na+-translocating V-type ATPase from Enterococcus hirae as target, I hypothesized the affinity change mechanism for the energy transduction of this ATPase. Here I describe several three dimensional structures of parts of the ATPase supporting my hypothesis. From such detailed and extensive researches on protein structure/function relationship, we can proceed toward the in silico biology, which I described previously in 2007 ([1] "Toward in silico biology").

  15. Functional Agents to Biologically Control Deoxynivalenol Contamination in Cereal Grains

    PubMed Central

    Tian, Ye; Tan, Yanglan; Liu, Na; Liao, Yucai; Sun, Changpo; Wang, Shuangxia; Wu, Aibo

    2016-01-01

    Mycotoxins, as microbial secondary metabolites, frequently contaminate cereal grains and pose a serious threat to human and animal health around the globe. Deoxynivalenol (DON), a commonly detected Fusarium mycotoxin, has drawn utmost attention due to high exposure levels and contamination frequency in the food chain. Biological control is emerging as a promising technology for the management of DON contamination. Functional biological control agents (BCAs), which include antagonistic microbes, natural fungicides derived from plants and detoxification enzymes, can be used to control DON contamination at different stages of grain production. In this review, studies regarding different biological agents for DON control in recent years are summarized for the first time. Furthermore, this article highlights the significance of BCAs for controlling DON contamination, as well as the need for more practical and efficient BCAs concerning food safety. PMID:27064760

  16. Modulation of leg joint function to produce emulated acceleration during walking and running in humans

    PubMed Central

    Raiteri, Brent J.

    2017-01-01

    Understanding how humans adapt gait mechanics for a wide variety of locomotor tasks is important for inspiring the design of robotic, prosthetic and wearable assistive devices. We aimed to elicit the mechanical adjustments made to leg joint functions that are required to generate accelerative walking and running, using metrics with direct relevance to device design. Twelve healthy male participants completed constant speed (CS) walking and running and emulated acceleration (ACC) trials on an instrumented treadmill. External force and motion capture data were combined in an inverse dynamics analysis. Ankle, knee and hip joint mechanics were described and compared using angles, moments, powers and normalized functional indexes that described each joint as relatively more: spring, motor, damper or strut-like. To accelerate using a walking gait, the ankle joint was switched from predominantly spring-like to motor-like, while the hip joint was maintained as a motor, with an increase in hip motor-like function. Accelerating while running involved no change in the primary function of any leg joint, but involved high levels of spring and motor-like function at the hip and ankle joints. Mechanical adjustments for ACC walking were achieved primarily via altered limb positioning, but ACC running needed greater joint moments. PMID:28405377

  17. Constructing biological pathway models with hybrid functional Petri nets.

    PubMed

    Doi, Atsushi; Fujita, Sachie; Matsuno, Hiroshi; Nagasaki, Masao; Miyano, Satoru

    2004-01-01

    In many research projects on modeling and analyzing biological pathways, the Petri net has been recognized as a promising method for representing biological pathways. From the pioneering works by Reddy et al., 1993, and Hofestädt, 1994, that model metabolic pathways by traditional Petri net, several enhanced Petri nets such as colored Petri net, stochastic Petri net, and hybrid Petri net have been used for modeling biological phenomena. Recently, Matsuno et al., 2003b, introduced the hybrid functional Petri net (HFPN) in order to give a more intuitive and natural modeling method for biological pathways than these existing Petri nets. Although the paper demonstrates the effectiveness of HFPN with two examples of gene regulation mechanism for circadian rhythms and apoptosis signaling pathway, there has been no detailed explanation about the method of HFPN construction for these examples. The purpose of this paper is to describe method to construct biological pathways with the HFPN step-by-step. The method is demonstrated by the well-known glycolytic pathway controlled by the lac operon gene regulatory mechanism.

  18. Constructing biological pathway models with hybrid functional petri nets.

    PubMed

    Doi, Atsushi; Fujita, Sachie; Matsuno, Hiroshi; Nagasaki, Masao; Miyano, Satoru

    2011-01-01

    In many research projects on modeling and analyzing biological pathways, the Petri net has been recognized as a promising method for representing biological pathways. From the pioneering works by Reddy et al., 1993, and Hofestädt, 1994, that model metabolic pathways by traditional Petri net, several enhanced Petri nets such as colored Petri net, stochastic Petri net, and hybrid Petri net have been used for modeling biological phenomena. Recently, Matsuno et al., 2003b, introduced the hybrid functional Petri net (HFPN) in order to give a more intuitive and natural modeling method for biological pathways than these existing Petri nets. Although the paper demonstrates the effectiveness of HFPN with two examples of gene regulation mechanism for circadian rhythms and apoptosis signaling pathway, there has been no detailed explanation about the method of HFPN construction for these examples. The purpose of this paper is to describe method to construct biological pathways with the HFPN step-by-step. The method is demonstrated by the well-known glycolytic pathway controlled by the lac operon gene regulatory mechanism.

  19. Chemical Biology for Investigating Epigenetic Functions of Lysine Acetyltransferases (KATs).

    PubMed

    He, Maomao; Han, Zhen; Liu, Liang; Zheng, Y George

    2017-08-07

    The side chain acetylation of lysine residues in histones and non-histone proteins catalyzed by lysine acetyltransferases (KATs) represents a widespread posttranslational modification (PTM) in the eukaryotic cells. Lysine acetylation plays regulatory roles in major cellular pathways inside and outside the nucleus. In particular, KAT-mediated histone acetylation impacts on all the DNA-templated epigenetic processes. Aberrant expression and activation of KATs are commonly observed in human diseases, especially cancer. Recent years have witnessed that study of KAT functions in biology and disease is greatly benefited by finely designed chemical biology tools and strategies. In this essay, we reviewed the past and current accomplishments in the design of chemical biology approaches for the interrogation of KAT activity and function. These methods and probes were classified according to their mechanisms of action and respective applications, with both strengths and limitations discussed. We also presented our perspectives on potential challenges facing chemical biology of protein acetylation and suggested possible future directions in the field. © 2017 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  20. Caveat on the Boltzmann distribution function use in biology.

    PubMed

    Sevcik, Carlos

    2017-08-01

    Sigmoid semilogarithmic functions with shape of Boltzmann equations, have become extremely popular to describe diverse biological situations. Part of the popularity is due to the easy availability of software which fits Boltzmann functions to data, without much knowledge of the fitting procedure or the statistical properties of the parameters derived from the procedure. The purpose of this paper is to explore the plasticity of the Boltzmann function to fit data, some aspects of the optimization procedure to fit the function to data and how to use this plastic function to differentiate the effect of treatment on data and to attest the statistical significance of treatment effect on the data. Copyright © 2017. Published by Elsevier Ltd.

  1. [Biological Function of The Small G Protein Rap].

    PubMed

    Li, Shan-Shan; Guo, Xiao-Xi; An, Shu; Yang, Yang; Liu, Ying; Xu, Tian-Rui

    2016-02-01

    Rap has different biological functions on intracellular signaling pathways, such as regulating cell polarity, cell proliferation, cell differentiation, cell adhesion and cell movement. Furthermore, at tissue and organ level, Rap controls the establishment of neural polarity, synaptic growth, synaptic plasticity, neuronal migration and so on. Rap belongs to Ras family which contains two subtypes, Rap1 and Rap2. By binding GTP or GDP Rap transform between active or inactive state, and plays an important role as a molecular switch. Moreover, in the signal pathway of tumor, Rap inhibits cell transformation induced by the oncogene Ras, therefore inhibits the proliferation, invasion and migration of certain cancer cells by interacting with its downstream target molecules. In this review, we summarized the biological functions of Rap and discussed It's significance in cancer therapy and drug treatment of neurological diseases.

  2. SU-E-T-54: Benefits of Biological Cost Functions

    SciTech Connect

    Demirag, N

    2014-06-01

    Purpose: To verify the benefits of the biological cost functions. Methods: TG166 patients were used for the test case scenarios. Patients were planned using Monaco V5.0 (CMS/Elekta, St.Louis, MO) Monaco has 3 biological and 8 physical CFs. In this study the plans were optimized using 3 different scenarios. 1- Biological CFs only 2-Physical CFs only 3- Combination of Physical and Biological CFsMonaco has 3 biological CFs. Target EUD used for the targets, derived from the poisson cell kill model, has an α value that controls the cold spots inside the target. α values used in the optimization were 0.5 and 0.8. if cold spots needs to be penalized α value increased. Serial CF: it's called serial to mimic the behaviour of the serial organs, if a high k value like 12 or 14 is used it controls the maximum dose. Serial CF has a k parameter that is used to shape the whole dvh curve. K value ranges between 1–20. k:1 is used to control the mean dose, lower k value controls the mean dose, higher k value controls the higher dose, using 2 serial CFs with different k values controls the whole DVH. Paralel CF controls the percentage of the volume that tolerates higher doses than the reference dose to mimic the behaviour of the paralel organs. Results: It was possible to achive clinically accepted plans in all 3 scenarios. The benefit of the biological cost functions were to control the mean dose for target and OAR, to shape the DVH curve using one EUD value and one k value simplifies the optimization process. Using the biological CFs alone, it was hard to control the dose at a point. Conclusion: Biological CFs in Monaco doesn't require the ntcp/tcp values from the labs and useful to shape the whole dvh curve. I work as an applications support specialist for Elekta and I am a Ph.D. Student in Istanbul University for radiation therapy physics.

  3. Accelerated remyelination during inflammatory demyelination prevents axonal loss and improves functional recovery

    PubMed Central

    Mei, Feng; Lehmann-Horn, Klaus; Shen, Yun-An A; Rankin, Kelsey A; Stebbins, Karin J; Lorrain, Daniel S; Pekarek, Kara; A Sagan, Sharon; Xiao, Lan; Teuscher, Cory; von Büdingen, H-Christian; Wess, Jürgen; Lawrence, J Josh; Green, Ari J; Fancy, Stephen PJ; Zamvil, Scott S; Chan, Jonah R

    2016-01-01

    Demyelination in MS disrupts nerve signals and contributes to axon degeneration. While remyelination promises to restore lost function, it remains unclear whether remyelination will prevent axonal loss. Inflammatory demyelination is accompanied by significant neuronal loss in the experimental autoimmune encephalomyelitis (EAE) mouse model and evidence for remyelination in this model is complicated by ongoing inflammation, degeneration and possible remyelination. Demonstrating the functional significance of remyelination necessitates selectively altering the timing of remyelination relative to inflammation and degeneration. We demonstrate accelerated remyelination after EAE induction by direct lineage analysis and hypothesize that newly formed myelin remains stable at the height of inflammation due in part to the absence of MOG expression in immature myelin. Oligodendroglial-specific genetic ablation of the M1 muscarinic receptor, a potent negative regulator of oligodendrocyte differentiation and myelination, results in accelerated remyelination, preventing axonal loss and improving functional recovery. Together our findings demonstrate that accelerated remyelination supports axonal integrity and neuronal function after inflammatory demyelination. DOI: http://dx.doi.org/10.7554/eLife.18246.001 PMID:27671734

  4. Biological framework for soil aggregation: Implications for ecological functions.

    NASA Astrophysics Data System (ADS)

    Ghezzehei, Teamrat; Or, Dani

    2016-04-01

    Soil aggregation is heuristically understood as agglomeration of primary particles bound together by biotic and abiotic cementing agents. The organization of aggregates is believed to be hierarchical in nature; whereby primary particles bond together to form secondary particles and subsequently merge to form larger aggregates. Soil aggregates are not permanent structures, they continuously change in response to internal and external forces and other drivers, including moisture, capillary pressure, temperature, biological activity, and human disturbances. Soil aggregation processes and the resulting functionality span multiple spatial and temporal scales. The intertwined biological and physical nature of soil aggregation, and the time scales involved precluded a universally applicable and quantifiable framework for characterizing the nature and function of soil aggregation. We introduce a biophysical framework of soil aggregation that considers the various modes and factors of the genesis, maturation and degradation of soil aggregates including wetting/drying cycles, soil mechanical processes, biological activity and the nature of primary soil particles. The framework attempts to disentangle mechanical (compaction and soil fragmentation) from in-situ biophysical aggregation and provides a consistent description of aggregate size, hierarchical organization, and life time. It also enables quantitative description of biotic and abiotic functions of soil aggregates including diffusion and storage of mass and energy as well as role of aggregates as hot spots of nutrient accumulation, biodiversity, and biogeochemical cycles.

  5. Bioclojure: a functional library for the manipulation of biological sequences

    PubMed Central

    Plieskatt, Jordan; Rinaldi, Gabriel; Brindley, Paul J.; Jia, Xinying; Potriquet, Jeremy; Bethony, Jeffrey; Mulvenna, Jason

    2014-01-01

    Motivation: BioClojure is an open-source library for the manipulation of biological sequence data written in the language Clojure. BioClojure aims to provide a functional framework for the processing of biological sequence data that provides simple mechanisms for concurrency and lazy evaluation of large datasets. Results: BioClojure provides parsers and accessors for a range of biological sequence formats, including UniProtXML, Genbank XML, FASTA and FASTQ. In addition, it provides wrappers for key analysis programs, including BLAST, SignalP, TMHMM and InterProScan, and parsers for analyzing their output. All interfaces leverage Clojure’s functional style and emphasize laziness and composability, so that BioClojure, and user-defined, functions can be chained into simple pipelines that are thread-safe and seamlessly integrate lazy evaluation. Availability and implementation: BioClojure is distributed under the Lesser GPL, and the source code is freely available from GitHub (https://github.com/s312569/clj-biosequence). Contact: jason.mulvenna@qimrberghofer.edu.au or jason.mulvenna@qimr.edu.au PMID:24794932

  6. Accelerated Integrated Science Sequence (AISS): An Introductory Biology, Chemistry, and Physics Course

    ERIC Educational Resources Information Center

    Purvis-Roberts, Kathleen L.; Edwalds-Gilbert, Gretchen; Landsberg, Adam S.; Copp, Newton; Ulsh, Lisa; Drew, David E.

    2009-01-01

    A new interdisciplinary, introductory science course was offered for the first time during the 2007-2008 school year. The purpose of the course is to introduce students to the idea of working at the intersections of biology, chemistry, and physics and to recognize interconnections between the disciplines. Interdisciplinary laboratories are a key…

  7. Accelerated Integrated Science Sequence (AISS): An Introductory Biology, Chemistry, and Physics Course

    ERIC Educational Resources Information Center

    Purvis-Roberts, Kathleen L.; Edwalds-Gilbert, Gretchen; Landsberg, Adam S.; Copp, Newton; Ulsh, Lisa; Drew, David E.

    2009-01-01

    A new interdisciplinary, introductory science course was offered for the first time during the 2007-2008 school year. The purpose of the course is to introduce students to the idea of working at the intersections of biology, chemistry, and physics and to recognize interconnections between the disciplines. Interdisciplinary laboratories are a key…

  8. Deducing protein function by forensic integrative cell biology.

    PubMed

    Earnshaw, William C

    2013-12-01

    Our ability to sequence genomes has provided us with near-complete lists of the proteins that compose cells, tissues, and organisms, but this is only the beginning of the process to discover the functions of cellular components. In the future, it's going to be crucial to develop computational analyses that can predict the biological functions of uncharacterised proteins. At the same time, we must not forget those fundamental experimental skills needed to confirm the predictions or send the analysts back to the drawing board to devise new ones.

  9. The biology, structure, and function of eyebrow hair.

    PubMed

    Nguyen, Jennifer V

    2014-01-01

    Eyebrow hair serves many important biologic and aesthetic functions. This article reviews the structure and function of the hair follicle, as well as hair follicle morphogenesis and cycling. Eyebrow hair follicles share the same basic structure as hair follicles elsewhere on the body, but are distinguished by their shorter anagen (growing) phase. Knowledge of the hair follicle structure and cycle is important for understanding the pathophysiology of alopecia, as diseases affecting the stem cell portion of the hair follicle in the bulge region may cause permanent hair loss. Furthermore, therapeutic agents that target distinct phases and hormones involved in the hair cycle may be useful for promoting hair growth.

  10. libKEDF: An accelerated library of kinetic energy density functionals.

    PubMed

    Dieterich, Johannes M; Witt, William C; Carter, Emily A

    2017-06-30

    Kinetic energy density functionals (KEDFs) approximate the kinetic energy of a system of electrons directly from its electron density. They are used in electronic structure methods that lack direct access to orbitals, for example, orbital-free density functional theory (OFDFT) and certain embedding schemes. In this contribution, we introduce libKEDF, an accelerated library of modern KEDF implementations that emphasizes nonlocal KEDFs. We discuss implementation details and assess the performance of the KEDF implementations for large numbers of atoms. We show that using libKEDF, a single computing node or (GPU) accelerator can provide easy computational access to mesoscale chemical and materials science phenomena using OFDFT algorithms. © 2017 Wiley Periodicals, Inc. © 2017 Wiley Periodicals, Inc.

  11. Accelerating self-consistent field convergence with the augmented Roothaan–Hall energy function

    PubMed Central

    Hu, Xiangqian; Yang, Weitao

    2010-01-01

    Based on Pulay’s direct inversion iterative subspace (DIIS) approach, we present a method to accelerate self-consistent field (SCF) convergence. In this method, the quadratic augmented Roothaan–Hall (ARH) energy function, proposed recently by Høst and co-workers [J. Chem. Phys. 129, 124106 (2008)], is used as the object of minimization for obtaining the linear coefficients of Fock matrices within DIIS. This differs from the traditional DIIS of Pulay, which uses an object function derived from the commutator of the density and Fock matrices. Our results show that the present algorithm, abbreviated ADIIS, is more robust and efficient than the energy-DIIS (EDIIS) approach. In particular, several examples demonstrate that the combination of ADIIS and DIIS (“ADIIS+DIIS”) is highly reliable and efficient in accelerating SCF convergence. PMID:20136307

  12. Obesity-induced oxidative stress, accelerated functional decline with age and increased mortality in mice.

    PubMed

    Zhang, Yiqiang; Fischer, Kathleen E; Soto, Vanessa; Liu, Yuhong; Sosnowska, Danuta; Richardson, Arlan; Salmon, Adam B

    2015-06-15

    Obesity is a serious chronic disease that increases the risk of numerous co-morbidities including metabolic syndrome, cardiovascular disease and cancer as well as increases risk of mortality, leading some to suggest this condition represents accelerated aging. Obesity is associated with significant increases in oxidative stress in vivo and, despite the well-explored relationship between oxidative stress and aging, the role this plays in the increased mortality of obese subjects remains an unanswered question. Here, we addressed this by undertaking a comprehensive, longitudinal study of a group of high fat-fed obese mice and assessed both their changes in oxidative stress and in their performance in physiological assays known to decline with aging. In female C57BL/6J mice fed a high-fat diet starting in adulthood, mortality was significantly increased as was oxidative damage in vivo. High fat-feeding significantly accelerated the decline in performance in several assays, including activity, gait, and rotarod. However, we also found that obesity had little effect on other markers of function and actually improved performance in grip strength, a marker of muscular function. Together, this first comprehensive assessment of longitudinal, functional changes in high fat-fed mice suggests that obesity may induce segmental acceleration of some of the aging process. Published by Elsevier Inc.

  13. Center of Mass Acceleration Feedback Control for Standing by Functional Neuromuscular Stimulation – a Simulation Study

    PubMed Central

    Audu, Musa L.; Kirsch, Robert F.; Triolo, Ronald J.

    2013-01-01

    The potential efficacy of total body center of mass (COM) acceleration for feedback control of standing balance by functional neuromuscular stimulation (FNS) following spinal cord injury (SCI) was investigated. COM acceleration may be a viable alternative to conventional joint kinematics due to its rapid responsiveness, focal representation of COM dynamics, and ease of measurement. A computational procedure was developed using an anatomically-realistic, three-dimensional, bipedal biomechanical model to determine optimal patterns of muscle excitations to produce targeted effects upon COM acceleration from erect stance. The procedure was verified with electromyographic data collected from standing able-bodied subjects undergoing systematic perturbations. Using 16 muscle groups targeted by existing implantable neuroprostheses, data were generated to train an artificial neural network (ANN)-based controller in simulation. During forward simulations, proportional feedback of COM acceleration drove the ANN to produce muscle excitation patterns countering the effects of applied perturbations. Feedback gains were optimized to minimize upper extremity (UE) loading required to stabilize against disturbances. Compared to the clinical case of maximum constant excitation, the controller reduced UE loading by 43% in resisting external perturbations and by 51% during simulated one-arm reaching. Future work includes performance assessment against expected measurement errors and developing user-specific control systems. PMID:22773529

  14. Harnessing systems biology approaches to engineer functional microvascular networks.

    PubMed

    Sefcik, Lauren S; Wilson, Jennifer L; Papin, Jason A; Botchwey, Edward A

    2010-06-01

    Microvascular remodeling is a complex process that includes many cell types and molecular signals. Despite a continued growth in the understanding of signaling pathways involved in the formation and maturation of new blood vessels, approximately half of all compounds entering clinical trials will fail, resulting in the loss of much time, money, and resources. Most pro-angiogenic clinical trials to date have focused on increasing neovascularization via the delivery of a single growth factor or gene. Alternatively, a focus on the concerted regulation of whole networks of genes may lead to greater insight into the underlying physiology since the coordinated response is greater than the sum of its parts. Systems biology offers a comprehensive network view of the processes of angiogenesis and arteriogenesis that might enable the prediction of drug targets and whether or not activation of the targets elicits the desired outcome. Systems biology integrates complex biological data from a variety of experimental sources (-omics) and analyzes how the interactions of the system components can give rise to the function and behavior of that system. This review focuses on how systems biology approaches have been applied to microvascular growth and remodeling, and how network analysis tools can be utilized to aid novel pro-angiogenic drug discovery.

  15. Obesity and diabetes as accelerators of functional decline: can lifestyle interventions maintain functional status in high risk older adults?

    PubMed

    Anton, Stephen D; Karabetian, Christy; Naugle, Kelly; Buford, Thomas W

    2013-09-01

    Obesity and diabetes are known risk factors for the development of physical disability among older adults. With the number of seniors with these conditions rising worldwide, the prevention and treatment of physical disability in these persons have become a major public health challenge. Sarcopenia, the progressive loss of muscle mass and strength, has been identified as a common pathway associated with the initial onset and progression of physical disability among older adults. A growing body of evidence suggests that metabolic dysregulation associated with obesity and diabetes accelerates the progression of sarcopenia, and subsequently functional decline in older adults. The focus of this brief review is on the contributions of obesity and diabetes in accelerating sarcopenia and functional decline among older adults. We also briefly discuss the underexplored interaction between obesity and diabetes that may further accelerate sarcopenia and place obese older adults with diabetes at particularly high risk of disability. Finally, we review findings from studies that have specifically tested the efficacy of lifestyle-based interventions in maintaining the functional status of older persons with obesity and/or diabetes.

  16. Obesity and Diabetes as Accelerators of Functional Decline; Can Lifestyle Interventions Maintain Functional Status in High Risk Older Adults?

    PubMed Central

    Anton, Stephen D.; Karabetian, Christy; Naugle, Kelly; Buford, Thomas W.

    2013-01-01

    Obesity and diabetes are known risk factors for the development of physical disability among older adults. With the number of seniors with these conditions rising worldwide, the prevention and treatment of physical disability in these persons has become a major public health challenge. Sarcopenia, the progressive loss of muscle mass and strength, has been identified as a common pathway associated with the initial onset and progression of physical disability among older adults. A growing body of evidence suggests that metabolic dysregulation associated with obesity and diabetes accelerates the progression of sarcopenia, and subsequently functional decline in older adults. The focus of this brief review is on the contributions of obesity and diabetes in accelerating sarcopenia and functional decline among older adults. We also briefly discuss the underexplored interaction between obesity and diabetes that may further accelerate sarcopenia and place obese older adults with diabetes at particularly high risk of disability. Finally, we review findings from studies that have specifically tested the efficacy of lifestyle-based interventions in maintaining the functional status of older persons with obesity and/or diabetes. PMID:23832077

  17. An accelerated framework for the classification of biological targets from solid-state micropore data.

    PubMed

    Hanif, Madiha; Hafeez, Abdul; Suleman, Yusuf; Mustafa Rafique, M; Butt, Ali R; Iqbal, Samir M

    2016-10-01

    Micro- and nanoscale systems have provided means to detect biological targets, such as DNA, proteins, and human cells, at ultrahigh sensitivity. However, these devices suffer from noise in the raw data, which continues to be significant as newer and devices that are more sensitive produce an increasing amount of data that needs to be analyzed. An important dimension that is often discounted in these systems is the ability to quickly process the measured data for an instant feedback. Realizing and developing algorithms for the accurate detection and classification of biological targets in realtime is vital. Toward this end, we describe a supervised machine-learning approach that records single cell events (pulses), computes useful pulse features, and classifies the future patterns into their respective types, such as cancerous/non-cancerous cells based on the training data. The approach detects cells with an accuracy of 70% from the raw data followed by an accurate classification when larger training sets are employed. The parallel implementation of the algorithm on graphics processing unit (GPU) demonstrates a speedup of three to four folds as compared to a serial implementation on an Intel Core i7 processor. This incredibly efficient GPU system is an effort to streamline the analysis of pulse data in an academic setting. This paper presents for the first time ever, a non-commercial technique using a GPU system for realtime analysis, paired with biological cluster targeting analysis. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

  18. Chemical and biological flocculation process to treat municipal sewage and analysis of biological function.

    PubMed

    Xia, Si-qing; Yang, Dian-hai; Xu, Bin; Zhao, Jian-fu

    2005-01-01

    The pilot-scale experimental apparatus and the procedure of the chemical and biological flocculation process to verify the feasibility in treating Shanghai municipal sewage were introduced in this paper. In addition, the biological function of the process was discussed. The results of optimal running showed that in the reaction tank, the concentration of mixed liquor suspended solid(MLSS) was 2 g/L, hydraulic retention time(HRT) was 35 min, dosage of liquid polyaluminium chloride(PAC) was 60 mg/L, and the concentration of polyacrylamide(PAM) was 0.5 mg/L. The effluent average concentrations of COD(Cr), TP, SS and BOD5 were 50 mg/L, 0.62 mg/L, 18 mg/L, and 17 mg/L, respectively. These were better than the designed demand. In addition, the existence of biological degradation in this system was proven by several methods. The removal efficiencies of the chemical and biological flocculation process were 20% higher than that of the chemical flocculation process above at the same coagulant dosage. The treatment process under different situations was evaluated on a pilot-scale experiment, and the results provided magnificent parameters and optimal condition for future operation of the plant.

  19. Advances in cell surface glycoengineering reveal biological function.

    PubMed

    Nischan, Nicole; Kohler, Jennifer J

    2016-08-01

    Cell surface glycans are critical mediators of cell-cell, cell-ligand, and cell-pathogen interactions. By controlling the set of glycans displayed on the surface of a cell, it is possible to gain insight into the biological functions of glycans. Moreover, control of glycan expression can be used to direct cellular behavior. While genetic approaches to manipulate glycosyltransferase gene expression are available, their utility in glycan engineering has limitations due to the combinatorial nature of glycan biosynthesis and the functional redundancy of glycosyltransferase genes. Biochemical and chemical strategies offer valuable complements to these genetic approaches, notably by enabling introduction of unnatural functionalities, such as fluorophores, into cell surface glycans. Here, we describe some of the most recent developments in glycoengineering of cell surfaces, with an emphasis on strategies that employ novel chemical reagents. We highlight key examples of how these advances in cell surface glycan engineering enable study of cell surface glycans and their function. Exciting new technologies include synthetic lipid-glycans, new chemical reporters for metabolic oligosaccharide engineering to allow tandem and in vivo labeling of glycans, improved chemical and enzymatic methods for glycoproteomics, and metabolic glycosyltransferase inhibitors. Many chemical and biochemical reagents for glycan engineering are commercially available, facilitating their adoption by the biological community.

  20. Biological properties of extracellular vesicles and their physiological functions

    PubMed Central

    Yáñez-Mó, María; Siljander, Pia R.-M.; Andreu, Zoraida; Zavec, Apolonija Bedina; Borràs, Francesc E.; Buzas, Edit I.; Buzas, Krisztina; Casal, Enriqueta; Cappello, Francesco; Carvalho, Joana; Colás, Eva; Silva, Anabela Cordeiro-da; Fais, Stefano; Falcon-Perez, Juan M.; Ghobrial, Irene M.; Giebel, Bernd; Gimona, Mario; Graner, Michael; Gursel, Ihsan; Gursel, Mayda; Heegaard, Niels H. H.; Hendrix, An; Kierulf, Peter; Kokubun, Katsutoshi; Kosanovic, Maja; Kralj-Iglic, Veronika; Krämer-Albers, Eva-Maria; Laitinen, Saara; Lässer, Cecilia; Lener, Thomas; Ligeti, Erzsébet; Linē, Aija; Lipps, Georg; Llorente, Alicia; Lötvall, Jan; Manček-Keber, Mateja; Marcilla, Antonio; Mittelbrunn, Maria; Nazarenko, Irina; Hoen, Esther N.M. Nolte-‘t; Nyman, Tuula A.; O'Driscoll, Lorraine; Olivan, Mireia; Oliveira, Carla; Pállinger, Éva; del Portillo, Hernando A.; Reventós, Jaume; Rigau, Marina; Rohde, Eva; Sammar, Marei; Sánchez-Madrid, Francisco; Santarém, N.; Schallmoser, Katharina; Ostenfeld, Marie Stampe; Stoorvogel, Willem; Stukelj, Roman; Van der Grein, Susanne G.; Vasconcelos, M. Helena; Wauben, Marca H. M.; De Wever, Olivier

    2015-01-01

    In the past decade, extracellular vesicles (EVs) have been recognized as potent vehicles of intercellular communication, both in prokaryotes and eukaryotes. This is due to their capacity to transfer proteins, lipids and nucleic acids, thereby influencing various physiological and pathological functions of both recipient and parent cells. While intensive investigation has targeted the role of EVs in different pathological processes, for example, in cancer and autoimmune diseases, the EV-mediated maintenance of homeostasis and the regulation of physiological functions have remained less explored. Here, we provide a comprehensive overview of the current understanding of the physiological roles of EVs, which has been written by crowd-sourcing, drawing on the unique EV expertise of academia-based scientists, clinicians and industry based in 27 European countries, the United States and Australia. This review is intended to be of relevance to both researchers already working on EV biology and to newcomers who will encounter this universal cell biological system. Therefore, here we address the molecular contents and functions of EVs in various tissues and body fluids from cell systems to organs. We also review the physiological mechanisms of EVs in bacteria, lower eukaryotes and plants to highlight the functional uniformity of this emerging communication system. PMID:25979354

  1. Mnk kinase pathway: Cellular functions and biological outcomes

    PubMed Central

    Joshi, Sonali; Platanias, Leonidas C

    2014-01-01

    The mitogen-activated protein kinase (MAPK) interacting protein kinases 1 and 2 (Mnk1 and Mnk2) play important roles in controlling signals involved in mRNA translation. In addition to the MAPKs (p38 or Erk), multiple studies suggest that the Mnk kinases can be regulated by other known kinases such as Pak2 and/or other unidentified kinases by phosphorylation of residues distinct from the sites phosphorylated by the MAPKs. Several studies have established multiple Mnk protein targets, including PSF, heterogenous nuclear ribonucleoprotein A1, Sprouty 2 and have lead to the identification of distinct biological functions and substrate specificity for the Mnk kinases. In this review we discuss the pathways regulating the Mnk kinases, their known substrates as well as the functional consequences of engagement of pathways controlled by Mnk kinases. These kinases play an important role in mRNA translation via their regulation of eukaryotic initiation factor 4E (eIF4E) and their functions have important implications in tumor biology as well as the regulation of drug resistance to anti-oncogenic therapies. Other studies have identified a role for the Mnk kinases in cap-independent mRNA translation, suggesting that the Mnk kinases can exert important functional effects independently of the phosphorylation of eIF4E. The role of Mnk kinases in inflammation and inflammation-induced malignancies is also discussed. PMID:25225600

  2. Systems analysis of biological networks in skeletal muscle function.

    PubMed

    Smith, Lucas R; Meyer, Gretchen; Lieber, Richard L

    2013-01-01

    Skeletal muscle function depends on the efficient coordination among subcellular systems. These systems are composed of proteins encoded by a subset of genes, all of which are tightly regulated. In the cases where regulation is altered because of disease or injury, dysfunction occurs. To enable objective analysis of muscle gene expression profiles, we have defined nine biological networks whose coordination is critical to muscle function. We begin by describing the expression of proteins necessary for optimal neuromuscular junction function that results in the muscle cell action potential. That action potential is transmitted to proteins involved in excitation-contraction coupling enabling Ca(2+) release. Ca(2+) then activates contractile proteins supporting actin and myosin cross-bridge cycling. Force generated by cross-bridges is transmitted via cytoskeletal proteins through the sarcolemma and out to critical proteins that support the muscle extracellular matrix. Muscle contraction is fueled through many proteins that regulate energy metabolism. Inflammation is a common response to injury that can result in alteration of many pathways within muscle. Muscle also has multiple pathways that regulate size through atrophy or hypertrophy. Finally, the isoforms associated with fast muscle fibers and their corresponding isoforms in slow muscle fibers are delineated. These nine networks represent important biological systems that affect skeletal muscle function. Combining high-throughput systems analysis with advanced networking software will allow researchers to use these networks to objectively study skeletal muscle systems. Copyright © 2012 Wiley Periodicals, Inc.

  3. Biological properties of extracellular vesicles and their physiological functions.

    PubMed

    Yáñez-Mó, María; Siljander, Pia R-M; Andreu, Zoraida; Zavec, Apolonija Bedina; Borràs, Francesc E; Buzas, Edit I; Buzas, Krisztina; Casal, Enriqueta; Cappello, Francesco; Carvalho, Joana; Colás, Eva; Cordeiro-da Silva, Anabela; Fais, Stefano; Falcon-Perez, Juan M; Ghobrial, Irene M; Giebel, Bernd; Gimona, Mario; Graner, Michael; Gursel, Ihsan; Gursel, Mayda; Heegaard, Niels H H; Hendrix, An; Kierulf, Peter; Kokubun, Katsutoshi; Kosanovic, Maja; Kralj-Iglic, Veronika; Krämer-Albers, Eva-Maria; Laitinen, Saara; Lässer, Cecilia; Lener, Thomas; Ligeti, Erzsébet; Linē, Aija; Lipps, Georg; Llorente, Alicia; Lötvall, Jan; Manček-Keber, Mateja; Marcilla, Antonio; Mittelbrunn, Maria; Nazarenko, Irina; Nolte-'t Hoen, Esther N M; Nyman, Tuula A; O'Driscoll, Lorraine; Olivan, Mireia; Oliveira, Carla; Pállinger, Éva; Del Portillo, Hernando A; Reventós, Jaume; Rigau, Marina; Rohde, Eva; Sammar, Marei; Sánchez-Madrid, Francisco; Santarém, N; Schallmoser, Katharina; Ostenfeld, Marie Stampe; Stoorvogel, Willem; Stukelj, Roman; Van der Grein, Susanne G; Vasconcelos, M Helena; Wauben, Marca H M; De Wever, Olivier

    2015-01-01

    In the past decade, extracellular vesicles (EVs) have been recognized as potent vehicles of intercellular communication, both in prokaryotes and eukaryotes. This is due to their capacity to transfer proteins, lipids and nucleic acids, thereby influencing various physiological and pathological functions of both recipient and parent cells. While intensive investigation has targeted the role of EVs in different pathological processes, for example, in cancer and autoimmune diseases, the EV-mediated maintenance of homeostasis and the regulation of physiological functions have remained less explored. Here, we provide a comprehensive overview of the current understanding of the physiological roles of EVs, which has been written by crowd-sourcing, drawing on the unique EV expertise of academia-based scientists, clinicians and industry based in 27 European countries, the United States and Australia. This review is intended to be of relevance to both researchers already working on EV biology and to newcomers who will encounter this universal cell biological system. Therefore, here we address the molecular contents and functions of EVs in various tissues and body fluids from cell systems to organs. We also review the physiological mechanisms of EVs in bacteria, lower eukaryotes and plants to highlight the functional uniformity of this emerging communication system.

  4. Probing the Xenopus laevis inner ear transcriptome for biological function

    PubMed Central

    2012-01-01

    Background The senses of hearing and balance depend upon mechanoreception, a process that originates in the inner ear and shares features across species. Amphibians have been widely used for physiological studies of mechanotransduction by sensory hair cells. In contrast, much less is known of the genetic basis of auditory and vestibular function in this class of animals. Among amphibians, the genus Xenopus is a well-characterized genetic and developmental model that offers unique opportunities for inner ear research because of the amphibian capacity for tissue and organ regeneration. For these reasons, we implemented a functional genomics approach as a means to undertake a large-scale analysis of the Xenopus laevis inner ear transcriptome through microarray analysis. Results Microarray analysis uncovered genes within the X. laevis inner ear transcriptome associated with inner ear function and impairment in other organisms, thereby supporting the inclusion of Xenopus in cross-species genetic studies of the inner ear. The use of gene categories (inner ear tissue; deafness; ion channels; ion transporters; transcription factors) facilitated the assignment of functional significance to probe set identifiers. We enhanced the biological relevance of our microarray data by using a variety of curation approaches to increase the annotation of the Affymetrix GeneChip® Xenopus laevis Genome array. In addition, annotation analysis revealed the prevalence of inner ear transcripts represented by probe set identifiers that lack functional characterization. Conclusions We identified an abundance of targets for genetic analysis of auditory and vestibular function. The orthologues to human genes with known inner ear function and the highly expressed transcripts that lack annotation are particularly interesting candidates for future analyses. We used informatics approaches to impart biologically relevant information to the Xenopus inner ear transcriptome, thereby addressing the

  5. Biological water: Its vital role in macromolecular structure and function.

    PubMed

    Despa, Florin

    2005-12-01

    Water in tissues and cells is confined by intervening cellular components and is subject to structural effects that are not present in its bulk counterpart. The structuring effects lower the dielectric susceptibility of water molecules and induce a "red shift" of their relaxation frequency. This is also a source of polarization fields that contribute to the effective interactions between macromolecules. The behavior of water molecules at hydrophilic sites is different from that at hydrophobic sites, and this dissimilar behavior promotes the anisotropy of the hydration shell of proteins. The anisotropy of the hydration shell is essential for the enzyme function, but it is also important in detecting denaturation of the protein (i.e., proteins expose their hydrophobic parts to water during unfolding). The most significant differences between biological and ordinary water will be presented along with how this information can be used to decipher patterns in dynamical behavior of biological water and to detect possible structural changes of the cellular components.

  6. Trajectories of Microbial Community Function in Response to Accelerated Remediation of Subsurface Metal Contaminants

    SciTech Connect

    Firestone, Mary

    2015-01-14

    Objectives of proposed research were to; Determine if the trajectories of microbial community composition and function following organic carbon amendment can be related to, and predicted by, key environmental determinants; Assess the relative importance of the characteristics of the indigenous microbial community, sediment, groundwater, and concentration of organic carbon amendment as the major determinants of microbial community functional response and bioremediation capacity; and Provide a fundamental understanding of the microbial community ecology underlying subsurface metal remediation requisite to successful application of accelerated remediation and long-term stewardship of DOE-IFC sites.

  7. Biological Manipulation of Migration Rate: The Use of Advanced Photoperiod to Accelerate Smoltification in Yearling Chinook Salmon, Annual Report 1989.

    SciTech Connect

    Giorgi, Albert E.; Muir, William D.; Zaugg, Waldo S.

    1991-01-01

    Research was conducted to assess the feasibility of biologically manipulating physiological development and migratory behavior of yearling spring chinook salmon, Oncorhynchus tshawytscha. At Dworshak National Fish Hatchery, treatment groups were exposed to a variety of advanced photoperiod cycles preceding release to accelerate smolt development. Physiological development and migratory performance were described for all groups. The treatments included a 14-week exposure to a 3-month advanced photoperiod cycle, an 18-week exposure to a 3-month advanced photoperiod cycle, and an 18-week exposure to a 4-month advanced photoperiod cycle. Two additional groups, an 18-week exposure to a 3-month advanced photoperiod and a control equivalent, were reared at an elevated water temperature (11{degrees}C) for 2 weeks prior to release. Results indicated that the treated fish which were the most physiologically advanced at release were detected in the highest proportion at collector dams and also migrated fastest downstream. 26 refs., 10 figs., 5 tabs.

  8. Considerations to improve functional annotations in biological databases.

    PubMed

    Benítez-Páez, Alfonso

    2009-12-01

    Despite the great effort to design efficient systems allowing the electronic indexation of information concerning genes, proteins, structures, and interactions published daily in scientific journals, some problems are still observed in specific tasks such as functional annotation. The annotation of function is a critical issue for bioinformatic routines, such as for instance, in functional genomics and the further prediction of unknown protein function, which are highly dependent of the quality of existing annotations. Some information management systems evolve to efficiently incorporate information from large-scale projects, but often, annotation of single records from the literature is difficult and slow. In this short report, functional characterizations of a representative sample of the entire set of uncharacterized proteins from Escherichia coli K12 was compiled from Swiss-Prot, PubMed, and EcoCyc and demonstrate a functional annotation deficit in biological databases. Some issues are postulated as causes of the lack of annotation, and different solutions are evaluated and proposed to avoid them. The hope is that as a consequence of these observations, there will be new impetus to improve the speed and quality of functional annotation and ultimately provide updated, reliable information to the scientific community.

  9. Biomarkers of Aging: From Function to Molecular Biology.

    PubMed

    Wagner, Karl-Heinz; Cameron-Smith, David; Wessner, Barbara; Franzke, Bernhard

    2016-06-02

    Aging is a major risk factor for most chronic diseases and functional impairments. Within a homogeneous age sample there is a considerable variation in the extent of disease and functional impairment risk, revealing a need for valid biomarkers to aid in characterizing the complex aging processes. The identification of biomarkers is further complicated by the diversity of biological living situations, lifestyle activities and medical treatments. Thus, there has been no identification of a single biomarker or gold standard tool that can monitor successful or healthy aging. Within this short review the current knowledge of putative biomarkers is presented, focusing on their application to the major physiological mechanisms affected by the aging process including physical capability, nutritional status, body composition, endocrine and immune function. This review emphasizes molecular and DNA-based biomarkers, as well as recent advances in other biomarkers such as microRNAs, bilirubin or advanced glycation end products.

  10. Biomarkers of Aging: From Function to Molecular Biology

    PubMed Central

    Wagner, Karl-Heinz; Cameron-Smith, David; Wessner, Barbara; Franzke, Bernhard

    2016-01-01

    Aging is a major risk factor for most chronic diseases and functional impairments. Within a homogeneous age sample there is a considerable variation in the extent of disease and functional impairment risk, revealing a need for valid biomarkers to aid in characterizing the complex aging processes. The identification of biomarkers is further complicated by the diversity of biological living situations, lifestyle activities and medical treatments. Thus, there has been no identification of a single biomarker or gold standard tool that can monitor successful or healthy aging. Within this short review the current knowledge of putative biomarkers is presented, focusing on their application to the major physiological mechanisms affected by the aging process including physical capability, nutritional status, body composition, endocrine and immune function. This review emphasizes molecular and DNA-based biomarkers, as well as recent advances in other biomarkers such as microRNAs, bilirubin or advanced glycation end products. PMID:27271660

  11. A synthetic biology framework for programming eukaryotic transcription functions.

    PubMed

    Khalil, Ahmad S; Lu, Timothy K; Bashor, Caleb J; Ramirez, Cherie L; Pyenson, Nora C; Joung, J Keith; Collins, James J

    2012-08-03

    Eukaryotic transcription factors (TFs) perform complex and combinatorial functions within transcriptional networks. Here, we present a synthetic framework for systematically constructing eukaryotic transcription functions using artificial zinc fingers, modular DNA-binding domains found within many eukaryotic TFs. Utilizing this platform, we construct a library of orthogonal synthetic transcription factors (sTFs) and use these to wire synthetic transcriptional circuits in yeast. We engineer complex functions, such as tunable output strength and transcriptional cooperativity, by rationally adjusting a decomposed set of key component properties, e.g., DNA specificity, affinity, promoter design, protein-protein interactions. We show that subtle perturbations to these properties can transform an individual sTF between distinct roles (activator, cooperative factor, inhibitory factor) within a transcriptional complex, thus drastically altering the signal processing behavior of multi-input systems. This platform provides new genetic components for synthetic biology and enables bottom-up approaches to understanding the design principles of eukaryotic transcriptional complexes and networks.

  12. Systemic Modeling of Biological Functions in Consideration of Physiome Project

    NASA Astrophysics Data System (ADS)

    Minamitani, Haruyuki

    Emerging of the physiome project provides various influences on the medical, biological and pharmaceutical development. In this paper, as an example of physiome research, neural network model analysis providing the conduction mechanisms of pain and tactile sensations was presented, and the functional relations between neural activities of the network cells and stimulus intensity applied on the peripheral receptive fields were described. The modeling presented here is based on the various assumptions made by the results of physiological and anatomical studies reported in the literature. The functional activities of spinothalamic and thalamocortical cells show a good agreement with the physiological and psychophysical functions of somatosensory system that are very instructive for covering the gap between physiologically and psychophysically aspects of pain and tactile sensation.

  13. The human glucocorticoid receptor: molecular basis of biologic function.

    PubMed

    Nicolaides, Nicolas C; Galata, Zoi; Kino, Tomoshige; Chrousos, George P; Charmandari, Evangelia

    2010-01-01

    The characterization of the subfamily of steroid hormone receptors has enhanced our understanding of how a set of hormonally derived lipophilic ligands controls cellular and molecular functions to influence development and help achieve homeostasis. The glucocorticoid receptor (GR), the first member of this subfamily, is a ubiquitously expressed intracellular protein, which functions as a ligand-dependent transcription factor that regulates the expression of glucocorticoid-responsive genes. The effector domains of the GR mediate transcriptional activation by recruiting coregulatory multi-subunit complexes that remodel chromatin, target initiation sites, and stabilize the RNA-polymerase II machinery for repeated rounds of transcription of target genes. This review summarizes the basic aspects of the structure and actions of the human (h) GR, and the molecular basis of its biologic functions.

  14. The Human Glucocorticoid Receptor: Molecular Basis of Biologic Function

    PubMed Central

    Nicolaides, Nicolas C.; Galata, Zoi; Kino, Tomoshige; Chrousos, George P.; Charmandari, Evangelia

    2009-01-01

    The characterization of the subfamily of steroid hormone receptors has enhanced our understanding of how a set of hormonally derived lipophilic ligands controls cellular and molecular functions to influence development and help achieve homeostasis. The glucocorticopid receptor (GR), the first member of this subfamily, is a ubiquitously expressed intracellular protein, which functions as a ligand-dependent transcription factor that regulates the expression of glucocorticoid-responsive genes. The effector domains of the GR mediate transcriptional activation by recruiting coregulatory multi-subunit complexes that remodel chromatin, target initiation sites, and stabilize the RNA polymerase II machinery for repeated rounds of transcription of target genes. This review summarizes the basic aspects of the structure and of the human (h) GR, and the molecular basis of its biologic function. PMID:19818358

  15. Protein science by DNA sequencing: how advances in molecular biology are accelerating biochemistry.

    PubMed

    Higgins, Sean Andrew; Savage, David F

    2017-10-09

    A fundamental goal of protein biochemistry is to determine the sequence-function relationship, but the vastness of sequence space makes comprehensive evaluation of this landscape difficult. However, advances in DNA synthesis and sequencing now allow researchers to assess the functional impact of every single mutation in many proteins, but challenges remain in library construction and the development of general assays applicable to a diverse range of protein functions. This perspective briefly outlines the technical innovations in DNA manipulation which allow massively parallel protein biochemistry, then summarizes the methods currently available for library construction and the functional assays of protein variants. Areas in need of future innovation are highlighted with a particular focus on assay development and the use of computational analysis with machine learning to effectively traverse the sequence-function landscape. Finally, applications in the fundamentals of protein biochemistry, disease prediction, and protein engineering are presented.

  16. Obesity-induced oxidative stress, accelerated functional decline with age and increased mortality in mice

    PubMed Central

    Zhang, Yiqiang; Fischer, Kathleen E.; Soto, Vanessa; Liu, Yuhong; Sosnowska, Danuta; Richardson, Arlan; Salmon, Adam B.

    2015-01-01

    Obesity is a serious chronic disease that increases the risk of numerous co-morbidities including metabolic syndrome, cardiovascular disease and cancer as well as increases risk of mortality leading some to suggest this represents accelerated aging. Obesity is associated with significant increases in oxidative stress in vivo and, despite the well-explored relationship between oxidative stress and aging, the role this plays in the increased mortality of obese subjects remains an unanswered question. Here, we addressed this by undertaking a comprehensive, longitudinal study of a group of high fat-fed obese mice and assessed both their changes in oxidative stress and in their performance in physiological assays known to decline with aging. In female C57BL/6J mice fed a high-fat diet starting in adulthood, mortality was significantly increased in high fat-fed mice as was oxidative damage in vivo. High fat-feeding significantly accelerated the decline in performance in several assays, including activity, gait, and rotarod. However, we also found that obesity had little effect on other markers and actually improved performance in grip strength, a marker of muscular function. Together, this first comprehensive assessment of longitudinal functional changes in high fat-fed mice suggests that obesity may induce segmental acceleration of some of the aging process. PMID:25558793

  17. Accelerator-Based Biological Irradiation Facility Simulating Neutron Exposure from an Improvised Nuclear Device

    PubMed Central

    Xu, Yanping; Randers-Pehrson, Gerhard; Turner, Helen C.; Marino, Stephen A.; Geard, Charles R.; Brenner, David J.; Garty, Guy

    2015-01-01

    We describe here an accelerator-based neutron irradiation facility, intended to expose blood or small animals to neutron fields mimicking those from an improvised nuclear device at relevant distances from the epicenter. Neutrons are generated by a mixed proton/deuteron beam on a thick beryllium target, generating a broad spectrum of neutron energies that match those estimated for the Hiroshima bomb at 1.5 km from ground zero. This spectrum, dominated by neutron energies between 0.2 and 9 MeV, is significantly different from the standard reactor fission spectrum, as the initial bomb spectrum changes when the neutrons are transported through air. The neutron and gamma dose rates were measured using a custom tissue-equivalent gas ionization chamber and a compensated Geiger-Mueller dosimeter, respectively. Neutron spectra were evaluated by unfolding measurements using a proton-recoil proportional counter and a liquid scintillator detector. As an illustration of the potential use of this facility we present micronucleus yields in single divided, cytokinesis-blocked human peripheral lymphocytes up to 1.5 Gy demonstrating 3- to 5-fold enhancement over equivalent X-ray doses. This facility is currently in routine use, irradiating both mice and human blood samples for evaluation of neutron-specific biodosimetry assays. Future studies will focus on dose reconstruction in realistic mixed neutron/photon fields. PMID:26414507

  18. Accelerator-Based Biological Irradiation Facility Simulating Neutron Exposure from an Improvised Nuclear Device.

    PubMed

    Xu, Yanping; Randers-Pehrson, Gerhard; Turner, Helen C; Marino, Stephen A; Geard, Charles R; Brenner, David J; Garty, Guy

    2015-10-01

    We describe here an accelerator-based neutron irradiation facility, intended to expose blood or small animals to neutron fields mimicking those from an improvised nuclear device at relevant distances from the epicenter. Neutrons are generated by a mixed proton/deuteron beam on a thick beryllium target, generating a broad spectrum of neutron energies that match those estimated for the Hiroshima bomb at 1.5 km from ground zero. This spectrum, dominated by neutron energies between 0.2 and 9 MeV, is significantly different from the standard reactor fission spectrum, as the initial bomb spectrum changes when the neutrons are transported through air. The neutron and gamma dose rates were measured using a custom tissue-equivalent gas ionization chamber and a compensated Geiger-Mueller dosimeter, respectively. Neutron spectra were evaluated by unfolding measurements using a proton-recoil proportional counter and a liquid scintillator detector. As an illustration of the potential use of this facility we present micronucleus yields in single divided, cytokinesis-blocked human peripheral lymphocytes up to 1.5 Gy demonstrating 3- to 5-fold enhancement over equivalent X-ray doses. This facility is currently in routine use, irradiating both mice and human blood samples for evaluation of neutron-specific biodosimetry assays. Future studies will focus on dose reconstruction in realistic mixed neutron/photon fields.

  19. mRNA capping: biological functions and applications

    PubMed Central

    Ramanathan, Anand; Robb, G. Brett; Chan, Siu-Hong

    2016-01-01

    The 5′ m7G cap is an evolutionarily conserved modification of eukaryotic mRNA. Decades of research have established that the m7G cap serves as a unique molecular module that recruits cellular proteins and mediates cap-related biological functions such as pre-mRNA processing, nuclear export and cap-dependent protein synthesis. Only recently has the role of the cap 2′O methylation as an identifier of self RNA in the innate immune system against foreign RNA has become clear. The discovery of the cytoplasmic capping machinery suggests a novel level of control network. These new findings underscore the importance of a proper cap structure in the synthesis of functional messenger RNA. In this review, we will summarize the current knowledge of the biological roles of mRNA caps in eukaryotic cells. We will also discuss different means that viruses and their host cells use to cap their RNA and the application of these capping machineries to synthesize functional mRNA. Novel applications of RNA capping enzymes in the discovery of new RNA species and sequencing the microbiome transcriptome will also be discussed. We will end with a summary of novel findings in RNA capping and the questions these findings pose. PMID:27317694

  20. Correction of dispersion and the betatron functions in the CEBAF accelerator

    SciTech Connect

    Lebedev, V.A.; Bickley, M.; Schaffner, S.; Zeijts, J. van; Krafft, G.A.; Watson, C.

    1996-10-01

    During the commissioning of the CEBAF accelerator, correction of dispersion and momentum compaction, and, to a lesser extent, transverse transfer matrices were essential for robust operation. With changing machine conditions, repeated correction was found necessary. To speed the diagnostic process the authors developed a method which allows one to rapidly track the machine optics. The method is based on measuring the propagation of 30 Hz modulated betatron oscillations downstream of a point of perturbation. Compared to the usual methods of dispersion or difference orbit measurement, synchronous detection of the beam displacement, as measured by beam position monitors, offers significantly improved speed and accuracy of the measurements. The beam optics of the accelerator was altered to decrease lattice sensitivity at critical points and to simplify control of the betatron function match. The calculation of the Courant-Snyder invariant from signals of each pair of nearby beam position monitors has allowed one to perform on-line measurement and correction of the lattice properties.

  1. Hyaluronan: A Simple Polysaccharide with Diverse Biological Functions

    PubMed Central

    Dicker, Kevin T.; Gurski, Lisa A.; Pradhan-Bhatt, Swati; Witt, Robert L.; Farach-Carson, Mary C.; Jia, Xinqiao

    2014-01-01

    Hyaluronan (HA) is a linear polysaccharide with disaccharide repeats of D-glucuronic acid and N-acetyl-D-glucosamine. It is evolutionary conserved and abundantly expressed in the extracellular matrix (ECM), on the cell surface and even inside cells. Being a simple polysaccharide, HA exhibits an astonishing array of biological functions. HA interacts with various proteins or proteoglycans to organize the ECM and to maintain tissue homeostasis. The unique physical and mechanical properties of HA contribute to the maintenance of tissue hydration, the mediation of solute diffusion through the extracellular space and the lubrication of certain tissues. The diverse biological functions of HA are manifested through its complex interactions with matrix components and resident cells. Binding of HA with cell surface receptors activates various signaling pathways that regulate cell function, tissue development, inflammation, wound healing and tumor progression and metastasis. Taking advantage of the inherent biocompatibility and biodegradability of HA, as well as its susceptibility to chemical modification, researchers have developed various HA-based biomaterials and tissue constructs with promising and broad clinical potential. In this article, we illustrate the properties of HA from a matrix biology perspective by first introducing principles underlying the biosynthesis and biodegradation of HA, as well as the interactions of HA with various proteins and proteoglycans. We next highlight the roles of HA in physiological and pathological states, including morphogenesis, wound healing and tumor metastasis. A deeper understanding of the mechanisms underlying the roles of HA in various physiological processes can provide new insights and tools for the engineering of complex tissues and tissue models. PMID:24361428

  2. Functionalization of polydopamine coated magnetic nanoparticles with biological entities

    NASA Astrophysics Data System (ADS)

    Mǎgeruşan, Lidia; Mrówczyński, Radosław; Turcu, Rodica

    2015-12-01

    New hybrid materials, obtained through introduction of cysteine, lysine and folic acid as biological entities into polydopamine-coated magnetite nanoparticles, are reported. The syntheses are straight forward and various methods were applied for structural and morphological characterization of the resulting nanoparticles. XPS proved a very powerful tool for surface chemical analysis and it evidences the functionalization of polydopamine coated magnetite nanoparticles. The superparamagnetic behavior and the high values of saturation magnetization recommend all products for further application where magnetism is important for targeting, separation, or heating by alternative magnetic fields.

  3. Molecular dynamics study of accelerated ion-induced shock waves in biological media

    NASA Astrophysics Data System (ADS)

    de Vera, Pablo; Mason, Nigel J.; Currell, Fred J.; Solov'yov, Andrey V.

    2016-09-01

    We present a molecular dynamics study of the effects of carbon- and iron-ion induced shock waves in DNA duplexes in liquid water. We use the CHARMM force field implemented within the MBN Explorer simulation package to optimize and equilibrate DNA duplexes in liquid water boxes of different sizes and shapes. The translational and vibrational degrees of freedom of water molecules are excited according to the energy deposited by the ions and the subsequent shock waves in liquid water are simulated. The pressure waves generated are studied and compared with an analytical hydrodynamics model which serves as a benchmark for evaluating the suitability of the simulation boxes. The energy deposition in the DNA backbone bonds is also monitored as an estimation of biological damage, something which is not possible with the analytical model.

  4. Spatio-temporal radiation biology with conventionally or laser-accelerated particles for ELIMED

    NASA Astrophysics Data System (ADS)

    Ristić-Fira, A.; Bulat, T.; Keta, O.; Romano, F.; Cirrone, P.; Cuttone, G.; Petrović, I.

    2013-07-01

    The aim of this study is to investigate the behavior of radio-resistant human malignant cells, thus enabling better understanding of radiobiological effects of ions in such a case. Radiation sources such as accelerated continuous ion beams and laser technology-based ultra short radiation sources with energy of around 10 MeV will be used. The HTB140 melanoma cells are chosen since it has been shown that they represent the limit case of cellular radio-resistance among the studied tumor cell lines. These cells are particularly interesting as they provide data on the very edge of inactivation capacity of each beam line that is tested. After exposing the cell monolayers to continuous radiations of low (γ-rays) and high (protons) linear energy transfer, the kinetics of disappearance of the phosphorylated histone H2AX (γ-H2AX) foci per cell will be determined. The same procedure will be performed with the pulsed high dose rate protons. Detection and quantification of γ-H2AX foci will be performed by immunohistochemical 3D time-dependent imaging analyses using laser scanning confocal microscopy. Immunoblotting will enable the follow-up of the relation between γ-H2AX and cell cycle arrest via the p53/p21 pathway. In such a way the spatio-temporal changes on sub-cellular level will be visualized, quantified and compared. These results will show whether there is a difference in the effects on cells between continuous and pulsed irradiation mode. Therefore, they will contribute to the data base that might promote pulsed sources for medical treatments of malignant growths.

  5. Spatio-temporal radiation biology with conventionally or laser-accelerated particles for ELIMED

    SciTech Connect

    Ristić-Fira, A.; Bulat, T.; Keta, O.; Petrović, I.; Romano, F.; Cirrone, P.; Cuttone, G.

    2013-07-26

    The aim of this study is to investigate the behavior of radio-resistant human malignant cells, thus enabling better understanding of radiobiological effects of ions in such a case. Radiation sources such as accelerated continuous ion beams and laser technology-based ultra short radiation sources with energy of around 10 MeV will be used. The HTB140 melanoma cells are chosen since it has been shown that they represent the limit case of cellular radio-resistance among the studied tumor cell lines. These cells are particularly interesting as they provide data on the very edge of inactivation capacity of each beam line that is tested. After exposing the cell monolayers to continuous radiations of low (γ-rays) and high (protons) linear energy transfer, the kinetics of disappearance of the phosphorylated histone H2AX (γ-H2AX) foci per cell will be determined. The same procedure will be performed with the pulsed high dose rate protons. Detection and quantification of γ-H2AX foci will be performed by immunohistochemical 3D time-dependent imaging analyses using laser scanning confocal microscopy. Immunoblotting will enable the follow-up of the relation between γ-H2AX and cell cycle arrest via the p53/p21 pathway. In such a way the spatio-temporal changes on sub-cellular level will be visualized, quantified and compared. These results will show whether there is a difference in the effects on cells between continuous and pulsed irradiation mode. Therefore, they will contribute to the data base that might promote pulsed sources for medical treatments of malignant growths.

  6. Biological soil crusts accelerate the nitrogen cycle through large NO and HONO emissions in drylands

    PubMed Central

    Wu, Dianming; Tamm, Alexandra; Ruckteschler, Nina; Rodríguez-Caballero, Emilio; Meusel, Hannah; Elbert, Wolfgang; Behrendt, Thomas; Sörgel, Matthias; Cheng, Yafang; Crutzen, Paul J.; Su, Hang; Pöschl, Ulrich

    2015-01-01

    Reactive nitrogen species have a strong influence on atmospheric chemistry and climate, tightly coupling the Earth’s nitrogen cycle with microbial activity in the biosphere. Their sources, however, are not well constrained, especially in dryland regions accounting for a major fraction of the global land surface. Here, we show that biological soil crusts (biocrusts) are emitters of nitric oxide (NO) and nitrous acid (HONO). Largest fluxes are obtained by dark cyanobacteria-dominated biocrusts, being ∼20 times higher than those of neighboring uncrusted soils. Based on laboratory, field, and satellite measurement data, we obtain a best estimate of ∼1.7 Tg per year for the global emission of reactive nitrogen from biocrusts (1.1 Tg a−1 of NO-N and 0.6 Tg a−1 of HONO-N), corresponding to ∼20% of global nitrogen oxide emissions from soils under natural vegetation. On continental scales, emissions are highest in Africa and South America and lowest in Europe. Our results suggest that dryland emissions of reactive nitrogen are largely driven by biocrusts rather than the underlying soil. They help to explain enigmatic discrepancies between measurement and modeling approaches of global reactive nitrogen emissions. As the emissions of biocrusts strongly depend on precipitation events, climate change affecting the distribution and frequency of precipitation may have a strong impact on terrestrial emissions of reactive nitrogen and related climate feedback effects. Because biocrusts also account for a large fraction of global terrestrial biological nitrogen fixation, their impacts should be further quantified and included in regional and global models of air chemistry, biogeochemistry, and climate. PMID:26621714

  7. Relative biological effectiveness in canine osteosarcoma cells irradiated with accelerated charged particles

    PubMed Central

    Maeda, Junko; Cartwright, Ian M.; Haskins, Jeremy S.; Fujii, Yoshihiro; Fujisawa, Hiroshi; Hirakawa, Hirokazu; Uesaka, Mitsuru; Kitamura, Hisashi; Fujimori, Akira; Thamm, Douglas H.; Kato, Takamitsu A.

    2016-01-01

    Heavy ions, characterized by high linear energy transfer (LET) radiation, have advantages compared with low LET protons and photons in their biological effects. The application of heavy ions within veterinary clinics requires additional background information to determine heavy ion efficacy. In the present study, comparison of the cell-killing effects of photons, protons and heavy ions was investigated in canine osteosarcoma (OSA) cells in vitro. A total of four canine OSA cell lines with various radiosensitivities were irradiated with 137Cs gamma-rays, monoenergetic proton beams, 50 keV/µm carbon ion spread out Bragg peak beams and 200 keV/µm iron ion monoenergetic beams. Clonogenic survival was examined using colony-forming as says, and relative biological effectiveness (RBE) values were calculated relative to gamma-rays using the D10 value, which is determined as the dose (Gy) resulting in 10% survival. For proton irradiation, the RBE values for all four cell lines were 1.0–1.1. For all four cell lines, exposure to carbon ions yielded a decreased cell survival compared with gamma-rays, with the RBE values ranging from 1.56–2.10. Iron ions yielded the lowest cell survival among tested radiation types, with RBE values ranging from 3.51–3.69 observed in the three radioresistant cell lines. The radiosensitive cell line investigated demonstrated similar cell survival for carbon and iron ion irradiation. The results of the present study suggest that heavy ions are more effective for killing radioresistant canine OSA cells when compared with gamma-rays and protons. This markedly increased efficiency of cell killing is an attractive reason for utilizing heavy ions for radioresistant canine OSA. PMID:27446477

  8. Leukocyte Telomere Length in Young Adults Born Preterm: Support for Accelerated Biological Ageing

    PubMed Central

    Smeets, Carolina C. J.; Codd, Veryan; Samani, Nilesh J.; Hokken-Koelega, Anita C. S.

    2015-01-01

    Background Subjects born preterm have an increased risk for age-associated diseases, such as cardiovascular disease in later life, but the underlying causes are largely unknown. Shorter leukocyte telomere length (LTL), a marker of biological age, is associated with increased risk of cardiovascular disease. Objectives To compare LTL between subjects born preterm and at term and to assess if LTL is associated with other putative cardiovascular risk factors at young adult age. Methods We measured mean LTL in 470 young adults. LTL was measured using a quantitative PCR assay and expressed as T/S ratio. We analyzed the influence of gestational age on LTL and compared LTL between subjects born preterm (n = 186) and at term (n = 284). Additionally, we analyzed the correlation between LTL and potential risk factors of cardiovascular disease. Results Gestational age was positively associated with LTL (r = 0.11, p = 0.02). Subjects born preterm had shorter LTL (mean (SD) T/S ratio = 3.12 (0.44)) than subjects born at term (mean (SD) T/S ratio = 3.25 (0.46)), p = 0.003). The difference remained significant after adjustment for gender and size at birth (p = 0.001). There was no association of LTL with any one of the putative risk factors analyzed. Conclusions Young adults born preterm have shorter LTL than young adults born at term. Although we found no correlation between LTL and risk for CVD at this young adult age, this biological ageing indicator may contribute to CVD and other adult onset diseases at a later age in those born preterm. PMID:26619005

  9. Biological soil crusts accelerate the nitrogen cycle through large NO and HONO emissions in drylands.

    PubMed

    Weber, Bettina; Wu, Dianming; Tamm, Alexandra; Ruckteschler, Nina; Rodríguez-Caballero, Emilio; Steinkamp, Jörg; Meusel, Hannah; Elbert, Wolfgang; Behrendt, Thomas; Sörgel, Matthias; Cheng, Yafang; Crutzen, Paul J; Su, Hang; Pöschl, Ulrich

    2015-12-15

    Reactive nitrogen species have a strong influence on atmospheric chemistry and climate, tightly coupling the Earth's nitrogen cycle with microbial activity in the biosphere. Their sources, however, are not well constrained, especially in dryland regions accounting for a major fraction of the global land surface. Here, we show that biological soil crusts (biocrusts) are emitters of nitric oxide (NO) and nitrous acid (HONO). Largest fluxes are obtained by dark cyanobacteria-dominated biocrusts, being ∼20 times higher than those of neighboring uncrusted soils. Based on laboratory, field, and satellite measurement data, we obtain a best estimate of ∼1.7 Tg per year for the global emission of reactive nitrogen from biocrusts (1.1 Tg a(-1) of NO-N and 0.6 Tg a(-1) of HONO-N), corresponding to ∼20% of global nitrogen oxide emissions from soils under natural vegetation. On continental scales, emissions are highest in Africa and South America and lowest in Europe. Our results suggest that dryland emissions of reactive nitrogen are largely driven by biocrusts rather than the underlying soil. They help to explain enigmatic discrepancies between measurement and modeling approaches of global reactive nitrogen emissions. As the emissions of biocrusts strongly depend on precipitation events, climate change affecting the distribution and frequency of precipitation may have a strong impact on terrestrial emissions of reactive nitrogen and related climate feedback effects. Because biocrusts also account for a large fraction of global terrestrial biological nitrogen fixation, their impacts should be further quantified and included in regional and global models of air chemistry, biogeochemistry, and climate.

  10. Biological degradation and microbial function effect of norfloxacin in a soil under different conditions.

    PubMed

    Yang, Ji-Feng; Ying, Guang-Guo; Liu, Shan; Zhou, Li-Jun; Zhao, Jian-Liang; Tao, Ran; Peng, Ping-An

    2012-01-01

    This paper investigated the degradation kinetics of norfloxacin in a soil, and its effects on soil respiration and nitrogen transformation under different conditions. Compared to the sterile control, the degradation rates of norfloxacin in the non-sterile soil were greatly enhanced, suggesting that microorganisms played a major role in the degradation. Accelerated degradation for norfloxacin in the soil was observed with decreasing concentrations (30 mg/kg to 5 mg/kg) with its half-life decreasing from 62 days to 31 days. Amending swine manure into the soil and increasing the soil moisture level enhanced the biological degradation of norfloxacin. No obvious inhibition of norfloxacin on soil respiration was observed in the soil, while only slight effect on nitrogen transformation was found. The results suggested that norfloxacin at the reported environmental concentrations (<100 mg/kg) would have little effect on microbial activity and functions in the soils.

  11. MicroRNAs in clear cell renal cell carcinoma: biological functions and applications

    PubMed Central

    2015-01-01

    MicroRNAs (miRs) are small noncoding RNAs that govern many biological processes. They frequently acquire a gain or a loss of function in cancer and hence play a causative role in the development and progression of neoplasms. They could be used as biomarkers to improve our knowledge on diagnosis, prognosis and drug resistance, and to attempt therapeutic approaches in several types of cancer including clear cell renal cell carcinoma (ccRCC). ccRCC is the most predominant subtype of RCC that accounts for about 90% of all renal cancers. Since ccRCC is generally asymptomatic until very late, it is difficult to diagnose early. Moreover, in the absence of preventive treatments for metastatic ccRCC after surgical resection of the primary cancer, predictive prognostic biomarkers are needed in order to achieve appropriate therapies. Herein the role of miRs in the biology of ccRCC and the potential applications of these molecules are discussed. Moreover, future applications in the diagnostic and prognostic field, as well as their impact on drug response and therapeutic targets are also explored. Their use in clinical practice as molecular biomarkers alone, or in combination with other biological markers could accelerate progress, help design personalized therapies, limit side effects, and improve quality of life of ccRCC patients.

  12. Effect of accelerated rehabilitation on function after ankle sprain: randomised controlled trial.

    PubMed

    Bleakley, Chris M; O'Connor, Seán R; Tully, Mark A; Rocke, Laurence G; Macauley, Domhnall C; Bradbury, Ian; Keegan, Stephen; McDonough, Suzanne M

    2010-05-10

    To compare an accelerated intervention incorporating early therapeutic exercise after acute ankle sprains with a standard protection, rest, ice, compression, and elevation intervention. Randomised controlled trial with blinded outcome assessor. Accident and emergency department and university based sports injury clinic. 101 patients with an acute grade 1 or 2 ankle sprain. Participants were randomised to an accelerated intervention with early therapeutic exercise (exercise group) or a standard protection, rest, ice, compression, and elevation intervention (standard group). The primary outcome was subjective ankle function (lower extremity functional scale). Secondary outcomes were pain at rest and on activity, swelling, and physical activity at baseline and at one, two, three, and four weeks after injury. Ankle function and rate of reinjury were assessed at 16 weeks. An overall treatment effect was in favour of the exercise group (P=0.0077); this was significant at both week 1 (baseline adjusted difference in treatment 5.28, 98.75% confidence interval 0.31 to 10.26; P=0.008) and week 2 (4.92, 0.27 to 9.57; P=0.0083). Activity level was significantly higher in the exercise group as measured by time spent walking (1.2 hours, 95% confidence interval 0.9 to 1.4 v 1.6, 1.3 to 1.9), step count (5621 steps, 95% confidence interval 4399 to 6843 v 7886, 6357 to 9416), and time spent in light intensity activity (53 minutes, 95% confidence interval 44 to 60 v 76, 58 to 95). The groups did not differ at any other time point for pain at rest, pain on activity, or swelling. The reinjury rate was 4% (two in each group). An accelerated exercise protocol during the first week after ankle sprain improved ankle function; the group receiving this intervention was more active during that week than the group receiving standard care. Current Controlled Trials ISRCTN13903946.

  13. Biological Effects of Particles with Very High Energy Deposition on Mammalian Cells Utilizing the Brookhaven Tandem Van de Graaff Accelerator

    NASA Technical Reports Server (NTRS)

    Saha, Janapriya; Cucinotta, Francis A.; Wang, Minli

    2013-01-01

    High LET radiation from GCR (Galactic Cosmic Rays) consisting mainly of high charge and energy (HZE) nuclei and secondary protons and neutrons, and secondaries from protons in SPE (Solar Particle Event) pose a major health risk to astronauts due to induction of DNA damage and oxidative stress. Experiments with high energy particles mimicking the space environment for estimation of radiation risk are being performed at NASA Space Radiation Laboratory at BNL. Experiments with low energy particles comparing to high energy particles of similar LET are of interest for investigation of the role of track structure on biological effects. For this purpose, we report results utilizing the Tandem Van de Graaff accelerator at BNL. The primary objective of our studies is to elucidate the influence of high vs low energy deposition on track structure, delta ray contribution and resulting biological responses. These low energy ions are of special relevance as these energies may occur following absorption through the spacecraft and shielding materials in human tissues and nuclear fragments produced in tissues by high energy protons and neutrons. This study will help to verify the efficiency of these low energy particles and better understand how various cell types respond to them.

  14. Structure, function, and behaviour of computational models in systems biology

    PubMed Central

    2013-01-01

    Background Systems Biology develops computational models in order to understand biological phenomena. The increasing number and complexity of such “bio-models” necessitate computer support for the overall modelling task. Computer-aided modelling has to be based on a formal semantic description of bio-models. But, even if computational bio-models themselves are represented precisely in terms of mathematical expressions their full meaning is not yet formally specified and only described in natural language. Results We present a conceptual framework – the meaning facets – which can be used to rigorously specify the semantics of bio-models. A bio-model has a dual interpretation: On the one hand it is a mathematical expression which can be used in computational simulations (intrinsic meaning). On the other hand the model is related to the biological reality (extrinsic meaning). We show that in both cases this interpretation should be performed from three perspectives: the meaning of the model’s components (structure), the meaning of the model’s intended use (function), and the meaning of the model’s dynamics (behaviour). In order to demonstrate the strengths of the meaning facets framework we apply it to two semantically related models of the cell cycle. Thereby, we make use of existing approaches for computer representation of bio-models as much as possible and sketch the missing pieces. Conclusions The meaning facets framework provides a systematic in-depth approach to the semantics of bio-models. It can serve two important purposes: First, it specifies and structures the information which biologists have to take into account if they build, use and exchange models. Secondly, because it can be formalised, the framework is a solid foundation for any sort of computer support in bio-modelling. The proposed conceptual framework establishes a new methodology for modelling in Systems Biology and constitutes a basis for computer-aided collaborative research

  15. Functions of MicroRNAs in Cardiovascular Biology and Disease

    PubMed Central

    Hata, Akiko

    2015-01-01

    In 1993, lin-4 was discovered as a critical modulator of temporal development in Caenorhabditis elegans and, most notably, as the first in the class of small, single-stranded noncoding RNAs now defined as microRNAs (miRNAs). Another eight years elapsed before miRNA expression was detected in mammalian cells. Since then, explosive advancements in the field of miRNA biology have elucidated the basic mechanism of miRNA biogenesis, regulation, and gene-regulatory function. The discovery of this new class of small RNAs has augmented the complexity of gene-regulatory programs as well as the understanding of developmental and pathological processes in the cardiovascular system. Indeed, the contributions of miRNAs in cardiovascular development and function have been widely explored, revealing the extensive role of these small regulatory RNAs in cardiovascular physiology. PMID:23157557

  16. Diffusion of innovations dynamics, biological growth and catenary function

    NASA Astrophysics Data System (ADS)

    Guseo, Renato

    2016-12-01

    The catenary function has a well-known role in determining the shape of chains and cables supported at their ends under the force of gravity. This enables design using a specific static equilibrium over space. Its reflected version, the catenary arch, allows the construction of bridges and arches exploiting the dual equilibrium property under uniform compression. In this paper, we emphasize a further connection with well-known aggregate biological growth models over time and the related diffusion of innovation key paradigms (e.g., logistic and Bass distributions over time) that determine self-sustaining evolutionary growth dynamics in naturalistic and socio-economic contexts. Moreover, we prove that the 'local entropy function', related to a logistic distribution, is a catenary and vice versa. This special invariance may be explained, at a deeper level, through the Verlinde's conjecture on the origin of gravity as an effect of the entropic force.

  17. The biology and functions of Th22 cells.

    PubMed

    Jia, Lei; Wu, Changyou

    2014-01-01

    T helper (Th) cells develop from naïve CD4(+) T cells under lineage-specific culture conditions and are nominated by their lineage-specific cytokines. Th22 cells, new players in adoptive immune responses, are identified by the production of interleukin (IL)-22. Plenty of observations are obtained over the past few years indicating that IL-22 is produced by activated T cells including Th22 cells, Th17 cells, Th1 cells, innate lymphoid cells and some nonlymphocytes. IL-22 functions synergistically with IL-17 or tumor necrosis factor (TNF), however, it plays different roles by IL-22/IL-22 receptor signal transductions in pathologic processes, including inflammations, autoimmunity, tumor, and digestive organs damages. In this chapter, we focus on the biology of IL-22, the generation and regulation of Th22 cells, the possible signal pathways that involved in the functions of Th22 cells, as well as the relationship between Th22 cells and various diseases.

  18. STAT6: its role in interleukin 4-mediated biological functions.

    PubMed

    Takeda, K; Kishimoto, T; Akira, S

    1997-05-01

    Interleukin (IL) 4 is known to be a cytokine which plays a central role in the regulation of immune response. Studies on cytokine signal transduction have clarified the mechanism by which IL4 exerts its functions. Two cytoplasmic proteins, signal transducer and activator of transcription (STAT) 6 and IL4-induced phosphotyrosine substrate/insulin receptor substrate 2 (4PS/IRS2), are activated in IL4 signal transduction. Recent studies from STAT6-deficient mice have revealed the essential role of STAT6 in IL4-mediated biological actions. In addition, STAT6 has also been demonstrated to be important for the functions mediated by IL13, which is related to IL4. IL4 and IL13 have been shown to induce the production of IgE, which is a major mediator in an allergic response. These findings indicate that STAT6 activation is involved in IL4- and IL13-mediated disorders such as allergy.

  19. Dynamics of Boolean networks controlled by biologically meaningful functions.

    PubMed

    Raeymaekers, L

    2002-10-07

    The remarkably stable dynamics displayed by randomly constructed Boolean networks is one of the most striking examples of the spontaneous emergence of self-organization in model systems composed of many interacting elements (Kauffman, S., J. theor. Biol.22, 437-467, 1969; The Origins of Order, Oxford University Press, Oxford, 1993). The dynamics of such networks is most stable for a connectivity of two inputs per element, and decreases dramatically with increasing number of connections. Whereas the simplicity of this model system allows the tracing of the dynamical trajectories, it leaves out many features of real biological connections. For instance, the dynamics has been studied in detail only for networks constructed by allowing all theoretically possible Boolean rules, whereas only a subset of them make sense in the material world. This paper analyses the effect on the dynamics of using only Boolean functions which are meaningful in a biological sense. This analysis is particularly relevant for nets with more than two inputs per element because biological networks generally appear to be more extensively interconnected. Sets of the meaningful functions were assembled for up to four inputs per element. The use of these rules results in a smaller number of distinct attractors which have a shorter length, with relatively little sensitivity to the size of the network and to the number of inputs per element. Forcing away the activator/inhibitor ratio from the expected value of 50% further enhances the stability. This effect is more pronounced for networks consisting of a majority of activators than for networks with a corresponding majority of inhibitors, indicating that the former allow the evolution of larger genetic networks. The data further support the idea of the usefulness of logical networks as a conceptual framework for the understanding of real-world phenomena.

  20. Event-based text mining for biology and functional genomics

    PubMed Central

    Thompson, Paul; Nawaz, Raheel; McNaught, John; Kell, Douglas B.

    2015-01-01

    The assessment of genome function requires a mapping between genome-derived entities and biochemical reactions, and the biomedical literature represents a rich source of information about reactions between biological components. However, the increasingly rapid growth in the volume of literature provides both a challenge and an opportunity for researchers to isolate information about reactions of interest in a timely and efficient manner. In response, recent text mining research in the biology domain has been largely focused on the identification and extraction of ‘events’, i.e. categorised, structured representations of relationships between biochemical entities, from the literature. Functional genomics analyses necessarily encompass events as so defined. Automatic event extraction systems facilitate the development of sophisticated semantic search applications, allowing researchers to formulate structured queries over extracted events, so as to specify the exact types of reactions to be retrieved. This article provides an overview of recent research into event extraction. We cover annotated corpora on which systems are trained, systems that achieve state-of-the-art performance and details of the community shared tasks that have been instrumental in increasing the quality, coverage and scalability of recent systems. Finally, several concrete applications of event extraction are covered, together with emerging directions of research. PMID:24907365

  1. Fluorochrome-functionalized nanoparticles for imaging DNA in biological systems.

    PubMed

    Cho, Hoonsung; Alcantara, David; Yuan, Hushan; Sheth, Rahul A; Chen, Howard H; Huang, Peng; Andersson, Sean B; Sosnovik, David E; Mahmood, Umar; Josephson, Lee

    2013-03-26

    Attaching DNA binding fluorochromes to nanoparticles (NPs) provides a way of obtaining NPs that bind to DNA through fluorochrome mediated interactions. To obtain a nanoparticle (NP) that bound to the DNA in biological systems, we attached the DNA binding fluorochrome, TO-PRO 1 (TO), to the surface of the Feraheme (FH) NP, to obtain a fluorochrome-functionalized NP denoted TO-FH. When reacted with DNA in vitro, TO-FH formed microaggregates that were characterized by fluorescence, light scattering, and T2 changes. The formation of DNA/TO-FH microaggregates was also characterized by AFM, with microaggregates exhibiting a median size of 200 nm, and consisting of DNA and multiple TO-FH NPs whose individual diameters were only 25-35 nm. TO-FH failed to bind normal cells in culture, but treatment with chemotherapeutic agents or detergents yielded necrotic cells that bound TO-FH and vital fluorochromes similarly. The uptake of TO-FH by HT-29 xenografts (treated with 5-FU and oxaliplatin) was evident by surface fluorescence and MRI. Attaching multiple DNA binding fluorochromes to magnetic nanoparticles provides a way of generating DNA binding NPs that can be used to detect DNA detection by microaggregate formation in vitro, for imaging the DNA of necrotic cells in culture, and for imaging the DNA of a tumor treated with a chemotherapeutic agent. Fluorochrome functionalized NPs are a multimodal (magnetic and fluorescent), highly multivalent (n ≈ 10 fluorochromes/NP) nanomaterials useful for imaging the DNA of biological systems.

  2. Sucrose metabolism gene families and their biological functions.

    PubMed

    Jiang, Shu-Ye; Chi, Yun-Hua; Wang, Ji-Zhou; Zhou, Jun-Xia; Cheng, Yan-Song; Zhang, Bao-Lan; Ma, Ali; Vanitha, Jeevanandam; Ramachandran, Srinivasan

    2015-11-30

    Sucrose, as the main product of photosynthesis, plays crucial roles in plant development. Although studies on general metabolism pathway were well documented, less information is available on the genome-wide identification of these genes, their expansion and evolutionary history as well as their biological functions. We focused on four sucrose metabolism related gene families including sucrose synthase, sucrose phosphate synthase, sucrose phosphate phosphatase and UDP-glucose pyrophosphorylase. These gene families exhibited different expansion and evolutionary history as their host genomes experienced differentiated rates of the whole genome duplication, tandem and segmental duplication, or mobile element mediated gene gain and loss. They were evolutionarily conserved under purifying selection among species and expression divergence played important roles for gene survival after expansion. However, we have detected recent positive selection during intra-species divergence. Overexpression of 15 sorghum genes in Arabidopsis revealed their roles in biomass accumulation, flowering time control, seed germination and response to high salinity and sugar stresses. Our studies uncovered the molecular mechanisms of gene expansion and evolution and also provided new insight into the role of positive selection in intra-species divergence. Overexpression data revealed novel biological functions of these genes in flowering time control and seed germination under normal and stress conditions.

  3. Sucrose metabolism gene families and their biological functions

    PubMed Central

    Jiang, Shu-Ye; Chi, Yun-Hua; Wang, Ji-Zhou; Zhou, Jun-Xia; Cheng, Yan-Song; Zhang, Bao-Lan; Ma, Ali; Vanitha, Jeevanandam; Ramachandran, Srinivasan

    2015-01-01

    Sucrose, as the main product of photosynthesis, plays crucial roles in plant development. Although studies on general metabolism pathway were well documented, less information is available on the genome-wide identification of these genes, their expansion and evolutionary history as well as their biological functions. We focused on four sucrose metabolism related gene families including sucrose synthase, sucrose phosphate synthase, sucrose phosphate phosphatase and UDP-glucose pyrophosphorylase. These gene families exhibited different expansion and evolutionary history as their host genomes experienced differentiated rates of the whole genome duplication, tandem and segmental duplication, or mobile element mediated gene gain and loss. They were evolutionarily conserved under purifying selection among species and expression divergence played important roles for gene survival after expansion. However, we have detected recent positive selection during intra-species divergence. Overexpression of 15 sorghum genes in Arabidopsis revealed their roles in biomass accumulation, flowering time control, seed germination and response to high salinity and sugar stresses. Our studies uncovered the molecular mechanisms of gene expansion and evolution and also provided new insight into the role of positive selection in intra-species divergence. Overexpression data revealed novel biological functions of these genes in flowering time control and seed germination under normal and stress conditions. PMID:26616172

  4. [Histidine triad protein superfamily--biological function and enzymatic activity].

    PubMed

    Krakowiak, Agnieszka; Fryc, Izabela

    2012-01-01

    The HIT superfamily consists of proteins that share the histidine triad motif, His-X-His-X-His-X-X (where X is a hydrophobic amino acid), which constitutes enzymatic catalytic center. These enzymes act as nucleotidylyl hydrolase or transferase, and the mutation of the second histidine in the triad abolishes their activity. HIT proteins were found ubiquitous in all organisms and they were classified into 5 branches, which are represented by human proteins: HINT1, FHIT, Aprataxin, GALT and DCPS. Because HINT1 orthologs, which belong to the evolutionally oldest family branch, were found from prokaryotes to eukaryotes, it is clear that HIT motif was conserved during the evolution what means that the enzymatic activity is necessary for functions of these proteins. However, in few cases, e.g. HINT1 and FHIT, the connection between the biological function and the enzymatic activity is still obscure. In this review, the relations between biology and activity for 7 HIT proteins, which were found in human, are highlighted.

  5. KEK digital accelerator

    NASA Astrophysics Data System (ADS)

    Iwashita, T.; Adachi, T.; Takayama, K.; Leo, K. W.; Arai, T.; Arakida, Y.; Hashimoto, M.; Kadokura, E.; Kawai, M.; Kawakubo, T.; Kubo, Tomio; Koyama, K.; Nakanishi, H.; Okazaki, K.; Okamura, K.; Someya, H.; Takagi, A.; Tokuchi, A.; Wake, M.

    2011-07-01

    The High Energy Accelerator Research Organization KEK digital accelerator (KEK-DA) is a renovation of the KEK 500 MeV booster proton synchrotron, which was shut down in 2006. The existing 40 MeV drift tube linac and rf cavities have been replaced by an electron cyclotron resonance (ECR) ion source embedded in a 200 kV high-voltage terminal and induction acceleration cells, respectively. A DA is, in principle, capable of accelerating any species of ion in all possible charge states. The KEK-DA is characterized by specific accelerator components such as a permanent magnet X-band ECR ion source, a low-energy transport line, an electrostatic injection kicker, an extraction septum magnet operated in air, combined-function main magnets, and an induction acceleration system. The induction acceleration method, integrating modern pulse power technology and state-of-art digital control, is crucial for the rapid-cycle KEK-DA. The key issues of beam dynamics associated with low-energy injection of heavy ions are beam loss caused by electron capture and stripping as results of the interaction with residual gas molecules and the closed orbit distortion resulting from relatively high remanent fields in the bending magnets. Attractive applications of this accelerator in materials and biological sciences are discussed.

  6. Investigation of the effect of high +Gz accelerations on human cardiac function.

    PubMed

    Jamshidi, M; Ahmadian, M T

    2013-11-01

    This study investigates the effect of body acceleration on human cardiac function. Finite element analysis is conducted to simulate geometrical and mechanical properties of human heart. Heart geometrical modeling in three-dimension is performed by segmentation of cardiac MRI images. The nonlinear mechanical behavior of myocardium is modeled by Mooney-Rivlin, Polynomial, Ogden and Yeoh hyperelastic material models. Stress-strain curves of myocardial tissue are obtained from experimental compression tests on bovine heart samples. The experimental results are employed for the evaluation of material coefficients by the nonlinear least squares method. Among hyperelastic models, the Yeoh model presents the best fit with experimental stress-strain curve and is used for finite element simulation of heart tissue. Obtained material coefficients are implemented into the constructed heart model and nonlinear finite element analysis is performed for different levels of acceleration in upward direction of vertical axis of body during the rapid filling phase of cardiac cycle. Based on the finite element analysis, ventricular volume change, stress and deformation of heart model are evaluated. It is revealed that when the body is subjected to high accelerations, structural changes in the heart reduce blood supply to body up to 7.2% at +6G. © 2013 Elsevier Ltd. All rights reserved.

  7. From old organisms to new molecules: integrative biology and therapeutic targets in accelerated human ageing.

    PubMed

    Cox, L S; Faragher, R G A

    2007-10-01

    Understanding the basic biology of human ageing is a key milestone in attempting to ameliorate the deleterious consequences of old age. This is an urgent research priority given the global demographic shift towards an ageing population. Although some molecular pathways that have been proposed to contribute to ageing have been discovered using classical biochemistry and genetics, the complex, polygenic and stochastic nature of ageing is such that the process as a whole is not immediately amenable to biochemical analysis. Thus, attempts have been made to elucidate the causes of monogenic progeroid disorders that recapitulate some, if not all, features of normal ageing in the hope that this may contribute to our understanding of normal human ageing. Two canonical progeroid disorders are Werner's syndrome and Hutchinson-Gilford progeroid syndrome (also known as progeria). Because such disorders are essentially phenocopies of ageing, rather than ageing itself, advances made in understanding their pathogenesis must always be contextualised within theories proposed to help explain how the normal process operates. One such possible ageing mechanism is described by the cell senescence hypothesis of ageing. Here, we discuss this hypothesis and demonstrate that it provides a plausible explanation for many of the ageing phenotypes seen in Werner's syndrome and Hutchinson-Gilford progeriod syndrome. The recent exciting advances made in potential therapies for these two syndromes are also reviewed.

  8. Machine learning in computational biology to accelerate high-throughput protein expression.

    PubMed

    Sastry, Anand; Monk, Jonathan; Tegel, Hanna; Uhlen, Mathias; Palsson, Bernhard O; Rockberg, Johan; Brunk, Elizabeth

    2017-08-15

    The Human Protein Atlas (HPA) enables the simultaneous characterization of thousands of proteins across various tissues to pinpoint their spatial location in the human body. This has been achieved through transcriptomics and high-throughput immunohistochemistry-based approaches, where over 40 000 unique human protein fragments have been expressed in E. coli. These datasets enable quantitative tracking of entire cellular proteomes and present new avenues for understanding molecular-level properties influencing expression and solubility. Combining computational biology and machine learning identifies protein properties that hinder the HPA high-throughput antibody production pipeline. We predict protein expression and solubility with accuracies of 70% and 80%, respectively, based on a subset of key properties (aromaticity, hydropathy and isoelectric point). We guide the selection of protein fragments based on these characteristics to optimize high-throughput experimentation. We present the machine learning workflow as a series of IPython notebooks hosted on GitHub (https://github.com/SBRG/Protein_ML). The workflow can be used as a template for analysis of further expression and solubility datasets. ebrunk@ucsd.edu or johanr@biotech.kth.se. Supplementary data are available at Bioinformatics online.

  9. Functional imaging of murine hearts using accelerated self-gated UTE cine MRI.

    PubMed

    Motaal, Abdallah G; Noorman, Nils; de Graaf, Wolter L; Hoerr, Verena; Florack, Luc M J; Nicolay, Klaas; Strijkers, Gustav J

    2015-01-01

    We introduce a fast protocol for ultra-short echo time (UTE) Cine magnetic resonance imaging (MRI) of the beating murine heart. The sequence involves a self-gated UTE with golden-angle radial acquisition and compressed sensing reconstruction. The self-gated acquisition is performed asynchronously with the heartbeat, resulting in a randomly undersampled kt-space that facilitates compressed sensing reconstruction. The sequence was tested in 4 healthy rats and 4 rats with chronic myocardial infarction, approximately 2 months after surgery. As a control, a non-accelerated self-gated multi-slice FLASH sequence with an echo time (TE) of 2.76 ms, 4.5 signal averages, a matrix of 192 × 192, and an acquisition time of 2 min 34 s per slice was used to obtain Cine MRI with 15 frames per heartbeat. Non-accelerated UTE MRI was performed with TE = 0.29 ms, a reconstruction matrix of 192 × 192, and an acquisition time of 3 min 47 s per slice for 3.5 averages. Accelerated imaging with 2×, 4× and 5× undersampled kt-space data was performed with 1 min, 30 and 15 s acquisitions, respectively. UTE Cine images up to 5× undersampled kt-space data could be successfully reconstructed using a compressed sensing algorithm. In contrast to the FLASH Cine images, flow artifacts in the UTE images were nearly absent due to the short echo time, simplifying segmentation of the left ventricular (LV) lumen. LV functional parameters derived from the control and the accelerated Cine movies were statistically identical.

  10. Epidermal growth factor and erythropoietin infusion accelerate functional recovery in combination with rehabilitation.

    PubMed

    Jeffers, Matthew S; Hoyles, Amy; Morshead, Cindi; Corbett, Dale

    2014-06-01

    Rehabilitation is the only treatment option for chronic stroke deficits, but unfortunately, it often provides incomplete recovery. In this study, a novel combination of growth factor administration and rehabilitation therapy was used to facilitate functional recovery in a rat model of cortical stroke. Ischemia was induced via injection of endothelin-1 into the sensorimotor cortex. This was followed by either a 2-week infusion of epidermal growth factor and erythropoietin or artificial cerebrospinal fluid into the ipsilateral lateral ventricle. Two weeks after ischemia, animals began an 8-week enriched rehabilitation program. Functional recovery was assessed after ischemia using the Montoya staircase-reaching task, beam-traversing, and cylinder test of forelimb asymmetry. The combination of growth factor infusion and rehabilitation led to a significant acceleration in recovery in the staircase task. When compared with controls, animals receiving the combination treatment attained significant recovery of function at 4 weeks after stroke, whereas those receiving rehabilitation alone did not recover until 10 weeks. Significant recovery was also observed on the beam-traversing and cylinder tasks. Combining behavioral rehabilitation with growth factor infusion accelerates motor recovery. These data suggest a promising new avenue of combination therapies that may have the potential to reduce the rehabilitation time necessary to recover from sensorimotor deficits arising from stroke. © 2014 American Heart Association, Inc.

  11. Ground Test of the Urine Processing Assembly for Accelerations and Transfer Functions

    NASA Technical Reports Server (NTRS)

    Houston, Janice; Almond, Deborah F. (Technical Monitor)

    2001-01-01

    This viewgraph presentation gives an overview of the ground test of the urine processing assembly for accelerations and transfer functions. Details are given on the test setup, test data, data analysis, analytical results, and microgravity assessment. The conclusions of the tests include the following: (1) the single input/multiple output method is useful if the data is acquired by tri-axial accelerometers and inputs can be considered uncorrelated; (2) tying coherence with the matrix yields higher confidence in results; (3) the WRS#2 rack ORUs need to be isolated; (4) and future work includes a plan for characterizing performance of isolation materials.

  12. Analogy between language and biology: a functional approach.

    PubMed

    Victorri, Bernard

    2007-03-01

    We adopt here a functional approach to the classical comparison between language and biology. We first parallel events which have a functional signification in each domain, by matching the utterance of a sentence with the release of a protein. The meaning of a protein is then defined by analogy as "the constant contribution of the biochemical material composing the protein to the effects produced by any release of the protein". The proteome of an organism corresponds to an I-language (the idiolect of an individual), and the proteome of a species is equivalent to an E-language (a language in the common sense). Proteins and sentences are both characterized by a complex hierarchical structure, but the language property of 'double articulation' has no equivalent in the biological domain in this analogy, contrary to previous proposals centered on the genetic code. Besides, the same intimate relation between structure and meaning holds in both cases (syntactic structure for sentences and three-dimensional conformation for proteins). An important disanalogy comes from the combinatorial power of language which is not shared by the proteome as a whole, but it must be noted that the immune system possesses interesting properties in this respect. Regarding evolutionary aspects, the analogy still works to a certain extent. Languages and proteomes can be both considered as belonging to a general class of systems, that we call "productive self-reproductive systems", characterized by the presence of two dynamics: a fast dynamics in an external domain where functional events occur (productive aspect), and a slow dynamics responsible for the evolution of the system itself, driven by the feed-back of events related to the reproduction process.

  13. Two-Axis Acceleration of Functional Connectivity Magnetic Resonance Imaging by Parallel Excitation of Phase-Tagged Slices and Half k-Space Acceleration

    PubMed Central

    Jesmanowicz, Andrzej; Nencka, Andrew S.; Li, Shi-Jiang

    2011-01-01

    Abstract Whole brain functional connectivity magnetic resonance imaging requires acquisition of a time course of gradient-recalled (GR) volumetric images. A method is developed to accelerate this acquisition using GR echo-planar imaging and radio frequency (RF) slice phase tagging. For N-fold acceleration, a tailored RF pulse excites N slices using a uniform-field transmit coil. This pulse is the Fourier transform of the profile for the N slices with a predetermined RF phase tag on each slice. A multichannel RF receive coil is used for detection. For n slices, there are n/N groups of slices. Signal-averaged reference images are created for each slice within each slice group for each member of the coil array and used to separate overlapping images that are simultaneously received. The time-overhead for collection of reference images is small relative to the acquisition time of a complete volumetric time course. A least-squares singular value decomposition method allows image separation on a pixel-by-pixel basis. Twofold slice acceleration is demonstrated using an eight-channel RF receive coil, with application to resting-state functional magnetic resonance imaging in the human brain. Data from six subjects at 3 T are reported. The method has been extended to half k-space acquisition, which not only provides additional acceleration, but also facilitates slice separation because of increased signal intensity of the central lines of k-space coupled with reduced susceptibility effects. PMID:22432957

  14. The chemical biology of protein hydropersulfides: Studies of a possible protective function of biological hydropersulfide generation.

    PubMed

    Millikin, Robert; Bianco, Christopher L; White, Corey; Saund, Simran S; Henriquez, Stephanie; Sosa, Victor; Akaike, Takaaki; Kumagai, Yoshito; Soeda, Shuhei; Toscano, John P; Lin, Joseph; Fukuto, Jon M

    2016-08-01

    The recent discovery of significant hydropersulfide (RSSH) levels in mammalian tissues, fluids and cells has led to numerous questions regarding their possible physiological function. Cysteine hydropersulfides have been found in free cysteine, small molecule peptides as well as in proteins. Based on their chemical properties and likely cellular conditions associated with their biosynthesis, it has been proposed that they can serve a protective function. That is, hydropersulfide formation on critical thiols may protect them from irreversible oxidative or electrophilic inactivation. As a prelude to understanding the possible roles and functions of hydropersulfides in biological systems, this study utilizes primarily chemical experiments to delineate the possible mechanistic chemistry associated with cellular protection. Thus, the ability of hydropersulfides to protect against irreversible electrophilic and oxidative modification was examined. The results herein indicate that hydropersulfides are very reactive towards oxidants and electrophiles and are modified readily. However, reduction of these oxidized/modified species is facile generating the corresponding thiol, consistent with the idea that hydropersulfides can serve a protective function for thiol proteins. Copyright © 2016 Elsevier Inc. All rights reserved.

  15. The Chemical Biology of Protein Hydropersulfides: Studies of a Possible Protective Function of Biological Hydropersulfide Generation

    PubMed Central

    Millikin, Robert; Bianco, Christopher L.; White, Corey; Saund, Simran S.; Henriquez, Stephanie; Sosa, Victor; Akaike, Takaaki; Kumagai, Yoshito; Soeda, Shuhei; Toscano, John P.; Lin, Joseph; Fukuto, Jon M.

    2016-01-01

    The recent discovery of significant hydropersulfide (RSSH) levels in mammalian tissues, fluids and cells has led to numerous questions regarding their possible physiological function. Cysteine hydropersulfides have been found in free cysteine, small molecule peptides as well as in proteins. Based on their chemical properties and likely cellular conditions associated with their biosynthesis, it has been proposed that they can serve a protective function. That is, hydropersulfide formation on critical thiols may protect them from irreversible oxidative or electrophilic inactivation. As a prelude to understanding the possible roles and functions of hydropersulfides in biological systems, this study utilizes primarily chemical experiments to delineate the possible mechanistic chemistry associated with cellular protection. Thus, the ability of hydropersulfides to protect against irreversible electrophilic and oxidative modification was examined. The results herein indicate that hydropersulfides are very reactive towards oxidants and electrophiles and are modified readily. However, reduction of these oxidized/modified species is facile generating the corresponding thiol, consistent with the idea that hydropersulfides can serve a protective function for thiol proteins. PMID:27242269

  16. Biological/Biomedical Accelerator Mass Spectrometry Targets. 2. Physical, Morphological, and Structural Characteristics

    PubMed Central

    2008-01-01

    The number of biological/biomedical applications that require AMS to achieve their goals is increasing, and so is the need for a better understanding of the physical, morphological, and structural traits of high quality of AMS targets. The metrics of quality included color, hardness/texture, and appearance (photo and SEM), along with FT-IR, Raman, and powder X-ray diffraction spectra that correlate positively with reliable and intense ion currents and accuracy, precision, and sensitivity of fraction modern (Fm). Our previous method produced AMS targets of gray-colored iron−carbon materials (ICM) 20% of the time and of graphite-coated iron (GCI) 80% of the time. The ICM was hard, its FT-IR spectra lacked the sp2 bond, its Raman spectra had no detectable G′ band at 2700 cm−1, and it had more iron carbide (Fe3C) crystal than nanocrystalline graphite or graphitizable carbon (g-C). ICM produced low and variable ion current whereas the opposite was true for the graphitic GCI. Our optimized method produced AMS targets of graphite-coated iron powder (GCIP) 100% of the time. The GCIP shared some of the same properties as GCI in that both were black in color, both produced robust ion current consistently, their FT-IR spectra had the sp2 bond, their Raman spectra had matching D, G, G′, D+G, and D′′ bands, and their XRD spectra showed matching crystal size. GCIP was a powder that was easy to tamp into AMS target holders that also facilitated high throughput. We concluded that AMS targets of GCIP were a mix of graphitizable carbon and Fe3C crystal, because none of their spectra, FT-IR, Raman, or XRD, matched exactly those of the graphite standard. Nevertheless, AMS targets of GCIP consistently produced the strong, reliable, and reproducible ion currents for high-throughput AMS analysis (270 targets per skilled analyst/day) along with accurate and precise Fm values. PMID:18785762

  17. Biological/biomedical accelerator mass spectrometry targets. 2. Physical, morphological, and structural characteristics.

    PubMed

    Kim, Seung-Hyun; Kelly, Peter B; Clifford, Andrew J

    2008-10-15

    The number of biological/biomedical applications that require AMS to achieve their goals is increasing, and so is the need for a better understanding of the physical, morphological, and structural traits of high quality of AMS targets. The metrics of quality included color, hardness/texture, and appearance (photo and SEM), along with FT-IR, Raman, and powder X-ray diffraction spectra that correlate positively with reliable and intense ion currents and accuracy, precision, and sensitivity of fraction modern ( F m). Our previous method produced AMS targets of gray-colored iron-carbon materials (ICM) 20% of the time and of graphite-coated iron (GCI) 80% of the time. The ICM was hard, its FT-IR spectra lacked the sp (2) bond, its Raman spectra had no detectable G' band at 2700 cm (-1), and it had more iron carbide (Fe 3C) crystal than nanocrystalline graphite or graphitizable carbon (g-C). ICM produced low and variable ion current whereas the opposite was true for the graphitic GCI. Our optimized method produced AMS targets of graphite-coated iron powder (GCIP) 100% of the time. The GCIP shared some of the same properties as GCI in that both were black in color, both produced robust ion current consistently, their FT-IR spectra had the sp (2) bond, their Raman spectra had matching D, G, G', D +G, and D '' bands, and their XRD spectra showed matching crystal size. GCIP was a powder that was easy to tamp into AMS target holders that also facilitated high throughput. We concluded that AMS targets of GCIP were a mix of graphitizable carbon and Fe 3C crystal, because none of their spectra, FT-IR, Raman, or XRD, matched exactly those of the graphite standard. Nevertheless, AMS targets of GCIP consistently produced the strong, reliable, and reproducible ion currents for high-throughput AMS analysis (270 targets per skilled analyst/day) along with accurate and precise F m values.

  18. Structure activity relationships: their function in biological prediction

    SciTech Connect

    Schultz, T.W.

    1982-01-01

    Quantitative structure activity relationships provide a means of ranking or predicting biological effects based on chemical structure. For each compound used to formulate a structure activity model two kinds of quantitative information are required: (1) biological activity and (2) molecular properties. Molecular properties are of three types: (1) molecular shape, (2) physiochemical parameters, and (3) abstract quantitations of molecular structure. Currently the two best descriptors are the hydrophobic parameter, log 1-octanol/water partition coefficient (log P), and the /sup 1/X/sup v/(one-chi-v) molecular connectivity index. Biological responses can be divided into three main categories: (1) non-specific effects due to membrane perturbation, (2) non-specific effects due to interaction with functional groups of proteins, and (3) specific effects due to interaction with receptors. Twenty-six synthetic fossil fuel-related nitrogen-containing aromatic compounds were examined to determine the quantitative correlation between log P and /sup 1/X/sup v/ and population growth impairment of Tetrahymena pyriformis. Nitro-containing compounds are the most active, followed by amino-containing compounds and azaarenes. Within each analog series activity increases with alkyl substitution and ring addition. The planar model log BR = 0.5564 log P + 0.3000 /sup 1/X/sup v/ -2.0138 was determined using mono-nitrogen substituted compounds. Attempts to extrapolate this model to dinitrogen-containing molecules were, for the most part, unsuccessful because of a change in mode of action from membrane perturbation to uncoupling of oxidative phosphoralation.

  19. Effect of plasma exchange in accelerating natalizumab clearance and restoring leukocyte function

    PubMed Central

    Khatri, B O.; Man, S; Giovannoni, G; Koo, A P.; Lee, J-C; Tucky, B; Lynn, F; Jurgensen, S; Woodworth, J; Goelz, S; Duda, P W.; Panzara, M A.; Ransohoff, R M.; Fox, R J.

    2009-01-01

    Background: Accelerating the clearance of therapeutic monoclonal antibodies (mAbs) from the body may be useful to address uncommon but serious complications from treatment, such as progressive multifocal leukoencephalopathy (PML). Treatment of PML requires immune reconstitution. Plasma exchange (PLEX) may accelerate mAb clearance, restoring the function of inhibited proteins and increasing the number or function of leukocytes entering the CNS. We evaluated the efficacy of PLEX in accelerating natalizumab (a therapy for multiple sclerosis [MS] and Crohn disease) clearance and α4-integrin desaturation. Restoration of leukocyte transmigratory capacity was evaluated using an in vitro blood–brain barrier (ivBBB). Methods: Twelve patients with MS receiving natalizumab underwent three 1.5-volume PLEX sessions over 5 or 8 days. Natalizumab concentrations and α4-integrin saturation were assessed daily throughout PLEX and three times over the subsequent 2 weeks, comparing results with the same patients the previous month. Peripheral blood mononuclear cell (PBMC) migration (induced by the chemokine CCL2) across an ivBBB was assessed in a subset of six patients with and without PLEX. Results: Serum natalizumab concentrations were reduced by a mean of 92% from baseline to 1 week after three PLEX sessions (p < 0.001). Although average α4-integrin saturation was not reduced after PLEX, it was reduced to less than 50% when natalizumab concentrations were below 1 μg/mL. PBMC transmigratory capacity increased 2.2-fold after PLEX (p < 0.006). Conclusions: Plasma exchange (PLEX) accelerated clearance of natalizumab, and at natalizumab concentrations below 1 μg/mL, desaturation of α4-integrin was observed. Also, CCL2-induced leukocyte transmigration across an in vitro blood–brain barrier was increased after PLEX. Therefore, PLEX may be effective in restoring immune effector function in natalizumab-treated patients. GLOSSARY AE = adverse event; BBB = blood–brain barrier; BW

  20. Olopatadine hydrochloride accelerates the recovery of skin barrier function in mice.

    PubMed

    Amano, T; Takeda, T; Yano, H; Tamura, T

    2007-05-01

    The skin barrier function in patients with atopic dermatitis is disrupted and prolonged topical steroid therapy produces epidermal barrier disturbance. Olopatadine hydrochloride (olopatadine; Allelock; Kyowa Hakko Kogyo Co., Ltd, Shizuoka, Japan) is an antiallergic drug with histamine H(1) receptor antagonistic action. This drug alleviates skin inflammation and decreases the number of scratching episodes in a murine model of chronic contact dermatitis. To investigate the effects of olopatadine and a steroid on the recovery of skin barrier function after barrier disruption in mice. The skin barrier of the ears of mice was disrupted by tape stripping. The recovery of skin barrier function was monitored by measurement of transepidermal water loss (TEWL) after barrier disruption. Epidermal hyperplasia was induced by repeated tape stripping for 7 days. Olopatadine was administered orally once daily from 3 days before the first barrier disruption. Betamethasone 17-valerate (betamethasone) was applied topically once daily from 3 days before barrier disruption. Tape stripping led to a significant increase in TEWL. TEWL decreased with time after tape stripping and the skin barrier function recovered by over 60% within 9 h after tape stripping. The recovery of skin barrier in olopatadine-treated mice was significantly accelerated, compared with that in vehicle-treated mice. In contrast, the skin barrier recovery in mice treated with topical betamethasone was significantly delayed, compared with that in vehicle-treated mice. Combined treatment with olopatadine and betamethasone ameliorated the delay in barrier recovery induced by topical treatment with betamethasone. In addition, olopatadine significantly prevented the increase in epidermal thickness induced by prolonged barrier disruption. These results suggest that systemic administration of olopatadine accelerates the recovery of skin barrier function and ameliorates the adverse effects of topical steroids on skin barrier

  1. Androgen Receptor Structure, Function and Biology: From Bench to Bedside

    PubMed Central

    Davey, Rachel A; Grossmann, Mathis

    2016-01-01

    The actions of androgens such as testosterone and dihydrotestosterone are mediated via the androgen receptor (AR), a ligand-dependent nuclear transcription factor and member of the steroid hormone nuclear receptor family. Given its widespread expression in many cells and tissues, the AR has a diverse range of biological actions including important roles in the development and maintenance of the reproductive, musculoskeletal, cardiovascular, immune, neural and haemopoietic systems. AR signalling may also be involved in the development of tumours in the prostate, bladder, liver, kidney and lung. Androgens can exert their actions via the AR in a DNA binding-dependent manner to regulate target gene transcription, or in a non-DNA binding-dependent manner to initiate rapid, cellular events such as the phosphorylation of 2nd messenger signalling cascades. More recently, ligand-independent actions of the AR have also been identified. Given the large volume of studies relating to androgens and the AR, this review is not intended as an extensive review of all studies investigating the AR, but rather as an overview of the structure, function, signalling pathways and biology of the AR as well as its important role in clinical medicine, with emphasis on recent developments in this field. PMID:27057074

  2. Discoveries of rhythms in human biological functions: a historical review.

    PubMed

    Lemmer, Björn

    2009-08-01

    Though there are very early and ancient observations on the daily variation in physiological and pathophysiological functions (e.g., bronchial asthma), more detailed and scientific reports were not published until the beginning of the 17th century. The aim of this review is to bring those reports to the attention of researchers of chronobiology and chronopharmacology. The ancient books and their contents, which constitute the basis for this review, are part of the personal library collection of the author; numerous observations and reports on biologic rhythms in man are presented here for the first time. The intent of this review is to demonstrate that the fields of chronobiology and chronopharmacology are not only a new and modern branch of science, but that it stands on the shoulders of wonderful and insightful observations and explanations made by our scientific forefathers. It is the hope that the reader will enjoy the richness of the ancient reports that contribute to our present knowledge achieved through astute early biologic rhythm research.

  3. Click Chemistry Mediated Functionalization of Vertical Nanowires for Biological Applications.

    PubMed

    Vutti, Surendra; Schoffelen, Sanne; Bolinsson, Jessica; Buch-Månson, Nina; Bovet, Nicolas; Nygård, Jesper; Martinez, Karen L; Meldal, Morten

    2016-01-11

    Semiconductor nanowires (NWs) are gaining significant importance in various biological applications, such as biosensing and drug delivery. Efficient and controlled immobilization of biomolecules on the NW surface is crucial for many of these applications. Here, we present for the first time the use of the Cu(I) -catalyzed alkyne-azide cycloaddition and its strain-promoted variant for the covalent functionalization of vertical NWs with peptides and proteins. The potential of the approach was demonstrated in two complementary applications of measuring enzyme activity and protein binding, which is of general interest for biological studies. The attachment of a peptide substrate provided NW arrays for the detection of protease activity. In addition, green fluorescent protein was immobilized in a site-specific manner and recognized by antibody binding to demonstrate the proof-of-concept for the use of covalently modified NWs for diagnostic purposes using minute amounts of material. © 2016 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  4. Insights into IL-23 biology: From structure to function.

    PubMed

    Floss, Doreen M; Schröder, Jutta; Franke, Manuel; Scheller, Jürgen

    2015-10-01

    Interleukin (IL-)23 is a central cytokine controlling TH17 development. Overshooting IL-23 signaling contribute to autoimmune diseases. Moreover, GWAS studies have identified several SNPs within the IL-23 receptor, which are associated with autoimmune diseases. IL-23 is a member of the IL-12-type cytokine family and consists of IL-23p19 and p40. Within the IL-12 family, IL-12 and IL-23 share the p40 cytokine subunit and the IL-12Rβ1 as one chain of the receptor complex. For signaling, IL-23 triggers heterodimerization of IL-12Rβ1 and the IL-23R. Subsequently, signal transduction pathways including JAK/STAT, MAPK and PI3K are activated. Most studies have investigated the biological relevance of IL-23 in the development of TH17 cells and autoimmunity, whereas less is known about the molecular context of IL-23 biology. Therefore, we focused on IL-23 receptor complex assembly, signal transduction and functional relevance of IL-23R SNPs in the context of IL-23-inhibitory principles. Copyright © 2015 Elsevier Ltd. All rights reserved.

  5. Proteomic profiling of high risk medulloblastoma reveals functional biology

    PubMed Central

    Staal, Jerome A.; Lau, Ling San; Zhang, Huizhen; Ingram, Wendy J.; Hallahan, Andrew R.; Northcott, Paul A.; Pfister, Stefan M.; Wechsler-Reya, Robert J.; Rusert, Jessica M.; Taylor, Michael D.; Cho, Yoon-Jae; Packer, Roger J.; Brown, Kristy J.; Rood, Brian R.

    2015-01-01

    Genomic characterization of medulloblastoma has improved molecular risk classification but struggles to define functional biological processes, particularly for the most aggressive subgroups. We present here a novel proteomic approach to this problem using a reference library of stable isotope labeled medulloblastoma-specific proteins as a spike-in standard for accurate quantification of the tumor proteome. Utilizing high-resolution mass spectrometry, we quantified the tumor proteome of group 3 medulloblastoma cells and demonstrate that high-risk MYC amplified tumors can be segregated based on protein expression patterns. We cross-validated the differentially expressed protein candidates using an independent transcriptomic data set and further confirmed them in a separate cohort of medulloblastoma tissue samples to identify the most robust proteogenomic differences. Interestingly, highly expressed proteins associated with MYC-amplified tumors were significantly related to glycolytic metabolic pathways via alternative splicing of pyruvate kinase (PKM) by heterogeneous ribonucleoproteins (HNRNPs). Furthermore, when maintained under hypoxic conditions, these MYC-amplified tumors demonstrated increased viability compared to non-amplified tumors within the same subgroup. Taken together, these findings highlight the power of proteomics as an integrative platform to help prioritize genetic and molecular drivers of cancer biology and behavior. PMID:25970789

  6. Proteomic profiling of high risk medulloblastoma reveals functional biology.

    PubMed

    Staal, Jerome A; Lau, Ling San; Zhang, Huizhen; Ingram, Wendy J; Hallahan, Andrew R; Northcott, Paul A; Pfister, Stefan M; Wechsler-Reya, Robert J; Rusert, Jessica M; Taylor, Michael D; Cho, Yoon-Jae; Packer, Roger J; Brown, Kristy J; Rood, Brian R

    2015-06-10

    Genomic characterization of medulloblastoma has improved molecular risk classification but struggles to define functional biological processes, particularly for the most aggressive subgroups. We present here a novel proteomic approach to this problem using a reference library of stable isotope labeled medulloblastoma-specific proteins as a spike-in standard for accurate quantification of the tumor proteome. Utilizing high-resolution mass spectrometry, we quantified the tumor proteome of group 3 medulloblastoma cells and demonstrate that high-risk MYC amplified tumors can be segregated based on protein expression patterns. We cross-validated the differentially expressed protein candidates using an independent transcriptomic data set and further confirmed them in a separate cohort of medulloblastoma tissue samples to identify the most robust proteogenomic differences. Interestingly, highly expressed proteins associated with MYC-amplified tumors were significantly related to glycolytic metabolic pathways via alternative splicing of pyruvate kinase (PKM) by heterogeneous ribonucleoproteins (HNRNPs). Furthermore, when maintained under hypoxic conditions, these MYC-amplified tumors demonstrated increased viability compared to non-amplified tumors within the same subgroup. Taken together, these findings highlight the power of proteomics as an integrative platform to help prioritize genetic and molecular drivers of cancer biology and behavior.

  7. Linking biological soil crust diversity to ecological functions

    NASA Astrophysics Data System (ADS)

    Glaser, Karin; Borchhardt, Nadine; Schulz, Karoline; Mikhailyuk, Tatiana; Baumann, Karen; Leinweber, Peter; Ulf, Karsten

    2016-04-01

    Biological soil crusts (BSCs) are an association of different microorganisms and soil particles in the top millimeters of the soil. They are formed by algae, cyanobacteria, microfungi, bacteria, bryophytes and lichens in various compositions. Our aim was to determine and compare the biodiversity of all occurring organisms in biogeographically different habitats, ranging from polar (both Arctic and Antarctic), subpolar (Scandinavia), temperate (Germany) to dry regions (Chile). The combination of microscopy and molecular techniques (next-generation sequencing) revealed highly diverse crust communities, whose composition clustered by region and correlates with habitat characteristics such as water content. The BSC biodiversity was then linked to the ecological function of the crusts. The functional role of the BSCs in the biogeochemical cycles of carbon, nitrogen and phosphorous is evaluated using an array of state of the art soil chemistry methods including Py-FIMS (pyrolysis field ionization mass spectrometry) and XANES (x-ray absorbance near edge structure). Total P as well as P fractions were quantified in all BSCs, adjacent soil underneath and comparable nearby soil of BSC-free areas revealing a remarkable accumulation of total phosphorous and a distinct pattern of P fractions in the crust. Further, we observed an indication of a different P-speciation composition in the crust compared with BSC-free soil. The data allow answering the question whether BSCs act as sink or source for these compounds, and how biodiversity controls the biogeochemical function of BSCs.

  8. A Synthetic Biology Framework for Programming Eukaryotic Transcription Functions

    PubMed Central

    Khalil, Ahmad S.; Lu, Timothy K.; Bashor, Caleb J.; Ramirez, Cherie L.; Pyenson, Nora C.; Joung, J. Keith; Collins, James J.

    2013-01-01

    SUMMARY Eukaryotic transcription factors (TFs) perform complex and combinatorial functions within transcriptional networks. Here, we present a synthetic framework for systematically constructing eukaryotic transcription functions using artificial zinc fingers, modular DNA-binding domains found within many eukaryotic TFs. Utilizing this platform, we construct a library of orthogonal synthetic transcription factors (sTFs) and use these to wire synthetic transcriptional circuits in yeast. We engineer complex functions, such as tunable output strength and transcriptional cooperativity, by rationally adjusting a decomposed set of key component properties, e.g., DNA specificity, affinity, promoter design, protein-protein interactions. We show that subtle perturbations to these properties can transform an individual sTF between distinct roles (activator, cooperative factor, inhibitory factor) within a transcriptional complex, thus drastically altering the signal processing behavior of multi-input systems. This platform provides new genetic components for synthetic biology and enables bottom-up approaches to understanding the design principles of eukaryotic transcriptional complexes and networks. PMID:22863014

  9. Biologically functionalized nanochannels on ferroelectric lead zirconium titanate surfaces.

    SciTech Connect

    Ocola, L. E.; Pan, W. C.; Kuo, M.; Tirumala, V. R.; Reiss, B. D.; Firestone, M. A.; Illinois Mathematics and Science Academy

    2005-01-01

    We recently started a program at Argonne to exploit patterned, polarizable ferroelectric surfaces, such as lead zirconium titanate (PZT), as a means to create field-responsive inorganic-biomolecule interfaces to study and manipulate biomatter on surfaces. In this paper we will discuss the integration of nanochannels on the surface of PZT films and their selective functionalization to create nanovalves to control nanofluidic flow. Microfluidic devices have been fabricated using a variety of methods, ranging from thermal decomposition of buried patterned channels, to fabricating trenches via plasma etch or hot embossing followed by trench capping. Our work focuses on an alternative method by using a bilayer resist in an inverted configuration normally used for T- and Gamma- gate fabrication. This method is capable of yielding sub-100 nm nanochannels with high aspect ratios and sub-500nm alignment. We have recently demonstrated that the polarization hysteresis loop of PZT is the same before and after exposure to an aqueous environment. This opens the possibility of selective surface modification of PZT via coupling of a wide range of biomolecules (e.g., peptides, proteins) and the use of the electric-field-responsive properties of PZT to manipulate the function (e.g., orientation) of the tethered biomolecules. We have used phage display techniques to evolve specific peptide motifs that selectively bind to PZT. The optimum heptapeptide that facilitates both the attachment of functional biological molecules to the surface of PZT has been identified.

  10. Automated ARGET ATRP Accelerates Catalyst Optimization for the Synthesis of Thiol-Functionalized Polymers

    PubMed Central

    Siegwart, Daniel J.; Leiendecker, Matthias; Langer, Robert; Anderson, Daniel G.

    2013-01-01

    Conventional synthesis of polymers by ATRP is relatively low throughput, involving iterative optimization of conditions in an inert atmosphere. Automated, high-throughput controlled radical polymerization was developed to accelerate catalyst optimization and production of disulfide-functionalized polymers without the need of an inert gas. Using ARGET ATRP, polymerization conditions were rapidly identified for eight different monomers, including the first ARGET ATRP of 2-(diethylamino)ethyl methacrylate and di(ethylene glycol) methyl ether methacrylate. In addition, butyl acrylate, oligo(ethylene glycol) methacrylate 300 and 475, 2-(dimethylamino)ethyl methacrylate, styrene, and methyl methacrylate were polymerized using bis(2-hydroxyethyl) disulfide bis(2-bromo-2-methylpropionate) as the initiator, tris(2-pyridylmethyl)amine as the ligand, and tin(II) 2-ethylhexanoate as the reducing agent. The catalyst and reducing agent concentration was optimized specifically for each monomer, and then a library of polymers was synthesized systematically using the optimized conditions. The disulfide-functionalized chains could be cleaved to two thiol-terminated chains upon exposure to dithiothreitol, which may have utility for the synthesis of polymer bioconjugates. Finally, we demonstrated that these new conditions translated perfectly to conventional batch polymerization. We believe the methods developed here may prove generally useful to accelerate the systematic optimization of a variety of chemical reactions and polymerizations. PMID:23599541

  11. Automated ARGET ATRP Accelerates Catalyst Optimization for the Synthesis of Thiol-Functionalized Polymers.

    PubMed

    Siegwart, Daniel J; Leiendecker, Matthias; Langer, Robert; Anderson, Daniel G

    2012-02-14

    Conventional synthesis of polymers by ATRP is relatively low throughput, involving iterative optimization of conditions in an inert atmosphere. Automated, high-throughput controlled radical polymerization was developed to accelerate catalyst optimization and production of disulfide-functionalized polymers without the need of an inert gas. Using ARGET ATRP, polymerization conditions were rapidly identified for eight different monomers, including the first ARGET ATRP of 2-(diethylamino)ethyl methacrylate and di(ethylene glycol) methyl ether methacrylate. In addition, butyl acrylate, oligo(ethylene glycol) methacrylate 300 and 475, 2-(dimethylamino)ethyl methacrylate, styrene, and methyl methacrylate were polymerized using bis(2-hydroxyethyl) disulfide bis(2-bromo-2-methylpropionate) as the initiator, tris(2-pyridylmethyl)amine as the ligand, and tin(II) 2-ethylhexanoate as the reducing agent. The catalyst and reducing agent concentration was optimized specifically for each monomer, and then a library of polymers was synthesized systematically using the optimized conditions. The disulfide-functionalized chains could be cleaved to two thiol-terminated chains upon exposure to dithiothreitol, which may have utility for the synthesis of polymer bioconjugates. Finally, we demonstrated that these new conditions translated perfectly to conventional batch polymerization. We believe the methods developed here may prove generally useful to accelerate the systematic optimization of a variety of chemical reactions and polymerizations.

  12. Friction properties of biological functional materials: PVDF membranes.

    PubMed

    Chen, Long; Di, Changan; Chen, Xuguang; Li, Zhengzhi; Luo, Jia

    2017-01-02

    Touch is produced by sensations that include approaching, sliding, pressing, and temperature. This concept has become a target of research in biotechnology, especially in the field of bionic biology. This study measured sliding and pressing with traditional tactile sensors in order to improve a machine operator's judgment of surface roughness. Based on the theory of acoustic emission, this study combined polyvinylidene fluoride (PVDF) with a sonic transducer to produce tactile sensors that can detect surface roughness. Friction between PVDF films and experimental materials generated tiny acoustic signals that were transferred into electrical signals through a sonic transducer. The characteristics of the acoustic signals for the various materials were then analyzed. The results suggest that this device can effectively distinguish among different objects based on roughness. Tactile sensors designed using this principle and structure function very similarly to the human body in recognizing the surface of an object.

  13. Biological activity of lactoferrin-functionalized biomimetic hydroxyapatite nanocrystals

    PubMed Central

    Nocerino, Nunzia; Fulgione, Andrea; Iannaccone, Marco; Tomasetta, Laura; Ianniello, Flora; Martora, Francesca; Lelli, Marco; Roveri, Norberto; Capuano, Federico; Capparelli, Rosanna

    2014-01-01

    The emergence of bacterial strains resistant to antibiotics is a general public health problem. Progress in developing new molecules with antimicrobial properties has been made. In this study, we evaluated the biological activity of a hybrid nanocomposite composed of synthetic biomimetic hydroxyapatite surface-functionalized by lactoferrin (LF-HA). We evaluated the antimicrobial, anti-inflammatory, and antioxidant properties of LF-HA and found that the composite was active against both Gram-positive and Gram-negative bacteria, and that it modulated proinflammatory and anti-inflammatory responses and enhanced antioxidant properties as compared with LF alone. These results indicate the possibility of using LF-HA as an antimicrobial system and biomimetic hydroxyapatite as a candidate for innovative biomedical applications. PMID:24623976

  14. Twenty years of protein interaction studies for biological function deciphering.

    PubMed

    Legrain, Pierre; Rain, Jean-Christophe

    2014-07-31

    Intensive methodological developments and technology innovation have been devoted to protein-protein interaction studies over 20years. Genetic indirect assays and sophisticated large scale biochemical analyses have jointly contributed to the elucidation of protein-protein interactions, still with a lot of drawbacks despite heavy investment in human resources and technologies. With the most recent developments in mass spectrometry and computational tools for studying protein content of complex samples, the initial goal of deciphering molecular bases of biological functions is now within reach. Here, we described the various steps of this process and gave examples of key milestones in this scientific story line. This article is part of a Special Issue entitled: 20years of Proteomics in memory of Viatliano Pallini. Guest Editors: Luca Bini, Juan J. Calvete, Natacha Turck, Denis Hochstrasser and Jean-Charles Sanchez.

  15. Biological activity of lactoferrin-functionalized biomimetic hydroxyapatite nanocrystals.

    PubMed

    Nocerino, Nunzia; Fulgione, Andrea; Iannaccone, Marco; Tomasetta, Laura; Ianniello, Flora; Martora, Francesca; Lelli, Marco; Roveri, Norberto; Capuano, Federico; Capparelli, Rosanna

    2014-01-01

    The emergence of bacterial strains resistant to antibiotics is a general public health problem. Progress in developing new molecules with antimicrobial properties has been made. In this study, we evaluated the biological activity of a hybrid nanocomposite composed of synthetic biomimetic hydroxyapatite surface-functionalized by lactoferrin (LF-HA). We evaluated the antimicrobial, anti-inflammatory, and antioxidant properties of LF-HA and found that the composite was active against both Gram-positive and Gram-negative bacteria, and that it modulated proinflammatory and anti-inflammatory responses and enhanced antioxidant properties as compared with LF alone. These results indicate the possibility of using LF-HA as an antimicrobial system and biomimetic hydroxyapatite as a candidate for innovative biomedical applications.

  16. Peptide Self-Assembly for Crafting Functional Biological Materials

    PubMed Central

    Matson, John B.; Zha, R. Helen; Stupp, Samuel I.

    2011-01-01

    Self-assembling, peptide-based scaffolds are frontrunners in the search for biomaterials with widespread impact in regenerative medicine. The inherent biocompatibility and cell signaling capabilities of peptides, in combination with control of secondary structure, has led to the development of a broad range of functional materials with potential for many novel therapies. More recently, membranes formed through complexation of peptide nanostructures with natural biopolymers have led to the development of hierarchically-structured constructs with potentially far-reaching applications in biology and medicine. In this review, we highlight recent advances in peptide-based gels and membranes, including work from our group and others. Specifically, we discuss the application of peptide-based materials in the regeneration of bone and enamel, cartilage, and the central nervous system, as well as the transplantation of islets, wound-healing, cardiovascular therapies, and treatment of erectile dysfunction after prostatectomy PMID:22125413

  17. Comparative genomics of pectinacetylesterases: Insight on function and biology

    PubMed Central

    de Souza, Amancio José; Pauly, Markus

    2015-01-01

    Pectin acetylation influences the gelling ability of this important plant polysaccharide for the food industry. Plant apoplastic pectinacetylesterases (PAEs) play a key role in regulating the degree of pectin acetylation and modifying their expression thus represents one way to engineer plant polysaccharides for food applications. Identifying the major active enzymes within the PAE gene family will aid in our understanding of this biological phenomena as well as provide the tools for direct trait manipulation. Using comparative genomics we propose that there is a minimal set of 4 distinct PAEs in plants. Possible functional diversification of the PAE family in the grasses is also explored with the identification of 3 groups of PAE genes specific to grasses. PMID:26237162

  18. Triboelectric Nanogenerator Accelerates Highly Efficient Nonviral Direct Conversion and In Vivo Reprogramming of Fibroblasts to Functional Neuronal Cells.

    PubMed

    Jin, Yoonhee; Seo, Jungmok; Lee, Jung Seung; Shin, Sera; Park, Hyun-Ji; Min, Sungjin; Cheong, Eunji; Lee, Taeyoon; Cho, Seung-Woo

    2016-09-01

    Triboelectric nanogenerators (TENGs) can be an effective cell reprogramming platform for producing functional neuronal cells for therapeutic applications. Triboelectric stimulation accelerates nonviral direct conversion of functional induced neuronal cells from fibroblasts, increases the conversion efficiency, and induces highly matured neuronal phenotypes with improved electrophysiological functionalities. TENG devices may also be used for biomedical in vivo reprogramming.

  19. Fluorochrome-Functionalized Nanoparticles for Imaging DNA in Biological Systems

    PubMed Central

    Cho, Hoonsung; Alcantara, David; Yuan, Hushan; Sheth, Rahul A.; Chen, Howard H.; Huang, Peng; Andersson, Sean B.; Sosnovik, David E.; Mahmood, Umar; Josephson, Lee

    2013-01-01

    Attaching DNA binding fluorochromes to nanoparticles (NPs) provides a way of obtaining NPs that bind to DNA through fluorochrome mediated interactions. To obtain a nanoparticle (NP) that bound to the DNA in biological systems, we attached the DNA binding fluorochrome, TO-PRO 1 (TO), to the surface of the Feraheme (FH) NP, to obtain a fluorochrome-functionalized NP denoted TO-FH. When reacted with DNA in vitro, TO-FH formed microaggregates that were characterized by fluorescence, light scattering, and T2 changes. The formation of DNA/TO-FH microaggregates was also characterized by AFM, with microaggregates exhibiting a median size of 200 nm, and consisting of DNA and multiple TO-FH NPs whose individual diameters were only 25–35 nm. TO-FH failed to bind normal cells in culture, but treatment with chemotherapeutic agents or detergents yielded necrotic cells that bound TO-FH and vital fluorochromes similarly. The uptake of TO-FH by HT-29 xenografts (treated with 5-FU and oxaliplatin) was evident by surface fluorescence and MRI. Attaching multiple DNA binding fluorochromes to magnetic nanoparticles provides a way of generating DNA binding NPs that can be used to detect DNA detection by microaggregate formation in vitro, for imaging the DNA of necrotic cells in culture, and for imaging the DNA of a tumor treated with a chemotherapeutic agent. Fluorochrome functionalized NPs are a multimodal (magnetic and fluorescent), highly multivalent (n ≈ 10 fluorochromes/NP) nanomaterials useful for imaging the DNA of biological systems. PMID:23373524

  20. Functionalized nanoparticles for biological imaging and detection applications

    NASA Astrophysics Data System (ADS)

    Mei, Bing C.

    Semiconductor quantum dots (QDs) and gold nanoparticles (AuNPs) have gained tremendous attention in the last decade as a result of their size-dependent spectroscopic properties. These nanoparticles have been a subject of intense study to bridge the gap between macroscopic and atomic behavior, as well as to generate new materials for novel applications in therapeutics, biological sensing, light emitting devices, microelectronics, lasers, and solar cells. One of the most promising areas for the use of these nanoparticles is in biotechnology, where their size-dependent optical properties are harnessed for imaging and sensing applications. However, these nanoparticles, as synthesized, are often not stable in aqueous media and lack simple and reliable means of covalently linking to biomolecules. The focus of this work is to advance the progress of these nanomaterials for biotechnology by synthesizing them, characterizing their optical properties and rendering them water-soluble and functional while maintaining their coveted optical properties. QDs were synthesized by an organometallic chemical procedure that utilizes coordinating solvents to provide brightly luminescent nanoparticles. The optical interactions of these QDs were studied as a function of concentration to identify particle size-dependent optimal concentrations, where scattering and indirection excitation are minimized and the amount light observed per particle is maximized. Both QDs and AuNPs were rendered water-soluble and stable in a broad range of biologically relevant conditions by using a series of ligands composed of dihydrolipoic acid (DHLA) appended to poly(ethylene glycol) methyl ether. By studying the stability of the surface modified AuNPs, we revealed some interesting information regarding the role of the surface ligand on the nanoparticle stability (i.e. solubility in high salt concentration, resistance to dithiothreitol competition and cyanide decomposition). Furthermore, the nanoparticles

  1. Lung function, biological monitoring, and biological effect monitoring of gemstone cutters exposed to beryls.

    PubMed

    Wegner, R; Heinrich-Ramm, R; Nowak, D; Olma, K; Poschadel, B; Szadkowski, D

    2000-02-01

    Gemstone cutters are potentially exposed to various carcinogenic and fibrogenic metals such as chromium, nickel, aluminium, and beryllium, as well as to lead. Increased beryllium concentrations had been reported in the air of workplaces of beryl cutters in Idar-Oberstein, Germany. The aim of the survey was to study the excretion of beryllium in cutters and grinders with occupational exposure to beryls--for example, aquamarines and emeralds--to examine the prevalence of beryllium sensitisation with the beryllium lymphocyte transformation test (BeLT), to examine the prevalence of lung disease induced by beryllium, to describe the internal load of the respective metals relative to work process, and to screen for genotoxic effects in this particular profession. In a cross sectional investigation, 57 out of 100 gemstone cutters working in 12 factories in Idar-Oberstein with occupational exposure to beryls underwent medical examinations, a chest radiograph, lung function testing (spirometry, airway resistance with the interrupter technique), and biological monitoring, including measurements of aluminium, chromium, and nickel in urine as well as lead in blood. Beryllium in urine was measured with a newly developed direct electrothermal atomic absorption spectroscopy technique with a measurement limit of 0.06 microgram/l. Also, cytogenetic tests (rates of micronuclei and sister chromatid exchange), and a BeLT were performed. Airborne concentrations of beryllium were measured in three factories. As no adequate local control group was available, the cutters were categorised into those with an exposure to beryls of > 4 hours/week (group A) and < or = 4 hours/week (group B). Clinical, radiological, or spirometric abnormalities indicating pneumoconiosis were detected in none of the gemstone cutters. Metal concentrations in biological material were far below the respective biological limit values, and beryllium in urine was only measurable in subjects of group A. Cytogenetic

  2. Quality of Graphite Target for Biological/Biomedical/Environmental Applications of 14C-Accelerator Mass Spectrometry

    PubMed Central

    2010-01-01

    Catalytic graphitization for 14C-accelerator mass spectrometry (14C-AMS) produced various forms of elemental carbon. Our high-throughput Zn reduction method (C/Fe = 1:5, 500 °C, 3 h) produced the AMS target of graphite-coated iron powder (GCIP), a mix of nongraphitic carbon and Fe3C. Crystallinity of the AMS targets of GCIP (nongraphitic carbon) was increased to turbostratic carbon by raising the C/Fe ratio from 1:5 to 1:1 and the graphitization temperature from 500 to 585 °C. The AMS target of GCIP containing turbostratic carbon had a large isotopic fractionation and a low AMS ion current. The AMS target of GCIP containing turbostratic carbon also yielded less accurate/precise 14C-AMS measurements because of the lower graphitization yield and lower thermal conductivity that were caused by the higher C/Fe ratio of 1:1. On the other hand, the AMS target of GCIP containing nongraphitic carbon had higher graphitization yield and better thermal conductivity over the AMS target of GCIP containing turbostratic carbon due to optimal surface area provided by the iron powder. Finally, graphitization yield and thermal conductivity were stronger determinants (over graphite crystallinity) for accurate/precise/high-throughput biological, biomedical, and environmental14C-AMS applications such as absorption, distribution, metabolism, elimination (ADME), and physiologically based pharmacokinetics (PBPK) of nutrients, drugs, phytochemicals, and environmental chemicals. PMID:20163100

  3. Quality of graphite target for biological/biomedical/environmental applications of 14C-accelerator mass spectrometry.

    PubMed

    Kim, Seung-Hyun; Kelly, Peter B; Ortalan, Volkan; Browning, Nigel D; Clifford, Andrew J

    2010-03-15

    Catalytic graphitization for (14)C-accelerator mass spectrometry ((14)C-AMS) produced various forms of elemental carbon. Our high-throughput Zn reduction method (C/Fe = 1:5, 500 degrees C, 3 h) produced the AMS target of graphite-coated iron powder (GCIP), a mix of nongraphitic carbon and Fe(3)C. Crystallinity of the AMS targets of GCIP (nongraphitic carbon) was increased to turbostratic carbon by raising the C/Fe ratio from 1:5 to 1:1 and the graphitization temperature from 500 to 585 degrees C. The AMS target of GCIP containing turbostratic carbon had a large isotopic fractionation and a low AMS ion current. The AMS target of GCIP containing turbostratic carbon also yielded less accurate/precise (14)C-AMS measurements because of the lower graphitization yield and lower thermal conductivity that were caused by the higher C/Fe ratio of 1:1. On the other hand, the AMS target of GCIP containing nongraphitic carbon had higher graphitization yield and better thermal conductivity over the AMS target of GCIP containing turbostratic carbon due to optimal surface area provided by the iron powder. Finally, graphitization yield and thermal conductivity were stronger determinants (over graphite crystallinity) for accurate/precise/high-throughput biological, biomedical, and environmental (14)C-AMS applications such as absorption, distribution, metabolism, elimination (ADME), and physiologically based pharmacokinetics (PBPK) of nutrients, drugs, phytochemicals, and environmental chemicals.

  4. Muscle mass, structural and functional investigations of senescence-accelerated mouse P8 (SAMP8)

    PubMed Central

    Guo, An Yun; Leung, Kwok Sui; Siu, Parco Ming Fai; Qin, Jiang Hui; Chow, Simon Kwoon Ho; Qin, Ling; Li, Chi Yu; Cheung, Wing Hoi

    2015-01-01

    Sarcopenia is an age-related systemic syndrome with progressive deterioration in skeletal muscle functions and loss in mass. Although the senescence-accelerated mouse P8 (SAMP8) was reported valid for muscular ageing research, there was no report on the details such as sarcopenia onset time. Therefore, this study was to investigate the change of muscle mass, structure and functions during the development of sarcopenia. Besides the average life span, muscle mass, structural and functional measurements were also studied. Male SAMP8 animals were examined at month 6, 7, 8, 9, and 10, in which the right gastrocnemius was isolated and tested for ex vivo contractile properties and fatigability while the contralateral one was harvested for muscle fiber cross-sectional area (FCSA) and typing assessments. Results showed that the peak of muscle mass appeared at month 7 and the onset of contractility decline was observed from month 8. Compared with month 8, most of the functional parameters at month 10 decreased significantly. Structurally, muscle fiber type IIA made up the largest proportion of the gastrocnemius, and the fiber size was found to peak at month 8. Based on the altered muscle mass, structural and functional outcomes, it was concluded that the onset of sarcopenia in SAMP8 animals was at month 8. SAMP8 animals at month 8 should be at pre-sarcopenia stage while month 10 at sarcopenia stage. It is confirmed that SAMP8 mouse can be used in sarcopenia research with established time line in this study. PMID:26193895

  5. Biosynthesis and biological functions of terpenoids in plants.

    PubMed

    Tholl, Dorothea

    2015-01-01

    Terpenoids (isoprenoids) represent the largest and most diverse class of chemicals among the myriad compounds produced by plants. Plants employ terpenoid metabolites for a variety of basic functions in growth and development but use the majority of terpenoids for more specialized chemical interactions and protection in the abiotic and biotic environment. Traditionally, plant-based terpenoids have been used by humans in the food, pharmaceutical, and chemical industries, and more recently have been exploited in the development of biofuel products. Genomic resources and emerging tools in synthetic biology facilitate the metabolic engineering of high-value terpenoid products in plants and microbes. Moreover, the ecological importance of terpenoids has gained increased attention to develop strategies for sustainable pest control and abiotic stress protection. Together, these efforts require a continuous growth in knowledge of the complex metabolic and molecular regulatory networks in terpenoid biosynthesis. This chapter gives an overview and highlights recent advances in our understanding of the organization, regulation, and diversification of core and specialized terpenoid metabolic pathways, and addresses the most important functions of volatile and nonvolatile terpenoid specialized metabolites in plants.

  6. Molecular Mechanisms and Biological Functions of siRNA.

    PubMed

    Dana, Hassan; Chalbatani, Ghanbar Mahmoodi; Mahmoodzadeh, Habibollah; Karimloo, Rezvan; Rezaiean, Omid; Moradzadeh, Amirreza; Mehmandoost, Narges; Moazzen, Fateme; Mazraeh, Ali; Marmari, Vahid; Ebrahimi, Mohammad; Rashno, Mohammad Menati; Abadi, Saeid Jan; Gharagouzlo, Elahe

    2017-06-01

    One of the most important advances in biology has been the discovery that siRNA (small interfering RNA) is able to regulate the expression of genes, by a phenomenon known as RNAi (RNA interference). The discovery of RNAi, first in plants and Caenorhabditis elegans and later in mammalian cells, led to the emergence of a transformative view in biomedical research. siRNA has gained attention as a potential therapeutic reagent due to its ability to inhibit specific genes in many genetic diseases. siRNAs can be used as tools to study single gene function both in vivo and in-vitro and are an attractive new class of therapeutics, especially against undruggable targets for the treatment of cancer and other diseases. The siRNA delivery systems are categorized as non-viral and viral delivery systems. The non-viral delivery system includes polymers; Lipids; peptides etc. are the widely studied delivery systems for siRNA. Effective pharmacological use of siRNA requires 'carriers' that can deliver the siRNA to its intended site of action. The carriers assemble the siRNA into supramolecular complexes that display functional properties during the delivery process.

  7. Translating Lung Function Genome-Wide Association Study (GWAS) Findings: New Insights for Lung Biology.

    PubMed

    Kheirallah, A K; Miller, S; Hall, I P; Sayers, I

    2016-01-01

    Chronic respiratory diseases are a major cause of worldwide mortality and morbidity. Although hereditary severe deficiency of α1 antitrypsin (A1AD) has been established to cause emphysema, A1AD accounts for only ∼ 1% of Chronic Obstructive Pulmonary Disease (COPD) cases. Genome-wide association studies (GWAS) have been successful at detecting multiple loci harboring variants predicting the variation in lung function measures and risk of COPD. However, GWAS are incapable of distinguishing causal from noncausal variants. Several approaches can be used for functional translation of genetic findings. These approaches have the scope to identify underlying alleles and pathways that are important in lung function and COPD. Computational methods aim at effective functional variant prediction by combining experimentally generated regulatory information with associated region of the human genome. Classically, GWAS association follow-up concentrated on manipulation of a single gene. However association data has identified genetic variants in >50 loci predicting disease risk or lung function. Therefore there is a clear precedent for experiments that interrogate multiple candidate genes in parallel, which is now possible with genome editing technology. Gene expression profiling can be used for effective discovery of biological pathways underpinning gene function. This information may be used for informed decisions about cellular assays post genetic manipulation. Investigating respiratory phenotypes in human lung tissue and specific gene knockout mice is a valuable in vivo approach that can complement in vitro work. Herein, we review state-of-the-art in silico, in vivo, and in vitro approaches that may be used to accelerate functional translation of genetic findings.

  8. Effector genomics accelerates discovery and functional profiling of potato disease resistance and phytophthora infestans avirulence genes.

    PubMed

    Vleeshouwers, Vivianne G A A; Rietman, Hendrik; Krenek, Pavel; Champouret, Nicolas; Young, Carolyn; Oh, Sang-Keun; Wang, Miqia; Bouwmeester, Klaas; Vosman, Ben; Visser, Richard G F; Jacobsen, Evert; Govers, Francine; Kamoun, Sophien; Van der Vossen, Edwin A G

    2008-08-06

    Potato is the world's fourth largest food crop yet it continues to endure late blight, a devastating disease caused by the Irish famine pathogen Phytophthora infestans. Breeding broad-spectrum disease resistance (R) genes into potato (Solanum tuberosum) is the best strategy for genetically managing late blight but current approaches are slow and inefficient. We used a repertoire of effector genes predicted computationally from the P. infestans genome to accelerate the identification, functional characterization, and cloning of potentially broad-spectrum R genes. An initial set of 54 effectors containing a signal peptide and a RXLR motif was profiled for activation of innate immunity (avirulence or Avr activity) on wild Solanum species and tentative Avr candidates were identified. The RXLR effector family IpiO induced hypersensitive responses (HR) in S. stoloniferum, S. papita and the more distantly related S. bulbocastanum, the source of the R gene Rpi-blb1. Genetic studies with S. stoloniferum showed cosegregation of resistance to P. infestans and response to IpiO. Transient co-expression of IpiO with Rpi-blb1 in a heterologous Nicotiana benthamiana system identified IpiO as Avr-blb1. A candidate gene approach led to the rapid cloning of S. stoloniferum Rpi-sto1 and S. papita Rpi-pta1, which are functionally equivalent to Rpi-blb1. Our findings indicate that effector genomics enables discovery and functional profiling of late blight R genes and Avr genes at an unprecedented rate and promises to accelerate the engineering of late blight resistant potato varieties.

  9. Cyclic-glycine-proline accelerates mammary involution by promoting apoptosis and inhibiting IGF-1 function.

    PubMed

    Singh-Mallah, Gagandeep; McMahon, Christopher D; Guan, Jian; Singh, Kuljeet

    2017-12-01

    In rodents, post-lactational involution of mammary glands is characterized by the loss of mammary epithelial cells via apoptosis, which is associated with a decline in the expression of insulin-like growth factor-1 (IGF-1). Overexpression of IGF-1 delays involution by inhibiting apoptosis of epithelial cells and preserving the remaining secretory alveoli. Cyclic-glycine-proline (cGP), a metabolite of IGF-1, normalizes IGF-1 function under pathological conditions by regulating the bioavailability of IGF-1. The present study investigated the effect of cGP on the physiological decline in IGF-1 function during post-lactational mammary involution. Rat dams were gavaged with either cGP (3 mg/kg) or saline once per day from post-natal d8-22. Before collecting tissue on post-natal d23, a pair of mammary glands were sealed on d20 (72 hr-engorgement, thus representative of late-involution) and d22 (24 hr-engorgement, thus representative of mid-involution), while the remaining glands were allowed to involute naturally (early-involution). During early-involution, cGP accelerated the loss of mammary cells through apoptosis, resulting in an earlier clearance of intact secretory alveoli compared with the control group. This coincided with an earlier up-regulation of the cell survival factors, Bcl-xl and IGF-1R, in the early-involution cGP glands compared with the control glands. During late-involution, cGP reduced the bioactivity of IGF-1, which was evident through decreased phosphorylation of IGF-1R in the regressed alveoli. Maternal administration of cGP did not alter milk production and composition during early-, peak-, or late-stage of lactation. These data show that cGP accelerates post-lactational involution by promoting apoptosis and the physiological decline in IGF-1 function. © 2017 Wiley Periodicals, Inc.

  10. Effector Genomics Accelerates Discovery and Functional Profiling of Potato Disease Resistance and Phytophthora Infestans Avirulence Genes

    PubMed Central

    Vleeshouwers, Vivianne G. A. A.; Rietman, Hendrik; Krenek, Pavel; Champouret, Nicolas; Young, Carolyn; Oh, Sang-Keun; Wang, Miqia; Bouwmeester, Klaas; Vosman, Ben; Visser, Richard G. F.; Jacobsen, Evert; Govers, Francine; Kamoun, Sophien; Van der Vossen, Edwin A. G.

    2008-01-01

    Potato is the world's fourth largest food crop yet it continues to endure late blight, a devastating disease caused by the Irish famine pathogen Phytophthora infestans. Breeding broad-spectrum disease resistance (R) genes into potato (Solanum tuberosum) is the best strategy for genetically managing late blight but current approaches are slow and inefficient. We used a repertoire of effector genes predicted computationally from the P. infestans genome to accelerate the identification, functional characterization, and cloning of potentially broad-spectrum R genes. An initial set of 54 effectors containing a signal peptide and a RXLR motif was profiled for activation of innate immunity (avirulence or Avr activity) on wild Solanum species and tentative Avr candidates were identified. The RXLR effector family IpiO induced hypersensitive responses (HR) in S. stoloniferum, S. papita and the more distantly related S. bulbocastanum, the source of the R gene Rpi-blb1. Genetic studies with S. stoloniferum showed cosegregation of resistance to P. infestans and response to IpiO. Transient co-expression of IpiO with Rpi-blb1 in a heterologous Nicotiana benthamiana system identified IpiO as Avr-blb1. A candidate gene approach led to the rapid cloning of S. stoloniferum Rpi-sto1 and S. papita Rpi-pta1, which are functionally equivalent to Rpi-blb1. Our findings indicate that effector genomics enables discovery and functional profiling of late blight R genes and Avr genes at an unprecedented rate and promises to accelerate the engineering of late blight resistant potato varieties. PMID:18682852

  11. Attenuated hypothalamic-pituitary-adrenal axis functioning predicts accelerated pubertal development in girls 1 year later.

    PubMed

    Saxbe, Darby E; Negriff, Sonya; Susman, Elizabeth J; Trickett, Penelope K

    2015-08-01

    Accelerated pubertal development has been linked to adverse early environments and may heighten subsequent mental and physical health risks. Hypothalamic-pituitary-adrenal axis functioning has been posited as a mechanism whereby stress may affect pubertal development, but the literature lacks prospective tests of this mechanism. The current study assessed 277 youth (M = 10.84 years, SD = 1.14), 138 boys and 139 girls, who reported on their pubertal development and underwent the Trier Social Stress Test for Children at baseline and returned to the laboratory approximately 1 year later (M = 1.12 years, range = 0.59-1.98 years). For girls, lower cortisol area under the curve (with respect to ground) at Time 1 predicted more advanced pubertal development at Time 2, controlling for Time 1 pubertal development. This association persisted after additional covariates including age, body mass index, race, and maltreatment history were introduced, and was driven by adrenal rather than gonadal development. Cortisol was not linked to boys' subsequent pubertal development, and no interaction by gender or by maltreatment appeared. These results suggest that attenuated cortisol, reported in other studies of children exposed to early adversity, may contribute to accelerated pubertal tempo in girls.

  12. Exosomes derived from endothelial progenitor cells attenuate vascular repair and accelerate reendothelialization by enhancing endothelial function.

    PubMed

    Li, Xiaocong; Chen, Chunyuan; Wei, Liming; Li, Qing; Niu, Xin; Xu, Yanjun; Wang, Yang; Zhao, Jungong

    2016-02-01

    Exosomes, a key component of cell paracrine secretion, can exert protective effects in various disease models. However, application of exosomes in vascular repair and regeneration has rarely been reported. In this study, we tested whether endothelial progenitor cell (EPC)-derived exosomes possessed therapeutic effects in rat models of balloon-induced vascular injury by accelerating reendothelialization. Exosomes were obtained from the conditioned media of EPCs isolated from human umbilical cord blood. Induction of the endothelial injury was performed in the rats' carotid artery, and the pro-re-endothelialization capacity of EPC-derived exosomes was measured. The in vitro effects of exosomes on the proliferation and migration of endothelial cells were investigated. We found that the EPC-derived exosomes accelerated the re-endothelialization in the early phase after endothelial damage in the rat carotid artery. We also demonstrated that these exosomes enhanced the proliferation and migration of endothelial cells in vitro. Moreover, endothelial cells stimulated with these exosomes showed increased expression of angiogenesis-related molecules. Taken together, our results indicate that exosomes are an active component of the paracrine secretion of human EPCs and can promote vascular repair in rat models of balloon injury by up-regulating endothelial cells function. Copyright © 2015. Published by Elsevier Inc.

  13. Commissioning of helium injector for coupled radio frequency quadrupole and separated function radio frequency quadrupole accelerator.

    PubMed

    Peng, Shixiang; Chen, Jia; Ren, Haitao; Zhao, Jie; Xu, Yuan; Zhang, Tao; Zhang, Ailing; Xia, Wenlong; Gao, Shuli; Wang, Zhi; Luo, Yuting; Guo, Zhiyu; Chen, Jia'er

    2014-02-01

    A project to study a new type of acceleration structure has been launched at Peking University, in which a traditional radio frequency quadrupole (RFQ) and a separated function radio frequency quadrupole are coupled in one cavity to accelerate the He+ beam. A helium injector for this project is developed. The injector consists of a 2.45 GHz permanent magnet electron cyclotron resonance ion source and a 1.16 m long low energy beam transport (LEBT). The commissioning of this injector was carried out and an onsite test was held in June 2013. A 14 mA He+ beam with the energy of 30 keV has been delivered to the end of the LEBT, where a diaphragm with the diameter of 7 mm is located. The position of the diaphragm corresponds to the entrance of the RFQ electrodes. The beam emittance and fraction were measured after the 7 mm diaphragm. Its rms emittance is about 0.14 π mm mrad and the fraction of He+ is about 99%.

  14. Commissioning of helium injector for coupled radio frequency quadrupole and separated function radio frequency quadrupole accelerator

    SciTech Connect

    Peng, Shixiang Chen, Jia; Ren, Haitao; Zhao, Jie; Xu, Yuan; Zhang, Tao; Xia, Wenlong; Gao, Shuli; Wang, Zhi; Luo, Yuting; Guo, Zhiyu; Zhang, Ailing; Chen, Jia'er

    2014-02-15

    A project to study a new type of acceleration structure has been launched at Peking University, in which a traditional radio frequency quadrupole (RFQ) and a separated function radio frequency quadrupole are coupled in one cavity to accelerate the He+ beam. A helium injector for this project is developed. The injector consists of a 2.45 GHz permanent magnet electron cyclotron resonance ion source and a 1.16 m long low energy beam transport (LEBT). The commissioning of this injector was carried out and an onsite test was held in June 2013. A 14 mA He+ beam with the energy of 30 keV has been delivered to the end of the LEBT, where a diaphragm with the diameter of 7 mm is located. The position of the diaphragm corresponds to the entrance of the RFQ electrodes. The beam emittance and fraction were measured after the 7 mm diaphragm. Its rms emittance is about 0.14 π mm mrad and the fraction of He+ is about 99%.

  15. Basis function repetitive and feedback control with application to a particle accelerator

    NASA Astrophysics Data System (ADS)

    Akogyeram, Raphael Akuete

    2002-09-01

    The thesis addresses three problem areas within repetitive control. Firstly, it addresses issues concerning the ability of repetitive control and feedback control systems to eliminate periodic disturbances occurring above the Nyquist frequency of the hardware. Methods are developed for decomposing and unfolding notch filter or comb filter feedback control so that disturbances above Nyquist frequency can be canceled. Phenomena affecting final error levels are discussed, including error in unfolding, coarseness of zero-order hold cancellation, and waterbed effects in the feedback control system frequency response for different sample rates. Secondly, matched basis function repetitive control laws are developed for batch mode and real time implementation to converge to zero tracking error in the presence of periodic disturbances. For both control methods, conditions are given that guarantee asymptotic and monotonic convergence. Stability tests are formulated to examine stability when the period of a disturbance is not an integer number of sample times, and when there are multiple unrelated periods whose common period is too long to use. Thirdly, an understanding is developed of the optimum division of labor between the objectives accomplished by feedback and the objectives accomplished by repetitive control action. Some experimental results of the particle accelerator testbed at Thomas Jefferson National Accelerator Facility, Newport News, Virginia, are reported.

  16. Attenuated hypothalamic–pituitary–adrenal axis functioning predicts accelerated pubertal development in girls 1 year later

    PubMed Central

    SAXBE, DARBY E.; NEGRIFF, SONYA; SUSMAN, ELIZABETH J.; TRICKETT, PENELOPE K.

    2015-01-01

    Accelerated pubertal development has been linked to adverse early environments and may heighten subsequent mental and physical health risks. Hypothalamic–pituitary–adrenal axis functioning has been posited as a mechanism whereby stress may affect pubertal development, but the literature lacks prospective tests of this mechanism. The current study assessed 277 youth (M = 10.84 years, SD = 1.14), 138 boys and 139 girls, who reported on their pubertal development and underwent the Trier Social Stress Test for Children at baseline and returned to the laboratory approximately 1 year later (M = 1.12 years, range = 0.59–1.98 years). For girls, lower cortisol area under the curve (with respect to ground) at Time 1 predicted more advanced pubertal development at Time 2, controlling for Time 1 pubertal development. This association persisted after additional covariates including age, body mass index, race, and maltreatment history were introduced, and was driven by adrenal rather than gonadal development. Cortisol was not linked to boys’ subsequent pubertal development, and no interaction by gender or by maltreatment appeared. These results suggest that attenuated cortisol, reported in other studies of children exposed to early adversity, may contribute to accelerated pubertal tempo in girls. PMID:25154521

  17. Using cheminformatics for the identification of biological functions of small molecules in metabolic pathway.

    PubMed

    Niu, Bing; Lu, Wencong

    2013-01-01

    Small molecules are involved in metabolic pathways responsible for many biological activities. Therefore it is essential to study them to uncover the unknown biological function of highly complex living systems. It is a crucial step in modern drug discovery to correctly and effectively discover small molecules' biological function since small molecules are related to many protein functions and biological processes. This paper presents the application of cheminformatics approaches in predicting small molecule's (ligand's) biological function in metabolic pathway. Many examples of success in identification and prediction in the area of small molecule metabolic pathway mapping and small molecule-protein interaction prediction have been discussed.

  18. Functionalized silk fibroin dressing with topical bioactive insulin release for accelerated chronic wound healing.

    PubMed

    Li, Xiufang; Liu, Yan; Zhang, Jian; You, Renchuan; Qu, Jing; Li, Mingzhong

    2017-03-01

    The healing of chronic wounds remains a key challenge in regenerative medicine. To promote wound healing, a bioactive wound dressing is required. In this study, a functionalized silk fibroin dressing with topical bioactive insulin release was prepared for the treatment of chronic wounds. For this purpose, insulin-encapsulated silk fibroin (SF) microparticles were prepared by coaxial electrospraying of aqueous SF solution under mild processing conditions. Insulin was successfully encapsulated in the inner layer of SF microparticles, providing a sustained insulin release for up to 28days. It was found that the insulin released from the microparticles could maintain original molecular conformation. Moreover, the cell migration assay based on human keratinocyte and endothelial cells confirmed that the insulin released from SF microparticles retained its native bioactivity. Furthermore, the insulin-encapsulated microparticles were loaded into a SF sponge, functioned as a bioactive wound dressing, and the in vivo therapeutic effect of the sponge dressing was evaluated on dorsal full thickness wounds of diabetic Sprague-Dawley rats. The results showed that an insulin-functionalized SF dressing accelerated wound closure, collagen deposition and vascularization, thus, significantly promoting wound healing. The insulin-functionalized SF dressing provides new treatment options for chronic wounds. Copyright © 2016 Elsevier B.V. All rights reserved.

  19. Polymer biomaterial constructs for regenerative medicine and functional biological systems

    NASA Astrophysics Data System (ADS)

    Meng, Linghui

    The use of collagen as a biomaterial is currently undergoing a renaissance in the tissue engineering field. The excellent biocompatibility and safety due to its biological characteristics, such as biodegradability and weak antigenicity, make collagen a primary material resource in medical applications. Described herein is work towards the development of novel collagen-based matrices, with additional multi-functionality imparted through a novel in-situ crosslinking approach. The process of electrospinning has become a widely used technique for the creation of fibrous scaffolds for tissue engineering applications due to its ability to rapidly create structures composed of nano-scale polymer fibers closely resembling the architecture of the extracellular matrix (ECM). Collagen-PCL sheath-core bicomponent fibrous scaffolds were fabricated using a novel variation on traditional electrospinning, known as co-axial electrospinning. The results showed that the addition of a synthetic polymer core into collagen nanofibers remarkably increased the mechanical strength of collagen matrices spun from the benign solvent system. A novel single-step, in-situ collagen crosslink approach was developed in order to solve the problems dominating traditional collagen crosslinking methods, such as dimensional shrinking and loss of porous morphology, and to simplify the crosslinking procedure for electrospun collagen scaffolds. The excess amount of NHS present in the crosslinking mixture was found to delay the EDC/collagen coupling reaction in a controlled fashion. Fundamental investigations into the development and characterization of in-situ crosslinked collagen matrices such as fibrous scaffolds, gels and sponges, as well as their biomedical applications including cell culture substrates, wound dressings, drug delivery matrices and bone regeneration substitutes, were performed. The preliminary mice studies indicated that the in-situ crosslinked collagen matrices could be good candidates

  20. Whittaker functions in beam driven plasma wakefield acceleration for a plasma with a parabolic density profile

    SciTech Connect

    Golian, Y.; Dorranian, D.; Aslaninejad, M.

    2016-01-15

    A model for the interaction of charged particle beams and plasma for a linear wakefield generation in a parabolic plasma channel is presented. The density profile has the maximum on the axis. A Gaussian proton beam is employed to excite the plasma wakefield in the channel. We have built a thorough analytical model and solved the governing equations for the wakefield acceleration of a charged particle beam. The longitudinal and radial wakefields are expressed by Whittaker functions, and for certain parameters of plasma and the beam, their behaviours in longitudinal and radial directions are investigated. It is observed that the radial electric field generated by the bunch increases with the distance behind the bunch.

  1. Water as a green solvent for efficient synthesis of isocoumarins through microwave-accelerated and Rh/Cu-catalyzed C-H/O-H bond functionalization

    SciTech Connect

    Li, Qiu; Yan, Yunnan; Wang, Xiaowei; Gong, Binwei; Tang, Xiaobo; Shi, JingJing; Xu, H. Eric; Yi, Wei

    2014-08-14

    Green chemistry that uses water as a solvent has recently received great attention in organic synthesis. Here we report an efficient synthesis of biologically important isocoumarins through direct cleavage of C–H/O–H bonds by microwave-accelerated and Rh/Cu-catalyzed oxidative annulation of various substituted benzoic acids, where water is used as the only solvent in the reactions. The remarkable features of this “green” methodology include high product yields, wide tolerance of various functional groups as substrates, and excellent region-/site-specificities, thus rendering this methodology a highly versatile and eco-friendly alternative to the existing methods for synthesizing isocoumarins and other biologically important derivatives such as isoquinolones.

  2. Lung function, biological monitoring, and biological effect monitoring of gemstone cutters exposed to beryls

    PubMed Central

    Wegner, R.; Heinrich-Ramm, R.; Nowak, D.; Olma, K.; Poschadel, B.; Szadkowski, D.

    2000-01-01

    OBJECTIVES—Gemstone cutters are potentially exposed to various carcinogenic and fibrogenic metals such as chromium, nickel, aluminium, and beryllium, as well as to lead. Increased beryllium concentrations had been reported in the air of workplaces of beryl cutters in Idar-Oberstein, Germany. The aim of the survey was to study the excretion of beryllium in cutters and grinders with occupational exposure to beryls—for example, aquamarines and emeralds—to examine the prevalence of beryllium sensitisation with the beryllium lymphocyte transformation test (BeLT), to examine the prevalence of lung disease induced by beryllium, to describe the internal load of the respective metals relative to work process, and to screen for genotoxic effects in this particular profession.
METHODS—In a cross sectional investigation, 57 out of 100 gemstone cutters working in 12 factories in Idar-Oberstein with occupational exposure to beryls underwent medical examinations, a chest radiograph, lung function testing (spirometry, airway resistance with the interrupter technique), and biological monitoring, including measurements of aluminium, chromium, and nickel in urine as well as lead in blood. Beryllium in urine was measured with a newly developed direct electrothermal atomic absorption spectroscopy technique with a measurement limit of 0.06 µg/l. Also, cytogenetic tests (rates of micronuclei and sister chromatid exchange), and a BeLT were performed. Airborne concentrations of beryllium were measured in three factories. As no adequate local control group was available, the cutters were categorised into those with an exposure to beryls of >4 hours/week (group A) and ⩽4 hours/week (group B).
RESULTS—Clinical, radiological, or spirometric abnormalities indicating pneumoconiosis were detected in none of the gemstone cutters. Metal concentrations in biological material were far below the respective biological limit values, and beryllium in urine was only measurable in

  3. Understanding Nuclear Receptor Form and Function Using Structural Biology

    PubMed Central

    Rastinejad, Fraydoon; Huang, Pengxiang; Chandra, Vikas; Khorasanizadeh, Sepideh

    2013-01-01

    Nuclear receptors (NR) are a major transcription factor family whose members selectively bind small molecule lipophilic ligands and transduce those signals into specific changes in gene programs. For over two decades, structural biology efforts were directed exclusively on the individual ligand binding domains (LBDs) or DNA binding domains (DBDs) of NRs. These analyses revealed the basis for both ligand and DNA binding, and also revealed receptor conformations representing both the activated and repressed states. Additionally, crystallographic studies explained how NR LBD surfaces recognize discrete portions of transcriptional coregulators. The many structural snapshots of LBDs have also guided the development of synthetic ligands with therapeutic potential. Yet, the exclusive structural focus on isolated NR domains has made it difficult to conceptualize how all the NR polypeptide segments are coordinated physically and functionally in the context of receptor quaternary architectures. Newly emerged crystal structures of the PPARγ-RXRα heterodimer and HNF-4α homodimer have recently revealed the higher order organizations of these receptor complexes on DNA, as well as the complexity and uniqueness of their domain-domain interfaces. These emerging structural advances promise to better explain how signals in one domain can be allosterically transmitted to distal receptor domains, also providing much better frameworks for guiding future drug discovery efforts. PMID:24103914

  4. Function and Regulation of Lipid Biology in Caenorhabditis elegans Aging

    PubMed Central

    Hou, Nicole Shangming; Taubert, Stefan

    2012-01-01

    Rapidly expanding aging populations and a concomitant increase in the prevalence of age-related diseases are global health problems today. Over the past three decades, a large body of work has led to the identification of genes and regulatory networks that affect longevity and health span, often benefiting from the tremendous power of genetics in vertebrate and invertebrate model organisms. Interestingly, many of these factors appear linked to lipids, important molecules that participate in cellular signaling, energy metabolism, and structural compartmentalization. Despite the putative link between lipids and longevity, the role of lipids in aging remains poorly understood. Emerging data from the model organism Caenorhabditis elegans suggest that lipid composition may change during aging, as several pathways that influence aging also regulate lipid metabolism enzymes; moreover, some of these enzymes apparently play key roles in the pathways that affect the rate of aging. By understanding how lipid biology is regulated during C. elegans aging, and how it impacts molecular, cellular, and organismal function, we may gain insight into novel ways to delay aging using genetic or pharmacological interventions. In the present review we discuss recent insights into the roles of lipids in C. elegans aging, including regulatory roles played by lipids themselves, the regulation of lipid metabolic enzymes, and the roles of lipid metabolism genes in the pathways that affect aging. PMID:22629250

  5. Biological function of a polysaccharide degrading enzyme in the periplasm.

    PubMed

    Wang, Yajie; Moradali, M Fata; Goudarztalejerdi, Ali; Sims, Ian M; Rehm, Bernd H A

    2016-11-08

    Carbohydrate polymers are industrially and medically important. For instance, a polysaccharide, alginate (from seaweed), is widely used in food, textile and pharmaceutical industries. Certain bacteria also produce alginate through membrane spanning multi-protein complexes. Using Pseudomonas aeruginosa as a model organism, we investigated the biological function of an alginate degrading enzyme, AlgL, in alginate production and biofilm formation. We showed that AlgL negatively impacts alginate production through its enzymatic activity. We also demonstrated that deletion of AlgL does not interfere with polymer length control, epimerization degree or stability of the biosynthesis complex, arguing that AlgL is a free periplasmic protein dispensable for alginate production. This was further supported by our protein-stability and interaction experiments. Interestingly, over-production of AlgL interfered with polymer length control, suggesting that AlgL could be loosely associated with the biosynthesis complex. In addition, chromosomal expression of algL enhanced alginate O-acetylation; both attachment and dispersal stages of the bacterial biofilm lifecycle were sensitive to the level of O-acetylation. Since this modification also protects the pathogen against host defences and enhances other virulence factors, chromosomal expression of algL could be important for the pathogenicity of this organism. Overall, this work improves our understanding of bacterial alginate production and provides new knowledge for alginate production and disease control.

  6. Biological function of a polysaccharide degrading enzyme in the periplasm

    PubMed Central

    Wang, Yajie; Moradali, M. Fata; Goudarztalejerdi, Ali; Sims, Ian M.; Rehm, Bernd H. A.

    2016-01-01

    Carbohydrate polymers are industrially and medically important. For instance, a polysaccharide, alginate (from seaweed), is widely used in food, textile and pharmaceutical industries. Certain bacteria also produce alginate through membrane spanning multi-protein complexes. Using Pseudomonas aeruginosa as a model organism, we investigated the biological function of an alginate degrading enzyme, AlgL, in alginate production and biofilm formation. We showed that AlgL negatively impacts alginate production through its enzymatic activity. We also demonstrated that deletion of AlgL does not interfere with polymer length control, epimerization degree or stability of the biosynthesis complex, arguing that AlgL is a free periplasmic protein dispensable for alginate production. This was further supported by our protein-stability and interaction experiments. Interestingly, over-production of AlgL interfered with polymer length control, suggesting that AlgL could be loosely associated with the biosynthesis complex. In addition, chromosomal expression of algL enhanced alginate O-acetylation; both attachment and dispersal stages of the bacterial biofilm lifecycle were sensitive to the level of O-acetylation. Since this modification also protects the pathogen against host defences and enhances other virulence factors, chromosomal expression of algL could be important for the pathogenicity of this organism. Overall, this work improves our understanding of bacterial alginate production and provides new knowledge for alginate production and disease control. PMID:27824067

  7. Functional Synchronization of Biological Rhythms in a Tritrophic System

    PubMed Central

    Zhang, Sufang; Wei, Jianing; Guo, Xiaojiao; Liu, Tong-Xian; Kang, Le

    2010-01-01

    In a tritrophic system formed by a plant, an herbivore and a natural enemy, each component has its own biological rhythm. However, the rhythm correlations among the three levels and the underlying mechanisms in any tritrophic system are largely unknown. Here, we report that the rhythms exhibited bidirectional correlations in a model tritrophic system involving a lima bean, a pea leafminer and a parasitoid. From the bottom-up perspective, the rhythm was initiated from herbivore feeding, which triggered the rhythms of volatile emissions; then the rhythmic pattern of parasitoid activities was affected, and these rhythms were synchronized by a light switch signal. Increased volatile concentration can enhance the intensity of parasitoid locomotion and oviposition only under light. From the top-down perspective, naive and oviposition-experienced parasitoids were able to utilize the different volatile rhythm information from the damaged plant to locate host leafminers respectively. Our results indicated that the three interacting organisms in this system can achieve rhythmic functional synchronization under a natural light-dark photoperiod, but not under constant light or darkness. These findings provide new insight into the rhythm synchronization of three key players that contribute to the utilization of light and chemical signals, and our results may be used as potential approaches for manipulating natural enemies. PMID:20552008

  8. Understanding nuclear receptor form and function using structural biology.

    PubMed

    Rastinejad, Fraydoon; Huang, Pengxiang; Chandra, Vikas; Khorasanizadeh, Sepideh

    2013-12-01

    Nuclear receptors (NRs) are a major transcription factor family whose members selectively bind small-molecule lipophilic ligands and transduce those signals into specific changes in gene programs. For over two decades, structural biology efforts were focused exclusively on the individual ligand-binding domains (LBDs) or DNA-binding domains of NRs. These analyses revealed the basis for both ligand and DNA binding and also revealed receptor conformations representing both the activated and repressed states. Additionally, crystallographic studies explained how NR LBD surfaces recognize discrete portions of transcriptional coregulators. The many structural snapshots of LBDs have also guided the development of synthetic ligands with therapeutic potential. Yet, the exclusive structural focus on isolated NR domains has made it difficult to conceptualize how all the NR polypeptide segments are coordinated physically and functionally in the context of receptor quaternary architectures. Newly emerged crystal structures of the peroxisome proliferator-activated receptor-γ-retinoid X receptor α (PPARγ-RXRα) heterodimer and hepatocyte nuclear factor (HNF)-4α homodimer have recently revealed the higher order organizations of these receptor complexes on DNA, as well as the complexity and uniqueness of their domain-domain interfaces. These emerging structural advances promise to better explain how signals in one domain can be allosterically transmitted to distal receptor domains, also providing much better frameworks for guiding future drug discovery efforts.

  9. Biological/biomedical accelerator mass spectrometry targets. 1. optimizing the CO2 reduction step using zinc dust.

    PubMed

    Kim, Seung-Hyun; Kelly, Peter B; Clifford, Andrew J

    2008-10-15

    Biological and biomedical applications of accelerator mass spectrometry (AMS) use isotope ratio mass spectrometry to quantify minute amounts of long-lived radioisotopes such as (14)C. AMS target preparation involves first the oxidation of carbon (in sample of interest) to CO 2 and second the reduction of CO 2 to filamentous, fluffy, fuzzy, or firm graphite-like substances that coat a -400-mesh spherical iron powder (-400MSIP) catalyst. Until now, the quality of AMS targets has been variable; consequently, they often failed to produce robust ion currents that are required for reliable, accurate, precise, and high-throughput AMS for biological/biomedical applications. Therefore, we described our optimized method for reduction of CO 2 to high-quality uniform AMS targets whose morphology we visualized using scanning electron microscope pictures. Key features of our optimized method were to reduce CO 2 (from a sample of interest that provided 1 mg of C) using 100 +/- 1.3 mg of Zn dust, 5 +/- 0.4 mg of -400MSIP, and a reduction temperature of 500 degrees C for 3 h. The thermodynamics of our optimized method were more favorable for production of graphite-coated iron powders (GCIP) than those of previous methods. All AMS targets from our optimized method were of 100% GCIP, the graphitization yield exceeded 90%, and delta (13)C was -17.9 +/- 0.3 per thousand. The GCIP reliably produced strong (12)C (-) currents and accurate and precise F m values. The observed F m value for oxalic acid II NIST SRM deviated from its accepted F m value of 1.3407 by only 0.0003 +/- 0.0027 (mean +/- SE, n = 32), limit of detection of (14)C was 0.04 amol, and limit of quantification was 0.07 amol, and a skilled analyst can prepare as many as 270 AMS targets per day. More information on the physical (hardness/color), morphological (SEMs), and structural (FT-IR, Raman, XRD spectra) characteristics of our AMS targets that determine accurate, precise, and high-hroughput AMS measurement are in the

  10. Graft-accelerated virus-induced gene silencing facilitates functional genomics in rose flowers.

    PubMed

    Yan, Huijun; Shi, Shaochuan; Ma, Nan; Cao, Xiaoqian; Zhang, Hao; Qiu, Xianqin; Wang, Qigang; Jian, Hongying; Zhou, Ningning; Zhang, Zhao; Tang, Kaixue

    2017-09-12

    Rose has emerged as a model ornamental plant for studies of flower development, senescence, and morphology, as well as the metabolism of floral fragrances and colors. Virus-induced gene silencing (VIGS) has long since been used in functional genomics studies of rose by vacuum infiltration of cuttings or seedlings with an Agrobacterium suspension carrying TRV-derived vectors. However, VIGS in rose flowers remains a challenge because of its low efficiency and long time to silencing. Here we present a novel and rapid VIGS method that can be used to analyze gene function in rose, called 'graft-accelerated VIGS', where axillary sprouts are cut off the rose plant and vacuum infiltrated with Agrobacterium. The inoculated scions are then grafted back onto the plants to flower and silencing phenotypes can be observed within five weeks post infiltration. Using this new method, we successfully silenced the expression of the RhDFR1, RhAG, and RhNUDX1 in rose flowers, and affected their color, petal number, as well as fragrance, respectively. This grafting method will facilitate high-throughput functional analysis of genes in rose flowers. Importantly, it may also be applied to other woody species that are not currently amenable to VIGS by conventional leaf or plantlet/seedling infiltration methods. This article is protected by copyright. All rights reserved.

  11. ACTH4 -10, Substance P, and Dizolcipine (Mk-801) Accelerate Functional Recovery After Hemilabyrinthectomy in Goldfish

    PubMed Central

    Mattioli, R.; Huston, J. P.; Spieler, R. E.

    2000-01-01

    In this study, we evaluated the goldfish model of hemilabyrinthectomy for investigating potential recovery-promoting drugs. In this lesion model, the unilateral removal of the labyrinth induces a postural imbalance in response to light (Dorsal Light Reflex), from which the animals can recover over time. The behavioral effects of two neuropeptides were tested–namely, of substance P and ACTH4-10, both of which are known to promote functional recovery in several other lesion models. Furthermore, the effect of MK- 801, an antagonist of the glutamatergic NMDAreceptor subtype, was tested because this substance has also been shown to exert a neuroprotective effect. After lesion of the right labyrinth, the animals (n=12) were treated intraperitoneally daily either with vehicle (n=12), substance P (n=11), ACTH4-10 (n=12), or MK- 801 (n=12). Another group (n=11), which served as a non-lesion control, did not receive hemilabyrinthectomy or systemic injections. The lesion group, treated post-operatively with vehicle, did not recover from the postural deviation over the 24-d testing period. In contrast, all three test substances accelerated the functional recovery after unilateral labyrinthectomy. The decrease of the dorsal light reflex persisted even after cessation of drug treatment after 20d. The results indicate that using the dorsal light reflex in the model of hemilabyrinthectomy in goldfish provides a useful approach to studying the ability of potential new neurotrophic or neuroprotective drugs to promote functional recovery. PMID:11486488

  12. A New Green's Function for the Wake Potential Calculation of the SLAC S-band Constant Gradient Accelerating Section

    SciTech Connect

    Novokhatski, A,; /SLAC

    2012-02-17

    The behavior of the longitudinal wake fields excited by a very short bunch in the SLAC S-band constant gradient accelerating structures has been studied. Wake potential calculations were performed for a bunch length of 10 microns using the author's code to obtain a numerical solution of Maxwell's equations in the time domain. We have calculated six accelerating sections in the series (60-ft) to find the stationary solution. While analyzing the computational results we have found a new formula for the Green's function. Wake potentials, which are calculated using this Green's function are in amazingly good agreement with numerical results over a wide range of bunch lengths. The Green's function simplifies the wake potential calculations and can be easily incorporated into the tracking codes. This is very useful for beam dynamics studies of the linear accelerators of LCLS and FACET.

  13. Phytochrome from Green Plants: Properties and biological Function

    SciTech Connect

    Quail, Peter H.

    2014-07-25

    Pfr conformer reverses this activity upon initial light exposure, inducing the switch to photomorphogenic development. This reversal involves light-triggered translocation of the photoactivated phy molecule into the nucleus where it interacts with PIF-family members, inducing rapid phosphorylation and degradation of the PIFs via the ubiquitin-proteasome system. This degradation in turn elicits rapid alterations in gene expression that drive the deetiolation transition. This project has made considerable progress in defining phy-PIF signaling activity in controlling the SAR. The biological functions of the multiple PIF-family members in controlling the SAR, including dissection of the relative contributions of the individual PIFs to this process, as well as to diurnal growth-control oscillations, have been investigated using higher-order pif-mutant combinations. Using microarray analysis of a quadruple pif mutant we have defined the shade-induced, PIF-regulated transcriptional network genome-wide. This has revealed that a dynamic antagonism between the phys and PIFs generates selective reciprocal responses during deetiolation and the SAR in a rapidly light-responsive transcriptional network. Using integrated RNA-seq and ChIP-seq analysis of higher order pif-mutant combinations, we have defined the direct gene-targets of PIF transcriptional regulation, and have obtained evidence that this regulation involves differential direct targeting of rapidly light-responsive genes by the individual PIF-family members. This project has provided significant advances in our understanding of the molecular mechanisms by which the phy-PIF photosensory signaling pathway regulates an important bioenergy-related plant response to the light environment. The identification of molecular targets in the primary transcriptional-regulatory circuitry of this pathway has the potential to enable genetic or reverse-genetic manipulation of the partitioning of carbon between reproductive and

  14. FPGA acceleration of the phylogenetic likelihood function for Bayesian MCMC inference methods

    PubMed Central

    2010-01-01

    Background Likelihood (ML)-based phylogenetic inference has become a popular method for estimating the evolutionary relationships among species based on genomic sequence data. This method is used in applications such as RAxML, GARLI, MrBayes, PAML, and PAUP. The Phylogenetic Likelihood Function (PLF) is an important kernel computation for this method. The PLF consists of a loop with no conditional behavior or dependencies between iterations. As such it contains a high potential for exploiting parallelism using micro-architectural techniques. In this paper, we describe a technique for mapping the PLF and supporting logic onto a Field Programmable Gate Array (FPGA)-based co-processor. By leveraging the FPGA's on-chip DSP modules and the high-bandwidth local memory attached to the FPGA, the resultant co-processor can accelerate ML-based methods and outperform state-of-the-art multi-core processors. Results We use the MrBayes 3 tool as a framework for designing our co-processor. For large datasets, we estimate that our accelerated MrBayes, if run on a current-generation FPGA, achieves a 10× speedup relative to software running on a state-of-the-art server-class microprocessor. The FPGA-based implementation achieves its performance by deeply pipelining the likelihood computations, performing multiple floating-point operations in parallel, and through a natural log approximation that is chosen specifically to leverage a deeply pipelined custom architecture. Conclusions Heterogeneous computing, which combines general-purpose processors with special-purpose co-processors such as FPGAs and GPUs, is a promising approach for high-performance phylogeny inference as shown by the growing body of literature in this field. FPGAs in particular are well-suited for this task because of their low power consumption as compared to many-core processors and Graphics Processor Units (GPUs) [1]. PMID:20385005

  15. Assessment of the setup dependence of detector response functions for mega-voltage linear accelerators

    SciTech Connect

    Fox, Christopher; Simon, Tom; Simon, Bill; Dempsey, James F.; Kahler, Darren; Palta, Jatinder R.; Liu Chihray; Yan Guanghua

    2010-02-15

    Purpose: Accurate modeling of beam profiles is important for precise treatment planning dosimetry. Calculated beam profiles need to precisely replicate profiles measured during machine commissioning. Finite detector size introduces perturbations into the measured profiles, which, in turn, impact the resulting modeled profiles. The authors investigate a method for extracting the unperturbed beam profiles from those measured during linear accelerator commissioning. Methods: In-plane and cross-plane data were collected for an Elekta Synergy linac at 6 MV using ionization chambers of volume 0.01, 0.04, 0.13, and 0.65 cm{sup 3} and a diode of surface area 0.64 mm{sup 2}. The detectors were orientated with the stem perpendicular to the beam and pointing away from the gantry. Profiles were measured for a 10x10 cm{sup 2} field at depths ranging from 0.8 to 25.0 cm and SSDs from 90 to 110 cm. Shaping parameters of a Gaussian response function were obtained relative to the Edge detector. The Gaussian function was deconvolved from the measured ionization chamber data. The Edge detector profile was taken as an approximation to the true profile, to which deconvolved data were compared. Data were also collected with CC13 and Edge detectors for additional fields and energies on an Elekta Synergy, Varian Trilogy, and Siemens Oncor linear accelerator and response functions obtained. Response functions were compared as a function of depth, SSD, and detector scan direction. Variations in the shaping parameter were introduced and the effect on the resulting deconvolution profiles assessed. Results: Up to 10% setup dependence in the Gaussian shaping parameter occurred, for each detector for a particular plane. This translated to less than a {+-}0.7 mm variation in the 80%-20% penumbral width. For large volume ionization chambers such as the FC65 Farmer type, where the cavity length to diameter ratio is far from 1, the scan direction produced up to a 40% difference in the shaping

  16. 2013 Russell Ross memorial lecture in vascular biology: cellular and molecular mechanisms of diabetes mellitus-accelerated atherosclerosis.

    PubMed

    Bornfeldt, Karin E

    2014-04-01

    Adults with diabetes mellitus are much more likely to have cardiovascular disease than those without diabetes mellitus. Genetically engineered mouse models have started to provide important insight into the mechanisms whereby diabetes mellitus promotes atherosclerosis. Such models have demonstrated that diabetes mellitus promotes formation of atherosclerotic lesions, progression of lesions into advanced hemorrhaged lesions, and that it prevents lesion regression. The proatherosclerotic effects of diabetes mellitus are driven in part by the altered function of myeloid cells. The protein S100A9 and the receptor for advanced glycation end-products are important modulators of the effect of diabetes mellitus on myelopoiesis, which might promote monocyte accumulation in lesions. Furthermore, myeloid cell expression of the enzyme acyl-CoA synthetase 1 (ACSL1), which converts long-chain fatty acids into their acyl-CoA derivatives, has emerged as causal to diabetes mellitus-induced lesion initiation. The protective effects of myeloid ACSL1-deficiency in diabetic mice, but not in nondiabetic mice, indicate that myeloid cells are activated by diabetes mellitus through mechanisms that play minor roles in the absence of diabetes mellitus. The roles of reactive oxygen species and insulin resistance in diabetes mellitus-accelerated atherosclerosis are also discussed, primarily in relation to endothelial cells. Translational studies addressing whether the mechanisms identified in mouse models are equally important in humans with diabetes mellitus will be paramount.

  17. Loss of Dnmt3b function upregulates the tumor modifier Ment and accelerates mouse lymphomagenesis.

    PubMed

    Hlady, Ryan A; Novakova, Slavomira; Opavska, Jana; Klinkebiel, David; Peters, Staci L; Bies, Juraj; Hannah, Jay; Iqbal, Javeed; Anderson, Kristi M; Siebler, Hollie M; Smith, Lynette M; Greiner, Timothy C; Bastola, Dhundy; Joshi, Shantaram; Lockridge, Oksana; Simpson, Melanie A; Felsher, Dean W; Wagner, Kay-Uwe; Chan, Wing C; Christman, Judith K; Opavsky, Rene

    2012-01-01

    DNA methyltransferase 3B (Dnmt3b) belongs to a family of enzymes responsible for methylation of cytosine residues in mammals. DNA methylation contributes to the epigenetic control of gene transcription and is deregulated in virtually all human tumors. To better understand the generation of cancer-specific methylation patterns, we genetically inactivated Dnmt3b in a mouse model of MYC-induced lymphomagenesis. Ablation of Dnmt3b function using a conditional knockout in T cells accelerated lymphomagenesis by increasing cellular proliferation, which suggests that Dnmt3b functions as a tumor suppressor. Global methylation profiling revealed numerous gene promoters as potential targets of Dnmt3b activity, the majority of which were demethylated in Dnmt3b-/- lymphomas, but not in Dnmt3b-/- pretumor thymocytes, implicating Dnmt3b in maintenance of cytosine methylation in cancer. Functional analysis identified the gene Gm128 (which we termed herein methylated in normal thymocytes [Ment]) as a target of Dnmt3b activity. We found that Ment was gradually demethylated and overexpressed during tumor progression in Dnmt3b-/- lymphomas. Similarly, MENT was overexpressed in 67% of human lymphomas, and its transcription inversely correlated with methylation and levels of DNMT3B. Importantly, knockdown of Ment inhibited growth of mouse and human cells, whereas overexpression of Ment provided Dnmt3b+/+ cells with a proliferative advantage. Our findings identify Ment as an enhancer of lymphomagenesis that contributes to the tumor suppressor function of Dnmt3b and suggest it could be a potential target for anticancer therapies.

  18. The value of isovolumic acceleration for the assessment of right ventricular function in acute pulmonary embolism.

    PubMed

    Selcuk, Murat; Sayar, Nurten; Demir, Serafettin; Rodi Tosua, Aydın; Aslan, Vedat

    2014-10-01

    The aim of this study was to assess the value of tricuspid annulus myocardial isovolumic acceleration (IVA) in the assessment of right ventricular function in patients with acute pulmonary embolism (PE). Fifteen patients (mean age 60.6±11.3 years) with acute PE were enrolled and a control group was formed of 15 patients with a similar mean age (60.3±11.5). Patients who were diagnosed with acute PE by thoracic computed tomography angiography underwent transthoracic echocardiography at the time of diagnosis and at one month after diagnosis. In the control group IVA was 2.8±0.2 m/s(2), while in the acute PE group, it was 2.0±0.1 m/s(2) at the time of diagnosis and 2.9±0.1 m/s(2) at the end of the first month. When IVA values of acute PE patients at the end of the first month were compared with their initial values and those of the control group, they had normalized (control and acute PE p<0.0001; control and PE at one-month follow-up p=0.983). In our study, IVA was shown to be a reliable marker of right ventricular systolic function in patients with acute PE. Copyright © 2013 Sociedade Portuguesa de Cardiologia. Published by Elsevier España. All rights reserved.

  19. Accelerated telomere erosion is associated with a declining immune function of caregivers of Alzheimer's disease patients.

    PubMed

    Damjanovic, Amanda K; Yang, Yinhua; Glaser, Ronald; Kiecolt-Glaser, Janice K; Nguyen, Huy; Laskowski, Bryon; Zou, Yixiao; Beversdorf, David Q; Weng, Nan-ping

    2007-09-15

    Caregivers of Alzheimer's disease patients endure chronic stress associated with a decline of immune function. To assess the psychological and immunological changes of caregivers, we compared depressive symptoms, PBMC composition, in vitro activation-induced proliferation and cytokine production, and telomere length and telomerase activity of 82 individuals (41 caregivers and 41 age- and gender-matched controls). We found depressive symptoms were significantly higher in caregivers than in controls (p < 0.001). Correspondingly, caregivers had significantly lower T cell proliferation but higher production of immune-regulatory cytokines (TNF-alpha and IL-10) than controls in response to stimulation in vitro. We examined the impact of these changes on cellular replicative lifespan and found that caregivers had significantly shorter telomere lengths in PBMC than controls (6.2 and 6.4 kb, respectively, p < 0.05) with similar shortening in isolated T cells and monocytes and that this telomere attrition in caregivers was not due to an increase of shorter telomere possessing T cell subsets in PBMC. Finally, we showed that basal telomerase activity in PBMC and T cells was significantly higher in caregivers than in controls (p < 0.0001), pointing to an unsuccessful attempt of cells to compensate the excessive loss of telomeres in caregivers. These findings demonstrate that chronic stress is associated with altered T cell function and accelerated immune cell aging as suggested by excessive telomere loss.

  20. FADTTSter: accelerating hypothesis testing with functional analysis of diffusion tensor tract statistics

    NASA Astrophysics Data System (ADS)

    Noel, Jean; Prieto, Juan C.; Styner, Martin

    2017-03-01

    Functional Analysis of Diffusion Tensor Tract Statistics (FADTTS) is a toolbox for analysis of white matter (WM) fiber tracts. It allows associating diffusion properties along major WM bundles with a set of covariates of interest, such as age, diagnostic status and gender, and the structure of the variability of these WM tract properties. However, to use this toolbox, a user must have an intermediate knowledge in scripting languages (MATLAB). FADTTSter was created to overcome this issue and make the statistical analysis accessible to any non-technical researcher. FADTTSter is actively being used by researchers at the University of North Carolina. FADTTSter guides non-technical users through a series of steps including quality control of subjects and fibers in order to setup the necessary parameters to run FADTTS. Additionally, FADTTSter implements interactive charts for FADTTS' outputs. This interactive chart enhances the researcher experience and facilitates the analysis of the results. FADTTSter's motivation is to improve usability and provide a new analysis tool to the community that complements FADTTS. Ultimately, by enabling FADTTS to a broader audience, FADTTSter seeks to accelerate hypothesis testing in neuroimaging studies involving heterogeneous clinical data and diffusion tensor imaging. This work is submitted to the Biomedical Applications in Molecular, Structural, and Functional Imaging conference. The source code of this application is available in NITRC.

  1. Relationship between neck acceleration and muscle activation in people with chronic neck pain: Implications for functional disability.

    PubMed

    Tsang, Sharon M H; Szeto, Grace P Y; Lee, Raymond Y W

    2016-06-01

    Previous study has found that people with chronic neck pain moved with a consistently compromised acceleration/deceleration at their cervical and thoracic spines. This study examined the strength of the association between the electromyographic activities and the acceleration/deceleration of the cervical and thoracic spine, and its correlation with the functional disabilities in individuals with neck pain. Time history of the cervical and thoracic acceleration/deceleration and EMG activity was acquired in thirty-four subjects with chronic neck pain and thirty-four age- and gender-matched asymptomatic subjects during active neck movements. The strength of the association between the electromyographic activity of spinal muscles and the cervical and thoracic acceleration/deceleration was determined using cross-correlation method. Relationship between the strength of this association and the severity of the functional disabilities in neck pain group was examined using correlation analysis. The strength of the association between cervical and thoracic acceleration/deceleration and electromyographic activities was significantly lower in neck pain group. Significant negative correlations were found between the functional disability level and the strength of this defined association in the symptomatic group. The compromised capability of the spinal muscles to produce acceleration/deceleration in the neck pain group may imply an impaired electromechanical coupling of these spinal muscles when performing neck movements. Significant negative correlation of the degree of functional disabilities suggests that the present approach can be used as an objective and specific evaluation of the dynamic performance of the spinal muscles and its relationship with the functional disabilities in neck pain subjects. Copyright © 2016. Published by Elsevier Ltd.

  2. Discovery of biological networks from diverse functional genomic data

    PubMed Central

    Myers, Chad L; Robson, Drew; Wible, Adam; Hibbs, Matthew A; Chiriac, Camelia; Theesfeld, Chandra L; Dolinski, Kara; Troyanskaya, Olga G

    2005-01-01

    We have developed a general probabilistic system for query-based discovery of pathway-specific networks through integration of diverse genome-wide data. This framework was validated by accurately recovering known networks for 31 biological processes in Saccharomyces cerevisiae and experimentally verifying predictions for the process of chromosomal segregation. Our system, bioPIXIE, a public, comprehensive system for integration, analysis, and visualization of biological network predictions for S. cerevisiae, is freely accessible over the worldwide web. PMID:16420673

  3. Computing biological functions using BioΨ, a formal description of biological processes based on elementary bricks of actions

    PubMed Central

    Pérès, Sabine; Felicori, Liza; Rialle, Stéphanie; Jobard, Elodie; Molina, Franck

    2010-01-01

    Motivation: In the available databases, biological processes are described from molecular and cellular points of view, but these descriptions are represented with text annotations that make it difficult to handle them for computation. Consequently, there is an obvious need for formal descriptions of biological processes. Results: We present a formalism that uses the BioΨ concepts to model biological processes from molecular details to networks. This computational approach, based on elementary bricks of actions, allows us to calculate on biological functions (e.g. process comparison, mapping structure–function relationships, etc.). We illustrate its application with two examples: the functional comparison of proteases and the functional description of the glycolysis network. This computational approach is compatible with detailed biological knowledge and can be applied to different kinds of systems of simulation. Availability: www.sysdiag.cnrs.fr/publications/supplementary-materials/BioPsi_Manager/ Contact: sabine.peres@sysdiag.cnrs.fr; franck.molina@sysdiag.cnrs.fr Supplementary information: Supplementary data are available at Bioinformatics online. PMID:20448138

  4. Center of Mass Acceleration Feedback Control of Functional Neuromuscular Stimulation for Standing in the Presence of Internal Postural Perturbations

    PubMed Central

    Audu, Musa L.; Triolo, Ronald J.

    2013-01-01

    This study determined the feasibility and performance of center of mass (COM) acceleration feedback control of a neuroprosthesis utilizing functional neuromuscular stimulation (FNS) to restore standing balance to a single subject paralyzed by a motor and sensory complete, thoracic-level spinal cord injury (SCI). An artificial neural network (ANN) was created to map gain-modulated changes in total body COM acceleration estimated from body-mounted sensors to optimal changes in stimulation required to maintain standing. Feedback gains were systematically tuned to minimize the upper extremity (UE) loads applied by the subject to an instrumented support device during internally generated postural perturbations produced by volitional reaching and object manipulation. Total body COM acceleration was accurately estimated (> 90% variance explained) from two three-dimensional (3-D) accelerometers mounted on the pelvis and torso. Compared to constant muscle stimulation employed clinically, COM acceleration feedback control of stimulation improved standing performance by reducing the UE loading required to resist internal postural disturbances by 27%. This case study suggests that COM acceleration feedback could potentially be advantageous in a standing neuroprosthesis since it can be implemented with only a few feedback parameters and requires minimal instrumentation for comprehensive, 3-D control of dynamic standing function. PMID:23299260

  5. Synthetic biology in cyanobacteria engineering and analyzing novel functions.

    PubMed

    Heidorn, Thorsten; Camsund, Daniel; Huang, Hsin-Ho; Lindberg, Pia; Oliveira, Paulo; Stensjö, Karin; Lindblad, Peter

    2011-01-01

    Cyanobacteria are the only prokaryotes capable of using sunlight as their energy, water as an electron donor, and air as a source of carbon and, for some nitrogen-fixing strains, nitrogen. Compared to algae and plants, cyanobacteria are much easier to genetically engineer, and many of the standard biological parts available for Synthetic Biology applications in Escherichia coli can also be used in cyanobacteria. However, characterization of such parts in cyanobacteria reveals differences in performance when compared to E. coli, emphasizing the importance of detailed characterization in the cellular context of a biological chassis. Furthermore, cyanobacteria possess special characteristics (e.g., multiple copies of their chromosomes, high content of photosynthetically active proteins in the thylakoids, the presence of exopolysaccharides and extracellular glycolipids, and the existence of a circadian rhythm) that have to be taken into account when genetically engineering them. With this chapter, the synthetic biologist is given an overview of existing biological parts, tools and protocols for the genetic engineering, and molecular analysis of cyanobacteria for Synthetic Biology applications. Copyright © 2011 Elsevier Inc. All rights reserved.

  6. DCC functions as an accelerator of thalamocortical axonal growth downstream of spontaneous thalamic activity

    PubMed Central

    Castillo-Paterna, Mar; Moreno-Juan, Verónica; Filipchuk, Anton; Rodríguez-Malmierca, Luis; Susín, Rafael; López-Bendito, Guillermina

    2015-01-01

    Controlling the axon growth rate is fundamental when establishing brain connections. Using the thalamocortical system as a model, we previously showed that spontaneous calcium activity influences the growth rate of thalamocortical axons by regulating the transcription of Robo1 through an NF-κB-binding site in its promoter. Robo1 acts as a brake on the growth of thalamocortical axons in vivo. Here, we have identified the Netrin-1 receptor DCC as an accelerator for thalamic axon growth. Dcc transcription is regulated by spontaneous calcium activity in thalamocortical neurons and activating DCC signaling restores normal axon growth in electrically silenced neurons. Moreover, we identified an AP-1-binding site in the Dcc promoter that is crucial for the activity-dependent regulation of this gene. In summary, we have identified the Dcc gene as a novel downstream target of spontaneous calcium activity involved in axon growth. Together with our previous data, we demonstrate a mechanism to control axon growth that relies on the activity-dependent regulation of two functionally opposed receptors, Robo1 and DCC. These two proteins establish a tight and efficient means to regulate activity-guided axon growth in order to correctly establish neuronal connections during development. PMID:25947198

  7. Accelerating bioelectric functional development of neural stem cells by graphene coupling: Implications for neural interfacing with conductive materials.

    PubMed

    Guo, Rongrong; Zhang, Shasha; Xiao, Miao; Qian, Fuping; He, Zuhong; Li, Dan; Zhang, Xiaoli; Li, Huawei; Yang, Xiaowei; Wang, Ming; Chai, Renjie; Tang, Mingliang

    2016-11-01

    In order to govern cell-specific behaviors in tissue engineering for neural repair and regeneration, a better understanding of material-cell interactions, especially the bioelectric functions, is extremely important. Graphene has been reported to be a potential candidate for use as a scaffold and neural interfacing material. However, the bioelectric evolvement of cell membranes on these conductive graphene substrates remains largely uninvestigated. In this study, we used a neural stem cell (NSC) model to explore the possible changes in membrane bioelectric properties - including resting membrane potentials and action potentials - and cell behaviors on graphene films under both proliferation and differentiation conditions. We used a combination of single-cell electrophysiological recordings and traditional cell biology techniques. Graphene did not affect the basic membrane electrical parameters (capacitance and input resistance), but resting membrane potentials of cells on graphene substrates were more strongly negative under both proliferation and differentiation conditions. Also, NSCs and their progeny on graphene substrates exhibited increased firing of action potentials during development compared to controls. However, graphene only slightly affected the electric characterizations of mature NSC progeny. The modulation of passive and active bioelectric properties on the graphene substrate was accompanied by enhanced NSC differentiation. Furthermore, spine density, synapse proteins expressions and synaptic activity were all increased in graphene group. Modeling of the electric field on conductive graphene substrates suggests that the electric field produced by the electronegative cell membrane is much higher on graphene substrates than that on control, and this might explain the observed changes of bioelectric development by graphene coupling. Our results indicate that graphene is able to accelerate NSC maturation during development, especially with regard to

  8. [Evolutionary-biological peculiarities of transglutaminase. Structure, physiological functions, application].

    PubMed

    Shleĭkin, A G; Danilov, N P

    2011-01-01

    Transglutaminasc (protein-glutamine gamma-glutamyltransferase, EC 2.3.2.13, TG) catalyzes reactions of the acyl transfer, which introduce the epsilon-(gamma-glutamyl)lysine bonds between proteins to create polymers of high mol. mass. Properties of the TG enzyme are described. Its structure is considered: there are characterized items of the TG life cycle and stability, its biological (physiological) role, and significance in pathology and medicine as well as obtaining of the purified enzyme preparations and their use. There are compared TG from different sources: of animal and microbial origin. Mechanism of catalysis of microbial TG is discussed. There are presented characteristics of isoenzymes from different biological sources.

  9. Decreased proteasomal function accelerates cigarette smoke-induced pulmonary emphysema in mice.

    PubMed

    Yamada, Yosuke; Tomaru, Utano; Ishizu, Akihiro; Ito, Tomoki; Kiuchi, Takayuki; Ono, Ayako; Miyajima, Syota; Nagai, Katsura; Higashi, Tsunehito; Matsuno, Yoshihiro; Dosaka-Akita, Hirotoshi; Nishimura, Masaharu; Miwa, Soichi; Kasahara, Masanori

    2015-06-01

    Chronic obstructive pulmonary disease (COPD) is a disease common in elderly people, characterized by progressive destruction of lung parenchyma and chronic inflammation of the airways. The pathogenesis of COPD remains unclear, but recent studies suggest that oxidative stress-induced apoptosis in alveolar cells contributes to emphysematous lung destruction. The proteasome is a multicatalytic enzyme complex that plays a critical role in proteostasis by rapidly destroying misfolded and modified proteins generated by oxidative and other stresses. Proteasome activity decreases with aging in many organs including lungs, and an age-related decline in proteasomal function has been implicated in various age-related pathologies. However, the role of the proteasome system in the pathogenesis of COPD has not been investigated. Recently, we have established a transgenic (Tg) mouse model with decreased proteasomal chymotrypsin-like activity, showing age-related phenotypes. Using this model, we demonstrate here that decreased proteasomal function accelerates cigarette smoke (CS)-induced pulmonary emphysema. CS-exposed Tg mice showed remarkable airspace enlargement and increased foci of inflammation compared with wild-type controls. Importantly, apoptotic cells were found in the alveolar walls of the affected lungs. Impaired proteasomal activity also enhanced apoptosis in cigarette smoke extract (CSE)-exposed fibroblastic cells derived from mice and humans in vitro. Notably, aggresome formation and prominent nuclear translocation of apoptosis-inducing factor were observed in CSE-exposed fibroblastic cells isolated from Tg mice. Collective evidence suggests that CS exposure and impaired proteasomal activity coordinately enhance apoptotic cell death in the alveolar walls that may be involved in the development and progression of emphysema in susceptible individuals such as the elderly.

  10. Intensive training accelerates the recovery of motor functions following cerebral ischemia-reperfusion in MCAO rats.

    PubMed

    Wang, Q; Wang, P-P; Meng, P-P; Han, C; Yue, S-W

    2016-09-01

    Cerebral ischemia-reperfusion is the major pathophysiological process in stroke and can cause severe and lasting sequel. However, an intensive exercise training can potentially effect a quick and efficient recovery. We used swimming training on rats with cerebral ischemia-reperfusion (CIR) and explore the underlying neuroprotective mechanism(s), including the effects of intensive training on the expression of semaphorin 3A (Sema3A) and its receptor Neuropilin-1 (NRP-1). The middle cerebral artery occlusion/reperfusion (MCAO/R) model was established by inserting a thread into the middle cerebral artery of Sprague-Dawley (SD) rats, and randomly dividing into the control group and training groups for different training intensities. The control group and the sham group received no training. All the rats in various groups were further randomly divided into three sub-groups for different postoperative time points (3, 7, and 14 days after operation). The apoptosis and the expression of Sema3A and NRP-1 were analyzed using immunohistochemistry (IHC), RT-PCR, and Western blotting methods respectively. The intensive training resulted in significant neurological function improvements at all the time points after MCAO, compared to that in the control group (p<0.05), with training group 3 (highest training intensity) showing the most remarkable recovery. The Sema3A and NP-1 expressions were significantly lower than those of the control group at all the time points (p<0.05), with training group 3 having the lowest levels (best recovery). Intensive training can reduce cerebral damage after ischemia and reperfusion in rats, inhibit the MCAO-induced Sema3A and NRP-1 expression, and accelerate the restoring process of motor nerve functions.

  11. [THE BIOLOGICAL FUNCTION OF NUTRITION, BIOLOGICAL REACTION OF EXOTROPHY, DEPOSITING AND ENDOTROPHY. THE VISCERAL FATTY CELLS AND ADIPOCYTES - PHYLOGENETICALLY, FUNCTIONALLY AND REGULATORY DIFFERENT POOLS OF FATTY TISSUE].

    PubMed

    Titov, V N

    2015-08-01

    For billions years, two phylogenetically, functionally and regulatory different pools of fatty cells - visceral fatty acids and adipocytes coexist in vivo. Their becoming occurred at different degrees of phylogenesis. The phylogenetically earlier pool of visceral fatty acids is meant to supply with fatty acids-substrates for gaining energy by those cells which implement biological function of nutrition (trophology), homeostasis, endoecology biological function of adaptation and continuation of species. They have no receptors to phylogenetically later insulin. The adipocytes, later in phylogenesis, implement one biological function - the function of locomotion and they are as insulin-dependent as skeletal myocytes, cardiomyocytes, adipocytes and periportal hepatocytes. The difference in regulation is traced on all levels of "biological perfection " - autocrine (cellular) level, in humoral regulated paracrin cenosises of cells and on the level of organism. In biological function of trophology, paracrin cenosises of visceral fatty acids and adipocytes implement subsequently three biological reactions: exotrophy, deposit of fatty acids and endotrophy. In conditions of humoral regulation of three functionally different biological reactions in paracrin cenosises synthesis of so many humoral mediators is required. The humoral mediators of mechanism of feedback at autocrine level, in paracrin cenosises and at the level of organism are leptin of visceral fatty acids and adiponectin of adipocytes. At the level of organism, phylogenetically earlier paracrin cenosises of fatty cells are regulated by endocrine system. The phylogenetically later paracrin cenosises are regulated by insulin and nuclei of hypothalamus. The metabolic syndrome is a pathology of phylogenetically earlier insulin-independent visceral fatty acids. The obesity is a pathology of phylogenetically later pool of insulin-dependent adipocytes.

  12. Oxidative metabolites of lycopene and their biological functions

    USDA-ARS?s Scientific Manuscript database

    To gain a better understanding of the beneficial biological activities of lycopene on cancer prevention, a greater knowledge of the metabolism of lycopene is needed. In particular, the identification of lycopene metabolites and oxidation products in vivo; the importance of tissue specific lycopene c...

  13. World views: Their nature and function in the biology classroom

    NASA Astrophysics Data System (ADS)

    Armstrong, Kerri Lynn

    There has been sufficient research in the area of conceptual change that indicates that students' conceptions or alternative theories are much more resistant to change than was previously thought. The work of cultural anthropologists and, more recently science educators, points to the role of individual world views in the learning of science concepts. A world view is one's fundamental assumptions and presuppositions concerning perceptions of reality. The purpose of this ethnographic investigation was to shed light on the dynamic interaction of individual world views within the college biology classroom in relation to understanding key biological concepts in genetics, evolution and natural selection, and ecology and ecological relationships. The subjects for this study were 22 students enrolled in an introductory level non-majors biology class at the Community College of Philadelphia. Ten of these students participated in the interviews reported here. The outcomes of this investigation revealed that students do not view themselves as part of science or nature. The investigation also uncovered students' views of the self, nonself, relationship and causality that affect their learning and apprehension of key biological concepts. This investigation provides further demonstration of the influence of world views and the interplay of those views with the notion of scientific literacy.

  14. Center of Mass Acceleration Feedback Control of Standing Balance by Functional Neuromuscular Stimulation against External Postural Perturbations

    PubMed Central

    Nataraj, Raviraj; Audu, Musa L.; Triolo, Ronald J.

    2013-01-01

    This study investigated the use of center of mass (COM) acceleration feedback for improving performance of a functional neuromuscular stimulation (FNS) control system to restore standing function to a subject with complete, thoracic-level spinal cord injury (SCI). The approach for linearly relating changes in muscle stimulation to changes in COM acceleration was verified experimentally and subsequently produced data to create an input-output map driven by sensor feedback. The feedback gains were systematically tuned to reduce upper extremity (UE) loads applied to an instrumented support device while resisting external postural disturbances. Total body COM acceleration was accurately estimated (> 89% variance explained) using three-dimensional (3-D) outputs of two accelerometers mounted on the pelvis and torso. Compared to constant muscle stimulation employed clinically, feedback control of stimulation reduced UE loading by 33%. COM acceleration feedback is advantageous in constructing a standing neuroprosthesis since it provides the basis for a comprehensive control synergy about a global, dynamic variable and requires minimal instrumentation. Future work should include tuning and testing the feedback control system during functional reaching activity that is more indicative of activities of daily living. PMID:22987499

  15. Comparing joint kinematics and center of mass acceleration as feedback for control of standing balance by functional neuromuscular stimulation

    PubMed Central

    2012-01-01

    Background The purpose of this study was to determine the comparative effectiveness of feedback control systems for maintaining standing balance based on joint kinematics or total body center of mass (COM) acceleration, and assess their clinical practicality for standing neuroprostheses after spinal cord injury (SCI). Methods In simulation, controller performance was measured according to the upper extremity effort required to stabilize a three-dimensional model of bipedal standing against a variety of postural disturbances. Three cases were investigated: proportional-derivative control based on joint kinematics alone, COM acceleration feedback alone, and combined joint kinematics and COM acceleration feedback. Additionally, pilot data was collected during external perturbations of an individual with SCI standing with functional neuromuscular stimulation (FNS), and the resulting joint kinematics and COM acceleration data was analyzed. Results Compared to the baseline case of maximal constant muscle excitations, the three control systems reduced the mean upper extremity loading by 51%, 43% and 56%, respectively against external force-pulse perturbations. Controller robustness was defined as the degradation in performance with increasing levels of input errors expected with clinical deployment of sensor-based feedback. At error levels typical for body-mounted inertial sensors, performance degradation due to sensor noise and placement were negligible. However, at typical tracking error levels, performance could degrade as much as 86% for joint kinematics feedback and 35% for COM acceleration feedback. Pilot data indicated that COM acceleration could be estimated with a few well-placed sensors and efficiently captures information related to movement synergies observed during perturbed bipedal standing following SCI. Conclusions Overall, COM acceleration feedback may be a more feasible solution for control of standing with FNS given its superior robustness and small

  16. Comparing joint kinematics and center of mass acceleration as feedback for control of standing balance by functional neuromuscular stimulation.

    PubMed

    Nataraj, Raviraj; Audu, Musa L; Triolo, Ronald J

    2012-05-06

    The purpose of this study was to determine the comparative effectiveness of feedback control systems for maintaining standing balance based on joint kinematics or total body center of mass (COM) acceleration, and assess their clinical practicality for standing neuroprostheses after spinal cord injury (SCI). In simulation, controller performance was measured according to the upper extremity effort required to stabilize a three-dimensional model of bipedal standing against a variety of postural disturbances. Three cases were investigated: proportional-derivative control based on joint kinematics alone, COM acceleration feedback alone, and combined joint kinematics and COM acceleration feedback. Additionally, pilot data was collected during external perturbations of an individual with SCI standing with functional neuromuscular stimulation (FNS), and the resulting joint kinematics and COM acceleration data was analyzed. Compared to the baseline case of maximal constant muscle excitations, the three control systems reduced the mean upper extremity loading by 51%, 43% and 56%, respectively against external force-pulse perturbations. Controller robustness was defined as the degradation in performance with increasing levels of input errors expected with clinical deployment of sensor-based feedback. At error levels typical for body-mounted inertial sensors, performance degradation due to sensor noise and placement were negligible. However, at typical tracking error levels, performance could degrade as much as 86% for joint kinematics feedback and 35% for COM acceleration feedback. Pilot data indicated that COM acceleration could be estimated with a few well-placed sensors and efficiently captures information related to movement synergies observed during perturbed bipedal standing following SCI. Overall, COM acceleration feedback may be a more feasible solution for control of standing with FNS given its superior robustness and small number of inputs required.

  17. Accelerating functional MRI using fixed‐rank approximations and radial‐cartesian sampling

    PubMed Central

    Graedel, Nadine N.; McNab, Jennifer A.; Smith, Stephen M.; Miller, Karla L.

    2016-01-01

    Purpose Recently, k‐t FASTER (fMRI Accelerated in Space‐time by means of Truncation of Effective Rank) was introduced for rank‐constrained acceleration of fMRI data acquisition. Here we demonstrate improvements achieved through a hybrid three‐dimensional radial‐Cartesian sampling approach that allows posthoc selection of acceleration factors, as well as incorporation of coil sensitivity encoding in the reconstruction. Methods The multicoil rank‐constrained reconstruction used hard thresholding and shrinkage on matrix singular values of the space‐time data matrix, using sensitivity encoding and the nonuniform Fast Fourier Transform to enforce data consistency in the multicoil non‐Cartesian k‐t domain. Variable acceleration factors were made possible using a radial increment based on the golden ratio. Both retrospective and prospectively under‐sampled data were used to assess the fidelity of the enhancements to the k‐t FASTER technique in resting and task‐fMRI data. Results The improved k‐t FASTER is capable of tailoring acceleration factors for recovery of different signal components, achieving up to R = 12.5 acceleration in visual‐motor task data. The enhancements reduce data matrix reconstruction errors even at much higher acceleration factors when compared directly with the original k‐t FASTER approach. Conclusion We have shown that k‐t FASTER can be used to significantly accelerate fMRI data acquisition with little penalty to data quality. Magn Reson Med 76:1825–1836, 2016. © 2016 The Authors Magnetic Resonance in Medicine published by Wiley Periodicals, Inc. on behalf of International Society for Magnetic Resonance in Medicine. This is an open access article under the terms of the Creative Commons Attribution License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited. PMID:26777798

  18. Accelerating functional MRI using fixed-rank approximations and radial-cartesian sampling.

    PubMed

    Chiew, Mark; Graedel, Nadine N; McNab, Jennifer A; Smith, Stephen M; Miller, Karla L

    2016-12-01

    Recently, k-t FASTER (fMRI Accelerated in Space-time by means of Truncation of Effective Rank) was introduced for rank-constrained acceleration of fMRI data acquisition. Here we demonstrate improvements achieved through a hybrid three-dimensional radial-Cartesian sampling approach that allows posthoc selection of acceleration factors, as well as incorporation of coil sensitivity encoding in the reconstruction. The multicoil rank-constrained reconstruction used hard thresholding and shrinkage on matrix singular values of the space-time data matrix, using sensitivity encoding and the nonuniform Fast Fourier Transform to enforce data consistency in the multicoil non-Cartesian k-t domain. Variable acceleration factors were made possible using a radial increment based on the golden ratio. Both retrospective and prospectively under-sampled data were used to assess the fidelity of the enhancements to the k-t FASTER technique in resting and task-fMRI data. The improved k-t FASTER is capable of tailoring acceleration factors for recovery of different signal components, achieving up to R = 12.5 acceleration in visual-motor task data. The enhancements reduce data matrix reconstruction errors even at much higher acceleration factors when compared directly with the original k-t FASTER approach. We have shown that k-t FASTER can be used to significantly accelerate fMRI data acquisition with little penalty to data quality. Magn Reson Med 76:1825-1836, 2016. © 2016 The Authors Magnetic Resonance in Medicine published by Wiley Periodicals, Inc. on behalf of International Society for Magnetic Resonance in Medicine. This is an open access article under the terms of the Creative Commons Attribution License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited. © 2016 The Authors Magnetic Resonance in Medicine published by Wiley Periodicals, Inc. on behalf of International Society for Magnetic Resonance in Medicine.

  19. Biological Effectiveness of Accelerated Particles for the Induction of Chromosome Damage Measured in Metaphase and Interphase Human Lymphocytes

    NASA Technical Reports Server (NTRS)

    George, Kerry; Durante, Marco; Willingham, Veronica; Wu, Honglu; Yang, Tracy C.; Cucinotta, Francis A.

    2003-01-01

    Chromosome aberrations were investigated in human lymphocytes after in vitro exposure to 1H-, 3He-, 12C-, 40Ar-, 28Si-, 56Fe-, or 197Au-ion beams, with LET ranging from approximately 0.4-1393 keV/microm in the dose range of 0.075-3 Gy. Dose-response curves for chromosome exchanges, measured at the first mitosis postirradiation using fluorescence in situ hybridization (FISH) with whole-chromosome probes, were fitted with linear or linear-quadratic functions. The relative biological effectiveness (RBE) was estimated from the initial slope of the dose-response curve for chromosomal damage with respect to low- or high-dose-rate gamma rays. Estimates of RBEmax values for mitotic spreads, which ranged from near 0.7 to 11.1 for total exchanges, increased with LET, reaching a maximum at about 150 keV/microm, and decreased with further increase in LET. RBEs for complex aberrations are undefined due to the lack of an initial slope for gamma rays. Additionally, the effect of mitotic delay on RBE values was investigated by measuring chromosome aberrations in interphase after chemically induced premature chromosome condensation (PCC), and values were up to threefold higher than for metaphase analysis.

  20. Biological Effectiveness of Accelerated Particles for the Induction of Chromosome Damage Measured in Metaphase and Interphase Human Lymphocytes

    NASA Technical Reports Server (NTRS)

    George, Kerry; Durante, Marco; Willingham, Veronica; Wu, Honglu; Yang, Tracy C.; Cucinotta, Francis A.

    2003-01-01

    Chromosome aberrations were investigated in human lymphocytes after in vitro exposure to 1H-, 3He-, 12C-, 40Ar-, 28Si-, 56Fe-, or 197Au-ion beams, with LET ranging from approximately 0.4-1393 keV/microm in the dose range of 0.075-3 Gy. Dose-response curves for chromosome exchanges, measured at the first mitosis postirradiation using fluorescence in situ hybridization (FISH) with whole-chromosome probes, were fitted with linear or linear-quadratic functions. The relative biological effectiveness (RBE) was estimated from the initial slope of the dose-response curve for chromosomal damage with respect to low- or high-dose-rate gamma rays. Estimates of RBEmax values for mitotic spreads, which ranged from near 0.7 to 11.1 for total exchanges, increased with LET, reaching a maximum at about 150 keV/microm, and decreased with further increase in LET. RBEs for complex aberrations are undefined due to the lack of an initial slope for gamma rays. Additionally, the effect of mitotic delay on RBE values was investigated by measuring chromosome aberrations in interphase after chemically induced premature chromosome condensation (PCC), and values were up to threefold higher than for metaphase analysis.

  1. Cumulative exposure to dust causes accelerated decline in lung function in tunnel workers

    PubMed Central

    Ulvestad, B; Bakke, B; Eduard, W; Kongerud, J; Lund, M

    2001-01-01

    most important risk factor for respiratory symptoms. The finding of accelerated decline in lung function in tunnel workers suggests that better control of exposures is needed.


Keywords: heavy construction; respirable dust; lung function PMID:11555688

  2. GENIUS: web server to predict local gene networks and key genes for biological functions.

    PubMed

    Puelma, Tomas; Araus, Viviana; Canales, Javier; Vidal, Elena A; Cabello, Juan M; Soto, Alvaro; Gutiérrez, Rodrigo A

    2017-03-01

    GENIUS is a user-friendly web server that uses a novel machine learning algorithm to infer functional gene networks focused on specific genes and experimental conditions that are relevant to biological functions of interest. These functions may have different levels of complexity, from specific biological processes to complex traits that involve several interacting processes. GENIUS also enriches the network with new genes related to the biological function of interest, with accuracies comparable to highly discriminative Support Vector Machine methods. GENIUS currently supports eight model organisms and is freely available for public use at http://networks.bio.puc.cl/genius . genius.psbl@gmail.com. Supplementary data are available at Bioinformatics online.

  3. X-ray phase contrast imaging of biological specimens with femtosecond pulses of betatron radiation from a compact laser plasma wakefield accelerator

    SciTech Connect

    Kneip, S.; McGuffey, C.; Dollar, F.; Chvykov, V.; Kalintchenko, G.; Krushelnick, K.; Maksimchuk, A.; Mangles, S. P. D.; Matsuoka, T.; Schumaker, W.; Thomas, A. G. R.; Yanovsky, V.; Bloom, M. S.; Najmudin, Z.; Palmer, C. A. J.; Schreiber, J.

    2011-08-29

    We show that x-rays from a recently demonstrated table top source of bright, ultrafast, coherent synchrotron radiation [Kneip et al., Nat. Phys. 6, 980 (2010)] can be applied to phase contrast imaging of biological specimens. Our scheme is based on focusing a high power short pulse laser in a tenuous gas jet, setting up a plasma wakefield accelerator that accelerates and wiggles electrons analogously to a conventional synchrotron, but on the centimeter rather than tens of meter scale. We use the scheme to record absorption and phase contrast images of a tetra fish, damselfly and yellow jacket, in particular highlighting the contrast enhancement achievable with the simple propagation technique of phase contrast imaging. Coherence and ultrafast pulse duration will allow for the study of various aspects of biomechanics.

  4. Cerenkov Radiation: A Multi-functional Approach for Biological Sciences

    NASA Astrophysics Data System (ADS)

    Ma, Xiaowei; Wang, Jing; Cheng, Zhen

    2014-02-01

    Cerenkov radiation (CR) has been used in various biological research fields, which has aroused lots of attention in recent years. Combining optical imaging instruments and most of nuclear medicine imaging or radiotherapy probes, the CR was developed as a new imaging modality for biology studies, called Cerenkov luminescence imaging (CLI). On the other hand, it was novelly used as an internal excitation source to activate some fluorophores for energy transfer imaging. However, it also has some shortages such as relatively weak luminescence intensity and low penetration in tissue. Thus some scientific groups demonstrated to optimize the CLI and demonstrated it to three-dimension tomography. In this article, we elaborate on its principle, history, and applications and discuss a number of directions for technical improvements. Then concluded some advantages and shortages of CR and discuss some prospects of it.

  5. Opposing Biological Functions of Tryptophan Catabolizing Enzymes During Intracellular Infection

    PubMed Central

    Divanovic, Senad; Sawtell, Nancy M.; Trompette, Aurelien; Warning, Jamie I.; Dias, Alexandra; Cooper, Andrea M.; Yap, George S.; Arditi, Moshe; Shimada, Kenichi; DuHadaway, James B.; Prendergast, George C.; Basaraba, Randall J.; Mellor, Andrew L.; Munn, David H.; Aliberti, Julio

    2012-01-01

    Recent studies have underscored physiological and pathophysiological roles for the tryptophan-degrading enzyme indolamine 2,3-dioxygenase (IDO) in immune counterregulation. However, IDO was first recognized as an antimicrobial effector, restricting tryptophan availability to Toxoplasma gondii and other pathogens in vitro. The biological relevance of these findings came under question when infectious phenotypes were not forthcoming in IDO-deficient mice. The recent discovery of an IDO homolog, IDO-2, suggested that the issue deserved reexamination. IDO inhibition during murine toxoplasmosis led to 100% mortality, with increased parasite burdens and no evident effects on the immune response. Similar studies revealed a counterregulatory role for IDO during leishmaniasis (restraining effector immune responses and parasite clearance), and no evident role for IDO in herpes simplex virus type 1 (HSV-1) infection. Thus, IDO plays biologically important roles in the host response to diverse intracellular infections, but the dominant nature of this role—antimicrobial or immunoregulatory—is pathogen-specific. PMID:21990421

  6. Identification of Molecular Markers of Delayed Graft Function Based on the Regulation of Biological Ageing

    PubMed Central

    McGuinness, Dagmara; Leierer, Johannes; Shapter, Olivier; Mohammed, Suhaib; Gingell-Littlejohn, Marc; Kingsmore, David B.; Little, Ann-Margaret; Kerschbaum, Julia; Schneeberger, Stefan; Maglione, Manuel; Nadalin, Silvio; Wagner, Sylvia; Königsrainer, Alfred; Aitken, Emma; Whalen, Henry; Clancy, Marc; McConnachie, Alex; Koppelstaetter, Christian; Stevenson, Karen S.; Shiels, Paul G.

    2016-01-01

    Introduction Delayed graft function is a prevalent clinical problem in renal transplantation for which there is no objective system to predict occurrence in advance. It can result in a significant increase in the necessity for hospitalisation post-transplant and is a significant risk factor for other post-transplant complications. Methodology The importance of microRNAs (miRNAs), a specific subclass of small RNA, have been clearly demonstrated to influence many pathways in health and disease. To investigate the influence of miRNAs on renal allograft performance post-transplant, the expression of a panel of miRNAs in pre-transplant renal biopsies was measured using qPCR. Expression was then related to clinical parameters and outcomes in two independent renal transplant cohorts. Results Here we demonstrate, in two independent cohorts of pre-implantation human renal allograft biopsies, that a novel pre-transplant renal performance scoring system (GRPSS), can determine the occurrence of DGF with a high sensitivity (>90%) and specificity (>60%) for donor allografts pre-transplant, using just three senescence associated microRNAs combined with donor age and type of organ donation. Conclusion These results demonstrate a relationship between pre-transplant microRNA expression levels, cellular biological ageing pathways and clinical outcomes for renal transplantation. They provide for a simple, rapid quantitative molecular pre-transplant assay to determine post-transplant allograft function and scope for future intervention. Furthermore, these results demonstrate the involvement of senescence pathways in ischaemic injury during the organ transplantation process and an indication of accelerated bio-ageing as a consequence of both warm and cold ischaemia. PMID:26734715

  7. Design and Synthesis of Functional Molecules Based on Complexation and Their Biological Applications.

    PubMed

    Hisamatsu, Yosuke

    2016-01-01

     In this review, we introduce the development of supermolecules, host-guest complexes, and metal complexes formed from the combination of non-covalent interactions and/or coordination bonds, as well as their biological applications. An adenine selective host molecule 1 provides a correctly oriented array of complementary hydrogen bonding sites for the adenine nucleobase. Furthermore, the new DDAA (D: hydrogen bond donor, A: hydrogen bond acceptor) module 4 and ADDA module 7 have been developed as quadruple hydrogen-bonding modules. A quadruple zwitterion 8 forms supramolecular gel in dimethyl sulfoxide, driven by the formation of ion-paired dimers between the zwitterionic units. The obtained supramolecular gel exhibits reversible gel-sol transitions in response to both acid, base, and heating. Self-assembly of a dimeric zinc(II) complex, dianion of cyanuric acid (CA) or 5,5-diethylbarbituric acid (Bar), and copper(II) ion (Cu(2+)) in an aqueous solution provides 4 : 4 : 4 and 2 : 2 : 2 supermolecules 10 and 11, respectively. These supermolecules possess Cu2(μ-OH)2 centers, and accelerate the hydrolysis of a phosphate monoester dianion, mono(4-nitrophenyl)phosphate (MNP), at neutral pH. Regioselective substitution reactions of tris-cyclometalated iridium (Ir) complexes at the 5'-position on 2-phenylpyridine type ligands, and their subsequent conversions to a variety of functional groups are described. For example, pH-sensitive Ir complexes having basic functional groups have been developed. Tris-cyclometalated Ir complexes containing cationic peptides, such as Lys-Lys-Gly-Gly (KKGG) peptides, work as inducers and detectors of cancer cell death. Mechanistic studies suggest that the Ir complex interacts with anionic molecules on the cell surface and/or membrane receptors to trigger an intracellular Ca(2+) response, resulting in necrosis accompanied by membrane disruption.

  8. Accelerating Computation of DCM for ERP in MATLAB by External Function Calls to the GPU

    PubMed Central

    Wang, Wei-Jen; Hsieh, I-Fan; Chen, Chun-Chuan

    2013-01-01

    This study aims to improve the performance of Dynamic Causal Modelling for Event Related Potentials (DCM for ERP) in MATLAB by using external function calls to a graphics processing unit (GPU). DCM for ERP is an advanced method for studying neuronal effective connectivity. DCM utilizes an iterative procedure, the expectation maximization (EM) algorithm, to find the optimal parameters given a set of observations and the underlying probability model. As the EM algorithm is computationally demanding and the analysis faces possible combinatorial explosion of models to be tested, we propose a parallel computing scheme using the GPU to achieve a fast estimation of DCM for ERP. The computation of DCM for ERP is dynamically partitioned and distributed to threads for parallel processing, according to the DCM model complexity and the hardware constraints. The performance efficiency of this hardware-dependent thread arrangement strategy was evaluated using the synthetic data. The experimental data were used to validate the accuracy of the proposed computing scheme and quantify the time saving in practice. The simulation results show that the proposed scheme can accelerate the computation by a factor of 155 for the parallel part. For experimental data, the speedup factor is about 7 per model on average, depending on the model complexity and the data. This GPU-based implementation of DCM for ERP gives qualitatively the same results as the original MATLAB implementation does at the group level analysis. In conclusion, we believe that the proposed GPU-based implementation is very useful for users as a fast screen tool to select the most likely model and may provide implementation guidance for possible future clinical applications such as online diagnosis. PMID:23840507

  9. TGF-beta(1) genotype and accelerated decline in lung function of patients with cystic fibrosis.

    PubMed

    Arkwright, P D; Laurie, S; Super, M; Pravica, V; Schwarz, M J; Webb, A K; Hutchinson, I V

    2000-06-01

    Polymorphisms in transforming growth factor (TGF)-beta(1) associated with variations in cytokine levels are linked to fibrosis in a number of tissues. However, the contribution of this cytokine to organ fibrosis in patients with cystic fibrosis is presently unclear. This study was undertaken to examine the association between TGF-beta(1) gene polymorphisms and the development of pulmonary dysfunction in patients with cystic fibrosis. Polymorphisms in the TGF-beta(1) gene defining amino acids of codons 10 and 25 were determined by ARMS-PCR using DNA stored on 171 Caucasian patients who were homozygous for the DeltaF508 mutation of the cystic fibrosis transmembrane conductance regulator (CFTR) gene. Clinical information on the patients was obtained from medical records. Patients with cystic fibrosis of a TGF-beta(1) high producer genotype for codon 10 had more rapid deterioration in lung function than those with a TGF-beta(1) low producer genotype. The relative risk of accelerated decline in forced expiratory volume in one second (FEV(1)) to 50% predicted and forced vital capacity (FVC) to 70% predicted of patients with a high producer genotype was 1.74 (95% CI 1.11 to 2. 73) compared with 1.95 (95% CI 1.24 to 3.06) for those with a low producer genotype. TGF-beta(1) genotypes may have a role in mediating pulmonary dysfunction in patients with cystic fibrosis. Further work is required to determine whether inhibition of TGF-beta(1) activity in these patients may slow disease progression.

  10. Accelerating Computation of DCM for ERP in MATLAB by External Function Calls to the GPU.

    PubMed

    Wang, Wei-Jen; Hsieh, I-Fan; Chen, Chun-Chuan

    2013-01-01

    This study aims to improve the performance of Dynamic Causal Modelling for Event Related Potentials (DCM for ERP) in MATLAB by using external function calls to a graphics processing unit (GPU). DCM for ERP is an advanced method for studying neuronal effective connectivity. DCM utilizes an iterative procedure, the expectation maximization (EM) algorithm, to find the optimal parameters given a set of observations and the underlying probability model. As the EM algorithm is computationally demanding and the analysis faces possible combinatorial explosion of models to be tested, we propose a parallel computing scheme using the GPU to achieve a fast estimation of DCM for ERP. The computation of DCM for ERP is dynamically partitioned and distributed to threads for parallel processing, according to the DCM model complexity and the hardware constraints. The performance efficiency of this hardware-dependent thread arrangement strategy was evaluated using the synthetic data. The experimental data were used to validate the accuracy of the proposed computing scheme and quantify the time saving in practice. The simulation results show that the proposed scheme can accelerate the computation by a factor of 155 for the parallel part. For experimental data, the speedup factor is about 7 per model on average, depending on the model complexity and the data. This GPU-based implementation of DCM for ERP gives qualitatively the same results as the original MATLAB implementation does at the group level analysis. In conclusion, we believe that the proposed GPU-based implementation is very useful for users as a fast screen tool to select the most likely model and may provide implementation guidance for possible future clinical applications such as online diagnosis.

  11. Amine functionalized magnetic nanoparticles for removal of oil droplets from produced water and accelerated magnetic separation

    NASA Astrophysics Data System (ADS)

    Ko, Saebom; Kim, Eun Song; Park, Siman; Daigle, Hugh; Milner, Thomas E.; Huh, Chun; Bennetzen, Martin V.; Geremia, Giuliano A.

    2017-04-01

    Magnetic nanoparticles (MNPs) with surface coatings designed for water treatment, in particular for targeted removal of contaminants from produced water in oil fields, have drawn considerable attention due to their environmental merit. The goal of this study was to develop an efficient method of removing very stable, micron-scale oil droplets dispersed in oilfield produced water. We synthesized MNPs in the laboratory with a prescribed surface coating. The MNPs were superparamagnetic magnetite, and the hydrodynamic size of amine functionalized MNPs ranges from 21 to 255 nm with an average size of 66 nm. The initial oil content of 0.25 wt.% was reduced by as much as 99.9% in separated water. The electrostatic attraction between negatively charged oil-in-water emulsions and positively charged MNPs controls, the attachment of MNPs to the droplet surface, and the subsequent aggregation of the electrically neutral oil droplets with attached MNPs (MNPs-oils) play a critical role in accelerated and efficient magnetic separation. The total magnetic separation time was dramatically reduced to as short as 1 s after MNPs, and oil droplets were mixed, in contrast with the case of free, individual MNPs with which separation took about 36˜72 h, depending on the MNP concentrations. Model calculations of magnetic separation velocity, accounting for the MNP magnetization and viscous drag, show that the total magnetic separation time will be approximately 5 min or less, when the size of the MNPs-oils is greater than 360 nm, which can be used as an optimum operating condition.

  12. Precision and accuracy in the quantitative analysis of biological samples by accelerator mass spectrometry: application in microdose absolute bioavailability studies.

    PubMed

    Gao, Lan; Li, Jing; Kasserra, Claudia; Song, Qi; Arjomand, Ali; Hesk, David; Chowdhury, Swapan K

    2011-07-15

    Determination of the pharmacokinetics and absolute bioavailability of an experimental compound, SCH 900518, following a 89.7 nCi (100 μg) intravenous (iv) dose of (14)C-SCH 900518 2 h post 200 mg oral administration of nonradiolabeled SCH 900518 to six healthy male subjects has been described. The plasma concentration of SCH 900518 was measured using a validated LC-MS/MS system, and accelerator mass spectrometry (AMS) was used for quantitative plasma (14)C-SCH 900518 concentration determination. Calibration standards and quality controls were included for every batch of sample analysis by AMS to ensure acceptable quality of the assay. Plasma (14)C-SCH 900518 concentrations were derived from the regression function established from the calibration standards, rather than directly from isotopic ratios from AMS measurement. The precision and accuracy of quality controls and calibration standards met the requirements of bioanalytical guidance (U.S. Department of Health and Human Services, Food and Drug Administration, Center for Drug Evaluation and Research, Center for Veterinary Medicine. Guidance for Industry: Bioanalytical Method Validation (ucm070107), May 2001. http://www.fda.gov/downloads/Drugs/GuidanceCompilanceRegulatoryInformation/Guidances/ucm070107.pdf ). The AMS measurement had a linear response range from 0.0159 to 9.07 dpm/mL for plasma (14)C-SCH 900158 concentrations. The CV and accuracy were 3.4-8.5% and 94-108% (82-119% for the lower limit of quantitation (LLOQ)), respectively, with a correlation coefficient of 0.9998. The absolute bioavailability was calculated from the dose-normalized area under the curve of iv and oral doses after the plasma concentrations were plotted vs the sampling time post oral dose. The mean absolute bioavailability of SCH 900518 was 40.8% (range 16.8-60.6%). The typical accuracy and standard deviation in AMS quantitative analysis of drugs from human plasma samples have been reported for the first time, and the impact of these

  13. Biological growth functions describe published site index curves for Lake States timber species.

    Treesearch

    Allen L. Lundgren; William A. Dolid

    1970-01-01

    Two biological growth functions, an exponential-monomolecular function and a simple monomolecular function, have been fit to published site index curves for 11 Lake States tree species: red, jack, and white pine, balsam fir, white and black spruce, tamarack, white-cedar, aspen, red oak, and paper birch. Both functions closely fit all published curves except those for...

  14. Special conference of the American Association for Cancer Research on molecular imaging in cancer: linking biology, function, and clinical applications in vivo.

    PubMed

    Luker, Gary D

    2002-04-01

    The AACR Special Conference on Molecular Imaging in Cancer: Linking Biology, Function, and Clinical Applications In Vivo, was held January 23-27, 2002, at the Contemporary Hotel, Walt Disney World, Orlando, FL. Co-Chairs David Piwnica-Worms, Patricia Price and Thomas Meade brought together researchers with diverse expertise in molecular biology, gene therapy, chemistry, engineering, pharmacology, and imaging to accelerate progress in developing and applying technologies for imaging specific cellular and molecular signals in living animals and humans. The format of the conference was the presentation of research that focused on basic and translational biology of cancer and current state-of-the-art techniques for molecular imaging in animal models and humans. This report summarizes the special conference on molecular imaging, highlighting the interfaces of molecular biology with animal models, instrumentation, chemistry, and pharmacology that are essential to convert the dreams and promise of molecular imaging into improved understanding, diagnosis, and management of cancer.

  15. Mining Functional Modules in Heterogeneous Biological Networks Using Multiplex PageRank Approach

    PubMed Central

    Li, Jun; Zhao, Patrick X.

    2016-01-01

    Identification of functional modules/sub-networks in large-scale biological networks is one of the important research challenges in current bioinformatics and systems biology. Approaches have been developed to identify functional modules in single-class biological networks; however, methods for systematically and interactively mining multiple classes of heterogeneous biological networks are lacking. In this paper, we present a novel algorithm (called mPageRank) that utilizes the Multiplex PageRank approach to mine functional modules from two classes of biological networks. We demonstrate the capabilities of our approach by successfully mining functional biological modules through integrating expression-based gene-gene association networks and protein-protein interaction networks. We first compared the performance of our method with that of other methods using simulated data. We then applied our method to identify the cell division cycle related functional module and plant signaling defense-related functional module in the model plant Arabidopsis thaliana. Our results demonstrated that the mPageRank method is effective for mining sub-networks in both expression-based gene-gene association networks and protein-protein interaction networks, and has the potential to be adapted for the discovery of functional modules/sub-networks in other heterogeneous biological networks. The mPageRank executable program, source code, the datasets and results of the presented two case studies are publicly and freely available at http://plantgrn.noble.org/MPageRank/. PMID:27446133

  16. [The becoming of fatty cells, biological function of trophology, biological reactions of exo- and endotrophy in phylogenesis. The functional difference between visceral fatty cells and subcutaneous adipocytes].

    PubMed

    Titov, V N

    2014-12-01

    The becoming of visceral fatty, cells in phylogenesis occurred many billions years before subcutaneous adipocytes. The pool of visceral fatty cells realizes biologic functions of trophology and homeostasis, endoecology, and adaptation from the early stages of phylogenesis. The subcutaneous adipocytes realize phylogenetically late biologic function of locomotion. The visceral fatty cells have no receptors to insulin and all subcutaneous adipocytes are insulin-dependent. In biologic function of trophology, both visceral fatty cells and subcutaneous adipocytes realize biologic reaction of exotrophy, biologic reaction of depositing and biologic reaction of endotrophy. It is supposed that the most common cause of obesity is disorder of biologic reaction of depositing of fatty acids in form of triglycerides. It is considered as a basis of that dysfunction of visceral fatty cells (metabolic syndrome) and insulin-dependent adipocytes (obesity) takes so often a character of metabolic pandemic. The fatty cells absorb fatty acids in form of non-polar triglycerides, deposit them in lipid drops and free fatty acids into intercelluar medium in form of polar unesterified fatty acids. The visceral fatty cells had been formed in paracrin cenosis of enterocytes and in it microsome protein transferring triglycerides formed early type of chylomicrons. The visceral fatty cells and adipocytles are phylogenetically, regulatory, functionally and pathophysiologically different cells. Therefore, they are to be considered separately. Not only visceral fatty cells and adipocytes but all cells of areolar tissue at level of cenosis of cells secrete many humoral mediators of paracrin regulation. The other modes of regulation are unknown. Leptin is a specific mediator of visceral fatty cells and adiponectin is a mediator of subcutaneous adipocytes.

  17. Functional Data Analysis of Spaceflight-Induced Changes in Coordination and Phase in Head Pitch Acceleration During Treadmill Walking

    NASA Technical Reports Server (NTRS)

    Miller, Christopher; Peters, Brian; Feiveson, Alan; Bloomberg, Jacob

    2011-01-01

    Astronauts returning from spaceflight experience neurovestibular disturbances during head movements and attempt to mitigate them by limiting head motion. Analyses to date of the head movements made during walking have concentrated on amplitude and variability measures extracted from ensemble averages of individual gait cycles. Phase shifts within each gait cycle can be determined by functional data analysis through the computation of time-warping functions. Large, localized variations in the timing of peaks in head kinematics may indicate changes in coordination. The purpose of this study was to determine timing changes in head pitch acceleration of astronauts during treadmill walking before and after flight. Six astronauts (5M/1F; age = 43.5+/-6.4yr) participated in the study. Subjects walked at 1.8 m/sec (4 mph) on a motorized treadmill while reading optotypes displayed on a computer screen 4 m in front of their eyes. Three-dimensional motion of the subject s head was recorded with an Inertial Measurement Unit (IMU) device. Data were recorded twice before flight and four times after landing. The head pitch acceleration was calculated by taking the time derivative of the pitch velocity data from the IMU. Data for each session with each subject were time-normalized into gait cycles, then registered to align significant features and create a mean curve. The mean curves of each postflight session for each subject were re-registered based on their preflight mean curve to create time-warping functions. The root mean squares (RMS) of these warping functions were calculated to assess the deviation of head pitch acceleration mean curves in each postflight session from the preflight mean curve. After landing, most crewmembers exhibited localized shifts within their head pitch acceleration regimes, with the greatest deviations in RMS occurring on landing day or 1 day after landing. These results show that the alteration of head pitch coordination due to spaceflight may be

  18. Accelerated Recovery of Consciousness after General Anesthesia Is Associated with Increased Functional Brain Connectivity in the High-Gamma Bandwidth

    PubMed Central

    Li, Duan; Hambrecht-Wiedbusch, Viviane S.; Mashour, George A.

    2017-01-01

    Recent data from our laboratory demonstrate that high-frequency gamma connectivity across the cortex is present during consciousness and depressed during unconsciousness. However, these data were derived from static and well-defined states of arousal rather than during transitions that would suggest functional relevance. We also recently found that subanesthetic ketamine administered during isoflurane anesthesia accelerates recovery upon discontinuation of the primary anesthetic and increases gamma power during emergence. In the current study we re-analyzed electroencephalogram (EEG) data to test the hypothesis that functional cortical connectivity between anterior and posterior cortical regions would be increased during accelerated recovery induced by ketamine when compared to saline-treated controls. Rodents were instrumented with intracranial EEG electrodes and general anesthesia was induced with isoflurane anesthesia. After 37.5 min of continuous isoflurane anesthesia, a subanesthetic dose of ketamine (25 mg/kg intraperitoneal) was administered, with evidence of a 44% reduction in emergence time. In this study, we analyzed gamma and theta coherence (measure of undirected functional connectivity) and normalized symbolic transfer entropy (measure of directed functional connectivity) between frontal and parietal cortices during various levels of consciousness, with a focus on emergence from isoflurane anesthesia. During accelerated emergence in the ketamine-treated group, there was increased frontal-parietal coherence {p = 0.005, 0.05–0.23 [95% confidence interval (CI)]} and normalized symbolic transfer entropy [frontal to parietal: p < 0.001, 0.010–0.026 (95% CI); parietal to frontal: p < 0.001, 0.009–0.025 (95% CI)] in high-frequency gamma bandwidth as compared with the saline-treated group. Surrogates of cortical information exchange in high-frequency gamma are increased in association with accelerated recovery from anesthesia. This finding adds evidence

  19. Functional significance of macrophages in pancreatic cancer biology.

    PubMed

    Hu, Hai; Jiao, Feng; Han, Ting; Wang, Li-Wei

    2015-12-01

    Pancreatic ductal adenocarcinoma (PDA) is a lethal disease that is usually diagnosed at late stage with few effective therapies. Despite the rapid progress on the genomics and proteomics of the neoplastic cells, therapies that targeted the pancreatic cancer cells proved to be inefficient, which promoted the researchers to turn their attentions to the microenvironment. Currently, various studies had proposed the microenvironment to be a contributing factor for PDA and pervasive researches showed that macrophages within the malignancy correlate with the malignant phenotype of the disease and were reported to a new therapeutic target. Generally, the pro-tumoral effects of macrophages can be summarized as angiogenesis promotion, immunosuppression, matrix remodeling and so on. Hence, a comprehensive understanding of the biologic behaviors of macrophages and their critical role in PDA development may provide new directions for the managements of the lethal disease. In this review, we will summarize the recent advancements on macrophages as pivotal players in PDA biology and the current knowledge about anti-macrophages as a novel strategy against cancer, with the expectation that more efficient therapies will be developed in the near future.

  20. [Biological problems of origin and development of various physiological functions (theory and application)].

    PubMed

    Ivanov, K P

    2001-01-01

    The author presents some idea about origin and development of some physiological functions: outer breathing, breath function of blood, blood circulation, thermoregulation, energy supply. The conclusions about main directions of evolution of these functions and duration of their development in phylogeny were drawn. The author gave some examples of abrupt changes of development of these functions in different groups of animals and discussed possible reasons of such changes. General quantitative estimation of the results of evolution of these functions from the position of their summArized efficiency was done. Quantitative characteristics of optimization and efficiency limits of physiological functions were suggested on the base of new data in general biology and comparative physiology. The author put toward the hypothesis about conventional "mistakes" of evolution and showed deep biological reasons of some seriOus illness. The examples of some applied problems in biology, physiology and medicine that can be solved with the data on evolution of physiological functions are presented.

  1. Hydrocarbon stapled peptides as modulators of biological function.

    PubMed

    Cromm, Philipp M; Spiegel, Jochen; Grossmann, Tom N

    2015-06-19

    Peptide-based drug discovery has experienced a significant upturn within the past decade since the introduction of chemical modifications and unnatural amino acids has allowed for overcoming some of the drawbacks associated with peptide therapeutics. Strengthened by such features, modified peptides become capable of occupying a niche that emerges between the two major classes of today's therapeutics-small molecules (<500 Da) and biologics (>5000 Da). Stabilized α-helices have proven particularly successful at impairing disease-relevant PPIs previously considered "undruggable." Among those, hydrocarbon stapled α-helical peptides have emerged as a novel class of potential peptide therapeutics. This review provides a comprehensive overview of the development and applications of hydrocarbon stapled peptides discussing the benefits and limitations of this technique.

  2. sBWT: memory efficient implementation of the hardware-acceleration-friendly Schindler transform for the fast biological sequence mapping.

    PubMed

    Chang, Chia-Hua; Chou, Min-Te; Wu, Yi-Chung; Hong, Ting-Wei; Li, Yun-Lung; Yang, Chia-Hsiang; Hung, Jui-Hung

    2016-11-15

    The Full-text index in Minute space (FM-index) derived from the Burrows-Wheeler transform (BWT) is broadly used for fast string matching in large genomes or a huge set of sequencing reads. Several graphic processing unit (GPU) accelerated aligners based on the FM-index have been proposed recently; however, the construction of the index is still handled by central processing unit (CPU), only parallelized in data level (e.g. by performing blockwise suffix sorting in GPU), or not scalable for large genomes. To fulfill the need for a more practical, hardware-parallelizable indexing and matching approach, we herein propose sBWT based on a BWT variant (i.e. Schindler transform) that can be built with highly simplified hardware-acceleration-friendly algorithms and still suffices accurate and fast string matching in repetitive references. In our tests, the implementation achieves significant speedups in indexing and searching compared with other BWT-based tools and can be applied to a variety of domains. sBWT is implemented in C ++ with CPU-only and GPU-accelerated versions. sBWT is open-source software and is available at http://jhhung.github.io/sBWT/Supplementary information: Supplementary data are available at Bioinformatics online. chyee@ntu.edu.tw or jhhung@nctu.edu.tw (also juihunghung@gmail.com). © The Author 2016. Published by Oxford University Press. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

  3. Chemically-functionalized microcantilevers for detection of chemical, biological and explosive material

    SciTech Connect

    Pinnaduwage, Lal A; Thundat, Thomas G; Brown, Gilbert M; Hawk, John Eric; Boiadjiev, Vassil I

    2007-04-24

    A chemically functionalized cantilever system has a cantilever coated on one side thereof with a reagent or biological species which binds to an analyte. The system is of particular value when the analyte is a toxic chemical biological warfare agent or an explosive.

  4. Beyond Iron: Non-Classical Biological Functions of Bacterial Siderophores

    PubMed Central

    Johnstone, Timothy C.; Nolan, Elizabeth M.

    2015-01-01

    Bacteria secrete small molecules known as siderophores to acquire iron from their surroundings. For over 60 years, investigations into the bioinorganic chemistry of these molecules, including fundamental coordination chemistry studies, have provided insight into the crucial role that siderophores play in bacterial iron homeostasis. The importance of understanding the fundamental chemistry underlying bacterial life has been highlighted evermore in recent years because of the emergence of antibiotic-resistant bacteria and the need to prevent the global rise of these superbugs. Increasing reports of siderophores functioning in capacities other than iron transport have appeared recently, but reports of “non-classical” siderophore functions have long paralleled those of iron transport. One particular non-classical function of these iron chelators, namely antibiotic activity, was even documented before the role of siderophores in iron transport was established. In this Perspective, we present an exposition of past and current work into non-classical functions of siderophores and highlight the directions in which we anticipate that this research is headed. Examples include the ability of siderophores to function as zincophores, chalkophores, and metallophores for a variety of other metals, sequester heavy metal toxins, transport boron, act as signalling molecules, regulate oxidative stress, and provide antibacterial activity. PMID:25764171

  5. Beyond iron: non-classical biological functions of bacterial siderophores.

    PubMed

    Johnstone, Timothy C; Nolan, Elizabeth M

    2015-04-14

    Bacteria secrete small molecules known as siderophores to acquire iron from their surroundings. For over 60 years, investigations into the bioinorganic chemistry of these molecules, including fundamental coordination chemistry studies, have provided insight into the crucial role that siderophores play in bacterial iron homeostasis. The importance of understanding the fundamental chemistry underlying bacterial life has been highlighted evermore in recent years because of the emergence of antibiotic-resistant bacteria and the need to prevent the global rise of these superbugs. Increasing reports of siderophores functioning in capacities other than iron transport have appeared recently, but reports of "non-classical" siderophore functions have long paralleled those of iron transport. One particular non-classical function of these iron chelators, namely antibiotic activity, was documented before the role of siderophores in iron transport was established. In this Perspective, we present an exposition of past and current work into non-classical functions of siderophores and highlight the directions in which we anticipate that this research is headed. Examples include the ability of siderophores to function as zincophores, chalkophores, and metallophores for a variety of other metals, sequester heavy metal toxins, transport boron, act as signalling molecules, regulate oxidative stress, and provide antibacterial activity.

  6. Rapidly restoring biological soil crusts and ecosystem functions in a severely disturbed desert ecosystem.

    PubMed

    Chiquoine, Lindsay P; Abella, Scott R; Bowker, Matthew A

    2016-06-01

    Restoring biological soil crusts (biocrusts) in degraded drylands can contribute to recovery of ecosystem functions that have global implications, including erosion resistance and nutrient cycling. To examine techniques for restoring biocrusts, we conducted a replicated, factorial experiment on recently abandoned road surfaces by applying biocrust inoculation (salvaged and stored dry for two years), salvaged topsoil, an abiotic soil amendment (wood shavings), and planting of a dominant perennial shrub (Ambrosia dumosa). Eighteen months after treatments, we measured biocrust abundance and species composition, soil chlorophyll a content and fertility, and soil resistance to erosion. Biocrust addition significantly accelerated biocrust recovery on disturbed soils, including increasing lichen and moss cover and cyanobacteria colonization. Compared to undisturbed controls, inoculated plots had similar lichen and moss composition, recovered 43% of total cyanobacteria density, had similar soil chlorophyll content, and exhibited recovery of soil fertility and soil stability. Inoculation was the only treatment that generated lichen and moss cover. Topsoil application resulted in partial recovery of the cyanobacteria community and soil properties. Compared to untreated disturbed plots, topsoil application without inoculum increased cyanobacteria density by 186% and moderately improved soil chlorophyll and ammonium content and soil stability. Topsoil application produced 22% and 51% of the cyanobacteria density g⁻¹ soil compared to undisturbed and inoculated plots, respectively. Plots not treated with either topsoil or inoculum had significantly lower cyanobacteria density, soil chlorophyll and ammonium concentrations, and significantly higher soil nitrate concentration. Wood shavings and Ambrosia had no influence on biocrust lichen and moss species recovery but did affect cyanobacteria composition and soil fertility. Inoculation of severely disturbed soil with native

  7. X-ray phase contrast imaging of biological samples using a betatron x-ray source generated in a laser wakefield accelerator

    NASA Astrophysics Data System (ADS)

    Chaulagain, U.; Bohacek, K.; Kozlova, M.; Nejdl, J.; Krus, M.; Horny, V.; Mahieu, B.; Ta-Phuoc, K.

    2017-05-01

    In a plasma wakefield accelerator, an intense laser pulse propagates in an under-dense plasma that drives a relativistic plasma wave in which electrons can be injected and accelerated to relativistic energies within a short distance. These accelerated electrons undergo betatron oscillation and emit a collimated X-ray beam along the direction of electron velocity. This X-ray source is characterised with a source size of the order of a micrometer, a pulse duration of the order of femtosecond, and with a high spectral brightness. This novel X-ray source provides an excellent imaging tool to achieve unprecedented high-resolution image through phase contrast imaging. The phase contrast technique has the potential to reveal structures which are invisible with the conventional absorption imaging. In the X-ray phase contrast imaging, the image contrast is obtained thanks to phase shifts induced on the X-rays passing through the sample. It involves the real part of refractive index of the object. Here we present high-resolution phase contrast X-ray images of two biological samples using laser-driven Betatron X-ray source.

  8. Island biology and ecosystem functioning in epiphytic soil communities.

    PubMed

    Wardle, David A; Yeates, Gregor W; Barker, Gary M; Bellingham, Peter J; Bonner, Karen I; Williamson, Wendy M

    2003-09-19

    Although island attributes such as size and accessibility to colonizing organisms can influence community structure, the consequences of these for ecosystem functioning are little understood. A study of the suspended soils of spatially discrete epiphytes or treetop "islands" in the canopies of New Zealand rainforest trees revealed that different components of the decomposer community responded either positively or negatively to island size, as well as to the tree species that the islands occurred in. This in turn led to important differences between islands in the rates of ecosystem processes driven by the decomposer biota. This system serves as a model for better understanding how attributes of both real and habitat islands may affect key ecosystem functions through determining the community structure of organisms that drive these functions.

  9. Accelerating Scientific Discovery Through Computation and Visualization III. Tight-Binding Wave Functions for Quantum Dots.

    PubMed

    Sims, James S; George, William L; Griffin, Terence J; Hagedorn, John G; Hung, Howard K; Kelso, John T; Olano, Marc; Peskin, Adele P; Satterfield, Steven G; Terrill, Judith Devaney; Bryant, Garnett W; Diaz, Jose G

    2008-01-01

    This is the third in a series of articles that describe, through examples, how the Scientific Applications and Visualization Group (SAVG) at NIST has utilized high performance parallel computing, visualization, and machine learning to accelerate scientific discovery. In this article we focus on the use of high performance computing and visualization for simulations of nanotechnology.

  10. Novel ESCRT functions in cell biology: spiraling out of control?

    PubMed

    Campsteijn, Coen; Vietri, Marina; Stenmark, Harald

    2016-08-01

    The endosomal sorting complex required for transport (ESCRT), originally identified for its role in endosomal protein sorting and biogenesis of multivesicular endosomes (MVEs), has proven to be a versatile machinery for involution and scission of narrow membrane invaginations filled with cytosol. Budding of enveloped viruses and cytokinetic abscission were early described functions for the ESCRT machinery, and recently a number of new ESCRT functions have emerged. These include cytokinetic abscission checkpoint control, plasma membrane repair, exovesicle release, quality control of nuclear pore complexes, neuron pruning, and sealing of the newly formed nuclear envelope. Here we review these novel ESCRT mechanisms and discuss similarities and differences between the various ESCRT-dependent activities.

  11. Does Sequence Conservation Provide Evidence for Biological Function?

    PubMed

    Omer, Seila; Harlow, Timothy J; Gogarten, Johann Peter

    2017-01-01

    Finding a signature of purifying selection in a gene is usually interpreted as evidence for the gene providing a function that is targeted by natural selection. This opinion offers a very different hypothesis: purifying selection may be due to removing harmful mutations from the population, that is, the gene and its encoded protein become harmful after a mutation occurred, possibly because the mutated protein interferes with the translation machinery, or because of toxicity of the misfolded protein. Finding a signature of purifying selection should not automatically be considered proof of the gene's selectable function.

  12. HDL abnormalities in familial hypercholesterolemia: Focus on biological functions.

    PubMed

    Ganjali, Shiva; Momtazi, Amir Abbas; Banach, Maciej; Kovanen, Petri T; Stein, Evan A; Sahebkar, Amirhossein

    2017-07-01

    Although a selective strong elevation in the plasma level of low-density lipoprotein (LDL) cholesterol is the hallmark of familial hypercholesterolemia (FH), also other plasma lipoprotein and lipid subspecies are changed in these patients. Several studies in FH patients have pointed to the qualitative abnormalities of high-density lipoprotein (HDL) particles, including their triglyceride and sphingomyelin enrichment, reduced capacity to promote cholesterol efflux from macrophages, impaired anti-inflammatory and anti-oxidant activities, and reduced plasma levels of miRs regulating HDL-dependent cholesterol efflux from macrophage foam cells, typical of atherosclerotic lesions. Thus, accurate understanding of HDL functionality and its disturbances in FH may serve a better estimation of the prognosis and also provide additional clues when searching for novel therapeutic choices in this disease. In spite of such a potential promise, there has been no prior comprehensive review focusing on indices of HDL function in FH patients. In the present review, we aim to fulfill this gap by identifying measures of HDL function that are impaired in FH, and by providing a concise summary on the impact of different lipid-modifying therapies on HDL functionality in FH. Copyright © 2017 Elsevier Ltd. All rights reserved.

  13. Exosome function: from tumor immunology to pathogen biology.

    PubMed

    Schorey, Jeffrey S; Bhatnagar, Sanchita

    2008-06-01

    Exosomes are the newest family member of 'bioactive vesicles' that function to promote intercellular communication. Exosomes are derived from the fusion of multivesicular bodies with the plasma membrane and extracellular release of the intraluminal vesicles. Recent studies have focused on the biogenesis and composition of exosomes as well as regulation of exosome release. Exosomes have been shown to be released by cells of hematopoietic and non-hematopoietic origin, yet their function remains enigmatic. Much of the prior work has focused on exosomes as a source of tumor antigens and in presentation of tumor antigens to T cells. However, new studies have shown that exosomes might also promote cell-to-cell spread of infectious agents. Moreover, exosomes isolated from cells infected with various intracellular pathogens, including Mycobacterium tuberculosis and Toxoplasma gondii, have been shown to contain microbial components and can promote antigen presentation and macrophage activation, suggesting that exosomes may function in immune surveillance. In this review, we summarize our understanding of exosome biogenesis but focus primarily on new insights into exosome function. We also discuss their possible use as disease biomarkers and vaccine candidates.

  14. Function-first antibody discovery: Embracing the unpredictable biology of antibodies.

    PubMed

    Frendéus, Björn

    2013-08-01

    Therapeutic antibodies may mediate antineoplastic effects by altering the biological functions of their target, by directly stimulating the demise of cancer cells or by activating antibody-dependent immune effector mechanisms. We have recently provided in vivo proof-of-concept for a "function-first" target and drug discovery platform in which antibodies against a multitude of tumor-associated antigens are screened for biological effects in a target-unbiased manner.

  15. 3D Printing Polymers with Supramolecular Functionality for Biological Applications.

    PubMed

    Pekkanen, Allison M; Mondschein, Ryan J; Williams, Christopher B; Long, Timothy E

    2017-09-11

    Supramolecular chemistry continues to experience widespread growth, as fine-tuned chemical structures lead to well-defined bulk materials. Previous literature described the roles of hydrogen bonding, ionic aggregation, guest/host interactions, and π-π stacking to tune mechanical, viscoelastic, and processing performance. The versatility of reversible interactions enables the more facile manufacturing of molded parts with tailored hierarchical structures such as tissue engineered scaffolds for biological applications. Recently, supramolecular polymers and additive manufacturing processes merged to provide parts with control of the molecular, macromolecular, and feature length scales. Additive manufacturing, or 3D printing, generates customizable constructs desirable for many applications, and the introduction of supramolecular interactions will potentially increase production speed, offer a tunable surface structure for controlling cell/scaffold interactions, and impart desired mechanical properties through reinforcing interlayer adhesion and introducing gradients or self-assembled structures. This review details the synthesis and characterization of supramolecular polymers suitable for additive manufacture and biomedical applications as well as the use of supramolecular polymers in additive manufacturing for drug delivery and complex tissue scaffold formation. The effect of supramolecular assembly and its dynamic behavior offers potential for controlling the anisotropy of the printed objects with exquisite geometrical control. The potential for supramolecular polymers to generate well-defined parts, hierarchical structures, and scaffolds with gradient properties/tuned surfaces provides an avenue for developing next-generation biomedical devices and tissue scaffolds.

  16. TERT biology and function in cancer: beyond immortalisation.

    PubMed

    Pestana, Ana; Vinagre, João; Sobrinho-Simões, Manuel; Soares, Paula

    2017-02-01

    Evasion of replicative senescence and proliferation without restriction, sometimes designated as immortalisation, is one of the hallmarks of cancer that may be attained through reactivation of telomerase in somatic cells. In contrast to most normal cells in which there is lack of telomerase activity, upregulation of TERT transcription/activity is detected in 80-90% of malignant tumours. In several types of cancer, there is a relationship between the presence of TERT promoter mutations, TERT mRNA expression and clinicopathological features, but the biological bridge between the occurrence of TERT promoter mutations and the aggressive/invasive features displayed by the tumours remains unidentified. We and others have associated the presence of TERT promoter mutations with metastisation/survival in several types of cancer. In follicular cell-derived thyroid cancer, such mutations are associated with worse prognostic features (age of patients, tumour size and tumour stage) as well as with distant metastases, worse response to treatment and poorer survival. In this review, we analyse the data reported in several studies that imply TERT transcription reactivation/activity with cell proliferation, tumour invasion and metastisation. A particular attention is given to the putative connections between TERT transcriptional reactivation and signalling pathways frequently altered in cancer, such as c-MYC, NF-κB and B-Catenin. © 2017 Society for Endocrinology.

  17. Holocarboxylase synthetase: correlation of protein localisation with biological function.

    PubMed

    Bailey, L M; Wallace, J C; Polyak, S W

    2010-04-01

    Holocarboxylase synthetase (HCS) governs the cellular fate of the essential micronutrient biotin (Vitamin H or B7). HCS is responsible for attaching biotin onto the biotin-dependent enzymes that reside in the cytoplasm and mitochondria. Evidence for an alternative role, viz the regulation of gene expression, has also been reported. Recent immunohistochemical studies reported HCS is primarily nuclear, inconsistent with the location of HCS activity. Improved understanding of biotin biology demands greater knowledge about HCS. Here, we investigated the localisation of HCS and its isoforms. Three variants were observed that differ at the N-terminus. All HCS isoforms were predominantly non-nuclear, consistent with the distribution of biotin protein ligase activity. Unlike the longer constructs, the Met(58) isoform was also detected in the nucleus--a novel observation suggesting shuttling activity between nucleus and cytoplasm. We resolved that the previous controversies in the literature are due to specificity and detection limitations that arise when using partially purified antibodies. 2010. Published by Elsevier Inc. All rights reserved.

  18. Structure, Biological Functions and Applications of the AB5 Toxins

    PubMed Central

    Beddoe, Travis; Paton, Adrienne W.; Le Nours, Jérôme; Rossjohn, Jamie; Paton, James C.

    2010-01-01

    AB5 toxins are important virulence factors for several major bacterial pathogens, including Bordetella pertussis, Vibrio cholerae, Shigella dysenteriae and at least two distinct pathotypes of Escherichia coli. The AB5 toxins are so termed because they comprise a catalytic A-subunit, which is responsible for disruption of essential host functions, and a pentameric B-subunit that binds to specific glycan receptors on the target cell surface. The molecular mechanisms by which these AB5 toxins cause disease have been largely unraveled, including recent insights into a novel AB5 toxin family, subtilase cytotoxin (SubAB). Furthermore, AB5 toxins have become a valuable tool for studying fundamental cellular functions, and are now being investigated for potential applications in the clinical treatment of human diseases. PMID:20202851

  19. Structure, biological functions and applications of the AB5 toxins.

    PubMed

    Beddoe, Travis; Paton, Adrienne W; Le Nours, Jérôme; Rossjohn, Jamie; Paton, James C

    2010-07-01

    AB(5) toxins are important virulence factors for several major bacterial pathogens, including Bordetella pertussis, Vibrio cholerae, Shigella dysenteriae and at least two distinct pathotypes of Escherichia coli. The AB(5) toxins are so named because they comprise a catalytic A-subunit, which is responsible for disruption of essential host functions, and a pentameric B-subunit that binds to specific glycan receptors on the target cell surface. The molecular mechanisms by which the AB(5) toxins cause disease have been largely unravelled, including recent insights into a novel AB(5) toxin family, subtilase cytotoxin (SubAB). Furthermore, AB(5) toxins have become a valuable tool for studying fundamental cellular functions, and are now being investigated for potential applications in the clinical treatment of human diseases. Copyright 2010 Elsevier Ltd. All rights reserved.

  20. Density functional theory across chemistry, physics and biology

    PubMed Central

    van Mourik, Tanja; Bühl, Michael; Gaigeot, Marie-Pierre

    2014-01-01

    The past decades have seen density functional theory (DFT) evolve from a rising star in computational quantum chemistry to one of its major players. This Theme Issue, which comes half a century after the publication of the Hohenberg–Kohn theorems that laid the foundations of modern DFT, reviews progress and challenges in present-day DFT research. Rather than trying to be comprehensive, this Theme Issue attempts to give a flavour of selected aspects of DFT. PMID:24516181

  1. Functional Nanostructured Platforms for Chemical and Biological Sensing

    SciTech Connect

    Letant, S E

    2006-03-20

    The central goal of our work is to combine semiconductor nanotechnology and surface functionalization in order to build platforms for the selective detection of bio-organisms ranging in size from bacteria (micron range) down to viruses, as well as for the detection of chemical agents (nanometer range). We will show on three porous silicon platforms how pore geometry and pore wall chemistry can be combined and optimized to capture and detect specific targets. We developed a synthetic route allowing to directly anchor proteins on silicon surfaces and illustrated the relevance of this technique by immobilizing live enzymes onto electrochemically etched luminescent nano-porous silicon. The powerful association of the specific enzymes with the transducing matrix led to a selective hybrid platform for chemical sensing. We also used light-assisted electrochemistry to produce periodic arrays of through pores on pre-patterned silicon membranes with controlled diameters ranging from many microns down to tens of nanometers. We demonstrated the first covalently functionalized silicon membranes and illustrated their selective capture abilities with antibody-coated micro-beads. These engineered membranes are extremely versatile and could be adapted to specifically recognize the external fingerprints (size and coat composition) of target bio-organisms. Finally, we fabricated locally functionalized single nanopores using a combination of focused ion beam drilling and ion beam assisted oxide deposition. We showed how a silicon oxide ring can be grown around a single nanopore and how it can be functionalized with DNA probes to detect single viral-sized beads. The next step for this platform is the detection of whole viruses and bacteria.

  2. Biological factors of natural and artificial ecosystems stable (unstable) functioning

    NASA Astrophysics Data System (ADS)

    Pechurkin, Nikolai S.

    The problem of sustainable development of humanity on Earth and the problem of supporting human life in space have the same scientific and methodological bases. The key to solve both problems is a long term maintenance of balanced material cycle. As a whole, natural or artificial ecosystems are to be more closed than open, but their elements (links of systems) are to be substantially open in interactions with each other. Prolonged stable interactions of different links have to have unique joint results - closed material cycling or biotic turnover. It is necessary to include, at least, three types of main links into any system to support real material cycling: producers, consumers, reducers. Producer links are now under studies in many laboratories. It is evident that the higher productivity of link, the lower link stability. Especially, it concerns with parasite impact to plants. As usual, artificial ecosystems are more simple (incomplete) than natural ecosystems, sometimes, they have not enough links for prolonged stable functioning. For example, life support system for space flight can be incomplete in consumer link, having only some crew persons, instead of interacting populations of consumers. As for reducer link, it is necessary to "organize" a special coordinated work of microbial biocenoses to fulfill proper cycling. Possible evolution of links, their self development is a matter of special attention for the maintenance of prolonged stable functioning. It's the most danger for systems with populations of quickly reproducing, so-called, R - strategists, according to symbols of logistic equation. From another side, quick reproduction of R - strategists is able to increase artificial ecosystems and their links functioning. After some damages of system, R - strategist's link can be quickly "self repaired" up to level of normal functioning. Some experimental data of this kind and mathematical models are to be discussed in the paper. This work is supported by

  3. Functional nanostructured platforms for chemical and biological sensing

    NASA Astrophysics Data System (ADS)

    Létant, S. E.

    2006-05-01

    The central goal of our work is to combine semiconductor nanotechnology and surface functionalization in order to build platforms for the selective detection of bio-organisms ranging in size from bacteria (micron range) down to viruses, as well as for the detection of chemical agents (nanometer range). We will show on three porous silicon platforms how pore geometry and pore wall chemistry can be combined and optimized to capture and detect specific targets. We developed a synthetic route allowing to directly anchor proteins on silicon surfaces and illustrated the relevance of this technique by immobilizing live enzymes onto electrochemically etched luminescent nano-porous silicon. The powerful association of the specific enzymes with the transducing matrix led to a selective hybrid platform for chemical sensing. We also used light-assisted electrochemistry to produce periodic arrays of through pores on pre-patterned silicon membranes with controlled diameters ranging from many microns down to tens of nanometers. We demonstrated the first covalently functionalized silicon membranes and illustrated their selective capture abilities with antibody-coated micro-beads. These engineered membranes are extremely versatile and could be adapted to specifically recognize the external fingerprints (size and coat composition) of target bio-organisms. Finally, we fabricated locally functionalized single nanopores using a combination of focused ion beam drilling and ion beam assisted oxide deposition. We showed how a silicon oxide ring can be grown around a single nanopore and how it can be functionalized with DNA probes to detect single viral-sized beads. The next step for this platform is the detection of whole viruses and bacteria.

  4. Density functional theory across chemistry, physics and biology.

    PubMed

    van Mourik, Tanja; Bühl, Michael; Gaigeot, Marie-Pierre

    2014-03-13

    The past decades have seen density functional theory (DFT) evolve from a rising star in computational quantum chemistry to one of its major players. This Theme Issue, which comes half a century after the publication of the Hohenberg-Kohn theorems that laid the foundations of modern DFT, reviews progress and challenges in present-day DFT research. Rather than trying to be comprehensive, this Theme Issue attempts to give a flavour of selected aspects of DFT.

  5. STRIPAK complexes: structure, biological function, and involvement in human diseases.

    PubMed

    Hwang, Juyeon; Pallas, David C

    2014-02-01

    The mammalian striatin family consists of three proteins, striatin, S/G2 nuclear autoantigen, and zinedin. Striatin family members have no intrinsic catalytic activity, but rather function as scaffolding proteins. Remarkably, they organize multiple diverse, large signaling complexes that participate in a variety of cellular processes. Moreover, they appear to be regulatory/targeting subunits for the major eukaryotic serine/threonine protein phosphatase 2A. In addition, striatin family members associate with germinal center kinase III kinases as well as other novel components, earning these assemblies the name striatin-interacting phosphatase and kinase (STRIPAK) complexes. Recently, there has been a great increase in functional and mechanistic studies aimed at identifying and understanding the roles of STRIPAK and STRIPAK-like complexes in cellular processes of multiple organisms. These studies have identified novel STRIPAK and STRIPAK-like complexes and have explored their roles in specific signaling pathways. Together, the results of these studies have sparked increased interest in striatin family complexes because they have revealed roles in signaling, cell cycle control, apoptosis, vesicular trafficking, Golgi assembly, cell polarity, cell migration, neural and vascular development, and cardiac function. Moreover, STRIPAK complexes have been connected to clinical conditions, including cardiac disease, diabetes, autism, and cerebral cavernous malformation. In this review, we discuss the expression, localization, and protein domain structure of striatin family members. Then we consider the diverse complexes these proteins and their homologs form in various organisms, emphasizing what is known regarding function and regulation. Finally, we explore possible roles of striatin family complexes in disease, especially cerebral cavernous malformation.

  6. Biology and Function of Fetal and Pediatric Skin

    PubMed Central

    Leung, Alice; Balaji, Swathi; Keswani, Sundeep G

    2013-01-01

    Synopsis The development of the integumentary system is a series of events, which start in utero and continue throughout life. Although at birth, skin in full-term infants is anatomically mature, functional maturity develops during the first year of life. Pediatric skin transitions again with the onset of puberty. At each stage, there are changes in transepidermal water loss, skin hydration, and skin acidity that define the specific period of development. PMID:23369584

  7. Social inclusion enhances biological motion processing: a functional near-infrared spectroscopy study.

    PubMed

    Bolling, Danielle Z; Pelphrey, Kevin A; Kaiser, Martha D

    2013-04-01

    Humans are especially tuned to the movements of other people. Neural correlates of this social attunement have been proposed to lie in and around the right posterior superior temporal sulcus (STS) region, which robustly responds to biological motion in contrast to a variety of non-biological motions. This response persists even when no form information is provided, as in point-light displays (PLDs). The aim of the current study was to assess the ability of functional near-infrared spectroscopy (fNIRS) to reliably measure brain responses to PLDs of biological motion, and determine the sensitivity of these responses to interpersonal contextual factors. To establish reliability, we measured brain activation to biological motion with fNIRS and functional magnetic resonance imaging (fMRI) during two separate sessions in an identical group of 12 participants. To establish sensitivity, brain responses to biological motion measured with fNIRS were subjected to an additional social manipulation where participants were either socially included or excluded before viewing PLDs of biological motion. Results revealed comparable brain responses to biological motion using fMRI and fNIRS in the right supramarginal gyrus. Further, social inclusion increased brain responses to biological motion in right supramarginal gyrus and posterior STS. Thus, fNIRS can reliably measure brain responses to biological motion and can detect social experience-dependent modulations of these brain responses.

  8. Acceleration modules in linear induction accelerators

    NASA Astrophysics Data System (ADS)

    Wang, Shao-Heng; Deng, Jian-Jun

    2014-05-01

    The Linear Induction Accelerator (LIA) is a unique type of accelerator that is capable of accelerating kilo-Ampere charged particle current to tens of MeV energy. The present development of LIA in MHz bursting mode and the successful application into a synchrotron have broadened LIA's usage scope. Although the transformer model is widely used to explain the acceleration mechanism of LIAs, it is not appropriate to consider the induction electric field as the field which accelerates charged particles for many modern LIAs. We have examined the transition of the magnetic cores' functions during the LIA acceleration modules' evolution, distinguished transformer type and transmission line type LIA acceleration modules, and re-considered several related issues based on transmission line type LIA acceleration module. This clarified understanding should help in the further development and design of LIA acceleration modules.

  9. Functionalized amphipols: a versatile toolbox suitable for applications of membrane proteins in synthetic biology.

    PubMed

    Della Pia, Eduardo Antonio; Hansen, Randi Westh; Zoonens, Manuela; Martinez, Karen L

    2014-10-01

    Amphipols are amphipathic polymers that stabilize membrane proteins isolated from their native membrane. They have been functionalized with various chemical groups in the past years for protein labeling and protein immobilization. This large toolbox of functionalized amphipols combined with their interesting physico-chemical properties give opportunities to selectively add multiple functionalities to membrane proteins and to tune them according to the needs. This unique combination of properties makes them one of the most versatile strategies available today for exploiting membrane proteins onto surfaces for various applications in synthetic biology. This review summarizes the properties of functionalized amphipols suitable for synthetic biology approaches.

  10. Developmental and functional biology of the primate fetal adrenal cortex.

    PubMed

    Mesiano, S; Jaffe, R B

    1997-06-01

    The unique characteristics of the primate (particularly human) fetal adrenal were first realized in the early 1900s when its morphology was examined in detail and compared with that of other species. The unusual architecture of the human fetal adrenal cortex, with its unique and disproportionately enlarged fetal zone, its compact definitive zone, and its dramatic remodeling soon after birth captured the interest of developmental anatomists. Many detailed anatomical studies describing the morphology of the developing human fetal adrenal were reported between 1920 and 1960, and these morphological descriptions have not changed significantly. More recently, it has become clear that fetal adrenal cortical growth involves cellular hypertrophy, hyperplasia, apoptosis, and migration and is best described by the migration theory, i.e. cells proliferate in the periphery, migrate centripetally, differentiate during their migration to form the functional cortical zones, and then likely undergo apoptosis in the center of the cortex. Consistent with this model, cells of intermediate phenotype, arranged in columnar cords typical of migration, have been identified between the definitive and fetal zones. This cortical area has been referred to as the transitional zone and, based on the expression of steroidogenic enzymes, we consider it to be a functionally distinct cortical zone. Elegant experiments during the 1950s and 1960s demonstrated the central role of the primate fetal adrenal cortex in establishing the estrogenic milieu of pregnancy. Those findings were among the first indications of the function and physiological role of the human fetal adrenal cortex and led Diczfalusy and co-workers to propose the concept of the feto-placental unit, in which DHEA-S produced by the fetal adrenal cortex is used by the placenta for estrogen synthesis. Tissue and cell culture techniques, together with improved steroid assays, revealed that the fetal zone is the primary source of DHEA

  11. Omega-6 and omega-3 fatty acids predict accelerated decline of peripheral nerve function in older persons

    PubMed Central

    Lauretani, F.; Bandinelli, S.; Benedetta, B.; Cherubini, A.; Iorio, A. D.; Blè, A.; Giacomini, V.; Corsi, A. M.; Guralnik, J. M.; Ferrucci, L.

    2009-01-01

    Pre-clinical studies suggest that both omega-6 and omega-3 fatty acids have beneficial effects on peripheral nerve function. Rats feed a diet rich in polyunsaturated fatty acids (PUFAs) showed modification of phospholipid fatty acid composition in nerve membranes and improvement of sciatic nerve conduction velocity (NCV). We tested the hypothesis that baseline plasma omega-6 and omega-3 fatty acids levels predict accelerated decline of peripheral nerve function. Changes between baseline and the 3-year follow-up in peripheral nerve function was assessed by standard surface ENG of the right peroneal nerve in 384 male and 443 female participants of the InCHIANTI study (age range: 24–97 years). Plasma concentrations of selected fatty acids assessed at baseline by gas chromatography. Independent of confounders, plasma omega-6 fatty acids and linoleic acid were significantly correlated with peroneal NCV at enrollment. Lower plasma PUFA, omega-6 fatty acids, linoleic acid, ratio omega-6/omega-3, arachidonic acid and docosahexanoic acid levels were significantly predicted a steeper decline in nerve function parameters over the 3-year follow-up. Low plasma omega-6 and omega-3 fatty acids levels were associated with accelerated decline of peripheral nerve function with aging. PMID:17594339

  12. The subcortical maternal complex: multiple functions for one biological structure?

    PubMed

    Bebbere, D; Masala, L; Albertini, D F; Ledda, S

    2016-11-01

    The subcortical maternal complex (SCMC) is a multiprotein complex uniquely expressed in mammalian oocytes and early embryos, essential for zygote progression beyond the first embryonic cell divisions. Similiar to other factors encoded by maternal effect genes, the physiological role of SCMC remains unclear, although recent evidence has provided important molecular insights into different possible functions. Its potential involvement in human fertility is attracting increasing attention; however, the complete story is far from being told. The present mini review provides an overview of recent findings related to the SCMC and discusses its potential physiological role/s with the aim of inspiring new directions for future research.

  13. Operative versus nonoperative treatment of acute Achilles tendon ruptures: a multicenter randomized trial using accelerated functional rehabilitation.

    PubMed

    Willits, Kevin; Amendola, Annunziato; Bryant, Dianne; Mohtadi, Nicholas G; Giffin, J Robert; Fowler, Peter; Kean, Crystal O; Kirkley, Alexandra

    2010-12-01

    To date, studies directly comparing the rerupture rate in patients with an Achilles tendon rupture who are treated with surgical repair with the rate in patients treated nonoperatively have been inconclusive but the pooled relative risk of rerupture favored surgical repair. In all but one study, the limb was immobilized for six to eight weeks. Published studies of animals and humans have shown a benefit of early functional stimulus to healing tendons. The purpose of the present study was to compare the outcomes of patients with an acute Achilles tendon rupture treated with operative repair and accelerated functional rehabilitation with the outcomes of similar patients treated with accelerated functional rehabilitation alone. Patients were randomized to operative or nonoperative treatment for acute Achilles tendon rupture. All patients underwent an accelerated rehabilitation protocol that featured early weight-bearing and early range of motion. The primary outcome was the rerupture rate as demonstrated by a positive Thompson squeeze test, the presence of a palpable gap, and loss of plantar flexion strength. Secondary outcomes included isokinetic strength, the Leppilahti score, range of motion, and calf circumference measured at three, six, twelve, and twenty-four months after injury. A total of 144 patients (seventy-two treated operatively and seventy-two treated nonoperatively) were randomized. There were 118 males and twenty-six females, and the mean age (and standard deviation) was 40.4 ± 8.8 years. Rerupture occurred in two patients in the operative group and in three patients in the nonoperative group. There was no clinically important difference between groups with regard to strength, range of motion, calf circumference, or Leppilahti score. There were thirteen complications in the operative group and six in the nonoperative group, with the main difference being the greater number of soft-tissue-related complications in the operative group. This study

  14. Influence of aeration cycles on mechanical characteristics of elastomeric diffusers in biological intermittent processes: Accelerated tests in real environment.

    PubMed

    Eusebi, Anna Laura; Bellezze, Tiziano; Chiappini, Gianluca; Sasso, Marco; Battistoni, Paolo

    2017-06-15

    The paper deals with the evaluation of the effect of on/off switching of diffuser membranes, in the intermittent aeration process of the urban wastewater treatments. Accelerated tests were done using two types of commercial EPDM diffusers, which were submitted to several consecutive cycles up to the simulation of more than 8 years of real working conditions. The effect of this switching on the mechanical characteristics of the membranes was evaluated in terms of pressure increment of the air operating at different flow rates (2, 3.5 and 6 m(3)/h/diff): during accelerated tests, such increment ranged from 2% to 18%. The intermittent phases emphasized the loss both of the original mechanical proprieties of the diffusers and of the initial pore shapes. The main cause of pressure increment was attributed to the fouling of the internal channels of the pores. Further analyses performed by scanning electron microscopy and by mechanical tests on EPDM membrane, using a traditional tensile test and a non destructive optical method, from which the Young's Modulus was obtained, supported previous conclusions. Any changes in terms of oxygen transfer parameters (KLa and SOTE%) were specifically founded by causing to the repeated on/off switching. Copyright © 2017. Published by Elsevier Ltd.

  15. Accelerated Recovery of Endothelium Function after Stent Implantation with the Use of a Novel Systemic Nanoparticle Curcumin

    PubMed Central

    Lu, Qi; Ye, Fang; Yang, Xiangjun; Gu, Qingqing; Wang, Peng; Zhu, Jianhua; Shen, Li; Gong, Feirong

    2015-01-01

    Curcumin was reported to exhibit a wide range of pharmacological effects including antioxidant, anti-inflammatory, and antiproliferative activities and significantly prevent smooth muscle cells migration. In the present study, a novel kind of curcumin loaded nanoparticles (Cur-NP) has been prepared and characterized with the aim of inhibiting inflammation formation and accelerating the healing process of the stented arteries. Cur-NP was administrated intravenously after stent implantation twice a week and detailed tissue responses were evaluated. The results demonstrated that intravenous administration of Cur-NP after stent implantation accelerated endothelial cells restoration and endothelium function recovery and may potentially be an effective therapeutic alternative to reduce adverse events for currently available drug eluting stents. PMID:26167481

  16. Estrogen Biology: New Insights into GPER Function and Clinical Opportunities

    PubMed Central

    Prossnitz, Eric R.; Barton, Matthias

    2014-01-01

    Estrogens play an important role in the regulation of normal physiology, aging and many disease states. Although the nuclear estrogen receptors have classically been described to function as ligand-activated transcription factors mediating genomic effects in hormonally regulated tissues, more recent studies reveal that estrogens also mediate rapid signaling events traditionally associated with G protein-coupled receptors. The G protein-coupled estrogen receptor GPER (formerly GPR30) has now become recognized as a major mediator of estrogen’s rapid cellular effects throughout the body. With the discovery of selective synthetic ligands for GPER, both agonists and antagonists, as well as the use of GPER knockout mice, significant advances have been made in our understanding of GPER function at the cellular, tissue and organismal levels. In many instances, the protective/beneficial effects of estrogen are mimicked by selective GPER agonism and are absent or reduced in GPER knockout mice, suggesting an essential or at least parallel role for GPER in the actions of estrogen. In this review, we will discuss recent advances and our current understanding of the role of GPER and certain drugs such as SERMs and SERDs in physiology and disease. We will also highlight novel opportunities for clinical development towards GPER-targeted therapeutics, for molecular imaging, as well as for theranostic approaches and personalized medicine. PMID:24530924

  17. Biological functions of iduronic acid in chondroitin/dermatan sulfate.

    PubMed

    Thelin, Martin A; Bartolini, Barbara; Axelsson, Jakob; Gustafsson, Renata; Tykesson, Emil; Pera, Edgar; Oldberg, Åke; Maccarana, Marco; Malmstrom, Anders

    2013-05-01

    The presence of iduronic acid in chondroitin/dermatan sulfate changes the properties of the polysaccharides because it generates a more flexible chain with increased binding potentials. Iduronic acid in chondroitin/dermatan sulfate influences multiple cellular properties, such as migration, proliferation, differentiation, angiogenesis and the regulation of cytokine/growth factor activities. Under pathological conditions such as wound healing, inflammation and cancer, iduronic acid has diverse regulatory functions. Iduronic acid is formed by two epimerases (i.e. dermatan sulfate epimerase 1 and 2) that have different tissue distribution and properties. The role of iduronic acid in chondroitin/dermatan sulfate is highlighted by the vast changes in connective tissue features in patients with a new type of Ehler-Danlos syndrome: adducted thumb-clubfoot syndrome. Future research aims to understand the roles of the two epimerases and their interplay with the sulfotransferases involved in chondroitin sulfate/dermatan sulfate biosynthesis. Furthermore, a better definition of chondroitin/dermatan sulfate functions using different knockout models is needed. In this review, we focus on the two enzymes responsible for iduronic acid formation, as well as the role of iduronic acid in health and disease.

  18. Spruce Budworm (Lepidoptera: Tortricidae) Oral Secretions I: Biology and Function.

    PubMed

    Eveleigh, Eldon; Silk, Peter; Leclair, Gaëtan; Mayo, Peter; Francis, Brittany; Williams, Martin

    2015-12-01

    The potential roles of the oral secretions (OS) of spruce budworm (SBW; Choristoneura fumiferana Clemens) larvae and factors that may affect the volume of OS disgorged were investigated in the laboratory. Experiments revealed that diet-fed SBW larvae readily disgorge OS when induced ("milked"), with minimal overall cost to their development and eventual pupal weight. Exposure of conspecific larvae to OS throughout larval development negatively affected survival and male pupal weight; however, male development time was faster when exposed to OS. Female pupal weight and development time were not affected. Preliminary experiments suggested that OS had a repellent effect on a co-occurring herbivore, the false hemlock looper, Nepytia canosaria (Walker). OS produced by larvae that fed on three host tree species and on artificial diet significantly increased the grooming time of ants (Camponotus sp.), indicating that SBW OS have an anti-predator function. The volume of OS is significantly greater in L6 than in L4 or L5, with the volume produced by L6 depending on weight and age as well as feeding history at time of milking. These findings indicate that SBW OS function as both an intra- and interspecific epideictic pheromone and as an anti-predator defensive mechanism, while incurring minimal metabolic costs. © Crown copyright 2015.

  19. Insect MicroRNAs: Biogenesis, Expression Profiling and Biological Functions

    PubMed Central

    Lucas, Keira; Raikhel, Alexander S.

    2012-01-01

    MicroRNAs (miRNA) are a class of endogenous regulatory RNA molecules 21-24 nucleotides in length that modulate gene expression at the post-transcriptional level via base pairing to target sites within messenger RNAs (mRNA). Typically, the miRNA “seed sequence” (nucleotides 2-8 at the 5′ end) binds complementary seed match sites within the 3′ untranslated region of mRNAs, resulting in either translational inhibition or mRNA degradation. MicroRNAs were first discovered in Caenorhabditis elegans and were shown to be involved in the timed regulation of developmental events. Since their discovery in the 1990s, thousands of potential miRNAs have since been identified in various organisms through small RNA cloning methods and/or computational prediction, and have been shown to play functionally important roles of gene regulation in invertebrates, vertebrates, plants, fungi and viruses. Numerous functions of miRNAs identified in Drosophila melanogaster have demonstrated a great significance of these regulatory molecules. However, elucidation of miRNA roles in non-drosophilid insects presents a challenging and important task. PMID:23165178

  20. Biochemical and biological functions of class I phosphatidylinositol transfer proteins.

    PubMed

    Cockcroft, Shamshad; Carvou, Nicolas

    2007-06-01

    Phosphoinositides function in a diverse array of cellular activities. They include a role as substrate for lipid kinases and phospholipases to generate second messengers, regulators of the cytoskeleton, of enzymes and of ion channels, and docking sites for reversible recruitment of proteins to membranes. Mammalian phosphatidylinositol transfer proteins, PITPalpha and PITPbeta are paralogs that share 77% sequence identity and contain a hydrophobic cavity that can sequester either phosphatidylinositol or phosphatidylcholine. A string of 11 amino acid residues at the C-terminal acts as a "lid" which shields the lipid from the aqueous environment. PITPs in vitro can facilitate inter-membrane lipid transfer and this requires the movement of the "lid" to allow the lipid cargo to be released. Thus PITPs are structurally designed for delivering lipid cargo and could thus participate in cellular events that are dependent on phosphatidylinositol or derivatives of phosphatidylinositol. Phosphatidylinositol, the precursor for all phosphoinositides is synthesised at the endoplasmic reticulum and its distribution to other organelles could be facilitated by PITPs. Here we highlight recent studies that report on the three-dimensional structures of the different PITP forms and suggest how PITPs are likely to dock at the membrane surface for lipid delivery and extraction. Additionally we discuss whether PITPs are important regulators of sphingomyelin metabolism, and finally describe recent studies that link the association of PITPs with diverse functions including membrane traffic at the Golgi, neurite outgrowth, cytokinesis and stem cell growth.

  1. [Adipogenic function and other biologic effects of insulin].

    PubMed

    Pankov, Y A

    2016-01-01

    Studies on experimental animals with knockout of the insulin receptor gene Insr (in the whole body or in certain tissues) and/or related genes encoding proteins involved in realization of insulin signal transduction in target cells, have made an important contribution to the elucidation of insulin regulation of metabolism, particularly fat metabolism. Since the whole insulin secreted by b-cells, together with the products of gastrointestinal tract digestion of proteins, fats, and carbohydrates reach the liver, the latter is the first organ on which this hormone acts. The liver employs released amino acids for synthesis of proteins, including apoproteins for various lipoproteins. Glucose is used for synthesis of glycogen, fatty acids, and triglycerides, which enter all the organs in very low density lipoproteins (VLDL). The LIRKO mice with knockout of the Insr gene in the liver demonstrated inhibition of synthesis of macromolecular compounds from amino acids, glucose, and fatty acids. Low molecular weight substances demonstrated increased entry to circulation, and together with other disorders induced hyperglycemia. In LIRKO mice blood glucose levels and glucose tolerance demonstrated time-dependent normalization and at later stages the increase in glucose levels was replaced by hypoglycemia. These changes can be well explained if we take into consideration that one of the main functions of insulin consists in stimulation of energy accumulation by means of activation of triglyceride deposition in adipose tissue. FIRKO mice with selective knockout of adipose tissue Insr were characterized by decreased uptake of glucose in adipocytes, and its transformation into lipids. However, the level of body fat in animals remained normal, possibly due to preserved insulin receptor in the liver and insulin-induced activation of triglyceride production which maintained normal levels of body fat stores, the effective functioning of adipose tissue and secretion of leptin by

  2. On Biological Functions Mapping to the Heterochromatin of DROSOPHILA MELANOGASTER

    PubMed Central

    Pimpinelli, Sergio; Sullivan, William; Prout, Mary; Sandler, L.

    1985-01-01

    We examined the behavior of an autosomal recessive maternal-effect mutation, abnormal-oocyte (abo), that is located in the euchromatin of the left arm of chromosome 2. When homozygous in females, abo results in a marked reduction in the probability that an egg produced by a mutant mother will develop into an adult. However, this probability is increased if the fertilizing sperm delivers to the egg either a normal allele of the maternal-effect gene or a specific type of heterochromatin (called ABO) that is located in small regions of the X and Y chromosome constitutive heterochromatin as well as in some autosomal heterochromatin. These regions, moreover, all react to Hoechst 33258 fluorescent dye identically and specifically. The amelioration of the maternal effect produced by this heterochromatin differs temporally from that caused by the normal allele of the euchromatic gene: the heterochromatin reduces only precellular blastoderm mortality, whereas the normal allele of the euchromatic gene reduces only postblastoderm mortality. Thus, although the genome of the preblastoderm Drosophila embryo is apparently mostly silent, the ABO-containing heterochromatin functions at this early time. Finally, preliminary data indicate that abo is but one member of a cluster of linked genes, each of which interacts with its own normal allele and with a different, locus-specific, heterochromatic factor. From these observations, it appears that Drosophila heterochromatin contains developmentally important genetic elements, and that a functional concomitant of heterochromatic location is gene action at a developmental stage during which the activity of the euchromatic genome is as yet undetectable. Some general implications of these inferences are considered. PMID:2580754

  3. GSK-3: Functional Insights from Cell Biology and Animal Models

    PubMed Central

    Kaidanovich-Beilin, Oksana; Woodgett, James Robert

    2011-01-01

    Glycogen synthase kinase-3 (GSK-3) is a widely expressed and highly conserved serine/threonine protein kinase encoded in mammals by two genes that generate two related proteins: GSK-3α and GSK-3β. GSK-3 is active in cells under resting conditions and is primarily regulated through inhibition or diversion of its activity. While GSK-3 is one of the few protein kinases that can be inactivated by phosphorylation, the mechanisms of GSK-3 regulation are more varied and not fully understood. Precise control appears to be achieved by a combination of phosphorylation, localization, and sequestration by a number of GSK-3-binding proteins. GSK-3 lies downstream of several major signaling pathways including the phosphatidylinositol 3′ kinase pathway, the Wnt pathway, Hedgehog signaling and Notch. Specific pools of GSK-3, which differ in intracellular localization, binding partner affinity, and relative amount are differentially sensitized to several distinct signaling pathways and these sequestration mechanisms contribute to pathway insulation and signal specificity. Dysregulation of signaling pathways involving GSK-3 is associated with the pathogenesis of numerous neurological and psychiatric disorders and there are data suggesting GSK-3 isoform-selective roles in several of these. Here, we review the current knowledge of GSK-3 regulation and targets and discuss the various animal models that have been employed to dissect the functions of GSK-3 in brain development and function through the use of conventional or conditional knockout mice as well as transgenic mice. These studies have revealed fundamental roles for these protein kinases in memory, behavior, and neuronal fate determination and provide insights into possible therapeutic interventions. PMID:22110425

  4. Mesoporous bioactive glass nanolayer-functionalized 3D-printed scaffolds for accelerating osteogenesis and angiogenesis

    NASA Astrophysics Data System (ADS)

    Zhang, Yali; Xia, Lunguo; Zhai, Dong; Shi, Mengchao; Luo, Yongxiang; Feng, Chun; Fang, Bing; Yin, Jingbo; Chang, Jiang; Wu, Chengtie

    2015-11-01

    The hierarchical microstructure, surface and interface of biomaterials are important factors influencing their bioactivity. Porous bioceramic scaffolds have been widely used for bone tissue engineering by optimizing their chemical composition and large-pore structure. However, the surface and interface of struts in bioceramic scaffolds are often ignored. The aim of this study is to incorporate hierarchical pores and bioactive components into the bioceramic scaffolds by constructing nanopores and bioactive elements on the struts of scaffolds and further improve their bone-forming activity. Mesoporous bioactive glass (MBG) modified β-tricalcium phosphate (MBG-β-TCP) scaffolds with a hierarchical pore structure and a functional strut surface (~100 nm of MBG nanolayer) were successfully prepared via 3D printing and spin coating. The compressive strength and apatite-mineralization ability of MBG-β-TCP scaffolds were significantly enhanced as compared to β-TCP scaffolds without the MBG nanolayer. The attachment, viability, alkaline phosphatase (ALP) activity, osteogenic gene expression (Runx2, BMP2, OPN and Col I) and protein expression (OPN, Col I, VEGF, HIF-1α) of rabbit bone marrow stromal cells (rBMSCs) as well as the attachment, viability and angiogenic gene expression (VEGF and HIF-1α) of human umbilical vein endothelial cells (HUVECs) in MBG-β-TCP scaffolds were significantly upregulated compared with conventional bioactive glass (BG)-modified β-TCP (BG-β-TCP) and pure β-TCP scaffolds. Furthermore, MBG-β-TCP scaffolds significantly enhanced the formation of new bone in vivo as compared to BG-β-TCP and β-TCP scaffolds. The results suggest that application of the MBG nanolayer to modify 3D-printed bioceramic scaffolds offers a new strategy to construct hierarchically porous scaffolds with significantly improved physicochemical and biological properties, such as mechanical properties, osteogenesis, angiogenesis and protein expression for bone tissue

  5. Functional tissue engineering of tendon: Establishing biological success criteria for improving tendon repair.

    PubMed

    Breidenbach, Andrew P; Gilday, Steven D; Lalley, Andrea L; Dyment, Nathaniel A; Gooch, Cynthia; Shearn, Jason T; Butler, David L

    2014-06-27

    Improving tendon repair using Functional Tissue Engineering (FTE) principles has been the focus of our laboratory over the last decade. Although our primary goals were initially focused only on mechanical outcomes, we are now carefully assessing the biological properties of our tissue-engineered tendon repairs so as to link biological influences with mechanics. However, given the complexities of tendon development and healing, it remains challenging to determine which aspects of tendon biology are the most important to focus on in the context of tissue engineering. To address this problem, we have formalized a strategy to identify, prioritize, and evaluate potential biological success criteria for tendon repair. We have defined numerous biological properties of normal tendon relative to cellular phenotype, extracellular matrix and tissue ultra-structure that we would like to reproduce in our tissue-engineered repairs and prioritized these biological criteria by examining their relative importance during both normal development and natural tendon healing. Here, we propose three specific biological criteria which we believe are essential for normal tendon function: (1) scleraxis-expressing cells; (2) well-organized and axially-aligned collagen fibrils having bimodal diameter distribution; and (3) a specialized tendon-to-bone insertion site. Moving forward, these biological success criteria will be used in conjunction with our already established mechanical success criteria to evaluate the effectiveness of our tissue-engineered tendon repairs. © 2013 Published by Elsevier Ltd.

  6. Functional Tissue Engineering of Tendon: Establishing Biological Success Criteria for Improving Tendon Repair

    PubMed Central

    Breidenbach, Andrew P; Gilday, Steven D; Lalley, Andrea L; Dyment, Nathaniel A; Gooch, Cynthia; Shearn, Jason T; Butler, David L

    2013-01-01

    Improving tendon repair using Functional Tissue Engineering (FTE) principles has been the focus of our laboratory over the last decade. Although our primary goals were initially focused only on mechanical outcomes, we are now carefully assessing the biological properties of our tissue-engineered tendon repairs so as to link biological influences with mechanics. However, given the complexities of tendon development and healing, it remains challenging to determine which aspects of tendon biology are the most important to focus on in the context of tissue engineering. To address this problem, we have formalized a strategy to identify, prioritize, and evaluate potential biological success criteria for tendon repair. We have defined numerous biological properties of normal tendon relative to cellular phenotype, extracellular matrix and tissue ultra-structure that we would like to reproduce in our tissue-engineered repairs and prioritized these biological criteria by examining their relative importance during both normal development and natural tendon healing. Here, we propose three specific biological criteria which we believe are essential for normal tendon function: 1) scleraxis-expressing cells; 2) well-organized and axially-aligned collagen fibrils having bimodal diameter distribution; and 3) a specialized tendon-to-bone insertion site. Moving forward, these biological success criteria will be used in conjunction with our already established mechanical success criteria to evaluate the effectiveness of our tissue-engineered tendon repairs. PMID:24200342

  7. Identifying effective and feasible interventions to accelerate functional recovery from hospitalization in older adults: A randomized controlled pilot trial.

    PubMed

    Deer, Rachel R; Dickinson, Jared M; Fisher, Steve R; Ju, Hyunsu; Volpi, Elena

    2016-07-01

    Hospitalization induces functional decline in older adults. Many geriatric patients fail to fully recover physical function after hospitalization, which increases the risk of frailty, disability, dependence, re-hospitalization, and mortality. There is a lack of evidence-based therapies that can be implemented following hospitalization to accelerate functional improvements. The aims of this Phase I clinical trial are to determine 1) the effect size and variability of targeted interventions in accelerating functional recovery from hospitalization and 2) the feasibility of implementing such interventions in community-dwelling older adults. Older patients (≥65years, n=100) will be recruited from a single site during hospitalization for an acute medical condition. Subjects will be randomized to one of five interventions initiated immediately upon discharge: 1. protein supplementation, 2. in-home rehabilitation plus placebo supplementation, 3. in-home rehabilitation plus protein supplementation, 4. single testosterone injection, or 5. isocaloric placebo supplementation. Testing will occur during hospitalization (baseline) and at 1 and 4weeks post-discharge. Each testing session will include measures of muscle strength, physical function/performance, body composition, and psychological function. Physical activity levels will be continuously monitored throughout study participation. Feasibility will be determined through collection of the number of eligible, contacted, and enrolled patients; intervention adherence and compliance; and reasons for declining enrollment and study withdrawal. This research will determine the feasibility of post-hospitalization strategies to improve physical function in older adults. These results will also provide a foundation for performing larger, multi-site clinical trials to improve physical function and reduce readmissions in geriatric patents.

  8. Combined small-molecule inhibition accelerates the derivation of functional cortical neurons from human pluripotent stem cells.

    PubMed

    Qi, Yuchen; Zhang, Xin-Jun; Renier, Nicolas; Wu, Zhuhao; Atkin, Talia; Sun, Ziyi; Ozair, M Zeeshan; Tchieu, Jason; Zimmer, Bastian; Fattahi, Faranak; Ganat, Yosif; Azevedo, Ricardo; Zeltner, Nadja; Brivanlou, Ali H; Karayiorgou, Maria; Gogos, Joseph; Tomishima, Mark; Tessier-Lavigne, Marc; Shi, Song-Hai; Studer, Lorenz

    2017-02-01

    Considerable progress has been made in converting human pluripotent stem cells (hPSCs) into functional neurons. However, the protracted timing of human neuron specification and functional maturation remains a key challenge that hampers the routine application of hPSC-derived lineages in disease modeling and regenerative medicine. Using a combinatorial small-molecule screen, we previously identified conditions to rapidly differentiate hPSCs into peripheral sensory neurons. Here we generalize the approach to central nervous system (CNS) fates by developing a small-molecule approach for accelerated induction of early-born cortical neurons. Combinatorial application of six pathway inhibitors induces post-mitotic cortical neurons with functional electrophysiological properties by day 16 of differentiation, in the absence of glial cell co-culture. The resulting neurons, transplanted at 8 d of differentiation into the postnatal mouse cortex, are functional and establish long-distance projections, as shown using iDISCO whole-brain imaging. Accelerated differentiation into cortical neuron fates should facilitate hPSC-based strategies for disease modeling and cell therapy in CNS disorders.

  9. 20 years of leptin: connecting leptin signaling to biological function.

    PubMed

    Allison, Margaret B; Myers, Martin G

    2014-10-01

    Hypothalamic leptin action promotes negative energy balance and modulates glucose homeostasis, as well as serving as a permissive signal to the neuroendocrine axes that control growth and reproduction. Since the initial discovery of leptin 20 years ago, we have learned a great deal about the molecular mechanisms of leptin action. An important aspect of this has been the dissection of the cellular mechanisms of leptin signaling, and how specific leptin signals influence physiology. Leptin acts via the long form of the leptin receptor LepRb. LepRb activation and subsequent tyrosine phosphorylation recruits and activates multiple signaling pathways, including STAT transcription factors, SHP2 and ERK signaling, the IRS-protein/PI3Kinase pathway, and SH2B1. Each of these pathways controls specific aspects of leptin action and physiology. Important inhibitory pathways mediated by suppressor of cytokine signaling proteins and protein tyrosine phosphatases also limit physiologic leptin action. This review summarizes the signaling pathways engaged by LepRb and their effects on energy balance, glucose homeostasis, and reproduction. Particular emphasis is given to the multiple mouse models that have been used to elucidate these functions in vivo.

  10. Biological catalysis of the hydrological cycle: life's thermodynamic function

    NASA Astrophysics Data System (ADS)

    Michaelian, K.

    2011-01-01

    Darwinian theory depicts life as being overwhelmingly consumed by a fight for survival in a hostile environment. However, from a thermodynamic perspective, life is a dynamic out of equilibrium process, stabilizing and coevolving in concert with its abiotic environment. The living component of the biosphere on the surface of the Earth of greatest biomass, the plants and cyanobacteria, are involved in the transpiration of a vast amount of water. Transpiration is part of the global water cycle, and it is this cycle that distinguishes Earth from its apparently life barren neighboring planets, Venus and Mars. The dissipation of sunlight into heat by organic molecules in the biosphere and its coupling to the water cycle (as well as other abiotic processes), is by far the greatest entropy producing process occurring on Earth. Life, from this perspective, can be viewed as performing an important thermodynamic function; acting as a dynamic catalyst by aiding irreversible abiotic process such as the water cycle, hurricanes, and ocean and wind currents to produce entropy. The role of animals in this view is that of unwitting but dedicated servants of the plants and cyanobacteria, helping them to grow and to spread into initially inhospitable areas.

  11. Functionalized diamond nanopowder for phosphopeptides enrichment from complex biological fluids.

    PubMed

    Hussain, Dilshad; Najam-ul-Haq, Muhammad; Jabeen, Fahmida; Ashiq, Muhammad N; Athar, Muhammad; Rainer, Matthias; Huck, Christian W; Bonn, Guenther K

    2013-05-02

    Diamond is known for its high affinity and biocompatibility towards biomolecules and is used exclusively in separation sciences and life science research. In present study, diamond nanopowder is derivatized as Immobilized Metal Ion Affinity Chromatographic (IMAC) material for the phosphopeptides enrichment and as Reversed Phase (C-18) media for the desalting of complex mixtures and human serum profiling through MALDI-TOF-MS. Functionalized diamond nanopowder is characterized by Fourier transform infrared (FT-IR) spectroscopy, scanning electron microscopy (SEM) and energy dispersive X-ray (EDX) spectroscopy. Diamond-IMAC is applied to the standard protein (β-casein), spiked human serum, egg yolk and non-fat milk for the phosphopeptides enrichment. Results show the selectivity of synthesized IMAC-diamond immobilized with Fe(3+) and La(3+) ions. To comprehend the elaborated use, diamond-IMAC is also applied to the serum samples from gall bladder carcinoma for the potential biomarkers. Database search is carried out by the Mascot program (www.matrixscience.com) for the assignment of phosphorylation sites. Diamond nanopowder is thus a separation media with multifunctional use and can be applied to cancer protein profiling for the diagnosis and biomarker identification. Copyright © 2013 Elsevier B.V. All rights reserved.

  12. Purification, biochemical characterization, and biological function of human esterase D.

    PubMed Central

    Lee, W H; Wheatley, W; Benedict, W F; Huang, C M; Lee, E Y

    1986-01-01

    Human esterase D (carboxylesterase; carboxylic-ester hydrolase, EC 3.1.1.1), a genetic marker of retinoblastoma, was purified to biochemical homogeneity from erythrocytes. The purification scheme including carboxymethylcellulose, phenyl-Sepharose, chromatofocusing, and hydroxylapatite chromatographies resulted in a 10,000-fold purification of the enzyme with 15% recovery of total activity. The Km of esterase D was estimated to be 10 X 10(-6) M using 4-methylumbelliferyl acetate as substrate. The enzymatic activity was inhibited by p-chloromercuribenzoate and HgCl2, suggesting an important role of SH group(s) in enzyme function. Specific rabbit polyclonal and mouse monoclonal antibodies against esterase D were prepared and recognized either denatured or native human esterase D protein. Moreover, the polyclonal antibodies immunoprecipitated a polypeptide with a molecular mass of about 33-34 kDa from various cell lines of different mammalian species, indicating that the esterase D protein is highly conserved. The highest levels of this enzyme were found in liver and kidney. Furthermore, the expression of esterase D was enhanced 3-fold in a promonocytic cell line treated with phenobarbital but not with phorbol myristate acetate, suggesting that esterase D may have a role in detoxification. The availability of the homogeneous protein and its specific antibodies allows for cloning of the esterase D gene and facilitates studies of retinoblastomas. Images PMID:3462728

  13. Towards understanding the biological function of hopanoids (Invited)

    NASA Astrophysics Data System (ADS)

    Doughty, D. M.; Hunter, R.; Summons, R. E.; Newman, D. K.

    2010-12-01

    Rhodopseudomonas palustris TIE-1 expresses bacterial hopanoid lipids that are structurally similar and evolutionarily related to eukaryotic sterols. The genome of R. palustris TIE-1 contains two copies of the hpnN gene (hpnN1 and hpnN2) that are orthologs of genes encoding eukaryotic sterol and lipid transporters. Hopanoid localization to the outer membrane was found to be dependent upon hpnN1. Since the cell cycle of R. palustris TIE-1 is obligately bimodal with each cell division resulting in the generation of one mother and one swarmer cell, evidence was obtained that hopanoids where specifically localized to the outer membrane of mother cells. The sequestration of hopanoids to the mother cells was also disrupted by the deletion of the hpnN1 gene. Mutants lacking the hopanoid transporters were able to grow normally at 30 °C but showed decreased growth at 38 °C. The hopanoid transporter mutant formed cellular filaments when grown at elevated temperature. Because sedimentary steranes and hopanes comprise some of the earliest evidence for the emergence of distinct bacteria and eukaryotic phyla, a better appreciation of the function of hopanoids will improve our ability to interpret the evolution of life on Earth.

  14. Strigolactone biology: genes, functional genomics, epigenetics and applications.

    PubMed

    Makhzoum, Abdullah; Yousefzadi, Morteza; Malik, Sonia; Gantet, Pascal; Tremouillaux-Guiller, Jocelyne

    2017-03-01

    Strigolactones (SLs) represent an important new plant hormone class marked by their multifunctional role in plant and rhizosphere interactions. These compounds stimulate hyphal branching in arbuscular mycorrhizal fungi (AMF) and seed germination of root parasitic plants. In addition, they are involved in the control of plant architecture by inhibiting bud outgrowth as well as many other morphological and developmental processes together with other plant hormones such as auxins and cytokinins. The biosynthetic pathway of SLs that are derived from carotenoids was partially decrypted based on the identification of mutants from a variety of plant species. Only a few SL biosynthetic and regulated genes and related regulatory transcription factors have been identified. However, functional genomics and epigenetic studies started to give first elements on the modality of the regulation of SLs related genes. Since they control plant architecture and plant-rhizosphere interaction, SLs start to be used for agronomical and biotechnological applications. Furthermore, the genes involved in the SL biosynthetic pathway and genes regulated by SL constitute interesting targets for plant breeding. Therefore, it is necessary to decipher and better understand the genetic determinants of their regulation at different levels.

  15. Production and biological function of volatile esters in Saccharomyces cerevisiae.

    PubMed

    Saerens, Sofie M G; Delvaux, Freddy R; Verstrepen, Kevin J; Thevelein, Johan M

    2010-03-01

    The need to understand and control ester synthesis is driven by the fact that esters play a key role in the sensorial quality of fermented alcoholic beverages like beer, wine and sake. As esters are synthesized in yeast via several complex metabolic pathways, there is a need to gain a clear understanding of ester metabolism and its regulation. The individual genes involved, their functions and regulatory mechanisms have to be identified. In alcoholic beverages, there are two important groups of esters: the acetate esters and the medium-chain fatty acid (MCFA) ethyl esters. For acetate ester synthesis, the genes involved have already been cloned and characterized. Also the biochemical pathways and the regulation of acetate ester synthesis are well defined. With respect to the molecular basis of MCFA ethyl ester synthesis, however, significant progress has only recently been made. Next to the characterization of the biochemical pathways and regulation of ester synthesis, a new and more important question arises: what is the advantage for yeast to produce these esters? Several hypotheses have been proposed in the past, but none was satisfactorily. This paper reviews the current hypotheses of ester synthesis in yeast in relation to the complex regulation of the alcohol acetyl transferases and the different factors that allow ester formation to be controlled during fermentation.

  16. Production and biological function of volatile esters in Saccharomyces cerevisiae

    PubMed Central

    Saerens, Sofie M. G.; Delvaux, Freddy R.; Verstrepen, Kevin J.; Thevelein, Johan M.

    2010-01-01

    Summary The need to understand and control ester synthesis is driven by the fact that esters play a key role in the sensorial quality of fermented alcoholic beverages like beer, wine and sake. As esters are synthesized in yeast via several complex metabolic pathways, there is a need to gain a clear understanding of ester metabolism and its regulation. The individual genes involved, their functions and regulatory mechanisms have to be identified. In alcoholic beverages, there are two important groups of esters: the acetate esters and the medium‐chain fatty acid (MCFA) ethyl esters. For acetate ester synthesis, the genes involved have already been cloned and characterized. Also the biochemical pathways and the regulation of acetate ester synthesis are well defined. With respect to the molecular basis of MCFA ethyl ester synthesis, however, significant progress has only recently been made. Next to the characterization of the biochemical pathways and regulation of ester synthesis, a new and more important question arises: what is the advantage for yeast to produce these esters? Several hypotheses have been proposed in the past, but none was satisfactorily. This paper reviews the current hypotheses of ester synthesis in yeast in relation to the complex regulation of the alcohol acetyl transferases and the different factors that allow ester formation to be controlled during fermentation. PMID:21255318

  17. Accelerator mass spectrometry analysis of 14C-oxaliplatin concentrations in biological samples and 14C contents in biological samples and antineoplastic agents

    NASA Astrophysics Data System (ADS)

    Toyoguchi, Teiko; Kobayashi, Takeshi; Konno, Noboru; Shiraishi, Tadashi; Kato, Kazuhiro; Tokanai, Fuyuki

    2015-10-01

    Accelerator mass spectrometry (AMS) is expected to play an important role in microdose trials. In this study, we measured the 14C concentration in 14C-oxaliplatin-spiked serum, urine and supernatant of fecal homogenate samples in our Yamagata University (YU) - AMS system. The calibration curves of 14C concentration in serum, urine and supernatant of fecal homogenate were linear (the correlation coefficients were ⩾0.9893), and the precision and accuracy was within the acceptance criteria. To examine a 14C content of water in three vacuum blood collection tubes and a syringe were measured. 14C was not detected from water in these devices. The mean 14C content in urine samples of 6 healthy Japanese volunteers was 0.144 dpm/mL, and the intra-day fluctuation of 14C content in urine from a volunteer was little. The antineoplastic agents are administered to the patients in combination. Then, 14C contents of the antineoplastic agents were quantitated. 14C contents were different among 10 antineoplastic agents; 14C contents of paclitaxel injection and docetaxel hydrate injection were higher than those of the other injections. These results indicate that our quantitation method using YU-AMS system is suited for microdosing studies and that measurement of baseline and co-administered drugs might be necessary for the studies in low concentrations.

  18. Nerve Regeneration: Understanding Biology and Its Influence on Return of Function After Nerve Transfers.

    PubMed

    Gordon, Tessa

    2016-05-01

    Poor functional outcomes are frequent after peripheral nerve injuries despite the regenerative support of Schwann cells. Motoneurons and, to a lesser extent, sensory neurons survive the injuries but outgrowth of axons across the injury site is slow. The neuronal regenerative capacity and the support of regenerating axons by the chronically denervated Schwann cells progressively declines with time and distance of the injury from the denervated targets. Strategies, including brief low-frequency electrical stimulation that accelerates target reinnervation and functional recovery, and the insertion of cross-bridges between a donor nerve and a recipient denervated nerve stump, are effective in promoting functional outcomes after complete and incomplete injuries.

  19. GENIUS: web server to predict local gene networks and key genes for biological functions

    PubMed Central

    Puelma, Tomas; Araus, Viviana; Canales, Javier; Vidal, Elena A.; Cabello, Juan M.; Soto, Alvaro

    2017-01-01

    Abstract Summary: GENIUS is a user-friendly web server that uses a novel machine learning algorithm to infer functional gene networks focused on specific genes and experimental conditions that are relevant to biological functions of interest. These functions may have different levels of complexity, from specific biological processes to complex traits that involve several interacting processes. GENIUS also enriches the network with new genes related to the biological function of interest, with accuracies comparable to highly discriminative Support Vector Machine methods. Availability and Implementation: GENIUS currently supports eight model organisms and is freely available for public use at http://networks.bio.puc.cl/genius. Contact: genius.psbl@gmail.com Supplementary information: Supplementary data are available at Bioinformatics online. PMID:27993775

  20. Schematic and realistic biological motion identification in children with high-functioning autism spectrum disorder

    PubMed Central

    Wright, Kristyn; Kelley, Elizabeth; Poulin-Dubois, Diane

    2014-01-01

    Research investigating biological motion perception in children with ASD has revealed conflicting findings concerning whether impairments in biological motion perception exist. The current study investigated how children with high-functioning ASD (HF-ASD) performed on two tasks of biological motion identification: a novel schematic motion identification task and a point-light biological motion identification task. Twenty-two HFASD children were matched with 21 TD children on gender, non-verbal mental, and chronological, age (M years = 6.72). On both tasks, HF-ASD children performed with similar accuracy as TD children. Across groups, children performed better on animate than on inanimate trials of both tasks. These findings suggest that HF-ASD children's identification of both realistic and schematic biological motion identification is unimpaired. PMID:25395988

  1. Accelerating the Pace of Protein Functional Annotation With Intel Xeon Phi Coprocessors.

    PubMed

    Feinstein, Wei P; Moreno, Juana; Jarrell, Mark; Brylinski, Michal

    2015-06-01

    Intel Xeon Phi is a new addition to the family of powerful parallel accelerators. The range of its potential applications in computationally driven research is broad; however, at present, the repository of scientific codes is still relatively limited. In this study, we describe the development and benchmarking of a parallel version of eFindSite, a structural bioinformatics algorithm for the prediction of ligand-binding sites in proteins. Implemented for the Intel Xeon Phi platform, the parallelization of the structure alignment portion of eFindSite using pragma-based OpenMP brings about the desired performance improvements, which scale well with the number of computing cores. Compared to a serial version, the parallel code runs 11.8 and 10.1 times faster on the CPU and the coprocessor, respectively; when both resources are utilized simultaneously, the speedup is 17.6. For example, ligand-binding predictions for 501 benchmarking proteins are completed in 2.1 hours on a single Stampede node equipped with the Intel Xeon Phi card compared to 3.1 hours without the accelerator and 36.8 hours required by a serial version. In addition to the satisfactory parallel performance, porting existing scientific codes to the Intel Xeon Phi architecture is relatively straightforward with a short development time due to the support of common parallel programming models by the coprocessor. The parallel version of eFindSite is freely available to the academic community at www.brylinski.org/efindsite.

  2. GPU accelerated non-rigid registration for the evaluation of cardiac function.

    PubMed

    Li, Bo; Young, Alistair A; Cowan, Brett R

    2008-01-01

    We present a method for the fast and efficient tracking of motion in cardiac magnetic resonance (CMR) cines. A GPU accelerated Levenberg-Marquardt non-linear least squares optimization procedure for finite element non-rigid registration was implemented on an NVIDIA graphics card using the OpenGL environment. Points were tracked from frame to frame using forward and backward incremental registration. The inner (endocardial) and outer (epicardial) boarders of the heart were tracked in six short axis cines with approximately 25 frames through the cardiac cycle in 36 patients with vascular disease. Contours placed by two independent expert observers using a semi-automatic ventricular analysis program (CIM version 4.6) were used as the gold standard. The method took 0.5 seconds per frame, and the maximum Hausdorff errors were less than 2 mm on average which was of the same order as the expert inter-observer error. In conclusion, GPU accelerated Levenberg-Marquardt non-linear optimization enables fast and accurate tracking of cardiac motion in CMR images.

  3. Sharing Structure and Function in Biological Design with SBOL 2.0.

    PubMed

    Roehner, Nicholas; Beal, Jacob; Clancy, Kevin; Bartley, Bryan; Misirli, Goksel; Grünberg, Raik; Oberortner, Ernst; Pocock, Matthew; Bissell, Michael; Madsen, Curtis; Nguyen, Tramy; Zhang, Michael; Zhang, Zhen; Zundel, Zach; Densmore, Douglas; Gennari, John H; Wipat, Anil; Sauro, Herbert M; Myers, Chris J

    2016-06-17

    The Synthetic Biology Open Language (SBOL) is a standard that enables collaborative engineering of biological systems across different institutions and tools. SBOL is developed through careful consideration of recent synthetic biology trends, real use cases, and consensus among leading researchers in the field and members of commercial biotechnology enterprises. We demonstrate and discuss how a set of SBOL-enabled software tools can form an integrated, cross-organizational workflow to recapitulate the design of one of the largest published genetic circuits to date, a 4-input AND sensor. This design encompasses the structural components of the system, such as its DNA, RNA, small molecules, and proteins, as well as the interactions between these components that determine the system's behavior/function. The demonstrated workflow and resulting circuit design illustrate the utility of SBOL 2.0 in automating the exchange of structural and functional specifications for genetic parts, devices, and the biological systems in which they operate.

  4. End-to-end automated microfluidic platform for synthetic biology: from design to functional analysis

    DOE PAGES

    Linshiz, Gregory; Jensen, Erik; Stawski, Nina; ...

    2016-02-02

    Synthetic biology aims to engineer biological systems for desired behaviors. The construction of these systems can be complex, often requiring genetic reprogramming, extensive de novo DNA synthesis, and functional screening. Here, we present a programmable, multipurpose microfluidic platform and associated software and apply the platform to major steps of the synthetic biology research cycle: design, construction, testing, and analysis. We show the platform’s capabilities for multiple automated DNA assembly methods, including a new method for Isothermal Hierarchical DNA Construction, and for Escherichia coli and Saccharomyces cerevisiae transformation. The platform enables the automated control of cellular growth, gene expression induction, andmore » proteogenic and metabolic output analysis. Finally, taken together, we demonstrate the microfluidic platform’s potential to provide end-to-end solutions for synthetic biology research, from design to functional analysis.« less

  5. Bioactive components and functional properties of biologically activated cereal grains: A bibliographic review.

    PubMed

    Singh, Arashdeep; Sharma, Savita

    2017-09-22

    Whole grains provide energy, nutrients, fibers, and bioactive compounds that may synergistically contribute to their protective effects. A wide range of these compounds is affected by germination. While some compounds, such as β-glucans are degraded, others, like antioxidants and total phenolics are increased by means of biological activation of grains. The water and oil absorption capacity as well as emulsion and foaming capacity of biologically activated grains are also improved. Application of biological activation of grains is of emerging interest, which may significantly enhance the nutritional, functional, and bioactive content of grains, as well as improve palatability of grain foods in a natural way. Therefore, biological activation of cereals can be a way to produce food grains enriched with health-promoting compounds and enhanced functional attributes.

  6. Towards a behavioral-matching based compilation of synthetic biology functions.

    PubMed

    Basso-Blandin, Adrien; Delaplace, Franck

    2015-09-01

    The field of synthetic biology is looking forward engineering framework for safely designing reliable de-novo biological functions. In this undertaking, Computer-Aided-Design (CAD) environments should play a central role for facilitating the design. Although, CAD environment is widely used to engineer artificial systems the application in synthetic biology is still in its infancy. In this article we address the problem of the design of a high level language which at the core of CAD environment. More specifically the Gubs (Genomic Unified Behavioural Specification) language is a specification language used to describe the observations of the expected behaviour. The compiler appropriately selects components such that the observation of the synthetic biological function resulting to their assembly complies to the programmed behaviour.

  7. Evolutionary cell biology: functional insight from “endless forms most beautiful”

    PubMed Central

    Richardson, Elisabeth; Zerr, Kelly; Tsaousis, Anastasios; Dorrell, Richard G.; Dacks, Joel B.

    2015-01-01

    In animal and fungal model organisms, the complexities of cell biology have been analyzed in exquisite detail and much is known about how these organisms function at the cellular level. However, the model organisms cell biologists generally use include only a tiny fraction of the true diversity of eukaryotic cellular forms. The divergent cellular processes observed in these more distant lineages are still largely unknown in the general scientific community. Despite the relative obscurity of these organisms, comparative studies of them across eukaryotic diversity have had profound implications for our understanding of fundamental cell biology in all species and have revealed the evolution and origins of previously observed cellular processes. In this Perspective, we will discuss the complexity of cell biology found across the eukaryotic tree, and three specific examples of where studies of divergent cell biology have altered our understanding of key functional aspects of mitochondria, plastids, and membrane trafficking. PMID:26668171

  8. End-to-end automated microfluidic platform for synthetic biology: from design to functional analysis

    SciTech Connect

    Linshiz, Gregory; Jensen, Erik; Stawski, Nina; Bi, Changhao; Elsbree, Nick; Jiao, Hong; Kim, Jungkyu; Mathies, Richard; Keasling, Jay D.; Hillson, Nathan J.

    2016-02-02

    Synthetic biology aims to engineer biological systems for desired behaviors. The construction of these systems can be complex, often requiring genetic reprogramming, extensive de novo DNA synthesis, and functional screening. Here, we present a programmable, multipurpose microfluidic platform and associated software and apply the platform to major steps of the synthetic biology research cycle: design, construction, testing, and analysis. We show the platform’s capabilities for multiple automated DNA assembly methods, including a new method for Isothermal Hierarchical DNA Construction, and for Escherichia coli and Saccharomyces cerevisiae transformation. The platform enables the automated control of cellular growth, gene expression induction, and proteogenic and metabolic output analysis. Finally, taken together, we demonstrate the microfluidic platform’s potential to provide end-to-end solutions for synthetic biology research, from design to functional analysis.

  9. End-to-end automated microfluidic platform for synthetic biology: from design to functional analysis

    DOE PAGES

    Linshiz, Gregory; Jensen, Erik; Stawski, Nina; ...

    2016-02-02

    Synthetic biology aims to engineer biological systems for desired behaviors. The construction of these systems can be complex, often requiring genetic reprogramming, extensive de novo DNA synthesis, and functional screening. Here, we present a programmable, multipurpose microfluidic platform and associated software and apply the platform to major steps of the synthetic biology research cycle: design, construction, testing, and analysis. We show the platform’s capabilities for multiple automated DNA assembly methods, including a new method for Isothermal Hierarchical DNA Construction, and for Escherichia coli and Saccharomyces cerevisiae transformation. The platform enables the automated control of cellular growth, gene expression induction, andmore » proteogenic and metabolic output analysis. Finally, taken together, we demonstrate the microfluidic platform’s potential to provide end-to-end solutions for synthetic biology research, from design to functional analysis.« less

  10. Esthetic-functional recovery of permanent posterior tooth using autogenous biological restoration.

    PubMed

    Botelho, A M; Tavano, K T A; Correa-Faria, P; Morato, L N S; Viana, M R

    2012-01-01

    Occlusal morphology and difficult access for cleaning permanent molars result in the buildup of bacterial plaque and the development of caries. One method known as biological restoration was carried out. This technique known as biological restoration, has as main restorative material a fragment obtained from a duly donated extracted human tooth. This case report describes the restoration of an extensively decayed molar through the bonding of a fragment obtained from a third molar extracted from the patient himself. Biological restoration is a low-cost option that offers satisfactory aesthetic, morphological and functional results.The morphological/functional reestablishment of posterior teeth can be obtained through biological restoration, which allows the recovery of properties inherent to the dental structure, offers satisfactory aesthetic results and low cost.

  11. End-to-end automated microfluidic platform for synthetic biology: from design to functional analysis

    SciTech Connect

    Linshiz, Gregory; Jensen, Erik; Stawski, Nina; Bi, Changhao; Elsbree, Nick; Jiao, Hong; Kim, Jungkyu; Mathies, Richard; Keasling, Jay D.; Hillson, Nathan J.

    2016-02-02

    Synthetic biology aims to engineer biological systems for desired behaviors. The construction of these systems can be complex, often requiring genetic reprogramming, extensive de novo DNA synthesis, and functional screening. Here, we present a programmable, multipurpose microfluidic platform and associated software and apply the platform to major steps of the synthetic biology research cycle: design, construction, testing, and analysis. We show the platform’s capabilities for multiple automated DNA assembly methods, including a new method for Isothermal Hierarchical DNA Construction, and for Escherichia coli and Saccharomyces cerevisiae transformation. The platform enables the automated control of cellular growth, gene expression induction, and proteogenic and metabolic output analysis. Finally, taken together, we demonstrate the microfluidic platform’s potential to provide end-to-end solutions for synthetic biology research, from design to functional analysis.

  12. Biological Manipulation of Migration Rate: The Use of Advanced Photoperiod to Accelerate Smoltification in Yearling Chinook Salmon, Annual Report of Research 1990.

    SciTech Connect

    Muir, William D.

    1992-06-01

    Research was conducted during 1990 to assess the feasibility of biologically manipulating physiological development and migratory behavior of yearling spring chinook salmon, Oncorhynchus tshawytscha. At Dworshak National Fish Hatchery, one treatment group was exposed to a 3-month advanced photoperiod schedule for 13 weeks preceding release to accelerate smolt development. Another group was exposed to the same advanced photoperiod schedule, but additionally was reared at an elevated water temperature (11.9{degrees}C) for 10 days prior to release. At Leavenworth National Fish Hatchery, a treatment group was exposed to a 3-month advanced photoperiod schedule for 17 weeks. Gill Na{sup +}-K{sup +}ATPase development and migratory performance were described for all groups. The treated fish which were the most physiologically advanced at release were detected in the highest proportions at collector dams and also migrated fastest downstream--similar to results obtained in 1988 and 1989.

  13. Application of transfer matrix and transfer function analysis to grating-type dielectric laser accelerators: Ponderomotive focusing of electrons

    NASA Astrophysics Data System (ADS)

    Szczepkowicz, Andrzej

    2017-08-01

    The question of suitability of transfer matrix description of electrons traversing grating-type dielectric laser acceleration (DLA) structures is addressed. It is shown that although matrix considerations lead to interesting insights, the basic transfer properties of DLA cells cannot be described by a matrix. A more general notion of a transfer function is shown to be a simple and useful tool for formulating problems of particle dynamics in DLA. As an example, a focusing structure is proposed which works simultaneously for all electron phases.

  14. Biological Manipulation of Migration Rate: The Use of Advanced Photoperiod to Accelerate Smoltification in Yearling Chinook Salmon, Annual Report 1988.

    SciTech Connect

    Giorgi, Albert E.; Muir, William D.; Zaugg, Waldo S.

    1990-02-01

    Research was conducted to assess the feasibility of biologically manipulating physiological development and migratory behavior of yearling spring chinook salmon, Oncorhynchus tshawytscha. At Dworshak National Fish Hatchery a treatment group was exposed to a 3-month advanced photoperiod cycle for 14 weeks preceding release. Physiological development and migratory performance of this group was compared to a control group. Changes in physiological indices indicated that exposing fish to an advanced photoperiod treatment increased the rate of smolt development. Photoperiod treatment also altered passage patterns and timing at Lower Granite Dam. 26 refs., 6 figs., 7 tabs.

  15. Diurnal rhythmicity in biological processes involved in bioavailability of functional food factors.

    PubMed

    Tsurusaki, Takashi; Sakakibara, Hiroyuki; Aoshima, Yoshiki; Yamazaki, Shunsuke; Sakono, Masanobu; Shimoi, Kayoko

    2013-05-01

    In the past few decades, many types of functional factors have been identified in dietary foods; for example, flavonoids are major groups widely distributed in the plant kingdom. However, the absorption rates of the functional food factors are usually low, and many of these are difficult to be absorbed in the intact forms because of metabolization by biological processes during absorption. To gain adequate beneficial effects, it is therefore mandatory to know whether functional food factors are absorbed in sufficient quantity, and then reach target organs while maintaining beneficial effects. These are the reasons why the bioavailability of functional food factors has been well investigated using rodent models. Recently, many of the biological processes have been reported to follow diurnal rhythms recurring every 24 h. Therefore, absorption and metabolism of functional food factors influenced by the biological processes may vary with time of day. Consequently, the evaluation of the bioavailability of functional food factors using rodent models should take into consideration the timing of consumption. In this review, we provide a perspective overview of the diurnal rhythm of biological processes involved in the bioavailability of functional food factors, particularly flavonoids.

  16. Diurnal rhythmicity in biological processes involved in bioavailability of functional food factors

    PubMed Central

    Tsurusaki, Takashi; Sakakibara, Hiroyuki; Aoshima, Yoshiki; Yamazaki, Shunsuke; Sakono, Masanobu; Shimoi, Kayoko

    2013-01-01

    In the past few decades, many types of functional factors have been identified in dietary foods; for example, flavonoids are major groups widely distributed in the plant kingdom. However, the absorption rates of the functional food factors are usually low, and many of these are difficult to be absorbed in the intact forms because of metabolization by biological processes during absorption. To gain adequate beneficial effects, it is therefore mandatory to know whether functional food factors are absorbed in sufficient quantity, and then reach target organs while maintaining beneficial effects. These are the reasons why the bioavailability of functional food factors has been well investigated using rodent models. Recently, many of the biological processes have been reported to follow diurnal rhythms recurring every 24 h. Therefore, absorption and metabolism of functional food factors influenced by the biological processes may vary with time of day. Consequently, the evaluation of the bioavailability of functional food factors using rodent models should take into consideration the timing of consumption. In this review, we provide a perspective overview of the diurnal rhythm of biological processes involved in the bioavailability of functional food factors, particularly flavonoids. PMID:23704810

  17. Proceedings of the Indo-U.S. bilateral workshop on accelerating botanicals/biologics agent development research for cancer chemoprevention, treatment, and survival

    PubMed Central

    B. Kumar, Nagi; Dhurandhar, Medha; Aggarwal, Bharat; Anant, Shrikant; Daniel, Kenyon; Deng, Gary; Djeu, Julie; Dou, Jinhui; Hawk, Ernest; Jayaram, B.; Jia, Libin; Joshi, Rajendra; Kararala, Madhuri; Karunagaran, Devarajan; Kucuk, Omer; Kumar, Lalit; Malafa, Mokenge; Samathanam, G. J.; Sarkar, Fazlul; Siddiqi, Maqsood; Singh, Rana P.; Srivastava, Anil; White, Jeffrey D.

    2013-01-01

    With the evolving evidence of the promise of botanicals/biologics for cancer chemoprevention and treatment, an Indo-U.S. collaborative Workshop focusing on “Accelerating Botanicals Agent Development Research for Cancer Chemoprevention and Treatment” was conducted at the Moffitt Cancer Center, 29–31 May 2012. Funded by the Indo-U.S. Science and Technology Forum, a joint initiative of Governments of India and the United States of America and the Moffitt Cancer Center, the overall goals of this workshop were to enhance the knowledge (agents, molecular targets, biomarkers, approaches, target populations, regulatory standards, priorities, resources) of a multinational, multidisciplinary team of researcher's to systematically accelerate the design, to conduct a successful clinical trials to evaluate botanicals/biologics for cancer chemoprevention and treatment, and to achieve efficient translation of these discoveries into the standards for clinical practice that will ultimately impact cancer morbidity and mortality. Expert panelists were drawn from a diverse group of stakeholders, representing the leadership from the National Cancer Institute's Office of Cancer Complementary and Alternative Medicine (OCCAM), NCI Experimental Therapeutics (NExT), Food and Drug Administration, national scientific leadership from India, and a distinguished group of population, basic and clinical scientists from the two countries, including leaders in bioinformatics, social sciences, and biostatisticians. At the end of the workshop, we established four Indo-U.S. working research collaborative teams focused on identifying and prioritizing agents targeting four cancers that are of priority to both countries. Presented are some of the key proceedings and future goals discussed in the proceedings of this workshop. PMID:24279005

  18. Accelerated Stability Studies on Dried Extracts of Centella asiatica Through Chemical, HPLC, HPTLC, and Biological Activity Analyses.

    PubMed

    Kaur, Ishtdeep; Suthar, Nancy; Kaur, Jasmeen; Bansal, Yogita; Bansal, Gulshan

    2016-10-01

    Regulatory guidelines recommend systematic stability studies on a herbal product to establish its shelf life. In the present study, commercial extracts (Types I and II) and freshly prepared extract (Type III) of Centella asiatica were subjected to accelerated stability testing for 6 months. Control and stability samples were evaluated for organoleptics, pH, moisture, total phenolic content (TPC), asiatic acid, kaempherol, and high-performance thin layer chromatography fingerprints, and for antioxidant and acetylcholinesterase inhibitory activities. Markers and TPC and both the activities of each extract decreased in stability samples with respect to control. These losses were maximum in Type I extract and minimum in Type III extract. Higher stability of Type III extract than others might be attributed to the additional phytoconstituents and/or preservatives in it. Pearson correlation analysis of the results suggested that TPC, asiatic acid, and kaempferol can be taken as chemical markers to assess chemical and therapeutic shelf lives of herbal products containing Centella asiatica. © The Author(s) 2016.

  19. Combinatorial biosynthesis of cyclic lipopeptide antibiotics: a model for synthetic biology to accelerate the evolution of secondary metabolite biosynthetic pathways.

    PubMed

    Baltz, Richard H

    2014-10-17

    Nonribosomal peptide synthetases (NRPSs) are giant multi-enzymes that carry out sequencial assembly line couplings of amino acids to generate linear or cyclic peptides. NRPSs are composed of repeating enzyme domains with modular organization to activate and couple specific amino acids in a particular order. From a synthetic biology perspective, they can be considered as peptide assembly machines composed of devices to couple fatty acids to l-amino acids, l-amino acids to l-amino acids, and d-amino acids to l-amino acids. The coupling devices are composed of specific parts that contain two or more enzyme domains that can be exchanged combinatorially to generate novel peptide assembly machines to produce novel peptides. The potent lipopeptide antibiotics daptomycin and A54145E have identical cyclic depsipeptide ring structures and stereochemistry but have divergent amino acid sequences. As their biosynthetic gene clusters are derived from an ancient ancestral lipopetide pathway, these lipopeptides provided an attractive model to develop combinatorial biosynthesis to generate antibiotics superior to daptomycin. These studies on combinatorial biosynthesis have helped generate guidelines for the successful assembly of NRPS parts and devices that can be used to generate novel lipopeptide structures and have established a basis for future synthetic biology studies to further develop combinatorial biosynthesis as a robust approach to natural product drug discovery.

  20. miR-590 accelerates lung adenocarcinoma migration and invasion through directly suppressing functional target OLFM4.

    PubMed

    Liu, Yanhong; Wang, Feng; Xu, Peng

    2017-02-01

    MicroRNA-590 (miR-590) shows oncogenic functions in various tumor types, but little is known about biological functions of miR-590 in lung adenocarcinoma. In this study, we observe that miR-590 is not only overexpressed in lung adenocarcinoma tissues and metastatic lymph nodes, but also significantly increased in lung adenocarcinoma cell lines. Moreover, gain-of-function and loss-of-function studies show miR-590 serve as a tumor suppressor regulating lung adenocarcinoma cells migration and invasion. Furthermore, OLFM4 is proved to as a functional target for miR-590 to regulate lung adenocarcinoma cells migration and invasion. In conclusion, miR-590 regulates lung adenocarcinoma metastasis through directly modulating functional target OLFM4. Copyright © 2016 Elsevier Masson SAS. All rights reserved.

  1. Composite Structural Motifs of Binding Sites for Delineating Biological Functions of Proteins

    PubMed Central

    Kinjo, Akira R.; Nakamura, Haruki

    2012-01-01

    Most biological processes are described as a series of interactions between proteins and other molecules, and interactions are in turn described in terms of atomic structures. To annotate protein functions as sets of interaction states at atomic resolution, and thereby to better understand the relation between protein interactions and biological functions, we conducted exhaustive all-against-all atomic structure comparisons of all known binding sites for ligands including small molecules, proteins and nucleic acids, and identified recurring elementary motifs. By integrating the elementary motifs associated with each subunit, we defined composite motifs that represent context-dependent combinations of elementary motifs. It is demonstrated that function similarity can be better inferred from composite motif similarity compared to the similarity of protein sequences or of individual binding sites. By integrating the composite motifs associated with each protein function, we define meta-composite motifs each of which is regarded as a time-independent diagrammatic representation of a biological process. It is shown that meta-composite motifs provide richer annotations of biological processes than sequence clusters. The present results serve as a basis for bridging atomic structures to higher-order biological phenomena by classification and integration of binding site structures. PMID:22347478

  2. Electromagnetic fields as structure-function zeitgebers in biological systems: environmental orchestrations of morphogenesis and consciousness

    PubMed Central

    Rouleau, Nicolas; Dotta, Blake T.

    2014-01-01

    Within a cell system structure dictates function. Any interaction between cells, or a cell and its environment, has the potential to have long term implications on the function of a given cell and emerging cell aggregates. The structure and function of cells are continuously subjected to modification by electrical and chemical stimuli. However, biological systems are also subjected to an ever-present influence: the electromagnetic (EM) environment. Biological systems have the potential to be influenced by subtle energies which are exchanged at atomic and subatomic scales as EM phenomena. These energy exchanges have the potential to manifest at higher orders of discourse and affect the output (behavior) of a biological system. Here we describe theoretical and experimental evidence of EM influence on cells and the integration of whole systems. Even weak interactions between EM energies and biological systems display the potential to affect a developing system. We suggest the growing literature of EM effects on biological systems has significant implications to the cell and its functional aggregates. PMID:25426035

  3. Functional polymer-dependent 3D culture accelerates the differentiation of HepaRG cells into mature hepatocytes.

    PubMed

    Higuchi, Yichiro; Kawai, Kenji; Kanaki, Tatsuro; Yamazaki, Hiroshi; Chesné, Christophe; Guguen-Guillouzo, Christiane; Suemizu, Hiroshi

    2016-09-01

    The hepatoma-derived cell line HepaRG is regarded as an in vitro model of drug metabolism because fully differentiated HepaRG cells demonstrate functional metabolic responses comparable to those of primary human hepatocytes. Recently, it was demonstrated that the 3D culture of HepaRG cells enhanced their metabolic functions and toxicological responses. We approached the mechanisms underlying these enhancement effects. We compared 2D-cultured HepaRG cells with 3D-cultured HepaRG spheroids in the gene expression patterns and the metabolic functions. In the present study, we performed 3D culture of HepaRG cells using functional polymers (FP). To reveal the in vivo differentiation ability, we transplanted the 3D-cultured HepaRG spheroids into TK-NOG mice. A comparison between 2D and 3D cultures revealed that 3D-cultured HepaRG spheroids demonstrated reductions in bile duct marker expression, accelerated expression of cytochrome P450 3A4, and increases in the ratio of albumin-expressing hepatocytes. Furthermore, catalytic activities of cytochrome P450 3A4 were modified by omeprazole and rifampicin in the 3D-cultured HepaRG spheroids. Transplantation analysis revealed that 3D-cultured HepaRG spheroids formed hepatocyte-like colonies rather than cholangiocytes in vivo. Our results indicated that the enhancement of hepatic functions in 3D-cultured HepaRG cells was induced by selective hepatocyte differentiation and accelerated hepatocyte maturation. HepaRG spheroids reproduced the metabolic responses of human hepatocytes. Therefore, FP-dependent 3D-cultured HepaRG cells may serve as an excellent in vitro model for evaluating the hepatic metabolism and toxicity. © 2016 The Authors. Hepatology Research published by John Wiley & Sons Australia, Ltd on behalf of Japan Society of Hepatology.

  4. The influence of shielding on the biological effectiveness of accelerated particles for the induction of chromosome damage

    NASA Astrophysics Data System (ADS)

    George, K.; Cucinotta, F. A.

    Several experiments were conduced aimed at studying the influence of shielding on biological effectiveness of high-energy ions Chromosome damage was assessed in human peripheral blood lymphocytes after in vitro exposure to the either 28 Si 490 or 600 MeV n 48 Ti 1000 MeV n or 56 Fe 600 1000 or 5000 MeV n LET values for these ions ranged from approximately 50 to 174 keV mu m and doses ranged from 10 to 200 cGy The effect of aluminum or polyethylene shielding on the induction of chromosome aberrations was investigated for each ion Chromosome exchanges were measured using fluorescence in situ hybridization FISH with whole chromosome probes in cells collected 48-56 hours after irradiation using a chemical-induced premature chromosome condensation PCC technique The yield of chromosomal aberrations increased linearly with dose The relative biological effectiveness RBE for the primary beams estimated from the initial slope of the dose response curve for total chromosomal exchanges with respect to gamma -rays ranged from 14 to 35 The RBE values increased with LET to a maximum for the 1 GeV n Fe ions with LET of 150 keV mu m and decreased with further increase in LET When the LET of the primary beam was in the region of increasing RBE below approximately 100 keV mu m the addition of shielding material increased the effectiveness per unit dose However shielding decreased the effectiveness per unit dose when the LET of the primary particle beam was higher than150 keV mu m

  5. Mining bridge and brick motifs from complex biological networks for functionally and statistically significant discovery.

    PubMed

    Cheng, Chia-Ying; Huang, Chung-Yuan; Sun, Chuen-Tsai

    2008-02-01

    A major task for postgenomic systems biology researchers is to systematically catalogue molecules and their interactions within living cells. Advancements in complex-network theory are being made toward uncovering organizing principles that govern cell formation and evolution, but we lack understanding of how molecules and their interactions determine how complex systems function. Molecular bridge motifs include isolated motifs that neither interact nor overlap with others, whereas brick motifs act as network foundations that play a central role in defining global topological organization. To emphasize their structural organizing and evolutionary characteristics, we define bridge motifs as consisting of weak links only and brick motifs as consisting of strong links only, then propose a method for performing two tasks simultaneously, which are as follows: 1) detecting global statistical features and local connection structures in biological networks and 2) locating functionally and statistically significant network motifs. To further understand the role of biological networks in system contexts, we examine functional and topological differences between bridge and brick motifs for predicting biological network behaviors and functions. After observing brick motif similarities between E. coli and S. cerevisiae, we note that bridge motifs differentiate C. elegans from Drosophila and sea urchin in three types of networks. Similarities (differences) in bridge and brick motifs imply similar (different) key circuit elements in the three organisms. We suggest that motif-content analyses can provide researchers with global and local data for real biological networks and assist in the search for either isolated or functionally and topologically overlapping motifs when investigating and comparing biological system functions and behaviors.

  6. Modeling photon propagation in biological tissues using a generalized Delta-Eddington phase function.

    PubMed

    Cong, W; Shen, H; Cong, A; Wang, Y; Wang, G

    2007-11-01

    Photon propagation in biological tissue is commonly described by the radiative transfer equation, while the phase function in the equation represents the scattering characteristics of the medium and has significant influence on the precision of solution and the efficiency of computation. In this work, we present a generalized Delta-Eddington phase function to simplify the radiative transfer equation to an integral equation with respect to photon fluence rate. Comparing to the popular diffusion approximation model, the solution of the integral equation is highly accurate to model photon propagation in the biological tissue over a broad range of optical parameters. This methodology is validated by Monte Carlo simulation.

  7. The Biological Effectiveness of Accelerated Particles for the Induction of Chromosome Damage: Track Structure Effects and Cytogenetic Signatures of High-LET Exposure

    NASA Technical Reports Server (NTRS)

    George, K.; Hada, M.; Chappell, L.; Cucinotta, F. A.

    2012-01-01

    Track structure models predict that at a fixed value of LET, particles with lower charge number, Z will have a higher biological effectiveness compared to particles with a higher Z. In this report we investigated how track structure effects induction of chromosomal aberration in human cells. Human lymphocytes were irradiated in vitro with various energies of accelerated iron, silicon, neon, or titanium ions and chromosome damage was assessed in using three color FISH chromosome painting in chemically induced PCC samples collected a first cell division post irradiation. The LET values for these ions ranged from 30 to 195 keV/micrometers. Of the particles studied, Neon ions have the highest biological effectiveness for induction of total chromosome damage, which is consistent with track structure model predictions. For complex-type exchanges 64 MeV/ u Neon and 450 MeV/u Iron were equally effective and induced the most complex damage. In addition we present data on chromosomes exchanges induced by six different energies of protons (5 MeV/u to 2.5 GeV/u). The linear dose response term was similar for all energies of protons suggesting that the effect of the higher LET at low proton energies is balanced by the production of nuclear secondaries from the high energy protons. All energies of protons have a much higher percentage of complex-type chromosome exchanges than gamma rays, signifying a cytogenetic signature for proton exposures.

  8. Low-dose neutron dose response of zebrafish embryos obtained from the Neutron exposure Accelerator System for Biological Effect Experiments (NASBEE) facility

    NASA Astrophysics Data System (ADS)

    Ng, C. Y. P.; Kong, E. Y.; Konishi, T.; Kobayashi, A.; Suya, N.; Cheng, S. H.; Yu, K. N.

    2015-09-01

    The dose response of embryos of the zebrafish, Danio rerio, irradiated at 5 h post fertilization (hpf) by 2-MeV neutrons with ≤100 mGy was determined. The neutron irradiations were made at the Neutron exposure Accelerator System for Biological Effect Experiments (NASBEE) facility in the National Institute of Radiological Sciences (NIRS), Chiba, Japan. A total of 10 neutron doses ranging from 0.6 to 100 mGy were employed (with a gamma-ray contribution of 14% to the total dose), and the biological effects were studied through quantification of apoptosis at 25 hpf. The responses for neutron doses of 10, 20, 25, and 50 mGy approximately fitted on a straight line, while those for neutron doses of 0.6, 1 and 2.5 mGy exhibited neutron hormetic effects. As such, hormetic responses were generically developed by different kinds of ionizing radiations with different linear energy transfer (LET) values. The responses for neutron doses of 70 and 100 mGy were significantly below the lower 95% confidence band of the best-fit line, which strongly suggested the presence of gamma-ray hormesis.

  9. HDFx: a novel biologic immunomodulator accelerates wound healing and is suggestive of unique regenerative powers: potential implications for the warfighter and disaster victims.

    PubMed

    Altura, Burton M; Carella, Anthony; Gebrewold, Asefa

    2012-01-01

    Recently, we reported on the discovery of a new, conserved biologic protein (35-40 KDa), termed HDFx, that protects rats, guinea-pigs, mice, and rabbits against lethal hemorrhage, endotoxins, intestinal ischemic-shock, and traumatic injuries. It was found to stimulate several arms of the immune system. The present report demonstrates, for the first time, that HDFx accelerates wound healing in two different models (excision wound model; and incision wound model) in rats. The results shown, herein, indicate that HDFx produces greater rates of wound contraction, greater tensile strength, and more rapid healing than controls. Our new data also show that this biologic increases hydroxyproline content of granulation tissue coupled with a reduction in superoxide dismutase (SOD). In addition, we show that HDFx increases the levels of serum ascorbic acid and stimulates the mononuclear cells of the reticuloendothelial system (RES). Overall, these data suggest that HDFx may possess unique regenerative powers. We, thus, believe that HDFx can be of great potential use in diverse types of wounds which, otherwise, could result in difficult to treat infections and thus prevent sepsis and loss of body parts from amputations.

  10. Accelerating self consistent field convergence by rubber sheeting of initial electronic wave functions.

    NASA Astrophysics Data System (ADS)

    Matthews, G. Eric; Holzwarth, N. A. W.; Martin, George; Keeling, Briana; Agopsowicz, Douglas

    2007-03-01

    We develop an algorithm for generating better initial electronic wave function estimates for density functional theory calculations following atomic movement. First principles molecular dynamics and atomic relaxation calculations involve successive movements of atoms followed by self consistent field (SCF) solutions for electronic wave functions. The SCF solutions converge most rapidly when starting from reasonably good estimates. Often estimates are generated directly from the wave functions of the previous atomic positions without adjustments for effects of position changes. Such estimates result in fast convergence to the correct wave function for small atomic movements, but for larger movements, convergence may be much slower. We present a method for improving the estimates of the new wave functions by using information from the movement of the atoms. Our algorithm is based on the ``rubber-sheeting'' method used in overlaying satellite imagery on geographic maps. A warping function is calculated that stretches and shrinks different regions of the wave function so that regions near nuclei are dragged along with the atoms. These estimates yield faster convergence for cases studied thus far.

  11. BeeSpace Navigator: exploratory analysis of gene function using semantic indexing of biological literature

    PubMed Central

    Sen Sarma, Moushumi; Arcoleo, David; Khetani, Radhika S.; Chee, Brant; Ling, Xu; He, Xin; Jiang, Jing; Mei, Qiaozhu; Zhai, ChengXiang; Schatz, Bruce

    2011-01-01

    With the rapid decrease in cost of genome sequencing, the classification of gene function is becoming a primary problem. Such classification has been performed by human curators who read biological literature to extract evidence. BeeSpace Navigator is a prototype software for exploratory analysis of gene function using biological literature. The software supports an automatic analogue of the curator process to extract functions, with a simple interface intended for all biologists. Since extraction is done on selected collections that are semantically indexed into conceptual spaces, the curation can be task specific. Biological literature containing references to gene lists from expression experiments can be analyzed to extract concepts that are computational equivalents of a classification such as Gene Ontology, yielding discriminating concepts that differentiate gene mentions from other mentions. The functions of individual genes can be summarized from sentences in biological literature, to produce results resembling a model organism database entry that is automatically computed. Statistical frequency analysis based on literature phrase extraction generates offline semantic indexes to support these gene function services. The website with BeeSpace Navigator is free and open to all; there is no login requirement at www.beespace.illinois.edu for version 4. Materials from the 2010 BeeSpace Software Training Workshop are available at www.beespace.illinois.edu/bstwmaterials.php. PMID:21558175

  12. BeeSpace Navigator: exploratory analysis of gene function using semantic indexing of biological literature.

    PubMed

    Sen Sarma, Moushumi; Arcoleo, David; Khetani, Radhika S; Chee, Brant; Ling, Xu; He, Xin; Jiang, Jing; Mei, Qiaozhu; Zhai, ChengXiang; Schatz, Bruce

    2011-07-01

    With the rapid decrease in cost of genome sequencing, the classification of gene function is becoming a primary problem. Such classification has been performed by human curators who read biological literature to extract evidence. BeeSpace Navigator is a prototype software for exploratory analysis of gene function using biological literature. The software supports an automatic analogue of the curator process to extract functions, with a simple interface intended for all biologists. Since extraction is done on selected collections that are semantically indexed into conceptual spaces, the curation can be task specific. Biological literature containing references to gene lists from expression experiments can be analyzed to extract concepts that are computational equivalents of a classification such as Gene Ontology, yielding discriminating concepts that differentiate gene mentions from other mentions. The functions of individual genes can be summarized from sentences in biological literature, to produce results resembling a model organism database entry that is automatically computed. Statistical frequency analysis based on literature phrase extraction generates offline semantic indexes to support these gene function services. The website with BeeSpace Navigator is free and open to all; there is no login requirement at www.beespace.illinois.edu for version 4. Materials from the 2010 BeeSpace Software Training Workshop are available at www.beespace.illinois.edu/bstwmaterials.php.

  13. The Influence of Shielding on the Biological Effectiveness of Accelerated Particles for the Induction of Chromosome Damages

    NASA Technical Reports Server (NTRS)

    George, K.; Cucinotta, F. A.

    2006-01-01

    Chromosome damage was assessed in human peripheral blood lymphocytes after in vitro exposure to the either Si-28 (490 or 600 MeV/n), Ti-48 (1000 MeV/n), or Fe-56 (600, 1000, or 5000 MeV/n). LET values for these ions ranged from approximately 50 to 174 keV/micrometers and doses ranged from 10 to 200 cGy. The effect of either aluminum or polyethylene shielding on the induction of chromosome aberrations was investigated for each ion. Chromosome exchanges were measured using fluorescence in situ hybridization (FISH) with whole chromosome probes in cells collected 48-56 hours after irradiation using a chemical-induced premature chromosome condensation (PCC) technique. The yield of chromosomal aberrations increased linearly with dose and the relative biological effectiveness (RBE) for the primary beams, estimated from the initial slope of the dose response curve for total chromosomal exchanges with respect to gamma-rays, ranged from 14 to 35. The RBE values increased with LET, reaching a maximum for the 1 GeV/n Fe ions with LET of 150 keV/micrometers, and decreased with further increases in LET. When LET of the primary beam was in the region of increasing RBE (i.e. below approximately 100 keV/micrometers), the addition of shielding material increased the effectiveness per unit dose. Whereas shielding decreased the effectiveness per unit dose when the LET of the primary particle beam was higher than 150 keV/micrometers.

  14. The influence of shielding on the biological effectiveness of accelerated particles for the induction of chromosome damage

    NASA Astrophysics Data System (ADS)

    George, K.; Cucinotta, F. A.

    Chromosome damage was assessed in human peripheral blood lymphocytes after in vitro exposure to 28Si (490 or 600 MeV/n), 48Ti (1000 MeV/n), or 56Fe (600, 1000, or 5000 MeV/n). LET values for these ions ranged from 51 to 184 keV/μm and doses ranged from 10 to 200 cGy. The effect of either aluminum or polyethylene shielding on the induction of chromosome aberrations was investigated for each ion. After chromosomes were prematurely condensed using calyculin-A, chromosome exchanges were measured using fluorescence in situ hybridization (FISH) with whole chromosome probes in cells collected at G2 and at mitosis in first division post-irradiation. The yield of chromosome aberrations increased linearly with dose, and the relative biological effectiveness (RBE) for the primary beams, estimated from the initial slope of the dose-response curve for total chromosome exchanges with respect to γ-rays, ranged from 9 to 35. The RBE values increased with LET, reaching a maximum for the 600 MeV/n Fe ions with LET of 184 keV/μm. When the LET of the primary beam was below about 100 keV/μm, the addition of shielding material increased the effectiveness per unit dose. When the LET of the primary beam was greater than 100 keV/μm, shielding decreased the effectiveness per unit dose.

  15. The Influence of Shielding on the Biological Effectiveness of Accelerated Particles for the Induction of Chromosome Damages

    NASA Technical Reports Server (NTRS)

    George, K.; Cucinotta, F. A.

    2006-01-01

    Chromosome damage was assessed in human peripheral blood lymphocytes after in vitro exposure to the either Si-28 (490 or 600 MeV/n), Ti-48 (1000 MeV/n), or Fe-56 (600, 1000, or 5000 MeV/n). LET values for these ions ranged from approximately 50 to 174 keV/micrometers and doses ranged from 10 to 200 cGy. The effect of either aluminum or polyethylene shielding on the induction of chromosome aberrations was investigated for each ion. Chromosome exchanges were measured using fluorescence in situ hybridization (FISH) with whole chromosome probes in cells collected 48-56 hours after irradiation using a chemical-induced premature chromosome condensation (PCC) technique. The yield of chromosomal aberrations increased linearly with dose and the relative biological effectiveness (RBE) for the primary beams, estimated from the initial slope of the dose response curve for total chromosomal exchanges with respect to gamma-rays, ranged from 14 to 35. The RBE values increased with LET, reaching a maximum for the 1 GeV/n Fe ions with LET of 150 keV/micrometers, and decreased with further increases in LET. When LET of the primary beam was in the region of increasing RBE (i.e. below approximately 100 keV/micrometers), the addition of shielding material increased the effectiveness per unit dose. Whereas shielding decreased the effectiveness per unit dose when the LET of the primary particle beam was higher than 150 keV/micrometers.

  16. Shining the spotlight on functional molecular complexes: The new science of single-molecule cell biology.

    PubMed

    Leake, Mark C

    2010-09-01

    Single-molecule research is emerging as one of the fastest growing fields within the biosciences. Historically, most of the techniques employed have operated largely in the world of the test tube in which the components of the biological system under investigation have been extracted and purified from cells to reduce them to just the key ingredients under study, and this research has involved novel, pioneering methods of biophysics to obtain single-molecule measurements. What has emerged recently is the technical ability to now perform key single-molecule experiments whilst retaining the native biological context-namely to do single-molecule experiments on functional living cells. This presents essentially a new science of "single-molecule cell biology", which combines classical cell biology approaches with modern single-molecule biophysics. Here, key recent studies which have pushed back the boundaries of this field are discussed.

  17. Linear Accelerators

    NASA Astrophysics Data System (ADS)

    Sidorin, Anatoly

    2010-01-01

    In linear accelerators the particles are accelerated by either electrostatic fields or oscillating Radio Frequency (RF) fields. Accordingly the linear accelerators are divided in three large groups: electrostatic, induction and RF accelerators. Overview of the different types of accelerators is given. Stability of longitudinal and transverse motion in the RF linear accelerators is briefly discussed. The methods of beam focusing in linacs are described.

  18. Linear Accelerators

    SciTech Connect

    Sidorin, Anatoly

    2010-01-05

    In linear accelerators the particles are accelerated by either electrostatic fields or oscillating Radio Frequency (RF) fields. Accordingly the linear accelerators are divided in three large groups: electrostatic, induction and RF accelerators. Overview of the different types of accelerators is given. Stability of longitudinal and transverse motion in the RF linear accelerators is briefly discussed. The methods of beam focusing in linacs are described.

  19. Functional stereotactic radiosurgery involving a dedicated linear accelerator and gamma unit: a comparison study.

    PubMed

    Solberg, Timothy D; Goetsch, Steven J; Selch, Michael T; Melega, William; Lacan, Goran; DeSalles, Antonio A F

    2004-11-01

    The purpose of this work was to investigate the targeting and dosimetric characteristics of a linear accelerator (LINAC) system dedicated for stereotactic radiosurgery compared with those of a commercial gamma knife (GK) unit. A phantom was rigidly affixed within a Leksell stereotactic frame and axial computerized tomography scans were obtained using an appropriate stereotactic localization device. Treatment plans were performed, film was inserted into a recessed area, and the phantom was positioned and treated according to each treatment plan. In the case of the LINAC system, four 140 degrees arcs, spanning +/-60 degrees of couch rotation, were used. In the case of the GK unit, all 201 sources were left unplugged. Radiation was delivered using 3- and 8-mm LINAC collimators and 4- and 8-mm collimators of the GK unit. Targeting ability was investigated independently on the dedicated LINAC by using a primate model. Measured 50% spot widths for multisource, single-shot radiation exceeded nominal values in all cases by 38 to 70% for the GK unit and 11 to 33% for the LINAC system. Measured offsets were indicative of submillimeter targeting precision on both devices. In primate studies, the appearance of an magnetic resonance imaging-enhancing lesion coincided with the intended target. Radiosurgery performed using the 3-mm collimator of the dedicated LINAC exhibited characteristics that compared favorably with those of a dedicated GK unit. Overall targeting accuracy in the submillimeter range can be achieved, and dose distributions with sharp falloff can be expected for both devices.

  20. Ubiquinol-10 Supplementation Activates Mitochondria Functions to Decelerate Senescence in Senescence-Accelerated Mice

    PubMed Central

    Tian, Geng; Sawashita, Jinko; Kubo, Hiroshi; Nishio, Shin-ya; Hashimoto, Shigenari; Suzuki, Nobuyoshi; Yoshimura, Hidekane; Tsuruoka, Mineko; Wang, Yaoyong; Liu, Yingye; Luo, Hongming; Xu, Zhe; Mori, Masayuki; Kitano, Mitsuaki; Hosoe, Kazunori; Takeda, Toshio; Usami, Shin-ichi

    2014-01-01

    Abstract Aim: The present study was conducted to define the relationship between the anti-aging effect of ubiquinol-10 supplementation and mitochondrial activation in senescence-accelerated mouse prone 1 (SAMP1) mice. Results: Here, we report that dietary supplementation with ubiquinol-10 prevents age-related decreases in the expression of sirtuin gene family members, which results in the activation of peroxisome proliferator-activated receptor γ coactivator 1α (PGC-1α), a major factor that controls mitochondrial biogenesis and respiration, as well as superoxide dismutase 2 (SOD2) and isocitrate dehydrogenase 2 (IDH2), which are major mitochondrial antioxidant enzymes. Ubiquinol-10 supplementation can also increase mitochondrial complex I activity and decrease levels of oxidative stress markers, including protein carbonyls, apurinic/apyrimidinic sites, malondialdehydes, and increase the reduced glutathione/oxidized glutathione ratio. Furthermore, ubiquinol-10 may activate Sirt1 and PGC-1α by increasing cyclic adenosine monophosphate (cAMP) levels that, in turn, activate cAMP response element-binding protein (CREB) and AMP-activated protein kinase (AMPK). Innovation and Conclusion: These results show that ubiquinol-10 may enhance mitochondrial activity by increasing levels of SIRT1, PGC-1α, and SIRT3 that slow the rate of age-related hearing loss and protect against the progression of aging and symptoms of age-related diseases. Antioxid. Redox Signal. 20, 2606–2620 PMID:24124769

  1. The Influence of Shielding on the Biological Effectiveness of Accelerated Particles for the Induction of Chromosome Damage

    NASA Technical Reports Server (NTRS)

    Goeorge, Kerry; Cucinotta, Francis A.

    2007-01-01

    Chromosome damage was assessed in human peripheral blood lymphocytes after in vitro exposure to the either Si-28 (490 or 600 MeV/n), Ti-48 (1000 MeV/n), or Fe-56 (600, 1000, or 5000 MeV/n). LET values for these ions ranged from 51 to 184 keV/micron and doses ranged from 10 to 200 cGy. The effect of either aluminum or polyethylene shielding on the induction of chromosome aberrations was investigated for each ion. Chromosome exchanges were measured using fluorescence in situ hybridization (FISH) with whole chromosome probes in cells collected at G2 and mitosis in first division post irradiation after chromosomes were prematurely condensed using calyculin-A. The yield of chromosomal aberrations increased linearly with dose and the relative biological effectiveness (RBE) for the primary beams, estimated from the initial slope of the dose response curve for total chromosomal exchanges with respect to gamma-rays, ranged from 9 to 35. The RBE values increased with LET, reaching a maximum for the 600 MeV/n Fe ions with LET of 184 keV/micron. When the LET of the primary beam was below approximately 100 keV/micron, the addition of shielding material increased the effectiveness per unit dose. Whereas shielding decreased the effectiveness per unit dose when the LET of primary beams was higher than 100 keV/micron. The yield of aberrations correlated with the dose-average LET of the beam after traversal through the shielding.

  2. Origin and evolution of viruses: escaped DNA/RNA sequences as evolutionary accelerators and natural biological weapons.

    PubMed

    Bubanovic, Ivan; Najman, Stevo; Andjelkovic, Zlatibor

    2005-01-01

    Knowledge of the origin and evolution of viruses could provide a better understanding of a number of phenomena in the field of evolution such as the origin and development of multi-cellular organisms, the rapid diversification of species over the last 600-700 million years and the lack of transitional forms in the evolution of species ("missing links") etc. One of the possible effects of escaped DNA/RNA sequences or viruses on the evolution of multi-cellular organisms, especially vertebrates, could be the phenomenon of horizontal transmission and dissemination of genes. Interestingly, if so, this effect could be considered as a model of primeval and natural genetic engineering. Other possible links between the evolution of multi-cellular organisms and viruses are connected with the fact that viruses represent the source of different forms of selective pressure such as epidemics of infectious diseases, autoimmunity, malignant alteration, reproductive efficiency, etc. At the same time, these two models of "long-term evolutionary relations" could represent "key factors" in the evolution between viruses and multi-cellular organisms. The capability of a genome to produce and emit DNA/RNA sequences or de novo created viruses which can be a vector of genes horizontal transmission and/or cause selective pressure on concurrent or predator species gives a new characteristic to viruses--the possibility of their acting as natural biological weapons. Finally, possibly evolutionary advantages of this genome capability could be one of explanations for the phenomena such as genome instability and its ability to emit DNA/RNA sequences and/or de novo created viruses, as well as evolutionary conservation of this unique phenomena.

  3. Community Structure Reveals Biologically Functional Modules in MEF2C Transcriptional Regulatory Network

    PubMed Central

    Alcalá-Corona, Sergio A.; Velázquez-Caldelas, Tadeo E.; Espinal-Enríquez, Jesús; Hernández-Lemus, Enrique

    2016-01-01

    Gene regulatory networks are useful to understand the activity behind the complex mechanisms in transcriptional regulation. A main goal in contemporary biology is using such networks to understand the systemic regulation of gene expression. In this work, we carried out a systematic study of a transcriptional regulatory network derived from a comprehensive selection of all potential transcription factor interactions downstream from MEF2C, a human transcription factor master regulator. By analyzing the connectivity structure of such network, we were able to find different biologically functional processes and specific biochemical pathways statistically enriched in communities of genes into the network, such processes are related to cell signaling, cell cycle and metabolism. In this way we further support the hypothesis that structural properties of biological networks encode an important part of their functional behavior in eukaryotic cells. PMID:27252657

  4. Pulmonary Function After Oxygen-Accelerated Decompressions from Repetitive Sub-Saturation Air Dives

    DTIC Science & Technology

    2005-04-01

    16 5 806 16 2 631 15 6 261 8 3 177 16 7 460 16 4 338 14 8 1068 16 n = the number of subjects for whom pulmonary function was measured after surfacing...function measurement session involved three successful repeats of each test, according to the American Thoracic Society standards.5 The average values from...capacity (DLCO) corrected for hemoglobin concentration. Flow volume loops were measured on each occasion, and diffusing capacity was measured at

  5. Exergames: neuroplastic hypothesis about cognitive improvement and biological effects on physical function of institutionalized older persons

    PubMed Central

    Monteiro-Junior, Renato Sobral; Vaghetti, César Augusto Otero; Nascimento, Osvaldo José M.; Laks, Jerson; Deslandes, Andrea Camaz

    2016-01-01

    Exergames can be considered a dual task because the games are performed by a man-videogame interface, requiring cognitive and motor functions simultaneously. Although the literature has shown improvements of cognitive and physical functions due to exergames, the intrinsic mechanisms involved in these functional changes have still not been elucidated. The aims of the present study were (1) to demonstrate the known biological mechanisms of physical exercise regarding muscle adaptation and establish a relationship with exergames; and (2) to present a neurobiological hypothesis about the neuroplastic effects of exergames on the cognitive function of institutionalized older persons. These hypotheses are discussed. PMID:27073355

  6. Impact of health disorders and culling reasons on functional and biological longevity in Warmblood breeding stallions.

    PubMed

    König von Borstel, U; Bernhard, V

    2013-08-01

    The objective of this study was to compare the impact of health disorders and reasons for culling on the functional and biological longevity of warmblood breeding stallions using semi-parametric survival analysis accounting for competing risks. Complete breeding records were collected from 455 warmblood stallions serving between 1975 and 2010 at Marbach State Stud in Germany. The median length of life (18.0 years) was twice as long as the median length of service (9.0 years). However, both figures increased significantly over the time period examined (e.g., functional longevity increased from 5 years in the 1970s to 8 years in the 1980s to 12 years in the 1990s). Compared to disorders of the musculoskeletal system, hazards for termination of functional life were higher for infectious diseases with a hazard ratio (HR) of 3.5, and for dissatisfaction with performance (HR, 2.0). Hazards were lower for disorders of the respiratory system (HR, 0.78), followed by accidents (HR, 0.58), disorders of the reproductive system (HR, 0.51), sale for non-breeding purposes (HR, 0.40), disorders of the gastrointestinal system (HR, 0.36), unknown reasons (HR, 0.32) and disorders of the cardiovascular system (HR, 0.25). For biological life, the relative importance of these disorders was similar. Factors linked to demand for stallions such as coat colour and several parameters of the stallions' genetic merit (negative influence) and own performance (positive influence) in dressage and particularly in show-jumping influenced (P<0.05) or tended to influence (P<0.1) functional, but not biological longevity. Furthermore, hazards for both functional and biological life declined with rising stud fees (both HR, 0.99; P<0.0001). A more direct consideration of both functional and biological longevity in breeding programmes might help to further enhance both figures, and therefore welfare of the horses.

  7. Functional genomics bridges the gap between quantitative genetics and molecular biology.

    PubMed

    Lappalainen, Tuuli

    2015-10-01

    Deep characterization of molecular function of genetic variants in the human genome is becoming increasingly important for understanding genetic associations to disease and for learning to read the regulatory code of the genome. In this paper, I discuss how recent advances in both quantitative genetics and molecular biology have contributed to understanding functional effects of genetic variants, lessons learned from eQTL studies, and future challenges in this field.

  8. Biological interpretation of genome-wide association studies using predicted gene functions.

    PubMed

    Pers, Tune H; Karjalainen, Juha M; Chan, Yingleong; Westra, Harm-Jan; Wood, Andrew R; Yang, Jian; Lui, Julian C; Vedantam, Sailaja; Gustafsson, Stefan; Esko, Tonu; Frayling, Tim; Speliotes, Elizabeth K; Boehnke, Michael; Raychaudhuri, Soumya; Fehrmann, Rudolf S N; Hirschhorn, Joel N; Franke, Lude

    2015-01-19

    The main challenge for gaining biological insights from genetic associations is identifying which genes and pathways explain the associations. Here we present DEPICT, an integrative tool that employs predicted gene functions to systematically prioritize the most likely causal genes at associated loci, highlight enriched pathways and identify tissues/cell types where genes from associated loci are highly expressed. DEPICT is not limited to genes with established functions and prioritizes relevant gene sets for many phenotypes.

  9. Finite element analysis (FEA): applying an engineering method to functional morphology in anthropology and human biology.

    PubMed

    Panagiotopoulou, O

    2009-01-01

    A fundamental research question for morphologists is how morphological variation in the skeleton relates to function. Traditional approaches have advanced our understanding of form-function relationships considerably but have limitations. Strain gauges can only record strains on a surface, and the geometry of the structure can limit where they can be bonded. Theoretical approaches, such as geometric abstractions, work well on problems with simple geometries and material properties but biological structures typically have neither of these. Finite element analysis (FEA) is a method that overcomes these problems by reducing a complex geometry into a finite number of elements with simple geometries. In addition, FEA allows strain to be modelled across the entire surface of the structure and throughout the internal structure. With advances in the processing power of computers, FEA has become more accessible and as such is becoming an increasingly popular tool to address questions about form-function relationships in development and evolution, as well as human biology generally. This paper provides an introduction to FEA including a review of the sequence of steps needed for the generation of biologically accurate finite element models that can be used for the testing of biological and functional morphology hypotheses.

  10. Integrated omics for the identification of key functionalities in biological wastewater treatment microbial communities.

    PubMed

    Narayanasamy, Shaman; Muller, Emilie E L; Sheik, Abdul R; Wilmes, Paul

    2015-05-01

    Biological wastewater treatment plants harbour diverse and complex microbial communities which prominently serve as models for microbial ecology and mixed culture biotechnological processes. Integrated omic analyses (combined metagenomics, metatranscriptomics, metaproteomics and metabolomics) are currently gaining momentum towards providing enhanced understanding of community structure, function and dynamics in situ as well as offering the potential to discover novel biological functionalities within the framework of Eco-Systems Biology. The integration of information from genome to metabolome allows the establishment of associations between genetic potential and final phenotype, a feature not realizable by only considering single 'omes'. Therefore, in our opinion, integrated omics will become the future standard for large-scale characterization of microbial consortia including those underpinning biological wastewater treatment processes. Systematically obtained time and space-resolved omic datasets will allow deconvolution of structure-function relationships by identifying key members and functions. Such knowledge will form the foundation for discovering novel genes on a much larger scale compared with previous efforts. In general, these insights will allow us to optimize microbial biotechnological processes either through better control of mixed culture processes or by use of more efficient enzymes in bioengineering applications. © 2015 The Authors. Microbial Biotechnology published by John Wiley & Sons Ltd and Society for Applied Microbiology.

  11. Late-stage diversification of biologically active pyridazinones via a direct C-H functionalization strategy.

    PubMed

    Li, Wei; Fan, Zhoulong; Geng, Kaijun; Xu, Youjun; Zhang, Ao

    2015-01-14

    Divergent C-H functionalization reactions (arylation, carboxylation, olefination, thiolation, acetoxylation, halogenation, naphthylation) using a pyridazinone moiety as an internal directing group were successfully established. This approach offers a late-stage, ortho-selective diversification of a biologically active pyridazinone scaffold. Seven series of novel pyridazinone analogues were synthesized conveniently as the synthetic precursors of potential sortase A (SrtA) inhibitors.

  12. Calculations of the Acceleration of Centrifugal Loading on Adherent Cells

    NASA Astrophysics Data System (ADS)

    Chen, Kang; Song, Yang; Liu, Qing; Zhang, Chunqiu

    2017-07-01

    Studies have shown that the morphology and function of living cells are greatly affected by the state of different high acceleration. Based on the centrifuge, we designed a centrifugal cell loading machine for the mechanical biology of cells under high acceleration loading. For the machine, the feasibility of the experiment was studied by means of constant acceleration or variable acceleration loading in the Petri dish fixture and/or culture flask. Here we analyzed the distribution of the acceleration of the cells with the change of position and size of the culturing device quantitatively. It is obtained that Petri dish fixture and/or culture flask can be used for constant acceleration loading by experiments; the centripetal acceleration of the adherent cells increases with the increase of the distance between the rotor center of the centrifuge and the fixture of the Petri dish and the size of the fixture. It achieves the idea that the general biology laboratory can conduct the study of mechanical biology at high acceleration. It also provides a basis for more accurate study of the law of high acceleration on mechanobiology of cells.

  13. CCR5 deficiency accelerates lipopolysaccharide-induced astrogliosis, amyloid-beta deposit and impaired memory function.

    PubMed

    Hwang, Chul Ju; Park, Mi Hee; Hwang, Jae Yeon; Kim, Ju Hwan; Yun, Na Young; Oh, Sang Yeon; Song, Ju Kyung; Seo, Hyun Ok; Kim, Yun-Bae; Hwang, Dae Yeon; Oh, Ki-Wan; Han, Sang-Bae; Hong, Jin Tae

    2016-03-15

    Chemokine receptors are implicated in inflammation and immune responses. Neuro-inflammation is associated with activation of astrocyte and amyloid-beta (Aβ) generations that lead to pathogenesis of Alzheimer disease (AD). Previous our study showed that deficiency of CC chemokine receptor 5 (CCR5) results in activation of astrocytes and Aβ deposit, and thus memory dysfunction through increase of CC chemokine receptor 2 (CCR2) expression. CCR5 knockout mice were used as an animal model with memory dysfunction. For the purpose LPS was injected i.p. daily (0.25 mg/kg/day). The memory dysfunctions were much higher in LPS-injected CCR5 knockout mice compared to CCR5 wild type mice as well as non-injected CCR5 knockout mice. Associated with severe memory dysfuction in LPS injected CCR5 knockout mice, LPS injection significant increase expression of inflammatory proteins, astrocyte activation, expressions of β-secretase as well as Aβ deposition in the brain of CCR5 knockout mice as compared with that of CCR5 wild type mice. In CCR5 knockout mice, CCR2 expressions were high and co-localized with GFAP which was significantly elevated by LPS. Expression of monocyte chemoattractant protein-1 (MCP-1) which ligands of CCR2 also increased by LPS injection, and increment of MCP-1 expression is much higher in CCR5 knockout mice. BV-2 cells treated with CCR5 antagonist, D-ala-peptide T-amide (DAPTA) and cultured astrocytes isolated from CCR5 knockout mice treated with LPS (1 μg/ml) and CCR2 antagonist, decreased the NF-ĸB activation and Aβ level. These findings suggest that the deficiency of CCR5 enhances response of LPS, which accelerates to neuro-inflammation and memory impairment.

  14. CCR5 deficiency accelerates lipopolysaccharide-induced astrogliosis, amyloid-beta deposit and impaired memory function

    PubMed Central

    Hwang, Jae Yeon; Kim, Ju Hwan; Yun, Na Young; Oh, Sang Yeon; Song, Ju Kyung; Seo, Hyun Ok; Kim, Yun-Bae; Hwang, Dae Yeon; Oh, Ki-Wan; Han, Sang-Bae; Hong, Jin Tae

    2016-01-01

    Chemokine receptors are implicated in inflammation and immune responses. Neuro-inflammation is associated with activation of astrocyte and amyloid-beta (Aβ) generations that lead to pathogenesis of Alzheimer disease (AD). Previous our study showed that deficiency of CC chemokine receptor 5 (CCR5) results in activation of astrocytes and Aβ deposit, and thus memory dysfunction through increase of CC chemokine receptor 2 (CCR2) expression. CCR5 knockout mice were used as an animal model with memory dysfunction. For the purpose LPS was injected i.p. daily (0.25 mg/kg/day). The memory dysfunctions were much higher in LPS-injected CCR5 knockout mice compared to CCR5 wild type mice as well as non-injected CCR5 knockout mice. Associated with severe memory dysfuction in LPS injected CCR5 knockout mice, LPS injection significant increase expression of inflammatory proteins, astrocyte activation, expressions of β-secretase as well as Aβ deposition in the brain of CCR5 knockout mice as compared with that of CCR5 wild type mice. In CCR5 knockout mice, CCR2 expressions were high and co-localized with GFAP which was significantly elevated by LPS. Expression of monocyte chemoattractant protein-1 (MCP-1) which ligands of CCR2 also increased by LPS injection, and increment of MCP-1 expression is much higher in CCR5 knockout mice. BV-2 cells treated with CCR5 antagonist, D-ala-peptide T-amide (DAPTA) and cultured astrocytes isolated from CCR5 knockout mice treated with LPS (1 μg/ml) and CCR2 antagonist, decreased the NF-ĸB activation and Aβ level. These findings suggest that the deficiency of CCR5 enhances response of LPS, which accelerates to neuro-inflammation and memory impairment. PMID:26910914

  15. Severe impingement of lumbar disc replacements increases the functional biological activity of polyethylene wear debris.

    PubMed

    Baxter, Ryan M; Macdonald, Daniel W; Kurtz, Steven M; Steinbeck, Marla J

    2013-06-05

    Wear, oxidation, and particularly rim impingement damage of ultra-high molecular weight polyethylene total disc replacement components have been observed following surgical revision. However, neither in vitro testing nor retrieval-based evidence has shown the effect(s) of impingement on the characteristics of polyethylene wear debris. Thus, we sought to determine (1) differences in polyethylene particle size, shape, number, or biological activity that correspond to mild or severe rim impingement and (2) in an analysis of all total disc replacements, regardless of impingement classification, whether there are correlations between the extent of regional damage and the characteristics of polyethylene wear debris. The extent of dome and rim damage was characterized for eleven retrieved polyethylene cores obtained at revision surgery after an average duration of implantation of 9.7 years (range, 4.6 to 16.1 years). Polyethylene wear debris was isolated from periprosthetic tissues with use of nitric acid and was imaged with use of environmental scanning electron microscopy. Subsequently, particle size, shape, number, biological activity, and chronic inflammation scores were determined. Grouping of particles by size ranges that represented high biological relevance (<0.1 to 1-μm particles), intermediate biological relevance (1 to 10-μm particles), and low biological relevance (>10-μm particles) revealed an increased volume fraction of particles in the <0.1 to 1-μm and 1 to 10-μm size ranges in the mild-impingement cohort as compared with the severe-impingement cohort. The increased volume fractions resulted in a higher specific biological activity per unit particle volume in the mild-impingement cohort than in the severe-impingement cohort. However, functional biological activity, which is normalized by particle volume (mm3/g of tissue), was significantly higher in the severe-impingement cohort. This increase was due to a larger volume of particles in all

  16. Severe Impingement of Lumbar Disc Replacements Increases the Functional Biological Activity of Polyethylene Wear Debris

    PubMed Central

    Baxter, Ryan M.; MacDonald, Daniel W.; Kurtz, Steven M.; Steinbeck, Marla J.

    2013-01-01

    Background: Wear, oxidation, and particularly rim impingement damage of ultra-high molecular weight polyethylene total disc replacement components have been observed following surgical revision. However, neither in vitro testing nor retrieval-based evidence has shown the effect(s) of impingement on the characteristics of polyethylene wear debris. Thus, we sought to determine (1) differences in polyethylene particle size, shape, number, or biological activity that correspond to mild or severe rim impingement and (2) in an analysis of all total disc replacements, regardless of impingement classification, whether there are correlations between the extent of regional damage and the characteristics of polyethylene wear debris. Methods: The extent of dome and rim damage was characterized for eleven retrieved polyethylene cores obtained at revision surgery after an average duration of implantation of 9.7 years (range, 4.6 to 16.1 years). Polyethylene wear debris was isolated from periprosthetic tissues with use of nitric acid and was imaged with use of environmental scanning electron microscopy. Subsequently, particle size, shape, number, biological activity, and chronic inflammation scores were determined. Results: Grouping of particles by size ranges that represented high biological relevance (<0.1 to 1-μm particles), intermediate biological relevance (1 to 10-μm particles), and low biological relevance (>10-μm particles) revealed an increased volume fraction of particles in the <0.1 to 1-μm and 1 to 10-μm size ranges in the mild-impingement cohort as compared with the severe-impingement cohort. The increased volume fractions resulted in a higher specific biological activity per unit particle volume in the mild-impingement cohort than in the severe-impingement cohort. However, functional biological activity, which is normalized by particle volume (mm3/g of tissue), was significantly higher in the severe-impingement cohort. This increase was due to a larger volume

  17. ACCELERATION INTEGRATOR

    DOEpatents

    Pope, K.E.

    1958-01-01

    This patent relates to an improved acceleration integrator and more particularly to apparatus of this nature which is gyrostabilized. The device may be used to sense the attainment by an airborne vehicle of a predetermined velocitv or distance along a given vector path. In its broad aspects, the acceleration integrator utilizes a magnetized element rotatable driven by a synchronous motor and having a cylin drical flux gap and a restrained eddy- current drag cap deposed to move into the gap. The angular velocity imparted to the rotatable cap shaft is transmitted in a positive manner to the magnetized element through a servo feedback loop. The resultant angular velocity of tae cap is proportional to the acceleration of the housing in this manner and means may be used to measure the velocity and operate switches at a pre-set magnitude. To make the above-described dcvice sensitive to acceleration in only one direction the magnetized element forms the spinning inertia element of a free gyroscope, and the outer housing functions as a gimbal of a gyroscope.

  18. Functional annotation of the vlinc class of non-coding RNAs using systems biology approach

    PubMed Central

    Laurent, Georges St.; Vyatkin, Yuri; Antonets, Denis; Ri, Maxim; Qi, Yao; Saik, Olga; Shtokalo, Dmitry; de Hoon, Michiel J.L.; Kawaji, Hideya; Itoh, Masayoshi; Lassmann, Timo; Arner, Erik; Forrest, Alistair R.R.; Nicolas, Estelle; McCaffrey, Timothy A.; Carninci, Piero; Hayashizaki, Yoshihide; Wahlestedt, Claes; Kapranov, Philipp

    2016-01-01

    Functionality of the non-coding transcripts encoded by the human genome is the coveted goal of the modern genomics research. While commonly relied on the classical methods of forward genetics, integration of different genomics datasets in a global Systems Biology fashion presents a more productive avenue of achieving this very complex aim. Here we report application of a Systems Biology-based approach to dissect functionality of a newly identified vast class of very long intergenic non-coding (vlinc) RNAs. Using highly quantitative FANTOM5 CAGE dataset, we show that these RNAs could be grouped into 1542 novel human genes based on analysis of insulators that we show here indeed function as genomic barrier elements. We show that vlincRNAs genes likely function in cis to activate nearby genes. This effect while most pronounced in closely spaced vlincRNA–gene pairs can be detected over relatively large genomic distances. Furthermore, we identified 101 vlincRNA genes likely involved in early embryogenesis based on patterns of their expression and regulation. We also found another 109 such genes potentially involved in cellular functions also happening at early stages of development such as proliferation, migration and apoptosis. Overall, we show that Systems Biology-based methods have great promise for functional annotation of non-coding RNAs. PMID:27001520

  19. Recent advances in food biopeptides: production, biological functionalities and therapeutic applications.

    PubMed

    Saadi, Sami; Saari, Nazamid; Anwar, Farooq; Hamid, Azizah Abdul; Mohd Ghazali, Hasanah

    2015-01-01

    The growing momentum of several common life-style diseases such as myocardial infarction, cardiovascular disorders, stroke, hypertension, diabetes, and atherosclerosis has become a serious global concern. Recent developments in the field of proteomics offering promising solutions to solving such health problems stimulates the uses of biopeptides as one of the therapeutic agents to alleviate disease-related risk factors. Functional peptides are typically produced from protein via enzymatic hydrolysis under in vitro or in vivo conditions using different kinds of proteolytic enzymes. An array of biological activities, including antioxidative, antihypertensive, antidiabetic and immunomodulating has been ascribed to different types of biopeptides derived from various food sources. In fact, biopeptides are nutritionally and functionally important for regulating some physiological functions in the body; however, these are yet to be extensively addressed with regard to their production through advance strategies, mechanisms of action and multiple biological functionalities. This review mainly focuses on recent biotechnological advances that are being made in the field of production in addition to covering the mode of action and biological activities, medicinal health functions and therapeutic applications of biopeptides. State-of-the-art strategies that can ameliorate the efficacy, bioavailability, and functionality of biopeptides along with their future prospects are likewise discussed.

  20. Integration of phosphoproteomic, chemical, and biological strategies for the functional analysis of targeted protein phosphorylation.

    PubMed

    Guo, Mingquan; Huang, Bill X

    2013-02-01

    Reversible phosphorylation, tightly controlled by protein kinases and phosphatases, plays a central role in mediating biological processes, such as protein-protein interactions, subcellular translocation, and activation of cellular enzymes. MS-based phosphoproteomics has now allowed the detection and quantification of tens of thousands of phosphorylation sites from a typical biological sample in a single experiment, which has posed new challenges in functional analysis of each and every phosphorylation site on specific signaling phosphoproteins of interest. In this article, we review recent advances in the functional analysis of targeted phosphorylation carried out by various chemical and biological approaches in combination with the MS-based phosphoproteomics. This review focuses on three types of strategies, including forward functional analysis, defined for the result-driven phosphoproteomics efforts in determining the substrates of a specific protein kinase; reverse functional analysis, defined for tracking the kinase(s) for specific phosphosite(s) derived from the discovery-driven phosphoproteomics efforts; and MS-based analysis on the structure-function relationship of phosphoproteins. It is expected that this review will provide a state-of-the-art overview of functional analysis of site-specific phosphorylation and explore new perspectives and outline future challenges.

  1. Accelerating the development of transparent graphene electrodes through basic science driven chemical functionalization.

    SciTech Connect

    Chan, Calvin; Beechem, III, Thomas Edwin; Ohta, Taisuke; Brumbach, Michael T.; Wheeler, David Roger; Veneman, Alexander; Gearba, I. Raluca; Stevenson, Keith J.

    2013-09-01

    Chemical functionalization is required to adapt graphenes properties to many applications. However, most covalent functionalization schemes are spontaneous or defect driven and are not suitable for applications requiring directed assembly of molecules on graphene substrates. In this work, we demonstrated electrochemically driven covalent bonding of phenyl iodoniums onto epitaxial graphene. The amount of chemisorption was demonstrated by varying the duration of the electrochemical driving potential. Chemical, electronic, and defect states of phenyl-modified graphene were studied by photoemission spectroscopy, spatially resolved Raman spectroscopy, and water contact angle measurement. Covalent attachment rehybridized some of the delocalized graphene sp2 orbitals to localized sp3 states. Control over the relative spontaneity (reaction rate) of covalent graphene functionalization is an important first step to the practical realization of directed molecular assembly on graphene. More than 10 publications, conference presentations, and program highlights were produced (some invited), and follow-on funding was obtained to continue this work.

  2. PARPs and ADP-ribosylation: recent advances linking molecular functions to biological outcomes

    PubMed Central

    Gupte, Rebecca; Liu, Ziying; Kraus, W. Lee

    2017-01-01

    The discovery of poly(ADP-ribose) >50 years ago opened a new field, leading the way for the discovery of the poly(ADP-ribose) polymerase (PARP) family of enzymes and the ADP-ribosylation reactions that they catalyze. Although the field was initially focused primarily on the biochemistry and molecular biology of PARP-1 in DNA damage detection and repair, the mechanistic and functional understanding of the role of PARPs in different biological processes has grown considerably of late. This has been accompanied by a shift of focus from enzymology to a search for substrates as well as the first attempts to determine the functional consequences of site-specific ADP-ribosylation on those substrates. Supporting these advances is a host of methodological approaches from chemical biology, proteomics, genomics, cell biology, and genetics that have propelled new discoveries in the field. New findings on the diverse roles of PARPs in chromatin regulation, transcription, RNA biology, and DNA repair have been complemented by recent advances that link ADP-ribosylation to stress responses, metabolism, viral infections, and cancer. These studies have begun to reveal the promising ways in which PARPs may be targeted therapeutically for the treatment of disease. In this review, we discuss these topics and relate them to the future directions of the field. PMID:28202539

  3. PARPs and ADP-ribosylation: recent advances linking molecular functions to biological outcomes.

    PubMed

    Gupte, Rebecca; Liu, Ziying; Kraus, W Lee

    2017-01-15

    The discovery of poly(ADP-ribose) >50 years ago opened a new field, leading the way for the discovery of the poly(ADP-ribose) polymerase (PARP) family of enzymes and the ADP-ribosylation reactions that they catalyze. Although the field was initially focused primarily on the biochemistry and molecular biology of PARP-1 in DNA damage detection and repair, the mechanistic and functional understanding of the role of PARPs in different biological processes has grown considerably of late. This has been accompanied by a shift of focus from enzymology to a search for substrates as well as the first attempts to determine the functional consequences of site-specific ADP-ribosylation on those substrates. Supporting these advances is a host of methodological approaches from chemical biology, proteomics, genomics, cell biology, and genetics that have propelled new discoveries in the field. New findings on the diverse roles of PARPs in chromatin regulation, transcription, RNA biology, and DNA repair have been complemented by recent advances that link ADP-ribosylation to stress responses, metabolism, viral infections, and cancer. These studies have begun to reveal the promising ways in which PARPs may be targeted therapeutically for the treatment of disease. In this review, we discuss these topics and relate them to the future directions of the field. © 2017 Gupte et al.; Published by Cold Spring Harbor Laboratory Press.

  4. Accelerated Testing and Modeling of Potential-Induced Degradation as a Function of Temperature and Relative Humidity

    SciTech Connect

    Hacke, Peter; Spataru, Sergiu; Terwilliger, Kent; Perrin, Greg; Glick, Stephen; Kurtz, Sarah; Wohlgemuth, John

    2015-06-14

    An acceleration model based on the Peck equation was applied to power performance of crystalline silicon cell modules as a function of time and of temperature and humidity, the two main environmental stress factors that promote potential-induced degradation. This model was derived from module power degradation data obtained semi-continuously and statistically by in-situ dark current-voltage measurements in an environmental chamber. The modeling enables prediction of degradation rates and times as functions of temperature and humidity. Power degradation could be modeled linearly as a function of time to the second power; additionally, we found that coulombs transferred from the active cell circuit to ground during the stress test is approximately linear with time. Therefore, the power loss could be linearized as a function of coulombs squared. With this result, we observed that when the module face was completely grounded with a condensed phase conductor, leakage current exceeded the anticipated corresponding degradation rate relative to the other tests performed in damp heat.

  5. Cocaine Reduces Thymic Endocrine Function: Another Mechanism for Accelerated HIV Disease Progression

    PubMed Central

    Campa, Adriana; Smith, Sylvia; Huffman, Fatma; Newman, Fred; Baum, Marianna K.

    2011-01-01

    Abstract Thymulin is a thymic peptide important for the maturation and differentiation of immature thymocytes, which have been found to be depressed in patients with low-level CD4+ cell recovery despite viral control. Substance use is associated with faster progression of HIV disease, which has been ascribed to poor adherence to antiretroviral medication. Recent findings of an association between cocaine use and decline in CD4+ cell counts independent of antiretroviral adherence indicate alternative mechanisms for disease progression. We evaluated the relationship between thymulin activity, CD4+ and CD8+ cell counts and the CD4+/CD8+ ratio, and the covariate effects of substance use cross-sectionally in 80 HIV+ active substance users and over 12 months in 40 participants. Thymulin activity was analyzed in plasma using a modification of the sheep rosette bioassay. Thymulin activity was negatively associated with cocaine use (β = −0.908,95% CI: −1.704, −0.112; p = 0.026). Compared to those who do not use cocaine, cocaine users were 37% less likely to have detectable thymulin activity (RR = 0.634, 95% CI: 0.406, 0.989 p = 0.045) and were 75 times more likely to show a decrease in thymulin activity (OR = 74.7, 95% CI: 1.59, 3519.74; p = 0.028) over time. CD4+ cell count was positively associated with thymulin activity (β = 0.127, 95% CI: 0.048,0.205; p = 0.002), detectable thymulin activity was 2.32 times more likely in those with a CD4 cell count ≥200 cells/μl (RR = 2.324, 95% CI: 1.196, 4.513, p = 0.013), and those with an increase in CD4 cell counts were more likely to show an increase in thymulin activity (OR = 1.02, 95% CI: 1.00, 1.034; p = 0.041) over time. Thymulin activity is predictive of HIV disease progression and is depressed in cocaine users independent of antiretroviral treatment (ART) and HIV viral load. Understanding the mechanisms for accelerated HIV disease progression provides

  6. Cocaine reduces thymic endocrine function: another mechanism for accelerated HIV disease progression.

    PubMed

    Rafie, Carlin; Campa, Adriana; Smith, Sylvia; Huffman, Fatma; Newman, Fred; Baum, Marianna K

    2011-08-01

    Thymulin is a thymic peptide important for the maturation and differentiation of immature thymocytes, which have been found to be depressed in patients with low-level CD4(+) cell recovery despite viral control. Substance use is associated with faster progression of HIV disease, which has been ascribed to poor adherence to antiretroviral medication. Recent findings of an association between cocaine use and decline in CD4(+) cell counts independent of antiretroviral adherence indicate alternative mechanisms for disease progression. We evaluated the relationship between thymulin activity, CD4(+) and CD8(+) cell counts and the CD4(+)/CD8(+) ratio, and the covariate effects of substance use cross-sectionally in 80 HIV(+) active substance users and over 12 months in 40 participants. Thymulin activity was analyzed in plasma using a modification of the sheep rosette bioassay. Thymulin activity was negatively associated with cocaine use (β = -0.908,95% CI: -1.704, -0.112; p = 0.026). Compared to those who do not use cocaine, cocaine users were 37% less likely to have detectable thymulin activity (RR = 0.634, 95% CI: 0.406, 0.989 p = 0.045) and were 75 times more likely to show a decrease in thymulin activity (OR = 74.7, 95% CI: 1.59, 3519.74; p = 0.028) over time. CD4(+) cell count was positively associated with thymulin activity (β = 0.127, 95% CI: 0.048,0.205; p = 0.002), detectable thymulin activity was 2.32 times more likely in those with a CD4 cell count ≥200 cells/μl (RR = 2.324, 95% CI: 1.196, 4.513, p = 0.013), and those with an increase in CD4 cell counts were more likely to show an increase in thymulin activity (OR = 1.02, 95% CI: 1.00, 1.034; p = 0.041) over time. Thymulin activity is predictive of HIV disease progression and is depressed in cocaine users independent of antiretroviral treatment (ART) and HIV viral load. Understanding the mechanisms for accelerated HIV disease progression provides opportunities to find alternative strategies to counteract

  7. Pedagogical Design for a Cross-Functional Course in the Accelerated MBA Program

    ERIC Educational Resources Information Center

    Balasubramnian, Bhanu; Steigner, Tanja; Coulson, Kevin R.

    2011-01-01

    The sub-prime financial crisis exposed weaknesses in the financial risk management of several prominent firms. A deficient risk management is mainly attributed to the lack of integration of finance with other business disciplines. In this paper, we describe a tested implementation of a cross-functional project that improves students' understanding…

  8. Accelerated Functional Recovery after Skeletal Muscle Ischemia-reperfusion Injury using Freshly Isolated Bone Marrow Cells

    DTIC Science & Technology

    2014-01-03

    nerve function in diabetic neuropathy . PLoS One 2011;6(11):e27458. [22] Corona BT, Wenke JC, Walters TJ, et al. Intramuscular transplantation and...211. [29] Lin CD, Allori AC, Macklin JE, et al. Topical lineage negative progenitor cell therapy for diabetic wounds. Plast Reconstr Surg 2008;122(5

  9. Nucleic acid-programmed assemblies: translating instruction into function in chemical biology.

    PubMed

    Winssinger, Nicolas

    2013-01-01

    The predictability of nucleic acid hybridization offers an attractive platform to program the assembly of tagged ligands or reactants. Hybridization can be used to display multiple ligands in order to gain affinity and/or selectivity through the cooperative interaction of each ligand. Additionally, hybridization of tagged reagents increases their effective concentration and accelerates reactions. In both cases, an oligonucleotide directs an assembly to yield a functional output in the form of enhanced binding, inhibition, or reaction; for example, a reaction can be used to unmask a fluorophore or a bioactive molecule. This review provides an account of our research in this area as well as future directions.

  10. Use of coherent control methods through scattering biological tissue to achieve functional imaging

    PubMed Central

    Dela Cruz, Johanna M.; Pastirk, Igor; Comstock, Matthew; Lozovoy, Vadim V.; Dantus, Marcos

    2004-01-01

    We test whether coherent control methods based on ultrashort-pulse phase shaping can be applied when the laser light propagates through biological tissue. Our results demonstrate experimentally that the spectral-phase properties of shaped laser pulses optimized to achieve selective two-photon excitation survive as the laser pulses propagate through tissue. This observation is used to obtain functional images based on selective two-photon excitation of a pH-sensitive chromophore in a sample that is placed behind a slice of biological tissue. Our observation of coherent control through scattering tissue suggests possibilities in multiphoton-based imaging and photodynamic therapy. PMID:15569924

  11. [Research advance in the function of quorum sensing in the biological aggregates].

    PubMed

    Dai, Xin; Zhou, Jia-Heng; Zhu, Liang; Xu, Xiang-Yang

    2014-04-01

    Quorum sensing is a microbial phenomenon that microorganisms use signal molecules to perceive environmental conditions and regulate specific gene expressions. As the communication function of quorum sensing is increasingly highlighted in the microbial field, researches on quorum sensing in the formation process of biological aggregates (biofilm and granules) attract wide attentions. The paper reviewed autoinducers (AI) classification and the corresponding regulation methods in quorum sensing, and provided an up-to-date account on research progress of AIs regulating biological aggregates formation and structural stability. New territories and future of quorum sensing were also outlined.

  12. Averaged Propulsive Body Acceleration (APBA) Can Be Calculated from Biologging Tags That Incorporate Gyroscopes and Accelerometers to Estimate Swimming Speed, Hydrodynamic Drag and Energy Expenditure for Steller Sea Lions

    PubMed Central

    Trites, Andrew W.; Rosen, David A. S.; Potvin, Jean

    2016-01-01

    Forces due to propulsion should approximate forces due to hydrodynamic drag for animals horizontally swimming at a constant speed with negligible buoyancy forces. Propulsive forces should also correlate with energy expenditures associated with locomotion—an important cost of foraging. As such, biologging tags containing accelerometers are being used to generate proxies for animal energy expenditures despite being unable to distinguish rotational movements from linear movements. However, recent miniaturizations of gyroscopes offer the possibility of resolving this shortcoming and obtaining better estimates of body accelerations of swimming animals. We derived accelerations using gyroscope data for swimming Steller sea lions (Eumetopias jubatus), and determined how well the measured accelerations correlated with actual swimming speeds and with theoretical drag. We also compared dive averaged dynamic body acceleration estimates that incorporate gyroscope data, with the widely used Overall Dynamic Body Acceleration (ODBA) metric, which does not use gyroscope data. Four Steller sea lions equipped with biologging tags were trained to swim alongside a boat cruising at steady speeds in the range of 4 to 10 kph. At each speed, and for each dive, we computed a measure called Gyro-Informed Dynamic Acceleration (GIDA) using a method incorporating gyroscope data with accelerometer data. We derived a new metric—Averaged Propulsive Body Acceleration (APBA), which is the average gain in speed per flipper stroke divided by mean stroke cycle duration. Our results show that the gyro-based measure (APBA) is a better predictor of speed than ODBA. We also found that APBA can estimate average thrust production during a single stroke-glide cycle, and can be used to estimate energy expended during swimming. The gyroscope-derived methods we describe should be generally applicable in swimming animals where propulsive accelerations can be clearly identified in the signal—and they should

  13. Averaged Propulsive Body Acceleration (APBA) Can Be Calculated from Biologging Tags That Incorporate Gyroscopes and Accelerometers to Estimate Swimming Speed, Hydrodynamic Drag and Energy Expenditure for Steller Sea Lions.

    PubMed

    Ware, Colin; Trites, Andrew W; Rosen, David A S; Potvin, Jean

    2016-01-01

    Forces due to propulsion should approximate forces due to hydrodynamic drag for animals horizontally swimming at a constant speed with negligible buoyancy forces. Propulsive forces should also correlate with energy expenditures associated with locomotion-an important cost of foraging. As such, biologging tags containing accelerometers are being used to generate proxies for animal energy expenditures despite being unable to distinguish rotational movements from linear movements. However, recent miniaturizations of gyroscopes offer the possibility of resolving this shortcoming and obtaining better estimates of body accelerations of swimming animals. We derived accelerations using gyroscope data for swimming Steller sea lions (Eumetopias jubatus), and determined how well the measured accelerations correlated with actual swimming speeds and with theoretical drag. We also compared dive averaged dynamic body acceleration estimates that incorporate gyroscope data, with the widely used Overall Dynamic Body Acceleration (ODBA) metric, which does not use gyroscope data. Four Steller sea lions equipped with biologging tags were trained to swim alongside a boat cruising at steady speeds in the range of 4 to 10 kph. At each speed, and for each dive, we computed a measure called Gyro-Informed Dynamic Acceleration (GIDA) using a method incorporating gyroscope data with accelerometer data. We derived a new metric-Averaged Propulsive Body Acceleration (APBA), which is the average gain in speed per flipper stroke divided by mean stroke cycle duration. Our results show that the gyro-based measure (APBA) is a better predictor of speed than ODBA. We also found that APBA can estimate average thrust production during a single stroke-glide cycle, and can be used to estimate energy expended during swimming. The gyroscope-derived methods we describe should be generally applicable in swimming animals where propulsive accelerations can be clearly identified in the signal-and they should also

  14. Axon-Sorting Multifunctional Nerve Guides: Accelerating Restoration of Nerve Function

    DTIC Science & Technology

    2014-10-01

    In this project we will develop a new type of nerve guide that improves the rate of nerve regeneration by directing subsets of axons to the...multifunctional nerve guides that can sort a mixed population of regenerating axons into sensory and motor tributaries. By guiding axons to...appropriate pathways, this novel nerve guide will improve clinical outcomes by enhancing both regeneration speed and the functional specificity of end organ

  15. Asymmetric neighborhood functions accelerate ordering process of self-organizing maps

    SciTech Connect

    Ota, Kaiichiro; Aoki, Takaaki; Kurata, Koji; Aoyagi, Toshio

    2011-02-15

    A self-organizing map (SOM) algorithm can generate a topographic map from a high-dimensional stimulus space to a low-dimensional array of units. Because a topographic map preserves neighborhood relationships between the stimuli, the SOM can be applied to certain types of information processing such as data visualization. During the learning process, however, topological defects frequently emerge in the map. The presence of defects tends to drastically slow down the formation of a globally ordered topographic map. To remove such topological defects, it has been reported that an asymmetric neighborhood function is effective, but only in the simple case of mapping one-dimensional stimuli to a chain of units. In this paper, we demonstrate that even when high-dimensional stimuli are used, the asymmetric neighborhood function is effective for both artificial and real-world data. Our results suggest that applying the asymmetric neighborhood function to the SOM algorithm improves the reliability of the algorithm. In addition, it enables processing of complicated, high-dimensional data by using this algorithm.

  16. Asymmetric neighborhood functions accelerate ordering process of self-organizing maps

    NASA Astrophysics Data System (ADS)

    Ota, Kaiichiro; Aoki, Takaaki; Kurata, Koji; Aoyagi, Toshio

    2011-02-01

    A self-organizing map (SOM) algorithm can generate a topographic map from a high-dimensional stimulus space to a low-dimensional array of units. Because a topographic map preserves neighborhood relationships between the stimuli, the SOM can be applied to certain types of information processing such as data visualization. During the learning process, however, topological defects frequently emerge in the map. The presence of defects tends to drastically slow down the formation of a globally ordered topographic map. To remove such topological defects, it has been reported that an asymmetric neighborhood function is effective, but only in the simple case of mapping one-dimensional stimuli to a chain of units. In this paper, we demonstrate that even when high-dimensional stimuli are used, the asymmetric neighborhood function is effective for both artificial and real-world data. Our results suggest that applying the asymmetric neighborhood function to the SOM algorithm improves the reliability of the algorithm. In addition, it enables processing of complicated, high-dimensional data by using this algorithm.

  17. Adaptive diffusion kernel learning from biological networks for protein function prediction

    PubMed Central

    Sun, Liang; Ji, Shuiwang; Ye, Jieping

    2008-01-01

    Background Machine-learning tools have gained considerable attention during the last few years for analyzing biological networks for protein function prediction. Kernel methods are suitable for learning from graph-based data such as biological networks, as they only require the abstraction of the similarities between objects into the kernel matrix. One key issue in kernel methods is the selection of a good kernel function. Diffusion kernels, the discretization of the familiar Gaussian kernel of Euclidean space, are commonly used for graph-based data. Results In this paper, we address the issue of learning an optimal diffusion kernel, in the form of a convex combination of a set of pre-specified kernels constructed from biological networks, for protein function prediction. Most prior work on this kernel learning task focus on variants of the loss function based on Support Vector Machines (SVM). Their extensions to other loss functions such as the one based on Kullback-Leibler (KL) divergence, which is more suitable for mining biological networks, lead to expensive optimization problems. By exploiting the special structure of the diffusion kernel, we show that this KL divergence based kernel learning problem can be formulated as a simple optimization problem, which can then be solved efficiently. It is further extended to the multi-task case where we predict multiple functions of a protein simultaneously. We evaluate the efficiency and effectiveness of the proposed algorithms using two benchmark data sets. Conclusion Results show that the performance of linearly combined diffusion kernel is better than every single candidate diffusion kernel. When the number of tasks is large, the algorithms based on multiple tasks are favored due to their competitive recognition performance and small computational costs. PMID:18366736

  18. The Structure of a Gene Co-Expression Network Reveals Biological Functions Underlying eQTLs

    PubMed Central

    Villa-Vialaneix, Nathalie; Liaubet, Laurence; Laurent, Thibault; Cherel, Pierre; Gamot, Adrien; SanCristobal, Magali

    2013-01-01

    What are the commonalities between genes, whose expression level is partially controlled by eQTL, especially with regard to biological functions? Moreover, how are these genes related to a phenotype of interest? These issues are particularly difficult to address when the genome annotation is incomplete, as is the case for mammalian species. Moreover, the direct link between gene expression and a phenotype of interest may be weak, and thus difficult to handle. In this framework, the use of a co-expression network has proven useful: it is a robust approach for modeling a complex system of genetic regulations, and to infer knowledge for yet unknown genes. In this article, a case study was conducted with a mammalian species. It showed that the use of a co-expression network based on partial correlation, combined with a relevant clustering of nodes, leads to an enrichment of biological functions of around 83%. Moreover, the use of a spatial statistics approach allowed us to superimpose additional information related to a phenotype; this lead to highlighting specific genes or gene clusters that are related to the network structure and the phenotype. Three main results are worth noting: first, key genes were highlighted as a potential focus for forthcoming biological experiments; second, a set of biological functions, which support a list of genes under partial eQTL control, was set up by an overview of the global structure of the gene expression network; third, pH was found correlated with gene clusters, and then with related biological functions, as a result of a spatial analysis of the network topology. PMID:23577081

  19. The structure of a gene co-expression network reveals biological functions underlying eQTLs.

    PubMed

    Villa-Vialaneix, Nathalie; Liaubet, Laurence; Laurent, Thibault; Cherel, Pierre; Gamot, Adrien; SanCristobal, Magali

    2013-01-01

    What are the commonalities between genes, whose expression level is partially controlled by eQTL, especially with regard to biological functions? Moreover, how are these genes related to a phenotype of interest? These issues are particularly difficult to address when the genome annotation is incomplete, as is the case for mammalian species. Moreover, the direct link between gene expression and a phenotype of interest may be weak, and thus difficult to handle. In this framework, the use of a co-expression network has proven useful: it is a robust approach for modeling a complex system of genetic regulations, and to infer knowledge for yet unknown genes. In this article, a case study was conducted with a mammalian species. It showed that the use of a co-expression network based on partial correlation, combined with a relevant clustering of nodes, leads to an enrichment of biological functions of around 83%. Moreover, the use of a spatial statistics approach allowed us to superimpose additional information related to a phenotype; this lead to highlighting specific genes or gene clusters that are related to the network structure and the phenotype. Three main results are worth noting: first, key genes were highlighted as a potential focus for forthcoming biological experiments; second, a set of biological functions, which support a list of genes under partial eQTL control, was set up by an overview of the global structure of the gene expression network; third, pH was found correlated with gene clusters, and then with related biological functions, as a result of a spatial analysis of the network topology.

  20. Triphosphate Tunnel Metalloenzyme Function in Senescence Highlights a Biological Diversification of This Protein Superfamily.

    PubMed

    Ung, Huoi; Karia, Purva; Ebine, Kazuo; Ueda, Takashi; Yoshioka, Keiko; Moeder, Wolfgang

    2017-09-01

    The triphosphate tunnel metalloenzyme (TTM) superfamily comprises a group of enzymes that hydrolyze organophosphate substrates. They exist in all domains of life, yet the biological role of most family members is unclear. Arabidopsis (Arabidopsis thaliana) encodes three TTM genes. We have previously reported that AtTTM2 displays pyrophosphatase activity and is involved in pathogen resistance. Here, we report the biochemical activity and biological function of AtTTM1 and diversification of the biological roles between AtTTM1 and 2 Biochemical analyses revealed that AtTTM1 displays pyrophosphatase activity similar to AtTTM2, making them the only TTMs characterized so far to act on a diphosphate substrate. However, knockout mutant analysis showed that AtTTM1 is not involved in pathogen resistance but rather in leaf senescence. AtTTM1 is transcriptionally up-regulated during leaf senescence, and knockout mutants of AtTTM1 exhibit delayed dark-induced and natural senescence. The double mutant of AtTTM1 and AtTTM2 did not show synergistic effects, further indicating the diversification of their biological function. However, promoter swap analyses revealed that they functionally can complement each other, and confocal microscopy revealed that both proteins are tail-anchored proteins that localize to the mitochondrial outer membrane. Additionally, transient overexpression of either gene in Nicotiana benthamiana induced senescence-like cell death upon dark treatment. Taken together, we show that two TTMs display the same biochemical properties but distinct biological functions that are governed by their transcriptional regulation. Moreover, this work reveals a possible connection of immunity-related programmed cell death and senescence through novel mitochondrial tail-anchored proteins. © 2017 American Society of Plant Biologists. All Rights Reserved.

  1. BABELOMICS: a systems biology perspective in the functional annotation of genome-scale experiments

    PubMed Central

    Al-Shahrour, Fátima; Minguez, Pablo; Tárraga, Joaquín; Montaner, David; Alloza, Eva; Vaquerizas, Juan M.; Conde, Lucía; Blaschke, Christian; Vera, Javier; Dopazo, Joaquín

    2006-01-01

    We present a new version of Babelomics, a complete suite of web tools for functional analysis of genome-scale experiments, with new and improved tools. New functionally relevant terms have been included such as CisRed motifs or bioentities obtained by text-mining procedures. An improved indexing has considerably speeded up several of the modules. An improved version of the FatiScan method for studying the coordinate behaviour of groups of functionally related genes is presented, along with a similar tool, the Gene Set Enrichment Analysis. Babelomics is now more oriented to test systems biology inspired hypotheses. Babelomics can be found at . PMID:16845052

  2. Disorder transitions and conformational diversity cooperatively modulate biological function in proteins

    PubMed Central

    Zea, Diego Javier; Monzon, Alexander Miguel; Gonzalez, Claudia; Fornasari, María Silvina; Tosatto, Silvio C. E.

    2016-01-01

    Abstract Structural differences between conformers sustain protein biological function. Here, we studied in a large dataset of 745 intrinsically disordered proteins, how ordered‐disordered transitions modulate structural differences between conformers as derived from crystallographic data. We found that almost 50% of the proteins studied show no transitions and have low conformational diversity while the rest show transitions and a higher conformational diversity. In this last subset, 60% of the proteins become more ordered after ligand binding, while 40% more disordered. As protein conformational diversity is inherently connected with protein function our analysis suggests differences in structure‐function relationships related to order‐disorder transitions. PMID:27038125

  3. Closure, function, emergence, semiosis, and life: the same idea? Reflections on the concrete and the abstract in theoretical biology.

    PubMed

    Emmeche, C

    2000-01-01

    In this note epistemological problems in general theories about living systems are considered; in particular, the question of hidden connections between different areas of experience, such as folk biology and scientific biology, and hidden connections between central concepts of theoretical biology, such as function, semiosis, closure, and life.

  4. Can Accelerators Accelerate Learning?

    NASA Astrophysics Data System (ADS)

    Santos, A. C. F.; Fonseca, P.; Coelho, L. F. S.

    2009-03-01

    The 'Young Talented' education program developed by the Brazilian State Funding Agency (FAPERJ) [1] makes it possible for high-schools students from public high schools to perform activities in scientific laboratories. In the Atomic and Molecular Physics Laboratory at Federal University of Rio de Janeiro (UFRJ), the students are confronted with modern research tools like the 1.7 MV ion accelerator. Being a user-friendly machine, the accelerator is easily manageable by the students, who can perform simple hands-on activities, stimulating interest in physics, and getting the students close to modern laboratory techniques.

  5. Can Accelerators Accelerate Learning?

    SciTech Connect

    Santos, A. C. F.; Fonseca, P.; Coelho, L. F. S.

    2009-03-10

    The 'Young Talented' education program developed by the Brazilian State Funding Agency (FAPERJ)[1] makes it possible for high-schools students from public high schools to perform activities in scientific laboratories. In the Atomic and Molecular Physics Laboratory at Federal University of Rio de Janeiro (UFRJ), the students are confronted with modern research tools like the 1.7 MV ion accelerator. Being a user-friendly machine, the accelerator is easily manageable by the students, who can perform simple hands-on activities, stimulating interest in physics, and getting the students close to modern laboratory techniques.

  6. PARTICLE ACCELERATOR

    DOEpatents

    Teng, L.C.

    1960-01-19

    ABS>A combination of two accelerators, a cyclotron and a ring-shaped accelerator which has a portion disposed tangentially to the cyclotron, is described. Means are provided to transfer particles from the cyclotron to the ring accelerator including a magnetic deflector within the cyclotron, a magnetic shield between the ring accelerator and the cyclotron, and a magnetic inflector within the ring accelerator.