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Sample records for molecular aspects integrative

  1. [Economic aspects of integrated care].

    PubMed

    Lange, A; Braun, S; Greiner, W

    2012-05-01

    For more than 10 years integrated care has been an inherent part of the German healthcare system. The aims of selective contracts are to minimize interface problems between outpatient and inpatient sectors, generalist und specialist care as well as to intensify competition. Despite repeated efforts by the legislator, comprehensive integrated healthcare is still limited to a few flagship projects. This is mainly due to low incentives on the part of both suppliers and customers. Therefore, this article focuses on the economic aspects of integrated care. From a theoretical perspective, integrated care improves efficiency in the healthcare sector by reducing interface problems and asymmetric information as well as by intensifying competition. In practice, however, there are a number of obstacles to implementation. Particularly noteworthy are the financial difficulties in addition to problems regarding sectoral budgeting and the long-term nature of investments. However, the political environment and thus the financial arrangements within the statutory health insurance seem to be more important for further development of integrated care in Germany than the financing issues. PMID:22526852

  2. Papillomaviruses: Molecular and clinical aspects

    SciTech Connect

    Howley, P.M.; Broker, T.R.

    1985-01-01

    This book contains nine sections, each consisting of several papers. The section headings are : Papillomaviruses and Human Genital Tract Diseases;Papillomaviruses and Human Cutaneous Diseases, Papillomaviruses and Human Oral and Laryngeal Diseases;Therapeutic Approaches to Papillomavirus Infections;Animal Papillomaviruses;Molecular Biology;Transcription, Replication, and Genome Organization;Epithelial Cell Culture;Papillomavirus Transformation;and Viral Vectors.

  3. Molecular aspects of charm physics

    SciTech Connect

    Fernandez, F.; Ortega, P. G.; Entem, D. R.

    2013-03-25

    We study the influence of possible molecular structures in the charmonium spectrum. We focus on the 0{sup ++}, 1{sup ++} and 1{sup --} sectors. In the first one we coupled the 2{sup 3}P{sub 0}cc pair with DD, J/{psi}{omega}, D{sub s}D{sub s} and J/{psi}{phi} channels and we obtain two states compatibles with the X(3945) and the Y(3940). In the second one we couple the 2{sup 3}P{sub 1}cc state with the DD{sup *} channel and we obtain a dressed state compatible with the X(3940) and a new state that we assign to the X(3872). In the third one we include the 3{sup 3}S{sub 1} and 2{sup 3}D{sub 1} charmonium states coupled to DD, DD{sup *}, D{sup *}D{sup *}, D{sub s}D{sub s}, D{sub s}D{sup *}s and D{sup *}{sub s}D{sup *}{sub s}. In this calculation we obtain a new molecular state that could be the G(3900) or the controversial Y(4008) and two cc states dressed by the molecular components assigned to the {psi}(4040) and the {psi}(4160). Finally we perform a calculation in the five quark sector where we can describe the {Lambda}{sub c}(2940){sup +} as a ND{sup *} molecular state and predict a {Lambda}{sub b}(6248){sup +} state.

  4. Melioidosis: Molecular Aspects of Pathogenesis

    PubMed Central

    Stone, Joshua K.; DeShazer, David; Brett, Paul J.; Burtnick, Mary N.

    2015-01-01

    SUMMARY Burkholderia pseudomallei is a Gram-negative bacterium that causes melioidosis, a multifaceted disease that is highly endemic in Southeast Asia and northern Australia. This facultative intracellular pathogen possesses a large genome that encodes a wide array of virulence factors that promote survival in vivo by manipulating host cell processes and disarming elements of the host immune system. Antigens and systems that play key roles in B. pseudomallei virulence include capsular polysaccharide, lipopolysaccharide, adhesins, specialized secretion systems, actin-based motility and various secreted factors. This review provides an overview of the current and steadily expanding knowledge regarding the molecular mechanisms used by this organism to survive within a host and their contribution to the pathogenesis of melioidosis. PMID:25312349

  5. Molecular aspects of vitamin D anticancer activity.

    PubMed

    Picotto, Gabriela; Liaudat, Ana C; Bohl, Luciana; Tolosa de Talamoni, Nori

    2012-10-01

    Environment may influence the development and prevention of cancer. Calcitriol has been associated with calcium homeostasis regulation. Many epidemiological, biochemical, and genetic studies have shown non-classic effects of vitamin D, such as its involvement in the progression of different cancers. Although vitamin D induces cellular arrest, triggers apoptotic pathways, inhibits angiogenesis, and alters cellular adhesion, the precise mechanisms of its action are still not completely established. This article will present a revision about the molecular aspects proposed to be involved in the anticancer action of calcitriol. Adequate levels of vitamin D to prevent cancer development will also be discussed. PMID:22963190

  6. Progressive multifocal leukoencephalopathy: Clinical and molecular aspects

    PubMed Central

    Tavazzi, Eleonora; White, Martyn K.; Khalili, Kamel

    2011-01-01

    The fatal CNS demyelinating disease, progressive multifocal leukoencephalopathy (PML), is rare and appears to occur almost always as a consequence of immune dysfunction. Thus it is associated with HIV/AIDS and also as a side-effect of certain immunomodulatory monoclonal antibody therapies. In contrast to the rarity of PML, the etiological agent of the disease, the polyomavirus JC (JCV) is widespread in populations worldwide. In the forty years since JCV was first isolated, much has been learned about the virus and the disease from laboratory and clinical observations. However, there are many aspects of the viral life cycle and the pathogenesis of the disease that still remain unclear and our understanding is constantly evolving. In this review, we will discuss our current understanding of the clinical features of PML and molecular characteristics of JCV and how they relate to each other. Clinical observations can inform molecular studies of the virus and likewise molecular findings concerning the life cycle of the virus can guide the development of novel therapeutic strategies. PMID:21936015

  7. Molecular aspects of monoamine oxidase B.

    PubMed

    Ramsay, Rona R

    2016-08-01

    Monoamine oxidases (MAO) influence the monoamine levels in brain by virtue of their role in neurotransmitter breakdown. MAO B is the predominant form in glial cells and in platelets. MAO B structure, function and kinetics are described as a background for the effect of alterations in its activity on behavior. The need to inhibit MAO B to combat decreased brain amines continues to drive the search for new drugs. Reversible and irreversible inhibitors are now designed using data-mining, computational screening, docking and molecular dynamics. Multi-target ligands designed to combat the elevated activity of MAO B in Alzheimer's and Parkinson's Diseases incorporate MAO inhibition (usually irreversible) as well as iron chelation, antioxidant or neuroprotective properties. The main focus of drug design is the catalytic activity of MAO, but the imidazoline I2 site in the entrance cavity of MAO B is also a pharmacological target. Endogenous regulation of MAO B expression is discussed briefly in light of new studies measuring mRNA, protein, or activity in healthy and degenerative samples, including the effect of DNA methylation on the expression. Overall, this review focuses on examples of recent research on the molecular aspects of the expression, activity, and inhibition of MAO B. PMID:26891670

  8. Ricin Toxicity: Clinical and Molecular Aspects.

    PubMed

    Moshiri, Mohammad; Hamid, Fatemeh; Etemad, Leila

    2016-04-01

    Seeds of the castor bean plant Ricinuscommunis L (CB) contain ricin toxin (RT), one of the most poisonous naturally-occurring substances known. Ricin toxin, a water-soluble glycoprotein that does not partition into the oil extract, is a ribosome-inactivating toxin composed of two chains, labeled A and B. Severity of the toxicity varies depending on the route of exposure to the toxin. Inhalational is the most toxic route, followed by oral ingestion. Orally-ingested RT accumulates in the liver and spleen but other cells are also affected. The main clinical manifestations are also related to the administration route. Oral ingestion of CB or RT results in abdominal pain, vomiting, diarrhea, and various types of gastrointestinal bleeding that leading to volume depletion, hypovolemic shock, and renal failure. Inhalation of the toxin presents with non-cardiogenic pulmonary edema, diffuse necrotizing pneumonia, interstitial and alveolar inflammation, and edema. Local injection of RT induces indurations at the injection site, swelling of regional lymph nodes, hypotension, and death. An enzyme-linked immunosorbent assay (ELISA) has been developed to detect RT in animal tissues and fluids. Ricinine, an alkaloid of CB, can be detected in rat urine within 48 h of RT exposure. Supportive care is the basic treatment and standard biowarfare decontamination protocols are used for RT intoxication. Dexamethasone and difluoromethylornithine might be effective treatments. This review examines the clinical and molecular aspects of ricin toxicity. PMID:27536698

  9. Ricin Toxicity: Clinical and Molecular Aspects

    PubMed Central

    Moshiri, Mohammad; Hamid, Fatemeh; Etemad, Leila

    2016-01-01

    Seeds of the castor bean plant Ricinuscommunis L (CB) contain ricin toxin (RT), one of the most poisonous naturally-occurring substances known. Ricin toxin, a water-soluble glycoprotein that does not partition into the oil extract, is a ribosome-inactivating toxin composed of two chains, labeled A and B. Severity of the toxicity varies depending on the route of exposure to the toxin. Inhalational is the most toxic route, followed by oral ingestion. Orally-ingested RT accumulates in the liver and spleen but other cells are also affected. The main clinical manifestations are also related to the administration route. Oral ingestion of CB or RT results in abdominal pain, vomiting, diarrhea, and various types of gastrointestinal bleeding that leading to volume depletion, hypovolemic shock, and renal failure. Inhalation of the toxin presents with non-cardiogenic pulmonary edema, diffuse necrotizing pneumonia, interstitial and alveolar inflammation, and edema. Local injection of RT induces indurations at the injection site, swelling of regional lymph nodes, hypotension, and death. An enzyme-linked immunosorbent assay (ELISA) has been developed to detect RT in animal tissues and fluids. Ricinine, an alkaloid of CB, can be detected in rat urine within 48 h of RT exposure. Supportive care is the basic treatment and standard biowarfare decontamination protocols are used for RT intoxication. Dexamethasone and difluoromethylornithine might be effective treatments. This review examines the clinical and molecular aspects of ricin toxicity. PMID:27536698

  10. Integration methods for molecular dynamics

    SciTech Connect

    Leimkuhler, B.J.; Reich, S.; Skeel, R.D.

    1996-12-31

    Classical molecular dynamics simulation of a macromolecule requires the use of an efficient time-stepping scheme that can faithfully approximate the dynamics over many thousands of timesteps. Because these problems are highly nonlinear, accurate approximation of a particular solution trajectory on meaningful time intervals is neither obtainable nor desired, but some restrictions, such as symplecticness, can be imposed on the discretization which tend to imply good long term behavior. The presence of a variety of types and strengths of interatom potentials in standard molecular models places severe restrictions on the timestep for numerical integration used in explicit integration schemes, so much recent research has concentrated on the search for alternatives that possess (1) proper dynamical properties, and (2) a relative insensitivity to the fastest components of the dynamics. We survey several recent approaches. 48 refs., 2 figs.

  11. DISACCHARIDE DIGESTION: CLINICAL AND MOLECULAR ASPECTS

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Sugars normally are absorbed in the small intestine. When carbohydrates are malabsorbed, the osmotic load produced by the high amount of low molecular weight sugars and partially digested starches in the small intestine can cause symptoms of intestinal distention, rapid peristalsis, and diarrhea. Co...

  12. [Practical aspects of molecular diagnostics in genodermatoses].

    PubMed

    Has, C; He, Y

    2016-01-01

    Genodermatoses are rare genetic disorders with a broad spectrum of cutaneous and extracutaneous manifestations that have a genetic background. A thorough clinical examination, laboratory workup and morphological analyses of the skin remain crucial for the diagnosis in the era of next generation sequencing (NGS). The diagnostic algorithm depends on the clinical and molecular heterogeneity and should be adapted for each group of genodermatoses. In cases with uncharacteristic phenotypes which cannot be classified, NGS-based testing accelerates the time to diagnosis and leads to the identification of new disorders and new disease-associated genes. The new knowledge on genotype-phenotype correlations should enable revision of the classification of genodermatoses on a molecular basis. PMID:26537890

  13. Endometrial cancer: molecular and therapeutic aspects.

    PubMed

    Tsikouras, Panagiotis; Bouchlariotou, Sofia; Vrachnis, Nikolaos; Dafopoulos, Alexandros; Galazios, Georgios; Csorba, Roland; von Tempelhoff, Georg Friedrich

    2013-07-01

    Endometrial cancer (EC) is the most commonly diagnosed gynecologic malignancy. Although early-stage EC is effectively treated surgically, commonly without adjuvant therapy, the treatment of high-risk and advanced disease is more complex. Chemotherapy has evolved into an important modality in high-risk early-stage and advanced-stage disease, and in recurrent EC. Multi-institutional trials are in progress to better define optimal adjuvant treatment for subsets of patients, as well as the role of surgical staging in reducing both overuse and underuse of radiation therapy. Understanding and identifying the molecular biology and genetics of EC are central to the development of novel therapies. A number of molecular and genetic events have been observed in ECs, which have enabled us to have a better understanding of the biology and development of the disease. For example, the PTEN/AKT pathway and its downstream targets and the mTOR pathway have been shown to play an important role in EC pathogenesis. This review summarizes the background of the known molecular alterations, and the management of patients with EC. PMID:23433742

  14. Molecular aspects of DNA splicing system

    NASA Astrophysics Data System (ADS)

    Yusof, Yuhani; Lim, Wen Li; Goode, T. Elizabeth; Sarmin, Nor Haniza; Heng, Fong Wan; Wahab, Mohd Firdaus Abd

    2015-05-01

    The pioneer model of deoxyribonucleic acid (DNA) splicing system in a framework of Formal Language Theory was introduced by Head that led to the existence of other models of splicing system, namely Paun, Pixton and Yusof-Goode. These entire models are inspired by the molecular biological process of DNA splicing. Hence, this paper focuses on the translucent DNA splicing process, particularly on the generated language. Starting with some preliminaries in a limit graph, this paper also provides the experimental design with the predicted and actual result.

  15. Molecular aspects of hereditary spastic paraplegia.

    PubMed

    Noreau, Anne; Dion, Patrick A; Rouleau, Guy A

    2014-07-01

    Hereditary spastic paraplegia (HSP) is a clinically and genetically heterogeneous group of neurodegenerative disorders characterized by progressive lower limbs spasticity and weakness. What was first thought to be a small group of rare Mendelian disorder has now become a large group that includes many complex syndromes. While large families with defined modes of inheritance were used for the initial HSP gene discovery, new sequencing technologies have recently allowed the study of small families, with the identification of many new disease causative genes. These discoveries are slowly leading to a better understanding of the molecular mechanisms underlying HSP with the identification of precise disease pathways. These insights may lead to new therapeutic strategies for what is a group of largely untreatable diseases. This review looks at the key players involved in HSP and where they act in their specific pathways. PMID:24631291

  16. [Glucotransporters: clinical, molecular and genetic aspects].

    PubMed

    Sandoval-Muñiz, Roberto de Jesús; Vargas-Guerrero, Belinda; Flores-Alvarado, Luis Javier; Gurrola-Díaz, Carmen Magdalena

    2016-01-01

    Oxidation of glucose is the major source of obtaining cell energy, this process requires glucose transport into the cell. However, cell membranes are not permeable to polar molecules such as glucose; therefore its internalization is accomplished by transporter proteins coupled to the cell membrane. In eukaryotic cells, there are two types of carriers coupled to the membrane: 1) cotransporter Na+-glucose (SGLT) where Na+ ion provides motive power for the glucose´s internalization, and 2) the glucotransporters (GLUT) act by facilitated diffusion. This review will focus on the 14 GLUT so far described. Despite the structural homology of GLUT, different genetic alterations of each GLUT cause specific clinical entities. Therefore, the aim of this review is to gather the molecular and biochemical available information of each GLUT as well as the particular syndromes and pathologies related with GLUT´s alterations and their clinical approaches. PMID:27595260

  17. Molecular aspects of the endocytic pathway.

    PubMed Central

    Clague, M J

    1998-01-01

    Observation of the flow of material along the endocytic pathway has lead to the description of the basic architecture of the pathway and provided insight into the relationship between compartments. Significant advances have been made in the study of endocytic transport steps at the molecular level, of which studies of cargo selection, vesicle budding and membrane fusion events comprise the major part. Progress in this area has been driven by two approaches, yeast genetics and in vitro or cell-free assays, which reconstitute particular transport steps and allow biochemical manipulation. The complex protein machineries that control vesicle budding and fusion are significantly conserved between the secretory and endocytic pathways such that proteins that regulate particular steps are often part of a larger family of proteins which exercise a conserved function at other locations within the cell. Well characterized examples include vesicle coat proteins, rabs (small GTPases) and soluble N-ethylmaleimide-sensitive fusion protein (NSF) attachment protein (SNAP) receptors (SNAREs). Intracompartmental pH, lipid composition and cytoskeletal organization have also been identified as important determinants of the orderly flow of material within the endocytic pathway. PMID:9820800

  18. Molecular and Clinical Aspects of Angelman Syndrome

    PubMed Central

    Dagli, A.; Buiting, K.; Williams, C.A.

    2012-01-01

    The Angelman syndrome is caused by disruption of the UBE3A gene and is clinically delineated by the combination of severe mental disability, seizures, absent speech, hypermotoric and ataxic movements, and certain remarkable behaviors. Those with the syndrome have a predisposition toward apparent happiness and paroxysms of laughter, and this finding helps distinguish Angelman syndrome from other conditions involving severe developmental handicap. Accurate diagnosis rests on a combination of clinical criteria and molecular and/or cytogenetic testing. Analysis of parent-specific DNA methylation imprints in the critical 15q11.2–q13 genomic region identifies 75–80% of all individuals with the syndrome, including those with cytogenetic deletions, imprinting center defects and paternal uniparental disomy. In the remaining group, UBE3A sequence analysis identifies an additional percentage of patients, but 5–10% will remain who appear to have the major clinical phenotypic features but do not have any identifiable genetic abnormalities. Genetic counseling for recurrence risk is complicated because multiple genetic mechanisms can disrupt the UBE3A gene, and there is also a unique inheritance pattern associated with UBE3A imprinting. Angelman syndrome is a prototypical developmental syndrome due to its remarkable behavioral phenotype and because UBE3A is so crucial to normal synaptic function and neural plasticity. PMID:22670133

  19. Atomic and Molecular Aspects of Astronomical Spectra

    NASA Astrophysics Data System (ADS)

    Sochi, Taha

    2012-11-01

    In the first section we present the atomic part where a C2+ atomic target was prepared and used to generate theoretical data to investigate recombination lines arising from electron-ion collisions in thin plasma. R-matrix method was used to describe the C2+ plus electron system. Theoretical data concerning bound and autoionizing states were generated in the intermediate-coupling approximation. The data were used to generate dielectronic recombination data for C+ which include transition lines, oscillator strengths, radiative transition probabilities, emissivities and dielectronic recombination coefficients. The data were cast in a line list containing 6187 optically-allowed transitions which include many C II lines observed in astronomical spectra. This line list was used to analyze the spectra from a number of astronomical objects, mainly planetary nebulae, and identify their electron temperature. The electron temperature investigation was also extended to include free electron energy analysis to investigate the long-standing problem of discrepancy between the results of recombination and forbidden lines analysis and its possible connection to the electron distribution. In the second section we present the results of our molecular investigation; the generation of a comprehensive, calculated line list of frequencies and transition probabilities for H2D+. The line list contains over 22 million rotational-vibrational transitions occurring between more than 33 thousand energy levels and covers frequencies up to 18500 cm-1. About 15% of these levels are fully assigned with approximate rotational and vibrational quantum numbers. A temperature-dependent partition function and cooling function are presented. Temperature-dependent synthetic spectra for the temperatures T=100, 500, 1000 and 2000 K in the frequency range 0-10000 cm-1 were also generated and presented graphically.

  20. Molecular and Biotechnological Aspects of Microbial Proteases†

    PubMed Central

    Rao, Mala B.; Tanksale, Aparna M.; Ghatge, Mohini S.; Deshpande, Vasanti V.

    1998-01-01

    diverse origins have been analyzed with the aim of studying their evolutionary relationships. Despite the extensive research on several aspects of proteases, there is a paucity of knowledge about the roles that govern the diverse specificity of these enzymes. Deciphering these secrets would enable us to exploit proteases for their applications in biotechnology. PMID:9729602

  1. Molecular aspects of intestinal calcium absorption.

    PubMed

    Diaz de Barboza, Gabriela; Guizzardi, Solange; Tolosa de Talamoni, Nori

    2015-06-21

    Intestinal Ca(2+) absorption is a crucial physiological process for maintaining bone mineralization and Ca(2+) homeostasis. It occurs through the transcellular and paracellular pathways. The first route comprises 3 steps: the entrance of Ca(2+) across the brush border membranes (BBM) of enterocytes through epithelial Ca(2+) channels TRPV6, TRPV5, and Cav1.3; Ca(2+) movement from the BBM to the basolateral membranes by binding proteins with high Ca(2+) affinity (such as CB9k); and Ca(2+) extrusion into the blood. Plasma membrane Ca(2+) ATPase (PMCA1b) and sodium calcium exchanger (NCX1) are mainly involved in the exit of Ca(2+) from enterocytes. A novel molecule, the 4.1R protein, seems to be a partner of PMCA1b, since both molecules co-localize and interact. The paracellular pathway consists of Ca(2+) transport through transmembrane proteins of tight junction structures, such as claudins 2, 12, and 15. There is evidence of crosstalk between the transcellular and paracellular pathways in intestinal Ca(2+) transport. When intestinal oxidative stress is triggered, there is a decrease in the expression of several molecules of both pathways that inhibit intestinal Ca(2+) absorption. Normalization of redox status in the intestine with drugs such as quercetin, ursodeoxycholic acid, or melatonin return intestinal Ca(2+) transport to control values. Calcitriol [1,25(OH)₂D₃] is the major controlling hormone of intestinal Ca(2+) transport. It increases the gene and protein expression of most of the molecules involved in both pathways. PTH, thyroid hormones, estrogens, prolactin, growth hormone, and glucocorticoids apparently also regulate Ca(2+) transport by direct action, indirect mechanism mediated by the increase of renal 1,25(OH)₂D₃ production, or both. Different physiological conditions, such as growth, pregnancy, lactation, and aging, adjust intestinal Ca(2+) absorption according to Ca(2+) demands. Better knowledge of the molecular details of intestinal Ca(2

  2. Molecular aspects of intestinal calcium absorption

    PubMed Central

    Diaz de Barboza, Gabriela; Guizzardi, Solange; Tolosa de Talamoni, Nori

    2015-01-01

    Intestinal Ca2+ absorption is a crucial physiological process for maintaining bone mineralization and Ca2+ homeostasis. It occurs through the transcellular and paracellular pathways. The first route comprises 3 steps: the entrance of Ca2+ across the brush border membranes (BBM) of enterocytes through epithelial Ca2+ channels TRPV6, TRPV5, and Cav1.3; Ca2+ movement from the BBM to the basolateral membranes by binding proteins with high Ca2+ affinity (such as CB9k); and Ca2+ extrusion into the blood. Plasma membrane Ca2+ ATPase (PMCA1b) and sodium calcium exchanger (NCX1) are mainly involved in the exit of Ca2+ from enterocytes. A novel molecule, the 4.1R protein, seems to be a partner of PMCA1b, since both molecules co-localize and interact. The paracellular pathway consists of Ca2+ transport through transmembrane proteins of tight junction structures, such as claudins 2, 12, and 15. There is evidence of crosstalk between the transcellular and paracellular pathways in intestinal Ca2+ transport. When intestinal oxidative stress is triggered, there is a decrease in the expression of several molecules of both pathways that inhibit intestinal Ca2+ absorption. Normalization of redox status in the intestine with drugs such as quercetin, ursodeoxycholic acid, or melatonin return intestinal Ca2+ transport to control values. Calcitriol [1,25(OH)2D3] is the major controlling hormone of intestinal Ca2+ transport. It increases the gene and protein expression of most of the molecules involved in both pathways. PTH, thyroid hormones, estrogens, prolactin, growth hormone, and glucocorticoids apparently also regulate Ca2+ transport by direct action, indirect mechanism mediated by the increase of renal 1,25(OH)2D3 production, or both. Different physiological conditions, such as growth, pregnancy, lactation, and aging, adjust intestinal Ca2+ absorption according to Ca2+ demands. Better knowledge of the molecular details of intestinal Ca2+ absorption could lead to the development of

  3. Eosinophilic cardiac disease: Molecular, clinical and imaging aspects.

    PubMed

    Séguéla, Pierre-Emmanuel; Iriart, Xavier; Acar, Philippe; Montaudon, Michel; Roudaut, Raymond; Thambo, Jean-Benoit

    2015-04-01

    Eosinophilia may be responsible for cardiac injuries of widely varying severity, from acute myocarditis to endomyocardial fibrosis. In this review, we present both the molecular mechanisms that are responsible for these lesions and their clinical and paraclinical aspects. Numerous aetiologies can lead to severe eosinophilia, but these are mainly represented by hypersensitivity reactions, rheumatological diseases and hypereosinophilic syndrome. Because cardiac involvement may be extremely severe, echocardiography should be always performed in the context of eosinophilia and appropriate therapeutics should be started rapidly in order to limit the progression of the disease. PMID:25858537

  4. Cellular and molecular aspects of plant adaptation to microgravity

    NASA Astrophysics Data System (ADS)

    Kordyum, Elizabeth; Kozeko, Liudmyla

    2016-07-01

    Elucidation of the range and mechanisms of the biological effects of microgravity is one of the urgent fundamental tasks of space and gravitational biology. The absence of forbidding on plant growth and development in orbital flight allows studying different aspects of plant adaptation to this factor that is directly connected with development of the technologies of bioregenerative life-support systems. Microgravity belongs to the environmental factors which cause adaptive reactions at the cellular and molecular levels in the range of physiological responses in the framework of genetically determined program of ontogenesis. It is known that cells of a multicellular organism not only take part in reactions of the organism but also carry out processes that maintain their integrity. In light of these principles, the problem of identification of biochemical, physiological and structural patterns that can have adaptive significance at the cellular and molecular levels in real and simulated microgravity is considered. It is pointed that plant cell responses in microgravity and under clinorotation vary according to growth phase, physiological state, and taxonomic position of the object. At the same time, the responses have, to some degree, a similar character reflecting the changes in the cell organelle functional load. The maintenance of the plasmalemma fluidity at the certain level, an activation of both the antioxidant system and expression of HSP genes, especially HSP70, under increasing reactive oxygen species, lipid peroxidation intensity and alteration in protein homeostasis, are a strategic paradigm of rapid (primary) cell adaptation to microgravity. In this sense, biological membranes, especially plasmalemma, and their properties and functions may be considered as the most sensitive indicators of the influence of gravity or altered gravity on a cell. The plasmalemma lipid bilayer is a border between the cell internal content and environment, so it is a mediator

  5. Cellular and molecular aspects of plant adaptation to microgravity

    NASA Astrophysics Data System (ADS)

    Kordyum, Elizabeth; Kozeko, Liudmyla

    2016-07-01

    Elucidation of the range and mechanisms of the biological effects of microgravity is one of the urgent fundamental tasks of space and gravitational biology. The absence of forbidding on plant growth and development in orbital flight allows studying different aspects of plant adaptation to this factor that is directly connected with development of the technologies of bioregenerative life-support systems. Microgravity belongs to the environmental factors which cause adaptive reactions at the cellular and molecular levels in the range of physiological responses in the framework of genetically determined program of ontogenesis. It is known that cells of a multicellular organism not only take part in reactions of the organism but also carry out processes that maintain their integrity. In light of these principles, the problem of identification of biochemical, physiological and structural patterns that can have adaptive significance at the cellular and molecular levels in real and simulated microgravity is considered. It is pointed that plant cell responses in microgravity and under clinorotation vary according to growth phase, physiological state, and taxonomic position of the object. At the same time, the responses have, to some degree, a similar character reflecting the changes in the cell organelle functional load. The maintenance of the plasmalemma fluidity at the certain level, an activation of both the antioxidant system and expression of HSP genes, especially HSP70, under increasing reactive oxygen species, lipid peroxidation intensity and alteration in protein homeostasis, are a strategic paradigm of rapid (primary) cell adaptation to microgravity. In this sense, biological membranes, especially plasmalemma, and their properties and functions may be considered as the most sensitive indicators of the influence of gravity or altered gravity on a cell. The plasmalemma lipid bilayer is a border between the cell internal content and environment, so it is a mediator

  6. Making mathematics and science integration happen: key aspects of practice

    NASA Astrophysics Data System (ADS)

    Ríordáin, Máire Ní; Johnston, Jennifer; Walshe, Gráinne

    2016-02-01

    The integration of mathematics and science teaching and learning facilitates student learning, engagement, motivation, problem-solving, criticality and real-life application. However, the actual implementation of an integrative approach to the teaching and learning of both subjects at classroom level, with in-service teachers working collaboratively, at second-level education, is under-researched due to the complexities of school-based research. This study reports on a year-long case study on the implementation of an integrated unit of learning on distance, speed and time, within three second-level schools in Ireland. This study employed a qualitative approach and examined the key aspects of practice that impact on the integration of mathematics and science teaching and learning. We argue that teacher perspective, teacher knowledge of the 'other subject' and of technological pedagogical content knowledge (TPACK), and teacher collaboration and support all impact on the implementation of an integrative approach to mathematics and science education.

  7. Molecular and Clinical Aspects of Drug-induced Gingival Overgrowth

    PubMed Central

    Kantarci, A.

    2015-01-01

    Drug-induced gingival overgrowth is a tissue-specific condition and is estimated to affect approximately one million North Americans. Lesions occur principally as side-effects from phenytoin, nifedipine, or ciclosporin therapy in approximately half of the people who take these agents. Due to new indications for these drugs, their use continues to grow. Here, we review the molecular and cellular characteristics of human gingival overgrowth lesions and highlight how they differ considerably as a function of the causative drug. Analyses of molecular signaling pathways in cultured human gingival fibroblasts have provided evidence for their unique aspects compared with fibroblasts from the lung and kidney. These findings provide insights into both the basis for tissue specificity and into possible therapeutic opportunities which are reviewed here. Although ciclosporin-induced gingival overgrowth lesions exhibit principally the presence of inflammation and little fibrosis, nifedipine- and especially phenytoin-induced lesions are highly fibrotic. The increased expression of markers of gingival fibrosis, particularly CCN2 [also known as connective tissue growth factor (CTGF)], markers of epithelial to mesenchymal transition, and more recently periostin and members of the lysyl oxidase family of enzymes have been documented in phenytoin or nifedipine lesions. Some oral fibrotic conditions such as leukoplakia and oral submucous fibrosis, after subsequent additional genetic damage, can develop into oral cancer. Since many pathways are shared, the study of gingival fibrosis and comparisons with characteristics and molecular drivers of oral cancer would likely enhance understandings and functional roles of molecular drivers of these oral pathologies. PMID:25680368

  8. Molecular and biological aspects of the bovine immunodeficiency virus.

    PubMed

    Corredor, Andrea G; St-Louis, Marie-Claude; Archambault, Denis

    2010-01-01

    The bovine immunodeficiency virus (BIV) was isolated in 1969 from a cow, R-29, with a wasting syndrome suggesting bovine leucosis. The virus, first designated bovine visna-like virus, remained unstudied until HIV was discovered in 1983. Then, it was demonstrated in 1987 that the bovine R-29 isolate was a lentivirus with striking similarity to the human immunodeficiency virus (HIV). Moreover, BIV has the most complex genomic structure among all identified lentiviruses shown by several regulatory/accessory genes encoding proteins, some of which are involved in the regulation of virus gene expression. This manuscript aims to review biological and molecular aspects of BIV, with emphasis on regulatory/accessory viral genes/proteins which are involved in virus expression. PMID:20210777

  9. Molecular Aspects of Bone Resorption in β-Thalassemia Major

    PubMed Central

    Saki, Najmaldin; Abroun, Saeid; Salari, Fatemeh; Rahim, Fakher; Shahjahani, Mohammad; Javad, Mohammadi-Asl

    2015-01-01

    β-thalassemia is the most common single gene disorder worldwide, in which hemoglobin β-chain production is decreased. Today, the life expectancy of thalassemic patients is increased because of a variety of treatment methods; however treatment related complications have also increased. The most common side effect is osteoporosis, which usually occurs in early adulthood as a consequence of increased bone resorption. Increased bone resorption mainly results from factors such as delayed puberty, diabetes mellitus, hypothyroidism, ineffective hematopoiesis as well as hyperplasia of the bone marrow, parathyroid gland dysfunction, toxic effect of iron on osteoblasts, growth hormone (GH) and insulin-like growth factor-1 (IGF-1) deficiency. These factors disrupt the balance between osteoblasts and osteoclasts by interfering with various molecular mechanisms and result in decreased bone density. Given the high prevalence of osteopenia and osteoporosis in thalassemic patients and complexity of their development process, the goal of this review is to evaluate the molecular aspects involved in osteopenia and osteoporosis in thalassemic patients, which may be useful for therapeutic purposes. PMID:26199898

  10. Atopic dermatitis: molecular mechanisms, clinical aspects and new therapeutical approaches.

    PubMed

    Galli, E; Cicconi, R; Rossi, P; Casati, A; Brunetti, E; Mancino, G

    2003-03-01

    Atopic dermatitis (AD) is a genetically determinated, chronic inflammatory skin disorder associated with cutaneous erythema and severe pruritus, affecting 10-15% of children with increasing incidence and socio-economical relevance. Frequently, AD is associated with development of allergic rhinitis and/or asthma later in childhood. In most of patients AD is associated with a sensitization to food and/or environmental allergens and increased serum-IgE, while only a fewer percentage missed links to the classical atopic diathesis. Currently investigated pathogenetic aspects of AD include imbalanced Th1/Th2 responses, altered prostaglandin metabolism, intrinsic defects in the keratinocyte function, delayed eosinophil apoptosis, and IgE-mediated facilitated antigen presentation by epidermal dendritic cells. An inflammatory response of the two-phase-type and the effects of staphylococcal superantigens (SAgs) are also reported. At present a standardized cure of AD and a consensus on therapeutical approach of the severe form of the disease have not been established. Current management of AD is directed to the reduction of cutaneous inflammation and infection, mainly by S. aureus, and to the elimination of exacerbating factors (irritants, allergens, emotional stresses). Since patient with AD show abnormalities in immunoregulation, therapy directed to adjustment of their immune function could represent an alternative approach, particularly in the severe form of the disease. In this review, we analyse the clinical and genetic aspects of AD, the related molecular mechanisms, and the immunobiology of the disease, focusing our attention on current treatments and future perspectives on this topic. PMID:12630559

  11. Porcine Endogenous Retroviruses in Xenotransplantation—Molecular Aspects

    PubMed Central

    Kimsa, Magdalena C.; Strzalka-Mrozik, Barbara; Kimsa, Malgorzata W.; Gola, Joanna; Nicholson, Peter; Lopata, Krzysztof; Mazurek, Urszula

    2014-01-01

    In the context of the shortage of organs and other tissues for use in human transplantation, xenotransplantation procedures with material taken from pigs have come under increased consideration. However, there are unclear consequences of the potential transmission of porcine pathogens to humans. Of particular concern are porcine endogenous retroviruses (PERVs). Three subtypes of PERV have been identified, of which PERV-A and PERV-B have the ability to infect human cells in vitro. The PERV-C subtype does not show this ability but recombinant PERV-A/C forms have demonstrated infectivity in human cells. In view of the risk presented by these observations, the International Xenotransplantation Association recently indicated the existence of four strategies to prevent transmission of PERVs. This article focuses on the molecular aspects of PERV infection in xenotransplantation and reviews the techniques available for the detection of PERV DNA, RNA, reverse transcriptase activity and proteins, and anti-PERV antibodies to enable carrying out these recommendations. These methods could be used to evaluate the risk of PERV transmission in human recipients, enhance the effectiveness and reliability of monitoring procedures, and stimulate discussion on the development of improved, more sensitive methods for the detection of PERVs in the future. PMID:24828841

  12. Quantitative Molecular Thermochemistry Based on Path Integrals

    SciTech Connect

    Glaesemann, K R; Fried, L E

    2005-03-14

    The calculation of thermochemical data requires accurate molecular energies and heat capacities. Traditional methods rely upon the standard harmonic normal mode analysis to calculate the vibrational and rotational contributions. We utilize path integral Monte Carlo (PIMC) for going beyond the harmonic analysis, to calculate the vibrational and rotational contributions to ab initio energies. This is an application and extension of a method previously developed in our group.

  13. Molecular Aspects of Transport in Thin Films of Controlled Architecture

    SciTech Connect

    Paul W. Bohn

    2009-04-16

    coupled to analyte sampling both by LIF and mass spectrometry. Detection of electrophoresis separation products by electrospray mass spectrometry was achieved through direct interfacing to an electrospray mass spectrometer. Pb(II) interactions with the DNAzyme have been realized in an NCAM-coupled integrated microfluidic structure allowing cation separations to be coupled to molecular beacon detection motifs for the determination of Pb(II) in an electroplating sludge reference material. By changing the DNAzyme to select for other compounds of interest, it is possible to incorporate multiple sensing systems within a single device, thereby achieving great flexibility.

  14. [Molecular aspects of head and neck, and lung cancer oncogenesis].

    PubMed

    Loriot, Y; Mordant, P; Fouret, P; Deutsch, E; Soria, J-C

    2009-01-01

    Lung and head and neck cancers result from a multistep process involving activation of oncogenes and inactivation of tumor-suppressor genes. These two processes share common features and molecular players, while their corresponding clinical entities are both triggered by the tobacco carcinogens. In many cases, the molecular abnormalities associated with these multi-step and multi-focal processes can be found in pre-malignant lesions and normal tissue. The growing knowledge of the molecular basis of lung and head and neck carcinogenesis allows to better selecting molecular alterations that can be modulated by molecular targeted agents either in a curative or in a chemopreventive approach. PMID:19433370

  15. Generalized Glucocorticoid Resistance: Clinical Aspects, Molecular Mechanisms, and Implications of a Rare Genetic Disorder

    PubMed Central

    Charmandari, Evangelia; Kino, Tomoshige; Ichijo, Takamasa; Chrousos, George P.

    2008-01-01

    Context: Primary generalized glucocorticoid resistance is a rare genetic condition characterized by generalized, partial, target-tissue insensitivity to glucocorticoids. We review the clinical aspects, molecular mechanisms, and implications of this disorder. Evidence Acquisition: We conducted a systematic review of the published, peer-reviewed medical literature using MEDLINE (1975 through February 2008) to identify original articles and reviews on this topic. Evidence Synthesis: We have relied on the experience of a number of experts in the field, including our extensive personal experience. Conclusions: The clinical spectrum of primary generalized glucocorticoid resistance is broad, ranging from asymptomatic to severe cases of hyperandrogenism, fatigue, and/or mineralocorticoid excess. The molecular basis of the condition has been ascribed to mutations in the human glucocorticoid receptor (hGR) gene, which impair glucocorticoid signal transduction and reduce tissue sensitivity to glucocorticoids. A consequent increase in the activity of the hypothalamic-pituitary-adrenal axis compensates for the reduced sensitivity of peripheral tissues to glucocorticoids at the expense of ACTH hypersecretion-related pathology. The study of functional defects of natural hGR mutants enhances our understanding of the molecular mechanisms of hGR action and highlights the importance of integrated cellular and molecular signaling mechanisms for maintaining homeostasis and preserving normal physiology. PMID:18319312

  16. Microelectromechanical systems integrating molecular spin crossover actuators

    NASA Astrophysics Data System (ADS)

    Manrique-Juarez, Maria D.; Rat, Sylvain; Mathieu, Fabrice; Saya, Daisuke; Séguy, Isabelle; Leïchlé, Thierry; Nicu, Liviu; Salmon, Lionel; Molnár, Gábor; Bousseksou, Azzedine

    2016-08-01

    Silicon MEMS cantilevers coated with a 200 nm thin layer of the molecular spin crossover complex [Fe(H2B(pz)2)2(phen)] (H2B(pz)2 = dihydrobis(pyrazolyl)borate and phen = 1,10-phenantroline) were actuated using an external magnetic field and their resonance frequency was tracked by means of integrated piezoresistive detection. The light-induced spin-state switching of the molecules from the ground low spin to the metastable high spin state at 10 K led to a well-reproducible shift of the cantilever's resonance frequency (Δfr = -0.52 Hz). Control experiments at different temperatures using coated as well as uncoated devices along with simple calculations support the assignment of this effect to the spin transition. This latter translates into changes in mechanical behavior of the cantilever due to the strong spin-state/lattice coupling. A guideline for the optimization of device parameters is proposed so as to efficiently harness molecular scale movements for large-scale mechanical work, thus paving the road for nanoelectromechanical systems (NEMS) actuators based on molecular materials.

  17. Molecular aspects of adaptation to extreme cold environments

    NASA Technical Reports Server (NTRS)

    Finegold, Leonard

    1986-01-01

    Some of the various strategies adopted by living organisms for survival at low temperatures are discussed from the molecular and membrane points of view. Two examples of connections between biological cold adaptation and the molecular level are considered: (1) antifreeze proteins in fish from cold sea water and (2) the fluidity characteristics of cell membranes in a wide variety of organisms. Emphasis is placed on the occurrence of s-phases.

  18. Molecular structure and elastic properties of thermotropic liquid crystals: Integrated molecular dynamics—Statistical mechanical theory vs molecular field approach

    NASA Astrophysics Data System (ADS)

    Capar, M. Ilk; Nar, A.; Ferrarini, A.; Frezza, E.; Greco, C.; Zakharov, A. V.; Vakulenko, A. A.

    2013-03-01

    The connection between the molecular structure of liquid crystals and their elastic properties, which control the director deformations relevant for electro-optic applications, remains a challenging objective for theories and computations. Here, we compare two methods that have been proposed to this purpose, both characterized by a detailed molecular level description. One is an integrated molecular dynamics-statistical mechanical approach, where the bulk elastic constants of nematics are calculated from the direct correlation function (DCFs) and the single molecule orientational distribution function [D. A. McQuarrie, Statistical Mechanics (Harper & Row, New York, 1973)]. The latter is obtained from atomistic molecular dynamics trajectories, together with the radial distribution function, from which the DCF is then determined by solving the Ornstein-Zernike equation. The other approach is based on a molecular field theory, where the potential of mean torque experienced by a mesogen in the liquid crystal phase is parameterized according to its molecular surface. In this case, the calculation of elastic constants is combined with the Monte Carlo sampling of single molecule conformations. Using these different approaches, but the same description, at the level of molecular geometry and torsional potentials, we have investigated the elastic properties of the nematic phase of two typical mesogens, 4'-n-pentyloxy-4-cyanobiphenyl and 4'-n-heptyloxy-4-cyanobiphenyl. Both methods yield K3(bend) >K1 (splay) >K2 (twist), although there are some discrepancies in the average elastic constants and in their anisotropy. These are interpreted in terms of the different approximations and the different ways of accounting for the structural properties of molecules in the two approaches. In general, the results point to the role of the molecular shape, which is modulated by the conformational freedom and cannot be fully accounted for by a single descriptor such as the aspect ratio.

  19. Molecular structure and elastic properties of thermotropic liquid crystals: integrated molecular dynamics--statistical mechanical theory vs molecular field approach.

    PubMed

    Ilk Capar, M; Nar, A; Ferrarini, A; Frezza, E; Greco, C; Zakharov, A V; Vakulenko, A A

    2013-03-21

    The connection between the molecular structure of liquid crystals and their elastic properties, which control the director deformations relevant for electro-optic applications, remains a challenging objective for theories and computations. Here, we compare two methods that have been proposed to this purpose, both characterized by a detailed molecular level description. One is an integrated molecular dynamics-statistical mechanical approach, where the bulk elastic constants of nematics are calculated from the direct correlation function (DCFs) and the single molecule orientational distribution function [D. A. McQuarrie, Statistical Mechanics (Harper & Row, New York, 1973)]. The latter is obtained from atomistic molecular dynamics trajectories, together with the radial distribution function, from which the DCF is then determined by solving the Ornstein-Zernike equation. The other approach is based on a molecular field theory, where the potential of mean torque experienced by a mesogen in the liquid crystal phase is parameterized according to its molecular surface. In this case, the calculation of elastic constants is combined with the Monte Carlo sampling of single molecule conformations. Using these different approaches, but the same description, at the level of molecular geometry and torsional potentials, we have investigated the elastic properties of the nematic phase of two typical mesogens, 4'-n-pentyloxy-4-cyanobiphenyl and 4'-n-heptyloxy-4-cyanobiphenyl. Both methods yield K3(bend) >K1 (splay) >K2 (twist), although there are some discrepancies in the average elastic constants and in their anisotropy. These are interpreted in terms of the different approximations and the different ways of accounting for the structural properties of molecules in the two approaches. In general, the results point to the role of the molecular shape, which is modulated by the conformational freedom and cannot be fully accounted for by a single descriptor such as the aspect ratio

  20. Molecular and cellular aspects of erythropoietin and erythropoiesis

    SciTech Connect

    Rich, I.N.

    1987-01-01

    This book contains over 30 papers. Some of the titles are: The Molecular Biology of Erythropoietin and the Expression of its Gene; The Molecolar Biology of Erythropoietin; Retroviral Vectors for Gene Transfer and Expression in Haematopietic Cells; Monocyte-Macrophage Mediated Suppression of Erythoropoieis in Renal Anemaia; and Standards for the Assay of Eythropoietin.

  1. Molecular aspects of prostate cancer with neuroendocrine differentiation

    PubMed Central

    Li, Qi; Zhang, Connie S.

    2016-01-01

    Neuroendocrine differentiation (NED), which is not uncommon in prostate cancer, is increases in prostate cancer after androgen-deprivation therapy (ADT) and generally appears in castration-resistant prostate cancer (CRPC). Neuroendocrine cells, which are found in normal prostate tissue, are a small subset of cells and have unique function in regulating the growth of prostate cells. Prostate cancer with NED includes different types of tumor, including focal NED, pure neuroendocrine tumor or mixed neuroendocrine-adenocarcinoma. Although more and more studies are carried out on NED in prostate cancer, the molecular components that are involved in NED are still poorly elucidated. We review neuroendocrine cells in normal prostate tissue, NED in prostate cancer, terminology of NED and biomarkers used for detecting NED in routine pathological practice. Some recently reported molecular components which drive NED in prostate cancer are listed in the review. PMID:27041934

  2. Molecular and genetic aspects of odontogenic tumors: a review.

    PubMed

    Garg, Kavita; Chandra, Shaleen; Raj, Vineet; Fareed, Wamiq; Zafar, Muhammad

    2015-06-01

    Odontogenic tumors contain a heterogeneous collection of lesions that are categorized from hamartomas to benign and malignant neoplasms of inconstant aggressiveness. Odontogenic tumors are usually extraordinary with assessed frequency of short of 0.5 cases/100,000 population for every year. The lesions such as odontogenic tumors are inferred from the components of the tooth-structuring contraption. They are discovered solely inside the maxillary and mandibular bones. This audit speaks to experiences and cooperation of the molecular and genetic variations connected to the development and movement of odontogenic tumors which incorporate oncogenes, tumor-silencer genes, APC gene, retinoblastoma genes, DNA repair genes, onco-viruses, development components, telomerase, cell cycle controllers, apoptosis-related elements, and regulators/conttrollers of tooth development. The reasonable and better understanding of the molecular components may prompt new ideas for their detection and administrating a better prognosis of odontogenic tumors. PMID:26221475

  3. Molecular and genetic aspects of odontogenic tumors: a review

    PubMed Central

    Garg, Kavita; Chandra, Shaleen; Raj, Vineet; Fareed, Wamiq; Zafar, Muhammad

    2015-01-01

    Odontogenic tumors contain a heterogeneous collection of lesions that are categorized from hamartomas to benign and malignant neoplasms of inconstant aggressiveness. Odontogenic tumors are usually extraordinary with assessed frequency of short of 0.5 cases/100,000 population for every year. The lesions such as odontogenic tumors are inferred from the components of the tooth-structuring contraption. They are discovered solely inside the maxillary and mandibular bones. This audit speaks to experiences and cooperation of the molecular and genetic variations connected to the development and movement of odontogenic tumors which incorporate oncogenes, tumor-silencer genes, APC gene, retinoblastoma genes, DNA repair genes, onco-viruses, development components, telomerase, cell cycle controllers, apoptosis-related elements, and regulators/conttrollers of tooth development. The reasonable and better understanding of the molecular components may prompt new ideas for their detection and administrating a better prognosis of odontogenic tumors. PMID:26221475

  4. Theoretical aspects of gas-phase molecular dynamics

    SciTech Connect

    Muckerman, J.T.

    1993-12-01

    Research in this program is focused on the development and application of time-dependent quantum mechanical and semiclassical methods for treating inelastic and reactive molecular collisions, and the photochemistry and photophysics of atoms and molecules in laser fields. Particular emphasis is placed on the development and application of grid methods based on discrete variable representations, on time-propagation methods, and, in systems with more that a few degrees of freedom, on the combined use of quantal wavepackets and classical trajectories.

  5. Cancer chemoresistance; biochemical and molecular aspects: a brief overview.

    PubMed

    Kachalaki, Saeed; Ebrahimi, Mina; Mohamed Khosroshahi, Leila; Mohammadinejad, Sina; Baradaran, Behzad

    2016-06-30

    The effectiveness of chemotherapy is one of the main challenges in cancer treatment and resistance to classic drugs and traditional treatment processes is an obstacle to this goal. Drug resistance that may be inherent or adventitious can cause poor treatment outcome and tumor relapse. In most cases, resistance to a drug can lead to resistance to many other drugs structure and function of which is not necessarily similar to the first drug. This phenomenon is the main mechanism behind failure of many of metastatic cancers. There are various molecular mechanisms involved in multidrug resistance, including change in the activity of membrane transporters (such as ABC transporters), increase of drug metabolism, change of the target enzyme (such as mutations that change thymidylate synthase and topoisomerases), promotion of DNA damage repair, and escape from drug induced apoptosis. Clinical and laboratory investigations on biomarkers involved in the response to chemotherapy have characterized the key factors behind the failure of treatments. Knowing the molecular factors involved in drug resistance may help us to develop new strategies for more promising chemotherapy and reduce the rate of relapse. In this brief review, molecular mechanisms and tumor microenvironment leading to decreased drug sensitivity, and strategies of reversing drug resistance are described. PMID:27094906

  6. Collective aspects of singlet fission in molecular crystals

    NASA Astrophysics Data System (ADS)

    Teichen, Paul E.; Eaves, Joel D.

    2015-07-01

    We present a model to describe collective features of singlet fission in molecular crystals and analyze it using many-body theory. The model we develop allows excitonic states to delocalize over several chromophores which is consistent with the character of the excited states in many molecular crystals, such as the acenes, where singlet fission occurs. As singlet states become more delocalized and triplet states more localized, the rate of singlet fission increases. We also determine the conditions under which the two triplets resulting from fission are correlated. Using the Bethe Ansatz and an entanglement measure for indistinguishable bipartite systems, we calculate the triplet-triplet entanglement as a function of the biexciton interaction strength. The biexciton interaction can produce bound biexciton states and provides a source of entanglement between the two triplets even when the triplets are spatially well separated. Significant entanglement between the triplet pair occurs well below the threshold for bound pair formation. Our results paint a dynamical picture that helps to explain why fission has been observed to be more efficient in molecular crystals than in their covalent dimer analogues and have consequences for photovoltaic efficiency models that assume that the two triplets can be extracted independently.

  7. Collective aspects of singlet fission in molecular crystals.

    PubMed

    Teichen, Paul E; Eaves, Joel D

    2015-07-28

    We present a model to describe collective features of singlet fission in molecular crystals and analyze it using many-body theory. The model we develop allows excitonic states to delocalize over several chromophores which is consistent with the character of the excited states in many molecular crystals, such as the acenes, where singlet fission occurs. As singlet states become more delocalized and triplet states more localized, the rate of singlet fission increases. We also determine the conditions under which the two triplets resulting from fission are correlated. Using the Bethe Ansatz and an entanglement measure for indistinguishable bipartite systems, we calculate the triplet-triplet entanglement as a function of the biexciton interaction strength. The biexciton interaction can produce bound biexciton states and provides a source of entanglement between the two triplets even when the triplets are spatially well separated. Significant entanglement between the triplet pair occurs well below the threshold for bound pair formation. Our results paint a dynamical picture that helps to explain why fission has been observed to be more efficient in molecular crystals than in their covalent dimer analogues and have consequences for photovoltaic efficiency models that assume that the two triplets can be extracted independently. PMID:26233118

  8. Collective aspects of singlet fission in molecular crystals

    SciTech Connect

    Teichen, Paul E.; Eaves, Joel D.

    2015-07-28

    We present a model to describe collective features of singlet fission in molecular crystals and analyze it using many-body theory. The model we develop allows excitonic states to delocalize over several chromophores which is consistent with the character of the excited states in many molecular crystals, such as the acenes, where singlet fission occurs. As singlet states become more delocalized and triplet states more localized, the rate of singlet fission increases. We also determine the conditions under which the two triplets resulting from fission are correlated. Using the Bethe Ansatz and an entanglement measure for indistinguishable bipartite systems, we calculate the triplet-triplet entanglement as a function of the biexciton interaction strength. The biexciton interaction can produce bound biexciton states and provides a source of entanglement between the two triplets even when the triplets are spatially well separated. Significant entanglement between the triplet pair occurs well below the threshold for bound pair formation. Our results paint a dynamical picture that helps to explain why fission has been observed to be more efficient in molecular crystals than in their covalent dimer analogues and have consequences for photovoltaic efficiency models that assume that the two triplets can be extracted independently.

  9. Monogenec Arrhythmic Syndromes: From Molecular and Genetic Aspects to Bedside

    PubMed Central

    E.Z., Golukhova; O.I., Gromova; R.A., Shomahov; N.I., Bulaeva; L.A., Bockeria

    2016-01-01

    The abrupt cessation of effective cardiac function that is generally due to heart rhythm disorders can cause sudden and unexpected death at any age and is referred to as a syndrome called “sudden cardiac death” (SCD). Annually, about 400,000 cases of SCD occur in the United States alone. Less than 5% of the resuscitation techniques are effective. The prevalence of SCD in a population rises with age according to the prevalence of coronary artery disease, which is the most common cause of sudden cardiac arrest. However, there is a peak in SCD incidence for the age below 5 years, which is equal to 17 cases per 100,000 of the population. This peak is due to congenital monogenic arrhythmic canalopathies. Despite their relative rarity, these cases are obviously the most tragic. The immediate causes, or mechanisms, of SCD are comprehensive. Generally, it is arrhythmic death due to ventricular tachyarrythmias – sustained ventricular tachycardia (VT) or ventricular fibrillation (VF). Bradyarrhythmias and pulseless electrical activity account for no more than 40% of all registered cardiac arrests, and they are more often the outcome of the abovementioned arrhythmias. Our current understanding of the mechanisms responsible for SCD has emerged from decades of basic science investigation into the normal electrophysiology of the heart, the molecular physiology of cardiac ion channels, the fundamental cellular and tissue events associated with cardiac arrhythmias, and the molecular genetics of monogenic disorders of the heart rhythm (for example, the long QT syndrome). This review presents an overview of the molecular and genetic basis of SCD in the long QT syndrome, Brugada syndrome, short QT syndrome, catecholaminergic polymorphic ventricular tachycardia and idiopathic ventricular fibrillation, and arrhythmogenic right ventricular dysplasia, and sudden cardiac death prevention strategies by modern techniques (including implantable cardioverter-defibrillator) PMID:27437140

  10. Monogenec Arrhythmic Syndromes: From Molecular and Genetic Aspects to Bedside.

    PubMed

    E Z, Golukhova; O I, Gromova; R A, Shomahov; N I, Bulaeva; L A, Bockeria

    2016-01-01

    The abrupt cessation of effective cardiac function that is generally due to heart rhythm disorders can cause sudden and unexpected death at any age and is referred to as a syndrome called "sudden cardiac death" (SCD). Annually, about 400,000 cases of SCD occur in the United States alone. Less than 5% of the resuscitation techniques are effective. The prevalence of SCD in a population rises with age according to the prevalence of coronary artery disease, which is the most common cause of sudden cardiac arrest. However, there is a peak in SCD incidence for the age below 5 years, which is equal to 17 cases per 100,000 of the population. This peak is due to congenital monogenic arrhythmic canalopathies. Despite their relative rarity, these cases are obviously the most tragic. The immediate causes, or mechanisms, of SCD are comprehensive. Generally, it is arrhythmic death due to ventricular tachyarrythmias - sustained ventricular tachycardia (VT) or ventricular fibrillation (VF). Bradyarrhythmias and pulseless electrical activity account for no more than 40% of all registered cardiac arrests, and they are more often the outcome of the abovementioned arrhythmias. Our current understanding of the mechanisms responsible for SCD has emerged from decades of basic science investigation into the normal electrophysiology of the heart, the molecular physiology of cardiac ion channels, the fundamental cellular and tissue events associated with cardiac arrhythmias, and the molecular genetics of monogenic disorders of the heart rhythm (for example, the long QT syndrome). This review presents an overview of the molecular and genetic basis of SCD in the long QT syndrome, Brugada syndrome, short QT syndrome, catecholaminergic polymorphic ventricular tachycardia and idiopathic ventricular fibrillation, and arrhythmogenic right ventricular dysplasia, and sudden cardiac death prevention strategies by modern techniques (including implantable cardioverter-defibrillator). PMID:27437140

  11. The Warburg effect: molecular aspects and therapeutic possibilities.

    PubMed

    Ngo, Hanh; Tortorella, Stephanie M; Ververis, Katherine; Karagiannis, Tom C

    2015-04-01

    It has been about nine decades since the proposal of Otto Warburg on the metabolism of cancer cells. Unlike normal cells which undergo glycolysis and oxidative phosphorylation in the presence of oxygen, proliferating and cancer cells exhibit an increased uptake of glucose and increased rate of glycolysis and predominantly undergo lactic acid fermentation. Whether this phenomenon is the consequence of genetic dysregulation in cancer or is the cause of cancer still remains unknown. However, there is certainly a strong link between the genetic factors, epigenetic modulation, cancer immunosurveillance and the Warburg effect, which will be discussed in this review. Dichloroacetate and 3-bromopyruvate are among the substances that have been studied as potential cancer therapies. With our expanding knowledge of cellular metabolism, therapies targeting the Warburg effect appear very promising. This review discusses different aspects of these emerging therapies. PMID:25253100

  12. [Progression of tumors: etiologic, morphologic and molecular-biological aspects].

    PubMed

    Turosov, V S

    1992-01-01

    Two aspects can be distinguished in multistage carcinogenesis: etiological one (every stage is induced by a specific for this stage agent) and morphobiological aspect (every stage is characterized by specific morphological, genetic and other properties). The schema of the multistage carcinogenesis is presented in which morphological stages (diffuse and focal hyperplasia, benign tumours, dysplasia, carcinoma in situ, various phases of malignant tumour progression) are placed against genetic alterations. L. Foulds concept of tumour progression is discussed with special emphasis on precancerous stages, possibilities of cancer development de novo, and independent progression of different tumour characters. The following types of carcinogenesis are listed on the basis of interrelationship between etiological and genetic factors: 1) carcinogenesis induced by genotoxic agents; a) one agent is acting at high dose and for a long time thus ensuring the activation of protooncogenes and all stages of tumour progression (initiation, promotion, various phases of malignant tumour); b) those acting during a very short time, however sufficient for developing the genetic program working automatically without further exposure to known carcinogens (irradiation in case of the atomic bomb explosion or effect of short-living alkylating agents): in this case there is no stage of promotion; 2) carcinogenesis by non-genotoxic carcinogens (their mode of action is still unclear, the only human example is carcinogenesis by hormones); 3) development of tumours in frane of the two (or three) stage carcinogenesis when every stage is provoked by its own etiological factor, no human examples are known as yet; 4) development of tumours due to the genetic mechanism making the organism highly susceptible to the minimal doses of carcinogens as is the case with skin cancer by ultraviolet light in patients with xeroderma pigmentosum, the genetic damage in itself has nothing to do with tumour formation; 5

  13. Molecular aspects of somatic-to-embryogenic transition in plants.

    PubMed

    Karami, Omid; Aghavaisi, Behzad; Mahmoudi Pour, Aghil

    2009-11-01

    Somatic embryogenesis (SE) is a model system for understanding the physiological, biochemical, and molecular biological events occurring during plant embryo development. Plant somatic cells have the ability to undergo sustained divisions and give rise to an entire organism. This remarkable feature is called plant cell totipotency. SE is a notable illustration of plant totipotency and involves reprogramming of development in somatic cells toward the embryogenic pathway. Plant growth regularities, especially auxins, are key components as their exogenous application recapitulates the embryogenic potential of the mitotically quiescent somatic cells. It has been observed that there are genetic and also physiological factors that trigger in vitro embryogenesis in various types of plant somatic cells. Analysis of the proteome and transcriptome has led to the identification and characterization of certain genes involved in SE. Most of these genes, however, are upregulated only in the late developmental stages, suggesting that they do not play a direct role in the vegetative-to-embryogenic transition. However, the molecular bases of those triggering factors and the genetic and biochemical mechanisms leading to in vitro embryogenesis are still unknown. Here, we describe the plant factors that participate in the vegetative-to-embryogenic transition and discuss their possible roles in this process. PMID:19763658

  14. Responses of plant seedlings to hypergravity: cellular and molecular aspects

    NASA Astrophysics Data System (ADS)

    Hoson, T.; Yoshioka, R.; Soga, K.; Wakabayashi, K.; Takeba, G.

    Hypergravity produced by centrifugation has been used to analyze the responses of plant seedlings to gravity stimulus. Elongation growth of stem organs is suppressed by hypergravity, which can be recognized as a way for plants to resist gravitational force. The mechanisms inducing growth suppression under hypergravity conditions were analyzed at cellular and molecular levels. When growth was suppressed by hypergravity, a decrease in the cell wall extensibility was brought about in various plants. Hypergravity also induced a cell wall thickening and an increase in the molecular mass of the certain hemicellulosic polysaccharides. Both a decrease in the activities hydrolyzing such polysaccharides and an increase in the apoplast pH were involved in such changes in the cell wall constituents. Thus, the cell wall metabolism is greatly modified under hypergravity conditions, which causes a decrease in the cell wall extensibility, thereby inhibiting elongation growth in stem organs. On the other hand, to identify genes involved in hypergravity-induced growth suppression, changes in gene expression by hypergravity treatment were analyzed in Arabidopsis hypocotyls by differential display method. Sixty-two genes were expressed differentially: expression levels of 39 genes increased, whereas those of 23 genes decreased under hypergravity conditions. The expression of these genes was further analyzed using RT-PCR. One of genes upregulated by hypergravity encoded hydroxymethylglutaryl-CoA reductase (HMGR), which catalyzes a reaction producing mevalonic acid, a key precursor of hormones such as gibberellic acid and abscisic acid. The expression of HMGR gene increased within several hours after hypergravity treatment. Also, compactin, an inhibitor of HMGR activity, prevented hypergravity-induced growth suppression, suggesting that HMGR is involved in suppression of Arabidopsis hypocotyl growth by hypergravity. In addition, hypergravity increased the expression levels of CCR1 and

  15. Molecular aspects of stress-gene regulation during spaceflight

    NASA Technical Reports Server (NTRS)

    Paul, Anna-Lisa; Ferl, Robert J.

    2002-01-01

    Spaceflight-associated stress has been the topic of investigation since the first terrestrial organisms were exposed to this unique environment. Organisms that evolved under the selection pressures of earth-normal environments can perceive spaceflight as a stress, either directly because gravity influences an intrinsic biological process, or indirectly because of secondary effects imparted by spaceflight upon environmental conditions. Different organisms and even different organs within an organism adapt to a spaceflight environment with a diversity of tactics. Plants are keenly sensitive to gravity for directed development, and are also sensitive to other stresses associated with closed-system spaceflight environments. Within the past decade, the tools of molecular biology have begun to provide a sophisticated evaluation of spaceflight-associated stress and the genetic responses that accompany metabolic adaptation to spaceflight.

  16. Angelman syndrome: review of clinical and molecular aspects

    PubMed Central

    Bird, Lynne M

    2014-01-01

    “Angelman syndrome” (AS) is a neurodevelopmental disorder whose main features are intellectual disability, lack of speech, seizures, and a characteristic behavioral profile. The behavioral features of AS include a happy demeanor, easily provoked laughter, short attention span, hypermotoric behavior, mouthing of objects, sleep disturbance, and an affinity for water. Microcephaly and subtle dysmorphic features, as well as ataxia and other movement disturbances, are additional features seen in most affected individuals. AS is due to deficient expression of the ubiquitin protein ligase E3A (UBE3A) gene, which displays paternal imprinting. There are four molecular classes of AS, and some genotype–phenotype correlations have emerged. Much remains to be understood regarding how insufficiency of E6-AP, the protein product of UBE3A, results in the observed neurodevelopmental deficits. Studies of mouse models of AS have implicated UBE3A in experience-dependent synaptic remodeling. PMID:24876791

  17. Autoimmune regulator and self-tolerance - molecular and clinical aspects.

    PubMed

    Abramson, Jakub; Husebye, Eystein S

    2016-05-01

    The establishment of central tolerance in the thymus is critical for avoiding deleterious autoimmune diseases. Autoimmune regulator (AIRE), the causative gene in autoimmune polyendocrine syndrome type-1 (APS-1), is crucial for the establishment of self-tolerance in the thymus by promoting promiscuous expression of a wide array of tissue-restricted self-antigens. This step is critical for elimination of high-affinity self-reactive T cells from the immunological repertoire, and for the induction of a specific subset of Foxp3(+) T-regulatory (Treg ) cells. In this review, we discuss the most recent advances in our understanding of how AIRE operates on molecular and cellular levels, as well as of how its loss of function results in breakdown of self-tolerance mechanisms characterized by a broad and heterogeneous repertoire of autoimmune phenotypes. PMID:27088911

  18. Nuclear receptors CAR and PXR: Molecular, functional, and biomedical aspects.

    PubMed

    di Masi, Alessandra; De Marinis, Elisabetta; Ascenzi, Paolo; Marino, Maria

    2009-10-01

    Nuclear receptors (NRs) are ligand-activated transcription factors sharing a common evolutionary history and having similar sequence features at the protein level. Selective ligand(s) for some NRs is not known, therefore these NRs have been named "orphan receptors". Whenever ligands have been recognized for any of the orphan receptor, it has been categorized and grouped as "adopted" orphan receptor. This group includes the constitutive androstane receptor (CAR) and the pregnane X receptor (PXR). They function as sensors of toxic byproducts derived from endogenous metabolites and of exogenous chemicals, in order to enhance their elimination. This unique function of CAR and PXR sets them apart from the steroid hormone receptors. The broad response profile has established that CAR and PXR are xenobiotic sensors that coordinately regulate xenobiotic clearance in the liver and intestine via induction of genes involved in drug and xenobiotic metabolism. In the past few years, research has revealed new and mostly unsuspected roles for CAR and PXR in modulating hormone, lipid, and energy homeostasis as well as cancer and liver steatosis. The purpose of this review is to highlight the structural and molecular bases of CAR and PXR impact on human health, providing information on mechanisms through which diet, chemical exposure, and environment ultimately impact health and disease. PMID:19427329

  19. Resistance to Tospoviruses in Vegetable Crops: Epidemiological and Molecular Aspects.

    PubMed

    Turina, Massimo; Kormelink, Richard; Resende, Renato O

    2016-08-01

    During the past three decades, the economic impact of tospoviruses has increased, causing high yield losses in a variety of crops and ornamentals. Owing to the difficulty in combating thrips vectors with insecticides, the best way to limit/prevent tospovirus-induced diseases involves a management strategy that includes virus resistance. This review briefly presents current tospovirus taxonomy, diversity, molecular biology, and cytopathology as an introduction to a more extensive description of the two main resistance genes employed against tospoviruses: the Sw5 gene in tomato and the Tsw in pepper. Natural and experimental resistance-breaking (RB) isolates allowed the identification of the viral avirulence protein triggering each of the two resistance gene products; epidemiology of RB isolates is discussed to reinforce the need for allelic variants and the need to search for new/alternative resistance genes. Ongoing efforts for alternative resistance strategies are described not only for Tomato spotted wilt virus (TSWV) in pepper and tomato but also for other vegetable crops heavily impacted by tospoviruses. PMID:27296139

  20. [Molecular and cellular aspects of radiation hormesis in Drosophila melanogaster].

    PubMed

    Vaĭserman, A M; Litoshenko, A Ia; Kvitnitskaia-Ryzhova, T Iu; Koshel', N M; Mozzhukhina, T G; Mikhal'skiĭ, S A; Voĭtenko, V P

    2003-01-01

    The long-term effects of the R-irradiation of D. melanogaster at the 1-hour egg stage with the dosages of 0.25, 0.50, 0.75, 1.0, 2.0 and 4.0 Gy were investigated. DNA samples were isolated from whole 5-6-days adult males. The aliquots of DNA were digested by S1-nuclease. Preimaginal stage lethality increased with irradiation dose increasing. At the same time, decrease in imaginal LS (life span) was observed after irradiation with the greatest dose (4 Gy) only. Moreover, hormesis by LS has revealed: in males irradiation with 0.25, 0.75 and 1 Gy increased the mean LS, and with 0.25 and 0.5 Gy caused the maximum LS; in females exposures with 0.25, 0.75 and 2 Gy increased the maximum LS. The densitometric assay of DNA electrophoregrams showed decrease by 39.2% of the part of high-molecular-weight DNA in control as a result of S1-nuclease action. Samples of DNA from the irradiated flies were more stable to enzyme action. The higher stability of DNA originated from the irradiated flies could be the result of reparation system activation. Ultrastructural changes induced at the egg stage by irradiation at the dose of 0.75 Gy testify the increased transcriptional activity of the brain cells. PMID:12945182

  1. Molecular layer interneurons of the cerebellum: developmental and morphological aspects.

    PubMed

    Sotelo, Constantino

    2015-10-01

    During the past 25 years, our knowledge on the development of basket and stellate cells (molecular layer interneurons [MLIs]) has completely changed, not only regarding their origin from the ventricular zone, corresponding to the primitive cerebellar neuroepithelium, instead of the external granular layer, but above all by providing an almost complete account of the genetic regulations (transcription factors and other genes) involved in their differentiation and synaptogenesis. Moreover, it has been shown that MLIs' precursors (dividing neuroblasts) and not young postmitotic neurons, as in other germinal neuroepithelia, leave the germinative zone and migrate all along a complex and lengthy path throughout the presumptive cerebellar white matter, which provides suitable niches exerting epigenetic influences on their ultimate neuronal identities. Recent studies carried out on the anatomical-functional properties of adult MLIs emphasize the importance of these interneurons in regulating PC inhibition, and point out the crucial role played by electrical synaptic transmission between MLIs as well as ephaptic interactions between them and Purkinje cells at the pinceaux level, in the regulation of this inhibition. PMID:25599913

  2. Ferric Enterochelin Transport in Yersinia enterocolitica: Molecular and Evolutionary Aspects

    PubMed Central

    Schubert, S.; Fischer, D.; Heesemann, J.

    1999-01-01

    Yersinia enterocolitica is well equipped for siderophore piracy, encompassing the utilization of siderophores such as ferrioxamine, ferrichrome, and ferrienterochelin. In this study, we report on the molecular and functional characterization of the Yersinia fep-fes gene cluster orthologous to the Escherichia coli ferrienterochelin transport genes (fepA, fepDGC, and fepB) and the esterase gene fes. In vitro transcription-translation analysis identified polypeptides of 30 and 35 kDa encoded by fepC and fes, respectively. A frameshift mutation within the fepA gene led to expression of a truncated polypeptide of 40 kDa. The fepD, fepG, and fes genes of Y. enterocolitica were shown to complement corresponding E. coli mutants. Insertional mutagenesis of fepD or fes genes abrogates enterochelin-supported growth of Y. enterocolitica on iron-chelated media. In contrast to E. coli, the fep-fes gene cluster in Y. enterocolitica consists solely of genes required for uptake and utilization of enterochelin (fep) and not of enterochelin synthesis genes such as entF. By Southern hybridization, fepDGC and fes sequences could be detected in Y. enterocolitica biotypes IB, IA, and II but not in biotype IV strains, Yersinia pestis, and Yersinia pseudotuberculosis strains. According to sequence alignment data and the coherent structure of the Yersinia fep-fes gene cluster, we suggest early genetic divergence of ferrienterochelin uptake determinants among species of the family Enterobacteriaceae. PMID:10515929

  3. Ferric enterochelin transport in Yersinia enterocolitica: molecular and evolutionary aspects.

    PubMed

    Schubert, S; Fischer, D; Heesemann, J

    1999-10-01

    Yersinia enterocolitica is well equipped for siderophore piracy, encompassing the utilization of siderophores such as ferrioxamine, ferrichrome, and ferrienterochelin. In this study, we report on the molecular and functional characterization of the Yersinia fep-fes gene cluster orthologous to the Escherichia coli ferrienterochelin transport genes (fepA, fepDGC, and fepB) and the esterase gene fes. In vitro transcription-translation analysis identified polypeptides of 30 and 35 kDa encoded by fepC and fes, respectively. A frameshift mutation within the fepA gene led to expression of a truncated polypeptide of 40 kDa. The fepD, fepG, and fes genes of Y. enterocolitica were shown to complement corresponding E. coli mutants. Insertional mutagenesis of fepD or fes genes abrogates enterochelin-supported growth of Y. enterocolitica on iron-chelated media. In contrast to E. coli, the fep-fes gene cluster in Y. enterocolitica consists solely of genes required for uptake and utilization of enterochelin (fep) and not of enterochelin synthesis genes such as entF. By Southern hybridization, fepDGC and fes sequences could be detected in Y. enterocolitica biotypes IB, IA, and II but not in biotype IV strains, Yersinia pestis, and Yersinia pseudotuberculosis strains. According to sequence alignment data and the coherent structure of the Yersinia fep-fes gene cluster, we suggest early genetic divergence of ferrienterochelin uptake determinants among species of the family Enterobacteriaceae. PMID:10515929

  4. [MELAS syndrome. Clinical aspects, MRI, biochemistry and molecular genetics].

    PubMed

    Damian, M S; Reichmann, H; Seibel, P; Bachmann, G; Schachenmayr, W; Dorndorf, W

    1994-04-01

    MELAS is a mitochondrial cytopathy characterized by encephalopathy with stroke-like episodes and lactic acidosis. Most patients exhibit an A-G transition mutation at np 3243 of mitochondrial DNA (tRNA(Leu)(UUR)). We present a family of four in which the mutation was discovered in blood and in muscle mt DNA. Two patients had the classic MELAS syndrome with multiple stroke-like episodes. Some episodes were precipitated by metabolic stress. The remaining two patients had an oligosymptomatic disease with mild chronic encephalopathy, small stature and hearing loss. MRI was followed over a period of 4-8 years, during which the MELAS patients showed progression from nonspecific multifocal signal change to typical extensive cortico-subcortical parieto-occipital lesions and progressive cerebral atrophy. MRI in the oligosymptomatic cases was normal, or showed non-progressive cerebellar atrophy. Biochemical findings were non-specific, indicating increased mitochondrial volume in all cases, and a relatively complex IV defect in one case. All patients were treated with coenzyme Q with varying clinical response. The percentage of mutant mt DNA in blood and muscle did not correlate with clinical severity. Pathogenetic theories based on molecular genetics, and the therapeutic regimen in terms of the underlying biochemical concepts are discussed. PMID:8015633

  5. [Gastrointestinal stromal tumors: molecular aspects and therapeutic implications].

    PubMed

    Italiano, Antoine; Bui, Binh

    2008-01-01

    Approximately 90 % of gastrointestinal tumors (GISTs) harbor an activating mutation in KIT or PDGFR alpha oncogene known to confer imatinib sensitivity. Imatinib is a tyrosine kinase inhibitor of KIT and PDGFRs that yields a 6-months progression-free survival (PFS) rate of 80 % in patients with advanced GISTs. Several studies have shown that response to imatinib in GIST patients mainly depends on the mutational status of KIT or PDGFR alpha. Moreover, most if not all patients treated with imatinib for advanced GIST will secondarily develop progressive disease under treatment. In the majority of cases, such progressions are the result of acquired resistance due to occurrence of secondary C-KIT mutations; especially for GIST with primary exon 11 mutations. Sunitinib is another approved drug and an inhibitor of multiple tyrosine kinases including KIT, PDGFR alpha as well as PDGFR beta and VEGFRs which are associated with angiogenesis. Sunitinib, in phase II and III trials was associated with durable clinical benefit in nearly 25 % of patients with advanced GIST resistant/intolerant to imatinib. Clearly, a better knowledge of the molecular mechanisms underlying the resistance to imatinib as well as the development of a new class of broad-spectrum tyrosine kinase inhibitors may allow in the near future new individualized therapeutic strategies for GISTs patients. PMID:18230576

  6. Molecular Aspects of Plasmodium falciparum Infection during Pregnancy

    PubMed Central

    Ndam, Nicaise Tuikue; Deloron, Philippe

    2007-01-01

    Cytoadherence of Plasmodium-falciparum-parasitized red blood cells (PRBCs) to host receptors is the key phenomenon in the pathological process of the malaria disease. Some of these interactions can originate poor outcomes responsible for 1 to 3 million annual deaths mostly occurring among children in sub-Saharan Africa. Pregnancy-associated malaria (PAM) represents an important exception of the disease occurring at adulthood in malaria endemic settings. Consequences of this are shared between the mother (maternal anemia) and the baby (low birth weight and infant mortality). Demonstrating that parasites causing PAM express specific variant surface antigens (VSAPAM), including the P. falciparum erythrocyte membrane protein 1 (P f EMP1) variant VAR2CSA, that are targets for protective immunity has strengthened the possibility for the development of PAM-specific vaccine. In this paper, we review the molecular basis of malaria pathogenesis attributable to the erythrocyte stages of the parasites, and findings supporting potential anti-PAM vaccine components evidenced in PAM. PMID:17641725

  7. Molecular aspects of bovine cystic ovarian disease pathogenesis.

    PubMed

    Ortega, Hugo H; Marelli, Belkis E; Rey, Florencia; Amweg, Ayelen N; Díaz, Pablo U; Stangaferro, Matías L; Salvetti, Natalia R

    2015-06-01

    Cystic ovarian disease (COD) is one of the main causes of reproductive failure in cattle and causes severe economic loss to the dairy farm industry because it increases both days open in the post partum period and replacement rates due to infertility. This disease is the consequence of the failure of a mature follicle to ovulate at the time of ovulation in the estrous cycle. This review examines the evidence for the role of altered steroid and gonadotropin signaling systems and the proliferation/apoptosis balance in the ovary with cystic structures. This evidence suggests that changes in the expression of ovarian molecular components associated with these cellular mechanisms could play a fundamental role in the pathogenesis of COD. The evidence also shows that gonadotropin receptor expression in bovine cystic follicles is altered, which suggests that changes in the signaling system of gonadotropins could play a fundamental role in the pathogenesis of conditions characterized by altered ovulation, such as COD. Ovaries from animals with COD exhibit a disrupted steroid receptor pattern with modifications in the expression of coregulatory proteins. These changes in the pathways of endocrine action would trigger the changes in proliferation and apoptosis underlying the aberrant persistence of follicular cysts. Free Spanish abstract: A Spanish translation of this abstract is freely available at http://www.reproduction-online.org/content/149/6/R251/suppl/DC1. PMID:25767139

  8. Biomining Microorganisms: Molecular Aspects and Applications in Biotechnology and Bioremediation

    NASA Astrophysics Data System (ADS)

    Jerez, Carlos A.

    The microbial solubilization of metals using chemolithoautotrophic microorganisms has successfully been used in industrial processes called biomining to extract metals such as copper, gold, uranium and others. The most studied leaching bacteria are from the genus Acidithiobacillus belonging to the Gram-negative γ-proteobacteria. Acidithiobacillus spp. obtain their energy from the oxidation of ferrous iron, elemental sulfur, or partially oxidized sulfur compounds. Other thermophilic archaeons capable of oxidizing sulfur and iron (II) have also been known for many years, and they are mainly from the genera Sulfolobus, Acidianus, Metallosphaera and Sulfurisphaera. Recently, some mesophilic iron (II)-oxidizing archaeons such as Ferroplasma acidiphilium and F. acidarmanus belonging to the Thermoplasmales have also been isolated and characterized. Recent studies of microorganisms consider them in their consortia, integrating fundamental biological knowledge with metagenomics, metaproteomics, and other data to obtain a global picture of how a microbial community functions. The understanding of microbial growth and activities in oxidizing metal ions will be useful for improving applied microbial biotechnologies such as biomining, bioshrouding, biomonitoring and bioremediation of metals in acidic environments.

  9. Beam dynamics aspects for the APT integrated linac

    SciTech Connect

    Nath, S.; Gray, E.R.; Wangler, T.P.

    1997-08-01

    The accelerator-based production of tritium calls for a high-power cw proton linac. The current Los Alamos design uses an integrated approach in terms of accelerating structure. The front part of the accelerator uses normal-conducting (NC) structures while most (>80%) of the linac structure is superconducting (SC). Here, the authors report the beam-dynamics rationale used in the integrated design and present particle simulation results.

  10. Symbolic programming language in molecular multicenter integral problem

    NASA Astrophysics Data System (ADS)

    Safouhi, Hassan; Bouferguene, Ahmed

    It is well known that in any ab initio molecular orbital (MO) calculation, the major task involves the computation of molecular integrals, among which the computation of three-center nuclear attraction and Coulomb integrals is the most frequently encountered. As the molecular system becomes larger, computation of these integrals becomes one of the most laborious and time-consuming steps in molecular systems calculation. Improvement of the computational methods of molecular integrals would be indispensable to further development in computational studies of large molecular systems. To develop fast and accurate algorithms for the numerical evaluation of these integrals over B functions, we used nonlinear transformations for improving convergence of highly oscillatory integrals. These methods form the basis of new methods for solving various problems that were unsolvable otherwise and have many applications as well. To apply these nonlinear transformations, the integrands should satisfy linear differential equations with coefficients having asymptotic power series in the sense of Poincaré, which in their turn should satisfy some limit conditions. These differential equations are very difficult to obtain explicitly. In the case of molecular integrals, we used a symbolic programming language (MAPLE) to demonstrate that all the conditions required to apply these nonlinear transformation methods are satisfied. Differential equations are obtained explicitly, allowing us to demonstrate that the limit conditions are also satisfied.

  11. Health-related aspects of integrated pest management.

    PubMed Central

    Smith, R F; Calvert, D J

    1976-01-01

    Basic concepts and philosophy of integrated pest management are presented in order to dispel several misconceptions and to provide the necessary background information for discussion of its relationship to the health-related effects of pesticide use. Implications for human health of current pesticide practices in Central America are examined to illustrate major problems associated with the injudicious use of insecticides, i.e., human pesticide poisonings, development of insect resistance, and persistence in the environment. Mitigation of these problems would ideally be achieved through the efforts and cooperation of a multidisciplinary team of scientists and technical people in the medical and agricultural sciences. The dilemma associated with the development of integrated pest control systems in developing countries is discussed. The FAO/UNEP Global Programme was reviewed. PMID:976225

  12. Translational neurocardiology: preclinical models and cardioneural integrative aspects.

    PubMed

    Ardell, J L; Andresen, M C; Armour, J A; Billman, G E; Chen, P-S; Foreman, R D; Herring, N; O'Leary, D S; Sabbah, H N; Schultz, H D; Sunagawa, K; Zucker, I H

    2016-07-15

    Neuronal elements distributed throughout the cardiac nervous system, from the level of the insular cortex to the intrinsic cardiac nervous system, are in constant communication with one another to ensure that cardiac output matches the dynamic process of regional blood flow demand. Neural elements in their various 'levels' become differentially recruited in the transduction of sensory inputs arising from the heart, major vessels, other visceral organs and somatic structures to optimize neuronal coordination of regional cardiac function. This White Paper will review the relevant aspects of the structural and functional organization for autonomic control of the heart in normal conditions, how these systems remodel/adapt during cardiac disease, and finally how such knowledge can be leveraged in the evolving realm of autonomic regulation therapy for cardiac therapeutics. PMID:27098459

  13. Internal radiation therapy: a neglected aspect of nuclear medicine in the molecular era

    PubMed Central

    Lin, Yansong

    2015-01-01

    Abstract With increasing evidence, internal radiation therapy, also known as brachytherapy, has become a neglected aspect of nuclear medicine in the molecular era. In this paper, recent developments regarding internal radiation therapy, including developments in radioiodine-131 (131I) and thyroid, radioimmunotherapy (RIT) for non-Hodgkin lymphoma (NHL), and radiopharmaceuticals for bone metastases. Relevant differences and status of their applications in China were mentioned as well. These molecular mediated internal radiation therapies are gaining increasing importance by providing palliative and curative treatments for an increasing number of diseases and becoming one of the important parts of molecular nuclear medicine. PMID:26445567

  14. Glycoprotein Biochemistry (Biosynthesis)--A Vehicle for Teaching Many Aspects of Biochemistry and Molecular Biology.

    ERIC Educational Resources Information Center

    Cole, Clair R.; Smith, Christopher A.

    1990-01-01

    Information about the biosynthesis of the carbohydrate portions or glycans of glycoproteins is presented. The teaching of glycosylation can be used to develop and emphasize many general aspects of biosynthesis, in addition to explaining specific biochemical and molecular biological features associated with producing the oligosaccharide portions of…

  15. Molecular basis of cell integrity and morphogenesis in Saccharomyces cerevisiae.

    PubMed Central

    Cid, V J; Durán, A; del Rey, F; Snyder, M P; Nombela, C; Sánchez, M

    1995-01-01

    In fungi and many other organisms, a thick outer cell wall is responsible for determining the shape of the cell and for maintaining its integrity. The budding yeast Saccharomyces cerevisiae has been a useful model organism for the study of cell wall synthesis, and over the past few decades, many aspects of the composition, structure, and enzymology of the cell wall have been elucidated. The cell wall of budding yeasts is a complex and dynamic structure; its arrangement alters as the cell grows, and its composition changes in response to different environmental conditions and at different times during the yeast life cycle. In the past few years, we have witnessed a profilic genetic and molecular characterization of some key aspects of cell wall polymer synthesis and hydrolysis in the budding yeast. Furthermore, this organism has been the target of numerous recent studies on the topic of morphogenesis, which have had an enormous impact on our understanding of the intracellular events that participate in directed cell wall synthesis. A number of components that direct polarized secretion, including those involved in assembly and organization of the actin cytoskeleton, secretory pathways, and a series of novel signal transduction systems and regulatory components have been identified. Analysis of these different components has suggested pathways by which polarized secretion is directed and controlled. Our aim is to offer an overall view of the current understanding of cell wall dynamics and of the complex network that controls polarized growth at particular stages of the budding yeast cell cycle and life cycle. PMID:7565410

  16. Some aspects of integrated water resources management in central Asia

    NASA Astrophysics Data System (ADS)

    Khaydarova, V.; Penkova, N.; Pak, E.; Poberejsky, L.; Beltrao, J.

    2003-04-01

    Two main tasks are to be implemented for elaboration of the governmental water distribution criteria in Central Asia: 1 -development of the common methodological basis for the intergovernmental water distribution; and 2 - to reopen and continue both theoretical and experimental researches of various aspects of the wastewater reuse. The prospects of socio economic development of all Central Asian countries are substantially defined by the water resources availability. The water resources of Central Asia belong, mainly, watersheds of the Syr-Darya and Amu Darya rivers. The basic flow of Amu Darya is formed in territory of Tajikistan. Then the Amu Darya river proceeds along border of Afghanistan with Uzbekistan, crosses Turkmenistan and again comes back to Uzbekistan and then runs into the Aral Sea. The Syr-Darya is second river on the water discharge and is first river on length in Central Asia. The basic flow of Syr Darya is formed in territory of Kyrgyzstan. Then the Syr-Darya river crosses of Uzbekistan and Tajikistan and runs into the Aral Sea in territory of Kazakhstan. During the Soviet Union the water resources of two river watersheds were divided among the Central Asian republics on the basis of the general plans developed by the center in Moscow. In the beginning of 90s years, after taking of sovereignty by the former Soviet republics, the unified control system of water resources management was abolished and the various approaches to its transformation caused by features of the national economy developing, elected models of transition from command to market mechanisms of economic activity, and also specificity of political and social processes in each of the states of region were planned. The distinctions of modern priorities of economic development of the states of region have generated the contradiction of interests in the intergovernmental water distribution that can in the long term become complicated even more in connection with the increasing of water

  17. Some aspects of integrated water resources management in central Asia

    NASA Astrophysics Data System (ADS)

    Khaydarova, V.; Penkova, N.; Pak, E.; Poberejsky, L.; Beltrao, J.

    2003-04-01

    Two main tasks are to be implemented for elaboration of the governmental water distribution criteria in Central Asia: 1 -development of the common methodological basis for the intergovernmental water distribution; and 2 - to reopen and continue both theoretical and experimental researches of various aspects of the wastewater reuse. The prospects of socio economic development of all Central Asian countries are substantially defined by the water resources availability. The water resources of Central Asia belong, mainly, watersheds of the Syr-Darya and Amu Darya rivers. The basic flow of Amu Darya is formed in territory of Tajikistan. Then the Amu Darya river proceeds along border of Afghanistan with Uzbekistan, crosses Turkmenistan and again comes back to Uzbekistan and then runs into the Aral Sea. The Syr-Darya is second river on the water discharge and is first river on length in Central Asia. The basic flow of Syr Darya is formed in territory of Kyrgyzstan. Then the Syr-Darya river crosses of Uzbekistan and Tajikistan and runs into the Aral Sea in territory of Kazakhstan. During the Soviet Union the water resources of two river watersheds were divided among the Central Asian republics on the basis of the general plans developed by the center in Moscow. In the beginning of 90s years, after taking of sovereignty by the former Soviet republics, the unified control system of water resources management was abolished and the various approaches to its transformation caused by features of the national economy developing, elected models of transition from command to market mechanisms of economic activity, and also specificity of political and social processes in each of the states of region were planned. The distinctions of modern priorities of economic development of the states of region have generated the contradiction of interests in the intergovernmental water distribution that can in the long term become complicated even more in connection with the increasing of water

  18. Non-equilibrium Aspects of Quantum Integrable Systems

    NASA Astrophysics Data System (ADS)

    Andrei, Natan

    The study of non-equilibrium dynamics of interacting many body systems is currently one of the main challenges of modern condensed matter physics, driven by the spectacular progress in the ability to create experimental systems - trapped cold atomic gases are a prime example - that can be isolated from their environment and be highly controlled. Many old and new questions can be addressed: thermalization of isolated systems, nonequilibrium steady states, the interplay between non equilibrium currents and strong correlations, quantum phase transitions in time, universality among others. In this talk I will describe nonequilibrium quench dynamics in integrable quantum systems. I'll discuss the time evolution of the Lieb-Liniger system, a gas of interacting bosons moving on the continuous infinite line and interacting via a short range potential. Considering a finite number of bosons on the line we find that for any value of repulsive coupling the system asymptotes towards a strongly repulsive gas for any initial state, while for an attractive coupling, the system forms a maximal bound state that dominates at longer times. In the thermodynamic limit -with the number of bosons and the system size sent to infinity at a constant density and the long time limit taken subsequently- I'll show that the density and density-density correlation functions for strong but finite positive coupling are described by GGE for translationally invariant initial states with short range correlations. As examples I'll discuss quenches from a Mott insulator initial state or a Newton's Cradle. Then I will show that if the initial state is strongly non translational invariant, e.g. a domain wall configuration, the system does not equilibrate but evolves into a nonequilibrium steady state (NESS). A related NESS arises when the quench consists of coupling a quantum dot to two leads held at different chemical potential, leading in the long time limit to a steady state current. Time permitting I

  19. Coupling, Q-Factor, and Integration Aspects of Microsphere Applications

    NASA Technical Reports Server (NTRS)

    Ilchenko, V. S.; Yao, X. S.; Maleki, L.

    2000-01-01

    With suggested applications varying from microlaser and cavity QED through optical locking of diode lasers to modulators and sensors, high-Q silica microspheres with whispering-gallery (WG) modes so far remain the subject of tabletop feasibility demonstrations. Despite the uniquely high quality-factor and submillimeter dimensions suitable for tight packaging, this novel type of high-finesse cavity still has to be adapted to fiber- and integrated-optic hardware. In the visible and near infrared-band experiments (633-850nm) measuring the ringdown time tau of free oscillations, Q = (0.6 to 0.8 ) x 10(exp 10) has been obtained in silica spheres of diameter -800 microns (corresponding tau = 3 to 4 microseconds). It was proved that under normal laboratory conditions, quality-factor is subject to deterioration within several-minute scale down to (2 ... 3 ) x 10(exp 9). The responsible mechanism was identified as adsorption of a monolayer of atmospheric water, so that preservation of the ultimate Q requires manipulation in dry environment, or fast packaging into sealed devices. Larger Q can be expected closer to minimum of attenuation in fused silica alpha = 0.2 dB/km; Q greater than or equal to 1 x 10(exp 11) at lambda=1.55 microns, with corresponding energy storage time tau approx. 0.1ms. Experiments are currently underway to determine whether this high Q can be realized experimentally. The evident difficulty is that OH-related optical absorption has its peaks located near the reported minimum of attenuation in silica. We can also mention here that some of proposed fiber materials, yet not ready for fiber drawing, have been predicted to have smaller attenuation than fused silica and may be suitable for microsphere fabrication (sodium-magnesium silicate glass, alpha = 0.06dB/km). WG modes possess very small radiative loss (it does not prevent Q-10(exp 20) and more) and therefore are electromagnetically isolated and cannot be excited by free-space beams. If no modification

  20. Integrated Multiscale Modeling of Molecular Computing Devices

    SciTech Connect

    Jerzy Bernholc

    2011-02-03

    will some day reach a miniaturization limit, forcing designers of Si-based electronics to pursue increased performance by other means. Any other alternative approach would have the unenviable task of matching the ability of Si technology to pack more than a billion interconnected and addressable devices on a chip the size of a thumbnail. Nevertheless, the prospects of developing alternative approaches to fabricate electronic devices have spurred an ever-increasing pace of fundamental research. One of the promising possibilities is molecular electronics (ME), self-assembled molecular-based electronic systems composed of single-molecule devices in ultra dense, ultra fast molecular-sized components. This project focused on developing accurate, reliable theoretical modeling capabilities for describing molecular electronics devices. The participants in the project are given in Table 1. The primary outcomes of this fundamental computational science grant are publications in the open scientific literature. As listed below, 62 papers have been published from this project. In addition, the research has also been the subject of more than 100 invited talks at conferences, including several plenary or keynote lectures. Many of the goals of the original proposal were completed. Specifically, the multi-disciplinary group developed a unique set of capabilities and tools for investigating electron transport in fabricated and self-assembled nanostructures at multiple length and time scales.

  1. Integrated Multiscale Modeling of Molecular Computing Devices

    SciTech Connect

    Weinan E

    2012-03-29

    The main bottleneck in modeling transport in molecular devices is to develop the correct formulation of the problem and efficient algorithms for analyzing the electronic structure and dynamics using, for example, the time-dependent density functional theory. We have divided this task into several steps. The first step is to developing the right mathematical formulation and numerical algorithms for analyzing the electronic structure using density functional theory. The second step is to study time-dependent density functional theory, particularly the far-field boundary conditions. The third step is to study electronic transport in molecular devices. We are now at the end of the first step. Under DOE support, we have made subtantial progress in developing linear scaling and sub-linear scaling algorithms for electronic structure analysis. Although there has been a huge amount of effort in the past on developing linear scaling algorithms, most of the algorithms developed suffer from the lack of robustness and controllable accuracy. We have made the following progress: (1) We have analyzed thoroughly the localization properties of the wave-functions. We have developed a clear understanding of the physical as well as mathematical origin of the decay properties. One important conclusion is that even for metals, one can choose wavefunctions that decay faster than any algebraic power. (2) We have developed algorithms that make use of these localization properties. Our algorithms are based on non-orthogonal formulations of the density functional theory. Our key contribution is to add a localization step into the algorithm. The addition of this localization step makes the algorithm quite robust and much more accurate. Moreover, we can control the accuracy of these algorithms by changing the numerical parameters. (3) We have considerably improved the Fermi operator expansion (FOE) approach. Through pole expansion, we have developed the optimal scaling FOE algorithm.

  2. Integrating influenza antigenic dynamics with molecular evolution

    PubMed Central

    Bedford, Trevor; Suchard, Marc A; Lemey, Philippe; Dudas, Gytis; Gregory, Victoria; Hay, Alan J; McCauley, John W; Russell, Colin A; Smith, Derek J; Rambaut, Andrew

    2014-01-01

    Influenza viruses undergo continual antigenic evolution allowing mutant viruses to evade host immunity acquired to previous virus strains. Antigenic phenotype is often assessed through pairwise measurement of cross-reactivity between influenza strains using the hemagglutination inhibition (HI) assay. Here, we extend previous approaches to antigenic cartography, and simultaneously characterize antigenic and genetic evolution by modeling the diffusion of antigenic phenotype over a shared virus phylogeny. Using HI data from influenza lineages A/H3N2, A/H1N1, B/Victoria and B/Yamagata, we determine patterns of antigenic drift across viral lineages, showing that A/H3N2 evolves faster and in a more punctuated fashion than other influenza lineages. We also show that year-to-year antigenic drift appears to drive incidence patterns within each influenza lineage. This work makes possible substantial future advances in investigating the dynamics of influenza and other antigenically-variable pathogens by providing a model that intimately combines molecular and antigenic evolution. DOI: http://dx.doi.org/10.7554/eLife.01914.001 PMID:24497547

  3. Choosing the right molecular genetic markers for studying biodiversity: from molecular evolution to practical aspects.

    PubMed

    Chenuil, Anne; Anne, Chenuil

    2006-05-01

    The use of molecular genetic markers (MGMs) has become widespread among evolutionary biologists, and the methods of analysis of genetic data improve rapidly, yet an organized framework in which scientists can work is lacking. Elements of molecular evolution are summarized to explain the origin of variation at the DNA level, its measures, and the relationships linking genetic variability to the biological parameters of the studied organisms. MGM are defined by two components: the DNA region(s) screened, and the technique used to reveal its variation. Criteria of choice belong to three categories: (1) the level of variability, (2) the nature of the information (e.g. dominance vs. codominance, ploidy, ... ) which must be determined according to the biological question and (3) some practical criteria which mainly depend on the equipment of the laboratory and experience of the scientist. A three-step procedure is proposed for drawing up MGMs suitable to answer given biological questions, and compiled data are organized to guide the choice at each step: (1) choice, determined by the biological question, of the level of variability and of the criteria of the nature of information, (2) choice of the DNA region and (3) choice of the technique. PMID:16850217

  4. An Integrated Biochemistry Laboratory, Including Molecular Modeling

    NASA Astrophysics Data System (ADS)

    Hall, Adele J. Wolfson Mona L.; Branham, Thomas R.

    1996-11-01

    ) experience with methods of protein purification; (iii) incorporation of appropriate controls into experiments; (iv) use of basic statistics in data analysis; (v) writing papers and grant proposals in accepted scientific style; (vi) peer review; (vii) oral presentation of results and proposals; and (viii) introduction to molecular modeling. Figure 1 illustrates the modular nature of the lab curriculum. Elements from each of the exercises can be separated and treated as stand-alone exercises, or combined into short or long projects. We have been able to offer the opportunity to use sophisticated molecular modeling in the final module through funding from an NSF-ILI grant. However, many of the benefits of the research proposal can be achieved with other computer programs, or even by literature survey alone. Figure 1.Design of project-based biochemistry laboratory. Modules (projects, or portions of projects) are indicated as boxes. Each of these can be treated independently, or used as part of a larger project. Solid lines indicate some suggested paths from one module to the next. The skills and knowledge required for protein purification and design are developed in three units: (i) an introduction to critical assays needed to monitor degree of purification, including an evaluation of assay parameters; (ii) partial purification by ion-exchange techniques; and (iii) preparation of a grant proposal on protein design by mutagenesis. Brief descriptions of each of these units follow, with experimental details of each project at the end of this paper. Assays for Lysozyme Activity and Protein Concentration (4 weeks) The assays mastered during the first unit are a necessary tool for determining the purity of the enzyme during the second unit on purification by ion exchange. These assays allow an introduction to the concept of specific activity (units of enzyme activity per milligram of total protein) as a measure of purity. In this first sequence, students learn a turbidimetric assay

  5. Clinical, genetic, and molecular aspects of split-hand/foot malformation: an update.

    PubMed

    Gurrieri, Fiorella; Everman, David B

    2013-11-01

    We here provide an update on the clinical, genetic, and molecular aspects of split-hand/foot malformation (SHFM). This rare condition, affecting 1 in 8,500-25,000 newborns, is extremely complex because of its variability in clinical presentation, irregularities in its inheritance pattern, and the heterogeneity of molecular genetic alterations that can be found in affected individuals. Both syndromal and nonsyndromal forms are reviewed and the major molecular genetic alterations thus far reported in association with SHFM are discussed. This updated overview should be helpful for clinicians in their efforts to make an appropriate clinical and genetic diagnosis, provide an accurate recurrence risk assessment, and formulate a management plan. PMID:24115638

  6. Quantum tunneling splittings from path-integral molecular dynamics.

    PubMed

    Mátyus, Edit; Wales, David J; Althorpe, Stuart C

    2016-03-21

    We illustrate how path-integral molecular dynamics can be used to calculate ground-state tunnelling splittings in molecules or clusters. The method obtains the splittings from ratios of density matrix elements between the degenerate wells connected by the tunnelling. We propose a simple thermodynamic integration scheme for evaluating these elements. Numerical tests on fully dimensional malonaldehyde yield tunnelling splittings in good overall agreement with the results of diffusion Monte Carlo calculations. PMID:27004863

  7. Confirming an integrated pathology of diabetes and its complications by molecular biomarker-target network analysis.

    PubMed

    Zhao, Zide; Zhang, Yingying; Gai, Fengchun; Wang, Ying

    2016-09-01

    Despite ongoing research into diabetes and its complications, the underlying molecular associations remain to be elucidated. The systematic identification of molecular interactions in associated diseases may be approached using a network analysis strategy. The biomarker-target interrelated molecules associated with diabetes and its complications were identified via the Comparative Toxicogenomics Database (CTD); the Search Tool for Recurring Instances of Neighboring Genes was utilized for network construction. Functional enrichment analysis was performed with Database for Annotation, Visualization and Integrated Discovery software to investigate connections between diabetes and its complications. A total of 142 (including 122 biomarkers, 10 therapeutic targets and 10 overlapping molecules) biomarker-target interrelated molecules associated with diabetes and its complications were identified via the CTD database, and analysis of the network yielded 1,087 biological processes and fifteen Kyoto Encyclopedia of Genes and Genomes pathways with significant P‑values. Various critical aspects of the networks were examined in the present study: a) Intermolecular horizontal and vertical combinations in biomarkers and therapeutic targets associated with diabetes and its complicationb) network topology properties associated with molecular pathological responsec) contribution of key molecules to integrated regulation; and d) crosstalk between multiple pathways. Based on a multi-dimensional analysis, it was concluded that the integrated molecular pathological development of diabetes and its complications does not proceed randomly, which suggests a requirement for integrated, multi-target intervention. PMID:27430657

  8. An Integrated Biochemistry Laboratory, Including Molecular Modeling

    NASA Astrophysics Data System (ADS)

    Hall, Adele J. Wolfson Mona L.; Branham, Thomas R.

    1996-11-01

    ) experience with methods of protein purification; (iii) incorporation of appropriate controls into experiments; (iv) use of basic statistics in data analysis; (v) writing papers and grant proposals in accepted scientific style; (vi) peer review; (vii) oral presentation of results and proposals; and (viii) introduction to molecular modeling. Figure 1 illustrates the modular nature of the lab curriculum. Elements from each of the exercises can be separated and treated as stand-alone exercises, or combined into short or long projects. We have been able to offer the opportunity to use sophisticated molecular modeling in the final module through funding from an NSF-ILI grant. However, many of the benefits of the research proposal can be achieved with other computer programs, or even by literature survey alone. Figure 1.Design of project-based biochemistry laboratory. Modules (projects, or portions of projects) are indicated as boxes. Each of these can be treated independently, or used as part of a larger project. Solid lines indicate some suggested paths from one module to the next. The skills and knowledge required for protein purification and design are developed in three units: (i) an introduction to critical assays needed to monitor degree of purification, including an evaluation of assay parameters; (ii) partial purification by ion-exchange techniques; and (iii) preparation of a grant proposal on protein design by mutagenesis. Brief descriptions of each of these units follow, with experimental details of each project at the end of this paper. Assays for Lysozyme Activity and Protein Concentration (4 weeks) The assays mastered during the first unit are a necessary tool for determining the purity of the enzyme during the second unit on purification by ion exchange. These assays allow an introduction to the concept of specific activity (units of enzyme activity per milligram of total protein) as a measure of purity. In this first sequence, students learn a turbidimetric assay

  9. Organisational Learning and the Organisational Life Cycle: The Differential Aspects of an Integrated Relationship in SMEs

    ERIC Educational Resources Information Center

    Tam, Steven; Gray, David E.

    2016-01-01

    Purpose: The purpose of this study is to relate the practice of organisational learning in small- and medium-sized enterprises (SMEs) to the organisational life cycle (OLC), contextualising the differential aspects of an integrated relationship between them. Design/methodology/approach: It is a mixed-method study with two consecutive phases. In…

  10. Inferring Diversity and Evolution in Fish by Means of Integrative Molecular Cytogenetics

    PubMed Central

    Artoni, Roberto Ferreira; Castro, Jonathan Pena; Jacobina, Uedson Pereira; Lima-Filho, Paulo Augusto; Félix da Costa, Gideão Wagner Werneck; Molina, Wagner Franco

    2015-01-01

    Fish constitute a paraphyletic and profusely diversified group that has historically puzzled ichthyologists. Hard efforts are necessary to better understand this group, due to its extensive diversity. New species are often identified and it leads to questions about their phylogenetic aspects. Cytogenetics is becoming an important biodiversity-detection tool also used to measure biodiversity evolutionary aspects. Molecular cytogenetics by fluorescence in situ hybridization (FISH) allowed integrating quantitative and qualitative data from DNA sequences and their physical location in chromosomes and genomes. Although there is no intention on presenting a broader review, the current study presents some evidences on the need of integrating molecular cytogenetic data to other evolutionary biology tools to more precisely infer cryptic species detection, population structuring in marine environments, intra- and interspecific karyoevolutionary aspects of freshwater groups, evolutionary dynamics of marine fish chromosomes, and the origin and differentiation of sexual and B chromosomes. The new cytogenetic field, called cytogenomics, is spreading due to its capacity to give resolute answers to countless questions that cannot be answered by traditional methodologies. Indeed, the association between chromosomal markers and DNA sequencing as well as between biological diversity analysis methodologies and phylogenetics triggers the will to search for answers about fish evolutionary, taxonomic, and structural features. PMID:26345638

  11. Molecular aspects of transport in thin films of controlled architecture. [Annual] technical summary, July 1, 1992--June 30, 1993

    SciTech Connect

    Not Available

    1993-12-01

    Work has progressed in two principal areas during the past year: diffusion in swollen polymer films with and without a barrier layer, and molecular aspects of swelling using enhanced Raman spectroscopy.

  12. High aspect ratio nanoneedle probes with an integrated electrode at the tip apex

    NASA Astrophysics Data System (ADS)

    Comstock, David J.; Elam, Jeffrey W.; Pellin, Michael J.; Hersam, Mark C.

    2012-11-01

    Many nanoscale characterization techniques require high aspect ratio nanoneedle probes with an integrated electrode that is electrically insulated everywhere except at the tip apex. We report the utilization of electron beam induced deposition, focused ion beam milling, and atomic layer deposition to fabricate such probes at the sub-100 nm length scale. This fabrication method is highly reproducible and enables precise control of the probe dimensions. Subsequent electrodeposition at the integrated electrode enables customized functionalization of the tip apex. These probes have clear applications in scanning electrochemical microscopy-atomic force microscopy, magnetic force microscopy, apertureless near-field optical microscopy, and tip-enhanced Raman spectroscopy.

  13. Nonlinear aspects of data integration for land-cover classification in a neural network environment

    SciTech Connect

    Suelena Santiago Barros, M.; Rodrigues, V. )

    1994-03-01

    Some results concerning the exploration of a neural network methodology's nonlinear aspects to provide land-cover in satellite imagery are presented. All required images are used in a Back-Error Propagation (BEP) network which is a nonlinear data integrator for spatial patterns classification. The network is trained to recognize the basic categories: grass, moisted soil, bare soil, forest, water and built-up areas. The results of a partial classification are used in a posterior analysis which is made to get the final classification in more detailed classes of land use. The performance results show how powerful is a neural-network based methodology for satellite imagery integration and classification.

  14. Monitoring molecular, functional and morphologic aspects of bone metastases using non-invasive imaging.

    PubMed

    Bauerle, Tobias; Komljenovic, Dorde; Semmler, Wolfhard

    2012-03-01

    Bone is among the most common locations of metastasis and therefore represents an important clinical target for diagnostic follow-up in cancer patients. In the pathogenesis of bone metastases, disseminated tumor cells proliferating in bone interact with the local microenvironment stimulating or inhibiting osteoclast and osteoblast activity. Non-invasive imaging methods monitor molecular, functional and morphologic changes in both compartments of these skeletal lesions - the bone and the soft tissue tumor compartment. In the bone compartment, morphologic information on skeletal destruction is assessed by computed tomography (CT) and radiography. Pathogenic processes of osteoclast and osteoblast activity, however, can be imaged using optical imaging, positron emission tomography (PET), single photon emission CT (SPECT) and skeletal scintigraphy. Accordingly, conventional magnetic resonance imaging (MRI) and CT as well as diffusion- weighted MRI and optical imaging are used to assess morphologic aspects on the macroscopic and cellular level of the soft tissue tumor compartment. Imaging methods such as PET, MR spectroscopy, dynamic contrast-enhanced techniques and vessel size imaging further elucidate on pathogenic processes in this compartment including information on metabolism and vascularization. By monitoring these aspects in bone lesions, new insights in the pathogenesis of skeletal metastases can be gained. In translation to the clinical situation, these novel methods for the monitoring of bone metastases might be applied in patients to improve follow-up of these lesions, in particular after therapeutic intervention. This review summarizes established and experimental imaging techniques for the monitoring of tumor and bone cell activity including molecular, functional and morphological aspects in bone metastases. PMID:22214500

  15. jAMVLE, A new integrated molecular visualization learning environment*.

    PubMed

    Bottomley, Steven; Chandler, David; Morgan, Eleanor; Helmerhorst, Erik

    2006-09-01

    A new computer-based molecular visualization tool has been developed for teaching, and learning, molecular structure. This java-based jmol Amalgamated Molecular Visualization Learning Environment (jAMVLE) is platform-independent, integrated, and interactive. It has an overall graphical user interface that is intuitive and easy to use. The application can be downloaded free from the internet at wabri.org.au/jamvle. A cohort of 28 third year undergraduate molecular biotechnology degree students evaluated the new application through an essay-style project. These were analyzed to identify themes expressed by students in the content of their evaluations. Most students were positive about the new jAMVLE learning environment, and five major benefits emerged from the analysis. In particular, the students perceived that jAMVLE has an appealing interface, is interactive, provides a useful integrated environment, is user friendly, and is an excellent learning tool. Overall, students found that the jAMVLE application stimulated their interest, was a more active learning environment, provided better guidance, and made learning fun. PMID:21638712

  16. Integrative molecular profiling of routine clinical prostate cancer specimens

    PubMed Central

    Grasso, C. S.; Cani, A. K.; Hovelson, D. H.; Quist, M. J.; Douville, N. J.; Yadati, V.; Amin, A. M.; Nelson, P. S.; Betz, B. L.; Liu, C-J.; Knudsen, K. E.; Cooney, K. A.; Feng, F. Y.; McDaniel, A. S.; Tomlins, S. A.

    2015-01-01

    Background Comprehensive molecular profiling led to the recognition of multiple prostate cancer (PCa) molecular subtypes and driving alterations, but translating these findings to clinical practice is challenging. Patients and methods We developed a formalin-fixed paraffin-embedded (FFPE) tissue compatible integrative assay for PCa molecular subtyping and interrogation of relevant genetic/transcriptomic alterations (MiPC). We applied MiPC, which combines capture-based next generation sequencing and quantitative reverse transcription PCR (qRT-PCR), to 53 FFPE PCa specimens representing cases not well represented in frozen tissue cohorts, including 8 paired primary tumor and lymph node metastases. Results were validated using multiplexed PCR based NGS and Sanger sequencing. Results We identified known and novel potential driving, somatic mutations and copy number alterations, including a novel BRAF T599_V600insHT mutation and CYP11B2 amplification in a patient treated with ketoconazole (a potent CYP11B2 inhibitor). qRT-PCR integration enabled comprehensive molecular subtyping and provided complementary information, such as androgen receptor (AR) target gene module assessment in advanced cases and SPINK1 over-expression. MiPC identified highly concordant profiles for all 8 tumor/lymph node metastasis pairs, consistent with limited heterogeneity amongst driving events. MiPC and exome sequencing were performed on separately isolated conventional acinar PCa and prostatic small cell carcinoma (SCC) components from the same FFPE resection specimen to enable direct comparison of histologically distinct components. While both components showed TMPRSS2:ERG fusions, the SCC component exclusively harbored complete TP53 inactivation (frameshift variant and copy loss) and two CREBBP mutations. Conclusions Our results demonstrate the feasibility of integrative profiling of routine PCa specimens, which may have utility for understanding disease biology and enabling personalized

  17. Integration of gender-specific aspects into medical curricula - status quo und future perspectives

    PubMed Central

    Pfleiderer, Bettina; Burghaus, Désirée; Bayer, Gudrun; Kindler-Röhrborn, Andrea; Heue, Matthias; Becker, Jan Carl

    2012-01-01

    The consideration of gender aspects in clinical routine is of high importance towards an individualized patient care and a starting point of diversity medicine. Gender-specific awareness is an indispensable basis for an optimized medical treatment. A current study at the medical faculties of Muenster and Duisburg-Essen University (Germany) revealed an insufficient knowledge among students and lecturers in this area. An interdisciplinary, international workshop took place in Muenster (Germany) in May 2012 on the topic how to integrate gender aspects into medical curricula in the future aiming at a better health care for both sexes in long term. This position paper summarizes the conclusions. It was suggested to teach gender-specific contents from the first semester comprehensively – using standardized definitions and a gender-neutral language, since it is crucial not to increase the students’ workload any further. The key to success is to implement gender aspects by using meaningful examples on a regular basis – ideally in a longitudinal manner. The content of teaching should be selected by the lecturers and full professors and be considered within students´ exams. To reach these goals, an absolute support of the respective medical faculties as well as the integration of these gender-specific learning objectives into the national competence-based learning catalogue for medical education (NKLM) is obligatory. PMID:23255960

  18. Numerical solution of boundary-integral equations for molecular electrostatics.

    PubMed

    Bardhan, Jaydeep P

    2009-03-01

    Numerous molecular processes, such as ion permeation through channel proteins, are governed by relatively small changes in energetics. As a result, theoretical investigations of these processes require accurate numerical methods. In the present paper, we evaluate the accuracy of two approaches to simulating boundary-integral equations for continuum models of the electrostatics of solvation. The analysis emphasizes boundary-element method simulations of the integral-equation formulation known as the apparent-surface-charge (ASC) method or polarizable-continuum model (PCM). In many numerical implementations of the ASC/PCM model, one forces the integral equation to be satisfied exactly at a set of discrete points on the boundary. We demonstrate in this paper that this approach to discretization, known as point collocation, is significantly less accurate than an alternative approach known as qualocation. Furthermore, the qualocation method offers this improvement in accuracy without increasing simulation time. Numerical examples demonstrate that electrostatic part of the solvation free energy, when calculated using the collocation and qualocation methods, can differ significantly; for a polypeptide, the answers can differ by as much as 10 kcal/mol (approximately 4% of the total electrostatic contribution to solvation). The applicability of the qualocation discretization to other integral-equation formulations is also discussed, and two equivalences between integral-equation methods are derived. PMID:19275391

  19. Modeling Molecular and Cellular Aspects of Human Disease using the Nematode Caenorhabditis elegans

    PubMed Central

    Silverman, Gary A.; Luke, Cliff J.; Bhatia, Sangeeta R.; Long, Olivia S.; Vetica, Anne C.; Perlmutter, David H.; Pak, Stephen C.

    2009-01-01

    As an experimental system, Caenorhabditis elegans, offers a unique opportunity to interrogate in vivo the genetic and molecular functions of human disease-related genes. For example, C. elegans has provided crucial insights into fundamental biological processes such as cell death and cell fate determinations, as well as pathological processes such as neurodegeneration and microbial susceptibility. The C. elegans model has several distinct advantages including a completely sequenced genome that shares extensive homology with that of mammals, ease of cultivation and storage, a relatively short lifespan and techniques for generating null and transgenic animals. However, the ability to conduct unbiased forward and reverse genetic screens in C. elegans remains one of the most powerful experimental paradigms for discovering the biochemical pathways underlying human disease phenotypes. The identification of these pathways leads to a better understanding of the molecular interactions that perturb cellular physiology, and forms the foundation for designing mechanism-based therapies. To this end, the ability to process large numbers of isogenic animals through automated work stations suggests that C. elegans, manifesting different aspects of human disease phenotypes, will become the platform of choice for in vivo drug discovery and target validation using high-throughput/content screening technologies. PMID:18852689

  20. Engineering aspects of design and integration of ECE diagnostic in ITER

    SciTech Connect

    Udintsev, V. S.; Taylor, G.; Pandya, H. K.B.; Austin, M. E.; Casal, N.; Catalin, R.; Clough, M.; Cuquel, B.; Dapena, M.; Drevon, J. -M.; Feder, R.; Friconneau, J. P.; Giacomin, T.; Guirao, J.; Henderson, M. A.; Hughes, S.; Iglesias, S.; Johnson, D.; Kumar, Siddhart; Kumar, Vina; Levesy, B.; Loesser, D.; Messineo, M.; Penot, C.; Portalès, M.; Oosterbeek, J. W.; Sirinelli, A; Vacas, C.; Vayakis, G.; Walsh, M. J.; Kubo, S.

    2015-03-12

    ITER ECE diagnostic [1] needs not only to meet measurement requirements, but also to withstand various loads, such as electromagnetic, mechanical, neutronic and thermal, and to be protected from stray ECH radiation at 170 GHz and other millimeter wave emission, like Collective Thomson scattering which is planned to operate at 60 GHz. Same or similar loads will be applied to other millimetre-wave diagnostics [2], located both in-vessel and in-port plugs. These loads must be taken into account throughout the design phases of the ECE and other microwave diagnostics to ensure their structural integrity and maintainability. The integration of microwave diagnostics with other ITER systems is another challenging activity which is currently ongoing through port integration and in-vessel integration work. Port Integration has to address the maintenance and the safety aspects of diagnostics, too. Engineering solutions which are being developed to support and to operate ITER ECE diagnostic, whilst complying with safety and maintenance requirements, are discussed in this paper.

  1. Engineering aspects of design and integration of ECE diagnostic in ITER

    DOE PAGESBeta

    Udintsev, V. S.; Taylor, G.; Pandya, H. K.B.; Austin, M. E.; Casal, N.; Catalin, R.; Clough, M.; Cuquel, B.; Dapena, M.; Drevon, J. -M.; et al

    2015-03-12

    ITER ECE diagnostic [1] needs not only to meet measurement requirements, but also to withstand various loads, such as electromagnetic, mechanical, neutronic and thermal, and to be protected from stray ECH radiation at 170 GHz and other millimeter wave emission, like Collective Thomson scattering which is planned to operate at 60 GHz. Same or similar loads will be applied to other millimetre-wave diagnostics [2], located both in-vessel and in-port plugs. These loads must be taken into account throughout the design phases of the ECE and other microwave diagnostics to ensure their structural integrity and maintainability. The integration of microwave diagnosticsmore » with other ITER systems is another challenging activity which is currently ongoing through port integration and in-vessel integration work. Port Integration has to address the maintenance and the safety aspects of diagnostics, too. Engineering solutions which are being developed to support and to operate ITER ECE diagnostic, whilst complying with safety and maintenance requirements, are discussed in this paper.« less

  2. Engineering aspects of design and integration of ECE diagnostic in ITER

    NASA Astrophysics Data System (ADS)

    Udintsev, V. S.; Taylor, G.; Pandya, H. K. B.; Austin, M. E.; Casal, N.; Catalin, R.; Clough, M.; Cuquel, B.; Dapena, M.; Drevon, J.-M.; Feder, R.; Friconneau, J. P.; Giacomin, T.; Guirao, J.; Henderson, M. A.; Hughes, S.; Iglesias, S.; Johnson, D.; Kumar, Siddhart; Kumar, Vina; Levesy, B.; Loesser, D.; Messineo, M.; Penot, C.; Portalès, M.; Oosterbeek, J. W.; Sirinelli, A.; Vacas, C.; Vayakis, G.; Walsh, M. J.

    2015-03-01

    ITER ECE diagnostic [1] needs not only to meet measurement requirements, but also to withstand various loads, such as electromagnetic, mechanical, neutronic and thermal, and to be protected from stray ECH radiation at 170 GHz and other millimeter wave emission, like Collective Thomson scattering which is planned to operate at 60 GHz. Same or similar loads will be applied to other millimetre-wave diagnostics [2], located both in-vessel and in-port plugs. These loads must be taken into account throughout the design phases of the ECE and other microwave diagnostics to ensure their structural integrity and maintainability. The integration of microwave diagnostics with other ITER systems is another challenging activity which is currently ongoing through port integration and in-vessel integration work. Port Integration has to address the maintenance and the safety aspects of diagnostics, too. Engineering solutions which are being developed to support and to operate ITER ECE diagnostic, whilst complying with safety and maintenance requirements, are discussed in this paper.

  3. Apert and Crouzon syndromes-Cognitive development, brain abnormalities, and molecular aspects.

    PubMed

    Fernandes, Marilyse B L; Maximino, Luciana P; Perosa, Gimol B; Abramides, Dagma V M; Passos-Bueno, Maria Rita; Yacubian-Fernandes, Adriano

    2016-06-01

    Apert and Crouzon are the most common craniosynostosis syndromes associated with mutations in the fibroblast growth factor receptor 2 (FGFR2) gene. We conducted a study to examine the molecular biology, brain abnormalities, and cognitive development of individuals with these syndromes. A retrospective longitudinal review of 14 patients with Apert and Crouzon syndromes seen at the outpatient Craniofacial Surgery Hospital for Rehabilitation of Craniofacial Anomalies in Brazil from January 1999 through August 2010 was performed. Patients between 11 and 36 years of age (mean 18.29 ± 5.80), received cognitive evaluations, cerebral magnetic resonance imaging, and molecular DNA analyses. Eight patients with Apert syndrome (AS) had full scale intelligence quotients (FSIQs) that ranged from 47 to 108 (mean 76.9 ± 20.2), and structural brain abnormalities were identified in five of eight patients. Six patients presented with a gain-of-function mutation (p.Ser252Trp) in FGFR2 and FSIQs in those patients ranged from 47 to78 (mean 67.2 ± 10.7). One patient with a gain-of-function mutation (p.Pro253Arg) had a FSIQ of 108 and another patient with an atypical splice mutation (940-2A →G) had a FSIQ of 104. Six patients with Crouzon syndrome had with mutations in exons IIIa and IIIc of FGFR2 and their FSIQs ranged from 82 to 102 (mean 93.5 ± 6.7). These reveal that molecular aspects are another factor that can be considered in studies of global and cognitive development of patients with Apert and Crouzon syndrome (CS). © 2016 Wiley Periodicals, Inc. PMID:27028366

  4. Emerging aspects of molecular biomarkers for diagnosis, prognosis and treatment response in rheumatoid arthritis.

    PubMed

    Márquez, Ana; Martín, Javier; Carmona, F David

    2016-06-01

    Important advances have occurred during the last decade in the understanding of the pathogenesis of rheumatoid arthritis (RA). However, we are still far from having a clear picture of the molecular network that predisposes an individual to develop the disease, to worsen the symptoms after that, or to successfully respond to a specific treatment. In this sense, different -omics fields (including transcriptomics, proteomics, metabolomics, genomics and epigenomics) have recently produced promising insights that could definitively help us to sharpen such picture if integrated trough a systems biology approach. In this review we will summarise and discuss the recent progress achieved in those fields and its possible impact on the discovery of suitable biomarkers for RA diagnosis, prognosis and treatment response. PMID:27043155

  5. Angular momentum in molecular quantum mechanical integral evaluation

    NASA Astrophysics Data System (ADS)

    Dunlap, Brett I.

    2005-01-01

    Solid-harmonic derivatives of quantum-mechanical integrals over Gaussian transforms of scalar, or radial, atomic basis functions create angular momentum about each center. Generalized Gaunt coefficients limit the amount of cross differentiation for multi-center integrals to ensure that cross differentiation does not affect the total angular momentum. The generalized Gaunt coefficients satisfy a number of other selection rules, which are exploited in a new computer code for computing forces in analytic density-functional theory based on robust and variational fitting of the Kohn-Sham potential. Two-center exponents are defined for four or more solid-harmonic differentiations of matrix elements. Those differentiations can either build up angular momentum about the centers or give forces on molecular potential-energy surfaces, thus generalized Gaunt coefficients of order greater than the number of centers are considered. These 4- j generalized Gaunt coefficients and two-center exponents are used to compute the first derivatives of all integrals involving all the Gaussian exponents on a triplet of centers at once. First all angular factors are contracted with the corresponding part of the linear-combination-of-atomic-orbitals density matrix. This intermediate quantity is then reused for the nuclear attraction integral and the integrals corresponding to each basis function in the analytic fit of the Kohn-Sham potential in the muffin-tin-like, but analytic, Slater-Roothaan method that allows molecules to dissociate into atoms having any desired energy, including the experimental electronic energy. The energy is stationary in all respects and all forces precisely agree with a previous code in tests on small molecules. During geometry optimization of an icosahedral C 720 fullerene computing these angular factors and transforming them via the 4- j generalized Gaunt coefficient takes more than sixty percent of the total computer time. These same angular factors could be used

  6. Clinical and molecular aspects of the live attenuated Oka varicella vaccine.

    PubMed

    Quinlivan, Mark; Breuer, Judy

    2014-07-01

    VZV is a ubiquitous member of the Herpesviridae family that causes varicella (chicken pox) and herpes zoster (shingles). Both manifestations can cause great morbidity and mortality and are therefore of significant economic burden. The introduction of varicella vaccination as part of childhood immunization programs has resulted in a remarkable decline in varicella incidence, and associated hospitalizations and deaths, particularly in the USA. The vaccine preparation, vOka, is a live attenuated virus produced by serial passage of a wild-type clinical isolate termed pOka in human and guinea pig cell lines. Although vOka is clinically attenuated, it can cause mild varicella, establish latency, and reactivate to cause herpes zoster. Sequence analysis has shown that vOka differs from pOka by at least 42 loci; however, not all genomes possess the novel vOka change at all positions, creating a heterogeneous population of genetically distinct haplotypes. This, together with the extreme cell-associated nature of VZV replication in cell culture and the lack of an animal model, in which the complete VZV life cycle can be replicated, has limited studies into the molecular basis for vOka attenuation. Comparative studies of vOka with pOka replication in T cells, dorsal root ganglia, and skin indicate that attenuation likely involves multiple mutations within ORF 62 and several other genes. This article presents an overview of the clinical aspects of the vaccine and current progress on understanding the molecular mechanisms that account for the clinical phenotype of reduced virulence. PMID:24687808

  7. Growth, modification and integration of carbon nanotubes into molecular electronics

    NASA Astrophysics Data System (ADS)

    Moscatello, Jason P.

    Molecules are the smallest possible elements for electronic devices, with active elements for such devices typically a few Angstroms in footprint area. Owing to the possibility of producing ultra-high density devices, tremendous effort has been invested in producing electronic junctions by using various types of molecules. The major issues for molecular electronics include (1) developing an effective scheme to connect molecules with the present micro- and nano-technology, (2) increasing the lifetime and stabilities of the devices, and (3) increasing their performance in comparison to the state-of-the-art devices. In this work, we attempt to use carbon nanotubes (CNTs) as the interconnecting nanoelectrodes between molecules and microelectrodes. The ultimate goal is to use two individual CNTs to sandwich molecules in a cross-bar configuration while having these CNTs connected with microelectrodes such that the junction displays the electronic character of the molecule chosen. We have successfully developed an effective scheme to connect molecules with CNTs, which is scalable to arrays of molecular electronic devices. To realize this far reaching goal, the following technical topics have been investigated. (1) Synthesis of multi-walled carbon nanotubes (MWCNTs) by thermal chemical vapor deposition (T-CVD) and plasma-enhanced chemical vapor deposition (PECVD) techniques (Chapter 3). We have evaluated the potential use of tubular and bamboo-like MWCNTs grown by T-CVD and PE-CVD in terms of their structural properties. (2) Horizontal dispersion of MWCNTs with and without surfactants, and the integration of MWCNTs to microelectrodes using deposition by dielectrophoresis (DEP) (Chapter 4). We have systematically studied the use of surfactant molecules to disperse and horizontally align MWCNTs on substrates. In addition, DEP is shown to produce impurityfree placement of MWCNTs, forming connections between microelectrodes. We demonstrate the deposition density is tunable by

  8. Integrated molecular portrait of non-small cell lung cancers

    PubMed Central

    2013-01-01

    Background Non-small cell lung cancer (NSCLC), a leading cause of cancer deaths, represents a heterogeneous group of neoplasms, mostly comprising squamous cell carcinoma (SCC), adenocarcinoma (AC) and large-cell carcinoma (LCC). The objectives of this study were to utilize integrated genomic data including copy-number alteration, mRNA, microRNA expression and candidate-gene full sequencing data to characterize the molecular distinctions between AC and SCC. Methods Comparative genomic hybridization followed by mutational analysis, gene expression and miRNA microarray profiling were performed on 123 paired tumor and non-tumor tissue samples from patients with NSCLC. Results At DNA, mRNA and miRNA levels we could identify molecular markers that discriminated significantly between the various histopathological entities of NSCLC. We identified 34 genomic clusters using aCGH data; several genes exhibited a different profile of aberrations between AC and SCC, including PIK3CA, SOX2, THPO, TP63, PDGFB genes. Gene expression profiling analysis identified SPP1, CTHRC1and GREM1 as potential biomarkers for early diagnosis of the cancer, and SPINK1 and BMP7 to distinguish between AC and SCC in small biopsies or in blood samples. Using integrated genomics approach we found in recurrently altered regions a list of three potential driver genes, MRPS22, NDRG1 and RNF7, which were consistently over-expressed in amplified regions, had wide-spread correlation with an average of ~800 genes throughout the genome and highly associated with histological types. Using a network enrichment analysis, the targets of these potential drivers were seen to be involved in DNA replication, cell cycle, mismatch repair, p53 signalling pathway and other lung cancer related signalling pathways, and many immunological pathways. Furthermore, we also identified one potential driver miRNA hsa-miR-944. Conclusions Integrated molecular characterization of AC and SCC helped identify clinically relevant markers

  9. Quantum Thermal Bath for Path Integral Molecular Dynamics Simulation.

    PubMed

    Brieuc, Fabien; Dammak, Hichem; Hayoun, Marc

    2016-03-01

    The quantum thermal bath (QTB) method has been recently developed to account for the quantum nature of the nuclei by using standard molecular dynamics (MD) simulation. QTB-MD is an efficient but approximate method when dealing with strongly anharmonic systems, while path integral molecular dynamics (PIMD) gives exact results but in a huge amount of computation time. The QTB and PIMD methods have been combined in order to improve the PIMD convergence or correct the failures of the QTB-MD technique. Therefore, a new power spectral density of the random force within the QTB has been developed. A modified centroid-virial estimator of the kinetic energy, especially adapted to QTB-PIMD, has also been proposed. The method is applied to selected systems: a one-dimensional double-well system, a ferroelectric phase transition, and the position distribution of an hydrogen atom in a fuel cell material. The advantage of the QTB-PIMD method is its ability to give exact results with a more reasonable computation time for strongly anharmonic systems. PMID:26799437

  10. Critical aspects of integrated monitoring systems for landslides risk management: strategies for a reliable approach

    NASA Astrophysics Data System (ADS)

    Castagnetti, C.; Bertacchini, E.; Capra, A.; Corsini, A.

    2012-04-01

    The use of advanced technologies for remotely monitor surface processes is a successful way for improving the knowledge of phenomena evolution. In addition, the integration of various techniques is becoming more and more common in order to implement early warning systems that can monitor the evolution of landslides in time and prevent emergencies. The reliability of those systems plays a key role when Public Administrations have to plan actions in case of disasters or for preventing an incoming emergency. To have confidence in the information given by the system is an essential condition for a successful policy aiming to protect the population. The research deals with the major critical aspects to be taken into account when implementing a reliable monitoring system for unstable slopes. The importance of those aspects is often neglected, unlike the effects of a not careful implementation and management of the system can lead to erroneous interpretations of the phenomenon itself. The case study which ruled the research and highlighted the actual need of guidelines for setting up a reliable monitoring system is the Valoria landslide, located in the Northern Italy. The system is based on the integration of an automatic Total Station (TS) measuring 45 reflectors and a master GPS, acting as the reference station for three rovers placed within the landslide. In order to monitor local disturbing effects, a bi-dimensional clinometer has been applied on the TS pillar. Topographic measurements have been also integrated with geotechnical sensors (inclinometers and piezometers) in a GIS for landslide risk management. At the very beginning, periodic measurements were carried out, while the system is now performing continuously since 2008. The system permitted to evaluate movements from few millimeter till some meters per day in most dangerous areas. A more spatially continuous description has been also provided by LiDAR and terrestrial SAR interferometry. Some of the most

  11. Drug Repositioning by Kernel-Based Integration of Molecular Structure, Molecular Activity, and Phenotype Data

    PubMed Central

    Wang, Yongcui; Chen, Shilong; Deng, Naiyang; Wang, Yong

    2013-01-01

    Computational inference of novel therapeutic values for existing drugs, i.e., drug repositioning, offers the great prospect for faster and low-risk drug development. Previous researches have indicated that chemical structures, target proteins, and side-effects could provide rich information in drug similarity assessment and further disease similarity. However, each single data source is important in its own way and data integration holds the great promise to reposition drug more accurately. Here, we propose a new method for drug repositioning, PreDR (Predict Drug Repositioning), to integrate molecular structure, molecular activity, and phenotype data. Specifically, we characterize drug by profiling in chemical structure, target protein, and side-effects space, and define a kernel function to correlate drugs with diseases. Then we train a support vector machine (SVM) to computationally predict novel drug-disease interactions. PreDR is validated on a well-established drug-disease network with 1,933 interactions among 593 drugs and 313 diseases. By cross-validation, we find that chemical structure, drug target, and side-effects information are all predictive for drug-disease relationships. More experimentally observed drug-disease interactions can be revealed by integrating these three data sources. Comparison with existing methods demonstrates that PreDR is competitive both in accuracy and coverage. Follow-up database search and pathway analysis indicate that our new predictions are worthy of further experimental validation. Particularly several novel predictions are supported by clinical trials databases and this shows the significant prospects of PreDR in future drug treatment. In conclusion, our new method, PreDR, can serve as a useful tool in drug discovery to efficiently identify novel drug-disease interactions. In addition, our heterogeneous data integration framework can be applied to other problems. PMID:24244318

  12. Integrative transcriptome, proteome, phosphoproteome and genetic mapping reveals new aspects in a fiberless mutant of cotton.

    PubMed

    Ma, Qi-Feng; Wu, Chun-Hui; Wu, Man; Pei, Wen-Feng; Li, Xing-Li; Wang, Wen-Kui; Zhang, Jinfa; Yu, Ji-Wen; Yu, Shu-Xun

    2016-01-01

    To investigate the molecular mechanisms of fiber initiation in cotton (Gossypium spp.), an integrated approach combining transcriptome, iTRAQ-based proteome and genetic mapping was taken to compare the ovules of the Xuzhou 142 wild type (WT) with its fuzzless-lintless (fl) mutant at -3 and 0 day post-anthesis. A total of 1,953 mRNAs, 187 proteins, and 131 phosphoproteins were differentially expressed (DE) between WT and fl, and the levels of transcripts and their encoded proteins and phosphoproteins were highly congruent. A functional analysis suggested that the abundance of proteins were mainly involved in amino sugar, nucleotide sugar and fatty acid metabolism, one carbon pool for folate metabolism and flavonoid biosynthesis. qRT-PCR, Western blotting, and enzymatic assays were performed to confirm the regulation of these transcripts and proteins. A molecular mapping located the lintless gene li3 in the fl mutant on chromosome 26 for the first time. A further in-silico physical mapping of DE genes with sequence variations between fl and WT identified one and four candidate genes in the li3 and n2 regions, respectively. Taken together, the transcript abundance, phosphorylation status of proteins at the fiber initiation stage and candidate genes have provided insights into regulatory processes underlying cotton fiber initiation. PMID:27075604

  13. Integrative transcriptome, proteome, phosphoproteome and genetic mapping reveals new aspects in a fiberless mutant of cotton

    PubMed Central

    Ma, Qi-Feng; Wu, Chun-Hui; Wu, Man; Pei, Wen-Feng; Li, Xing-Li; Wang, Wen-Kui; Zhang, Jinfa; Yu, Ji-Wen; Yu, Shu-Xun

    2016-01-01

    To investigate the molecular mechanisms of fiber initiation in cotton (Gossypium spp.), an integrated approach combining transcriptome, iTRAQ-based proteome and genetic mapping was taken to compare the ovules of the Xuzhou 142 wild type (WT) with its fuzzless-lintless (fl) mutant at −3 and 0 day post-anthesis. A total of 1,953 mRNAs, 187 proteins, and 131 phosphoproteins were differentially expressed (DE) between WT and fl, and the levels of transcripts and their encoded proteins and phosphoproteins were highly congruent. A functional analysis suggested that the abundance of proteins were mainly involved in amino sugar, nucleotide sugar and fatty acid metabolism, one carbon pool for folate metabolism and flavonoid biosynthesis. qRT-PCR, Western blotting, and enzymatic assays were performed to confirm the regulation of these transcripts and proteins. A molecular mapping located the lintless gene li3 in the fl mutant on chromosome 26 for the first time. A further in-silico physical mapping of DE genes with sequence variations between fl and WT identified one and four candidate genes in the li3 and n2 regions, respectively. Taken together, the transcript abundance, phosphorylation status of proteins at the fiber initiation stage and candidate genes have provided insights into regulatory processes underlying cotton fiber initiation. PMID:27075604

  14. Some Aspects of the Implementation of Double Group Symmetry and Electron Correlation in Molecular 4-Component Calculations

    NASA Technical Reports Server (NTRS)

    Dyall, Kenneth G.; Arnold, James O. (Technical Monitor)

    1994-01-01

    The efficient implementation of method for electron correlation in molecular 4-component calculations demands that symmetry be exploited where possible. Algorithms for the construction of matrices and the transformation of integrals over symmetry-adapted basis functions, where the point group is restricted to D(sub 2h) and subgroups, will be presented. The merits of keeping the primitive integrals in the scalar basis will be compared with those of transforming them to the 2-spinor basis.

  15. Environmental Epigenetics and a Unified Theory of the Molecular Aspects of Evolution: A Neo-Lamarckian Concept that Facilitates Neo-Darwinian Evolution

    PubMed Central

    Skinner, Michael K.

    2015-01-01

    Environment has a critical role in the natural selection process for Darwinian evolution. The primary molecular component currently considered for neo-Darwinian evolution involves genetic alterations and random mutations that generate the phenotypic variation required for natural selection to act. The vast majority of environmental factors cannot directly alter DNA sequence. Epigenetic mechanisms directly regulate genetic processes and can be dramatically altered by environmental factors. Therefore, environmental epigenetics provides a molecular mechanism to directly alter phenotypic variation generationally. Lamarck proposed in 1802 the concept that environment can directly alter phenotype in a heritable manner. Environmental epigenetics and epigenetic transgenerational inheritance provide molecular mechanisms for this process. Therefore, environment can on a molecular level influence the phenotypic variation directly. The ability of environmental epigenetics to alter phenotypic and genotypic variation directly can significantly impact natural selection. Neo-Lamarckian concept can facilitate neo-Darwinian evolution. A unified theory of evolution is presented to describe the integration of environmental epigenetic and genetic aspects of evolution. PMID:25917417

  16. TOPICAL REVIEW: New aspects of π-d interactions in magnetic molecular conductors

    NASA Astrophysics Data System (ADS)

    Sugimoto, Toyonari; Fujiwara, Hideki; Noguchi, Satoru; Murata, Keizo

    2009-04-01

    The 2 : 1 cation radical salts of bent donor molecules of ethylenedithio-tetrathiafulvalenoquinone-1,3-dithiolemethide (EDT-TTFVO), ethylenedithio-diselenadithiafulvalenoquinone-1,3-dithiolemethide (EDT-DSDTFVO), ethylenedithio-diselenadithiafulvalenothioquinone-1,3-diselenolemethide (EDT-DSDTFVSDS), ethylenedioxy-tetrathiafulvalenoquinone-1,3-dithiolemethide (EDO-TTFVO) and ethylenedioxy-tetrathiafulvalenoquinone-1,3-diselenolemethide (EDO-TTFVODS) with FeX4- (X = Cl, Br) ions are prepared by electrocrystallization. The crystal structures of these salts are composed of alternately stacked donor molecule and magnetic anion layers. The band structures of the donor molecule layers are calculated using the overlap integrals between neighboring donor molecules and are compared with the observed electronic transport properties. The magnetic ordering of the Fe(III) d spins of FeX4- ions is determined from magnetization and heat capacity measurements. The magnetic ordering temperatures are estimated by considering a combination of a direct d-d interaction between the d spins and an indirect π-d interaction between the conduction π electron and the d spins, whose magnitudes are separately calculated from the crystal structures with an extended Hückel molecular orbital method. The occurrence of a π-d interaction is proved by the negative magnetoresistance, and the magnitude of magnetoresistance reflects the strength of the π-d interaction. The effect of pressure on the magnetoresistance is studied, and the result indicates that the magnitude of magnetoresistance increases, namely, the π-d interaction is enhanced with increasing pressure. From these experimental results it is shown that (EDT-TTFVO)2•FeBr4 is a ferromagnetic semiconductor, (EDT-DSDTFVO)2•FeX4 (X = Cl, Br) and (EDT-DSDTFVSDS)2•FeBr4 are metals exhibiting antiferromagnetic ordering of the d spins, and (EDO-TTFVO)2•FeCl4 and (EDO-TTFVODS)2•FeBr4•(DCE)0.5 (DCE =-dichloroethane) are genuine

  17. The Center for Integrated Molecular Brain Imaging (Cimbi) database.

    PubMed

    Knudsen, Gitte M; Jensen, Peter S; Erritzoe, David; Baaré, William F C; Ettrup, Anders; Fisher, Patrick M; Gillings, Nic; Hansen, Hanne D; Hansen, Lars Kai; Hasselbalch, Steen G; Henningsson, Susanne; Herth, Matthias M; Holst, Klaus K; Iversen, Pernille; Kessing, Lars V; Macoveanu, Julian; Madsen, Kathrine Skak; Mortensen, Erik L; Nielsen, Finn Årup; Paulson, Olaf B; Siebner, Hartwig R; Stenbæk, Dea S; Svarer, Claus; Jernigan, Terry L; Strother, Stephen C; Frokjaer, Vibe G

    2016-01-01

    We here describe a multimodality neuroimaging containing data from healthy volunteers and patients, acquired within the Lundbeck Foundation Center for Integrated Molecular Brain Imaging (Cimbi) in Copenhagen, Denmark. The data is of particular relevance for neurobiological research questions related to the serotonergic transmitter system with its normative data on the serotonergic subtype receptors 5-HT1A, 5-HT1B, 5-HT2A, and 5-HT4 and the 5-HT transporter (5-HTT), but can easily serve other purposes. The Cimbi database and Cimbi biobank were formally established in 2008 with the purpose to store the wealth of Cimbi-acquired data in a highly structured and standardized manner in accordance with the regulations issued by the Danish Data Protection Agency as well as to provide a quality-controlled resource for future hypothesis-generating and hypothesis-driven studies. The Cimbi database currently comprises a total of 1100 PET and 1000 structural and functional MRI scans and it holds a multitude of additional data, such as genetic and biochemical data, and scores from 17 self-reported questionnaires and from 11 neuropsychological paper/computer tests. The database associated Cimbi biobank currently contains blood and in some instances saliva samples from about 500 healthy volunteers and 300 patients with e.g., major depression, dementia, substance abuse, obesity, and impulsive aggression. Data continue to be added to the Cimbi database and biobank. PMID:25891375

  18. Integration of the stratigraphic aspects of very large sea-floor databases using information processing

    USGS Publications Warehouse

    Jenkins, Clinton N.; Flocks, J.; Kulp, M.

    2006-01-01

    Information-processing methods are described that integrate the stratigraphic aspects of large and diverse collections of sea-floor sample data. They efficiently convert common types of sea-floor data into database and GIS (geographical information system) tables, visual core logs, stratigraphic fence diagrams and sophisticated stratigraphic statistics. The input data are held in structured documents, essentially written core logs that are particularly efficient to create from raw input datasets. Techniques are described that permit efficient construction of regional databases consisting of hundreds of cores. The sedimentological observations in each core are located by their downhole depths (metres below sea floor - mbsf) and also by a verbal term that describes the sample 'situation' - a special fraction of the sediment or position in the core. The main processing creates a separate output event for each instance of top, bottom and situation, assigning top-base mbsf values from numeric or, where possible, from word-based relative locational information such as 'core catcher' in reference to sampler device, and recovery or penetration length. The processing outputs represent the sub-bottom as a sparse matrix of over 20 sediment properties of interest, such as grain size, porosity and colour. They can be plotted in a range of core-log programs including an in-built facility that better suits the requirements of sea-floor data. Finally, a suite of stratigraphic statistics are computed, including volumetric grades, overburdens, thicknesses and degrees of layering. ?? The Geological Society of London 2006.

  19. Behavioral, molecular and integrative mechanisms of amphibian osmoregulation.

    PubMed

    Hillyard, S D

    1999-06-01

    Amphibian water balance has been studied at many levels of biological order. Terrestrial species must react to environmental cues that relate to water availability while some arboreal species have cutaneous skin secretions that can reduce evaporative water loss. The Indian tree frog. Polypedates maculatus, uses cutaneous secretions and wiping behavior to lower evaporation but also relies on moist microclimates to endure prolonged survival away from water. The related species, P. leucomystax, inhabits wetter forest habitats. Preliminary studies with this species are unable to demonstrate the expression of wiping behavior, indicating that arid habitats may be a powerful selective force for this behavior. Laboratory experiments on rehydrating toads in the genus Bufo indicate that animals are able to detect changes in barometric pressure and humidity that might result in the availability of water under field situations. Experiments with Bufonid species and with spadefoot toads, Scaphiopus couchi, show that the peptide hormone, angiotensin II, stimulates cutaneous drinking in a similar manner seen for oral drinking by other vertebrate classes. Amphibian tissues have long been used as a model for the study of basic physiological principles of epithelial ion and water transport. Recent progress with tissue cultures has provided information on the molecular structure of ion and water channels that can be applied to obtain a better understanding, at the molecular level, of ion and water balance strategies used by the wide variety of amphibian species. Terrestrial amphibians are more tolerant of dehydration than are other vertebrates and are able to store dilute urine in their urinary bladder. Toads appear to be able to detect the presence of water in their bladders in addition to the availability of water in their environment. Dehydrated toads are able to rehydrate very rapidly by the coordination of behavioral and physiological mechanisms to enhance cutaneous water

  20. Final Report for Integrated Multiscale Modeling of Molecular Computing Devices

    SciTech Connect

    Glotzer, Sharon C.

    2013-08-28

    In collaboration with researchers at Vanderbilt University, North Carolina State University, Princeton and Oakridge National Laboratory we developed multiscale modeling and simulation methods capable of modeling the synthesis, assembly, and operation of molecular electronics devices. Our role in this project included the development of coarse-grained molecular and mesoscale models and simulation methods capable of simulating the assembly of millions of organic conducting molecules and other molecular components into nanowires, crossbars, and other organized patterns.

  1. Molecular Assemblies, Genes and Genomics Integrated Efficiently (MAGGIE)

    SciTech Connect

    Baliga, Nitin S

    2011-05-26

    Final report on MAGGIE. We set ambitious goals to model the functions of individual organisms and their community from molecular to systems scale. These scientific goals are driving the development of sophisticated algorithms to analyze large amounts of experimental measurements made using high throughput technologies to explain and predict how the environment influences biological function at multiple scales and how the microbial systems in turn modify the environment. By experimentally evaluating predictions made using these models we will test the degree to which our quantitative multiscale understanding wilt help to rationally steer individual microbes and their communities towards specific tasks. Towards this end we have made substantial progress towards understanding evolution of gene families, transcriptional structures, detailed structures of keystone molecular assemblies (proteins and complexes), protein interactions, biological networks, microbial interactions, and community structure. Using comparative analysis we have tracked the evolutionary history of gene functions to understand how novel functions evolve. One level up, we have used proteomics data, high-resolution genome tiling microarrays, and 5' RNA sequencing to revise genome annotations, discover new genes including ncRNAs, and map dynamically changing operon structures of five model organisms: For Desulfovibrio vulgaris Hildenborough, Pyrococcus furiosis, Sulfolobus solfataricus, Methanococcus maripaludis and Haiobacterium salinarum NROL We have developed machine learning algorithms to accurately identify protein interactions at a near-zero false positive rate from noisy data generated using tagfess complex purification, TAP purification, and analysis of membrane complexes. Combining other genome-scale datasets produced by ENIGMA (in particular, microarray data) and available from literature we have been able to achieve a true positive rate as high as 65% at almost zero false positives when

  2. Physical, Spatial, and Molecular Aspects of Extracellular Matrix of In Vivo Niches and Artificial Scaffolds Relevant to Stem Cells Research.

    PubMed

    Akhmanova, Maria; Osidak, Egor; Domogatsky, Sergey; Rodin, Sergey; Domogatskaya, Anna

    2015-01-01

    Extracellular matrix can influence stem cell choices, such as self-renewal, quiescence, migration, proliferation, phenotype maintenance, differentiation, or apoptosis. Three aspects of extracellular matrix were extensively studied during the last decade: physical properties, spatial presentation of adhesive epitopes, and molecular complexity. Over 15 different parameters have been shown to influence stem cell choices. Physical aspects include stiffness (or elasticity), viscoelasticity, pore size, porosity, amplitude and frequency of static and dynamic deformations applied to the matrix. Spatial aspects include scaffold dimensionality (2D or 3D) and thickness; cell polarity; area, shape, and microscale topography of cell adhesion surface; epitope concentration, epitope clustering characteristics (number of epitopes per cluster, spacing between epitopes within cluster, spacing between separate clusters, cluster patterns, and level of disorder in epitope arrangement), and nanotopography. Biochemical characteristics of natural extracellular matrix molecules regard diversity and structural complexity of matrix molecules, affinity and specificity of epitope interaction with cell receptors, role of non-affinity domains, complexity of supramolecular organization, and co-signaling by growth factors or matrix epitopes. Synergy between several matrix aspects enables stem cells to retain their function in vivo and may be a key to generation of long-term, robust, and effective in vitro stem cell culture systems. PMID:26351461

  3. Physical, Spatial, and Molecular Aspects of Extracellular Matrix of In Vivo Niches and Artificial Scaffolds Relevant to Stem Cells Research

    PubMed Central

    Akhmanova, Maria; Osidak, Egor; Domogatsky, Sergey; Rodin, Sergey; Domogatskaya, Anna

    2015-01-01

    Extracellular matrix can influence stem cell choices, such as self-renewal, quiescence, migration, proliferation, phenotype maintenance, differentiation, or apoptosis. Three aspects of extracellular matrix were extensively studied during the last decade: physical properties, spatial presentation of adhesive epitopes, and molecular complexity. Over 15 different parameters have been shown to influence stem cell choices. Physical aspects include stiffness (or elasticity), viscoelasticity, pore size, porosity, amplitude and frequency of static and dynamic deformations applied to the matrix. Spatial aspects include scaffold dimensionality (2D or 3D) and thickness; cell polarity; area, shape, and microscale topography of cell adhesion surface; epitope concentration, epitope clustering characteristics (number of epitopes per cluster, spacing between epitopes within cluster, spacing between separate clusters, cluster patterns, and level of disorder in epitope arrangement), and nanotopography. Biochemical characteristics of natural extracellular matrix molecules regard diversity and structural complexity of matrix molecules, affinity and specificity of epitope interaction with cell receptors, role of non-affinity domains, complexity of supramolecular organization, and co-signaling by growth factors or matrix epitopes. Synergy between several matrix aspects enables stem cells to retain their function in vivo and may be a key to generation of long-term, robust, and effective in vitro stem cell culture systems. PMID:26351461

  4. Physical aspects of the structure and function of helicases as rotary molecular motors

    NASA Astrophysics Data System (ADS)

    Pikin, S. A.

    2009-11-01

    Helicases were shown to have common physical properties with rotary molecular motors, such as F 0 F 1-ATP synthase and type I restriction-modification (RM) enzymes. The necessary conditions for action of molecular motors are chirality, the presence of the C 2 (or lower) symmetry axis within rather large atomic groups, and polarization properties. The estimates were made for the material parameters of helicases, which translocate DNA due to moving chiral kinks without DNA cleavage and are characterized by higher viscosity, low mobility, and smaller chiral kinetic coefficients than type II RM enzymes. This paper discusses the efficiency of helicases with opposite polarities that drive DNA translocation in opposite directions.

  5. Solution of multi-center molecular integrals of Slater-type orbitals

    NASA Technical Reports Server (NTRS)

    Tai, H.

    1989-01-01

    The troublesome multi-center molecular integrals of Slater-type orbitals (STO) in molecular physics calculations can be evaluated by using the Fourier transform and proper coupling of the two center exchange integrals. A numerical integration procedure is then readily rendered to the final expression in which the integrand consists of well known special functions of arguments containing the geometrical arrangement of the nuclear centers and the exponents of the atomic orbitals. A practical procedure was devised for the calculation of a general multi-center molecular integrals coupling arbitrary Slater-type orbitals. Symmetry relations and asymptotic conditions are discussed. Explicit expressions of three-center one-electron nuclear-attraction integrals and four-center two-electron repulsion integrals for STO of principal quantum number n=2 are listed. A few numerical results are given for the purpose of comparison.

  6. Atomic and molecular collision aspects of thermospheric uranium-vapor releases. Technical report, 15 February 1980-31 December 1985

    SciTech Connect

    Hamlin, D.A.

    1990-05-01

    The DNA Uranium (Oxides) LWIR Review Committee considered the effectiveness of field measurements of the LWIR from uranium oxides produced by (hypothetical) controlled releases of uranium vapor from rockets in the thermosphere. Collated here is the writer's work supporting the committee on atomic and molecular collision aspects of such releases. Included is an essential auxiliary study to (a) understand, in terms of atomic and molecular parameters, coefficients for Ba+ diffusion along the magnetic field as measured and predicted for Ba-release events and (b) apply that (limited) understanding to U-release studies. For particles colliding with neutral atmospheric species, several interaction potentials are used to compute velocity-dependent momentum-transfer cross sections, stopping power and range versus energy, and diffusion coefficients. The momentum-transfer cross sections are also compared with cross sections for certain uranium oxide reactions specially atom-transfer reactions.

  7. T2D-Db: An integrated platform to study the molecular basis of Type 2 diabetes

    PubMed Central

    Agrawal, Shipra; Dimitrova, Nevenka; Nathan, Prasanthi; Udayakumar, K; Lakshmi, S Sai; Sriram, S; Manjusha, N; Sengupta, Urmi

    2008-01-01

    Background Type 2 Diabetes Mellitus (T2DM) is a non insulin dependent, complex trait disease that develops due to genetic predisposition and environmental factors. The advanced stage in type 2 diabetes mellitus leads to several micro and macro vascular complications like nephropathy, neuropathy, retinopathy, heart related problems etc. Studies performed on the genetics, biochemistry and molecular biology of this disease to understand the pathophysiology of type 2 diabetes mellitus has led to the generation of a surfeit of data on candidate genes and related aspects. The research is highly progressive towards defining the exact etiology of this disease. Results T2D-Db (Type 2 diabetes Database) is a comprehensive web resource, which provides integrated and curated information on almost all known molecular components involved in the pathogenesis of type 2 diabetes mellitus in the three widely studied mammals namely human, mouse and rat. Information on candidate genes, SNPs (Single Nucleotide Polymorphism) in candidate genes or candidate regions, genome wide association studies (GWA), tissue specific gene expression patterns, EST (Expressed Sequence Tag) data, expression information from microarray data, pathways, protein-protein interactions and disease associated risk factors or complications have been structured in this on line resource. Conclusion Information available in T2D-Db provides an integrated platform for the better molecular level understanding of type 2 diabetes mellitus and its pathogenesis. Importantly, the resource facilitates graphical presentation of the gene/genome wide map of SNP markers and protein-protein interaction networks, besides providing the heat map diagram of the selected gene(s) in an organism across microarray expression experiments from either single or multiple studies. These features aid to the data interpretation in an integrative way. T2D-Db is to our knowledge the first publicly available resource that can cater to the needs of

  8. Final technical report for DOE Computational Nanoscience Project: Integrated Multiscale Modeling of Molecular Computing Devices

    SciTech Connect

    Cummings, P. T.

    2010-02-08

    This document reports the outcomes of the Computational Nanoscience Project, "Integrated Multiscale Modeling of Molecular Computing Devices". It includes a list of participants and publications arising from the research supported.

  9. Physical aspects of the structure and function of helicases as rotary molecular motors

    SciTech Connect

    Pikin, S. A.

    2009-11-15

    Helicases were shown to have common physical properties with rotary molecular motors, such as F{sub 0}F{sub 1}-ATP synthase and type I restriction-modification (RM) enzymes. The necessary conditions for action of molecular motors are chirality, the presence of the C{sub 2} (or lower) symmetry axis within rather large atomic groups, and polarization properties. The estimates were made for the material parameters of helicases, which translocate DNA due to moving chiral kinks without DNA cleavage and are characterized by higher viscosity, low mobility, and smaller chiral kinetic coefficients than type II RM enzymes. This paper discusses the efficiency of helicases with opposite polarities that drive DNA translocation in opposite directions.

  10. [Primary sarcomas and sarcoma metastases in the liver: morphological and molecular aspects].

    PubMed

    Mechtersheimer, G; Penzel, R; Hofmann, W J; Schirmacher, P

    2006-07-01

    The considerable progress made in radiology, in surgical management with curative intent, and in the identification of molecularly targeted small molecules, such as the tyrosine kinase inhibitor imatinib mesylate, in the treatment of gastrointestinal stromal tumors has greatly influenced the treatment of sarcoma manifestations within the liver. This requires not only the unequivocal pathomorphological differentiation of sarcomas from other tumor entities, e. g. spindle cell dedifferentiated/pleomorphic carcinomas, aggressive non-Hodgkin lymphomas or amelanotic malignant melanomas, but also an accurate subtyping of this complex group of tumors. Additionally to macroscopic and histological findings, the recognition of characteristic immunophenotypic constellations and, at least in some types of sarcoma, the identification of molecular signatures, have greatly expanded the diagnostic tools in pathology. PMID:16773310

  11. Methodological aspects of the molecular and histological study of prostate cancer: Focus on PTEN

    PubMed Central

    Ugalde-Olano, Aitziber; Egia, Ainara; Fernández-Ruiz, Sonia; Loizaga-Iriarte, Ana; Zuñiga-García, Patricia; Garcia, Stephane; Royo, Félix; Lacasa-Viscasillas, Isabel; Castro, Erika; Cortazar, Ana R.; Zabala-Letona, Amaia; Martín-Martín, Natalia; Arruabarrena-Aristorena, Amaia; Torrano-Moya, Verónica; Valcárcel-Jiménez, Lorea; Sánchez-Mosquera, Pilar; Caro-Maldonado, Alfredo; González-Tampan, Jorge; Cachi-Fuentes, Guido; Bilbao, Elena; Montero, Rocío; Fernández, Sara; Arrieta, Edurne; Zorroza, Kerman; Castillo-Martín, Mireia; Serra, Violeta; Salazar, Eider; Macías-Cámara, Nuria; Tabernero, Jose; Baselga, Jose; Cordón-Cardo, Carlos; Aransay, Ana M.; Villar, Amaia Del; Iovanna, Juan L.; Falcón-Pérez, Juan M.; Unda, Miguel; Bilbao, Roberto; Carracedo, Arkaitz

    2015-01-01

    Prostate cancer is among the most frequent cancers in men, and despite its high rate of cure, the high number of cases results in an elevated mortality worldwide. Importantly, prostate cancer incidence is dramatically increasing in western societies in the past decades, suggesting that this type of tumor is exquisitely sensitive to lifestyle changes. Prostate cancer frequently exhibits alterations in the PTEN gene (inactivating mutations or gene deletions) or at the protein level (reduced protein expression or altered sub-cellular compartmentalization). The relevance of PTEN in this type of cancer is further supported by the fact that the sole deletion of PTEN in the murine prostate epithelium recapitulates many of the features of the human disease. In order to study the molecular alterations in prostate cancer, we need to overcome the methodological challenges that this tissue imposes. In this review we present protocols and methods, using PTEN as proof of concept, to study different molecular characteristics of prostate cancer. PMID:25697760

  12. Penicillium marneffei Infection and Recent Advances in the Epidemiology and Molecular Biology Aspects

    PubMed Central

    Vanittanakom, Nongnuch; Cooper, Chester R.; Fisher, Matthew C.; Sirisanthana, Thira

    2006-01-01

    Penicillium marneffei infection is an important emerging public health problem, especially among patients infected with human immunodeficiency virus in the areas of endemicity in southeast Asia, India, and China. Within these regions, P. marneffei infection is regarded as an AIDS-defining illness, and the severity of the disease depends on the immunological status of the infected individual. Early diagnosis by serologic and molecular assay-based methods have been developed and are proving to be important in diagnosing infection. The occurrence of natural reservoirs and the molecular epidemiology of P. marneffei have been studied; however, the natural history and mode of transmission of the organism remain unclear. Soil exposure, especially during the rainy season, has been suggested to be a critical risk factor. Using a highly discriminatory molecular technique, multilocus microsatellite typing, to characterize this fungus, several isolates from bamboo rats and humans were shown to share identical multilocus genotypes. These data suggest either that transmission of P. marneffei may occur from rodents to humans or that rodents and humans are coinfected from common environmental sources. These putative natural cycles of P. marneffei infection need further investigation. Studies on the fungal genetics of P. marneffei have been focused on the characterization of genetic determinants that may play important roles in asexual development, mycelial-to-yeast phase transition, and the expression of antigenic determinants. Molecular studies have identified several genes involved in germination, hyphal development, conidiogenesis, and yeast cell polarity. A number of functionally important genes, such as the malate synthase- and catalase-peroxidase protein-encoding genes, have been identified as being upregulated in the yeast phase. Future investigations pertaining to the roles of these genes in host-fungus interactions may provide the key knowledge to understanding the

  13. Integrable perturbed magnetic fields in toroidal geometry: An exact analytical flux surface label for large aspect ratio

    SciTech Connect

    Kallinikos, N.; Isliker, H.; Vlahos, L.; Meletlidou, E.

    2014-06-15

    An analytical description of magnetic islands is presented for the typical case of a single perturbation mode introduced to tokamak plasma equilibrium in the large aspect ratio approximation. Following the Hamiltonian structure directly in terms of toroidal coordinates, the well known integrability of this system is exploited, laying out a precise and practical way for determining the island topology features, as required in various applications, through an analytical and exact flux surface label.

  14. Methodological and Clinical Aspects of the Molecular Epidemiology of Mycobacterium tuberculosis and Other Mycobacteria.

    PubMed

    Jagielski, Tomasz; Minias, Alina; van Ingen, Jakko; Rastogi, Nalin; Brzostek, Anna; Żaczek, Anna; Dziadek, Jarosław

    2016-04-01

    Molecular typing has revolutionized epidemiological studies of infectious diseases, including those of a mycobacterial etiology. With the advent of fingerprinting techniques, many traditional concepts regarding transmission, infectivity, or pathogenicity of mycobacterial bacilli have been revisited, and their conventional interpretations have been challenged. Since the mid-1990s, when the first typing methods were introduced, a plethora of other modalities have been proposed. So-called molecular epidemiology has become an essential subdiscipline of modern mycobacteriology. It serves as a resource for understanding the key issues in the epidemiology of tuberculosis and other mycobacterial diseases. Among these issues are disclosing sources of infection, quantifying recent transmission, identifying transmission links, discerning reinfection from relapse, tracking the geographic distribution and clonal expansion of specific strains, and exploring the genetic mechanisms underlying specific phenotypic traits, including virulence, organ tropism, transmissibility, or drug resistance. Since genotyping continues to unravel the biology of mycobacteria, it offers enormous promise in the fight against and prevention of the diseases caused by these pathogens. In this review, molecular typing methods for Mycobacterium tuberculosis and nontuberculous mycobacteria elaborated over the last 2 decades are summarized. The relevance of these methods to the epidemiological investigation, diagnosis, evolution, and control of mycobacterial diseases is discussed. PMID:26912567

  15. Diversification of Neoaves: integration of molecular sequence data and fossils

    PubMed Central

    Ericson, Per G.P; Anderson, Cajsa L; Britton, Tom; Elzanowski, Andrzej; Johansson, Ulf S; Källersjö, Mari; Ohlson, Jan I; Parsons, Thomas J; Zuccon, Dario; Mayr, Gerald

    2006-01-01

    Patterns of diversification and timing of evolution within Neoaves, which includes almost 95% of all bird species, are virtually unknown. On the other hand, molecular data consistently indicate a Cretaceous origin of many neoavian lineages and the fossil record seems to support an Early Tertiary diversification. Here, we present the first well-resolved molecular phylogeny for Neoaves, together with divergence time estimates calibrated with a large number of stratigraphically and phylogenetically well-documented fossils. Our study defines several well-supported clades within Neoaves. The calibration results suggest that Neoaves, after an initial split from Galloanseres in Mid-Cretaceous, diversified around or soon after the K/T boundary. Our results thus do not contradict palaeontological data and show that there is no solid molecular evidence for an extensive pre-Tertiary radiation of Neoaves. PMID:17148284

  16. Membrane curvature in cell biology: An integration of molecular mechanisms.

    PubMed

    Jarsch, Iris K; Daste, Frederic; Gallop, Jennifer L

    2016-08-15

    Curving biological membranes establishes the complex architecture of the cell and mediates membrane traffic to control flux through subcellular compartments. Common molecular mechanisms for bending membranes are evident in different cell biological contexts across eukaryotic phyla. These mechanisms can be intrinsic to the membrane bilayer (either the lipid or protein components) or can be brought about by extrinsic factors, including the cytoskeleton. Here, we review examples of membrane curvature generation in animals, fungi, and plants. We showcase the molecular mechanisms involved and how they collaborate and go on to highlight contexts of curvature that are exciting areas of future research. Lessons from how membranes are bent in yeast and mammals give hints as to the molecular mechanisms we expect to see used by plants and protists. PMID:27528656

  17. Integration of Mitochondrial Targeting for Molecular Cancer Therapeutics

    PubMed Central

    Marchetti, Philippe; Guerreschi, Pierre; Mortier, Laurent; Kluza, Jerome

    2015-01-01

    Mitochondrial metabolism greatly influences cancer cell survival, invasion, metastasis, and resistance to many anticancer drugs. Furthermore, molecular-targeted therapies (e.g., oncogenic kinase inhibitors) create a dependence of surviving cells on mitochondrial metabolism. For these reasons, inhibition of mitochondrial metabolism represents promising therapeutic pathways in cancer. This review provides an overview of mitochondrial metabolism in cancer and discusses the limitations of mitochondrial inhibition for cancer treatment. Finally, we present preclinical evidence that mitochondrial inhibition could be associated with oncogenic “drivers” inhibitors, which may lead to innovative drug combinations for improving the efficacy of molecular-targeted therapy. PMID:26713093

  18. Network integration and graph analysis in mammalian molecular systems biology

    PubMed Central

    Ma'ayan, A.

    2009-01-01

    Abstraction of intracellular biomolecular interactions into networks is useful for data integration and graph analysis. Network analysis tools facilitate predictions of novel functions for proteins, prediction of functional interactions and identification of intracellular modules. These efforts are linked with drug and phenotype data to accelerate drug-target and biomarker discovery. This review highlights the currently available varieties of mammalian biomolecular networks, and surveys methods and tools to construct, compare, integrate, visualise and analyse such networks. PMID:19045817

  19. Food allergens: molecular and immunological aspects, allergen databases and cross-reactivity.

    PubMed

    Lorenz, Anne-Regine; Scheurer, Stephan; Vieths, Stefan

    2015-01-01

    The currently known food allergens are assigned to a relatively small number of protein families. Food allergens grouped into protein families share common functional and structural features that can be attributed to the allergenic potency and potential cross-reactivity of certain proteins. Molecular data, in terms of structural information, biochemical characteristics and clinical relevance for each known allergen, including isoforms and variants, are mainly compiled into four open-access databases. Allergens are designated according to defined criteria by the World Health Organization and the International Union of Immunological Societies Allergen Nomenclature Sub-committee. Food allergies are caused by primary sensitisation to the disease-eliciting food allergens (class I food allergen), or they can be elicited as a consequence of a primary sensitisation to inhalant allergens and subsequent IgE cross-reaction to homologous proteins in food (class II food allergens). Class I and class II allergens display different clinical significance in children and adults and are characterised by different molecular features. In line with this, high stability when exposed to gastrointestinal digestion and heat treatment is attributed to many class I food allergens that frequently induce severe reactions. The stability of a food allergen is determined by its molecular characteristics and can be influenced by structural (chemical) modifications due to thermal processing. Moreover, the immunogenicity and allergenicity of food allergens further depends on specific T cell and B cell epitopes. Although the T cell epitope pattern can be highly diverse for individual patients, several immuno-prominent T cell epitopes have been identified. Such conserved T cell epitopes and IgE cross-reactive B cell epitopes contribute to cross-reactivity between food allergens of the same family and to clinical cross-reactivity, similar to the birch pollen-food syndrome. PMID:26022861

  20. Mechanical aspects of nitrile hydratase enzymatic activity. Steered molecular dynamics simulations of Pseudonocardia thermophila JCM 3095

    NASA Astrophysics Data System (ADS)

    Peplowski, L.; Kubiak, K.; Nowak, W.

    2008-12-01

    Nitrile hydratase (NHase), an important biotechnological enzyme, has been investigated using a steered molecular dynamics computer modelling for the first time. An external force applied to the docked ligands was used to determine transport paths for acrylonitrile (substrate) and acrylamide (product). The average drag force of 120 pN within the enzyme channel is 50% higher than that in model water. The major hindrance of 500 pN is generated by βPhe37 residue. This region may be responsible for the stereoselectivity of NHases.

  1. Morphological, molecular and ecological aspects of the South American hypogeous fungus Alpova austroalnicola sp. nov.

    PubMed

    Nouhra, Eduardo R; Dominguez, Laura S; Becerra, Alejandra G; Trappe, James M

    2005-01-01

    Field studies in Argentina's Yunga District revealed Alpova austroalnicola sp. nov., a hypogeous fungus associated with Alnus acuminata ssp. acuminata. Morphological and molecular studies based on amplification and sequencing of the nuclear LSU rDNA gene showed its unique identity within Alpova. Related genera included in the analyses were Boletus edulis, Rhizopogon spp., Suillus luteus and Truncocolumella citrina. Additional observations of animal diggings around the sites and microscopic examination of fecal pellets of the nine-banded armadillo (Dasypus novemcinctus novemcinctus) indicate A. austroalnicola is consumed and its spores dispersed by animals. PMID:16392248

  2. [The Molecular Aspect of the Antitumor Effect of Oxaliplatin in Combination with 5-FU].

    PubMed

    Kitao, Hiroyuki; Kiyonari, Shinichi; Iimori, Makoto; Niimi, Shinichiro; Kataoka, Yuki; Akiyama, Shingo; Edahiro, Keitaro; Nakanishi, Ryota; Tokunaga, Eriko; Saeki, Hiroshi; Oki, Eiji; Kanaji, Shingo; Kakeji, Yoshihiro; Maehara, Yoshihiko

    2016-06-01

    Platinum-based chemotherapeutic drugs as a component of combination chemotherapy are widely used in the treatment of cancer. In particular, oxaliplatin(L-OHP), one such platinum-based chemotherapeutic drug, has a synergistic effect in combination with 5-FU and Leucovorin for the treatment of advanced colorectal cancer. However, the underlying molecular mechanism of this synergistic effect has not been fully clarified yet. In this review, we summarize several updates about the in vitro action of oxaliplatin in human tumor cells and discuss the underlying mechanism of its synergistic effect with 5-FU. PMID:27306806

  3. Multiple time step integrators in ab initio molecular dynamics

    SciTech Connect

    Luehr, Nathan; Martínez, Todd J.; Markland, Thomas E.

    2014-02-28

    Multiple time-scale algorithms exploit the natural separation of time-scales in chemical systems to greatly accelerate the efficiency of molecular dynamics simulations. Although the utility of these methods in systems where the interactions are described by empirical potentials is now well established, their application to ab initio molecular dynamics calculations has been limited by difficulties associated with splitting the ab initio potential into fast and slowly varying components. Here we present two schemes that enable efficient time-scale separation in ab initio calculations: one based on fragment decomposition and the other on range separation of the Coulomb operator in the electronic Hamiltonian. We demonstrate for both water clusters and a solvated hydroxide ion that multiple time-scale molecular dynamics allows for outer time steps of 2.5 fs, which are as large as those obtained when such schemes are applied to empirical potentials, while still allowing for bonds to be broken and reformed throughout the dynamics. This permits computational speedups of up to 4.4x, compared to standard Born-Oppenheimer ab initio molecular dynamics with a 0.5 fs time step, while maintaining the same energy conservation and accuracy.

  4. Integrated Multiscale Modeling of Molecular Computing Devices. Final Report

    SciTech Connect

    Tim Schulze

    2012-11-01

    The general theme of this research has been to expand the capabilities of a simulation technique, Kinetic Monte Carlo (KMC) and apply it to study self-assembled nano-structures on epitaxial thin films. KMC simulates thin film growth and evolution by replacing the detailed dynamics of the system's evolution, which might otherwise be studied using molecular dynamics, with an appropriate stochastic process.

  5. AlphaSpectrum ASPECT analysis code for background correction & peak integration

    Energy Science and Technology Software Center (ESTSC)

    2005-04-13

    The ASPECT code provides a means for rapid analysis of energy-resolved spectra obtained by multi-channel pulse-height analysis (MCA) during (or after) counting of alpha-emissions from a filter air sample (or other suitably prepared sample) utilizing a solid-state detector, or other detector having sufficient energy resolution indiviual radioisotope peaks indentified in a spectrum are fitted using a peak shape algorithm by non-linear least-square fitting procedures that minimize Chi-square differences between the data and a fitted peakmore » function. The code accomplishes the identification of all significant peaks present in the spectrum with automatic recalibration to the 7.68 Po-214 alpha peak from the Radon-222 decay chain, the subtraction of all radon progeny interference overlaps with lower energy peaks in the energy range of Pu-238, Am-241, Pu-239, and U-234/Th-232, and the integration of the counts in any peak identified for these transuranic radionuclides. The output is therefore in the form of isotope specific net transuranic CPM, DPM or concentration, available in near real-time during air sampling. In this "copyright" version, the assumption is made that the alpha spectra to be analyzed have been stored by unique name in sequential form: "FileName(i)", where "FileName" can be any name and i is the index number of the file saved (e.g., i = 1,2, ..., n). this format is one automatically generated by the alpha Environmental Continuous Air Monitor (ECAM), developed by Los Alamos National Laboratory, and manufactured by Canberra Industries, a Laboratory Industrial Partner for this technology. It is assumed in this version of the code that the alpha spectrum data are stored in a 256 channel spectrum, although a larger num ber of channels could be easily accommodated by small code changes. The ECAM data output format is RADNET compliant (an inidustry standard developed at Los Alamos), and include, in addition to a 256-channel alpha spectrum, data on the

  6. AlphaSpectrum ASPECT analysis code for background correction & peak integration

    SciTech Connect

    Rodgers, John C.

    2005-04-13

    The ASPECT code provides a means for rapid analysis of energy-resolved spectra obtained by multi-channel pulse-height analysis (MCA) during (or after) counting of alpha-emissions from a filter air sample (or other suitably prepared sample) utilizing a solid-state detector, or other detector having sufficient energy resolution indiviual radioisotope peaks indentified in a spectrum are fitted using a peak shape algorithm by non-linear least-square fitting procedures that minimize Chi-square differences between the data and a fitted peak function. The code accomplishes the identification of all significant peaks present in the spectrum with automatic recalibration to the 7.68 Po-214 alpha peak from the Radon-222 decay chain, the subtraction of all radon progeny interference overlaps with lower energy peaks in the energy range of Pu-238, Am-241, Pu-239, and U-234/Th-232, and the integration of the counts in any peak identified for these transuranic radionuclides. The output is therefore in the form of isotope specific net transuranic CPM, DPM or concentration, available in near real-time during air sampling. In this "copyright" version, the assumption is made that the alpha spectra to be analyzed have been stored by unique name in sequential form: "FileName(i)", where "FileName" can be any name and i is the index number of the file saved (e.g., i = 1,2, ..., n). this format is one automatically generated by the alpha Environmental Continuous Air Monitor (ECAM), developed by Los Alamos National Laboratory, and manufactured by Canberra Industries, a Laboratory Industrial Partner for this technology. It is assumed in this version of the code that the alpha spectrum data are stored in a 256 channel spectrum, although a larger num ber of channels could be easily accommodated by small code changes. The ECAM data output format is RADNET compliant (an inidustry standard developed at Los Alamos), and include, in addition to a 256-channel alpha spectrum, data on the count time

  7. The (FHCl)- molecular anion - Structural aspects, global surface, and vibrational eigenspectrum

    NASA Technical Reports Server (NTRS)

    Klepeis, Neil E.; East, Allan L. L.; Csaszar, Attila G.; Allen, Wesley D.; Lee, Timothy J.; Schwenke, David W.

    1993-01-01

    State of the art ab initio electronic structure methods have been used to investigate the (FHCl)- molecular anion. It is proposed that the geometric structure and binding energies of the complex are r(e)(H-F) = 0.963 +/- 0.003 A, R(e)(H-Cl) = 1.925 +/- 0.015 A, and D0(HF + Cl(-)) = 21.8 +/- 0.4 kcal/mol. A Morokuma decomposition of the ion-molecular bonding give the following electrostatic, polarization, exchange repulsion, dispersion, and charge-transfer plus higher-order mixing components of the vibrationless complexation energy: -27.3, -5.2, +18.3, -4.5, and -5.0 kcal/mol, respectively. A couples cluster single and doubles global surface is constructed from 208 and 228 energy points for linear and bent configurations, respectively, these being fit to rms errors of only 3.9 and 9.3/cm, respectively, below 8000/cm. Converged J = 0 and J = 1 variational eigenstates of the (FHCl)- surface to near the HF + Cl(-) dissociation threshold are determined. The fundamental vibrational frequencies are found to be nu1 = 247/cm, nu2 = 876/cm, and nu3 = 2884/cm. The complete vibrational eigenspectrum is analyzed.

  8. Molecular aspects and clinical methods for preserving ovarian reserves in women receiving cancer treatment.

    PubMed

    Thomakos, N; Trachana, S P; Koutroumpa, I; Rodolakis, A; Gavalas, N G

    2015-01-01

    Cancer prevalence is high, and of importance to cancer sufferers is the long term survival and normal activities resumption. Moreover, pregnancy is drawing interest for preserving ovarian reserves in post-chemotherapy affected women, especially of younger ages. The gonadotoxic effect of cancer treatment, involves mechanisms that are not fully understood, mainly due to the variety of molecular pathways triggered once therapeutic agents applied. Reported rates of premature ovarian failure after the treatment effect and the application of various treatment protocols, differ extensively due to the protocol itself but also due to the age of treated patients. Several options for preserving ovarian reserves are currently employed in the clinique, such as ovarian transposition, embryos cryopreservation and the use of gonadotropin-releasing hormone (GnRH) and its agonists/antagonists, but most of them are still under investigation. This paper reviews these methods and the molecular mechanisms that are possibly involved in the action of agents such as GnRH. PMID:26411202

  9. General morphological and biological features of neoplasms: integration of molecular findings.

    PubMed

    Diaz-Cano, S J

    2008-07-01

    This review highlights the importance of morphology-molecular correlations for a proper implementation of new markers. It covers both general aspects of tumorigenesis (which are normally omitted in papers analysing molecular pathways) and the general mechanisms for the acquired capabilities of neoplasms. The mechanisms are also supported by appropriate diagrams for each acquired capability that include overlooked features such as mobilization of cellular resources and changes in chromatin, transcription and epigenetics; fully accepted oncogenes and tumour suppressor genes are highlighted, while the pathways are also presented as activating or inactivating with appropriate colour coding. Finally, the concepts and mechanisms presented enable us to understand the basic requirements for the appropriate implementation of molecular tests in clinical practice. In summary, the basic findings are presented to serve as a bridge to clinical applications. The current definition of neoplasm is descriptive and difficult to apply routinely. Biologically, neoplasms develop through acquisition of capabilities that involve tumour cell aspects and modified microenvironment interactions, resulting in unrestricted growth due to a stepwise accumulation of cooperative genetic alterations that affect key molecular pathways. The correlation of these molecular aspects with morphological changes is essential for better understanding of essential concepts as early neoplasms/precancerous lesions, progression/dedifferentiation, and intratumour heterogeneity. The acquired capabilities include self-maintained replication (cell cycle dysregulation), extended cell survival (cell cycle arrest, apoptosis dysregulation, and replicative lifespan), genetic instability (chromosomal and microsatellite), changes of chromatin, transcription and epigenetics, mobilization of cellular resources, and modified microenvironment interactions (tumour cells, stromal cells, extracellular, endothelium). The acquired

  10. Adolescent Risk-Taking: Integrating Personal, Cognitive, and Social Aspects of Judgment

    ERIC Educational Resources Information Center

    Boyer, Ty W.; Byrnes, James P.

    2009-01-01

    Developmental research has examined individual differences, cognitive developmental bases, and psychosocial factors of adolescent risk-taking. The current paper presents a general adolescent risk-taking model that adopts aspects of each of these primarily independent areas. This model is based on the premise that adolescents take risks when (a)…

  11. Exploring Social Equity Aspects in Integrating Technology in Primary Mathematics Education

    ERIC Educational Resources Information Center

    Stoilescu, Dorian

    2014-01-01

    This research focus on aspects of equity related to the introduction of using technology in classrooms. Technology has the potential to support mathematics pedagogy with visual representations and offer modelling and simulation facilities, increasing the creativity of the learning and teaching processes (Kaput, Ness, & Hoyles, 2008; Stoilescu…

  12. [Not only optic neuropathy: new molecular and clinical aspects of OPA1 gene mutations].

    PubMed

    Ołdak, Monika; Sciezyńska, Aneta; Szulborski, Kamil; Szaflik, Jacek P; Szaflik, Jerzy

    2014-01-01

    Autosomal dominant optic nerve atrophy is the most frequent dominantly inherited optic neuropathy. The main causesof the disease are OPA1 gene mutations, which are detected in about 60% of patients. Encoded by the nuclear genome the OPA1 protein plays an important role in a wide variety of processes crucial to the proper functioning of mitochondria, the role of OPAl in many of them has been discovered recently. A detailed study of patients with mutations in the OPA1 gene has shown that about 20% of them present symptoms of a multiple system disease, which may include hearing loss, progressive external ophthalmoplegia, ataxia, myopathy, peripheral neuropathy, spastic paraparesis and multiple sclerosis-like illness. This clinical manifestation is difficult to differentiate from other neurodegenerative diseases, that is why genetic testing is very important in order to determine the molecular basis of the disease in these patients. PMID:25137924

  13. Batten Disease: Clinical Aspects, Molecular Mechanisms, Translational Science, and Future Directions

    PubMed Central

    Dolisca, Sarah-Bianca; Mehta, Mitali; Pearce, David A.; Mink, Jonathan W.; Maria, Bernard L.

    2014-01-01

    The neuronal ceroid lipofuscinoses, collectively the most common neurodegenerative disorders of childhood, are primarily caused by an autosomal recessive genetic mutation leading to a lysosomal storage disease. Clinically these diseases manifest at varying ages of onset, and associated symptoms include cognitive decline, movement disorders, seizures, and retinopathy. The underlying cell biology and biochemistry that cause the clinical phenotypes of neuronal ceroid lipofuscinoses are still being elaborated. The 2012 Neurobiology of Disease in Children Symposium, held in conjunction with the 41st Annual Meeting of the Child Neurology Society, aimed to (1) provide a survey of the currently accepted forms of neuronal ceroid lipofuscinoses and their associated genetic mutations and clinical phenotypes; (2) highlight the specific pathology of Batten disease; (3) discuss the contemporary understanding of the molecular mechanisms that lead to pathology; and (4) introduce strategies that are being translated from bench to bedside as potential therapeutics. PMID:23838031

  14. Mitochondrial Disease: Clinical Aspects, Molecular Mechanisms, Translational Science, and Clinical Frontiers

    PubMed Central

    Thornton, Ben; Cohen, Bruce; Copeland, William; Maria, Bernard L.

    2015-01-01

    Mitochondrial medicine provides a metabolic perspective on the pathology of conditions linked with inadequate oxidative phosphorylation. Dysfunction in the mitochondrial machinery can result in improper energy production, leading to cellular injury or even apoptosis. Clinical presentations are often subtle, so clinicians must have a high index of suspicion to make early diagnoses. Symptoms could include muscle weakness and pain, seizures, loss of motor control, decreased visual and auditory functions, metabolic acidosis, acute developmental regression, and immune system dysfunction. The 2013 Neurobiology of Disease in Children Symposium, held in conjunction with the 42nd Annual Meeting of the Child Neurology Society, aimed to (1) describe accepted clinical phenotypes of mitochondrial disease produced from various mitochondrial mutations, (2) discuss contemporary understanding of molecular mechanisms that contribute to disease pathology, (3) highlight the systemic effects produced by dysfunction within the mitochondrial machinery, and (4) introduce current strategies that are being translated from bench to bedside as potential therapeutics. PMID:24916430

  15. [Molecular aspects of the antiviral response against hepatitis C virus implicated in vaccines development].

    PubMed

    Llanes, María Soledad; Palacios, Natalia Soledad; Piccione, Magalí; Ruiz, María Guillermina; Layana, Carla

    2015-04-01

    Hepatitis C is a contagious liver disease caused by hepacivirus of the Flaviviridae family. It has a RNA genome, a unique highly variable molecule. It encodes ten proteins which are necessary to infect cells and multiply. Replication occurs only in hepatocytes. Because of its wide genomic variability and the absence of symptoms, it is difficult to make an early diagnosis and successful treatment. In this review we analyze the molecular mechanism by which the virus infects the hepatocytes and causes the disease. We focused the analysis on different therapies, with the possibility of improving treatment with the use of new specific vaccines. We highlight the use of new therapies based on nucleic acids, mainly DNA vectors. In the near future, once this treatment is adequately evaluated in clinical trials, and the costs are calculated, it could be a very beneficial alternative to conventional methods. PMID:24529681

  16. Molecular aspects of high-level resistance to sulbactam-cefoperazone in Klebsiella oxytoca clinical isolates.

    PubMed Central

    Kimura, K; Arakawa, Y; Ohsuka, S; Ito, H; Suzuki, K; Kurokawa, H; Kato, N; Ohta, M

    1996-01-01

    Nine Klebsiella oxytoca strains which demonstrated resistance to the combination of sulbactam and cefoperazone were isolated from geographically separate hospitals in Japan in 1995. Among them, K. oxytoca SB23 showed high-level resistance to sulbactam-cefoperazone (MIC > 128 micrograms/ml) and aztreonam (MIC, 128 micrograms/ml). The sulbactam-cefoperazone resistance was not transferred from strain SB23 to Escherichia coli CSH2 by conjugation, beta-Lactamase RbiA, produced by strain SB23, was purified, and the molecular mass was estimated to be 29 kDa by sodium dodecyl sulfate-polyacrylamide gel electrophoresis. Kinetic parameters for RbiA revealed that cefoperazone and aztreonam were hydrolyzed efficiently by this enzyme. Moreover, ceftazidime and imipenem were also hydrolyzed weakly by RbiA, although strain SB23 did not show any resistance to these agents. Clavulanate, sulbactam, and tazobactam failed to block the hydrolysis of cefoperazone by RbiA. The structural gene of RbiA (blaRBI) was cloned and sequenced, and the deduced amino acid sequence of RbiA demonstrated high-level similarities to those of the beta-lactamases found in K. oxytoca D488, E23004, and plasmid-mediated MEN-1, which have been classified into Bush functional group 2be. Although RbiA demonstrates high-level molecular similarity to the enzymes in group 2be, from an enzymological point of view, this enzyme might be differentiated from the enzymes in that group. Hybridization analysis revealed that beta-lactamase genes highly similar to blaRBI were generally encoded on the chromosome of the sulbactam-cefoperazone-resistant clinical isolates of K. oxytoca tested in the study, despite their different derivations. This observation suggests that sulbactam-cefoperazone-resistant A. oxytoca strains which produce RbiA-type beta-lactamases have been proliferating in many hospitals in Japan. PMID:8878568

  17. Intermolecular transfer integrals for organic molecular materials: can basis set convergence be achieved?

    NASA Astrophysics Data System (ADS)

    Huang, Jingsong; Kertesz, Miklos

    2004-05-01

    Intermolecular transfer integrals, and associated band-structures of organic molecular materials can be calculated through a dimer approach. Extensive numerical studies are performed on an ethylene π-dimer to investigate the basis sets dependence of transfer integrals. Convergence of calculated transfer integrals is achieved with respect to both Gaussian and plane-wave basis sets, provided the same level of theory is used. Effects of diffuse and polarization Gaussian functions on transfer integrals are identified. Comparison of experimental and theoretical values of transfer integrals of the TTF-TCNQ charge transfer salt is also presented.

  18. Multicenter molecular integrals for Slater orbitals of higher principal quantum numbers

    NASA Technical Reports Server (NTRS)

    Tai, H.

    1989-01-01

    As was shown earlier by Tai (1979), by using the Fourier-transform technique and properly coupling a pair of two-center exchange integrals, the multicenter molecular integrals can be cast into a simple expression upon which numerical procedures can be directly applied. In this paper, the procedure of Tai is extended to integrals involving orbitals with arbitrarily higher principal quantum number. The derivation is outlined, and the explicit expressions are presented for a three-center nuclear attraction integral and a four-center two-electron Coulomb repulsion integral of arbitrary higher states.

  19. Current insights into the "antiphospholipid" syndrome: clinical, immunological, and molecular aspects.

    PubMed

    Kandiah, D A; Sali, A; Sheng, Y; Victoria, E J; Marquis, D M; Coutts, S M; Krilis, S A

    1998-01-01

    Advances in defining the target antigen(s) for the autoantibodies in the APS highlight the inadequacies of the current classification of these autoantibodies into anticardiolipin and LA antibodies. The discovery that beta 2GPI is the target antigen for the autoantibodies detected in solid-phase immunoassays has opened a number of areas of research linking these autoantibodies to atherogenesis and thrombus formation. Although the role of beta 2GPI in the regulation of blood coagulation in unclear, current evidence suggests that anti-beta 2GPI antibodies interfere with its "normal" role and appear to promote a procoagulant tendency. The expansion of research in this area and the diversity of the clinical manifestations of patients with APS have resulted in the inclusion of molecular biologists and pharmaceutical companies joining immunologists, hematologists, rheumatologists, obstetricians, neurologists, vascular surgeons, and protein and lipid biochemists in attempting to understand the pathophysiology of this condition. Although the published literature may result in conflicting results and introduce new controversies, developing standardized laboratory methods and extrapolation of in vitro experimental results to the vivo situation will advance our understanding of the regulation of the immune system and its interaction with normal hemostatic mechanisms. Since the authors' last review in 1991, the study and understanding of the pathophysiology of APS have evolved from lipid biochemistry to molecular techniques that may eventually provide specific therapies for the clinical manifestations of this condition. Although current treatment has improved the morbidity associated with this condition, especially in improving pregnancy outcomes, future therapies, as outlined in this review, may specifically address the biological abnormalities and have fewer side effects. Better diagnostic tools, such as magnetic resonance imaging with perfusion studies, will allow the study

  20. [Advances in the studies on the molecular and genetic aspects of epilepsy].

    PubMed

    Wang, Xu; Wang, Tao; Yuan, Ming-xiong; Liu, Mu-gen; Wang, Qing

    2005-06-01

    Epilepsy is one of the most common and debilitating neurological diseases that affects more than 40 million people worldwide. Genetic factors contribute to the pathogenesis of epilepsy. Molecular genetic studies have identified 15 disease-causing genes for epilepsy. The majority of the genes encode ion channels, including voltage-gated potassium channels KCNQ2 and KCNQ3, sodium channels SCN1A, SCN2A, and SCN1B, chloride channels CLCN2, and ligand-gated ion channels CHRNA4, CHRNB2, GABRG2, and GABRA1. Interestingly, non-ion channel genes have also been identified as epilepsy genes, and these genes include G-protein-coupled receptor MASS1/VLGR1, GM3 synthase, and proteins with unknown functions such as LGI1, NHLRC1, and EFHC1. These studies make genetic testing possible in some patients, and further characterization of the identified epilepsy genes may lead to the development of new drugs and new treatments for patients with epilepsy. PMID:16038283

  1. Cellular and molecular aspects of the pathomechanism and therapy of murine experimental allergic encephalomyelitis.

    PubMed

    Tabira, T

    1989-01-01

    Experimental allergic encephalomyelitis (EAE) is an autoimmune disease of the central nervous system (CNS). Its immune mechanism is well understood at the cellular and molecular levels, which is herein reviewed. Susceptibility to EAE is under the control of the genes partially inside and partially outside the H-2 complex. There are two myelin constituents known to be encephalitogenic, myelin basic protein and proteolipid apoprotein. EAE is mediated by effector T cells sensitized to the encephalitogen. Effector T cells bear surface phenotypes of Lyt1+2-, L3T4+, and they are activated by the encephalitogen/self Ia complex or certain alloantigens and acquire encephalitogenic activity. By unknown homing mechanisms, the effector T cells invade the CNS and induce the target phase phenomena, which include Ia-antigen expression in the local tissue, activation of procoagulant activity, breakdown of the blood-brain barrier, and excretion of lymphokines which induce inflammation and demyelination, resulting in functional alteration. Possibility of specific immune therapy is postulated as a model for human autoimmune disease. PMID:2484301

  2. DOE contractors' workshop: Cellular and molecular aspects of radiation induced DNA damage and repair

    SciTech Connect

    Not Available

    1987-01-01

    For four decades the US Department of Energy and its predecessors have been the lead federal agency in supporting radiation biology research. Over the years emphasis in this program has gradually shifted from dose-effect studies on animals to research on the effects of radiations of various qualities on cells and molecules. Mechanistic studies on the action of radiation at the subcellular level are few in number and there is a need for more research in this area if we are to gain a better understanding of how radiation affects living cells. The intent of this workshop was to bring together DOE contractors and grantees who are investigating the effects of radiation at the cellular and molecular levels. The aims were to foster the exchange of information on research projects and experimental results, promote collaborative research efforts, and obtain an overview of research currently supported by the Health Effects Research Division of the Office of Health and Environmental Research. The latter is needed by the Office for program planning purposes. This report on the workshop which took place in Albuquerque, New Mexico on March 10-11, 1987, includes an overview with future research recommendations, extended abstracts of the plenary presentations, shorter abstracts of each poster presentation, a workshop agenda and the names and addresses of the attendees.

  3. Molecular and genetic aspects of controlling the soilborne necrotrophic pathogens Rhizoctonia and Pythium.

    PubMed

    Okubara, Patricia A; Dickman, Martin B; Blechl, Ann E

    2014-11-01

    The soilborne necrotrophic pathogens Rhizoctonia and Pythium infect a wide range of crops in the US and worldwide. These pathogens pose challenges to growers because the diseases they cause are not adequately controlled by fungicides, rotation or, for many hosts, natural genetic resistance. Although a combination of management practices are likely to be required for control of Rhizoctonia and Pythium, genetic resistance remains a key missing component. This review discusses the recent deployment of introduced genes and genome-based information for control of Rhizoctonia, with emphasis on three pathosystems: Rhizoctonia solani AG8 and wheat, R. solani AG1-IA and rice, and R. solani AG3 or AG4 and potato. Molecular mechanisms underlying disease suppression will be addressed, if appropriate. Although less is known about genes and factors suppressive to Pythium, pathogen genomics and biological control studies are providing useful leads to effectors and antifungal factors. Prospects for resistance to Rhizoctonia and Pythium spp. will continue to improve with growing knowledge of pathogenicity strategies, host defense gene action relative to the pathogen infection process, and the role of environmental factors on pathogen-host interactions. PMID:25438786

  4. Comparative Proteomic Study Reveals the Molecular Aspects of Delayed Ocular Symptoms Induced by Sulfur Mustard

    PubMed Central

    Pashandi, Zaiddodine; Saraygord-Afshari, Neda; Naderi-Manesh, Hossein; Naderi, Mostafa

    2015-01-01

    Objective. Sulfur mustard (SM) is a highly reactive alkylating agent which produces ocular, respiratory, and skin damages. Eyes are the most sensitive organ to SM due to high intrinsic metabolic and rapid turnover rate of corneal epithelium and aqueous-mucous interfaces of the cornea and conjunctiva. Here we investigate underlying molecular mechanism of SM exposure delayed effects which is still a controversial issue after about 30 years. Materials and Methods. Following ethical approval, we have analyzed serum proteome of ten severe SM exposed male patients with delayed eye symptoms with two-dimensional electrophoresis followed by matrix-assisted laser desorption/ionization time-of-flight/time-of-flight mass spectrometry. The western blotting was used to confirm the proteins that have been identified. Results. We have identified thirteen proteins including albumin, haptoglobin, and keratin isoforms as well as immunoglobulin kappa chain which showed upregulation while transferrin and alpha 1 antitrypsin revealed downregulation in these patients in comparison with healthy control group. Conclusions. Our results elevated participation of free iron circulatory imbalance and local matrix-metalloproteinase activity in development of delayed ocular symptoms induced by SM. It demonstrates that SM induced systemic toxicity leads to some serum protein changes that continually and gradually exacerbate the ocular surface injuries. PMID:25685557

  5. Molecular aspects of lipoic acid in the prevention of diabetes complications.

    PubMed

    Packer, L; Kraemer, K; Rimbach, G

    2001-10-01

    Alpha-lipoic acid (LA) and its reduced form, dihydrolipoic acid, are powerful antioxidants. LA scavenges hydroxyl radicals, hypochlorous acid, peroxynitrite, and singlet oxygen. Dihydrolipoic acid also scavenges superoxide and peroxyl radicals and can regenerate thioredoxin, vitamin C, and glutathione, which in turn can recycle vitamin E. There are several possible sources of oxidative stress in diabetes including glycation reactions, decompartmentalization of transition metals, and a shift in the reduced-oxygen status of the diabetic cells. Diabetics have increased levels of lipid hydroperoxides, DNA adducts, and protein carbonyls. Available data strongly suggest that LA, because of its antioxidant properties, is particularly suited to the prevention and/or treatment of diabetic complications that arise from an overproduction of reactive oxygen and nitrogen species. In addition to its antioxidant properties, LA increases glucose uptake through recruitment of the glucose transporter-4 to plasma membranes, a mechanism that is shared with insulin-stimulated glucose uptake. Further, recent trials have demonstrated that LA improves glucose disposal in patients with type II diabetes. In experimental and clinical studies, LA markedly reduced the symptoms of diabetic pathologies, including cataract formation, vascular damage, and polyneuropathy. To develop a better understanding of the preventative and therapeutic potentials of LA, much of the current interest is focused on elucidating its molecular mechanisms in redox dependent gene expression. PMID:11684397

  6. Physiological and Molecular Aspects of Tolerance to Environmental Constraints in Grain and Forage Legumes.

    PubMed

    Adnane, Bargaz; Mainassara, Zaman-Allah; Mohamed, Farissi; Mohamed, Lazali; Jean-Jacques, Drevon; Rim, Maougal T; Georg, Carlsson

    2015-01-01

    Despite the agronomical and environmental advantages of the cultivation of legumes, their production is limited by various environmental constraints such as water or nutrient limitation, frost or heat stress and soil salinity, which may be the result of pedoclimatic conditions, intensive use of agricultural lands, decline in soil fertility and environmental degradation. The development of more sustainable agroecosystems that are resilient to environmental constraints will therefore require better understanding of the key mechanisms underlying plant tolerance to abiotic constraints. This review provides highlights of legume tolerance to abiotic constraints with a focus on soil nutrient deficiencies, drought, and salinity. More specifically, recent advances in the physiological and molecular levels of the adaptation of grain and forage legumes to abiotic constraints are discussed. Such adaptation involves complex multigene controlled-traits which also involve multiple sub-traits that are likely regulated under the control of a number of candidate genes. This multi-genetic control of tolerance traits might also be multifunctional, with extended action in response to a number of abiotic constraints. Thus, concrete efforts are required to breed for multifunctional candidate genes in order to boost plant stability under various abiotic constraints. PMID:26287163

  7. [Clinical and morphological parallels and molecular aspects of the morphogenesis of adenomyosis].

    PubMed

    Kogan, E A; Unanian, A L; Demura, T A; Grechukhina, O M; Sidorova, I S; Kiselev, V I

    2008-01-01

    The purpose of the study was to reveal clinical and morphological parallels and to define molecular mechanisms, the regulation of proliferation, apoptosis, neoangiogenesis, and the extent of abnormal tissue in adenomyosis (AM). The surgical material obtained from 492 patients of late reproductive age was examined. The data of clinico-anamnestic and instrumental diagnostic studies and a morphological study with hematoxylin and eosin staining were analyzed. An immunohistochemical study was carried out on serial paraffin sections (n = 115), by applying antibodies to Apo-CAS, Ki67, PCNA, CD-34, MMP-1, MMP-2, MMP-7, MMP-9, TIMP-1, TIMP-3, TIMP-4, and E-cadherin. The specific features of their morphological structure and the clinical course of the disease allowed identification of its active and inactive forms. Immunohistochemically active AM is characterized by high proliferation, diminished apoptosis, and increased expression of MMPs along with lower expression of TIMPs by glandular and stromal cells as compared with inactive AM. At the same time, there was a high activity of stromal cells in the foci of active AM. The results of the study may be used to predict the course of the disease and to elaborate target therapy for AM. PMID:19137775

  8. Molecular Aspects of Plant Adaptation to Life in the Chernobyl Zone1[w

    PubMed Central

    Kovalchuk, Igor; Abramov, Vladimir; Pogribny, Igor; Kovalchuk, Olga

    2004-01-01

    With each passing year since the Chernobyl accident of 1986, more questions arise about the potential for organisms to adapt to radiation exposure. Often this is thought to be attributed to somatic and germline mutation rates in various organisms. We analyzed the adaptability of native Arabidopsis plants collected from areas with different levels of contamination around the Chernobyl nuclear power plant from 1986 to 1992. Notably, progeny of Chernobyl plants resisted higher concentrations of the mutagens Rose Bengal and methyl methane sulfonate. We analyzed the possible molecular mechanisms of their resistance to mutagens and found a more than 10-fold lower frequency of extrachromosomal homologous recombination, significant differences in the expression of radical scavenging (CAT1 and FSD3) and DNA-repair (RAD1 and RAD51-like) genes upon exposure to mutagens (Rose Bengal and x-rays), and a higher level of global genome methylation. This data suggests that adaptation to ionizing radiation is a complex process involving epigenetic regulation of gene expression and genome stabilization that improves plants' resistance to environmental mutagens. PMID:15133154

  9. Molecular organization of type IV collagen: polymer liquid crystal-like aspects.

    PubMed

    Gathercole, L J; Barnard, K; Atkins, E D

    1989-12-01

    A new X-ray diffraction pattern from type IV collagen is described, which can be interpreted on the basis of crystalline and liquid crystalline origins of the reflections. Bovine anterior lens capsules extracted with 1 M NaCl and oriented by extension of 60% under constant load gave medium angle X-ray diffraction patterns showing many of the characteristics typical of liquid crystals. Prominent features, apart from those wide angle features attributable to the collagen triple helix, are (1) a four-point pattern of broad reflections at d-spacing 3.9 nm, and layer line spacing near 5 nm. (2) A broad intense equatorial peak centred at 1.24 nm, indicative of liquid-like lateral molecular associations. (3) A set of five sharp, streaked meridional reflections (previously obscured by the broad peak near 5 nm in unextracted capsules). (4) A further six higher angle reflections of a diffuse, arced and broad appearance on the meridian. The sharp streaked meridional reflections emanate from a long-range periodicity of units 8-9 nm in diameter. These features form a self-consistent system if interpreted on the basis of a staggered liquid crystal-like array of collagen molecules, in which case the first five meridionals and remaining broad reflections, sampled on the meridian, can all be indexed as orders of 21 nm. PMID:2489101

  10. Molecular aspects and chemoprevention of dimethylaminoazobenzene-induced hepatocarcinogenesis: A review.

    PubMed

    Thomas, Nisha Susan; George, Kiran; Namasivayam, Nalini

    2016-01-01

    The lipophilic azo dye dimethylaminoazobenzene (DAB) is a potent hepatocarcinogen accounted as a group-2B carcinogen causing risk to humans. DAB is commonly used as a coloring agent in food, pharmaceuticals, beverages, soap and polishes. The exploration of DAB-induced hepatocarcinogenesis in animal models helped to an extent to perceive the histological, biochemical and molecular mechanisms of DAB carcinogenesis and also the severity of DAB exposure to humans. In experimental animal models, it is well-proved that the procarcinogen DAB is predominantly metabolized by cytochrome P450 enzymes giving rise to the formation of toxic electrophiles and reactive oxygen species (ROS), which further forms DNA adducts leading to the development of hepatic tumors. Recently, research evidence suggests that dietary phytochemicals and plant polyphenols are promising agents to control the incidence of DAB-induced hepatocarcinogenesis by preventing the generation of toxic electrophiles and ROS thereby inhibiting the formation of DNA adducts. This review highlights the role of specific dietary factors, biotransformation of DAB, phenotypic and genotypic alterations, and significance of certain chemopreventive agents against DAB-induced hepatocarcinogenesis. PMID:26272071

  11. Physiological and Molecular Aspects of Tolerance to Environmental Constraints in Grain and Forage Legumes

    PubMed Central

    Bargaz, Adnane; Zaman-Allah, Mainassara; Farissi, Mohamed; Lazali, Mohamed; Drevon, Jean-Jacques; Maougal, Rim T.; Carlsson, Georg

    2015-01-01

    Despite the agronomical and environmental advantages of the cultivation of legumes, their production is limited by various environmental constraints such as water or nutrient limitation, frost or heat stress and soil salinity, which may be the result of pedoclimatic conditions, intensive use of agricultural lands, decline in soil fertility and environmental degradation. The development of more sustainable agroecosystems that are resilient to environmental constraints will therefore require better understanding of the key mechanisms underlying plant tolerance to abiotic constraints. This review provides highlights of legume tolerance to abiotic constraints with a focus on soil nutrient deficiencies, drought, and salinity. More specifically, recent advances in the physiological and molecular levels of the adaptation of grain and forage legumes to abiotic constraints are discussed. Such adaptation involves complex multigene controlled-traits which also involve multiple sub-traits that are likely regulated under the control of a number of candidate genes. This multi-genetic control of tolerance traits might also be multifunctional, with extended action in response to a number of abiotic constraints. Thus, concrete efforts are required to breed for multifunctional candidate genes in order to boost plant stability under various abiotic constraints. PMID:26287163

  12. Concepts and Molecular Aspects in the Polypharmacology of PARP-1 Inhibitors.

    PubMed

    Passeri, Daniela; Camaioni, Emidio; Liscio, Paride; Sabbatini, Paola; Ferri, Martina; Carotti, Andrea; Giacchè, Nicola; Pellicciari, Roberto; Gioiello, Antimo; Macchiarulo, Antonio

    2016-06-20

    Recent years have witnessed a renewed interest in PARP-1 inhibitors as promising anticancer agents with multifaceted functions. Particularly exciting developments include the approval of olaparib (Lynparza) for the treatment of refractory ovarian cancer in patients with BRCA1/2 mutations, and the increasing understanding of the polypharmacology of PARP-1 inhibitors. The aim of this review article is to provide the reader with a comprehensive overview of the distinct levels of the polypharmacology of PARP-1 inhibitors, including 1) inter-family polypharmacology, 2) intra-family polypharmacology, and 3) multi-signaling polypharmacology. Progress made in gaining insight into the molecular basis of these multiple target-independent and target-dependent activities of PARP-1 inhibitors are discussed, with an outlook on the potential impact that a better understanding of polypharmacology may have in aiding the explanation as to why some drug candidates work better than others in clinical settings, albeit acting on the same target with similar inhibitory potency. PMID:26424664

  13. The Effect of Diabetes Mellitus on Apoptosis in Hippocampus: Cellular and Molecular Aspects

    PubMed Central

    Sadeghi, Akram; Hami, Javad; Razavi, Shahnaz; Esfandiary, Ebrahim; Hejazi, Zahra

    2016-01-01

    Background: Diabetes mellitus is associated with cognitive deficits in humans and animals. These deficits are paralleled by neurophysiological and structural changes in brain. In diabetic animals, impairments of spatial learning, memory, and cognition occur in association with distinct changes in hippocampus, a key brain area for many forms of learning and memory and are particularly sensitive to changes in glucose homeostasis. However, the multifactorial pathogenesis of diabetic encephalopathy is not yet completely understood. Apoptosis plays a crucial role in diabetes-induce neuronal loss in hippocampus. Methods: The effects of diabetes on hippocampus and cognitive/behavioral dysfunctions in experimental models of diabetes are reviewed, with a focus on the negative impact on increased neuronal apoptosis and related cellular and molecular mechanisms. Results: Of all articles that were assessed, most of the experimental studies clearly showed that diabetes causes neuronal apoptosis in hippocampus through multiple mechanisms, including oxidative stress, inhibition of caspases, disturbance in expression of apoptosis regulator genes, as well as deficits in mitochondrial function. The balance between pro-apoptotic and anti-apoptotic signaling may determine the neuronal apoptotic outcome in vitro and in vivo models of experimental diabetes. Conclusions: Dissecting out the mechanisms responsible for diabetes-related changes in the hippocampal cell apoptosis helps improve treatment of impaired cognitive and memory functions in diabetic individuals. PMID:27076895

  14. Cellular and molecular aspects of diabetic nephropathy; the role of VEGF-A.

    PubMed

    Carranza, Katherine; Veron, Dolores; Cercado, Alicia; Bautista, Noemi; Pozo, Wilson; Tufro, Alda; Veron, Delma

    2015-01-01

    The prevalence of diabetes mellitus increased during the last century and it is estimated that 45% of the patients are not diagnosed. In South America the prevalence of diabetes and chronic kidney disease (CKD) increased, with a great disparity among the countries with respect to access to dialysis. In Ecuador it is one of the main causes of mortality, principally in the provinces located on the coast of the Pacific Ocean. The greatest single cause of beginning dialysis is diabetic nephropathy (DN). Even using the best therapeutic options for DN, the residual risk of proteinuria and of terminal CKD remains high. In this review we indicate the importance of the problem globally and in our region. We analyse relevant cellular and molecular studies that illustrate the crucial significance of glomerular events in DN development and evolution and in insulin resistance. We include basic anatomical, pathophysiological and clinical concepts, with special attention to the role of angiogenic factors such as the vascular endothelial growth factor (VEGF-A) and their relationship to the insulin receptor, endothelial isoform of nitric oxide synthase (eNOS) and angiopoietins. We also propose various pathways that have therapeutic potential in our opinion. Greater in-depth study of VEGF-A and angiopoietins, the state of glomerular VEGF resistance, the relationship of VEGF receptor 2/nephrin, VEGF/insulin receptors/nephrin and the relationship of VEGF/eNOS-NO at glomerular level could provide solutions to the pressing world problem of DN and generate new treatment alternatives. PMID:26300505

  15. Biochemical and molecular aspects of mammalian susceptibility to aflatoxin B{sub 1} carcinogenicity

    SciTech Connect

    Massey, T.E.; Stewart, R.K.; Daniels, J.M.

    1995-03-01

    Aflatoxin B{sub 1} (AFB{sub 1}) is a fungal toxin that has been implicated as a causative agent in human hepatic and extrahepatic carcinogenesis. In this review, the mechanisms involved in AFB{sub 1} toxicity are delineated, in order to describe the features that make a specific cell, tissue, or species susceptible to the mycotoxin. Important considerations include: (i) different mechanisms for bioactivation of AFB{sub 1} to its ultimate carcinogenic epoxide metabolite; (ii) the balance between bioactivation to and detoxification of the epoxide; (iii) the interaction of AFB{sub 1} epoxide with DNA and the mutational events leading to neoplastic transformation; (iv) the role of cytotoxicity in AFB{sub 1} carcinogenesis; (v) the significance of nonepoxide metabolites in toxicity; and (vi) the contribution of mycotoxin-unrelated disease processes. Although considerable controversy remains about the importance of specific events, a great deal has been learned about biochemical and molecular actions of AFB{sub 1}. 157 refs., 4 figs., 1 tab.

  16. JINN, an integrated software package for molecular geneticists.

    PubMed Central

    Johnsen, M

    1984-01-01

    I describe JINN, a microcomputer-based system designed to maintain and search a strain collection, to enter, modify and analyze sequences, and to use the EMBL Sequence Data Base. The major objective during development of this program has been integration of individual program modules to ensure a consistent and helpful user interface. The system is running under the CP/M operating system and requires little in the way of particular hardware configuration. PMID:6320101

  17. Excited states of ribosome translocation revealed through integrative molecular modeling

    PubMed Central

    Whitford, Paul C.; Ahmed, Aqeel; Yu, Yanan; Hennelly, Scott P.; Tama, Florence; Spahn, Christian M. T.; Onuchic, José N.; Sanbonmatsu, Karissa Y.

    2011-01-01

    The dynamic nature of biomolecules leads to significant challenges when characterizing the structural properties associated with function. While X-ray crystallography and imaging techniques (such as cryo-electron microscopy) can reveal the structural details of stable molecular complexes, strategies must be developed to characterize configurations that exhibit only marginal stability (such as intermediates) or configurations that do not correspond to minima on the energy landscape (such as transition-state ensembles). Here, we present a methodology (MDfit) that utilizes molecular dynamics simulations to generate configurations of excited states that are consistent with available biophysical and biochemical measurements. To demonstrate the approach, we present a sequence of configurations that are suggested to be associated with transfer RNA (tRNA) movement through the ribosome (translocation). The models were constructed by combining information from X-ray crystallography, cryo-electron microscopy, and biochemical data. These models provide a structural framework for translocation that may be further investigated experimentally and theoretically to determine the precise energetic character of each configuration and the transition dynamics between them. PMID:22080606

  18. Excited states of ribosome translocation revealed through integrative molecular modeling.

    PubMed

    Whitford, Paul C; Ahmed, Aqeel; Yu, Yanan; Hennelly, Scott P; Tama, Florence; Spahn, Christian M T; Onuchic, José N; Sanbonmatsu, Karissa Y

    2011-11-22

    The dynamic nature of biomolecules leads to significant challenges when characterizing the structural properties associated with function. While X-ray crystallography and imaging techniques (such as cryo-electron microscopy) can reveal the structural details of stable molecular complexes, strategies must be developed to characterize configurations that exhibit only marginal stability (such as intermediates) or configurations that do not correspond to minima on the energy landscape (such as transition-state ensembles). Here, we present a methodology (MDfit) that utilizes molecular dynamics simulations to generate configurations of excited states that are consistent with available biophysical and biochemical measurements. To demonstrate the approach, we present a sequence of configurations that are suggested to be associated with transfer RNA (tRNA) movement through the ribosome (translocation). The models were constructed by combining information from X-ray crystallography, cryo-electron microscopy, and biochemical data. These models provide a structural framework for translocation that may be further investigated experimentally and theoretically to determine the precise energetic character of each configuration and the transition dynamics between them. PMID:22080606

  19. Molecular aspect ratio and anchoring strength effects in a confined Gay-Berne liquid crystal

    NASA Astrophysics Data System (ADS)

    Cañeda-Guzmán, E.; Moreno-Razo, J. A.; Díaz-Herrera, E.; Sambriski, E. J.

    2014-04-01

    Phase diagrams for Gay-Berne (GB) fluids were obtained from molecular dynamics simulations for GB(2, 5, 1, 2) (i.e. short mesogens) and GB(3, 5, 1, 2) (i.e. long mesogens), which yield isotropic, nematic, and smectic-B phases. The long-mesogen fluid also yields the smectic-A phase. Ordered phases of the long-mesogen fluid form at higher temperatures and lower densities when compared to those of the short-mesogen fluid. The effect of confinement under weak and strong substrate couplings in slab geometry was investigated. Compared to the bulk, the isotropic-nematic transition does not shift in temprature significantly for the weakly coupled substrate in either mesogen fluid. However, the strongly coupled substrate shifts the transition to lower temperature. Confinement induces marked stratification in the short-mesogen fluid. This effect diminishes with distance from the substrate, yielding bulk-like behaviour in the slab central region. Fluid stratification is very weak for the long-mesogen fluid, but the strongly coupled substrate induces 'smectisation', an ordering effect that decays with distance. Orientation of the fluid on the substrate depends on the mesogen. There is no preferred orientation in a plane parallel to the substrate for the weakly coupled case. In the strongly coupled case, the mesogen orientation mimics that of adjacent fluid layers. Planar anchoring is observed with a broad distribution of orientations in the weakly coupled case. In the strongly coupled case, the distribution leans toward planar orientations for the short-mesogen fluid, while a marginal preference for tilting persists in the long-mesogen fluid.

  20. Integration of molecular pathology, epidemiology and social science for global precision medicine.

    PubMed

    Nishi, Akihiro; Milner, Danny A; Giovannucci, Edward L; Nishihara, Reiko; Tan, Andy S; Kawachi, Ichiro; Ogino, Shuji

    2016-01-01

    The precision medicine concept and the unique disease principle imply that each patient has unique pathogenic processes resulting from heterogeneous cellular genetic and epigenetic alterations and interactions between cells (including immune cells) and exposures, including dietary, environmental, microbial and lifestyle factors. As a core method field in population health science and medicine, epidemiology is a growing scientific discipline that can analyze disease risk factors and develop statistical methodologies to maximize utilization of big data on populations and disease pathology. The evolving transdisciplinary field of molecular pathological epidemiology (MPE) can advance biomedical and health research by linking exposures to molecular pathologic signatures, enhancing causal inference and identifying potential biomarkers for clinical impact. The MPE approach can be applied to any diseases, although it has been most commonly used in neoplastic diseases (including breast, lung and colorectal cancers) because of availability of various molecular diagnostic tests. However, use of state-of-the-art genomic, epigenomic and other omic technologies and expensive drugs in modern healthcare systems increases racial, ethnic and socioeconomic disparities. To address this, we propose to integrate molecular pathology, epidemiology and social science. Social epidemiology integrates the latter two fields. The integrative social MPE model can embrace sociology, economics and precision medicine, address global health disparities and inequalities, and elucidate biological effects of social environments, behaviors and networks. We foresee advancements of molecular medicine, including molecular diagnostics, biomedical imaging and targeted therapeutics, which should benefit individuals in a global population, by means of an interdisciplinary approach of integrative MPE and social health science. PMID:26636627

  1. Variational path integral molecular dynamics and hybrid Monte Carlo algorithms using a fourth order propagator with applications to molecular systems.

    PubMed

    Kamibayashi, Yuki; Miura, Shinichi

    2016-08-21

    In the present study, variational path integral molecular dynamics and associated hybrid Monte Carlo (HMC) methods have been developed on the basis of a fourth order approximation of a density operator. To reveal various parameter dependence of physical quantities, we analytically solve one dimensional harmonic oscillators by the variational path integral; as a byproduct, we obtain the analytical expression of the discretized density matrix using the fourth order approximation for the oscillators. Then, we apply our methods to realistic systems like a water molecule and a para-hydrogen cluster. In the HMC, we adopt two level description to avoid the time consuming Hessian evaluation. For the systems examined in this paper, the HMC method is found to be about three times more efficient than the molecular dynamics method if appropriate HMC parameters are adopted; the advantage of the HMC method is suggested to be more evident for systems described by many body interaction. PMID:27544094

  2. Integrating genomics, proteomics and bioinformatics in translational studies of molecular medicine.

    PubMed

    Ostrowski, Jerzy; Wyrwicz, Lucjan S

    2009-09-01

    Understanding the molecular mechanisms of disease requires the introduction of molecular diagnostics into medical practice. Current medicine employs only elements of molecular diagnostics, which are usually applied on the scale of single genes. Medicine in the postgenomic era will utilize thousands of disease-associated molecular markers provided by high-throughput sequencing and functional genomic, proteomic and metabolomic studies. Such a spectrum of techniques will link clinical medicine based on molecularly oriented diagnostics with the prediction and prevention of disease. To achieve this task, large-scale and genome-wide biological and medical data must be combined with biostatistical and bioinformatic analyses to model biological systems. Collecting, cataloging and comparing data from molecular studies, and the subsequent development of conclusions, creates the fundamentals of systems biology. This highly complex analytical process reflects a new scientific paradigm known as integrative genomics. PMID:19732006

  3. Integrative genomics--a basic and essential tool for the development of molecular medicine.

    PubMed

    Ostrowski, Jerzy

    2008-01-01

    Understanding the molecular mechanisms of disease requires the introduction of molecular diagnostics into medical practice. Current medicine employs only elements of molecular diagnostics, and usually on the scale of single genes. Medicine in the post-genomic era will utilize thousands of molecular markers associated with disease that are provided by high-throughput sequencing and functional genomic, proteomic and metabolomic studies. Such a spectrum of techniques will link clinical medicine based on molecularly oriented diagnostics with the prediction and prevention of disease. To achieve this task, large-scale and genome-wide biological and medical data must be combined with biostatistical analyses and bioinformatic modeling of biological systems. The collecting, cataloging and comparison of data from molecular studies and the subsequent development of conclusions create the fundamentals of systems biology. This highly complex analytical process reflects a new scientific paradigm called integrative genomics. PMID:19172842

  4. Simple DFT-LSDA modeling of the molecular-like aspects of ultra-thin film properties

    SciTech Connect

    Trickey, S.B.; Mathar, R.J.; Boettger, J.C.

    1996-09-01

    Ordered ultra-thin films (UTF`s) are atomic n-layers (n = 1,2,3,...) with translational symmetry in-plane and molecular-like inter-planar spacings. Though commonly used (especially at relatively large n-values) as models of crystalline surfaces, they are intrinsically interesting and of growing technological significance as the basic building blocks of multi-layer electronic devices. Predicting the structure and properties of even a simple diatomic 1-layer means addressing aspects of molecular binding (and boundary conditions) in the context of an extended, periodically bounded system. At the level of refinement provided by the local spin density approximation to Density Functional Theory, the baseline standard of today`s predictive, chemically specific solid-state calculations, a number of technical and fundamental issues arise. The authors focus on treatment of the isolated atoms, on basis sets, and on numerical precision, as illustrated by the Fe atom and BN 1- and 2-layer calculations. Computational requirements are illustrated by a brief summary of recently completed calculations on crystalline sapphire, {alpha}-Al{sub 2}O{sub 3}, which used the same code.

  5. Balancing an accurate representation of the molecular surface in generalized born formalisms with integrator stability in molecular dynamics simulations.

    PubMed

    Chocholousová, Jana; Feig, Michael

    2006-04-30

    Different integrator time steps in NVT and NVE simulations of protein and nucleic acid systems are tested with the GBMV (Generalized Born using Molecular Volume) and GBSW (Generalized Born with simple SWitching) methods. The simulation stability and energy conservation is investigated in relation to the agreement with the Poisson theory. It is found that very close agreement between generalized Born methods and the Poisson theory based on the commonly used sharp molecular surface definition results in energy drift and simulation artifacts in molecular dynamics simulation protocols with standard 2-fs time steps. New parameters are proposed for the GBMV method, which maintains very good agreement with the Poisson theory while providing energy conservation and stable simulations at time steps of 1 to 1.5 fs. PMID:16518883

  6. Impulsivity and Concussion in Juvenile Rats: Examining Molecular and Structural Aspects of the Frontostriatal Pathway

    PubMed Central

    Hehar, Harleen; Yeates, Keith; Kolb, Bryan; Esser, Michael J.; Mychasiuk, Richelle

    2015-01-01

    the need to tailor treatment strategies for mTBI in light of an individual’s premorbid characteristics, given significant differences in molecular profiles of the frontostriatal circuits that depend upon sex and the etiology of the behavioural phenotype. PMID:26448536

  7. Hb H disease with various β hemoglobinopathies: molecular, hematological and diagnostic aspects.

    PubMed

    Fucharoen, Supan; Fucharoen, Goonnapa

    2012-01-01

    We report the molecular, hematological and diagnostic features of three Thai patients with Hb H (β4) disease in combination with different β hemoglobinopathies. The first case was a boy with a hitherto undescribed condition of Hb H-Hb Tak (HBB:c.441_442insAC) syndrome. The second case was an adult male with the Hb H-Hb Hope (HBB:c.410G>A) disease. The last case was a male patient with a combination of Hb H-Hb Constant Spring (Hb CS) (HBA2:c.427T>C) and a high Hbs A(2)/F β(0)-thalassemia (β-thal) trait (the 3.4 kb deletion). In all cases, no Hb H was detected and Hb H inclusion was absent, accurate diagnosis could be obtained after DNA analysis. All of them had mild hypochromic microcytic anemia with hemoglobin (Hb) values ranging from 8.8-10.4 g/dL, PCV 0.31-0.36 L/L and MCV 57.6-66.9 fL and none had ever received a blood transfusion. The levels of Hb Tak (7.8%) and Hb Hope (21.6%), respectively, observed in the first two cases were relatively lower than values found in heterozygotes for these two variants. In the last case, the level of Hb A(2) (4.8%) was within the diagnostic range for a β-thal trait. The Hb F level was not elevated but a small amount of Hb Bart's was observed. Hematological findings and diagnostics using combined Hb and polymerase chain reaction (PCR) analyses are presented and compared with those of the other Thai patients with Hb H-β(0)-thal, Hb H-Hb CS-Hb J-Bangkok (HBB:c.170G>A) and Hb H-Hb CS-Hb Pyrgos (HBB:c.251G>A) previously observed in our series. PMID:22145566

  8. Critical issues of complex, epitaxial oxide growth and integration with silicon by molecular beam epitaxy

    NASA Astrophysics Data System (ADS)

    Lettieri, James

    Molecular beam epitaxy was used to grow epitaxial oxides on silicon substrates. The growth of BaO, SrO, EuO, and SrTiO3 are discussed with a focus on the general theme of integration of functional, epitaxial oxides into a silicon environment. Oxidation studies of various metal systems relevant for oxide on silicon epitaxy and integration are reported. Results demonstrate the catalytic nature of an alkaline earth metal at small concentrations to enable the oxidation of the poorly oxidizing metals at pressures lower than during deposition of the pure metal alone. Results from the deposition of various elements are presented. The aspects of the growth of alkaline earth oxides on silicon are explained. The transition from the silicon to the alkaline earth oxide as described through reflection high energy electron diffraction (RHEED) is presented and used to understand issues related to each stage of the growth. High quality, commensurate alkaline earth oxides are grown on silicon at room temperature and P O2 background ˜ 3 x 10-8 Torr. The growth of alkaline earth and rare earth oxide solid solutions and rare earth oxides (EuO) are described. The first reported epitaxial EuO on silicon is reported, enabled by the use of a thin buffer layer (13 A) of SrO. Using a strategy of transition from simple structures to the more complex, the growth of a perovskite (SrTiO3) on silicon is demonstrated. Growth of a structurally optimized perovskite structure entails the transformation of a thin interfacial alkaline earth oxide layer into the initial perovskite cells. SrTiO3 and La-doped SrTiO3 on silicon are used to integrate a piezoelectric relevant for microelectromechanical systems (MEMS) applications and a ferroelectric relevant for a ferroelectric random access memory (FRAM) architecture. A d33 value of over 400 pm/V under bias is measured for the piezoelectric (Pb(Mn1/3Nb 2/3)O3 -PbTiO3) and a remanent polarization of 25 muC/cm2 and fatigue free behavior (>1012 cycles) for a

  9. The Integration of Pedagogical Aspects in Environmental Management Systems in Selected South African Primary Schools

    ERIC Educational Resources Information Center

    Kanyimba, Alex; Richter, Barry; Raath, Schalk

    2015-01-01

    Environmental management systems implemented in schools are regarded by many as a mechanism for the integration of environmental matters in all the operational functions of the school. The links, however, between environmental management and curriculum practice have not been adequately addressed in the literature. This article reports on the…

  10. WebQuests: An Aspect of Technology Integration for Training Preservice Teachers.

    ERIC Educational Resources Information Center

    Summerville, Jennifer

    2000-01-01

    Explains WebQuests, Internet-based lessons that integrate technology into the classrooms without the risks of exposing students to inappropriate Web sites. Examples are given of WebQuests that students created in various grade levels, as well as an assignment for teacher education students to design a WebQuest. (LRW)

  11. Quantifying biopsychosocial aspects in everyday contexts: an integrative methodological approach from the behavioral sciences

    PubMed Central

    Portell, Mariona; Anguera, M Teresa; Hernández-Mendo, Antonio; Jonsson, Gudberg K

    2015-01-01

    Contextual factors are crucial for evaluative research in psychology, as they provide insights into what works, for whom, in what circumstances, in what respects, and why. Studying behavior in context, however, poses numerous methodological challenges. Although a comprehensive framework for classifying methods seeking to quantify biopsychosocial aspects in everyday contexts was recently proposed, this framework does not contemplate contributions from observational methodology. The aim of this paper is to justify and propose a more general framework that includes observational methodology approaches. Our analysis is rooted in two general concepts: ecological validity and methodological complementarity. We performed a narrative review of the literature on research methods and techniques for studying daily life and describe their shared properties and requirements (collection of data in real time, on repeated occasions, and in natural settings) and classification criteria (eg, variables of interest and level of participant involvement in the data collection process). We provide several examples that illustrate why, despite their higher costs, studies of behavior and experience in everyday contexts offer insights that complement findings provided by other methodological approaches. We urge that observational methodology be included in classifications of research methods and techniques for studying everyday behavior and advocate a renewed commitment to prioritizing ecological validity in behavioral research seeking to quantify biopsychosocial aspects. PMID:26089708

  12. Eco-innovative design approach: Integrating quality and environmental aspects in prioritizing and solving engineering problems

    NASA Astrophysics Data System (ADS)

    Chakroun, Mahmoud; Gogu, Grigore; Pacaud, Thomas; Thirion, François

    2014-09-01

    This study proposes an eco-innovative design process taking into consideration quality and environmental aspects in prioritizing and solving technical engineering problems. This approach provides a synergy between the Life Cycle Assessment (LCA), the nonquality matrix, the Theory of Inventive Problem Solving (TRIZ), morphological analysis and the Analytical Hierarchy Process (AHP). In the sequence of these tools, LCA assesses the environmental impacts generated by the system. Then, for a better consideration of environmental aspects, a new tool is developed, the non-quality matrix, which defines the problem to be solved first from an environmental point of view. The TRIZ method allows the generation of new concepts and contradiction resolution. Then, the morphological analysis offers the possibility of extending the search space of solutions in a design problem in a systematic way. Finally, the AHP identifies the promising solution(s) by providing a clear logic for the choice made. Their usefulness has been demonstrated through their application to a case study involving a centrifugal spreader with spinning discs.

  13. Mechanistic and clinical aspects of fatigue of ultrahigh molecular weight polyethylene

    NASA Astrophysics Data System (ADS)

    Furmanski, Jevan

    Ultrahigh molecular weight polyethylene (UHMWPE) is a tough semi-crystalline polymer employed widely as a bearing material in total joint replacements. While UHMWPE has been tremendously successful in this application, debris generated due to frictional contact may lead ultimately to an adverse biological reaction and failure of the implant. Radiation cross-linking of the polymer has been undertaken in order to improve its wear resistance, but this also reduces its strength, toughness, and ductility. The majority of implants using highly cross-linked UHMWPE seem to be functioning as designed, but a number of recent reports detail unexpected apparently brittle surface cracking and fracture of such devices. The work presented in this dissertation first documents and analyzes two series of clinical failures of total hip replacements employing highly cross-linked UHMWPE. In the first failure study, an implant was removed shortly after implantation due to infection, and the surface of the implant had sustained extensive surface cracking. An analysis showed that the femoral head contained an asphericity in the main weight bearing region, and a finite element analysis concluded that such a defect doubles the peak contact pressure in the bearing. The increased pressure and decreased toughness were then inferred to have cooperatively resulted in the observed surface cracking. A series of four catastrophically fractured UHMWPE total hip replacement bearings was also analyzed. In all cases, cracks initiated at a sharp notch in the periphery of the implant and propagated into the bulk. Finite element analysis predicted that these locations experienced maximal values of principal stress, and that the stress was of a magnitude and orientation appropriate to agree with the observed crack initiation. The brittle nature of fatigue crack propagation (FCP) in UHMWPE was then explored from a fundamental perspective, with special attention paid to the static mode nature of the process

  14. Integrability aspects and soliton solutions for the inhomogeneous reduced Maxwell-Bloch system in nonlinear optics with symbolic computation

    NASA Astrophysics Data System (ADS)

    Hao, Hui-Qin; Zhang, Jian-Wen

    2015-05-01

    In this paper, we investigate the inhomogeneous reduced Maxwell-Bloch system, which describes the propagation of the intense ultra-short optical pulses through an inhomogeneous two-level dielectric medium. Through symbolic computation, the integrability aspects including the Painlevé integrable condition, Lax pair and infinite conservation laws are derived. By virtue of the Darboux transformation method, one- and two-soliton solutions are generated on the nonvanishing background, including the bright solitons, dark solitons, periodic solutions and some two-soliton solutions. The asymptotic analysis method is performed to verify the elastic interaction between two solitons. Furthermore, by virtue of some figures, the dynamic properties of those solitons are discussed. The results may be useful in the study of the ultrashort pulses propagation in such situations as the model of the two-level dielectric media.

  15. Integrative molecular characterization of head and neck cancer cell model genomes

    PubMed Central

    Tsui, Ivy F.L.; Garnis, Cathie

    2010-01-01

    Background Cell lines are invaluable model systems for the investigation of cancer. Knowledge of the molecular alterations that exist within cell models is required to define the mechanisms governing cellular phenotypes. Methods Five tongue squamous cell carcinomas cell lines and one submaxillary salivary gland epidermoid carcinoma cell line were analyzed for copy number and mRNA expression by tiling-path DNA microarrays and Agilent Whole Human Genome Oligoarrays, respectively. Results Integrative analysis of genetic and expression alterations revealed the molecular landscape of each cell line. Molecular results for individual cell lines and across all samples have been summarized and made available for easy reference. Conclusion Our integrative genomic analyses have defined the DNA and RNA alterations for each individual line. These data will be useful to anyone modelling oral cancer behaviour, providing a molecular context that will be useful for deciphering cell phenotypes. PMID:20014447

  16. Molecular clock integration of brown adipose tissue formation and function.

    PubMed

    Nam, Deokhwa; Yechoor, Vijay K; Ma, Ke

    2016-01-01

    The circadian clock is an essential time-keeping mechanism that entrains internal physiology to environmental cues. Despite the well-established link between the molecular clock and metabolic homeostasis, an intimate interplay between the clock machinery and the metabolically active brown adipose tissue (BAT) is only emerging. Recently, we came to appreciate that the formation and metabolic functions of BAT, a key organ for body temperature maintenance, are under an orchestrated circadian clock regulation. Two complementary studies from our group uncover that the cell-intrinsic clock machinery exerts concerted control of brown adipogenesis with consequent impacts on adaptive thermogenesis, which adds a previously unappreciated temporal dimension to the regulatory mechanisms governing BAT development and function. The essential clock transcriptional activator, Bmal1, suppresses adipocyte lineage commitment and differentiation, whereas the clock repressor, Rev-erbα, promotes these processes. This newly discovered temporal mechanism in fine-tuning BAT thermogenic capacity may enable energy utilization and body temperature regulation in accordance with external timing signals during development and functional recruitment. Given the important role of BAT in whole-body metabolic homeostasis, pharmacological interventions targeting the BAT-modulatory activities of the clock circuit may offer new avenues for the prevention and treatment of metabolic disorders, particularly those associated with circadian dysregulation. PMID:27385482

  17. Molecular clock integration of brown adipose tissue formation and function

    PubMed Central

    Nam, Deokhwa; Yechoor, Vijay K.; Ma, Ke

    2016-01-01

    Abstract The circadian clock is an essential time-keeping mechanism that entrains internal physiology to environmental cues. Despite the well-established link between the molecular clock and metabolic homeostasis, an intimate interplay between the clock machinery and the metabolically active brown adipose tissue (BAT) is only emerging. Recently, we came to appreciate that the formation and metabolic functions of BAT, a key organ for body temperature maintenance, are under an orchestrated circadian clock regulation. Two complementary studies from our group uncover that the cell-intrinsic clock machinery exerts concerted control of brown adipogenesis with consequent impacts on adaptive thermogenesis, which adds a previously unappreciated temporal dimension to the regulatory mechanisms governing BAT development and function. The essential clock transcriptional activator, Bmal1, suppresses adipocyte lineage commitment and differentiation, whereas the clock repressor, Rev-erbα, promotes these processes. This newly discovered temporal mechanism in fine-tuning BAT thermogenic capacity may enable energy utilization and body temperature regulation in accordance with external timing signals during development and functional recruitment. Given the important role of BAT in whole-body metabolic homeostasis, pharmacological interventions targeting the BAT-modulatory activities of the clock circuit may offer new avenues for the prevention and treatment of metabolic disorders, particularly those associated with circadian dysregulation. PMID:27385482

  18. Dynamic aspects of voluntary turnover: an integrated approach to curvilinearity in the performance-turnover relationship.

    PubMed

    Becker, William J; Cropanzano, Russell

    2011-03-01

    Previous research pertaining to job performance and voluntary turnover has been guided by 2 distinct theoretical perspectives. First, the push-pull model proposes that there is a quadratic or curvilinear relationship existing between these 2 variables. Second, the unfolding model of turnover posits that turnover is a dynamic process and that a downward performance change may increase the likelihood of organizational separation. Drawing on decision theory, we propose and test an integrative framework. This approach incorporates both of these earlier models. Specifically, we argue that individuals are most likely to voluntarily exit when they are below-average performers who are also experiencing a downward performance change. Furthermore, the interaction between this downward change and performance partially accounts for the curvilinear relationship proposed by the push-pull model. Findings from a longitudinal field study supported this integrative theory. PMID:20853945

  19. Integrating molecular dynamics simulations with chemical probing experiments using SHAPE-FIT.

    PubMed

    Kirmizialtin, Serdal; Hennelly, Scott P; Schug, Alexander; Onuchic, Jose N; Sanbonmatsu, Karissa Y

    2015-01-01

    Integration and calibration of molecular dynamics simulations with experimental data remain a challenging endeavor. We have developed a novel method to integrate chemical probing experiments with molecular simulations of RNA molecules by using a native structure-based model. Selective 2'-hydroxyl acylation by primer extension (SHAPE) characterizes the mobility of each residue in the RNA. Our method, SHAPE-FIT, automatically optimizes the potential parameters of the force field according to measured reactivities from SHAPE. The optimized parameter set allows simulations of dynamics highly consistent with SHAPE probing experiments. Such atomistic simulations, thoroughly grounded in experiment, can open a new window on RNA structure-function relations. PMID:25726467

  20. Integrating molecular dynamics simulations with chemical probing experiments using SHAPE-FIT

    PubMed Central

    Kirmizialtin, Serdal; Hennelly, Scott P.; Schug, Alexander; Onuchic, Jose N.; Sanbonmatsu, Karissa Y.

    2016-01-01

    Integration and calibration of molecular dynamics simulations with experimental data remains a challenging endeavor. We have developed a novel method to integrate chemical probing experiments with molecular simulations of RNA molecules by using a native structure-based model. Selective 2’-hydroxyl acylation by primer extension (SHAPE) characterizes the mobility of each residue in the RNA. Our method, SHAPE-FIT, automatically optimizes the potential parameters of the forcefield according to measured reactivities from SHAPE. The optimized parameter set allows simulations of dynamics highly consistent with SHAPE probing experiments. Such atomistic simulations, thoroughly grounded in experiment, can open a new window on RNA structure-function relations. PMID:25726467

  1. Integrated molecular mechanism directing nucleosome reorganization by human FACT

    PubMed Central

    Tsunaka, Yasuo; Fujiwara, Yoshie; Oyama, Takuji; Hirose, Susumu; Morikawa, Kosuke

    2016-01-01

    Facilitates chromatin transcription (FACT) plays essential roles in chromatin remodeling during DNA transcription, replication, and repair. Our structural and biochemical studies of human FACT–histone interactions present precise views of nucleosome reorganization, conducted by the FACT-SPT16 (suppressor of Ty 16) Mid domain and its adjacent acidic AID segment. AID accesses the H2B N-terminal basic region exposed by partial unwrapping of the nucleosomal DNA, thereby triggering the invasion of FACT into the nucleosome. The crystal structure of the Mid domain complexed with an H3–H4 tetramer exhibits two separate contact sites; the Mid domain forms a novel intermolecular β structure with H4. At the other site, the Mid–H2A steric collision on the H2A-docking surface of the H3–H4 tetramer within the nucleosome induces H2A–H2B displacement. This integrated mechanism results in disrupting the H3 αN helix, which is essential for retaining the nucleosomal DNA ends, and hence facilitates DNA stripping from histone. PMID:26966247

  2. Integrated molecular mechanism directing nucleosome reorganization by human FACT.

    PubMed

    Tsunaka, Yasuo; Fujiwara, Yoshie; Oyama, Takuji; Hirose, Susumu; Morikawa, Kosuke

    2016-03-15

    Facilitates chromatin transcription (FACT) plays essential roles in chromatin remodeling during DNA transcription, replication, and repair. Our structural and biochemical studies of human FACT-histone interactions present precise views of nucleosome reorganization, conducted by the FACT-SPT16 (suppressor of Ty 16) Mid domain and its adjacent acidic AID segment. AID accesses the H2B N-terminal basic region exposed by partial unwrapping of the nucleosomal DNA, thereby triggering the invasion of FACT into the nucleosome. The crystal structure of the Mid domain complexed with an H3-H4 tetramer exhibits two separate contact sites; the Mid domain forms a novel intermolecular β structure with H4. At the other site, the Mid-H2A steric collision on the H2A-docking surface of the H3-H4 tetramer within the nucleosome induces H2A-H2B displacement. This integrated mechanism results in disrupting the H3 αN helix, which is essential for retaining the nucleosomal DNA ends, and hence facilitates DNA stripping from histone. PMID:26966247

  3. Integrative systems medicine approaches to identify molecular targets in lymphoid malignancies.

    PubMed

    Frazzi, Raffaele; Auffray, Charles; Ferrari, Angela; Filippini, Perla; Rutella, Sergio; Cesario, Alfredo

    2016-01-01

    Although survival rates for lymphoproliferative disorders are steadily increasing both in the US and in Europe, there is need for optimizing front-line therapies and developing more effective salvage strategies. Recent advances in molecular genetics have highlighted the biological diversity of lymphoproliferative disorders. In particular, integrative approaches including whole genome sequencing, whole exome sequencing, and transcriptome or RNA sequencing have been instrumental to the identification of molecular targets for treatment. Herein, we will discuss how genomic, epigenomic and proteomic approaches in lymphoproliferative disorders have supported the discovery of molecular lesions and their therapeutic targeting in the clinic. PMID:27580852

  4. Molecular Characterization and Biochemical and Histopathological Aspects of the Parasitism of Haemoproteus spp. in Southern Caracaras (Caracara plancus).

    PubMed

    Tostes, Raquel; Martinele, Isabel; Vashist, Usha; Castañon, Maria C M N; Pinto, Priscila de Faria; Daemon, Erik; D'Agosto, Marta

    2015-12-01

    Haemoproteid species have a wide global distribution, and they have been described in falcon species in several parts of the world. However, few studies in South America have focused on these birds. Haemoproteus spp. infections have been reported as the causative agents of serious histopathological changes, which can lead to the death of the host. Thus, this study aimed to molecularly and phylogenetically characterize Haemoproteus spp. in Caracara plancus, to characterize aspects of parasitism through clinical analysis and biochemical parameters, and to describe the histopathology of infection. To examine these aspects, 5 southern caracaras were examined clinically, and blood samples were collected. Blood smears were subsequently utilized in parasitemia calculations, PCR amplification, and serum biochemical investigations. Histological sections of the liver, kidneys, spleen, and heart were examined to check for possible histopathological changes. The birds showed clinical signs such as pallor and prostration that are consistent with Haemoproteus spp. infection. Moreover, the examination of the blood smears revealed 0.07% parasitemia in young gametocytes only. The PCR and sequencing results confirmed that the parasites belonged to Haemoproteus spp. The activity of aspartate aminotransferase (AST) and alanine aminotransferase (ALT) enzymes, albumin, total serum proteins, and enzymatic urea were first described in C. plancus and serve as reference for future studies of bird species parasitized by Haemoproteus spp. Histopathology results showed signs of injury that were consistent with haemosporidian infection in the tissues of the analyzed organs. The present study is preliminary, and additional studies of Haemoproteus spp. infections in other bird species are needed to better understand the relationship between parasites and hosts, because despite the low parasitemia recorded, biochemical and histopathological changes in various organs were observed. PMID:26200719

  5. Computational and numerical aspects of using the integral equation method for adhesive layer fracture mechanics analysis

    SciTech Connect

    Giurgiutiu, V.; Ionita, A.; Dillard, D.A.; Graffeo, J.K.

    1996-12-31

    Fracture mechanics analysis of adhesively bonded joints has attracted considerable attention in recent years. A possible approach to the analysis of adhesive layer cracks is to study a brittle adhesive between 2 elastic half-planes representing the substrates. A 2-material 3-region elasticity problem is set up and has to be solved. A modeling technique based on the work of Fleck, Hutchinson, and Suo is used. Two complex potential problems using Muskelishvili`s formulation are set up for the 3-region, 2-material model: (a) a distribution of edge dislocations is employed to simulate the crack and its near field; and (b) a crack-free problem is used to simulate the effect of the external loading applied in the far field. Superposition of the two problems is followed by matching tractions and displacements at the bimaterial boundaries. The Cauchy principal value integral is used to treat the singularities. Imposing the traction-free boundary conditions over the entire crack length yielded a linear system of two integral equations. The parameters of the problem are Dundurs` elastic mismatch coefficients, {alpha} and {beta}, and the ratio c/H representing the geometric position of the crack in the adhesive layer.

  6. Some Aspects of Satellite Imagery Integration from Eros B and Landsat 8

    NASA Astrophysics Data System (ADS)

    Fryskowska, A.; Wojtkowska, M.; Delis, P.; Grochala, A.

    2016-06-01

    The Landsat 8 satellite which was launched in 2013 is a next generation of the Landsat remote sensing satellites series. It is equipped with two new sensors: the Operational Land Imager (OLI) and the Thermal Infrared Sensor (TIRS). What distinguishes this satellite from the previous is four new bands (coastal aerosol, cirrus and two thermal infrared TIRS bands). Similar to its antecedent, Landsat 8 records electromagnetic radiation in a panchromatic band at a range of 0.5‐0.9 μm with a spatial resolution equal to 15 m. In the paper, multispectral imagery integration capabilities of Landsat 8 with data from the new high resolution panchromatic EROS B satellite are analyzed. The range of panchromatic band for EROS B is 0.4‐0.9 μm and spatial resolution is 0.7 m. Research relied on improving the spatial resolution of natural color band combinations (bands: 4,3,2) and of desired false color band composition of Landsat 8 satellite imagery. For this purpose, six algorithms have been tested: Brovey's, Mulitplicative, PCA, IHS, Ehler's, HPF. On the basis of the visual assessment, it was concluded that the best results of multispectral and panchromatic image integration, regardless land cover, are obtained for the multiplicative method. These conclusions were confirmed by statistical analysis using correlation coefficient, ERGAS and R-RMSE indicators.

  7. Updating the Mitochondrial Free Radical Theory of Aging: An Integrated View, Key Aspects, and Confounding Concepts

    PubMed Central

    2013-01-01

    Abstract An updated version of the mitochondrial free radical theory of aging (MFRTA) and longevity is reviewed. Key aspects of the theory are emphasized. Another main focus concerns common misconceptions that can mislead investigators from other specialties, even to wrongly discard the theory. Those different issues include (i) the main reactive oxygen species (ROS)-generating site in the respiratory chain in relation to aging and longevity: complex I; (ii) the close vicinity or even contact between that site and the mitochondrial DNA, in relation to the lack of local efficacy of antioxidants and to sub-cellular compartmentation; (iii) the relationship between mitochondrial ROS production and oxygen consumption; (iv) recent criticisms on the MFRTA; (v) the widespread assumption that ROS are simple “by-products” of the mitochondrial respiratory chain; (vi) the unnecessary postulation of “vicious cycle” hypotheses of mitochondrial ROS generation which are not central to the free radical theory of aging; and (vii) the role of DNA repair concerning endogenous versus exogenous damage. After considering the large body of data already available, two general characteristics responsible for the high maintenance degree of long-lived animals emerge: (i) a low generation rate of endogenous damage: and (ii) the possession of tissue macromolecules that are highly resistant to oxidative modification. Antioxid. Redox Signal. 19, 1420–1445. PMID:23642158

  8. A unified scheme for the calculation of differentiated and undifferentiated molecular integrals over solid-harmonic Gaussians.

    PubMed

    Reine, Simen; Tellgren, Erik; Helgaker, Trygve

    2007-09-14

    Utilizing the fact that solid-harmonic combinations of Cartesian and Hermite Gaussian atomic orbitals are identical, a new scheme for the evaluation of molecular integrals over solid-harmonic atomic orbitals is presented, where the integration is carried out over Hermite rather than Cartesian atomic orbitals. Since Hermite Gaussians are defined as derivatives of spherical Gaussians, the corresponding molecular integrals become the derivatives of integrals over spherical Gaussians, whose transformation to the solid-harmonic basis is performed in the same manner as for integrals over Cartesian Gaussians, using the same expansion coefficients. The presented solid-harmonic Hermite scheme simplifies the evaluation of derivative molecular integrals, since differentiation by nuclear coordinates merely increments the Hermite quantum numbers, thereby providing a unified scheme for undifferentiated and differentiated four-center molecular integrals. For two- and three-center two-electron integrals, the solid-harmonic Hermite scheme is particularly efficient, significantly reducing the cost relative to the Cartesian scheme. PMID:17712455

  9. IVSPlat 1.0: an integrated virtual screening platform with a molecular graphical interface

    PubMed Central

    2012-01-01

    Background The virtual screening (VS) of lead compounds using molecular docking and pharmacophore detection is now an important tool in drug discovery. VS tasks typically require a combination of several software tools and a molecular graphics system. Thus, the integration of all the requisite tools in a single operating environment could reduce the complexity of running VS experiments. However, only a few freely available integrated software platforms have been developed. Results A free open-source platform, IVSPlat 1.0, was developed in this study for the management and automation of VS tasks. We integrated several VS-related programs into a molecular graphics system to provide a comprehensive platform for the solution of VS tasks based on molecular docking, pharmacophore detection, and a combination of both methods. This tool can be used to visualize intermediate and final results of the VS execution, while also providing a clustering tool for the analysis of VS results. A case study was conducted to demonstrate the applicability of this platform. Conclusions IVSPlat 1.0 provides a plug-in-based solution for the management, automation, and visualization of VS tasks. IVSPlat 1.0 is an open framework that allows the integration of extra software to extend its functionality and modified versions can be freely distributed. The open source code and documentation are available at http://kyc.nenu.edu.cn/IVSPlat/. PMID:22222098

  10. Conducting Polymer Nanostructures and Nanocomposites with Carbon Nanotubes: Hierarchical Assembly by Molecular Electrochemistry, Growth Aspects and Property Characterization.

    PubMed

    Gupta, Sanju; Price, Carson; Heintzman, Eli

    2016-01-01

    Conducting (or π-conjugated) polymers are promising materials for preparing supramolecular nano-structures and nanocomposites. We report controlled nanostructure syntheses of polypyrrole (PPy) and poylaniline (PANi) via electropolymerization (i.e., in-situ electrochemical anodic oxidation). The density, shape, caliber and thickness of self-assembled PPy micro-containers are regulated by electrochemical potential window for H2 bubbles and number of cyclic voltammetric (potentiodynamic) scans. Likewise, we employed amperometry, chronopotentiometry and potentiodynamic modes using hydrochloric acid as oxidizing agent to prepare PANi nanoparticles and nanotubules. We present our findings from the viewpoint of molecular electrochemistry with growth kinetic aspects yielding mechanistic details (initially forming dimers and oligomers as nucleating agents followed by polymer growth). Also targeted is forming nanocomposites with functionalized single- and multi-walled carbon nanotubes (FSWCNTs and FMWCNTs) as reinforced agent to optimize structural and functional properties. All of these novel nanomaterials are characterized using a range of complementary techniques to establish microscopic structure-property-function relationship. PMID:27398466

  11. Source quality variations tied to sequence development: Integration of physical and chemical aspects, Lower to Middle Triassic, western Barents Sea

    SciTech Connect

    Bohacs, K.M.; Isaksen, G.H. )

    1991-03-01

    Triassic mudrocks from the Barents Sea area demonstrate to covariance of physical and chemical properties of mudrocks deposited in shelfal environments and the aspect of depositional sequences in distal settings. The tie of physical parameters to chemical character within a detailed sequence-stratigraphic framework enables the construction of depositional-facies models to predict organic-matter content and quality. This allows the explorer to more closely constrain and predict the nature of potential source rocks using seismic and well-log data. Changes in lithology, bedding geometry, sedimentary structures, body and trace-fossil assemblages, and inorganic, bulk-organic, and molecular geochemistry revealed the detailed depositional environments. The depositional environments stack predictably, according to their position in the depositional sequence: from aerobic lower-shoreface--offshore transition environments in lowstand systems tracts to dysaerobic-anaerobic distal open-marine-shelf environment in transgressive and early highstand systems tracts. Quantitative molecular geochemistry also revealed variations within this distal setting and strong covariance with sequence position. Input of organic matter from terrigenous higher plants dominates the lowstands whereas marine-algal organic matter is most prevalent within transgressive and highstand systems tracts. Specifically, the abundance of C{sub 30} steranes, total steranes, and moretane reflected development of the sequences.

  12. MR compatibility aspects of a silicon photomultiplier-based PET/RF insert with integrated digitisation.

    PubMed

    Weissler, Bjoern; Gebhardt, Pierre; Lerche, Christoph W; Wehner, Jakob; Solf, Torsten; Goldschmidt, Benjamin; Mackewn, Jane E; Marsden, Paul K; Kiessling, Fabian; Perkuhn, Michael; Heberling, Dirk; Schulz, Volkmar

    2014-09-01

    The combination of Positron Emission Tomography (PET) and Magnetic Resonance Imaging (MRI) into a single device is being considered a promising tool for molecular imaging as it combines the high sensitivity of PET with the functional and anatomical images of MRI. For highest performance, a scalable, MR compatible detector architecture with a small form factor is needed, targeting at excellent PET signal-to-noise ratios and time-of-flight information. Therefore it is desirable to use silicon photo multipliers and to digitize their signals directly in the detector modules inside the MRI bore. A preclinical PET/RF insert for clinical MRI scanner was built to demonstrate a new architecture and to study the interactions between the two modalities.The disturbance of the MRI's static magnetic field stays below 2 ppm peak-to-peak within a diameter of 56 mm (90 mm using standard automatic volume shimming). MRI SNR is decreased by 14%, RF artefacts (dotted lines) are only visible in sequences with very low SNR. Ghosting artefacts are visible to the eye in about 26% of the EPI images, severe ghosting only in 7.6%. Eddy-current related heating effects during long EPI sequences are noticeable but with low influence of 2% on the coincidences count rate. The time resolution of 2.5 ns, the energy resolution of 29.7% and the volumetric spatial resolution of 1.8 mm(3) in the PET isocentre stay unaffected during MRI operation. Phantom studies show no signs of other artefacts or distortion in both modalities. A living rat was simultaneously imaged after the injection with (18)F-Fluorodeoxyglucose (FDG) proving the in vivo capabilities of the system. PMID:25122591

  13. Behavioral aspects of clinical trials. An integrated framework from behavior theory.

    PubMed

    Morrow, G R; Hickok, J T; Burish, T G

    1994-11-01

    A less-than-optimal proportion of patients with cancer are entered into National Cancer Institute-sponsored clinical trials. This article reviews the literature on accrual in oncology clinical trials to characterize the extent of the problem, identify reasons for low accrual, and suggest ways to promote accrual. Four well known theories of health behavior (the Health Belief Model, Subjective Expected Utility Theory, Protection Motivation Theory, and the Theory of Reasoned Action) point to central concepts involved in understanding patient health-related behavior: (1) the probability that an unwelcomed health event will happen to a patient, (2) the severity of that event if it does occur, (3) the effectiveness of a particular behavior (such as taking part in a clinical trial) to modify the severity, and (4) the cost of adopting that behavior. These concepts form a framework for integrating the available information about accrual to clinical oncology trials. Patient and physician factors previously related to clinical trials suggest specific recommendations for increasing accrual to clinical oncology trials. PMID:7954285

  14. Cognitive and Neural Aspects of Information Processing in Major Depressive Disorder: An Integrative Perspective

    PubMed Central

    Foland-Ross, Lara C.; Gotlib, Ian H.

    2012-01-01

    Researchers using experimental paradigms to examine cognitive processes have demonstrated that Major Depressive Disorder (MDD) is associated not with a general deficit in cognitive functioning, but instead with more specific anomalies in the processing of negatively valenced material. Indeed, cognitive theories of depression posit that negative biases in the processing of information play a critical role in influencing the onset, maintenance, and recurrence of depressive episodes. In this paper we review findings from behavioral studies documenting that MDD is associated with specific difficulties in attentional disengagement from negatively valenced material, with tendencies to interpret information in a negative manner, with deficits in cognitive control in the processing of negative material, and with enhanced memory for negative material. To gain a better understanding of the neurobiological basis of these abnormalities, we also examine findings from functional neuroimaging studies of depression and show that dysfunction in neural systems that subserve emotion processing, inhibition, and attention may underlie and contribute to the deficits in cognition that have been documented in depressed individuals. Finally, we briefly review evidence from studies of children who are at high familial risk for depression that indicates that abnormalities in cognition and neural function are observable before the onset of MDD and, consequently, may represent a risk factor for the development of this disorder. By integrating research from cognitive and neural investigations of depression, we can gain a more comprehensive understanding not only of how cognitive and biological factors interact to affect the onset, maintenance, and course of MDD, but also of how such research can aid in the development of targeted strategies for the prevention and treatment of this debilitating disorder. PMID:23162521

  15. Macroscopic contraction of a gel induced by the integrated motion of light-driven molecular motors

    NASA Astrophysics Data System (ADS)

    Li, Quan; Fuks, Gad; Moulin, Emilie; Maaloum, Mounir; Rawiso, Michel; Kulic, Igor; Foy, Justin T.; Giuseppone, Nicolas

    2015-02-01

    Making molecular machines that can be useful in the macroscopic world is a challenging long-term goal of nanoscience. Inspired by the protein machinery found in biological systems, and based on the theoretical understanding of the physics of motion at the nanoscale, organic chemists have developed a number of molecules that can produce work by contraction or rotation when triggered by various external chemical or physical stimuli. In particular, basic molecular switches that commute between at least two thermodynamic minima and more advanced molecular motors that behave as dissipative units working far from equilibrium when fuelled with external energy have been reported. However, despite recent progress, the ultimate challenge of coordinating individual molecular motors in a continuous mechanical process that can have a measurable effect at the macroscale has remained elusive. Here, we show that by integrating light-driven unidirectional molecular rotors as reticulating units in a polymer gel, it is possible to amplify their individual motions to achieve macroscopic contraction of the material. Our system uses the incoming light to operate under far-from-equilibrium conditions, and the work produced by the motor in the photostationary state is used to twist the entangled polymer chains up to the collapse of the gel. Our design could be a starting point to integrate nanomotors in metastable materials to store energy and eventually to convert it.

  16. The need for novel informatics tools for integrating and planning research in molecular and cellular cognition.

    PubMed

    Silva, Alcino J; Müller, Klaus-Robert

    2015-09-01

    The sheer volume and complexity of publications in the biological sciences are straining traditional approaches to research planning. Nowhere is this problem more serious than in molecular and cellular cognition, since in this neuroscience field, researchers routinely use approaches and information from a variety of areas in neuroscience and other biology fields. Additionally, the multilevel integration process characteristic of this field involves the establishment of experimental connections between molecular, electrophysiological, behavioral, and even cognitive data. This multidisciplinary integration process requires strategies and approaches that originate in several different fields, which greatly increases the complexity and demands of this process. Although causal assertions, where phenomenon A is thought to contribute or relate to B, are at the center of this integration process and key to research in biology, there are currently no tools to help scientists keep track of the increasingly more complex network of causal connections they use when making research decisions. Here, we propose the development of semiautomated graphical and interactive tools to help neuroscientists and other biologists, including those working in molecular and cellular cognition, to track, map, and weight causal evidence in research papers. There is a great need for a concerted effort by biologists, computer scientists, and funding institutions to develop maps of causal information that would aid in integration of research findings and in experiment planning. PMID:26286658

  17. Influence of platelet aspect ratio on the mechanical behaviour of bio-inspired nanocomposites using molecular dynamics.

    PubMed

    Mathiazhagan, S; Anup, S

    2016-06-01

    Superior mechanical properties of biocomposites such as nacre and bone are attributed to their basic building blocks. These basic building blocks have nanoscale features and play a major role in achieving combined stiffening, strengthening and toughening mechanisms. Bioinspired nanocomposites based on these basic building blocks, regularly and stairwise staggered arrangements of hard platelets in soft matrix, have huge potential for developing advanced materials. The study of applicability of mechanical principles of biological materials to engineered materials will guide designing advanced materials. To probe the generic mechanical characteristics of these bioinspired nanocomposites, the model material concept in molecular dynamics (MD) is used. In this paper, the effect of platelets aspect ratio (AR) on the mechanical behaviour of bioinspired nanocomposites is investigated. The obtained Young׳s moduli of both the models and the strengths of the regularly staggered models agree with the available theories. However, the strengths of the stairwise staggered models show significant difference. For the stairwise staggered model, we demonstrate the existence of two critical ARs, a smaller critical AR above which platelet fracture occurs and a higher critical AR above which composite strength remains constant. Our MD study also shows the existence of mechanisms of platelet pull-out and breakage for lower and higher ARs. Pullout mechanism acts as a major source of plasticity. Further, we find that the regularly staggered model can achieve an optimal combination of high Young׳s modulus, flow strength and toughness, and the stairwise staggered model is efficient in obtaining high Young׳s modulus and tensile strength. PMID:26741376

  18. Molecular 'OR' and 'AND' logic gates integrated in a single molecule

    NASA Astrophysics Data System (ADS)

    Ami, S.; Hliwa, M.; Joachim, C.

    2003-01-01

    Based on the N electrodes elastic scattering quantum chemistry (NESQC) technique, an intramolecular circuit simulator is presented for the design of electronic logic functions integrated inside a single molecule interconnected to the N electrodes. Using molecular rectifier groups, a molecule-OR and a molecule-AND are designed, their current-voltage characteristics calculated and their logic response presented. Both the OR and AND molecules have approximatively the targeted function. The running current of the OR gate, 10 fA, is quite low and the AND gate works only in an output voltage mode. This forbids the design of larger logic functions inside a single molecule with molecular rectifiers.

  19. A simple and accurate algorithm for path integral molecular dynamics with the Langevin thermostat.

    PubMed

    Liu, Jian; Li, Dezhang; Liu, Xinzijian

    2016-07-14

    We introduce a novel simple algorithm for thermostatting path integral molecular dynamics (PIMD) with the Langevin equation. The staging transformation of path integral beads is employed for demonstration. The optimum friction coefficients for the staging modes in the free particle limit are used for all systems. In comparison to the path integral Langevin equation thermostat, the new algorithm exploits a different order of splitting for the phase space propagator associated to the Langevin equation. While the error analysis is made for both algorithms, they are also employed in the PIMD simulations of three realistic systems (the H2O molecule, liquid para-hydrogen, and liquid water) for comparison. It is shown that the new thermostat increases the time interval of PIMD by a factor of 4-6 or more for achieving the same accuracy. In addition, the supplementary material shows the error analysis made for the algorithms when the normal-mode transformation of path integral beads is used. PMID:27421393

  20. A simple and accurate algorithm for path integral molecular dynamics with the Langevin thermostat

    NASA Astrophysics Data System (ADS)

    Liu, Jian; Li, Dezhang; Liu, Xinzijian

    2016-07-01

    We introduce a novel simple algorithm for thermostatting path integral molecular dynamics (PIMD) with the Langevin equation. The staging transformation of path integral beads is employed for demonstration. The optimum friction coefficients for the staging modes in the free particle limit are used for all systems. In comparison to the path integral Langevin equation thermostat, the new algorithm exploits a different order of splitting for the phase space propagator associated to the Langevin equation. While the error analysis is made for both algorithms, they are also employed in the PIMD simulations of three realistic systems (the H2O molecule, liquid para-hydrogen, and liquid water) for comparison. It is shown that the new thermostat increases the time interval of PIMD by a factor of 4-6 or more for achieving the same accuracy. In addition, the supplementary material shows the error analysis made for the algorithms when the normal-mode transformation of path integral beads is used.

  1. Strategic approaches to drug design. I. An integrated software framework for molecular modelling.

    PubMed

    Vinter, J G; Davis, A; Saunders, M R

    1987-04-01

    An integrated molecular graphics and computational chemistry framework is described which has been designed primarily to handle small molecules of up to 300 atoms. The system provides a means of integrating software from any source into a single framework. It is split into two functional subsystems. The first subsystem, called COSMIC, runs on low-cost, serial-linked colour graphics terminals and allows the user to prepare and examine structural data and to submit them for extensive computational chemistry. Links also allow access to databases, other modelling systems and user-written modules. Much of the output from COSMIC cannot be examined with low level graphics. A second subsystem, called ASTRAL, has been developed for the high-resolution Evans & Sutherland PS300 colour graphics terminal and is designed to manipulate complex display structures. The COSMIC minimisers, geometry investigators, molecular orbital displays, electrostatic isopotential generators and various interfaces and utilities are described. PMID:3505586

  2. Plasma DNA integrity index as a potential molecular diagnostic marker for breast cancer.

    PubMed

    Kamel, Azza M; Teama, Salwa; Fawzy, Amal; El Deftar, Mervat

    2016-06-01

    Plasma DNA integrity index is increased in various malignancies including breast cancer, the most common cancer in women worldwide; early detection is crucial for successful treatment. Current screening methods fail to detect many cases of breast cancer at an early stage. In this study, we evaluated the level of plasma DNA integrity index in 260 females (95 with breast cancer, 95 with benign breast lesions, and 70 healthy controls) to verify its potential value in discriminating malignant from benign breast lesions. The criteria of the American Joint Committee on Cancer were used for staging of breast cancer patients. DNA integrity index was measured by real-time PCR. DNA integrity index was significantly higher in breast cancer than in benign breast patients and healthy subjects (P = <0.001). DNA integrity index is correlated with TNM stage. Given 100 % specificity, the highest sensitivity achieved in detecting cancer group was 85.3 % at 0.55 DNA integrity index cutoff. In conclusion, the plasma DNA integrity index may be a promising molecular diagnostic marker of malignancy in breast lesions. PMID:26684805

  3. i-PI: A Python interface for ab initio path integral molecular dynamics simulations

    NASA Astrophysics Data System (ADS)

    Ceriotti, Michele; More, Joshua; Manolopoulos, David E.

    2014-03-01

    Recent developments in path integral methodology have significantly reduced the computational expense of including quantum mechanical effects in the nuclear motion in ab initio molecular dynamics simulations. However, the implementation of these developments requires a considerable programming effort, which has hindered their adoption. Here we describe i-PI, an interface written in Python that has been designed to minimise the effort required to bring state-of-the-art path integral techniques to an electronic structure program. While it is best suited to first principles calculations and path integral molecular dynamics, i-PI can also be used to perform classical molecular dynamics simulations, and can just as easily be interfaced with an empirical forcefield code. To give just one example of the many potential applications of the interface, we use it in conjunction with the CP2K electronic structure package to showcase the importance of nuclear quantum effects in high-pressure water. Catalogue identifier: AERN_v1_0 Program summary URL: http://cpc.cs.qub.ac.uk/summaries/AERN_v1_0.html Program obtainable from: CPC Program Library, Queen’s University, Belfast, N. Ireland Licensing provisions: GNU General Public License, version 3 No. of lines in distributed program, including test data, etc.: 138626 No. of bytes in distributed program, including test data, etc.: 3128618 Distribution format: tar.gz Programming language: Python. Computer: Multiple architectures. Operating system: Linux, Mac OSX, Windows. RAM: Less than 256 Mb Classification: 7.7. External routines: NumPy Nature of problem: Bringing the latest developments in the modelling of nuclear quantum effects with path integral molecular dynamics to ab initio electronic structure programs with minimal implementational effort. Solution method: State-of-the-art path integral molecular dynamics techniques are implemented in a Python interface. Any electronic structure code can be patched to receive the atomic

  4. Temperature Dependence of NMR Parameters Calculated from Path Integral Molecular Dynamics Simulations.

    PubMed

    Dračínský, Martin; Bouř, Petr; Hodgkinson, Paul

    2016-03-01

    The influence of temperature on NMR chemical shifts and quadrupolar couplings in model molecular organic solids is explored using path integral molecular dynamics (PIMD) and density functional theory (DFT) calculations of shielding and electric field gradient (EFG) tensors. An approach based on convoluting calculated shielding or EFG tensor components with probability distributions of selected bond distances and valence angles obtained from DFT-PIMD simulations at several temperatures is used to calculate the temperature effects. The probability distributions obtained from the quantum PIMD simulations, which includes nuclear quantum effects, are significantly broader and less temperature dependent than those obtained with conventional DFT molecular dynamics or with 1D scans through the potential energy surface. Predicted NMR observables for the model systems were in excellent agreement with experimental data. PMID:26857802

  5. Integrated Operational Taxonomic Units (IOTUs) in Echolocating Bats: A Bridge between Molecular and Traditional Taxonomy

    PubMed Central

    Galimberti, Andrea; Spada, Martina; Russo, Danilo; Mucedda, Mauro; Agnelli, Paolo; Crottini, Angelica; Ferri, Emanuele; Martinoli, Adriano; Casiraghi, Maurizio

    2012-01-01

    Background Nowadays, molecular techniques are widespread tools for the identification of biological entities. However, until very few years ago, their application to taxonomy provoked intense debates between traditional and molecular taxonomists. To prevent every kind of disagreement, it is essential to standardize taxonomic definitions. Along these lines, we introduced the concept of Integrated Operational Taxonomic Unit (IOTU). IOTUs come from the concept of Operational Taxonomic Unit (OTU) and paralleled the Molecular Operational Taxonomic Unit (MOTU). The latter is largely used as a standard in many molecular-based works (even if not always explicitly formalized). However, while MOTUs are assigned solely on molecular variation criteria, IOTUs are identified from patterns of molecular variation that are supported by at least one more taxonomic characteristic. Methodology/Principal Findings We tested the use of IOTUs on the widest DNA barcoding dataset of Italian echolocating bats species ever assembled (i.e. 31 species, 209 samples). We identified 31 molecular entities, 26 of which corresponded to the morphologically assigned species, two MOTUs and three IOTUs. Interestingly, we found three IOTUs in Myotis nattereri, one of which is a newly described lineage found only in central and southern Italy. In addition, we found a level of molecular variability within four vespertilionid species deserving further analyses. According to our scheme two of them (i.e. M. bechsteinii and Plecotus auritus) should be ranked as unconfirmed candidate species (UCS). Conclusions/Significance From a systematic point of view, IOTUs are more informative than the general concept of OTUs and the more recent MOTUs. According to information content, IOTUs are closer to species, although it is important to underline that IOTUs are not species. Overall, the use of a more precise panel of taxonomic entities increases the clarity in the systematic field and has the potential to fill the gaps

  6. Molecular evidence-based medicine: evolution and integration of information in the genomic era.

    PubMed

    Ioannidis, J P A

    2007-05-01

    Evidence-based medicine and molecular medicine have both been influential in biomedical research in the last 15 years. Despite following largely parallel routes to date, the goals and principles of evidence-based and molecular medicine are complementary and they should be converging. I define molecular evidence-based medicine as the study of medical information that makes sense of the advances of molecular biological disciplines and where errors and biases are properly appreciated and placed in context. Biomedical measurement capacity improves very rapidly. The exponentially growing mass of hypotheses being tested requires a new approach to both statistical and biological inference. Multidimensional biology requires careful exact replication of research findings, but indirect corroboration is often all that is achieved at best. Besides random error, bias remains a major threat. It is often difficult to separate bias from the spirit of scientific inquiry to force data into coherent and 'significant' biological stories. Transparency and public availability of protocols, data, analyses and results may be crucial to make sense of the complex biology of human disease and avoid being flooded by spurious research findings. Research efforts should be integrated across teams in an open, sharing environment. Most research in the future may be designed, performed, and integrated in the public cyberspace. PMID:17461979

  7. Antioxidant Capacity of Melatonin on Preimplantation Development of Fresh and Vitrified Rabbit Embryos: Morphological and Molecular Aspects

    PubMed Central

    Mehaisen, Gamal M. K.; Saeed, Ayman M.; Gad, Ahmed; Abass, Ahmed O.; Arafa, Mahmoud; El-Sayed, Ashraf

    2015-01-01

    Embryo cryopreservation remains an important technique to enhance the reconstitution and distribution of animal populations with high genetic merit. One of the major detrimental factors to this technique is the damage caused by oxidative stress. Melatonin is widely known as an antioxidant with multi-faceted ways to counteract the oxidative stress. In this paper, we investigated the role of melatonin in protecting rabbit embryos during preimplantation development from the potential harmful effects of oxidative stress induced by in vitro culture or vitrification. Rabbit embryos at morula stages were cultured for 2 hr with 0 or 10−3 M melatonin (C or M groups). Embryos of each group were either transferred to fresh culture media (CF and MF groups) or vitrified/devitrified (CV and MV groups), then cultured in vitro for 48 hr until the blastocyst stage. The culture media were used to measure the activity of antioxidant enzymes: glutathione-s-transferase (GST) and superoxide dismutase (SOD), as well as the levels of two oxidative substrates: lipid peroxidation (LPO) and nitric oxide (NO). The blastocysts from each group were used to measure the expression of developmental-related genes (GJA1, POU5F1 and Nanog) and oxidative-stress-response-related genes (NFE2L2, SOD1 and GPX1). The data showed that melatonin promoted significantly (P<0.05) the blastocyst rate by 17% and 12% in MF and MV groups compared to their controls (CF and CV groups). The GST and SOD activity significantly increased by the treatment of melatonin in fresh or vitrified embryos, while the levels of LPO and NO decreased (P<0.05). Additionally, melatonin considerably stimulated the relative expression of GJA1, NFE2L2 and SOD1 genes in MF and MV embryos compared to CF group. Furthermore, melatonin significantly ameliorated the reduction of POU5F1 and GPX1 expression induced by vitrification. The results obtained from the current investigation provide new and clear molecular aspects regarding the

  8. New methods for accelerating the convergence of molecular electronic integrals over exponential type orbitals

    NASA Astrophysics Data System (ADS)

    Safouhi, Hassan; Hoggan, Philip

    2003-01-01

    This review on molecular integrals for large electronic systems (MILES) places the problem of analytical integration over exponential-type orbitals (ETOs) in a historical context. After reference to the pioneering work, particularly by Barnett, Shavitt and Yoshimine, it focuses on recent progress towards rapid and accurate analytic solutions of MILES over ETOs. Software such as the hydrogenlike wavefunction package Alchemy by Yoshimine and collaborators is described. The review focuses on convergence acceleration of these highly oscillatory integrals and in particular it highlights suitable nonlinear transformations. Work by Levin and Sidi is described and applied to MILES. A step by step description of progress in the use of nonlinear transformation methods to obtain efficient codes is provided. The recent approach developed by Safouhi is also presented. The current state of the art in this field is summarized to show that ab initio analytical work over ETOs is now a viable option.

  9. The semantic metadatabase (SEMEDA): ontology based integration of federated molecular biological data sources.

    PubMed

    Köhler, Jacob; Schulze-Kremer, Steffen

    2002-01-01

    A system for "intelligent" semantic integration and querying of federated databases is being implemented by using three main components: A component which enables SQL access to integrated databases by database federation (MARGBench), an ontology based semantic metadatabase (SEMEDA) and an ontology based query interface (SEMEDA-query). In this publication we explain and demonstrate the principles, architecture and the use of SEMEDA. Since SEMEDA is implemented as 3 tiered web application database providers can enter all relevant semantic and technical information about their databases by themselves via a web browser. SEMEDA' s collaborative ontology editing feature is not restricted to database integration, and might also be useful for ongoing ontology developments, such as the "Gene Ontology" [2]. SEMEDA can be found at http://www-bm.cs.uni-magdeburg.de/semeda/. We explain how this ontologically structured information can be used for semantic database integration. In addition, requirements to ontologies for molecular biological database integration are discussed and relevant existing ontologies are evaluated. We further discuss how ontologies and structured knowledge sources can be used in SEMEDA and whether they can be merged supplemented or updated to meet the requirements for semantic database integration. PMID:12542408

  10. Model for integrated management of quality, labor risks prevention, environment and ethical aspects, applied to R&D&I and production processes in an organization

    NASA Astrophysics Data System (ADS)

    González, M. R.; Torres, F.; Yoldi, V.; Arcega, F.; Plaza, I.

    2012-04-01

    It is proposed an integrated management model for an organization. This model is based on the continuous improvement Plan-Do-Check-Act cycle and it intends to integrate the environmental, risk prevention and ethical aspects as well as research, development and innovation projects management in the general quality management structure proposed by ISO 9001:2008. It aims to fulfill the standards ISO 9001, ISO 14001, OSHAS 18001, SGE 21 y 166002.

  11. Dimensionality aspects of nano micro integrated metal oxide based early stage leak detection room temperature hydrogen sensor

    NASA Astrophysics Data System (ADS)

    Deshpande, Sameer Arun

    .). Highly porous SnO2 nanoparticles thin film (synthesized using template assisted) showed response time of about 25 seconds and sensitivity 4. The one dimensional tin oxide nanostructures (nanowires) based sensor showed a sensitivity of 4 and response time of 20 sec. Effect of aspect ratio of the nanowires on diffusion of hydrogen molecules in the tin oxide nanowires, effect of catalyst adsorption on nanowire surface and corresponding effect on sensor properties has been studied in detail. Nanotubes of TiO2 prepared using hydrothermal synthesis showed a sensitivity 30 with response time as low as 20 seconds where as, TiO 2 nanotubes synthesized using anodization showed poor sensitivity. The difference is mainly attributed to the issues related to integration of the anodized nanotubes with the MEMS devices. The effect of MEMS device architecture modulation, such as, finger spacing, number and length of fingers and electrode materials were studied. It has been found that faster sensor response (˜ 10 sec) was observed for smaller finger spacing. A diffusion model is proposed for elucidating the effect of inter-electrode distance variation on conductance change of a nano-micro integrated hydrogen sensor for room temperature operation. Both theoretical and experimental results showed a faster response upon exposure to hydrogen when sensor electrode gap was smaller. Also, a linear increase in the sensor sensitivity from 500 to 80000 was observed on increasing the electrode spacing from 2 to 20 mum. The improvement in sensitivity is attributed to the higher reactive sites available for the gaseous species to react on the sensor surface. This phenomenon also correlated to surface adsorbed oxygen vacancies (O-) and the rate of change of surface adsorbed oxygen vacancies. This dissertation studied in detail dimensionality aspects of materials as well as device in detecting hydrogen at room temperature.

  12. The multi-facet aspects of cell sentience and their relevance for the integrative brain actions: role of membrane protein energy landscape.

    PubMed

    Agnati, Luigi F; Marcoli, Manuela; Maura, Guido; Fuxe, Kjell; Guidolin, Diego

    2016-06-01

    Several ion channels can be randomly and spontaneously in an open state, allowing the exchange of ion fluxes between extracellular and intracellular environments. We propose that the random changes in the state of ion channels could be also due to proteins exploring their energy landscapes. Indeed, proteins can modify their steric conformation under the effects of the physicochemical parameters of the environments with which they are in contact, namely, the extracellular, intramembrane and intracellular environments. In particular, it is proposed that the random walk of proteins in their energy landscape is towards attractors that can favor the open or close condition of the ion channels and/or intrinsic activity of G-protein-coupled receptors. The main aspect of the present proposal is that some relevant physicochemical parameters of the environments (e.g. molecular composition, temperature, electrical fields) with which some signaling-involved plasma membrane proteins are in contact alter their conformations. In turn, these changes can modify their information handling via a modulatory action on their random walk towards suitable attractors of their energy landscape. Thus, spontaneous and/or signal-triggered electrical activities of neurons occur that can have emergent properties capable of influencing the integrative actions of brain networks. Against this background, Cook's hypothesis on 'cell sentience' is developed by proposing that physicochemical parameters of the environments with which the plasma-membrane proteins of complex cellular networks are in contact fulfill a fundamental role in their spontaneous and/or signal-triggered activity. Furthermore, it is proposed that a specialized organelle, the primary cilium, which is present in most cells (also neurons and astrocytes), could be of peculiar importance to pick up chemical signals such as ions and transmitters and to detect physical signals such as pressure waves, thermal gradients, and local field

  13. Validation of intermolecular transfer integral and bandwidth calculations for organic molecular materials.

    PubMed

    Huang, Jingsong; Kertesz, Miklos

    2005-06-15

    We present an interpretation of the intermolecular transfer integral that is independent from the origin of the energy scale allowing convergence studies of this important parameter of organic molecular materials. We present extensive numerical studies by using an ethylene pi dimer to investigate the dependence of transfer integrals on the level of theory and intermolecular packing. Transfer integrals obtained from semiempirical calculations differ substantially from one another and from ab initio results. The ab initio results are consistent across all the levels used including Hartree-Fock, outer valence Green's function, and various forms of density functional theory (DFT). Validation of transfer integrals and bandwidths is performed by comparing the calculated values with the experimental values of tetrathiafulvalene-tetracyanoquinodimethane (TTF-TCNQ), bis[1,2,5]thiadiazolo-p-quinobis(1,3-dithiole), (BTQBT) K-TCNQ, and hexagonal graphite. DFT in one of its presently popular forms, such as Perdew-Wang functionals (PW91), in combination with sufficient basis sets provides reliable transfer integrals, and therefore can serve as a basis for energy band calculations for soft organic materials with van der Waals gaps. PMID:16008473

  14. The integration of molecular dynamics simulations with imposed temperature and stress

    NASA Astrophysics Data System (ADS)

    Lill, J. V.

    1994-04-01

    Nonlinear molecular dynamics equations for the simulation of crystals under the conditions of imposed temperature and tensorial pressure are summarized. The physical effects included in these equations, but absent from previous linear and nonlinear theories, is the elastic response of the material being modeled. The physical effect is expressed through satisfaction of the nonlinear tensorial virial theorem. We transform these equations in Hamiltonian form to an equivalent set of Lagrangian equations, and present an algorithm for their numerical integration. The method uses a combination of Verlet and leap-frog algorithms to integrate the atomic positions and velocities as scaled by dynamical lattice vectors of the crystal, the elements of deformation gradient and its velocity, and the Nosé-Hoover time scale and generalized friction. A consistent error analysis is performed for the combined integration of each degree of freedom. A symmetrization procedure to eliminate rigid rotations of the crystal is introduced. Molecular dynamics simulations of a Martensitic tranformation are presented that demonstrate the validity of the nonlinear tensorial virial theorem throughout the transformation; complementary Metropolis Monte Carlo simulations verify that the correct distribution is sampled.

  15. Molecular radiotherapy: The NUKFIT software for calculating the time-integrated activity coefficient

    SciTech Connect

    Kletting, P.; Schimmel, S.; Luster, M.; Kestler, H. A.; Hänscheid, H.; Fernández, M.; Lassmann, M.; Bröer, J. H.; Nosske, D.; Glatting, G.

    2013-10-15

    Purpose: Calculation of the time-integrated activity coefficient (residence time) is a crucial step in dosimetry for molecular radiotherapy. However, available software is deficient in that it is either not tailored for the use in molecular radiotherapy and/or does not include all required estimation methods. The aim of this work was therefore the development and programming of an algorithm which allows for an objective and reproducible determination of the time-integrated activity coefficient and its standard error.Methods: The algorithm includes the selection of a set of fitting functions from predefined sums of exponentials and the choice of an error model for the used data. To estimate the values of the adjustable parameters an objective function, depending on the data, the parameters of the error model, the fitting function and (if required and available) Bayesian information, is minimized. To increase reproducibility and user-friendliness the starting values are automatically determined using a combination of curve stripping and random search. Visual inspection, the coefficient of determination, the standard error of the fitted parameters, and the correlation matrix are provided to evaluate the quality of the fit. The functions which are most supported by the data are determined using the corrected Akaike information criterion. The time-integrated activity coefficient is estimated by analytically integrating the fitted functions. Its standard error is determined assuming Gaussian error propagation. The software was implemented using MATLAB.Results: To validate the proper implementation of the objective function and the fit functions, the results of NUKFIT and SAAM numerical, a commercially available software tool, were compared. The automatic search for starting values was successfully tested for reproducibility. The quality criteria applied in conjunction with the Akaike information criterion allowed the selection of suitable functions. Function fit

  16. Evaluation of Kirkwood-Buff integrals via finite size scaling: a large scale molecular dynamics study

    NASA Astrophysics Data System (ADS)

    Dednam, W.; Botha, A. E.

    2015-01-01

    Solvation of bio-molecules in water is severely affected by the presence of co-solvent within the hydration shell of the solute structure. Furthermore, since solute molecules can range from small molecules, such as methane, to very large protein structures, it is imperative to understand the detailed structure-function relationship on the microscopic level. For example, it is useful know the conformational transitions that occur in protein structures. Although such an understanding can be obtained through large-scale molecular dynamic simulations, it is often the case that such simulations would require excessively large simulation times. In this context, Kirkwood-Buff theory, which connects the microscopic pair-wise molecular distributions to global thermodynamic properties, together with the recently developed technique, called finite size scaling, may provide a better method to reduce system sizes, and hence also the computational times. In this paper, we present molecular dynamics trial simulations of biologically relevant low-concentration solvents, solvated by aqueous co-solvent solutions. In particular we compare two different methods of calculating the relevant Kirkwood-Buff integrals. The first (traditional) method computes running integrals over the radial distribution functions, which must be obtained from large system-size NVT or NpT simulations. The second, newer method, employs finite size scaling to obtain the Kirkwood-Buff integrals directly by counting the particle number fluctuations in small, open sub-volumes embedded within a larger reservoir that can be well approximated by a much smaller simulation cell. In agreement with previous studies, which made a similar comparison for aqueous co-solvent solutions, without the additional solvent, we conclude that the finite size scaling method is also applicable to the present case, since it can produce computationally more efficient results which are equivalent to the more costly radial distribution

  17. Site-controlled Ag nanocrystals grown by molecular beam epitaxy-Towards plasmonic integration technology

    SciTech Connect

    Urbanczyk, Adam; Noetzel, Richard

    2012-12-15

    We demonstrate site-controlled growth of epitaxial Ag nanocrystals on patterned GaAs substrates by molecular beam epitaxy with high degree of long-range uniformity. The alignment is based on lithographically defined holes in which position controlled InAs quantum dots are grown. The Ag nanocrystals self-align preferentially on top of the InAs quantum dots. No such ordering is observed in the absence of InAs quantum dots, proving that the ordering is strain-driven. The presented technique facilitates the placement of active plasmonic nanostructures at arbitrarily defined positions enabling their integration into complex devices and plasmonic circuits.

  18. Phase Behavior of Active Swimmers in Depletants: Molecular Dynamics and Integral Equation Theory

    NASA Astrophysics Data System (ADS)

    Das, Subir K.; Egorov, Sergei A.; Trefz, Benjamin; Virnau, Peter; Binder, Kurt

    2014-05-01

    We study the structure and phase behavior of a binary mixture where one of the components is self-propelling in nature. The interparticle interactions in the system are taken from the Asakura-Oosawa model for colloid-polymer mixtures for which the phase diagram is known. In the current model version, the colloid particles are made active using the Vicsek model for self-propelling particles. The resultant active system is studied by molecular dynamics methods and integral equation theory. Both methods produce results consistent with each other and demonstrate that the Vicsek model-based activity facilitates phase separation, thus, broadening the coexistence region.

  19. Phase behavior of active swimmers in depletants: molecular dynamics and integral equation theory.

    PubMed

    Das, Subir K; Egorov, Sergei A; Trefz, Benjamin; Virnau, Peter; Binder, Kurt

    2014-05-16

    We study the structure and phase behavior of a binary mixture where one of the components is self-propelling in nature. The interparticle interactions in the system are taken from the Asakura-Oosawa model for colloid-polymer mixtures for which the phase diagram is known. In the current model version, the colloid particles are made active using the Vicsek model for self-propelling particles. The resultant active system is studied by molecular dynamics methods and integral equation theory. Both methods produce results consistent with each other and demonstrate that the Vicsek model-based activity facilitates phase separation, thus, broadening the coexistence region. PMID:24877969

  20. Efficient molecular dynamics using geodesic integration and solvent–solute splitting

    PubMed Central

    Leimkuhler, Benedict

    2016-01-01

    We present an approach to Langevin dynamics in the presence of holonomic constraints based on decomposition of the system into components representing geodesic flow, constrained impulse and constrained diffusion. We show that a particular ordering of the components results in an integrator that is an order of magnitude more accurate for configurational averages than existing alternatives. Moreover, by combining the geodesic integration method with a solvent–solute force splitting, we demonstrate that stepsizes of at least 8 fs can be used for solvated biomolecules with high sampling accuracy and without substantially altering diffusion rates, approximately increasing by a factor of two the efficiency of molecular dynamics sampling for such systems. The methods described in this article are easily implemented using the standard apparatus of modern simulation codes. PMID:27279779

  1. Toward Integrated Molecular Diagnostic System (iMDx): Principles and Applications

    PubMed Central

    Park, Seung-min; Sabour, Andrew F.; Son, Jun Ho; Lee, Sang Hun

    2014-01-01

    Integrated molecular diagnostic systems (iMDx), which are automated, sensitive, specific, user-friendly, robust, rapid, easy-to-use, and portable, can revolutionize future medicine. This review will first focus on the components of sample extraction, preservation, and filtration necessary for all point-of-care devices to include for practical use. Subsequently, we will look for low-powered and precise methods for both sample amplification and signal transduction, going in-depth to the details behind their principles. The final field of total device integration and its application to the clinical field will also be addressed to discuss the practicality for future patient care. We envision that microfluidic systems hold the potential to breakthrough the number of problems brought into the field of medical diagnosis today. PMID:24759281

  2. Auxiliary functions for molecular integrals with Slater-type orbitals. II. Gauss transform methods

    NASA Astrophysics Data System (ADS)

    Ema, I.; López, R.; Fernández, J. J.; Ramírez, G.; Rico, J. F.

    The Gauss transform of Slater-type orbitals is used to express several types of molecular integrals involving these functions in terms of simple auxiliary functions. After reviewing this transform and the way it can be combined with the shift operator technique, a master formula for overlap integrals is derived and used to obtain multipolar moments associated to fragments of two-center distributions and overlaps of derivatives of Slater functions. Moreover, it is proved that integrals involving two-center distributions and irregular harmonics placed at arbitrary points (which determine the electrostatic potential, field and field gradient, as well as higher order derivatives of the potential) can be expressed in terms of auxiliary functions of the same type as those appearing in the overlap. The recurrence relations and series expansions of these functions are thoroughly studied, and algorithms for their calculation are presented. The usefulness and efficiency of this procedure are tested by developing two independent codes: one for the derivatives of the overlap integrals with respect to the centers of the functions, and another for derivatives of the potential (electrostatic field, field gradient, and so forth) at arbitrary points.0

  3. Network-based integration of molecular and physiological data elucidates regulatory mechanisms underlying adaptation to high-fat diet.

    PubMed

    Derous, Davina; Kelder, Thomas; van Schothorst, Evert M; van Erk, Marjan; Voigt, Anja; Klaus, Susanne; Keijer, Jaap; Radonjic, Marijana

    2015-07-01

    Health is influenced by interplay of molecular, physiological and environmental factors. To effectively maintain health and prevent disease, health-relevant relations need to be understood at multiple levels of biological complexity. Network-based methods provide a powerful platform for integration and mining of data and knowledge characterizing different aspects of health. Previously, we have reported physiological and gene expression changes associated with adaptation of murine epididymal white adipose tissue (eWAT) to 5 days and 12 weeks of high-fat diet (HFD) and low-fat diet feeding (Voigt et al. in Mol Nutr Food Res 57:1423-1434, 2013. doi: 10.1002/mnfr.201200671 ). In the current study, we apply network analysis on this dataset to comprehensively characterize mechanisms driving the short- and long-term adaptation of eWAT to HFD across multiple levels of complexity. We built a three-layered interaction network comprising enriched biological processes, their transcriptional regulators and associated changes in physiological parameters. The multi-layered network model reveals that early eWAT adaptation to HFD feeding involves major changes at a molecular level, including activation of TGF-β signalling pathway, immune and stress response and downregulation of mitochondrial functioning. Upon prolonged HFD intake, initial transcriptional response tails off, mitochondrial functioning is even further diminished, and in turn the relation between eWAT gene expression and physiological changes becomes more prominent. In particular, eWAT weight and total energy intake negatively correlate with cellular respiration process, revealing mitochondrial dysfunction as a hallmark of late eWAT adaptation to HFD. Apart from global understanding of the time-resolved adaptation to HFD, the multi-layered network model allows several novel mechanistic hypotheses to emerge: (1) early activation of TGF-β signalling as a trigger for structural and morphological changes in

  4. Using non-invasive molecular spectroscopic techniques to detect unique aspects of protein Amide functional groups and chemical properties of modeled forage from different sourced-origins

    NASA Astrophysics Data System (ADS)

    Ji, Cuiying; Zhang, Xuewei; Yu, Peiqiang

    2016-03-01

    The non-invasive molecular spectroscopic technique-FT/IR is capable to detect the molecular structure spectral features that are associated with biological, nutritional and biodegradation functions. However, to date, few researches have been conducted to use these non-invasive molecular spectroscopic techniques to study forage internal protein structures associated with biodegradation and biological functions. The objectives of this study were to detect unique aspects and association of protein Amide functional groups in terms of protein Amide I and II spectral profiles and chemical properties in the alfalfa forage (Medicago sativa L.) from different sourced-origins. In this study, alfalfa hay with two different origins was used as modeled forage for molecular structure and chemical property study. In each forage origin, five to seven sources were analyzed. The molecular spectral profiles were determined using FT/IR non-invasive molecular spectroscopy. The parameters of protein spectral profiles included functional groups of Amide I, Amide II and Amide I to II ratio. The results show that the modeled forage Amide I and Amide II were centered at 1653 cm- 1 and 1545 cm- 1, respectively. The Amide I spectral height and area intensities were from 0.02 to 0.03 and 2.67 to 3.36 AI, respectively. The Amide II spectral height and area intensities were from 0.01 to 0.02 and 0.71 to 0.93 AI, respectively. The Amide I to II spectral peak height and area ratios were from 1.86 to 1.88 and 3.68 to 3.79, respectively. Our results show that the non-invasive molecular spectroscopic techniques are capable to detect forage internal protein structure features which are associated with forage chemical properties.

  5. Revealing potential molecular targets bridging colitis and colorectal cancer based on multidimensional integration strategy

    PubMed Central

    Hu, Yongfei; Li, Xiaobo; Wang, Xishan; Fan, Huihui; Wang, Guiyu; Wang, Dong

    2015-01-01

    Chronic inflammation may play a vital role in the pathogenesis of inflammation-associated tumors. However, the underlying mechanisms bridging ulcerative colitis (UC) and colorectal cancer (CRC) remain unclear. Here, we integrated multidimensional interaction resources, including gene expression profiling, protein-protein interactions (PPIs), transcriptional and post-transcriptional regulation data, and virus-host interactions, to tentatively explore potential molecular targets that functionally link UC and CRC at a systematic level. In this work, by deciphering the overlapping genes, crosstalking genes and pivotal regulators of both UC- and CRC-associated functional module pairs, we revealed a variety of genes (including FOS and DUSP1, etc.), transcription factors (including SMAD3 and ETS1, etc.) and miRNAs (including miR-155 and miR-196b, etc.) that may have the potential to complete the connections between UC and CRC. Interestingly, further analyses of the virus-host interaction network demonstrated that several virus proteins (including EBNA-LP of EBV and protein E7 of HPV) frequently inter-connected to UC- and CRC-associated module pairs with their validated targets significantly enriched in both modules of the host. Together, our results suggested that multidimensional integration strategy provides a novel approach to discover potential molecular targets that bridge the connections between UC and CRC, which could also be extensively applied to studies on other inflammation-related cancers. PMID:26461477

  6. Integrated Observations of ICME - Driven Substorm - Storm Evolution on 7 August 1998: Traditional and Non-Traditional Aspects.

    NASA Astrophysics Data System (ADS)

    Farrugia, C. J.; Sandholt, P. E.; Torbert, R. B.

    2015-12-01

    The aim of this study is to obtain an integrated view of substorm-storm evolution in relation to well-defined interplanetary (IP) conditions, and to identify traditional and non-traditional aspects of the DP1 and DP2 current systems during substorm activity. Specifically, we report a case study of substorm/storm evolution driven by an ICME from ground observations around the oval in relation to geoeffective IP parameters (Kan-Lee electric field, E-KL, and dynamic pressure, Pdyn), geomagnetic indices (AL, SYM-H and PCN) and satellite observations (from DMSP F13 and F14, Geotail, and GOES spacecraft). A sudden enhancement of E-KL at a southward turning of the IMF led to an initial transient phase (PCN-enhancement) followed by a persistent stage of solar wind-magnetosphere-ionosphere coupling. The persistent phase terminated abruptly at a steep E-KL reduction when the ICME magnetic field turned north after a 3-hour-long interval of enhanced E-KL. The persistent phase consisted of (i) a 45-min-long substorm growth phase (DP2 current) followed by (ii) a classical substorm onset (DP1 current) in the 0100 - 0300 MLT sector, (ii) a 30-min-long expansion phase, maximizing in the same sector, and (iii) a phase lasting for 1.5 hr of 10-15 min-long DP1 events in the 2100 - 2300 and 0400 - 0600 MLT sectors. In the morning sector the expansion phase was characterized by Ps6 pulsations and omega bands. The SYM-H evolution reached the level of a major storm after a 2.5-hour-long interval of E-KL ˜5 mV/m and elevated Pdyn in the substorm expansion phase. Magetosphere - Ionosphere (M - I) coupling during a localized electrojet event at 0500 MLT in the late stage of the substorm expansion is studied by ground - satellite conjunction data (Iceland - Geotail). The DP1 and DP2 components of geomagnetic activity are discussed in relation to M - I current systems and substorm current wedge morphology.

  7. Integrating Nanostructured Artificial Receptors with Whispering Gallery Mode Optical Microresonators via Inorganic Molecular Imprinting Techniques.

    PubMed

    Hammond, G Denise; Vojta, Adam L; Grant, Sheila A; Hunt, Heather K

    2016-01-01

    The creation of label-free biosensors capable of accurately detecting trace contaminants, particularly small organic molecules, is of significant interest for applications in environmental monitoring. This is achieved by pairing a high-sensitivity signal transducer with a biorecognition element that imparts selectivity towards the compound of interest. However, many environmental pollutants do not have corresponding biorecognition elements. Fortunately, biomimetic chemistries, such as molecular imprinting, allow for the design of artificial receptors with very high selectivity for the target. Here, we perform a proof-of-concept study to show how artificial receptors may be created from inorganic silanes using the molecular imprinting technique and paired with high-sensitivity transducers without loss of device performance. Silica microsphere Whispering Gallery Mode optical microresonators are coated with a silica thin film templated by a small fluorescent dye, fluorescein isothiocyanate, which serves as our model target. Oxygen plasma degradation and solvent extraction of the template are compared. Extracted optical devices are interacted with the template molecule to confirm successful sorption of the template. Surface characterization is accomplished via fluorescence and optical microscopy, ellipsometry, optical profilometry, and contact angle measurements. The quality factors of the devices are measured to evaluate the impact of the coating on device sensitivity. The resulting devices show uniform surface coating with no microstructural damage with Q factors above 10⁶. This is the first report demonstrating the integration of these devices with molecular imprinting techniques, and could lead to new routes to biosensor creation for environmental monitoring. PMID:27314397

  8. Integrating Nanostructured Artificial Receptors with Whispering Gallery Mode Optical Microresonators via Inorganic Molecular Imprinting Techniques

    PubMed Central

    Hammond, G. Denise; Vojta, Adam L.; Grant, Sheila A.; Hunt, Heather K.

    2016-01-01

    The creation of label-free biosensors capable of accurately detecting trace contaminants, particularly small organic molecules, is of significant interest for applications in environmental monitoring. This is achieved by pairing a high-sensitivity signal transducer with a biorecognition element that imparts selectivity towards the compound of interest. However, many environmental pollutants do not have corresponding biorecognition elements. Fortunately, biomimetic chemistries, such as molecular imprinting, allow for the design of artificial receptors with very high selectivity for the target. Here, we perform a proof-of-concept study to show how artificial receptors may be created from inorganic silanes using the molecular imprinting technique and paired with high-sensitivity transducers without loss of device performance. Silica microsphere Whispering Gallery Mode optical microresonators are coated with a silica thin film templated by a small fluorescent dye, fluorescein isothiocyanate, which serves as our model target. Oxygen plasma degradation and solvent extraction of the template are compared. Extracted optical devices are interacted with the template molecule to confirm successful sorption of the template. Surface characterization is accomplished via fluorescence and optical microscopy, ellipsometry, optical profilometry, and contact angle measurements. The quality factors of the devices are measured to evaluate the impact of the coating on device sensitivity. The resulting devices show uniform surface coating with no microstructural damage with Q factors above 106. This is the first report demonstrating the integration of these devices with molecular imprinting techniques, and could lead to new routes to biosensor creation for environmental monitoring. PMID:27314397

  9. From molecule to man: integrating molecular biology with whole organ physiology in studying respiratory disease.

    PubMed

    Königshoff, Melanie; Uhl, Franziska; Gosens, Reinoud

    2011-10-01

    Chronic lung diseases such as asthma, chronic obstructive pulmonary disease (COPD), and idiopathic pulmonary fibrosis (IPF) are all characterized by structural changes of the airways and/or lungs that limit airflow and/or gas exchange. Currently, there is no therapy available that adequately targets the structural remodeling of the airways and lungs in these diseases. This underscores the great need for insight into the mechanisms that underpin the development of airway remodeling, fibrosis and emphysema in these diseases, in order to identify suitable drug targets. It is increasingly evident that structural cell-cell communication within the lung is central to the development of remodeling, indicating that a more integrative approach should be considered when studying molecular and cellular mechanisms of remodeling. Therefore, there is a great need to study molecular and cellular physiological and pathophysiological mechanisms in as much detail as possible, but with as little as possible loss of the physiological context. Here, we will review the use of models such as cellular co-culture, tissue culture, and lung slice culture, in which cell-cell communication and tissue architecture are better preserved or mimicked than in cell culture, and zoom in on the usefulness of molecular and cellular biological tools in these complex model systems to read out or control signaling and gene/protein regulation. PMID:21356323

  10. Implicit Time Integration for Multiscale Molecular Dynamics Using Transcendental Padé Approximants.

    PubMed

    Abi Mansour, Andrew; Ortoleva, Peter J

    2016-04-12

    Molecular dynamics systems evolve through the interplay of collective and localized disturbances. As a practical consequence, there is a restriction on the time step imposed by the broad spectrum of time scales involved. To resolve this restriction, multiscale factorization was introduced for molecular dynamics as a method that exploits the separation of time scales by coevolving the coarse-grained and atom-resolved states via Trotter factorization. Developing a stable time-marching scheme for this coevolution, however, is challenging because the coarse-grained dynamical equations depend on the microstate; therefore, these equations cannot be expressed in closed form. The objective of this paper is to develop an implicit time integration scheme for multiscale simulation of large systems over long periods of time and with high accuracy. The scheme uses Padé approximants to account for both the stochastic and deterministic features of the coarse-grained dynamics. The method is demonstrated for a protein either undergoing a conformational change or migrating under the influence of an external force. The method shows promise in accelerating multiscale molecular dynamics without a loss of atomic precision or the need to conjecture the form of coarse-grained governing equations. PMID:26845510