Introduction

NASA Astrophysics Data System (ADS)

Assmann, R. W.; Ferrario, M.

2016-09-01

Particle accelerators are a field of continuing and growing success. Today about 30,000 accelerators are operated with various types of particles, including electrons, positrons, protons, neutrinos and various kinds of ions. These particles are used for the investigation of fundamental particles and forces in our universe. In parallel a fast growing field of accelerator-based photon science has developed since the 1970"s. Modern particle beams produce unique photon pulses that are used in ground-breaking studies on fast processes in chemistry and biology, on structures of viruses and bacteria, on the phenomenon of multi-resistivity to medication, on the functioning of photo-synthesis at the electronic level and on other important challenges for human mankind. Last not least, numerous particle accelerators are being used every day for industrial and medical applications, including the irradiation of tumors in human patients.

Protein aggregates as depots for the release of biologically active compounds.

PubMed

Artemova, Natalya V; Kasakov, Alexei S; Bumagina, Zoya M; Lyutova, Elena M; Gurvits, Bella Ya

2008-12-12

Protein misfolding and aggregation is one of the most serious problems in cell biology, molecular medicine, and biotechnology. Misfolded proteins interact with each other or with other proteins in non-productive or damaging ways. However, a new paradigm arises that protein aggregation may be exploited by nature to perform specific functions in different biological contexts. From this consideration, acceleration of stress-induced protein aggregation triggered by any factor resulting in the formation of soluble aggregates may have paradoxical positive consequences. Here, we suggest that amorphous aggregates can act as a source for the release of biologically active proteins after removal of stress conditions. To address this concept, we investigated the kinetics of thermal aggregation in vitro of yeast alcohol dehydrogenase (ADH) as a model substrate in the presence of two amphiphilic peptides: Arg-Phe or Ala-Phe-Lys. Using dynamic light scattering (DLS) and turbidimetry, we have demonstrated that under mild stress conditions the concentration-dependent acceleration of ADH aggregation by these peptides results in formation of large but soluble complexes of proteins prone to refolding.

Microfluidic Technologies for Synthetic Biology

PubMed Central

Vinuselvi, Parisutham; Park, Seongyong; Kim, Minseok; Park, Jung Min; Kim, Taesung; Lee, Sung Kuk

2011-01-01

Microfluidic technologies have shown powerful abilities for reducing cost, time, and labor, and at the same time, for increasing accuracy, throughput, and performance in the analysis of biological and biochemical samples compared with the conventional, macroscale instruments. Synthetic biology is an emerging field of biology and has drawn much attraction due to its potential to create novel, functional biological parts and systems for special purposes. Since it is believed that the development of synthetic biology can be accelerated through the use of microfluidic technology, in this review work we focus our discussion on the latest microfluidic technologies that can provide unprecedented means in synthetic biology for dynamic profiling of gene expression/regulation with high resolution, highly sensitive on-chip and off-chip detection of metabolites, and whole-cell analysis. PMID:21747695

Rational Design of an Ultrasensitive Quorum-Sensing Switch.

PubMed

Zeng, Weiqian; Du, Pei; Lou, Qiuli; Wu, Lili; Zhang, Haoqian M; Lou, Chunbo; Wang, Hongli; Ouyang, Qi

2017-08-18

One of the purposes of synthetic biology is to develop rational methods that accelerate the design of genetic circuits, saving time and effort spent on experiments and providing reliably predictable circuit performance. We applied a reverse engineering approach to design an ultrasensitive transcriptional quorum-sensing switch. We want to explore how systems biology can guide synthetic biology in the choice of specific DNA sequences and their regulatory relations to achieve a targeted function. The workflow comprises network enumeration that achieves the target function robustly, experimental restriction of the obtained candidate networks, global parameter optimization via mathematical analysis, selection and engineering of parts based on these calculations, and finally, circuit construction based on the principles of standardization and modularization. The performance of realized quorum-sensing switches was in good qualitative agreement with the computational predictions. This study provides practical principles for the rational design of genetic circuits with targeted functions.

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.

Neurotrophin-3 accelerates wound healing in diabetic mice by promoting a paracrine response in mesenchymal stem cells.

PubMed

Shen, Lei; Zeng, Wen; Wu, Yang-Xiao; Hou, Chun-Li; Chen, Wen; Yang, Ming-Can; Li, Li; Zhang, Ya-Fang; Zhu, Chu-Hong

2013-01-01

Angiogenesis is a major obstacle for wound healing in patients with diabetic foot wounds. Mesenchymal stem cells (MSCs) have an important function in wound repair, and neurotrophin-3 (NT-3) can promote nerve regeneration and angiogenesis. We investigated the effect of NT-3 on accelerating wound healing in the diabetic foot by improving human bone marrow MSC (hMSC) activation. In vitro, NT-3 significantly promoted VEGF, NGF, and BDNF secretion in hMSCs. NT-3 improved activation of the hMSC conditioned medium, promoted human umbilical vein endothelial cell (HUVEC) proliferation and migration, and significantly improved the closure rate of HUVEC scratches. In addition, we produced nanofiber mesh biological tissue materials through the electrospinning technique using polylactic acid, mixed silk, and collagen. The hMSCs stimulated by NT-3 were implanted into the material. Compared with the control group, the NT-3-stimulated hMSCs in the biological tissue material significantly promoted angiogenesis in the feet of diabetic C57BL/6J mice and accelerated diabetic foot wound healing. These results suggest that NT-3 significantly promotes hMSC secretion of VEGF, NGF, and other vasoactive factors and that it accelerates wound healing by inducing angiogenesis through improved activation of vascular endothelial cells. The hMSCs stimulated by NT-3 can produce materials that accelerate wound healing in the diabetic foot and other ischemic ulcers.

Small-scale laser based electron accelerators for biology and medicine: a comparative study of the biological effectiveness

NASA Astrophysics Data System (ADS)

Labate, Luca; Andreassi, Maria Grazia; Baffigi, Federica; Basta, Giuseppina; Bizzarri, Ranieri; Borghini, Andrea; Candiano, Giuliana C.; Casarino, Carlo; Cresci, Monica; Di Martino, Fabio; Fulgentini, Lorenzo; Ghetti, Francesco; Gilardi, Maria Carla; Giulietti, Antonio; Köster, Petra; Lenci, Francesco; Levato, Tadzio; Oishi, Yuji; Russo, Giorgio; Sgarbossa, Antonella; Traino, Claudio; Gizzi, Leonida A.

2013-05-01

Laser-driven electron accelerators based on the Laser Wakefield Acceleration process has entered a mature phase to be considered as alternative devices to conventional radiofrequency linear accelerators used in medical applications. Before entering the medical practice, however, deep studies of the radiobiological effects of such short bunches as the ones produced by laser-driven accelerators have to be performed. Here we report on the setup, characterization and first test of a small-scale laser accelerator for radiobiology experiments. A brief description of the experimental setup will be given at first, followed by an overview of the electron bunch characterization, in particular in terms of dose delivered to the samples. Finally, the first results from the irradiation of biological samples will be briefly discussed.

Biological age and tempos of aging in women over 60 in connection with their morphofunctional characteristics

PubMed Central

2014-01-01

Background The study of aging processes and the changes in morphological, physiological, and functional characteristics that are associated with aging is of great interest not only for researchers, but also for the general public. The aim of the present paper is to study the biological age and tempos of aging in women older than 60 years, including long-lived females (over 90-years-old), and their associations with morphofunctional characteristics. Results Somatic traits, body mass components, and functional characteristics were investigated in 119 elderly (between 60 and 74-years-old) and long-lived (over 90-years-old) women in Tiraspol. With the special PC software ‘Diagnostics of Aging: BioAge’ (National Gerontological Center, Moscow, Russia) the biological age and tempos of aging were evaluated in the study participants. The results show close connections between morphofunctional changes, particularly in body mass components, and biological age. The software demonstrated its validity in the estimation of biological age in the group of elderly women. In the homogenous (according to their chronological age) group of women, three subgroups were separated with different tempos of aging: those with lower rates of aging (biological age less than chronological age by two years or more); those consistent with their chronological age, and those with accelerated tempos of aging (biological age higher than chronological age by two years or more). Conclusions Morphofunctional characteristics in the studied groups of women demonstrate the trends of age-involutive changes which can be traced through all groups, from those with slow rates of aging, to those with average rates, to those with accelerated tempos of aging, and finally in long-lived women. The results of comparative analysis show that women with accelerated aging are characterized with such traits as lower skeletal muscle mass, lower hand grip strength, and higher metabolic rate. Canonical discriminant analysis revealed a number of morphofunctional characteristics which differentiate the early-aging women from women with average rates of aging: higher BMI values, excessive fat mass, lower skeletal muscle mass and low values of hand grip strength. Thus the presence of such characteristics in elderly women can be considered as additional risk factor towards the early onset of the aging process. PMID:24887211

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.

Multi-walled carbon nanotubes and metallic nanoparticles and their application in biomedicine.

PubMed

Rojas-Chapana, Jose A; Giersig, Michael

2006-02-01

Interdisciplinary research has become a matter of paramount importance for novel applications of nanomaterials in biology and medicine. As such, many disciplines-physics, chemistry, microbiology, cell biology, and material science-all contribute to the design, synthesis and fabrication of functional and biocompatible devices at the nanometer scale. Since the most areas of cell biology and biomedicine deal with functional entities such as DNA and proteins, mimicry of these structures and function in the nanosize range offers exciting opportunities for the development of biosensors, biochips, and bioplatforms. In this report we highlight the potential benefits and challenges that arise in the manufacture of biocompatible nanoparticles and nano-networks that can be coupled with biological objects. Among the challenges facing us are those concerned with making the necessary advances in enabling affordability, innovation, and quality of manufactured nanodevices for rapid progress in the emerging field of bio-nanotechnology. The convergence of nanotechnology and biomedicine makes nanoscale research highly promising for new discoveries that can cost-effectively accelerate progress in moving from basic research to practical prototypes and products.

FPGA acceleration of rigid-molecule docking codes

PubMed Central

Sukhwani, B.; Herbordt, M.C.

2011-01-01

Modelling the interactions of biological molecules, or docking, is critical both to understanding basic life processes and to designing new drugs. The field programmable gate array (FPGA) based acceleration of a recently developed, complex, production docking code is described. The authors found that it is necessary to extend their previous three-dimensional (3D) correlation structure in several ways, most significantly to support simultaneous computation of several correlation functions. The result for small-molecule docking is a 100-fold speed-up of a section of the code that represents over 95% of the original run-time. An additional 2% is accelerated through a previously described method, yielding a total acceleration of 36× over a single core and 10× over a quad-core. This approach is found to be an ideal complement to graphics processing unit (GPU) based docking, which excels in the protein–protein domain. PMID:21857870

Genome-Wide Identification of Regulatory Sequences Undergoing Accelerated Evolution in the Human Genome.

PubMed

Dong, Xinran; Wang, Xiao; Zhang, Feng; Tian, Weidong

2016-10-01

Accelerated evolution of regulatory sequence can alter the expression pattern of target genes, and cause phenotypic changes. In this study, we used DNase I hypersensitive sites (DHSs) to annotate putative regulatory sequences in the human genome, and conducted a genome-wide analysis of the effects of accelerated evolution on regulatory sequences. Working under the assumption that local ancient repeat elements of DHSs are under neutral evolution, we discovered that ∼0.44% of DHSs are under accelerated evolution (ace-DHSs). We found that ace-DHSs tend to be more active than background DHSs, and are strongly associated with epigenetic marks of active transcription. The target genes of ace-DHSs are significantly enriched in neuron-related functions, and their expression levels are positively selected in the human brain. Thus, these lines of evidences strongly suggest that accelerated evolution on regulatory sequences plays important role in the evolution of human-specific phenotypes. © The Author 2016. Published by Oxford University Press on behalf of the Society for Molecular Biology and Evolution.

Accelerating the design of biomimetic materials by integrating RNA-seq with proteomics and materials science.

PubMed

Guerette, Paul A; Hoon, Shawn; Seow, Yiqi; Raida, Manfred; Masic, Admir; Wong, Fong T; Ho, Vincent H B; Kong, Kiat Whye; Demirel, Melik C; Pena-Francesch, Abdon; Amini, Shahrouz; Tay, Gavin Z; Ding, Dawei; Miserez, Ali

2013-10-01

Efforts to engineer new materials inspired by biological structures are hampered by the lack of genomic data from many model organisms studied in biomimetic research. Here we show that biomimetic engineering can be accelerated by integrating high-throughput RNA-seq with proteomics and advanced materials characterization. This approach can be applied to a broad range of systems, as we illustrate by investigating diverse high-performance biological materials involved in embryo protection, adhesion and predation. In one example, we rapidly engineer recombinant squid sucker ring teeth proteins into a range of structural and functional materials, including nanopatterned surfaces and photo-cross-linked films that exceed the mechanical properties of most natural and synthetic polymers. Integrating RNA-seq with proteomics and materials science facilitates the molecular characterization of natural materials and the effective translation of their molecular designs into a wide range of bio-inspired materials.

Toward Engineering Synthetic Microbial Metabolism

PubMed Central

McArthur, George H.; Fong, Stephen S.

2010-01-01

The generation of well-characterized parts and the formulation of biological design principles in synthetic biology are laying the foundation for more complex and advanced microbial metabolic engineering. Improvements in de novo DNA synthesis and codon-optimization alone are already contributing to the manufacturing of pathway enzymes with improved or novel function. Further development of analytical and computer-aided design tools should accelerate the forward engineering of precisely regulated synthetic pathways by providing a standard framework for the predictable design of biological systems from well-characterized parts. In this review we discuss the current state of synthetic biology within a four-stage framework (design, modeling, synthesis, analysis) and highlight areas requiring further advancement to facilitate true engineering of synthetic microbial metabolism. PMID:20037734

MeSH-informed enrichment analysis and MeSH-guided semantic similarity among functional terms and gene products in chicken

USDA-ARS?s Scientific Manuscript database

Such Biomedical vocabularies and ontologies aid in recapitulating biological knowledge. The annotation of gene products is mainly accelerated by Gene Ontology (GO) and more recently by Medical Subject Headings (MeSH). MeSH is the National Library of Medicine's controlled vocabulary and it is making ...

Multi-scale Functional and Molecular Photoacoustic Tomography

PubMed Central

Yao, Junjie; Xia, Jun; Wang, Lihong V.

2015-01-01

Photoacoustic tomography (PAT) combines rich optical absorption contrast with the high spatial resolution of ultrasound at depths in tissue. The high scalability of PAT has enabled anatomical imaging of biological structures ranging from organelles to organs. The inherent functional and molecular imaging capabilities of PAT have further allowed it to measure important physiological parameters and track critical cellular activities. Integration of PAT with other imaging technologies provides complementary capabilities and can potentially accelerate the clinical translation of PAT. PMID:25933617

Selenocysteine in thiol/disulfide-like exchange reactions.

PubMed

Hondal, Robert J; Marino, Stefano M; Gladyshev, Vadim N

2013-05-01

Among trace elements used as cofactors in enzymes, selenium is unique in that it is incorporated into proteins co-translationally in the form of an amino acid, selenocysteine (Sec). Sec differs from cysteine (Cys) by only one atom (selenium versus sulfur), yet this switch dramatically influences important aspects of enzyme reactivity. The main focus of this review is an updated and critical discussion on how Sec might be used to accelerate thiol/disulfide-like exchange reactions in natural selenoenzymes, compared with their Cys-containing homologs. We discuss in detail three major aspects associated with thiol/disulfide exchange reactions: (i) nucleophilicity of the attacking thiolate (or selenolate); (ii) electrophilicity of the center sulfur (or selenium) atom; and (iii) stability of the leaving group (sulfur or selenium). In all these cases, we analyze the benefits that selenium might provide in these types of reactions. It is the biological thiol oxidoreductase-like function that benefits from the use of Sec, since Sec functions to chemically accelerate the rate of these reactions. We review various hypotheses that could help explain why Sec is used in enzymes, particularly with regard to competitive chemical advantages provided by the presence of the selenium atom in enzymes. Ultimately, these chemical advantages must be connected to biological functions of Sec.

Radiation effects in Caenorhabditis elegans - Mutagenesis by high and low LET ionizing radiation

NASA Technical Reports Server (NTRS)

Nelson, Gregory A.; Schubert, Wayne W.; Marshall, Tamara M.; Benton, Eric R.; Benton, Eugene V.

1989-01-01

The nematode C. elegans was used to measure the effectiveness of high-energy ionized particles in the induction of three types of genetic lesions. Recessive lethal mutations in a 40-map unit autosomal region, sterility, and X-chromosome nondisjunction or damage were investigated. Induction rates were measured as a function of linear energy transfer, LET(infinity), for nine ions of atomic nunmber 1-57 accelerated at the BEVALAC accelerator. Linear kinetics were observed for all three types of lesions within the dose/fluence ranges tested and were found to vary strongly as a function of particle LET(infinity). Relative biological effectiveness (RBE) values of up to 4.2 were measured, and action cross sections were calculated and compared to mutagenic responses in other systems.

Ion beams provided by small accelerators for material synthesis and characterization

NASA Astrophysics Data System (ADS)

Mackova, Anna; Havranek, Vladimir

2017-06-01

The compact, multipurpose electrostatic tandem accelerators are extensively used for production of ion beams with energies in the range from 400 keV to 24 MeV of almost all elements of the periodic system for the trace element analysis by means of nuclear analytical methods. The ion beams produced by small accelerators have a broad application, mainly for material characterization (Rutherford Back-Scattering spectrometry, Particle Induced X ray Emission analysis, Nuclear Reaction Analysis and Ion-Microprobe with 1 μm lateral resolution among others) and for high-energy implantation. Material research belongs to traditionally progressive fields of technology. Due to the continuous miniaturization, the underlying structures are far beyond the analytical limits of the most conventional methods. Ion Beam Analysis (IBA) techniques provide this possibility as they use probes of similar or much smaller dimensions (particles, radiation). Ion beams can be used for the synthesis of new progressive functional nanomaterials for optics, electronics and other applications. Ion beams are extensively used in studies of the fundamental energetic ion interaction with matter as well as in the novel nanostructure synthesis using ion beam irradiation in various amorphous and crystalline materials in order to get structures with extraordinary functional properties. IBA methods serve for investigation of materials coming from material research, industry, micro- and nano-technology, electronics, optics and laser technology, chemical, biological and environmental investigation in general. Main research directions in laboratories employing small accelerators are also the preparation and characterization of micro- and nano-structured materials which are of interest for basic and oriented research in material science, and various studies of biological, geological, environmental and cultural heritage artefacts are provided too.

Systems Proteomics for Translational Network Medicine

PubMed Central

Arrell, D. Kent; Terzic, Andre

2012-01-01

Universal principles underlying network science, and their ever-increasing applications in biomedicine, underscore the unprecedented capacity of systems biology based strategies to synthesize and resolve massive high throughput generated datasets. Enabling previously unattainable comprehension of biological complexity, systems approaches have accelerated progress in elucidating disease prediction, progression, and outcome. Applied to the spectrum of states spanning health and disease, network proteomics establishes a collation, integration, and prioritization algorithm to guide mapping and decoding of proteome landscapes from large-scale raw data. Providing unparalleled deconvolution of protein lists into global interactomes, integrative systems proteomics enables objective, multi-modal interpretation at molecular, pathway, and network scales, merging individual molecular components, their plurality of interactions, and functional contributions for systems comprehension. As such, network systems approaches are increasingly exploited for objective interpretation of cardiovascular proteomics studies. Here, we highlight network systems proteomic analysis pipelines for integration and biological interpretation through protein cartography, ontological categorization, pathway and functional enrichment and complex network analysis. PMID:22896016

Free-falling Crystals: Biological Macromolecular Crystal Growth Studies in Low Earth Orbit

NASA Technical Reports Server (NTRS)

Judge, Russell A.; Snell, E. H.; Pusey, M. L.; Whitaker, Ann F. (Technical Monitor)

2001-01-01

Spacecraft orbiting the earth experience a reduced acceleration environment due to being in a state of continuous free-fall. This state colloquially termed microgravity, has produced improved X-ray diffraction quality crystals of biological macromolecules. Improvements in X-ray diffraction resolution (detail) or signal to noise, provide greater detail in the three-dimensional molecular structure providing information about the molecule, how it works, how to improve its function or how to impede it. Greater molecular detail obtained by crystallization in microgravity, has important implications for structural biology. In this article we examine the theories behind macromolecule crystal quality improvement in microgravity using results obtained from studies with the model protein, chicken egg white lysozyme.

Guidelines for investigating causality of sequence variants in human disease

PubMed Central

MacArthur, D. G.; Manolio, T. A.; Dimmock, D. P.; Rehm, H. L.; Shendure, J.; Abecasis, G. R.; Adams, D. R.; Altman, R. B.; Antonarakis, S. E.; Ashley, E. A.; Barrett, J. C.; Biesecker, L. G.; Conrad, D. F.; Cooper, G. M.; Cox, N. J.; Daly, M. J.; Gerstein, M. B.; Goldstein, D. B.; Hirschhorn, J. N.; Leal, S. M.; Pennacchio, L. A.; Stamatoyannopoulos, J. A.; Sunyaev, S. R.; Valle, D.; Voight, B. F.; Winckler, W.; Gunter, C.

2014-01-01

The discovery of rare genetic variants is accelerating, and clear guidelines for distinguishing disease-causing sequence variants from the many potentially functional variants present in any human genome are urgently needed. Without rigorous standards we risk an acceleration of false-positive reports of causality, which would impede the translation of genomic research findings into the clinical diagnostic setting and hinder biological understanding of disease. Here we discuss the key challenges of assessing sequence variants in human disease, integrating both gene-level and variant-level support for causality. We propose guidelines for summarizing confidence in variant pathogenicity and highlight several areas that require further resource development. PMID:24759409

Guidelines for investigating causality of sequence variants in human disease.

PubMed

MacArthur, D G; Manolio, T A; Dimmock, D P; Rehm, H L; Shendure, J; Abecasis, G R; Adams, D R; Altman, R B; Antonarakis, S E; Ashley, E A; Barrett, J C; Biesecker, L G; Conrad, D F; Cooper, G M; Cox, N J; Daly, M J; Gerstein, M B; Goldstein, D B; Hirschhorn, J N; Leal, S M; Pennacchio, L A; Stamatoyannopoulos, J A; Sunyaev, S R; Valle, D; Voight, B F; Winckler, W; Gunter, C

2014-04-24

The discovery of rare genetic variants is accelerating, and clear guidelines for distinguishing disease-causing sequence variants from the many potentially functional variants present in any human genome are urgently needed. Without rigorous standards we risk an acceleration of false-positive reports of causality, which would impede the translation of genomic research findings into the clinical diagnostic setting and hinder biological understanding of disease. Here we discuss the key challenges of assessing sequence variants in human disease, integrating both gene-level and variant-level support for causality. We propose guidelines for summarizing confidence in variant pathogenicity and highlight several areas that require further resource development.

Testing the hypothesis of accelerated cerebral white matter aging in schizophrenia and major depression.

PubMed

Kochunov, Peter; Glahn, David C; Rowland, Laura M; Olvera, Rene L; Winkler, Anderson; Yang, Yi-Hong; Sampath, Hemalatha; Carpenter, Will T; Duggirala, Ravindranath; Curran, Joanne; Blangero, John; Hong, L Elliot

2013-03-01

Elevated rate of aging-related biological and functional decline, termed "accelerated aging," is reported in patients with schizophrenia (SCZ) and major depressive disorder (MDD). We used diffusion tensor imaging derived fractional anisotropy (FA) as a biomarker of aging-related decline in white matter (WM) integrity to test the hypotheses of accelerated aging in SCZ and MDD. The SCZ cohort comprised 58 SCZ patients and 60 controls (aged 20-60 years). The MDD cohort comprised 136 MDD patients and 351 controls (aged 20-79 years). The main outcome measures were the diagnosis-by-age interaction on whole-brain-averaged WM FA values and FA values from 12 major WM tracts. Diagnosis-by-age interaction for the whole-brain average FA was significant for the SCZ (p = .04) but not the MDD (p = .80) cohort. Diagnosis-by-age interaction was nominally significant (p<.05) for five WM tracts for SCZ and for none of the tracts in the MDD cohort. Tract-specific heterochronicity of the onset of age-related decline in SCZ demonstrated strong negative correlations with the age-of-peak myelination and the rates of age-related decline obtained from normative sample (r =-.61 and-.80, p<.05, respectively). No such trends existed for MDD cohort. Cerebral WM showed accelerated aging in SCZ but not in MDD, suggesting some difference in the pathophysiology underlying their WM aging changes. Tract-specific heterochronicity of WM development modulated presentation of accelerated aging in SCZ: WM tracts that matured later in life appeared more sensitive to the pathophysiology of SCZ and demonstrated more susceptibility to disorder-related accelerated decline in FA values with age. This trend was not observed in MDD cohort. Copyright © 2013 Society of Biological Psychiatry. Published by Elsevier Inc. All rights reserved.

Second International Conference on Accelerating Biopharmaceutical Development

PubMed Central

2009-01-01

The Second International Conference on Accelerating Biopharmaceutical Development was held in Coronado, California. The meeting was organized by the Society for Biological Engineering (SBE) and the American Institute of Chemical Engineers (AIChE); SBE is a technological community of the AIChE. Bob Adamson (Wyeth) and Chuck Goochee (Centocor) were co-chairs of the event, which had the theme “Delivering cost-effective, robust processes and methods quickly and efficiently.” The first day focused on emerging disruptive technologies and cutting-edge analytical techniques. Day two featured presentations on accelerated cell culture process development, critical quality attributes, specifications and comparability, and high throughput protein formulation development. The final day was dedicated to discussion of technology options and new analysis methods provided by emerging disruptive technologies; functional interaction, integration and synergy in platform development; and rapid and economic purification process development. PMID:20065637

Selenocysteine in Thiol/Disulfide-Like Exchange Reactions

PubMed Central

Marino, Stefano M.

2013-01-01

Abstract Significance: Among trace elements used as cofactors in enzymes, selenium is unique in that it is incorporated into proteins co-translationally in the form of an amino acid, selenocysteine (Sec). Sec differs from cysteine (Cys) by only one atom (selenium versus sulfur), yet this switch dramatically influences important aspects of enzyme reactivity. Recent Advances: The main focus of this review is an updated and critical discussion on how Sec might be used to accelerate thiol/disulfide-like exchange reactions in natural selenoenzymes, compared with their Cys-containing homologs. Critical Issues: We discuss in detail three major aspects associated with thiol/disulfide exchange reactions: (i) nucleophilicity of the attacking thiolate (or selenolate); (ii) electrophilicity of the center sulfur (or selenium) atom; and (iii) stability of the leaving group (sulfur or selenium). In all these cases, we analyze the benefits that selenium might provide in these types of reactions. Future Directions: It is the biological thiol oxidoreductase-like function that benefits from the use of Sec, since Sec functions to chemically accelerate the rate of these reactions. We review various hypotheses that could help explain why Sec is used in enzymes, particularly with regard to competitive chemical advantages provided by the presence of the selenium atom in enzymes. Ultimately, these chemical advantages must be connected to biological functions of Sec. Antioxid. Redox Signal. 18, 1675–1689. PMID:23121622

Evolutionary biology of harvestmen (Arachnida, Opiliones).

PubMed

Giribet, Gonzalo; Sharma, Prashant P

2015-01-07

Opiliones are one of the largest arachnid orders, with more than 6,500 species in 50 families. Many of these families have been erected or reorganized in the last few years since the publication of The Biology of Opiliones. Recent years have also seen an explosion in phylogenetic work on Opiliones, as well as in studies using Opiliones as test cases to address biogeographic and evolutionary questions more broadly. Accelerated activity in the study of Opiliones evolution has been facilitated by the discovery of several key fossils, including the oldest known Opiliones fossil, which represents a new, extinct suborder. Study of the group's biology has also benefited from rapid accrual of genomic resources, particularly with respect to transcriptomes and functional genetic tools. The rapid emergence and utility of Phalangium opilio as a model for evolutionary developmental biology of arthropods serve as demonstrative evidence of a new area of study in Opiliones biology, made possible through transcriptomic data.

New technologies accelerate the exploration of non-coding RNAs in horticultural plants

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

Liu, Degao; Mewalal, Ritesh; Hu, Rongbin

Non-coding RNAs (ncRNAs), that is, RNAs not translated into proteins, are crucial regulators of a variety of biological processes in plants. While protein-encoding genes have been relatively well-annotated in sequenced genomes, accounting for a small portion of the genome space in plants, the universe of plant ncRNAs is rapidly expanding. Recent advances in experimental and computational technologies have generated a great momentum for discovery and functional characterization of ncRNAs. Here we summarize the classification and known biological functions of plant ncRNAs, review the application of next-generation sequencing (NGS) technology and ribosome profiling technology to ncRNA discovery in horticultural plants andmore » discuss the application of new technologies, especially the new genome-editing tool clustered regularly interspaced short palindromic repeat (CRISPR)/CRISPR-associated protein 9 (Cas9) systems, to functional characterization of plant ncRNAs.« less

New technologies accelerate the exploration of non-coding RNAs in horticultural plants

PubMed Central

Liu, Degao; Mewalal, Ritesh; Hu, Rongbin; Tuskan, Gerald A; Yang, Xiaohan

2017-01-01

Non-coding RNAs (ncRNAs), that is, RNAs not translated into proteins, are crucial regulators of a variety of biological processes in plants. While protein-encoding genes have been relatively well-annotated in sequenced genomes, accounting for a small portion of the genome space in plants, the universe of plant ncRNAs is rapidly expanding. Recent advances in experimental and computational technologies have generated a great momentum for discovery and functional characterization of ncRNAs. Here we summarize the classification and known biological functions of plant ncRNAs, review the application of next-generation sequencing (NGS) technology and ribosome profiling technology to ncRNA discovery in horticultural plants and discuss the application of new technologies, especially the new genome-editing tool clustered regularly interspaced short palindromic repeat (CRISPR)/CRISPR-associated protein 9 (Cas9) systems, to functional characterization of plant ncRNAs. PMID:28698797

Visitation rates to the Apostle Islands National Lakeshore and the introduction of the non-native species Lymantria dispar (L.)

Treesearch

Patrick C. Tobin; Julie Van Stappen; Laura M. Blackburn

2011-01-01

The introduction of non-native species has accelerated due to increasing levels of global trade and travel, threatening the composition and function of ecosystems. Upon arrival and successful establishment, biological invaders begin to spread and often do so with considerable assistance from humans. Recreational areas can be especially prone to the problem of...

Human visitation rates to the Apostle Islands National Lakeshore and the introduction of the non-native species Lymantria dispar (L.)

Treesearch

Patrick C. Tobin; Julie Van Stappen; Laura M. Blackburn

2010-01-01

The introduction of non-native species has accelerated due to increasing levels of global trade and travel, threatening the composition and function of ecosystems. Upon arrival and successful establishment, biological invaders begin to spread and often do so with considerable assistance from humans. Recreational areas can be especially prone to the problem of...

Using ruthenium polypyridyl functionalized ZnO mesocrystals and gold nanoparticle dotted graphene composite for biological recognition and electrochemiluminescence biosensing

NASA Astrophysics Data System (ADS)

Liu, Suli; Zhang, Jinxing; Tu, Wenwen; Bao, Jianchun; Dai, Zhihui

2014-01-01

Using ruthenium polypyridyl functionalized ZnO mesocrystals as bionanolabels, a universal biological recognition and biosensing platform based on gold nanoparticle (AuNP) dotted reduced graphene oxide (rGO) composite was developed. AuNP-rGO accelerated electron transfer between the detection probe and the electrode, and increased the surface area of the working electrode to load greater amounts of the capture antibodies. The large surface area of ZnO mesocrystals was beneficial for loading a high content ruthenium polypyridyl complex, leading to an enhanced electrochemiluminescence signal. Using α-fetoprotein (AFP) as a model, a simple and sensitive sandwich-type electrochemiluminescence biosensor with tripropylamine (TPrA) as a coreactant for detection of AFP was constructed. The designed biosensor provided a good linear range from 0.04 to 500 ng mL-1 with a low detection limit of 0.031 ng mL-1 at a S/N of 3 for AFP determination. The proposed biological recognition and biosensing platform extended the application of ruthenium polypyridyl functionalized ZnO mesocrystals, which provided a new promising prospect.

Increased gibberellin contents contribute to accelerated growth and development of transgenic tobacco overexpressing a wheat ubiquitin gene.

PubMed

Wang, Guo-Kun; Zhang, Meng; Gong, Jiang-Feng; Guo, Qi-Fang; Feng, Ya-Nan; Wang, Wei

2012-12-01

Overexpressing TaUb2 promoted stem growth and resulted in early flowering in transgenic tobacco plants. Ubiquitin are involved in the production, metabolism and proper function of gibberellin. The ubiquitin-26S proteasome system (UPS), in which ubiquitin (Ub) functions as a marker, is a post-translational regulatory system that plays a prominent role in various biological processes. To investigate the impact of different Ub levels on plant growth and development, transgenic tobacco (Nicotiana tabacum L.) plants were engineered to express an Ub gene (TaUb2) from wheat (Triticum aestivum L.) under the control of cauliflower mosaic virus 35S promoter. Transgenic tobacco plants overexpressing TaUb2 demonstrated an accelerated growth rate at early stage and an early flowering phenotype in development. The preceding expression of MADS-box genes also corresponded to the accelerated developmental phenotypes of the transgenic tobacco plants compared to that of wild-type (WT). Total gibberellin (GA) and active GA contents in transgenic tobacco plants were higher than those in WT at the corresponding developmental stages, and some GA metabolism genes were upregulated. Treatment with GA(3) conferred a similarly accelerated grown rate in WT plants to that of transgenic tobacco plants, while growth was inhibited when transgenic tobacco plants were treated with a GA biosynthesis inhibitor. Thus, the results suggest that Ub are involved in the production, metabolism and proper function of GA, which is important in the regulation of plant growth and development.

Frontier applications of electrostatic accelerators

NASA Astrophysics Data System (ADS)

Liu, Ke-Xin; Wang, Yu-Gang; Fan, Tie-Shuan; Zhang, Guo-Hui; Chen, Jia-Er

2013-10-01

Electrostatic accelerator is a powerful tool in many research fields, such as nuclear physics, radiation biology, material science, archaeology and earth sciences. Two electrostatic accelerators, one is the single stage Van de Graaff with terminal voltage of 4.5 MV and another one is the EN tandem with terminal voltage of 6 MV, were installed in 1980s and had been put into operation since the early 1990s at the Institute of Heavy Ion Physics. Many applications have been carried out since then. These two accelerators are described and summaries of the most important applications on neutron physics and technology, radiation biology and material science, as well as accelerator mass spectrometry (AMS) are presented.

Cell inactivation, repair and mutation induction in bacteria after heavy ion exposure: results from experiments at accelerators and in space.

PubMed

Horneck, G; Schafer, M; Baltschukat, K; Weisbrod, U; Micke, U; Facius, R; Bucker, H

1989-01-01

To understand the mechanisms of accelerated heavy ions on biological matter, the responses of spores of B. subtilis to this structured high LET radiation was investigated applying two different approaches. 1) By the use of the Biostack concept, the inactivation probability as a function of radial distance to single particles' trajectory (i.e. impact parameter) was determined in space experiments as well as at accelerators using low fluences of heavy ions. It was found that spores can survive even a central hit and that the effective range of inactivation extends far beyond impact parameters where inactivation by delta-ray dose would be effective. Concerning the space experiment, the inactivation cross section exceeds those from comparable accelerator experiments by roughly a factor of 20. 2) From fluence effect curves, cross sections for inactivation and mutation induction, and the efficiency of repair processes were determined. They are influenced by the ions characteristics in a complex manner. According to dependence on LET, at least 3 LET ranges can be differentiated: A low LET range (app. < 200 keV/micrometers), where cross sections for inactivation and mutation induction follow a common curve for different ions and where repair processes are effective; an intermediate LET range of the so-called saturation cross section with negligible mutagenic and repair efficiency; and a high LET range (>1000 keV/micrometers) where the biological endpoints are majorly dependent on atomic mass and energy of the ion under consideration.

Second International Conference on Accelerating Biopharmaceutical Development: March 9-12, 2009, Coronado, CA USA.

PubMed

Reichert, Janice M; Jacob, Nitya; Amanullah, Ashraf

2009-01-01

The Second International Conference on Accelerating Biopharmaceutical Development was held in Coronado, California. The meeting was organized by the Society for Biological Engineering (SBE) and the American Institute of Chemical Engineers (AIChE); SBE is a technological community of the AIChE. Bob Adamson (Wyeth) and Chuck Goochee (Centocor) were co-chairs of the event, which had the theme "Delivering cost-effective, robust processes and methods quickly and efficiently." The first day focused on emerging disruptive technologies and cutting-edge analytical techniques. Day two featured presentations on accelerated cell culture process development, critical quality attributes, specifications and comparability, and high throughput protein formulation development. The final day was dedicated to discussion of technology options and new analysis methods provided by emerging disruptive technologies; functional interaction, integration and synergy in platform development; and rapid and economic purification process development.

Second International Conference on Accelerating Biopharmaceutical Development: March 9-12, 2009, Coronado, CA, USA.

PubMed

Reichert, Janice M; Jacob, Nitya M; Amanullah, Ashraf

2009-01-01

The Second International Conference on Accelerating Biopharmaceutical Development was held in Coronado, California. The meeting was organized by the Society for Biological Engineering (SBE) and the American Institute of Chemical Engineers (AIChE); SBE is a technological community of the AIChE. Bob Adamson (Wyeth) and Chuck Goochee (Centocor) were co-chairs of the event, which had the theme "Delivering cost-effective, robust processes and methods quickly and efficiently." The first day focused on emerging disruptive technologies and cutting-edge analytical techniques. Day two featured presentations on accelerated cell culture process development, critical quality attributes, specifications and comparability, and high throughput protein formulation development. The final day was dedicated to discussion of technology options and new analysis methods provided by emerging disruptive technologies; functional interaction, integration and synergy in platform development; and rapid and economic purification process development.

Synthetic biology for microbial heavy metal biosensors.

PubMed

Kim, Hyun Ju; Jeong, Haeyoung; Lee, Sang Jun

2018-02-01

Using recombinant DNA technology, various whole-cell biosensors have been developed for detection of environmental pollutants, including heavy metal ions. Whole-cell biosensors have several advantages: easy and inexpensive cultivation, multiple assays, and no requirement of any special techniques for analysis. In the era of synthetic biology, cutting-edge DNA sequencing and gene synthesis technologies have accelerated the development of cell-based biosensors. Here, we summarize current technological advances in whole-cell heavy metal biosensors, including the synthetic biological components (bioparts), sensing and reporter modules, genetic circuits, and chassis cells. We discuss several opportunities for improvement of synthetic cell-based biosensors. First, new functional modules must be discovered in genome databases, and this knowledge must be used to upgrade specific bioparts through molecular engineering. Second, modules must be assembled into functional biosystems in chassis cells. Third, heterogeneity of individual cells in the microbial population must be eliminated. In the perspectives, the development of whole-cell biosensors is also discussed in the aspects of cultivation methods and synthetic cells.

No Time To Kill: Entrainment and Accelerating Courseware Development.

ERIC Educational Resources Information Center

Millington, Paula Crnkovich

This paper examines the concept of time in multimedia, World Wide Web-based courseware development. The biological concept of entrainment (the alignment of rhythms within and between systems) to accelerate courseware development is explored. The discussion begins with the foundational concepts of entrainment from biological systems and social…

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

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

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)

Molecular communication among biological nanomachines: a layered architecture and research issues.

PubMed

Nakano, Tadashi; Suda, Tatsuya; Okaie, Yutaka; Moore, Michael J; Vasilakos, Athanasios V

2014-09-01

Molecular communication is an emerging communication paradigm for biological nanomachines. It allows biological nanomachines to communicate through exchanging molecules in an aqueous environment and to perform collaborative tasks through integrating functionalities of individual biological nanomachines. This paper develops the layered architecture of molecular communication and describes research issues that molecular communication faces at each layer of the architecture. Specifically, this paper applies a layered architecture approach, traditionally used in communication networks, to molecular communication, decomposes complex molecular communication functionality into a set of manageable layers, identifies basic functionalities of each layer, and develops a descriptive model consisting of key components of the layer for each layer. This paper also discusses open research issues that need to be addressed at each layer. In addition, this paper provides an example design of targeted drug delivery, a nanomedical application, to illustrate how the layered architecture helps design an application of molecular communication. The primary contribution of this paper is to provide an in-depth architectural view of molecular communication. Establishing a layered architecture of molecular communication helps organize various research issues and design concerns into layers that are relatively independent of each other, and thus accelerates research in each layer and facilitates the design and development of applications of molecular communication.

Cadmium-containing quantum dots: properties, applications, and toxicity.

PubMed

Mo, Dan; Hu, Liang; Zeng, Guangming; Chen, Guiqiu; Wan, Jia; Yu, Zhigang; Huang, Zhenzhen; He, Kai; Zhang, Chen; Cheng, Min

2017-04-01

The marriage of biology with nanomaterials has significantly accelerated advancement of biological techniques, profoundly facilitating practical applications in biomedical fields. With unique optical properties (e.g., tunable broad excitation, narrow emission spectra, robust photostability, and high quantum yield), fluorescent quantum dots (QDs) have been reasonably functionalized with controllable interfaces and extensively used as a new class of optical probe in biological researches. In this review, we summarize the recent progress in synthesis and properties of QDs. Moreover, we provide an overview of the outstanding potential of QDs for biomedical research and innovative methods of drug delivery. Specifically, the applications of QDs as novel fluorescent nanomaterials for biomedical sensing and imaging have been detailedly highlighted and discussed. In addition, recent concerns on potential toxicity of QDs are also introduced, ranging from cell researches to animal models.

Evolution of functional specialization and division of labor.

PubMed

Rueffler, Claus; Hermisson, Joachim; Wagner, Günter P

2012-02-07

Division of labor among functionally specialized modules occurs at all levels of biological organization in both animals and plants. Well-known examples include the evolution of specialized enzymes after gene duplication, the evolution of specialized cell types, limb diversification in arthropods, and the evolution of specialized colony members in many taxa of marine invertebrates and social insects. Here, we identify conditions favoring the evolution of division of labor by means of a general mathematical model. Our starting point is the assumption that modules contribute to two different biological tasks and that the potential of modules to contribute to these tasks is traded off. Our results are phrased in terms of properties of performance functions that map the phenotype of modules to measures of performance. We show that division of labor is favored by three factors: positional effects that predispose modules for one of the tasks, accelerating performance functions, and synergistic interactions between modules. If modules can be lost or damaged, selection for robustness can counteract selection for functional specialization. To illustrate our theory we apply it to the evolution of specialized enzymes coded by duplicated genes.

Bioimaging of cells and tissues using accelerator-based sources.

PubMed

Petibois, Cyril; Cestelli Guidi, Mariangela

2008-07-01

A variety of techniques exist that provide chemical information in the form of a spatially resolved image: electron microprobe analysis, nuclear microprobe analysis, synchrotron radiation microprobe analysis, secondary ion mass spectrometry, and confocal fluorescence microscopy. Linear (LINAC) and circular (synchrotrons) particle accelerators have been constructed worldwide to provide to the scientific community unprecedented analytical performances. Now, these facilities match at least one of the three analytical features required for the biological field: (1) a sufficient spatial resolution for single cell (< 1 mum) or tissue (<1 mm) analyses, (2) a temporal resolution to follow molecular dynamics, and (3) a sensitivity in the micromolar to nanomolar range, thus allowing true investigations on biological dynamics. Third-generation synchrotrons now offer the opportunity of bioanalytical measurements at nanometer resolutions with incredible sensitivity. Linear accelerators are more specialized in their physical features but may exceed synchrotron performances. All these techniques have become irreplaceable tools for developing knowledge in biology. This review highlights the pros and cons of the most popular techniques that have been implemented on accelerator-based sources to address analytical issues on biological specimens.

Cell and Tissue Engineering for Liver Disease

PubMed Central

Bhatia, Sangeeta N.; Underhill, Gregory H.; Zaret, Kenneth S.; Fox, Ira J.

2015-01-01

Despite the tremendous hurdles presented by the complexity of the liver’s structure and function, advances in liver physiology, stem cell biology and reprogramming, and the engineering of tissues and devices are accelerating the development of cell-based therapies for treating liver disease and liver failure. This State of the Art Review discusses both the near and long-term prospects for such cell-based therapies and the unique challenges for clinical translation. PMID:25031271

Mutational robustness accelerates the origin of novel RNA phenotypes through phenotypic plasticity.

PubMed

Wagner, Andreas

2014-02-18

Novel phenotypes can originate either through mutations in existing genotypes or through phenotypic plasticity, the ability of one genotype to form multiple phenotypes. From molecules to organisms, plasticity is a ubiquitous feature of life, and a potential source of exaptations, adaptive traits that originated for nonadaptive reasons. Another ubiquitous feature is robustness to mutations, although it is unknown whether such robustness helps or hinders the origin of new phenotypes through plasticity. RNA is ideal to address this question, because it shows extensive plasticity in its secondary structure phenotypes, a consequence of their continual folding and unfolding, and these phenotypes have important biological functions. Moreover, RNA is to some extent robust to mutations. This robustness structures RNA genotype space into myriad connected networks of genotypes with the same phenotype, and it influences the dynamics of evolving populations on a genotype network. In this study I show that both effects help accelerate the exploration of novel phenotypes through plasticity. My observations are based on many RNA molecules sampled at random from RNA sequence space, and on 30 biological RNA molecules. They are thus not only a generic feature of RNA sequence space but are relevant for the molecular evolution of biological RNA. Copyright © 2014 Biophysical Society. Published by Elsevier Inc. All rights reserved.

Long-term exposure to air pollution is associated with biological aging.

PubMed

Ward-Caviness, Cavin K; Nwanaji-Enwerem, Jamaji C; Wolf, Kathrin; Wahl, Simone; Colicino, Elena; Trevisi, Letizia; Kloog, Itai; Just, Allan C; Vokonas, Pantel; Cyrys, Josef; Gieger, Christian; Schwartz, Joel; Baccarelli, Andrea A; Schneider, Alexandra; Peters, Annette

2016-11-15

Long-term exposure to air pollution is associated with age-related diseases. We explored the association between accelerated biological aging and air pollution, a potential mechanism linking air pollution and health. We estimated long-term exposure to PM10, PM2.5, PM2.5 absorbance/black carbon (BC), and NOx via land-use regression models in individuals from the KORA F4 cohort. Accelerated biological aging was assessed using telomere length (TeloAA) and three epigenetic measures: DNA methylation age acceleration (DNAmAA), extrinsic epigenetic age acceleration (correlated with immune cell counts, EEAA), and intrinsic epigenetic age acceleration (independent of immune cell counts, IEAA). We also investigated sex-specific associations between air pollution and biological aging, given the published association between sex and aging measures. In KORA an interquartile range (0.97 µg/m3) increase in PM2.5 was associated with a 0.33 y increase in EEAA (CI = 0.01, 0.64; P = 0.04). BC and NOx (indicators or traffic exposure) were associated with DNAmAA and IEAA in women, while TeloAA was inversely associated with BC in men. We replicated this inverse BC-TeloAA association in the Normative Aging Study, a male cohort based in the USA. A multiple phenotype analysis in KORA F4 combining all aging measures showed that BC and PM10 were broadly associated with biological aging in men. Thus, we conclude that long-term exposure to air pollution is associated with biological aging measures, potentially in a sex-specific manner. However, many of the associations were relatively weak and further replication of overall and sex-specific associations is warranted.

Long-term exposure to air pollution is associated with biological aging

PubMed Central

Ward-Caviness, Cavin K.; Nwanaji-Enwerem, Jamaji C.; Wolf, Kathrin; Wahl, Simone; Colicino, Elena; Trevisi, Letizia; Kloog, Itai; Just, Allan C.; Vokonas, Pantel; Cyrys, Josef; Gieger, Christian; Schwartz, Joel; Baccarelli, Andrea A.; Schneider, Alexandra; Peters, Annette

2016-01-01

Long-term exposure to air pollution is associated with age-related diseases. We explored the association between accelerated biological aging and air pollution, a potential mechanism linking air pollution and health. We estimated long-term exposure to PM10, PM2.5, PM2.5 absorbance/black carbon (BC), and NOx via land-use regression models in individuals from the KORA F4 cohort. Accelerated biological aging was assessed using telomere length (TeloAA) and three epigenetic measures: DNA methylation age acceleration (DNAmAA), extrinsic epigenetic age acceleration (correlated with immune cell counts, EEAA), and intrinsic epigenetic age acceleration (independent of immune cell counts, IEAA). We also investigated sex-specific associations between air pollution and biological aging, given the published association between sex and aging measures. In KORA an interquartile range (0.97 μg/m3) increase in PM2.5 was associated with a 0.33 y increase in EEAA (CI = 0.01, 0.64; P = 0.04). BC and NOx (indicators or traffic exposure) were associated with DNAmAA and IEAA in women, while TeloAA was inversely associated with BC in men. We replicated this inverse BC-TeloAA association in the Normative Aging Study, a male cohort based in the USA. A multiple phenotype analysis in KORA F4 combining all aging measures showed that BC and PM10 were broadly associated with biological aging in men. Thus, we conclude that long-term exposure to air pollution is associated with biological aging measures, potentially in a sex-specific manner. However, many of the associations were relatively weak and further replication of overall and sex-specific associations is warranted. PMID:27793020

Using the brain's fight-or-flight response for predicting mental illness on the human space flight program

NASA Astrophysics Data System (ADS)

Losik, L.

A predictive medicine program allows disease and illness including mental illness to be predicted using tools created to identify the presence of accelerated aging (a.k.a. disease) in electrical and mechanical equipment. When illness and disease can be predicted, actions can be taken so that the illness and disease can be prevented and eliminated. A predictive medicine program uses the same tools and practices from a prognostic and health management program to process biological and engineering diagnostic data provided in analog telemetry during prelaunch readiness and space exploration missions. The biological and engineering diagnostic data necessary to predict illness and disease is collected from the pre-launch spaceflight readiness activities and during space flight for the ground crew to perform a prognostic analysis on the results from a diagnostic analysis. The diagnostic, biological data provided in telemetry is converted to prognostic (predictive) data using the predictive algorithms. Predictive algorithms demodulate telemetry behavior. They illustrate the presence of accelerated aging/disease in normal appearing systems that function normally. Mental illness can predicted using biological diagnostic measurements provided in CCSDS telemetry from a spacecraft such as the ISS or from a manned spacecraft in deep space. The measurements used to predict mental illness include biological and engineering data from an astronaut's circadian and ultranian rhythms. This data originates deep in the brain that is also damaged from the long-term exposure to cortisol and adrenaline anytime the body's fight or flight response is activated. This paper defines the brain's FOFR; the diagnostic, biological and engineering measurements needed to predict mental illness, identifies the predictive algorithms necessary to process the behavior in CCSDS analog telemetry to predict and thus prevent mental illness from occurring on human spaceflight missions.

Explorative solid-phase extraction (E-SPE) for accelerated microbial natural product discovery, dereplication, and purification.

PubMed

Månsson, Maria; Phipps, Richard K; Gram, Lone; Munro, Murray H G; Larsen, Thomas O; Nielsen, Kristian F

2010-06-25

Microbial natural products (NP) cover a high chemical diversity, and in consequence extracts from microorganisms are often complex to analyze and purify. A distribution analysis of calculated pK(a) values from the 34390 records in Antibase2008 revealed that within pH 2-11, 44% of all included compounds had an acidic functionality, 17% a basic functionality, and 9% both. This showed a great potential for using ion-exchange chromatography as an integral part of the separation procedure, orthogonal to the classic reversed-phase strategy. Thus, we investigated the use of an "explorative solid-phase extraction" (E-SPE) protocol using SAX, Oasis MAX, SCX, and LH-20 columns for targeted exploitation of chemical functionalities. E-SPE provides a minimum of fractions (15) for chemical and biological analyses and implicates development into a preparative scale methodology. Overall, this allows fast extract prioritization, easier dereplication, mapping of biological activities, and formulation of a purification strategy.

Subattomole sensitivity in biological accelerator mass spectrometry.

PubMed

Salehpour, Mehran; Possnert, Göran; Bryhni, Helge

2008-05-15

The Uppsala University 5 MV Pelletron tandem accelerator has been used to study (14)C-labeled biological samples utilizing accelerator mass spectrometry (AMS) technology. We have adapted a sample preparation method for small biological samples down to a few tens of micrograms of carbon, involving among others, miniaturizing of the graphitization reactor. Standard AMS requires about 1 mg of carbon with a limit of quantitation of about 10 amol. Results are presented for a range of small sample sizes with concentrations down to below 1 pM of a pharmaceutical substance in human blood. It is shown that (14)C-labeled molecular markers can be routinely measured from the femtomole range down to a few hundred zeptomole (10 (-21) mol), without the use of any additional separation methods.

Engineering CNDP's of dendrimers containing phosphorous interior compositions to produce new emerging properties

NASA Astrophysics Data System (ADS)

Caminade, Anne-Marie; Majoral, Jean-Pierre

2018-03-01

Phosphorus-containing dendrimers are defined as dendrimers having at least one phosphorus atom at each branching point. In this review, we will show how phosphorhydrazone dendrimers can be modified at will at the level of the core and of the branches, to afford specific properties, such as fluorescence to image biological events. Accelerated methods of synthesis of phosphorus (one step for one generation) will be also displayed, as well as the specific reactivity of P=N-P=S linkages obtained in most of these accelerated method of synthesis, which has led to particularly original dendritic architectures, such as dendrons included in dendrimers. Finally, we will display how modifications of the internal structure of a series of dendrimers having the same type and number of terminal functions can deeply modify their biological anti-inflammatory properties. Among the six critical nanoscale design parameters (CNDP), we will show how two of them, i.e., architecture and elemental composition, have been particularly engineered to modify phosphorus-containing dendrimers, in order to fulfill the desired properties.

Structural and functional photoacoustic molecular tomography aided by emerging contrast agents

PubMed Central

Nie, Liming

2015-01-01

Photoacoustic tomography (PAT) can offer structural, functional and molecular contrasts at scalable observation level. By ultrasonically overcoming the strong optical scattering, this imaging technology can reach centimeters penetration depth while retaining high spatial resolution in biological tissue. Recent extensive research has been focused on developing new contrast agents to improve the imaging sensitivity, specificity and efficiency. These emerging materials have substantially accelerated PAT applications in signal sensing, functional imaging, biomarker labeling and therapy monitoring etc. Here, the potentials of different optical probes as PAT contrast agents were elucidated. We first describe the instrumental embodiments and the measured functional parameters, then focus on emerging contrast agent-based PAT applications, and finally discuss the challenges and prospects. PMID:24967718

Highly parallel genome-wide expression profiling of individual cells using nanoliter droplets

PubMed Central

Macosko, Evan Z.; Basu, Anindita; Satija, Rahul; Nemesh, James; Shekhar, Karthik; Goldman, Melissa; Tirosh, Itay; Bialas, Allison R.; Kamitaki, Nolan; Martersteck, Emily M.; Trombetta, John J.; Weitz, David A.; Sanes, Joshua R.; Shalek, Alex K.; Regev, Aviv; McCarroll, Steven A.

2015-01-01

Summary Cells, the basic units of biological structure and function, vary broadly in type and state. Single-cell genomics can characterize cell identity and function, but limitations of ease and scale have prevented its broad application. Here we describe Drop-Seq, a strategy for quickly profiling thousands of individual cells by separating them into nanoliter-sized aqueous droplets, associating a different barcode with each cell’s RNAs, and sequencing them all together. Drop-Seq analyzes mRNA transcripts from thousands of individual cells simultaneously while remembering transcripts’ cell of origin. We analyzed transcriptomes from 44,808 mouse retinal cells and identified 39 transcriptionally distinct cell populations, creating a molecular atlas of gene expression for known retinal cell classes and novel candidate cell subtypes. Drop-Seq will accelerate biological discovery by enabling routine transcriptional profiling at single-cell resolution. PMID:26000488

Gravity as a factor in the animal environment.

NASA Technical Reports Server (NTRS)

Smith, A. H.

1972-01-01

Review of current knowledge, research, and research planning on the influence of gravity upon living organisms. Discussed factors affecting the adaptability of animals to increased acceleration fields include age, sex, posture, and body size. Affected functions and aspects reviewed cover growth and mature body size, body composition, maintenance feed requirements, and feed utilization efficiency. It is expected that research involving the exposure of animals to altered gravity states will lead to new biological concepts of very broad importance.

Modeling the biophysical effects in a carbon beam delivery line by using Monte Carlo simulations

NASA Astrophysics Data System (ADS)

Cho, Ilsung; Yoo, SeungHoon; Cho, Sungho; Kim, Eun Ho; Song, Yongkeun; Shin, Jae-ik; Jung, Won-Gyun

2016-09-01

The Relative biological effectiveness (RBE) plays an important role in designing a uniform dose response for ion-beam therapy. In this study, the biological effectiveness of a carbon-ion beam delivery system was investigated using Monte Carlo simulations. A carbon-ion beam delivery line was designed for the Korea Heavy Ion Medical Accelerator (KHIMA) project. The GEANT4 simulation tool kit was used to simulate carbon-ion beam transport into media. An incident energy carbon-ion beam with energy in the range between 220 MeV/u and 290 MeV/u was chosen to generate secondary particles. The microdosimetric-kinetic (MK) model was applied to describe the RBE of 10% survival in human salivary-gland (HSG) cells. The RBE weighted dose was estimated as a function of the penetration depth in the water phantom along the incident beam's direction. A biologically photon-equivalent Spread Out Bragg Peak (SOBP) was designed using the RBE-weighted absorbed dose. Finally, the RBE of mixed beams was predicted as a function of the depth in the water phantom.

Simultaneous biologging of heart rate and acceleration, and their relationships with energy expenditure in free-swimming sockeye salmon (Oncorhynchus nerka).

PubMed

Clark, Timothy Darren; Sandblom, E; Hinch, S G; Patterson, D A; Frappell, P B; Farrell, A P

2010-06-01

Monitoring the physiological status and behaviour of free-swimming fishes remains a challenging task, although great promise stems from techniques such as biologging and biotelemetry. Here, implanted data loggers were used to simultaneously measure heart rate (f (H)), visceral temperature, and a derivation of acceleration in two groups of wild adult sockeye salmon (Oncorhynchus nerka) held at two different water speeds (slow and fast). Calibration experiments performed with individual fish in a swim tunnel respirometer generated strong relationships between acceleration, f (H), tail beat frequency and energy expenditure over a wide range of swimming velocities. The regression equations were then used to estimate the overall energy expenditure of the groups of fish held at different water speeds. As expected, fish held at faster water speeds exhibited greater f (H) and acceleration, and correspondingly a higher estimated energy expenditure than fish held at slower water speeds. These estimates were consistent with gross somatic energy density of fish at death, as determined using proximate analyses of a dorsal tissue sample. Heart rate alone and in combination with acceleration, rather than acceleration alone, provided the most accurate proxies for energy expenditure in these studies. Even so, acceleration provided useful information on the behaviour of fish and may itself prove to be a valuable proxy for energy expenditure under different environmental conditions, using a different derivation of the acceleration data, and/or with further calibration experiments. These results strengthen the possibility that biologging or biotelemetry of f (H) and acceleration may be usefully applied to migrating sockeye salmon to monitor physiology and behaviour, and to estimate energy use in the natural environment.

Simbios: an NIH national center for physics-based simulation of biological structures.

PubMed

Delp, Scott L; Ku, Joy P; Pande, Vijay S; Sherman, Michael A; Altman, Russ B

2012-01-01

Physics-based simulation provides a powerful framework for understanding biological form and function. Simulations can be used by biologists to study macromolecular assemblies and by clinicians to design treatments for diseases. Simulations help biomedical researchers understand the physical constraints on biological systems as they engineer novel drugs, synthetic tissues, medical devices, and surgical interventions. Although individual biomedical investigators make outstanding contributions to physics-based simulation, the field has been fragmented. Applications are typically limited to a single physical scale, and individual investigators usually must create their own software. These conditions created a major barrier to advancing simulation capabilities. In 2004, we established a National Center for Physics-Based Simulation of Biological Structures (Simbios) to help integrate the field and accelerate biomedical research. In 6 years, Simbios has become a vibrant national center, with collaborators in 16 states and eight countries. Simbios focuses on problems at both the molecular scale and the organismal level, with a long-term goal of uniting these in accurate multiscale simulations.

Network news: prime time for systems biology of the plant circadian clock.

PubMed

McClung, C Robertson; Gutiérrez, Rodrigo A

2010-12-01

Whole-transcriptome analyses have established that the plant circadian clock regulates virtually every plant biological process and most prominently hormonal and stress response pathways. Systems biology efforts have successfully modeled the plant central clock machinery and an iterative process of model refinement and experimental validation has contributed significantly to the current view of the central clock machinery. The challenge now is to connect this central clock to the output pathways for understanding how the plant circadian clock contributes to plant growth and fitness in a changing environment. Undoubtedly, systems approaches will be needed to integrate and model the vastly increased volume of experimental data in order to extract meaningful biological information. Thus, we have entered an era of systems modeling, experimental testing, and refinement. This approach, coupled with advances from the genetic and biochemical analyses of clock function, is accelerating our progress towards a comprehensive understanding of the plant circadian clock network. Copyright © 2010 Elsevier Ltd. All rights reserved.

Simbios: an NIH national center for physics-based simulation of biological structures

PubMed Central

Delp, Scott L; Ku, Joy P; Pande, Vijay S; Sherman, Michael A

2011-01-01

Physics-based simulation provides a powerful framework for understanding biological form and function. Simulations can be used by biologists to study macromolecular assemblies and by clinicians to design treatments for diseases. Simulations help biomedical researchers understand the physical constraints on biological systems as they engineer novel drugs, synthetic tissues, medical devices, and surgical interventions. Although individual biomedical investigators make outstanding contributions to physics-based simulation, the field has been fragmented. Applications are typically limited to a single physical scale, and individual investigators usually must create their own software. These conditions created a major barrier to advancing simulation capabilities. In 2004, we established a National Center for Physics-Based Simulation of Biological Structures (Simbios) to help integrate the field and accelerate biomedical research. In 6 years, Simbios has become a vibrant national center, with collaborators in 16 states and eight countries. Simbios focuses on problems at both the molecular scale and the organismal level, with a long-term goal of uniting these in accurate multiscale simulations. PMID:22081222

A novel approach to enhance biological nutrient removal using a culture supernatant from Micrococcus luteus containing resuscitation-promoting factor (Rpf) in SBR process.

PubMed

Liu, Yindong; Su, Xiaomei; Lu, Lian; Ding, Linxian; Shen, Chaofeng

2016-03-01

A culture supernatant from Micrococcus luteus containing resuscitation-promoting factor (SRpf) was used to enhance the biological nutrient removal of potentially functional bacteria. The obtained results suggest that SRpf accelerated the start-up process and significantly enhanced the biological nutrient removal in sequencing batch reactor (SBR). PO4 (3-)-P removal efficiency increased by over 12 % and total nitrogen removal efficiency increased by over 8 % in treatment reactor acclimated by SRpf compared with those without SRpf addition. The Illumina high-throughput sequencing analysis showed that SRpf played an essential role in shifts in the composition and diversity of bacterial community. The phyla of Proteobacteria and Actinobacteria, which were closely related to biological nutrient removal, were greatly abundant after SRpf addition. This study demonstrates that SRpf acclimation or addition might hold great potential as an efficient and cost-effective alternative for wastewater treatment plants (WWTPs) to meet more stringent operation conditions and legislations.

Neutron-energy-dependent cell survival and oncogenic transformation.

PubMed

Miller, R C; Marino, S A; Martin, S G; Komatsu, K; Geard, C R; Brenner, D J; Hall, E J

1999-12-01

Both cell lethality and neoplastic transformation were assessed for C3H10T1/2 cells exposed to neutrons with energies from 0.040 to 13.7 MeV. Monoenergetic neutrons with energies from 0.23 to 13.7 MeV and two neutron energy spectra with average energies of 0.040 and 0.070 MeV were produced with a Van de Graaff accelerator at the Radiological Research Accelerator Facility (RARAF) in the Center for Radiological Research of Columbia University. For determination of relative biological effectiveness (RBE), cells were exposed to 250 kVp X rays. With exposures to 250 kVp X rays, both cell survival and radiation-induced oncogenic transformation were curvilinear. Irradiation of cells with neutrons at all energies resulted in linear responses as a function of dose for both biological endpoints. Results indicate a complex relationship between RBEm and neutron energy. For both survival and transformation, RBEm was greatest for cells exposed to 0.35 MeV neutrons. RBEm was significantly less at energies above or below 0.35 MeV. These results are consistent with microdosimetric expectation. These results are also compatible with current assessments of neutron radiation weighting factors for radiation protection purposes. Based on calculations of dose-averaged LET, 0.35 MeV neutrons have the greatest LET and therefore would be expected to be more biologically effective than neutrons of greater or lesser energies.

Human RecQL4 helicase plays multifaceted roles in the genomic stability of normal and cancer cells.

PubMed

Mo, Dongliang; Zhao, Yongliang; Balajee, Adayabalam S

2018-01-28

Human RecQ helicases that share homology with E. coli RecQ helicase play critical roles in diverse biological activities such as DNA replication, transcription, recombination and repair. Mutations in three of the five human RecQ helicases (RecQ1, WRN, BLM, RecQL4 and RecQ5) result in autosomal recessive syndromes characterized by accelerated aging symptoms and cancer incidence. Mutational inactivation of Werner (WRN) and Bloom (BLM) genes results in Werner syndrome (WS) and Bloom syndrome (BS) respectively. However, mutations in RecQL4 result in three human disorders: (I) Rothmund-Thomson syndrome (RTS), (II) RAPADILINO and (III) Baller-Gerold syndrome (BGS). Cells from WS, BS and RTS are characterized by a unique chromosomal anomaly indicating that each of the RecQ helicases performs specialized function(s) in a non-redundant manner. Elucidating the biological functions of RecQ helicases will enable us to understand not only the aging process but also to determine the cause for age-associated human diseases. Recent biochemical and molecular studies have given new insights into the multifaceted roles of RecQL4 that range from genomic stability to carcinogenesis and beyond. This review summarizes some of the existing and emerging knowledge on diverse biological functions of RecQL4 and its significance as a potential molecular target for cancer therapy. Copyright © 2017 Elsevier B.V. All rights reserved.

Plant Metabolomics: An Indispensable System Biology Tool for Plant Science

PubMed Central

Hong, Jun; Yang, Litao; Zhang, Dabing; Shi, Jianxin

2016-01-01

As genomes of many plant species have been sequenced, demand for functional genomics has dramatically accelerated the improvement of other omics including metabolomics. Despite a large amount of metabolites still remaining to be identified, metabolomics has contributed significantly not only to the understanding of plant physiology and biology from the view of small chemical molecules that reflect the end point of biological activities, but also in past decades to the attempts to improve plant behavior under both normal and stressed conditions. Hereby, we summarize the current knowledge on the genetic and biochemical mechanisms underlying plant growth, development, and stress responses, focusing further on the contributions of metabolomics to practical applications in crop quality improvement and food safety assessment, as well as plant metabolic engineering. We also highlight the current challenges and future perspectives in this inspiring area, with the aim to stimulate further studies leading to better crop improvement of yield and quality. PMID:27258266

Damage-free vibrational spectroscopy of biological materials in the electron microscope

PubMed Central

Rez, Peter; Aoki, Toshihiro; March, Katia; Gur, Dvir; Krivanek, Ondrej L.; Dellby, Niklas; Lovejoy, Tracy C.; Wolf, Sharon G.; Cohen, Hagai

2016-01-01

Vibrational spectroscopy in the electron microscope would be transformative in the study of biological samples, provided that radiation damage could be prevented. However, electron beams typically create high-energy excitations that severely accelerate sample degradation. Here this major difficulty is overcome using an ‘aloof' electron beam, positioned tens of nanometres away from the sample: high-energy excitations are suppressed, while vibrational modes of energies <1 eV can be ‘safely' investigated. To demonstrate the potential of aloof spectroscopy, we record electron energy loss spectra from biogenic guanine crystals in their native state, resolving their characteristic C–H, N–H and C=O vibrational signatures with no observable radiation damage. The technique opens up the possibility of non-damaging compositional analyses of organic functional groups, including non-crystalline biological materials, at a spatial resolution of ∼10 nm, simultaneously combined with imaging in the electron microscope. PMID:26961578

Genetic mitigation strategies to tackle agricultural GHG emissions: The case for biological nitrification inhibition technology.

PubMed

Subbarao, G V; Arango, J; Masahiro, K; Hooper, A M; Yoshihashi, T; Ando, Y; Nakahara, K; Deshpande, S; Ortiz-Monasterio, I; Ishitani, M; Peters, M; Chirinda, N; Wollenberg, L; Lata, J C; Gerard, B; Tobita, S; Rao, I M; Braun, H J; Kommerell, V; Tohme, J; Iwanaga, M

2017-09-01

Accelerated soil-nitrifier activity and rapid nitrification are the cause of declining nitrogen-use efficiency (NUE) and enhanced nitrous oxide (N 2 O) emissions from farming. Biological nitrification inhibition (BNI) is the ability of certain plant roots to suppress soil-nitrifier activity, through production and release of nitrification inhibitors. The power of phytochemicals with BNI-function needs to be harnessed to control soil-nitrifier activity and improve nitrogen-cycling in agricultural systems. Transformative biological technologies designed for genetic mitigation are needed, so that BNI-enabled crop-livestock and cropping systems can rein in soil-nitrifier activity, to help reduce greenhouse gas (GHG) emissions and globally make farming nitrogen efficient and less harmful to environment. This will reinforce the adaptation or mitigation impact of other climate-smart agriculture technologies. Copyright © 2017 Elsevier B.V. All rights reserved.

Damage-free vibrational spectroscopy of biological materials in the electron microscope.

PubMed

Rez, Peter; Aoki, Toshihiro; March, Katia; Gur, Dvir; Krivanek, Ondrej L; Dellby, Niklas; Lovejoy, Tracy C; Wolf, Sharon G; Cohen, Hagai

2016-03-10

Vibrational spectroscopy in the electron microscope would be transformative in the study of biological samples, provided that radiation damage could be prevented. However, electron beams typically create high-energy excitations that severely accelerate sample degradation. Here this major difficulty is overcome using an 'aloof' electron beam, positioned tens of nanometres away from the sample: high-energy excitations are suppressed, while vibrational modes of energies <1 eV can be 'safely' investigated. To demonstrate the potential of aloof spectroscopy, we record electron energy loss spectra from biogenic guanine crystals in their native state, resolving their characteristic C-H, N-H and C=O vibrational signatures with no observable radiation damage. The technique opens up the possibility of non-damaging compositional analyses of organic functional groups, including non-crystalline biological materials, at a spatial resolution of ∼10 nm, simultaneously combined with imaging in the electron microscope.

Plant Metabolomics: An Indispensable System Biology Tool for Plant Science.

PubMed

Hong, Jun; Yang, Litao; Zhang, Dabing; Shi, Jianxin

2016-06-01

As genomes of many plant species have been sequenced, demand for functional genomics has dramatically accelerated the improvement of other omics including metabolomics. Despite a large amount of metabolites still remaining to be identified, metabolomics has contributed significantly not only to the understanding of plant physiology and biology from the view of small chemical molecules that reflect the end point of biological activities, but also in past decades to the attempts to improve plant behavior under both normal and stressed conditions. Hereby, we summarize the current knowledge on the genetic and biochemical mechanisms underlying plant growth, development, and stress responses, focusing further on the contributions of metabolomics to practical applications in crop quality improvement and food safety assessment, as well as plant metabolic engineering. We also highlight the current challenges and future perspectives in this inspiring area, with the aim to stimulate further studies leading to better crop improvement of yield and quality.

Damage-free vibrational spectroscopy of biological materials in the electron microscope

DOE PAGES

Rez, Peter; Aoki, Toshihiro; March, Katia; ...

2016-03-10

Vibrational spectroscopy in the electron microscope would be transformative in the study of biological samples, provided that radiation damage could be prevented. However, electron beams typically create high-energy excitations that severely accelerate sample degradation. Here this major difficulty is overcome using an ‘aloof’ electron beam, positioned tens of nanometres away from the sample: high-energy excitations are suppressed, while vibrational modes of energies o1 eV can be ‘safely’ investigated. To demonstrate the potential of aloof spectroscopy, we record electron energy loss spectra from biogenic guanine crystals in their native state, resolving their characteristic C–H, N–H and C=O vibrational signatures with nomore » observable radiation damage. Furthermore, the technique opens up the possibility of non-damaging compositional analyses of organic functional groups, including non-crystalline biological materials, at a spatial resolution of ~10nm, simultaneously combined with imaging in the electron microscope.« less

Damage-free vibrational spectroscopy of biological materials in the electron microscope

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

Rez, Peter; Aoki, Toshihiro; March, Katia

Vibrational spectroscopy in the electron microscope would be transformative in the study of biological samples, provided that radiation damage could be prevented. However, electron beams typically create high-energy excitations that severely accelerate sample degradation. Here this major difficulty is overcome using an ‘aloof’ electron beam, positioned tens of nanometres away from the sample: high-energy excitations are suppressed, while vibrational modes of energies o1 eV can be ‘safely’ investigated. To demonstrate the potential of aloof spectroscopy, we record electron energy loss spectra from biogenic guanine crystals in their native state, resolving their characteristic C–H, N–H and C=O vibrational signatures with nomore » observable radiation damage. Furthermore, the technique opens up the possibility of non-damaging compositional analyses of organic functional groups, including non-crystalline biological materials, at a spatial resolution of ~10nm, simultaneously combined with imaging in the electron microscope.« less

Speeding up biomolecular interactions by molecular sledding

DOE PAGES

Turkin, Alexander; Zhang, Lei; Marcozzi, Alessio; ...

2015-10-07

In numerous biological processes associations involve a protein with its binding partner, an event that is preceded by a diffusion-mediated search bringing the two partners together. Often hindered by crowding in biologically relevant environments, three-dimensional diffusion can be slow and result in long bimolecular association times. Moreover, the initial association step between two binding partners often represents a rate-limiting step in biotechnologically relevant reactions. We also demonstrate the practical use of an 11-a.a. DNA-interacting peptide derived from adenovirus to reduce the dimensionality of diffusional search processes and speed up associations between biological macromolecules. We functionalize binding partners with the peptidemore » and demonstrate that the ability of the peptide to one-dimensionally diffuse along DNA results in a 20-fold reduction in reaction time. We also show that modifying PCR primers with the peptide sled enables significant acceleration of standard PCR reactions.« less

Speed and convergence properties of gradient algorithms for optimization of IMRT.

PubMed

Zhang, Xiaodong; Liu, Helen; Wang, Xiaochun; Dong, Lei; Wu, Qiuwen; Mohan, Radhe

2004-05-01

Gradient algorithms are the most commonly employed search methods in the routine optimization of IMRT plans. It is well known that local minima can exist for dose-volume-based and biology-based objective functions. The purpose of this paper is to compare the relative speed of different gradient algorithms, to investigate the strategies for accelerating the optimization process, to assess the validity of these strategies, and to study the convergence properties of these algorithms for dose-volume and biological objective functions. With these aims in mind, we implemented Newton's, conjugate gradient (CG), and the steepest decent (SD) algorithms for dose-volume- and EUD-based objective functions. Our implementation of Newton's algorithm approximates the second derivative matrix (Hessian) by its diagonal. The standard SD algorithm and the CG algorithm with "line minimization" were also implemented. In addition, we investigated the use of a variation of the CG algorithm, called the "scaled conjugate gradient" (SCG) algorithm. To accelerate the optimization process, we investigated the validity of the use of a "hybrid optimization" strategy, in which approximations to calculated dose distributions are used during most of the iterations. Published studies have indicated that getting trapped in local minima is not a significant problem. To investigate this issue further, we first obtained, by trial and error, and starting with uniform intensity distributions, the parameters of the dose-volume- or EUD-based objective functions which produced IMRT plans that satisfied the clinical requirements. Using the resulting optimized intensity distributions as the initial guess, we investigated the possibility of getting trapped in a local minimum. For most of the results presented, we used a lung cancer case. To illustrate the generality of our methods, the results for a prostate case are also presented. For both dose-volume and EUD based objective functions, Newton's method far outperforms other algorithms in terms of speed. The SCG algorithm, which avoids expensive "line minimization," can speed up the standard CG algorithm by at least a factor of 2. For the same initial conditions, all algorithms converge essentially to the same plan. However, we demonstrate that for any of the algorithms studied, starting with previously optimized intensity distributions as the initial guess but for different objective function parameters, the solution frequently gets trapped in local minima. We found that the initial intensity distribution obtained from IMRT optimization utilizing objective function parameters, which favor a specific anatomic structure, would lead to a local minimum corresponding to that structure. Our results indicate that from among the gradient algorithms tested, Newton's method appears to be the fastest by far. Different gradient algorithms have the same convergence properties for dose-volume- and EUD-based objective functions. The hybrid dose calculation strategy is valid and can significantly accelerate the optimization process. The degree of acceleration achieved depends on the type of optimization problem being addressed (e.g., IMRT optimization, intensity modulated beam configuration optimization, or objective function parameter optimization). Under special conditions, gradient algorithms will get trapped in local minima, and reoptimization, starting with the results of previous optimization, will lead to solutions that are generally not significantly different from the local minimum.

Accelerated ageing and renal dysfunction links lower socioeconomic status and dietary phosphate intake.

PubMed

McClelland, Ruth; Christensen, Kelly; Mohammed, Suhaib; McGuinness, Dagmara; Cooney, Josephine; Bakshi, Andisheh; Demou, Evangelia; MacDonald, Ewan; Caslake, Muriel; Stenvinkel, Peter; Shiels, Paul G

2016-05-01

We have sought to explore the impact of dietary Pi intake on human age related health in the pSoBid cohort (n=666) to explain the disparity between health and deprivation status in this cohort. As hyperphosphataemia is a driver of accelerated ageing in rodent models of progeria we tested whether variation in Pi levels in man associate with measures of biological ageing and health. We observed significant relationships between serum Pi levels and markers of biological age (telomere length (p=0.040) and DNA methylation content (p=0.028), gender and chronological age (p=0.032). When analyses were adjusted for socio-economic status and nutritional factors, associations were observed between accelerated biological ageing (telomere length, genomic methylation content) and dietary derived Pi levels among the most deprived males, directly related to the frequency of red meat consumption. Accelerated ageing is associated with high serum Pi levels and frequency of red meat consumption. Our data provide evidence for a mechanistic link between high intake of Pi and age-related morbidities tied to socio-economic status.

Suppression of Metastasis by Primary Tumor and Acceleration of Metastasis Following Primary Tumor Resection: A Natural Law?

PubMed

Hanin, Leonid; Rose, Jason

2018-03-01

We study metastatic cancer progression through an extremely general individual-patient mathematical model that is rooted in the contemporary understanding of the underlying biomedical processes yet is essentially free of specific biological assumptions of mechanistic nature. The model accounts for primary tumor growth and resection, shedding of metastases off the primary tumor and their selection, dormancy and growth in a given secondary site. However, functional parameters descriptive of these processes are assumed to be essentially arbitrary. In spite of such generality, the model allows for computing the distribution of site-specific sizes of detectable metastases in closed form. Under the assumption of exponential growth of metastases before and after primary tumor resection, we showed that, regardless of other model parameters and for every set of site-specific volumes of detected metastases, the model-based likelihood-maximizing scenario is always the same: complete suppression of metastatic growth before primary tumor resection followed by an abrupt growth acceleration after surgery. This scenario is commonly observed in clinical practice and is supported by a wealth of experimental and clinical studies conducted over the last 110 years. Furthermore, several biological mechanisms have been identified that could bring about suppression of metastasis by the primary tumor and accelerated vascularization and growth of metastases after primary tumor resection. To the best of our knowledge, the methodology for uncovering general biomedical principles developed in this work is new.

Craniofacial Anomalies And Biostereometrics

NASA Astrophysics Data System (ADS)

Christiansen, Richard L.

1980-07-01

Man's oral-facial structures are vital for the functions of breathing, mastication, swallowing, vision, and communication. When defective development of these tissues occurs, function becomes impaired and the anatomic features of the afflicted individual will frequently deviate from the norm. This error of form and function will classify the individual as being physically and psychosocially handicapped. The successful habilitation regimen of the handicapped person depends on the accurate analysis of both craniofacial anatomy and physiology of these individuals, as well as psychological implications of the disfigurement. Biostereometrics can contribute to the establishment of operationally valid measures for assessing the severity of the handicapping conditions. The heterogeneous nature of diverse disfigurement suggest that an improved classification of malformations would be beneficial. Three-dimensional analysis may also have significant influence on the accuracy of the diagnosis, and the establishment of a biologically sound treatment plan. Biostereometrics will contribute more fully if the three-dimensional surface analysis can be coordinated with a study of 1) the underlying skeletal structures, and 2) the operational musculature. Increased communication between the stereometric experts and the biological scientists should accelerate the application of this technique to the health problem.

Transiently disordered tails accelerate folding of globular proteins.

PubMed

Mallik, Saurav; Ray, Tanaya; Kundu, Sudip

2017-07-01

Numerous biological proteins exhibit intrinsic disorder at their termini, which are associated with multifarious functional roles. Here, we show the surprising result that an increased percentage of terminal short transiently disordered regions with enhanced flexibility (TstDREF) is associated with accelerated folding rates of globular proteins. Evolutionary conservation of predicted disorder at TstDREFs and drastic alteration of folding rates upon point-mutations suggest critical regulatory role(s) of TstDREFs in shaping the folding kinetics. TstDREFs are associated with long-range intramolecular interactions and the percentage of native secondary structural elements physically contacted by TstDREFs exhibit another surprising positive correlation with folding kinetics. These results allow us to infer probable molecular mechanisms behind the TstDREF-mediated regulation of folding kinetics that challenge protein biochemists to assess by direct experimental testing. © 2017 Federation of European Biochemical Societies.

Physicochemical stability and biological activity of Withania somnifera extract under real-time and accelerated storage conditions.

PubMed

Patil, Dada; Gautam, Manish; Jadhav, Umesh; Mishra, Sanjay; Karupothula, Suresh; Gairola, Sunil; Jadhav, Suresh; Patwardhan, Bhushan

2010-03-01

Stability testing at preformulation stages is a crucial part of drug development. We studied physicochemical stability and biological activity of Withania somnifera (ashwagandha) dried root aqueous extract during six months real-time and under accelerated storage conditions. The characteristic constituents of ashwagandha roots include withanolides such as withaferin A and withanolide A. We modified and validated the HPLC-DAD method for quantitative measurement of withanolides and fingerprint analysis. The results suggest a significant decline in withaferin A and withanolide A content under real and accelerated conditions. The HPLC fingerprint analysis showed significant changes in some peaks during real and accelerated storage (> 20 %). We also observed incidences of clump formation and moisture sensitivity (> 10 %) under real-time and accelerated storage conditions. These changes were concurrent with a significant decline in immunomodulatory activity (p < 0.01) during the third month of the accelerated storage. Thus, adequate control of temperature and humidity is important for WSE containing formulations. This study may help in proposing suitable guidance for storage conditions and shelf life of ashwagandha formulations. (c) Georg Thieme Verlag KG Stuttgart . New York.

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 also prove useful for dead-reckoning and improving estimates of energy expenditures from locomotion. PMID:27285467

Accelerated aging in adults with knee osteoarthritis pain: consideration for frequency, intensity, time, and total pain sites

PubMed Central

Sibille, Kimberly T.; Chen, Huaihou; Bartley, Emily J.; Riley, Joseph; Glover, Toni L.; King, Christopher D.; Zhang, Hang; Cruz-Almeida, Yenisel; Goodin, Burel R.; Sotolongo, Adriana; Petrov, Megan E.; Herbert, Matthew; Bulls, Hailey W.; Edberg, Jeffrey C.; Staud, Roland; Redden, David; Bradley, Laurence A.; Fillingim, Roger B.

2017-01-01

Abstract Introduction: Individuals with osteoarthritis (OA) show increased morbidity and mortality. Telomere length, a measure of cellular aging, predicts increased morbidity and mortality. Telomeres shorten with persisting biological and psychosocial stress. Living with chronic OA pain is stressful. Previous research exploring telomere length in people with OA has produced inconsistent results. Considering pain severity may clarify the relationship between OA and telomeres. Objectives: We hypothesized that individuals with high OA chronic pain severity would have shorter telomeres than those with no or low chronic pain severity. Methods: One hundred thirty-six adults, ages 45 to 85 years old, with and without symptomatic knee OA were included in the analysis. Peripheral blood leukocyte telomere length was measured, and demographic, clinical, and functional data were collected. Participants were categorized into 5 pain severity groups based on an additive index of frequency, intensity, time or duration, and total number of pain sites (FITT). Covariates included age, sex, race or ethnicity, study site, and knee pain status. Results: The no or low chronic pain severity group had significantly longer telomeres compared with the high pain severity group, P = 0.025. A significant chronic pain severity dose response emerged for telomere length, P = 0.034. The FITT chronic pain severity index was highly correlated with the clinical and functional OA pain measures. However, individual clinical and functional measures were not associated with telomere length. Conclusion: Results demonstrate accelerated cellular aging with high knee OA chronic pain severity and provide evidence for the potential utility of the FITT chronic pain severity index in capturing the biological burden of chronic pain. PMID:29392207

How accelerated biological aging can affect solar reflective polymeric based building materials

NASA Astrophysics Data System (ADS)

Ferrari, C.; Santunione, G.; Libbra, A.; Muscio, A.; Sgarbi, E.

2017-11-01

Among the main issues concerning building materials, in particular outdoor ones, one can identify the colonization by microorganisms referred to as biological aggression. This can affect not only the aesthetical aspect but also the thermal performance of solar reflective materials. In order to improve the reliability of tests aimed to assess the resistance to biological aggression and contextually reduce the test duration, an accelerated test method has been developed. It is based on a lab reproducible setup where specific and controlled environmental and boundary conditions are imposed to accelerate as much as possible biological growth on building materials. Due to their widespread use, polymeric materials have been selected for the present analysis, in the aim of reaching an advanced bio-aged level in a relatively short time (8 weeks or less) and at the same time comparatively evaluate different materials under a given set of ageing conditions. Surface properties before, during and after ageing have been investigated by surface, microstructural and chemical analyses, as well as by examination of time progressive images to assess bacterial and algal growth rate.

Clustering and Network Analysis of Reverse Phase Protein Array Data.

PubMed

Byron, Adam

2017-01-01

Molecular profiling of proteins and phosphoproteins using a reverse phase protein array (RPPA) platform, with a panel of target-specific antibodies, enables the parallel, quantitative proteomic analysis of many biological samples in a microarray format. Hence, RPPA analysis can generate a high volume of multidimensional data that must be effectively interrogated and interpreted. A range of computational techniques for data mining can be applied to detect and explore data structure and to form functional predictions from large datasets. Here, two approaches for the computational analysis of RPPA data are detailed: the identification of similar patterns of protein expression by hierarchical cluster analysis and the modeling of protein interactions and signaling relationships by network analysis. The protocols use freely available, cross-platform software, are easy to implement, and do not require any programming expertise. Serving as data-driven starting points for further in-depth analysis, validation, and biological experimentation, these and related bioinformatic approaches can accelerate the functional interpretation of RPPA data.

FPGA accelerator for protein secondary structure prediction based on the GOR algorithm

PubMed Central

2011-01-01

Background Protein is an important molecule that performs a wide range of functions in biological systems. Recently, the protein folding attracts much more attention since the function of protein can be generally derived from its molecular structure. The GOR algorithm is one of the most successful computational methods and has been widely used as an efficient analysis tool to predict secondary structure from protein sequence. However, the execution time is still intolerable with the steep growth in protein database. Recently, FPGA chips have emerged as one promising application accelerator to accelerate bioinformatics algorithms by exploiting fine-grained custom design. Results In this paper, we propose a complete fine-grained parallel hardware implementation on FPGA to accelerate the GOR-IV package for 2D protein structure prediction. To improve computing efficiency, we partition the parameter table into small segments and access them in parallel. We aggressively exploit data reuse schemes to minimize the need for loading data from external memory. The whole computation structure is carefully pipelined to overlap the sequence loading, computing and back-writing operations as much as possible. We implemented a complete GOR desktop system based on an FPGA chip XC5VLX330. Conclusions The experimental results show a speedup factor of more than 430x over the original GOR-IV version and 110x speedup over the optimized version with multi-thread SIMD implementation running on a PC platform with AMD Phenom 9650 Quad CPU for 2D protein structure prediction. However, the power consumption is only about 30% of that of current general-propose CPUs. PMID:21342582

We have AN Increasing Need to Model Ourselves

NASA Astrophysics Data System (ADS)

Farmer, J. Doyne

Pierre Teilhard de Chardin referred to the fusion of biological life, human culture, and technology as the noosphere. Technological improvement is causing the noosphere to evolve rapidly, driving the enormous increase in human population over the last 10,000 years and the transformation (and devastation) of the biosphere. The rapid proliferation of the internet is changing human culture, including everything from the way we find mates to the way democracy functions, or fails to function. The emergence of the BINC (Bio, Info, Nano, Cogno) technologies promises to further accelerate this change. We are acquiring an ever-increasing ability to engineer devices at a molecular level, to control the genome, and to create new forms of life and intelligence...

Protein Science by DNA Sequencing: How Advances in Molecular Biology Are Accelerating Biochemistry.

PubMed

Higgins, Sean A; Savage, David F

2018-01-09

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 that allow massively parallel protein biochemistry and 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.

Directional acceleration vector-driven displacement of fluids (DAVD-DOF)

NASA Technical Reports Server (NTRS)

Clarke, Mark S. F. (Inventor); Feeback, Daniel L. (Inventor)

2004-01-01

Centrifugal analyzer and method for staining biological or non-biological samples in microgravity, wherein the method utilizes an increase in weight of a fluid sample as a function of g-load, to overcome cohesive and frictional forces from preventing its movement in a preselected direction. Apparatus is characterized by plural specimen reservoirs and channels in a slide, each channel being of differing cross-section, wherein respective samples are selectively dispensed, from the reservoirs in response to an imposed g-factor, precedent to sample staining. Within the method, one thus employs microscope slides which define channels, each being of a differing cross-section dimension relative to others. In combination therewith, centrifugal slide mounting apparatus controllably imposes g-vectors of differing magnitudes within a defined structure of the centrifuge such as a chip array.

At a glance: cellular biology for engineers.

PubMed

Khoshmanesh, K; Kouzani, A Z; Nahavandi, S; Baratchi, S; Kanwar, J R

2008-10-01

Engineering contributions have played an important role in the rise and evolution of cellular biology. Engineering technologies have helped biologists to explore the living organisms at cellular and molecular levels, and have created new opportunities to tackle the unsolved biological problems. There is now a growing demand to further expand the role of engineering in cellular biology research. For an engineer to play an effective role in cellular biology, the first essential step is to understand the cells and their components. However, the stumbling block of this step is to comprehend the information given in the cellular biology literature because it best suits the readers with a biological background. This paper aims to overcome this bottleneck by describing the human cell components as micro-plants that form cells as micro-bio-factories. This concept can accelerate the engineers' comprehension of the subject. In this paper, first the structure and function of different cell components are described. In addition, the engineering attempts to mimic various cell components through numerical modelling or physical implementation are highlighted. Next, the interaction of different cell components that facilitate complicated chemical processes, such as energy generation and protein synthesis, are described. These complex interactions are translated into simple flow diagrams, generally used by engineers to represent multi-component processes.

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

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

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 acceleratorsmore » 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.« less

Molecular and physiological manifestations and measurement of aging in humans.

PubMed

Khan, Sadiya S; Singer, Benjamin D; Vaughan, Douglas E

2017-08-01

Biological aging is associated with a reduction in the reparative and regenerative potential in tissues and organs. This reduction manifests as a decreased physiological reserve in response to stress (termed homeostenosis) and a time-dependent failure of complex molecular mechanisms that cumulatively create disorder. Aging inevitably occurs with time in all organisms and emerges on a molecular, cellular, organ, and organismal level with genetic, epigenetic, and environmental modulators. Individuals with the same chronological age exhibit differential trajectories of age-related decline, and it follows that we should assess biological age distinctly from chronological age. In this review, we outline mechanisms of aging with attention to well-described molecular and cellular hallmarks and discuss physiological changes of aging at the organ-system level. We suggest methods to measure aging with attention to both molecular biology (e.g., telomere length and epigenetic marks) and physiological function (e.g., lung function and echocardiographic measurements). Finally, we propose a framework to integrate these molecular and physiological data into a composite score that measures biological aging in humans. Understanding the molecular and physiological phenomena that drive the complex and multifactorial processes underlying the variable pace of biological aging in humans will inform how researchers assess and investigate health and disease over the life course. This composite biological age score could be of use to researchers seeking to characterize normal, accelerated, and exceptionally successful aging as well as to assess the effect of interventions aimed at modulating human aging. © 2017 The Authors. Aging Cell published by the Anatomical Society and John Wiley & Sons Ltd.

Radiobiological research at JINR's accelerators

NASA Astrophysics Data System (ADS)

Krasavin, E. A.

2016-04-01

The half-a-century development of radiobiological studies at the Joint Institute for Nuclear Research (JINR) is reviewed on a stage-by-stage basis. With the use of the institute's accelerators, some key aspects of radiation biology have been settled, including the relative biological effectiveness (RBE) of various types of ionizing radiation with different physical characteristics; radiation-induced mutagenesis mechanisms, and the formation and repair of genetic structure damage. Practical space radiobiology problems that can be solved using high-energy charged particles are discussed.

Organ-On-A-Chip Platforms: A Convergence of Advanced Materials, Cells, and Microscale Technologies.

PubMed

Ahadian, Samad; Civitarese, Robert; Bannerman, Dawn; Mohammadi, Mohammad Hossein; Lu, Rick; Wang, Erika; Davenport-Huyer, Locke; Lai, Ben; Zhang, Boyang; Zhao, Yimu; Mandla, Serena; Korolj, Anastasia; Radisic, Milica

2018-01-01

Significant advances in biomaterials, stem cell biology, and microscale technologies have enabled the fabrication of biologically relevant tissues and organs. Such tissues and organs, referred to as organ-on-a-chip (OOC) platforms, have emerged as a powerful tool in tissue analysis and disease modeling for biological and pharmacological applications. A variety of biomaterials are used in tissue fabrication providing multiple biological, structural, and mechanical cues in the regulation of cell behavior and tissue morphogenesis. Cells derived from humans enable the fabrication of personalized OOC platforms. Microscale technologies are specifically helpful in providing physiological microenvironments for tissues and organs. In this review, biomaterials, cells, and microscale technologies are described as essential components to construct OOC platforms. The latest developments in OOC platforms (e.g., liver, skeletal muscle, cardiac, cancer, lung, skin, bone, and brain) are then discussed as functional tools in simulating human physiology and metabolism. Future perspectives and major challenges in the development of OOC platforms toward accelerating clinical studies of drug discovery are finally highlighted. © 2017 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Unexpected Levels of Biological Activity during the Polar Night Offer New Perspectives on a Warming Arctic.

PubMed

Berge, Jørgen; Daase, Malin; Renaud, Paul E; Ambrose, William G; Darnis, Gerald; Last, Kim S; Leu, Eva; Cohen, Jonathan H; Johnsen, Geir; Moline, Mark A; Cottier, Finlo; Varpe, Øystein; Shunatova, Natalia; Bałazy, Piotr; Morata, Nathalie; Massabuau, Jean-Charles; Falk-Petersen, Stig; Kosobokova, Ksenia; Hoppe, Clara J M; Węsławski, Jan Marcin; Kukliński, Piotr; Legeżyńska, Joanna; Nikishina, Daria; Cusa, Marine; Kędra, Monika; Włodarska-Kowalczuk, Maria; Vogedes, Daniel; Camus, Lionel; Tran, Damien; Michaud, Emma; Gabrielsen, Tove M; Granovitch, Andrei; Gonchar, Anya; Krapp, Rupert; Callesen, Trine A

2015-10-05

The current understanding of Arctic ecosystems is deeply rooted in the classical view of a bottom-up controlled system with strong physical forcing and seasonality in primary-production regimes. Consequently, the Arctic polar night is commonly disregarded as a time of year when biological activities are reduced to a minimum due to a reduced food supply. Here, based upon a multidisciplinary ecosystem-scale study from the polar night at 79°N, we present an entirely different view. Instead of an ecosystem that has entered a resting state, we document a system with high activity levels and biological interactions across most trophic levels. In some habitats, biological diversity and presence of juvenile stages were elevated in winter months compared to the more productive and sunlit periods. Ultimately, our results suggest a different perspective regarding ecosystem function that will be of importance for future environmental management and decision making, especially at a time when Arctic regions are experiencing accelerated environmental change [1]. Copyright © 2015 Elsevier Ltd. All rights reserved.

Hydrolysis of tRNA(sup Phe) on Suspensions of Amino Acids

NASA Technical Reports Server (NTRS)

Gao, Kui; Orgel, Leslie E.

2001-01-01

RNA is adsorbed strongly on suspensions of many moderately soluble organic solids. In some cases, the hydrolysis of tRNA(sup Phe) is greatly accelerated by adsorption, and the major sites of hydrolysis are changed from those that are important in homogeneous solution. Here we show that the hydrolysis is greatly accelerated by suspensions of aspartic acid and beta-glutamic acid but not by suspensions of alpha-glutamic acid, asparagine, or glutamine. The non-enzymatic hydrolysis of RNA has been studied extensively, especially because of its relevance to the mechanisms of action of ribozymes and to biotechnology and therapy. Many ribonucleases, ribozymes, and non-biological catalysts function via acid-base catalysis of an intramolecular transesterification mechanism in which the 2'-OH group attacks the adjacent phosphate group. The pentacoordinated phosphorane intermediate may collapse back to starting material, or yield isomerized or cleaved products.

Systems Biology-Based Platforms to Accelerate Research of Emerging Infectious Diseases.

PubMed

Oh, Soo Jin; Choi, Young Ki; Shin, Ok Sarah

2018-03-01

Emerging infectious diseases (EIDs) pose a major threat to public health and security. Given the dynamic nature and significant impact of EIDs, the most effective way to prevent and protect against them is to develop vaccines in advance. Systems biology approaches provide an integrative way to understand the complex immune response to pathogens. They can lead to a greater understanding of EID pathogenesis and facilitate the evaluation of newly developed vaccine-induced immunity in a timely manner. In recent years, advances in high throughput technologies have enabled researchers to successfully apply systems biology methods to analyze immune responses to a variety of pathogens and vaccines. Despite recent advances, computational and biological challenges impede wider application of systems biology approaches. This review highlights recent advances in the fields of systems immunology and vaccinology, and presents ways that systems biology-based platforms can be applied to accelerate a deeper understanding of the molecular mechanisms of immunity against EIDs. © Copyright: Yonsei University College of Medicine 2018.

Systems Biology-Based Platforms to Accelerate Research of Emerging Infectious Diseases

PubMed Central

2018-01-01

Emerging infectious diseases (EIDs) pose a major threat to public health and security. Given the dynamic nature and significant impact of EIDs, the most effective way to prevent and protect against them is to develop vaccines in advance. Systems biology approaches provide an integrative way to understand the complex immune response to pathogens. They can lead to a greater understanding of EID pathogenesis and facilitate the evaluation of newly developed vaccine-induced immunity in a timely manner. In recent years, advances in high throughput technologies have enabled researchers to successfully apply systems biology methods to analyze immune responses to a variety of pathogens and vaccines. Despite recent advances, computational and biological challenges impede wider application of systems biology approaches. This review highlights recent advances in the fields of systems immunology and vaccinology, and presents ways that systems biology-based platforms can be applied to accelerate a deeper understanding of the molecular mechanisms of immunity against EIDs. PMID:29436184

Gene Editing and Human Pluripotent Stem Cells: Tools for Advancing Diabetes Disease Modeling and Beta-Cell Development.

PubMed

Millette, Katelyn; Georgia, Senta

2017-10-05

This review will focus on the multiple approaches to gene editing and address the potential use of genetically modified human pluripotent stem cell-derived beta cells (SC-β) as a tool to study human beta-cell development and model their function in diabetes. We will explore how new variations of CRISPR/Cas9 gene editing may accelerate our understanding of beta-cell developmental biology, elucidate novel mechanisms that establish and regulate beta-cell function, and assist in pioneering new therapeutic modalities for treating diabetes. Improvements in CRISPR/Cas9 target specificity and homology-directed recombination continue to advance its use in engineering stem cells to model and potentially treat disease. We will review how CRISPR/Cas9 gene editing is informing our understanding of beta-cell development and expanding the therapeutic possibilities for treating diabetes and other diseases. Here we focus on the emerging use of gene editing technology, specifically CRISPR/Cas9, as a means of manipulating human gene expression to gain novel insights into the roles of key factors in beta-cell development and function. Taken together, the combined use of SC-β cells and CRISPR/Cas9 gene editing will shed new light on human beta-cell development and function and accelerate our progress towards developing new therapies for patients with diabetes.

Accelerated telomere attrition is associated with relative household income, diet and inflammation in the pSoBid cohort.

PubMed

Shiels, Paul G; McGlynn, Liane M; MacIntyre, Alan; Johnson, Paul C D; Batty, G David; Burns, Harry; Cavanagh, Jonathan; Deans, Kevin A; Ford, Ian; McConnachie, Alex; McGinty, Agnes; McLean, Jennifer S; Millar, Keith; Sattar, Naveed; Tannahill, Carol; Velupillai, Yoga N; Packard, Chris J

2011-01-01

It has previously been hypothesized that lower socio-economic status can accelerate biological ageing, and predispose to early onset of disease. This study investigated the association of socio-economic and lifestyle factors, as well as traditional and novel risk factors, with biological-ageing, as measured by telomere length, in a Glasgow based cohort that included individuals with extreme socio-economic differences. A total of 382 blood samples from the pSoBid study were available for telomere analysis. For each participant, data was available for socio-economic status factors, biochemical parameters and dietary intake. Statistical analyses were undertaken to investigate the association between telomere lengths and these aforementioned parameters. The rate of age-related telomere attrition was significantly associated with low relative income, housing tenure and poor diet. Notably, telomere length was positively associated with LDL and total cholesterol levels, but inversely correlated to circulating IL-6. These data suggest lower socio-economic status and poor diet are relevant to accelerated biological ageing. They also suggest potential associations between elevated circulating IL-6, a measure known to predict cardiovascular disease and diabetes with biological ageing. These observations require further study to tease out potential mechanistic links.

Radiobiological study by using laser-driven proton beams

NASA Astrophysics Data System (ADS)

Yogo, A.; Sato, K.; Nishikino, M.; Mori, M.; Teshima, T.; Numasaki, H.; Murakami, M.; Demizu, Y.; Akagi, S.; Nagayama, S.; Ogura, K.; Sagisaka, A.; Orimo, S.; Nishiuchi, M.; Pirozhkov, A. S.; Ikegami, M.; Tampo, M.; Sakaki, H.; Suzuki, M.; Daito, I.; Oishi, Y.; Sugiyama, H.; Kiriyama, H.; Okada, H.; Kanazawa, S.; Kondo, S.; Shimomura, T.; Nakai, Y.; Tanoue, M.; Sugiyama, H.; Sasao, H.; Wakai, D.; Kawachi, T.; Nishimura, H.; Bolton, P. R.; Daido, H.

2009-07-01

Particle acceleration driven by high-intensity laser systems is widely attracting interest as a potential alternative to conventional ion acceleration, including ion accelerator applications to tumor therapy. Recent works have shown that a high intensity laser pulse can produce single proton bunches of a high current and a short pulse duration. This unique feature of laser-ion acceleration can lead to progress in the development of novel ion sources. However, there has been no experimental study of the biological effects of laser-driven ion beams. We describe in this report the first demonstrated irradiation effect of laser-accelerated protons on human lung cancer cells. In-vitro A549 cells are irradiated with a proton dose of 20 Gy, resulting in a distinct formation of γ-H2AX foci as an indicator of DNA double-strand breaks. This is a pioneering result that points to future investigations of the radiobiological effects of laser-driven ion beams. The laser-driven ion beam is apotential excitation source for time-resolved determination of hydroxyl (OH) radical yield, which will explore relationship between the fundamental chemical reactions of radiation effects and consequent biological processes.

Biomimetic approaches with smart interfaces for bone regeneration.

PubMed

Sailaja, G S; Ramesh, P; Vellappally, Sajith; Anil, Sukumaran; Varma, H K

2016-11-05

A 'smart tissue interface' is a host tissue-biomaterial interface capable of triggering favourable biochemical events inspired by stimuli responsive mechanisms. In other words, biomaterial surface is instrumental in dictating the interface functionality. This review aims to investigate the fundamental and favourable requirements of a 'smart tissue interface' that can positively influence the degree of healing and promote bone tissue regeneration. A biomaterial surface when interacts synergistically with the dynamic extracellular matrix, the healing process become accelerated through development of a smart interface. The interface functionality relies equally on bound functional groups and conjugated molecules belonging to the biomaterial and the biological milieu it interacts with. The essential conditions for such a special biomimetic environment are discussed. We highlight the impending prospects of smart interfaces and trying to relate the design approaches as well as critical factors that determine species-specific functionality with special reference to bone tissue regeneration.

Mutagenic effect of accelerated heavy ions on bacterial cells

NASA Astrophysics Data System (ADS)

Boreyko, A. V.; Krasavin, E. A.

2011-11-01

The heavy ion accelerators of the Joint Institute for Nuclear Research were used to study the regularities and mechanisms of formation of different types of mutations in prokaryote cells. The induction of direct (lac-, ton B-, col B) mutations for Esherichia coli cells and reverse his- → His+ mutations of Salmonella typhimurium, Bacillus subtilis cells under the action of radiation in a wide range of linear energy transfer (LET) was studied. The regularities of formation of gene and structural (tonB trp-) mutations for Esherichia coli bacteria under the action of accelerated heavy ions were studied. It was demonstrated that the rate of gene mutations as a function of the dose under the action of Γ rays and accelerated heavy ions is described by linear-quadratic functions. For structural mutations, linear "dose-effect" dependences are typical. The quadratic character of mutagenesis dose curves is determined by the "interaction" of two independent "hitting" events in the course of SOS repair of genetic structures. The conclusion made was that gene mutations under the action of accelerated heavy ions are induced by δ electron regions of charged particle tracks. The methods of SOS chromotest, SOS lux test, and λ prophage induction were used to study the regularities of SOS response of cells under the action of radiations in a wide LET range. The following proposition was substantiated: the molecular basis for formation of gene mutations are cluster single-strand DNA breaks, and that for structural mutations, double-strand DNA breaks. It was found out that the LET dependence of the relative biological efficiency of accelerated ions is described by curves with a local maximum. It was demonstrated that the biological efficiency of ionizing radiations with different physical characteristics on cells with different genotype, estimated by the lethal action, induction of gene and deletion mutations, precision excision of transposons, is determined by the specific features of energy transfer of the radiations that affect the character of induced DNA damage, and the efficiency inducible and constitutive cell repair systems. The growth of relative biological efficiency of heavy charged particles is determined by the growth of the damage yield of the DNA participating in the formation of radiation-induced effects, and higher efficiency of inducible repair systems. It was established that the LET value ( L max) for which the maximum (according to the applied irradiation criteria) coefficients of relative biological efficiency are observed varies depending on the character of the registered radiation induced effect. It was demonstrated that for gene mutations and induction of precision excision of mobile elements the values of L max are realized in a LET range of ≈20 keV/μm. For lethal effects of irradiation and induction of deletion mutations the value of L max is ≈ 100 and 50 keV/μm, respectively. The differences in the L max for the studied radiation gene effectis are determined by the different type of DNA damage participating in the mutation process. A molecular model of the formation of gene mutations in Escherichia coli cells under the action of ionizing radiation was proposed. Basic DNA radiation damage and main repair ways were considered in the framework of this model. The basis is the idea of the decisive role of mutagenic, error-prone, branch of SOS repair in fixing premutation DNA damage into point mutations. It was demonstrated that the central mechanism in this process is the formation of an inducible multi-enzymatic complex including the DNA polymerase V (Umu C), RecA-protease, SSB proteins, subunits of DNA polymerase III, performing erroneous DNA synthesis on the damaged matrix. A mathematical model of induction of gene mutations under ultraviolet cell irradiation was developed based on the molecular model.

Extracellular mass transport considerations for space flight research concerning suspended and adherent in vitro cell cultures

NASA Technical Reports Server (NTRS)

Klaus, David M.; Benoit, Michael R.; Nelson, Emily S.; Hammond, Timmothy G.

2004-01-01

Conducting biological research in space requires consideration be given to isolating appropriate control parameters. For in vitro cell cultures, numerous environmental factors can adversely affect data interpretation. A biological response attributed to microgravity can, in theory, be explicitly correlated to a specific lack of weight or gravity-driven motion occurring to, within or around a cell. Weight can be broken down to include the formation of hydrostatic gradients, structural load (stress) or physical deformation (strain). Gravitationally induced motion within or near individual cells in a fluid includes sedimentation (or buoyancy) of the cell and associated shear forces, displacement of cytoskeleton or organelles, and factors associated with intra- or extracellular mass transport. Finally, and of particular importance for cell culture experiments, the collective effects of gravity must be considered for the overall system consisting of the cells, their environment and the device in which they are contained. This does not, however, rule out other confounding variables such as launch acceleration, on orbit vibration, transient acceleration impulses or radiation, which can be isolated using onboard centrifuges or vibration isolation techniques. A framework is offered for characterizing specific cause-and-effect relationships for gravity-dependent responses as a function of the above parameters.

Boundary layer drag reduction research hypotheses derived from bio-inspired surface and recent advanced applications.

PubMed

Luo, Yuehao; Yuan, Lu; Li, Jianhua; Wang, Jianshe

2015-12-01

Nature has supplied the inexhaustible resources for mankind, and at the same time, it has also progressively developed into the school for scientists and engineers. Through more than four billions years of rigorous and stringent evolution, different creatures in nature gradually exhibit their own special and fascinating biological functional surfaces. For example, sharkskin has the potential drag-reducing effect in turbulence, lotus leaf possesses the self-cleaning and anti-foiling function, gecko feet have the controllable super-adhesion surfaces, the flexible skin of dolphin can accelerate its swimming velocity. Great profits of applying biological functional surfaces in daily life, industry, transportation and agriculture have been achieved so far, and much attention from all over the world has been attracted and focused on this field. In this overview, the bio-inspired drag-reducing mechanism derived from sharkskin is explained and explored comprehensively from different aspects, and then the main applications in different fluid engineering are demonstrated in brief. This overview will inevitably improve the comprehension of the drag reduction mechanism of sharkskin surface and better understand the recent applications in fluid engineering. Copyright © 2015 Elsevier Ltd. All rights reserved.

On the application of accelerated molecular dynamics to liquid water simulations.

PubMed

de Oliveira, César Augusto F; Hamelberg, Donald; McCammon, J Andrew

2006-11-16

Our group recently proposed a robust bias potential function that can be used in an efficient all-atom accelerated molecular dynamics (MD) approach to simulate the transition of high energy barriers without any advance knowledge of the potential-energy landscape. The main idea is to modify the potential-energy surface by adding a bias, or boost, potential in regions close to the local minima, such that all transitions rates are increased. By applying the accelerated MD simulation method to liquid water, we observed that this new simulation technique accelerates the molecular motion without losing its microscopic structure and equilibrium properties. Our results showed that the application of a small boost energy on the potential-energy surface significantly reduces the statistical inefficiency of the simulation while keeping all the other calculated properties unchanged. On the other hand, although aggressive acceleration of the dynamics simulation increases the self-diffusion coefficient of water molecules greatly and dramatically reduces the correlation time of the simulation, configurations representative of the true structure of liquid water are poorly sampled. Our results also showed the strength and robustness of this simulation technique, which confirm this approach as a very useful and promising tool to extend the time scale of the all-atom simulations of biological system with explicit solvent models. However, we should keep in mind that there is a compromise between the strength of the boost applied in the simulation and the reproduction of the ensemble average properties.

BATMAN-TCM: a Bioinformatics Analysis Tool for Molecular mechANism of Traditional Chinese Medicine.

PubMed

Liu, Zhongyang; Guo, Feifei; Wang, Yong; Li, Chun; Zhang, Xinlei; Li, Honglei; Diao, Lihong; Gu, Jiangyong; Wang, Wei; Li, Dong; He, Fuchu

2016-02-16

Traditional Chinese Medicine (TCM), with a history of thousands of years of clinical practice, is gaining more and more attention and application worldwide. And TCM-based new drug development, especially for the treatment of complex diseases is promising. However, owing to the TCM's diverse ingredients and their complex interaction with human body, it is still quite difficult to uncover its molecular mechanism, which greatly hinders the TCM modernization and internationalization. Here we developed the first online Bioinformatics Analysis Tool for Molecular mechANism of TCM (BATMAN-TCM). Its main functions include 1) TCM ingredients' target prediction; 2) functional analyses of targets including biological pathway, Gene Ontology functional term and disease enrichment analyses; 3) the visualization of ingredient-target-pathway/disease association network and KEGG biological pathway with highlighted targets; 4) comparison analysis of multiple TCMs. Finally, we applied BATMAN-TCM to Qishen Yiqi dripping Pill (QSYQ) and combined with subsequent experimental validation to reveal the functions of renin-angiotensin system responsible for QSYQ's cardioprotective effects for the first time. BATMAN-TCM will contribute to the understanding of the "multi-component, multi-target and multi-pathway" combinational therapeutic mechanism of TCM, and provide valuable clues for subsequent experimental validation, accelerating the elucidation of TCM's molecular mechanism. BATMAN-TCM is available at http://bionet.ncpsb.org/batman-tcm.

Bioinformatics: A History of Evolution "In Silico"

ERIC Educational Resources Information Center

Ondrej, Vladan; Dvorak, Petr

2012-01-01

Bioinformatics, biological databases, and the worldwide use of computers have accelerated biological research in many fields, such as evolutionary biology. Here, we describe a primer of nucleotide sequence management and the construction of a phylogenetic tree with two examples; the two selected are from completely different groups of organisms:…

Space Resources for Teachers: Biology, Including Suggestions for Classroom Activities and Laboratory Experiments.

ERIC Educational Resources Information Center

Lee, Tom E.; And Others

This compilation of resource units concerns the latest developments in space biology. Some of the topics included are oxygen consumption, temperature, radiation, rhythms, weightlessness, acceleration and vibration stress, toxicity, and sensory and perceptual problems. Many of the topics are interdisciplinary and relate biology, physiology,…

The Scanning Electron Microscope As An Accelerator For The Undergraduate Advanced Physics Laboratory

NASA Astrophysics Data System (ADS)

Peterson, Randolph S.; Berggren, Karl K.; Mondol, Mark

2011-06-01

Few universities or colleges have an accelerator for use with advanced physics laboratories, but many of these institutions have a scanning electron microscope (SEM) on site, often in the biology department. As an accelerator for the undergraduate, advanced physics laboratory, the SEM is an excellent substitute for an ion accelerator. Although there are no nuclear physics experiments that can be performed with a typical 30 kV SEM, there is an opportunity for experimental work on accelerator physics, atomic physics, electron-solid interactions, and the basics of modern e-beam lithography.

Many human accelerated regions are developmental enhancers

PubMed Central

Capra, John A.; Erwin, Genevieve D.; McKinsey, Gabriel; Rubenstein, John L. R.; Pollard, Katherine S.

2013-01-01

The genetic changes underlying the dramatic differences in form and function between humans and other primates are largely unknown, although it is clear that gene regulatory changes play an important role. To identify regulatory sequences with potentially human-specific functions, we and others used comparative genomics to find non-coding regions conserved across mammals that have acquired many sequence changes in humans since divergence from chimpanzees. These regions are good candidates for performing human-specific regulatory functions. Here, we analysed the DNA sequence, evolutionary history, histone modifications, chromatin state and transcription factor (TF) binding sites of a combined set of 2649 non-coding human accelerated regions (ncHARs) and predicted that at least 30% of them function as developmental enhancers. We prioritized the predicted ncHAR enhancers using analysis of TF binding site gain and loss, along with the functional annotations and expression patterns of nearby genes. We then tested both the human and chimpanzee sequence for 29 ncHARs in transgenic mice, and found 24 novel developmental enhancers active in both species, 17 of which had very consistent patterns of activity in specific embryonic tissues. Of these ncHAR enhancers, five drove expression patterns suggestive of different activity for the human and chimpanzee sequence at embryonic day 11.5. The changes to human non-coding DNA in these ncHAR enhancers may modify the complex patterns of gene expression necessary for proper development in a human-specific manner and are thus promising candidates for understanding the genetic basis of human-specific biology. PMID:24218637

MCAM: multiple clustering analysis methodology for deriving hypotheses and insights from high-throughput proteomic datasets.

PubMed

Naegle, Kristen M; Welsch, Roy E; Yaffe, Michael B; White, Forest M; Lauffenburger, Douglas A

2011-07-01

Advances in proteomic technologies continue to substantially accelerate capability for generating experimental data on protein levels, states, and activities in biological samples. For example, studies on receptor tyrosine kinase signaling networks can now capture the phosphorylation state of hundreds to thousands of proteins across multiple conditions. However, little is known about the function of many of these protein modifications, or the enzymes responsible for modifying them. To address this challenge, we have developed an approach that enhances the power of clustering techniques to infer functional and regulatory meaning of protein states in cell signaling networks. We have created a new computational framework for applying clustering to biological data in order to overcome the typical dependence on specific a priori assumptions and expert knowledge concerning the technical aspects of clustering. Multiple clustering analysis methodology ('MCAM') employs an array of diverse data transformations, distance metrics, set sizes, and clustering algorithms, in a combinatorial fashion, to create a suite of clustering sets. These sets are then evaluated based on their ability to produce biological insights through statistical enrichment of metadata relating to knowledge concerning protein functions, kinase substrates, and sequence motifs. We applied MCAM to a set of dynamic phosphorylation measurements of the ERRB network to explore the relationships between algorithmic parameters and the biological meaning that could be inferred and report on interesting biological predictions. Further, we applied MCAM to multiple phosphoproteomic datasets for the ERBB network, which allowed us to compare independent and incomplete overlapping measurements of phosphorylation sites in the network. We report specific and global differences of the ERBB network stimulated with different ligands and with changes in HER2 expression. Overall, we offer MCAM as a broadly-applicable approach for analysis of proteomic data which may help increase the current understanding of molecular networks in a variety of biological problems. © 2011 Naegle et al.

[Physico-chemical features of dinitrosyl iron complexes with natural thiol-containing ligands underlying biological activities of these complexes].

PubMed

Vanin, A F; Borodulin, R R; Kubrina, L N; Mikoian, V D; Burbaev, D Sh

2013-01-01

Current notions and new experimental data of the authors on physico-chemical features of dinitrosyl iron complexes with natural thiol-containing ligands (glutathione or cysteine), underlying the ability of the complexes to act as NO molecule and nitrosonium ion donors, are considered. This ability determines various biological activities of dinitrosyl iron complexes--inducing long-lasting vasodilation and thereby long-lasting hypotension in human and animals, inhibiting pellet aggregation, increasing red blood cell elasticity, thereby stimulating microcirculation, and reducing necrotic zone in animals with myocardial infarction. Moreover, dinitrosyl iron complexes are capable of accelerating skin wound healing, improving the function of penile cavernous tissue, blocking apoptosis development in cell cultures. When decomposed dinitrosyl iron complexes can exert cytotoxic effect that can be used for curing infectious and carcinogenic pathologies.

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

PubMed

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

2017-02-10

Conservation of species and ecosystems is increasingly difficult because anthropogenic impacts are pervasive and accelerating. Under this rapid global change, maximizing conservation success requires a paradigm shift from maintaining ecosystems in idealized past states toward facilitating their adaptive and functional capacities, even as species ebb and flow individually. Developing effective strategies under this new paradigm will require deeper understanding of the long-term dynamics that govern ecosystem persistence and reconciliation of conflicts among approaches to conserving historical versus novel ecosystems. Integrating emerging information from conservation biology, paleobiology, and the Earth sciences is an important step forward on the path to success. Maintaining nature in all its aspects will also entail immediately addressing the overarching threats of growing human population, overconsumption, pollution, and climate change. Copyright © 2017, American Association for the Advancement of Science.

Human development II: we need an integrated theory for matter, life and consciousness to understand life and healing.

PubMed

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

2006-07-06

For almost a decade, we have experimented with supporting the philosophical development of severely ill patients to induce recovery and spontaneous healing. Recently, we have observed a new pattern of extremely rapid, spontaneous healing that apparently can facilitate even the spontaneous remission of cancer and the spontaneous recovery of mental diseases like schizophrenia and borderline schizophrenia. Our working hypothesis is that the accelerated healing is a function of the patient's brain-mind and body-mind coming closer together due to the development of what we call "deep" cosmology. To understand and describe what happens at a biological level, we have suggested naming the process adult human metamorphosis, a possibility that is opened by the human genome showing full generic equipment for metamorphosis. To understand the mechanistic details in the complicated interaction between consciousness and biology, we need an adequate theory for biological information. In a series of papers, we propose what we call "holistic biology for holistic medicine". We suggest that a relatively simple model based on interacting wholenesses instead of isolated parts can shed a new light on a number of difficult issues that we need to explain and understand in biology and medicine in order to understand and use metamorphosis in the holistic medical clinic. We aim to give a holistic theoretical interpretation of biological phenomena at large, morphogenesis, evolution, immune system regulation (self-nonself discrimination), brain function, consciousness, and health in particular. We start at the most fundamental problem: what is biological information at the subcellular, cellular, and supracellular levels if we presume that it is the same phenomenon on all levels (using Occam's razor), and how can this be described scientifically? The problems we address are all connected to the information flow in the functioning, living organism: function of the brain and consciousness, the regulations of the immune system and cell growth, the dynamics of health and disease. We suggest that life utilizes an unseen fine structure of the physical energy of the universe at a subparticular or quantum level to give information-directed self-organization; we give a first sketch of a possible fractal structure of the energy able to both contain and communicate biological information and carry individual and collective consciousness. Finally, thorough our analysis, we put up a model for adult human metamorphosis.

DNA methylation age is not accelerated in brain or blood of subjects with schizophrenia.

PubMed

McKinney, Brandon C; Lin, Huang; Ding, Ying; Lewis, David A; Sweet, Robert A

2017-10-05

Individuals with schizophrenia (SZ) exhibit multiple premature age-related phenotypes and die ~20years prematurely. The accelerated aging hypothesis of SZ has been advanced to explain these observations, it posits that SZ-associated factors accelerate the progressive biological changes associated with normal aging. Testing the hypothesis has been limited by the absence of robust, meaningful, and multi-tissue measures of biological age. Recently, a method was described in which DNA methylation (DNAm) levels at 353 genomic sites are used to produce "DNAm age", an estimate of biological age with advantages over existing measures. We used this method and 3 publicly-available DNAm datasets, 1 from brain and 2 from blood, to test the hypothesis. The brain dataset was composed of data from the dorsolateral prefrontal cortex of 232 non-psychiatric control (NPC) and 195 SZ subjects. Blood dataset #1 was composed of data from whole blood of 304 NPC and 332 SZ subjects, and blood dataset #2 was composed of data from whole blood of 405 NPC and 260 SZ subjects. DNAm age and chronological age correlated strongly (r=0.92-0.95, p<0.0001) in both NPC and SZ subjects in all 3 datasets. DNAm age acceleration did not differ between NPC and SZ subjects in the brain dataset (t=0.52, p=0.60), blood dataset #1 (t=1.51, p=0.13), or blood dataset #2 (t=0.93, p=0.35). Consistent with our previous findings from a smaller study of postmortem brains, our findings suggest there is no acceleration of brain or blood aging in SZ and, thus, do not support the accelerated aging hypothesis of SZ. Copyright © 2017 Elsevier B.V. All rights reserved.

A Native Threonine Coordinates Ordered Water to Tune Light-Oxygen-Voltage (LOV) Domain Photocycle Kinetics and Osmotic Stress Signaling in Trichoderma reesei ENVOY.

PubMed

Lokhandwala, Jameela; Silverman Y de la Vega, Rafael I; Hopkins, Hilary C; Britton, Collin W; Rodriguez-Iglesias, Aroa; Bogomolni, Roberto; Schmoll, Monika; Zoltowski, Brian D

2016-07-08

Light-oxygen-voltage (LOV) domain-containing proteins function as small light-activated modules capable of imparting blue light control of biological processes. Their small modular nature has made them model proteins for allosteric signal transduction and optogenetic devices. Despite intense research, key aspects of their signal transduction mechanisms and photochemistry remain poorly understood. In particular, ordered water has been identified as a possible key mediator of photocycle kinetics, despite the lack of ordered water in the LOV active site. Herein, we use recent crystal structures of a fungal LOV protein ENVOY to interrogate the role of Thr(101) in recruiting water to the flavin active site where it can function as an intrinsic base to accelerate photocycle kinetics. Kinetic and molecular dynamic simulations confirm a role in solvent recruitment to the active site and identify structural changes that correlate with solvent recruitment. In vivo analysis of T101I indicates a direct role of the Thr(101) position in mediating adaptation to osmotic stress, thereby verifying biological relevance of ordered water in LOV signaling. The combined studies identify position 101 as a mediator of both allostery and photocycle catalysis that can impact organism physiology. © 2016 by The American Society for Biochemistry and Molecular Biology, Inc.

Recent developments of ion sources for life-science studies at the Heavy Ion Medical Accelerator in Chiba (invited)

NASA Astrophysics Data System (ADS)

Kitagawa, A.; Drentje, A. G.; Fujita, T.; Muramatsu, M.; Fukushima, K.; Shiraishi, N.; Suzuki, T.; Takahashi, K.; Takasugi, W.; Biri, S.; Rácz, R.; Kato, Y.; Uchida, T.; Yoshida, Y.

2016-02-01

With about 1000-h of relativistic high-energy ion beams provided by Heavy Ion Medical Accelerator in Chiba, about 70 users are performing various biology experiments every year. A rich variety of ion species from hydrogen to xenon ions with a dose rate of several Gy/min is available. Carbon, iron, silicon, helium, neon, argon, hydrogen, and oxygen ions were utilized between 2012 and 2014. Presently, three electron cyclotron resonance ion sources (ECRISs) and one Penning ion source are available. Especially, the two frequency heating techniques have improved the performance of an 18 GHz ECRIS. The results have satisfied most requirements for life-science studies. In addition, this improved performance has realized a feasible solution for similar biology experiments with a hospital-specified accelerator complex.

Biologische Wirkungen der Bestrahlung mit schweren Ionen

NASA Astrophysics Data System (ADS)

Kiefer, Jürgen

1982-06-01

Experiments with accelerated heavy ions may contribute to the understanding of biological radiation action. After outlining the theoretical background experiments are described which were carried out at the UNILAC-machine (Gesellschaft für Schwerionenforschung, Darmstadt, Germany) where ions up to uranium can be accelerated to maximal specific energies of 10 MeV/u. Yeast cells served as biological test systems with the synthesis of ribosomal RNA (r-RNA), colony-forming ability and mutation induction as experimental endpoints. A relationship between action and energy deposition by individual particles can be demonstrated for the inhibition of r-RNA synthesis, in other cases the ion energy plays also an important role indicating that the interaction of δ-electrons from different particles contributes significantly to the biological effect.

Acceleration of recovery in acute renal failure: from cellular mechanisms of tubular repair to innovative targeted therapies.

PubMed

Abbate, M; Remuzzi, G

1996-05-01

Kidney repair from injury is a major focus of interest for research, both clinical and basic, in the field of acute renal failure. This is so because very little progress has been made during the past several years to improve mortality in hospitalized patients with acute renal failure despite the unique potential of the kidney for complete structural and functional recovery. Novel therapeutic options have recently emerged from the knowledge of molecular mechanisms of tissue injury after ischemia, including pathways of endothelial-leukocyte interaction and epithelial cell aggregation mediated by integrin molecules. These strategies are promising because they may target early mechanisms of leukocyte infiltration and tubular obstruction. However, it seems clear that additional interventions should address the reparative program that potentially leads to the full restoration of kidney structure and function. Thus, acceleration of repair from acute renal failure is achieved experimentally by growth factors which besides different renal actions seem to have in common the ability to stimulate proliferation of surviving tubular epithelial cells. We direct attention to cellular processes which characterize, and possibly have role in, renal repair from acute tubular injury as potential targets of therapy. In addition to proliferation, they include epithelial differentiation and apoptosis. Further investigation in the biology of repair should set the stage for rational design of targeted therapies which may accelerate the pace of recovery and hopefully decrease mortality in such a dramatic and potentially reversible setting.

Estimating the kinetic parameters of activated sludge storage using weighted non-linear least-squares and accelerating genetic algorithm.

PubMed

Fang, Fang; Ni, Bing-Jie; Yu, Han-Qing

2009-06-01

In this study, weighted non-linear least-squares analysis and accelerating genetic algorithm are integrated to estimate the kinetic parameters of substrate consumption and storage product formation of activated sludge. A storage product formation equation is developed and used to construct the objective function for the determination of its production kinetics. The weighted least-squares analysis is employed to calculate the differences in the storage product concentration between the model predictions and the experimental data as the sum of squared weighted errors. The kinetic parameters for the substrate consumption and the storage product formation are estimated to be the maximum heterotrophic growth rate of 0.121/h, the yield coefficient of 0.44 mg CODX/mg CODS (COD, chemical oxygen demand) and the substrate half saturation constant of 16.9 mg/L, respectively, by minimizing the objective function using a real-coding-based accelerating genetic algorithm. Also, the fraction of substrate electrons diverted to the storage product formation is estimated to be 0.43 mg CODSTO/mg CODS. The validity of our approach is confirmed by the results of independent tests and the kinetic parameter values reported in literature, suggesting that this approach could be useful to evaluate the product formation kinetics of mixed cultures like activated sludge. More importantly, as this integrated approach could estimate the kinetic parameters rapidly and accurately, it could be applied to other biological processes.

Managing the future: the Special Virus Leukemia Program and the acceleration of biomedical research.

PubMed

Scheffler, Robin Wolfe

2014-12-01

After the end of the Second World War, cancer virus research experienced a remarkable revival, culminating in the creation in 1964 of the United States National Cancer Institute's Special Virus Leukemia Program (SVLP), an ambitious program of directed biomedical research to accelerate the development of a leukemia vaccine. Studies of cancer viruses soon became the second most highly funded area of research at the Institute, and by far the most generously funded area of biological research. Remarkably, this vast infrastructure for cancer vaccine production came into being before a human leukemia virus was shown to exist. The origins of the SVLP were rooted in as much as shifts in American society as laboratory science. The revival of cancer virus studies was a function of the success advocates and administrators achieved in associating cancer viruses with campaigns against childhood diseases such as polio and leukemia. To address the urgency borne of this new association, the SVLP's architects sought to lessen the power of peer review in favor of centralized Cold War management methods, fashioning viruses as "administrative objects" in order to accelerate the tempo of biomedical research and discovery.

Inertial attitude control of a bat-like morphing-wing air vehicle.

PubMed

Colorado, J; Barrientos, A; Rossi, C; Parra, C

2013-03-01

This paper presents a novel bat-like unmanned aerial vehicle inspired by the morphing-wing mechanism of bats. The goal of this paper is twofold. Firstly, a modelling framework is introduced for analysing how the robot should manoeuvre by means of changing wing morphology. This allows the definition of requirements for achieving forward and turning flight according to the kinematics of the wing modulation. Secondly, an attitude controller named backstepping+DAF is proposed. Motivated by biological evidence about the influence of wing inertia on the production of body accelerations, the attitude control law incorporates wing inertia information to produce desired roll (ϕ) and pitch (θ) acceleration commands (desired angular acceleration function (DAF)). This novel control approach is aimed at incrementing net body forces (F(net)) that generate propulsion. Simulations and wind-tunnel experimental results have shown an increase of about 23% in net body force production during the wingbeat cycle when the wings are modulated using the DAF as a part of the backstepping control law. Results also confirm accurate attitude tracking in spite of high external disturbances generated by aerodynamic loads at airspeeds up to 5 ms⁻¹.

Microarray-based characterization of differential gene expression during vocal fold wound healing in rats

PubMed Central

Welham, Nathan V.; Ling, Changying; Dawson, John A.; Kendziorski, Christina; Thibeault, Susan L.; Yamashita, Masaru

2015-01-01

The vocal fold (VF) mucosa confers elegant biomechanical function for voice production but is susceptible to scar formation following injury. Current understanding of VF wound healing is hindered by a paucity of data and is therefore often generalized from research conducted in skin and other mucosal systems. Here, using a previously validated rat injury model, expression microarray technology and an empirical Bayes analysis approach, we generated a VF-specific transcriptome dataset to better capture the system-level complexity of wound healing in this specialized tissue. We measured differential gene expression at 3, 14 and 60 days post-injury compared to experimentally naïve controls, pursued functional enrichment analyses to refine and add greater biological definition to the previously proposed temporal phases of VF wound healing, and validated the expression and localization of a subset of previously unidentified repair- and regeneration-related genes at the protein level. Our microarray dataset is a resource for the wider research community and has the potential to stimulate new hypotheses and avenues of investigation, improve biological and mechanistic insight, and accelerate the identification of novel therapeutic targets. PMID:25592437

Decoding the complex genetic causes of heart diseases using systems biology.

PubMed

Djordjevic, Djordje; Deshpande, Vinita; Szczesnik, Tomasz; Yang, Andrian; Humphreys, David T; Giannoulatou, Eleni; Ho, Joshua W K

2015-03-01

The pace of disease gene discovery is still much slower than expected, even with the use of cost-effective DNA sequencing and genotyping technologies. It is increasingly clear that many inherited heart diseases have a more complex polygenic aetiology than previously thought. Understanding the role of gene-gene interactions, epigenetics, and non-coding regulatory regions is becoming increasingly critical in predicting the functional consequences of genetic mutations identified by genome-wide association studies and whole-genome or exome sequencing. A systems biology approach is now being widely employed to systematically discover genes that are involved in heart diseases in humans or relevant animal models through bioinformatics. The overarching premise is that the integration of high-quality causal gene regulatory networks (GRNs), genomics, epigenomics, transcriptomics and other genome-wide data will greatly accelerate the discovery of the complex genetic causes of congenital and complex heart diseases. This review summarises state-of-the-art genomic and bioinformatics techniques that are used in accelerating the pace of disease gene discovery in heart diseases. Accompanying this review, we provide an interactive web-resource for systems biology analysis of mammalian heart development and diseases, CardiacCode ( http://CardiacCode.victorchang.edu.au/ ). CardiacCode features a dataset of over 700 pieces of manually curated genetic or molecular perturbation data, which enables the inference of a cardiac-specific GRN of 280 regulatory relationships between 33 regulator genes and 129 target genes. We believe this growing resource will fill an urgent unmet need to fully realise the true potential of predictive and personalised genomic medicine in tackling human heart disease.

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.

Testing the hypothesis of accelerated cerebral white matter aging in schizophrenia and major depression

PubMed Central

Kochunov, P.; Glahn, D.C.; Rowland, L.M.; Olvera, R.L.; Winkler, A; Yang, Y.H.; Sampath, H.; Carpenter, W.T.; Dugarrila, R.; Curran, J.; Blangero, J.; Hong, L.E.

2012-01-01

Introduction Elevated rate of aging-related biological and functional decline, termed accelerated aging, is reported in patients with schizophrenia (SCZ) and major depressive disorder (MDD). We used diffusion tensor imaging (DTI) derived fractional anisotropy (FA) as biomarkers of aging-related decline in white matter (WM) integrity to test the hypotheses of accelerated aging in SCZ and MDD. Methods The SCZ cohort was composed of 58/60 SCZ patients/controls (age=20–60years). MDD cohort was composed of 136/351 MDD patients/controls (age=20–79years). Main outcome measures were the diagnosis-by-age interaction on whole-brain-averaged WM FA values and FA values from twelve major WM tracts. Results Diagnosis-by-age interaction for the whole-brain average FA was significant for the SCZ (p=0.04) but not in MDD cohort (p=0.80). Diagnosis-by-age interaction was nominally significant (p<0.05) for five WM tracts for SCZ and for none of the tracts in the MDD cohort. Tract-specific heterochronicity of the onset of age-related decline in SCZ demonstrated strong negative correlations with the age-of- peak myelination and the rates of age-related decline obtained from normative sample (r=−0.61 and −0.80, p<0.05, respectively). No such trends existed for MDD cohort. Conclusion Cerebral WM showed accelerated aging in SCZ but not in MDD, suggesting some difference in the pathophysiology underlying their WM aging changes. Tract-specific heterochronicity of WM development modulated presentation of accelerated aging in SCZ: white matter tracts that matured later in life appeared more sensitive to the pathophysiology of SCZ and demonstrated more susceptibility to disorder-related accelerated decline in FA values with age. This trend was not observed in MDD cohort. PMID:23200529

Rapid Analyses of Polyetheretherketone Wear Characteristics by Accelerated Wear Testing with Microfabricated Surfaces for Artificial Joint Systems

PubMed Central

Kuo, Chien-Wei

2017-01-01

Wear particle-induced biological responses are the major factors resulting in the loosening and then failure of total joint arthroplasties. It is feasible to improve the lubrication and reduce the wear of artificial joint system. Polyetheretherketone (PEEK) is considered as a potential bearing material due to its mechanical characteristics of resistance to fatigue strain. The PEEK wear particles have been indicated to be involved in biological responses in vitro, and further studies regarding the wear phenomena and wear particle generation are needed. In this study, we have established an accelerated wear testing system with microfabricated surfaces. Various contact pressures and lubricants have been utilized in the accelerated wear tests. Our results showed that increasing contact pressure resulted in an increase of wear particle sizes and wear rate, and the size of PEEK wear particles can be controlled by the feature size of microfabricated surfaces. These results provided the information rapidly about factors that affect the morphology and amount of PEEK wear particles and can be applied in the future for application of PEEK on the biological articulation system. PMID:29230411

Rapid Analyses of Polyetheretherketone Wear Characteristics by Accelerated Wear Testing with Microfabricated Surfaces for Artificial Joint Systems.

PubMed

Su, Chen-Ying; Kuo, Chien-Wei; Fang, Hsu-Wei

2017-01-01

Wear particle-induced biological responses are the major factors resulting in the loosening and then failure of total joint arthroplasties. It is feasible to improve the lubrication and reduce the wear of artificial joint system. Polyetheretherketone (PEEK) is considered as a potential bearing material due to its mechanical characteristics of resistance to fatigue strain. The PEEK wear particles have been indicated to be involved in biological responses in vitro, and further studies regarding the wear phenomena and wear particle generation are needed. In this study, we have established an accelerated wear testing system with microfabricated surfaces. Various contact pressures and lubricants have been utilized in the accelerated wear tests. Our results showed that increasing contact pressure resulted in an increase of wear particle sizes and wear rate, and the size of PEEK wear particles can be controlled by the feature size of microfabricated surfaces. These results provided the information rapidly about factors that affect the morphology and amount of PEEK wear particles and can be applied in the future for application of PEEK on the biological articulation system.

Advanced Accelerators for Medical Applications

NASA Astrophysics Data System (ADS)

Uesaka, Mitsuru; Koyama, Kazuyoshi

We review advanced accelerators for medical applications with respect to the following key technologies: (i) higher RF electron linear accelerator (hereafter “linac”); (ii) optimization of alignment for the proton linac, cyclotron and synchrotron; (iii) superconducting magnet; (iv) laser technology. Advanced accelerators for medical applications are categorized into two groups. The first group consists of compact medical linacs with high RF, cyclotrons and synchrotrons downsized by optimization of alignment and superconducting magnets. The second group comprises laser-based acceleration systems aimed of medical applications in the future. Laser plasma electron/ion accelerating systems for cancer therapy and laser dielectric accelerating systems for radiation biology are mentioned. Since the second group has important potential for a compact system, the current status of the established energy and intensity and of the required stability are given.

Advanced Accelerators for Medical Applications

NASA Astrophysics Data System (ADS)

Uesaka, Mitsuru; Koyama, Kazuyoshi

We review advanced accelerators for medical applications with respect to the following key technologies: (i) higher RF electron linear accelerator (hereafter "linac"); (ii) optimization of alignment for the proton linac, cyclotron and synchrotron; (iii) superconducting magnet; (iv) laser technology. Advanced accelerators for medical applications are categorized into two groups. The first group consists of compact medical linacs with high RF, cyclotrons and synchrotrons downsized by optimization of alignment and superconducting magnets. The second group comprises laserbased acceleration systems aimed of medical applications in the future. Laser plasma electron/ion accelerating systems for cancer therapy and laser dielectric accelerating systems for radiation biology are mentioned. Since the second group has important potential for a compact system, the current status of the established energy and intensity and of the required stability are given.

Microfabricated biocatalytic fuel cells: a new approach to accelerating the orthodontic tooth movement.

PubMed

Kolahi, Jafar; Abrishami, Mohamadreza; Davidovitch, Zéev

2009-09-01

Direct electric current is a potent biologic mean to accelerate periodontal tissue turnover and orthodontic tooth movement. The main problem associated with this approach is the source of electricity. A noninvasive, removable enzymatic micro-battery, will administer minute electric currents to the alveolar bone and oral soft tissues, utilizing glucose as a fuel, becoming a possible source of the electrical power required for accelerating the velocity of orthodontic tooth movement.

[The adaptive biological control system with electromyographic feedback in the treatment of Bell's palsy].

PubMed

Lobzin, V S; Tsatskina, N D

1989-01-01

A total of 192 patients with Bell paralysis were studied. In 32 a technique of biofeedback training was applied to accelerate the restoration of mimetic muscles with EMG feedback. Clinical and electrophysiological data confirmed the efficiency of this technique in terms of considerably accelerated rehabilitation.

Massive Exploration of Perturbed Conditions of the Blood Coagulation Cascade through GPU Parallelization

PubMed Central

Cazzaniga, Paolo; Nobile, Marco S.; Besozzi, Daniela; Bellini, Matteo; Mauri, Giancarlo

2014-01-01

The introduction of general-purpose Graphics Processing Units (GPUs) is boosting scientific applications in Bioinformatics, Systems Biology, and Computational Biology. In these fields, the use of high-performance computing solutions is motivated by the need of performing large numbers of in silico analysis to study the behavior of biological systems in different conditions, which necessitate a computing power that usually overtakes the capability of standard desktop computers. In this work we present coagSODA, a CUDA-powered computational tool that was purposely developed for the analysis of a large mechanistic model of the blood coagulation cascade (BCC), defined according to both mass-action kinetics and Hill functions. coagSODA allows the execution of parallel simulations of the dynamics of the BCC by automatically deriving the system of ordinary differential equations and then exploiting the numerical integration algorithm LSODA. We present the biological results achieved with a massive exploration of perturbed conditions of the BCC, carried out with one-dimensional and bi-dimensional parameter sweep analysis, and show that GPU-accelerated parallel simulations of this model can increase the computational performances up to a 181× speedup compared to the corresponding sequential simulations. PMID:25025072

Next-generation mammalian genetics toward organism-level systems biology.

PubMed

Susaki, Etsuo A; Ukai, Hideki; Ueda, Hiroki R

2017-01-01

Organism-level systems biology in mammals aims to identify, analyze, control, and design molecular and cellular networks executing various biological functions in mammals. In particular, system-level identification and analysis of molecular and cellular networks can be accelerated by next-generation mammalian genetics. Mammalian genetics without crossing, where all production and phenotyping studies of genome-edited animals are completed within a single generation drastically reduce the time, space, and effort of conducting the systems research. Next-generation mammalian genetics is based on recent technological advancements in genome editing and developmental engineering. The process begins with introduction of double-strand breaks into genomic DNA by using site-specific endonucleases, which results in highly efficient genome editing in mammalian zygotes or embryonic stem cells. By using nuclease-mediated genome editing in zygotes, or ~100% embryonic stem cell-derived mouse technology, whole-body knock-out and knock-in mice can be produced within a single generation. These emerging technologies allow us to produce multiple knock-out or knock-in strains in high-throughput manner. In this review, we discuss the basic concepts and related technologies as well as current challenges and future opportunities for next-generation mammalian genetics in organism-level systems biology.

Recent developments of ion sources for life-science studies at the Heavy Ion Medical Accelerator in Chiba (invited)

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

Kitagawa, A.; Drentje, A. G.; Fujita, T.

With about 1000-h of relativistic high-energy ion beams provided by Heavy Ion Medical Accelerator in Chiba, about 70 users are performing various biology experiments every year. A rich variety of ion species from hydrogen to xenon ions with a dose rate of several Gy/min is available. Carbon, iron, silicon, helium, neon, argon, hydrogen, and oxygen ions were utilized between 2012 and 2014. Presently, three electron cyclotron resonance ion sources (ECRISs) and one Penning ion source are available. Especially, the two frequency heating techniques have improved the performance of an 18 GHz ECRIS. The results have satisfied most requirements for life-sciencemore » studies. In addition, this improved performance has realized a feasible solution for similar biology experiments with a hospital-specified accelerator complex.« less

Relating Time-Dependent Acceleration and Height Using an Elevator

ERIC Educational Resources Information Center

Kinser, Jason M.

2015-01-01

A simple experiment in relating a time-dependent linear acceleration function to height is explored through the use of a smartphone and an elevator. Given acceleration as a function of time, a(t), the velocity function and position functions are determined through integration as in v(t)=? a(t) dt (1) and x(t)=? v(t) dt. Mobile devices such as…

Hip1-related Mutant Mice Grow and Develop Normally but Have Accelerated Spinal Abnormalities and Dwarfism in the Absence of HIP1†

PubMed Central

Hyun, Teresa S.; Li, Lina; Oravecz-Wilson, Katherine I.; Bradley, Sarah V.; Provot, Melissa M.; Munaco, Anthony J.; Mizukami, Ikuko F.; Sun, Hanshi; Ross, Theodora S.

2004-01-01

In mice and humans, there are two known members of the Huntingtin interacting protein 1 (HIP1) family, HIP1 and HIP1-related (HIP1r). Based on structural and functional data, these proteins participate in the clathrin trafficking network. The inactivation of Hip1 in mice leads to spinal, hematopoietic, and testicular defects. To investigate the biological function of HIP1r, we generated a Hip1r mutant allele in mice. Hip1r homozygous mutant mice are viable and fertile without obvious morphological abnormalities. In addition, embryonic fibroblasts derived from these mice do not have gross abnormalities in survival, proliferation, or clathrin trafficking pathways. Altogether, this demonstrates that HIP1r is not necessary for normal development of the embryo or for normal adulthood and suggests that HIP1 or other functionally related members of the clathrin trafficking network can compensate for HIP1r absence. To test the latter, we generated mice deficient in both HIP1 and HIP1r. These mice have accelerated development of abnormalities seen in Hip1 -deficient mice, including kypholordosis and growth defects. The severity of the Hip1r/Hip1 double-knockout phenotype compared to the Hip1 knockout indicates that HIP1r partially compensates for HIP1 function in the absence of HIP1 expression, providing strong evidence that HIP1 and HIP1r have overlapping roles in vivo. PMID:15121852

Hip1-related mutant mice grow and develop normally but have accelerated spinal abnormalities and dwarfism in the absence of HIP1.

PubMed

Hyun, Teresa S; Li, Lina; Oravecz-Wilson, Katherine I; Bradley, Sarah V; Provot, Melissa M; Munaco, Anthony J; Mizukami, Ikuko F; Sun, Hanshi; Ross, Theodora S

2004-05-01

In mice and humans, there are two known members of the Huntingtin interacting protein 1 (HIP1) family, HIP1 and HIP1-related (HIP1r). Based on structural and functional data, these proteins participate in the clathrin trafficking network. The inactivation of Hip1 in mice leads to spinal, hematopoietic, and testicular defects. To investigate the biological function of HIP1r, we generated a Hip1r mutant allele in mice. Hip1r homozygous mutant mice are viable and fertile without obvious morphological abnormalities. In addition, embryonic fibroblasts derived from these mice do not have gross abnormalities in survival, proliferation, or clathrin trafficking pathways. Altogether, this demonstrates that HIP1r is not necessary for normal development of the embryo or for normal adulthood and suggests that HIP1 or other functionally related members of the clathrin trafficking network can compensate for HIP1r absence. To test the latter, we generated mice deficient in both HIP1 and HIP1r. These mice have accelerated development of abnormalities seen in Hip1 -deficient mice, including kypholordosis and growth defects. The severity of the Hip1r/Hip1 double-knockout phenotype compared to the Hip1 knockout indicates that HIP1r partially compensates for HIP1 function in the absence of HIP1 expression, providing strong evidence that HIP1 and HIP1r have overlapping roles in vivo.

Lgr proteins in epithelial stem cell biology.

PubMed

Barker, Nick; Tan, Shawna; Clevers, Hans

2013-06-01

The ultimate success of global efforts to exploit adult stem cells for regenerative medicine will depend heavily on the availability of robust, highly selective stem cell surface markers that facilitate the isolation of stem cells from human tissues. Any subsequent expansion or manipulation of isolated stem cells will also require an intimate knowledge of the mechanisms that regulate these cells, to ensure maintenance of their regenerative capacities and to minimize the risk of introducing undesirable growth traits that could pose health risks for patients. A subclass of leucine-rich repeat-containing G-protein-coupled receptor (Lgr) proteins has recently gained prominence as adult stem cell markers with crucial roles in maintaining stem cell functions. Here, we discuss the major impact that their discovery has had on our understanding of adult stem cell biology in various self-renewing tissues and in accelerating progress towards the development of effective stem cell therapies.

[Serum anticholinergic activity: relationship with clinical symptoms in Alzheimer's disease and proposal of new biological marker].

PubMed

Hori, Koji; Konishi, Kimiko; Hachisu, Mitsugu

2011-06-01

We reviewed the importance of measuring serum anticholinergic activity (SAA) in patients with Alzheimer's disease (AD). Since Tune and Coyle reported a simple method for assessing SAA using radioreceptor-binding assay, SAA is assumed to be the cumulative activity of parent medications and their metabolites and its relationship with delirium and cognitive functions has been debated. However, we evaluated the SAA in AD patients and SAA was correlated with prescription of antipsychotic medications, cognitive dysfunctions, severity of AD and psychotic symptoms, especially, with delusion and diurnal rhythm disturbance. From these results, we should not only pay attention to avoiding the prescription of medications with anticholinergic activity but also we speculated that AA appeared endogenously in AD and accelerated AD pathology. Moreover, there might be the possibility that SAA has predictive value for assessing the progressiveness of AD and as a biological marker for AD.

Beyond nC60: strategies for identification of transformation products of fullerene oxidation in aquatic and biological samples

PubMed Central

Pycke, Benny F. G.; Chao, Tzu-Chiao; Herckes, Pierre; Westerhoff, Paul

2013-01-01

Owing to their exceptional properties and versatility, fullerenes are in widespread use for numerous applications. Increased production and use of fullerenes will inevitably result in accelerated environmental release. However, study of the occurrence, fate, and transport of fullerenes in the environment is complicated because a variety of surface modifications can occur as a result of either intentional functionalization or natural processes. To gain a better understanding of the effect and risk of fullerenes on environmental health, it is necessary to acquire reliable data on the parent compounds and their congeners. Whereas currently established quantification methods generally focus on analysis of unmodified fullerenes, we discuss in this review the occurrence and analysis of oxidized fullerene congeners (i.e., their corresponding epoxides and polyhydroxylated derivatives) in the environment and in biological specimens. We present possible strategies for detection and quantification of parent nanomaterials and their various derivatives. PMID:22644149

Platelet Rich Plasma and Knee Surgery

PubMed Central

Sánchez, Mikel; Sánchez, Pello; Orive, Gorka; Anitua, Eduardo; Padilla, Sabino

2014-01-01

In orthopaedic surgery and sports medicine, the knee joint has traditionally been considered the workhorse. The reconstruction of every damaged element in this joint is crucial in achieving the surgeon's goal to restore the knee function and prevent degeneration towards osteoarthritis. In the last fifteen years, the field of regenerative medicine is witnessing a boost of autologous blood-derived platelet rich plasma products (PRPs) application to effectively mimic and accelerate the tissue healing process. The scientific rationale behind PRPs is the delivery of growth factors, cytokines, and adhesive proteins present in platelets and plasma, as well as other biologically active proteins conveyed by the plasma such as fibrinogen, prothrombin, and fibronectin; with this biological engineering approach, new perspectives in knee surgery were opened. This work describes the use of PRP to construct and repair every single anatomical structure involved in knee surgery, detailing the process conducted in ligament, meniscal, and chondral surgery. PMID:25302310

Advances and perspectives on the use of CRISPR/Cas9 systems in plant genomics research

DOE PAGES

Liu, Degao; Hu, Rongbin; Palla, Kaitlin J.; ...

2016-02-18

Genome editing with site-specific nucleases has become a powerful tool for functional characterization of plant genes and genetic improvement of agricultural crops. Among the various site-specific nuclease-based technologies available for genome editing, the clustered regularly interspaced short palindromic repeat (CRISPR)/CRISPR-associated protein 9 (Cas9) systems have shown the greatest potential for rapid and efficient editing of genomes in plant species. Here, this article reviews the current status of application of CRISPR/Cas9 to plant genomics research, with a focus on loss-of-function and gain-of-function analysis of individual genes in the context of perennial plants and the potential application of CRISPR/Cas9 to perturbation ofmore » gene expression, as well as identification and analysis of gene modules as part of an accelerated domestication and synthetic biology effort.« less

Advances and perspectives on the use of CRISPR/Cas9 systems in plant genomics research

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

Liu, Degao; Hu, Rongbin; Palla, Kaitlin J.

Genome editing with site-specific nucleases has become a powerful tool for functional characterization of plant genes and genetic improvement of agricultural crops. Among the various site-specific nuclease-based technologies available for genome editing, the clustered regularly interspaced short palindromic repeat (CRISPR)/CRISPR-associated protein 9 (Cas9) systems have shown the greatest potential for rapid and efficient editing of genomes in plant species. Here, this article reviews the current status of application of CRISPR/Cas9 to plant genomics research, with a focus on loss-of-function and gain-of-function analysis of individual genes in the context of perennial plants and the potential application of CRISPR/Cas9 to perturbation ofmore » gene expression, as well as identification and analysis of gene modules as part of an accelerated domestication and synthetic biology effort.« less

Probing Functional Heteromeric Chemokine Protein-Protein Interactions through Conformation-Assisted Oxime Ligation.

PubMed

Agten, Stijn M; Koenen, Rory R; Ippel, Hans; Eckardt, Veit; von Hundelshausen, Philipp; Mayo, Kevin H; Weber, Christian; Hackeng, Tilman M

2016-11-21

Protein-protein interactions (PPIs) govern most processes in living cells. Current drug development strategies are aimed at disrupting or stabilizing PPIs, which require a thorough understanding of PPI mechanisms. Examples of such PPIs are heteromeric chemokine interactions that are potentially involved in pathological disorders such as cancer, atherosclerosis, and HIV. It remains unclear whether this functional modulation is mediated by heterodimer formation or by the additive effects of mixed chemokines on their respective receptors. To address this issue, we report the synthesis of a covalent RANTES-PF4 heterodimer (termed OPRAH) by total chemical synthesis and oxime ligation, with an acceleration of the final ligation step driven by PPIs between RANTES and PF4. Compared to mixed separate chemokines, OPRAH exhibited increased biological activity, thus providing evidence that physical formation of the heterodimer indeed mediates enhanced function. © 2016 The Authors. Published by Wiley-VCH Verlag GmbH & Co. KGaA.

Probing Functional Heteromeric Chemokine Protein–Protein Interactions through Conformation‐Assisted Oxime Ligation

PubMed Central

Agten, Stijn M.; Koenen, Rory R.; Ippel, Hans; Eckardt, Veit; von Hundelshausen, Philipp; Mayo, Kevin H.; Weber, Christian

2016-01-01

Abstract Protein–protein interactions (PPIs) govern most processes in living cells. Current drug development strategies are aimed at disrupting or stabilizing PPIs, which require a thorough understanding of PPI mechanisms. Examples of such PPIs are heteromeric chemokine interactions that are potentially involved in pathological disorders such as cancer, atherosclerosis, and HIV. It remains unclear whether this functional modulation is mediated by heterodimer formation or by the additive effects of mixed chemokines on their respective receptors. To address this issue, we report the synthesis of a covalent RANTES‐PF4 heterodimer (termed OPRAH) by total chemical synthesis and oxime ligation, with an acceleration of the final ligation step driven by PPIs between RANTES and PF4. Compared to mixed separate chemokines, OPRAH exhibited increased biological activity, thus providing evidence that physical formation of the heterodimer indeed mediates enhanced function. PMID:27785869

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

Sunden, Fanny; Peck, Ariana; Salzman, Julia

Enzymes enable life by accelerating reaction rates to biological timescales. Conventional studies have focused on identifying the residues that have a direct involvement in an enzymatic reaction, but these so-called ‘catalytic residues’ are embedded in extensive interaction networks. Although fundamental to our understanding of enzyme function, evolution, and engineering, the properties of these networks have yet to be quantitatively and systematically explored. We dissected an interaction network of five residues in the active site of Escherichia coli alkaline phosphatase. Analysis of the complex catalytic interdependence of specific residues identified three energetically independent but structurally interconnected functional units with distinct modesmore » of cooperativity. From an evolutionary perspective, this network is orders of magnitude more probable to arise than a fully cooperative network. From a functional perspective, new catalytic insights emerge. Further, such comprehensive energetic characterization will be necessary to benchmark the algorithms required to rationally engineer highly efficient enzymes.« less

Moonshot Objectives: Catalyze New Scientific Breakthroughs-Proteogenomics.

PubMed

Rodland, Karin D; Piehowski, Paul; Smith, Richard D

Breaking down the silos between disciplines to accelerate the pace of cancer research is a key paradigm for the Cancer Moonshot. Molecular analyses of cancer biology have tended to segregate between a focus on nucleic acids-DNA, RNA, and their modifications-and a focus on proteins and protein function. Proteogenomics represents a fusion of those two approaches, leveraging the strengths of each to provide a more integrated vision of the flow of information from DNA to RNA to protein and eventually function at the molecular level. Proteogenomic studies have been incorporated into multiple activities associated with the Cancer Moonshot, demonstrating substantial added value. Innovative study designs integrating genomic, transcriptomic, and proteomic data, particularly those using clinically relevant samples and involving clinical trials, are poised to provide new insights regarding cancer risk, progression, and response to therapy.

Late-Stage Functionalization of Arylacetic Acids by Photoredox-Catalyzed Decarboxylative Carbon-Heteroatom Bond Formation.

PubMed

Sakakibara, Yota; Ito, Eri; Fukushima, Tomohiro; Murakami, Kei; Itami, Kenichiro

2018-05-02

The rapid transformation of pharmaceuticals and agrochemicals enables access to unexplored chemical space and thus has accelerated the discovery of novel bioactive molecules. Because arylacetic acids are regarded as key structures in bioactive compounds, new transformations of these structures could contribute to drug/agrochemical discovery and chemical biology. This work reports carbon-nitrogen and carbon-oxygen bond formation through the photoredox-catalyzed decarboxylation of arylacetic acids. The reaction shows good functional group compatibility without pre-activation of the nitrogen- or oxygen-based coupling partners. Under similar reaction conditions, carbon-chlorine bond formation was also feasible. This efficient derivatization of arylacetic acids makes it possible to synthesize pharmaceutical analogues and bioconjugates of pharmaceuticals and natural products. © 2018 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.

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

Accelerated molecular dynamics simulations of the octopamine receptor using GPUs: discovery of an alternate agonist-binding position.

PubMed

Kastner, Kevin W; Izaguirre, Jesús A

2016-10-01

Octopamine receptors (OARs) perform key biological functions in invertebrates, making this class of G-protein coupled receptors (GPCRs) worth considering for insecticide development. However, no crystal structures and very little research exists for OARs. Furthermore, GPCRs are large proteins, are suspended in a lipid bilayer, and are activated on the millisecond timescale, all of which make conventional molecular dynamics (MD) simulations infeasible, even if run on large supercomputers. However, accelerated Molecular Dynamics (aMD) simulations can reduce this timescale to even hundreds of nanoseconds, while running the simulations on graphics processing units (GPUs) would enable even small clusters of GPUs to have processing power equivalent to hundreds of CPUs. Our results show that aMD simulations run on GPUs can successfully obtain the active and inactive state conformations of a GPCR on this reduced timescale. Furthermore, we discovered a potential alternate active-state agonist-binding position in the octopamine receptor which has yet to be observed and may be a novel GPCR agonist-binding position. These results demonstrate that a complex biological system with an activation process on the millisecond timescale can be successfully simulated on the nanosecond timescale using a simple computing system consisting of a small number of GPUs. Proteins 2016; 84:1480-1489. © 2016 Wiley Periodicals, Inc. © 2016 Wiley Periodicals, Inc.

BATMAN-TCM: a Bioinformatics Analysis Tool for Molecular mechANism of Traditional Chinese Medicine

NASA Astrophysics Data System (ADS)

Liu, Zhongyang; Guo, Feifei; Wang, Yong; Li, Chun; Zhang, Xinlei; Li, Honglei; Diao, Lihong; Gu, Jiangyong; Wang, Wei; Li, Dong; He, Fuchu

2016-02-01

Traditional Chinese Medicine (TCM), with a history of thousands of years of clinical practice, is gaining more and more attention and application worldwide. And TCM-based new drug development, especially for the treatment of complex diseases is promising. However, owing to the TCM’s diverse ingredients and their complex interaction with human body, it is still quite difficult to uncover its molecular mechanism, which greatly hinders the TCM modernization and internationalization. Here we developed the first online Bioinformatics Analysis Tool for Molecular mechANism of TCM (BATMAN-TCM). Its main functions include 1) TCM ingredients’ target prediction; 2) functional analyses of targets including biological pathway, Gene Ontology functional term and disease enrichment analyses; 3) the visualization of ingredient-target-pathway/disease association network and KEGG biological pathway with highlighted targets; 4) comparison analysis of multiple TCMs. Finally, we applied BATMAN-TCM to Qishen Yiqi dripping Pill (QSYQ) and combined with subsequent experimental validation to reveal the functions of renin-angiotensin system responsible for QSYQ’s cardioprotective effects for the first time. BATMAN-TCM will contribute to the understanding of the “multi-component, multi-target and multi-pathway” combinational therapeutic mechanism of TCM, and provide valuable clues for subsequent experimental validation, accelerating the elucidation of TCM’s molecular mechanism. BATMAN-TCM is available at http://bionet.ncpsb.org/batman-tcm.

BATMAN-TCM: a Bioinformatics Analysis Tool for Molecular mechANism of Traditional Chinese Medicine

PubMed Central

Liu, Zhongyang; Guo, Feifei; Wang, Yong; Li, Chun; Zhang, Xinlei; Li, Honglei; Diao, Lihong; Gu, Jiangyong; Wang, Wei; Li, Dong; He, Fuchu

2016-01-01

Traditional Chinese Medicine (TCM), with a history of thousands of years of clinical practice, is gaining more and more attention and application worldwide. And TCM-based new drug development, especially for the treatment of complex diseases is promising. However, owing to the TCM’s diverse ingredients and their complex interaction with human body, it is still quite difficult to uncover its molecular mechanism, which greatly hinders the TCM modernization and internationalization. Here we developed the first online Bioinformatics Analysis Tool for Molecular mechANism of TCM (BATMAN-TCM). Its main functions include 1) TCM ingredients’ target prediction; 2) functional analyses of targets including biological pathway, Gene Ontology functional term and disease enrichment analyses; 3) the visualization of ingredient-target-pathway/disease association network and KEGG biological pathway with highlighted targets; 4) comparison analysis of multiple TCMs. Finally, we applied BATMAN-TCM to Qishen Yiqi dripping Pill (QSYQ) and combined with subsequent experimental validation to reveal the functions of renin-angiotensin system responsible for QSYQ’s cardioprotective effects for the first time. BATMAN-TCM will contribute to the understanding of the “multi-component, multi-target and multi-pathway” combinational therapeutic mechanism of TCM, and provide valuable clues for subsequent experimental validation, accelerating the elucidation of TCM’s molecular mechanism. BATMAN-TCM is available at http://bionet.ncpsb.org/batman-tcm. PMID:26879404

Microwave-assisted intramolecular dehydrogenative Diels-Alder reactions for the synthesis of functionalized naphthalenes/solvatochromic dyes.

PubMed

Kocsis, Laura S; Benedetti, Erica; Brummond, Kay M

2013-04-01

Functionalized naphthalenes have applications in a variety of research fields ranging from the synthesis of natural or biologically active molecules to the preparation of new organic dyes. Although numerous strategies have been reported to access naphthalene scaffolds, many procedures still present limitations in terms of incorporating functionality, which in turn narrows the range of available substrates. The development of versatile methods for direct access to substituted naphthalenes is therefore highly desirable. The Diels-Alder (DA) cycloaddition reaction is a powerful and attractive method for the formation of saturated and unsaturated ring systems from readily available starting materials. A new microwave-assisted intramolecular dehydrogenative DA reaction of styrenyl derivatives described herein generates a variety of functionalized cyclopenta[b]naphthalenes that could not be prepared using existing synthetic methods. When compared to conventional heating, microwave irradiation accelerates reaction rates, enhances yields, and limits the formation of undesired byproducts. The utility of this protocol is further demonstrated by the conversion of a DA cycloadduct into a novel solvatochromic fluorescent dye via a Buchwald-Hartwig palladium-catalyzed cross-coupling reaction. Fluorescence spectroscopy, as an informative and sensitive analytical technique, plays a key role in research fields including environmental science, medicine, pharmacology, and cellular biology. Access to a variety of new organic fluorophores provided by the microwave-assisted dehydrogenative DA reaction allows for further advancement in these fields.

Microwave-assisted Intramolecular Dehydrogenative Diels-Alder Reactions for the Synthesis of Functionalized Naphthalenes/Solvatochromic Dyes

PubMed Central

Kocsis, Laura S.; Benedetti, Erica; Brummond, Kay M.

2013-01-01

Functionalized naphthalenes have applications in a variety of research fields ranging from the synthesis of natural or biologically active molecules to the preparation of new organic dyes. Although numerous strategies have been reported to access naphthalene scaffolds, many procedures still present limitations in terms of incorporating functionality, which in turn narrows the range of available substrates. The development of versatile methods for direct access to substituted naphthalenes is therefore highly desirable. The Diels-Alder (DA) cycloaddition reaction is a powerful and attractive method for the formation of saturated and unsaturated ring systems from readily available starting materials. A new microwave-assisted intramolecular dehydrogenative DA reaction of styrenyl derivatives described herein generates a variety of functionalized cyclopenta[b]naphthalenes that could not be prepared using existing synthetic methods. When compared to conventional heating, microwave irradiation accelerates reaction rates, enhances yields, and limits the formation of undesired byproducts. The utility of this protocol is further demonstrated by the conversion of a DA cycloadduct into a novel solvatochromic fluorescent dye via a Buchwald-Hartwig palladium-catalyzed cross-coupling reaction. Fluorescence spectroscopy, as an informative and sensitive analytical technique, plays a key role in research fields including environmental science, medicine, pharmacology, and cellular biology. Access to a variety of new organic fluorophores provided by the microwave-assisted dehydrogenative DA reaction allows for further advancement in these fields. PMID:23609566

Enhanced degradation of phenolic compounds in coal gasification wastewater by a novel integration of micro-electrolysis with biological reactor (MEBR) under the micro-oxygen condition.

PubMed

Ma, Weiwei; Han, Yuxing; Xu, Chunyan; Han, Hongjun; Ma, Wencheng; Zhu, Hao; Li, Kun; Wang, Dexin

2018-03-01

The aim of this work was to study an integration of micro-electrolysis with biological reactor (MEBR) for strengthening removal of phenolic compounds in coal gasification wastewater (CGW). The results indicated MEBR achieved high efficiencies in removal of COD and phenolic compounds as well as improvement of biodegradability of CGW under the micro-oxygen condition. The integrated MEBR process was more favorable to improvement of the structural stability of activated sludge and biodiversity of specific functional microbial communities. Especially, Shewanella and Pseudomonas were enriched to accelerate the extracellular electron transfer, finally facilitating the degradation of phenolic compounds. Moreover, MEBR process effectively relieved passivation of Fe-C filler surface and prolonged lifespan of Fe-C filler. Accordingly, the synergetic effect between iron-carbon micro-electrolysis (ICME) and biological action played a significant role in performance of the integrated process. Therefore, the integrated MEBR was a promising practical process for enhancing CGW treatment. Copyright © 2017 Elsevier Ltd. All rights reserved.

78 FR 38349 - Draft Guidance for Industry on Expedited Programs for Serious Conditions-Drugs and Biologics...

Federal Register 2010, 2011, 2012, 2013, 2014

2013-06-26

... approval, and priority review designation. DATES: Although you can comment on any guidance at any time (see... designation, (3) accelerated approval, and (4) priority review designation. The draft guidance describes... (the FD&C Act) (Enhancement of Accelerated Approval Access to New Medical Treatments) within 1 year of...

Evidence of accelerated aging among African Americans and its implications for mortality.

PubMed

Levine, M E; Crimmins, E M

2014-10-01

Blacks experience morbidity and mortality earlier in the life course compared to whites. Such premature declines in health may be indicative of an acceleration of the aging process. The current study uses data on 7644 black and white participants, ages 30 and above, from the third National Health and Nutrition Examination Survey, to compare the biological ages of blacks and whites as indicated from a combination of ten biomarkers and to determine if such differences in biological age relative to chronological age account for racial disparities in mortality. At a specified chronological age, blacks are approximately 3 years older biologically than whites. Differences in biological age between blacks and whites appear to increase up until ages 60-65 and then decline, presumably due to mortality selection. Finally, differences in biological age were found to completely account for higher levels of all-cause, cardiovascular and cancer mortality among blacks. Overall, these results suggest that being black is associated with significantly higher biological age at a given chronological age and that this is a pathway to early death both overall and from the major age-related diseases. Copyright © 2014 Elsevier Ltd. All rights reserved.

Learning a peptide-protein binding affinity predictor with kernel ridge regression

PubMed Central

2013-01-01

Background The cellular function of a vast majority of proteins is performed through physical interactions with other biomolecules, which, most of the time, are other proteins. Peptides represent templates of choice for mimicking a secondary structure in order to modulate protein-protein interaction. They are thus an interesting class of therapeutics since they also display strong activity, high selectivity, low toxicity and few drug-drug interactions. Furthermore, predicting peptides that would bind to a specific MHC alleles would be of tremendous benefit to improve vaccine based therapy and possibly generate antibodies with greater affinity. Modern computational methods have the potential to accelerate and lower the cost of drug and vaccine discovery by selecting potential compounds for testing in silico prior to biological validation. Results We propose a specialized string kernel for small bio-molecules, peptides and pseudo-sequences of binding interfaces. The kernel incorporates physico-chemical properties of amino acids and elegantly generalizes eight kernels, comprised of the Oligo, the Weighted Degree, the Blended Spectrum, and the Radial Basis Function. We provide a low complexity dynamic programming algorithm for the exact computation of the kernel and a linear time algorithm for it’s approximation. Combined with kernel ridge regression and SupCK, a novel binding pocket kernel, the proposed kernel yields biologically relevant and good prediction accuracy on the PepX database. For the first time, a machine learning predictor is capable of predicting the binding affinity of any peptide to any protein with reasonable accuracy. The method was also applied to both single-target and pan-specific Major Histocompatibility Complex class II benchmark datasets and three Quantitative Structure Affinity Model benchmark datasets. Conclusion On all benchmarks, our method significantly (p-value ≤ 0.057) outperforms the current state-of-the-art methods at predicting peptide-protein binding affinities. The proposed approach is flexible and can be applied to predict any quantitative biological activity. Moreover, generating reliable peptide-protein binding affinities will also improve system biology modelling of interaction pathways. Lastly, the method should be of value to a large segment of the research community with the potential to accelerate the discovery of peptide-based drugs and facilitate vaccine development. The proposed kernel is freely available at http://graal.ift.ulaval.ca/downloads/gs-kernel/. PMID:23497081

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

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

Kneip, S.; Center for Ultrafast Optical Science, University of Michigan, Ann Arbor 48109; McGuffey, C.

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 highlightingmore » 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.« less

Extensive site-directed mutagenesis reveals interconnected functional units in the alkaline phosphatase active site

PubMed Central

Sunden, Fanny; Peck, Ariana; Salzman, Julia; Ressl, Susanne; Herschlag, Daniel

2015-01-01

Enzymes enable life by accelerating reaction rates to biological timescales. Conventional studies have focused on identifying the residues that have a direct involvement in an enzymatic reaction, but these so-called ‘catalytic residues’ are embedded in extensive interaction networks. Although fundamental to our understanding of enzyme function, evolution, and engineering, the properties of these networks have yet to be quantitatively and systematically explored. We dissected an interaction network of five residues in the active site of Escherichia coli alkaline phosphatase. Analysis of the complex catalytic interdependence of specific residues identified three energetically independent but structurally interconnected functional units with distinct modes of cooperativity. From an evolutionary perspective, this network is orders of magnitude more probable to arise than a fully cooperative network. From a functional perspective, new catalytic insights emerge. Further, such comprehensive energetic characterization will be necessary to benchmark the algorithms required to rationally engineer highly efficient enzymes. DOI: http://dx.doi.org/10.7554/eLife.06181.001 PMID:25902402

Extensive site-directed mutagenesis reveals interconnected functional units in the alkaline phosphatase active site

DOE PAGES

Sunden, Fanny; Peck, Ariana; Salzman, Julia; ...

2015-04-22

Enzymes enable life by accelerating reaction rates to biological timescales. Conventional studies have focused on identifying the residues that have a direct involvement in an enzymatic reaction, but these so-called ‘catalytic residues’ are embedded in extensive interaction networks. Although fundamental to our understanding of enzyme function, evolution, and engineering, the properties of these networks have yet to be quantitatively and systematically explored. We dissected an interaction network of five residues in the active site of Escherichia coli alkaline phosphatase. Analysis of the complex catalytic interdependence of specific residues identified three energetically independent but structurally interconnected functional units with distinct modesmore » of cooperativity. From an evolutionary perspective, this network is orders of magnitude more probable to arise than a fully cooperative network. From a functional perspective, new catalytic insights emerge. Further, such comprehensive energetic characterization will be necessary to benchmark the algorithms required to rationally engineer highly efficient enzymes.« less

Building biological foundries for next-generation synthetic biology.

PubMed

Chao, Ran; Yuan, YongBo; Zhao, HuiMin

2015-07-01

Synthetic biology is an interdisciplinary field that takes top-down approaches to understand and engineer biological systems through design-build-test cycles. A number of advances in this relatively young field have greatly accelerated such engineering cycles. Specifically, various innovative tools were developed for in silico biosystems design, DNA de novo synthesis and assembly, construct verification, as well as metabolite analysis, which have laid a solid foundation for building biological foundries for rapid prototyping of improved or novel biosystems. This review summarizes the state-of-the-art technologies for synthetic biology and discusses the challenges to establish such biological foundries.

Foundations of space biology and medicine. Volume 2, book 1: Ecological and physiological bases of space biology and medicine

NASA Technical Reports Server (NTRS)

Calvin, M. (Editor); Gazenko, O. G. (Editor)

1975-01-01

Barometric pressure, gas composition, toxicity, and thermal exchange of spacecraft cabin atmospheres are discussed. Effects of gravitation, acceleration, weightlessness, noise, and vibration on human behavior and performance during space flight are also described.

Huntington's disease accelerates epigenetic aging of human brain and disrupts DNA methylation levels.

PubMed

Horvath, Steve; Langfelder, Peter; Kwak, Seung; Aaronson, Jeff; Rosinski, Jim; Vogt, Thomas F; Eszes, Marika; Faull, Richard L M; Curtis, Maurice A; Waldvogel, Henry J; Choi, Oi-Wa; Tung, Spencer; Vinters, Harry V; Coppola, Giovanni; Yang, X William

2016-07-01

Age of Huntington's disease (HD) motoric onset is strongly related to the number of CAG trinucleotide repeats in the huntingtin gene, suggesting that biological tissue age plays an important role in disease etiology. Recently, a DNA methylation based biomarker of tissue age has been advanced as an epigenetic aging clock. We sought to inquire if HD is associated with an accelerated epigenetic age. DNA methylation data was generated for 475 brain samples from various brain regions of 26 HD cases and 39 controls. Overall, brain regions from HD cases exhibit a significant epigenetic age acceleration effect (p=0.0012). A multivariate model analysis suggests that HD status increases biological age by 3.2 years. Accelerated epigenetic age can be observed in specific brain regions (frontal lobe, parietal lobe, and cingulate gyrus). After excluding controls, we observe a negative correlation (r=-0.41, p=5.5×10-8) between HD gene CAG repeat length and the epigenetic age of HD brain samples. Using correlation network analysis, we identify 11 co-methylation modules with a significant association with HD status across 3 broad cortical regions. In conclusion, HD is associated with an accelerated epigenetic age of specific brain regions and more broadly with substantial changes in brain methylation levels.

Huntington's disease accelerates epigenetic aging of human brain and disrupts DNA methylation levels

PubMed Central

Horvath, Steve; Langfelder, Peter; Kwak, Seung; Aaronson, Jeff; Rosinski, Jim; Vogt, Thomas F.; Eszes, Marika; Faull, Richard L.M.; Curtis, Maurice A.; Waldvogel, Henry J.; Choi, Oi-Wa; Tung, Spencer; Vinters, Harry V.; Coppola, Giovanni; Yang, X. William

2016-01-01

Age of Huntington's disease (HD) motoric onset is strongly related to the number of CAG trinucleotide repeats in the huntingtin gene, suggesting that biological tissue age plays an important role in disease etiology. Recently, a DNA methylation based biomarker of tissue age has been advanced as an epigenetic aging clock. We sought to inquire if HD is associated with an accelerated epigenetic age. DNA methylation data was generated for 475 brain samples from various brain regions of 26 HD cases and 39 controls. Overall, brain regions from HD cases exhibit a significant epigenetic age acceleration effect (p=0.0012). A multivariate model analysis suggests that HD status increases biological age by 3.2 years. Accelerated epigenetic age can be observed in specific brain regions (frontal lobe, parietal lobe, and cingulate gyrus). After excluding controls, we observe a negative correlation (r=−0.41, p=5.5×10−8) between HD gene CAG repeat length and the epigenetic age of HD brain samples. Using correlation network analysis, we identify 11 co-methylation modules with a significant association with HD status across 3 broad cortical regions. In conclusion, HD is associated with an accelerated epigenetic age of specific brain regions and more broadly with substantial changes in brain methylation levels. PMID:27479945

The identification of protein domains that mediate functional interactions between Rab-GTPases and RabGAPs using 3D protein modeling.

PubMed

Davie, Jeremiah J; Faitar, Silviu L

2017-01-01

Currently, time-consuming serial in vitro experimentation involving immunocytochemistry or radiolabeled materials is required to identify which of the numerous Rab-GTPases (Rab) and Rab-GTPase activating proteins (RabGAP) are capable of functional interactions. These interactions are essential for numerous cellular functions, and in silico methods of reducing in vitro trial and error would accelerate the pace of research in cell biology. We have utilized a combination of three-dimensional protein modeling and protein bioinformatics to identify domains present in Rab proteins that are predictive of their functional interaction with a specific RabGAP. The RabF2 and RabSF1 domains appear to play functional roles in mediating the interaction between Rabs and RabGAPs. Moreover, the RabSF1 domain can be used to make in silico predictions of functional Rab/RabGAP pairs. This method is expected to be a broadly applicable tool for predicting protein-protein interactions where existing crystal structures for homologs of the proteins of interest are available.

Relating Time-Dependent Acceleration and Height Using an Elevator

NASA Astrophysics Data System (ADS)

Kinser, Jason M.

2015-04-01

A simple experiment in relating a time-dependent linear acceleration function to height is explored through the use of a smartphone and an elevator. Given acceleration as a function of time1, a(t), the velocity function and position functions are determined through integration as in v (t ) =∫ a (t ) d t (1) and x (t ) =∫ v (t ) dt. Mobile devices such as smartphones or tablets have accelerometers that capture slowly evolving acceleration with respect to time and can deliver those measurements as a CSV file. A recent example measured the oscillations of the elevator as it starts its motion.2 In the application presented here the mobile device is used to estimate the height of the elevator ride. By estimating the functional form of the acceleration of an elevator ride, it is possible to estimate the height of the ride through Eqs. (1) and (2).

Accelerating rates of cognitive decline and imaging markers associated with β-amyloid pathology.

PubMed

Insel, Philip S; Mattsson, Niklas; Mackin, R Scott; Schöll, Michael; Nosheny, Rachel L; Tosun, Duygu; Donohue, Michael C; Aisen, Paul S; Jagust, William J; Weiner, Michael W

2016-05-17

To estimate points along the spectrum of β-amyloid pathology at which rates of change of several measures of neuronal injury and cognitive decline begin to accelerate. In 460 patients with mild cognitive impairment (MCI), we estimated the points at which rates of florbetapir PET, fluorodeoxyglucose (FDG) PET, MRI, and cognitive and functional decline begin to accelerate with respect to baseline CSF Aβ42. Points of initial acceleration in rates of decline were estimated using mixed-effects regression. Rates of neuronal injury and cognitive and even functional decline accelerate substantially before the conventional threshold for amyloid positivity, with rates of florbetapir PET and FDG PET accelerating early. Temporal lobe atrophy rates also accelerate prior to the threshold, but not before the acceleration of cognitive and functional decline. A considerable proportion of patients with MCI would not meet inclusion criteria for a trial using the current threshold for amyloid positivity, even though on average, they are experiencing cognitive/functional decline associated with prethreshold levels of CSF Aβ42. Future trials in early Alzheimer disease might consider revising the criteria regarding β-amyloid thresholds to include the range of amyloid associated with the first signs of accelerating rates of decline. © 2016 American Academy of Neurology.

Accelerating rates of cognitive decline and imaging markers associated with β-amyloid pathology

PubMed Central

Mattsson, Niklas; Mackin, R. Scott; Schöll, Michael; Nosheny, Rachel L.; Tosun, Duygu; Donohue, Michael C.; Aisen, Paul S.; Jagust, William J.; Weiner, Michael W.

2016-01-01

Objective: To estimate points along the spectrum of β-amyloid pathology at which rates of change of several measures of neuronal injury and cognitive decline begin to accelerate. Methods: In 460 patients with mild cognitive impairment (MCI), we estimated the points at which rates of florbetapir PET, fluorodeoxyglucose (FDG) PET, MRI, and cognitive and functional decline begin to accelerate with respect to baseline CSF Aβ42. Points of initial acceleration in rates of decline were estimated using mixed-effects regression. Results: Rates of neuronal injury and cognitive and even functional decline accelerate substantially before the conventional threshold for amyloid positivity, with rates of florbetapir PET and FDG PET accelerating early. Temporal lobe atrophy rates also accelerate prior to the threshold, but not before the acceleration of cognitive and functional decline. Conclusions: A considerable proportion of patients with MCI would not meet inclusion criteria for a trial using the current threshold for amyloid positivity, even though on average, they are experiencing cognitive/functional decline associated with prethreshold levels of CSF Aβ42. Future trials in early Alzheimer disease might consider revising the criteria regarding β-amyloid thresholds to include the range of amyloid associated with the first signs of accelerating rates of decline. PMID:27164667

Accelerating rates of cognitive decline and imaging markers associated with β-amyloid pathology

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

Insel, Philip S.; Mattsson, Niklas; Mackin, R. Scott

Objective: Our objective is to estimate points along the spectrum of β-amyloid pathology at which rates of change of several measures of neuronal injury and cognitive decline begin to accelerate. Methods: In 460 patients with mild cognitive impairment (MCI), we estimated the points at which rates of florbetapir PET, fluorodeoxyglucose (FDG) PET, MRI, and cognitive and functional decline begin to accelerate with respect to baseline CSF Aβ 42. Points of initial acceleration in rates of decline were estimated using mixed-effects regression. Results: Rates of neuronal injury and cognitive and even functional decline accelerate substantially before the conventional threshold for amyloidmore » positivity, with rates of florbetapir PET and FDG PET accelerating early. Temporal lobe atrophy rates also accelerate prior to the threshold, but not before the acceleration of cognitive and functional decline. Conclusions: A considerable proportion of patients with MCI would not meet inclusion criteria for a trial using the current threshold for amyloid positivity, even though on average, they are experiencing cognitive/functional decline associated with prethreshold levels of CSF Aβ 42. Lastly, future trials in early Alzheimer disease might consider revising the criteria regarding β-amyloid thresholds to include the range of amyloid associated with the first signs of accelerating rates of decline.« less

Accelerating rates of cognitive decline and imaging markers associated with β-amyloid pathology

DOE PAGES

Insel, Philip S.; Mattsson, Niklas; Mackin, R. Scott; ...

2016-04-15

Objective: Our objective is to estimate points along the spectrum of β-amyloid pathology at which rates of change of several measures of neuronal injury and cognitive decline begin to accelerate. Methods: In 460 patients with mild cognitive impairment (MCI), we estimated the points at which rates of florbetapir PET, fluorodeoxyglucose (FDG) PET, MRI, and cognitive and functional decline begin to accelerate with respect to baseline CSF Aβ 42. Points of initial acceleration in rates of decline were estimated using mixed-effects regression. Results: Rates of neuronal injury and cognitive and even functional decline accelerate substantially before the conventional threshold for amyloidmore » positivity, with rates of florbetapir PET and FDG PET accelerating early. Temporal lobe atrophy rates also accelerate prior to the threshold, but not before the acceleration of cognitive and functional decline. Conclusions: A considerable proportion of patients with MCI would not meet inclusion criteria for a trial using the current threshold for amyloid positivity, even though on average, they are experiencing cognitive/functional decline associated with prethreshold levels of CSF Aβ 42. Lastly, future trials in early Alzheimer disease might consider revising the criteria regarding β-amyloid thresholds to include the range of amyloid associated with the first signs of accelerating rates of decline.« less

Accelerated molecular dynamics: A promising and efficient simulation method for biomolecules

NASA Astrophysics Data System (ADS)

Hamelberg, Donald; Mongan, John; McCammon, J. Andrew

2004-06-01

Many interesting dynamic properties of biological molecules cannot be simulated directly using molecular dynamics because of nanosecond time scale limitations. These systems are trapped in potential energy minima with high free energy barriers for large numbers of computational steps. The dynamic evolution of many molecular systems occurs through a series of rare events as the system moves from one potential energy basin to another. Therefore, we have proposed a robust bias potential function that can be used in an efficient accelerated molecular dynamics approach to simulate the transition of high energy barriers without any advance knowledge of the location of either the potential energy wells or saddle points. In this method, the potential energy landscape is altered by adding a bias potential to the true potential such that the escape rates from potential wells are enhanced, which accelerates and extends the time scale in molecular dynamics simulations. Our definition of the bias potential echoes the underlying shape of the potential energy landscape on the modified surface, thus allowing for the potential energy minima to be well defined, and hence properly sampled during the simulation. We have shown that our approach, which can be extended to biomolecules, samples the conformational space more efficiently than normal molecular dynamics simulations, and converges to the correct canonical distribution.

Development Biology Worksheet Oriented Accelerated Learning on Plantae and Ecosystems for 10th-Grade Senior High School Students

NASA Astrophysics Data System (ADS)

Dipuja, D. A.; Lufri, L.; Ahda, Y.

2018-04-01

The problem that found are learning outcomes student is low on the plantae and ecosystems. Students less motivated and passive learning because learning is teacher center and teaching materials not facilitate student. Therefore, it is necessary to design a worksheet oriented accelerated learning. Accelerated learning approach that can improve motivation and learning activities. The purpose of the research was to produce worksheet oriented accelerated learning on plantae and ecosystems. This research is designed as a research and development by using Plomp model, consists of the preliminary, prototyping, and assessment phase. Data was collected through questionnaires, observation sheet, test, and documentation. The results of the research was worksheet oriented accelerated learning on plantae and ecosystems is very valid.

Constitutive expression of tdTomato protein as a cytotoxicity and proliferation marker for space radiation biology

NASA Astrophysics Data System (ADS)

Chishti, Arif A.; Hellweg, Christine E.; Berger, Thomas; Baumstark-Khan, Christa; Feles, Sebastian; Kätzel, Thorben; Reitz, Günther

2015-01-01

The radiation risk assessment for long-term space missions requires knowledge on the biological effectiveness of different space radiation components, e.g. heavy ions, on the interaction of radiation and other space environmental factors such as microgravity, and on the physical and biological dose distribution in the human body. Space experiments and ground-based experiments at heavy ion accelerators require fast and reliable test systems with an easy readout for different endpoints. In order to determine the effect of different radiation qualities on cellular proliferation and the biological depth dose distribution after heavy ion exposure, a stable human cell line expressing a novel fluorescent protein was established and characterized. tdTomato, a red fluorescent protein of the new generation with fast maturation and high fluorescence intensity, was selected as reporter of cell proliferation. Human embryonic kidney (HEK/293) cells were stably transfected with a plasmid encoding tdTomato under the control of the constitutively active cytomegalovirus (CMV) promoter (ptdTomato-N1). The stably transfected cell line was named HEK-ptdTomato-N1 8. This cytotoxicity biosensor was tested by ionizing radiation (X-rays and accelerated heavy ions) exposure. As biological endpoints, the proliferation kinetics and the cell density reached 100 h after irradiation reflected by constitutive expression of the tdTomato were investigated. Both were reduced dose-dependently after radiation exposure. Finally, the cell line was used for biological weighting of heavy ions of different linear energy transfer (LET) as space-relevant radiation quality. The relative biological effectiveness of accelerated heavy ions in reducing cellular proliferation peaked at an LET of 91 keV/μm. The results of this study demonstrate that the HEK-ptdTomato-N1 reporter cell line can be used as a fast and reliable biosensor system for detection of cytotoxic damage caused by ionizing radiation.

[Folic acid in physiology and pathology].

PubMed

Czeczot, Hanna

2008-08-13

This paper presents current knowledge of the biological functions of folic acid, the effects of its deficiency in the organism, as well as the possibilities of its therapeutic use. Folic acid (folate, B9) is a vitamin of special importance in normal cellular functions. Tetrahydrofolate (TH4-folate) is the biologically active form of folic acid. The main role of folic acid in biochemistry is the single-carbon transfer reaction (e.g. transfer of a methyl, methylene, or formyl group). Folic acid is involved in the transformation of certain amino acids as well as in the synthesis of purines and dTMP (2'-deoxythymidine-5'-phosphate) needed for the synthesis of nucleic acid (DNA), required by all rapidly growing cells. In humans, folate deficiency results in serious pathologies, the most important of which are neural tube defects, megablastic anemia, acceleration of the arteriosclerotic process, changes in the central nervous system, and the development of certain types of cancer. To increase the intake of folic acid, preventive actions include dietary education, the main objectives of which are to increase the intake of natural folate in the daily diet, add folic acid to selected dietary products (e.g. fl our, pasta, rice), and encourage supplementation with folic acid-containing pharmaceuticals.

Taking Systems Medicine to Heart.

PubMed

Trachana, Kalliopi; Bargaje, Rhishikesh; Glusman, Gustavo; Price, Nathan D; Huang, Sui; Hood, Leroy E

2018-04-27

Systems medicine is a holistic approach to deciphering the complexity of human physiology in health and disease. In essence, a living body is constituted of networks of dynamically interacting units (molecules, cells, organs, etc) that underlie its collective functions. Declining resilience because of aging and other chronic environmental exposures drives the system to transition from a health state to a disease state; these transitions, triggered by acute perturbations or chronic disturbance, manifest as qualitative shifts in the interactions and dynamics of the disease-perturbed networks. Understanding health-to-disease transitions poses a high-dimensional nonlinear reconstruction problem that requires deep understanding of biology and innovation in study design, technology, and data analysis. With a focus on the principles of systems medicine, this Review discusses approaches for deciphering this biological complexity from a novel perspective, namely, understanding how disease-perturbed networks function; their study provides insights into fundamental disease mechanisms. The immediate goals for systems medicine are to identify early transitions to cardiovascular (and other chronic) diseases and to accelerate the translation of new preventive, diagnostic, or therapeutic targets into clinical practice, a critical step in the development of personalized, predictive, preventive, and participatory (P4) medicine. © 2018 American Heart Association, Inc.

Space Station Biological Research Project.

PubMed

Johnson, C C; Wade, C E; Givens, J J

1997-06-01

To meet NASA's objective of using the unique aspects of the space environment to expand fundamental knowledge in the biological sciences, the Space Station Biological Research Project at Ames Research Center is developing, or providing oversight, for two major suites of hardware which will be installed on the International Space Station (ISS). The first, the Gravitational Biology Facility, consists of Habitats to support plants, rodents, cells, aquatic specimens, avian and reptilian eggs, and insects and the Habitat Holding Rack in which to house them at microgravity; the second, the Centrifuge Facility, consists of a 2.5 m diameter centrifuge that will provide acceleration levels between 0.01 g and 2.0 g and a Life Sciences Glovebox. These two facilities will support the conduct of experiments to: 1) investigate the effect of microgravity on living systems; 2) what level of gravity is required to maintain normal form and function, and 3) study the use of artificial gravity as a countermeasure to the deleterious effects of microgravity observed in the crew. Upon completion, the ISS will have three complementary laboratory modules provided by NASA, the European Space Agency and the Japanese space agency, NASDA. Use of all facilities in each of the modules will be available to investigators from participating space agencies. With the advent of the ISS, space-based gravitational biology research will transition from 10-16 day short-duration Space Shuttle flights to 90-day-or-longer ISS increments.

Space Station Biological Research Project

NASA Technical Reports Server (NTRS)

Johnson, C. C.; Wade, C. E.; Givens, J. J.

1997-01-01

To meet NASA's objective of using the unique aspects of the space environment to expand fundamental knowledge in the biological sciences, the Space Station Biological Research Project at Ames Research Center is developing, or providing oversight, for two major suites of hardware which will be installed on the International Space Station (ISS). The first, the Gravitational Biology Facility, consists of Habitats to support plants, rodents, cells, aquatic specimens, avian and reptilian eggs, and insects and the Habitat Holding Rack in which to house them at microgravity; the second, the Centrifuge Facility, consists of a 2.5 m diameter centrifuge that will provide acceleration levels between 0.01 g and 2.0 g and a Life Sciences Glovebox. These two facilities will support the conduct of experiments to: 1) investigate the effect of microgravity on living systems; 2) what level of gravity is required to maintain normal form and function, and 3) study the use of artificial gravity as a countermeasure to the deleterious effects of microgravity observed in the crew. Upon completion, the ISS will have three complementary laboratory modules provided by NASA, the European Space Agency and the Japanese space agency, NASDA. Use of all facilities in each of the modules will be available to investigators from participating space agencies. With the advent of the ISS, space-based gravitational biology research will transition from 10-16 day short-duration Space Shuttle flights to 90-day-or-longer ISS increments.

Pulse - Accelerator Science in Medicine

Science.gov Websites

the structure of biological molecules. They use the energy that charged particles emit when powerful than the sun and focused on a pinpoint. Deciphering the structure of proteins is key to understanding biological processes and healing disease. To determine a protein’s structure, researchers direct

Biocellion: accelerating computer simulation of multicellular biological system models.

PubMed

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

2014-11-01

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. 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. 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. © The Author 2014. Published by Oxford University Press. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

High-throughput screens in mammalian cells using the CRISPR-Cas9 system.

PubMed

Peng, Jingyu; Zhou, Yuexin; Zhu, Shiyou; Wei, Wensheng

2015-06-01

As a powerful genome-editing tool, the clustered regularly interspaced short palindromic repeats (CRISPR)-clustered regularly interspaced short palindromic repeats-associated protein 9 (Cas9) system has been quickly developed into a large-scale function-based screening strategy in mammalian cells. This new type of genetic library is constructed through the lentiviral delivery of single-guide RNA collections that direct Cas9 or inactive dead Cas9 fused with effectors to interrogate gene function or regulate gene transcription in targeted cells. Compared with RNA interference screening, the CRISPR-Cas9 system demonstrates much higher levels of effectiveness and reliability with respect to both loss-of-function and gain-of-function screening. Unlike the RNA interference strategy, a CRISPR-Cas9 library can target both protein-coding sequences and regulatory elements, including promoters, enhancers and elements transcribing microRNAs and long noncoding RNAs. This powerful genetic tool will undoubtedly accelerate the mechanistic discovery of various biological processes. In this mini review, we summarize the general procedure of CRISPR-Cas9 library mediated functional screening, system optimization strategies and applications of this new genetic toolkit. © 2015 FEBS.

Facilities for Biological Research Aboard the International Space Station

NASA Technical Reports Server (NTRS)

Souza, Kenneth A.; Yost, Bruce D.; Berry, William E.; Johnson, Catherine C.

1996-01-01

A centrifuge designed as part of an integrated biological facility for installation onboard the International Space Station is presented. The requirements for the 2.5 m diameter centrifuge, which is designed for the support of biological experiments are discussed. The scientific objectives of the facility are to: provide a means of conducting fundamental studies in which gravitational acceleration is a controllable variable; provide a 1g control; determine the threshold acceleration for physiological response, and determine the value of centrifugation as a potential countermeasure for the biomedical problems associated with space flight. The implementation of the facility is reported on, and the following aspects of the facility are described: the host resources systems supply requirements such as power and data control; the habitat holding rack; the life sciences glove box; the centrifuge; the different habitats for cell culture, aquatic studies, plant research and insect research; the egg incubator, and the laboratory support equipment.

Biology is only part of the story ...

PubMed

Read, Dwight; van der Leeuw, Sander

2008-06-12

The origins and development of human cognition constitute one of the most interesting questions to which archaeology can contribute today. In this paper, we do so by presenting an overview of the evolution of artefact technology from the maker's point of view, and linking that development to some hypotheses on the evolution of human cognitive capacity. Our main hypothesis is that these data indicate that, in the first part of the trajectory, biological limits to cognitive capacity were a major constraint that limited technology, whereas, in the second part, this biological constraint seems to have been lifted and others have come in its place. But these are modifiable by means of conceptual frameworks that facilitate concept innovation and therefore enable learning, thereby permitting acceleration in the pace of change in technology. In the last part of the paper, we elaborate on some of the consequences of that acceleration.

Analyzing radial acceleration with a smartphone acceleration sensor

NASA Astrophysics Data System (ADS)

Vogt, Patrik; Kuhn, Jochen

2013-03-01

This paper continues the sequence of experiments using the acceleration sensor of smartphones (for description of the function and the use of the acceleration sensor, see Ref. 1) within this column, in this case for analyzing the radial acceleration.

Controlling Mass Transport in Microfluidic Devices

PubMed Central

Kuo, Jason S.; Chiu, Daniel T.

2017-01-01

Microfluidic platforms offer exquisite capabilities in controlling mass transport for biological studies. In this review, we focus on recent developments in manipulating chemical concentrations at the microscale. Some techniques prevent or accelerate mixing, whereas others shape the concentration gradients of chemical and biological molecules. We also highlight several in vitro biological studies in the areas of organ engineering, cancer, and blood coagulation that have benefited from accurate control of mass transfer. PMID:21456968

Recursive formulas for determining perturbing accelerations in intermediate satellite motion

NASA Astrophysics Data System (ADS)

Stoianov, L.

Recursive formulas for Legendre polynomials and associated Legendre functions are used to obtain recursive relationships for determining acceleration components which perturb intermediate satellite motion. The formulas are applicable in all cases when the perturbation force function is presented as a series in spherical functions (gravitational, tidal, thermal, geomagnetic, and other perturbations of intermediate motion). These formulas can be used to determine the order of perturbing accelerations.

Photochemical Acceleration of DNA Strand Displacement by Using Ultrafast DNA Photo-crosslinking.

PubMed

Nakamura, Shigetaka; Hashimoto, Hirokazu; Kobayashi, Satoshi; Fujimoto, Kenzo

2017-10-18

DNA strand displacement is an essential reaction in genetic recombination, biological processes, and DNA nanotechnology. In particular, various DNA nanodevices enable complicated calculations. However, it takes time before the output is obtained, so acceleration of DNA strand displacement is required for a rapid-response DNA nanodevice. Herein, DNA strand displacement by using DNA photo-crosslinking to accelerate this displacement is evaluated. The DNA photo-crosslinking of 3-cyanovinylcarbazole ( CNV K) was accelerated at least 20 times, showing a faster DNA strand displacement. The rate of photo-crosslinking is a key factor and the rate of DNA strand displacement is accelerated through ultrafast photo-crosslinking. The rate of DNA strand displacement was regulated by photoirradiation energy. © 2017 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.

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.

Ground-based research with heavy ions for space radiation protection

NASA Astrophysics Data System (ADS)

Durante, M.; Kronenberg, A.

Human exposure to ionizing radiation is one of the acknowledged potential showstoppers for long duration manned interplanetary missions. Human exploratory missions cannot be safely performed without a substantial reduction of the uncertainties associated with different space radiation health risks, and the development of effective countermeasures. Most of our knowledge of the biological effects of heavy charged particles comes from accelerator-based experiments. During the 35th COSPAR meeting, recent ground-based experiments with high-energy iron ions were discussed, and these results are briefly summarised in this paper. High-quality accelerator-based research with heavy ions will continue to be the main source of knowledge of space radiation health effects and will lead to reductions of the uncertainties in predictions of human health risks. Efforts in materials science, nutrition and pharmaceutical sciences and their rigorous evaluation with biological model systems in ground-based accelerator experiments will lead to the development of safe and effective countermeasures to permit human exploration of the Solar System.

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.

Collective behavior of large-scale neural networks with GPU acceleration.

PubMed

Qu, Jingyi; Wang, Rubin

2017-12-01

In this paper, the collective behaviors of a small-world neuronal network motivated by the anatomy of a mammalian cortex based on both Izhikevich model and Rulkov model are studied. The Izhikevich model can not only reproduce the rich behaviors of biological neurons but also has only two equations and one nonlinear term. Rulkov model is in the form of difference equations that generate a sequence of membrane potential samples in discrete moments of time to improve computational efficiency. These two models are suitable for the construction of large scale neural networks. By varying some key parameters, such as the connection probability and the number of nearest neighbor of each node, the coupled neurons will exhibit types of temporal and spatial characteristics. It is demonstrated that the implementation of GPU can achieve more and more acceleration than CPU with the increasing of neuron number and iterations. These two small-world network models and GPU acceleration give us a new opportunity to reproduce the real biological network containing a large number of neurons.

Combined ultraviolet and water exposure as a preconditioning method in laboratory fungal durability testing

Treesearch

Rebecca E. Ibach; Craig M. Clemons; Nicole M. Stark

2003-01-01

During outdoor exposure, woodfiber-plastic composites (WPC) are subject to biological, moisture, and ultraviolet (UV) degradation. The purpose of laboratory evaluations is to simulate outdoor conditions and accelerate the testing for quicker results. Traditionally, biological, moisture, and W laboratory tests are done separately, and only combined in outdoor field...

Rapid cycling medical synchrotron and beam delivery system

DOEpatents

Peggs, Stephen G [Port Jefferson, NY; Brennan, J Michael [East Northport, NY; Tuozzolo, Joseph E [Sayville, NY; Zaltsman, Alexander [Commack, NY

2008-10-07

A medical synchrotron which cycles rapidly in order to accelerate particles for delivery in a beam therapy system. The synchrotron generally includes a radiofrequency (RF) cavity for accelerating the particles as a beam and a plurality of combined function magnets arranged in a ring. Each of the combined function magnets performs two functions. The first function of the combined function magnet is to bend the particle beam along an orbital path around the ring. The second function of the combined function magnet is to focus or defocus the particle beam as it travels around the path. The radiofrequency (RF) cavity is a ferrite loaded cavity adapted for high speed frequency swings for rapid cycling acceleration of the particles.

Acceleration of Lateral Equilibration in Mixed Lipid Bilayers Using Replica Exchange with Solute Tempering

PubMed Central

2015-01-01

The lateral heterogeneity of cellular membranes plays an important role in many biological functions such as signaling and regulating membrane proteins. This heterogeneity can result from preferential interactions between membrane components or interactions with membrane proteins. One major difficulty in molecular dynamics simulations aimed at studying the membrane heterogeneity is that lipids diffuse slowly and collectively in bilayers, and therefore, it is difficult to reach equilibrium in lateral organization in bilayer mixtures. Here, we propose the use of the replica exchange with solute tempering (REST) approach to accelerate lateral relaxation in heterogeneous bilayers. REST is based on the replica exchange method but tempers only the solute, leaving the temperature of the solvent fixed. Since the number of replicas in REST scales approximately only with the degrees of freedom in the solute, REST enables us to enhance the configuration sampling of lipid bilayers with fewer replicas, in comparison with the temperature replica exchange molecular dynamics simulation (T-REMD) where the number of replicas scales with the degrees of freedom of the entire system. We apply the REST method to a cholesterol and 1,2-dipalmitoyl-sn-glycero-3-phosphocholine (DPPC) bilayer mixture and find that the lateral distribution functions of all molecular pair types converge much faster than in the standard MD simulation. The relative diffusion rate between molecules in REST is, on average, an order of magnitude faster than in the standard MD simulation. Although REST was initially proposed to study protein folding and its efficiency in protein folding is still under debate, we find a unique application of REST to accelerate lateral equilibration in mixed lipid membranes and suggest a promising way to probe membrane lateral heterogeneity through molecular dynamics simulation. PMID:25328493

HIP/PAP accelerates liver regeneration and protects against acetaminophen injury in mice.

PubMed

Lieu, Hanh-Tu; Batteux, Frédéric; Simon, Marie-Thérèse; Cortes, Alexandre; Nicco, Carole; Zavala, Flora; Pauloin, Alain; Tralhao, José Guilherme; Soubrane, Olivier; Weill, Bernard; Bréchot, Christian; Christa, Laurence

2005-09-01

Human hepatocarcinoma-intestine-pancreas/pancreatic-associated protein HIP/PAP is a secreted C-type lectin belonging to group VII, according to Drickamer's classification. HIP/PAP is overexpressed in liver carcinoma; however, its functional role remains unclear. In this study, we demonstrate that HIP/PAP is a paracrine hepatic growth factor promoting both proliferation and viability of liver cells in vivo. First, a low number of implanted hepatocytes deriving from HIP/PAP-transgenic mice (<1:1,000) was sufficient to stimulate overall recipient severe combined immunodeficiency liver regeneration after partial hepatectomy. After a single injection of HIP/PAP protein, the percentages of bromodeoxyuridine-positive nuclei and mitosis were statistically higher than after saline injection, indicating that HIP/PAP acts as a paracrine mitogenic growth factor for the liver. Comparison of the early events posthepatectomy in control and transgenic mice indicated that HIP/PAP accelerates the accumulation/degradation of nuclear phospho-signal transducer activator transcription factor 3 and tumor necrosis factor alpha level, thus reflecting that HIP/PAP accelerates liver regeneration. Second, we showed that 80% of the HIP/PAP-transgenic mice versus 25% of the control mice were protected against lethal acetaminophen-induced fulminate hepatitis. A single injection of recombinant HIP/PAP induced a similar cytoprotective effect, demonstrating the antiapoptotic effect of HIP/PAP. Comparison of Cu/Zn superoxide dismutase activity and glutathione reductase-like effects in control and transgenic liver mice indicated that HIP/PAP exerts an antioxidant activity and prevents reactive oxygen species-induced mitochondrial damage by acetaminophen overdose. In conclusion, the present data offer new insights into the biological functions of C-type lectins. In addition, HIP/PAP is a promising candidate for the prevention and treatment of liver failure.

Acceleration of Lateral Equilibration in Mixed Lipid Bilayers Using Replica Exchange with Solute Tempering.

PubMed

Huang, Kun; García, Angel E

2014-10-14

The lateral heterogeneity of cellular membranes plays an important role in many biological functions such as signaling and regulating membrane proteins. This heterogeneity can result from preferential interactions between membrane components or interactions with membrane proteins. One major difficulty in molecular dynamics simulations aimed at studying the membrane heterogeneity is that lipids diffuse slowly and collectively in bilayers, and therefore, it is difficult to reach equilibrium in lateral organization in bilayer mixtures. Here, we propose the use of the replica exchange with solute tempering (REST) approach to accelerate lateral relaxation in heterogeneous bilayers. REST is based on the replica exchange method but tempers only the solute, leaving the temperature of the solvent fixed. Since the number of replicas in REST scales approximately only with the degrees of freedom in the solute, REST enables us to enhance the configuration sampling of lipid bilayers with fewer replicas, in comparison with the temperature replica exchange molecular dynamics simulation (T-REMD) where the number of replicas scales with the degrees of freedom of the entire system. We apply the REST method to a cholesterol and 1,2-dipalmitoyl- sn -glycero-3-phosphocholine (DPPC) bilayer mixture and find that the lateral distribution functions of all molecular pair types converge much faster than in the standard MD simulation. The relative diffusion rate between molecules in REST is, on average, an order of magnitude faster than in the standard MD simulation. Although REST was initially proposed to study protein folding and its efficiency in protein folding is still under debate, we find a unique application of REST to accelerate lateral equilibration in mixed lipid membranes and suggest a promising way to probe membrane lateral heterogeneity through molecular dynamics simulation.

The biology of color.

PubMed

Cuthill, Innes C; Allen, William L; Arbuckle, Kevin; Caspers, Barbara; Chaplin, George; Hauber, Mark E; Hill, Geoffrey E; Jablonski, Nina G; Jiggins, Chris D; Kelber, Almut; Mappes, Johanna; Marshall, Justin; Merrill, Richard; Osorio, Daniel; Prum, Richard; Roberts, Nicholas W; Roulin, Alexandre; Rowland, Hannah M; Sherratt, Thomas N; Skelhorn, John; Speed, Michael P; Stevens, Martin; Stoddard, Mary Caswell; Stuart-Fox, Devi; Talas, Laszlo; Tibbetts, Elizabeth; Caro, Tim

2017-08-04

Coloration mediates the relationship between an organism and its environment in important ways, including social signaling, antipredator defenses, parasitic exploitation, thermoregulation, and protection from ultraviolet light, microbes, and abrasion. Methodological breakthroughs are accelerating knowledge of the processes underlying both the production of animal coloration and its perception, experiments are advancing understanding of mechanism and function, and measurements of color collected noninvasively and at a global scale are opening windows to evolutionary dynamics more generally. Here we provide a roadmap of these advances and identify hitherto unrecognized challenges for this multi- and interdisciplinary field. Copyright © 2017 The Authors, some rights reserved; exclusive licensee American Association for the Advancement of Science. No claim to original U.S. Government Works.

Eukaryote-like Ser/Thr protein kinase PrkA modulates sporulation via regulating the transcriptional factor σ(K) in Bacillus subtilis.

PubMed

Yan, Jinyuan; Zou, Wei; Fang, Juan; Huang, Xiaowei; Gao, Feng; He, Zeying; Zhang, Keqin; Zhao, Ninghui

2015-01-01

Protein kinase A (PrkA), also known as AMP-activated protein kinase, functions as a serine/threonine protein kinase (STPK), has been shown to be involved in a variety of important biologic processes, including pathogenesis of many important diseases in mammals. However, the biological functions of PrkA are less known in prokaryote cells. Here, we explored the function of PrkA as well as its underlying molecular mechanisms using the model bacterium Bacillus subtilis168. When PrkA is inhibited by 9-β-D-arabinofuranosyladenine (ara-A) in the wild type strain or deleted in the ΔprkA mutant strain, we observed sporulation defects in B. subtilis 168, suggesting that PrkA functions as a sporulation-related protein. Transcriptional analysis using the lacZ reporter gene demonstrated that deletion of prkA significantly reduced the expression of the transcriptional factor σ(K) and its downstream genes. Complementation of sigK gene in prkA knockout mutant partially rescued the phenotype of ΔprkA, further supporting the hypothesis that the decreased σ(K) expression should be one of the reasons for the sporulation defect resulting from prkA disruption. Finally, our data confirmed that Hpr (ScoC) negatively controlled the expression of transcriptional factor σ(K), and thus PrkA accelerated sporulation and the expression of σ(K) by suppression of Hpr (ScoC). Taken together, our study discovered a novel function of the eukaryotic-like STPK PrkA in spore development as well as its underlying molecular mechanism in B. subtilis.

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.

An investigation into the probabilistic combination of quasi-static and random accelerations

NASA Technical Reports Server (NTRS)

Schock, R. W.; Tuell, L. P.

1984-01-01

The development of design load factors for aerospace and aircraft components and experiment support structures, which are subject to a simultaneous vehicle dynamic vibration (quasi-static) and acoustically generated random vibration, require the selection of a combination methodology. Typically, the procedure is to define the quasi-static and the random generated response separately, and arithmetically add or root sum square to get combined accelerations. Since the combination of a probabilistic and a deterministic function yield a probabilistic function, a viable alternate approach would be to determine the characteristics of the combined acceleration probability density function and select an appropriate percentile level for the combined acceleration. The following paper develops this mechanism and provides graphical data to select combined accelerations for most popular percentile levels.

Beam deceleration for block-face scanning electron microscopy of embedded biological tissue.

PubMed

Ohta, Keisuke; Sadayama, Shoji; Togo, Akinobu; Higashi, Ryuhei; Tanoue, Ryuichiro; Nakamura, Kei-ichiro

2012-04-01

The beam deceleration (BD) method for scanning electron microscopes (SEM) also referred to as "retarding" was applied to back-scattered electron (BSE) imaging of the flat block face of a resin embedded biological specimen under low accelerating voltage and low beam current conditions. BSE imaging was performed with 0-4 kV of BD on en bloc stained rat hepatocyte. BD drastically enhanced the compositional contrast of the specimen and also improved the resolution at low landing energy levels (1.5-3 keV) and a low beam current (10 pA). These effects also functioned in long working distance observation, however, stage tilting caused uncorrectable astigmatism in BD observation. Stage tilting is mechanically required for a FIB/SEM, so we designed a novel specimen holder to minimize the unfavorable tilting effect. The FIB/SEM 3D reconstruction using the new holder showed a reasonable contrast and resolution high enough to analyze individual cell organelles and also the mitochondrial cristae structures (~5 nm) of the hepatocyte. These results indicate the advantages of BD for block face imaging of biological materials such as cells and tissues under low-voltage and low beam current conditions. Copyright © 2011 Elsevier Ltd. All rights reserved.

Peptidomics: the integrated approach of MS, hyphenated techniques and bioinformatics for neuropeptide analysis.

PubMed

Boonen, Kurt; Landuyt, Bart; Baggerman, Geert; Husson, Steven J; Huybrechts, Jurgen; Schoofs, Liliane

2008-02-01

MS is currently one of the most important analytical techniques in biological and medical research. ESI and MALDI launched the field of MS into biology. The performance of mass spectrometers increased tremendously over the past decades. Other technological advances increased the analytical power of biological MS even more. First, the advent of the genome projects allowed an automated analysis of mass spectrometric data. Second, improved separation techniques, like nanoscale HPLC, are essential for MS analysis of biomolecules. The recent progress in bioinformatics is the third factor that accelerated the biochemical analysis of macromolecules. The first part of this review will introduce the basics of these techniques. The field that integrates all these techniques to identify endogenous peptides is called peptidomics and will be discussed in the last section. This integrated approach aims at identifying all the present peptides in a cell, organ or organism (the peptidome). Today, peptidomics is used by several fields of research. Special emphasis will be given to the identification of neuropeptides, a class of short proteins that fulfil several important intercellular signalling functions in every animal. MS imaging techniques and biomarker discovery will also be discussed briefly.

FUSION-Guided Hypothesis Development Leads to the Identification of N6,N6-Dimethyladenosine, a Marine-Derived AKT Pathway Inhibitor

PubMed Central

Vaden, Rachel M.; Oswald, Nathaniel W.; Potts, Malia B.; MacMillan, John B.; White, Michael A.

2017-01-01

Chemicals found in nature have evolved over geological time scales to productively interact with biological molecules, and thus represent an effective resource for pharmaceutical development. Marine-derived bacteria are rich sources of chemically diverse, bioactive secondary metabolites, but harnessing this diversity for biomedical benefit is limited by challenges associated with natural product purification and determination of biochemical mechanism. Using Functional Signature Ontology (FUSION), we report the parallel isolation and characterization of a marine-derived natural product, N6,N6-dimethyladenosine, that robustly inhibits AKT signaling in a variety of non-small cell lung cancer cell lines. Upon validation of the elucidated structure by comparison with a commercially available sample, experiments were initiated to understand the small molecule’s breadth of effect in a biological setting. One such experiment, a reverse phase protein array (RPPA) analysis of >50 kinases, indicated a specific cellular response to treatment. In all, leveraging the FUSION platform allowed for the rapid generation and validation of a biological mechanism of action hypothesis for an unknown natural product and permitted accelerated purification of the bioactive component from a chemically complex fraction. PMID:28294973

A Novel Mouse Model of Penetrating Brain Injury

PubMed Central

Cernak, Ibolja; Wing, Ian D.; Davidsson, Johan; Plantman, Stefan

2014-01-01

Penetrating traumatic brain injury (pTBI) has been difficult to model in small laboratory animals, such as rats or mice. Previously, we have established a non-fatal, rat model for pTBI using a modified air-rifle that accelerates a pellet, which hits a small probe that then penetrates the experimental animal’s brain. Knockout and transgenic strains of mice offer attractive tools to study biological reactions induced by TBI. Hence, in the present study, we adapted and modified our model to be used with mice. The technical characterization of the impact device included depth and speed of impact, as well as dimensions of the temporary cavity formed in a brain surrogate material after impact. Biologically, we have focused on three distinct levels of severity (mild, moderate, and severe), and characterized the acute phase response to injury in terms of tissue destruction, neural degeneration, and gliosis. Functional outcome was assessed by measuring bodyweight and motor performance on rotarod. The results showed that this model is capable of reproducing major morphological and neurological changes of pTBI; as such, we recommend its utilization in research studies aiming to unravel the biological events underlying injury and regeneration after pTBI. PMID:25374559

Design and development of synthetic microbial platform cells for bioenergy

PubMed Central

Lee, Sang Jun; Lee, Sang-Jae; Lee, Dong-Woo

2013-01-01

The finite reservation of fossil fuels accelerates the necessity of development of renewable energy sources. Recent advances in synthetic biology encompassing systems biology and metabolic engineering enable us to engineer and/or create tailor made microorganisms to produce alternative biofuels for the future bio-era. For the efficient transformation of biomass to bioenergy, microbial cells need to be designed and engineered to maximize the performance of cellular metabolisms for the production of biofuels during energy flow. Toward this end, two different conceptual approaches have been applied for the development of platform cell factories: forward minimization and reverse engineering. From the context of naturally minimized genomes,non-essential energy-consuming pathways and/or related gene clusters could be progressively deleted to optimize cellular energy status for bioenergy production. Alternatively, incorporation of non-indigenous parts and/or modules including biomass-degrading enzymes, carbon uptake transporters, photosynthesis, CO2 fixation, and etc. into chassis microorganisms allows the platform cells to gain novel metabolic functions for bioenergy. This review focuses on the current progress in synthetic biology-aided pathway engineering in microbial cells and discusses its impact on the production of sustainable bioenergy. PMID:23626588

Targeting inflammation in the prevention of cardiovascular disease in patients with inflammatory arthritis.

PubMed

Shen, Jiayun; Shang, Qing; Tam, Lai-Shan

2016-01-01

Patients with inflammatory arthritis have increased risk of cardiovascular diseases (CVDs) compared with the general population. Subclinical carotid atherosclerosis and increased arterial stiffness are also common in these patients, which may serve as surrogate end points for cardiovascular (CV) events in clinical trials. Although exact mechanisms are still unclear, persistent systemic inflammation in patients with inflammatory arthritis may contribute to the development of CVD. Dysregulated innate immunity pathways in these patients may also play a role in accelerating atherosclerosis. During the last decade, effective suppression of inflammation by biological disease-modifying antirheumatic drugs has improved the disease outcome dramatically in patients with inflammatory arthritis. Growing evidence suggests that antitumor necrosis factor (TNF) therapy may prevent CVD in patients with rheumatoid arthritis. Nonetheless, data on non-TNF biologics are limited. Whether anti-TNF therapy may prevent CVD in patients with spondyloarthritis also remained unclear. In this review, we summarized the effect of both anti-TNF and non-TNF biologics on the CV system, including traditional CVD risk factors, endothelial function, arterial stiffness, subclinical atherosclerosis, and clinical CVD in patients with inflammatory arthritis. Copyright © 2016 Elsevier Inc. All rights reserved.

LCM-seq reveals the crucial role of LsSOC1 in heat-promoted bolting of lettuce (Lactuca sativa L.).

PubMed

Chen, Zijing; Zhao, Wensheng; Ge, Danfeng; Han, Yingyan; Ning, Kang; Luo, Chen; Wang, Shenglin; Liu, Renyi; Zhang, Xiaolan; Wang, Qian

2018-05-17

Lettuce (Lactuca sativa L.) is one of the most economically important vegetables. The floral transition in lettuce is accelerated under high temperatures, which can significantly decrease yields. However, the molecular mechanism underlying the floral tranition in lettuce is poorly known. Using laser capture microdissection coupled with RNA sequencing, we isolated shoot apical meristem cells from the bolting-sensitive lettuce line S39 at four critical stages of development. Subsequently, we screened specifically for the flowering-related gene LsSOC1 during the floral transition through comparative transcriptomic analysis. Molecular biology, developmental biology, and biochemical tools were combined to investigate the biological function of LsSOC1 in lettuce. LsSOC1 knockdown by RNA interference resulted in a significant delay in the timing of bolting and insensitivity to high temperature, which indicated that LsSOC1 functions as an activator during heat-promoted bolting in lettuce. We determined that two heat-shock transcription factors, HsfA1e and HsfA4c, bound to the promoter of LsSOC1 to confirm that LsSOC1 played an important role in heat-promoted bolting. This study indicates that LsSOC1 plays a crucial role in the heat-promoted bolting process in lettuce. Further investigation of LsSOC1 may be useful for clarification of the bolting mechanism in lettuce. This article is protected by copyright. All rights reserved. This article is protected by copyright. All rights reserved.

Nano/micromotors for security/defense applications. A review.

PubMed

Singh, Virendra V; Wang, Joseph

2015-12-14

The new capabilities of man-made micro/nanomotors open up considerable opportunities for diverse security and defense applications. This review highlights new micromotor-based strategies for enhanced security monitoring and detoxification of chemical and biological warfare agents (CBWA). The movement of receptor-functionalized nanomotors offers great potential for sensing and isolating target bio-threats from complex samples. New mobile reactive materials based on zeolite or activated carbon offer considerable promise for the accelerated removal of chemical warfare agents. A wide range of proof-of-concept motor-based approaches, including the detection and destruction of anthrax spores, 'on-off' nerve-agent detection or effective neutralization of chemical warfare agents have thus been demonstrated. The propulsion of micromotors and their corresponding bubble tails impart significant mixing that greatly accelerates such detoxification processes. These nanomotors will thus empower sensing and destruction where stirring large quantities of decontaminating reagents and controlled mechanical agitation are impossible or undesired. New technological breakthroughs and greater sophistication of micro/nanoscale machines will lead to rapid translation of the micromotor research activity into practical defense applications, addressing the escalating threat of CBWA.

Nano/micromotors for security/defense applications. A review

NASA Astrophysics Data System (ADS)

Singh, Virendra V.; Wang, Joseph

2015-11-01

The new capabilities of man-made micro/nanomotors open up considerable opportunities for diverse security and defense applications. This review highlights new micromotor-based strategies for enhanced security monitoring and detoxification of chemical and biological warfare agents (CBWA). The movement of receptor-functionalized nanomotors offers great potential for sensing and isolating target bio-threats from complex samples. New mobile reactive materials based on zeolite or activated carbon offer considerable promise for the accelerated removal of chemical warfare agents. A wide range of proof-of-concept motor-based approaches, including the detection and destruction of anthrax spores, `on-off' nerve-agent detection or effective neutralization of chemical warfare agents have thus been demonstrated. The propulsion of micromotors and their corresponding bubble tails impart significant mixing that greatly accelerates such detoxification processes. These nanomotors will thus empower sensing and destruction where stirring large quantities of decontaminating reagents and controlled mechanical agitation are impossible or undesired. New technological breakthroughs and greater sophistication of micro/nanoscale machines will lead to rapid translation of the micromotor research activity into practical defense applications, addressing the escalating threat of CBWA.

Development of a high-content screening assay panel to accelerate mechanism of action studies for oncology research.

PubMed

Towne, Danli L; Nicholl, Emily E; Comess, Kenneth M; Galasinski, Scott C; Hajduk, Philip J; Abraham, Vivek C

2012-09-01

Efficient elucidation of the biological mechanism of action of novel compounds remains a major bottleneck in the drug discovery process. To address this need in the area of oncology, we report the development of a multiparametric high-content screening assay panel at the level of single cells to dramatically accelerate understanding the mechanism of action of cell growth-inhibiting compounds on a large scale. Our approach is based on measuring 10 established end points associated with mitochondrial apoptosis, cell cycle disruption, DNA damage, and cellular morphological changes in the same experiment, across three multiparametric assays. The data from all of the measurements taken together are expected to help increase our current understanding of target protein functions, constrain the list of possible targets for compounds identified using phenotypic screens, and identify off-target effects. We have also developed novel data visualization and phenotypic classification approaches for detailed interpretation of individual compound effects and navigation of large collections of multiparametric cellular responses. We expect this general approach to be valuable for drug discovery across multiple therapeutic areas.

Accelerator shield design of KIPT neutron source facility

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

Zhong, Z.; Gohar, Y.

Argonne National Laboratory (ANL) of the United States and Kharkov Institute of Physics and Technology (KIPT) of Ukraine have been collaborating on the design development of a neutron source facility at KIPT utilizing an electron-accelerator-driven subcritical assembly. Electron beam power is 100 kW, using 100 MeV electrons. The facility is designed to perform basic and applied nuclear research, produce medical isotopes, and train young nuclear specialists. The biological shield of the accelerator building is designed to reduce the biological dose to less than 0.5-mrem/hr during operation. The main source of the biological dose is the photons and the neutrons generatedmore » by interactions of leaked electrons from the electron gun and accelerator sections with the surrounding concrete and accelerator materials. The Monte Carlo code MCNPX serves as the calculation tool for the shield design, due to its capability to transport electrons, photons, and neutrons coupled problems. The direct photon dose can be tallied by MCNPX calculation, starting with the leaked electrons. However, it is difficult to accurately tally the neutron dose directly from the leaked electrons. The neutron yield per electron from the interactions with the surrounding components is less than 0.01 neutron per electron. This causes difficulties for Monte Carlo analyses and consumes tremendous computation time for tallying with acceptable statistics the neutron dose outside the shield boundary. To avoid these difficulties, the SOURCE and TALLYX user subroutines of MCNPX were developed for the study. The generated neutrons are banked, together with all related parameters, for a subsequent MCNPX calculation to obtain the neutron and secondary photon doses. The weight windows variance reduction technique is utilized for both neutron and photon dose calculations. Two shielding materials, i.e., heavy concrete and ordinary concrete, were considered for the shield design. The main goal is to maintain the total dose outside the shield boundary at less than 0.5-mrem/hr. The shield configuration and parameters of the accelerator building have been determined and are presented in this paper. (authors)« less

Tribbles pseudokinases: novel targets for chemical biology and drug discovery?

PubMed

Foulkes, Daniel M; Byrne, Dominic P; Bailey, Fiona P; Eyers, Patrick A

2015-10-01

Tribbles (TRIB) proteins are pseudokinase mediators of eukaryotic signalling that have evolved important roles in lipoprotein metabolism, immune function and cellular differentiation and proliferation. In addition, an evolutionary-conserved modulation of PI3K/AKT signalling pathways highlights them as novel and rather unusual pharmaceutical targets. The three human TRIB family members are uniquely defined by an acidic pseudokinase domain containing a 'broken' α C-helix and a MEK (MAPK/ERK)-binding site at the end of the putative C-lobe and a distinct C-terminal peptide motif that interacts directly with a small subset of cellular E3 ubiquitin ligases. This latter interaction drives proteasomal-dependent degradation of networks of transcription factors, whose rate of turnover determines the biological attributes of individual TRIB family members. Defining the function of individual Tribs has been made possible through evaluation of individual TRIB knockout mice, siRNA/overexpression approaches and genetic screening in flies, where the single TRIB gene was originally described 15 years ago. The rapidly maturing TRIB field is primed to exploit chemical biology approaches to evaluate endogenous TRIB signalling events in intact cells. This will help define how TRIB-driven protein-protein interactions and the atypical TRIB ATP-binding site, fit into cellular signalling modules in experimental scenarios where TRIB-signalling complexes remain unperturbed. In this mini-review, we discuss how small molecules can reveal rate-limiting signalling outputs and functions of Tribs in cells and intact organisms, perhaps serving as guides for the development of new drugs. We predict that appropriate small molecule TRIB ligands will further accelerate the transition of TRIB pseudokinase analysis into the mainstream of cell signalling. © 2015 Authors; published by Portland Press Limited.

CHIP promotes thyroid cancer proliferation via activation of the MAPK and AKT pathways.

PubMed

Zhang, Li; Liu, Lianyong; He, Xiaohua; Shen, Yunling; Liu, Xuerong; Wei, Jing; Yu, Fang; Tian, Jianqing

2016-08-26

The carboxyl terminus of Hsp70-interacting protein (CHIP) is a U box-type ubiquitin ligase that plays crucial roles in various biological processes, including tumor progression. To date, the functional mechanism of CHIP in thyroid cancer remains unknown. Here, we obtained evidence of upregulation of CHIP in thyroid cancer tissues and cell lines. CHIP overexpression markedly enhanced thyroid cancer cell viability and colony formation in vitro and accelerated tumor growth in vivo. Conversely, CHIP knockdown impaired cell proliferation and tumor growth. Notably, CHIP promoted cell growth through activation of MAPK and AKT pathways, subsequently decreasing p27 and increasing cyclin D1 and p-FOXO3a expression. Our findings collectively indicate that CHIP functions as an oncogene in thyroid cancer, and is therefore a potential therapeutic target for this disease. Copyright © 2016 Elsevier Inc. All rights reserved.

Dimerization controls the lipid raft partitioning of uPAR/CD87 and regulates its biological functions

PubMed Central

Cunningham, Orla; Andolfo, Annapaola; Santovito, Maria Lisa; Iuzzolino, Lucia; Blasi, Francesco; Sidenius, Nicolai

2003-01-01

The urokinase-type plasminogen activator receptor (uPAR/CD87) is a glycosylphosphatidylinositol-anchored membrane protein with multiple functions in extracellular proteolysis, cell adhesion, cell migration and proliferation. We now report that cell surface uPAR dimerizes and that dimeric uPAR partitions preferentially to detergent-resistant lipid rafts. Dimerization of uPAR did not require raft partitioning as the lowering of membrane cholesterol failed to reduce dimerization and as a transmembrane uPAR chimera, which does not partition to lipid rafts, also dimerized efficiently. While uPA bound to uPAR independently of its membrane localization and dimerization status, uPA-induced uPAR cleavage was strongly accelerated in lipid rafts. In contrast to uPA, the binding of Vn occurred preferentially to raft- associated dimeric uPAR and was completely blocked by cholesterol depletion. PMID:14609946

The interplay between immunity and aging in Drosophila.

PubMed

Garschall, Kathrin; Flatt, Thomas

2018-01-01

Here, we provide a brief review of the mechanistic connections between immunity and aging-a fundamental biological relationship that remains poorly understood-by considering two intertwined questions: how does aging affect immunity, and how does immunity affect aging? On the one hand, aging contributes to the deterioration of immune function and predisposes the organism to infections ("immuno-senescence"). On the other hand, excessive activation of the immune system can accelerate degenerative processes, cause inflammation and immunopathology, and thus promote aging ("inflammaging"). Interestingly, several recent lines of evidence support the hypothesis that restrained or curbed immune activity at old age (that is, optimized age-dependent immune homeostasis) might actually improve realized immune function and thereby promote longevity. We focus mainly on insights from Drosophila , a powerful genetic model system in which both immunity and aging have been extensively studied, and conclude by outlining several unresolved questions in the field.

Comparison of slow and accelerated rehabilitation protocol after arthroscopic rotator cuff repair: pain and functional activity.

PubMed

Düzgün, Irem; Baltacı, Gül; Atay, O Ahmet

2011-01-01

In this study, we sought to compare the effects of the slow and accelerated protocols on pain and functional activity level after arthroscopic rotator cuff repair. The study included 29 patients (3 men, 26 women) who underwent arthroscopic repair of stage 2 and 3 rotator cuff tears. Patients were randomized in two groups: the accelerated protocol group (n=13) and slow protocol group (n=16). Patients in the accelerated protocol group participated in a preoperative rehabilitation program for 4-6 weeks. Patients were evaluated preoperatively and for 24 weeks postoperatively. Pain was assessed by visual analog scale, and functional activity level was assessed by The Disabilities of The Arm Shoulder and Hand (DASH) questionnaire. The active range of motion was initiated at week 3 after surgery for the accelerated rehabilitation protocol and at week 6 for the slow protocol. The rehabilitation program was completed by the 8th week with the accelerated protocol and by the 22nd week with the slow protocol. There was no significant difference between the slow and accelerated protocols with regard to pain at rest (p>0.05). However, the accelerated protocol was associated with less pain during activity at weeks 5 and 16, and with less pain at night during week 5 (p<0.05). The accelerated protocol was superior to the slow protocol in terms of functional activity level, as determined by DASH at weeks 8, 12, and 16 after surgery (p<0.05). The accelerated protocol is recommended to physical therapists during rehabilitation after arthroscopic rotator cuff repair to prevent the negative effects of immobilization and to support rapid reintegration to daily living activities.

Signal transduction and amplification through enzyme-triggered ligand release and accelerated catalysis.

PubMed

Goggins, Sean; Marsh, Barrie J; Lubben, Anneke T; Frost, Christopher G

2015-08-01

Signal transduction and signal amplification are both important mechanisms used within biological signalling pathways. Inspired by this process, we have developed a signal amplification methodology that utilises the selectivity and high activity of enzymes in combination with the robustness and generality of an organometallic catalyst, achieving a hybrid biological and synthetic catalyst cascade. A proligand enzyme substrate was designed to selectively self-immolate in the presence of the enzyme to release a ligand that can bind to a metal pre-catalyst and accelerate the rate of a transfer hydrogenation reaction. Enzyme-triggered catalytic signal amplification was then applied to a range of catalyst substrates demonstrating that signal amplification and signal transduction can both be achieved through this methodology.

WE-H-BRA-09: Application of a Modified Microdosimetric-Kinetic Model to Analyze Relative Biological Effectiveness of Ions Relevant to Light Ion Therapy Using the Particle Heavy Ion Transport System

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

Butkus, M; Palmer, T

Purpose: To evaluate the dose and biological effectiveness of various ions that could potentially be used for actively scanned particle therapy. Methods: The PHITS Monte Carlo code paired with a microscopic analytical function was used to determine probability distribution functions of the lineal energy in 0.3µm diameter spheres throughout a water phantom. Twenty million primary particles for 1H beams and ten million particles for 4He, 7Li, 10B, 12C, 14N, 16O, and 20Ne were simulated for 0.6cm diameter pencil beams. Beam energies corresponding to Bragg peak depths of 50, 100, 150, 200, 250, and 300mm were used and evaluated transversely everymore » millimeter and radially in annuli with outer radius of 1.0, 2.0, 3.0, 3.2, 3.4, 3.6, 4.0, 5.0, 10.0, 15.0, 20.0 and 25.0mm. The acquired probability distributions were reduced to dose-mean lineal energies and applied to the modified microdosimetric kinetic model for five different cell types to calculate relative biological effectiveness (RBE) compared to 60Co beams at the 10% survival threshold. The product of the calculated RBEs and the simulated physical dose was taken to create biological dose and comparisons were then made between the various ions. Results: Transversely, the 10B beam was seen to minimize relative biological dose in both the constant and accelerated dose change regions, proximal to the Bragg Peak, for all beams traveling greater than 50mm. For the 50mm beam, 7Li was seen to provide the most optimal biological dose profile. Radially small fluctuations (<4.2%) were seen in RBE while physical dose was greater than 1% for all beams. Conclusion: Even with the growing usage of 12C, it may not be the most optimal ion in all clinical situations. Boron was calculated to have slightly enhanced RBE characteristics, leading to lower relative biological doses.« less

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…

Dynamics of the Exchange of Carbon Dioxide in Arctic and Subarctic Regions,

DTIC Science & Technology

1973-01-01

snow, at temperatures too low for significant biological activity. The phenomena of gas evasion under conditions of 3 freezing soil solution , confirmed...1972) have observed a de- pression rather than an acceleration in soil respiration, as the soil solution undergoes a phase change near 0C. On the other...temperatures are too low for significant biological activity. CO2 from biological sources expressed by freezing the soil solution , evidently leaks to the

Accelerator boom hones China's engineering expertise

NASA Astrophysics Data System (ADS)

Normile, Dennis

2018-02-01

In raising the curtain on the China Spallation Neutron Source, China has joined just four other nations in having mastered the technology of accelerating and controlling beams of protons. The $277 million facility, set to open to users this spring in Dongguan, is expected to yield big dividends in materials science, chemistry, and biology. More world class machines are on the way, as China this year starts construction on four other major accelerator facilities. The building boom is prompting a scramble to find enough engineers and technicians to finish the projects. But if they all come off as planned, the facilities would position China to tackle the next global megaproject: a giant accelerator that would pick up where Europe's Large Hadron Collider leaves off.

[Sub-maximal aerobic capacity and quality of life of patients with rheumatoid arthritis].

PubMed

Lataoui, S; Belghali, S; Zeglaoui, H; Bouajina, E; Ben Saad, H

2017-01-01

Studies about sub-maximal aerobic capacity of patients with rheumatoid arthritis are scarce. To assess the sub-maximal aerobic capacity of these patients through the 6-min walk test, estimated age of the "muscular and cardiorespiratory" chain. Thirty-seven consecutive patients (aged 20 to 60 years) with newly diagnosed rheumatoid arthritis will be included. Non-inclusion criteria will be: use of drugs (e.g.; methotrexate, beta-blockers), orthopaedic or rheumatologic conditions (other than rheumatoid arthritis) that may alter walking ability and recent infections. Exclusion criteria will be: 6-min walking test contra-indications and imperfect performance of the required lung function and walking maneuvers. Signs of walking intolerance will be: test interruption, distance ≤lower limit of normal, dyspnea score ≥5/10 (visual analogue scale) at the end of the test, haemoglobin oxygen saturation (SpO 2 ) drop ≥5%, cardiac frequency at the end of the test ≤60% of maximum predicted. An estimated "muscular and cardiorespiratory chain" age higher than the chronological one will be considered as a sign of accelerated ageing. A high percentage of patients suffering from rheumatoid arthritis would show evidences of walking limitation and accelerated "muscular and cardiorespiratory chain" ageing. There would be a significant correlation between the walking test and clinical, biological, radiological and pulmonary function data and the patients' quality-of-life status. Copyright © 2016 SPLF. Published by Elsevier Masson SAS. All rights reserved.

The Protective Effect of Antarctic Krill Oil on Cognitive Function by Inhibiting Oxidative Stress in the Brain of Senescence-Accelerated Prone Mouse Strain 8 (SAMP8) Mice.

PubMed

Li, Qian; Wu, Fengjuan; Wen, Min; Yanagita, Teruyoshi; Xue, Changhu; Zhang, Tiantian; Wang, Yuming

2018-02-01

Alzheimer's disease (AD) is a common neurodegenerative disorder, and oxidative stress plays a vital role in its progression. Antarctic krill oil (AKO) is rich in polyunsaturated fatty acids, which has various biological activities, such as improving insulin sensitivity, alleviating inflammation and ameliorating oxidative stress. In this study, the protective effect of AKO against AD were investigated in senescence-accelerated prone mouse strain 8 (SAMP8) mice. Results showed that treatment with AKO could effectively ameliorate learning and memory deficits and ease the anxiety in SAMP8 mice by Morris water maze, Barnes maze test and open-field test. Further analysis indicated that AKO might reduce β-amyloid (Aβ) accumulation in hippocampus through decreasing the contents of malondialdehyde (MDA) and 7,8-dihydro-8-oxoguanine (8-oxo-G), increasing the superoxide dismutase (SOD) and glutathione peroxidase (GSH-Px) activities in the brain of SAMP8 mice. The results of Morris water maze, Barnes maze test and open-field test indicated that Antarctic krill oil (AKO) improved the cognitive function and anxiety of SAMP8 mice. AKO reduced the Aβ 42 level in hippocampus of SAMP8 mice. AKO ameliorated oxidative stress in brain rather than in serum and liver of SAMP8 mice. © 2018 Institute of Food Technologists®.

Proceedings of the First International Symposium on the Biological Interpretation of Dose from Accelerator-Produced Radiation, Held at the Lawrence Radiation Laboratory, Berkeley, California, March 13--16, 1967

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

Wallace, R.

1967-03-13

The objective of the meeting was to provide a companion meeting to the ''First Symposium on Accelerator Radiation Dosimetry and Experience'' which was held November 3-5, 1965, at the Brookhaven National Laboratory. This first symposium was limited in scope to an intensified discussion of dosimetry techniques. The biology which is associated with high energy radiation was specifically excluded, since it was the original plan to hold a second symposium devoted entirely to biology. Thus the present Symposium was a sequel to the first and they were inseparable in their objectives. Since those attending the BNL Symposium were almost entirely healthmore » physicists with a background in physical science and actively engaged in the solution of radiation protection problems at high energy accelerators, it was felt that it would be necessary to begin the BID Symposium with a general review session on radiation biology, in order to provide a biological background for the proper understanding of the later sessions. This first session was arranged to give the health physicist a meaningful transition from fundamental radiobiological considerations to current new research activities in high energy biology. In our opinion, and also based on the comments of several of those attending these objectives were quite well attained. The talks by Bond, Robertson, Brustad, Wolff, and Patt were quite exhaustive as an introduction to the several areas of specialization in radiobiology. The overall purpose of the meeting was of course to inform the health physicists about the state of knowledge in advanced biological research as it might apply to their problems. It has often been said that it takes a long time for laboratory findings to be applied in practical situations, but this is certainly not true in radiobiology. Through this conference and others like it, the most recent understanding of high energy radiobiology is available to the practicing health physicist and is probably used fairly effectively. In addition, much of this material applies equally well to reactor and space radiation problems, and some of the participants were from these areas as well.« less

Status and Prospects of Hirfl Experiments on Nuclear Physics

NASA Astrophysics Data System (ADS)

Xu, H. S.; Zheng, C.; Xiao, G. Q.; Zhan, W. L.; Zhou, X. H.; Zhang, Y. H.; Sun, Z. Y.; Wang, J. S.; Gan, Z. G.; Huang, W. X.; Ma, X. W.

HIRFL is an accelerator complex consisting of 3 accelerators, 2 radioactive beams lines, 1 storage rings and a number of experimental setups. The research activities at HIRFL cover the fields of radio-biology, material science, atomic physics, and nuclear physics. This report mainly concentrates on the experiments of nuclear physics with the existing and planned experimental setups such as SHANS, RIBLL1, ETF, CSRe, PISA and HPLUS at HIRFL.

Open source bioimage informatics for cell biology.

PubMed

Swedlow, Jason R; Eliceiri, Kevin W

2009-11-01

Significant technical advances in imaging, molecular biology and genomics have fueled a revolution in cell biology, in that the molecular and structural processes of the cell are now visualized and measured routinely. Driving much of this recent development has been the advent of computational tools for the acquisition, visualization, analysis and dissemination of these datasets. These tools collectively make up a new subfield of computational biology called bioimage informatics, which is facilitated by open source approaches. We discuss why open source tools for image informatics in cell biology are needed, some of the key general attributes of what make an open source imaging application successful, and point to opportunities for further operability that should greatly accelerate future cell biology discovery.

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

Dinitrosyl iron complexes with thiol-containing ligands as a "working form" of endogenous nitric oxide.

PubMed

Vanin, Anatoly F

2016-04-01

The material presented herein is an overview of the results obtained by our research team during the many years' study of biological activities and occurrence of dinitrosyl iron complexes (DNIC) with thiol-containing ligands in human and animal organisms. With regard to their dose dependence and vast diversity of biological activities, DNIC are similar to the system of endogenous NO, one of the most universal regulators of biological processes. The role of biologically active components in DNIC is played by their iron-dinitrosyl fragments, [Fe(NO)2], endowed with the ability to generate neutral NO molecules and nitrosonium ions (NO(+)). Their release is effected by heme-and thiol-containing proteins, which fulfill the function of biological targets and acceptors of NO and NO(+). Beneficial regulatory effects of DNIC on physiological and metabolic processes are numerous and diverse and include, among other things, lowering of arterial pressure and accelerated healing of skin wounds. In the course of fast decomposition of their Fe(NO)2 fragments (e.g., in the presence of iron chelators), DNIC produce adverse (cytotoxic) effects, which can best be exemplified by their ability to suppress the development of experimental endometriosis in animals. In animal tissues, DNIC with thiol-containing ligands are predominantly represented by the binuclear form, which, contrary to mononuclear DNIC detectable by the 2.03 signal, is EPR-silent. The ample body of evidence on biological activities and occurrence of DNIC gained so far clearly demonstrates that in human and animal organisms DNIC with thiol-containing ligands represent a "working form" of the system of endogenous NO responsible for its accumulation and stabilization in animal tissues as well as its further transfer to its biological targets. Copyright © 2016 Elsevier Inc. All rights reserved.

Radiobiological effectiveness of laser accelerated electrons in comparison to electron beams from a conventional linear accelerator.

PubMed

Laschinsky, Lydia; Baumann, Michael; Beyreuther, Elke; Enghardt, Wolfgang; Kaluza, Malte; Karsch, Leonhard; Lessmann, Elisabeth; Naumburger, Doreen; Nicolai, Maria; Richter, Christian; Sauerbrey, Roland; Schlenvoigt, Hans-Peter; Pawelke, Jörg

2012-01-01

The notable progress in laser particle acceleration technology promises potential medical application in cancer therapy through compact and cost effective laser devices that are suitable for already existing clinics. Previously, consequences on the radiobiological response by laser driven particle beams characterised by an ultra high peak dose rate have to be investigated. Therefore, tumour and non-malignant cells were irradiated with pulsed laser accelerated electrons at the JETI facility for the comparison with continuous electrons of a conventional therapy LINAC. Dose response curves were measured for the biological endpoints clonogenic survival and residual DNA double strand breaks. The overall results show no significant differences in radiobiological response for in vitro cell experiments between laser accelerated pulsed and clinical used electron beams. These first systematic in vitro cell response studies with precise dosimetry to laser driven electron beams represent a first step toward the long term aim of the application of laser accelerated particles in radiotherapy.

Effects of live and video form action observation training on upper limb function in children with hemiparetic cerebral palsy.

PubMed

Kim, Do Hyun; An, Duk-Hyun; Yoo, Won-Gyu

2018-04-20

The purpose of this study was to investigate the effects of live and video form action observation training (AOT) on upper limb (UL) movement acceleration and function in children with cerebral palsy (CP). In total, 12 children (7 boys, 5 girls) with CP participated in this study. The children were allocated randomly to live (experimental) and video (control) AOT groups. All children completed 20 treatment sessions, each 30 minutes in duration, 5 days per week for a month. Mediolateral (ML) and vertical (VT) acceleration data, Jebsen-Taylor Hand Function (JTHF) scores, and Box and Block Test (BBT) scores were obtained at baseline and at 4 weeks after the intervention. ML and VT movement acceleration and JTHF scores were significantly lower in the live group (p< 0.05). The BBT score was significantly higher in the live than in the video group (p< 0.05). Our findings suggest that live AOT is more effective than video AOT for improving UL movement acceleration and function. Clinically, our findings offer important insights for clinicians when planning AOT interventions to reduce UL movement acceleration and improve UL function.

Engineering biological systems using automated biofoundries

PubMed Central

Chao, Ran; Mishra, Shekhar; Si, Tong; Zhao, Huimin

2017-01-01

Engineered biological systems such as genetic circuits and microbial cell factories have promised to solve many challenges in the modern society. However, the artisanal processes of research and development are slow, expensive, and inconsistent, representing a major obstacle in biotechnology and bioengineering. In recent years, biological foundries or biofoundries have been developed to automate design-build-test engineering cycles in an effort to accelerate these processes. This review summarizes the enabling technologies for such biofoundries as well as their early successes and remaining challenges. PMID:28602523

Distribution uniformity of laser-accelerated proton beams

NASA Astrophysics Data System (ADS)

Zhu, Jun-Gao; Zhu, Kun; Tao, Li; Xu, Xiao-Han; Lin, Chen; Ma, Wen-Jun; Lu, Hai-Yang; Zhao, Yan-Ying; Lu, Yuan-Rong; Chen, Jia-Er; Yan, Xue-Qing

2017-09-01

Compared with conventional accelerators, laser plasma accelerators can generate high energy ions at a greatly reduced scale, due to their TV/m acceleration gradient. A compact laser plasma accelerator (CLAPA) has been built at the Institute of Heavy Ion Physics at Peking University. It will be used for applied research like biological irradiation, astrophysics simulations, etc. A beamline system with multiple quadrupoles and an analyzing magnet for laser-accelerated ions is proposed here. Since laser-accelerated ion beams have broad energy spectra and large angular divergence, the parameters (beam waist position in the Y direction, beam line layout, drift distance, magnet angles etc.) of the beamline system are carefully designed and optimised to obtain a radially symmetric proton distribution at the irradiation platform. Requirements of energy selection and differences in focusing or defocusing in application systems greatly influence the evolution of proton distributions. With optimal parameters, radially symmetric proton distributions can be achieved and protons with different energy spread within ±5% have similar transverse areas at the experiment target. Supported by National Natural Science Foundation of China (11575011, 61631001) and National Grand Instrument Project (2012YQ030142)

Be together, not the same: Spatiotemporal organization of different cilia types generates distinct transport functions

NASA Astrophysics Data System (ADS)

Nawroth, Janna; Guo, Hanliang; Ruby, Edward; Dabiri, John; McFall-Ngai, Margaret; Kanso, Eva

2016-11-01

Motile cilia are microscopic, hair-like structures on the cell surface that can sense and propel the extracellular fluid environment. Cilia are often thought to be limited to stereotypic morphologies, beat kinematics and non-discriminatory clearance functions, but we find that the spatiotemporal organization of different cilia types and beat behaviors can generate complex flow patterns and transport functions. Here, we present a case study in the Hawaiian bobtail squid where collective ciliary activity and resulting flow fields help recruit symbiont bacteria to the animal host. In particular, we demonstrate empirically and computationally how the squid's internal cilia act like a microfluidic device that actively filters the water for potential bacterial candidates and also provides a sheltered zone allowing for accumulation of mucus and bacteria into a biofilm. Moreover, in this sheltered zone, different cilia-driven flows enhance diffusion of biochemical signals, which could accelerate specific bacteria-host recognition. These results suggest that studying cilia activity on the population level might reveal a diverse range of biological transport and sensing functions. Moreover, understanding cilia as functional building blocks could inspire the design of ciliated robots and devices.

Recurrent bridgehead effects accelerate global alien ant spread

Treesearch

Cleo Bertelsmeier; Sébastien Ollier; Andrew M. Liebhold; Eckehard G. Brockerhoff; Darren Ward; Laurent Keller

2018-01-01

Biological invasions are a major threat to biological diversity, agriculture, and human health. To predict and prevent new invasions, it is crucial to develop a better understanding of the drivers of the invasion process. The analysis of 4,533 border interception events revealed that at least 51 different alien ant species were intercepted at US ports over a period of...

Descriptive vs. mechanistic network models in plant development in the post-genomic era.

PubMed

Davila-Velderrain, J; Martinez-Garcia, J C; Alvarez-Buylla, E R

2015-01-01

Network modeling is now a widespread practice in systems biology, as well as in integrative genomics, and it constitutes a rich and diverse scientific research field. A conceptually clear understanding of the reasoning behind the main existing modeling approaches, and their associated technical terminologies, is required to avoid confusions and accelerate the transition towards an undeniable necessary more quantitative, multidisciplinary approach to biology. Herein, we focus on two main network-based modeling approaches that are commonly used depending on the information available and the intended goals: inference-based methods and system dynamics approaches. As far as data-based network inference methods are concerned, they enable the discovery of potential functional influences among molecular components. On the other hand, experimentally grounded network dynamical models have been shown to be perfectly suited for the mechanistic study of developmental processes. How do these two perspectives relate to each other? In this chapter, we describe and compare both approaches and then apply them to a given specific developmental module. Along with the step-by-step practical implementation of each approach, we also focus on discussing their respective goals, utility, assumptions, and associated limitations. We use the gene regulatory network (GRN) involved in Arabidopsis thaliana Root Stem Cell Niche patterning as our illustrative example. We show that descriptive models based on functional genomics data can provide important background information consistent with experimentally supported functional relationships integrated in mechanistic GRN models. The rationale of analysis and modeling can be applied to any other well-characterized functional developmental module in multicellular organisms, like plants and animals.

Parallel Implementation of MAFFT on CUDA-Enabled Graphics Hardware.

PubMed

Zhu, Xiangyuan; Li, Kenli; Salah, Ahmad; Shi, Lin; Li, Keqin

2015-01-01

Multiple sequence alignment (MSA) constitutes an extremely powerful tool for many biological applications including phylogenetic tree estimation, secondary structure prediction, and critical residue identification. However, aligning large biological sequences with popular tools such as MAFFT requires long runtimes on sequential architectures. Due to the ever increasing sizes of sequence databases, there is increasing demand to accelerate this task. In this paper, we demonstrate how graphic processing units (GPUs), powered by the compute unified device architecture (CUDA), can be used as an efficient computational platform to accelerate the MAFFT algorithm. To fully exploit the GPU's capabilities for accelerating MAFFT, we have optimized the sequence data organization to eliminate the bandwidth bottleneck of memory access, designed a memory allocation and reuse strategy to make full use of limited memory of GPUs, proposed a new modified-run-length encoding (MRLE) scheme to reduce memory consumption, and used high-performance shared memory to speed up I/O operations. Our implementation tested in three NVIDIA GPUs achieves speedup up to 11.28 on a Tesla K20m GPU compared to the sequential MAFFT 7.015.

Comparison of trunk acceleration ratios during stair negotiation in old-old females.

PubMed

Shin, Sun-Shil; Yoo, Won-Gyu

2016-06-01

[Purpose] This study compared trunk acceleration ratios in old-old adult females during stair negotiation. [Subjects and Methods] Twelve old-old adult females who could walk independently volunteered for this study. This study measured gait time and trunk acceleration ratios using an accelerometer during ascending and descending stairs [Results] The trunk acceleration ratio when descending stairs was significantly higher than that when ascending stairs. [Conclusion] These findings suggest that old-old females have greater deterioration of upper trunk control function for descending than for ascending stairs, regardless of task time. In addition, the trunk acceleration ratio during stair negotiation is a useful clinical marker to predict function and balance control ability in old-old females.

Regulating Ion Transport in Peptide Nanotubes by Tailoring the Nanotube Lumen Chemistry.

PubMed

Ruiz, Luis; Benjamin, Ari; Sullivan, Matthew; Keten, Sinan

2015-05-07

We use atomistic nonequilibrium molecular dynamics simulations to demonstrate how specific ionic flux in peptide nanotubes can be regulated by tailoring the lumen chemistry through single amino acid substitutions. By varying the size and polarity of the functional group inserted into the nanotube interior, we are able to adjust the Na(+) flux by over an order of magnitude. Cl(-) is consistently denied passage. Bulky, nonpolar groups encourage interactions between the Na(+) and the peptide backbone carbonyl groups, disrupting the Na(+) solvation shell and slowing the transport of Na(+). Small groups have the opposite effect and accelerate flow. These results suggest that relative ion flux and selectivity can be precisely regulated in subnanometer pores by molecularly defining the lumen according to biological principles.

Selective transformations of complex molecules are enabled by aptameric protective groups

NASA Astrophysics Data System (ADS)

Bastian, Andreas A.; Marcozzi, Alessio; Herrmann, Andreas

2012-10-01

Emerging trends in drug discovery are prompting a renewed interest in natural products as a source of chemical diversity and lead structures. However, owing to the structural complexity of many natural compounds, the synthesis of derivatives is not easily realized. Here, we demonstrate a conceptually new approach using oligonucleotides as aptameric protective groups. These block several functionalities by non-covalent interactions in a complex molecule and enable the highly chemo- and regioselective derivatization (>99%) of natural antibiotics in a single synthetic step with excellent conversions of up to 83%. This technique reveals an important structure-activity relationship in neamine-based antibiotics and should help both to accelerate the discovery of new biologically active structures and to avoid potentially costly and cumbersome synthetic routes.

Nocturnal Hypoxia and Loss of Kidney Function

PubMed Central

Ahmed, Sofia B.; Ronksley, Paul E.; Hemmelgarn, Brenda R.; Tsai, Willis H.; Manns, Braden J.; Tonelli, Marcello; Klarenbach, Scott W.; Chin, Rick; Clement, Fiona M.; Hanly, Patrick J.

2011-01-01

Background Although obstructive sleep apnea (OSA) is more common in patients with kidney disease, whether nocturnal hypoxia affects kidney function is unknown. Methods We studied all adult subjects referred for diagnostic testing of sleep apnea between July 2005 and December 31 2007 who had serial measurement of their kidney function. Nocturnal hypoxia was defined as oxygen saturation (SaO2) below 90% for ≥12% of the nocturnal monitoring time. The primary outcome, accelerated loss of kidney function, was defined as a decline in estimated glomerular filtration rate (eGFR) ≥4 ml/min/1.73 m2 per year. Results 858 participants were included and followed for a mean study period of 2.1 years. Overall 374 (44%) had nocturnal hypoxia, and 49 (5.7%) had accelerated loss of kidney function. Compared to controls without hypoxia, patients with nocturnal hypoxia had a significant increase in the adjusted risk of accelerated kidney function loss (odds ratio (OR) 2.89, 95% confidence interval [CI] 1.25, 6.67). Conclusion Nocturnal hypoxia was independently associated with an increased risk of accelerated kidney function loss. Further studies are required to determine whether treatment and correction of nocturnal hypoxia reduces loss of kidney function. PMID:21559506

Sparking Thinking: Studying Modern Precision Medicine Will Accelerate the Progression of Traditional Chinese Medicine Patterns.

PubMed

Liu, Bao-Cheng; Ji, Guang

2017-07-01

Incorporating "-omics" studies with environmental interactions could help elucidate the biological mechanisms responsible for Traditional Chinese Medicine (TCM) patterns. Based on the authors' own experiences, this review outlines a model of an ideal combination of "-omics" biomarkers, environmental factors, and TCM pattern classifications; provides a narrative review of the relevant genetic and TCM studies; and lists several successful integrative examples. Two integration tools are briefly introduced. The first is the integration of modern devices into objective diagnostic methods of TCM patterning, which would improve current clinical decision-making and practice. The second is the use of biobanks and data platforms, which could broadly support biological and medical research. Such efforts will transform current medical management and accelerate the progression of precision medicine.

Oxidative stress-induced telomeric erosion as a mechanism underlying airborne particulate matter-related cardiovascular disease

PubMed Central

2012-01-01

Particulate matter (PM) pollution is responsible for hundreds of thousands of deaths worldwide, the majority due to cardiovascular disease (CVD). While many potential pathophysiological mechanisms have been proposed, there is not yet a consensus as to which are most important in causing pollution-related morbidity/mortality. Nor is there consensus regarding which specific types of PM are most likely to affect public health in this regard. One toxicological mechanism linking exposure to airborne PM with CVD outcomes is oxidative stress, a contributor to the development of CVD risk factors including atherosclerosis. Recent work suggests that accelerated shortening of telomeres and, thus, early senescence of cells may be an important pathway by which oxidative stress may accelerate biological aging and the resultant development of age-related morbidity. This pathway may explain a significant proportion of PM-related adverse health outcomes, since shortened telomeres accelerate the progression of many diseases. There is limited but consistent evidence that vehicular emissions produce oxidative stress in humans. Given that oxidative stress is associated with accelerated erosion of telomeres, and that shortened telomeres are linked with acceleration of biological ageing and greater incidence of various age-related pathology, including CVD, it is hypothesized that associations noted between certain pollution types and sources and oxidative stress may reflect a mechanism by which these pollutants result in CVD-related morbidity and mortality, namely accelerated aging via enhanced erosion of telomeres. This paper reviews the literature providing links among oxidative stress, accelerated erosion of telomeres, CVD, and specific sources and types of air pollutants. If certain PM species/sources might be responsible for adverse health outcomes via the proposed mechanism, perhaps the pathway to reducing mortality/morbidity from PM would become clearer. Not only would pollution reduction imperatives be more focused, but interventions which could reduce oxidative stress would become all the more important. PMID:22713210

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

PubMed

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

2016-09-27

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.

Characterization of the radiation environment at the UNLV accelerator facility during operation of the Varian M6 linac

NASA Astrophysics Data System (ADS)

Hodges, M.; Barzilov, A.; Chen, Y.; Lowe, D.

2016-10-01

The bremsstrahlung photon flux from the UNLV particle accelerator (Varian M6 model) was determined using MCNP5 code for 3 MeV and 6 MeV incident electrons. Human biological equivalent dose rates due to accelerator operation were evaluated using the photon flux with the flux-to-dose conversion factors. Dose rates were computed for the accelerator facility for M6 linac use under different operating conditions. The results showed that the use of collimators and linac internal shielding significantly reduced the dose rates throughout the facility. It was shown that the walls of the facility, in addition to the earthen berm enveloping the building, provide equivalent shielding to reduce dose rates outside to below the 2 mrem/h limit.

Effect of dynamic factors of space flights on the green alga Chlorella vulgaris.

PubMed

Moskvitin, E V; Vaulina, E N

1974-01-01

The biological effects of vibrational and linear acceleration on the alga Chlorella vulgaris were studied. Periodic vibration in the frequency range of 4-4000 Hz with vibrational acceleration up to 16 g did not affect the survival and mutability of Chlorella cells and did not modify the effects of acute gamma-radiation. However, random vibration similar to that occurring during launch of spaceships, combined with linear acceleration increased the radiation damage to algae produced by acute gamma-radiation at a dose of 10000 r. This effect is seen only in cells at the beginning of the G1 stage, which precedes DNA synthesis.

Acceleration of Wound Healing by α-gal Nanoparticles Interacting with the Natural Anti-Gal Antibody

PubMed Central

Galili, Uri

2015-01-01

Application of α-gal nanoparticles to wounds and burns induces accelerated healing by harnessing the natural anti-Gal antibody which constitutes ~1% of human immunoglobulins. α-gal nanoparticles present multiple α-gal epitopes (Galα1-3Galβ1-4GlcNAc-R), the carbohydrate ligand of anti-Gal. Studied α-gal nanoparticles were comprised of glycolipids with α-gal epitopes, phospholipids, and cholesterol. Binding of anti-Gal to α-gal nanoparticles in wounds activates the complement cascade, resulting in formation of chemotactic complement cleavage peptides that induce rapid recruitment of many macrophages. The Fc/Fcγ receptors interaction between anti-Gal coating α-gal nanoparticles and the recruited macrophages activates macrophages to produce cytokines/growth factors that promote wound healing and recruit stem cells. Studies of wound healing by α-gal nanoparticles were feasible in α1,3galactosyltransferase knockout mice and pigs. In contrast to other nonprimate mammals, these mice and pigs lack the α-gal epitope, and thus they are not immunotolerant to it and produce anti-Gal. Treatment of skin wounds and burns with α-gal nanoparticles resulted in 40–60% decrease in healing time in comparison with control wounds treated with saline. This accelerated healing is associated with increased recruitment of macrophages and extensive angiogenesis in wounds, faster regrowth of epidermis, and regeneration of the dermis. The accelerated healing further decreases and may completely eliminate fibrosis and scar formation in wounds. Since healing of internal injuries is mediated by mechanisms similar to those in external wound healing, it is suggested that α-gal nanoparticles treatment may also improve regeneration and restoration of biological function following internal injuries such as surgical incisions, myocardial ischemia following infarction, and nerve injuries. PMID:25922849

A New Improved and Extended Version of the Multicell Bacterial Simulator gro.

PubMed

Gutiérrez, Martín; Gregorio-Godoy, Paula; Pérez Del Pulgar, Guillermo; Muñoz, Luis E; Sáez, Sandra; Rodríguez-Patón, Alfonso

2017-08-18

gro is a cell programming language developed in Klavins Lab for simulating colony growth and cell-cell communication. It is used as a synthetic biology prototyping tool for simulating multicellular biocircuits and microbial consortia. In this work, we present several extensions made to gro that improve the performance of the simulator, make it easier to use, and provide new functionalities. The new version of gro is between 1 and 2 orders of magnitude faster than the original version. It is able to grow microbial colonies with up to 10 5 cells in less than 10 min. A new library, CellEngine, accelerates the resolution of spatial physical interactions between growing and dividing cells by implementing a new shoving algorithm. A genetic library, CellPro, based on Probabilistic Timed Automata, simulates gene expression dynamics using simplified and easy to compute digital proteins. We also propose a more convenient language specification layer, ProSpec, based on the idea that proteins drive cell behavior. CellNutrient, another library, implements Monod-based growth and nutrient uptake functionalities. The intercellular signaling management was improved and extended in a library called CellSignals. Finally, bacterial conjugation, another local cell-cell communication process, was added to the simulator. To show the versatility and potential outreach of this version of gro, we provide studies and novel examples ranging from synthetic biology to evolutionary microbiology. We believe that the upgrades implemented for gro have made it into a powerful and fast prototyping tool capable of simulating a large variety of systems and synthetic biology designs.

Open source bioimage informatics for cell biology

PubMed Central

Swedlow, Jason R.; Eliceiri, Kevin W.

2009-01-01

Significant technical advances in imaging, molecular biology and genomics have fueled a revolution in cell biology, in that the molecular and structural processes of the cell are now visualized and measured routinely. Driving much of this recent development has been the advent of computational tools for the acquisition, visualization, analysis and dissemination of these datasets. These tools collectively make up a new subfield of computational biology called bioimage informatics, which is facilitated by open source approaches. We discuss why open source tools for image informatics in cell biology are needed, some of the key general attributes of what make an open source imaging application successful, and point to opportunities for further operability that should greatly accelerate future cell biology discovery. PMID:19833518

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

PubMed Central

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. PMID:24225319

The Emory Chemical Biology Discovery Center: leveraging academic innovation to advance novel targets through HTS and beyond.

PubMed

Johns, Margaret A; Meyerkord-Belton, Cheryl L; Du, Yuhong; Fu, Haian

2014-03-01

The Emory Chemical Biology Discovery Center (ECBDC) aims to accelerate high throughput biology and translation of biomedical research discoveries into therapeutic targets and future medicines by providing high throughput research platforms to scientific collaborators worldwide. ECBDC research is focused at the interface of chemistry and biology, seeking to fundamentally advance understanding of disease-related biology with its HTS/HCS platforms and chemical tools, ultimately supporting drug discovery. Established HTS/HCS capabilities, university setting, and expertise in diverse assay formats, including protein-protein interaction interrogation, have enabled the ECBDC to contribute to national chemical biology efforts, empower translational research, and serve as a training ground for young scientists. With these resources, the ECBDC is poised to leverage academic innovation to advance biology and therapeutic discovery.

Characteristics comparison between a cyclotron-based neutron source and KUR-HWNIF for boron neutron capture therapy

NASA Astrophysics Data System (ADS)

Tanaka, H.; Sakurai, Y.; Suzuki, M.; Masunaga, S.; Kinashi, Y.; Kashino, G.; Liu, Y.; Mitsumoto, T.; Yajima, S.; Tsutsui, H.; Maruhashi, A.; Ono, K.

2009-06-01

At Kyoto University Research Reactor Institute (KURRI), 275 clinical trials of boron neutron capture therapy (BNCT) have been performed as of March 2006, and the effectiveness of BNCT has been revealed. In order to further develop BNCT, it is desirable to supply accelerator-based epithermal-neutron sources that can be installed near the hospital. We proposed the method of filtering and moderating fast neutrons, which are emitted from the reaction between a beryllium target and 30-MeV protons accelerated by a cyclotron accelerator, using an optimum moderator system composed of iron, lead, aluminum and calcium fluoride. At present, an epithermal-neutron source is under construction from June 2008. This system consists of a cyclotron accelerator, beam transport system, neutron-yielding target, filter, moderator and irradiation bed. In this article, an overview of this system and the properties of the treatment neutron beam optimized by the MCNPX Monte Carlo neutron transport code are presented. The distribution of biological effect weighted dose in a head phantom compared with that of Kyoto University Research Reactor (KUR) is shown. It is confirmed that for the accelerator, the biological effect weighted dose for a deeply situated tumor in the phantom is 18% larger than that for KUR, when the limit dose of the normal brain is 10 Gy-eq. The therapeutic time of the cyclotron-based neutron sources are nearly one-quarter of that of KUR. The cyclotron-based epithermal-neutron source is a promising alternative to reactor-based neutron sources for treatments by BNCT.

Informatic innovations in glycobiology: relevance to drug discovery.

PubMed

Mamitsuka, Hiroshi

2008-02-01

The recent development and applications of tree-based informatics on glycans have accelerated the biological analysis on glycans, particularly from structural viewpoints. We review three major aspects of recent informatics innovations on glycan structures: maturity of well-organized databases on glycan structures linking with other biological information, implementation of glycan structure matching algorithms and extensive development of methods for mining frequent patterns from glycan structures.

Small molecules, big players: the National Cancer Institute's Initiative for Chemical Genetics.

PubMed

Tolliday, Nicola; Clemons, Paul A; Ferraiolo, Paul; Koehler, Angela N; Lewis, Timothy A; Li, Xiaohua; Schreiber, Stuart L; Gerhard, Daniela S; Eliasof, Scott

2006-09-15

In 2002, the National Cancer Institute created the Initiative for Chemical Genetics (ICG), to enable public research using small molecules to accelerate the discovery of cancer-relevant small-molecule probes. The ICG is a public-access research facility consisting of a tightly integrated team of synthetic and analytical chemists, assay developers, high-throughput screening and automation engineers, computational scientists, and software developers. The ICG seeks to facilitate the cross-fertilization of synthetic chemistry and cancer biology by creating a research environment in which new scientific collaborations are possible. To date, the ICG has interacted with 76 biology laboratories from 39 institutions and more than a dozen organic synthetic chemistry laboratories around the country and in Canada. All chemistry and screening data are deposited into the ChemBank web site (http://chembank.broad.harvard.edu/) and are available to the entire research community within a year of generation. ChemBank is both a data repository and a data analysis environment, facilitating the exploration of chemical and biological information across many different assays and small molecules. This report outlines how the ICG functions, how researchers can take advantage of its screening, chemistry and informatic capabilities, and provides a brief summary of some of the many important research findings.

[Pharmacological correction of central nervous system function in exposure to Coriolis acceleration].

PubMed

Karkishchenko, N N; Dimitriadi, N A; Molchanovskiĭ, V V

1986-01-01

Healthy volunteers with a low vestibular tolerance were exposed to Coriolis acceleration. Potassium orotate, pyracetame and riboxine were used as prophylactic measures against disorders in the function of the vestibular apparatus and higher compartments of the higher nervous system. The central nervous function was assessed with respect to the spectral power of electroencephalograms, short-term memory and mental performance. Potassium orotate given at a dose of 40 mg/kg body weight/day during 12-14 days as well as pyracetame given at a dose of 30 mg/kg body weight/day during 3 or 7 days increased significantly statokinetic tolerance and produced a protective effect on the central nervous function against Coriolis acceleration.

Defeating copper tolerance: an example of how “omics” research can accelerate discovery of new wood protection compounds

Treesearch

Juliet D. Tang; Tina Ciaramitaro; Darrel D. Nicholas; Maria Tomaso-Peterson; Susan V. Diehl

2017-01-01

Imagine if you could measure all the genes being expressed at any one time in an organism and you knew what all the genes did in a cell. The power of this knowledge would allow you to determine how organisms regulate gene activity to survive. This is the essence of how “omics” science accelerates biological understanding. From a wood protections standpoint,...

Satellite RNA Increases DNA Damage and Accelerates Tumor Formation in Mouse Models of Pancreatic Cancer.

PubMed

Kishikawa, Takahiro; Otsuka, Motoyuki; Suzuki, Tatsunori; Seimiya, Takahiro; Sekiba, Kazuma; Ishibashi, Rei; Tanaka, Eri; Ohno, Motoko; Yamagami, Mari; Koike, Kazuhiko

2018-05-10

Highly repetitive tandem arrays such as satellite sequences in the centromeric and pericentromeric regions of chromosomes, which were previously considered to be silent, are actively transcribed in various biological processes, including cancers. In the pancreas, this aberrant expression occurs even in Kras-mutated pancreatic intraepithelial neoplasia (PanIN) tissues, which are precancerous lesions. To determine the biological role of satellite RNAs in carcinogenesis in vivo , we constructed mouse major satellite (MajSAT) RNA-expressing transgenic mice. However, these transgenic mice did not show spontaneous malignant tumor formation under normal breeding. Importantly, however, DNA damage was increased in pancreatic tissues induced by caerulein treatment or high-fat diet, which may be due to impaired nuclear localization of Y-Box Binding Protein 1 (YBX1), a component of the DNA damage repair machinery. In addition, when crossed with pancreas-specific Kras-mutant mice, MajSAT RNA expression resulted in an earlier increase in PanIN formation. These results suggest that aberrant MajSAT RNA expression accelerates oncogenesis by increasing the probability of a second driver mutation, thus accelerating cells to exit from the breakthrough phase to the expansion phase. Implications: Aberrant expression of satellite RNAs accelerates oncogenesis through a mechanism involving increased DNA damage. Mol Cancer Res; 1-8. ©2018 AACR. ©2018 American Association for Cancer Research.

Theoretical implications of the galactic radial acceleration relation of McGaugh, Lelli, and Schombert

NASA Astrophysics Data System (ADS)

Nesbet, Robert K.

2018-05-01

Velocities in stable circular orbits about galaxies, a measure of centripetal gravitation, exceed the expected Kepler/Newton velocity as orbital radius increases. Standard Λ cold dark matter (ΛCDM) attributes this anomaly to galactic dark matter. McGaugh et al. have recently shown for 153 disc galaxies that observed radial acceleration is an apparently universal function of classical acceleration computed for observed galactic baryonic mass density. This is consistent with the empirical modified Newtonian dynamics (MOND) model, not requiring dark matter. It is shown here that suitably constrained ΛCDM and conformal gravity (CG) also produce such a universal correlation function. ΛCDM requires a very specific dark matter distribution, while the implied CG non-classical acceleration must be independent of galactic mass. All three constrained radial acceleration functions agree with the empirical baryonic v4 Tully-Fisher relation. Accurate rotation data in the nominally flat velocity range could distinguish between MOND, ΛCDM, and CG.

Nuclear accumulation of epidermal growth factor receptor and acceleration of G1/S stage by Epstein-Barr-encoded oncoprotein latent membrane protein 1

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

Tao Yongguang; Song Xing; Deng Xiyun

Epstein-Barr virus (EBV)-encoded latent membrane protein 1 (LMP1) is considered to be the major oncogenic protein of EBV-encoded proteins and has always been the core of the oncogenic mechanism of EBV. Advanced studies on nuclear translocation of the epidermal growth factor receptor (EGFR) family have greatly improved our knowledge of the biological function of cell surface receptors. In this study, we used the Tet-on LMP1 HNE2 cell line as a cell model, which is a dual-stable LMP1-integrated nasopharyngeal carcinoma (NPC) cell line and the expression of LMP1 which could be regulated by the Tet system. We found that LMP1 couldmore » regulate the nuclear accumulation of EGFR in a dose-dependent manner quantitatively and qualitatively. We also demonstrated that the nuclear localization sequence of EGFR played some roles in the location of the protein within the nucleus under LMP1 regulation and EGFR in the nucleus could bind to the promoters of cyclinD1 and cyclinE, respectively. We further demonstrated that EGFR is involved in the acceleration of the G1/S phase transition by LMP1 through binding to cyclinD1 and cyclinE directly. These findings provided a novel view that the acceleration of LMP1 on the G1/S transition via the nuclear accumulation of EGFR was critical in the process of nasopharyngeal carcinoma.« less

Mutation induction by charged particles of defined linear energy transfer.

PubMed

Hei, T K; Chen, D J; Brenner, D J; Hall, E J

1988-07-01

The mutagenic potential of charged particles of defined linear energy transfer (LET) was assessed using the hypoxanthine-guanine phosphoribosyl transferase locus (HGPRT) in primary human fibroblasts. Exponentially growing cultures of early passaged fibroblasts were grown as monolayers on thin mylar sheets and were irradiated with accelerated protons, deuterons or helium-3 ions. The mutation rates were compared with those generated by 137Cs gamma-rays. LET values for charged particles accelerated at the Radiological Research Accelerator Facility, using the track segment mode, ranged from 10 to 150 keV/micron. After irradiation, cells were trypsinized, subcultured and assayed for both cytotoxicity and 6-thioguanine resistance. For gamma-rays, and for the charged particles of lower LET, the dose-response curves for cell survival were characterized by a marked initial shoulder, but approximated to an exponential function of dose for higher LETs. Mutation frequencies, likewise, showed a direct correlation to LET over the dose range examined. Relative biological effectiveness (RBE) for mutagenesis, based on the initial slopes of the dose-response curves, ranged from 1.30 for 10 keV/micron protons to 9.40 for 150 keV/micron helium-3 ions. Results of the present studies indicate that high-LET radiations, apart from being efficient inducers of cell lethality, are even more efficient in mutation induction as compared to low-LET ionizing radiation. These data are consistent with results previously obtained with both rodent and human fibroblast cell lines.

Radiation-induced hemopoietic death in mice as a function of photon energy and dose rate

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

Gengozian, N.; Taylor, T.; Jameson, H.

1986-03-01

Radiation-induced hemopoietic death was measured in mice exposed to photons of four different energies: 250-kVp X rays, /sup 60/Co gamma rays (1.25 MeV), and 6- and 25-MV photons from a linear accelerator. For each radiation source, the lethal dose which killed 50% of the population in 30 days (LD50/30) associated with the hemopoietic syndrome was determined in groups of mice exposed to graded doses from 600 to 1150 cGy at dose rates of 20, 40, and 80 cGy/min. The calculated LD50/30 values for 25 and 6 MV were significantly different from each other at all exposure rates while no differencemore » was observed between 6 MV and /sup 60/Co. Using /sup 60/Co gamma rays as the standard, the relative biologic effectiveness was as follows: 250 kVp greater than 25 MV greater than 6 MV = /sup 60/Co. The data suggest that there may be a greater damage to tissue within the marrow cavities following exposure to very high megavoltage radiation, a factor which must be considered with the increasing utilization of linear accelerators in the clinic and laboratory.« less

Major Depressive Disorder and Measures of Cellular Aging: An Integrative Review

PubMed Central

Kinser, Patricia Anne; Lyon, Debra E.

2013-01-01

Major depressive disorder (MDD) affects millions of individuals and causes significant suffering worldwide. It has been speculated that MDD is associated with accelerated aging-related biological and functional decline. To examine the accelerated aging hypothesis, one of the biomarkers under study is leukocyte telomeres, and specifically the measure of telomere length and telomerase activity. This review integrates findings from eleven human studies which evaluated telomere length and telomerase activity, in order to synthesize the state of the current science and to inform the development of new knowledge and enhance nursing research of depression using appropriate biobehavioral measures. Although preliminary, the findings from this integrated review suggest that there is evidence to support a conceptualization of depression as a stress-related condition in which telomeres shorten over time in relation to cumulative exposure to the chronic stress of depression. For the purposes of testing in future nursing research, visual representations of the theoretical connection between stress vulnerabilities, depression, and health outcomes and key moderators and mediators involved in this conceptualization are provided. The findings from this review and the conceptual framework provided may be a useful step towards advancing therapeutic nursing interventions for this debilitating chronic condition. PMID:23691300

Treatment of wrist and hand fractures with natural magnets: preliminary report.

PubMed

Costantino, Cosimo; Pogliacomi, Francesco; Passera, Francesco; Concari, Galeazzo

2007-12-01

The Authors, after having defined the phenomenon and the biological characteristics of natural magnets, evaluate their ability in accelerating the formation of bone callus in hand and wrist fractures compared to treatment with immobilization in a plaster cast. Forty patients (4 females and 37 males) between 20 and 86 years of age were treated. A small natural magnet was inserted in each of the plaster casts (diameter: 2cm, height: 0.5cm) made of 4 blocks in Neodymium-Iron-Boron, capable of generating 4 magnetic poles (2 positive and 2 negative) of diagonal alternate polarity that produced a symmetric, quadruple static magnetic field. The created magnetic flow was wavelike, concentrated in one direction, and developed a force up to 12,500 gauss. From this study it has emerged that inserting a quadruple magnet in a plaster cast in hand and wrist fractures results in the formation of bone callus in an average time that is 35% inferior to the "standard" time. Accelerating the healing of the fracture is important since it reduces immobilization time for the joints involved, avoiding subsequent weakness and stiffness and allowing the patient to begin rehabilitative physiotherapy sooner, which permits a faster functional recovery.

Molecular Aging of Human Liver: An Epigenetic/Transcriptomic Signature.

PubMed

Bacalini, Maria Giulia; Franceschi, Claudio; Gentilini, Davide; Ravaioli, Francesco; Zhou, Xiaoyuan; Remondini, Daniel; Pirazzini, Chiara; Giuliani, Cristina; Marasco, Elena; Gensous, Noémie; Di Blasio, Anna Maria; Ellis, Ewa; Gramignoli, Roberto; Castellani, Gastone; Capri, Miriam; Strom, Stephen; Nardini, Christine; Cescon, Matteo; Grazi, Gian Luca; Garagnani, Paolo

2018-03-15

The feasibility of liver transplantation from old healthy donors suggests that this organ is able to preserve its functionality during aging. To explore the biological basis of this phenomenon, we characterized the epigenetic profile of liver biopsies collected from 45 healthy liver donors ranging from 13 to 90 years old using the Infinium HumanMethylation450 BeadChip. The analysis indicates that a large remodeling in DNA methylation patterns occurs, with 8823 age-associated differentially methylated CpG probes. Notably, these age-associated changes tended to level off after the age of 60, as confirmed by Horvath's clock. Using stringent selection criteria we further identified a DNA methylation signature of aging liver including 75 genomic regions. We demonstrated that this signature is specific for liver compared to other tissues and that it is able to detect biological age-acceleration effects associated with obesity. Finally we combined DNA methylation measurements with available expression data. Although the intersection between the two omic characterizations was low, both approaches suggested a previously unappreciated role of epithelial-mesenchymal transition and Wnt signaling pathways in the aging of human liver.

Optimizations of Human Restraint Systems for Short-Period Acceleration

NASA Technical Reports Server (NTRS)

Payne, P. R.

1963-01-01

A restraint system's main function is to restrain its occupant when his vehicle is subjected to acceleration. If the restraint system is rigid and well-fitting (to eliminate slack) then it will transmit the vehicle acceleration to its occupant without modifying it in any way. Few present-day restraint systems are stiff enough to give this one-to-one transmission characteristic, and depending upon their dynamic characteristics and the nature of the vehicle's acceleration-time history, they will either magnify or attenuate the acceleration. Obviously an optimum restraint system will give maximum attenuation of an input acceleration. In the general case of an arbitrary acceleration input, a computer must be used to determine the optimum dynamic characteristics for the restraint system. Analytical solutions can be obtained for certain simple cases, however, and these cases are considered in this paper, after the concept of dynamic models of the human body is introduced. The paper concludes with a description of an analog computer specially developed for the Air Force to handle completely general mechanical restraint optimization programs of this type, where the acceleration input may be any arbitrary function of time.

ANNUAL REPORT ON PHYSICAL SCIENCES, ENGINEERING AND LIFE SCIENCES , JULY 1, 1961

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

None

1962-10-31

The research program at Brooknaven is described. Current activities in physics, high-energy accelerators, instrumentation, chemistry, nuclear engineering, applied mathematics, biology, and medical research are outlined. (D.L.C.)

Toward Safer Use of Pesticides

ERIC Educational Resources Information Center

Moats, Sheila; Moats, William A.

1970-01-01

Gives information on costs and benefits of pesticides, and on specific injurious effects on humans and fish and wild life. Suggests restriction of use of certain pesticides and acceleration of research on biological control. (EB)

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

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

Friedman, Douglas C.

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 newmore » 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.« less

A general mechanism for competitor-induced dissociation of molecular complexes

PubMed Central

Paramanathan, Thayaparan; Reeves, Daniel; Friedman, Larry J.; Kondev, Jane; Gelles, Jeff

2014-01-01

The kinetic stability of non-covalent macromolecular complexes controls many biological phenomena. Here we find that physical models of complex dissociation predict that competitor molecules will in general accelerate the breakdown of isolated bimolecular complexes by occluding rapid rebinding of the two binding partners. This prediction is largely independent of molecular details. We confirm the prediction with single-molecule fluorescence experiments on a well-characterized DNA strand dissociation reaction. Contrary to common assumptions, competitor–induced acceleration of dissociation can occur in biologically relevant competitor concentration ranges and does not necessarily implyternary association of competitor with the bimolecular complex. Thus, occlusion of complex rebinding may play a significant role in a variety of biomolecular processes. The results also show that single-molecule colocalization experiments can accurately measure dissociation rates despite their limited spatio temporal resolution. PMID:25342513

Bacteriophage-based synthetic biology for the study of infectious diseases

PubMed Central

Lu, Timothy K.

2014-01-01

Since their discovery, bacteriophages have contributed enormously to our understanding of molecular biology as model systems. Furthermore, bacteriophages have provided many tools that have advanced the fields of genetic engineering and synthetic biology. Here, we discuss bacteriophage-based technologies and their application to the study of infectious diseases. New strategies for engineering genomes have the potential to accelerate the design of novel phages as therapies, diagnostics, and tools. Though almost a century has elapsed since their discovery, bacteriophages continue to have a major impact on modern biological sciences, especially with the growth of multidrug-resistant bacteria and interest in the microbiome. PMID:24997401

Role of genomics and transcriptomics in selection of reintroduction source populations.

PubMed

He, Xiaoping; Johansson, Mattias L; Heath, Daniel D

2016-10-01

The use and importance of reintroduction as a conservation tool to return a species to its historical range from which it has been extirpated will increase as climate change and human development accelerate habitat loss and population extinctions. Although the number of reintroduction attempts has increased rapidly over the past 2 decades, the success rate is generally low. As a result of population differences in fitness-related traits and divergent responses to environmental stresses, population performance upon reintroduction is highly variable, and it is generally agreed that selecting an appropriate source population is a critical component of a successful reintroduction. Conservation genomics is an emerging field that addresses long-standing challenges in conservation, and the potential for using novel molecular genetic approaches to inform and improve conservation efforts is high. Because the successful establishment and persistence of reintroduced populations is highly dependent on the functional genetic variation and environmental stress tolerance of the source population, we propose the application of conservation genomics and transcriptomics to guide reintroduction practices. Specifically, we propose using genome-wide functional loci to estimate genetic variation of source populations. This estimate can then be used to predict the potential for adaptation. We also propose using transcriptional profiling to measure the expression response of fitness-related genes to environmental stresses as a proxy for acclimation (tolerance) capacity. Appropriate application of conservation genomics and transcriptomics has the potential to dramatically enhance reintroduction success in a time of rapidly declining biodiversity and accelerating environmental change. © 2016 Society for Conservation Biology.

MO-F-16A-02: Simulation of a Medical Linear Accelerator for Teaching Purposes

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

Carlone, M; Lamey, M; Anderson, R

Purpose: Detailed functioning of linear accelerator physics is well known. Less well developed is the basic understanding of how the adjustment of the linear accelerator's electrical components affects the resulting radiation beam. Other than the text by Karzmark, there is very little literature devoted to the practical understanding of linear accelerator functionality targeted at the radiotherapy clinic level. The purpose of this work is to describe a simulation environment for medical linear accelerators with the purpose of teaching linear accelerator physics. Methods: Varian type lineacs were simulated. Klystron saturation and peak output were modelled analytically. The energy gain of anmore » electron beam was modelled using load line expressions. The bending magnet was assumed to be a perfect solenoid whose pass through energy varied linearly with solenoid current. The dose rate calculated at depth in water was assumed to be a simple function of the target's beam current. The flattening filter was modelled as an attenuator with conical shape, and the time-averaged dose rate at a depth in water was determined by calculating kerma. Results: Fifteen analytical models were combined into a single model called SIMAC. Performance was verified systematically by adjusting typical linac control parameters. Increasing klystron pulse voltage increased dose rate to a peak, which then decreased as the beam energy was further increased due to the fixed pass through energy of the bending magnet. Increasing accelerator beam current leads to a higher dose per pulse. However, the energy of the electron beam decreases due to beam loading and so the dose rate eventually maximizes and the decreases as beam current was further increased. Conclusion: SIMAC can realistically simulate the functionality of a linear accelerator. It is expected to have value as a teaching tool for both medical physicists and linear accelerator service personnel.« less

Sustained performance of 8 MeV Microtron

NASA Astrophysics Data System (ADS)

Sanjeev, Ganesh

2012-11-01

Energetic electrons and intense bremsstrahlung radiation from 8 MeV Microtron are being utilized in variety of collaborative research programs in radiation physics and allied sciences involving premier institutions of the country and sister universities of the region. The first of its kind electron accelerator in the country, set up at Mangalore University in collaboration with RRCAT Indore and BARC Mumbai, has been facilitating researchers since its inception with its inherent simplicity, ease of construction, low cost and excellent beam quality. A bird's eye view on the reliable aspects of the machine, efforts behind the continuous operation of the accelerator and important applications of the accelerator in physical and biological sciences are presented in this paper.

Optical fiber pressure and acceleration sensor fabricated on a fiber endface

DOEpatents

Zhu, Yizheng; Wang, Xingwei; Xu, Juncheng; Wang, Anbo

2006-05-30

A fiber optic sensor has a hollow tube bonded to the endface of an optical fiber, and a diaphragm bonded to the hollow tube. The fiber endface and diaphragm comprise an etalon cavity. The length of the etalon cavity changes when applied pressure or acceleration flexes the diaphragm. The entire structure can be made of fused silica. The fiber, tube, and diaphragm can be bonded with a fusion splice. The present sensor is particularly well suited for measuring pressure or acceleration in high temperature, high pressure and corrosive environments (e.g., oil well downholes and jet engines). The present sensors are also suitable for use in biological and medical applications.

Genome-scale biological models for industrial microbial systems.

PubMed

Xu, Nan; Ye, Chao; Liu, Liming

2018-04-01

The primary aims and challenges associated with microbial fermentation include achieving faster cell growth, higher productivity, and more robust production processes. Genome-scale biological models, predicting the formation of an interaction among genetic materials, enzymes, and metabolites, constitute a systematic and comprehensive platform to analyze and optimize the microbial growth and production of biological products. Genome-scale biological models can help optimize microbial growth-associated traits by simulating biomass formation, predicting growth rates, and identifying the requirements for cell growth. With regard to microbial product biosynthesis, genome-scale biological models can be used to design product biosynthetic pathways, accelerate production efficiency, and reduce metabolic side effects, leading to improved production performance. The present review discusses the development of microbial genome-scale biological models since their emergence and emphasizes their pertinent application in improving industrial microbial fermentation of biological products.

Physical, chemical, and biological properties of soil under soybean cultivation and at an adjacent rainforest in Amazonia

Treesearch

T.P. Beldini; R.C. Oliveira Junior; Michael Keller; P.B. de Camargo; P.M. Crill; A. Damasceno da Silva; D. Bentes dos Santos; D. Rocha de Oliveira

2015-01-01

Land-use change in the Amazon basin has occurred at an accelerated pace during the last decade, and it is important that the effects induced by these changes on soil properties are better understood. This study investigated the chemical, physical, and biological properties of soil in a field under cultivation of soy and rice, and at an adjacent primary rain forest....

Economic value of biological control in integrated pest management of managed plant systems.

PubMed

Naranjo, Steven E; Ellsworth, Peter C; Frisvold, George B

2015-01-07

Biological control is an underlying pillar of integrated pest management, yet little focus has been placed on assigning economic value to this key ecosystem service. Setting biological control on a firm economic foundation would help to broaden its utility and adoption for sustainable crop protection. Here we discuss approaches and methods available for valuation of biological control of arthropod pests by arthropod natural enemies and summarize economic evaluations in classical, augmentative, and conservation biological control. Emphasis is placed on valuation of conservation biological control, which has received little attention. We identify some of the challenges of and opportunities for applying economics to biological control to advance integrated pest management. Interaction among diverse scientists and stakeholders will be required to measure the direct and indirect costs and benefits of biological control that will allow farmers and others to internalize the benefits that incentivize and accelerate adoption for private and public good.

Designer nanomaterials using chiral self-assembling peptide systems and their emerging benefit for society.

PubMed

Luo, Zhongli; Zhang, Shuguang

2012-07-07

Chirality is absolutely central in chemistry and biology. The recent findings of chiral self-assembling peptides' remarkable chemical complementarity and structural compatibility make it one of the most inspired designer materials and structures in nanobiotechnology. The emerging field of designer chemistry and biology further explores biological and medical applications of these simple D,L- amino acids through producing marvellous nanostructures under physiological conditions. These self-assembled structures include well-ordered nanofibers, nanotubes and nanovesicles. These structures have been used for 3-dimensional tissue cultures of primary cells and stem cells, sustained release of small molecules, growth factors and monoclonal antibodies, accelerated wound-healing in reparative and regenerative medicine as well as tissue engineering. Recent advances in molecular designs have also led to the development of 3D fine-tuned bioactive tissue culture scaffolds. They are also used to stabilize membrane proteins including difficult G-protein coupled receptors for designing nanobiodevices. One of the self-assembling peptides has been used in human clinical trials for accelerated wound-healings. It is our hope that these peptide materials will open doors for more and diverse clinical uses. The field of chiral self-assembling peptide nanobiotechnology is growing in a number of directions that has led to many surprises in areas of novel materials, synthetic biology, clinical medicine and beyond.

Theoretical considerations concerning the effect of relativistic velocities on the rate of biological processes.

PubMed

Heneine, I F

1997-06-01

Theoretical considerations were advanced on the reaction rate of biological systems in a rocket accelerated at fractional levels of the velocity of light. The values of mass increase in reacting molecules and length contraction of space under these relativistic velocities attained by the hypothetical rocket were inserted in equations of the absolute reaction rate theory. The equations employed were for the frequency of collisions, and for the internal kinetic energy of molecular reactions. Results of both sets of equations indicated that reduction of reaction rates were correlated to the mass increase. This would imply a general slowing of all chemical, biochemical and biological processes taking place. A human would suffer a related decrease in metabolic rate. Contrary to what is generally accepted, the biological aging of the space traveler under velocities bearable by humans, namely under 0.50c, would follow a pace very similar to that of an observer remaining in the resting frame of reference. With increased increments of the velocity, the space traveler would display a more intense lowering of the metabolic rate, with signs and symptoms comparable to body core hypothermia. Metabolic rates at insufficient levels to maintain the vital functions would be attained at 0.70c and higher, leading swiftly to coma and death. The presence of an endocrine dysfunction such as hypothyroidism or obesity in the space traveler would aggravate the signs and symptoms. Space travel at efficient velocities would be unbearable for a warm-blooded animal.

Adaptive force produced by stress-induced regulation of random variation intensity.

PubMed

Shimansky, Yury P

2010-08-01

The Darwinian theory of life evolution is capable of explaining the majority of related phenomena. At the same time, the mechanisms of optimizing traits beneficial to a population as a whole but not directly to an individual remain largely unclear. There are also significant problems with explaining the phenomenon of punctuated equilibrium. From another perspective, multiple mechanisms for the regulation of the rate of genetic mutations according to the environmental stress have been discovered, but their precise functional role is not well understood yet. Here a novel mathematical paradigm called a Kinetic-Force Principle (KFP), which can serve as a general basis for biologically plausible optimization methods, is introduced and its rigorous derivation is provided. Based on this principle, it is shown that, if the rate of random changes in a biological system is proportional, even only roughly, to the amount of environmental stress, a virtual force is created, acting in the direction of stress relief. It is demonstrated that KFP can provide important insights into solving the above problems. Evidence is presented in support of a hypothesis that the nature employs KFP for accelerating adaptation in biological systems. A detailed comparison between KFP and the principle of variation and natural selection is presented and their complementarity is revealed. It is concluded that KFP is not a competing alternative, but a powerful addition to the principle of variation and natural selection. It is also shown KFP can be used in multiple ways for adaptation of individual biological organisms.

Galactic Cosmic Ray Simulator at the NASA Space Radiation Laboratory

NASA Technical Reports Server (NTRS)

Norbury, John W.; Slaba, Tony C.; Rusek, Adam

2015-01-01

The external Galactic Cosmic Ray (GCR) spectrum is significantly modified when it passes through spacecraft shielding and astronauts. One approach for simulating the GCR space radiation environment is to attempt to reproduce the unmodified, external GCR spectrum at a ground based accelerator. A possibly better approach would use the modified, shielded tissue spectrum, to select accelerator beams impinging on biological targets. NASA plans for implementation of a GCR simulator at the NASA Space Radiation Laboratory (NSRL) at Brookhaven National Laboratory will be discussed.

Patella fractures associated with accelerated ACL rehabilitation in patients with autogenous patella tendon reconstructions.

PubMed

Brownstein, B; Bronner, S

1997-09-01

Patella fracture is a recognized complication of ACL reconstruction with an autogenous patella tendon graft. Typically, fracture occurs as a result of a fall. The incidence of fracture is approximately 0.5%. Accelerated rehabilitation protocols can place stress on the patella, especially in the initial stages of recovery. Therapists are reminded to observe constraints placed on patients by biological tissues, recovering neuromuscular status, and previous level of conditioning. Rehabilitation protocols should be revised according to these factors.

Fast Hydrazone Reactants: Electronic and Acid/Base Effects Strongly Influence Rate at Biological pH

PubMed Central

Kool, Eric T.; Park, Do-Hyoung; Crisalli, Pete

2013-01-01

Kinetics studies with structurally varied aldehydes and ketones in aqueous buffer at pH 7.4 reveal that carbonyl compounds with neighboring acid/base groups form hydrazones at accelerated rates. Similarly, tests of a hydrazine with a neighboring carboxylic acid group show that it also reacts at an accelerated rate. Rate constants for the fastest carbonyl/hydrazine combinations are 2–20 M−1sec−1, which is faster than recent strain-promoted cycloaddition reactions. PMID:24224646

Towards precision prevention: Technologies for identifying healthy individuals with high risk of disease.

PubMed

Nagel, Zachary D; Engelward, Bevin P; Brenner, David J; Begley, Thomas J; Sobol, Robert W; Bielas, Jason H; Stambrook, Peter J; Wei, Qingyi; Hu, Jennifer J; Terry, Mary Beth; Dilworth, Caroline; McAllister, Kimberly A; Reinlib, Les; Worth, Leroy; Shaughnessy, Daniel T

2017-08-01

The rise of advanced technologies for characterizing human populations at the molecular level, from sequence to function, is shifting disease prevention paradigms toward personalized strategies. Because minimization of adverse outcomes is a key driver for treatment decisions for diseased populations, developing personalized therapy strategies represent an important dimension of both precision medicine and personalized prevention. In this commentary, we highlight recently developed enabling technologies in the field of DNA damage, DNA repair, and mutagenesis. We propose that omics approaches and functional assays can be integrated into population studies that fuse basic, translational and clinical research with commercial expertise in order to accelerate personalized prevention and treatment of cancer and other diseases linked to aberrant responses to DNA damage. This collaborative approach is generally applicable to efforts to develop data-driven, individualized prevention and treatment strategies for other diseases. We also recommend strategies for maximizing the use of biological samples for epidemiological studies, and for applying emerging technologies to clinical applications. Copyright © 2017 Elsevier B.V. All rights reserved.

R4 RGS Proteins: Regulation of G Protein Signaling and Beyond

PubMed Central

Bansal, Geetanjali; Druey, Kirk M.; Xie, Zhihui

2007-01-01

The Regulators of G protein Signaling (RGS) proteins were initially characterized as inhibitors of signal transduction cascades initiated by G-protein-coupled receptors (GPCRs) because of their ability to increase the intrinsic GTPase activity of heterotrimeric G proteins. This GTPase accelerating (GAP) activity enhances G protein deactivation and promotes desensitization. However, in addition to this signature trait, emerging data have revealed an expanding network of proteins, lipids, and ions that interact with RGS proteins and confer additional regulatory functions. This review highlights recent advances in our understanding of the physiological functions of one subfamily of RGS proteins with a high degree of homology (B/R4) gleaned from recent studies of knockout mice or cells with reduced RGS expression. We also discuss some of the newly-appreciated interactions of RGS proteins with cellular factors that suggest RGS control of several components of G-protein-mediated pathways as well as a diverse array of non-GPCR-mediated biological responses. PMID:18006065

The impact of winning and losing on family interactions: a biological approach to family therapy.

PubMed

Sloman, Leon; Sturman, Edward D

2012-10-01

To examine the connection between winning and losing and family functioning. We do this by hypothesizing a link between successful outcomes in individual competition and in functional family interaction. This enables us to show how therapeutic interventions can be directed toward the attachment system, by lowering anxiety and fostering mutual trust, and toward the social rank system, by promoting success and feelings of empowerment. A search of online databases was conducted with key search terms related to winning and losing, and their effects on attachment patterns and family interactions. Winning in agonistic encounters has been associated with lowered dysphoria, anxiety, and hostility. These affective states trigger positive patterns of family interaction through their effect on the social rank and attachment systems. Continued success promotes adaptive cycles of interaction, whereas inability to accept loss has the reverse effect. Early humans, who were more successful in competition, were better able to promote the survival and well-being of other family members, which would have accelerated our phylogenetic adaptation.

Cold plasma: A new technology to modify wheat flour functionality

PubMed Central

Bahrami, Niloufar; Bayliss, Danny; Chope, Gemma; Penson, Simon; Perehinec, Tania; Fisk, Ian D.

2016-01-01

Atmospheric pressure cold plasma has the potential to modify biological chemistry and modulate physical surface properties. Wheat flour was treated by low levels of cold plasma (air, 15 V and 20 V) for 60 or 120 s. There was no change in the total aerobic bacterial count or total mould count as a result of treatment. Treatment did not impact the concentration of total non-starch lipids, or non-polar and glycolipids. However, treatment did reduce total free fatty acids and phospholipids and was dose dependent. Oxidation markers (hydroperoxide value and head space n-hexanal) increased with treatment time and voltage, which confirmed the acceleration of lipid oxidation. Total proteins were not significantly influenced by treatment although there was a trend towards higher molecular weight fractions which indicated protein oxidation and treated flour did produce a stronger dough. This study confirms the potential of cold plasma as a tool to modify flour functionality. PMID:26920291

Towards precision prevention: Technologies for identifying healthy individuals with high risk of disease

PubMed Central

Nagel, Zachary D.; Engelward, Bevin P.; Brenner, David J.; Begley, Thomas J.; Sobol, Robert W.; Bielas, Jason H.; Stambrook, Peter J.; Wei, Qingyi; Hu, Jennifer J.; Terry, Mary Beth; Dilworth, Caroline; McAllister, Kimberly A.; Reinlib, Les; Worth, Leroy; Shaughnessy, Daniel T.

2018-01-01

The rise of advanced technologies for characterizing human populations at the molecular level, from sequence to function, is shifting disease prevention paradigms toward personalized strategies. Because minimization of adverse outcomes is a key driver for treatment decisions for diseased populations, developing personalized therapy strategies represent an important dimension of both precision medicine and personalized prevention. In this commentary, we highlight recently developed enabling technologies in the field of DNA damage, DNA repair, and mutagenesis. We propose that omics approaches and functional assays can be integrated into population studies that fuse basic, translational and clinical research with commercial expertise in order to accelerate personalized prevention and treatment of cancer and other diseases linked to aberrant responses to DNA damage. This collaborative approach is generally applicable to efforts to develop data-driven, individualized prevention and treatment strategies for other diseases. We also recommend strategies for maximizing the use of biological samples for epidemiological studies, and for applying emerging technologies to clinical applications. PMID:28458064

Advancing therapeutic strategies for inherited retinal degeneration: recommendations from the Monaciano Symposium.

PubMed

Thompson, Debra A; Ali, Robin R; Banin, Eyal; Branham, Kari E; Flannery, John G; Gamm, David M; Hauswirth, William W; Heckenlively, John R; Iannaccone, Alessandro; Jayasundera, K Thiran; Khan, Naheed W; Molday, Robert S; Pennesi, Mark E; Reh, Thomas A; Weleber, Richard G; Zacks, David N

2015-02-09

Although rare in the general population, retinal dystrophies occupy a central position in current efforts to develop innovative therapies for blinding diseases. This status derives, in part, from the unique biology, accessibility, and function of the retina, as well as from the synergy between molecular discoveries and transformative advances in functional assessment and retinal imaging. The combination of these factors has fueled remarkable progress in the field, while at the same time creating complex challenges for organizing collective efforts aimed at advancing translational research. The present position paper outlines recent progress in gene therapy and cell therapy for this group of disorders, and presents a set of recommendations for addressing the challenges remaining for the coming decade. It is hoped that the formulation of these recommendations will stimulate discussions among researchers, funding agencies, industry, and policy makers that will accelerate the development of safe and effective treatments for retinal dystrophies and related diseases. Copyright 2015 The Association for Research in Vision and Ophthalmology, Inc.

The effect of blood acceleration on the ultrasound power Doppler spectrum

NASA Astrophysics Data System (ADS)

Matchenko, O. S.; Barannik, E. A.

2017-09-01

The purpose of the present work was to study the influence of blood acceleration and time window length on the power Doppler spectrum for Gaussian ultrasound beams. The work has been carried out on the basis of continuum model of the ultrasound scattering from inhomogeneities in fluid flow. Correlation function of fluctuations has been considered for uniformly accelerated scatterers, and the resulting power Doppler spectra have been calculated. It is shown that within the initial phase of systole uniformly accelerated slow blood flow in pulmonary artery and aorta tends to make the correlation function about 4.89 and 7.83 times wider, respectively, than the sensitivity function of typical probing system. Given peak flow velocities, the sensitivity function becomes, vice versa, about 4.34 and 3.84 times wider, respectively, then the correlation function. In these limiting cases, the resulting spectra can be considered as Gaussian. The optimal time window duration decreases with increasing acceleration of blood flow and equals to 11.62 and 7.54 ms for pulmonary artery and aorta, respectively. The width of the resulting power Doppler spectrum is shown to be defined mostly by the wave vector of the incident field, the duration of signal and the acceleration of scatterers in the case of low flow velocities. In the opposite case geometrical properties of probing field and the average velocity itself are more essential. In the sense of signal-noise ratio, the optimal duration of time window can be found. Abovementioned results may contribute to the improved techniques of Doppler ultrasound diagnostics of cardiovascular system.

Materiomics for Oral Disease Diagnostics and Personal Health Monitoring: Designer Biomaterials for the Next Generation Biomarkers

PubMed Central

Zhang, Wenjun; Wang, Ming L.; Khalili, Sammy

2016-01-01

Abstract We live in exciting times for a new generation of biomarkers being enabled by advances in the design and use of biomaterials for medical and clinical applications, from nano- to macro-materials, and protein to tissue. Key challenges arise, however, due to both scientific complexity and compatibility of the interface of biology and engineered materials. The linking of mechanisms across scales by using a materials science approach to provide structure–process–property relations characterizes the emerging field of ‘materiomics,’ which offers enormous promise to provide the hitherto missing tools for biomaterial development for clinical diagnostics and the next generation biomarker applications towards personal health monitoring. Put in other words, the emerging field of materiomics represents an essentially systematic approach to the investigation of biological material systems, integrating natural functions and processes with traditional materials science perspectives. Here we outline how materiomics provides a game-changing technology platform for disruptive innovation in biomaterial science to enable the design of tailored and functional biomaterials—particularly, the design and screening of DNA aptamers for targeting biomarkers related to oral diseases and oral health monitoring. Rigorous and complementary computational modeling and experimental techniques will provide an efficient means to develop new clinical technologies in silico, greatly accelerating the translation of materiomics-driven oral health diagnostics from concept to practice in the clinic. PMID:26760957

Stimulation of Wound Healing by Electroactive, Antibacterial, and Antioxidant Polyurethane/Siloxane Dressing Membranes: In Vitro and in Vivo Evaluations.

PubMed

Gharibi, Reza; Yeganeh, Hamid; Rezapour-Lactoee, Alireza; Hassan, Zuhair M

2015-11-04

A series of novel polyurethane/siloxane-based wound dressing membranes was prepared through sol-gel reaction of methoxysilane end-functionalized urethane prepolymers composed of castor oil and ricinoleic methyl ester as well as methoxysilane functional aniline tetramer (AT) moieties. The samples were fully characterized and their physicochemical, mechanical, electrical, and biological properties were assayed. The biological activity of these dressings against fibroblast cells and couple of microbes was also studied. It was revealed that samples that displayed electroactivity by introduction of AT moieties showed a broad range of antimicrobial activity toward different microorganisms, promising antioxidant (radical scavenging) efficiency and significant activity for stimulation of fibroblast cell growth and proliferation. Meanwhile, these samples showed appropriate tensile strength and ability for maintaining a moist environment over a wound by controlled equilibrium water absorption and water vapor transmission rate. The selected electroactive dressing was subjected to an in vivo assay using a rat animal model and the wound healing process was monitored and compared with analogous dressing without AT moieties. The recorded results showed that the electroactive dressings induced an increase in the rate of wound contraction, promoted collagen deposition, and encouraged vascularization in the wounded area. On the basis of the results of in vitro and in vivo assays, the positive influence of designed dressings for accelerated healing of a wound model was confirmed.

Accelerating research through reagent repositories: the genome editing example.

PubMed

Joung, J Keith; Voytas, Daniel F; Kamens, Joanne

2015-11-20

Keith Joung, Dan Voytas and Joanne Kamens share insights into how the genome editing field was advanced by early access to biological resources and the role in this process that plasmid repositories play.

Titration of biologically active amyloid–β seeds in a transgenic mouse model of Alzheimer's disease

PubMed Central

Morales, Rodrigo; Bravo-Alegria, Javiera; Duran-Aniotz, Claudia; Soto, Claudio

2015-01-01

Experimental evidence in animal models suggests that misfolded Amyloid-β (Aβ) spreads in disease following a prion-like mechanism. Several properties characteristics of infectious prions have been shown for the induction of Aβ aggregates. However, a detailed titration of Aβ misfolding transmissibility and estimation of the minimum concentration of biologically active Aβ seeds able to accelerate pathological changes has not yet been performed. In this study, brain extracts from old tg2576 animals were serially diluted and intra-cerebrally injected into young subjects from the same transgenic line. Animals were sacrificed several months after treatment and brain slices were analyzed for amyloid pathology. We observed that administration of misfolded Aβ was able to significantly accelerate amyloid deposition in young mice, even when the original sample was diluted a million times. The titration curve obtained in this experiment was compared to the natural Aβ load spontaneously accumulated by these mice overtime. Our findings suggest that administration of the largest dose of Aβ seeds led to an acceleration of pathology equivalent to over a year. These results show that active Aβ seeds present in the brain can seed amyloidosis in a titratable manner, similarly as observed for infectious prions. PMID:25879692

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.

Constraint methods that accelerate free-energy simulations of biomolecules.

PubMed

Perez, Alberto; MacCallum, Justin L; Coutsias, Evangelos A; Dill, Ken A

2015-12-28

Atomistic molecular dynamics simulations of biomolecules are critical for generating narratives about biological mechanisms. The power of atomistic simulations is that these are physics-based methods that satisfy Boltzmann's law, so they can be used to compute populations, dynamics, and mechanisms. But physical simulations are computationally intensive and do not scale well to the sizes of many important biomolecules. One way to speed up physical simulations is by coarse-graining the potential function. Another way is to harness structural knowledge, often by imposing spring-like restraints. But harnessing external knowledge in physical simulations is problematic because knowledge, data, or hunches have errors, noise, and combinatoric uncertainties. Here, we review recent principled methods for imposing restraints to speed up physics-based molecular simulations that promise to scale to larger biomolecules and motions.

New discoveries in the transmission biology of sleeping sickness parasites: applying the basics.

PubMed

MacGregor, Paula; Matthews, Keith R

2010-09-01

The sleeping sickness parasite, Trypanosoma brucei, must differentiate in response to the changing environments that it encounters during its complex life cycle. One developmental form, the bloodstream stumpy stage, plays an important role in infection dynamics and transmission of the parasite. Recent advances have shed light on the molecular mechanisms by which these stumpy forms differentiate as they are transmitted from the mammalian host to the insect vector of sleeping sickness, tsetse flies. These molecular advances now provide improved experimental tools for the study of stumpy formation and function within the mammalian bloodstream. They also offer new routes to therapy via high-throughput screens for agents that accelerate parasite development. Here, we shall discuss the recent advances that have been made and the prospects for future research now available.

[Ru(bipy)3]2+ nanoparticle-incorporate dental light cure resin to promote photobiomodulation therapy for enhanced vital pulp tissue repair

NASA Astrophysics Data System (ADS)

Mosca, Rodrigo C.; Young, Nicholas; Zeituni, Carlos A.; Arany, Praveen R.

2018-02-01

The use of nanoparticle on dental light cure resin is not new, currently several compounds (nanoadditives) are used to promote better communication between the restorative material and biological tissues. The interest for this application is growing up to enhance mechanical proprieties to dental tissue cells regeneration. Bioactive nanoparticles and complex compounds with multiple functions are the major target for optimizing the restorative materials. In this work, we incorporate [Ru(bipy)3]2+ nanoparticles, that absorbs energy at 450 nm (blue-light) and emits strongly at 620 nm (red-light), in PLGA Microspheres and insert it in Dental Light Cure Resin to promote the Photobiomodulation Therapy (PBM) effects to accelerate dental pulp repair by in vitro using cytotoxicity and proliferation assay.

Carbohydrate CuAAC click chemistry for therapy and diagnosis.

PubMed

He, Xiao-Peng; Zeng, Ya-Li; Zang, Yi; Li, Jia; Field, Robert A; Chen, Guo-Rong

2016-06-24

Carbohydrates are important as signaling molecules and for cellular recognition events, therefore offering scope for the development of carbohydrate-mimetic diagnostics and drug candidates. As a consequence, the construction of carbohydrate-based bioactive compounds and sensors has become an active research area. While the advent of click chemistry has greatly accelerated the progress of medicinal chemistry and chemical biology, recent literature has seen an extensive use of such approaches to construct functionally diverse carbohydrate derivatives. Here we summarize some of the progress, covering the period 2010 to mid-2015, in Cu(I)-catalyzed azide-alkyne 1,3-dipolar cycloaddition CuAAC "click chemistry" of carbohydrate derivatives, in the context of potential therapeutic and diagnostic tool development. Copyright © 2016 The Authors. Published by Elsevier Ltd.. All rights reserved.

Hydrogen-rich saline attenuates spinal cord hemisection-induced testicular injury in rats.

PubMed

Ge, Li; Wei, Li-Hua; Du, Chang-Qing; Song, Guo-Hua; Xue, Ya-Zhuo; Shi, Hao-Shen; Yang, Ming; Yin, Xin-Xin; Li, Run-Ting; Wang, Xue-Er; Wang, Zhen; Song, Wen-Gang

2017-06-27

To study how hydrogen-rich saline (HS) promotes the recovery of testicular biological function in a hemi-sectioned spinal cord injury (hSCI) rat model, a right hemisection was performed at the T11-T12 of the spinal cord in Wistar rats. Animals were divided into four groups: normal group; vehicle group: sham-operated rats administered saline; hSCI group: subjected to hSCI and administered saline; HRST group: subjected to hSCI and administered HS. Hind limb neurological function, testis index, testicular morphology, mean seminiferous tubular diameter (MSTD) and seminiferous epithelial thickness (MSET), the expression of heme oxygenase-1 (HO-1), mitofusin-2 (MFN-2), and high-mobility group box 1 (HMGB-1), cell ultrastructure, and apoptosis of spermatogenic cells were studied. The results indicated that hSCI significantly decreased the hind limb neurological function, testis index, MSTD, and MSET, and induced severe testicular morphological injury. The MFN-2 level was decreased, and HO-1 and HMGB-1 were overexpressed in testicular tissues. In addition, hSCI accelerated the apoptosis of spermatogenic cells and the ultrastructural damage of cells in the hypophysis and testis. After HS administration, all these parameters were considerably improved, and the characteristics of hSCI testes were similar to those of normal control testes. Taken together, HS administration can promote the recovery of testicular biological function by anti-oxidative, anti-inflammatory, and anti-apoptotic action. More importantly, HS can inhibit the hSCI-induced ultrastructural changes in gonadotrophs, ameliorate the abnormal regulation of the hypothalamic-pituitary-testis axis, and thereby promote the recovery of testicular injury. HS administration also inhibited the hSCI-induced ultrastructural changes in testicular spermatogenic cells, Sertoli cells and interstitial cells.

Hydrogen-rich saline attenuates spinal cord hemisection-induced testicular injury in rats

PubMed Central

Ge, Li; Wei, Li-Hua; Du, Chang-Qing; Song, Guo-Hua; Xue, Ya-Zhuo; Shi, Hao-Shen; Yang, Ming; Yin, Xin-Xin; Li, Run-Ting; Wang, Xue-er; Wang, Zhen; Song, Wen-Gang

2017-01-01

To study how hydrogen-rich saline (HS) promotes the recovery of testicular biological function in a hemi-sectioned spinal cord injury (hSCI) rat model, a right hemisection was performed at the T11–T12 of the spinal cord in Wistar rats. Animals were divided into four groups: normal group; vehicle group: sham-operated rats administered saline; hSCI group: subjected to hSCI and administered saline; HRST group: subjected to hSCI and administered HS. Hind limb neurological function, testis index, testicular morphology, mean seminiferous tubular diameter (MSTD) and seminiferous epithelial thickness (MSET), the expression of heme oxygenase-1 (HO-1), mitofusin-2 (MFN-2), and high-mobility group box 1 (HMGB-1), cell ultrastructure, and apoptosis of spermatogenic cells were studied. The results indicated that hSCI significantly decreased the hind limb neurological function, testis index, MSTD, and MSET, and induced severe testicular morphological injury. The MFN-2 level was decreased, and HO-1 and HMGB-1 were overexpressed in testicular tissues. In addition, hSCI accelerated the apoptosis of spermatogenic cells and the ultrastructural damage of cells in the hypophysis and testis. After HS administration, all these parameters were considerably improved, and the characteristics of hSCI testes were similar to those of normal control testes. Taken together, HS administration can promote the recovery of testicular biological function by anti-oxidative, anti-inflammatory, and anti-apoptotic action. More importantly, HS can inhibit the hSCI-induced ultrastructural changes in gonadotrophs, ameliorate the abnormal regulation of the hypothalamic-pituitary-testis axis, and thereby promote the recovery of testicular injury. HS administration also inhibited the hSCI-induced ultrastructural changes in testicular spermatogenic cells, Sertoli cells and interstitial cells. PMID:28404953

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…

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. © 2012 German Botanical Society and The Royal Botanical Society of the Netherlands.

Towards fast, rigorous and efficient conformational sampling of biomolecules: Advances in accelerated molecular dynamics.

PubMed

Doshi, Urmi; Hamelberg, Donald

2015-05-01

Accelerated molecular dynamics (aMD) has been proven to be a powerful biasing method for enhanced sampling of biomolecular conformations on general-purpose computational platforms. Biologically important long timescale events that are beyond the reach of standard molecular dynamics can be accessed without losing the detailed atomistic description of the system in aMD. Over other biasing methods, aMD offers the advantages of tuning the level of acceleration to access the desired timescale without any advance knowledge of the reaction coordinate. Recent advances in the implementation of aMD and its applications to small peptides and biological macromolecules are reviewed here along with a brief account of all the aMD variants introduced in the last decade. In comparison to the original implementation of aMD, the recent variant in which all the rotatable dihedral angles are accelerated (RaMD) exhibits faster convergence rates and significant improvement in statistical accuracy of retrieved thermodynamic properties. RaMD in conjunction with accelerating diffusive degrees of freedom, i.e. dual boosting, has been rigorously tested for the most difficult conformational sampling problem, protein folding. It has been shown that RaMD with dual boosting is capable of efficiently sampling multiple folding and unfolding events in small fast folding proteins. RaMD with the dual boost approach opens exciting possibilities for sampling multiple timescales in biomolecules. While equilibrium properties can be recovered satisfactorily from aMD-based methods, directly obtaining dynamics and kinetic rates for larger systems presents a future challenge. This article is part of a Special Issue entitled Recent developments of molecular dynamics. Copyright © 2014 Elsevier B.V. All rights reserved.

SU-F-BRD-07: Fast Monte Carlo-Based Biological Optimization of Proton Therapy Treatment Plans for Thyroid Tumors

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

Wan Chan Tseung, H; Ma, J; Ma, D

2015-06-15

Purpose: To demonstrate the feasibility of fast Monte Carlo (MC) based biological planning for the treatment of thyroid tumors in spot-scanning proton therapy. Methods: Recently, we developed a fast and accurate GPU-based MC simulation of proton transport that was benchmarked against Geant4.9.6 and used as the dose calculation engine in a clinically-applicable GPU-accelerated IMPT optimizer. Besides dose, it can simultaneously score the dose-averaged LET (LETd), which makes fast biological dose (BD) estimates possible. To convert from LETd to BD, we used a linear relation based on cellular irradiation data. Given a thyroid patient with a 93cc tumor volume, we createdmore » a 2-field IMPT plan in Eclipse (Varian Medical Systems). This plan was re-calculated with our MC to obtain the BD distribution. A second 5-field plan was made with our in-house optimizer, using pre-generated MC dose and LETd maps. Constraints were placed to maintain the target dose to within 25% of the prescription, while maximizing the BD. The plan optimization and calculation of dose and LETd maps were performed on a GPU cluster. The conventional IMPT and biologically-optimized plans were compared. Results: The mean target physical and biological doses from our biologically-optimized plan were, respectively, 5% and 14% higher than those from the MC re-calculation of the IMPT plan. Dose sparing to critical structures in our plan was also improved. The biological optimization, including the initial dose and LETd map calculations, can be completed in a clinically viable time (∼30 minutes) on a cluster of 25 GPUs. Conclusion: Taking advantage of GPU acceleration, we created a MC-based, biologically optimized treatment plan for a thyroid patient. Compared to a standard IMPT plan, a 5% increase in the target’s physical dose resulted in ∼3 times as much increase in the BD. Biological planning was thus effective in escalating the target BD.« less

ELIMED: a new hadron therapy concept based on laser driven ion beams

NASA Astrophysics Data System (ADS)

Cirrone, Giuseppe A. P.; Margarone, Daniele; Maggiore, Mario; Anzalone, Antonello; Borghesi, Marco; Jia, S. Bijan; Bulanov, Stepan S.; Bulanov, Sergei; Carpinelli, Massimo; Cavallaro, Salvatore; Cutroneo, Mariapompea; Cuttone, Giacomo; Favetta, Marco; Gammino, Santo; Klimo, Ondrej; Manti, Lorenzo; Korn, Georg; La Malfa, Giuseppe; Limpouch, Jiri; Musumarra, Agatino; Petrovic, Ivan; Prokupek, Jan; Psikal, Jan; Ristic-Fira, Aleksandra; Renis, Marcella; Romano, Francesco P.; Romano, Francesco; Schettino, Giuseppe; Schillaci, Francesco; Scuderi, Valentina; Stancampiano, Concetta; Tramontana, Antonella; Ter-Avetisyan, Sargis; Tomasello, Barbara; Torrisi, Lorenzo; Tudisco, Salvo; Velyhan, Andriy

2013-05-01

Laser accelerated proton beams have been proposed to be used in different research fields. A great interest has risen for the potential replacement of conventional accelerating machines with laser-based accelerators, and in particular for the development of new concepts of more compact and cheaper hadrontherapy centers. In this context the ELIMED (ELI MEDical applications) research project has been launched by INFN-LNS and ASCR-FZU researchers within the pan-European ELI-Beamlines facility framework. The ELIMED project aims to demonstrate the potential clinical applicability of optically accelerated proton beams and to realize a laser-accelerated ion transport beamline for multi-disciplinary user applications. In this framework the eye melanoma, as for instance the uveal melanoma normally treated with 62 MeV proton beams produced by standard accelerators, will be considered as a model system to demonstrate the potential clinical use of laser-driven protons in hadrontherapy, especially because of the limited constraints in terms of proton energy and irradiation geometry for this particular tumour treatment. Several challenges, starting from laser-target interaction and beam transport development up to dosimetry and radiobiology, need to be overcome in order to reach the ELIMED final goals. A crucial role will be played by the final design and realization of a transport beamline capable to provide ion beams with proper characteristics in terms of energy spectrum and angular distribution which will allow performing dosimetric tests and biological cell irradiation. A first prototype of the transport beamline has been already designed and other transport elements are under construction in order to perform a first experimental test with the TARANIS laser system by the end of 2013. A wide international collaboration among specialists of different disciplines like Physics, Biology, Chemistry, Medicine and medical doctors coming from Europe, Japan, and the US is growing up around the ELIMED project with the aim to work on the conceptual design, technical and experimental realization of this core beamline of the ELI Beamlines facility.

Low-gravity Orbiting Research Laboratory Environment Potential Impact on Space Biology Research

NASA Technical Reports Server (NTRS)

Jules, Kenol

2006-01-01

One of the major objectives of any orbital space research platform is to provide a quiescent low gravity, preferably a zero gravity environment, to perform fundamental as well as applied research. However, small disturbances exist onboard any low earth orbital research platform. The impact of these disturbances must be taken into account by space research scientists during their research planning, design and data analysis in order to avoid confounding factors in their science results. The reduced gravity environment of an orbiting research platform in low earth orbit is a complex phenomenon. Many factors, among others, such as experiment operations, equipment operation, life support systems and crew activity (if it is a crewed platform), aerodynamic drag, gravity gradient, rotational effects as well as the vehicle structural resonance frequencies (structural modes) contribute to form the overall reduced gravity environment in which space research is performed. The contribution of these small disturbances or accelerations is precisely why the environment is NOT a zero gravity environment, but a reduced acceleration environment. This paper does not discuss other factors such as radiation, electromagnetic interference, thermal and pressure gradient changes, acoustic and CO2 build-up to name a few that affect the space research environment as well, but it focuses solely on the magnitude of the acceleration level found on orbiting research laboratory used by research scientists to conduct space research. For ease of analysis this paper divides the frequency spectrum relevant to most of the space research disciplines into three regimes: a) quasi-steady, b) vibratory and c) transient. The International Space Station is used as an example to illustrate the point. The paper discusses the impact of these three regimes on space biology research and results from space flown experiments are used to illustrate the potential negative impact of these disturbances (accelerations) on space biology research.

Association of Wnt1-inducible signaling pathway protein-1 with the proliferation, migration and invasion in gastric cancer cells.

PubMed

Jia, Shuqin; Qu, Tingting; Feng, Mengmeng; Ji, Ke; Li, Ziyu; Jiang, Wenguo; Ji, Jiafu

2017-06-01

Wnt1-inducible signaling pathway protein-1 is a cysteine-rich protein that belongs to the CCN family, which has been implicated in mediating the occurrence and progression through distinct molecular mechanisms in several tumor types. However, the association of Wnt1-inducible signaling pathway protein-1 with gastric cancer and the related molecular mechanisms remain to be elucidated. Therefore, this study aimed to clarify the biological role of Wnt1-inducible signaling pathway protein-1 in the proliferation, migration, and invasion in gastric cancer cells and further investigated the associated molecular mechanism on these biological functions. We first detected the expression level of Wnt1-inducible signaling pathway protein-1 in gastric cancer, and the reverse transcription polymerase chain reaction have shown that Wnt1-inducible signaling pathway protein-1 expression levels were upregulated in gastric cancer tissues. The expression of Wnt1-inducible signaling pathway protein-1 in gastric cancer cell lines was also detected by quantitative real-time polymerase chain reaction and Western blotting. Furthermore, two gastric cancer cell lines with high expression of Wnt1-inducible signaling pathway protein-1 were selected to explore the biological function of Wnt1-inducible signaling pathway protein-1 in gastric cancer. Function assays indicated that knockdown of Wnt1-inducible signaling pathway protein-1 suppressed cell proliferation, migration, and invasion in BGC-823 and AGS gastric cancer cells. Further investigation of mechanisms suggested that cyclinD1 was identified as one of Wnt1-inducible signaling pathway protein-1 related genes to accelerate proliferation in gastric cancer cells. In addition, one pathway of Wnt1-inducible signaling pathway protein-1 induced migration and invasion was mainly through the enhancement of epithelial-to-mesenchymal transition progression. Taken together, our findings presented the first evidence that Wnt1-inducible signaling pathway protein-1 was upregulated in gastric cancer and acted as an oncogene by promoting proliferation, migration, and invasion in gastric cancer cells.

Application of ecological criteria in selecting marine reserves and developing reserve networks

USGS Publications Warehouse

Roberts, Callum M.; Branch, George; Bustamante, Rodrigo H.; Castilla, Juan Carlos; Dugan, Jenifer; Halpern, Benjamin S.; Lafferty, Kevin D.; Leslie, Heather; McArdle, Deborah; Ruckelshaus, Mary; Warner, Robert R.

2003-01-01

Marine reserves are being established worldwide in response to a growing recognition of the conservation crisis that is building in the oceans. However, designation of reserves has been largely opportunistic, or protective measures have been implemented (often overlapping and sometimes in conflict) by different entities seeking to achieve different ends. This has created confusion among both users and enforcers, and the proliferation of different measures provides a false sense of protection where little is offered. This paper sets out a procedure grounded in current understanding of ecological processes, that allows the evaluation and selection of reserve sites in order to develop functional, interconnected networks of fully protected reserves that will fulfill multiple objectives. By fully protected we mean permanently closed to fishing and other resource extraction. We provide a framework that unifies the central aims of conservation and fishery management, while also meeting other human needs such as the provision of ecosystem services (e.g., maintenance of coastal water quality, shoreline protection, and recreational opportunities). In our scheme, candidate sites for reserves are evaluated against 12 criteria focused toward sustaining the biological integrity and productivity of marine systems at both local and regional scales. While a limited number of sites will be indispensable in a network, many will be of similar value as reserves, allowing the design of numerous alternative, biologically adequate networks. Devising multiple network designs will help ensure that ecological functionality is preserved throughout the socioeconomic evaluation process. Too often, socioeconomic criteria have dominated the process of reserve selection, potentially undermining their efficacy. We argue that application of biological criteria must precede and inform socioeconomic evaluation, since maintenance of ecosystem functioning is essential for meeting all of the goals for reserves. It is critical that stakeholders are fully involved throughout this process. Application of the proposed criteria will lead to networks whose multifunctionality will help unite the objectives of different management entities, so accelerating progress toward improved stewardship of the oceans.

Research on effect of ginkgo aglucone flavone to human body organs and immune function.

PubMed

Wang, Xiong

2014-07-01

Ginkgo aglucone flavone is a kind of effective natural antioxidant. Lots of researches show that ginkgo aglucone flavone has various biological activities and it is of great importance to antioxidant, anti-aging, free radial scavenging and immunoregulation. However, researches on effect of ginkgo aglucone flavone to immune function are rare so far. Thus, it is important to go into the effect of ginkgo aglucone flavone to immune function. We can find out more effective measurement that resist immunosuppression through research and provide referable science activity form and suggestion of sports nutrition supplements. It can guide people to improve habitus through supports and establish important basis for new area development of folium ginkgo extract. This paper aims to discuss the effect of ginkgo aglucone flavone to human body organs and immune function. Patients with ginkgo aglucone flavone indications are selected for experiment. Their peripheral blood T lymphocyte subsets and content of serum immunoglobin is detected before and two weeks after drug use. The result shows that specific ratio of T lymphocyte subsets CD3 and CD4 and the content of serum IgG significantly increase after pharmacy of patients. It can be concluded that ginkgo aglucone flavone have acceleration on immune system function.

Temporal effects of post-fire check dam construction on soil functionality in SE Spain.

PubMed

González-Romero, J; Lucas-Borja, M E; Plaza-Álvarez, P A; Sagra, J; Moya, D; De Las Heras, J

2018-06-09

Wildfire has historically been an alteration factor in Mediterranean basins. Despite Mediterranean ecosystems' high resilience, wildfire accelerates erosion and degradation processes, and also affects soil functionality by affecting nutrient cycles and soil structure. In semi-arid Mediterranean basins, check dams are usually built in gullies and channels after fire as a measure against soil erosion. Although check dams have proven efficient action to reduce erosion rates, studies about how they affect soil functionality are lacking. Our approach focuses on how soil functionality, defined as a combination of physico-chemical and biological indicators, is locally affected by check dam construction and the evolution of this effect over time. Soils were sampled in eight check dams in two semi-arid areas at SE Spain, which were affected by wildfire in 2012 and 2016. The study findings reveal that by altering sediments cycle and transport, check dams influence soil's main physico-chemical and biochemical characteristics. Significant differences were found between check dam-affected zones and the control ones for many indicators such as organic matter content, electrical conductivity or enzymatic activity. According to the ANOVA results, interaction between check dams influence and time after fire, was a crucial factor. PCA results clearly showed check-dams influence on soil functionality. Copyright © 2018. Published by Elsevier B.V.

Phylogenetic profiles reveal structural/functional determinants of TRPC3 signal-sensing antennae

PubMed Central

Ko, Kyung Dae; Bhardwaj, Gaurav; Hong, Yoojin; Chang, Gue Su; Kiselyov, Kirill

2009-01-01

Biochemical assessment of channel structure/function is incredibly challenging. Developing computational tools that provide these data would enable translational research, accelerating mechanistic experimentation for the bench scientist studying ion channels. Starting with the premise that protein sequence encodes information about structure, function and evolution (SF&E), we developed a unified framework for inferring SF&E from sequence information using a knowledge-based approach. The Gestalt Domain Detection Algorithm-Basic Local Alignment Tool (GDDA-BLAST) provides phylogenetic profiles that can model, ab initio, SF&E relationships of biological sequences at the whole protein, single domain and single-amino acid level.1,2 In our recent paper,4 we have applied GDDA-BLAST analysis to study canonical TRP (TRPC) channels1 and empirically validated predicted lipid-binding and trafficking activities contained within the TRPC3 TRP_2 domain of unknown function. Overall, our in silico, in vitro, and in vivo experiments support a model in which TRPC3 has signal-sensing antennae which are adorned with lipid-binding, trafficking and calmodulin regulatory domains. In this Addendum, we correlate our functional domain analysis with the cryo-EM structure of TRPC3.3 In addition, we synthesize recent studies with our new findings to provide a refined model on the mechanism(s) of TRPC3 activation/deactivation. PMID:19704910

Compact laser accelerators for X-ray phase-contrast imaging

PubMed Central

Najmudin, Z.; Kneip, S.; Bloom, M. S.; Mangles, S. P. D.; Chekhlov, O.; Dangor, A. E.; Döpp, A.; Ertel, K.; Hawkes, S. J.; Holloway, J.; Hooker, C. J.; Jiang, J.; Lopes, N. C.; Nakamura, H.; Norreys, P. A.; Rajeev, P. P.; Russo, C.; Streeter, M. J. V.; Symes, D. R.; Wing, M.

2014-01-01

Advances in X-ray imaging techniques have been driven by advances in novel X-ray sources. The latest fourth-generation X-ray sources can boast large photon fluxes at unprecedented brightness. However, the large size of these facilities means that these sources are not available for everyday applications. With advances in laser plasma acceleration, electron beams can now be generated at energies comparable to those used in light sources, but in university-sized laboratories. By making use of the strong transverse focusing of plasma accelerators, bright sources of betatron radiation have been produced. Here, we demonstrate phase-contrast imaging of a biological sample for the first time by radiation generated by GeV electron beams produced by a laser accelerator. The work was performed using a greater than 300 TW laser, which allowed the energy of the synchrotron source to be extended to the 10–100 keV range. PMID:24470414

Mercury BLASTP: Accelerating Protein Sequence Alignment

PubMed Central

Jacob, Arpith; Lancaster, Joseph; Buhler, Jeremy; Harris, Brandon; Chamberlain, Roger D.

2008-01-01

Large-scale protein sequence comparison is an important but compute-intensive task in molecular biology. BLASTP is the most popular tool for comparative analysis of protein sequences. In recent years, an exponential increase in the size of protein sequence databases has required either exponentially more running time or a cluster of machines to keep pace. To address this problem, we have designed and built a high-performance FPGA-accelerated version of BLASTP, Mercury BLASTP. In this paper, we describe the architecture of the portions of the application that are accelerated in the FPGA, and we also describe the integration of these FPGA-accelerated portions with the existing BLASTP software. We have implemented Mercury BLASTP on a commodity workstation with two Xilinx Virtex-II 6000 FPGAs. We show that the new design runs 11-15 times faster than software BLASTP on a modern CPU while delivering close to 99% identical results. PMID:19492068

Recent biological trends in management of fracture non-union

PubMed Central

Emara, Khaled M; Diab, Ramy Ahmed; Emara, Ahmed Khaled

2015-01-01

Bone regeneration is a complex, well-orchestrated physiological process of bone formation, which can be seen during normal fracture healing, and is involved in continuous remodelling throughout adult life. Currently, there is a plethora of different strategies to augment the impaired or “insufficient” bone-regeneration process, including the “gold standard” autologous bone graft, free fibula vascularised graft, allograft implantation, and use of growth factors, osteoconductive scaffolds, osteoprogenitor cells and distraction osteogenesis. Improved “local” strategies in terms of tissue engineering and gene therapy, or even “systemic” enhancement of bone repair, are under intense investigation, in an effort to overcome the limitations of the current methods, to produce bone-graft substitutes with biomechanical properties that are as identical to normal bone as possible, to accelerate the overall regeneration process, or even to address systemic conditions, such as skeletal disorders and osteoporosis. An improved understanding of the molecular and cellular events that occur during bone repair and remodeling has led to the development of biologic agents that can augment the biological microenvironment and enhance bone repair. Orthobiologics, including stem cells, osteoinductive growth factors, osteoconductive matrices, and anabolic agents, are available clinically for accelerating fracture repair and treatment of compromised bone repair situations like delayed unions and nonunions. A lack of standardized outcome measures for comparison of biologic agents in clinical fracture repair trials, frequent off-label use, and a limited understanding of the biological activity of these agents at the bone repair site have limited their efficacy in clinical applications. PMID:26396938

[The biological reaction of inflammation, methylglyoxal of blood plasma, functional and structural alterations in elastic type arteries at the early stage of hypertension disease].

PubMed

Titov, V N; Dmitriev, V A; Oshchepkov, E V; Balakhonova, T V; Tripoten', M I; Shiriaeva, Iu K

2012-08-01

The article deals with studying of the relationship between biologic reaction of inflammation with glycosylation reaction and content of methylglyoxal in blood serum. The positive correlation between pulse wave velocity and content of methylglyoxal, C-reactive protein in intercellular medium and malleolar brachial index value was established. This data matches the experimental results concerning involvement of biological reaction of inflammation into structural changes of elastic type arteries under hypertension disease, formation of arteries' rigidity and increase of pulse wave velocity. The arterial blood pressure is a biological reaction of hydrodynamic pressure which is used in vivo by several biological functions: biological function of homeostasis, function of endoecology, biological function of adaptation and function of locomotion. The biological reaction of hydrodynamic (hydraulic) pressure is a mode of compensation of derangement of several biological functions which results in the very high rate of hypertension disease in population. As a matter of fact, hypertension disease is a syndrome of lingering pathological compensation by higher arterial blood pressure of the biological functions derangements occurring in the distal section at the level of paracrine cenoses of cells. The arterial blood pressure is a kind of in vivo integral indicator of deranged metabolism. The essential hypertension disease pathogenically is a result of the derangement of three biological functions: biological function of homeostasis, biological function of trophology - nutrition (biological reaction of external feeding - exotrophia) and biological function of endoecology. In case of "littering" of intercellular medium in vivo with nonspecific endogenic flogogens a phylogenetically earlier activation of biological reactions of excretion, inflammation and hydrodynamic arterial blood pressure occur. In case of derangement of biological function of homeostasis, decreasing of perfusion even in single paracrine cenoses and derangement of biological function of endoecology ("purity" of intercellular medium) the only response always will be the increase of arterial blood pressure.

Measurements of carbon-14 with cavity ring-down spectroscopy

DOE PAGES

McCartt, A. D.; Ognibene, T.; Bench, G.; ...

2015-06-13

Accelerator Mass Spectrometry (AMS) is the most sensitive method for quantitation of 14C in biological samples. This technology has been used in a variety of low dose, human health related studies over the last 20 years when very high sensitivity was needed. AMS helped pioneer these scientific methods, but its expensive facilities and requirements for highly trained technical staff have limited their proliferation. Quantification of 14C by cavity ring-down spectroscopy (CRDS) offers an approach that eliminates many of the shortcomings of an accelerator-based system and would supplement the use of AMS in biomedical research. Our initial prototype, using a non-idealmore » wavelength laser and under suboptimal experimental conditions, has a 3.5-modern, 1-σ precision for detection of milligram-sized, carbon-14-elevated samples. Furthermore, these results demonstrate proof of principle and provided a starting point for the development of a spectrometer capable of biologically relevant sensitivities.« less

Department of Defense Joint Chemical and Biological Defense Program 2009 Annual Report to Congress

DTIC Science & Technology

2009-03-27

completion at the ECBC on the Edgewood Area of Aberdeen Proving Ground (APG), MD. The SRF is a collaborative effort, funded by the DoD, DHS, and...Accelerated Manufacture of Pharmaceuticals APB Acquisition Program Baseline APG Aberdeen Proving Ground ARC Annual Report to Congress ASC Active...Critical Reagents Program CUGV Chemical, Biological, Radiological, and Nuclear Unmanned Ground Vehicle CW Chemical Weapons CWA Chemical Warfare Agent CWC

Illustrations of mathematical modeling in biology: epigenetics, meiosis, and an outlook.

PubMed

Richards, D; Berry, S; Howard, M

2012-01-01

In the past few years, mathematical modeling approaches in biology have begun to fulfill their promise by assisting in the dissection of complex biological systems. Here, we review two recent examples of predictive mathematical modeling in plant biology. The first involves the quantitative epigenetic silencing of the floral repressor gene FLC in Arabidopsis, mediated by a Polycomb-based system. The second involves the spatiotemporal dynamics of telomere bouquet formation in wheat-rye meiosis. Although both the biology and the modeling framework of the two systems are different, both exemplify how mathematical modeling can help to accelerate discovery of the underlying mechanisms in complex biological systems. In both cases, the models that developed were relatively minimal, including only essential features, but both nevertheless yielded fundamental insights. We also briefly review the current state of mathematical modeling in biology, difficulties inherent in its application, and its potential future development.

sbv IMPROVER: Modern Approach to Systems Biology.

PubMed

Guryanova, Svetlana; Guryanova, Anna

2017-01-01

The increasing amount and variety of data in biosciences call for innovative methods of visualization, scientific verification, and pathway analysis. Novel approaches to biological networks and research quality control are important because of their role in development of new products, improvement, and acceleration of existing health policies and research for novel ways of solving scientific challenges. One such approach is sbv IMPROVER. It is a platform that uses crowdsourcing and verification to create biological networks with easy public access. It contains 120 networks built in Biological Expression Language (BEL) to interpret data from PubMed articles with high-quality verification available for free on the CBN database. Computable, human-readable biological networks with a structured syntax are a powerful way of representing biological information generated from high-density data. This article presents sbv IMPROVER, a crowd-verification approach for the visualization and expansion of biological networks.

Are Anxiety Disorders Associated with Accelerated Aging? A Focus on Neuroprogression

PubMed Central

Perna, Giampaolo; Iannone, Giuseppe; Alciati, Alessandra; Caldirola, Daniela

2016-01-01

Anxiety disorders (AnxDs) are highly prevalent throughout the lifespan, with detrimental effects on daily-life functioning, somatic health, and quality of life. An emerging perspective suggested that AnxDs may be associated with accelerated aging. In this paper, we explored the association between AnxDs and hallmarks of accelerated aging, with a specific focus on neuroprogression. We reviewed animal and human findings that suggest an overlap between processes of impaired neurogenesis, neurodegeneration, structural, functional, molecular, and cellular modifications in AnxDs, and aging. Although this research is at an early stage, our review suggests a link between anxiety and accelerated aging across multiple processes involved in neuroprogression. Brain structural and functional changes that accompany normal aging were more pronounced in subjects with AnxDs than in coevals without AnxDs, including reduced grey matter density, white matter alterations, impaired functional connectivity of large-scale brain networks, and poorer cognitive performance. Similarly, molecular correlates of brain aging, including telomere shortening, Aβ accumulation, and immune-inflammatory and oxidative/nitrosative stress, were overrepresented in anxious subjects. No conclusions about causality or directionality between anxiety and accelerated aging can be drawn. Potential mechanisms of this association, limitations of the current research, and implications for treatments and future studies are discussed. PMID:26881136

[Biological experiments on "Kosmos-1887"].

PubMed

Alpatov, A M; I'lin, E A; Antipov, V V; Tairbekov, M G

1989-01-01

In the 13-ray space flight on Kosmos-1887 various experiments in the field of cell biology, genetics, biorhythm, developmental biology and regeneration were performed using bacteria, protozoa, plants, worms, insects, fish and amphibia. Paramecia showed enhanced cell proliferation, spheroidization and diminished protein content. Experiments on fruit-flies, newt oocytes and primate lymphocytes confirmed involvement of the cell genetic apparatus in responses to microgravity. Beetles exhibited a reduction of the length of the spontaneous period of freely running circadian rhythms. Carausius morosus developed latent changes in early embryogenesis which manifested at later stages of ontogenesis. Exposure to microgravity did not prevent recovery of injured tissues; moreover their regeneration may be accelerated after recovery. Biology research programs in future biosatellite flights are discussed.

Acceleration of O+ from the cusp to the plasma sheet

NASA Astrophysics Data System (ADS)

Liao, J.; Kistler, L. M.; Mouikis, C. G.; Klecker, B.; Dandouras, I.

2015-02-01

Heavy ions from the ionosphere that are accelerated in the cusp/cleft have been identified as a direct source for the hot plasma in the plasma sheet. However, the details of the acceleration and transport that transforms the originally cold ions into the hot plasma sheet population are not fully understood. The polar orbit of the Cluster satellites covers the main transport path of the O+ from the cusp to the plasma sheet, so Cluster is ideal for tracking its velocity changes. However, because the cusp outflow is dispersed according to its velocity as it is transported to the tail, due to the velocity filter effect, the observed changes in beam velocity over the Cluster orbit may simply be the result of the spacecraft accessing different spatial regions and not necessarily evidence of acceleration. Using the Cluster Ion Spectrometry/Composition Distribution Function instrument onboard Cluster, we compare the distribution function of streaming O+ in the tail lobes with the initial distribution function observed over the cusp and reveal that the observations of energetic streaming O+ in the lobes around -20 RE are predominantly due to the velocity filter effect during nonstorm times. During storm times, the cusp distribution is further accelerated. In the plasma sheet boundary layer, however, the average O+ distribution function is above the upper range of the outflow distributions at the same velocity during both storm and nonstorm times, indicating that acceleration has taken place. Some of the velocity increase is in the direction perpendicular to the magnetic field, indicating that the E × B velocity is enhanced. However, there is also an increase in the parallel direction, which could be due to nonadiabatic acceleration at the boundary or wave heating.

Engineering biological systems using automated biofoundries.

PubMed

Chao, Ran; Mishra, Shekhar; Si, Tong; Zhao, Huimin

2017-07-01

Engineered biological systems such as genetic circuits and microbial cell factories have promised to solve many challenges in the modern society. However, the artisanal processes of research and development are slow, expensive, and inconsistent, representing a major obstacle in biotechnology and bioengineering. In recent years, biological foundries or biofoundries have been developed to automate design-build-test engineering cycles in an effort to accelerate these processes. This review summarizes the enabling technologies for such biofoundries as well as their early successes and remaining challenges. Copyright © 2017 International Metabolic Engineering Society. Published by Elsevier Inc. All rights reserved.

Source-to-accelerator quadrupole matching section for a compact linear accelerator

NASA Astrophysics Data System (ADS)

Seidl, P. A.; Persaud, A.; Ghiorso, W.; Ji, Q.; Waldron, W. L.; Lal, A.; Vinayakumar, K. B.; Schenkel, T.

2018-05-01

Recently, we presented a new approach for a compact radio-frequency (RF) accelerator structure and demonstrated the functionality of the individual components: acceleration units and focusing elements. In this paper, we combine these units to form a working accelerator structure: a matching section between the ion source extraction grids and the RF-acceleration unit and electrostatic focusing quadrupoles between successive acceleration units. The matching section consists of six electrostatic quadrupoles (ESQs) fabricated using 3D-printing techniques. The matching section enables us to capture more beam current and to match the beam envelope to conditions for stable transport in an acceleration lattice. We present data from an integrated accelerator consisting of the source, matching section, and an ESQ doublet sandwiched between two RF-acceleration units.

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

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.

Assessing and Exploiting Functional Diversity in Germplasm Pools to Enhance Abiotic Stress Adaptation and Yield in Cereals and Food Legumes

PubMed Central

Dwivedi, Sangam L.; Scheben, Armin; Edwards, David; Spillane, Charles; Ortiz, Rodomiro

2017-01-01

There is a need to accelerate crop improvement by introducing alleles conferring host plant resistance, abiotic stress adaptation, and high yield potential. Elite cultivars, landraces and wild relatives harbor useful genetic variation that needs to be more easily utilized in plant breeding. We review genome-wide approaches for assessing and identifying alleles associated with desirable agronomic traits in diverse germplasm pools of cereals and legumes. Major quantitative trait loci and single nucleotide polymorphisms (SNPs) associated with desirable agronomic traits have been deployed to enhance crop productivity and resilience. These include alleles associated with variation conferring enhanced photoperiod and flowering traits. Genetic variants in the florigen pathway can provide both environmental flexibility and improved yields. SNPs associated with length of growing season and tolerance to abiotic stresses (precipitation, high temperature) are valuable resources for accelerating breeding for drought-prone environments. Both genomic selection and genome editing can also harness allelic diversity and increase productivity by improving multiple traits, including phenology, plant architecture, yield potential and adaptation to abiotic stresses. Discovering rare alleles and useful haplotypes also provides opportunities to enhance abiotic stress adaptation, while epigenetic variation has potential to enhance abiotic stress adaptation and productivity in crops. By reviewing current knowledge on specific traits and their genetic basis, we highlight recent developments in the understanding of crop functional diversity and identify potential candidate genes for future use. The storage and integration of genetic, genomic and phenotypic information will play an important role in ensuring broad and rapid application of novel genetic discoveries by the plant breeding community. Exploiting alleles for yield-related traits would allow improvement of selection efficiency and overall genetic gain of multigenic traits. An integrated approach involving multiple stakeholders specializing in management and utilization of genetic resources, crop breeding, molecular biology and genomics, agronomy, stress tolerance, and reproductive/seed biology will help to address the global challenge of ensuring food security in the face of growing resource demands and climate change induced stresses. PMID:28900432

Assessing and Exploiting Functional Diversity in Germplasm Pools to Enhance Abiotic Stress Adaptation and Yield in Cereals and Food Legumes.

PubMed

Dwivedi, Sangam L; Scheben, Armin; Edwards, David; Spillane, Charles; Ortiz, Rodomiro

2017-01-01

There is a need to accelerate crop improvement by introducing alleles conferring host plant resistance, abiotic stress adaptation, and high yield potential. Elite cultivars, landraces and wild relatives harbor useful genetic variation that needs to be more easily utilized in plant breeding. We review genome-wide approaches for assessing and identifying alleles associated with desirable agronomic traits in diverse germplasm pools of cereals and legumes. Major quantitative trait loci and single nucleotide polymorphisms (SNPs) associated with desirable agronomic traits have been deployed to enhance crop productivity and resilience. These include alleles associated with variation conferring enhanced photoperiod and flowering traits. Genetic variants in the florigen pathway can provide both environmental flexibility and improved yields. SNPs associated with length of growing season and tolerance to abiotic stresses (precipitation, high temperature) are valuable resources for accelerating breeding for drought-prone environments. Both genomic selection and genome editing can also harness allelic diversity and increase productivity by improving multiple traits, including phenology, plant architecture, yield potential and adaptation to abiotic stresses. Discovering rare alleles and useful haplotypes also provides opportunities to enhance abiotic stress adaptation, while epigenetic variation has potential to enhance abiotic stress adaptation and productivity in crops. By reviewing current knowledge on specific traits and their genetic basis, we highlight recent developments in the understanding of crop functional diversity and identify potential candidate genes for future use. The storage and integration of genetic, genomic and phenotypic information will play an important role in ensuring broad and rapid application of novel genetic discoveries by the plant breeding community. Exploiting alleles for yield-related traits would allow improvement of selection efficiency and overall genetic gain of multigenic traits. An integrated approach involving multiple stakeholders specializing in management and utilization of genetic resources, crop breeding, molecular biology and genomics, agronomy, stress tolerance, and reproductive/seed biology will help to address the global challenge of ensuring food security in the face of growing resource demands and climate change induced stresses.

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

Proceedings of the Indo-U.S. bilateral workshop on accelerating botanicals/biologics agent development research for cancer chemoprevention, treatment, and survival.

PubMed

Kumar, Nagi B; 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

2013-02-01

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.

ICON-MIC: Implementing a CPU/MIC Collaboration Parallel Framework for ICON on Tianhe-2 Supercomputer.

PubMed

Wang, Zihao; Chen, Yu; Zhang, Jingrong; Li, Lun; Wan, Xiaohua; Liu, Zhiyong; Sun, Fei; Zhang, Fa

2018-03-01

Electron tomography (ET) is an important technique for studying the three-dimensional structures of the biological ultrastructure. Recently, ET has reached sub-nanometer resolution for investigating the native and conformational dynamics of macromolecular complexes by combining with the sub-tomogram averaging approach. Due to the limited sampling angles, ET reconstruction typically suffers from the "missing wedge" problem. Using a validation procedure, iterative compressed-sensing optimized nonuniform fast Fourier transform (NUFFT) reconstruction (ICON) demonstrates its power in restoring validated missing information for a low-signal-to-noise ratio biological ET dataset. However, the huge computational demand has become a bottleneck for the application of ICON. In this work, we implemented a parallel acceleration technology ICON-many integrated core (MIC) on Xeon Phi cards to address the huge computational demand of ICON. During this step, we parallelize the element-wise matrix operations and use the efficient summation of a matrix to reduce the cost of matrix computation. We also developed parallel versions of NUFFT on MIC to achieve a high acceleration of ICON by using more efficient fast Fourier transform (FFT) calculation. We then proposed a hybrid task allocation strategy (two-level load balancing) to improve the overall performance of ICON-MIC by making full use of the idle resources on Tianhe-2 supercomputer. Experimental results using two different datasets show that ICON-MIC has high accuracy in biological specimens under different noise levels and a significant acceleration, up to 13.3 × , compared with the CPU version. Further, ICON-MIC has good scalability efficiency and overall performance on Tianhe-2 supercomputer.

Accelerated approval of oncology products: a decade of experience.

PubMed

Dagher, Ramzi; Johnson, John; Williams, Grant; Keegan, Patricia; Pazdur, Richard

2004-10-20

We review the regulatory history of the accelerated approval process and summarize the U.S. Food and Drug Administration experience with accelerated approvals in oncology. The accelerated approval regulations, promulgated in 1992, allow approval of drugs for serious or life-threatening diseases on the basis of a surrogate endpoint that is reasonably likely to predict clinical benefit, such as survival or symptom benefit, pending completion of studies designed to confirm clinical benefit, referred to as phase 4 commitments, which are required to be conducted with due diligence. From 1992 to 2004, 22 applications involving anticancer drugs or biologics were approved. Of these 22 applications, accelerated approval was granted to 15 on the basis of findings from studies without an active comparator (i.e., single-arm studies or studies comparing two dose levels) and to the remaining seven on the basis of one or more randomized studies. Of the 22 approved applications, six (i.e., applications for dexrazoxane, irinotecan, capecitabine, docetaxel, imatinib mesylate, and oxaliplatin) have had one or more indications converted to regular approval. This review reports information that was presented at an Oncologic Drugs Advisory Committee meeting held in March 2003; it also presents a discussion of accelerated approval study designs, the study populations evaluated in the accelerated approval and confirmatory settings, and the integration of accelerated approval into a comprehensive drug development plan.

SU-E-T-26: A Study On the Influence of Photonuclear Reactions On the Biological Effectiveness of Therapeutic High Energy X-Ray Beam

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

Wakita, A; National Cancer Center Hospital, Chuo-ku, Tokyo; Matsufuji, N

2014-06-01

Purpose: Photons from a modern high-energy therapeutic linear accelerator used in X-ray radiotherapy causes photonuclear reactions in an accelerator or patient's body. The aim of this study is to evaluate the biological effectiveness including these particles by Microdosimetric Kinetic Model (MKM) based on microdosimetry. Methods: A linear accelerator operating at 15 MV was used. CR-39 was used to obtain LET spectra of secondary ions selectively, as CR-39 is regarded insensitive to photons. CR-39 was put on the central axis of the X-ray beam at depths of 0, 5 and 10 cm in plastic phantom at a source to detector distancemore » of 100 cm. Pits formed by the traversal of ions were etched then analyzed to obtain restricted LET distribution. Frequency-mean and dose-mean lineal energy was evaluated from the relationship between the restricted LET and the lineal energy required to evaluate the biological effectiveness by MKM. The relationship was calculated by Monte Carlo simulations with GEANT4. Results: Restricted LET distributions of secondary particles showed broad distributions that decreases exponentially with increasing LET. Frequency-mean and dose-mean lineal energy were determined uniquely within the scope of the energies of secondary particles generated from photons of 15 MeV. The frequency-mean lineal energies at the depth of 0, 5 and 10 cm were 15.1, 16.0 and 19.7 keV/μm respectively, and the dose-mean lineal energies were 18.6, 20.5 and 19.6 keV/μm, respectively. RBE of secondary particles for HSG cell evaluated by MKM was about 2.0 at all depths, and RBE of all particles including photons was evaluated 1.0. Conclusion: We investigated the biological effectiveness of secondary particles by photonuclear reactions. The method to evaluate RBE by MKM was established with measurements and simulations. However, the influence of these secondary ions on RBE was found negligible in the entire biological effectiveness of the high-energy X-ray. This study has been supported by JSPS KAKENHI Grant Number 25861144.« less

Body size and chronic acceleration

NASA Technical Reports Server (NTRS)

Pitts, G. C.

1976-01-01

Experiments were conducted to study body composition as a function of acceleration (1-4.7 G) in mice and rats. It is shown that fat-free body mass is a predictable function of acceleration, and that of nine components of the fat-free body mass only skeletal muscle, liver and heart contributed to observed changes induced by delta G. Fat-free body mass was found to pass through a maximum at 1 G when it was plotted vs G for mice, rats and monkeys (1-4.7 G) and men (0-1 G).

Directed evolution and synthetic biology applications to microbial systems.

PubMed

Bassalo, Marcelo C; Liu, Rongming; Gill, Ryan T

2016-06-01

Biotechnology applications require engineering complex multi-genic traits. The lack of knowledge on the genetic basis of complex phenotypes restricts our ability to rationally engineer them. However, complex phenotypes can be engineered at the systems level, utilizing directed evolution strategies that drive whole biological systems toward desired phenotypes without requiring prior knowledge of the genetic basis of the targeted trait. Recent developments in the synthetic biology field accelerates the directed evolution cycle, facilitating engineering of increasingly complex traits in biological systems. In this review, we summarize some of the most recent advances in directed evolution and synthetic biology that allows engineering of complex traits in microbial systems. Then, we discuss applications that can be achieved through engineering at the systems level. Copyright © 2016 Elsevier Ltd. All rights reserved.

Accelerator tube construction and characterization for a tandem-electrostatic-quadrupole for accelerator-based boron neutron capture therapy.

PubMed

Cartelli, D; Vento, V Thatar; Castell, W; Di Paolo, H; Kesque, J M; Bergueiro, J; Valda, A A; Erhardt, J; Kreiner, A J

2011-12-01

The accelerator tubes are essential components of the accelerator. Their function is to transport and accelerate a very intense proton or deuteron beam through the machine, from the ion source to the neutron production target, without significant losses. In this contribution, we discuss materials selected for the tube construction, the procedures used for their assembly and the testing performed to meet the stringent requirements to which it is subjected. Copyright © 2011 Elsevier Ltd. All rights reserved.

Helium-3 and helium-4 acceleration by high power laser pulses for hadron therapy

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

Bulanov, S. S.; Esarey, E.; Schroeder, C. B.

The laser driven acceleration of ions is considered a promising candidate for an ion source for hadron therapy of oncological diseases. Though proton and carbon ion sources are conventionally used for therapy, other light ions can also be utilized. Whereas carbon ions require 400 MeV per nucleon to reach the same penetration depth as 250 MeV protons, helium ions require only 250 MeV per nucleon, which is the lowest energy per nucleon among the light ions (heavier than protons). This fact along with the larger biological damage to cancer cells achieved by helium ions, than that by protons, makes thismore » species an interesting candidate for the laser driven ion source. Two mechanisms (magnetic vortex acceleration and hole-boring radiation pressure acceleration) of PW-class laser driven ion acceleration from liquid and gaseous helium targets are studied with the goal of producing 250 MeV per nucleon helium ion beams that meet the hadron therapy requirements. We show that He3 ions, having almost the same penetration depth as He4 with the same energy per nucleon, require less laser power to be accelerated to the required energy for the hadron therapy.« less

Helium-3 and helium-4 acceleration by high power laser pulses for hadron therapy

DOE PAGES

Bulanov, S. S.; Esarey, E.; Schroeder, C. B.; ...

2015-06-24

The laser driven acceleration of ions is considered a promising candidate for an ion source for hadron therapy of oncological diseases. Though proton and carbon ion sources are conventionally used for therapy, other light ions can also be utilized. Whereas carbon ions require 400 MeV per nucleon to reach the same penetration depth as 250 MeV protons, helium ions require only 250 MeV per nucleon, which is the lowest energy per nucleon among the light ions (heavier than protons). This fact along with the larger biological damage to cancer cells achieved by helium ions, than that by protons, makes thismore » species an interesting candidate for the laser driven ion source. Two mechanisms (magnetic vortex acceleration and hole-boring radiation pressure acceleration) of PW-class laser driven ion acceleration from liquid and gaseous helium targets are studied with the goal of producing 250 MeV per nucleon helium ion beams that meet the hadron therapy requirements. We show that He3 ions, having almost the same penetration depth as He4 with the same energy per nucleon, require less laser power to be accelerated to the required energy for the hadron therapy.« less

Accelerating Adverse Outcome Pathway Development via Systems Approaches

EPA Science Inventory

The Adverse Outcome Pathway has emerged as an internationally harmonized mechanism for organizing biological information in a chemical agnostic manner. This construct is valuable for interpreting the results from high-throughput toxicity (HTT) assessment by providing a mechanisti...

Inviscid linear stability analysis of two vertical columns of different densities in a gravitational acceleration field

DOE PAGES

Prathama, Aditya Heru; Pantano, Carlos

2017-08-09

Here, we study the inviscid linear stability of a vertical interface separating two fluids of different densities and subject to a gravitational acceleration field parallel to the interface. In this arrangement, the two free streams are constantly accelerated, which means that the linear stability analysis is not amenable to Fourier or Laplace solution in time. Instead, we derive the equations analytically by the initial-value problem method and express the solution in terms of the well-known parabolic cylinder function. The results, which can be classified as an accelerating Kelvin–Helmholtz configuration, show that even in the presence of surface tension, the interfacemore » is unconditionally unstable at all wavemodes. This is a consequence of the ever increasing momentum of the free streams, as gravity accelerates them indefinitely. The instability can be shown to grow as the exponential of a quadratic function of time.« less

Electron Bulk Acceleration and Thermalization at Earth's Quasiperpendicular Bow Shock.

PubMed

Chen, L-J; Wang, S; Wilson, L B; Schwartz, S; Bessho, N; Moore, T; Gershman, D; Giles, B; Malaspina, D; Wilder, F D; Ergun, R E; Hesse, M; Lai, H; Russell, C; Strangeway, R; Torbert, R B; F-Vinas, A; Burch, J; Lee, S; Pollock, C; Dorelli, J; Paterson, W; Ahmadi, N; Goodrich, K; Lavraud, B; Le Contel, O; Khotyaintsev, Yu V; Lindqvist, P-A; Boardsen, S; Wei, H; Le, A; Avanov, L

2018-06-01

Electron heating at Earth's quasiperpendicular bow shock has been surmised to be due to the combined effects of a quasistatic electric potential and scattering through wave-particle interaction. Here we report the observation of electron distribution functions indicating a new electron heating process occurring at the leading edge of the shock front. Incident solar wind electrons are accelerated parallel to the magnetic field toward downstream, reaching an electron-ion relative drift speed exceeding the electron thermal speed. The bulk acceleration is associated with an electric field pulse embedded in a whistler-mode wave. The high electron-ion relative drift is relaxed primarily through a nonlinear current-driven instability. The relaxed distributions contain a beam traveling toward the shock as a remnant of the accelerated electrons. Similar distribution functions prevail throughout the shock transition layer, suggesting that the observed acceleration and thermalization is essential to the cross-shock electron heating.

Electron Bulk Acceleration and Thermalization at Earth's Quasiperpendicular Bow Shock

NASA Astrophysics Data System (ADS)

Chen, L.-J.; Wang, S.; Wilson, L. B.; Schwartz, S.; Bessho, N.; Moore, T.; Gershman, D.; Giles, B.; Malaspina, D.; Wilder, F. D.; Ergun, R. E.; Hesse, M.; Lai, H.; Russell, C.; Strangeway, R.; Torbert, R. B.; F.-Vinas, A.; Burch, J.; Lee, S.; Pollock, C.; Dorelli, J.; Paterson, W.; Ahmadi, N.; Goodrich, K.; Lavraud, B.; Le Contel, O.; Khotyaintsev, Yu. V.; Lindqvist, P.-A.; Boardsen, S.; Wei, H.; Le, A.; Avanov, L.

2018-06-01

Electron heating at Earth's quasiperpendicular bow shock has been surmised to be due to the combined effects of a quasistatic electric potential and scattering through wave-particle interaction. Here we report the observation of electron distribution functions indicating a new electron heating process occurring at the leading edge of the shock front. Incident solar wind electrons are accelerated parallel to the magnetic field toward downstream, reaching an electron-ion relative drift speed exceeding the electron thermal speed. The bulk acceleration is associated with an electric field pulse embedded in a whistler-mode wave. The high electron-ion relative drift is relaxed primarily through a nonlinear current-driven instability. The relaxed distributions contain a beam traveling toward the shock as a remnant of the accelerated electrons. Similar distribution functions prevail throughout the shock transition layer, suggesting that the observed acceleration and thermalization is essential to the cross-shock electron heating.

Electron bulk acceleration and thermalization at Earth's quasi-perpendicular bow shock

NASA Astrophysics Data System (ADS)

Chen, L.-J.; Wang, S.; Wilson, L. B., III; Schwartz, S. J.; Bessho, N.; Moore, T. E.; Gershman, D. J.; Giles, B. L.; Malaspina, D. M.; Wilder, F. D.; Ergun, R. E.; Hesse, M.; Lai, H.; Russell, C. T.; Strangeway, R. J.; Torbert, R. B.; Vinas, A. F.-; Burch, J. L.; Lee, S.; Pollock, C.; Dorelli, J.; Paterson, W. R.; Ahmadi, N.; Goodrich, K. A.; Lavraud, B.; Le Contel, O.; Khotyaintsev, Yu. V.; Lindqvist, P.-A.; Boardsen, S.; Wei, H.; Le, A.; Avanov, L. A.

2018-05-01

Electron heating at Earth's quasiperpendicular bow shock has been surmised to be due to the combined effects of a quasistatic electric potential and scattering through wave-particle interaction. Here we report the observation of electron distribution functions indicating a new electron heating process occurring at the leading edge of the shock front. Incident solar wind electrons are accelerated parallel to the magnetic field toward downstream, reaching an electron-ion relative drift speed exceeding the electron thermal speed. The bulk acceleration is associated with an electric field pulse embedded in a whistler-mode wave. The high electron-ion relative drift is relaxed primarily through a nonlinear current-driven instability. The relaxed distributions contain a beam traveling toward the shock as a remnant of the accelerated electrons. Similar distribution functions prevail throughout the shock transition layer, suggesting that the observed acceleration and thermalization is essential to the cross-shock electron heating.

Impaired associative learning in schizophrenia: behavioral and computational studies

PubMed Central

Diwadkar, Vaibhav A.; Flaugher, Brad; Jones, Trevor; Zalányi, László; Ujfalussy, Balázs; Keshavan, Matcheri S.

2008-01-01

Associative learning is a central building block of human cognition and in large part depends on mechanisms of synaptic plasticity, memory capacity and fronto–hippocampal interactions. A disorder like schizophrenia is thought to be characterized by altered plasticity, and impaired frontal and hippocampal function. Understanding the expression of this dysfunction through appropriate experimental studies, and understanding the processes that may give rise to impaired behavior through biologically plausible computational models will help clarify the nature of these deficits. We present a preliminary computational model designed to capture learning dynamics in healthy control and schizophrenia subjects. Experimental data was collected on a spatial-object paired-associate learning task. The task evinces classic patterns of negatively accelerated learning in both healthy control subjects and patients, with patients demonstrating lower rates of learning than controls. Our rudimentary computational model of the task was based on biologically plausible assumptions, including the separation of dorsal/spatial and ventral/object visual streams, implementation of rules of learning, the explicit parameterization of learning rates (a plausible surrogate for synaptic plasticity), and learning capacity (a plausible surrogate for memory capacity). Reductions in learning dynamics in schizophrenia were well-modeled by reductions in learning rate and learning capacity. The synergy between experimental research and a detailed computational model of performance provides a framework within which to infer plausible biological bases of impaired learning dynamics in schizophrenia. PMID:19003486

Beamlets from stochastic acceleration

NASA Astrophysics Data System (ADS)

Perri, Silvia; Carbone, Vincenzo

2008-09-01

We investigate the dynamics of a realization of the stochastic Fermi acceleration mechanism. The model consists of test particles moving between two oscillating magnetic clouds and differs from the usual Fermi-Ulam model in two ways. (i) Particles can penetrate inside clouds before being reflected. (ii) Particles can radiate a fraction of their energy during the process. Since the Fermi mechanism is at work, particles are stochastically accelerated, even in the presence of the radiated energy. Furthermore, due to a kind of resonance between particles and oscillating clouds, the probability density function of particles is strongly modified, thus generating beams of accelerated particles rather than a translation of the whole distribution function to higher energy. This simple mechanism could account for the presence of beamlets in some space plasma physics situations.

Accelerated epigenetic aging in Down syndrome

PubMed Central

Horvath, Steve; Garagnani, Paolo; Bacalini, Maria Giulia; Pirazzini, Chiara; Salvioli, Stefano; Gentilini, Davide; Di Blasio, Anna Maria; Giuliani, Cristina; Tung, Spencer; Vinters, Harry V; Franceschi, Claudio

2015-01-01

Down Syndrome (DS) entails an increased risk of many chronic diseases that are typically associated with older age. The clinical manifestations of accelerated aging suggest that trisomy 21 increases the biological age of tissues, but molecular evidence for this hypothesis has been sparse. Here, we utilize a quantitative molecular marker of aging (known as the epigenetic clock) to demonstrate that trisomy 21 significantly increases the age of blood and brain tissue (on average by 6.6 years, P = 7.0 × 10−14). PMID:25678027

Onion-shell model of cosmic ray acceleration in supernova remnants

NASA Technical Reports Server (NTRS)

Bogdan, T. J.; Volk, H. J.

1983-01-01

A method is devised to approximate the spatially averaged momentum distribution function for the accelerated particles at the end of the active lifetime of a supernova remnant. The analysis is confined to the test particle approximation and adiabatic losses are oversimplified, but unsteady shock motion, evolving shock strength, and non-uniform gas flow effects on the accelerated particle spectrum are included. Monoenergetic protons are injected at the shock front. It is found that the dominant effect on the resultant accelerated particle spectrum is a changing spectral index with shock strength. High energy particles are produced in early phases, and the resultant distribution function is a slowly varying power law over several orders of magnitude, independent of the specific details of the supernova remnant.

Transverse particle acceleration and diffusion in a planetary magnetic field

NASA Technical Reports Server (NTRS)

Barbosa, D. D.

1994-01-01

A general model of particle acceleration by plasma waves coupled with adiabatic radial diffusion in a planetary magnetic field is developed. The model assumes that a spectrum of lower hybird waves is present to resonantly accelerate ions transverse to the magnetic field. The steady state Green's function for the combined radial diffusion and wave acceleration equation is found in terms of a series expansion. The results provide a rigorous demonstration of how a quasi-Maxwellian distribution function is formed in the absence of particle collisons and elucidate the nature of turbulent heating of magnetospheric plasmas. The solution is applied to the magnetosphere of Neptune for which a number of examples are given illustrating how the spectrum of pickup N(+) ions from Triton evolves.

Visual reaction times during prolonged angular acceleration parallel the subjective perception of rotation

NASA Technical Reports Server (NTRS)

Mattson, D. L.

1975-01-01

The effect of prolonged angular acceleration on choice reaction time to an accelerating visual stimulus was investigated, with 10 commercial airline pilots serving as subjects. The pattern of reaction times during and following acceleration was compared with the pattern of velocity estimates reported during identical trials. Both reaction times and velocity estimates increased at the onset of acceleration, declined prior to the termination of acceleration, and showed an aftereffect. These results are inconsistent with the torsion-pendulum theory of semicircular canal function and suggest that the vestibular adaptation is of central origin.

Plant biology research and training for the 21st century

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

Kelly, K.

1992-12-31

The committee was assembled in response to a request from the National Science Foundation (NSF), the US Department of Agriculture (USDA), and the US Department of Energy (DoE). The leadership of these agencies asked the National Academy of Sciences through the National Research Council (NRC) to assess the status of plant-science research in the United States in light of the opportunities arising from advances inother areas of biology. NRC was asked to suggest ways of accelerating the application of these new biologic concepts and tools to research in plant science with the aim of enhancing the acquisition of new knowledgemore » about plants. The charge to the committee was to examine the following: Organizations, departments, and institutions conducting plant biology research; human resources involved in plant biology research; graduate training programs in plant biology; federal, state, and private sources of support for plant-biology research; the role of industry in conducting and supporting plant-biology research; the international status of US plant-biology research; and the relationship of plant biology to leading-edge research in biology.« less

Plant biology research and training for the 21st century

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

Kelly, K.

1992-01-01

The committee was assembled in response to a request from the National Science Foundation (NSF), the US Department of Agriculture (USDA), and the US Department of Energy (DoE). The leadership of these agencies asked the National Academy of Sciences through the National Research Council (NRC) to assess the status of plant-science research in the United States in light of the opportunities arising from advances inother areas of biology. NRC was asked to suggest ways of accelerating the application of these new biologic concepts and tools to research in plant science with the aim of enhancing the acquisition of new knowledgemore » about plants. The charge to the committee was to examine the following: Organizations, departments, and institutions conducting plant biology research; human resources involved in plant biology research; graduate training programs in plant biology; federal, state, and private sources of support for plant-biology research; the role of industry in conducting and supporting plant-biology research; the international status of US plant-biology research; and the relationship of plant biology to leading-edge research in biology.« less

Where are we now? And where are we going? A report from the Accelerate Brain Cancer Cure (ABC2) Low-grade Glioma Research Workshop

PubMed Central

Huse, Jason T.; Wallace, Max; Aldape, Kenneth D.; Berger, Mitchel S.; Bettegowda, Chetan; Brat, Daniel J.; Cahill, Daniel P.; Cloughesy, Timothy; Haas-Kogan, Daphne A.; Marra, Marco; Miller, C. Ryan; Nelson, Sarah J.; Salama, Sofie R.; Soffietti, Riccardo; Wen, Patrick Y.; Yip, Stephen; Yen, Katharine; Costello, Joseph F.; Chang, Susan

2014-01-01

Diffuse gliomas consist of both low- and high-grade varieties, each with distinct morphological and biological features. The often extended periods of relative indolence exhibited by low-grade gliomas (LGG; WHO grade II) differ sharply from the aggressive, rapidly fatal clinical course of primary glioblastoma (GBM; WHO grade IV). Nevertheless, until recently, the molecular foundations underlying this stark biological contrast between glioma variants remained largely unknown. The discoveries of distinctive and highly recurrent genomic and epigenomic abnormalities in LGG have both informed a more accurate classification scheme and pointed to viable avenues for therapeutic development. As such, the field of neuro-oncology now seems poised to capitalize on these gains to achieve significant benefit for LGG patients. This report will briefly recount the proceedings of a workshop held in January 2013 and hosted by Accelerate Brain Cancer Cure (ABC2) on the subject of LGG. While much of the meeting covered recent insights into LGG biology, its focus remained on how best to advance the clinical management, whether by improved preclinical modeling, more effective targeted therapeutics and clinical trial design, or innovative imaging technology. PMID:24305708

The cutting of ultrathin sections with the thickness less than 20 nm from biological specimens embedded in resin blocks.

PubMed

Nebesářová, Jana; Hozák, Pavel; Frank, Luděk; Štěpan, Petr; Vancová, Marie

2016-06-01

Low voltage electron microscopes working in transmission mode, like LVEM5 (Delong Instruments, Czech Republic) working at accelerating voltage 5 kV or scanning electron microscope working in transmission mode with accelerating voltage below 1 kV, require ultrathin sections with the thickness below 20 nm. Decreasing of the primary electron energy leads to enhancement of image contrast, which is especially useful in the case of biological samples composed of elements with low atomic numbers. As a result treatments with heavy metals, like post-fixation with osmium tetroxide or ultrathin section staining, can by omitted. The disadvantage is reduced penetration ability of incident electrons influencing the usable thickness of the specimen resulting in the need of ultrathin sections of under 20 nm thickness. In this study we want to answer basic questions concerning the cutting of extremely ultrathin sections: Is it possible routinely and reproducibly to cut extremely thin sections of biological specimens embedded in commonly used resins with contemporary ultramicrotome techniques and under what conditions? Microsc. Res. Tech. 79:512-517, 2016. © 2016 Wiley Periodicals, Inc. © 2016 Wiley Periodicals, Inc.

Accelerator mass spectrometry for measurement of long-lived radioisotopes.

PubMed

Elmore, D; Phillips, F M

1987-05-01

Particle accelerators, such as those built for research in nuclear physics, can also be used together with magnetic and electrostatic mass analyzers to measure rare isotopes at very low abundance ratios. All molecular ions can be eliminated when accelerated to energies of millions of electron volts. Some atomic isobars can be eliminated with the use of negative ions; others can be separated at high energies by measuring their rate of energy loss in a detector. The long-lived radioisotopes (10)Be, (14)C,(26)A1, 36Cl, and (129)1 can now be measured in small natural samples having isotopic abundances in the range 10(-12) to 10(- 5) and as few as 10(5) atoms. In the past few years, research applications of accelerator mass spectrometry have been concentrated in the earth sciences (climatology, cosmochemistry, environmental chemistry, geochronology, glaciology, hydrology, igneous petrogenesis, minerals exploration, sedimentology, and volcanology), in anthropology and archeology (radiocarbon dating), and in physics (searches for exotic particles and measurement of halflives). In addition, accelerator mass spectrometry may become an important tool for the materials and biological sciences.

Accelerator Mass Spectrometry for Measurement of Long-Lived Radioisotopes

NASA Astrophysics Data System (ADS)

Elmore, David; Phillips, Fred M.

1987-05-01

Particle accelerators, such as those built for research in nuclear physics, can also be used together with magnetic and electrostatic mass analyzers to measure rare isotopes at very low abundance ratios. All molecular ions can be eliminated when accelerated to energies of millions of electron volts. Some atomic isobars can be eliminated with the use of negative ions; others can be separated at high energies by measuring their rate of energy loss in a detector. The long-lived radioisotopes 10Be, 14C, 26Al, 36Cl, and 129I can now be measured in small natural samples having isotopic abundances in the range 10-12 to 10-15 and as few as 105 atoms. In the past few years, research applications of accelerator mass spectrometry have been concentrated in the earth sciences (climatology, cosmochemistry, environmental chemistry, geochronology, glaciology, hydrology, igneous petrogenesis, minerals exploration, sedimentology, and volcanology), in anthropology and archeology (radiocarbon dating), and in physics (searches for exotic particles and measurement of half-lives). In addition, accelerator mass spectrometry may become an important tool for the materials and biological sciences.

GPU-accelerated non-uniform fast Fourier transform-based compressive sensing spectral domain optical coherence tomography.

PubMed

Xu, Daguang; Huang, Yong; Kang, Jin U

2014-06-16

We implemented the graphics processing unit (GPU) accelerated compressive sensing (CS) non-uniform in k-space spectral domain optical coherence tomography (SD OCT). Kaiser-Bessel (KB) function and Gaussian function are used independently as the convolution kernel in the gridding-based non-uniform fast Fourier transform (NUFFT) algorithm with different oversampling ratios and kernel widths. Our implementation is compared with the GPU-accelerated modified non-uniform discrete Fourier transform (MNUDFT) matrix-based CS SD OCT and the GPU-accelerated fast Fourier transform (FFT)-based CS SD OCT. It was found that our implementation has comparable performance to the GPU-accelerated MNUDFT-based CS SD OCT in terms of image quality while providing more than 5 times speed enhancement. When compared to the GPU-accelerated FFT based-CS SD OCT, it shows smaller background noise and less side lobes while eliminating the need for the cumbersome k-space grid filling and the k-linear calibration procedure. Finally, we demonstrated that by using a conventional desktop computer architecture having three GPUs, real-time B-mode imaging can be obtained in excess of 30 fps for the GPU-accelerated NUFFT based CS SD OCT with frame size 2048(axial) × 1,000(lateral).

ANNUAL REPORT, JULY 1, 1960

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

None

1961-10-31

Research facilities, general construction progress, research activities, and administration are discussed and a financial statement is given. Fairly detailed accounts are given of research programs in the fields of physics, accelerator development, instrumentation, applied mathematics, chemistry, nuclear engineering, biology, and medicine. (M.C.G.)

Computational systems biology and dose-response modeling in relation to new directions in toxicity testing.

PubMed

Zhang, Qiang; Bhattacharya, Sudin; Andersen, Melvin E; Conolly, Rory B

2010-02-01

The new paradigm envisioned for toxicity testing in the 21st century advocates shifting from the current animal-based testing process to a combination of in vitro cell-based studies, high-throughput techniques, and in silico modeling. A strategic component of the vision is the adoption of the systems biology approach to acquire, analyze, and interpret toxicity pathway data. As key toxicity pathways are identified and their wiring details elucidated using traditional and high-throughput techniques, there is a pressing need to understand their qualitative and quantitative behaviors in response to perturbation by both physiological signals and exogenous stressors. The complexity of these molecular networks makes the task of understanding cellular responses merely by human intuition challenging, if not impossible. This process can be aided by mathematical modeling and computer simulation of the networks and their dynamic behaviors. A number of theoretical frameworks were developed in the last century for understanding dynamical systems in science and engineering disciplines. These frameworks, which include metabolic control analysis, biochemical systems theory, nonlinear dynamics, and control theory, can greatly facilitate the process of organizing, analyzing, and understanding toxicity pathways. Such analysis will require a comprehensive examination of the dynamic properties of "network motifs"--the basic building blocks of molecular circuits. Network motifs like feedback and feedforward loops appear repeatedly in various molecular circuits across cell types and enable vital cellular functions like homeostasis, all-or-none response, memory, and biological rhythm. These functional motifs and associated qualitative and quantitative properties are the predominant source of nonlinearities observed in cellular dose response data. Complex response behaviors can arise from toxicity pathways built upon combinations of network motifs. While the field of computational cell biology has advanced rapidly with increasing availability of new data and powerful simulation techniques, a quantitative orientation is still lacking in life sciences education to make efficient use of these new tools to implement the new toxicity testing paradigm. A revamped undergraduate curriculum in the biological sciences including compulsory courses in mathematics and analysis of dynamical systems is required to address this gap. In parallel, dissemination of computational systems biology techniques and other analytical tools among practicing toxicologists and risk assessment professionals will help accelerate implementation of the new toxicity testing vision.

Upregulation of nuclear transporter, Kpnβ1, contributes to accelerated cell proliferation- and cell adhesion-mediated drug resistance (CAM-DR) in diffuse large B-cell lymphoma.

PubMed

He, Song; Miao, Xiaobing; Wu, Yaxun; Zhu, Xinghua; Miao, Xianjing; Yin, Haibing; He, Yunhua; Li, Chunsun; Liu, Yushan; Lu, Xiaoyun; Chen, Yali; Wang, Yuchan; Xu, Xiaohong

2016-03-01

The Karyopherin proteins are involved in the shuttling of cargo proteins, and certain RNAs, across the nuclear pore complex into and out of the cell nucleus. Karyopherin β1 (Kpnβ1) is a member of the Karyopherin β superfamily of nuclear transport proteins. In addition to the nuclear import function, Kpnβ1 is associated with the occurrence of tumors. This study investigated the expression and biologic function of Kpnβ1 in diffuse large B-cell lymphoma (DLBCL). The prognostic value of Kpnβ1 expression was evaluated using immunohistochemical staining. The role of Kpnβ1 on cell proliferation- and cell adhesion-mediated drug resistance (CAM-DR) was also determined. We demonstrated that Kpnβ1 mRNA and protein expression levels were significantly higher in DLBCL B-cells and DLBCL cell lines than in normal CD19 purified B-cells. Immunohistochemical analysis suggested that the expression of Kpnβ1 was correlated with Ki-67 (P < 0.001). Kaplan-Meier curve showed that high expression of Kpnβ1 was significantly associated with shorter overall survival. In addition, Kpnβ1 was associated with the proliferation of DLBCL cells. Importantly, we found that Kpnβ1 could interact with p65 and promote CAM-DR via accelerating NF-κB activation in DLBCL. Patients with tumors highly expressing Kpnβ1 have poorer overall survivals. Kpnβ1 interacts with p65 and enhances CAM-DR.

A magnetorheological haptic cue accelerator for manual transmission vehicles

NASA Astrophysics Data System (ADS)

Han, Young-Min; Noh, Kyung-Wook; Lee, Yang-Sub; Choi, Seung-Bok

2010-07-01

This paper proposes a new haptic cue function for manual transmission vehicles to achieve optimal gear shifting. This function is implemented on the accelerator pedal by utilizing a magnetorheological (MR) brake mechanism. By combining the haptic cue function with the accelerator pedal, the proposed haptic cue device can transmit the optimal moment of gear shifting for manual transmission to a driver without requiring the driver's visual attention. As a first step to achieve this goal, a MR fluid-based haptic device is devised to enable rotary motion of the accelerator pedal. Taking into account spatial limitations, the design parameters are optimally determined using finite element analysis to maximize the relative control torque. The proposed haptic cue device is then manufactured and its field-dependent torque and time response are experimentally evaluated. Then the manufactured MR haptic cue device is integrated with the accelerator pedal. A simple virtual vehicle emulating the operation of the engine of a passenger vehicle is constructed and put into communication with the haptic cue device. A feed-forward torque control algorithm for the haptic cue is formulated and control performances are experimentally evaluated and presented in the time domain.

Meaningful crosstalk between biologists and physical scientists is essential for modern biology to progress.

PubMed

Dev, Sukhendu B

2009-01-01

The advances in biological sciences have been phenomenal since the structure of DNA was decoded, especially if one considers the input from physical sciences, not only in terms of analytical tools, but also understanding and solving some of the key problems in biology. In this article, I trace briefly the history of this transition, from physical sciences to biology, and argue that progress in modern biology can be accelerated if there is far more meaningful crosstalk between the biologists and the physical scientists, simply because biology has become far more complex and interdisciplinary, and the need for such crosstalk cannot be overemphasized. Without a concerted effort in this area progress will be hindered, and the two camps will continue to work on their own, using their own specialized language, thus making communication highly ineffective. I support my argument giving a vast array of examples and also quoting leading authorities.

Artifical Pancreas

NASA Astrophysics Data System (ADS)

Fei, Jiangfeng

2013-03-01

In 2006, JDRF launched the Artificial Pancreas Project (APP) to accelerate the development of a commercially-viable artificial pancreas system to closely mimic the biological function of the pancreas individuals with insulin-dependent diabetes, particularly type 1 diabetes. By automating detection of blood sugar levels and delivery of insulin in response to those levels, an artificial pancreas has the potential to transform the lives of people with type 1 diabetes. The 6-step APP development pathway serves as JDRF's APP strategic funding plan and defines the priorities of product research and development. Each step in the plan represents incremental advances in automation beginning with devices that shut off insulin delivery to prevent episodes of low blood sugar and progressing ultimately to a fully automated ``closed loop'' system that maintains blood glucose at a target level without the need to bolus for meals or adjust for exercise.

Cytogenetic effects of energetic ions with shielding

NASA Astrophysics Data System (ADS)

Yang, T. C.; George, K. A.; Wu, H.; Miller, D.; Miller, J.

1998-11-01

In order to understand the effects of shielding on the induction of biological damages by charged particles, we conducted experiments with accelerated protons (250 MeV) and iron particles (1 GeV/u). Human lymphocytes in vitro were exposed to particle beams through polyethylene with various thickness, and chromosomal aberrations were determined using FISH technique. Dose response curves for chromosome aberrations were obtained and compared for various particle types. Experimental results indicated that for a given absorbed dose at the cell, the effectiveness of protons and iron particles in the induction of chromosomal aberrations was not significantly altered by polyethylene with thickness up to 30-cm and 15-cm respectively. Comparing with gamma rays, charged particles were very effective in producing complex chromosomal damages, which may be an important mechanism in alterating functions in non-dividing tissues, such as nervous systems.

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

PubMed

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

2015-10-05

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

Cell biological mechanisms of multidrug resistance in tumors.

PubMed

Simon, S M; Schindler, M

1994-04-26

Multidrug resistance (MDR) is a generic term for the variety of strategies tumor cells use to evade the cytotoxic effects of anticancer drugs. MDR is characterized by a decreased sensitivity of tumor cells not only to the drug employed for chemotherapy but also to a broad spectrum of drugs with neither obvious structural homology nor common targets. This pleiotropic resistance is one of the major obstacles to the successful treatment of tumors. MDR may result from structural or functional changes at the plasma membrane or within the cytoplasm, cellular compartments, or nucleus. Molecular mechanisms of MDR are discussed in terms of modifications in detoxification and DNA repair pathways, changes in cellular sites of drug sequestration, decreases in drug-target affinity, synthesis of specific drug inhibitors within cells, altered or inappropriate targeting of proteins, and accelerated removal or secretion of drugs.

Microfabrication of biocompatible hydrogels by proton beam writing

NASA Astrophysics Data System (ADS)

Nagasawa, Naotsugu; Kimura, Atsushi; Idesaki, Akira; Yamada, Naoto; Koka, Masashi; Satoh, Takahiro; Ishii, Yasuyuki; Taguchi, Mitsumasa

2017-10-01

Functionalization of biocompatible materials is expected to be widely applied in biomedical engineering and regenerative medicine fields. Hydrogel has been expected as a biocompatible scaffold which support to keep an organ shape during cell multiplying in regenerative medicine. Therefore, it is important to understanding a surface microstructure (minute shape, depth of flute) and a chemical characteristic of the hydrogel affecting the cell culture. Here, we investigate the microfabrication of biocompatible polymeric materials, such as the water-soluble polysaccharide derivatives hydroxypropyl cellulose and carboxymethyl cellulose, by use of proton beam writing (PBW). These polymeric materials were dissolved thoroughly in pure water using a planetary centrifugal mixer, and a sample sheet (1 mm thick) was formed on polyethylene terephthalate (PET) film. Crosslinking to form hydrogels was induced using a 3.0 MeV focused proton beam from the single-ended accelerator at Takasaki Ion Accelerators for Advanced Radiation Application. The aqueous samples were horizontally irradiated with the proton beam through the PET cover film, and then rinsed with deionized water. Microstructured hydrogels were obtained on the PET film using the PBW technique without toxic crosslinking reagents. Cell adhesion and proliferation on the microfabricated biocompatible hydrogels were investigated. Microfabrication of HPC and CMC by the use of PBW is expected to produce new biocompatible materials that can be applied in biological and medical applications.

Evaluation of gelatin-hyaluronic acid composite hydrogels for accelerating wound healing.

PubMed

Wu, Song; Deng, Liang; Hsia, Hanson; Xu, Kai; He, Yu; Huang, Qiangru; Peng, Yi; Zhou, Zhihua; Peng, Cheng

2017-05-01

Excellent wound dressings maintain a warm and moist environment, thus accelerating wound healing. In this study, we cross-linked gelatin and hyaluronic acid with ethyl-3-(3-dimethylaminopropyl) carbodiimide hydrochloride in different ratios (gelatin/hyaluronic acid = 8:2, gelatin/hyaluronic acid = 5:5, gelatin/hyaluronic acid = 2:8), and explored the effects and mechanisms of gelatinhyaluronic acid hydrogels on wound healing. This was done by examining dressing properties, such as fluid uptake ability, water vapor transmission rate, and the rate of water evaporation. We further verified biological function by using in vitro and in vivo wound models. The hydrogels display appropriate fluid uptake ability and good water vapor transmission rate and rate of water evaporation all of which can provide an adequate moisture environment for wound healing. Cell cytotoxicity and proliferation tests show that the hydrogels have no cytotoxicity, furthermore, gelatin/hyaluronic acid = 8:2 hydrogels have the potential to promote cell proliferation. Animal wound models demonstrate that the hydrogels can effectively promote wound healing in vivo, in particular, the gelatin/hyaluronic acid = 8:2 group which promoted the most rapid healing. Accordingly, gelatin-hyaluronic acid dressings, especially the gelatin/hyaluronic acid = 8:2 hydrogels, have a promising outlook for clinical applications in wound healing.

Laboratory Directed Research and Development Program

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

Ogeka, G.J.; Romano, A.J.

This report briefly discusses the following research: Advances in Geoexploration; Transvenous Coronary Angiography with Synchrotron X-Rays; Borehole Measurements of Global Warming; Molecular Ecology: Development of Field Methods for Microbial Growth Rate and Activity Measurements; A New Malaria Enzyme - A Potential Source for a New Diagnostic Test for Malaria and a Target for a New Antimalarial Drug; Basic Studies on Thoron and Thoron Precursors; Cloning of the cDNA for a Human Serine/Threonine Protein Kinase that is Activated Specifically by Double-Stranded DNA; Development of an Ultra-Fast Laser System for Accelerator Applications; Cluster Impact Fusion; Effect of a Bacterial Spore Protein onmore » Mutagenesis; Structure and Function of Adenovirus Penton Base Protein; High Resolution Fast X-Ray Detector; Coherent Synchrotron Radiation Longitudinal Bunch Shape Monitor; High Grain Harmonic Generation Experiment; BNL Maglev Studies; Structural Investigations of Pt-Based Catalysts; Studies on the Cellular Toxicity of Cocaine and Cocaethylene; Human Melanocyte Transformation; Exploratory Applications of X-Ray Microscopy; Determination of the Higher Ordered Structure of Eukaryotic Chromosomes; Uranium Neutron Capture Therapy; Tunneling Microscopy Studies of Nanoscale Structures; Nuclear Techiques for Study of Biological Channels; RF Sources for Accelerator Physics; Induction and Repair of Double-Strand Breaks in the DNA of Human Lymphocytes; and An EBIS Source of High Charge State Ions up to Uranium.« less

Laboratory Directed Research and Development Program. Annual report

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

Ogeka, G.J.; Romano, A.J.

This report briefly discusses the following research: Advances in Geoexploration; Transvenous Coronary Angiography with Synchrotron X-Rays; Borehole Measurements of Global Warming; Molecular Ecology: Development of Field Methods for Microbial Growth Rate and Activity Measurements; A New Malaria Enzyme - A Potential Source for a New Diagnostic Test for Malaria and a Target for a New Antimalarial Drug; Basic Studies on Thoron and Thoron Precursors; Cloning of the cDNA for a Human Serine/Threonine Protein Kinase that is Activated Specifically by Double-Stranded DNA; Development of an Ultra-Fast Laser System for Accelerator Applications; Cluster Impact Fusion; Effect of a Bacterial Spore Protein onmore » Mutagenesis; Structure and Function of Adenovirus Penton Base Protein; High Resolution Fast X-Ray Detector; Coherent Synchrotron Radiation Longitudinal Bunch Shape Monitor; High Grain Harmonic Generation Experiment; BNL Maglev Studies; Structural Investigations of Pt-Based Catalysts; Studies on the Cellular Toxicity of Cocaine and Cocaethylene; Human Melanocyte Transformation; Exploratory Applications of X-Ray Microscopy; Determination of the Higher Ordered Structure of Eukaryotic Chromosomes; Uranium Neutron Capture Therapy; Tunneling Microscopy Studies of Nanoscale Structures; Nuclear Techiques for Study of Biological Channels; RF Sources for Accelerator Physics; Induction and Repair of Double-Strand Breaks in the DNA of Human Lymphocytes; and An EBIS Source of High Charge State Ions up to Uranium.« less

Insights into hominid evolution from the gorilla genome sequence

PubMed Central

Scally, Aylwyn; Dutheil, Julien Y.; Hillier, LaDeana W.; Jordan, Greg E.; Goodhead, Ian; Herrero, Javier; Hobolth, Asger; Lappalainen, Tuuli; Mailund, Thomas; Marques-Bonet, Tomas; McCarthy, Shane; Montgomery, Stephen H.; Schwalie, Petra C.; Tang, Y. Amy; Ward, Michelle C.; Xue, Yali; Yngvadottir, Bryndis; Alkan, Can; Andersen, Lars N.; Ayub, Qasim; Ball, Edward V.; Beal, Kathryn; Bradley, Brenda J.; Chen, Yuan; Clee, Chris M.; Fitzgerald, Stephen; Graves, Tina A.; Gu, Yong; Heath, Paul; Heger, Andreas; Karakoc, Emre; Kolb-Kokocinski, Anja; Laird, Gavin K.; Lunter, Gerton; Meader, Stephen; Mort, Matthew; Mullikin, James C.; Munch, Kasper; O’Connor, Timothy D.; Phillips, Andrew D.; Prado-Martinez, Javier; Rogers, Anthony S.; Sajjadian, Saba; Schmidt, Dominic; Shaw, Katy; Simpson, Jared T.; Stenson, Peter D.; Turner, Daniel J.; Vigilant, Linda; Vilella, Albert J.; Whitener, Weldon; Zhu, Baoli; Cooper, David N.; de Jong, Pieter; Dermitzakis, Emmanouil T.; Eichler, Evan E.; Flicek, Paul; Goldman, Nick; Mundy, Nicholas I.; Ning, Zemin; Odom, Duncan T.; Ponting, Chris P.; Quail, Michael A.; Ryder, Oliver A.; Searle, Stephen M.; Warren, Wesley C.; Wilson, Richard K.; Schierup, Mikkel H.; Rogers, Jane; Tyler-Smith, Chris; Durbin, Richard

2012-01-01

Summary Gorillas are humans’ closest living relatives after chimpanzees, and are of comparable importance for the study of human origins and evolution. Here we present the assembly and analysis of a genome sequence for the western lowland gorilla, and compare the whole genomes of all extant great ape genera. We propose a synthesis of genetic and fossil evidence consistent with placing the human-chimpanzee and human-chimpanzee-gorilla speciation events at approximately 6 and 10 million years ago (Mya). In 30% of the genome, gorilla is closer to human or chimpanzee than the latter are to each other; this is rarer around coding genes, indicating pervasive selection throughout great ape evolution, and has functional consequences in gene expression. A comparison of protein coding genes reveals approximately 500 genes showing accelerated evolution on each of the gorilla, human and chimpanzee lineages, and evidence for parallel acceleration, particularly of genes involved in hearing. We also compare the western and eastern gorilla species, estimating an average sequence divergence time 1.75 million years ago, but with evidence for more recent genetic exchange and a population bottleneck in the eastern species. The use of the genome sequence in these and future analyses will promote a deeper understanding of great ape biology and evolution. PMID:22398555

Modeling Dynamic Regulatory Processes in Stroke.

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

McDermott, Jason E.; Jarman, Kenneth D.; Taylor, Ronald C.

2012-10-11

The ability to examine in silico the behavior of biological systems can greatly accelerate the pace of discovery in disease pathologies, such as stroke, where in vivo experimentation is lengthy and costly. In this paper we describe an approach to in silico examination of blood genomic responses to neuroprotective agents and subsequent stroke through the development of dynamic models of the regulatory processes observed in the experimental gene expression data. First, we identified functional gene clusters from these data. Next, we derived ordinary differential equations (ODEs) relating regulators and functional clusters from the data. These ODEs were used to developmore » dynamic models that simulate the expression of regulated functional clusters using system dynamics as the modeling paradigm. The dynamic model has the considerable advantage of only requiring an initial starting state, and does not require measurement of regulatory influences at each time point in order to make accurate predictions. The manipulation of input model parameters, such as changing the magnitude of gene expression, made it possible to assess the behavior of the networks through time under varying conditions. We report that an optimized dynamic model can provide accurate predictions of overall system behavior under several different preconditioning paradigms.« less

S1P and the birth of platelets

PubMed Central

Galvani, Sylvain; Rafii, Shahin; Nachman, Ralph

2012-01-01

Recent work has highlighted the multitude of biological functions of sphingosine 1-phosphate (S1P), which include roles in hematopoietic cell trafficking, organization of immune organs, vascular development, and neuroinflammation. Indeed, a functional antagonist of S1P1 receptor, FTY720/Gilenya, has entered the clinic as a novel therapeutic for multiple sclerosis. In this issue of the JEM, Zhang et al. highlight yet another function of this lipid mediator: thrombopoiesis. The S1P1 receptor is required for the growth of proplatelet strings in the bloodstream and the shedding of platelets into the circulation. Notably, the sharp gradient of S1P between blood and the interstitial fluids seems to be essential to ensure the production of platelets, and S1P appears to cooperate with the CXCL12–CXCR4 axis. Pharmacologic modulation of the S1P1 receptor altered circulating platelet numbers acutely, suggesting a potential therapeutic strategy for controlling thrombocytopenic states. However, the S1P4 receptor may also regulate thrombopoiesis during stress-induced accelerated platelet production. This work reveals a novel physiological action of the S1P/S1P1 duet that could potentially be harnessed for clinical translation. PMID:23166370

The story of protein arginine methylation: characterization, regulation, and function.

PubMed

Peng, Chao; Wong, Catherine Cl

2017-02-01

Arginine methylation is an important post-translational modification (PTM) in cells, which is catalyzed by a group of protein arginine methyltransferases (PRMTs). It plays significant roles in diverse cellular processes and various diseases. Misregulation and aberrant expression of PRMTs can provide potential biomarkers and therapeutic targets for drug discovery. Areas covered: Herein, we review the arginine methylation literature and summarize the methodologies for the characterization of this modification, as well as describe the recent insights into arginine methyltransferases and their biological functions in diseases. Expert commentary: Benefits from the enzyme-based large-scale screening approach, the novel affinity enrichment strategies, arginine methylated protein family is the focus of attention. Although a number of arginine methyltransferases and related substrates are identified, the catalytic mechanism of different types of PRMTs remains unclear and few related demethylases are characterized. Novel functional studies continuously reveal the importance of this modification in the cell cycle and diseases. A deeper understanding of arginine methylated proteins, modification sites, and their mechanisms of regulation is needed to explore their role in life processes, especially their relationship with diseases, thus accelerating the generation of potent, selective, cell-penetrant drug candidates.

Consistent global structures of complex RNA states through multidimensional chemical mapping

PubMed Central

Cheng, Clarence Yu; Chou, Fang-Chieh; Kladwang, Wipapat; Tian, Siqi; Cordero, Pablo; Das, Rhiju

2015-01-01

Accelerating discoveries of non-coding RNA (ncRNA) in myriad biological processes pose major challenges to structural and functional analysis. Despite progress in secondary structure modeling, high-throughput methods have generally failed to determine ncRNA tertiary structures, even at the 1-nm resolution that enables visualization of how helices and functional motifs are positioned in three dimensions. We report that integrating a new method called MOHCA-seq (Multiplexed •OH Cleavage Analysis with paired-end sequencing) with mutate-and-map secondary structure inference guides Rosetta 3D modeling to consistent 1-nm accuracy for intricately folded ncRNAs with lengths up to 188 nucleotides, including a blind RNA-puzzle challenge, the lariat-capping ribozyme. This multidimensional chemical mapping (MCM) pipeline resolves unexpected tertiary proximities for cyclic-di-GMP, glycine, and adenosylcobalamin riboswitch aptamers without their ligands and a loose structure for the recently discovered human HoxA9D internal ribosome entry site regulon. MCM offers a sequencing-based route to uncovering ncRNA 3D structure, applicable to functionally important but potentially heterogeneous states. DOI: http://dx.doi.org/10.7554/eLife.07600.001 PMID:26035425

Accelerated healing of full-thickness wounds by genipin-crosslinked silk sericin/PVA scaffolds.

PubMed

Aramwit, Pornanong; Siritienthong, Tippawan; Srichana, Teerapol; Ratanavaraporn, Juthamas

2013-01-01

Silk sericin has recently been studied for its advantageous biological properties, including its ability to promote wound healing. This study developed a delivery system to accelerate the healing of full-thickness wounds. Three-dimensional scaffolds were fabricated from poly(vinyl alcohol) (PVA), glycerin (as a plasticizer) and genipin (as a crosslinking agent), with or without sericin. The physical and biological properties of the genipin-crosslinked sericin/PVA scaffolds were investigated and compared with those of scaffolds without sericin. The genipin-crosslinked sericin/PVA scaffolds exhibited a higher compressive modulus and greater swelling in water than the scaffolds without sericin. Sericin also exhibited controlled release from the scaffolds. The genipin-crosslinked sericin/PVA scaffolds promoted the attachment and proliferation of L929 mouse fibroblasts. After application to full-thickness rat wounds, the wounds treated with genipin-crosslinked sericin/PVA scaffolds showed a significantly greater reduction in wound size, collagen formation and epithelialization compared with the control scaffolds without sericin but lower numbers of macrophages and multinucleated giant cells. These results indicate that the delivery of sericin from the novel genipin-crosslinked scaffolds efficiently healed the wound. Therefore, these genipin-crosslinked sericin/PVA scaffolds represent a promising candidate for the accelerated healing of full-thickness wounds. Copyright © 2013 S. Karger AG, Basel.

Accelerating pathway evolution by increasing the gene dosage of chromosomal segments.

PubMed

Tumen-Velasquez, Melissa; Johnson, Christopher W; Ahmed, Alaa; Dominick, Graham; Fulk, Emily M; Khanna, Payal; Lee, Sarah A; Schmidt, Alicia L; Linger, Jeffrey G; Eiteman, Mark A; Beckham, Gregg T; Neidle, Ellen L

2018-06-18

Experimental evolution is a critical tool in many disciplines, including metabolic engineering and synthetic biology. However, current methods rely on the chance occurrence of a key step that can dramatically accelerate evolution in natural systems, namely increased gene dosage. Our studies sought to induce the targeted amplification of chromosomal segments to facilitate rapid evolution. Since increased gene dosage confers novel phenotypes and genetic redundancy, we developed a method, Evolution by Amplification and Synthetic Biology (EASy), to create tandem arrays of chromosomal regions. In Acinetobacter baylyi , EASy was demonstrated on an important bioenergy problem, the catabolism of lignin-derived aromatic compounds. The initial focus on guaiacol (2-methoxyphenol), a common lignin degradation product, led to the discovery of Amycolatopsis genes ( gcoAB ) encoding a cytochrome P450 enzyme that converts guaiacol to catechol. However, chromosomal integration of gcoAB in Pseudomonas putida or A. baylyi did not enable guaiacol to be used as the sole carbon source despite catechol being a growth substrate. In ∼1,000 generations, EASy yielded alleles that in single chromosomal copy confer growth on guaiacol. Different variants emerged, including fusions between GcoA and CatA (catechol 1,2-dioxygenase). This study illustrates the power of harnessing chromosomal gene amplification to accelerate the evolution of desirable traits.

Accelerating Smith-Waterman Algorithm for Biological Database Search on CUDA-Compatible GPUs

NASA Astrophysics Data System (ADS)

Munekawa, Yuma; Ino, Fumihiko; Hagihara, Kenichi

This paper presents a fast method capable of accelerating the Smith-Waterman algorithm for biological database search on a cluster of graphics processing units (GPUs). Our method is implemented using compute unified device architecture (CUDA), which is available on the nVIDIA GPU. As compared with previous methods, our method has four major contributions. (1) The method efficiently uses on-chip shared memory to reduce the data amount being transferred between off-chip video memory and processing elements in the GPU. (2) It also reduces the number of data fetches by applying a data reuse technique to query and database sequences. (3) A pipelined method is also implemented to overlap GPU execution with database access. (4) Finally, a master/worker paradigm is employed to accelerate hundreds of database searches on a cluster system. In experiments, the peak performance on a GeForce GTX 280 card reaches 8.32 giga cell updates per second (GCUPS). We also find that our method reduces the amount of data fetches to 1/140, achieving approximately three times higher performance than a previous CUDA-based method. Our 32-node cluster version is approximately 28 times faster than a single GPU version. Furthermore, the effective performance reaches 75.6 giga instructions per second (GIPS) using 32 GeForce 8800 GTX cards.

Design Considerations for Proposed Fermilab Integrable RCS

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

Eldred, Jeffrey; Valishev, Alexander

2017-03-02

Integrable optics is an innovation in particle accelerator design that provides strong nonlinear focusing while avoiding parametric resonances. One promising application of integrable optics is to overcome the traditional limits on accelerator intensity imposed by betatron tune-spread and collective instabilities. The efficacy of high-intensity integrable accelerators will be undergo comprehensive testing over the next several years at the Fermilab Integrable Optics Test Accelerator (IOTA) and the University of Maryland Electron Ring (UMER). We propose an integrable Rapid-Cycling Synchrotron (iRCS) as a replacement for the Fermilab Booster to achieve multi-MW beam power for the Fermilab high-energy neutrino program. We provide amore » overview of the machine parameters and discuss an approach to lattice optimization. Integrable optics requires arcs with integer-pi phase advance followed by drifts with matched beta functions. We provide an example integrable lattice with features of a modern RCS - long dispersion-free drifts, low momentum compaction, superperiodicity, chromaticity correction, separate-function magnets, and bounded beta functions.« less

"No practical capabilities": American biological and chemical warfare programs during the Korean war.

PubMed

Crane, Conrad C

2002-01-01

Much controversy still surrounds accusations that American forces in the Far East during the Korean War used biological warfare against North Korea and China. An analysis of recently declassified documents reveals that, although the United States attempted to accelerate its development and acquisition of such weapons during that period, its efforts to create a viable biological warfare capability were unsuccessful. Plans to similarly expand chemical warfare stocks and capabilities were also frustrated. Technological difficulties, personnel shortages, bureaucratic battles between the armed services, and policy limitations combined to hold back advances in American chemical and biological warfare. In light of the recent fears of terrorist attacks with such weapons, this analysis highlights the great difficulties involved in developing, acquiring, and delivering such capabilities.

Electrical stimulation accelerates motor functional recovery in autograft-repaired 10 mm femoral nerve gap in rats.

PubMed

Huang, Jinghui; Hu, Xueyu; Lu, Lei; Ye, Zhengxu; Wang, Yuqing; Luo, Zhuojing

2009-10-01

Electrical stimulation has been shown to enhance peripheral nerve regeneration after nerve injury. However, the impact of electrical stimulation on motor functional recovery after nerve injuries, especially over long nerve gap lesions, has not been investigated in a comprehensive manner. In the present study, we aimed to determine whether electrical stimulation (1 h, 20 Hz) is beneficial for motor functional recovery after a 10 mm femoral nerve gap lesion in rats. The proximal nerve stump was electrically stimulated for 1 h at 20 Hz frequency prior to nerve repair with an autologous graft. The rate of motor functional recovery was evaluated by single frame motion analysis and electrophysiological studies, and the nerve regeneration was investigated by double labeling and histological analysis. We found that brief electrical stimulation significantly accelerated motor functional recovery and nerve regeneration. Although the final outcome, both in functional terms and morphological terms, was not improved by electrical stimulation, the observed acceleration of functional recovery and axon regeneration may be of therapeutic importance in clinical setting.

Genome-wide ENU mutagenesis for the discovery of novel male fertility regulators.

PubMed

Jamsai, Duangporn; O'Bryan, Moira K

2010-06-01

The completion of genome sequencing projects has provided an extensive knowledge of the contents of the genomes of human, mouse, and many other organisms. Despite this, the function of most of the estimated 25,000 human genes remains largely unknown. Attention has now turned to elucidating gene function and identifying biological pathways that contribute to human diseases, including male infertility. Our understanding of the genetic regulation of male fertility has been accelerated through the use of genetically modified mouse models including knockout, knock-in, gene-trapped, and transgenic mice. Such reverse genetic approaches however, require some fore-knowledge of a gene's function and, as such, bias against the discovery of completely novel genes and biological pathways. To facilitate high throughput gene discovery, genome-wide mouse mutagenesis via the use of a potent chemical mutagen, N-ethyl-N-nitrosourea (ENU), has been developed over the past decade. This forward genetic, or phenotype-driven, approach relies upon observing a phenotype first, then subsequently defining the underlining genetic defect. Mutations are randomly introduced into the mouse genome via ENU exposure. Through a controlled breeding scheme, mutations causing a phenotype of interest (e.g., male infertility) are then identified by linkage analysis and candidate gene sequencing. This approach allows for the possibility of revealing comprehensive phenotype-genotype relationships for a range of genes and pathways i.e. in addition to null alleles, mice containing partial loss of function or gain-of-function mutations, can be recovered. Such point mutations are likely to be more reflective of those that occur within the human population. Many research groups have successfully used this approach to generate infertile mouse lines and some novel male fertility genes have been revealed. In this review, we focus on the utility of ENU mutagenesis for the discovery of novel male fertility regulators.

An overview of bioinformatics methods for modeling biological pathways in yeast

PubMed Central

Hou, Jie; Acharya, Lipi; Zhu, Dongxiao

2016-01-01

The advent of high-throughput genomics techniques, along with the completion of genome sequencing projects, identification of protein–protein interactions and reconstruction of genome-scale pathways, has accelerated the development of systems biology research in the yeast organism Saccharomyces cerevisiae. In particular, discovery of biological pathways in yeast has become an important forefront in systems biology, which aims to understand the interactions among molecules within a cell leading to certain cellular processes in response to a specific environment. While the existing theoretical and experimental approaches enable the investigation of well-known pathways involved in metabolism, gene regulation and signal transduction, bioinformatics methods offer new insights into computational modeling of biological pathways. A wide range of computational approaches has been proposed in the past for reconstructing biological pathways from high-throughput datasets. Here we review selected bioinformatics approaches for modeling biological pathways in S. cerevisiae, including metabolic pathways, gene-regulatory pathways and signaling pathways. We start with reviewing the research on biological pathways followed by discussing key biological databases. In addition, several representative computational approaches for modeling biological pathways in yeast are discussed. PMID:26476430

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

PubMed

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 suggesting a functional significance of high-gamma information transfer in consciousness.

Computational Approaches to Phenotyping

PubMed Central

Lussier, Yves A.; Liu, Yang

2007-01-01

The recent completion of the Human Genome Project has made possible a high-throughput “systems approach” for accelerating the elucidation of molecular underpinnings of human diseases, and subsequent derivation of molecular-based strategies to more effectively prevent, diagnose, and treat these diseases. Although altered phenotypes are among the most reliable manifestations of altered gene functions, research using systematic analysis of phenotype relationships to study human biology is still in its infancy. This article focuses on the emerging field of high-throughput phenotyping (HTP) phenomics research, which aims to capitalize on novel high-throughput computation and informatics technology developments to derive genomewide molecular networks of genotype–phenotype associations, or “phenomic associations.” The HTP phenomics research field faces the challenge of technological research and development to generate novel tools in computation and informatics that will allow researchers to amass, access, integrate, organize, and manage phenotypic databases across species and enable genomewide analysis to associate phenotypic information with genomic data at different scales of biology. Key state-of-the-art technological advancements critical for HTP phenomics research are covered in this review. In particular, we highlight the power of computational approaches to conduct large-scale phenomics studies. PMID:17202287

High-content screening of small compounds on human embryonic stem cells.

PubMed

Barbaric, Ivana; Gokhale, Paul J; Andrews, Peter W

2010-08-01

Human ES (embryonic stem) cells and iPS (induced pluripotent stem) cells have been heralded as a source of differentiated cells that could be used in the treatment of degenerative diseases, such as Parkinson's disease or diabetes. Despite the great potential for their use in regenerative therapy, the challenge remains to understand the basic biology of these remarkable cells, in order to differentiate them into any functional cell type. Given the scale of the task, high-throughput screening of agents and culture conditions offers one way to accelerate these studies. The screening of small-compound libraries is particularly amenable to such high-throughput methods. Coupled with high-content screening technology that enables simultaneous assessment of multiple cellular features in an automated and quantitative way, this approach is proving powerful in identifying both small molecules as tools for manipulating stem cell fates and novel mechanisms of differentiation not previously associated with stem cell biology. Such screens performed on human ES cells also demonstrate the usefulness of human ES/iPS cells as cellular models for pharmacological testing of drug efficacy and toxicity, possibly a more imminent use of these cells than in regenerative medicine.

Towards functional antibody-based vaccines to prevent pre-erythrocytic malaria infection.

PubMed

Sack, Brandon; Kappe, Stefan H I; Sather, D Noah

2017-05-01

An effective malaria vaccine would be considered a milestone of modern medicine, yet has so far eluded research and development efforts. This can be attributed to the extreme complexity of the malaria parasites, presenting with a multi-stage life cycle, high genome complexity and the parasite's sophisticated immune evasion measures, particularly antigenic variation during pathogenic blood stage infection. However, the pre-erythrocytic (PE) early infection forms of the parasite exhibit relatively invariant proteomes, and are attractive vaccine targets as they offer multiple points of immune system attack. Areas covered: We cover the current state of and roadblocks to the development of an effective, antibody-based PE vaccine, including current vaccine candidates, limited biological knowledge, genetic heterogeneity, parasite complexity, and suboptimal preclinical models as well as the power of early stage clinical models. Expert commentary: PE vaccines will need to elicit broad and durable immunity to prevent infection. This could be achievable if recent innovations in studying the parasites' infection biology, rational vaccine selection and design as well as adjuvant formulation are combined in a synergistic and multipronged approach. Improved preclinical assays as well as the iterative testing of vaccine candidates in controlled human malaria infection trials will further accelerate this effort.

Frequency characteristics of vibration generated by dual acoustic radiation force for estimating viscoelastic properties of biological tissues

NASA Astrophysics Data System (ADS)

Watanabe, Ryoichi; Arakawa, Mototaka; Kanai, Hiroshi

2018-07-01

We proposed a new method for estimating the viscoelastic property of the local region of a sample. The viscoelastic parameters of the phantoms simulating the biological tissues were quantitatively estimated by analyzing the frequency characteristics of displacement generated by acoustic excitation. The samples were locally strained by irradiating them with the ultrasound simultaneously generated from two point-focusing transducers by applying the sum of two signals with slightly different frequencies of approximately 1 MHz. The surface of a phantom was excited in the frequency range of 20–2,000 Hz, and its displacement was measured. The frequency dependence of the acceleration provided by the acoustic radiation force was also measured. From these results, we determined the frequency characteristics of the transfer function from the stress to the strain and estimated the ratio of the elastic modulus to the viscosity modulus (K/η) by fitting the data to the Maxwell model. Moreover, the elastic modulus K was separately estimated from the measured sound velocity and density of the phantom, and the viscosity modulus η was evaluated by substituting the estimated elastic modulus into the obtained K/η ratio.

Airway Basal Cells. The “Smoking Gun” of Chronic Obstructive Pulmonary Disease

PubMed Central

2014-01-01

The earliest abnormality in the lung associated with smoking is hyperplasia of airway basal cells, the stem/progenitor cells of the ciliated and secretory cells that are central to pulmonary host defense. Using cell biology and ’omics technologies to assess basal cells isolated from bronchoscopic brushings of nonsmokers, smokers, and smokers with chronic obstructive pulmonary disease (COPD), compelling evidence has been provided in support of the concept that airway basal cells are central to the pathogenesis of smoking-associated lung diseases. When confronted by the chronic stress of smoking, airway basal cells become disorderly, regress to a more primitive state, behave as dictated by their inheritance, are susceptible to acquired changes in their genome, lose the capacity to regenerate the epithelium, are responsible for the major changes in the airway that characterize COPD, and, with persistent stress, can undergo malignant transformation. Together, these observations led to the conclusion that accelerated loss of lung function in susceptible individuals begins with disordered airway basal cell biology (i.e., that airway basal cells are the “smoking gun” of COPD, a potential target for the development of therapies to prevent smoking-related lung disorders). PMID:25354273

Biology of the Heat Shock Response and Protein Chaperones: Budding Yeast (Saccharomyces cerevisiae) as a Model System

PubMed Central

Verghese, Jacob; Abrams, Jennifer; Wang, Yanyu

2012-01-01

Summary: The eukaryotic heat shock response is an ancient and highly conserved transcriptional program that results in the immediate synthesis of a battery of cytoprotective genes in the presence of thermal and other environmental stresses. Many of these genes encode molecular chaperones, powerful protein remodelers with the capacity to shield, fold, or unfold substrates in a context-dependent manner. The budding yeast Saccharomyces cerevisiae continues to be an invaluable model for driving the discovery of regulatory features of this fundamental stress response. In addition, budding yeast has been an outstanding model system to elucidate the cell biology of protein chaperones and their organization into functional networks. In this review, we evaluate our understanding of the multifaceted response to heat shock. In addition, the chaperone complement of the cytosol is compared to those of mitochondria and the endoplasmic reticulum, organelles with their own unique protein homeostasis milieus. Finally, we examine recent advances in the understanding of the roles of protein chaperones and the heat shock response in pathogenic fungi, which is being accelerated by the wealth of information gained for budding yeast. PMID:22688810

DNA Array-Based Gene Profiling

PubMed Central

Mocellin, Simone; Provenzano, Maurizio; Rossi, Carlo Riccardo; Pilati, Pierluigi; Nitti, Donato; Lise, Mario

2005-01-01

Cancer is a heterogeneous disease in most respects, including its cellularity, different genetic alterations, and diverse clinical behaviors. Traditional molecular analyses are reductionist, assessing only 1 or a few genes at a time, thus working with a biologic model too specific and limited to confront a process whose clinical outcome is likely to be governed by the combined influence of many genes. The potential of functional genomics is enormous, because for each experiment, thousands of relevant observations can be made simultaneously. Accordingly, DNA array, like other high-throughput technologies, might catalyze and ultimately accelerate the development of knowledge in tumor cell biology. Although in its infancy, the implementation of DNA array technology in cancer research has already provided investigators with novel data and intriguing new hypotheses on the molecular cascade leading to carcinogenesis, tumor aggressiveness, and sensitivity to antiblastic agents. Given the revolutionary implications that the use of this technology might have in the clinical management of patients with cancer, principles of DNA array-based tumor gene profiling need to be clearly understood for the data to be correctly interpreted and appreciated. In the present work, we discuss the technical features characterizing this powerful laboratory tool and review the applications so far described in the field of oncology. PMID:15621987

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

Studer, Anthony

Current pressures on the global food supply have accelerated the urgency for a second green revolution using novel and sustainable approaches to increase crop yield and efficiency. This proposal outlines experiments to address fundamental questions regarding the biology of C 4 photosynthesis, the method of carbon fixation utilized by the most productive food, feed and bioenergy crops. Carbonic anhydrase (CA) has been implicated in multiple cellular functions including nitrogen metabolism, water use efficiency, and photosynthesis. CA catalyzes the first dedicated step in C 4 photosynthesis, the hydration of CO 2 into bicarbonate, and is potentially rate limiting in C 4more » grasses. Using insertional mutagenesis, we have generated CA mutants in maize, and propose the characterization of these mutants using phenotypic, physiological, and transcriptomic profiling to assay the plant’s response to altered CA activity. In addition, florescent protein tagging experiments will be employed to study the subcellular localization of CA paralogs, providing critical data for modeling carbon fixation in C 4 plants. Finally, I propose parallel experiments in Setaria viridis to explore its relevance as model C 4 grass. Using a multifaceted approach, this proposal addresses important questions in basic biology, as well as the need for translation research in response to looming global food challenges.« less

Current Status and Future Prospects of Marine Natural Products (MNPs) as Antimicrobials.

PubMed

Choudhary, Alka; Naughton, Lynn M; Montánchez, Itxaso; Dobson, Alan D W; Rai, Dilip K

2017-08-28

The marine environment is a rich source of chemically diverse, biologically active natural products, and serves as an invaluable resource in the ongoing search for novel antimicrobial compounds. Recent advances in extraction and isolation techniques, and in state-of-the-art technologies involved in organic synthesis and chemical structure elucidation, have accelerated the numbers of antimicrobial molecules originating from the ocean moving into clinical trials. The chemical diversity associated with these marine-derived molecules is immense, varying from simple linear peptides and fatty acids to complex alkaloids, terpenes and polyketides, etc. Such an array of structurally distinct molecules performs functionally diverse biological activities against many pathogenic bacteria and fungi, making marine-derived natural products valuable commodities, particularly in the current age of antimicrobial resistance. In this review, we have highlighted several marine-derived natural products (and their synthetic derivatives), which have gained recognition as effective antimicrobial agents over the past five years (2012-2017). These natural products have been categorized based on their chemical structures and the structure-activity mediated relationships of some of these bioactive molecules have been discussed. Finally, we have provided an insight into how genome mining efforts are likely to expedite the discovery of novel antimicrobial compounds.

Cosmic heavy ion tracks in mesoscopic biological test objects

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

Facius, R.

1994-12-31

Since more than 20 years ago, when the National Academy of Sciences and the National Research Council of the U.S.A. released their report on `HZE particle effects in manned spaced flight`, it has been emphasized how difficult - if not even impossible - it is to assess their radiobiological impact on man from conventional studies where biological test organisms are stochastically exposed to `large` fluences of heavy ions. An alternative, competing approach had been realized in the BIOSTACK experiments, where the effects of single cosmic as well as accelerator - heavy ions on individual biological test organisms could be investigated.more » Although presented from the beginning as the preferable approach for terrestrial investigations with accelerator heavy ions too (`The BIOSTACK as an approach to high LET radiation research`), only recently this insight is gaining more widespread recognition. In space flight experiments, additional constraints imposed by the infrastructure of the vehicle or satellite further impede such investigations. Restrictions concern the physical detector systems needed for the registration of the cosmic heavy ions` trajectories as well as the biological systems eligible as test organisms. Such optimized procedures and techniques were developed for the investigations on chromosome aberrations induced by cosmic heavy ions in cells of the stem meristem of lettuce seeds (Lactuca sativa) and for the investigation of the radiobiological response of Wolffia arriza, which is the smallest flowering (water) plant. The biological effects were studied by the coworkers of the Russian Institute of Biomedical Problems (IBMP) which in cooperation with the European Space Agency ESA organized the exposure in the Biosatellites of the Cosmos series.« less

DNA methylation age of human tissues and cell types

PubMed Central

2013-01-01

Background It is not yet known whether DNA methylation levels can be used to accurately predict age across a broad spectrum of human tissues and cell types, nor whether the resulting age prediction is a biologically meaningful measure. Results I developed a multi-tissue predictor of age that allows one to estimate the DNA methylation age of most tissues and cell types. The predictor, which is freely available, was developed using 8,000 samples from 82 Illumina DNA methylation array datasets, encompassing 51 healthy tissues and cell types. I found that DNA methylation age has the following properties: first, it is close to zero for embryonic and induced pluripotent stem cells; second, it correlates with cell passage number; third, it gives rise to a highly heritable measure of age acceleration; and, fourth, it is applicable to chimpanzee tissues. Analysis of 6,000 cancer samples from 32 datasets showed that all of the considered 20 cancer types exhibit significant age acceleration, with an average of 36 years. Low age-acceleration of cancer tissue is associated with a high number of somatic mutations and TP53 mutations, while mutations in steroid receptors greatly accelerate DNA methylation age in breast cancer. Finally, I characterize the 353 CpG sites that together form an aging clock in terms of chromatin states and tissue variance. Conclusions I propose that DNA methylation age measures the cumulative effect of an epigenetic maintenance system. This novel epigenetic clock can be used to address a host of questions in developmental biology, cancer and aging research. PMID:24138928

A Study of Laminar Compressible Viscous Pipe Flow Accelerated by an Axial Body Force, with Application to Magnetogasdynamics

NASA Technical Reports Server (NTRS)

Martin, E. Dale

1961-01-01

A study is made of the steady laminar flow of a compressible viscous fluid in a circular pipe when the fluid is accelerated by an axial body force. The application of the theory to the magnetofluidmechanics of an electrically conducting gas accelerated by electric and magnetic fields is discussed. Constant viscosity, thermal conductivity, and electrical conductivity are assumed. Fully developed flow velocity and temperature profiles are shown, and detailed results of the accelerating flow development, including velocity and pressure as functions of distance, are given for the case where the axial body force is constant and for the case where it is a linear function of velocity. From these results are determined the pipe entry length and the pressure difference required.

Optimization of motion control laws for tether crawler or elevator systems

NASA Technical Reports Server (NTRS)

Swenson, Frank R.; Von Tiesenhausen, Georg

1988-01-01

Based on the proposal of a motion control law by Lorenzini (1987), a method is developed for optimizing motion control laws for tether crawler or elevator systems in terms of the performance measures of travel time, the smoothness of acceleration and deceleration, and the maximum values of velocity and acceleration. The Lorenzini motion control law, based on powers of the hyperbolic tangent function, is modified by the addition of a constant-velocity section, and this modified function is then optimized by parameter selections to minimize the peak acceleration value for a selected travel time or to minimize travel time for the selected peak values of velocity and acceleration. It is shown that the addition of a constant-velocity segment permits further optimization of the motion control law performance.

[PSYCHO PHYSIOLOGICAL MARKERS OF ACCELERATED AGING AMONG THOSE WORKING WITH OCCUPATIONAL HAZARDS].

PubMed

Bashkireva, A S; Kachan, Ye Yu; Kulapina, M E

2015-01-01

We assessed the significance of psycho physiological markers of accelerated aging of the function of attention using comparative analysis of two occupational groups in order to reveal how the working process affects mental work capacity. We revealed peculiarities of systemic structure of functions which determine mental work capacity depending on the age and length of service in lorry drivers. It was proved that decrease in the mnestic functions of lorry-drivers takes place 10-15 years earlier compared to the control group. Psycho physiological indices, reflecting the functioning of attention, decreased not only with aging but also with longer driving experience. Our results show that it is necessary to conduct further studies of psycho physiological markers of age-related decrease in short-term memory depending on the activities at work in order to prevent accelerated aging and achieve professional longevity.

Biological invasions, ecological resilience and adaptive governance

EPA Science Inventory

In a world of increasing interconnections in global trade as well as rapid change in climate and land cover, the accelerating introduction and spread of invasive species is a critical concern due to associated negative social and ecological impacts, both real and perceived. Much...

Irradiation chamber and sample changer for biological samples

NASA Astrophysics Data System (ADS)

Kraft, G.; Daues, H. W.; Fischer, B.; Kopf, U.; Liebold, H. P.; Quis, D.; Stelzer, H.; Kiefer, J.; Schöpfer, F.; Schneider, E.; Weber, K.; Wulf, H.; Dertinger, H.

1980-01-01

This paper describes an irradiation system with which living cells of different origin are irradiated with heavy ion beams (18⩽ Z⩽92) at energies up to 10 MeV/amu. The system consists of a beam monitor connected to the vacuum system of the accelerator and the irradiation chamber, containing the biological samples under atmospheric pressure. The requirements and aims of the set up are discussed. The first results with saccharomyces cerevisiae and Chinese Hamster tissue cells are presented.

Enhanced Bone Formation in Segmental Defects with BMP2 in a Biologically Relevant Molecular Context

DTIC Science & Technology

2016-10-16

gun shots . These do not heal on their own once a ‘critical size’ segment of bone is missing. One strategy to induce healing is to use bone-inducing...accelerate BMP2-induced bone formation by presenting the growth factor in a more biologically relevant context. This is based on our observation...that manganese increases the binding of BMP2 to COMP. The next steps are to validate these observations using BMP2:COMP on HA/PLG scaffolds in-vitro

Biological activity of a leached chernozem contaminated with the products of combustion of petroleum gas and its restoration upon phytoremediation

NASA Astrophysics Data System (ADS)

Kireeva, N. A.; Novoselova, E. I.; Shamaeva, A. A.; Grigoriadi, A. S.

2009-04-01

It is shown that contamination of leached chernozems by combustion products of petroleum gas favors changes in the biological activity of the soil: the number of hydrocarbon-oxidizing bacteria and micromycetes has increased, as well as the activity of catalase and lipase and phytotoxicity. Bromopsis inermis Leys used as a phytoameliorant has accelerated the destruction of hydrocarbons in the rhizosphere. The benzpyrene concentration in plants on contaminated soils considerably exceeds its background concentration.

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.

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

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

Baturin, Stanislav; Zholents, A.

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.

Transcriptome Analysis of the Octopus vulgaris Central Nervous System

PubMed Central

Zhang, Xiang; Mao, Yong; Huang, Zixia; Qu, Meng; Chen, Jun; Ding, Shaoxiong; Hong, Jingni; Sun, Tiantian

2012-01-01

Background Cephalopoda are a class of Mollusca species found in all the world's oceans. They are an important model organism in neurobiology. Unfortunately, the lack of neuronal molecular sequences, such as ESTs, transcriptomic or genomic information, has limited the development of molecular neurobiology research in this unique model organism. Results With high-throughput Illumina Solexa sequencing technology, we have generated 59,859 high quality sequences from 12,918,391 paired-end reads. Using BLASTx/BLASTn, 12,227 contigs have blast hits in the Swissprot, NR protein database and NT nucleotide database with E-value cutoff 1e−5. The comparison between the Octopus vulgaris central nervous system (CNS) library and the Aplysia californica/Lymnaea stagnalis CNS ESTs library yielded 5.93%/13.45% of O. vulgaris sequences with significant matches (1e−5) using BLASTn/tBLASTx. Meanwhile the hit percentage of the recently published Schistocerca gregaria, Tilapia or Hirudo medicinalis CNS library to the O. vulgaris CNS library is 21.03%–46.19%. We constructed the Phylogenetic tree using two genes related to CNS function, Synaptotagmin-7 and Synaptophysin. Lastly, we demonstrated that O. vulgaris may have a vertebrate-like Blood-Brain Barrier based on bioinformatic analysis. Conclusion This study provides a mass of molecular information that will contribute to further molecular biology research on O. vulgaris. In our presentation of the first CNS transcriptome analysis of O. vulgaris, we hope to accelerate the study of functional molecular neurobiology and comparative evolutionary biology. PMID:22768275

Circular RNAs in Cancer – Lessons Learned From microRNAs

PubMed Central

Dragomir, Mihnea; Calin, George A.

2018-01-01

Circular RNAs (circRNA) are RNA molecules built from fragments of linear pre-messenger RNAs and other linear RNA species through a process termed “back-splicing” in which the 3′ and 5′ ends are joined together giving rise to a covalently uninterrupted loop. circRNAs are not new members of the RNA world; they were first discovered in the early 1990s. The novelty is their abundance in the mammalian cells, as recently thousands of circRNAs were discovered and annotated. The biogenesis of circRNAs is a partially characterized process, regulated by three different mechanisms: exon skipping, intron pairing, and RNA-binding proteins. On the other hand, the function of circRNAs remains largely unknown and only a handful of singular reports describe in detail the biological roles of some circular transcripts. In a very short period of time, numerous circRNAs were associated with various cancer types and were also identified in bodily fluids with the potential of being disease-specific biomarkers. In this review, we briefly describe the biogenesis and function of circRNAs and present the circular transcripts that were more than once reported in literature to be associated with cancer. Finally, we point out some of the difficulties encountered in the study of circRNAs in cancer, as we consider that taking these into account could accelerate and improve our understanding of the biologic and translational use of circRNAs in human diseases. PMID:29911069

Biological invasions, ecological resilience and adaptive governance

USGS Publications Warehouse

Chaffin, Brian C.; Garmestani, Ahjond S.; Angeler, David G.; Herrmann, Dustin L.; Stow, Craig A.; Nystrom, Magnus; Sendzimir, Jan; Hopton, Matthew E.; Kolasa, Jurek; Allen, Craig R.

2016-01-01

In a world of increasing interconnections in global trade as well as rapid change in climate and land cover, the accelerating introduction and spread of invasive species is a critical concern due to associated negative social and ecological impacts, both real and perceived. Much of the societal response to invasive species to date has been associated with negative economic consequences of invasions. This response has shaped a war-like approach to addressing invasions, one with an agenda of eradications and intense ecological restoration efforts towards prior or more desirable ecological regimes. This trajectory often ignores the concept of ecological resilience and associated approaches of resilience-based governance. We argue that the relationship between ecological resilience and invasive species has been understudied to the detriment of attempts to govern invasions, and that most management actions fail, primarily because they do not incorporate adaptive, learning-based approaches. Invasive species can decrease resilience by reducing the biodiversity that underpins ecological functions and processes, making ecosystems more prone to regime shifts. However, invasions do not always result in a shift to an alternative regime; invasions can also increase resilience by introducing novelty, replacing lost ecological functions or adding redundancy that strengthens already existing structures and processes in an ecosystem. This paper examines the potential impacts of species invasions on the resilience of ecosystems and suggests that resilience-based approaches can inform policy by linking the governance of biological invasions to the negotiation of tradeoffs between ecosystem services.

Biological invasions, ecological resilience and adaptive governance.

PubMed

Chaffin, Brian C; Garmestani, Ahjond S; Angeler, David G; Herrmann, Dustin L; Stow, Craig A; Nyström, Magnus; Sendzimir, Jan; Hopton, Matthew E; Kolasa, Jurek; Allen, Craig R

2016-12-01

In a world of increasing interconnections in global trade as well as rapid change in climate and land cover, the accelerating introduction and spread of invasive species is a critical concern due to associated negative social and ecological impacts, both real and perceived. Much of the societal response to invasive species to date has been associated with negative economic consequences of invasions. This response has shaped a war-like approach to addressing invasions, one with an agenda of eradications and intense ecological restoration efforts towards prior or more desirable ecological regimes. This trajectory often ignores the concept of ecological resilience and associated approaches of resilience-based governance. We argue that the relationship between ecological resilience and invasive species has been understudied to the detriment of attempts to govern invasions, and that most management actions fail, primarily because they do not incorporate adaptive, learning-based approaches. Invasive species can decrease resilience by reducing the biodiversity that underpins ecological functions and processes, making ecosystems more prone to regime shifts. However, invasions do not always result in a shift to an alternative regime; invasions can also increase resilience by introducing novelty, replacing lost ecological functions or adding redundancy that strengthens already existing structures and processes in an ecosystem. This paper examines the potential impacts of species invasions on the resilience of ecosystems and suggests that resilience-based approaches can inform policy by linking the governance of biological invasions to the negotiation of tradeoffs between ecosystem services. Copyright © 2016. Published by Elsevier Ltd.

Adaptation, allometry, and hypertension.

PubMed

Weder, A B; Schork, N J

1994-08-01

Essential hypertension is a "disease of civilization" but has a clear genetic component. From an evolutionary perspective, persistence in the human genome of elements capable of raising blood pressure presupposes their adaptive significance. Recently, two hypotheses that explicitly appeal to selectionist arguments, the "slavery" and "thrifty gene" theories, have been forwarded. We find neither completely successful, and we advance an alternative explanation of the adaptive importance of genes responsible for hypertension. We propose that blood pressure rises during childhood and adolescence to subserve homeostatic needs of the organism. Specifically, we contend that blood pressure is a flexible element in the repertoire of renal homeostatic mechanisms serving to match renal function to growth. The effect of modern diet and lifestyle on human growth stimulates earlier and more vigorous development, straining biologically necessary relationships between renal and general somatic growth and requiring compensation via homeostatic mechanisms preserved during evolution. Prime among such mechanisms is blood pressure, which rises as a compensation to maintain renal function in the face of greater growth. Since virtually all members of acculturated societies share in the modern lifestyle, the demands imposed by accelerated growth and development result in a populational shift to higher blood pressures, with a consequent increase in the prevalence of hypertension. We propose that hypertension is the product of maladaptation of highly genetically conserved mechanisms subserving important biological homeostatic needs. Elucidation of the mechanisms underlying hypertension will require approaches that examine the developmental processes linking growth to blood pressure.

International Collaboration for Galactic Cosmic Ray Simulation at the NASA Space Radiation Laboratory

NASA Technical Reports Server (NTRS)

Norbury, John W.; Slaba, Tony C.; Rusek, Adam; Durante, Marco; Reitz, Guenther

2015-01-01

An international collaboration on Galactic Cosmic Ray (GCR) simulation is being formed to make recommendations on how to best simulate the GCR spectrum at ground based accelerators. The external GCR spectrum is significantly modified when it passes through spacecraft shielding and astronauts. One approach for simulating the GCR space radiation environment at ground based accelerators would use the modified spectrum, rather than the external spectrum, in the accelerator beams impinging on biological targets. Two recent workshops have studied such GCR simulation. The first workshop was held at NASA Langley Research Center in October 2014. The second workshop was held at the NASA Space Radiation Investigators' workshop in Galveston, Texas in January 2015. The anticipated outcome of these and other studies may be a report or journal article, written by an international collaboration, making accelerator beam recommendations for GCR simulation. This poster describes the status of GCR simulation at the NASA Space Radiation Laboratory and encourages others to join the collaboration.

A simple ion implanter for material modifications in agriculture and gemmology

NASA Astrophysics Data System (ADS)

Singkarat, S.; Wijaikhum, A.; Suwannakachorn, D.; Tippawan, U.; Intarasiri, S.; Bootkul, D.; Phanchaisri, B.; Techarung, J.; Rhodes, M. W.; Suwankosum, R.; Rattanarin, S.; Yu, L. D.

2015-12-01

In our efforts in developing ion beam technology for novel applications in biology and gemmology, an economic simple compact ion implanter especially for the purpose was constructed. The designing of the machine was aimed at providing our users with a simple, economic, user friendly, convenient and easily operateable ion implanter for ion implantation of biological living materials and gemstones for biotechnological applications and modification of gemstones, which would eventually contribute to the national agriculture, biomedicine and gem-industry developments. The machine was in a vertical setup so that the samples could be placed horizontally and even without fixing; in a non-mass-analyzing ion implanter style using mixed molecular and atomic nitrogen (N) ions so that material modifications could be more effective; equipped with a focusing/defocusing lens and an X-Y beam scanner so that a broad beam could be possible; and also equipped with a relatively small target chamber so that living biological samples could survive from the vacuum period during ion implantation. To save equipment materials and costs, most of the components of the machine were taken from decommissioned ion beam facilities. The maximum accelerating voltage of the accelerator was 100 kV, ideally necessary for crop mutation induction and gem modification by ion beams from our experience. N-ion implantation of local rice seeds and cut gemstones was carried out. Various phenotype changes of grown rice from the ion-implanted seeds and improvements in gemmological quality of the ion-bombarded gemstones were observed. The success in development of such a low-cost and simple-structured ion implanter provides developing countries with a model of utilizing our limited resources to develop novel accelerator-based technologies and applications.

PREFACE: Nanobiology: from physics and engineering to biology

NASA Astrophysics Data System (ADS)

Nussinov, Ruth; Alemán, Carlos

2006-03-01

Biological systems are inherently nano in scale. Unlike nanotechnology, nanobiology is characterized by the interplay between physics, materials science, synthetic organic chemistry, engineering and biology. Nanobiology is a new discipline, with the potential of revolutionizing medicine: it combines the tools, ideas and materials of nanoscience and biology; it addresses biological problems that can be studied and solved by nanotechnology; it devises ways to construct molecular devices using biomacromolecules; and it attempts to build molecular machines utilizing concepts seen in nature. Its ultimate aim is to be able to predictably manipulate these, tailoring them to specified needs. Nanobiology targets biological systems and uses biomacromolecules. Hence, on the one hand, nanobiology is seemingly constrained in its scope as compared to general nanotechnology. Yet the amazing intricacy of biological systems, their complexity, and the richness of the shapes and properties provided by the biological polymers, enrich nanobiology. Targeting biological systems entails comprehension of how they work and the ability to use their components in design. From the physical standpoint, ultimately, if we are to understand biology we need to learn how to apply physical principles to figure out how these systems actually work. The goal of nanobiology is to assist in probing these systems at the appropriate length scale, heralding a new era in the biological, physical and chemical sciences. Biology is increasingly asking quantitative questions. Quantitation is essential if we are to understand how the cell works, and the details of its regulation. The physical sciences provide tools and strategies to obtain accurate measurements and simulate the information to allow comprehension of the processes. Nanobiology is at the interface of the physical and the biological sciences. Biology offers to the physical sciences fascinating problems, sophisticated systems and a rich repertoire of shapes and materials. Inspection of the protein structure databank illustrates the breadth of scaffolds, shapes and properties that protein molecules and their building blocks can provide. Via a shape-guided self-assembly strategy, these can be put together toward a specific function. Further, by inserting synthetic non-natural residues at judiciously selected positions, or synthetic peptide linkers, we may selectively rigidify the construct, or obtain a totally new world of shapes and scaffolds. Such broadening of the chemical space may lead to an almost unlimited range of nanosystems and architectures. Merging computation with experiment will accelerate nanodesign. Computational modeling will enhance the application of nanotechnology to key areas such as drug delivery and biomaterial design. Nanobiology is a field where interdisciplinary collaborations are essential and disciplines converge. Discipline convergence should enable the quantitation, leading to a better understanding of the regulatory networks within cells and between cells of an organism. These networks dictate how a cell responds to external stimuli, which in turn activate signaling cascades. It should allow the addressing of a broad range of questions on the structure and function of the cytoskeleton; the nuclear envelope; signal transduction by membrane embedded receptors; the nanomechanical properties of the extracellular matrix; nuclear transport; and voltage induced channel gating. For successful nanostructure design, we need to figure out and be able to control the intermolecular associations. For a stable functional construct, there are two key elements: first, the conformations of the building blocks in the designed structure should follow their natural tendencies; and second, the associations should be favorable. Molecules interact through their surfaces. Thus, favorable associations derive from shape complementarity and contributions of the various physical components. Nanobiology is in its infancy. Yet, biology provides an enormous range of engaging and stimulating problems with many in vivo examples of intricate, complex, fascinating biological systems. Understanding, mimicking and controlling the devices which target these processes and which are constructed from these molecules is a tremendous challenge to the converging disciplines in nanobiology.

Blueprints for green biotech: development and application of standards for plant synthetic biology.

PubMed

Patron, Nicola J

2016-06-15

Synthetic biology aims to apply engineering principles to the design and modification of biological systems and to the construction of biological parts and devices. The ability to programme cells by providing new instructions written in DNA is a foundational technology of the field. Large-scale de novo DNA synthesis has accelerated synthetic biology by offering custom-made molecules at ever decreasing costs. However, for large fragments and for experiments in which libraries of DNA sequences are assembled in different combinations, assembly in the laboratory is still desirable. Biological assembly standards allow DNA parts, even those from multiple laboratories and experiments, to be assembled together using the same reagents and protocols. The adoption of such standards for plant synthetic biology has been cohesive for the plant science community, facilitating the application of genome editing technologies to plant systems and streamlining progress in large-scale, multi-laboratory bioengineering projects. © 2016 The Author(s). published by Portland Press Limited on behalf of the Biochemical Society.

Cosmic heavy ion tracks in mesoscopic biological test objects

NASA Technical Reports Server (NTRS)

Facius, R.

1994-01-01

Since more than 20 years ago, when the National Academy of Sciences and the National Research Council of the U.S.A. released their report on 'HZE particle effects in manned spaced flight', it has been emphasized how difficult - if not even impossible - it is to assess their radiobiological impact on man from conventional studies where biological test organisms are stochastically exposed to 'large' fluences of heavy ions. An alternative, competing approach had been realized in the BIOSTACK experiments, where the effects of single cosmic as well as accelerator - heavy ions on individual biological test organisms could be investigated. Although presented from the beginning as the preferable approach for terrestrial investigations with accelerator heavy ions too ('The BIOSTACK as an approach to high LET radiation research'), only recently this insight is gaining more widespread recognition. In space flight experiments, additional constraints imposed by the infrastructure of the vehicle or satellite further impede such investigations. Restrictions concern the physical detector systems needed for the registration of the cosmic heavy ions' trajectories as well as the biological systems eligible as test organisms. Such optimized procedures and techniques were developed for the investigations on chromosome aberrations induced by cosmic heavy ions in cells of the stem meristem of lettuce seeds (Lactuca sativa) and for the investigation of the radiobiological response of Wolffia arriza, which is the smallest flowering (water) plant. The biological effects were studied by the coworkers of the Russian Institute of Biomedical Problems (IBMP) which in cooperation with the European Space Agency ESA organized the exposure in the Biosatellites of the Cosmos series. Since biological investigations and physical measurements of particle tracks had to be performed in laboratories widely separated, the preferred fixed contact between biological test objects and the particle detectors until the geometrical correlation between tracks and organisms has been established could not be maintained. This gave rise to half a dozen of coordinate systems for different measurements which finally had to be related to a single stack reference system.

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

Wan Chan Tseung, Hok Seum, E-mail: wanchantseung.hok@mayo.edu; Ma, Jiasen; Kreofsky, Cole R.

Purpose: Our aim is to demonstrate the feasibility of fast Monte Carlo (MC)–based inverse biological planning for the treatment of head and neck tumors in spot-scanning proton therapy. Methods and Materials: Recently, a fast and accurate graphics processor unit (GPU)–based MC simulation of proton transport was developed and used as the dose-calculation engine in a GPU-accelerated intensity modulated proton therapy (IMPT) optimizer. Besides dose, the MC can simultaneously score the dose-averaged linear energy transfer (LET{sub d}), which makes biological dose (BD) optimization possible. To convert from LET{sub d} to BD, a simple linear relation was assumed. By use of thismore » novel optimizer, inverse biological planning was applied to 4 patients, including 2 small and 1 large thyroid tumor targets, as well as 1 glioma case. To create these plans, constraints were placed to maintain the physical dose (PD) within 1.25 times the prescription while maximizing target BD. For comparison, conventional intensity modulated radiation therapy (IMRT) and IMPT plans were also created using Eclipse (Varian Medical Systems) in each case. The same critical-structure PD constraints were used for the IMRT, IMPT, and biologically optimized plans. The BD distributions for the IMPT plans were obtained through MC recalculations. Results: Compared with standard IMPT, the biologically optimal plans for patients with small tumor targets displayed a BD escalation that was around twice the PD increase. Dose sparing to critical structures was improved compared with both IMRT and IMPT. No significant BD increase could be achieved for the large thyroid tumor case and when the presence of critical structures mitigated the contribution of additional fields. The calculation of the biologically optimized plans can be completed in a clinically viable time (<30 minutes) on a small 24-GPU system. Conclusions: By exploiting GPU acceleration, MC-based, biologically optimized plans were created for small–tumor target patients. This optimizer will be used in an upcoming feasibility trial on LET{sub d} painting for radioresistant tumors.« less

Space Biophysics: Accomplishments, Trends, Challenges

NASA Technical Reports Server (NTRS)

Smith, Jeffrey D.

2015-01-01

Physics and biology are inextricably linked. All the chemical and biological processes of life are dutifully bound to follow the rules and laws of physics. In space, these physical laws seem to turn on their head and biological systems, from microbes to humans, adapt and evolve in myriad ways to cope with the changed physical influences of the space environment. Gravity is the most prominent change in space that influences biology. In microgravity, the physical processes of sedimentation, density-driven convective flow, influence of surface tension and fluid pressure profoundly influence biology at the molecular and cellular level as well as at the whole-body level. Gravity sensing mechanisms are altered, structural and functional components of biology (such as bone and muscle) are reduced and changes in the way fluids and gasses behave also drive the way microbial systems and biofilms grow as well as the way plants and animals adapt. The radiation environment also effects life in space. Solar particle events and high energy cosmic radiation can cause serious damage to DNA and other biomolecules. The results can cause mutation, cellular damage or death, leading to health consequences of acute radiation damage or long-term health consequences such as increased cancer risk. Space Biophysics is the study and utilization of physical changes in space that cause changes in biological systems. The unique physical environment in space has been used successfully to grow high-quality protein crystals and 3D tissue cultures that could not be grown in the presence of unidirectional gravitational acceleration here on Earth. All biological processes that change in space have their root in a biophysical alteration due to microgravity and/or the radiation environment of space. In order to fully-understand the risks to human health in space and to fully-understand how humans, plants, animals and microbes can safely and effectively travel and eventually live for long periods beyond the protective environment of Earth, the biophysical properties underlying these changes must be studied, characterized and understood. This lecture reviews the current state of NASA biophysics research accomplishments and identifies future trends and challenges for biophysics research on the International Space Station and beyond.

Systematic discovery of novel eukaryotic transcriptional regulators using sequence homology independent prediction.

PubMed

Bossi, Flavia; Fan, Jue; Xiao, Jun; Chandra, Lilyana; Shen, Max; Dorone, Yanniv; Wagner, Doris; Rhee, Seung Y

2017-06-26

The molecular function of a gene is most commonly inferred by sequence similarity. Therefore, genes that lack sufficient sequence similarity to characterized genes (such as certain classes of transcriptional regulators) are difficult to classify using most function prediction algorithms and have remained uncharacterized. To identify novel transcriptional regulators systematically, we used a feature-based pipeline to screen protein families of unknown function. This method predicted 43 transcriptional regulator families in Arabidopsis thaliana, 7 families in Drosophila melanogaster, and 9 families in Homo sapiens. Literature curation validated 12 of the predicted families to be involved in transcriptional regulation. We tested 33 out of the 195 Arabidopsis putative transcriptional regulators for their ability to activate transcription of a reporter gene in planta and found twelve coactivators, five of which had no prior literature support. To investigate mechanisms of action in which the predicted regulators might work, we looked for interactors of an Arabidopsis candidate that did not show transactivation activity in planta and found that it might work with other members of its own family and a subunit of the Polycomb Repressive Complex 2 to regulate transcription. Our results demonstrate the feasibility of assigning molecular function to proteins of unknown function without depending on sequence similarity. In particular, we identified novel transcriptional regulators using biological features enriched in transcription factors. The predictions reported here should accelerate the characterization of novel regulators.

An acellular biologic scaffold does not regenerate appreciable de novo muscle tissue in rat models of volumetric muscle loss injury.

PubMed

Aurora, Amit; Roe, Janet L; Corona, Benjamin T; Walters, Thomas J

2015-10-01

Extracellular matrix (ECM) derived scaffolds continue to be investigated for the treatment of volumetric muscle loss (VML) injuries. Clinically, ECM scaffolds have been used for lower extremity VML repair; in particular, MatriStem™, a porcine urinary bladder matrix (UBM), has shown improved functional outcomes and vascularization, but limited myogenesis. However, efficacy of the scaffold for the repair of traumatic muscle injuries has not been examined systematically. In this study, we demonstrate that the porcine UBM scaffold when used to repair a rodent gastrocnemius musculotendinous junction (MTJ) and tibialis anterior (TA) VML injury does not support muscle tissue regeneration. In the MTJ model, the scaffold was completely resorbed without tissue remodeling, suggesting that the scaffold may not be suitable for the clinical repair of muscle-tendon injuries. In the TA VML injury, the scaffold remodeled into a fibrotic tissue and showed functional improvement, but not due to muscle fiber regeneration. The inclusion of physical rehabilitation also did not improve functional response or tissue remodeling. We conclude that the porcine UBM scaffold when used to treat VML injuries may hasten the functional recovery through the mechanism of scaffold mediated functional fibrosis. Thus for appreciable muscle regeneration, repair strategies that incorporate myogenic cells, vasculogenic accelerant and a myoconductive scaffold need to be developed. Published by Elsevier Ltd.

Modeling Acceleration of a System of Two Objects Using the Concept of Limits

ERIC Educational Resources Information Center

Sokolowski, Andrzej

2018-01-01

Traditional school laboratory exercises on a system of moving objects connected by strings involve deriving expressions for the system acceleration, a = (?F)/m, and sketching a graph of acceleration vs. force. While being in the form of rational functions, these expressions present great opportunities for broadening the scope of the analysis by…

Optical manipulation for optogenetics: otoliths manipulation in zebrafish (Conference Presentation)

NASA Astrophysics Data System (ADS)

Favre-Bulle, Itia A.; Scott, Ethan; Rubinsztein-Dunlop, Halina

2016-03-01

Otoliths play an important role in Zebrafish in terms of hearing and sense of balance. Many studies have been conducted to understand its structure and function, however the encoding of its movement in the brain remains unknown. Here we developed a noninvasive system capable of manipulating the otolith using optical trapping while we image its behavioral response and brain activity. We'll also present our tools for behavioral response detection and brain activity mapping. Acceleration is sensed through movements of the otoliths in the inner ear. Because experimental manipulations involve movements, electrophysiology and fluorescence microscopy are difficult. As a result, the neural codes underlying acceleration sensation are poorly understood. We have developed a technique for optically trapping otoliths, allowing us to simulate acceleration in stationary larval zebrafish. By applying forces to the otoliths, we can elicit behavioral responses consistent with compensation for perceived acceleration. Since the animal is stationary, we can use calcium imaging in these animals' brains to identify the functional circuits responsible for mediating responses to acceleration in natural settings.

Advances in molecular labeling, high throughput imaging and machine intelligence portend powerful functional cellular biochemistry tools.

PubMed

Price, Jeffrey H; Goodacre, Angela; Hahn, Klaus; Hodgson, Louis; Hunter, Edward A; Krajewski, Stanislaw; Murphy, Robert F; Rabinovich, Andrew; Reed, John C; Heynen, Susanne

2002-01-01

Cellular behavior is complex. Successfully understanding systems at ever-increasing complexity is fundamental to advances in modern science and unraveling the functional details of cellular behavior is no exception. We present a collection of prospectives to provide a glimpse of the techniques that will aid in collecting, managing and utilizing information on complex cellular processes via molecular imaging tools. These include: 1) visualizing intracellular protein activity with fluorescent markers, 2) high throughput (and automated) imaging of multilabeled cells in statistically significant numbers, and 3) machine intelligence to analyze subcellular image localization and pattern. Although not addressed here, the importance of combining cell-image-based information with detailed molecular structure and ligand-receptor binding models cannot be overlooked. Advanced molecular imaging techniques have the potential to impact cellular diagnostics for cancer screening, clinical correlations of tissue molecular patterns for cancer biology, and cellular molecular interactions for accelerating drug discovery. The goal of finally understanding all cellular components and behaviors will be achieved by advances in both instrumentation engineering (software and hardware) and molecular biochemistry. Copyright 2002 Wiley-Liss, Inc.

Alignment of SWNTs by protein-ligand interaction of functionalized magnetic particles under low magnetic fields.

PubMed

Park, Tae Jung; Park, Jong Pil; Lee, Seok Jae; Jung, Dae-Hwan; Ko, Young Koan; Jung, Hee-Tae; Lee, Sang Yup

2011-05-01

Carbon nanotubes (CNTs) have attracted considerable attention for applications using their superior mechanical, thermal and electrical properties. A simple method to controllably align single-walled CNTs (SWNTs) by using magnetic particles embedded with superparamagnetic iron oxide as an accelerator under the magnetic field was developed. The functionalization of SWNTs using biotin, interacted with streptavidin-coupled magnetic particles (micro-to-nano in diameter), and layer-by-layer assembly were performed for the alignment of a particular direction onto the clean silicon and the gold substrate at very low magnetic forces (0.02-0.89 T) at room temperature. The successful alignment of the SWNTs with multi-layer film was observed by scanning electron microscopy (SEM) and transmission electron microscopy (TEM). By changing the orientation and location of the substrates, crossed-networks of SWNTs-magnetic particle complex could easily be fabricated. We suggest that this approach, which consists of a combination of biological interaction among streptavidin-biotin and magnetite particles, should be useful for lateral orientation of individual SWNTs with controllable direction.

Bulgarian contributions to the development of space biology and medicine

NASA Technical Reports Server (NTRS)

Serafimov, K.

1980-01-01

Several aspects of aerospace medicine are discussed. Particular attention is given to the following: the effects of anoxia; the effects of positive radial acceleration; and the effects of various degrees of athletic conditioning and drugs on the tolerance of space flight factors.

Parallel replica dynamics method for bistable stochastic reaction networks: Simulation and sensitivity analysis

NASA Astrophysics Data System (ADS)

Wang, Ting; Plecháč, Petr

2017-12-01

Stochastic reaction networks that exhibit bistable behavior are common in systems biology, materials science, and catalysis. Sampling of stationary distributions is crucial for understanding and characterizing the long-time dynamics of bistable stochastic dynamical systems. However, simulations are often hindered by the insufficient sampling of rare transitions between the two metastable regions. In this paper, we apply the parallel replica method for a continuous time Markov chain in order to improve sampling of the stationary distribution in bistable stochastic reaction networks. The proposed method uses parallel computing to accelerate the sampling of rare transitions. Furthermore, it can be combined with the path-space information bounds for parametric sensitivity analysis. With the proposed methodology, we study three bistable biological networks: the Schlögl model, the genetic switch network, and the enzymatic futile cycle network. We demonstrate the algorithmic speedup achieved in these numerical benchmarks. More significant acceleration is expected when multi-core or graphics processing unit computer architectures and programming tools such as CUDA are employed.

Rapid Prototyping of Microbial Cell Factories via Genome-scale Engineering

PubMed Central

Si, Tong; Xiao, Han; Zhao, Huimin

2014-01-01

Advances in reading, writing and editing genetic materials have greatly expanded our ability to reprogram biological systems at the resolution of a single nucleotide and on the scale of a whole genome. Such capacity has greatly accelerated the cycles of design, build and test to engineer microbes for efficient synthesis of fuels, chemicals and drugs. In this review, we summarize the emerging technologies that have been applied, or are potentially useful for genome-scale engineering in microbial systems. We will focus on the development of high-throughput methodologies, which may accelerate the prototyping of microbial cell factories. PMID:25450192

Neutrons produced by known energies of ions abundant in space

NASA Technical Reports Server (NTRS)

Wadman, W. W., III

1972-01-01

Particle accelerator radiation measurements are applied to the problem of calculating biological dose from radiation produced in the walls of a spacecraft by various ions in space. Neutrons, one of the products of the interactions of energetic ions with matter, are usually quite penetrating and have large values of Q.F. or R.B.E. Ions of helium, boron, carbon, nitrogen, and oxygen were accelerated and directed onto target materials of copper or tantalum. The secondary neutron production was determined. Studies were made of the angular distribution and an inferred neutron spectrum was calculated from activities of threshold reaction detectors.

A self-learning algorithm for biased molecular dynamics

PubMed Central

Tribello, Gareth A.; Ceriotti, Michele; Parrinello, Michele

2010-01-01

A new self-learning algorithm for accelerated dynamics, reconnaissance metadynamics, is proposed that is able to work with a very large number of collective coordinates. Acceleration of the dynamics is achieved by constructing a bias potential in terms of a patchwork of one-dimensional, locally valid collective coordinates. These collective coordinates are obtained from trajectory analyses so that they adapt to any new features encountered during the simulation. We show how this methodology can be used to enhance sampling in real chemical systems citing examples both from the physics of clusters and from the biological sciences. PMID:20876135

Galactic Cosmic Ray Simulation at the NASA Space Radiation Laboratory

NASA Technical Reports Server (NTRS)

Norbury, John W.; Slaba, Tony C.; Rusek, Adam

2015-01-01

The external Galactic Cosmic Ray (GCR) spectrum is significantly modified when it passes through spacecraft shielding and astronauts. One approach for simulating the GCR space radiation environment at ground based accelerators would use the modified spectrum, rather than the external spectrum, in the accelerator beams impinging on biological targets. Two recent workshops have studied such GCR simulation. The first workshop was held at NASA Langley Research Center in October 2014. The second workshop was held at the NASA Space Radiation Investigators' workshop in Galveston, Texas in January 2015. The results of these workshops will be discussed in this paper.

Transforming Growth Factor-β1 Accelerates Resorption of a Calcium Carbonate Biomaterial in Periodontal Defects.

PubMed

Koo, Ki-Tae; Susin, Cristiano; Wikesjö, Ulf M E; Choi, Seong-Ho; Kim, Chong-Kwan

2007-04-01

In a previous study, recombinant human transforming growth factor-beta1 (rhTGF-β 1 ) in a calcium carbonate carrier was implanted into critical-size, supraalveolar periodontal defects under conditions for guided tissue regeneration (GTR) to study whether rhTGF-β 1 would enhance or accelerate periodontal regeneration. The results showed minimal benefits of rhTGF-β 1 , and a clear account for this could not be offered. One potential cause may be that the rhTGF-β 1 formulation was biologically inactive. Several growth or differentiation factors have been suggested to accelerate degradation of biomaterials used as carriers. The objective of this study was to evaluate possible activity of rhTGF-β 1 on biodegradation of the calcium carbonate carrier. rhTGF-β 1 in a putty-formulated particulate calcium carbonate carrier was implanted into critical-size, supraalveolar periodontal defects under conditions for GTR in five beagle dogs. Contralateral defects received the calcium carbonate carrier combined with GTR without rhTGF-β 1 (control). The animals were euthanized at week 4 post-surgery and block biopsies of the defect sites were collected for histologic and histometric analysis. Radiographs were obtained at defect creation and weeks 2 and 4 after defect creation. No statistically significant differences were observed in new bone formation (bone height and area) among the treatments. However, total residual carrier was significantly reduced in sites receiving rhTGF-β 1 compared to control (P = 0.04). Similarly, carrier density was considerably reduced in sites receiving rhTGF-β 1 compared to control; the difference was borderline statistically significant (P = 0.06). Within the limitations of the study, it may be concluded that rhTGF-β 1 accelerates biodegradation of a particulate calcium carbonate biomaterial, indicating a biologic activity of the rhTGF-β 1 formulation apparently not encompassing enhanced or accelerated periodontal regeneration. © 2007 American Academy of Periodontology.

Transforming growth factor-beta1 accelerates resorption of a calcium carbonate biomaterial in periodontal defects.

PubMed

Koo, Ki-Tae; Susin, Cristiano; Wikesjö, Ulf M E; Choi, Seong-Ho; Kim, Chong-Kwan

2007-04-01

In a previous study, recombinant human transforming growth factor-beta1 (rhTGF-beta(1)) in a calcium carbonate carrier was implanted into critical-size, supraalveolar periodontal defects under conditions for guided tissue regeneration (GTR) to study whether rhTGF-beta(1) would enhance or accelerate periodontal regeneration. The results showed minimal benefits of rhTGF-beta(1), and a clear account for this could not be offered. One potential cause may be that the rhTGF-beta(1) formulation was biologically inactive. Several growth or differentiation factors have been suggested to accelerate degradation of biomaterials used as carriers. The objective of this study was to evaluate possible activity of rhTGF-beta(1) on biodegradation of the calcium carbonate carrier. rhTGF-beta(1) in a putty-formulated particulate calcium carbonate carrier was implanted into critical-size, supraalveolar periodontal defects under conditions for GTR in five beagle dogs. Contralateral defects received the calcium carbonate carrier combined with GTR without rhTGF-beta(1) (control). The animals were euthanized at week 4 post-surgery and block biopsies of the defect sites were collected for histologic and histometric analysis. Radiographs were obtained at defect creation and weeks 2 and 4 after defect creation. No statistically significant differences were observed in new bone formation (bone height and area) among the treatments. However, total residual carrier was significantly reduced in sites receiving rhTGF-beta(1) compared to control (P = 0.04). Similarly, carrier density was considerably reduced in sites receiving rhTGF-beta(1) compared to control; the difference was borderline statistically significant (P = 0.06). Within the limitations of the study, it may be concluded that rhTGF-beta(1) accelerates biodegradation of a particulate calcium carbonate biomaterial, indicating a biologic activity of the rhTGF-beta(1) formulation apparently not encompassing enhanced or accelerated periodontal regeneration.

Epigenetic Age Acceleration Assessed with Human White-Matter Images.

PubMed

Hodgson, Karen; Carless, Melanie A; Kulkarni, Hemant; Curran, Joanne E; Sprooten, Emma; Knowles, Emma E; Mathias, Samuel; Göring, Harald H H; Yao, Nailin; Olvera, Rene L; Fox, Peter T; Almasy, Laura; Duggirala, Ravi; Blangero, John; Glahn, David C

2017-05-03

The accurate estimation of age using methylation data has proved a useful and heritable biomarker, with acceleration in epigenetic age predicting a number of age-related phenotypes. Measures of white matter integrity in the brain are also heritable and highly sensitive to both normal and pathological aging processes across adulthood. We consider the phenotypic and genetic interrelationships between epigenetic age acceleration and white matter integrity in humans. Our goal was to investigate processes that underlie interindividual variability in age-related changes in the brain. Using blood taken from a Mexican-American extended pedigree sample ( n = 628; age = 23.28-93.11 years), epigenetic age was estimated using the method developed by Horvath (2013). For n = 376 individuals, diffusion tensor imaging scans were also available. The interrelationship between epigenetic age acceleration and global white matter integrity was investigated with variance decomposition methods. To test for neuroanatomical specificity, 16 specific tracts were additionally considered. We observed negative phenotypic correlations between epigenetic age acceleration and global white matter tract integrity (ρ pheno = -0.119, p = 0.028), with evidence of shared genetic (ρ gene = -0.463, p = 0.013) but not environmental influences. Negative phenotypic and genetic correlations with age acceleration were also seen for a number of specific white matter tracts, along with additional negative phenotypic correlations between granulocyte abundance and white matter integrity. These findings (i.e., increased acceleration in epigenetic age in peripheral blood correlates with reduced white matter integrity in the brain and shares common genetic influences) provide a window into the neurobiology of aging processes within the brain and a potential biomarker of normal and pathological brain aging. SIGNIFICANCE STATEMENT Epigenetic measures can be used to predict age with a high degree of accuracy and so capture acceleration in biological age, relative to chronological age. The white matter tracts within the brain are also highly sensitive to aging processes. We show that increased biological aging (measured using epigenetic data from blood samples) is correlated with reduced integrity of white matter tracts within the human brain (measured using diffusion tensor imaging) with data from a large sample of Mexican-American families. Given the family design of the sample, we are also able to demonstrate that epigenetic aging and white matter tract integrity also share common genetic influences. Therefore, epigenetic age may be a potential, and accessible, biomarker of brain aging. Copyright © 2017 the authors 0270-6474/17/374735-09$15.00/0.

Acceleration and stability of a high-current ion beam in induction fields

NASA Astrophysics Data System (ADS)

Karas', V. I.; Manuilenko, O. V.; Tarakanov, V. P.; Federovskaya, O. V.

2013-03-01

A one-dimensional nonlinear analytic theory of the filamentation instability of a high-current ion beam is formulated. The results of 2.5-dimensional numerical particle-in-cell simulations of acceleration and stability of an annular compensated ion beam (CIB) in a linear induction particle accelerator are presented. It is shown that additional transverse injection of electron beams in magnetically insulated gaps (cusps) improves the quality of the ion-beam distribution function and provides uniform beam acceleration along the accelerator. The CIB filamentation instability in both the presence and the absence of an external magnetic field is considered.

Superresolution parallel magnetic resonance imaging: Application to functional and spectroscopic imaging

PubMed Central

Otazo, Ricardo; Lin, Fa-Hsuan; Wiggins, Graham; Jordan, Ramiro; Sodickson, Daniel; Posse, Stefan

2009-01-01

Standard parallel magnetic resonance imaging (MRI) techniques suffer from residual aliasing artifacts when the coil sensitivities vary within the image voxel. In this work, a parallel MRI approach known as Superresolution SENSE (SURE-SENSE) is presented in which acceleration is performed by acquiring only the central region of k-space instead of increasing the sampling distance over the complete k-space matrix and reconstruction is explicitly based on intra-voxel coil sensitivity variation. In SURE-SENSE, parallel MRI reconstruction is formulated as a superresolution imaging problem where a collection of low resolution images acquired with multiple receiver coils are combined into a single image with higher spatial resolution using coil sensitivities acquired with high spatial resolution. The effective acceleration of conventional gradient encoding is given by the gain in spatial resolution, which is dictated by the degree of variation of the different coil sensitivity profiles within the low resolution image voxel. Since SURE-SENSE is an ill-posed inverse problem, Tikhonov regularization is employed to control noise amplification. Unlike standard SENSE, for which acceleration is constrained to the phase-encoding dimension/s, SURE-SENSE allows acceleration along all encoding directions — for example, two-dimensional acceleration of a 2D echo-planar acquisition. SURE-SENSE is particularly suitable for low spatial resolution imaging modalities such as spectroscopic imaging and functional imaging with high temporal resolution. Application to echo-planar functional and spectroscopic imaging in human brain is presented using two-dimensional acceleration with a 32-channel receiver coil. PMID:19341804

Accelerated and accentuated neurocognitive aging in HIV infection.

PubMed

Sheppard, David P; Iudicello, Jennifer E; Morgan, Erin E; Kamat, Rujvi; Clark, Lindsay R; Avci, Gunes; Bondi, Mark W; Woods, Steven Paul

2017-06-01

There is debate as to whether the neurocognitive changes associated with HIV infection represent an acceleration of the typical aging process or more simply reflect a greater accentuated risk for age-related declines. We aimed to determine whether accelerated neurocognitive aging is observable in a sample of older HIV-infected individuals compared to age-matched seronegatives and older old (i.e., aged ≥65) seronegative adults. Participants in a cross-sectional design included 48 HIV-seronegative (O-) and 40 HIV-positive (O+) participants between the ages of 50-65 (mean ages = 55 and 56, respectively) and 40 HIV-seronegative participants aged ≥65 (OO-; mean age = 74) who were comparable for other demographics. All participants were administered a brief neurocognitive battery of attention, episodic memory, speeded executive functions, and confrontation naming (i.e., Boston Naming Test). The O+ group performed more poorly than the O- group (i.e., accentuated aging), but not differently from the OO- on digit span and initial recall of a supraspan word list, consistent with an accelerating aging profile. However, the O+ group's performance was comparable to the O- group on all other neurocognitive tests (ps > 0.05). These data partially support a model of accelerated neurocognitive aging in HIV infection, which was observed in the domain of auditory verbal attention, but not in the areas of memory, language, or speeded executive functions. Future studies should examine whether HIV-infected adults over 65 evidence accelerated aging in downstream neurocognitive domains and subsequent everyday functioning outcomes.

Local Improvement Results for Anderson Acceleration with Inaccurate Function Evaluations

DOE PAGES

Toth, Alex; Ellis, J. Austin; Evans, Tom; ...

2017-10-26

Here, we analyze the convergence of Anderson acceleration when the fixed point map is corrupted with errors. We also consider uniformly bounded errors and stochastic errors with infinite tails. We prove local improvement results which describe the performance of the iteration up to the point where the accuracy of the function evaluation causes the iteration to stagnate. We illustrate the results with examples from neutronics.

Local Improvement Results for Anderson Acceleration with Inaccurate Function Evaluations

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

Toth, Alex; Ellis, J. Austin; Evans, Tom

Here, we analyze the convergence of Anderson acceleration when the fixed point map is corrupted with errors. We also consider uniformly bounded errors and stochastic errors with infinite tails. We prove local improvement results which describe the performance of the iteration up to the point where the accuracy of the function evaluation causes the iteration to stagnate. We illustrate the results with examples from neutronics.

Systems biology solutions for biochemical production challenges.

PubMed

Hansen, Anne Sofie Lærke; Lennen, Rebecca M; Sonnenschein, Nikolaus; Herrgård, Markus J

2017-06-01

There is an urgent need to significantly accelerate the development of microbial cell factories to produce fuels and chemicals from renewable feedstocks in order to facilitate the transition to a biobased society. Methods commonly used within the field of systems biology including omics characterization, genome-scale metabolic modeling, and adaptive laboratory evolution can be readily deployed in metabolic engineering projects. However, high performance strains usually carry tens of genetic modifications and need to operate in challenging environmental conditions. This additional complexity compared to basic science research requires pushing systems biology strategies to their limits and often spurs innovative developments that benefit fields outside metabolic engineering. Here we survey recent advanced applications of systems biology methods in engineering microbial production strains for biofuels and -chemicals. Copyright © 2017 The Authors. Published by Elsevier Ltd.. All rights reserved.

Multi-tissue DNA methylation age predictor in mouse.

PubMed

Stubbs, Thomas M; Bonder, Marc Jan; Stark, Anne-Katrien; Krueger, Felix; von Meyenn, Ferdinand; Stegle, Oliver; Reik, Wolf

2017-04-11

DNA methylation changes at a discrete set of sites in the human genome are predictive of chronological and biological age. However, it is not known whether these changes are causative or a consequence of an underlying ageing process. It has also not been shown whether this epigenetic clock is unique to humans or conserved in the more experimentally tractable mouse. We have generated a comprehensive set of genome-scale base-resolution methylation maps from multiple mouse tissues spanning a wide range of ages. Many CpG sites show significant tissue-independent correlations with age which allowed us to develop a multi-tissue predictor of age in the mouse. Our model, which estimates age based on DNA methylation at 329 unique CpG sites, has a median absolute error of 3.33 weeks and has similar properties to the recently described human epigenetic clock. Using publicly available datasets, we find that the mouse clock is accurate enough to measure effects on biological age, including in the context of interventions. While females and males show no significant differences in predicted DNA methylation age, ovariectomy results in significant age acceleration in females. Furthermore, we identify significant differences in age-acceleration dependent on the lipid content of the diet. Here we identify and characterise an epigenetic predictor of age in mice, the mouse epigenetic clock. This clock will be instrumental for understanding the biology of ageing and will allow modulation of its ticking rate and resetting the clock in vivo to study the impact on biological age.

The isolation limits of stochastic vibration

NASA Technical Reports Server (NTRS)

Knopse, C. R.; Allaire, P. E.

1993-01-01

The vibration isolation problem is formulated as a 1D kinematic problem. The geometry of the stochastic wall trajectories arising from the stroke constraint is defined in terms of their significant extrema. An optimal control solution for the minimum acceleration return path determines a lower bound on platform mean square acceleration. This bound is expressed in terms of the probability density function on the significant maxima and the conditional fourth moment of the first passage time inverse. The first of these is found analytically while the second is found using a Monte Carlo simulation. The rms acceleration lower bound as a function of available space is then determined through numerical quadrature.

Miniature penetrator (MinPen) acceleration recorder development test

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

Franco, R.J.; Platzbecker, M.R.

1998-08-01

The Telemetry Technology Development Department at Sandia National Laboratories actively develops and tests acceleration recorders for penetrating weapons. This new acceleration recorder (MinPen) utilizes a microprocessor-based architecture for operational flexibility while maintaining electronics and packaging techniques developed over years of penetrator testing. MinPen has been demonstrated to function in shock environments up to 20,000 Gs. The MinPen instrumentation development has resulted in a rugged, versatile, miniature acceleration recorder and is a valuable tool for penetrator testing in a wide range of applications.

Response of long, flexible cantilever beams applied root motions. [spacecraft structures

NASA Technical Reports Server (NTRS)

Fralich, R. W.

1976-01-01

Results are presented for an analysis of the response of long, flexible cantilever beams to applied root rotational accelerations. Maximum values of deformation, slope, bending moment, and shear are found as a function of magnitude and duration of acceleration input. Effects of tip mass and its eccentricity and rotatory inertia on the response are also investigated. It is shown that flexible beams can withstand large root accelerations provided the period of applied acceleration can be kept small relative to the beam fundamental period.

Cosmic-ray shock acceleration in oblique MHD shocks

NASA Technical Reports Server (NTRS)

Webb, G. M.; Drury, L. OC.; Volk, H. J.

1986-01-01

A one-dimensional, steady-state hydrodynamical model of cosmic-ray acceleration at oblique MHD shocks is presented. Upstream of the shock the incoming thermal plasma is subject to the adverse pressure gradient of the accelerated particles, the J x B force, as well as the thermal gas pressure gradient. The efficiency of the acceleration of cosmic-rays at the shock as a function of the upstream magnetic field obliquity and upstream plasma beta is investigated. Astrophysical applications of the results are briefly discussed.

Testing relativistic electron acceleration mechanisms

NASA Astrophysics Data System (ADS)

Green, Janet Carol

2002-09-01

This dissertation tests models of relativistic electron acceleration in the earth's outer radiation belt. The models fall into two categories: external and internal. External acceleration models transport and accelerate electrons from a source region in the outer magnetosphere to the inner magnetosphere. Internal acceleration models accelerate a population of electrons already present in the inner magnetosphere. In this dissertation, we test one specific external acceleration mechanism, perform a general test that differentiates between internal and external acceleration models, and test one promising internal acceleration model. We test the models using Polar-HIST data that we transform into electron phase space density (PSD) as a function of adiabatic invariants. We test the ultra low frequency (ULF) wave enhanced radial diffusion external acceleration mechanism by looking for a causal relationship between increased wave power and increased electron PSD at three L* values. One event with increased wave power at two L* values and no subsequent PSD increase does not support the model suggesting that ULF wave power alone is not sufficient to cause an electron response. Excessive loss of electrons and the duration of wave power do not explain the lack of a PSD enhancement at low L*. We differentiate between internal and external acceleration mechanisms by examining the radial profile of electron PSD. We observe PSD profiles that depend on local time. Nightside profiles are highly dependent on the magnetic field model used to calculate PSD as a function of adiabatic invariants and are not reliable. Dayside PSD profiles are more robust and consistent with internal acceleration of electrons. We test one internal acceleration model, the whistler/electromagnetic ion cyclotron wave model, by comparing observed pitch angle distributions to those predicted by the model using a superposed epoch analysis. The observations show pitch angle distributions corresponding to electrons with energy >=4.0 MeV becoming more peaked at 90° during the storm recovery phase. The observation is consistent with but does not confirm the model. Our tests indicate that relativistic electrons are accelerated by an internal source acceleration mechanism but we do not identify a unique mechanism.

Engineering plant metabolism into microbes: from systems biology to synthetic biology.

PubMed

Xu, Peng; Bhan, Namita; Koffas, Mattheos A G

2013-04-01

Plant metabolism represents an enormous repository of compounds that are of pharmaceutical and biotechnological importance. Engineering plant metabolism into microbes will provide sustainable solutions to produce pharmaceutical and fuel molecules that could one day replace substantial portions of the current fossil-fuel based economy. Metabolic engineering entails targeted manipulation of biosynthetic pathways to maximize yields of desired products. Recent advances in Systems Biology and the emergence of Synthetic Biology have accelerated our ability to design, construct and optimize cell factories for metabolic engineering applications. Progress in predicting and modeling genome-scale metabolic networks, versatile gene assembly platforms and delicate synthetic pathway optimization strategies has provided us exciting opportunities to exploit the full potential of cell metabolism. In this review, we will discuss how systems and synthetic biology tools can be integrated to create tailor-made cell factories for efficient production of natural products and fuel molecules in microorganisms. Copyright © 2012 Elsevier Ltd. All rights reserved.

Applications of laser wakefield accelerator-based light sources

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

Albert, Felicie; Thomas, Alec G. R.

Laser-wakefield accelerators (LWFAs) were proposed more than three decades ago, and while they promise to deliver compact, high energy particle accelerators, they will also provide the scientific community with novel light sources. In a LWFA, where an intense laser pulse focused onto a plasma forms an electromagnetic wave in its wake, electrons can be trapped and are now routinely accelerated to GeV energies. From terahertz radiation to gamma-rays, this article reviews light sources from relativistic electrons produced by LWFAs, and discusses their potential applications. Betatron motion, Compton scattering and undulators respectively produce x-rays or gamma-rays by oscillating relativistic electrons inmore » the wakefield behind the laser pulse, a counter-propagating laser field, or a magnetic undulator. Other LWFA-based light sources include bremsstrahlung and terahertz radiation. Here, we first evaluate the performance of each of these light sources, and compare them with more conventional approaches, including radio frequency accelerators or other laser-driven sources. We have then identified applications, which we discuss in details, in a broad range of fields: medical and biological applications, military, defense and industrial applications, and condensed matter and high energy density science.« less

Applications of laser wakefield accelerator-based light sources

DOE PAGES

Albert, Felicie; Thomas, Alec G. R.

2016-10-01

Laser-wakefield accelerators (LWFAs) were proposed more than three decades ago, and while they promise to deliver compact, high energy particle accelerators, they will also provide the scientific community with novel light sources. In a LWFA, where an intense laser pulse focused onto a plasma forms an electromagnetic wave in its wake, electrons can be trapped and are now routinely accelerated to GeV energies. From terahertz radiation to gamma-rays, this article reviews light sources from relativistic electrons produced by LWFAs, and discusses their potential applications. Betatron motion, Compton scattering and undulators respectively produce x-rays or gamma-rays by oscillating relativistic electrons inmore » the wakefield behind the laser pulse, a counter-propagating laser field, or a magnetic undulator. Other LWFA-based light sources include bremsstrahlung and terahertz radiation. Here, we first evaluate the performance of each of these light sources, and compare them with more conventional approaches, including radio frequency accelerators or other laser-driven sources. We have then identified applications, which we discuss in details, in a broad range of fields: medical and biological applications, military, defense and industrial applications, and condensed matter and high energy density science.« less

Accelerated Evolution and Functional Divergence of the Dim Light Visual Pigment Accompanies Cichlid Colonization of Central America.

PubMed

Hauser, Frances E; Ilves, Katriina L; Schott, Ryan K; Castiglione, Gianni M; López-Fernández, Hernán; Chang, Belinda S W

2017-10-01

Cichlids encompass one of the most diverse groups of fishes in South and Central America, and show extensive variation in life history, morphology, and colouration. While studies of visual system evolution in cichlids have focussed largely on the African rift lake species flocks, Neotropical cichlids offer a unique opportunity to investigate visual system evolution at broader temporal and geographic scales. South American cichlid colonization of Central America has likely promoted accelerated rates of morphological evolution in Central American lineages as they encountered reduced competition, renewed ecological opportunity, and novel aquatic habitats. To investigate whether such transitions have influenced molecular evolution of vision in Central American cichlids, we sequenced the dim-light rhodopsin gene in 101 Neotropical cichlid species, spanning the diversity of the clade. We find strong evidence for increased rates of evolution in Central American cichlid rhodopsin relative to South American lineages, and identify several sites under positive selection in rhodopsin that likely contribute to adaptation to different photic environments. We expressed a Neotropical cichlid rhodopsin protein invitro for the first time, and found that while its spectral tuning properties were characteristic of typical vertebrate rhodopsin pigments, the rate of decay of its active signalling form was much slower, consistent with dim light adaptation in other vertebrate rhodopsins. Using site-directed mutagenesis combined with spectroscopic assays, we found that a key amino acid substitution present in some Central American cichlids accelerates the rate of decay of active rhodopsin, which may mediate adaptation to clear water habitats. © The Author 2017. Published by Oxford University Press on behalf of the Society for Molecular Biology and Evolution. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

Study on Online Analysis of Transfer Function of Variable-Speed Rolling Mill Motor with Shaft Torsional Vibration Systems

NASA Astrophysics Data System (ADS)

Tamaoki, Toshifumi; Takanezawa, Makoto; Kimoto, Masanori; Morita, Noboru; Hoshino, Takeo; Hashizume, Kenji

The torsional vibration between metal rolling rolls and a rolling mill motor, may occur in recent days, as a result of higher speed response adjustment for variable speed rolling mill motor drive system. Issues in this paper are focused on excess acceleration value, in tangential direction of the mill motor rotor, which is caused by the motor shaft torsional resonance at the white noise signal superposition to the speed reference signal of the motor drive system for the online transfer function analysis. As a result of the acceleration analysis, the acceleration values in “G” (Relative acceleration value on the basis of Gravity) can be plotted on “Bode-Diagram”, which is namely frequency response for the speed signal amplitude transmission ratio. In addition, relation between the white noise amplitude reduction and the transfer function analysis accuracy deterioration is also examined, in this paper. As the amplitude of the white noise decreases, the analysis error increases because of the reduction in the resolution when the amplitude of the white noise signal is small.

Atypical basic movement kinematics in autism spectrum conditions

PubMed Central

Blakemore, Sarah-Jayne; Press, Clare

2013-01-01

Individuals with autism spectrum conditions have difficulties in understanding and responding appropriately to others. Additionally, they demonstrate impaired perception of biological motion and problems with motor control. Here we investigated whether individuals with autism move with an atypical kinematic profile, which might help to explain perceptual and motor impairments, and in principle may contribute to some of their higher level social problems. We recorded trajectory, velocity, acceleration and jerk while adult participants with autism and a matched control group conducted horizontal sinusoidal arm movements. Additionally, participants with autism took part in a biological motion perception task in which they classified observed movements as ‘natural’ or ‘unnatural’. Results show that individuals with autism moved with atypical kinematics; they did not minimize jerk to the same extent as the matched typical control group, and moved with greater acceleration and velocity. The degree to which kinematics were atypical was correlated with a bias towards perceiving biological motion as ‘unnatural’ and with the severity of autism symptoms as measured by the Autism Diagnostic Observation Schedule. We suggest that fundamental differences in movement kinematics in autism might help to explain their problems with motor control. Additionally, developmental experience of their own atypical kinematic profiles may lead to disrupted perception of others’ actions. PMID:23983031

The role of epigenetics in cardiovascular health and ageing: A focus on physical activity and nutrition.

PubMed

Wallace, Robert G; Twomey, Laura C; Custaud, Marc-Antoine; Turner, Jonathan D; Moyna, Niall; Cummins, Philip M; Murphy, Ronan P

2017-11-16

The cardiovascular system is responsible for transport of blood and nutrients to tissues, and is pivotal to the physiological health and longevity. Epigenetic modification is a natural, age-associated process resulting in highly contextualised gene expression with clear implications for cell differentiation and disease onset. Biological/epigenetic age is independent of chronological age, constituting a highly reflective snapshot of an individual's overall health. Accelerated vascular ageing is of major concern, effectively lowering disease threshold. Age-related chronic illness involves a complex interplay between many biological processes and is modulated by non-modifiable and modifiable risk factors. These alter the static genome by a number of epigenetic mechanisms, which change gene expression in an age and lifestyle dependent manner. This 'epigenetic drift' impacts health and contributes to the etiology of chronic illness. Lifestyle factors may cause acceleration of this epigenetic "clock", pre-disposing individuals to cardiovascular disease. Nutrition and physical activity are modifiable lifestyle choices, synergistically contributing to cardiovascular health. They represent a powerful potential epigenetic intervention point for effective cardiovascular protective and management strategies. Thus, together with traditional risk factors, monitoring the epigenetic signature of ageing may prove beneficial for tailoring lifestyle to fit biology - supporting the increasingly popular concept of "ageing well". Copyright © 2017 Elsevier B.V. All rights reserved.

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.

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.

Effective correlator for RadioAstron project

NASA Astrophysics Data System (ADS)

Sergeev, Sergey

This paper presents the implementation of programme FX-correlator for Very Long Baseline Interferometry, adapted for the project "RadioAstron". Software correlator implemented for heterogeneous computing systems using graphics accelerators. It is shown that for the task interferometry implementation of the graphics hardware has a high efficiency. The host processor of heterogeneous computing system, performs the function of forming the data flow for graphics accelerators, the number of which corresponds to the number of frequency channels. So, for the Radioastron project, such channels is seven. Each accelerator is perform correlation matrix for all bases for a single frequency channel. Initial data is converted to the floating-point format, is correction for the corresponding delay function and computes the entire correlation matrix simultaneously. Calculation of the correlation matrix is performed using the sliding Fourier transform. Thus, thanks to the compliance of a solved problem for architecture graphics accelerators, managed to get a performance for one processor platform Kepler, which corresponds to the performance of this task, the computing cluster platforms Intel on four nodes. This task successfully scaled not only on a large number of graphics accelerators, but also on a large number of nodes with multiple accelerators.

Particle acceleration magnetic field generation, and emission in Relativistic pair jets

NASA Technical Reports Server (NTRS)

Nishikawa, K.-I.; Ramirez-Ruiz, E.; Hardee, P.; Hededal, C.; Kouveliotou, C.; Fishman, G. J.

2005-01-01

Plasma waves and their associated instabilities (e.g., the Buneman instability, two-streaming instability, and the Weibel instability) are responsible for particle acceleration in relativistic pair jets. Using a 3-D relativistic electromagnetic particle (REMP) code, we have investigated particle acceleration associated with a relativistic pair jet propagating through a pair plasma. Simulations show that the Weibel instability created in the collisionless shock accelerates particles perpendicular and parallel to the jet propagation direction. Simulation results show that this instability generates and amplifies highly nonuniform, small-scale magnetic fields, which contribute to the electron's transverse deflection behind the jet head. The "jitter' I radiation from deflected electrons can have different properties than synchrotron radiation which is calculated in a uniform magnetic field. This jitter radiation may be important to understanding the complex time evolution and/or spectral structure in gamma-ray bursts, relativistic jets, and supernova remnants. The growth rate of the Weibel instability and the resulting particle acceleration depend on the magnetic field strength and orientation, and on the initial particle distribution function. In this presentation we explore some of the dependencies of the Weibel instability and resulting particle acceleration on the magnetic field strength and orientation, and the particle distribution function.

Microgravity acceleration measurement and environment characterization science (17-IML-1)

NASA Technical Reports Server (NTRS)

1992-01-01

The Space Acceleration Measurement System (SAMS) is a general purpose instrumentation system designed to measure the accelerations onboard the Shuttle Orbiter and Shuttle/Spacelab vehicles. These measurements are used to support microgravity experiments and investigation into the microgravity environment of the vehicle. Acceleration measurements can be made at locations remote from the SAMS main instrumentation unit by the use of up to three remote triaxial sensor heads. The prime objective for SAMS on the International Microgravity Lab (IML-1) mission will be to measure the accelerations experienced by the Fluid Experiment System (FES). The SAMS acceleration measurements for FES will be complemented by low level, low frequency acceleration measurements made by the Orbital Acceleration Research Experiment (OARE) installed on the shuttle. Secondary objectives for SAMS will be to measure accelerations at several specific locations to enable the acceleration transfer function of the Spacelab module to be analyzed. This analysis effort will be in conjunction with similar measurements analyses on other Spacelab missions.

Non-constant thermal regimes enhance overwintering success and accelerate diapause development for Smicronyx fulvus (Coleoptera: Curculionidae)

USDA-ARS?s Scientific Manuscript database

Recent populations of the red sunflower seed weevil, Smicronyx fulvus LeConte (Coleoptera: Curculionidae) have been inconsistent or declining, particularly in North Dakota. Consequently, field and laboratory research on weevil biology, including development of resistant germplasm, have been limited....

Subsurface drainage erodes forested granitic terrane

Treesearch

Philip Durgin

1984-01-01

Abstract - Solution and landsliding, the dominant erosion processes in undisturbed forested mountainous watersheds, are both influenced by subsurface drainage. Biological processes that generate organic acids accelerate loss of dissolved solids by promoting the dissolution of primary minerals in granitic rock. These organic acids can also disperse the secondary...

ANNUAL REPORT

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

None

1959-07-01

The national laboratory concept, laboratory objectives, the staff, research facilities. research activities, and administration are discussed in general terms and a financial statement is given. Fairly detailed accounts are given for the research programs in the fields of physics, accelerator development, instrumentation, applied mathematics, chemistry, nuclear engineering, biology, and medicine. (W.D.M.)

Introduction of biological agents into vegetative buffer to enhance rhizodegradation of atrazine

USDA-ARS?s Scientific Manuscript database

Introducing atrazine (ATR) degraders into riparian vegetative buffer strips (VBS) can be a promising bioremediation approach to accelerate the degradation of ATR and its degradation products deposited into VBS by surface runoff. A growth chamber study was conducted to investigated the synergistic ef...

Phase II, Compact AMS System for Biological Tracer Detection Final Report CRADA No. TSV-1533-96

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

Brown, T. A.; Hamm, R. W.

2017-11-01

The objective of this collaboration between LLNL and AccSys Technology, Inc. of Pleasanton, California was to build and demonstrate a low cost, compact tritium (3H) Accelerator Mass Spectrometer (AMS) system matched to the requirements of biomedical research.

Testing of a Loop Heat Pipe Subjective to Variable Accelerations. Part 2; Temperature Stability

NASA Technical Reports Server (NTRS)

Ku, Jentung; Ottenstein, Laura; Kaya, Taril; Rogers, Paul; Hoff, Craig

2000-01-01

The effect of accelerating forces on the performance of loop heat pipes (LHP) is of interest and importance to terrestrial and space applications. LHP's are being considered for cooling of military combat vehicles and for spinning spacecraft. In order to investigate the effect of an accelerating force on LHP operation, a miniature LHP was installed on a spin table. Variable accelerating forces were imposed on the LHP by spinning the table at different angular speeds. Several patterns of accelerating forces were applied, i.e. continuous spin at different speeds and periodic spin at different speeds and frequencies. The resulting accelerations ranged from 1.17 g's to 4.7 g's. This paper presents the second part of the experimental study, i.e. the effect of an accelerating force on the LHP operating temperature. It has been known that in stationary tests the LHP operating temperature is a function of the evaporator power and the condenser sink temperature when the compensation temperature is not actively controlled. Results of this test program indicate that any change in the accelerating force will result in a chance in the LHP operating temperature through its influence on the fluid distribution in the evaporator, condenser and compensation chamber. However, the effect is not universal, rather it is a function of other test conditions. A steady, constant acceleration may result in an increase or decrease of the operating temperature, while a periodic spin will lead to a quasi-steady operating temperature over a sufficient time interval. In addition, an accelerating force may lead to temperature hysteresis and changes in the temperature oscillation. In spite of all these effects, the LHP continued to operate without any problems in all tests.

JDiffraction: A GPGPU-accelerated JAVA library for numerical propagation of scalar wave fields

NASA Astrophysics Data System (ADS)

Piedrahita-Quintero, Pablo; Trujillo, Carlos; Garcia-Sucerquia, Jorge

2017-05-01

JDiffraction, a GPGPU-accelerated JAVA library for numerical propagation of scalar wave fields, is presented. Angular spectrum, Fresnel transform, and Fresnel-Bluestein transform are the numerical algorithms implemented in the methods and functions of the library to compute the scalar propagation of the complex wavefield. The functionality of the library is tested with the modeling of easy to forecast numerical experiments and also with the numerical reconstruction of a digitally recorded hologram. The performance of JDiffraction is contrasted with a library written for C++, showing great competitiveness in the apparently less complex environment of JAVA language. JDiffraction also includes JAVA easy-to-use methods and functions that take advantage of the computation power of the graphic processing units to accelerate the processing times of 2048×2048 pixel images up to 74 frames per second.

Life's role in environmental regulation

NASA Astrophysics Data System (ADS)

Kump, L. R.

2016-12-01

The fusion of geological and biological perspectives on the operation of the Earth system is revolutionizing the way we think about the interactions of life and environment. No longer does life simply adapt to environmental change; those adaptations in turn modify the environment. Emerging from these interactions is the possibility of environmental regulation, the essence of Lovelock's Gaia Hypothesis. The long-term carbon cycle, for example, reflects a balance between the sources and sinks of carbon including volcanism, weathering of rocks exposed subaerially or on the seafloor, carbonate mineral formation, and the burial of organic carbon. The traditional view of these processes limits biological influences to the production and remineralization of organic matter and the formation of mineral skeletons. With the geobiological revolution we now also recognize the important role biological activity plays in accelerating weathering processes. Weathering rates depend on a variety of factors that we represent in numerical models with rate laws we adapt from inorganic chemistry. These can be characterized as zero-order (independent), first-order (linear), etc. and these functions are all monotonic. Yet one of the hallmark features of life is that it responds to changes in its environment parabolically: rates of physiological processes exhibit minima, optima, and maxima with respect to environment variables (temperature, pH, salinity, pO2, pCO2, . . .). Incorporation of physiological-style rate laws, and in general the explicit representation of life in models of Earth surface processes, demonstrates how the biota influence environmental stability on geologic time scales.

Stem Cells: A Renaissance in Human Biology Research.

PubMed

Wu, Jun; Izpisua Belmonte, Juan Carlos

2016-06-16

The understanding of human biology and how it relates to that of other species represents an ancient quest. Limited access to human material, particularly during early development, has restricted researchers to only scratching the surface of this inherently challenging subject. Recent technological innovations, such as single cell "omics" and human stem cell derivation, have now greatly accelerated our ability to gain insights into uniquely human biology. The opportunities afforded to delve molecularly into scarce material and to model human embryogenesis and pathophysiological processes are leading to new insights of human development and are changing our understanding of disease and choice of therapy options. Copyright © 2016 Elsevier Inc. All rights reserved.

Electrical Chips for Biological Point-of-Care Detection.

PubMed

Reddy, Bobby; Salm, Eric; Bashir, Rashid

2016-07-11

As the future of health care diagnostics moves toward more portable and personalized techniques, there is immense potential to harness the power of electrical signals for biological sensing and diagnostic applications at the point of care. Electrical biochips can be used to both manipulate and sense biological entities, as they can have several inherent advantages, including on-chip sample preparation, label-free detection, reduced cost and complexity, decreased sample volumes, increased portability, and large-scale multiplexing. The advantages of fully integrated electrical biochip platforms are particularly attractive for point-of-care systems. This review summarizes these electrical lab-on-a-chip technologies and highlights opportunities to accelerate the transition from academic publications to commercial success.

Designer diatom episomes delivered by bacterial conjugation

DOE PAGES

Karas, Bogumil J.; Diner, Rachel E.; Lefebvre, Stephane C.; ...

2015-04-21

Eukaryotic microalgae hold great promise for the bioproduction of fuels and higher value chemicals. However, compared with model genetic organisms such as Escherichia coli and Saccharomyces cerevisiae, characterization of the complex biology and biochemistry of algae and strain improvement has been hampered by the inefficient genetic tools. To date, many algal species are transformable only via particle bombardment, and the introduced DNA is integrated randomly into the nuclear genome. Here we describe the first nuclear episomal vector for diatoms and a plasmid delivery method via conjugation from Escherichia coli to the diatoms Phaeodactylum tricornutum and Thalassiosira pseudonana. We identify amore » yeast-derived sequence that enables stable episome replication in these diatoms even in the absence of antibiotic selection and show that episomes are maintained as closed circles at copy number equivalent to native chromosomes. This highly efficient genetic system facilitates high-throughput functional characterization of algal genes and accelerates molecular phytoplankton research.« less

Sophisticated digestive systems in early arthropods.

PubMed

Vannier, Jean; Liu, Jianni; Lerosey-Aubril, Rudy; Vinther, Jakob; Daley, Allison C

2014-05-02

Understanding the way in which animals diversified and radiated during their early evolutionary history remains one of the most captivating of scientific challenges. Integral to this is the 'Cambrian explosion', which records the rapid emergence of most animal phyla, and for which the triggering and accelerating factors, whether environmental or biological, are still unclear. Here we describe exceptionally well-preserved complex digestive organs in early arthropods from the early Cambrian of China and Greenland with functional similarities to certain modern crustaceans and trace these structures through the early evolutionary lineage of fossil arthropods. These digestive structures are assumed to have allowed for more efficient digestion and metabolism, promoting carnivory and macrophagy in early arthropods via predation or scavenging. This key innovation may have been of critical importance in the radiation and ecological success of Arthropoda, which has been the most diverse and abundant invertebrate phylum since the Cambrian.

Discovery and characterization of new O-methyltransferase from the genome of the lignin-degrading fungus Phanerochaete chrysosporium for enhanced lignin degradation.

PubMed

Thanh Mai Pham, Le; Kim, Yong Hwan

2016-01-01

Using bioinformatic homology search tools, this study utilized sequence phylogeny, gene organization and conserved motifs to identify members of the family of O-methyltransferases from lignin-degrading fungus Phanerochaete chrysosporium. The heterologous expression and characterization of O-methyltransferases from P. chrysosporium were studied. The expressed protein utilized S-(5'-adenosyl)-L-methionine p-toluenesulfonate salt (SAM) and methylated various free-hydroxyl phenolic compounds at both meta and para site. In the same motif, O-methyltransferases were also identified in other white-rot fungi including Bjerkandera adusta, Ceriporiopsis (Gelatoporia) subvermispora B, and Trametes versicolor. As free-hydroxyl phenolic compounds have been known as inhibitors for lignin peroxidase, the presence of O-methyltransferases in white-rot fungi suggested their biological functions in accelerating lignin degradation in white-rot basidiomycetes by converting those inhibitory groups into non-toxic methylated phenolic ones. Copyright © 2015 Elsevier Inc. All rights reserved.

Model-free inference of direct network interactions from nonlinear collective dynamics.

PubMed

Casadiego, Jose; Nitzan, Mor; Hallerberg, Sarah; Timme, Marc

2017-12-19

The topology of interactions in network dynamical systems fundamentally underlies their function. Accelerating technological progress creates massively available data about collective nonlinear dynamics in physical, biological, and technological systems. Detecting direct interaction patterns from those dynamics still constitutes a major open problem. In particular, current nonlinear dynamics approaches mostly require to know a priori a model of the (often high dimensional) system dynamics. Here we develop a model-independent framework for inferring direct interactions solely from recording the nonlinear collective dynamics generated. Introducing an explicit dependency matrix in combination with a block-orthogonal regression algorithm, the approach works reliably across many dynamical regimes, including transient dynamics toward steady states, periodic and non-periodic dynamics, and chaos. Together with its capabilities to reveal network (two point) as well as hypernetwork (e.g., three point) interactions, this framework may thus open up nonlinear dynamics options of inferring direct interaction patterns across systems where no model is known.

Designer diatom episomes delivered by bacterial conjugation

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

Karas, Bogumil J.; Diner, Rachel E.; Lefebvre, Stephane C.

Eukaryotic microalgae hold great promise for the bioproduction of fuels and higher value chemicals. However, compared with model genetic organisms such as Escherichia coli and Saccharomyces cerevisiae, characterization of the complex biology and biochemistry of algae and strain improvement has been hampered by the inefficient genetic tools. To date, many algal species are transformable only via particle bombardment, and the introduced DNA is integrated randomly into the nuclear genome. Here we describe the first nuclear episomal vector for diatoms and a plasmid delivery method via conjugation from Escherichia coli to the diatoms Phaeodactylum tricornutum and Thalassiosira pseudonana. We identify amore » yeast-derived sequence that enables stable episome replication in these diatoms even in the absence of antibiotic selection and show that episomes are maintained as closed circles at copy number equivalent to native chromosomes. This highly efficient genetic system facilitates high-throughput functional characterization of algal genes and accelerates molecular phytoplankton research.« less

Enhanced bioactivity of internally functionalized cationic dendrimers with PEG cores

PubMed Central

Albertazzi, Lorenzo; Mickler, Frauke M.; Pavan, Giovanni M.; Salomone, Fabrizio; Bardi, Giuseppe; Panniello, Mariangela; Amir, Elizabeth; Kang, Taegon; Killops, Kato L.; Bräuchle, Christoph; Amir, Roey J.; Hawker, Craig J.

2012-01-01

Hybrid dendritic-linear block copolymers based on a 4-arm polyethylene glycol (PEG) core were synthesized using an accelerated AB2/CD2 dendritic growth approach through orthogonal amine/epoxy and thiol-yne chemistries. The biological activity of these 4-arm and the corresponding 2-arm hybrid dendrimers revealed an enhanced, dendritic effect with an exponential increase in cell internalization concomitant with increasing amine end-groups and low cytotoxicity. Furthermore, the ability of these hybrid dendrimers to induce endosomal escape combined with their facile and efficient synthesis makes them attractive platforms for gene transfection. The 4-arm-based dendrimer showed significantly improved DNA binding and gene transfection capabilities in comparison with the 2-arm derivative. These results combined with the MD simulation indicate a significant effect of both the topology of the PEG core and the multivalency of these hybrid macromolecules, on their DNA binding and delivery capablities. PMID:23140570

Review of cyclotron production and quality control of ``High specific activity'' radionuclides for biomedical, biological, industrial and environmental applications at INFN-LASA

NASA Astrophysics Data System (ADS)

Birattari, C.; Bonardi, M.; Groppi, F.; Gini, L.

2001-12-01

At the "Radiochemistry Laboratory" of Accelerators and Applied Superconductivity Laboratory, LASA, a wide range of high specific activity radionuclides, RNs, have been produced in No Carrier Added form, for both basic research and application purposes. Use was made of the AVF proton cyclotron (K=45) of Milan University (up to 1987). More recently, the irradiations were carried out at the Scanditronix MC40 cyclotron (K=38; p, d, He-4 and He-3) of JRC-Ispra, Italy, of the European Community. In order to optimize the irradiation conditions for radioisotope production, a series of thin- and thick-target excitation functions have been experimentally determined. For each RN, a specific radiochemical separation has been developed in order to obtain GBq (mCi) amounts of the radiotracers in "high specific activity" No Carrier Added form (NCA).

Boosted Regeneration and Reduced Denervated Muscle Atrophy by NeuroHeal in a Pre-clinical Model of Lumbar Root Avulsion with Delayed Reimplantation.

PubMed

Romeo-Guitart, David; Forés, Joaquim; Navarro, Xavier; Casas, Caty

2017-09-20

The "gold standard" treatment of patients with spinal root injuries consists of delayed surgical reconnection of nerves. The sooner, the better, but problems such as injury-induced motor neuronal death and muscle atrophy due to long-term denervation mean that normal movement is not restored. Herein we describe a preclinical model of root avulsion with delayed reimplantation of lumbar roots that was used to establish a new adjuvant pharmacological treatment. Chronic treatment (up to 6 months) with NeuroHeal, a new combination drug therapy identified using a systems biology approach, exerted long-lasting neuroprotection, reduced gliosis and matrix proteoglycan content, accelerated nerve regeneration by activating the AKT pathway, promoted the formation of functional neuromuscular junctions, and reduced denervation-induced muscular atrophy. Thus, NeuroHeal is a promising treatment for spinal nerve root injuries and axonal regeneration after trauma.

Inferring time derivatives including cell growth rates using Gaussian processes

NASA Astrophysics Data System (ADS)

Swain, Peter S.; Stevenson, Keiran; Leary, Allen; Montano-Gutierrez, Luis F.; Clark, Ivan B. N.; Vogel, Jackie; Pilizota, Teuta

2016-12-01

Often the time derivative of a measured variable is of as much interest as the variable itself. For a growing population of biological cells, for example, the population's growth rate is typically more important than its size. Here we introduce a non-parametric method to infer first and second time derivatives as a function of time from time-series data. Our approach is based on Gaussian processes and applies to a wide range of data. In tests, the method is at least as accurate as others, but has several advantages: it estimates errors both in the inference and in any summary statistics, such as lag times, and allows interpolation with the corresponding error estimation. As illustrations, we infer growth rates of microbial cells, the rate of assembly of an amyloid fibril and both the speed and acceleration of two separating spindle pole bodies. Our algorithm should thus be broadly applicable.

Termites as targets and models for biotechnology.

PubMed

Scharf, Michael E

2015-01-07

Termites have many unique evolutionary adaptations associated with their eusocial lifestyles. Recent omics research has created a wealth of new information in numerous areas of termite biology (e.g., caste polyphenism, lignocellulose digestion, and microbial symbiosis) with wide-ranging applications in diverse biotechnological niches. Termite biotechnology falls into two categories: (a) termite-targeted biotechnology for pest management purposes, and (b) termite-modeled biotechnology for use in various industrial applications. The first category includes several candidate termiticidal modes of action such as RNA interference, digestive inhibition, pathogen enhancement, antimicrobials, endocrine disruption, and primer pheromone mimicry. In the second category, termite digestomes are deep resources for host and symbiont lignocellulases and other enzymes with applications in a variety of biomass, industrial, and processing applications. Moving forward, one of the most important approaches for accelerating advances in both termite-targeted and termite-modeled biotechnology will be to consider host and symbiont together as a single functional unit.

An overview of bioinformatics methods for modeling biological pathways in yeast.

PubMed

Hou, Jie; Acharya, Lipi; Zhu, Dongxiao; Cheng, Jianlin

2016-03-01

The advent of high-throughput genomics techniques, along with the completion of genome sequencing projects, identification of protein-protein interactions and reconstruction of genome-scale pathways, has accelerated the development of systems biology research in the yeast organism Saccharomyces cerevisiae In particular, discovery of biological pathways in yeast has become an important forefront in systems biology, which aims to understand the interactions among molecules within a cell leading to certain cellular processes in response to a specific environment. While the existing theoretical and experimental approaches enable the investigation of well-known pathways involved in metabolism, gene regulation and signal transduction, bioinformatics methods offer new insights into computational modeling of biological pathways. A wide range of computational approaches has been proposed in the past for reconstructing biological pathways from high-throughput datasets. Here we review selected bioinformatics approaches for modeling biological pathways inS. cerevisiae, including metabolic pathways, gene-regulatory pathways and signaling pathways. We start with reviewing the research on biological pathways followed by discussing key biological databases. In addition, several representative computational approaches for modeling biological pathways in yeast are discussed. © The Author 2015. Published by Oxford University Press. All rights reserved. For permissions, please email: journals.permissions@oup.com.

Microbially mediated carbon mineralization: Geoengineering a carbon-neutral mine

NASA Astrophysics Data System (ADS)

Power, I. M.; McCutcheon, J.; Harrison, A. L.; Wilson, S. A.; Dipple, G. M.; Southam, G.

2013-12-01

Ultramafic and mafic mine tailings are a potentially valuable feedstock for carbon mineralization, affording the mining industry an opportunity to completely offset their carbon emissions. Passive carbon mineralization has previously been documented at the abandoned Clinton Creek asbestos mine, and the active Diavik diamond mine and Mount Keith nickel mine, yet the majority of tailings remain unreacted. Examples of microbe-carbonate interactions at each mine suggest that biological pathways could be harnessed to promote carbon mineralization. In suitable environmental conditions, microbes can mediate geochemical processes to accelerate mineral dissolution, increase the supply of carbon dioxide (CO2), and induce carbonate precipitation, all of which may accelerate carbon mineralization. Tailings mineralogy and the availability of a CO2 point source are key considerations in designing tailings storage facilities (TSF) for optimizing carbon mineralization. We evaluate the efficacy of acceleration strategies including bioleaching, biologically induced carbonate precipitation, and heterotrophic oxidation of waste organics, as well as abiotic strategies including enhancing passive carbonation through modifying tailings management practices and use of CO2 point sources (Fig. 1). With the aim of developing carbon-neutral mines, implementation of carbon mineralization strategies into TSF design will be driven by economic incentives and public pressure for environmental sustainability in the mining industry. Figure 1. Schematic illustrating geoengineered scenarios for carbon mineralization of ultramafic mine tailings. Scenarios A and B are based on non-point and point sources of CO2, respectively.

Transport calculations and accelerator experiments needed for radiation risk assessment in space.

PubMed

Sihver, Lembit

2008-01-01

The major uncertainties on space radiation risk estimates in humans are associated to the poor knowledge of the biological effects of low and high LET radiation, with a smaller contribution coming from the characterization of space radiation field and its primary interactions with the shielding and the human body. However, to decrease the uncertainties on the biological effects and increase the accuracy of the risk coefficients for charged particles radiation, the initial charged-particle spectra from the Galactic Cosmic Rays (GCRs) and the Solar Particle Events (SPEs), and the radiation transport through the shielding material of the space vehicle and the human body, must be better estimated Since it is practically impossible to measure all primary and secondary particles from all possible position-projectile-target-energy combinations needed for a correct risk assessment in space, accurate particle and heavy ion transport codes must be used. These codes are also needed when estimating the risk for radiation induced failures in advanced microelectronics, such as single-event effects, etc., and the efficiency of different shielding materials. It is therefore important that the models and transport codes will be carefully benchmarked and validated to make sure they fulfill preset accuracy criteria, e.g. to be able to predict particle fluence, dose and energy distributions within a certain accuracy. When validating the accuracy of the transport codes, both space and ground based accelerator experiments are needed The efficiency of passive shielding and protection of electronic devices should also be tested in accelerator experiments and compared to simulations using different transport codes. In this paper different multipurpose particle and heavy ion transport codes will be presented, different concepts of shielding and protection discussed, as well as future accelerator experiments needed for testing and validating codes and shielding materials.

Stepping into the omics era: Opportunities and challenges for biomaterials science and engineering.

PubMed

Groen, Nathalie; Guvendiren, Murat; Rabitz, Herschel; Welsh, William J; Kohn, Joachim; de Boer, Jan

2016-04-01

The research paradigm in biomaterials science and engineering is evolving from using low-throughput and iterative experimental designs towards high-throughput experimental designs for materials optimization and the evaluation of materials properties. Computational science plays an important role in this transition. With the emergence of the omics approach in the biomaterials field, referred to as materiomics, high-throughput approaches hold the promise of tackling the complexity of materials and understanding correlations between material properties and their effects on complex biological systems. The intrinsic complexity of biological systems is an important factor that is often oversimplified when characterizing biological responses to materials and establishing property-activity relationships. Indeed, in vitro tests designed to predict in vivo performance of a given biomaterial are largely lacking as we are not able to capture the biological complexity of whole tissues in an in vitro model. In this opinion paper, we explain how we reached our opinion that converging genomics and materiomics into a new field would enable a significant acceleration of the development of new and improved medical devices. The use of computational modeling to correlate high-throughput gene expression profiling with high throughput combinatorial material design strategies would add power to the analysis of biological effects induced by material properties. We believe that this extra layer of complexity on top of high-throughput material experimentation is necessary to tackle the biological complexity and further advance the biomaterials field. In this opinion paper, we postulate that converging genomics and materiomics into a new field would enable a significant acceleration of the development of new and improved medical devices. The use of computational modeling to correlate high-throughput gene expression profiling with high throughput combinatorial material design strategies would add power to the analysis of biological effects induced by material properties. We believe that this extra layer of complexity on top of high-throughput material experimentation is necessary to tackle the biological complexity and further advance the biomaterials field. Copyright © 2016. Published by Elsevier Ltd.

Chemical genetic inhibition of Mps1 in stable human cell lines reveals novel aspects of Mps1 function in mitosis.

PubMed

Sliedrecht, Tale; Zhang, Chao; Shokat, Kevan M; Kops, Geert J P L

2010-04-22

Proper execution of chromosome segregation relies on tight control of attachment of chromosomes to spindle microtubules. This is monitored by the mitotic checkpoint that allows chromosome segregation only when all chromosomes are stably attached. Proper functioning of the attachment and checkpoint processes is thus important to prevent chromosomal instability. Both processes rely on the mitotic kinase Mps1. We present here two cell lines in which endogenous Mps1 has been stably replaced with a mutant kinase (Mps1-as) that is specifically inhibited by bulky PP1 analogs. Mps1 inhibition in these cell lines is highly penetrant and reversible. Timed inhibition during bipolar spindle assembly shows that Mps1 is critical for attachment error-correction and confirms its role in Aurora B regulation. We furthermore show that Mps1 has multiple controls over mitotic checkpoint activity. Mps1 inhibition precludes Mad1 localization to unattached kinetochores but also accelerates mitosis. This acceleration correlates with absence of detectable mitotic checkpoint complex after Mps1 inhibition. Finally, we show that short-term inhibition of Mps1 catalytic activity is sufficient to kill cells. Mps1 is involved in the regulation of multiple key processes that ensure correct chromosome segregation and is a promising target for inhibition in anti-cancer strategies. We report here two cell lines that allow specific and highly penetrant inhibition of Mps1 in a reproducible manner through the use of chemical genetics. Using these cell lines we confirm previously suggested roles for Mps1 activity in mitosis, present evidence for novel functions and examine cell viability after short and prolonged Mps1 inhibition. These cell lines present the best cellular model system to date for investigations into Mps1 biology and the effects of penetrance and duration of Mps1 inhibition on cell viability.

Hardware accelerator of convolution with exponential function for image processing applications

NASA Astrophysics Data System (ADS)

Panchenko, Ivan; Bucha, Victor

2015-12-01

In this paper we describe a Hardware Accelerator (HWA) for fast recursive approximation of separable convolution with exponential function. This filter can be used in many Image Processing (IP) applications, e.g. depth-dependent image blur, image enhancement and disparity estimation. We have adopted this filter RTL implementation to provide maximum throughput in constrains of required memory bandwidth and hardware resources to provide a power-efficient VLSI implementation.

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.

Experimental Investigation of Hexagon Stability in Two Frequency Forced Faraday Waves

NASA Astrophysics Data System (ADS)

Ding, Yu; Umbanhowar, Paul

2003-03-01

We have conducted experiments on a deep layer of silicone oil vertically oscillated with an acceleration a(t) = Am sin(m ω t + φ_m) + An sin(n ω t + φ_n). The stability of hexagonal surface wave patterns is investigated as a function of the overall acceleration, the ratio m:n, and the phase of the two rationally related driving frequencies. When the ratio A_m/An is chosen so the system is near a co-dimension two point, the stability of hexagons above onset is determined by the acceleration amplitude and the relative phase. Recent results by Porter and Silver (J. Porter and M. Silber, Phys. Rev. Lett. 084501, 2002) predicts that the range of pattern stability above onset as a function of acceleration is determined by cos(Φ), where Φ = π/4 - m φn / 2- n φm /2. We have tested this prediction for a number of m:n ratios and for various values of the dimensionless damping coefficient γ. We find that the patterns exhibit the predicted functional dependence on s(Φ) but with an additional phase offset. We measure the phase offset as a function of m:n and γ for varying frequency ω and fluid viscosity 5 cS <= ν <= 30 cS.