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Sample records for molecular aspects integrative

  1. Shuttle payload integration - Contamination aspects

    NASA Technical Reports Server (NTRS)

    Jacobs, S.; Leger, L. J.; Ehlers, H. K. F.

    1982-01-01

    As part of the development of the Space Shuttle, a payload integration system has been established. This integration system or process encompasses several technical disciplines, one of which is concerned with the control of molecular and particulate contamination. Specific integration procedures and documentation have evolved that reflect the incorporation of payload/Space Transportation System contamination requirements and capabilities. Of the 38 payloads in the payload integration system currently, about 20% are considered sensitive to contamination in that special precautions must be taken to ensure that contamination from the Space Shuttle Orbiter does not impair payload function. Most of these payload requirements have been satisfied by the incorporation of controlled ground operations discipline and installation of a payload bay liner, which isolates the payload from the Orbiter systems. Some payloads, however, provide covers for sensitive payload instrumentation.

  2. Flower senescence: some molecular aspects.

    PubMed

    Shahri, Waseem; Tahir, Inayatullah

    2014-02-01

    Some molecular aspects of flower senescence have been reviewed. The isolation, identification and characterization of different genes from various flowers (mainly from petals) associated with senescence have been discussed. The isolated genes were divided into different groups. A large proportion of genes have been found to be upregulated during flower senescence while some genes were also found to be downregulated indicating that there exists a complex interplay between the expression patterns of various genes. The genes involved in petal expansion are found to be upregulated during normal flower development from anthesis to open flower stage, but XTH (Xyloglucan endotransglucosylase hydrolase) is found to be involved in petal expansion as well as abscission. Cysteine proteases or the genes encoding cysteine proteases (assigned a central role in protein degradation) have been identified from various flower systems, but no cysteine protease has been identified from senescing Mirabilis jalapa flowers. In addition to proteases, the genes encoding ubiquitin (exhibiting proteasomal degradation by 26S proteasomes) have also been identified suggesting the two alternate pathways for protein degradation. Genes encoding specific nucleases have also been identified, but they displayed an early increase in transcript abundance before the senescence symptoms become evident and characterize the involvement of PCD during flower senescence. A range of transcription factors are described and their possible role in flower senescence has been discussed. A detailed description of genes involved in ethylene synthesis and the components involved in ethylene signaling have been presented.

  3. [MOLECULAR ASPECTS OF BRUCELLA PERSISTENCE].

    PubMed

    Kulakov Yu K

    2016-01-01

    Brucellosis is a dangerous zoonotic disease of animals and humans caused by bacteria of the genus Brucella, which are able to survive, multiply, and persist in host cells. The review is devoted to the Brucella species persistence connected to the molecular mechanisms of escape from innate and adaptive immunity of the host and active interaction of effector proteins of the type IV secretion system with the host's signaling pathways. Understanding of the molecular mechanisms used by Brucella for the intracellular persistence in the host organism can allow us to develop new and effective means for the prevention and treatment of chronic brucellosis infection.

  4. 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.

  5. Molecular aspects of renal senescence.

    PubMed

    Schmitt, Roland; Susnik, Nathan; Melk, Anette

    2015-08-01

    The aging kidney undergoes profound changes that lead to a reduction in stress resistance and impaired repair capacity. In order to improve the outcome of acute and chronic kidney damage, it is instrumental to understand the mechanisms that cause these changes. Cellular senescence has emerged as an important cellular process that contributes to age-associated kidney changes and chronic kidney disease progression. New mechanistic insights into excessive intracellular glucose, advanced glycation end products and endoplasmatic reticulum stress further support the importance of cellular senescence in the development of diabetic nephropathy. As telomere length of leukocytic DNA is increasingly used as a biomarker to estimate senescence in clinical cohort studies, this review also summarizes the literature on telomere length with respect to the kidney and evaluates the strengths and weaknesses of this methodology. Furthermore, novel findings on the relationships among telomeres, senescence and autophagy are discussed. Cellular senescence contributes to the decline in renal function during aging and defective regeneration in kidney diseases. Further insight into the underlying molecular mechanisms of senescence will establish a basis for preventive strategies that improve renal stress resistance and regenerative capacity.

  6. Some aspects of inventory integration

    Treesearch

    Jerry Leech

    2000-01-01

    Integrating such disparate topics as are covered by this conference is daunting, because to do it well requires in-depth expertise of many complex technical methodologies. Based on experiences in Asia and Australia, it is suggested that there can never be one inventory design or one planning system, it will increasingly be necessary to implement specialized inventories...

  7. Alport syndrome. Molecular genetic aspects.

    PubMed

    Hertz, Jens Michael

    2009-08-01

    for 47% of all mutations and 89% if the missense mutations. Frame-shift mutations accounted for 17% of the mutations, splice site mutations for 13%, nonsense mutations for 11%, in-frame deletions for 4%, and larger structural rearrangements for 6%. In addition, 5 different non-pathogenic sequence variations, polymorphisms and mutations of unknown effect on the phenotype, were found. Nineteen of the mutations are new and have not previously been published, and 55 of the mutations have exclusively been detected in this material. Two of the mutations (3%) are de novo mutations, and it has been possible to trace the mutation back in six of the families, and to determine the parental origin of the mutation in these six families. The origin of the mutation was found to be paternal in 4 of the families (67%), and maternal in 2 of the families (33%). We have demonstrated a highly efficient and sensitive molecular diagnostic approach for analysing the COL4A5 gene in putative AS cases. Based on the present results and the litterature, an algorithm for molecular genetic analysis of the COL4A5 gene is suggested. The overall mutation detection rate was found to be 53%. The mutation detection rate was 72% in patients fulfilling >or= 3 of the clinical criteria for AS, and 82% in families clearly demonstrating X-linked inheritance. No COL4A5 mutation could be detected in 63 (47%) of the families. X-linked inheritance could be excluded in seven of these families solely based on a pedigree analysis, and a diagnosis of Epstein syndrome was established in one of the patients by MYH9 mutation analysis. We found that the underlying COL4A5 mutation, truncating or non-truncating, can significantly predict the age at ESRD in male patients. Truncating mutations, comprising nonsense mutations, frame-shifts, and larger structural rearrangements, were found to cause a juvenile form of the disease with a mean age at ESRD of 21.6 years, compared to 33.1 years in patients with a non

  8. [Molecular Pathological Aspects in Visceral Surgery].

    PubMed

    Unger, T; Sändig, I; Wittekind, C

    2016-04-01

    New insights gained in the field of molecular medicine have led to fundamental progress in the diagnosis and treatment of tumour patients. Individualised treatment has been essentially facilitated by molecular diagnostics, which, by identifying and interpreting characteristic genetic alterations (biomarkers) in single cells and tissues, provide specific information to confirm the diagnosis and support the treatment of numerous diseases. Particularly with regard to the use of new targeted drugs, which often require the presence or absence of specific target structures or genetic alterations to induce response, the molecular pathological determination of predictive biomarkers plays an increasing role and helps clinicians to decide on optimal therapies for individual patients. The aim of this review is to highlight general aspects of molecular tumour pathology for relevant tumour entities and to present available targeted therapies.

  9. Molecular aspects of bile formation and cholestasis.

    PubMed

    Arrese, Marco; Trauner, Michael

    2003-12-01

    Recent insights into the cellular and molecular mechanisms that control the function and regulation of hepatobiliary transport have led to a greater understanding of the physiological significance of bile secretion. Individual carriers for bile acids and other organic anions in both liver and intestine have now been cloned from several species. In addition, complex networks of signals that regulate key enzymes and membrane transporters located in cells that participate in the metabolism or transport of biliary constituents are being unraveled. This knowledge has major implications for the pathogenesis of cholestatic liver diseases. Here, we review recent information on molecular aspects of hepatobiliary secretory function and its regulation in cholestasis. Potential implications of this knowledge for the design of new therapies of cholestatic disorders are also discussed.

  10. [Migrant workers. The critical aspects of integration].

    PubMed

    Berra, Alessandro

    2011-01-01

    The integration of migrant poplulations with the indigeneous population is regulated by the Italian Decree, D.Lgs 9/7/2003 n. 215 in enforcement of the directive 2000/43/EC implementing the principle of equal treatment between persons irrespective of racial or ethnic origin. The Italian decree, D.Lgs 215/2003, at present in force, according to regulation stipulated as to the equal treatment of diverse cohabiting populations, explicitly forbids any form of discrimination whatsoever, be it direct or indirect. A first description of today's migrant panorama is offered by the Caritas Migrantes and the CNEL (Italian National Council of the Economy of Labour). The most critical aspects on the integration of migrants are described and discussed in the text.

  11. Ginger and its health claims: molecular aspects.

    PubMed

    Butt, Masood Sadiq; Sultan, M Tauseef

    2011-05-01

    Recent research has rejuvenated centuries-old traditional herbs to cure various ailments by using modern tools like diet-based therapy and other regimens. Ginger is one of the classic examples of an herb used for not only culinary preparations but also for unique therapeutic significance owing to its antioxidant, antimicrobial, and anti-inflammatory potential. The pungent fractions of ginger, namely gingerols, shogaols, paradols, and volatile constituents like sesquiterpenes and monoterpenes, are mainly attributed to the health-enhancing perspectives of ginger. This review elucidates the health claims of ginger and the molecular aspects and targets, with special reference to anticancer perspectives, immunonutrition, antioxidant potential, and cardiovascular cure. The molecular targets involved in chemoprevention like the inhibition of NF-κB activation via impairing nuclear translocation, suppresses cIAP1 expression, increases caspase-3/7 activation, arrests cell cycle in G2 + M phases, up-regulates Cytochrome-c, Apaf-1, activates PI3K/Akt/I kappaB kinases IKK, suppresses cell proliferation, and inducts apoptosis and chromatin condensation. Similarly, facts are presented regarding the anti-inflammatory response of ginger components and molecular targets including inhibition of prostaglandin and leukotriene biosynthesis and suppression of 5-lipoxygenase. Furthermore, inhibition of phosphorylation of three mitogen-activated protein kinases (MAPKs), extracellular signal-regulated kinases 1 and 2 (ERK1/2), and c-Jun N-terminal kinase (JNK) are also discussed. The role of ginger in reducing the extent of cardiovascular disorders, diabetes mellitus, and digestive problems has also been described in detail. Although, current review articles summarized the literature pertaining to ginger and its components. However, authors are still of the view that further research should be immediately carried out for meticulousness.

  12. 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

  13. Physiological and molecular aspects of cobalamin transport.

    PubMed

    Fedosov, Sergey N

    2012-01-01

    Minute doses of a complex cofactor cobalamin (Cbl, vitamin B12) are essential for metabolism. The nutritional chain for humans includes: (1) production of Cbl by bacteria in the intestinal tract of herbivores; (2) accumulation of the absorbed Cbl in animal tissues; (3) consumption of food of animal origin. Most biological sources contain both Cbl and its analogues, i.e. Cbl-resembling compounds physiologically inactive in animal cells. Selective assimilation of the true vitamin requires an interplay between three transporting proteins - haptocorrin (HC), intrinsic factor (IF), transcobalamin (TC) - and several receptors. HC is present in many biological fluids, including gastric juice, where it assists in disposal of analogues. Gastric IF selectively binds dietary Cbl and enters the intestinal cells via receptor-mediated endocytosis. Absorbed Cbl is transmitted to TC and delivered to the tissues with blood flow. The complex transport system guarantees a very efficient uptake of the vitamin, but failure at any link causes Cbl-deficiency. Early detection of a negative B12 balance is highly desirable to prevent irreversible neurological damages, anaemia and death in aggravated cases. The review focuses on the molecular mechanisms of cobalamin transport with emphasis on interaction of corrinoids with the specific proteins and protein-receptor recognition. The last section briefly describes practical aspects of recent basic research concerning early detection of B12-related disorders, medical application of Cbl-conjugates, and purification of corrinoids from biological samples.

  14. Molecular and Cellular Aspects of Rhabdovirus Entry

    PubMed Central

    Albertini, Aurélie A. V.; Baquero, Eduard; Ferlin, Anna; Gaudin, Yves

    2012-01-01

    Rhabdoviruses enter the cell via the endocytic pathway and subsequently fuse with a cellular membrane within the acidic environment of the endosome. Both receptor recognition and membrane fusion are mediated by a single transmembrane viral glycoprotein (G). Fusion is triggered via a low-pH induced structural rearrangement. G is an atypical fusion protein as there is a pH-dependent equilibrium between its pre- and post-fusion conformations. The elucidation of the atomic structures of these two conformations for the vesicular stomatitis virus (VSV) G has revealed that it is different from the previously characterized class I and class II fusion proteins. In this review, the pre- and post-fusion VSV G structures are presented in detail demonstrating that G combines the features of the class I and class II fusion proteins. In addition to these similarities, these G structures also reveal some particularities that expand our understanding of the working of fusion machineries. Combined with data from recent studies that revealed the cellular aspects of the initial stages of rhabdovirus infection, all these data give an integrated view of the entry pathway of rhabdoviruses into their host cell. PMID:22355455

  15. Aspects of integrable and conformal field theories

    NASA Astrophysics Data System (ADS)

    Moriconi, Marco

    1997-08-01

    In this thesis we study integrable N = 1 supersymmetric theories in two dimensions that are described as deformations of certain superconformal field theories. These superconformal field theories are non-unitary minimal models of central charges given by cn = [- ]3n(4n + 3)/(2n + 2)/ (cn models) where n = 1,2,/.... These models are the supersymmetrization of the generalized Yang-Lee model and can be obtained as reductions of the supersymmetric sine-Gordon model at some specific values of the coupling constant. After an introduction where we review some of the main aspects of two-dimensional CFT and factorizable scattering we study the thermodynamics of the supersymmetric generalized Yang-Lee models and diagonalize the transfer matrix, obtaining the Thermodynamic Bethe Ansatz (TBA) equations. These equations allow us to compute the ground state energy for a system of N particles in a circle of radius R and we compare the results against the predictions from CFT. This check rules out the necessity of CDD factors and confirms the conjectured S-matrix. We prove a conjecture put forward by E. Melzer relating some TBA systems of N = 2 models and the ones we study. We study the supersymmetric generalized Yang-Lee models on a half-line and find their exact reflection matrix. We prove that the ratio of the amplitudes of reflection for bosons and fermions in the same super-multiplet is universal and extend these results to systems with topological charges. We also find the reflection matrices fur the breathers in the susy sine-Gordon model. Based on a semiclassical analysis we relate the reflection matrices to the actions that preserve integrability and supersymmetry proposed by Inami, Odake and Zhang.

  16. Clinical and molecular aspects of malaria fever.

    PubMed

    Oakley, Miranda S; Gerald, Noel; McCutchan, Thomas F; Aravind, L; Kumar, Sanjai

    2011-10-01

    Although clinically benign, malaria fever is thought to have significant relevance in terms of parasite growth and survival and its virulence which in turn may alter the clinical course of illness. In this article, the historical literature is reviewed, providing some evolutionary perspective on the genesis and biological relevance of malaria fever, and the available molecular data on the febrile-temperature-inducible parasite factors that may contribute towards the regulation of parasite density and alteration of virulence in the host is also discussed. The potential molecular mechanisms that could be responsible for the induction and regulation of cyclical malaria fevers caused by different species of Plasmodium are also discussed.

  17. [Congenital fructose intolerance. New molecular aspects].

    PubMed

    Larsen, K; Adnanes, O; Aarskog, N K; Runde, I; Ogreid, D

    1994-11-20

    Hereditary fructose intolerance is a human autosomal recessive disease caused by a deficiency of aldolase B that results in an inability to metabolize fructose and related sugars. Molecular analyses have shown that most defects are caused by point mutations in critical regions of the aldolase B gene. We have performed PCR-based DNA analysis of members of two Norwegian families with hereditary fructose intolerance. The affected individuals from both families contained a point mutation (A149P) in exon 5 of the aldolase B gene. Molecular diagnosis of fructose intolerance is rapid and specific, and causes no inconvenience to the patient. It should be preferred to conventional fructose intolerance tests and visceral biopsy analyses.

  18. 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.

  19. Cytogenetic and molecular aspects of lung cancer.

    PubMed

    Panani, Anna D; Roussos, Charis

    2006-07-28

    Lung cancer is one of the most common cancers worldwide and its pathogenesis is closely associated with tobacco smoking. Continuous exposure of smoking carcinogens results in the accumulation of several alterations of tumorigenesis related genes leading to neoplastic bronchial lesions. Lung cancer is divided in two main histological groups, non-small cell lung carcinomas (NSCLCs) and small cell lung carcinomas (SCLCs). It seems that lung tumorigenesis is a multistep process in which a number of genetic events including alterations of oncogenes and tumor suppressor genes have been occurred. Cytogenetic abnormalities in lung cancer are very complex. However, a number of recurrent cytogenetic abnormalities have been identified. Many of these changes are common in both major histological groups of lung cancer while certain chromosomal abnormalities have been correlated with the stage or the grade of the tumors. In addition, several molecular alterations have been constantly found. Some of them are common in different histological subtypes of lung cancer and they appear to play an important role in the pathogenesis of lung cancer. A good understanding of the underlying genetic changes of lung tumorigenesis will provide new perspectives for early diagnosis and screening of high-risk individuals. In addition, a number of genetical prognostic factors have been identified as possibly helpful parameters in the evaluation of lung cancer patients. Further research is required in order to systematically investigate genetical alterations in lung cancer contributing to improvement of lung cancer classification and staging and to development of new molecular targeted therapies.

  20. [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.

  1. Cellular and molecular aspects of Goodpasture syndrome.

    PubMed

    Alenzi, Faris Q; Salem, Mohamed L; Alenazi, Fawwaz A; Wyse, Richard K

    2012-01-01

    Goodpasture syndrome, a rare human autoimmune disorder, is characterized by the presence of pathogenic autoantibodies that react with the components of the glomerular basement membrane. The clinical condition of the Goodpasture syndrome is characterized by an acute necrotizing glomerulonephritis, often with accompanying pulmonary hemorrhage. Notably, the Goodpasture antigen has been localized to the noncollagenous domain of the alpha3 chain of type IV collagen. Additionally, human leukocyte antigen-DR2, and to a lesser extent human leukocyte antigen-DR4, have been identified as important restriction elements. The role of T cells in Goodpasture syndrome is indicated by the highly restricted specificity of the antibody response and the strong major histocompatibility complex class II association. In this review article, we briefly describe the latest views on the molecular and cellular themes of Goodpasture syndrome.

  2. Obesity: genetic, molecular, and environmental aspects.

    PubMed

    Barness, Lewis A; Opitz, John M; Gilbert-Barness, Enid

    2007-12-15

    Obesity has emerged as one of the most serious public health concerns in the 21st century. Obese children tend to become obese adults. The dramatic rise in pediatric obesity closely parallels the rapid increase in the prevalence of adult obesity. As overweight children become adults they face the multitude of health problems associated with obesity at younger ages. The morbidity and mortality associated with obesity continue to increase. Obesity is one of the leading causes of preventable death. Complications of obesity include cardiovascular risks, hypertension, dyslipidemia, endothelial dysfunction, type 2 diabetes mellitus and impaired glucose tolerance, acanthosis nigricans, hepatic steatosis, premature puberty, hypogonadism and polycystic ovary syndrome, obstructive sleep disorder, orthopedic complications, cholelithiasis and pseudotumor cerebri. Genetic and molecular and environmental factors play an important role in the assessment and management of obesity.

  3. Clinical and molecular aspects of severe malaria.

    PubMed

    Kirchgatter, Karin; Del Portillo, Hernando A

    2005-09-01

    The erythrocytic cycle of Plasmodium falciparum presents a particularity in relation to other Plasmodium species that infect man. Mature trophozoites and schizonts are sequestered from the peripheral circulation due to adhesion of infected erythrocytes to host endothelial cells. Modifications in the surface of infected erythrocytes, termed knobs, seem to facilitate adhesion to endothelium and other erythrocytes. Adhesion provides better maturation in the microaerophilic venous atmosphere and allows the parasite to escape clearance by the spleen which recognizes the erythrocytes loss of deformability. Adhesion to the endothelium, or cytoadherence, has an important role in the pathogenicity of the disease, causing occlusion of small vessels and contributing to failure of many organs. Cytoadherence can also describe adhesion of infected erythrocytes to uninfected erythrocytes, a phenomenon widely known as rosetting. Clinical aspects of severe malaria, as well as the host receptors and parasite ligands involved in cytoadherence and rosetting, are reviewed here. The erythrocyte membrane protein 1 of P. falciparum (PfEMP1) appears to be the principal adhesive ligand of infected erythrocytes and will be discussed in more detail. Understanding the role of host receptors and parasite ligands in the development of different clinical syndromes is urgently needed to identify vaccination targets in order to decrease the mortality rates of this disease.

  4. [Molecular-genetic aspects of congenital hypothyroidism].

    PubMed

    Lacka, Katarzyna; Ogrodowicz, Agnieszka

    2004-01-01

    Congenital hypothyroidism manifests a complex of symptoms caused by a total lack or significant deficiency of thyroxine (T4) and triiodothyronine (T3) in foetal life and in the first years of child's life. The incidence of congenital hypothyroidism is 1 per 3000-4000 newborns in the world and l per 4800 in Poland. There are two main causes of congenital hypothyroidism: defects of thyroid development (about 90%), defects of thyroid hormones biosynthesis (~10%), and the more seldom occurring defects of the TBG proteins (thyroxine binding globulin) or resistance. syndrome to thyroid hormones. Defects of thyroid gland development include ectopia, hypoplasia or complete lack of the thyroid (athyreosis). These defects are caused by immunological, factors, drugs as well as genetic factors such as: TSH receptor gene or thyroid transcription factors: PAX 8. TTF l, TTF 2, Pit 1, Prop 1. Defects of thyroid hormones biosynthesis are inherited as autosomal recessive. There are 5 main defects of thyroid hormones biosynthesis: iodide transport (mutation of hNIS gene), iodine oxygenation (mutation of TPO, THOX, PDS genes), the iodination of the tyrosine of thyroglobulin and their conjunction (the mutation of TPO TG, PDS genes), the hydrolysis of the T3 and T4 as well as deiodination. Searching molecular-genetic basis of congenital hypothyroidism may improve its diagnostics, make possible to introduce genetic examination among patients with congenital hypothyroidism and their family members and may make gene therapy possible in the future.

  5. Molecular and Clinical Aspects of Angelman Syndrome.

    PubMed

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

    2012-04-01

    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.

  6. 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

  7. Molecular aspects of flower development in grasses.

    PubMed

    Ciaffi, Mario; Paolacci, Anna Rita; Tanzarella, Oronzo Antonio; Porceddu, Enrico

    2011-12-01

    The grass family (Poaceae) of the monocotyledons includes about 10,000 species and represents one of the most important taxa among angiosperms. Their flower morphology is remarkably different from those of other monocotyledons and higher eudicots. The peculiar floral structure of grasses is the floret, which contains carpels and stamens, like eudicots, but lacks petals and sepals. The reproductive organs are surrounded by two lodicules, which correspond to eudicot petals, and by a palea and lemma, whose correspondence to eudicot organs remains controversial. The molecular and genetic analysis of floral morphogenesis and organ specification, primarily performed in eudicot model species, led to the ABCDE model of flower development. Several genes required for floral development in grasses correspond to class A, B, C, D, and E genes of eudicots, but others appear to have unique and diversified functions. In this paper, we outline the present knowledge on the evolution and diversification of grass genes encoding MIKC-type MADS-box transcription factors, based on information derived from studies in rice, maize, and wheat. Moreover, we review recent advances in studying the genes involved in the control of flower development and the extent of structural and functional conservation of these genes between grasses and eudicots.

  8. 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

  9. Noonan Syndrome: Clinical Aspects and Molecular Pathogenesis

    PubMed Central

    Tartaglia, M.; Zampino, G.; Gelb, B.D.

    2010-01-01

    Noonan syndrome (NS) is a relatively common, clinically variable and genetically heterogeneous developmental disorder characterized by postnatally reduced growth, distinctive facial dysmorphism, cardiac defects and variable cognitive deficits. Other associated features include ectodermal and skeletal defects, cryptorchidism, lymphatic dysplasias, bleeding tendency, and, rarely, predisposition to hematologic malignancies during childhood. NS is caused by mutations in the PTPN11, SOS1, KRAS, RAF1, BRAF and MEK1 (MAP2K1) genes, accounting for approximately 70% of affected individuals. SHP2 (encoded by PTPN11), SOS1, BRAF, RAF1 and MEK1 positively contribute to RAS-MAPK signaling, and possess complex autoinhibitory mechanisms that are impaired by mutations. Similarly, reduced GTPase activity or increased guanine nucleotide release underlie the aberrant signal flow through the MAPK cascade promoted by most KRAS mutations. More recently, a single missense mutation in SHOC2, which encodes a cytoplasmic scaffold positively controlling RAF1 activation, has been discovered to cause a closely related phenotype previously termed Noonan-like syndrome with loose anagen hair. This mutation promotes aberrantly acquired N-myristoylation of the protein, resulting in its constitutive targeting to the plasma membrane and dysregulated function. PTPN11, BRAF and RAF1 mutations also account for approximately 95% of LEOPARD syndrome, a condition which resembles NS phenotypically but is characterized by multiple lentigines dispersed throughout the body, café-au-lait spots, and a higher prevalence of electrocardiographic conduction abnormalities, obstructive cardiomyopathy and sensorineural hearing deficits. These recent discoveries demonstrate that the substantial phenotypic variation characterizing NS and related conditions can be ascribed, in part, to the gene mutated and even the specific molecular lesion involved. PMID:20648242

  10. 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

  11. 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

  12. [Methodological aspects of integrated care pathways].

    PubMed

    Gomis, R; Mata Cases, M; Mauricio Puente, D; Artola Menéndez, S; Ena Muñoz, J; Mediavilla Bravo, J J; Miranda Fernández-Santos, C; Orozco Beltrán, D; Rodríguez Mañas, L; Sánchez Villalba, C; Martínez, J A

    An Integrated Healthcare Pathway (PAI) is a tool which has as its aim to increase the effectiveness of clinical performance through greater coordination and to ensure continuity of care. PAI places the patient as the central focus of the organisation of health services. It is defined as the set of activities carried out by the health care providers in order to increase the level of health and satisfaction of the population receiving services. The development of a PAI requires the analysis of the flow of activities, the inter-relationships between professionals and care teams, and patient expectations. The methodology for the development of a PAI is presented and discussed in this article, as well as the success factors for its definition and its effective implementation. It also explains, as an example, the recent PAI for Hypoglycaemia in patients with Type 2 Diabetes Mellitus developed by a multidisciplinary team and supported by several scientific societies. Copyright © 2017 SECA. Publicado por Elsevier España, S.L.U. All rights reserved.

  13. Aspects of molecular diagnostics and therapy in obstetrics and gynecology.

    PubMed

    Beckmann, Matthias W; Strick, Reiner; Strissel, Pamela L; Fasching, Peter A; Oppelt, Peter; Pöhls, Uwe D; Malur, Sabine U; Ackermann, Sven

    2003-05-01

    Scientific progress and information relating to the theoretical and clinical work being carried out in the field of obstetrics and gynecology has dramatically increased due to recent developments in molecular biology. Molecular obstetrics and gynecology is therefore the link between the different sections in obstetrics and gynecology. At present, the molecular understanding of cellular pathways is much greater than that of the direct integration of molecular diagnostics and therapy in routine clinical practice. The use of molecular diagnostics, such as preimplantation diagnostics or predictive genetic testing, still has technical problems as well as novel, and to date unclear, social, ethical and legal implications. To date, the technical elements of molecular therapy have not yet fulfilled their expectations. In the broad spectrum of obstetrics and gynecology, new molecular discoveries are influenced not only by technical but also by socioeconomic and political considerations. These include, for example, free access to genetic testing, patents for genes and the financial monopoly over molecular medication. Society must propose rules for the potential integration of the knowledge of molecular obstetrics and gynecology into the daily care of those seeking aid or advice.

  14. New intracellular and molecular aspects in pathophysiology of colorectal cancer

    PubMed Central

    Ziapour, Payman; Shadifar, Mohammad; Vaillancourt, Cathy; Ahmadi, Ali; Jafari-Sabet, Majid; Ataee, Amin

    2011-01-01

    Colorectal cancer is one of the most common malignancy in the world and the second cancer-related death, many molecular and genetic aspects of this disease have been cleared as chromosomal instability and the role of some key proteins as WNT/β catenin, trypsin and others. Also recently the role of folate turnover and some neurotransmitters as serotonin were also considered. The scope of this review is to describe some details about new molecular pathways suggested for occurrence or progress of this disease. PMID:24834156

  15. Molecular and functional aspects of menstruation in the macaque.

    PubMed

    Brenner, Robert M; Slayden, Ov D

    2012-12-01

    Much of our understanding of the molecular control of menstruation arises from laboratory models that experimentally recapitulate some, but not all, aspects of uterine bleeding observed in women. These models include: in vitro culture of endometrial explants or isolated endometrial cells, transplantation of human endometrial tissue into immunodeficient mice and the induction of endometrial breakdown in appropriately pretreated mice. Each of these models has contributed to our understanding of molecular and cellular mechanisms of menstruation, but nonhuman primates, especially macaques, are the animal model of choice for evaluating therapies for menstrual disorders. In this chapter we review some basic aspects of menstruation, with special emphasis on the macaque model and its relevance to the clinical issues of irregular and heavy menstrual bleeding (HMB).

  16. 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.

  17. Bacteroides thetaiotaomicron in the gut: molecular aspects of their interaction.

    PubMed

    Zocco, M A; Ainora, M E; Gasbarrini, G; Gasbarrini, A

    2007-08-01

    The gut microflora can be considered a metabolically active organ composed of a vast and complex community of microorganisms that has an important role in the stability and functional activity of the intestinal ecosystem. Recently, thanks to microarray technology, a global screening of the microflora's regulated genes has allowed the analysis of the complex bacteria-host interplay. In particular, most of our knowledge comes from studies on Bacteroides thetaiotaomicron, a prominent member of the intestinal microflora of mice and humans. The results of published studies have revealed that Bacteroides thetaiotaomicron modulate the expression of a large quantity of genes implicated in different aspect of host physiology. This review aims to illustrate the specific contributions of this intestinal microorganism in three important aspects of host physiology: mucosal barrier reinforcement, immune system modulation and nutrients metabolism. In particular, we focus on recent insights about the molecular mechanisms by which Bacteroides thetaiotaomicron help the host in these important functions.

  18. 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

  19. Quality control and integration aspects of vehicle location systems

    NASA Astrophysics Data System (ADS)

    Tiberius, C. C. J. M.

    1991-08-01

    Quality control and integration aspects of vehicle location systems are addressed in a feasibility study of an integrated navigation system for vehicle location applications. The data handling of such an integrated navigation system is implemented by means of a Kalman filter. The Kalman filter model consists of a dynamic model, which describes the motions of the vehicle, and a measurement model, which relates all kinds of observables to the system. Simulations were carried out in order to gain insight in the process of designing an optimal filter (optimal in the sense of precision and reliability). The theory of quality control appears to be feasible to operate in vehicle navigation. The navigation system considered consists of an arbitrary radio or satellite positioning system (coordinate observables), an (differential) odometer (observable velocity or distance travelled), and a magnetic compass (observable heading). The results of this system may serve as an indication of how to design a vehicle location system.

  20. Photophysical aspects of molecular probes near nanostructured gold surfaces.

    PubMed

    Ghosh, Sujit Kumar; Pal, Tarasankar

    2009-05-28

    Highly ordered, self-organized assemblies of organic molecules at surfaces of metal particles with sizes in the nanometer regime have been a subject of immense interest in recent years. Amongst the metal nanoparticles, considering the nobility of gold, organic fluoroprobes have often been attached to the surfaces of gold nanoparticles to form an extended network for potential technological applications. These organic-inorganic hybrid nanoassemblies offer an efficient route for the patterning of surfaces with functional nanometer-scale architectures utilizing several non-covalent intermolecular bonding interactions, e.g., hydrogen bonding, coordination bonding, etc. There is a growing recognition of fluorescence spectroscopy to achieve a molecular level understanding of the physical and chemical aspects of the molecule-surface interactions. The fluorophore-bound gold nanoparticles provide a convenient way to examine the mechanistic details of various deactivation pathways of the photoexcited fluoroprobes, such as energy and electron transfer to the particles as well as different types of intermolecular interactions involved in producing the bottom-up assembly of tailored nanostructures with a wide variety of structures and properties. The understanding of electronic absorption and dynamics in nanoparticulate systems is essential before assembling them into devices, which is essentially the future goal of the use of nanostructured systems. It is, therefore, important to elucidate the particle size and distance dependence on the interaction between excited molecular probes and the gold nanoparticles. The potential impact of the derived nanopatterned surfaces ranges from applications in molecular electronics to selective sensors to diagnostic devices. The greatest promise of these systems lies in the potential to tune functional aspects of the supramolecular assemblies at surfaces by manipulation of the interactions governing the derivation of supramolecular function

  1. Energy Aspects of Thermal Molecular Switching: Molecular Thermal Hysteresis of Helicene Oligomers.

    PubMed

    Shigeno, Masanori; Kushida, Yo; Yamaguchi, Masahiko

    2015-07-20

    Molecular switching is a phenomenon by which a molecule reversibly changes its structure and state in response to external stimuli or energy. Herein, molecular switching is discussed from thermodynamic and kinetic aspects in terms of energy supply with an emphasis on the thermal switching exhibited by helicene oligomers. It includes the inversion of relative thermodynamic stability induced by temperature changes and molecular thermal hysteresis in a closed system. The thermal phenomenon associated with the oligomers involves population/concentration changes between metastable states under nonequilibrium thermodynamic control.

  2. Molecular aspects of cyclophilins mediating therapeutic actions of their ligands.

    PubMed

    Galat, Andrzej; Bua, Jacqueline

    2010-10-01

    Cyclosporine A (CsA) is an immunosuppressive cyclic peptide that binds with a high affinity to 18 kDa human cyclophilin-A (hCyPA). CsA and its several natural derivatives have some pharmacological potential in treatment of diverse immune disorders. More than 20 paralogues of CyPA are expressed in the human body while expression levels and functions of numerous ORFs encoding cyclophilin-like sequences remain unknown. Certain derivatives of CsA devoid of immunosuppressive activity may have some potential in treatments of Alzheimer diseases, Hepatitis C and HIV infections, amyotrophic lateral sclerosis, congenital muscular dystrophy, asthma and various parasitic infections. Here, we discuss structural and functional aspects of the human cyclophilins and their interaction with various intra-cellular targets that can be under the control of CsA or its complexes with diverse cyclophilins that are selectively expressed in different cellular compartments. Some molecular aspects of the cyclophilins expressed in parasites invading humans and causing diseases were also analyzed.

  3. 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

  4. Integrating molecular biology into the veterinary curriculum.

    PubMed

    Ryan, Marion T; Sweeney, Torres

    2007-01-01

    The modern discipline of molecular biology is gaining increasing relevance in the field of veterinary medicine. This trend must be reflected in the curriculum if veterinarians are to capitalize on opportunities arising from this field and direct its development toward their own goals as a profession. This review outlines current applications of molecular-based technologies that are relevant to the veterinary profession. In addition, the current techniques and technologies employed within the field of molecular biology are discussed. Difficulties associated with teaching a subject such as molecular biology within a veterinary curriculum can be alleviated by effectively integrating molecular topics throughout the curriculum, pitching the subject at an appropriate depth, and employing varied teaching methods throughout.

  5. Molecular Slater Integrals for Electronic Energy Calculations

    DTIC Science & Technology

    2010-10-15

    Facultad de Ciencias . Departamento de Quı́mica Fı́sica Aplicada. C-XIV. Abstract The algorithms for computing molecular integrals with Slater functions...and propulsion sciences research programs. This extension requires a thorough revision on the performance of the algorithms currently available and

  6. Cellular and Molecular Aspects of Dyssynchrony and Resynchronization

    PubMed Central

    Kirk, Jonathan A.; Kass, David A.

    2015-01-01

    Synopsis Dyssynchronous contraction of the ventricle, arising from electrical activation delays, significantly worsens morbidity and mortality in heart failure (HF) patients. Approximately one third of HF patients have cardiac dyssynchrony and are candidates for the pacemaker therapy Cardiac Resynchronization Therapy (CRT), which uses bi-ventricular pacing to recoordinate contraction. The initial understanding of both dyssynchrony and CRT was in terms of global mechanics and hemodynamics, but lack of clinical benefit in a sizable sub-group of recipients who appear otherwise appropriate has challenged this paradigm. Using large animal models and some human data, a framework of complex molecular and cellular mechanisms of cardiac dyssynchrony and CRT is emerging. Heart failure with dyssynchrony exhibits depressed myocyte and myofilament function, calcium handling, survival signaling, interstitial remolding, altered mitochondrial function, bioenergetics, myocyte structure, and other defects. Many of these are improved by CRT, and in a manner that seems unique to this treatment. Here we review current understanding of these cellular and sub-cellular mechanisms, making the case that these aspects are key to improving CRT utilization, as well as translating its benefits to a wider heart failure population. PMID:26596804

  7. 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

  8. Physical and material science aspects of integrated optoelectronics

    NASA Astrophysics Data System (ADS)

    Ermakov, Oleg N.

    2007-05-01

    Physical, material science and technological aspects (adequate material and substrate choice, different physical effects and limitations of modern simulation methods) are discussed. Analysis of modern microelectronics and optoelectronics development trends shows that rigid boundaries between microoelectronics and optoelectronics are smearing. Wide materials range previously used only in optoelectronics ( A 3 B 5 - , A2 B 6 -, A 4 B 4 - compounds, their sold alloys, diamond, organic material etc.) are now of interest for LSI designers also. Although wide range of different substrates types (organic and inorganic, single crystalline and amorphous, rigid and flexible) are now used in optoelectronics optically transparent and electrically insulating substrates are preferable for integrated optoelectronics. One type of such substrates namely sapphire is of essential practical interest now because silicon on sapphire (SOS) structures are used for LSI implementation and gallium nitride and its alloys on sapphire stwctures (GNS) are used for super bright LEDs, LDs and photodetectors fabrication. Special attention is paid to optical properties of organic structures as very promising media both for integrated optoelectronics and microelectronics. Different physical effects (band structure, quantum, disorder, strain, carrier heating effects) as well as limitations of modern simulation methods are discussed.

  9. Brugada Syndrome: Clinical, Genetic, Molecular, Cellular, and Ionic Aspects.

    PubMed

    Antzelevitch, Charles; Patocskai, Bence

    2016-01-01

    Brugada syndrome (BrS) is an inherited cardiac arrhythmia syndrome first described as a new clinical entity in 1992. Electrocardiographically characterized by distinct coved type ST segment elevation in the right-precordial leads, the syndrome is associated with a high risk for sudden cardiac death in young adults, and less frequently in infants and children. The electrocardiographic manifestations of BrS are often concealed and may be unmasked or aggravated by sodium channel blockers, a febrile state, vagotonic agents, as well as by tricyclic and tetracyclic antidepressants. An implantable cardioverter defibrillator is the most widely accepted approach to therapy. Pharmacologic therapy is designed to produce an inward shift in the balance of currents active during the early phases of the right ventricular action potential (AP) and can be used to abort electrical storms or as an adjunct or alternative to device therapy when use of an implantable cardioverter defibrillator is not possible. Isoproterenol, cilostazol, and milrinone boost calcium channel current and drugs like quinidine, bepridil, and the Chinese herb extract Wenxin Keli inhibit the transient outward current, acting to diminish the AP notch and thus to suppress the substrate and trigger for ventricular tachycardia or fibrillation. Radiofrequency ablation of the right ventricular outflow tract epicardium of patients with BrS has recently been shown to reduce arrhythmia vulnerability and the electrocardiographic manifestation of the disease, presumably by destroying the cells with more prominent AP notch. This review provides an overview of the clinical, genetic, molecular, and cellular aspects of BrS as well as the approach to therapy.

  10. Brugada Syndrome. Clinical, Genetic, Molecular, Cellular and Ionic Aspects

    PubMed Central

    Antzelevitch, Charles; Patocskai, Bence

    2015-01-01

    The Brugada syndrome (BrS) is an inherited cardiac arrhythmia syndrome first described as a new clinical entity in 1992. Electrocardiographically characterized by distinct coved type ST segment elevation in the right precordial leads, the syndrome is associated with a high risk for sudden cardiac death in young adults, and less frequently in infants and children. The ECG manifestations of the BrS are often concealed and may be unmasked or aggravated by sodium channel blockers, a febrile state, vagotonic agents, as well as by tricyclic and tetracyclic antidepressants. An implantable cardioverter defibrillator (ICD) is the most widely accepted approach to therapy. Pharmacological therapy is designed to produce an inward shift in the balance of currents active during the early phases of the right ventricular action potential and can be used to abort electrical storms or as an adjunct or alternative to device therapy when use of an ICD is not possible. Isoproterenol, cilostazol and milrinone boost calcium channel current and drugs like quinidine, bepridil and the Chinese herb extract Wenxin Keli inhibit the transient outward current, acting to diminish the action potential (AP) notch and thus to suppress the substrate and trigger for VT/VF. Radiofrequency ablation of the right ventricular outflow tract epicardium of BrS patients has recently been shown to reduce arrhythmia-vulnerability and the ECG-manifestation of the disease, presumably by destroying the cells with more prominent AP notch. This review provides an overview of the clinical, genetic, molecular and cellular aspects of the BrS as well as the approach to therapy. PMID:26671757

  11. [Williams syndrome: its clinical aspects and molecular bases].

    PubMed

    Antonell, A; Del Campo, M; Flores, R; Campuzano, V; Perez-Jurado, L A

    2006-01-07

    Williams syndrome is a developmental disorder with an estimated prevalence of 1 in 7,500 newborns. Its phenotype is characterized by distinctive facial features, mild to moderate mental retardation and general cognitive deficits with a non-uniform profile, having problems in some areas (psychomotricity, visuospatial integration) and relative preservation of others (language, musicality), friendly personality, occasional hypercalcemia of infancy, and a vasculopathy with supravalvular aortic stenosis. Williams syndrome is caused by a submicroscopic deletion of 1.55 Mb in the chromosome band 7q11.23, which includes 26-28 genes. The mutational mechanism consists in a misalignment between regions of almost identical sequence and the subsequent unequal recombination. The reciprocal product of this rearrangement is the duplication of this region, causing a language specific disorder. Clinical-molecular correlations establishment through a good phenotypic characterization and the precise analysis of breakpoints in patients with atypical and typical deletions, altogether with the design of animal models and functional studies in vitro for the genes of the interval will be important to be able to determine the exact contribution of the genes to the phenotype, to know their pathogenesis and physiopathology, and to identify therapeutic methods.

  12. Clinical, Cellular, and Molecular Aspects in the Pathophysiology of Rosacea

    PubMed Central

    Steinhoff, Martin; Buddenkotte, Jörg; Aubert, Jerome; Sulk, Mathias; Novak, Pawel; Schwab, Verena D.; Mess, Christian; Cevikbas, Ferda; Rivier, Michel; Carlavan, Isabelle; Déret, Sophie; Rosignoli, Carine; Metze, Dieter; Luger, Thomas A.; Voegel, Johannes J.

    2013-01-01

    Rosacea is a chronic inflammatory skin disease of unknown etiology. Although described centuries ago, the pathophysiology of this disease is still poorly understood. Epidemiological studies indicate a genetic component, but a rosacea gene has not been identified yet. Four subtypes and several variants of rosacea have been described. It is still unclear whether these subtypes represent a “developmental march” of different stages or are merely part of a syndrome that develops independently but overlaps clinically. Clinical and histopathological characteristics of rosacea make it a fascinating “human disease model” for learning about the connection between the cutaneous vascular, nervous, and immune systems. Innate immune mechanisms and dysregulation of the neurovascular system are involved in rosacea initiation and perpetuation, although the complex network of primary induction and secondary reaction of neuroimmune communication is still unclear. Later, rosacea may result in fibrotic facial changes, suggesting a strong connection between chronic inflammatory processes and skin fibrosis development. This review highlights recent molecular (gene array) and cellular findings and aims to integrate the different body defense mechanisms into a modern concept of rosacea pathophysiology. PMID:22076321

  13. Molecular Imaging in Breast Cancer – Potential Future Aspects

    PubMed Central

    Pinker, Katja; Bogner, Wolfgang; Gruber, Stephan; Brader, Peter; Trattnig, Siegfried; Karanikas, Georgios; Helbich, Thomas H.

    2011-01-01

    Summary Molecular imaging aims to visualize and quantify biological, physiological, and pathological processes at cellular and molecular levels. Recently, molecular imaging has been introduced into breast cancer imaging. In this review, we will present a survey of the molecular imaging techniques that are either clinically available or are being introduced into clinical imaging. We will discuss nuclear imaging and multiparametric magnetic resonance imaging as well as the combined application of molecular imaging in the assessment of breast lesions. In addition, we will briefly discuss other evolving molecular imaging techniques, such as phosphorus magnetic resonance spectroscopic imaging and sodium imaging. PMID:21673821

  14. Quantitative molecular thermochemistry based on path integrals.

    PubMed

    Glaesemann, Kurt R; Fried, Laurence E

    2005-07-15

    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 for going beyond the harmonic analysis and to calculate the vibrational and rotational contributions to ab initio energies. This is an application and an extension of a method previously developed in our group [J. Chem. Phys. 118, 1596 (2003)].

  15. 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.

  16. 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.

  17. Bead-Fourier path integral molecular dynamics.

    PubMed

    Ivanov, Sergei D; Lyubartsev, Alexander P; Laaksonen, Aatto

    2003-06-01

    Molecular dynamics formulation of Bead-Fourier path integral method for simulation of quantum systems at finite temperatures is presented. Within this scheme, both the bead coordinates and Fourier coefficients, defining the path representing the quantum particle, are treated as generalized coordinates with corresponding generalized momenta and masses. Introduction of the Fourier harmonics together with the center-of-mass thermostating scheme is shown to remove the ergodicity problem, known to pose serious difficulties in standard path integral molecular dynamics simulations. The method is tested for quantum harmonic oscillator and hydrogen atom (Coulombic potential). The simulation results are compared with the exact analytical solutions available for both these systems. Convergence of the results with respect to the number of beads and Fourier harmonics is analyzed. It was shown that addition of a few Fourier harmonics already improves the simulation results substantially, even for a relatively small number of beads. The proposed Bead-Fourier path integral molecular dynamics is a reliable and efficient alternative to simulations of quantum systems.

  18. Bead-Fourier path integral molecular dynamics

    NASA Astrophysics Data System (ADS)

    Ivanov, Sergei D.; Lyubartsev, Alexander P.; Laaksonen, Aatto

    2003-06-01

    Molecular dynamics formulation of Bead-Fourier path integral method for simulation of quantum systems at finite temperatures is presented. Within this scheme, both the bead coordinates and Fourier coefficients, defining the path representing the quantum particle, are treated as generalized coordinates with corresponding generalized momenta and masses. Introduction of the Fourier harmonics together with the center-of-mass thermostating scheme is shown to remove the ergodicity problem, known to pose serious difficulties in standard path integral molecular dynamics simulations. The method is tested for quantum harmonic oscillator and hydrogen atom (Coulombic potential). The simulation results are compared with the exact analytical solutions available for both these systems. Convergence of the results with respect to the number of beads and Fourier harmonics is analyzed. It was shown that addition of a few Fourier harmonics already improves the simulation results substantially, even for a relatively small number of beads. The proposed Bead-Fourier path integral molecular dynamics is a reliable and efficient alternative to simulations of quantum systems.

  19. Integrating anticipated nutrigenomics bioscience applications with ethical aspects.

    PubMed

    Lévesque, Lise; Ozdemir, Vural; Gremmen, Bart; Godard, Béatrice

    2008-03-01

    Nutrigenomics is a subspecialty of nutrition science which aims to understand how gene-diet interactions influence individuals' response to food, disease susceptibility, and population health. Yet ethical enquiry into this field is being outpaced by nutrigenomics bioscience. The ethical issues surrounding nutrigenomics face the challenges of a rapidly evolving field which bring forward the additional dimension of crossdisciplinary integrative research between social and biomedical sciences. This article outlines the emerging nutrigenomics definitions and concepts and analyzes the existing ethics literature concerning personalized nutrition and presents "points to consider" over ethical issues regarding future nutrigenomics applications. The interest in nutrigenomics coincides with a shift in emphasis in medicine and biosciences toward prevention of future disease susceptibilities rather than treatment of already established disease. Hence, unique ethical issues emerge concerning the extent to which nutrigenomics can alter our relation to food, boundaries between health and disease, and the folklore of medical practice. Nutrigenomics can result in new social values, norms, and responsibilities for both individuals and societies. Nutrigenomics is not only another new application of "-omics" technologies in the context of gene-diet interactions. Nutrigenomics may fundamentally change the way we perceive human illness while shifting the focus and broadening the scope of health interventions from patients to healthy individuals. In resource- and time-limited healthcare settings, this creates unique ethical dilemmas and distributive justice issues. Ethical aspects of nutrigenomics applications should be addressed proactively, as this new science develops and increasingly coalesces with other applications of genomics in medicine and public health.

  20. STM studies of single molecules: molecular orbital aspects.

    PubMed

    Li, Bin; Li, Zhenyu; Yang, Jinlong; Hou, J G

    2011-03-14

    As a fundamental and frequently referred concept in modern chemistry, the molecular orbital plays a vital role in the science of single molecules, which has become an active field in recent years. For the study of single molecules, scanning tunneling microscopy (STM) has been proven to be a powerful scientific technique. Utilizing specific distribution of the molecular orbitals at spatial, energy, and spin scales, STM can explore many properties of single molecule systems, such as geometrical configuration, electronic structure, magnetic polarization, and so on. Various interactions between the substrate and adsorbed molecules are also understood in terms of the molecular orbitals. Molecular engineering methods, such as mode-selective chemistry based on the molecular orbitals, and resonance tunneling between the molecular orbitals of the molecular sample and STM tip, have stimulated new advances of single molecule science.

  1. 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

  2. [Aspects of molecular immunology and immunogenetics in autoimmune uveitis].

    PubMed

    Istrate, Bogdan

    2012-01-01

    Generally speaking, the uveitis comprises a relative complex group of autoimmune diseases or other autoimmune associated illness. Until now, a little from molecular and cellular mechanisms are known in the autoimmunity of uveitis. The uveitis may cause a visual handicap as well, leading even to blindness. This paper tries to bring into focus some of the molecular mechanisms and immunogenetic features of the disease.

  3. Integrating evolutionary and molecular genetics of aging.

    PubMed

    Flatt, Thomas; Schmidt, Paul S

    2009-10-01

    Aging or senescence is an age-dependent decline in physiological function, demographically manifest as decreased survival and fecundity with increasing age. Since aging is disadvantageous it should not evolve by natural selection. So why do organisms age and die? In the 1940s and 1950s evolutionary geneticists resolved this paradox by positing that aging evolves because selection is inefficient at maintaining function late in life. By the 1980s and 1990s this evolutionary theory of aging had received firm empirical support, but little was known about the mechanisms of aging. Around the same time biologists began to apply the tools of molecular genetics to aging and successfully identified mutations that affect longevity. Today, the molecular genetics of aging is a burgeoning field, but progress in evolutionary genetics of aging has largely stalled. Here we argue that some of the most exciting and unresolved questions about aging require an integration of molecular and evolutionary approaches. Is aging a universal process? Why do species age at different rates? Are the mechanisms of aging conserved or lineage-specific? Are longevity genes identified in the laboratory under selection in natural populations? What is the genetic basis of plasticity in aging in response to environmental cues and is this plasticity adaptive? What are the mechanisms underlying trade-offs between early fitness traits and life span? To answer these questions evolutionary biologists must adopt the tools of molecular biology, while molecular biologists must put their experiments into an evolutionary framework. The time is ripe for a synthesis of molecular biogerontology and the evolutionary biology of aging.

  4. Integrating Advanced Molecular Technologies into Public Health.

    PubMed

    Gwinn, Marta; MacCannell, Duncan R; Khabbaz, Rima F

    2017-03-01

    Advances in laboratory and information technologies are transforming public health microbiology. High-throughput genome sequencing and bioinformatics are enhancing our ability to investigate and control outbreaks, detect emerging infectious diseases, develop vaccines, and combat antimicrobial resistance, all with increased accuracy, timeliness, and efficiency. The Advanced Molecular Detection (AMD) initiative has allowed the Centers for Disease Control and Prevention (CDC) to provide leadership and coordination in integrating new technologies into routine practice throughout the U.S. public health laboratory system. Collaboration and partnerships are the key to navigating this transition and to leveraging the next generation of methods and tools most effectively for public health.

  5. 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.

  6. Aspects of HI behaviour in the birth of molecular clouds

    NASA Astrophysics Data System (ADS)

    Joncas, Gilles; Fortier, Pierre; Scholtys, Jeremy; Miville-Deschenes, Marc-Antoine

    2015-08-01

    Understanding the processes related to the formation and evolution of molecular clouds is essential to our understanding of the interstellar medium (ISM) at large and of star formation. High galactic latitude clouds are ideal laboratories for studying the physics of the ISM as only turbulence, magnetic fields and the interstellar radiation field come into play. Using clues from UV H2 absorption lines and by comparing IRAS dust emission to HI column density from aperture synthesis observations obtained using the DRAO interferometer, we have probed the morphology and dynamics of 14 potential molecular sites (totaling 151 square degrees), in the hopes of identifying molecular clouds at different stages of evolution. Seven sites have confirmed molecular clouds. Most are new, four of which have been observed in CO using the Onsala 20m telescope. The HI line shows varying degrees of velocity shears very probably related to the age of the molecular site. Our newobservations will be presented. Simulations of turbulent HI fields have recently been acquired andwill be compared to our observations.

  7. Molecular and Cellular Aspects of Amphibian Lens Regeneration

    PubMed Central

    Henry, Jonathan J.; Tsonis, Panagiotis A.

    2012-01-01

    Lens regeneration among vertebrates is basically restricted to some amphibians. The most notable cases are the ones that occur in premetamorphic frogs and in adult newts. Frogs and newts regenerate their lens in very different ways. In frogs the lens is regenerated by transdifferentiation of the cornea and is limited only to a time before metamorphosis. On the other hand, regeneration in newts is mediated by transdifferentiation of the pigment epithelial cells of the dorsal iris and is possible in adult animals as well. Thus, the study of both systems could provide important information about the process. Molecular tools have been developed in frogs and recently also in newts. Thus, the process has been studied at the molecular and cellular levels. A synthesis describing both systems was long due. In this review we describe the process in both Xenopus and the newt. The known molecular mechanisms are described and compared. PMID:20638484

  8. Fluorescence probes of spectroscopic and dynamical aspects of molecular photoionization

    NASA Astrophysics Data System (ADS)

    Poliakoff, Erwin D.

    1988-11-01

    Studies were made of vibrationally resolved aspects of shape resonant excitation in the photoionization of N(2)0. This experiment was performed by generating dispersed fluorescence spectra from electronically excited photoions. These results are the first vibrationally resolved results on a polyatomic shape resonance. In vibrationally resolved measurements, different internuclear configurations are probed by sampling alternative vibrational levels of the ion. As a result, the continuum electron behavior can be mapped out most clearly, and the qualitative aspects of the electron ejection can be understood clearly. A central motivation for studying polyatomic shape resonances is that alternative vibrational modes may be explored, revealing facets that are nonexistent for diatomic systems, which are the only systems that have been characterized previously.

  9. 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.

  10. Microelectromechanical systems integrating molecular spin crossover actuators

    SciTech Connect

    Manrique-Juarez, Maria D.; Rat, Sylvain; Salmon, Lionel; Molnár, Gábor; Bousseksou, Azzedine E-mail: azzedine.bousseksou@lcc-toulouse.fr; Mathieu, Fabrice; Saya, Daisuke; Séguy, Isabelle; Leïchlé, Thierry; Nicu, Liviu E-mail: azzedine.bousseksou@lcc-toulouse.fr

    2016-08-08

    Silicon MEMS cantilevers coated with a 200 nm thin layer of the molecular spin crossover complex [Fe(H{sub 2}B(pz){sub 2}){sub 2}(phen)] (H{sub 2}B(pz){sub 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 (Δf{sub r} = −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.

  11. 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.

  12. Report of the Integrative Molecular Cancer Epidemiology International Symposium, Lyon, France.

    PubMed

    Raimondi, S

    2008-01-01

    An International Symposium on Integrative Molecular Cancer Epidemiology took place in Lyon, France, on 3-5 July 2008. The Symposium focused on aetiological and mechanistic aspects of molecular and genetic cancer epidemiology research and was divided into the following three sections: Molecular epidemiology-application of novel molecular markers to cancer epidemiology.Genomic epidemiology in the era of whole genome scan.INTEGRATIVE MOLECULAR EPIDEMIOLOGY: visions for the future.Participants included epidemiologists, geneticists, biochemical and molecular biologists, pharmacologists, pathologists and all researchers interested in this field. The Symposium provided a complete and clear overview of the present and future programmes in molecular cancer epidemiology. It also served to encourage international scientific collaboration between investigators working in this specific research field, and to stimulate transdisciplinary research with experts of other research areas. Highlights of each of the scientific presentations are summarized below.

  13. Molecular aspects of renal cell carcinoma: a review

    PubMed Central

    Koul, Hari; Huh, Jung-Sik; Rove, Kyle O; Crompton, Luiza; Koul, Sweaty; Meacham, Randall B; Kim, Fernando J

    2011-01-01

    Renal cell carcinoma (RCC) is a disease in which cancer cells form in the tubules of the kidney. RCC, the incidence of which is increasing annually, represents five percent of adult epithelial cancers. Clear cell carcinoma represents the most frequent histological subtype. RCC is characterized by a lack of early warning signs, diverse clinical manifestations. Incidentally detected tumors in asymptomatic individuals have been steadily increasing owing to the increased usage of various imaging technologies. Currently there are no recommendations for screening to detect and make an early diagnosis of renal cancer. But in recent years, the discovery of new molecular and cytogenetic markers has led to the recognition and classification of several novel subtypes of RCC, and the introduction of molecular-targeted therapy for advanced-stage RCC. We performed a literature review using PubMed and discuss current knowledge of epidemiology, pathophysiology, evaluation, treatment, and future research directions of RCC. PMID:21969126

  14. 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

  15. Pathologic and molecular aspects of soft tissue sarcomas.

    PubMed

    Czerniak, Bogdan

    2003-04-01

    This article retains the conventional approach to the classification of soft tissue sarcomas, dividing them into several major histogenetic categories based on their overall microscopic appearance, tissue differentiation pattern, and biologic potential. The author advocates a multimodal approach, in which four distinctive data sets--clinical, radiographic, microscopic, and, in some cases, molecular--are considered to establish the diagnosis and treatment plan. Such step-wise analysis is more likely to lead to consistency and accuracy as compared with an intuitive approach based on fragmentary data. The author describes individual lesions of soft tissue as clinicopathologic entities and believes that they can be more accurately diagnosed and appropriately treated with the help of data generated by a multidisciplinary team. In addition, this article emphasizes the need to use emerging molecular techniques that can provide important clues for both diagnosis and prognosis.

  16. Molecular approaches to epidemiology and clinical aspects of malaria.

    PubMed

    Brown, G V; Beck, H P; Molyneux, M; Marsh, K

    2000-10-01

    Malaria is a problem of global importance, responsible for 1-2 million deaths per year, mainly in African children, as well as considerable morbidity manifested as severe anaemia and encephalopathy in young children. Fundamental to the development of new tools for malaria control in humans is an increased understanding of key features of malaria infection, such as the diversity of outcome in different individuals, the understanding of different manifestations of the disease and of the mechanisms of immunity that allow clinical protection in the face of ongoing low-grade infection (concomitant immunity or premunition). Here, Graham Brown and colleagues review some of the ways in which molecular approaches might be used to increase our understanding of the epidemiology and clinical manifestations of malaria, as discussed at the Molecular Approaches to Malaria conference (MAM2000), Lorne, Australia, 2-5 February 2000.

  17. Wntless in Wnt secretion: molecular, cellular and genetic aspects.

    PubMed

    Das, Soumyashree; Yu, Shiyan; Sakamori, Ryotaro; Stypulkowski, Ewa; Gao, Nan

    2012-12-01

    Throughout the animal kingdom, Wnt-triggered signal transduction pathways play fundamental roles in embryonic development and tissue homeostasis. Wnt proteins are modified as glycolipoproteins and are secreted into the extracellular environment as morphogens. Recent studies on the intracellular trafficking of Wnt proteins demonstrate multiple layers of regulation along its secretory pathway. These findings have propelled a great deal of interest among researchers to further investigate the molecular mechanisms that control the release of Wnts and hence the level of Wnt signaling. This review is dedicated to Wntless, a putative G-protein coupled receptor that transports Wnts intracellularly for secretion. Here, we highlight the conclusions drawn from the most recent cellular, molecular and genetic studies that affirm the role of Wntless in the secretion of Wnt proteins.

  18. Familial renal cell carcinoma: clinical and molecular genetic aspects

    PubMed Central

    Maher, E.R.; Yates, J.R.W.

    1991-01-01

    Renal cell carcinoma (RCC) accounts for 2% of all human cancer, but familial cases are infrequent. Riches (1963) and Griffin et al. (1984) in a population-based case-control study found a family history of renal cell carcinoma in 2.4% of affected patients compared to 1.4% of controls. Nevertheless the importance of inherited tumours in clinical practice and medical research is disproportionate to their frequency. In clinical practice recognition of familial RCC can provide opportunities to prevent morbidity and mortality by appropriate screening. In medical research recent advances in molecular genetics offer the prospect of isolating the genes involved in the pathogenesis of familial RCC and of the more common sporadic cases. In this article we review the clinical and molecular genetics of inherited renal cell carcinoma (adenocarcinoma or hypernephroma). PMID:1997093

  19. 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.

  20. Molecular diagnosis of sepsis: New aspects and recent developments

    PubMed Central

    Lehman, L.; Hunfeld, K.-P.; Kost, G.

    2014-01-01

    By shortening the time to pathogen identification and allowing for detection of organisms missed by blood culture, new molecular methods may provide clinical benefits for the management of patients with sepsis. While a number of reviews on the diagnosis of sepsis have recently been published we here present up-to-date new developments including multiplex PCR, mass spectrometry and array techniques. We focus on those techniques that are commercially available and for which clinical studies have been performed and published. PMID:24678402

  1. Molecular aspects of anti-atherosclerotic effects of short peptides.

    PubMed

    Khavinson, V Kh; Lin'kova, N S; Evlashkina, E V; Durnova, A O; Kozlov, K L; Gutop, O E

    2014-11-01

    We studied molecular mechanisms of the vasoprotective effects of tripeptide T-38 and dipeptide RR-1. Short peptides T-38 and the RR-1 activate the processes of cell renewal in organotypic and dissociated cultures of vascular cells during aging by increasing the expression of Ki-67 and reducing the synthesis of p53 protein. T-38 and RR-1 reduce the synthesis of E-selectin, adhesion molecule involved in the formation of atherosclerotic plaques.

  2. 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.

  3. 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

  4. Universal aspects of the chemomechanical coupling for molecular motors.

    PubMed

    Lipowsky, R

    2000-11-13

    The directed movement of molecular motors is studied theoretically within a general class of nonuniform ratchet models in which the motor can attain M internal states and undergo transitions between these states at K spatial locations. The functional relationship between the motor velocity and the concentration of the fuel molecule is analyzed for arbitrary values of M and K. This relationship is found to exhibit universal features which depend on the number of unbalanced transitions per motor cycle arising from the enzymatic motor activity. This agrees with experimental results on dimeric kinesin and is predicted to apply to other cytoskeletal motors.

  5. ASPECT

    EPA Pesticide Factsheets

    Able to deploy within one hour of notification, EPA's Airborne Spectral Photometric Environmental Collection Technology (ASPECT) is the nation’s only airborne real-time chemical and radiological detection, infrared and photographic imagery platform.

  6. Andersen-Tawil syndrome: clinical and molecular aspects.

    PubMed

    Nguyen, Hoai-Linh; Pieper, Gerard H; Wilders, Ronald

    2013-12-05

    Andersen–Tawil syndrome (ATS) is a rare hereditary multisystem disorder. Ventricular arrhythmias, periodic paralysis and dysmorphic features constitute the classic triad of ATS symptoms. The expressivity of these symptoms is, however, extremely variable, even within single ATS affected families, and not all ATS patients present with the full triad of symptoms. ATS patients may show a prolongation of the QT interval,which explains the classification as long QT syndrome type 7 (LQT7), and specific neurological or neurocognitive defects. In ATS type 1 (ATS1), the syndrome is associated with a loss-of-function mutation in the KCNJ2 gene,which encodes the Kir2.1 inward rectifier potassium channel. In ATS type 2 (ATS2), which does not differ from ATS1 in its clinical symptoms, the genetic defect is unknown. Consequently, ATS2 comprises all cases of ATS in which genetic testing did not reveal a mutation in KCNJ2. The loss-of-function mutations in KCNJ2 in ATS1 affect the excitability of both skeletal and cardiac muscle, which underlies the cardiac arrhythmias and periodic paralysis associated with ATS. Thus far, the molecular mechanism of the dysmorphic features is only poorly understood. In this review, we summarize the clinical symptoms, the underlying genetic and molecular defects, and the management and treatment of ATS.

  7. Molecular aspects of nitrogen mobilization and recycling in trees.

    PubMed

    Cantón, Francisco R; Suárez, María Fernanda; Cánovas, Francisco M

    2005-01-01

    Plants have developed a variety of molecular strategies to use limiting nutrients with a maximum efficiency. N assimilated into biomolecules can be released in the form of ammonium by plant metabolic activities in various physiological processes such as photorespiration, the biosynthesis of phenylpropanoids or the mobilization of stored reserves. Thus, efficient reassimilation mechanisms are required to reincorporate liberated ammonium into metabolism and maintain N plant economy. Although the biochemistry and molecular biology of ammonium recycling in annual herbaceous plants has been previously reported, the recent advances in woody plants need to be reviewed. Moreover, it is important to point out that N recycling is quantitatively massive during some of these metabolic processes in trees, including seed germination, the onset of dormancy and resumption of active growth or the biosynthesis of lignin that takes place during wood formation. Therefore, woody plants constitute an excellent system as a model to study N mobilization and recycling. The aim of this paper is to provide an overview of different physiological processes in woody perennials that challenge the overall plant N economy by releasing important amounts of inorganic N in the form of ammonium.

  8. Amorphous drug delivery systems: molecular aspects, design, and performance.

    PubMed

    Kaushal, Aditya Mohan; Gupta, Piyush; Bansal, Arvind Kumar

    2004-01-01

    The biopharmaceutical properties-especially the solubility and permeability-of a molecule contribute to its overall therapeutic efficacy. The newer tools of drug discovery have caused a shift in the properties of drug-like compounds, resulting in drugs with poor aqueous solubility and permeability, which offer delivery challenges, thus requiring considerable pharmaceutical manning. The modulation of solubility is a more viable option for enhancing bioavailability than permeability, because of the lack of "safe" approaches to enhance the latter. Solid-state manipulation in general, and amorphization in particular, are preferred ways of enhancing solubility and optimizing delivery of poorly soluble drugs. This review attempts to address the diverse issues pertaining to amorphous drug delivery systems. We discuss the various thermodynamic phenomenon such as glass transition, fragility, molecular mobility, devitrification kinetics, and molecular-level chemical interactions that contribute to the ease of formation, the solubility advantage, and the stability of amorphous drugs. The engineering of pharmaceutical alloys by solubilizing and stabilizing carriers, commonly termed solid dispersions, provide avenues for exploiting the benefits of amorphous systems. Carrier properties, mechanisms of drug release, and study of release kinetics help to improve the predictability of performance. The review also addresses the various barriers in the design of amorphous delivery systems, use of amorphous form in controlled release delivery systems, and their in vivo performance.

  9. 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.

  10. 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.

  11. 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

  12. Molecular Aspects of Head and Neck Cancer Therapy

    PubMed Central

    Puram, Sidharth V.; Rocco, James W.

    2015-01-01

    Synopsis In spite of a rapidly expanding understanding of head and neck tumor biology as well as optimization of radiation, chemotherapy, and surgical treatment modalities, head and neck squamous cell carcinoma (HNSCC) remains a major cause of cancer related morbidity and mortality. Although our biologic understanding of these tumors had largely been limited to pathways driving proliferation, survival, and differentiation, the identification of HPV as a major driver of HNSCC, specifically oropharyngeal SCC, as well as recent genomic sequencing analyses of HNSCC has dramatically influenced our understanding of the underlying biology behind carcinogenesis, and in part, our approach to therapy. In particular, we are at a major molecular and clinical crossroads with an explosion of promising diagnostic and therapeutic agents that hold great promise. Here, we summarize our current understanding of HNSCC biology, including a review of recent sequencing analyses, and identify promising areas for potential diagnostic and therapeutic agents. PMID:26568543

  13. 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.

  14. 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

  15. Angelman syndrome: review of clinical and molecular aspects.

    PubMed

    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.

  16. 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.

  17. Molecular and cellular aspects of protein misfolding and disease.

    PubMed

    Herczenik, Eszter; Gebbink, Martijn F B G

    2008-07-01

    Proteins are essential elements for life. They are building blocks of all organisms and the operators of cellular functions. Humans produce a repertoire of at least 30,000 different proteins, each with a different role. Each protein has its own unique sequence and shape (native conformation) to fulfill its specific function. The appearance of incorrectly shaped (misfolded) proteins occurs on exposure to environmental changes. Protein misfolding and the subsequent aggregation is associated with various, often highly debilitating, diseases for which no sufficient cure is available yet. In the first part of this review we summarize the structural composition of proteins and the current knowledge of underlying forces that lead proteins to lose their native structure. In the second and third parts we describe the molecular and cellular mechanisms that are associated with protein misfolding in disease. Finally, in the last part we portray recent efforts to develop treatments for protein misfolding diseases.

  18. Molecular and thermodynamic aspects of solubility advantage from solid dispersions.

    PubMed

    Bansal, Shyam Sunder; Kaushal, Aditya Mohan; Bansal, Arvind Kumar

    2007-01-01

    The solubility behavior of solid dispersions of two drugs with similar structures was studied. Valdecoxib (VLB) and etoricoxib (ETB) were used as model drugs, and their solid dispersions were prepared with 1, 2, 5, 10, 15, and 20% w/w poly(vinylpyrrolidone) (PVP) by the quench cooling method. The interactions between the drug and polymer molecules were studied by Fourier transform infrared spectroscopy (FT-IR). The thermodynamic aspects of solubility behavior were studied by plotting van't Hoff plots. Both the drugs showed significant differences in their solubility behavior. In the case of VLB, solubility was found to increase significantly with increasing PVP concentration. ETB however did not show any significant solubility enhancement and was found to have decreased solubility at high PVP concentrations. H-bonding interactions were established between VLB and PVP molecules, while none were observed in ETB-PVP dispersions. Solution thermodynamics of amorphous and crystalline forms of both the drugs were studied by van't Hoff plots. The results obtained showed very high negative value of Gibbs free energy for VLB as compared to ETB, thus demonstrating high spontaneity of VLB solubilization. Entropy of amorphous VLB was found to be highly favorable, while being slightly unfavorable for ETB. From this study H-bonding interactions were found to play a major role in dictating the solubility behavior of these drugs from solid dispersions.

  19. Developing a general practice medical workstation: the integration aspect.

    PubMed Central

    Frassine, R.; Bertelli, S.; Innocenti, E. B.

    1993-01-01

    ISAAC (Integrated System Architecture for Advanced Primary Care) is a project aiming at developing information technology and telematic support in the specific field of General Practice--and more broadly in the Primary Health Care sector--within the health care systems of different European Countries. The project aims at improving the work of the General Practitioners through the development of a useful and usable medical workstation for day-to-day patient care. Moreover ISAAC has the goal of prototyping an integration architecture for the improvement of the communications between the ISAAC workstation and heterogeneous application environments, namely other components of the health care system. This paper deals with a general description of the design along with a discussion of the adopted approach to fulfill the integration requirements. PMID:8130469

  20. 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.

  1. 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. © 2015 Society for Reproduction and Fertility.

  2. Biochemical and molecular aspects of spectral diagnosis in calcinosis cutis.

    PubMed

    Lin, Shan-Yang

    2014-03-11

    Calcinosis cutis (CC) is a type of calcinosis wherein insoluble compounds or salts deposited on the skin. Clinical diagnosis of CC is usually achieved through time consuming histopathological or immunohistochemical procedures, but it can only be empirically identified by experienced practitioners. The use of advanced vibrational spectroscopy has been recently shown to have great potential as a diagnostic technique for various diseased tissues because it analyses the chemical composition of diseased tissue rather than its anatomy and predicts disease progression. This review article includes a summary of the application of Fourier transform infrared (FT-IR) and Raman spectroscopic or microspectroscopic analysis for the rapid diagnosis and identification of the chemical composition of skin calcified deposits in patients with various CC symptoms. Both advanced techniques not only can detect the types of insoluble salts such as calcium phosphate, calcium carbonate, and monosodium urate, and β-carotene in the calcified deposits of human skin tissue but also can directly differentiate the carbonate substitution in the apatite structure of the skin calcified deposits. In particular, the combination of both vibrational techniques may provide complementary information to simultaneously assess the intact components of the calcified deposits. In the future, both FT-IR and Raman vibrational microspectroscopic techniques will become available tools to support the standard test techniques currently used in some clinical diagnoses. Molecular spectroscopy technique is rapidly changing disease diagnosis and management.

  3. Clinical, molecular, and pharmacological aspects of FMR1 related disorders.

    PubMed

    Pugin, A; Faundes, V; Santa María, L; Curotto, B; Aliaga, S; Salas, I; Soto, P; Bravo, P; Peña, M I; Alliende, M A

    2017-05-01

    Fragile X syndrome, the most common inherited cause of intellectual disability, is associated with a broad spectrum of disorders across different generations of a single family. This study reviews the clinical manifestations of fragile X-associated disorders as well as the spectrum of mutations of the fragile X mental retardation 1 gene (FMR1) and the neurobiology of the fragile X mental retardation protein (FMRP), and also provides an overview of the potential therapeutic targets and genetic counselling. This disorder is caused by expansion of the CGG repeat (>200 repeats) in the 5 prime untranslated region of FMR1, resulting in a deficit or absence of FMRP. FMRP is an RNA-binding protein that regulates the translation of several genes that are important in synaptic plasticity and dendritic maturation. It is believed that CGG repeat expansions in the premutation range (55 to 200 repeats) elicit an increase in mRNA levels of FMR1, which may cause neuronal toxicity. These changes manifest clinically as developmental problems such as autism and learning disabilities as well as neurodegenerative diseases including fragile X-associated tremor/ataxia syndrome (FXTAS). Advances in identifying the molecular basis of fragile X syndrome may help us understand the causes of neuropsychiatric disorders, and they will probably contribute to development of new and specific treatments. Copyright © 2014 Sociedad Española de Neurología. Publicado por Elsevier España, S.L.U. All rights reserved.

  4. [Dicentric Y chromosomes. First part: cytogenetic and molecular aspects].

    PubMed

    Bouayed Abdelmoula, N; Amouri, A

    2005-01-01

    Dicentric Y chromosomes have been reviewed twice in 1994 by Hsu et al. and in 1995 by Tuck-Muller et al. who showed that dic(Y) are the most common Y structural abnormalities and that their influence on gonadal and somatic development is extremely variable. The prediction of their phenotypic consequences is often difficult because of the variety of genomic sequences concerned by duplications and deletions, because of the variable degrees of mosaicism (cell line 45,X in particular) and at the end, because of identification and analysis technical difficulties of the structure of the rearranged Y chromosome. The clinical specter of this cytogenetic abnormality is rather wide going from almost-normal or infertile males, to females with or without stigmas of Turner syndrome. Middle phenotypes consist of various degrees of genital ambiguities. However, clinical expression seems to be related to the genomic capital of the Y chromosome, mainly the Y genes involved in the control of the process of the determination of gonads (Yp) and spermatogenesis (Yq) as well as control of the growth and the skeletal development (Yp). Here, we report a third comprehensive review of the literature concerning dicentric Y chromosomes reported since 1994. In the light of previous reviews as well as the recent data of the genetic cartography of the Y chromosome, we try, in this first part, to determine characteristics of reported dicentric Y chromosomes as well as their chromosomal mechanics, their mitotic stability and finally their cytogenetic and molecular investigations.

  5. Molecular and karyological aspects of Batoidea (Chondrichthyes, Elasmobranchi) phylogeny.

    PubMed

    Rocco, Lucia; Liguori, Innocenza; Costagliola, Domenico; Morescalchi, Maria A; Tinti, Fausto; Stingo, Vincenzo

    2007-03-01

    Although considerable progress has been made in elucidating the relationships within the Chondrichthyes, there is no agreement as it concerns the systematics of Batoidea, the most derived superorder among cartilaginous fishes, and many different interpretations exist. Our investigation provides the first assessment of relationships among the described batoid species using sequences from both mtDNA and nuclear genes as well as karyological morphology. Our work consists primarily in reconstructing the phylogenetic relationships of Batoidea by examining the mtDNA (16S) and nuclear gene (18S) sequences from 11 batoid species. The three analytical methods (NJ, MP and Bayesian analysis) grouped Rajiformes, Myliobatiformes and Rhinobatiformes. In these trees the two torpedoes diverge from the other batoid fishes. We also compare the molecular data with the available karyological evidence, which consist of the diploid number and the karyotype morphology of eight species belonging to the four orders examined. The results show that the karyological structure in the different species is generally consistent with the various phylogenetical trees, and that Torpediniformes confirm their unique genome organization.

  6. Sex chromosome changes in leukemia: cytogenetics and molecular aspects.

    PubMed

    Shahrabi, Saeid; Khodadi, Elahe; Saba, Fakhredin; Shahjahani, Mohammad; Saki, Najmaldin

    2017-09-10

    Sex chromosome loss (SCL) can occur in older men as a physiological phenomenon or as an acquired abnormality in leukemia. Loss of chromosome Y and loss of chromosome X are acquired disorders that are mainly observed in patients over 80 years as well as in myeloid and lymphoid malignancies. In this review, we examine the cytogenetic and molecular changes of sex chromosomes in leukemia. Relevant English language literature were searched and retrieved from PubMed search engine (1990-2016). The following keywords were used: 'Sex chromosomes', 'Leukemia' and 'Cytogenetics'. The loss of tumor suppressor genes along with these chromosomal abnormalities in the majority of malignant cells in bone marrow (BM) has raised the question whether this is an age-related phenomenon or has occurred as a result of clonal abnormality. On the other hand, the presence of these chromosomal abnormalities in a number of genetic diseases associated with leukemia leads to progression of malignancy, and their role in peripheral blood stem cell transplantation confirm the finding that these chromosomal abnormalities can play an important role in clonal abnormality. The presence of these abnormalities can cause genetic instability in BM and result in the development of a malignant clone and progression of the disease. In addition, the evaluation of SCL together with the genes involved in these chromosomes can contribute to predict the disease prognosis as well as monitoring of malignancy.

  7. 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.

  8. Biopsychosocial and spiritual aspects of Parkinson disease: an integrative review.

    PubMed

    Hermanns, Melinda; Deal, Belinda; Haas, Barbara

    2012-08-01

    The purpose of this study is to systematically examine the scientific literature and report the biopsychosocial and spiritual aspects of persons with Parkinson disease and their adaptation to the disease, to discuss methodological challenges associated with researching this phenomenon, and to propose future research. Synthesis of the literature will reveal the state of the science on the holistic approach to care in persons with Parkinson disease. An exhaustive review of the English language peer-reviewed literature published from January 1961 to July 2011 was conducted utilizing Academic Search Premier, MEDLINE, CINAHL, Psych Articles, Psych Info, PubMed, Wiley InterScience, the Cochrane Center Register for Control Trials, Health and Psychosocial Instruments, and SpringerLink databases. Ninety studies were reviewed. Although numerous medical studies focusing on pharmacological agents for Parkinson disease are reported, there are gaps in the literature on the biopsychosocial, spiritual, and holistic approaches in Parkinson disease care. More research is needed to examine the biopsychosocial and spiritual aspects of persons with Parkinson disease.

  9. 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.

  10. New aspects of molecular imaging in prostate cancer.

    PubMed

    Ceci, Francesco; Castellucci, Paolo; Cerci, Juliano J; Fanti, Stefano

    2017-07-13

    Nowadays several new imaging modalities are available for investigating prostate cancer (PCa) such as magnet resonance imaging (MRI) in the form of whole body MRI and pelvic multiparametric MRI and positron emission tomography (PET) using choline as radiotracers. Nevertheless, these modalities proved sub-optimal accuracy for detecting PCa metastases, particularly in the recurrence setting. A new molecular probe targeting the prostate specific membrane antigen (PSMA) has been recently developed for PET imaging. PSMA, the glutamate carboxypeptidase II, is a membrane bound metallo-peptidase over-expressed in PCa cells. It has been shown that PSMA based imaging offers higher tumor detection rate compared to choline PET/CT and radiological conventional imaging, especially at very low PSA levels during biochemical recurrence. In addition PSMA, as theranostics agent, allows both radiolabeling with diagnostic (e.g. 68Ga, 18F) or therapeutic nuclides (e.g. 177Lu, 225Ac). Initial results show that PSMA-targeted radioligand therapy can potentially delay disease progression in metastatic castrate-resistant PCa. Despite still investigational, the bombesin-based radiotracers and antagonist of gastrin releasing-peptide receptor (GRP) (RM2) and anti1-amino-3-18Ffluorocyclobutane-1-carboxylic acid (18F-FACBC) are emerging as possible alternatives for investigating PCa. Considering the wide diffusion of PCa in the Europe and the United States, the presence of these new diagnostic techniques able to detect the disease with high sensitivity and specificity might have a clinical impact on the management of patients. PET/CT imaging with new radiopharmaceuticals can implement the patient management identifying lesion(s) not detectable with conventional imaging procedures. In this review article will be discussed the most promising new PET radiopharmaceuticals (68Ga-PSMA-11, 18F-FACBC, 68Ga-RM2) available at the moment, focusing the attention on their accuracy and their impact on

  11. On integrability aspects of the supersymmetric sine-Gordon equation

    NASA Astrophysics Data System (ADS)

    Bertrand, S.

    2017-04-01

    In this paper we study certain integrability properties of the supersymmetric sine-Gordon equation. We construct Lax pairs with their zero-curvature representations which are equivalent to the supersymmetric sine-Gordon equation. From the fermionic linear spectral problem, we derive coupled sets of super Riccati equations and the auto-Bäcklund transformation of the supersymmetric sine-Gordon equation. In addition, a detailed description of the associated Darboux transformation is presented and non-trivial super multisoliton solutions are constructed. These integrability properties allow us to provide new explicit geometric characterizations of the bosonic supersymmetric version of the Sym–Tafel formula for the immersion of surfaces in a Lie superalgebra. These characterizations are expressed only in terms of the independent bosonic and fermionic variables.

  12. Translational neurocardiology: preclinical models and cardioneural integrative aspects

    PubMed Central

    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.

    2016-01-01

    Abstract 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. Sociological aspects of cleft palate adults: IV. Social integration.

    PubMed

    Peter, J P; Chinsky, R R; Fisher, M J

    1975-07-01

    The patterns of social integration of adults with primary and secondary groups were evaluated for 196 adult cleft subjects, their 190 siblings and 209 random controls. Results indicated that cleft adults tended to rely on the extended family for mutual aid and social activities. They also participated less frequently in voluntary associations and relied on a few one-to-one friendships. Social activities tended to be that of informal visiting patterns. While it would be inaccurate to characterize the cleft adult family as grossly different from other American families, they are a definable population experiencing some degree of limitation associated with having a cleft.

  14. Theoretical aspects of VLSI (Very Large Scale Integration) circuit design

    NASA Astrophysics Data System (ADS)

    Leighton, F. T.

    1986-01-01

    During the period covered by the grant, two books and ten research papers were written under grant sponsorship. In addition nineteen of the research papers were written and published in conference proceeding. Ten other research manuscripts are now nearing completion. Titles of some of the completed work include: Eigenvalues and Expanders, A Framework of Solving VLSI Graph Layout Problems, Tight Bounds on the Complexity of Parallel Sorting, Wafer-Scale Integration of Systolic Arrays, and The Average Case Analysis of Some On-Line Algorithms for Bin Packing.

  15. Structural integrity and containment aspects of small gas turbine engines

    NASA Astrophysics Data System (ADS)

    Gupta, S. S.; Gomuc, R.

    1994-03-01

    Structural integrity of rotating components in gas turbine engines is very crucial since their failure implies high impact energy, which, if uncontained, could mean damage to aircraft structures, controls, and so forth, and, in the worst scenario, even loss of lives. This final consequence has led to very stringent airworthiness regulations for engine/aircraft certifications. This paper discusses the historical statistics of noncontainment events in turbofans, turboprops, and turboshafts and shows how the damage severity varies between different applications and how changes to regulations are continuing in order to improve the reliability of aircraft/rotorcraft. The paper also presents design challenges resulting from the analysis complexity of containment/noncontainment event and the way Pratt & Whitney Canada design/analysis/test system caters to all the requirements. The weight and cost impact of possible changes to current regulations are also presented.

  16. jAMVLE, a New Integrated Molecular Visualization Learning Environment

    ERIC Educational Resources Information Center

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

    2006-01-01

    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…

  17. Oropouche Virus: Clinical, Epidemiological, and Molecular Aspects of a Neglected Orthobunyavirus

    PubMed Central

    Travassos da Rosa, Jorge Fernando; de Souza, William Marciel; Pinheiro, Francisco de Paula; Figueiredo, Mário Luiz; Cardoso, Jedson Ferreira; Acrani, Gustavo Olszanski; Nunes, Márcio Roberto Teixeira

    2017-01-01

    Oropouche virus (OROV) is an important cause of arboviral illness in Latin American countries, more specifically in the Amazon region of Brazil, Venezuela and Peru, as well as in other countries such as Panama. In the past decades, the clinical, epidemiological, pathological, and molecular aspects of OROV have been published and provide the basis for a better understanding of this important human pathogen. Here, we describe the milestones in a comprehensive review of OROV epidemiology, pathogenesis, and molecular biology, including a description of the first isolation of the virus, the outbreaks during the past six decades, clinical aspects of OROV infection, diagnostic methods, genome and genetic traits, evolution, and viral dispersal. PMID:28167595

  18. Oropouche Virus: Clinical, Epidemiological, and Molecular Aspects of a Neglected Orthobunyavirus.

    PubMed

    Travassos da Rosa, Jorge Fernando; de Souza, William Marciel; Pinheiro, Francisco de Paula; Figueiredo, Mário Luiz; Cardoso, Jedson Ferreira; Acrani, Gustavo Olszanski; Nunes, Márcio Roberto Teixeira

    2017-05-01

    AbstractOropouche virus (OROV) is an important cause of arboviral illness in Latin American countries, more specifically in the Amazon region of Brazil, Venezuela and Peru, as well as in other countries such as Panama. In the past decades, the clinical, epidemiological, pathological, and molecular aspects of OROV have been published and provide the basis for a better understanding of this important human pathogen. Here, we describe the milestones in a comprehensive review of OROV epidemiology, pathogenesis, and molecular biology, including a description of the first isolation of the virus, the outbreaks during the past six decades, clinical aspects of OROV infection, diagnostic methods, genome and genetic traits, evolution, and viral dispersal.

  19. 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

  20. 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

  1. 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.

  2. 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

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

    PubMed

    Lin, Yansong

    2015-09-01

    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 ((131)I) 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.

  4. 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…

  5. The integration of molecular tools into veterinary and spatial epidemiology.

    PubMed

    Muellner, Petra; Zadoks, Ruth N; Perez, Andres M; Spencer, Simon E F; Schukken, Ynte H; French, Nigel P

    2011-09-01

    At the interface of molecular biology and epidemiology, the emerging discipline of molecular epidemiology offers unique opportunities to advance the study of diseases through the investigation of infectious agents at the molecular level. Molecular tools can increase our understanding of the factors that shape the spatial and temporal distribution of pathogens and disease. Both spatial and molecular aspects have always been important to the field of infectious disease epidemiology, but recently news tools have been developed which increase our ability to consider both elements within a common framework. This enables the epidemiologist to make inferences about disease patterns in space and time. This paper introduces some basic concepts of molecular epidemiology in a veterinary context and illustrates the application of molecular tools at a range of spatio-temporal scales. Case studies - a multi-state outbreak of Serratia mastitis, a national control program for campylobacteriosis, and evolution of foot-and-mouth-disease viruses - are used to demonstrate the importance of considering molecular aspects in modern epidemiological studies. The discipline of molecular epidemiology is in its infancy and our contribution aims to promote awareness, understanding and uptake of molecular epidemiology in veterinary science. Copyright © 2011 Elsevier Ltd. All rights reserved.

  6. Molecular mechanisms of retroviral integration site selection

    PubMed Central

    Kvaratskhelia, Mamuka; Sharma, Amit; Larue, Ross C.; Serrao, Erik; Engelman, Alan

    2014-01-01

    Retroviral replication proceeds through an obligate integrated DNA provirus, making retroviral vectors attractive vehicles for human gene-therapy. Though most of the host cell genome is available for integration, the process of integration site selection is not random. Retroviruses differ in their choice of chromatin-associated features and also prefer particular nucleotide sequences at the point of insertion. Lentiviruses including HIV-1 preferentially integrate within the bodies of active genes, whereas the prototypical gammaretrovirus Moloney murine leukemia virus (MoMLV) favors strong enhancers and active gene promoter regions. Integration is catalyzed by the viral integrase protein, and recent research has demonstrated that HIV-1 and MoMLV targeting preferences are in large part guided by integrase-interacting host factors (LEDGF/p75 for HIV-1 and BET proteins for MoMLV) that tether viral intasomes to chromatin. In each case, the selectivity of epigenetic marks on histones recognized by the protein tether helps to determine the integration distribution. In contrast, nucleotide preferences at integration sites seem to be governed by the ability for the integrase protein to locally bend the DNA duplex for pairwise insertion of the viral DNA ends. We discuss approaches to alter integration site selection that could potentially improve the safety of retroviral vectors in the clinic. PMID:25147212

  7. 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

  8. Medium scale integration of molecular logic gates in an automaton.

    PubMed

    Macdonald, Joanne; Li, Yang; Sutovic, Marko; Lederman, Harvey; Pendri, Kiran; Lu, Wanhong; Andrews, Benjamin L; Stefanovic, Darko; Stojanovic, Milan N

    2006-11-01

    The assembly of molecular automata that perform increasingly complex tasks, such as game playing, presents an unbiased test of molecular computation. We now report a second-generation deoxyribozyme-based automaton, MAYA-II, which plays a complete game of tic-tac-toe according to a perfect strategy. In silicon terminology, MAYA-II represents the first "medium-scale integrated molecular circuit", integrating 128 deoxyribozyme-based logic gates, 32 input DNA molecules, and 8 two-channel fluorescent outputs across 8 wells.

  9. Symplectic integrator for molecular dynamics of a protein in water

    NASA Astrophysics Data System (ADS)

    Ishida, Hisashi; Nagai, Yoshinori; Kidera, Akinori

    1998-01-01

    The symplectic integrator is an algorithm for solving equations of motion, preserving the volume in phase space and ensuring a stable simulation. We carried out molecular dynamics simulations of liquid water and a protein in water using several variations of symplectic integrators. It was found that a fourth-order symplectic integrator of Calvo and Sanz-Serna generated a trajectory of much higher accuracy than the conventional Verlet and Gear methods with the same requirements for CPU time.

  10. 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…

  11. Towards A Phenomenography of Learning. I: Integrating Experiential Aspects. 1982:06.

    ERIC Educational Resources Information Center

    Marton, Ference

    This paper is the first of a series of three which attempt to integrate categories of description aimed at characterizing the experience of learning in terms of the logical relationships that exist between them. The description of the qualitatively different ways in which various aspects of reality are experienced and conceptualized, and the…

  12. 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…

  13. CIF: A Framework for Managing Integrity in Aspect-Oriented Composition

    NASA Astrophysics Data System (ADS)

    Camilleri, Andrew; Coulson, Geoffrey; Blair, Lynne

    Aspect Oriented Programming (AOP) is becoming increasingly accepted as an approach to deal with crosscutting concerns in software development. However, AOP is known to raise software integrity issues. For example, join point shadows may easily omit crucial join points or include inappropriate ones. In this paper, we propose an extensible framework called CIF that constrains aspect-oriented software design and composition with the intent to maintain the integrity of the final composed system. CIF controls the composition of aspects and the base application in three dimensions: where the composition occurs, how the composition is carried out and what exactly is being composed. The framework is intended to be used in a team-based software development environment. We demonstrate the applicability of the framework through an application case study.

  14. 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.

  15. COMPREHENSIVE ASSESSMENT OF COMPLEX TECHNOLOGIES: INTEGRATING VARIOUS ASPECTS IN HEALTH TECHNOLOGY ASSESSMENT.

    PubMed

    Lysdahl, Kristin Bakke; Mozygemba, Kati; Burns, Jacob; Brönneke, Jan Benedikt; Chilcott, James B; Ward, Sue; Hofmann, Bjørn

    2017-08-07

    Despite recent development of health technology assessment (HTA) methods, there are still methodological gaps for the assessment of complex health technologies. The INTEGRATE-HTA guidance for effectiveness, economic, ethical, socio-cultural, and legal aspects, deals with challenges when assessing complex technologies, such as heterogeneous study designs, multiple stakeholder perspectives, and unpredictable outcomes. The objective of this article is to outline this guidance and describe the added value of integrating these assessment aspects. Different methods were used to develop the various parts of the guidance, but all draw on existing, published knowledge and were supported by stakeholder involvement. The guidance was modified after application in a case study and in response to feedback from internal and external reviewers. The guidance consists of five parts, addressing five core aspects of HTA, all presenting stepwise approaches based on the assessment of complexity, context, and stakeholder involvement. The guidance on effectiveness, health economics and ethics aspects focus on helping users choose appropriate, or further develop, existing methods. The recommendations are based on existing methods' applicability for dealing with problems arising with complex interventions. The guidance offers new frameworks to identify socio-cultural and legal issues, along with overviews of relevant methods and sources. The INTEGRATE-HTA guidance outlines a wide range of methods and facilitates appropriate choices among them. The guidance enables understanding of how complexity matters for HTA and brings together assessments from disciplines, such as epidemiology, economics, ethics, law, and social theory. This indicates relevance for a broad range of technologies.

  16. Hybrid CMOS/Molecular Integrated Circuits

    NASA Astrophysics Data System (ADS)

    Stan, M. R.; Rose, G. S.; Ziegler, M. M.

    CMOS silicon technologies are likely to run out of steam in the next 10-15 years despite revolutionary advances in the past few decades. Molecular and other nanoscale technologies show significant promise but it is unlikely that they will completely replace CMOS, at least in the near term. This chapter explores opportunities for using CMOS and nanotechnology to enhance and complement each other in hybrid circuits. As an example of such a hybrid CMOS/nano system, a nanoscale programmable logic array (PLA) based on majority logic is described along with its supplemental CMOS circuitry. It is believed that such systems will be able to sustain the historical advances in the semiconductor industry while addressing manufacturability, yield, power, cost, and performance challenges.

  17. 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.

  18. 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

  19. Variational path integral molecular dynamics study of a water molecule

    NASA Astrophysics Data System (ADS)

    Miura, Shinichi

    2013-08-01

    In the present study, a variational path integral molecular dynamics method developed by the author [Chem. Phys. Lett. 482, 165 (2009)] is applied to a water molecule on the adiabatic potential energy surface. The method numerically generates an exact wavefunction using a trial wavefunction of the target system. It has been shown that even if a poor trial wavefunction is employed, the exact quantum distribution is numerically extracted, demonstrating the robustness of the variational path integral method.

  20. Quantum tunneling splittings from path-integral molecular dynamics

    NASA Astrophysics Data System (ADS)

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

    2016-03-01

    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.

  1. 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

  2. Hereditary nonpolyposis colorectal cancer: Review of clinical, molecular genetics, and counseling aspects

    SciTech Connect

    Bellacosa, A.; Genuardi, M.; Anti, M.; Viel, A.; Ponz de Leon, M.

    1996-04-24

    Lynch syndrome, or hereditary nonpolyposis colon cancer (HNPCC), is an autosomal dominant disease accounting for approximately 1-5% of all colorectal cancer cases. Due to the lack of pathognomonic morphological or biomolecular markers, HNPCC has traditionally posed unique problems to clinicians and geneticists alike, both in terms of diagnosis and clinical management. Recently, novel insight into the pathogenesis of this syndrome has been provided by the identification of its molecular basis. In HNPCC families, germline mutations in any of four genes encoding proteins of a specialized DNA repair system, the mismatch repair, predispose to cancer development. Mutations in mismatch repair genes lead to an overall increase of the mutation rate and are associated with a phenotype of length instability of microsatellite loci. The present report summarizes the clinicopathological aspects of HNPCC and reviews the most recent molecular and biochemical findings. 115 refs., 2 figs., 3 tabs.

  3. Current Molecular and Genetic Aspects of Pancreatic Cancer, the Role of Metastasis Associated Proteins (MTA): A Review.

    PubMed

    Pavlidis, Efstathios T; Pavlidis, Theodoros E

    2017-01-06

    Purpose/aim: To focus on current molecular and genetic aspects and MTA proteins, since pancreatic cancer is a lethal malignant with poor prognosis. Early diagnosis is essential step, contributing to potential curative resection.

  4. HBV DNA Integration: Molecular Mechanisms and Clinical Implications

    PubMed Central

    Tu, Thomas; Budzinska, Magdalena A.; Shackel, Nicholas A.; Urban, Stephan

    2017-01-01

    Chronic infection with the Hepatitis B Virus (HBV) is a major cause of liver-related morbidity and mortality. One peculiar observation in cells infected with HBV (or with closely‑related animal hepadnaviruses) is the presence of viral DNA integration in the host cell genome, despite this form being a replicative dead-end for the virus. The frequent finding of somatic integration of viral DNA suggests an evolutionary benefit for the virus; however, the mechanism of integration, its functions, and the clinical implications remain unknown. Here we review the current body of knowledge of HBV DNA integration, with particular focus on the molecular mechanisms and its clinical implications (including the possible consequences of replication-independent antigen expression and its possible role in hepatocellular carcinoma). HBV DNA integration is likely to influence HBV replication, persistence, and pathogenesis, and so deserves greater attention in future studies. PMID:28394272

  5. Integrating molecular diagnostics into histopathology training: the Belfast model.

    PubMed

    Flynn, C; James, J; Maxwell, P; McQuaid, S; Ervine, A; Catherwood, M; Loughrey, M B; McGibben, D; Somerville, J; McManus, D T; Gray, M; Herron, B; Salto-Tellez, M

    2014-07-01

    Molecular medicine is transforming modern clinical practice, from diagnostics to therapeutics. Discoveries in research are being incorporated into the clinical setting with increasing rapidity. This transformation is also deeply changing the way we practise pathology. The great advances in cell and molecular biology which have accelerated our understanding of the pathogenesis of solid tumours have been embraced with variable degrees of enthusiasm by diverse medical professional specialties. While histopathologists have not been prompt to adopt molecular diagnostics to date, the need to incorporate molecular pathology into the training of future histopathologists is imperative. Our goal is to create, within an existing 5-year histopathology training curriculum, the structure for formal substantial teaching of molecular diagnostics. This specialist training has two main goals: (1) to equip future practising histopathologists with basic knowledge of molecular diagnostics and (2) to create the option for those interested in a subspecialty experience in tissue molecular diagnostics to pursue this training. It is our belief that this training will help to maintain in future the role of the pathologist at the centre of patient care as the integrator of clinical, morphological and molecular information. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.

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

    PubMed

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

  7. 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

  8. High aspect ratio sharp nanotip for nanocantilever integration at CMOS compatible temperature

    NASA Astrophysics Data System (ADS)

    Wang, P.; Michael, A.; Kwok, CY

    2017-08-01

    In this paper, we demonstrate a novel low temperature nanofabrication approach that enables the formation of ultra-sharp high aspect ratio (HAR) and high density nanotip structures and their integration onto nanoscale cantilever beams. The nanotip structure consists of a nanoscale thermally evaporated Cr Spindt tip on top of an amorphous silicon rod. An apex radius of the tip, as small as 2.5 nm, has been achieved, and is significantly smaller than any other Spindt tips reported so far. 100 nm wide tips with aspect ratio of more than 50 and tip density of more than 5 × 109 tips cm-2 have been fabricated. The HAR tips have been integrated onto an array of 460 nm wide cantilever beams with high precision and yield. In comparison with other approaches, this approach allows the integration of HAR sharp nanotips with nano-mechanical structures in a parallel and CMOS compatible fashion for the first time to our knowledge. Potential applications include on-chip high-speed atomic force microscopy and field emission devices.

  9. High aspect ratio sharp nanotip for nanocantilever integration at CMOS compatible temperature.

    PubMed

    Wang, P; Michael, A; Kwok, C Y

    2017-08-11

    In this paper, we demonstrate a novel low temperature nanofabrication approach that enables the formation of ultra-sharp high aspect ratio (HAR) and high density nanotip structures and their integration onto nanoscale cantilever beams. The nanotip structure consists of a nanoscale thermally evaporated Cr Spindt tip on top of an amorphous silicon rod. An apex radius of the tip, as small as 2.5 nm, has been achieved, and is significantly smaller than any other Spindt tips reported so far. 100 nm wide tips with aspect ratio of more than 50 and tip density of more than 5 × 10(9) tips cm(-2) have been fabricated. The HAR tips have been integrated onto an array of 460 nm wide cantilever beams with high precision and yield. In comparison with other approaches, this approach allows the integration of HAR sharp nanotips with nano-mechanical structures in a parallel and CMOS compatible fashion for the first time to our knowledge. Potential applications include on-chip high-speed atomic force microscopy and field emission devices.

  10. Integration of molecular network data reconstructs Gene Ontology

    PubMed Central

    Gligorijević, Vladimir; Janjić, Vuk; Pržulj, Nataša

    2014-01-01

    Motivation: Recently, a shift was made from using Gene Ontology (GO) to evaluate molecular network data to using these data to construct and evaluate GO. Dutkowski et al. provide the first evidence that a large part of GO can be reconstructed solely from topologies of molecular networks. Motivated by this work, we develop a novel data integration framework that integrates multiple types of molecular network data to reconstruct and update GO. We ask how much of GO can be recovered by integrating various molecular interaction data. Results: We introduce a computational framework for integration of various biological networks using penalized non-negative matrix tri-factorization (PNMTF). It takes all network data in a matrix form and performs simultaneous clustering of genes and GO terms, inducing new relations between genes and GO terms (annotations) and between GO terms themselves. To improve the accuracy of our predicted relations, we extend the integration methodology to include additional topological information represented as the similarity in wiring around non-interacting genes. Surprisingly, by integrating topologies of bakers’ yeasts protein–protein interaction, genetic interaction (GI) and co-expression networks, our method reports as related 96% of GO terms that are directly related in GO. The inclusion of the wiring similarity of non-interacting genes contributes 6% to this large GO term association capture. Furthermore, we use our method to infer new relationships between GO terms solely from the topologies of these networks and validate 44% of our predictions in the literature. In addition, our integration method reproduces 48% of cellular component, 41% of molecular function and 41% of biological process GO terms, outperforming the previous method in the former two domains of GO. Finally, we predict new GO annotations of yeast genes and validate our predictions through GIs profiling. Availability and implementation: Supplementary Tables of new GO

  11. Integration of molecular network data reconstructs Gene Ontology.

    PubMed

    Gligorijević, Vladimir; Janjić, Vuk; Pržulj, Nataša

    2014-09-01

    Recently, a shift was made from using Gene Ontology (GO) to evaluate molecular network data to using these data to construct and evaluate GO. Dutkowski et al. provide the first evidence that a large part of GO can be reconstructed solely from topologies of molecular networks. Motivated by this work, we develop a novel data integration framework that integrates multiple types of molecular network data to reconstruct and update GO. We ask how much of GO can be recovered by integrating various molecular interaction data. We introduce a computational framework for integration of various biological networks using penalized non-negative matrix tri-factorization (PNMTF). It takes all network data in a matrix form and performs simultaneous clustering of genes and GO terms, inducing new relations between genes and GO terms (annotations) and between GO terms themselves. To improve the accuracy of our predicted relations, we extend the integration methodology to include additional topological information represented as the similarity in wiring around non-interacting genes. Surprisingly, by integrating topologies of bakers' yeasts protein-protein interaction, genetic interaction (GI) and co-expression networks, our method reports as related 96% of GO terms that are directly related in GO. The inclusion of the wiring similarity of non-interacting genes contributes 6% to this large GO term association capture. Furthermore, we use our method to infer new relationships between GO terms solely from the topologies of these networks and validate 44% of our predictions in the literature. In addition, our integration method reproduces 48% of cellular component, 41% of molecular function and 41% of biological process GO terms, outperforming the previous method in the former two domains of GO. Finally, we predict new GO annotations of yeast genes and validate our predictions through GIs profiling. Supplementary Tables of new GO term associations and predicted gene annotations are

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

    DOE PAGES

    Udintsev, V. S.; Taylor, G.; Pandya, H. K.B.; ...

    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

  13. 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.

  14. An integrative characterization of recurrent molecular aberrations in glioblastoma genomes.

    PubMed

    Sintupisut, Nardnisa; Liu, Pei-Ling; Yeang, Chen-Hsiang

    2013-10-01

    Glioblastoma multiforme (GBM) is the most common and malignant primary brain tumor in adults. Decades of investigations and the recent effort of the Cancer Genome Atlas (TCGA) project have mapped many molecular alterations in GBM cells. Alterations on DNAs may dysregulate gene expressions and drive malignancy of tumors. It is thus important to uncover causal and statistical dependency between 'effector' molecular aberrations and 'target' gene expressions in GBMs. A rich collection of prior studies attempted to combine copy number variation (CNV) and mRNA expression data. However, systematic methods to integrate multiple types of cancer genomic data-gene mutations, single nucleotide polymorphisms, CNVs, DNA methylations, mRNA and microRNA expressions and clinical information-are relatively scarce. We proposed an algorithm to build 'association modules' linking effector molecular aberrations and target gene expressions and applied the module-finding algorithm to the integrated TCGA GBM data sets. The inferred association modules were validated by six tests using external information and datasets of central nervous system tumors: (i) indication of prognostic effects among patients; (ii) coherence of target gene expressions; (iii) retention of effector-target associations in external data sets; (iv) recurrence of effector molecular aberrations in GBM; (v) functional enrichment of target genes; and (vi) co-citations between effectors and targets. Modules associated with well-known molecular aberrations of GBM-such as chromosome 7 amplifications, chromosome 10 deletions, EGFR and NF1 mutations-passed the majority of the validation tests. Furthermore, several modules associated with less well-reported molecular aberrations-such as chromosome 11 CNVs, CD40, PLXNB1 and GSTM1 methylations, and mir-21 expressions-were also validated by external information. In particular, modules constituting trans-acting effects with chromosome 11 CNVs and cis-acting effects with chromosome

  15. Ab initio Path Integral Molecular Dynamics Based on Fragment Molecular Orbital Method

    NASA Astrophysics Data System (ADS)

    Fujita, Takatoshi; Watanabe, Hirofumi; Tanaka, Shigenori

    2009-10-01

    We have developed an ab initio path integral molecular dynamics method based on the fragment molecular orbital method. This “FMO-PIMD” method can treat both nuclei and electrons quantum mechanically, and is useful to simulate large hydrogen-bonded systems with high accuracy. After a benchmark calculation for water monomer, water trimer and glycine pentamer have been studied using the FMO-PIMD method to investigate nuclear quantum effects on structure and molecular interactions. The applicability of the present approach is demonstrated through a number of test calculations.

  16. Monolithic integration of microelectronics and photonics using molecularly engineered materials

    NASA Astrophysics Data System (ADS)

    Kubacki, Ronald M.

    2005-03-01

    The monolithic integration of CMOS microelectronics with photonics is inevitable and benefits both technologies. Photonic integration to microelectronics provides such solutions as overcoming microprocessor communication roadblocks through the use of optical interconnection. Microelectronic integration can provide benefits to photonic structures by optimizing electronic signals generated by photonic biosensors for example. Photonic integration must complement, build on, and enhance the existing state of CMOS microelectronic technology. Photonic approaches that ignore the realities of CMOS architectures (such as power and thermal limitations), provide little benefit to the CMOS device performance, are incompatible with CMOS silicon manufacturing processes, or are incapable of achieving levels of long term reliability already well demonstrated by microelectronic devices, give little reason for photonic/microelectronic integration. Practical implementation of photonics on chip, monolithically with CMOS type microelectronic devices, remains in the laboratory. This work presents architectures to integrate photonics and microelectronics that address CMOS fabrication realities, increase performance of both the electronic and optical functions, and retain current levels of reliability. Fabricating these structures with the limited CMOS material set and/or typical photonic materials requires materials to be molecularly engineered to provide required properties. Materials have been investigated that enable economic fabrication of photonic structures for monolithic integration. Low loss self assembled silicon nanocomposite VIPIR waveguide structures are combined with long term stable non-linear poled polymers for fabrication of electro-optic active devices. Materials are fabricated using low temperature plasma enhanced chemical vapor deposition (PECVD).

  17. Anti-Adhesion Therapies in Inflammatory Bowel Disease-Molecular and Clinical Aspects.

    PubMed

    Zundler, Sebastian; Becker, Emily; Weidinger, Carl; Siegmund, Britta

    2017-01-01

    The number of biologicals for the therapy of immunologically mediated diseases is constantly growing. In contrast to other agents that were previously introduced in rheumatologic or dermatologic diseases and only later adopted for the treatment of inflammatory bowel diseases (IBDs), the field of IBD was ground breaking for the concept of anti-adhesion blockade. Anti-adhesion antibodies selectively target integrins controlling cell homing to the intestine, which leads to reduction of inflammatory infiltration to the gut in chronic intestinal inflammation. Currently, the anti-α4β7-antibody vedolizumab is successfully used for both Crohn's disease and ulcerative colitis worldwide. In this mini-review, we will summarize the fundamental basis of intestinal T cell homing and explain the molecular groundwork underlying current and potential future anti-adhesion therapies. Finally, we will comment on noteworthy clinical aspects of anti-adhesion therapy and give an outlook to the future of anti-integrin antibodies and inhibitors.

  18. Efficient Calculation of Molecular Integrals over London Atomic Orbitals.

    PubMed

    Irons, Tom J P; Zemen, Jan; Teale, Andrew M

    2017-08-08

    The use of London atomic orbitals (LAOs) in a nonperturbative manner enables the determination of gauge-origin invariant energies and properties for molecular species in arbitrarily strong magnetic fields. Central to the efficient implementation of such calculations for molecular systems is the evaluation of molecular integrals, particularly the electron repulsion integrals (ERIs). We present an implementation of several different algorithms for the evaluation of ERIs over Gaussian-type LAOs at arbitrary magnetic field strengths. The efficiencies of generalized McMurchie-Davidson (MD), Head-Gordon-Pople (HGP), and Rys quadrature schemes are compared. For the Rys quadrature implementation, we avoid the use of high precision arithmetic and interpolation schemes in the computation of the quadrature roots and weights, enabling the application of this algorithm seamlessly to a wide range of magnetic fields. The efficiency of each generalized algorithm is compared by numerical application, classifying the ERIs according to their total angular momenta and evaluating their performance for primitive and contracted basis sets. In common with zero-field integral evaluation, no single algorithm is optimal for all angular momenta; thus, a simple mixed scheme is put forward that selects the most efficient approach to calculate the ERIs for each shell quartet. The mixed approach is significantly more efficient than the exclusive use of any individual algorithm.

  19. 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. © 2016 Wiley Periodicals, Inc.

  20. Coupling molecular spin centers to microwave planar resonators: towards integration of molecular qubits in quantum circuits.

    PubMed

    Bonizzoni, C; Ghirri, A; Bader, K; van Slageren, J; Perfetti, M; Sorace, L; Lan, Y; Fuhr, O; Ruben, M; Affronte, M

    2016-11-14

    We present spectroscopic measurements looking for the coherent coupling between molecular magnetic centers and microwave photons. The aim is to find the optimal conditions and the best molecular features to achieve the quantum strong coupling regime, for which coherent dynamics of hybrid photon-spin states take place. To this end, we used a high critical temperature YBCO superconducting planar resonator working at 7.7 GHz and at low temperatures to investigate three molecular mononuclear coordination compounds, namely (PPh4)2[Cu(mnt)2] (where mnt(2-) = maleonitriledithiolate), [ErPc2](-)TBA(+) (where pc(2-) is the phtalocyaninato and TBA(+) is the tetra-n-butylammonium cation) and Dy(trensal) (where H3trensal = 2,2',2''-tris(salicylideneimino)triethylamine). Although the strong coupling regime was not achieved in these preliminary experiments, the results provided several hints on how to design molecular magnetic centers to be integrated into hybrid quantum circuits.

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

    SciTech Connect

    Bardhan, J.; Mathematics and Computer Science; Rush Univ.

    2009-03-07

    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.

  2. 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.

  3. Integrative network analysis reveals molecular mechanisms of blood pressure regulation

    PubMed Central

    Huan, Tianxiao; Meng, Qingying; Saleh, Mohamed A; Norlander, Allison E; Joehanes, Roby; Zhu, Jun; Chen, Brian H; Zhang, Bin; Johnson, Andrew D; Ying, Saixia; Courchesne, Paul; Raghavachari, Nalini; Wang, Richard; Liu, Poching; O'Donnell, Christopher J; Vasan, Ramachandran; Munson, Peter J; Madhur, Meena S; Harrison, David G; Yang, Xia; Levy, Daniel

    2015-01-01

    Genome-wide association studies (GWAS) have identified numerous loci associated with blood pressure (BP). The molecular mechanisms underlying BP regulation, however, remain unclear. We investigated BP-associated molecular mechanisms by integrating BP GWAS with whole blood mRNA expression profiles in 3,679 individuals, using network approaches. BP transcriptomic signatures at the single-gene and the coexpression network module levels were identified. Four coexpression modules were identified as potentially causal based on genetic inference because expression-related SNPs for their corresponding genes demonstrated enrichment for BP GWAS signals. Genes from the four modules were further projected onto predefined molecular interaction networks, revealing key drivers. Gene subnetworks entailing molecular interactions between key drivers and BP-related genes were uncovered. As proof-of-concept, we validated SH2B3, one of the top key drivers, using Sh2b3−/− mice. We found that a significant number of genes predicted to be regulated by SH2B3 in gene networks are perturbed in Sh2b3−/− mice, which demonstrate an exaggerated pressor response to angiotensin II infusion. Our findings may help to identify novel targets for the prevention or treatment of hypertension. PMID:25882670

  4. Molecular pathology - the value of an integrative approach.

    PubMed

    Salto-Tellez, Manuel; James, Jacqueline A; Hamilton, Peter W

    2014-10-01

    Molecular Pathology (MP) is at the heart of modern diagnostics and translational research, but the controversy on how MP is best developed has not abated. The lack of a proper model or trained pathologists to support the diagnostic and research missions makes MP a rare commodity overall. Here we analyse the scientific and technology areas, in research and diagnostics, which are encompassed by MP of solid tumours; we highlight the broad overlap of technologies and analytical capabilities in tissue research and diagnostics; and we describe an integrated model that rationalizes technical know-how and pathology talent for both. The model is based on a single, accredited laboratory providing a single standard of high-quality for biomarker discovery, biomarker validation and molecular diagnostics.

  5. [Molecular and morphological aspects of endometrial receptivity disorders at chronic endometritis].

    PubMed

    Kogan, E A; Demura, T A; Vodianoĭ, V Ia; Shurshalina, A V

    2012-01-01

    The endometrial receptivity is a complex of structure-functional characteristics of endometrium with clear temporal and spatial constants, conditioning the ability of endometrium to the implantation. The aim of our research was a studying of morphological and molecular aspects of the endometrial receptivity disorders at chronic endometritis. The basic studied group included cases of chronic endometritis (CE) with unknown etiology (30 patients) and with CE under autoimmune thyroiditis (26 patients with presence of antithyroid antibodies--ATA). All patients had different disorders of reproductive function; some of them were infertile. More over 73% of all studied patients were of the 26-40 ages old. The control group was presented by endometrium of healthy surrogate mothers (10 cases). The research was done on the Pipelle biopsies of endometrium, which was taken in the secretory phase (the period of "implantation window"). For confirmation of the CE diagnosis, the endometrium of women with ATA was taken in the proliferative phase too. Morphological, immunohistochemical and statistical (nonparametric analysis of Mann-Whitney) methods were used. As the primary antibodies were used CD68, CD138, CD56, Ki-67, Apaf-1, LIE The structure analysis of pinopodes was carried out by stained paraffin slices (CytoViva Technologies Inc., Auburn, AL, USA) with using of the traditional and luminescent microscopy (the definition is over 100 nm). Structure and molecular changes of endometrium at CE include inflammatory infiltration, fibroblastic reactions and alteration of extracellular matrix; apoptosis of functional layer leading to its insusceptibility to the regulatory signals. Disorders of endometrial remodeling in the "implantation window" determine the result of implantation and can be reason of the infertility. The reduced receptivity at CE is characterized by decrease of mature pinopodes and low expression of LIF in the surface epithelium.

  6. 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

  7. Path integral molecular dynamics at zero thermal temperature

    NASA Astrophysics Data System (ADS)

    Willow, Soohaeng Yoo

    2017-04-01

    Path integral molecular dynamics (PIMD) simulations at the zero thermal temperature still remain inconceivable. Herein, the quantum-mechanical partition function is revised in conjunction with the time-independent Schrödinger equation. The imaginary temperature for the quantum-mechanical partition function is introduced as an independent variable and defined under the guidance of the virial theorem. In the end, computational evidences are provided showing that this revised PIMD simulation at the zero thermal temperature reproduces both the zero-point energy and the probability density obtained from the Schrödinger equation for the harmonic oscillator.

  8. Towards an integrated molecular model of plant-virus interactions.

    PubMed

    Elena, Santiago F; Rodrigo, Guillermo

    2012-12-01

    The application in recent years of network theory methods to the study of host-virus interactions is providing a new perspective to the way viruses manipulate the host to promote their own replication. An integrated molecular model of such pathosystems require three detailed maps describing, firstly, the interactions between viral elements, secondly, the interactions between host elements, and thirdly, the cross-interactions between viral and host elements. Here, we compile available information for Potyvirus infecting Arabidopsis thaliana. With an integrated model, it is possible to analyze the mode of virus action and how the perturbation of the virus targets propagates along the network. These studies suggest that viral pathogenicity results not only from the alteration of individual elements but it is a systemic property. Copyright © 2012 Elsevier B.V. All rights reserved.

  9. Towards an integration of software-ergonomic aspects in formal specifications of graphical user interfaces

    SciTech Connect

    Sucrow, B.E.

    1996-12-31

    Well functioning graphical user interfaces today represent an important part of every interactive system. However, achieving a really good graphical user interface involves quite complex tasks. One of the most important points is to think about the requirements how the interface has to appear and how to behave. Due to the importance of user-friendliness of graphical user interfaces and easy-to-use interfaces these requirements highly concern software-ergonomic aspects, and are mostly non-functional. Thus, the design of a graphical user interface has to arise in an application specific and as well as for the user comfortable manner. In this paper we will investigate how such software-ergonomic aspects can be integrated in the specification process of graphical user interfaces. More precisely, we consider, how the process of specifying software-ergonomic features of graphical user interfaces can be carried out continuously within a constructive interplay between the requirements stage and the design stage. This continuity can be achieved by using a flexible and powerful specification method. We use graph grammars as a means to specify intuitively and at the same time formally as well.

  10. A unified scheme for ab initio molecular orbital theory and path integral molecular dynamics

    NASA Astrophysics Data System (ADS)

    Shiga, Motoyuki; Tachikawa, Masanori; Miura, Shinichi

    2001-11-01

    We present a general approach for accurate calculation of chemical substances which treats both nuclei and electrons quantum mechanically, adopting ab initio molecular orbital theory for the electronic structure and path integral molecular dynamics for the nuclei. The present approach enables the evaluation of physical quantities dependent on the nuclear configuration as well as the electronic structure, within the framework of Born-Oppenheimer adiabatic approximation. As an application, we give the path integral formulation of electric response properties—dipole moment and polarizability, which characterize the changes both in electronic structure and nuclear configuration at a given temperature when uniform electrostatic field is present. We also demonstrate the calculation of a water molecule using the present approach and the result of temperature and isotope effects is discussed.

  11. Anti-Adhesion Therapies in Inflammatory Bowel Disease—Molecular and Clinical Aspects

    PubMed Central

    Zundler, Sebastian; Becker, Emily; Weidinger, Carl; Siegmund, Britta

    2017-01-01

    The number of biologicals for the therapy of immunologically mediated diseases is constantly growing. In contrast to other agents that were previously introduced in rheumatologic or dermatologic diseases and only later adopted for the treatment of inflammatory bowel diseases (IBDs), the field of IBD was ground breaking for the concept of anti-adhesion blockade. Anti-adhesion antibodies selectively target integrins controlling cell homing to the intestine, which leads to reduction of inflammatory infiltration to the gut in chronic intestinal inflammation. Currently, the anti-α4β7-antibody vedolizumab is successfully used for both Crohn’s disease and ulcerative colitis worldwide. In this mini-review, we will summarize the fundamental basis of intestinal T cell homing and explain the molecular groundwork underlying current and potential future anti-adhesion therapies. Finally, we will comment on noteworthy clinical aspects of anti-adhesion therapy and give an outlook to the future of anti-integrin antibodies and inhibitors. PMID:28804488

  12. Retinal blinding disorders and gene therapy--molecular and clinical aspects.

    PubMed

    Lorenz, Birgit; Preising, Markus; Stieger, Knut

    2010-10-01

    Retinal blinding disorders together have a prevalence of 1 in 2000 humans world wide and represent a significant impact on the quality of life as well as the possibility to attain personal achievements. Mutations in genes that are expressed either in RPE cells, photoreceptors or bipolar cells can cause varying forms of degenerative or stationary retinal disorders, as the presence of the encoded proteins is crucial for normal function, maintenance and synaptic interaction. The degree of damage caused by different mutations depends upon the type of mutation within the gene, resulting in either total absence or the presence of a non-functional or potentially toxic protein. Potential treatment strategies require the identification of the cell type, in which the mutated gene is expressed for later targeting by viral vector mediated gene transfer. In the first part of this review, the authors present different cellular pathways that take place either in the RPE, photoreceptors, or bipolar cells. Furthermore, the authors demonstrate why genetic and molecular testing methods, which clearly identify the disease causing mutations, are crucial for attaining the correct diagnosis in order to identify patients suitable to be treated by upcoming new therapeutic methods. In the second part, a short clinical classification of the most important forms of retinal blinding disorders is given, together with clinical aspects concerning the problems that arise when facing low residual visual perception and the enormous heterogeneity of symptoms within these disorders.

  13. Concomitant MDS with isolated 5q deletion and MGUS: case report and review of molecular aspects.

    PubMed

    Nolte, Florian; Mossner, Maximilian; Jann, Johann-Christoph; Nowak, Daniel; Boch, Tobias; Müller, Nadine Zoe; Hofmann, Wolf-Karsten; Metzgeroth, Georgia

    2017-03-01

    Patients with monoclonal gammopathy of undetermined significance (MGUS) have a higher risk for the development of concomitant primary cancers such as multiple myeloma (MM) and myelodysplastic syndrome (MDS). We report the case of patient initially suffering from MGUS of the IgG lambda subtype for more than 10 yr, which evolved to MM and MDS with deletion (5q) with severe pancytopenia. Due to pancytopenia, he received dose-reduced treatment with lenalidomide and dexamethasone. He achieved an ongoing transfusion independency after about 1 month of treatment. Bone marrow taken 14 months after start of treatment showed a complete cytogenetic response of the del(5q) clone and a plasma cell infiltration below 5%. In contrast to the development of MM in MGUS patients, the subsequent occurrence of MDS after diagnosis of MGUS is infrequent. Moreover, the biological association of MDS with MGUS is not sufficiently understood, but the non-treatment-related occurrence supports the pathogenetic role of pre-existing alterations of stem cells. Here, we summarize data on concomitant MDS and MGUS/MM with particular emphasis on molecular aspects.

  14. Aspects of Piaget's cognitive developmental psychology and neurobiology of psychotic disorders - an integrative model.

    PubMed

    Gebhardt, Stefan; Grant, Phillip; von Georgi, Richard; Huber, Martin T

    2008-09-01

    Psychological, neurobiological and neurodevelopmental approaches have frequently been used to provide pathogenic concepts on psychotic disorders. However, aspects of cognitive developmental psychology have hardly been considered in current models. Using a hypothesis-generating approach an integration of these concepts was conducted. According to Piaget (1896-1980), assimilation and accommodation as forms of maintenance and modification of cognitive schemata represent fundamental processes of the brain. In general, based on the perceived input stimuli, cognitive schemata are developed resulting in a conception of the world, the realistic validity and the actuality of which is still being controlled and modified by cognitive adjustment processes. In psychotic disorders, however, a disproportion of environmental demands and the ability to activate required neuronal adaptation processes occurs. We therefore hypothesize a failure of the adjustment of real and requested output patterns. As a consequence autonomous cognitive schemata are generated, which fail to adjust with reality resulting in psychotic symptomatology. Neurobiological, especially neuromodulatory and neuroplastic processes play a central role in these perceptive and cognitive processes. In conclusion, integration of cognitive developmental psychology into the existing pathogenic concepts of psychotic disorders leads to interesting insights into basic disease mechanisms and also guides future research in the cognitive neuroscience of such disorders.

  15. Integrated genomic and molecular characterization of cervical cancer.

    PubMed

    2017-03-16

    Cervical cancer remains one of the leading causes of cancer-related deaths worldwide. Here we report the extensive molecular characterization of 228 primary cervical cancers, one of the largest comprehensive genomic studies of cervical cancer to date. We observed notable APOBEC mutagenesis patterns and identified SHKBP1, ERBB3, CASP8, HLA-A and TGFBR2 as novel significantly mutated genes in cervical cancer. We also discovered amplifications in immune targets CD274 (also known as PD-L1) and PDCD1LG2 (also known as PD-L2), and the BCAR4 long non-coding RNA, which has been associated with response to lapatinib. Integration of human papilloma virus (HPV) was observed in all HPV18-related samples and 76% of HPV16-related samples, and was associated with structural aberrations and increased target-gene expression. We identified a unique set of endometrial-like cervical cancers, comprised predominantly of HPV-negative tumours with relatively high frequencies of KRAS, ARID1A and PTEN mutations. Integrative clustering of 178 samples identified keratin-low squamous, keratin-high squamous and adenocarcinoma-rich subgroups. These molecular analyses reveal new potential therapeutic targets for cervical cancers.

  16. Efficient stochastic thermostatting of path integral molecular dynamics

    NASA Astrophysics Data System (ADS)

    Ceriotti, Michele; Parrinello, Michele; Markland, Thomas E.; Manolopoulos, David E.

    2010-09-01

    The path integral molecular dynamics (PIMD) method provides a convenient way to compute the quantum mechanical structural and thermodynamic properties of condensed phase systems at the expense of introducing an additional set of high frequency normal modes on top of the physical vibrations of the system. Efficiently sampling such a wide range of frequencies provides a considerable thermostatting challenge. Here we introduce a simple stochastic path integral Langevin equation (PILE) thermostat which exploits an analytic knowledge of the free path integral normal mode frequencies. We also apply a recently developed colored noise thermostat based on a generalized Langevin equation (GLE), which automatically achieves a similar, frequency-optimized sampling. The sampling efficiencies of these thermostats are compared with that of the more conventional Nosé-Hoover chain (NHC) thermostat for a number of physically relevant properties of the liquid water and hydrogen-in-palladium systems. In nearly every case, the new PILE thermostat is found to perform just as well as the NHC thermostat while allowing for a computationally more efficient implementation. The GLE thermostat also proves to be very robust delivering a near-optimum sampling efficiency in all of the cases considered. We suspect that these simple stochastic thermostats will therefore find useful application in many future PIMD simulations.

  17. Structural and dynamical aspects of Streptococcus gordonii FabH through molecular docking and MD simulations.

    PubMed

    Shamim, Amen; Abbasi, Sumra Wajid; Azam, Syed Sikander

    2015-07-01

    β-Ketoacyl-ACP-synthase III (FabH or KAS III) has become an attractive target for the development of new antibacterial agents which can overcome the multidrug resistance. Unraveling the fatty acid biosynthesis (FAB) metabolic pathway and understanding structural coordinates of FabH will provide valuable insights to target Streptococcus gordonii for curing oral infection. In this study, we designed inhibitors against therapeutic target FabH, in order to block the FAB pathway. As compared to other targets, FabH has more interactions with other proteins, located on the leading strand with higher codon adaptation index value and associated with lipid metabolism category of COG. Current study aims to gain in silico insights into the structural and dynamical aspect of S. gordonii FabH via molecular docking and molecular dynamics (MD) simulations. The FabH protein is catalytically active in dimerization while it can lock in monomeric state. Current study highlights two residues Pro88 and Leu315 that are close to each other by dimerization. The active site of FabH is composed of the catalytic triad formed by residues Cys112, His249, and Asn279 in which Cys112 is involved in acetyl transfer, while His249 and Asn279 play an active role in decarboxylation. Docking analysis revealed that among the studied compounds, methyl-CoA disulfide has highest GOLD score (82.75), binding affinity (-11 kcal/mol) and exhibited consistently better interactions. During MD simulations, the FabH structure remained stable with the average RMSD value of 1.7 Å and 1.6 Å for undocked protein and docked complex, respectively. Further, crucial hydrogen bonding of the conserved catalytic triad for exhibiting high affinity between the FabH protein and ligand is observed by RDF analysis. The MD simulation results clearly demonstrated that binding of the inhibitor with S. gordonii FabH enhanced the structure and stabilized the dimeric FabH protein. Therefore, the inhibitor has the potential to become

  18. Digital Aquifer - Integrating modeling, technical, software and policy aspects to develop a groundwater management tool

    NASA Astrophysics Data System (ADS)

    Tirupathi, S.; McKenna, S. A.; Fleming, K.; Wambua, M.; Waweru, P.; Ondula, E.

    2016-12-01

    Groundwater management has traditionally been observed as a study for long term policy measures to ensure that the water resource is sustainable. IBM Research, in association with the World Bank, extended this traditional analysis to include realtime groundwater management by building a context-aware, water rights management and permitting system. As part of this effort, one of the primary objectives was to develop a groundwater flow model that can help the policy makers with a visual overview of the current groundwater distribution. In addition, the system helps the policy makers simulate a range of scenarios and check the sustainability of the groundwater resource in a given region. The system also enables a license provider to check the effect of the introduction of a new well on the existing wells in the domain as well as the groundwater resource in general. This process simplifies how an engineer will determine if a new well should be approved. Distance to the nearest well neighbors and the maximum decreases in water levels of nearby wells are continually assessed and presented as evidence for an engineer to make the final judgment on approving the permit. The system also facilitates updated insights on the amount of groundwater left in an area and provides advice on how water fees should be structured to balance conservation and economic development goals. In this talk, we will discuss the concept of Digital Aquifer, the challenges in integrating modeling, technical and software aspects to develop a management system that helps policy makers and license providers with a robust decision making tool. We will concentrate on the groundwater model developed using the analytic element method that plays a very important role in the decision making aspects. Finally, the efficiency of this system and methodology is shown through a case study in Laguna Province, Philippines, which was done in collaboration with the National Water Resource Board, Philippines and World

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

    PubMed

    Skinner, Michael K

    2015-04-26

    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. © The Author(s) 2015. Published by Oxford University Press on behalf of the Society for Molecular Biology and Evolution.

  20. 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

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

    PubMed

    Lazar, Vladimir; Suo, Chen; Orear, Cedric; van den Oord, Joost; Balogh, Zsofia; Guegan, Justine; Job, Bastien; Meurice, Guillaume; Ripoche, Hugues; Calza, Stefano; Hasmats, Johanna; Lundeberg, Joakim; Lacroix, Ludovic; Vielh, Philippe; Dufour, Fabienne; Lehtiö, Janne; Napieralski, Rudolf; Eggermont, Alexander; Schmitt, Manfred; Cadranel, Jacques; Besse, Benjamin; Girard, Philippe; Blackhall, Fiona; Validire, Pierre; Soria, Jean-Charles; Dessen, Philippe; Hansson, Johan; Pawitan, Yudi

    2013-12-03

    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. 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. 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, CTHRC1 and 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. Integrated molecular characterization of AC and SCC helped identify clinically relevant markers and potential drivers, which are

  2. 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

  3. 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.

  4. Integrated Transcriptome Map Highlights Structural and Functional Aspects of the Normal Human Heart.

    PubMed

    Caracausi, Maria; Piovesan, Allison; Vitale, Lorenza; Pelleri, Maria Chiara

    2017-04-01

    A systematic meta-analysis of the available gene expression profiling datasets for the whole normal human heart generated a quantitative transcriptome reference map of this organ. Transcriptome Mapper (TRAM) software integrated 32 gene expression profile datasets from different sources returning a reference value of expression for each of the 43,360 known, mapped transcripts assayed by any of the experimental platforms used in this regard. Main findings include the visualization at the gene and chromosomal levels of the classical description of the basic histology and physiology of the heart, the identification of suitable housekeeping reference genes, the analysis of stoichiometry of gene products, and the focusing on chromosome 21 genes, which are present in one excess copy in Down syndrome subjects, presenting cardiovascular defects in 30-40% of cases. Independent in vitro validation showed an excellent correlation coefficient (r = 0.98) with the in silico data. Remarkably, heart/non-cardiac tissue expression ratio may also be used to anticipate that effects of mutations will most probably affect or not the heart. The quantitative reference global portrait of gene expression in the whole normal human heart illustrates the structural and functional aspects of the whole organ and is a general model to understand the mechanisms underlying heart pathophysiology. J. Cell. Physiol. 232: 759-770, 2017. © 2016 Wiley Periodicals, Inc. © 2016 Wiley Periodicals, Inc.

  5. [The German Clinical Trials Register: reasons, general and technical aspects, international integration].

    PubMed

    Dreier, G; Hasselblatt, H; Antes, G; Schumacher, M

    2009-04-01

    In order to provide a central portal for information on clinical research in Germany and thus to facilitate the search of planned, ongoing and completed clinical trials, the German Clinical Trials Register (GermanCTR) was implemented in cooperation with the WHO's registries network. It is an open access online register of clinical trials conducted in Germany, which allows all users to search for, register and share information on clinical trials. The project is funded by the Federal Ministry of Education and Research and is implemented at the Institute for Medical Biometry and Medical Informatics of the University Medical Center Freiburg as a joint project of the Clinical Trials Center Freiburg and the German Cochrane Center. Since October 2008 the GermanCTR is an approved WHO Primary Registry and allows clinical trial registration in Germany according to the requirements of the International Committee of Medical Journal Editors (ICMJE). Reasons for a national trials register, general and technical aspects of implementing the GermanCTR as well as the national and international integration are described here.

  6. RICOR's new development of a highly reliable integral rotary cooler: engineering and reliability aspects

    NASA Astrophysics Data System (ADS)

    Filis, Avishai; Pundak, Nachman; Barak, Moshe; Porat, Ze'ev; Jaeger, Mordechai

    2011-06-01

    The growing demand for EO applications that work around the clock 24hr/7days a week, such as in border surveillance systems, emphasizes the need for a highly reliable cryocooler having increased operational availability and decreased integrated system Life Cycle (ILS) cost. In order to meet this need RICOR has developed a new rotary Stirling cryocooler, model K508N, intended to double the K508's operating MTTF achieving 20,000 operating MTTF hours. The K508N employs RICOR's latest mechanical design technologies such as optimized bearings and greases, bearings preloading, advanced seals, laser welded cold finger and robust design structure with increased natural frequency compared to the K508 model. The cooler enhanced MTTF was demonstrated by a Validation and Verification (V&V) plan comprising analytical means and a comparative accelerated life test between the standard K508 and the K508N models. Particularly, point estimate and confidence interval for the MTTF improvement factor where calculated periodically during and after the test. The (V&V) effort revealed that the K508N meets its MTTF design goal. The paper will focus on the technical and engineering aspects of the new design. In addition it will discuss the market needs and expectations, investigate the reliability data of the present reference K508 model; and report the accelerate life test data and the statistical analysis methodology as well as its underlying assumptions and results.

  7. Integrating the Ontological, Epistemological, and Sociocultural Aspects: A Holistic View of Teacher Education

    ERIC Educational Resources Information Center

    Huang, Teng

    2016-01-01

    The three aspects of teacher change--ontological, epistemological, and sociocultural--are traditionally regarded as independent. Usually only the epistemological aspect is highlighted in formal teacher education. In this paper, I argue that a holistic and interdependent view of these aspects is needed. Thus, this paper aims to explore the process…

  8. TCMID: Traditional Chinese Medicine integrative database for herb molecular mechanism analysis.

    PubMed

    Xue, Ruichao; Fang, Zhao; Zhang, Meixia; Yi, Zhenghui; Wen, Chengping; Shi, Tieliu

    2013-01-01

    As an alternative to modern western medicine, Traditional Chinese Medicine (TCM) is receiving increasingly attention worldwide. Great efforts have been paid to TCM's modernization, which tries to bridge the gap between TCM and modern western medicine. As TCM and modern western medicine share a common aspect at molecular level that the compound(s) perturb human's dysfunction network and restore human normal physiological condition, the relationship between compounds (in herb, refer to ingredients) and their targets (proteins) should be the key factor to connect TCM and modern medicine. Accordingly, we construct this Traditional Chinese Medicine Integrated Database (TCMID, http://www.megabionet.org/tcmid/), which records TCM-related information collected from different resources and through text-mining method. To enlarge the scope of the TCMID, the data have been linked to common drug and disease databases, including Drugbank, OMIM and PubChem. Currently, our TCMID contains ∼47 000 prescriptions, 8159 herbs, 25 210 compounds, 6828 drugs, 3791 diseases and 17 521 related targets, which is the largest data set for related field. Our web-based software displays a network for integrative relationships between herbs and their treated diseases, the active ingredients and their targets, which will facilitate the study of combination therapy and understanding of the underlying mechanisms for TCM at molecular level.

  9. Integrating fossils with molecular phylogenies improves inference of trait evolution.

    PubMed

    Slater, Graham J; Harmon, Luke J; Alfaro, Michael E

    2012-12-01

    Comparative biologists often attempt to draw inferences about tempo and mode in evolution by comparing the fit of evolutionary models to phylogenetic comparative data consisting of a molecular phylogeny with branch lengths and trait measurements from extant taxa. These kinds of approaches ignore historical evidence for evolutionary pattern and process contained in the fossil record. In this article, we show through simulation that incorporation of fossil information dramatically improves our ability to distinguish among models of quantitative trait evolution using comparative data. We further suggest a novel Bayesian approach that allows fossil information to be integrated even when explicit phylogenetic hypotheses are lacking for extinct representatives of extant clades. By applying this approach to a comparative dataset comprising body sizes for caniform carnivorans, we show that incorporation of fossil information not only improves ancestral state estimates relative to those derived from extant taxa alone, but also results in preference of a model of evolution with trend toward large body size over alternative models such as Brownian motion or Ornstein-Uhlenbeck processes. Our approach highlights the importance of considering fossil information when making macroevolutionary inference, and provides a way to integrate the kind of sparse fossil information that is available to most evolutionary biologists.

  10. Integrated molecular profiling of SOD2 expression in multiple myeloma.

    PubMed

    Hurt, Elaine M; Thomas, Suneetha B; Peng, Benjamin; Farrar, William L

    2007-05-01

    Reactive oxygen species are known to be involved in several cellular processes, including cell signaling. SOD2 is a key enzyme in the conversion of reactive oxygen species and has been implicated in a host of disease states, including cancer. Using an integrated, whole-cell approach encompassing epigenetics, genomics, and proteomics, we have defined the role of SOD2 in multiple myeloma. We show that the SOD2 promoter is methylated in several cell lines and there is a correlative decrease in expression. Furthermore, myeloma patient samples have decreased SOD2 expression compared with healthy donors. Overexpression of SOD2 results in decreased proliferation and altered sensitivity to 2-methoxyestradiol-induced DNA damage and apoptosis. Genomic profiling revealed regulation of 65 genes, including genes involved in tumorigenesis, and proteomic analysis identified activation of the JAK/STAT pathway. Analysis of nearly 400 activated transcription factors identified 31 transcription factors with altered DNA binding activity, including XBP1, NFAT, forkhead, and GAS binding sites. Integration of data from our gestalt molecular analysis has defined a role for SOD2 in cellular proliferation, JAK/STAT signaling, and regulation of several transcription factors.

  11. Path-integral molecular dynamics simulation of diamond

    NASA Astrophysics Data System (ADS)

    Ramírez, Rafael; Herrero, Carlos P.; Hernández, Eduardo R.

    2006-06-01

    Diamond is studied by path-integral molecular dynamics simulations of the atomic nuclei in combination with a tight-binding Hamiltonian to describe its electronic structure and total energy. This approach allows us to quantify the influence of quantum zero-point vibrations and finite temperatures on both the electronic and vibrational properties of diamond. The electron-phonon coupling mediated by the zero-point vibration reduces the direct electronic gap of diamond by 10%. The calculated decrease of the direct gap with temperature shows good agreement with the experimental data available up to 700K . Anharmonic vibrational frequencies of the crystal have been obtained from a linear-response approach based on the path integral formalism. In particular, the temperature dependence of the zone-center optical phonon has been derived from the simulations. The anharmonicity of the interatomic potential produces a red shift of this phonon frequency. At temperatures above 500K , this shift is overestimated in comparison to available experimental data. The predicted temperature shift of the elastic constant c44 displays reasonable agreement with the available experimental results.

  12. 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

  13. 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.

  14. Molecular aspects of soybean cultivar-specific nodulation by Sinorhizobium fredii USDA257.

    PubMed

    Annapurna, K; Krishnan, Hari B

    2003-10-01

    Sinorhizobium fredii USDA257 forms nitrogen-fixing nodules in association with the primitive soybean cultivar 'Peking' but fails to initiate nodules on many advanced soybean cultivars, including 'McCall'. This distinction is controlled by a set of nodulation genes termed nolXWBTUV. Inactivation of any of these genes enables USDA257 to nodulate McCall and many other improved soybean cultivars. Mutation in the nolXWBTUV locus also alters the Nod factor structure resulting in the production of a novel molecule with glucose incorporated into the chitin backbone. Some of the genes located in the nolXWBTUV locus reveal sequence homologies to known components of the type III secretion system (TTSS) of plant and animal pathogenic bacteria. Recent studies have demonstrated the presence of a complete TTSS in USDA257 and few other symbiotic bacteria. The TTSS cluster of USDA257 contains 27 open reading frames out of which 10 code for the structural components of the TTSS. USDA257, when grown in presence of flavonoids, secrete several proteins called Nops (Nodulation Outer Proteins) into the extracellular environment. Genes located in the TTSS of USDA257 encode some of the extracellular proteins, such as NopX, NopB, and NopL. These type III secreted proteins appear to play an important role in regulating nodulation in a host-dependent manner. Failure to elaborate the Nops results in a drastic phenotypic effect on soybean nodulation, indicating that these proteins may play a pivotal role in soybean cultivar specificity. The secretion of Nops appears to be facilitated by novel filamentous appendages (pili) that are produced by USDA257 upon induction by flavonoids. Biochemical studies have demonstrated the close association of several Nops with the purified pili. However, it remains to be seen if the filamentous appendages can function as conduits for delivery of Nops into the host cell. This review examines the current state of our knowledge on the molecular aspects of soybean

  15. New aspects of π–d interactions in magnetic molecular conductors

    PubMed Central

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

    2009-01-01

    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

  16. Molecular integrals involving hulthén-type functions ( n = l STO) in relativistic quantum chemistry

    NASA Astrophysics Data System (ADS)

    Malli, Gulzari

    1981-03-01

    Dirac-Fock-Roothaan (DFR) treatment of molecules (with STO as basis) leads to molecular integrals involving n = l STOs which are known in nuclear physics as Hulthén-type functions (HTFs) It is pointed out. that with minor modifications, the existing non-relativistic molecular integral programs which use STO as basis can be used to evaluate molecular integrals involving Hulthén-type functions

  17. 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

  18. Ab initio molecular orbital calculation considering the quantum mechanical effect of nuclei by path integral molecular dynamics

    NASA Astrophysics Data System (ADS)

    Shiga, Motoyuki; Tachikawa, Masanori; Miura, Shinichi

    2000-12-01

    We present an accurate calculational scheme for many-body systems composed of electrons and nuclei, by path integral molecular dynamics technique combined with the ab initio molecular orbital theory. Based upon the scheme, the simulation of a water molecule at room temperature is demonstrated, applying all-electron calculation at the Hartree-Fock level of theory.

  19. A portable, integrated analyzer for microfluidic - based molecular analysis.

    PubMed

    Qiu, Xianbo; Chen, Dafeng; Liu, Changchun; Mauk, Michael G; Kientz, Terry; Bau, Haim H

    2011-10-01

    A portable, fully automated analyzer that provides actuation and flow control to a disposable, self-contained, microfluidic cassette ("chip") for point-of-care, molecular testing is described. The analyzer provides mechanical actuation to compress pouches that pump liquids in the cassette, to open and close diaphragm valves for flow control, and to induce vibrations that enhance stirring. The analyzer also provides thermal actuation for the temperature cycling needed for polymerase chain reaction (PCR) amplification of nucleic acids and for various drying processes. To improve the temperature uniformity of the PCR chamber, the system utilizes a double-sided heating/cooling scheme with a custom feedforward, variable, structural proportional-integral-derivative (FVSPID) controller. The analyzer includes a programmable central processing unit that directs the sequence and timing of the various operations and that is interfaced with a computer. The disposable cassette receives a sample, and it carries out cell lysis, nucleic acid isolation, concentration, and purification, thermal cycling, and either real time or lateral flow (LF) based detection. The system's operation was demonstrated by processing saliva samples spiked with B. cereus cells. The amplicons were detected with a lateral flow assay using upconverting phosphor reporter particles. This system is particularly suited for use in regions lacking centralized laboratory facilities and skilled personnel.

  20. 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.

  1. Integrating multiple disturbance aspects: management of an invasive thistle, Carduus nutans

    PubMed Central

    Zhang, Rui; Shea, Katriona

    2012-01-01

    Background and Aims Disturbances occur in most ecological systems, and play an important role in biological invasions. We delimit five key disturbance aspects: intensity, frequency, timing, duration and extent. Few studies address more than one of these aspects, yet interactions and interdependence between aspects may lead to complex outcomes. Methods In a two-cohort experimental study, we examined how multiple aspects (intensity, frequency and timing) of a mowing disturbance regime affect the survival, phenology, growth and reproduction of an invasive thistle Carduus nutans (musk thistle). Key Results Our results show that high intensity and late timing strongly delay flowering phenology and reduce plant survival, capitulum production and plant height. A significant interaction between intensity and timing further magnifies the main effects. Unexpectedly, high frequency alone did not effectively reduce reproduction. However, a study examining only frequency and intensity, and not timing, would have erroneously attributed the importance of timing to frequency. Conclusions We used management of an invasive species as an example to demonstrate the importance of a multiple-aspect disturbance framework. Failure to consider possible interactions, and the inherent interdependence of certain aspects, could result in misinterpretation and inappropriate management efforts. This framework can be broadly applied to improve our understanding of disturbance effects on individual responses, population dynamics and community composition. PMID:22199031

  2. 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

  3. The Glutamatergic Aspects of Schizophrenia Molecular Pathophysiology: Role of the Postsynaptic Density, and Implications for Treatment

    PubMed Central

    Iasevoli, Felice; Tomasetti, Carmine; Buonaguro, Elisabetta F.; de Bartolomeis, Andrea

    2014-01-01

    Schizophrenia is one of the most debilitating psychiatric diseases with a lifetime prevalence of approximately 1%. Although the specific molecular underpinnings of schizophrenia are still unknown, evidence has long linked its pathophysiology to postsynaptic abnormalities. The postsynaptic density (PSD) is among the molecular structures suggested to be potentially involved in schizophrenia. More specifically, the PSD is an electron-dense thickening of glutamatergic synapses, including ionotropic and metabotropic glutamate receptors, cytoskeletal and scaffolding proteins, and adhesion and signaling molecules. Being implicated in the postsynaptic signaling of multiple neurotransmitter systems, mostly dopamine and glutamate, the PSD constitutes an ideal candidate for studying dopamine-glutamate disturbances in schizophrenia. Recent evidence suggests that some PSD proteins, such as PSD-95, Shank, and Homer are implicated in severe behavioral disorders, including schizophrenia. These findings, further corroborated by genetic and animal studies of schizophrenia, offer new insights for the development of pharmacological strategies able to overcome the limitations in terms of efficacy and side effects of current schizophrenia treatment. Indeed, PSD proteins are now being considered as potential molecular targets against this devastating illness. The current paper reviews the most recent hypotheses on the molecular mechanisms underlying schizophrenia pathophysiology. First, we review glutamatergic dysfunctions in schizophrenia and we provide an update on postsynaptic molecules involvement in schizophrenia pathophysiology by addressing both human and animal studies. Finally, the possibility that PSD proteins may represent potential targets for new molecular interventions in psychosis will be discussed. PMID:24851087

  4. Kinetic Aspects of Lattice Mismatch in Molecular Beam Epitaxial Growth on Planar and Patterned Substrates

    DTIC Science & Technology

    1993-03-31

    operating wavelength regime of InGaAs/InAlGaAs based optical devices, opens the way for monolithic integration of such RTD’s with modulator and...detector devices, such as proposed for the monolithic opto-electronic transistor (MOET). The results obtained here were therefore used as a leverage for...potential candidate for a digital optical switch in the context of the AFOSR sponsored USC URI on Integration of Optical Computing in which this

  5. 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.

  6. [Molecular-physiological aspects of peptide regulation of function of the retina in retinitis pigmentosa].

    PubMed

    Khavinson, V Kh; Proniaeva, V E; Lin'kova, N S; Trofimova, S V; Umnpv, R S

    2014-01-01

    Peptide's bioregulators promotes restoration of the physiological activity of the retina in retinitis pigmentosa in older adults and in animal models. The molecular mechanism of physiological activity of peptides is connected with its ability to regulate synthesis of protein markers of differentiation of neurons and retinal pigment epithelium epigenetically.

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

    Treesearch

    Eduardo R. Nouhra; Laura S. Domínguez; Alejandra G. Becerra; James M. Trappe

    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 ...

  8. Particular aspects in the cytogenetics and molecular biology of salivary gland tumours – current review of reports

    PubMed Central

    Osuch-Wójcikiewicz, Ewa

    2016-01-01

    Salivary gland tumours are a group of lesions whose heterogeneity of biological and pathological features is widely reflected in the molecular aspect. This is demonstrated by an increasing number of studies in the field of genetics of these tumours. The aim of this study was to collect the most significant scientific reports on the cytogenetic and molecular data concerning these tumours, which might facilitate the identification of potential biomarkers and therapeutic targets. The analysis covered 71 papers included in the PubMed database. We focused on the most common tumours, such as pleomorphic adenoma, Warthin tumour, mucoepidermoid carcinoma, and others. The aim of this study is to present current knowledge about widely explored genotypic alterations (such as PLAG1 gene in pleomorphic adenoma or MECT1 gene in mucoepidermoid carcinoma), and also about rare markers, like Mena or SOX10 protein, which might also be associated with tumourigenesis and carcinogenesis of these tumours. PMID:27688723

  9. 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.

  10. 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.

  11. Quantitative Aspects of Single-Word Free Associations to Sentences Varying in Semantic Integration.

    ERIC Educational Resources Information Center

    Rosenberg, Sheldon

    It was anticipated that the single-word free association responses to sentences varying in degree of semantic integration (as indexed by sentence norms) would differ quantitatively. One group of 60 undergraduates was given a list of 16 sentences characterized by high semantic integration (HSI), while another group of 60 undergraduates received a…

  12. 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

  13. Low-temperature Fabrication Process for Integrated High-Aspect Ratio Metal Oxide Nanostructure Semiconductor Gas Sensors

    NASA Astrophysics Data System (ADS)

    Clavijo, William P.

    This work presents a new low-temperature fabrication process of metal oxide nanostructures that allows high-aspect ratio zinc oxide (ZnO) and titanium dioxide (TiO2) nanowires and nanotubes to be readily integrated with microelectronic devices for sensor applications. This process relies on a new method of forming a close-packed array of self-assembled high-aspect-ratio nanopores in an anodized aluminum oxide (AAO) template in a thin (2.5 microm) aluminum film deposited on a silicon and lithium niobate substrate (LiNbO3). This technique is in sharp contrast to traditional free-standing thick film methods and the use of an integrated thin aluminum film greatly enhances the utility of such methods. We have demonstrated the method by integrating ZnO nanowires, TiO2 nanowires, and multiwall TiO2 nanotubes onto the metal gate of a MOSFET (Metal-Oxide-Semiconductor Field-Effect Transistor), and the delay line of a surface acoustic wave (SAW) device to form an integrated ChemFET (Chemical Field-Effect Transistor) and a orthogonal frequency coded (OFC) SAW gas sensor. The resulting metal oxide nanostructures of 1-1.7 microm in height and 40-100 nm in diameter offer an increase of up to 220X the surface area over a standard flat metal oxide film for sensing applications.

  14. 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

  15. Molecular Aspects of Mucoadhesive Carrier Development for Drug Delivery and Improved Absorption

    PubMed Central

    Peppas, Nicholas A; Thomas, J. Brock; McGinity, James

    2011-01-01

    Although the oral route remains the most favored route of drug administration, major scientific obstacles prevent the effective and efficient delivery of low-molecular-mass drugs, peptides and proteins that exhibit poor solubility and permeability. Mucoadhesive dosage forms and the associated drug carriers have the ability to interact at a molecular level with the mucus gel layer that lines the epithelial surfaces of the major absorptive regions of the body. This interaction provides an increased residence time of the therapeutic formulation while localizing the drug at the site of administration. Such local, non-specific targeting leads to an increase in both oral absorption and bioavailability. Fundamental understanding of the biological processes encountered along the gastrointestinal tract can provide a sufficient engineer of carriers that are capable to provide this increase in residence time. Here we discuss the theoretical framework for achieving mucoadhesive systems as related to biomaterials science and the structure of the biomaterials used. PMID:19105897

  16. 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…

  17. Integrating the Epistemic and Ontological Aspects of Content Knowledge in Science Teaching and Learning

    ERIC Educational Resources Information Center

    Papadouris, Nicos; Constantinou, Constantinos P.

    2017-01-01

    Promoting facility with content knowledge is one of the most important objectives of science teaching. Conventionally, the focus for this objective is placed on the substantive side of content knowledge (e.g. science concepts/laws), whereas its epistemic or ontological aspects (e.g. why do we construct concepts?) rarely receive explicit attention.…

  18. 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)…

  19. 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

  20. [Hereditary palmoplantar keratoderma - a focus on clinical and molecular genetic aspects].

    PubMed

    Kamaleswaran, Shailajah; Ousager, Lilian Bomme; Bach, Rasmus Overgaard; Bygum, Anette

    2014-02-10

    Hereditary palmoplantar keratoderma comprises a heterogenous group of genodermatoses. The clinical spectrum of palmoplantar keratoderma can range from pure skin thickening, restricted to palmoplantar skin to complex conditions with dental anomalies, eye symptoms, deafness, cardiac disease and cancer. The classification of hereditary palmoplantar keratoderma has been complicated. In recent years the molecular genetic background has been clarified for an increasing number of palmoplantar keratodermas, which makes it possible to make a more accurate diagnosis.

  1. Some aspects of radical chemistry in the assembly of complex molecular architectures

    PubMed Central

    Quiclet-Sire, Béatrice

    2013-01-01

    Summary This review article describes briefly some of the radical processes developed in the authors’ laboratory as they pertain to the concise assembly of complex molecular scaffolds. The emphasis is placed on the use of nitrogen-centred radicals, on the degenerate addition–transfer of xanthates, especially on its potential for intermolecular carbon–carbon bond formation, and on the generation and capture of radicals through electron transfer processes. PMID:23616797

  2. 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.

  3. Effects of molecular symmetry on quantum reaction dynamics: novel aspects of photoinduced nonadiabatic dynamics.

    PubMed

    Al-Jabour, Salih; Leibscher, Monika

    2015-01-15

    Nonadiabatic coupling terms (NACTs) between different electronic states lead to fast radiationless decay in photoexcited molecules. Using molecular symmetry, i.e., symmetry with respect to permutation of identical nuclei and inversion of the molecule in space, the irreducible representations of the NACTs can be determined with a combination of molecular symmetry arguments and quantization rules. Here, we extend these symmetry rules for electronic states and coupling elements and demonstrate the importance of molecular symmetry for nonadiabatic nuclear dynamics. As an example, we consider the NACTs related to the torsion around the CN bond in C5H4NH. We present the results of quantum dynamical simulations of the photoinduced large amplitude torsion on three coupled electronic states and show how the interference between wavepackets leads to radiationless decay, which depends on the symmetry of the NACTs. Moreover, we show that the nuclear spin of the system determines the symmetry of the initial nuclear wave function and thus influences the torsional dynamics. This may open new possibilities for nuclear spin selective laser control of nuclear dynamics.

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

    PubMed Central

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

    2016-01-01

    SUMMARY 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

  5. Analytic evaluation of two-center molecular integrals

    NASA Technical Reports Server (NTRS)

    Tai, H.

    1986-01-01

    By using the Fourier-transform technique, the explicit expressions for the one-electron - two-center overlap integrals of Slater-type atomic orbitals up to 3d are derived. The final expressions are analytic, simple, and independent of local coordinates. Furthermore, they do not contain the nonclosed-form of exponential integrals which were presented in expressions given in earlier work. It is shown that the two-electron - two-center Coulomb integrals, as well as the hybrid integrals, can simply be expressed in terms of these integrals. The numerical instability arising from the situation in which the exponents of the two orbitals are almost equal is discussed, and a solution for this problem based on a Taylor-series expansion of the integral is suggested.

  6. 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.

  7. Clinical and molecular aspects of familial hypercholesterolemia in Ibero-American countries.

    PubMed

    Santos, Raul D; Bourbon, Mafalda; Alonso, Rodrigo; Cuevas, Ada; Vasques-Cardenas, Norma Alexandra; Pereira, Alexandre C; Merchan, Alonso; Alves, Ana Catarina; Medeiros, Ana Margarida; Jannes, Cinthia E; Krieger, Jose E; Schreier, Laura; Perez de Isla, Leopoldo; Magaña-Torres, Maria Teresa; Stoll, Mario; Mata, Nelva; Dell Oca, Nicolas; Corral, Pablo; Asenjo, Sylvia; Bañares, Virginia G; Reyes, Ximena; Mata, Pedro

    There is little information about familial hypercholesterolemia (FH) epidemiology and care in Ibero-American countries. The Ibero-American FH network aims at reducing the gap on diagnosis and treatment of this disease in the region. To describe clinical, molecular, and organizational characteristics of FH diagnosis in Argentina, Brazil, Chile, Colombia, Mexico, Portugal, Spain, and Uruguay. Descriptive analysis of country data related to FH cascade screening, molecular diagnosis, clinical practice guidelines, and patient organization presence in Ibero-America. From a conservative estimation of an FH prevalence of 1 of 500 individuals, there should be 1.2 million heterozygous FH individuals in Ibero-America and roughly 27,400 were diagnosed so far. Only Spain, Brazil, Portugal, and Uruguay have active cascade screening programs. The prevalence of cardiovascular disease ranged from 10% to 42% in member countries, and the highest molecular identification rates are seen in Spain, 8.3%, followed by Portugal, 3.8%, and Uruguay with 2.5%. In the 3 countries with more FH patients identified (Spain, Portugal, and Brazil) between 10 and 15 mutations are responsible for 30% to 47% of all FH cases. Spain and Portugal share 5 of the 10 most common mutations (4 in low density lipoprotein receptor [LDLR] and the APOB3527). Spain and Spanish-speaking Latin American countries share 6 of the most common LDLR mutations and the APOB3527. LDL apheresis is available only in Spain and Portugal and not all countries have specific FH diagnostic and treatment guidelines as well as patient organizations. Ibero-American countries share similar mutations and gaps in FH care. Copyright © 2016 National Lipid Association. Published by Elsevier Inc. All rights reserved.

  8. Pathophysiology and molecular aspects of diffuse large B-cell lymphoma

    PubMed Central

    Gouveia, Gisele Rodrigues; Siqueira, Sheila Aparecida Coelho; Pereira, Juliana

    2012-01-01

    Diffuse large B-Cell lymphoma is the most common subtype of non-Hodgkin lymphoma in the West. In Brazil, it is the fifth cause of cancer, with more than 55,000 cases and 26,000 deaths per year. At Hospital das Clínicas da Faculdade de Medicina da Universidade de São Paulo - HCFMUSP, diffuse large B-Cell lymphoma represents 49.7% of all non-Hodgkin lymphoma cases. Initially, the classification of non-Hodgkin lymphoma was based on morphology, but advances in immunology and molecular medicine allowed the introduction of a biological classification for these diseases. As for other cancers, non-Hodgkin lymphoma involves patterns of multifactorial pathogenesis with environmental factors, as well as genetic, occupational and dietary factors, contributing to its development. Multiple lesions involving molecular pathways of B-cell proliferation and differentiation may result in the activation of oncogenes such as the BCL2, BCL6, and MYC genes and the inactivation of tumor suppressor genes such as p53 and INK4, as well as other important transcription factors such as OCT-1 and OCT-2. A dramatic improvement in survival was seen after the recent introduction of the anti-CD20 monoclonal antibody. The association of this antibody to the cyclophosphamide, hydroxydaunorubicin, oncovin and prednisolone (CHOP) regimen has increased overall survival of diffuse large B-Cell lymphoma and follicular lymphoma patients by 20%. However, 50% of all diffuse large B-Cell lymphoma patients remain incurable, creating a demand for more research with new advances in treatment. Thus, it is important to know and understand the key factors and molecular pathways involved in the pathogenesis of diffuse large B-Cell lymphoma. PMID:23323070

  9. 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.

  10. Charcot-Marie-Tooth disease and related hereditary polyneuropathies: molecular diagnostics determine aspects of medical management.

    PubMed

    Szigeti, Kinga; Garcia, Carlos A; Lupski, James R

    2006-02-01

    An evidence-based approach was used to determine the frequency distribution of genes contributing to the Charcot-Marie-Tooth (CMT) disease phenotype. We performed a combined analysis of 11 population-based studies from various ethnic backgrounds to generate an evidence-based testing scheme. To estimate the relative frequencies of the responsible genes for which population-based studies are not available, we used our cohort of clinically classified patients with CMT and related neuropathies collected before the availability of genetic testing. Similar mutation frequencies were detected in the various studies, revealing a uniform distribution of pathogenic mutations. In CMT1 70% of patients harbor the CMT1A duplication, followed by GJB1 mutations at 8.8%. MPZ and PMP22 mutations are less common, identified on average in 2.9% and 1.5% of patients, respectively. Other genes not tested in population-based studies contribute to less than 1% of disease individually. In CMT2 MFN2 mutations are the most common, although population-based studies are not yet available. CMT represents a heterogeneous group of disorders at the molecular level. Nevertheless, testing for the CMT1A duplication (i.e., duplication of PMP22) alone yields an accurate molecular diagnosis in approximately half of all patients. If one further specifies the clinical type (demyelinating vs. axonal), the yield of detecting a molecular defect increases to 75% to 80% in the demyelinating or CMT1 group with a screening test that evaluates for CMT1A duplication/hereditary neuropathy with liability to pressure palsies deletion and GJB1 point mutations.

  11. Molecular aspects of aromatic C additions to soils: Implications of char quality for ecosystem functionality

    NASA Astrophysics Data System (ADS)

    Keiluweit, M.; Nico, P. S.; Johnson, M. G.; Kleber, M.

    2009-12-01

    Solid residues of incomplete combustion (biochar or char) are continuously being added to soils due to natural vegetation fires in many ecosystems. However, new strategies for carbon sequestration in soils are likely to include the active addition of biochar to soils. Since biochar is a highly aromatic organic material such additions will modify the native molecular structure of soil organic matter and thus alter interactions with the global atmosphere and hydrosphere. Here we present a molecular level assessment of the physical organization and chemical complexity of biomass-derived chars and, specifically, that of aromatic carbon in char structures. Differences among wood and grass charred at temperatures from 100 to 700°C are investigated. BET-N2 surface area, X-ray diffraction (XRD), synchrotron-based Near-edge X-ray Absorption Fine Structure (NEXAFS) and Fourier transform infrared (FT-IR) spectroscopy results demonstrate how the two plant precursor materials undergo analogous, but quantitatively different physical-chemical transitions as charring intensity increases. These changes suggest the existence of four distinct physical and chemical categories of char. We find that each category of char consists of a unique mixture of chemical phases and physical states: (i) in transition chars the crystalline character of the precursor materials is preserved, (ii) in amorphous chars the heat-altered molecules and incipient aromatic polycondensates are randomly mixed, (iii) composite chars consist of poorly ordered graphene stacks embedded in amorphous phases, and (iv) turbostratic chars are dominated by turbostratic (disordered) graphitic crystallites. There is wide variation in both the chemical and the physical nature of aromatic carbon among these char categories. In this presentation we will point out how molecular variations among the aromatic components of the different char categories translate into differences in their ability to: (i) persist in the

  12. Regeneration in the Pituitary After Cell-Ablation Injury: Time-Related Aspects and Molecular Analysis.

    PubMed

    Willems, Christophe; Fu, Qiuli; Roose, Heleen; Mertens, Freya; Cox, Benoit; Chen, Jianghai; Vankelecom, Hugo

    2016-02-01

    We recently showed that the mouse pituitary holds regenerative competence. Young-adult GHCre/iDTR mice, expressing diphtheria toxin (DT) receptor in GH-producing cells, regenerate the GH(+) cells, as ablated by 3-day DT treatment (3DT), up to 60% after 5 months. The pituitary's stem cells participate in this restoration process. Here, we characterized this regenerative capacity in relation to age and recovery period and started to search for underlying molecular mechanisms. Extending the recovery period (up to 19 mo) does not result in higher regeneration levels. In addition, the regenerative competence disappears at older age, coinciding with a reduction in pituitary stem cell number and fitness. Surprisingly, prolonging DT treatment of young-adult mice to 10 days (10DT) completely blocks the regeneration, although the stem cell compartment still reacts by promptly expanding, and retains in vitro stem cell functionality. To obtain a first broad view on molecular grounds underlying reparative capacity and/or failure, the stem cell-clustering side population was analyzed by whole-genome expression analysis. A number of stemness factors and components of embryonic, epithelial-mesenchymal transition, growth factor and Hippo pathways are higher expressed in the stem cell-clustering side population of the regenerating pituitary (after 3DT) when compared with the basal gland and to the nonregenerating pituitary (after 10DT). Together, the regenerative capacity of the pituitary is limited both in age-related terms and final efficacy, and appears to rely on stem cell-associated pathway activation. Dissection of the molecular profiles may eventually identify targets to induce or boost regeneration in situations of (injury-related) pituitary deficiency.

  13. 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.

  14. Molecular and genetic aspects in the etiopathogenesis of ameloblastoma: An update

    PubMed Central

    Nagi, Ravleen; Sahu, Shashikant; Rakesh, N

    2016-01-01

    Ameloblastoma is the second most common benign epithelial odontogenic tumor and though it is of a benign nature, it is locally invasive, has a high recurrence rate and could potentially become malignant. Many theories have been proposed to explain the pathogenesis of ameloblastoma. Proper understanding of the pathogenic mechanism involved in ameloblastoma and its proliferation aids in constituting proper treatment of choice at an early stage, preventing morbidity associated with extensive therapy. An attempt has been made to discuss the current concepts related to molecular and genetic changes that occur in ameloblastoma as these could affect treatment plan and prognosis. PMID:27721617

  15. Primary melanocytic tumors of the central nervous system: a review with focus on molecular aspects.

    PubMed

    Küsters-Vandevelde, Heidi V N; Küsters, Benno; van Engen-van Grunsven, Adriana C H; Groenen, Patricia J T A; Wesseling, Pieter; Blokx, Willeke A M

    2015-03-01

    Primary melanocytic tumors of the central nervous system (CNS) represent a spectrum of rare tumors. They can be benign or malignant and occur in adults as well as in children, the latter often in the context of neurocutaneous melanosis. Until recently, the genetic alterations in these tumors were largely unknown. This is in contrast with cutaneous and uveal melanomas, which are known to harbor distinct oncogenic mutations that can be used as targets for treatment with small-molecule inhibitors in the advanced setting. Recently, novel insights in the molecular alterations underlying primary melanocytic tumors of the CNS were obtained, including different oncogenic mutations in tumors in adult patients (especially GNAQ, GNA11) vs. children (especially NRAS). In this review, the focus is on molecular characteristics of primary melanocytic tumors of the CNS. We summarize what is known about their genetic alterations and discuss implications for pathogenesis and differential diagnosis with other pigmented tumors in or around the CNS. Finally, new therapeutic options with targeted therapy are discussed. © 2014 International Society of Neuropathology.

  16. Molecular aspects of the interaction of spermidine and α-chymotrypsin.

    PubMed

    Farhadian, Sadegh; Shareghi, Behzad; Saboury, Ali A; Babaheydari, Ali Kazemi; Raisi, Fatame; Heidari, Ehsan

    2016-11-01

    Polyamines such as spermidine are essential for survival. The purpose of the present study was to investigate how spermidine could influence the conformation, thermal stability and the activity of α-chymotrypsin. The influence of spermidine on the structure and stability of α-Chymotrypsin (α-Chy) explored using different spectroscopy method and molecular docking simulations. The stability and activity of α-Chy were increased in the presence of spermidine. Increasing of the α-Chy absorption in the presence of spermidine was as a result of the formation of a spermidine - α-Chy complex. The results of fluorescence spectroscopic measurements suggested that spermidine has a vigorous ability to quench the intrinsic fluorescence of α-Chy through the dynamic quenching procedure. Near and Far-UV CD studies also confirmed the transfer of aromatic residues to a more flexible environment. The absorption increasing of α-Chy in the presence of spermidine was as a result of the formation of spermidine - α-Chy complex. Molecular docking results also revealed the presence of one binding site with a negative value for the Gibbs free energy of the binding of spermidine to α-Chy. Further, the docking study revealed that van der Waals interactions and hydrogen bonds play a main role in stabilizing the complex.

  17. Selective Modulators of PPAR-γ Activity: Molecular Aspects Related to Obesity and Side-Effects

    PubMed Central

    Zhang, Fang; Lavan, Brian E.; Gregoire, Francine M.

    2007-01-01

    Peroxisome proliferator-activated receptor γ (PPAR-γ) is a key regulator of lipid metabolism and energy balance implicated in the development of insulin resistance and obesity. The identification of putative natural and synthetic ligands and activators of PPAR-γ has helped to unravel the molecular basis of its function, including molecular details regarding ligand binding, conformational changes of the receptor, and cofactor binding, leading to the emergence of the concept of selective PPAR-γ modulators (SPPARγMs). SPPARγMs bind in distinct manners to the ligand-binding pocket of PPAR-γ, leading to alternative receptor conformations, differential cofactor recruitment/displacement, differential gene expression, and ultimately differential biological responses. Based on this concept, new and improved antidiabetic agents for the treatment of diabetes are in development. This review summarizes the current knowledge on the mechanism of action and biological effects of recently characterized SPPARγMs, including metaglidasen/halofenate, PA-082, and the angiotensin receptor antagonists, recently characterized as a new class of SPPARγMs. PMID:17389769

  18. 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.

  19. On an aspect of calculated molecular descriptors in QSAR studies of quinolone antibacterials.

    PubMed

    Ghosh, Payel; Thanadath, Megha; Bagchi, Manish C

    2006-08-01

    The re-emergence of tuberculosis infections, which are resistant to conventional drug therapy, has steadily risen in the last decade and as a result of that, fluoroquinolone drugs are being used as the second line of action. But there is hardly any study to examine specific structure activity relationships of quinolone antibacterials against mycobacteria. In this paper, an attempt has been made to establish a quantitative structure activity relationship modeling for a series of quinolone compounds against Mycobacterium fortuitum and Mycobacterium smegmatis. Due to lack of sufficient physicochemical data for the anti-mycobacterial compounds, it becomes very difficult to develop predictive methods based on experimental data. The present paper is an effort for the development of QSARs from the standpoint of physicochemical, constitutional, geometrical, electrostatic and topological indices. Molecular descriptors have been calculated solely from the chemical structure of N-1, C-7 and 8 substituted quinolone compounds and ridge regression models have been developed which can explain a better structure-activity relationship. Consideration of an intermolecular similarity analysis approach that led to a successful computer program development in PERL language has been used for comparing the influence of various molecular descriptors in different data subsets. The comparison of relative effectiveness of the calculated descriptors in our ridge regression model gives rise to some interesting results.

  20. Regulation of K+ channel activities in plants: from physiological to molecular aspects.

    PubMed

    Chérel, Isabelle

    2004-02-01

    Plant voltage-gated channels belonging to the Shaker family participate in sustained K+ transport processes at the cell and whole plant levels, such as K+ uptake from the soil solution, long-distance K+ transport in the xylem and phloem, and K+ fluxes in guard cells during stomatal movements. The attention here is focused on the regulation of these transport systems by protein-protein interactions. Clues to the identity of the regulatory mechanisms have been provided by electrophysiological approaches in planta or in heterologous systems, and through analogies with their animal counterparts. It has been shown that, like their animal homologues, plant voltage-gated channels can assemble as homo- or heterotetramers associating polypeptides encoded by different Shaker genes, and that they can bind auxiliary subunits homologous to those identified in mammals. Furthermore, several regulatory processes (involving, for example, protein kinases and phosphatases, G proteins, 14-3-3s, or syntaxins) might be common to plant and animal Shakers. However, the molecular identification of plant channel partners is still at its beginning. This paper reviews current knowledge on plant K+ channel regulation at the physiological and molecular levels, in the light of the corresponding knowledge in animal cells, and discusses perspectives for the deciphering of regulatory networks in the future.

  1. Methodological aspects of the molecular and histological study of prostate cancer: focus on PTEN.

    PubMed

    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

    2015-05-01

    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. Copyright © 2015. Published by Elsevier Inc.

  2. Mathematical aspects of molecular replacement. I. Algebraic properties of motion spaces

    PubMed Central

    Chirikjian, Gregory S.

    2011-01-01

    Molecular replacement (MR) is a well established method for phasing of X-ray diffraction patterns for crystals composed of biological macromolecules of known chemical structure but unknown conformation. In MR, the starting point is known structural domains that are presumed to be similar in shape to those in the macromolecular structure which is to be determined. A search is then performed over positions and orientations of the known domains within a model of the crystallographic asymmetric unit so as to best match a computed diffraction pattern with experimental data. Unlike continuous rigid-body motions in Euclidean space and the discrete crystallographic space groups, the set of motions over which molecular replacement searches are performed does not form a group under the operation of composition, which is shown here to lack the associative property. However, the set of rigid-body motions in the asymmetric unit forms another mathematical structure called a quasigroup, which can be identified with right-coset spaces of the full group of rigid-body motions with respect to the chiral space group of the macromolecular crystal. The algebraic properties of this space of motions are articulated here. PMID:21844648

  3. Molecular Aspects of Wound Healing and the Rise of Venous Leg Ulceration: Omics Approaches to Enhance Knowledge and Aid Diagnostic Discovery

    PubMed Central

    Broszczak, Daniel A; Sydes, Elizabeth R; Wallace, Daniel; Parker, Tony J

    2017-01-01

    Chronic wounds, in particular venous leg ulcers (VLU), represent a substantial burden for economies, healthcare systems and societies worldwide. This burden is exacerbated by the recalcitrant nature of these wounds, despite best practice, evidence-based care, which substantially reduces the quality of life of patients. Furthermore, co-morbidities such as diabetes and cardiovascular disease within ageing populations further contribute to the increasing prevalence in developed countries. This review provides an overview of the literature concerning the cellular and molecular mechanisms of wound healing and aspects where this process fails, resulting in a chronic wound. VLU may arise from chronic venous disease, which presents with many clinical manifestations and can lead to a highly complex disease state. Efforts to comprehend this state using various omics based approaches have delivered some insight into the underlying biology of chronic wounds and revealed markers of differentiation at the genomic, transcriptomic, proteomic and metabolomic levels. Furthermore, this review outlines the array of analytical tools and approaches that have been utilised for capturing multivariate data at each of these molecular levels. Future developments in spatiotemporal analysis of wounds along with the integration of multiple omics datasets may provide much needed information on the key molecules that drive wound chronicity. Such biomarkers have the potential to be developed into clinically relevant diagnostic tools to aid in personalised wound management. PMID:28798504

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

    PubMed

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

    2008-07-07

    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. 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. 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 researchers working on

  5. 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.

  6. 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

  7. Porcine Teschoviruses Comprise at Least Eleven Distinct Serotypes: Molecular and Evolutionary Aspects

    PubMed Central

    Zell, Roland; Dauber, Malte; Krumbholz, Andi; Henke, Andreas; Birch-Hirschfeld, Eckhard; Stelzner, Axel; Prager, Dieter; Wurm, Rudiger

    2001-01-01

    Nucleotide sequencing and phylogenetic analysis of 10 recognized prototype strains of the porcine enterovirus (PEV) cytopathic effect (CPE) group I reveals a close relationship of the viral genomes to the previously sequenced strain F65, supporting the concept of a reclassification of this virus group into a new picornavirus genus. Also, nucleotide sequences of the polyprotein-encoding genome region or the P1 region of 28 historic strains and recent field isolates were determined. The data suggest that several closely related but antigenically and molecular distinct serotypes constitute one species within the proposed genus Teschovirus. Based on sequence data and serological data, we propose a new serotype with strain Dresden as prototype. This hitherto unrecognized serotype is closely related to porcine teschovirus 1 (PTV-1, former PEV-1), but induces type-specific neutralizing antibodies. Sequencing of field isolates collected from animals presenting with neurological disorders prove that other serotypes than PTV-1 may also cause polioencephalomyelitis of swine. PMID:11160660

  8. Mitochondrial disease: clinical aspects, molecular mechanisms, translational science, and clinical frontiers.

    PubMed

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

    2014-09-01

    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.

  9. Batten disease: clinical aspects, molecular mechanisms, translational science, and future directions.

    PubMed

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

    2013-09-01

    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.

  10. 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

  11. The why and how of enabling the integration of social and ethical aspects in research and development.

    PubMed

    Flipse, Steven M; van der Sanden, Maarten C A; Osseweijer, Patricia

    2013-09-01

    New and Emerging Science and Technology (NEST) based innovations, e.g. in the field of Life Sciences or Nanotechnology, frequently raise societal and political concerns. To address these concerns NEST researchers are expected to deploy socially responsible R&D practices. This requires researchers to integrate social and ethical aspects (SEAs) in their daily work. Many methods can facilitate such integration. Still, why and how researchers should and could use SEAs remains largely unclear. In this paper we aim to relate motivations for NEST researchers to include SEAs in their work, and the requirements to establish such integration from their perspectives, to existing approaches that can be used to establish integration of SEAs in the daily work of these NEST researchers. Based on our analyses, we argue that for the successful integration of SEAs in R&D practice, collaborative approaches between researchers and scholars from the social sciences and humanities seem the most successful. The only way to explore whether that is in fact the case, is by embarking on collaborative research endeavours.

  12. Compact beam splitters with deep gratings for miniature photonic integrated circuits: design and implementation aspects.

    PubMed

    Chen, Chin-Hui; Klamkin, Jonathan; Nicholes, Steven C; Johansson, Leif A; Bowers, John E; Coldren, Larry A

    2009-09-01

    We present an extensive study of an ultracompact grating-based beam splitter suitable for photonic integrated circuits (PICs) that have stringent density requirements. The 10 microm long beam splitter exhibits equal splitting, low insertion loss, and also provides a high extinction ratio in an integrated coherent balanced receiver. We further present the design strategies for avoiding mode distortion in the beam splitter and discuss optimization of the widths of the detectors to improve insertion loss and extinction ratio of the coherent receiver circuit. In our study, we show that the grating-based beam splitter is a competitive technology having low fabrication complexity for ultracompact PICs.

  13. Molecular, cellular, morphological, physiological and behavioral aspects of gonadotropin-inhibitory hormone.

    PubMed

    Ubuka, Takayoshi; Son, You Lee; Tsutsui, Kazuyoshi

    2016-02-01

    Gonadotropin-inhibitory hormone (GnIH) is a hypothalamic neuropeptide that was isolated from the brains of Japanese quail in 2000, which inhibited luteinizing hormone release from the anterior pituitary gland. Here, we summarize the following fifteen years of researches that investigated on the mechanism of GnIH actions at molecular, cellular, morphological, physiological, and behavioral levels. The unique molecular structure of GnIH peptide is in its LPXRFamide (X=L or Q) motif at its C-terminal. The primary receptor for GnIH is GPR147. The cell signaling pathway triggered by GnIH is initiated by inhibiting adenylate cyclase and decreasing cAMP production in the target cell. GnIH neurons regulate not only gonadotropin synthesis and release in the pituitary, but also regulate various neurons in the brain, such as GnRH1, GnRH2, dopamine, POMC, NPY, orexin, MCH, CRH, oxytocin, and kisspeptin neurons. GnIH and GPR147 are also expressed in gonads and they may regulate steroidogenesis and germ cell maturation in an autocrine/paracrine manner. GnIH regulates reproductive development and activity. In female mammals, GnIH may regulate estrous or menstrual cycle. GnIH is also involved in the regulation of seasonal reproduction, but GnIH may finely tune reproductive activities in the breeding seasons. It is involved in stress responses not only in the brain but also in gonads. GnIH may inhibit male socio-sexual behavior by stimulating the activity of cytochrome P450 aromatase in the brain and stimulates feeding behavior by modulating the activities of hypothalamic and central amygdala neurons. Copyright © 2015 Elsevier Inc. All rights reserved.

  14. Expression of galectin-8 on human endometrium: Molecular and cellular aspects

    PubMed Central

    Nikzad, Hossein; Haddad Kashani, Hamed; Kabir-Salmani, Maryam; Akimoto, Yoshihiro; Iwashita, Mitsutoshi

    2013-01-01

    Background: The up-regulation of galectin-3, galectin-9, and galectin-15 expression in the luminal and glandular epithelium was reported in preparation of the endometrium for embryo implantation at the midlutheal phase. However, no data was available regarding the expression and the distribution pattern of galectin-8 in the human endometrium during a regular menstrual cycle. Objective: The current study designed to investigate the expression and the distribution pattern of galectin-8, a beta-galactoside-binding lectin in the human endometrium during both proliferative and luteal phases of a regular menstrual cycle. Materials and Methods: Endometrial biopsies were obtained from the anterior wall of the uterine cavity of 16 women (proliferative phase: n=4, lutheal phase: n=12). All female patients with mean age of 37.5 years were fertile (range 25-45). Each biopsy was divided into three pieces; one piece was fixed in formaldehyde for light microscopy and immunohistochemistry. The second portion fixed in glutaraldehyde for scanning electron microscopy and the third portion was prepared for western blot analysis. Results: Data of immunoblotting revealed a molecular weight of 34 kD band with high intensity in the lutheal phase samples. The immunohistochemistry staining demonstrated that galectin-8 expressed at a very low concentration during the proliferative phase, but showed a high expression throughout the lutheal phase. The expression of galectin-8 observed in luminal surface epithelium, glandular epithelium and stroma. Conclusion: The up-regulation of the expression of galectin-8 during lutheal phase may suggest galectin-8 as one of the potential molecular marker of the endometrial receptivity. These data propose that galectin-8 may play an important role during the initial events of human embryo implantation. PMID:24639695

  15. Mechanisms of fibrogenesis in liver cirrhosis: The molecular aspects of epithelial-mesenchymal transition

    PubMed Central

    Lee, Sun-Jae; Kim, Kyung-Hyun; Park, Kwan-Kyu

    2014-01-01

    Liver injuries are repaired by fibrosis and regeneration. The cause of fibrosis and diminished regeneration, especially in liver cirrhosis, is still unknown. Epithelial-mesenchymal transition (EMT) has been found to be associated with liver fibrosis. The possibility that EMT could contribute to hepatic fibrogenesis reinforced the concept that activated hepatic stellate cells are not the only key players in the hepatic fibrogenic process and that other cell types, either hepatic or bone marrow-derived cells could contribute to this process. Following an initial enthusiasm for the discovery of this novel pathway in fibrogenesis, more recent research has started to cast serious doubts upon the real relevance of this phenomenon in human fibrogenetic disorders. The debate on the authenticity of EMT or on its contribution to the fibrogenic process has become very animated. The overall result is a general confusion on the meaning and on the definition of several key aspects. The aim of this article is to describe how EMT participates to hepatic fibrosis and discuss the evidence of supporting this possibility in order to reach reasonable and useful conclusions. PMID:24799989

  16. Topical delivery of cosmetics and drugs. Molecular aspects of percutaneous absorption and delivery.

    PubMed

    Förster, Matthias; Bolzinger, Marie-Alexandrine; Fessi, Hatem; Briançon, Stephanie

    2009-01-01

    Percutaneous penetration/permeation is a useful tool for obtaining qualitative and/or quantitative information on the amount of a drug, a cosmetic substance, or any chemical that may enter a skin compartment or the systemic circulation of the human body for pharmaceutical or cosmetic purposes, or for toxicological studies. In the latter case, the extent entering can then be taken into consideration in order to calculate the margin of safety using the NOAEL (No Observed Adverse Effect Level) of an appropriate repeated dose toxicity study with the respective substance. This paper is a short overview of various aspects of skin penetration/permeation of drugs or cosmetic agents. The literature reports numerous studies on skin structure and skin properties influencing drug/cosmetic agent permeation profiles and kinetic parameters. The extensive research concerning the skin structure for determining the key parameters of the penetration/permeation process is therefore described first. Mathematical models of the skin absorption process for a drug are then discussed. Finally new developments in pharmaceutical and cosmetic fields to enhance drug permeation or to modify the stratum corneum structure are considered.

  17. Molecular and cellular aspects and regulation of intestinal lactase-phlorizin hydrolase.

    PubMed

    Naim, H Y

    2001-04-01

    Carbohydrates are hydrolyzed in the intestinal lumen by specific enzymes to monosaccharides before transport across the brush border membrane of epithelial cells into the cell interior. The enzymes implicated in the digestion of carbohydrates in the intestinal lumen are membrane-bound glycoproteins that are expressed at the apical domain of the enterocytes. Absent or reduced activity of one of these enzymes is the cause of disaccharide intolerance and malabsorption, the symptoms of which are abdominal pain, cramps or distention, flatulence, nausea and osmotic diarrhea. Lactose intolerance is the most common intestinal disorder that is associated with an absence or drastically reduced levels of an intestinal enzyme, in this case lactase-phlorizin hydrolase (LPH). The pattern of reduction of activity has been termed late onset of lactase deficiency or adult type hypolactasia. It was thought that the regulation of LPH was post-translational and was associated with altered structural features of the enzyme. Recent studies, however, suggest that the major mechanism of regulation of LPH is transcriptional. Other forms of lactose intolerance include the rare congenital lactase deficiency and secondary forms, such as those caused by mucosal injury, due to infectious gastroenteritis, celiac disease, parasitic infection, drug-induced enteritis and Crohn's disease. This review will shed light on important strucural and biosynthetic aspects of LPH, the role played by particular regions of the LPH protein in its transport, polarized sorting, and function, as well as on the gene expession and regulation of the activity of the enzyme.

  18. Molecular aspects of alpha-tocotrienol antioxidant action and cell signalling.

    PubMed

    Packer, L; Weber, S U; Rimbach, G

    2001-02-01

    Vitamin E, the most important lipid-soluble antioxidant, was discovered at the University of California at Berkeley in 1922 in the laboratory of Herbert M. Evans (Science 1922, 55: 650). At least eight vitamin E isoforms with biological activity have been isolated from plant sources. Since its discovery, mainly antioxidant and recently also cell signaling aspects of tocopherols and tocotrienols have been studied. Tocopherols and tocotrienols are part of an interlinking set of antioxidant cycles, which has been termed the antioxidant network. Although the antioxidant activity of tocotrienols is higher than that of tocopherols, tocotrienols have a lower bioavailability after oral ingestion. Tocotrienols penetrate rapidly through skin and efficiently combat oxidative stress induced by UV or ozone. Tocotrienols have beneficial effects in cardiovascular diseases both by inhibiting LDL oxidation and by down-regulating 3-hydroxyl-3-methylglutaryl-coenzyme A (HMG CoA) reductase, a key enzyme of the mevalonate pathway. Important novel antiproliferative and neuroprotective effects of tocotrienols, which may be independent of their antioxidant activity, have also been described.

  19. A variational path integral molecular dynamics study of a solid helium-4

    NASA Astrophysics Data System (ADS)

    Miura, Shinichi

    2011-01-01

    In the present study, a variational path integral molecular dynamics method developed by the author [Chem. Phys. Lett. 482 (2009) 165] is applied to a solid helium-4 in the ground state. The method is a molecular dynamics algorithm for a variational path integral method which can be used to generate the exact ground state numerically. The solid state is shown to successfully be realized by the method, although a poor trial wavefunction that cannot describe the solid state is used.

  20. A minimally invasive blood-extraction system: elastic self-recovery actuator integrated with an ultrahigh- aspect-ratio microneedle.

    PubMed

    Li, Cheng Guo; Lee, Kwang; Lee, Chang Yeol; Dangol, Manita; Jung, Hyungil

    2012-08-28

    A minimally invasive blood-extraction system is fabricated by the integration of an elastic self-recovery actuator and an ultrahigh-aspect-ratio microneedle. The simple elastic self-recovery actuator converts finger force to elastic energy to provide power for blood extraction and transport without requiring an external source of power. This device has potential utility in the biomedical field within the framework of complete micro-electromechanical systems. Copyright © 2012 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  1. Integrating Spatial Components into FIA Models of Forest Resources: Some Technical Aspects

    Treesearch

    Pat Terletzky; Tracey Frescino

    2005-01-01

    We examined two software packages to determine their feasibility of implementing spatially explicit, forest resource models that integrate Forest Inventory and Analysis data (FIA). ARCINFO and Interactive Data Language (IDL) were examined for their input requirements, speed of processing, storage requirements, and flexibility of implementing. Implementations of two...

  2. 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…

  3. 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…

  4. Molecular and behavioral aspects of the actions of alcohol on the adult and developing brain.

    PubMed

    Alfonso-Loeches, Silvia; Guerri, Consuelo

    2011-01-01

    The brain is one of the major target organs of alcohol actions. Alcohol abuse can lead to alterations in brain structure and functions and, in some cases, to neurodegeneration. Cognitive deficits and alcohol dependence are highly damaging consequences of alcohol abuse. Clinical and experimental studies have demonstrated that the developing brain is particularly vulnerable to alcohol, and that drinking during gestation can lead to a range of physical, learning and behavioral defects (fetal alcohol spectrum disorders), with the most dramatic presentation corresponding to fetal alcohol syndrome. Recent findings also indicate that adolescence is a stage of brain maturation and that heavy drinking at this stage can have a negative impact on brain structure and functions causing important short- and long-term cognitive and behavioral consequences. The effects of alcohol on the brain are not uniform; some brain areas or cell populations are more vulnerable than others. The prefrontal cortex, the hippocampus, the cerebellum, the white matter and glial cells are particularly susceptible to the effects of ethanol. The molecular actions of alcohol on the brain are complex and involve numerous mechanisms and signaling pathways. Some of the mechanisms involved are common for the adult brain and for the developing brain, while others depend on the developmental stage. During brain ontogeny, alcohol causes irreversible alterations to the brain structure. It also impairs several molecular, neurochemical and cellular events taking place during normal brain development, including alterations in both gene expression regulation and the molecules involved in cell-cell interactions, interference with the mitogenic and growth factor response, enhancement of free radical formation and derangements of glial cell functions. However, in both adult and adolescent brains, alcohol damages specific brain areas through mechanisms involving excitotoxicity, free radical formation and

  5. 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.

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

    PubMed Central

    Daste, Frederic

    2016-01-01

    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

  7. 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

  8. 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

  9. 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.

  10. Genetic and molecular analyses of PEG10 reveal new aspects of genomic organization, transcription and translation.

    PubMed

    Lux, Heike; Flammann, Heiko; Hafner, Mathias; Lux, Andreas

    2010-01-13

    The paternally expressed gene PEG10 is a retrotransposon derived gene adapted through mammalian evolution located on human chromosome 7q21. PEG10 codes for at least two proteins, PEG10-RF1 and PEG10-RF1/2, by -1 frameshift translation. Overexpression or reinduced PEG10 expression was seen in malignancies, like hepatocellular carcinoma or B-cell acute and chronic lymphocytic leukemia. PEG10 was also shown to promote adipocyte differentiation. Experimental evidence suggests that the PEG10-RF1 protein is an inhibitor of apoptosis and mediates cell proliferation. Here we present new data on the genomic organization of PEG10 by identifying the major transcription start site, a new splice variant and report the cloning and analysis of 1.9 kb of the PEG10 promoter. Furthermore, we show for the first time that PEG10 translation is initiated at a non-AUG start codon upstream of the previously predicted AUG codon as well as at the AUG codon. The finding that PEG10 translation is initiated at different sides adds a new aspect to the already interesting feature of PEG10's -1 frameshift translation mechanism. It is now important to unravel the cellular functions of the PEG10 protein variants and how they are related to normal or pathological conditions. The generated promoter-reporter constructs can be used for future studies to investigate how PEG10 expression is regulated. In summary, our study provides new data on the genomic organization as well as expression and translation of PEG10, a prerequisite in order to study and understand the role of PEG10 in cancer, embryonic development and normal cell homeostasis.

  11. 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

  12. Molecular aspects of muco- and bioadhesion: tethered structures and site-specific surfaces.

    PubMed

    Huang, Y; Leobandung, W; Foss, A; Peppas, N A

    2000-03-01

    Mucoadhesive controlled-release devices can improve the effectiveness of a drug by maintaining the drug concentration between the effective and toxic levels, inhibiting the dilution of the drug in the body fluids, and allowing targeting and localization of a drug at a specific site. Acrylic-based hydrogels have been used extensively as mucoadhesive systems. They are well suited for bioadhesion due to their flexibility and nonabrasive characteristics in the partially swollen state, which reduce damage-causing attrition to the tissues in contact. Crosslinked polymeric devices may be rendered adhesive to the mucosa. For example, adhesive capabilities of these hydrogels can be improved by tethering of long flexible chains to their surfaces. Tethering of long poly(ethylene glycol) (PEG) chains on poly(acrylic acid) hydrogels and their copolymers can be achieved by grafting reactions, or by copolymerization in the presence of several PEG-containing acrylates. The ensuing hydrogels exhibit mucoadhesive properties due to enhanced anchoring of the chains with the mucosa. Theoretical calculations can lead to optimization of the tethered structure. Experimental results indicate that the chain interpenetration is a strong function of the PEG molecular weight, the polymer swelling ratio and the mucosa composition.

  13. Milk proteins-derived bioactive peptides in dairy products: molecular, biological and methodological aspects.

    PubMed

    Dziuba, Bartłomiej; Dziuba, Marta

    2014-01-01

    Proteins are one of the primary components of the food, both in terms of nutrition and function. They are main source of amino acids, essential for synthesis of proteins, and also source of energy. Additionally, many proteins exhibit specific biological activities, which may have effect on functional or pro-health properties of food products. These proteins and their hydrolysis products, peptides, may influence the properties of food and human organism. The number of commercially available food products containing bioactive peptides is very low, apart from that milk proteins are their rich source. It could be supposed that number of available products with declared activity will rise in near future because of observed strong uptrend on interest in such products. Molecular and biological properties of milk proteins, as precursors of bioactive peptides was characterised in the work. Therefore, the strategy of research and obtaining of such peptides both in laboratory and industrial scale, as well as the range of their commercial application, was presented. Several examples of research efforts presenting high potential to develop new products containing bioactive peptides from milk proteins and predetermined as nutraceuticals was described.

  14. 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.

  15. 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

    2015-08-13

    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.

  16. 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.

  17. 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

  18. 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

  19. 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

  20. Clinical aspects and pathogenesis of congenital dyserythropoietic anemias: from morphology to molecular approach.

    PubMed

    Iolascon, Achille; Esposito, Maria Rosaria; Russo, Roberta

    2012-12-01

    Congenital dyserythropoietic anemias belong to a group of inherited conditions characterized by a maturation arrest during erythropoiesis with a reduced reticulocyte production in contrast with erythroid hyperplasia in bone marrow. The latter shows specific morphological abnormalities that allowed for a morphological classification of these conditions mainly represented by congenital dyserythropoietic anemias types I and II. The identification of their causative genes provided evidence that these conditions have different molecular mechanisms that induce abnormal cell maturation and division. Some altered proteins seem to be involved in the chromatin assembly, such as codanin-1 in congenital dyserythropoietic anemia I. The gene involved in congenital dyserythropoietic anemia II, the most frequent form, is SEC23B. This condition seems to belong to a group of diseases attributable to defects in the transport of newly synthesized proteins from endoplasmic reticulum to the Golgi. This review will analyze recent insights in congenital dyserythropoietic anemias types I and II. It will also attempt to clarify the relationship between mutations in causative genes and the clinical phenotype of these conditions.

  1. Diagnosis and molecular aspects of solid-pseudopapillary neoplasms of the pancreas.

    PubMed

    Terris, Benoît; Cavard, Catherine

    2014-11-01

    Solid-pseudopapillary neoplasm of the pancreas (SPN) is an uncommon low-grade malignant neoplasm occurring mostly in young women. In addition to its distinctive pathological appearance of pseudopapillae with poorly cohesive neoplastic cells, rare variants exist raising the differential diagnosis especially with neuroendocrine neoplasms. The overall prognosis for patients with SPNs is excellent after surgical resection. Nevertheless, 10% of cases may have malignant behavior characterized by tumor recurrence and/or metastasis. Despite numerous studies, the histogenesis of this neoplasm remains unclear. Distinctive molecular alterations such as the presence of CTNNB1 mutations are observed in nearly all cases, while mutations classically observed in ductal adenocarcinoma, such as KRAS, TP53, and SMAD4, are not observed in SPNs, reinforcing its distinct nature compared to all other pancreatic neoplasms. Recent transcriptional studies have shown that activation of the Wnt/beta-catenin pathway in these tumors is associated with the upregulation of genes belonging to Notch, Hedgehog, and androgen receptor signaling pathways.

  2. The Role of c-MYC in B-Cell Lymphomas: Diagnostic and Molecular Aspects

    PubMed Central

    Nguyen, Lynh; Papenhausen, Peter; Shao, Haipeng

    2017-01-01

    c-MYC is one of the most essential transcriptional factors, regulating a diverse array of cellular functions, including proliferation, growth, and apoptosis. Dysregulation of c-MYC is essential in the pathogenesis of a number of B-cell lymphomas, but is rarely reported in T-cell lymphomas. c-MYC dysregulation induces lymphomagenesis by loss of the tight control of c-MYC expression, leading to overexpression of intact c-MYC protein, in contrast to the somatic mutations or fusion proteins seen in many other oncogenes. Dysregulation of c-MYC in B-cell lymphomas occurs either as a primary event in Burkitt lymphoma, or secondarily in aggressive lymphomas such as diffuse large B-cell lymphoma, plasmablastic lymphoma, mantle cell lymphoma, or double-hit lymphoma. Secondary c-MYC changes include gene translocation and gene amplification, occurring against a background of complex karyotype, and most often confer aggressive clinical behavior, as evidenced in the double-hit lymphomas. In low-grade B-cell lymphomas, acquisition of c-MYC rearrangement usually results in transformation into highly aggressive lymphomas, with some exceptions. In this review, we discuss the role that c-MYC plays in the pathogenesis of B-cell lymphomas, the molecular alterations that lead to c-MYC dysregulation, and their effect on prognosis and diagnosis in specific types of B-cell lymphoma. PMID:28379189

  3. Diagnosis and management of congenital adrenal hyperplasia: clinical, molecular and prenatal aspects.

    PubMed

    Mathur, R; Kabra, M; Menon, P S

    2001-01-01

    Congenital adrenal hyperplasia (CAH) is the most common cause of female pseudohermaphroditism in Indian children. It is caused by enzymatic defects in the steroidogenic pathway of the adrenal glands and is characterized by impaired cortisol and aldosterone synthesis and overproduction of androgens. The disease usually presents with life-threatening problems and virilization, with long term physical and psychological effects. The clinical and laboratory diagnoses play an important role in deciding the course of treatment, which continues lifelong. To ensure proper growth and development of the patient, optimized disease management and treatment with steroids is required. Often the patient also requires surgical correction. Recent developments in molecular genetics have greatly helped in understanding the pathogenesis of the disease. The gene encoding for steroid 21-hydroxylase, CYP21, is located on the short arm of chromosome 6 in the HLA region and is amplified for genetic diagnosis. Rapid characterization of point mutations is possible using the allele-specific polymerase chain reaction technique in affected children. Counselling, prenatal diagnosis and treatment are recommended in all pregnant women with a positive family history to reduce or eliminate the effects in affected foetuses. This spares the female newborn the consequences of genital ambiguity and problems of gender identity.

  4. Developmental origins of obesity and type 2 diabetes: molecular aspects and role of chemicals.

    PubMed

    Inadera, Hidekuni

    2013-05-01

    Obesity is a leading risk factor for impaired glucose tolerance and type 2 diabetes (T2D). Although the cause of the obesity epidemic is multi-factorial and not entirely clear, the recent acceleration in incidence is too rapid to be accounted for only by genetics, the wide availability of calorie-rich foods, and increasingly sedentary lifestyles. Accumulating data suggest that the important causes of the obesity epidemic may be related to developmental and early life environmental conditions. The concept of the developmental origins of health and disease (DOHaD) suggests that adverse influences early in development, particularly during intrauterine life, may result in permanent changes in the physiology and metabolism of the infant, which in turn result in an increased risk of non-communicable diseases in adulthood. For example, undernutrition during pregnancy and rapid postnatal weight gain are associated with obesity and T2D in the adult offspring. Moreover, increasing evidence suggests that early-life exposure to a wide range of chemicals has a significant impact on the causes of metabolic disorders. Although the underlying molecular mechanisms remain to be determined, these factors can affect epigenetic processes, such as DNA methylation, allowing the developmental environment to modulate gene transcription. The objective of this review article was to summarize recent progress in the biomedical implications of the DOHaD concept, focusing on the pathogenesis of obesity and T2D, and to discuss a future direction for preventive strategies from a public health perspective.

  5. [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. Copyright © 2013 Elsevier España, S.L.U. y Sociedad Española de Enfermedades Infecciosas y Microbiología Clínica. All rights reserved.

  6. 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.

  7. The Role of c-MYC in B-Cell Lymphomas: Diagnostic and Molecular Aspects.

    PubMed

    Nguyen, Lynh; Papenhausen, Peter; Shao, Haipeng

    2017-04-05

    c-MYC is one of the most essential transcriptional factors, regulating a diverse array of cellular functions, including proliferation, growth, and apoptosis. Dysregulation of c-MYC is essential in the pathogenesis of a number of B-cell lymphomas, but is rarely reported in T-cell lymphomas. c-MYC dysregulation induces lymphomagenesis by loss of the tight control of c-MYC expression, leading to overexpression of intact c-MYC protein, in contrast to the somatic mutations or fusion proteins seen in many other oncogenes. Dysregulation of c-MYC in B-cell lymphomas occurs either as a primary event in Burkitt lymphoma, or secondarily in aggressive lymphomas such as diffuse large B-cell lymphoma, plasmablastic lymphoma, mantle cell lymphoma, or double-hit lymphoma. Secondary c-MYC changes include gene translocation and gene amplification, occurring against a background of complex karyotype, and most often confer aggressive clinical behavior, as evidenced in the double-hit lymphomas. In low-grade B-cell lymphomas, acquisition of c-MYC rearrangement usually results in transformation into highly aggressive lymphomas, with some exceptions. In this review, we discuss the role that c-MYC plays in the pathogenesis of B-cell lymphomas, the molecular alterations that lead to c-MYC dysregulation, and their effect on prognosis and diagnosis in specific types of B-cell lymphoma.

  8. Tiny percutaneous needle biopsy: An efficient method for studying cellular and molecular aspects of skeletal muscle in humans.

    PubMed

    Pietrangelo, Tiziana; D'Amelio, Luigi; Doria, Christian; Mancinelli, Rosa; Fulle, Stefania; Fanò, Giorgio

    2011-03-01

    Needle biopsy is widely used to obtain specimens for physiological, anatomical and biochemical studies of skeletal muscle (SM). We optimized a procedure which we termed tiny percutaneous needle biopsy (TPNB), to efficiently gather good numbers of human satellite cells and single dissociated fibers for the functional study of skeletal muscle; these samples permit isolation of high-quality RNA and sufficient amounts of proteins to allow molecular analysis. Moreover, TPNB showed a clear advantage in that the technique was easier than other procedures used on healthy volunteers in human trials. TPNB is a very safe minor surgical procedure. It is less traumatic than needle aspiration biopsy, and significant complications are improbable. TPNB should become established as an important tool in the investigation of SM and may be employed to study various physiological aspects of SM in human subjects. We suggest that TPNB should also be used in the study of muscle diseases and disorders including muscular dystrophy, congenital myopathy, and metabolic defects.

  9. 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.

  10. Integrated PET/CT in lung cancer imaging: history and technical aspects.

    PubMed

    De Wever, W; Stroobants, S; Verschakelen, J A

    2007-01-01

    Integrated PET/CT is a new anatomo-metabolic imaging modality combining two different techniques: Computed Tomography (CT) that provides very detailed anatomic information and Positron Emission Tomography (PET) that provides metabolic information. Integrated PET/CT has several advantages. One of the advantages is the use of CT data for attenuation correction that is significantly faster compared to that in conventional PET systems. Due to the use of CT data for attenuation correction, artefacts can be generated on PET images related to the use of intravenous or oral CT contrast agents, CT beam-hardening artefacts due to metallic implants and motion artefacts (respiratory motion, physical bowel motion, cardiac motion). The purpose of this review is to discuss some technical considerations concerning the CT protocol that can be used for PET/CT in lung cancer imaging and to give a short overview of the initial results of staging of non-small cell lung cancer (NSCLC).

  11. Strategic, Organizational and Standardization Aspects of Integrated Information Systems. Volume 6.

    DTIC Science & Technology

    1987-12-01

    CIS MODEL FOR STRATEGIC APPLICATIONS (Technical Report #22) 5 INFORMATION TECHNOLOGIES AND INTER-ORGANIZATIONAL NETWORKS: STRATEGIC AND ORGANIZATIONAL...approach technological obsolescence by the time it is ready for use. GKS is a good example of this. GKS is an adequate model for the technology of the...supposed to cut across several areas and help generate generic entities for the integrated model : manufacturing technology committee This committee is

  12. Practical aspects of integrating allergy and pulmonology management into a rhinology practice: the Vanderbilt ASAP experience.

    PubMed

    Duncavage, James; Hagaman, David D

    2013-02-01

    In the aftermath of reforms in healthcare laws, there is a focused conversation concerning healthcare delivery with an increasing emphasis on quality, cost containment, improved outcomes and access. Concurrently, providers are experiencing pressure as patient volume escalates yet while funding levels fail to keep pace. Addressing these issues is imperative to the medical practices. In this review, the integration of an allergy and rhinology practice into a center focused on managing chronic airway disease is detailed in the examination of an existing practice. In 2010, healthcare spending in the Unites States was nearly US$ 2.6 trillion, 17.9% of the nation's gross domestic product and 10 times 1980 levels. Insurance premiums have increased 113% since 2001 and continue to outpace income gains. Seventy-five percent of spending is attributed to chronic diseases such as stroke, cancer, heart disease, diabetes, Parkinson's disease and Alzheimer's. Airway disease (rhinitis, sinusitis, asthma, chronic obstructive pulmonary disease) is one of the largest chronic disease states. In fact, more patients suffer from airway disease than the aforementioned diseases in total. Any effort to affect costs must include a chronic disease strategy. This review will focus on the nature of the integrated program and its relation to the nature of airway diseases; a detailed description of how it works and why it is different from traditional models. This integrated model of healthcare will improve the quality of care provided to airway disease patients as well as help contain overall healthcare cost.

  13. 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.

  14. 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.

  15. Cytochemical, biochemical and molecular aspects of the process of keratinization in the epidermis of reptilian scales.

    PubMed

    Alibardi, Lorenzo; Toni, Mattia

    2006-01-01

    The characteristics of scaled skin of reptiles is one of their main features that distinguish them from the other amniotes, birds and mammals. The different scale patterns observed in extant reptiles result from a long evolutive history that allowed each species to adapt to its specific environment. The present review deals with comparative aspects of epidermal keratinization in reptiles, chelonians (turtles and tortoises), lepidosaurian (lizards, snakes, sphenodontids), archosaurians (crocodilians). Initially the morphology and cytology of reptilian scales is outlined to show the diversity in the epidermis among different groups. The structural proteins (alpha-keratins and associated proteins), and enzymes utilized to form the corneous layer of the epidermis are presented. Aside cytokeratins (alpha-keratins), used for making the cytoskeleton, reptilian alpha-keratinocytes produce interkeratin (matrix) and corneous cell envelope proteins. Keratin bundles and degraded cell organelles constitute most of the corneous material of alpha-keratinocytes. Matrix, histidine-rich and sulfur-rich proteins are produced in the soft epidermis and accumulated in the cornified cell envelope. Main emphasis is given to the composition and to the evolution of the hard keratins (beta-keratins). Beta-keratins constitute the hard corneous material of scales. These small proteins are synthesized in beta-keratinocytes and are accumulated into small packets that rapidly merge into a compact corneous material and form densely cornified layers. Beta-keratins are smaller proteins (8-20 kDa) in comparison to alpha-keratins (40-70 kDa), and this size may determine their dense packing in corneocytes. Both glycine-sulfur-rich and glycine-proline-rich proteins have been so far sequenced in the corneous material of scales in few reptilian species. The latter keratins possess C- and N-amino terminal amino acid regions with sequence homology with those of mammalian hard keratins. Also, reptilian beta

  16. HTLV-3/STLV-3 and HTLV-4 Viruses: Discovery, Epidemiology, Serology and Molecular Aspects

    PubMed Central

    Mahieux, Renaud; Gessain, Antoine

    2011-01-01

    Human T cell leukemia/lymphoma virus Type 1 and 2 (HTLV-1 and HTLV-2), together with their simian counterparts (STLV-1, STLV-2), belong to the Primate T lymphotropic viruses group (PTLV). The high percentage of homologies between HTLV-1 and STLV-1 strains, led to the demonstration that most HTLV-1 subtypes arose from interspecies transmission between monkeys and humans. STLV-3 viruses belong to the third PTLV type and are equally divergent from both HTLV-1 and HTLV-2. They are endemic in several monkey species that live in West, Central and East Africa. In 2005, we, and others reported the discovery of the human homolog (HTLV-3) of STLV-3 in two asymptomatic inhabitants from South Cameroon whose sera exhibited HTLV indeterminate serologies. More recently, two other cases of HTLV-3 infection in persons living in Cameroon were reported suggesting that this virus is not extremely rare in the human population living in Central Africa. Together with STLV-3, these human viral strains belong to the PTLV-3 group. A fourth HTLV type (HTLV-4) was also discovered in the same geographical area. The overall PTLV-3 and PTLV-4 genomic organization is similar to that of HTLV-1 and HTLV-2 with the exception of their long terminal repeats (LTRs) that contain only two 21 bp repeats. As in HTLV-1, HTLV-3 Tax contains a PDZ binding motif while HTLV-4 does not. An antisense transcript was also described in HTLV-3 transfected cells. PTLV-3 molecular clones are now available and will allow scientists to study the viral cycle, the tropism and the possible pathogenicity in vivo. Current studies are also aimed at determining the prevalence, distribution, and modes of transmission of these viruses, as well as their possible association with human diseases. Here we will review the characteristics of these new simian and human retroviruses, whose discovery has opened new avenues of research in the retrovirology field. PMID:21994771

  17. Molecular Aspects of a Robust Assay for Ferroxidase Function of Ceruloplasmin.

    PubMed

    Cortes, Laura; Roberts, Blaine R; Wedd, Anthony G; Xiao, Zhiguang

    2017-05-01

    Ceruloplasmin (Cp) is one of the most complex multicopper oxidase enzymes and plays an essential role in the metabolism of iron in mammals. Ferrous ion supplied by the ferroportin exporter is converted by Cp to ferric ion that is accepted by plasma metallo-chaperone transferrin. Study of the enzyme at the atomic and molecular level has been hampered by the lack of a suitable ferrous substrate. We have developed the classic chromophoric complex Fe(II)Hx(Tar)2 (H2Tar, 4-(2-thiazolylazo)resorcinol; x = 0-2; overall charge omitted) as a robust substrate for evaluation of the ferroxidase function of Cp and related enzymes. The catalysis can be followed conveniently in real time by monitoring the solution absorbance at 720 nm, a fingerprint of Fe(II)Hx(Tar)2. The complex is oxidized to its ferric form Fe(III)Hx(Tar)2 via the overall reaction sequence Fe(II)Hx(Tar)2 → Fe(II)-Cp → Fe(III)-Cp → Fe(III)Hx(Tar)2: i.e., Fe(II) is transferred formally from Fe(II)Hx(Tar)2 to the substrate docking/oxidation (SDO) site(s) in Cp, followed by oxidation to product Fe(III) that is trapped again by the ligand. Each Tar ligand in the above bis-complex coordinates the metal center in a meridional tridentate mode involving a pH-sensitive -OH group (pKa > 12), and this imposes rapid Fe(II) and Fe(III) transfer kinetics to facilitate the catalytic process. The formation constants of both the ferrous and ferric complexes at pH 7.0 were determined (log β2' = 13.6 and 21.6, respectively), as well as an average dissociation constant of the SDO site(s) in Cp (log KD' = -7.2).

  18. HAMLET kills tumor cells by an apoptosis-like mechanism--cellular, molecular, and therapeutic aspects.

    PubMed

    Svanborg, Catharina; Agerstam, Helena; Aronson, Annika; Bjerkvig, Rolf; Düringer, Caroline; Fischer, Walter; Gustafsson, Lotta; Hallgren, Oskar; Leijonhuvud, Irene; Linse, Sara; Mossberg, Ann-Kristin; Nilsson, Hanna; Pettersson, Jenny; Svensson, Malin

    2003-01-01

    HAMLET (human alpha-lactalbumin made lethal to tumor cells) is a protein-lipid complex that induces apoptosis-like death in tumor cells, but leaves fully differentiated cells unaffected. This review summarizes the information on the in vivo effects of HAMLET in patients and tumor models on the tumor cell biology, and on the molecular characteristics of the complex. HAMLET limits the progression of human glioblastomas in a xenograft model and removes skin papillomas in patients. This broad anti-tumor activity includes >40 different lymphomas and carcinomas and apoptosis is independent of p53 or bcl-2. In tumor cells HAMLET enters the cytoplasm, translocates to the perinuclear area, and enters the nuclei where it accumulates. HAMLET binds strongly to histones and disrupts the chromatin organization. In the cytoplasm, HAMLET targets ribosomes and activates caspases. The formation of HAMLET relies on the propensity of alpha-lactalbumin to alter its conformation when the strongly bound Ca2+ ion is released and the protein adopts the apo-conformation that exposes a new fatty acid binding site. Oleic acid (C18:1,9 cis) fits this site with high specificity, and stabilizes the altered protein conformation. The results illustrate how protein folding variants may be beneficial, and how their formation in peripheral tissues may depend on the folding change and the availability of the lipid cofactor. One example is the acid pH in the stomach of the breast-fed child that promotes the formation of HAMLET. This mechanism may contribute to the protective effect of breastfeeding against childhood tumors. We propose that HAMLET should be explored as a novel approach to tumor therapy.

  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. [FOXP2 and the molecular biology of language: new evidence. I. Phenotypic aspects and animal models].

    PubMed

    Benítez-Burraco, A

    FOXP2 is the first gene linked to a hereditary variant of specific language impairment and seems to code for a transcriptional repressor that intervenes in the regulation of development and the functioning of certain thalamic-cortical-striatal circuits. In the last three years significant progress has been made in the analysis of the structural and functional properties of the gene. The most notable advances have been made in the genotypic and phenotypic characterisation of new alterations in its sequencing in human beings; the determination in vivo of the functional properties of the mutated proteins generated from said variants; the cloning and characterisation of new orthologues of the gene; the generation of the first knockout and knockdown organisms for it; and a more precise molecular characterisation of the biological role played by the orthologues corresponding to species that are also capable of learning the articulatory patterns of the vocalisations they use to communicate. The latest clinical evidence and that obtained from analysing animal models generated to date appear to suggest the presence of a 'sensory-motor disorder' as the central deficit behind the different phenotypes associated to the different mutations of the gene in the human species, the functionality of the gene FOXP2 during development of the embryo and during the adult phase, its involvement in the development and functioning of the thalamic-cortical-striatal circuits associated to motor planning, sequential behaviour and procedural learning, and significant old age, in developmental terms, of a part of the neuroanatomical substrate that is involved in processing linguistic stimuli in our species.

  1. Benchmark values for molecular three-center integrals arising in the Dirac equation

    NASA Astrophysics Data System (ADS)

    Baǧcı, A.; Hoggan, P. E.

    2015-10-01

    Previous papers by the authors report that they obtained compact, arbitrarily accurate expressions for two-center, one- and two-electron relativistic molecular integrals expressed over Slater-type orbitals. In the present study, accuracy limits of expressions given are examined for three-center nuclear attraction integrals, which are one-electron, three-center integrals with no analytically closed-form expression. In this work new molecular auxiliary functions are used. They are obtained via Neumann expansion of the Coulomb interaction. The numerical global adaptive method is used to evaluate these integrals for arbitrary values of orbital parameters and quantum numbers. Several methods, such as Laplace expansion of Coulomb interaction, single-center expansion, and the Fourier transformation method, have previously been used to evaluate these integrals considering the values of principal quantum numbers in the set of positive integer numbers. This study of three-center integrals places no restrictions on quantum numbers in all ranges of orbital parameters.

  2. Benchmark values for molecular three-center integrals arising in the Dirac equation.

    PubMed

    Bağcı, A; Hoggan, P E

    2015-10-01

    Previous papers by the authors report that they obtained compact, arbitrarily accurate expressions for two-center, one- and two-electron relativistic molecular integrals expressed over Slater-type orbitals. In the present study, accuracy limits of expressions given are examined for three-center nuclear attraction integrals, which are one-electron, three-center integrals with no analytically closed-form expression. In this work new molecular auxiliary functions are used. They are obtained via Neumann expansion of the Coulomb interaction. The numerical global adaptive method is used to evaluate these integrals for arbitrary values of orbital parameters and quantum numbers. Several methods, such as Laplace expansion of Coulomb interaction, single-center expansion, and the Fourier transformation method, have previously been used to evaluate these integrals considering the values of principal quantum numbers in the set of positive integer numbers. This study of three-center integrals places no restrictions on quantum numbers in all ranges of orbital parameters.

  3. Ab initio path integral ring polymer molecular dynamics: Vibrational spectra of molecules

    NASA Astrophysics Data System (ADS)

    Shiga, Motoyuki; Nakayama, Akira

    2008-01-01

    The path integral ring polymer molecular dynamics method is combined with 'on-the-fly' ab initio electronic structure calculations and applied to vibrational spectra of small molecules, LiH and H 2O, at the room temperature. The results are compared with those of the numerically exact solution and ab initio path integral centroid molecular dynamics calculation. The peak positions in the calculated spectra are found to be reasonable, showing the red-shift due to potential anharmonicity. This unification enables the investigation of real-time quantum dynamics of chemically complex molecular systems on the ab initio Born-Oppenheimer potential energy surface.

  4. 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.

  5. 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.

  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. [Maturation, separation and social integration. Some developmental psychology aspects of childhood sports].

    PubMed

    Günter, Michael

    2002-04-01

    The unfolding of motorical and social experiences with one's own body is a core element of ego-development and identity in childhood and adolescence. This paper describes essential elements of this process in different age stages. Especially in adolescence, the maturational and separational development are determined by the complex interaction between integration into the peer group and separation from adults, between search for appreciation and oppositional tendencies. On the one hand sport plays an important role for many adolescents during this process. On the other hand adolescent conflicts have a great impact on practising sport. These considerations are illustrated by two case vignettes.

  8. Frequency and clinical and molecular aspects of familial hypercholesterolemia in an endocrinology unit in Ciudad Bolívar, Venezuela.

    PubMed

    Lima-Martínez, Marcos M; Paoli, Mariela; Vázquez-Cárdenas, Alejandra; Magaña-Torres, María Teresa; Guevara, Ornella; Muñoz, María Carolina; Parrilla-Alvarez, Alberto; Márquez, Yuliangelys; Medeiros, Ana; Bourbon, Mafalda

    2017-10-01

    To assess the frequency and the clinical, biochemical, and molecular aspects of familial hypercholesterolemia (FH) in subjects attending an endocrinology unit. An observational, descriptive study evaluating 3,140 subjects attending the endocrinology unit of Centro Médico Orinoco in Ciudad Bolívar, Venezuela, from 7 January 2013 to 9 December 2016. The index cases were selected using the Dutch Lipid Clinic Network criteria. Plasma lipid levels were measured, and a molecular analysis was performed by DNA sequencing of the LDLR and APOB genes. Ten (0.32%) of the 3,140 study patients had clinical and biochemical characteristics consistent with FH. All but one were female. Three had first-degree relatives with prior premature coronary artery; and none had a personal history of this condition. Three patients were obese; three had high blood pressure; and no one suffered from diabetes. Three patients had a history of tendon xanthomas, and one of corneal arcus. LDL-C levels ranged from 191 to 486mg/dL. Two patients were on statin therapy. The genetic causes of FH were identified in four patients, and were LDLR gene mutations in three of them and an APOB gene mutation in exon 26 in the other. Approximately, one out of every 300 people attending this endocrinology unit in those four years had FH, and LDLR gene mutations were the most prevalent cause. Copyright © 2017 SEEN. Publicado por Elsevier España, S.L.U. All rights reserved.

  9. Metabolic and molecular aspects of ethanolamine phospholipid biosynthesis: the role of CTP:phosphoethanolamine cytidylyltransferase (Pcyt2).

    PubMed

    Bakovic, Marica; Fullerton, Morgan D; Michel, Vera

    2007-06-01

    The CDP-ethanolamine branch of the Kennedy pathway is the major route for the formation of ethanolamine-derived phospholipids, including diacyl phosphatidylethanolamine and alkenylacyl phosphatidylethanolamine derivatives, known as plasmalogens. Ethanolamine phospholipids are essential structural components of the cell membranes and play regulatory roles in cell division, cell signaling, activation, autophagy, and phagocytosis. The physiological importance of plasmalogens has not been not fully elucidated, although they are known for their antioxidant properties and deficiencies in a number of inherited peroxisomal disorders. This review highlights important aspects of ethanolamine phospholipid metabolism and reports current molecular information on 1 of the regulatory enzymes in their synthesis, CTP:phosphoethanolamine cytidylyltransferase (Pcyt2). Pcyt2 is encoded by a single, nonredundant gene in animal species that could be alternatively spliced into 2 potential protein products. We describe properties of the mouse and human Pcyt2 genes and their regulatory promoters and provide molecular evidence for the existence of 2 distinct Pcyt2 proteins. The goal is to obtain more insight into Pcyt2 catalytic function and regulation to facilitate a better understanding of the production of ethanolamine phospholipids via the CDP-ethanolamine branch of the Kennedy pathway.

  10. On the applicability of centroid and ring polymer path integral molecular dynamics for vibrational spectroscopy

    NASA Astrophysics Data System (ADS)

    Witt, Alexander; Ivanov, Sergei D.; Shiga, Motoyuki; Forbert, Harald; Marx, Dominik

    2009-05-01

    Centroid molecular dynamics (CMD) and ring polymer molecular dynamics (RPMD) are two conceptually distinct extensions of path integral molecular dynamics that are able to generate approximate quantum dynamics of complex molecular systems. Both methods can be used to compute quasiclassical time correlation functions which have direct application in molecular spectroscopy; in particular, to infrared spectroscopy via dipole autocorrelation functions. The performance of both methods for computing vibrational spectra of several simple but representative molecular model systems is investigated systematically as a function of temperature and isotopic substitution. In this context both CMD and RPMD feature intrinsic problems which are quantified and investigated in detail. Based on the obtained results guidelines for using CMD and RPMD to compute infrared spectra of molecular systems are provided.

  11. 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

  12. 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.

  13. 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.

  14. Identification of HBV-MLL4 Integration and Its Molecular Basis in Chinese Hepatocellular Carcinoma

    PubMed Central

    Zhu, Xuehua; Zhu, Guanshan; Chen, Yunqin; Xie, Xiaoying; Ye, Qinghai; Zang, Jie; Ren, Zhenggang; Ji, Qunsheng

    2015-01-01

    To gain molecular insights of HBV integration that may contribute to HCC tumorigenesis, we performed whole transcriptome sequencing and whole genome copy number profiling of hepatocellular carcinoma (HCC) samples from 50 Chinese patients. We identified a total of 33 HBV-human integration sites in 16 of 44 HBV-positive HCC tissues, which were enriched in HBV genotype C-infected patients. In addition, significantly recurrent HBV-MLL4 integration (18%; 8/44) was found in this cohort of patients. Using long-range PCR and Sanger sequencing, we comprehensively characterized gDNA and cDNA sequences that encode for the HBV-MLL4 transcripts, and we revealed that HBV integration into MLL4 exons led to much higher mRNA expression of MLL4 than the integration into MLL4 introns due to an alternative splicing mechanism. Moreover, the HBV-MLL4 integration occurred almost exclusively in CTNNB1 and TP53 wild-type patients. The integration was also associated with a distinct gene expression profile. In conclusion, this is the first report on the molecular basis of the MLL4 integration driving MLL4 over-expression. HBV-MLL4 integration occurred frequently in Chinese HCC patients, representing a unique molecular segment for HCC with HBV infection. PMID:25901726

  15. 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

  16. Container Closure Integrity Testing-Practical Aspects and Approaches in the Pharmaceutical Industry.

    PubMed

    Brown, Helen; Mahler, Hanns-Christian; Mellman, James; Nieto, Alejandra; Wagner, Daniel; Schaar, Matthias; Mathaes, Roman; Kossinna, Juergen; Schmitting, Franz; Dreher, Sascha; Roehl, Holger; Hemminger, Markus; Wuchner, Klaus

    2017-01-01

    The assurance of sterility of a parenteral drug product, prior to any human use, is a regulatory requirement. Hence, all strategies related to container closure integrity (CCI) must demonstrate absence of microbial contamination through leaks as part of the container closure system (CCS) qualification, during manufacturing, for quality control purposes and to ensure microbiological integrity (sterility) during storage and shipment up to the end of product shelf life. Current regulatory guidances, which differ between countries and regions, provide limited detail on how to assess CCI. The new revision of USP <1207> aims to provide extensive and detailed guidance for CCI assessments for sterile products. However, practical questions and considerations are yet to be addressed by the pharmaceutical industry. These may include: (1) choice of method, for example whether a deterministic CCI method (e.g., helium leak) is preferable over the probabilistic CCI method (e.g., microbial ingress), (2) the type of primary packaging (e.g., vial, syringe, device), (3) dosage form (e.g., liquid versus lyophilisate), (4) suitable acceptance criteria, (5) appropriate sample size, (6) the most appropriate way to introduce artificial leaks into the CCS, (7) ensuring suitable assurance of CCI during drug product manufacturing, and (8) evaluating CCI under intended shipment and storage conditions (e.g., in the frozen state).A group of European industry peers have met to discuss these and other related questions in order to provide their viewpoint and best practice on practical approaches to CCI. Their perspective is provided in this white paper. Through these discussions, it became clear that there is currently no gold standard for CCI test methods or for the generation of artificial leaks; therefore flexibility toward CCI approaches is required. Although there should be flexibility, any CCI approach must consider the intended use (e.g., CCS qualification, routine manufacturing, or

  17. Molecular Integrity of Mitochondria Alters by Potassium Chloride.

    PubMed

    Mishra, Suman; Mishra, Rajnikant

    2015-01-01

    Potassium chloride (KCl) has been commonly used in homogenization buffer and procedures of protein extraction. It is known to facilitate release of membrane-associated molecules but the higher concentration of KCl may affect the integrity of mitochondria by breaching the electrostatic force between the lipids and proteins. Therefore, it has been intended to explore the effect of KCl on mitochondrial proteome. The mitochondria were isolated from the mice liver and sub-fractionated into mitochondrial matrix and outer mitochondrial membrane fraction. The fractions were analysed by denaturing polyacrylamide gel electrophoresis (PAGE) and 2D-PAGE. The analysis of ultrastructure and protein profiles by MALDI-MS and data-mining reveals KCl-associated alterations in the integrity of mitochondria and its proteome. The mitochondrial membrane, cristae, and the matrix proteins appear altered under the influence of KCl.

  18. 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

  19. Benchmark values for molecular two-electron integrals arising from the Dirac equation.

    PubMed

    Bağcı, A; Hoggan, P E

    2015-02-01

    The two-center two-electron Coulomb and hybrid integrals arising in relativistic and nonrelativistic ab initio calculations on molecules are evaluated. Compact, arbitrarily accurate expressions are obtained. They are expressed through molecular auxiliary functions and evaluated with the numerical Global-adaptive method for arbitrary values of parameters in the noninteger Slater-type orbitals. Highly accurate benchmark values are presented for these integrals. The convergence properties of new molecular auxiliary functions are investigated. The comparison for two-center two-electron integrals is made with results obtained from single center expansions by translation of the wave function to a single center with integer principal quantum numbers and results obtained from the Cuba numerical integration algorithm, respectively. The procedures discussed in this work are capable of yielding highly accurate two-center two-electron integrals for all ranges of orbital parameters.

  20. Benchmark values for molecular two-electron integrals arising from the Dirac equation

    NASA Astrophysics Data System (ADS)

    Baǧcı, A.; Hoggan, P. E.

    2015-02-01

    The two-center two-electron Coulomb and hybrid integrals arising in relativistic and nonrelativistic ab initio calculations on molecules are evaluated. Compact, arbitrarily accurate expressions are obtained. They are expressed through molecular auxiliary functions and evaluated with the numerical Global-adaptive method for arbitrary values of parameters in the noninteger Slater-type orbitals. Highly accurate benchmark values are presented for these integrals. The convergence properties of new molecular auxiliary functions are investigated. The comparison for two-center two-electron integrals is made with results obtained from single center expansions by translation of the wave function to a single center with integer principal quantum numbers and results obtained from the Cuba numerical integration algorithm, respectively. The procedures discussed in this work are capable of yielding highly accurate two-center two-electron integrals for all ranges of orbital parameters.

  1. Molecular Characterization of Pediatric Restrictive Cardiomyopathy from Integrative Genomics

    PubMed Central

    Rindler, Tara N.; Hinton, Robert B.; Salomonis, Nathan; Ware, Stephanie M.

    2017-01-01

    Pediatric restrictive cardiomyopathy (RCM) is a genetically heterogeneous heart disease with limited therapeutic options. RCM cases are largely idiopathic; however, even within families with a known genetic cause for cardiomyopathy, there is striking variability in disease severity. Although accumulating evidence implicates both gene expression and alternative splicing in development of dilated cardiomyopathy (DCM), there have been no detailed molecular characterizations of underlying pathways dysregulated in RCM. RNA-Seq on a cohort of pediatric RCM patients compared to other forms of adult cardiomyopathy and controls identified transcriptional differences highly common to the cardiomyopathies, as well as those unique to RCM. Transcripts selectively induced in RCM include many known and novel G-protein coupled receptors linked to calcium handling and contractile regulation. In-depth comparisons of alternative splicing revealed splicing events shared among cardiomyopathy subtypes, as well as those linked solely to RCM. Genes identified with altered alternative splicing implicate RBM20, a DCM splicing factor, as a potential mediator of alternative splicing in RCM. We present the first comprehensive report on molecular pathways dysregulated in pediatric RCM including unique/shared pathways identified compared to other cardiomyopathy subtypes and demonstrate that disruption of alternative splicing patterns in pediatric RCM occurs in the inverse direction as DCM. PMID:28098235

  2. Molecular Characterization of Pediatric Restrictive Cardiomyopathy from Integrative Genomics.

    PubMed

    Rindler, Tara N; Hinton, Robert B; Salomonis, Nathan; Ware, Stephanie M

    2017-01-18

    Pediatric restrictive cardiomyopathy (RCM) is a genetically heterogeneous heart disease with limited therapeutic options. RCM cases are largely idiopathic; however, even within families with a known genetic cause for cardiomyopathy, there is striking variability in disease severity. Although accumulating evidence implicates both gene expression and alternative splicing in development of dilated cardiomyopathy (DCM), there have been no detailed molecular characterizations of underlying pathways dysregulated in RCM. RNA-Seq on a cohort of pediatric RCM patients compared to other forms of adult cardiomyopathy and controls identified transcriptional differences highly common to the cardiomyopathies, as well as those unique to RCM. Transcripts selectively induced in RCM include many known and novel G-protein coupled receptors linked to calcium handling and contractile regulation. In-depth comparisons of alternative splicing revealed splicing events shared among cardiomyopathy subtypes, as well as those linked solely to RCM. Genes identified with altered alternative splicing implicate RBM20, a DCM splicing factor, as a potential mediator of alternative splicing in RCM. We present the first comprehensive report on molecular pathways dysregulated in pediatric RCM including unique/shared pathways identified compared to other cardiomyopathy subtypes and demonstrate that disruption of alternative splicing patterns in pediatric RCM occurs in the inverse direction as DCM.

  3. An Integrated Approach to Economic and Environmental Aspects of Air Pollution and Climate Interactions

    NASA Astrophysics Data System (ADS)

    Sarofim, M. C.

    2007-12-01

    Emissions of greenhouses gases and conventional pollutants are closely linked through shared generation processes and thus policies directed toward long-lived greenhouse gases affect emissions of conventional pollutants and, similarly, policies directed toward conventional pollutants affect emissions of greenhouse gases. Some conventional pollutants such as aerosols also have direct radiative effects. NOx and VOCs are ozone precursors, another substance with both radiative and health impacts, and these ozone precursors also interact with the chemistry of the hydroxyl radical which is the major methane sink. Realistic scenarios of future emissions and concentrations must therefore account for both air pollution and greenhouse gas policies and how they interact economically as well as atmospherically, including the regional pattern of emissions and regulation. We have modified a 16 region computable general equilibrium economic model (the MIT Emissions Prediction and Policy Analysis model) by including elasticities of substitution for ozone precursors and aerosols in order to examine these interactions between climate policy and air pollution policy on a global scale. Urban emissions are distributed based on population density, and aged using a reduced form urban model before release into an atmospheric chemistry/climate model (the earth systems component of the MIT Integrated Global Systems Model). This integrated approach enables examination of the direct impacts of air pollution on climate, the ancillary and complementary interactions between air pollution and climate policies, and the impact of different population distribution algorithms or urban emission aging schemes on global scale properties. This modeling exercise shows that while ozone levels are reduced due to NOx and VOC reductions, these reductions lead to an increase in methane concentrations that eliminates the temperature effects of the ozone reductions. However, black carbon reductions do have

  4. 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.

  5. Integration of FDG-PET/CT into external beam radiation therapy planning: technical aspects and recommendations on methodological approaches.

    PubMed

    Thorwarth, D; Beyer, T; Boellaard, R; de Ruysscher, D; Grgic, A; Lee, J A; Pietrzyk, U; Sattler, B; Schaefer, A; van Elmpt, W; Vogel, W; Oyen, W J G; Nestle, U

    2012-01-01

    This work addresses the clinical adoption of FDG-PET/CT for image-guided radiation therapy planning (RTP). As such, important technical and methodological aspects of PET/CT-based RTP are reviewed and practical recommendations are given for routine patient management and clinical studies. First, recent developments in PET/CT hardware that are relevant to RTP are reviewed in the context of quality control and system calibration procedures that are mandatory for a reproducible adoption of PET/CT in RTP. Second, recommendations are provided on image acquisition and reconstruction to support the standardization of imaging protocols. A major prerequisite for routine RTP is a complete and secure data transfer to the actual planning system. Third, state-of-the-art tools for image fusion and co-registration are discussed briefly in the context of PET/CT imaging pre- and post-RTP. This includes a brief review of state-of-the-art image contouring algorithms relevant to PET/CT-guided RTP. Finally, practical aspects of clinical workflow and patient management, such as patient setup and requirements for staff training are emphasized. PET/CT-guided RTP mandates attention to logistical aspects, patient set-up and acquisition parameters as well as an in-depth appreciation of quality control and protocol standardization. Upon fulfilling the requirements to perform PET/CT for RTP, a new dimension of molecular imaging can be added to traditional morphological imaging. As a consequence, PET/CT imaging will support improved RTP and better patient care. This document serves as a guidance on practical and clinically validated instructions that are deemed useful to the staff involved in PET/CT-guided RTP.

  6. Building the body: active learning laboratories that emphasize practical aspects of anatomy and integration with radiology.

    PubMed

    Zumwalt, Ann C; Lufler, Rebecca S; Monteiro, Joseph; Shaffer, Kitt

    2010-01-01

    Active learning exercises were developed to allow advanced medical students to revisit and review anatomy in a clinically meaningful context. In our curriculum, students learn anatomy two to three years before they participate in the radiology clerkship. These educational exercises are designed to review anatomy content while highlighting its relevance to the study of radiology. Laboratory exercises were developed using inexpensive materials in the form of hands-on stations designed for use by students working together in small groups. Station exercises include model building, exploring relevant radiological imaging, and practicing clinical techniques. Students are encouraged to move from abstract conceptualization of the anatomy using models to applying knowledge to living tissues by using a portable ultrasound to explore superficial anatomy on each other. Stations are designed to integrate knowledge and reemphasize concepts in different contexts, so that upon completion students have a reinforced understanding of the three-dimensional anatomy of the region in question, the appearance of the anatomy on radiological images, and an appreciation of the relevance of the anatomy to radiological procedures.

  7. 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

    2014-09-07

    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.

  8. Host-Guest Chemistry in Integrated Porous Space Formed by Molecular Self-Assembly at Liquid-Solid Interfaces.

    PubMed

    Iritani, Kohei; Tahara, Kazukuni; De Feyter, Steven; Tobe, Yoshito

    2017-02-23

    Host-guest chemistry in two-dimensional (2D) space, that is, physisorbed monolayers of a single atom or a single molecular thickness on surfaces, has become a subject of intense current interest because of perspectives for various applications in molecular-scale electronics, selective sensors, and tailored catalysis. Scanning tunneling microscopy has been used as a powerful tool for the visualization of molecules in real space on a conducting substrate surface. For more than a decade, we have been investigating the self-assembly of a series of triangle-shaped phenylene-ethynylene macrocycles called dehydrobenzo[12]annulenes (DBAs). These molecules are substituted with six alkyl chains and are capable of forming hexagonal porous 2D molecular networks via van der Waals interactions between interdigitated alkyl chains at the interface of organic solvents and graphite. The dimension of the nanoporous space or nanowell formed by the self-assembly of DBAs can be controlled from 1.6 to 4.7 nm by simply changing the alkyl chain length from C6 to C20. Single molecules as well as homoclusters and heteroclusters are capable of coadsorbing within the host matrix using shape- and size-complementarity principles. Moreover, on the basis of the versatility of the DBA molecules that allows chemical modification of the alkyl chain terminals, we were able to decorate the interior space of the nanoporous networks with functional groups such as azobenzenedicarboxylic acid for photoresponsive guest adsorption/desorption or fluoroalkanes and tetraethylene glycol groups for selective guest binding by electrostatic interactions and zinc-porphyrin units for complexation with a guest by charge-transfer interactions. In this Feature Article, we describe the general aspects of molecular self-assembly at liquid/solid interfaces, followed by the formation of programmed porous molecular networks using rationally designed molecular building blocks. We focus on our own work involving host

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

    NASA Astrophysics Data System (ADS)

    Kamibayashi, Yuki; Miura, Shinichi

    2016-08-01

    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.

  10. 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.

  11. 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.

  12. 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.

  13. Communication: Kirkwood-Buff integrals in the thermodynamic limit from small-sized molecular dynamics simulations

    NASA Astrophysics Data System (ADS)

    Cortes-Huerto, R.; Kremer, K.; Potestio, R.

    2016-10-01

    We present an accurate and efficient method to obtain Kirkwood-Buff (KB) integrals in the thermodynamic limit from small-sized molecular dynamics simulations. By introducing finite size effects into integral equations of statistical mechanics, we derive an analytical expression connecting the KB integrals of the bulk system with the fluctuations of the number of molecules in the corresponding closed system. We validate the method by calculating the activity coefficients of aqueous urea mixtures and the KB integrals of Lennard-Jones fluids. Moreover, our results demonstrate how to identify simulation conditions under which computer simulations reach the thermodynamic limit.

  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. 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.

  16. [Molecular aspects of bioelectrogenesis].

    PubMed

    Schoffeniels, E

    1989-10-01

    The action potential is a dissipative process producing entropy and using free energy. This is well demonstrated by: 1) the evolution of the Na conductance under voltage clamping conditions, 2) the microcalorimetric measurements, 3) the analysis of heat evolution during the conductance changes. The most appropriate explanation must involve an exogenous energy source since the energy dissipated by the ionic flows or even the applied stimulus depolarization are far too small to account for the overall energy balance. Thiamine triphosphate is a likely candidate as specific operating substance. The more so, since it is specifically hydrolyzed by a triphosphatase the activity of which is modulated by various anions. It is therefore suggested that the control of the Cl-permeability, a process requiring the hydrolysis of thiamine triphosphate, is the key to our understanding of the energetics of the action potential.

  17. Ab initio centroid path integral molecular dynamics: Application to vibrational dynamics of diatomic molecular systems

    NASA Astrophysics Data System (ADS)

    Ohta, Yasuhito; Ohta, Koji; Kinugawa, Kenichi

    2004-01-01

    An ab initio centroid molecular dynamics (CMD) method is developed by combining the CMD method with the ab initio molecular orbital method. The ab initio CMD method is applied to vibrational dynamics of diatomic molecules, H2 and HF. For the H2 molecule, the temperature dependence of the peak frequency of the vibrational spectral density is investigated. The results are compared with those obtained by the ab initio classical molecular dynamics method and exact quantum mechanical treatment. It is shown that the vibrational frequency obtained from the ab initio CMD approaches the exact first excitation frequency as the temperature lowers. For the HF molecule, the position autocorrelation function is also analyzed in detail. The present CMD method is shown to well reproduce the exact quantum result for the information on the vibrational properties of the system.

  18. DNA-enabled integrated molecular systems for computation and sensing.

    PubMed

    LaBoda, Craig; Duschl, Heather; Dwyer, Chris L

    2014-06-17

    CONSPECTUS: Nucleic acids have become powerful building blocks for creating supramolecular nanostructures with a variety of new and interesting behaviors. The predictable and guided folding of DNA, inspired by nature, allows designs to manipulate molecular-scale processes unlike any other material system. Thus, DNA can be co-opted for engineered and purposeful ends. This Account details a small portion of what can be engineered using DNA within the context of computer architectures and systems. Over a decade of work at the intersection of DNA nanotechnology and computer system design has shown several key elements and properties of how to harness the massive parallelism created by DNA self-assembly. This work is presented, naturally, from the bottom-up beginning with early work on strand sequence design for deterministic, finite DNA nanostructure synthesis. The key features of DNA nanostructures are explored, including how the use of small DNA motifs assembled in a hierarchical manner enables full-addressability of the final nanostructure, an important property for building dense and complicated systems. A full computer system also requires devices that are compatible with DNA self-assembly and cooperate at a higher level as circuits patterned over many, many replicated units. Described here is some work in this area investigating nanowire and nanoparticle devices, as well as chromophore-based circuits called resonance energy transfer (RET) logic. The former is an example of a new way to bring traditional silicon transistor technology to the nanoscale, which is increasingly problematic with current fabrication methods. RET logic, on the other hand, introduces a framework for optical computing at the molecular level. This Account also highlights several architectural system studies that demonstrate that even with low-level devices that are inferior to their silicon counterparts and a substrate that harbors abundant defects, self-assembled systems can still

  19. 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

  20. Ixodes ventalloi: morphological and molecular support for species integrity.

    PubMed

    Latrofa, Maria Stefania; Giannelli, Alessio; Persichetti, Maria Flaminia; Pennisi, Maria Grazia; Solano-Gallego, Laia; Brianti, Emanuele; Parisi, Antonio; Wall, Richard; Dantas-Torres, Filipe; Otranto, Domenico

    2017-01-01

    Despite their medical and veterinary importance, some tick species are so poorly studied, that their role within pathogen vector transmission cycles is difficult to assess. The tick Ixodes ventalloi is one such species, and its biology and phylogenetic status remain an issue of debate. In the present study, specimens of adult I. ventalloi (n = 65 females; n = 31 males) infesting cats in the Lipari Island (Aeolian archipelago, Sicily, southern Italy) were characterized morphologically and molecularly, the latter based on mitochondrial 16S rRNA and cytochrome c oxidase subunit 1 (cox1) genes. The genetic data and phylogenetic analyses for both mitochondrial genes suggest the existence of two distinct genogroups. The ecological and epidemiological significance of the genetic structure within the I. ventalloi endemic population remains to be determined. The results highlight the need for further analysis of this tick species, including whole mitochondrial genome sequencing and crossbreeding studies, which will be pivotal to complement features of its status as a vector of pathogens.

  1. Integrated Development of Serum Molecular Markers for Early Diagnosis of Breast Cancer

    DTIC Science & Technology

    2006-09-01

    Molecular Makers for Early Diagnosis of Breast Cancer PRINCIPAL INVESTIGATOR: Anna Lokshin, Ph.D. CONTRACTING ORGANIZATION: University of...NUMBER Integrated Development of Serum Molecular Makers for Early Diagnosis of Breast Cancer 5b. GRANT NUMBER DAMD17-03-1-0696 5c. PROGRAM...Therefore, studies at this stage involve screening people and lead to diagnosis and treatment. The aims of this phase include assessment of (i) the

  2. 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.

  3. Molecular and cellular aspects of mental retardation in the Fragile X syndrome: from gene mutation/s to spine dysmorphogenesis.

    PubMed

    De Rubeis, Silvia; Fernández, Esperanza; Buzzi, Andrea; Di Marino, Daniele; Bagni, Claudia

    2012-01-01

    The Fragile X syndrome (FXS) is the most frequent form of inherited mental retardation and also considered a monogenic cause of Autism Spectrum Disorder. FXS symptoms include neurodevelopmental delay, anxiety, hyperactivity, and autistic-like behavior. The disease is due to mutations or loss of the Fragile X Mental Retardation Protein (FMRP), an RNA-binding protein abundant in the brain and gonads, the two organs mainly affected in FXS patients. FMRP has multiple functions in RNA metabolism, including mRNA decay, dendritic targeting of mRNAs, and protein synthesis. In neurons lacking FMRP, a wide array of mRNAs encoding proteins involved in synaptic structure and function are altered. As a result of this complex dysregulation, in the absence of FMRP, spine morphology and functioning is impaired. Consistently, model organisms for the study of the syndrome recapitulate the phenotype observed in FXS patients, such as dendritic spine anomalies and defects in learning. Here, we review the fundamentals of genetic and clinical aspects of FXS, devoting a specific attention to ASD comorbidity and FXS-related diseases. We also review the current knowledge on FMRP functions through structural, molecular, and cellular findings. Finally, we discuss the neuroanatomical, electrophysiological, and behavioral defects caused by FMRP loss, as well as the current treatments able to partially revert some of the FXS abnormalities.

  4. Molecular and Clinical Aspects of the Target Therapy with the Calcimimetic Cinacalcet in the Treatment of Parathyroid Tumors.

    PubMed

    Mingione, Alessandra; Verdelli, Chiara; Terranegra, Annalisa; Soldati, Laura; Corbetta, Sabrina

    2015-01-01

    Parathyroid tumors are almost invariably associated with parathormone (PTH) hypersecretion resulting in primary (PHPT) or secondary (SHPT) hyperparathyroidism. PHPT is the third most common endocrine disorder with a prevalence of 1-2% in post-menopausal women; SHPT is a major complication of chronic kidney failure, the prevalence of which is increasing. The calciumsensing receptor (CASR) is the key molecule regulating PTH synthesis and release from the parathyroid cells in response to changes in extracellular calcium concentrations. A potent calcimimetic, cinacalcet, has been developed in the last ten years and made available for medical treatment of both PHPT and SHPT. Cinacalcet has been demonstrated to be effective in inhibiting PTH secretion, though the drug fails to normalize PTH release, both in PHPT and SHPT patients with different degrees of disease severity, including patients with parathyroid carcinomas and with MEN1-related parathyroid tumors. Here we reviewed the molecular aspects of CASR target therapy and the effect of the CASR gene single nucleotide polymorphisms. Clinical data concerning the efficacy and safety of cinacalcet in controlling hyperparathyroidism are reported, focusing on the treatment of the different types of parathyroid tumors. Finally, limits of this target therapy are analyzed, pointing out the lack of efficacy in improving kidney and bone morbidities in PHPT and cardiovascular diseases in SHPT. Though cinacalcet is a target therapeutic option for parathyroid tumors, further approaches are warranted to fully control these metabolic disorders and the underlying tumors.

  5. 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

  6. Algorithms and novel applications based on the isokinetic ensemble. I. Biophysical and path integral molecular dynamics

    NASA Astrophysics Data System (ADS)

    Minary, Peter; Martyna, Glenn J.; Tuckerman, Mark E.

    2003-02-01

    In this paper (Paper I) and a companion paper (Paper II), novel new algorithms and applications of the isokinetic ensemble as generated by Gauss' principle of least constraint, pioneered for use with molecular dynamics 20 years ago, are presented for biophysical, path integral, and Car-Parrinello based ab initio molecular dynamics. In Paper I, a new "extended system" version of the isokinetic equations of motion that overcomes the ergodicity problems inherent in the standard approach, is developed using a new theory of non-Hamiltonian phase space analysis [M. E. Tuckerman et al., Europhys. Lett. 45, 149 (1999); J. Chem. Phys. 115, 1678 (2001)]. Reversible multiple time step integrations schemes for the isokinetic methods, first presented by Zhang [J. Chem. Phys. 106, 6102 (1997)] are reviewed. Next, holonomic constraints are incorporated into the isokinetic methodology for use in fast efficient biomolecular simulation studies. Model and realistic examples are presented in order to evaluate, critically, the performance of the new isokinetic molecular dynamic schemes. Comparisons are made to the, now standard, canonical dynamics method, Nosé-Hoover chain dynamics [G. J. Martyna et al., J. Chem. Phys. 97, 2635 (1992)]. The new isokinetic techniques are found to yield more efficient sampling than the Nosé-Hoover chain method in both path integral molecular dynamics and biophysical molecular dynamics calculations. In Paper II, the use of isokinetic methods in Car-Parrinello based ab initio molecular dynamics calculations is presented.

  7. Time reversible and symplectic integrators for molecular dynamics simulations of rigid molecules

    NASA Astrophysics Data System (ADS)

    Kamberaj, H.; Low, R. J.; Neal, M. P.

    2005-06-01

    Molecular dynamics integrators are presented for translational and rotational motion of rigid molecules in microcanonical, canonical, and isothermal-isobaric ensembles. The integrators are all time reversible and are also, in some approaches, symplectic for the microcanonical ensembles. They are developed utilizing the quaternion representation on the basis of the Trotter factorization scheme using a Hamiltonian formalism. The structure is similar to that of the velocity Verlet algorithm. Comparison is made with standard integrators in terms of stability and it is found that a larger time step is stable with the new integrators. The canonical and isothermal-isobaric molecular dynamics simulations are defined by using a chain thermostat approach according to generalized Nosé-Hoover and Andersen methods.

  8. Operational aspects of SO2 removal and microbial population in an integrated-bioreactor with two bioreaction zones.

    PubMed

    Li, Lin; Yang, Kaixiong; Lin, Jian; Liu, Junxin

    2017-02-01

    An integrated-bioreactor, which consisted of a suspended zone and an immobilized zone, was applied to treat gases containing SO2. The removal of SO2 in suspended zone differed slightly from that in immobilized zone. The influences of operational aspects such as SO2 load, temperature, and pH on integrated-bioreactor performance and bacterial community composition were investigated. The synergistic action of the two zones led to effective reduction of SO2, and the total removal efficiencies with the inlet concentration of 91-117 mg/m(3), were over 85 % in steady state. Paenibacillus sp. and Lysinibacillus sp. dominated both zones as desulfurization bacteria. Results of polymerase chain reaction-denaturing gradient gel electrophoresis followed by clone library analysis indicated that temporal shifts in bacterial community composition in both zones developed differently. Differences in the concentration of introduced SO2 and supported mode of microorganisms for survival, confirmed that bacterial community composition and abundance significantly differed among individual zones.

  9. 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.

  10. 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

  11. Molecular basis of voltage dependence of connexin channels: an integrative appraisal.

    PubMed

    González, Daniel; Gómez-Hernández, Juan M; Barrio, Luis C

    2007-01-01

    The importance of electrical and molecular signaling through connexin (Cx) channels is now widely recognized. The transfer of ions and other small molecules between adjacent cells is regulated by multiple stimuli, including voltage. Indeed, Cx channels typically exhibit complex voltage sensitivity. Most channels are sensitive to the voltage difference between the cell interiors (or transjunctional voltage, V(j)), while other channels are also sensitive to absolute inside-outside voltage (i.e., the membrane potential, V(m)). The first part of this review is focused on the description of the distinct forms of voltage sensitivity and the gating mechanisms that regulate hemichannel activity, both individually and as components of homotypic and heterotypic gap junctions. We then provide an up to date and precise picture of the molecular and structural aspects of how V(j) and V(m) are sensed, and how they, therefore, control channel opening and closing. Mutagenic strategies coupled with structural, biochemical and electrophysical studies are providing significant insights into how distinct forms of voltage dependence are brought about. The emerging picture indicates that Cx channels can undergo transitions between multiple conductance states driven by distinct voltage-gating mechanisms. Each hemichannel may contain a set of two V(j) gates, one fast and one slow, which mediate the transitions between the main open state to the residual state and to the fully closed state, respectively. Eventually, a V(m) gate regulates channel transitions between the open and closed states. Clusters of charged residues within separate domains of the Cx molecule have been identified as integral parts of the V(j) and V(m) sensors. The charges at the first positions of the amino terminal cytoplasmic domain determine the magnitude and polarity of the sensitivity to fast V(j)-gating, as well as contributing to the V(j)-rectifying properties of ion permeation. Additionally, important advances

  12. Isotope effects in water as investigated by neutron diffraction and path integral molecular dynamics

    NASA Astrophysics Data System (ADS)

    Zeidler, Anita; Salmon, Philip S.; Fischer, Henry E.; Neuefeind, Jörg C.; Simonson, J. Mike; Markland, Thomas E.

    2012-07-01

    The structures of heavy and light water at 300 K were investigated by using a joint approach in which the method of neutron diffraction with oxygen isotope substitution was complemented by path integral molecular dynamics simulations. The diffraction results, which give intra-molecular O-D and O-H bond distances of 0.985(5) and 0.990(5) Å, were found to be in best agreement with those obtained by using the flexible anharmonic TTM3-F water model. Both techniques show a difference of ≃ 0.5% between the O-D and O-H intra-molecular bond lengths, and the results support a competing quantum effects model for water in which its structural and dynamical properties are governed by an offset between intra-molecular and inter-molecular quantum contributions. Further consideration of the O-O correlations is needed in order to improve agreement with experiment.

  13. 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.

  14. A model for integrating molecular-based testing in transfusion services

    PubMed Central

    Sandler, S. Gerald; Horn, Trina; Keller, Jessica; Langeberg, Al; Keller, Margaret A.

    2016-01-01

    Background Molecular-based laboratory tests can predict blood group antigens and supplement serological methods, adding a unique technology to assist in resolving discrepant or incomplete blood group typing or antibody identification. Hospital transfusion services have options for integrating molecular-based methods in their routine operations. We describe here the model of a hospital-reference laboratory partnership. Materials and methods Blood samples for compatibility testing were obtained from patients in a 609-bed hospital serving an urban multiethnic and multiracial population. When results of blood group phenotyping by serological methods were inconclusive, samples were referred for molecular-based testing. The reference laboratory used several methods for genotyping, including polymerase chain reaction followed by restriction enzyme-linked polymorphism analysis, sequence-specific primer polymerase chain reaction and array-based approaches. Human erythrocyte antigen, RHCE and RHD single nucleotide polymorphism arrays were integrated into the laboratory as they became commercially available. Results The hospital-reference laboratory model made it possible to integrate blood group genotyping promptly by current technology without the expense of new laboratory equipment or adding personnel with technical expertise. We describe ten cases that illustrate the categories of serological problems that were resolved by molecular methods. Discussion In-hospital molecular testing for transfusion services has logistical advantages, but is financially impractical for most hospitals. Our model demonstrates the advantages of a hospital-reference laboratory partnership. In conclusion, hospital transfusion services can integrate molecular-based testing in their routine services without delay by establishing a partnership with a molecular blood group reference laboratory. The hospital reference-laboratory model promotes genomic medicine without the expense of new equipment and

  15. Analytical evaluation of molecular electronic integrals using Poisson's equation: Exponential-type orbitals and atom pairs

    NASA Astrophysics Data System (ADS)

    Absi, Noureddine; Hoggan, Philip

    The integral bottleneck in evaluating molecular energies arises from the two-electron contributions. These are difficult and time-consuming to evaluate, especially over exponential type orbitals, used here to ensure the correct behavior of atomic orbitals. The two-center two-electron integrals are essential to describe atom pairs in molecules and distinguish those that are bound. In this work on analytical integration, it is shown that the two-center Coulomb integrals involved can be expressed as one-electron kinetic energy-like integrals. This is accomplished using the fact that the Coulomb operator is a Green's function of the Laplacian. The ensuing integrals may be further simplified by defining spectral forms for the one-electron potential satisfying Poisson's equation therein. A sum of overlap integrals with the atomic orbital energy eigenvalue as a factor is then obtained to give the Coulomb energy. This is most easily evaluated by direct integration. The orbitals involved in three and four center integrals are translated to two centers. This is discussed very briefly. The evaluation of exchange energy is a straightforward extension of this work. The summation coefficients in spectral forms are evaluated analytically from Gaunt coefficients. The Poisson method may be used to calculate Coulomb energy integrals efficiently. For a single processor, gains of CPU time for a given chemical accuracy exceed a factor of 4. This method lends itself to efficient evaluation on a parallel computer.

  16. The vanilloid receptor family of calcium-permeable channels: molecular integrators of microenvironmental stimuli.

    PubMed

    O'Neil, Roger G; Brown, Rachel C

    2003-12-01

    The TRPV subfamily of calcium-permeable channels is widely distributed in sensory and nonsensory cells from nematodes to mammals. These channels can be variably activated by a diverse range of stimuli (osmotic/mechanical stress, noxious chemicals and heat, endogenous mediators) that often converge on the same channel. Evidence is presented that TRPV channels function as novel "molecular integrators" of diverse microenvironmental stimuli.

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

    PubMed

    Sun, Yin Xue; Huang, Yan Xin; Li, Feng Li; Wang, Hong Yan; Fan, Cong; Bao, Yong Li; Sun, Lu Guo; Ma, Zhi Qiang; Kong, Jun; Li, Yu Xin

    2012-01-05

    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. 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. 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/.

  18. An integrated molecular cytogenetic map of Cucumis sativus L. chromosome 2

    PubMed Central

    2011-01-01

    Background Integration of molecular, genetic and cytological maps is still a challenge for most plant species. Recent progress in molecular and cytogenetic studies created a basis for developing integrated maps in cucumber (Cucumis sativus L.). Results In this study, eleven fosmid clones and three plasmids containing 45S rDNA, the centromeric satellite repeat Type III and the pericentriomeric repeat CsRP1 sequences respectively were hybridized to cucumber metaphase chromosomes to assign their cytological location on chromosome 2. Moreover, an integrated molecular cytogenetic map of cucumber chromosomes 2 was constructed by fluorescence in situ hybridization (FISH) mapping of 11 fosmid clones together with the cucumber centromere-specific Type III sequence on meiotic pachytene chromosomes. The cytogenetic map was fully integrated with genetic linkage map since each fosmid clone was anchored by a genetically mapped simple sequence repeat marker (SSR). The relationship between the genetic and physical distances along chromosome was analyzed. Conclusions Recombination was not evenly distributed along the physical length of chromosome 2. Suppression of recombination was found in centromeric and pericentromeric regions. Our results also indicated that the molecular markers composing the linkage map for chromosome 2 provided excellent coverage of the chromosome. PMID:21272311

  19. Parallel higher-order boundary integral electrostatics computation on molecular surfaces with curved triangulation

    NASA Astrophysics Data System (ADS)

    Geng, Weihua

    2013-05-01

    In this paper, we present a parallel higher-order boundary integral method to solve the linear Poisson-Boltzmann (PB) equation. In our method, a well-posed boundary integral formulation is used to ensure the fast convergence of Krylov subspace linear solver such as GMRES. The molecular surfaces are first discretized with flat triangles and then converted to curved triangles with the assistance of normal information at vertices. To maintain the desired accuracy, four-point Gauss-Radau quadratures are used on regular triangles and sixteen-point Gauss-Legendre quadratures together with regularization transformations are applied on singular triangles. To speed up our method, we take advantage of the embarrassingly parallel feature of boundary integral formulation, and parallelize the schemes with the message passing interface (MPI) implementation. Numerical tests show significantly improved accuracy and convergence of the proposed higher-order boundary integral Poisson-Boltzmann (HOBI-PB) solver compared with boundary integral PB solver using often-seen centroid collocation on flat triangles. The higher-order accuracy results achieved by present method are important to sensitive solvation analysis of biomolecules, particularly when accurate electrostatic surface potentials are critical in the molecular simulation. In addition, the higher-order boundary integral schemes presented here and their associated parallelization potentially can be applied to solving boundary integral equations in a general sense.

  20. Improving the convergence of closed and open path integral molecular dynamics via higher order Trotter factorization schemes

    NASA Astrophysics Data System (ADS)

    Pérez, Alejandro; Tuckerman, Mark E.

    2011-08-01

    Higher order factorization schemes are developed for path integral molecular dynamics in order to improve the convergence of estimators for physical observables as a function of the Trotter number. The methods are based on the Takahashi-Imada and Susuki decompositions of the Boltzmann operator. The methods introduced improve the averages of the estimators by using the classical forces needed to carry out the dynamics to construct a posteriori weighting factors for standard path integral molecular dynamics. The new approaches are straightforward to implement in existing path integral codes and carry no significant overhead. The Suzuki higher order factorization was also used to improve the end-to-end distance estimator in open path integral molecular dynamics. The new schemes are tested in various model systems, including an ab initio path integral molecular dynamics calculation on the hydrogen molecule and a quantum water model. The proposed algorithms have potential utility for reducing the cost of path integral molecular dynamics calculations of bulk systems.

  1. Improving the convergence of closed and open path integral molecular dynamics via higher order Trotter factorization schemes.

    PubMed

    Pérez, Alejandro; Tuckerman, Mark E

    2011-08-14

    Higher order factorization schemes are developed for path integral molecular dynamics in order to improve the convergence of estimators for physical observables as a function of the Trotter number. The methods are based on the Takahashi-Imada and Susuki decompositions of the Boltzmann operator. The methods introduced improve the averages of the estimators by using the classical forces needed to carry out the dynamics to construct a posteriori weighting factors for standard path integral molecular dynamics. The new approaches are straightforward to implement in existing path integral codes and carry no significant overhead. The Suzuki higher order factorization was also used to improve the end-to-end distance estimator in open path integral molecular dynamics. The new schemes are tested in various model systems, including an ab initio path integral molecular dynamics calculation on the hydrogen molecule and a quantum water model. The proposed algorithms have potential utility for reducing the cost of path integral molecular dynamics calculations of bulk systems.

  2. Sarcoptes-World Molecular Network (Sarcoptes-WMN): integrating research on scabies.

    PubMed

    Alasaad, Samer; Walton, Shelley; Rossi, Luca; Bornstein, Set; Abu-Madi, Marawan; Soriguer, Ramón C; Fitzgerald, Scott; Zhu, Xing-Quan; Zimmermann, Werner; Ugbomoiko, Uade Samuel; Pei, Kurtis Jai-Chyi; Heukelbach, Jörg

    2011-05-01

    Parasites threaten human and animal health globally. It is estimated that more than 60% of people on planet Earth carry at least one parasite, many of them several different species. Unfortunately, parasite studies suffer from duplications and inconsistencies between different investigator groups. Hence, groups need to collaborate in an integrated manner in areas including parasite control, improved therapy strategies, diagnostic and surveillance tools, and public awareness. Parasite studies will be better served if there is coordinated management of field data and samples across multidisciplinary approach plans, among academic and non-academic organizations worldwide. In this paper we report the first 'Living organism-World Molecular Network', with the cooperation of 167 parasitologists from 88 countries on all continents. This integrative approach, the 'Sarcoptes-World Molecular Network', seeks to harmonize Sarcoptes epidemiology, diagnosis, treatment, and molecular studies from all over the world, with the aim of decreasing mite infestations in humans and animals.

  3. Simulations of one- and two-electron systems by Bead-Fourier path integral molecular dynamics

    NASA Astrophysics Data System (ADS)

    Ivanov, Sergei D.; Lyubartsev, Alexander P.

    2005-07-01

    The Bead-Fourier path integral molecular dynamics technique introduced earlier [S. D. Ivanov, A. P. Lyubartsev, and A. Laaksonen, Phys. Rev. E 67 066710 (2003)] is applied for simulation of electrons in the simplest molecules: molecular hydrogen, helium atom, and their ions. Special attention is paid to the correct description of electrons in the core region of a nucleus. In an attempt to smooth the Coulomb potential at small distances, a recipe is suggested. The simulation results are in excellent agreement with the analytical solution for the "harmonic helium atom", as well as with the vibrational potential of the H2 molecule and He ionization energies. It is demonstrated, that the Bead-Fourier path integral molecular dynamics technique is able to provide the accuracy required for the description of electron structure and chemical bonds in cases when electron exchange effects need not be taken into account.

  4. 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.

  5. XML-based approaches for the integration of heterogeneous bio-molecular data

    PubMed Central

    Mesiti, Marco; Jiménez-Ruiz, Ernesto; Sanz, Ismael; Berlanga-Llavori, Rafael; Perlasca, Paolo; Valentini, Giorgio; Manset, David

    2009-01-01

    Background The today's public database infrastructure spans a very large collection of heterogeneous biological data, opening new opportunities for molecular biology, bio-medical and bioinformatics research, but raising also new problems for their integration and computational processing. Results In this paper we survey the most interesting and novel approaches for the representation, integration and management of different kinds of biological data by exploiting XML and the related recommendations and approaches. Moreover, we present new and interesting cutting edge approaches for the appropriate management of heterogeneous biological data represented through XML. Conclusion XML has succeeded in the integration of heterogeneous biomolecular information, and has established itself as the syntactic glue for biological data sources. Nevertheless, a large variety of XML-based data formats have been proposed, thus resulting in a difficult effective integration of bioinformatics data schemes. The adoption of a few semantic-rich standard formats is urgent to achieve a seamless integration of the current biological resources. PMID:19828083

  6. Interdisciplinary education to integrate pathology and epidemiology: towards molecular and population-level health science.

    PubMed

    Ogino, Shuji; King, Emily E; Beck, Andrew H; Sherman, Mark E; Milner, Danny A; Giovannucci, Edward

    2012-10-15

    In recent decades, epidemiology, public health, and medical sciences have been increasingly compartmentalized into narrower disciplines. The authors recognize the value of integration of divergent scientific fields in order to create new methods, concepts, paradigms, and knowledge. Herein they describe the recent emergence of molecular pathological epidemiology (MPE), which represents an integration of population and molecular biologic science to gain insights into the etiologies, pathogenesis, evolution, and outcomes of complex multifactorial diseases. Most human diseases, including common cancers (such as breast, lung, prostate, and colorectal cancers, leukemia, and lymphoma) and other chronic diseases (such as diabetes mellitus, cardiovascular diseases, hypertension, autoimmune diseases, psychiatric diseases, and some infectious diseases), are caused by alterations in the genome, epigenome, transcriptome, proteome, metabolome, microbiome, and interactome of all of the above components. In this era of personalized medicine and personalized prevention, we need integrated science (such as MPE) which can decipher diseases at the molecular, genetic, cellular, and population levels simultaneously. The authors believe that convergence and integration of multiple disciplines should be commonplace in research and education. We need to be open-minded and flexible in designing integrated education curricula and training programs for future students, clinicians, practitioners, and investigators.

  7. Interdisciplinary Education to Integrate Pathology and Epidemiology: Towards Molecular and Population-Level Health Science

    PubMed Central

    Ogino, Shuji; King, Emily E.; Beck, Andrew H.; Sherman, Mark E.; Milner, Danny A.; Giovannucci, Edward

    2012-01-01

    In recent decades, epidemiology, public health, and medical sciences have been increasingly compartmentalized into narrower disciplines. The authors recognize the value of integration of divergent scientific fields in order to create new methods, concepts, paradigms, and knowledge. Herein they describe the recent emergence of molecular pathological epidemiology (MPE), which represents an integration of population and molecular biologic science to gain insights into the etiologies, pathogenesis, evolution, and outcomes of complex multifactorial diseases. Most human diseases, including common cancers (such as breast, lung, prostate, and colorectal cancers, leukemia, and lymphoma) and other chronic diseases (such as diabetes mellitus, cardiovascular diseases, hypertension, autoimmune diseases, psychiatric diseases, and some infectious diseases), are caused by alterations in the genome, epigenome, transcriptome, proteome, metabolome, microbiome, and interactome of all of the above components. In this era of personalized medicine and personalized prevention, we need integrated science (such as MPE) which can decipher diseases at the molecular, genetic, cellular, and population levels simultaneously. The authors believe that convergence and integration of multiple disciplines should be commonplace in research and education. We need to be open-minded and flexible in designing integrated education curricula and training programs for future students, clinicians, practitioners, and investigators. PMID:22935517

  8. Integration of Molecular Pathology, Epidemiology, and Social Science for Global Precision Medicine

    PubMed Central

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

    2015-01-01

    Summary 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

  9. Integrating multiple aspects of mitochondrial dynamics in neurons: Age-related differences and dynamic changes in a chronic rotenone model

    PubMed Central

    Arnold, Beth; Cassady, Steven J.; Van Laar, Victor S.; Berman, Sarah B.

    2010-01-01

    Changes in dynamic properties of mitochondria are increasingly implicated in neurodegenerative diseases, particularly Parkinson’s disease (PD). Static changes in mitochondrial morphology, often under acutely toxic conditions, are commonly utilized as indicators of changes in mitochondrial fission and fusion. However, in neurons, mitochondrial fission and fusion occur in a dynamic system of axonal/dendritic transport, biogenesis and degradation, and thus, likely interact and change over time. We sought to explore this using a chronic neuronal model (nonlethal low-concentration rotenone over several weeks), examining distal neurites, which may give insight into the earliest changes occurring in PD. Using this model, in live primary neurons, we directly quantified mitochondrial fission, fusion, and transport over time and integrated multiple aspects of mitochondrial dynamics, including morphology and growth/mitophagy. We found that rates of mitochondrial fission and fusion change as neurons age. In addition, we found that chronic rotenone exposure initially increased the ratio of fusion to fission, but later, this was reversed. Surprisingly, despite changes in rates of fission and fusion, mitochondrial morphology was minimally affected, demonstrating that morphology can be an inaccurate indicator of fission/fusion changes. In addition, we found evidence of subcellular compartmentalization of compensatory changes, as mitochondrial density increased in distal neurites first, which may be important in PD, where pathology may begin distally. We propose that rotenone-induced early changes such as in mitochondrial fusion are compensatory, accompanied later by detrimental fission. As evidence, in a dopaminergic neuronal model, in which chronic rotenone caused loss of neurites before cell death (like PD pathology), inhibiting fission protected against the neurite loss. This suggests that aberrant mitochondrial dynamics may contribute to the earliest neuropathologic

  10. The adenovirus L4-22K protein is multifunctional and is an integral component of crucial aspects of infection.

    PubMed

    Wu, Kai; Orozco, Diana; Hearing, Patrick

    2012-10-01

    A variety of cellular and viral processes are coordinately regulated during adenovirus (Ad) infection to achieve optimal virus production. The Ad late gene product L4-22K has been associated with disparate activities during infection, including the regulation of late gene expression, viral DNA packaging, and infectious virus production. We generated and characterized two L4-22K mutant viruses to further explore L4-22K functions during viral infection. Our results show that L4-22K is indeed important for temporal control of viral gene expression not only because it activates late gene expression but also because it suppresses early gene expression. We also show that the L4-22K protein binds to viral packaging sequences in vivo and is essential to recruit two other packaging proteins, IVa2 and L1-52/55K, to this region. The elimination of L4-22K gave rise to the production of only empty virus capsids and not mature virions, which confirms that the L4-22K protein is required for Ad genome packaging. Finally, L4-22K contributes to adenovirus-induced cell death by regulating the expression of the adenovirus death protein. Thus, the adenovirus L4-22K protein is multifunctional and an integral component of crucial aspects of infection.

  11. The Adenovirus L4-22K Protein Is Multifunctional and Is an Integral Component of Crucial Aspects of Infection

    PubMed Central

    Wu, Kai; Orozco, Diana

    2012-01-01

    A variety of cellular and viral processes are coordinately regulated during adenovirus (Ad) infection to achieve optimal virus production. The Ad late gene product L4-22K has been associated with disparate activities during infection, including the regulation of late gene expression, viral DNA packaging, and infectious virus production. We generated and characterized two L4-22K mutant viruses to further explore L4-22K functions during viral infection. Our results show that L4-22K is indeed important for temporal control of viral gene expression not only because it activates late gene expression but also because it suppresses early gene expression. We also show that the L4-22K protein binds to viral packaging sequences in vivo and is essential to recruit two other packaging proteins, IVa2 and L1-52/55K, to this region. The elimination of L4-22K gave rise to the production of only empty virus capsids and not mature virions, which confirms that the L4-22K protein is required for Ad genome packaging. Finally, L4-22K contributes to adenovirus-induced cell death by regulating the expression of the adenovirus death protein. Thus, the adenovirus L4-22K protein is multifunctional and an integral component of crucial aspects of infection. PMID:22811519

  12. Integrative Genomic Analysis of Cholangiocarcinoma Identifies Distinct IDH-Mutant Molecular Profiles.

    PubMed

    Farshidfar, Farshad; Zheng, Siyuan; Gingras, Marie-Claude; Newton, Yulia; Shih, Juliann; Robertson, A Gordon; Hinoue, Toshinori; Hoadley, Katherine A; Gibb, Ewan A; Roszik, Jason; Covington, Kyle R; Wu, Chia-Chin; Shinbrot, Eve; Stransky, Nicolas; Hegde, Apurva; Yang, Ju Dong; Reznik, Ed; Sadeghi, Sara; Pedamallu, Chandra Sekhar; Ojesina, Akinyemi I; Hess, Julian M; Auman, J Todd; Rhie, Suhn K; Bowlby, Reanne; Borad, Mitesh J; Zhu, Andrew X; Stuart, Josh M; Sander, Chris; Akbani, Rehan; Cherniack, Andrew D; Deshpande, Vikram; Mounajjed, Taofic; Foo, Wai Chin; Torbenson, Michael S; Kleiner, David E; Laird, Peter W; Wheeler, David A; McRee, Autumn J; Bathe, Oliver F; Andersen, Jesper B; Bardeesy, Nabeel; Roberts, Lewis R; Kwong, Lawrence N

    2017-03-14

    Cholangiocarcinoma (CCA) is an aggressive malignancy of the bile ducts, with poor prognosis and limited treatment options. Here, we describe the integrated analysis of somatic mutations, RNA expression, copy number, and DNA methylation by The Cancer Genome Atlas of a set of predominantly intrahepatic CCA cases and propose a molecular classification scheme. We identified an IDH mutant-enriched subtype with distinct molecular features including low expression of chromatin modifiers, elevated expression of mitochondrial genes, and increased mitochondrial DNA copy number. Leveraging the multi-platform data, we observed that ARID1A exhibited DNA hypermethylation and decreased expression in the IDH mutant subtype. More broadly, we found that IDH mutations are associated with an expanded histological spectrum of liver tumors with molecular features that stratify with CCA. Our studies reveal insights into the molecular pathogenesis and heterogeneity of cholangiocarcinoma and provide classification information of potential therapeutic significance. Copyright © 2017 The Authors. Published by Elsevier Inc. All rights reserved.

  13. Toward molecular trait-based ecology through integration of biogeochemical, geographical and metagenomic data

    PubMed Central

    Raes, Jeroen; Letunic, Ivica; Yamada, Takuji; Jensen, Lars Juhl; Bork, Peer

    2011-01-01

    Using metagenomic ‘parts lists' to infer global patterns on microbial ecology remains a significant challenge. To deduce important ecological indicators such as environmental adaptation, molecular trait dispersal, diversity variation and primary production from the gene pool of an ecosystem, we integrated 25 ocean metagenomes with geographical, meteorological and geophysicochemical data. We find that climatic factors (temperature, sunlight) are the major determinants of the biomolecular repertoire of each sample and the main limiting factor on functional trait dispersal (absence of biogeographic provincialism). Molecular functional richness and diversity show a distinct latitudinal gradient peaking at 20°N and correlate with primary production. The latter can also be predicted from the molecular functional composition of an environmental sample. Together, our results show that the functional community composition derived from metagenomes is an important quantitative readout for molecular trait-based biogeography and ecology. PMID:21407210

  14. Toward molecular trait-based ecology through integration of biogeochemical, geographical and metagenomic data.

    PubMed

    Raes, Jeroen; Letunic, Ivica; Yamada, Takuji; Jensen, Lars Juhl; Bork, Peer

    2011-03-15

    Using metagenomic 'parts lists' to infer global patterns on microbial ecology remains a significant challenge. To deduce important ecological indicators such as environmental adaptation, molecular trait dispersal, diversity variation and primary production from the gene pool of an ecosystem, we integrated 25 ocean metagenomes with geographical, meteorological and geophysicochemical data. We find that climatic factors (temperature, sunlight) are the major determinants of the biomolecular repertoire of each sample and the main limiting factor on functional trait dispersal (absence of biogeographic provincialism). Molecular functional richness and diversity show a distinct latitudinal gradient peaking at 20° N and correlate with primary production. The latter can also be predicted from the molecular functional composition of an environmental sample. Together, our results show that the functional community composition derived from metagenomes is an important quantitative readout for molecular trait-based biogeography and ecology.

  15. Determination of the experimental equilibrium structure of solid nitromethane using path-integral molecular dynamics simulations

    NASA Astrophysics Data System (ADS)

    Reilly, Anthony M.; Habershon, Scott; Morrison, Carole A.; Rankin, David W. H.

    2010-03-01

    Path-integral molecular dynamics (PIMD) simulations with an empirical interaction potential have been used to determine the experimental equilibrium structure of solid nitromethane at 4.2 and 15 K. By comparing the time-averaged molecular structure determined in a PIMD simulation to the calculated minimum-energy (zero-temperature) molecular structure, we have derived structural corrections that describe the effects of thermal motion. These corrections were subsequently used to determine the equilibrium structure of nitromethane from the experimental time-averaged structure. We find that the corrections to the intramolecular and intermolecular bond distances, as well as to the torsion angles, are quite significant, particularly for those atoms participating in the anharmonic motion of the methyl group. Our results demonstrate that simple harmonic models of thermal motion may not be sufficiently accurate, even at low temperatures, while molecular simulations employing more realistic potential-energy surfaces can provide important insight into the role and magnitude of anharmonic atomic motions.

  16. MelanomaDB: A Web Tool for Integrative Analysis of Melanoma Genomic Information to Identify Disease-Associated Molecular Pathways

    PubMed Central

    Trevarton, Alexander J.; Mann, Michael B.; Knapp, Christoph; Araki, Hiromitsu; Wren, Jonathan D.; Stones-Havas, Steven; Black, Michael A.; Print, Cristin G.

    2013-01-01

    Despite on-going research, metastatic melanoma survival rates remain low and treatment options are limited. Researchers can now access a rapidly growing amount of molecular and clinical information about melanoma. This information is becoming difficult to assemble and interpret due to its dispersed nature, yet as it grows it becomes increasingly valuable for understanding melanoma. Integration of this information into a comprehensive resource to aid rational experimental design and patient stratification is needed. As an initial step in this direction, we have assembled a web-accessible melanoma database, MelanomaDB, which incorporates clinical and molecular data from publically available sources, which will be regularly updated as new information becomes available. This database allows complex links to be drawn between many different aspects of melanoma biology: genetic changes (e.g., mutations) in individual melanomas revealed by DNA sequencing, associations between gene expression and patient survival, data concerning drug targets, biomarkers, druggability, and clinical trials, as well as our own statistical analysis of relationships between molecular pathways and clinical parameters that have been produced using these data sets. The database is freely available at http://genesetdb.auckland.ac.nz/melanomadb/about.html. A subset of the information in the database can also be accessed through a freely available web application in the Illumina genomic cloud computing platform BaseSpace at http://www.biomatters.com/apps/melanoma-profiler-for-research. The MelanomaDB database illustrates dysregulation of specific signaling pathways across 310 exome-sequenced melanomas and in individual tumors and identifies the distribution of somatic variants in melanoma. We suggest that MelanomaDB can provide a context in which to interpret the tumor molecular profiles of individual melanoma patients relative to biological information and available drug therapies. PMID:23875173

  17. 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.

  18. 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.

  19. Calculation of heat capacities of light and heavy water by path-integral molecular dynamics

    NASA Astrophysics Data System (ADS)

    Shiga, Motoyuki; Shinoda, Wataru

    2005-10-01

    As an application of atomistic simulation methods to heat capacities, path-integral molecular dynamics has been used to calculate the constant-volume heat capacities of light and heavy water in the gas, liquid, and solid phases. While the classical simulation based on conventional molecular dynamics has estimated the heat capacities too high, the quantum simulation based on path-integral molecular dynamics has given reasonable results based on the simple point-charge/flexible potential model. The calculated heat capacities (divided by the Boltzmann constant) in the quantum simulation are 3.1 in the vapor H2O at 300 K, 6.9 in the liquid H2O at 300 K, and 4.1 in the ice IhH2O at 250 K, respectively, which are comparable to the experimental data of 3.04, 8.9, and 4.1, respectively. The quantum simulation also reproduces the isotope effect. The heat capacity in the liquid D2O has been calculated to be 10% higher than that of H2O, while it is 13% higher in the experiment. The results demonstrate that the path-integral simulation is a promising approach to quantitatively evaluate the heat capacities for molecular systems, taking account of quantum-mechanical vibrations as well as strongly anharmonic motions.

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

    PubMed Central

    Müller, Klaus-Robert

    2015-01-01

    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

  1. 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.

  2. 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.

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

    PubMed

    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.

  4. Integration and mining of malaria molecular, functional and pharmacological data: how far are we from a chemogenomic knowledge space?

    PubMed Central

    Birkholtz, Lyn-Marie; Bastien, Olivier; Wells, Gordon; Grando, Delphine; Joubert, Fourie; Kasam, Vinod; Zimmermann, Marc; Ortet, Philippe; Jacq, Nicolas; Saïdani, Nadia; Roy, Sylvaine; Hofmann-Apitius, Martin; Breton, Vincent; Louw, Abraham I; Maréchal, Eric

    2006-01-01

    The organization and mining of malaria genomic and post-genomic data is important to significantly increase the knowledge of the biology of its causative agents, and is motivated, on a longer term, by the necessity to predict and characterize new biological targets and new drugs. Biological targets are sought in a biological space designed from the genomic data from Plasmodium falciparum, but using also the millions of genomic data from other species. Drug candidates are sought in a chemical space containing the millions of small molecules stored in public and private chemolibraries. Data management should, therefore, be as reliable and versatile as possible. In this context, five aspects of the organization and mining of malaria genomic and post-genomic data were examined: 1) the comparison of protein sequences including compositionally atypical malaria sequences, 2) the high throughput reconstruction of molecular phylogenies, 3) the representation of biological processes, particularly metabolic pathways, 4) the versatile methods to integrate genomic data, biological representations and functional profiling obtained from X-omic experiments after drug treatments and 5) the determination and prediction of protein structures and their molecular docking with drug candidate structures. Recent progress towards a grid-enabled chemogenomic knowledge space is discussed. PMID:17112376

  5. Integration and mining of malaria molecular, functional and pharmacological data: how far are we from a chemogenomic knowledge space?

    PubMed

    Birkholtz, Lyn-Marie; Bastien, Olivier; Wells, Gordon; Grando, Delphine; Joubert, Fourie; Kasam, Vinod; Zimmermann, Marc; Ortet, Philippe; Jacq, Nicolas; Saïdani, Nadia; Roy, Sylvaine; Hofmann-Apitius, Martin; Breton, Vincent; Louw, Abraham I; Maréchal, Eric

    2006-11-17

    The organization and mining of malaria genomic and post-genomic data is important to significantly increase the knowledge of the biology of its causative agents, and is motivated, on a longer term, by the necessity to predict and characterize new biological targets and new drugs. Biological targets are sought in a biological space designed from the genomic data from Plasmodium falciparum, but using also the millions of genomic data from other species. Drug candidates are sought in a chemical space containing the millions of small molecules stored in public and private chemolibraries. Data management should, therefore, be as reliable and versatile as possible. In this context, five aspects of the organization and mining of malaria genomic and post-genomic data were examined: 1) the comparison of protein sequences including compositionally atypical malaria sequences, 2) the high throughput reconstruction of molecular phylogenies, 3) the representation of biological processes, particularly metabolic pathways, 4) the versatile methods to integrate genomic data, biological representations and functional profiling obtained from X-omic experiments after drug treatments and 5) the determination and prediction of protein structures and their molecular docking with drug candidate structures. Recent progress towards a grid-enabled chemogenomic knowledge space is discussed.

  6. 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.

  7. 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.

  8. 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

  9. A comprehensive protein-centric ID mapping service for molecular data integration

    PubMed Central

    Huang, Hongzhan; Suzek, Baris E.; Mazumder, Raja; Zhang, Jian; Chen, Yongxing; Wu, Cathy H.

    2011-01-01

    Motivation: Identifier (ID) mapping establishes links between various biological databases and is an essential first step for molecular data integration and functional annotation. ID mapping allows diverse molecular data on genes and proteins to be combined and mapped to functional pathways and ontologies. We have developed comprehensive protein-centric ID mapping services providing mappings for 90 IDs derived from databases on genes, proteins, pathways, diseases, structures, protein families, protein interaction, literature, ontologies, etc. The services are widely used and have been regularly updated since 2006. Availability: www.uniprot.org/mappingandproteininformation-resource.org/pirwww/search/idmapping.shtml Contact: huang@dbi.udel.edu PMID:21478197

  10. Adaptive multi-stage integrators for optimal energy conservation in molecular simulations

    NASA Astrophysics Data System (ADS)

    Fernández-Pendás, Mario; Akhmatskaya, Elena; Sanz-Serna, J. M.

    2016-12-01

    We introduce a new Adaptive Integration Approach (AIA) to be used in a wide range of molecular simulations. Given a simulation problem and a step size, the method automatically chooses the optimal scheme out of an available family of numerical integrators. Although we focus on two-stage splitting integrators, the idea may be used with more general families. In each instance, the system-specific integrating scheme identified by our approach is optimal in the sense that it provides the best conservation of energy for harmonic forces. The AIA method has been implemented in the BCAM-modified GROMACS software package. Numerical tests in molecular dynamics and hybrid Monte Carlo simulations of constrained and unconstrained physical systems show that the method successfully realizes the fail-safe strategy. In all experiments, and for each of the criteria employed, the AIA is at least as good as, and often significantly outperforms the standard Verlet scheme, as well as fixed parameter, optimized two-stage integrators. In particular, for the systems where harmonic forces play an important role, the sampling efficiency found in simulations using the AIA is up to 5 times better than the one achieved with other tested schemes.

  11. On using a too large integration time step in molecular dynamics simulations of coarse-grained molecular models.

    PubMed

    Winger, Moritz; Trzesniak, Daniel; Baron, Riccardo; van Gunsteren, Wilfred F

    2009-03-28

    The use of a coarse-grained (CG) model that is widely used in molecular dynamics simulations of biomolecular systems is investigated with respect to the dependence of a variety of quantities upon the size of the used integration time step and cutoff radius. The results suggest that when using a non-bonded interaction-cutoff radius of 1.4 nm a time step of maximally 10 fs should be used, in order not to produce energy sinks or wells. Using a too-large time step, e.g. 50 fs with a cutoff of 1.2 nm, as is done in the coarse-grained model of Marrink et al. (J. Phys. Chem. B, 2004, 108, 250 and 2007, 111, 7812), induces errors due to the linear approximation of the integrators that are commonly used to integrate the equations of motion. As a spin-off of the investigation of the mentioned CG models, we found that the parameters of the CG water model place it at physiological temperatures well into the solid phase of the phase diagram.

  12. Transport coefficients of normal liquid helium-4 calculated by path integral centroid molecular dynamics simulation

    NASA Astrophysics Data System (ADS)

    Imaoka, Haruna; Kinugawa, Kenichi

    2017-03-01

    Thermal conductivity, shear viscosity, and bulk viscosity of normal liquid 4He at 1.7-4.0 K are calculated using path integral centroid molecular dynamics (CMD) simulations. The calculated thermal conductivity and shear viscosity above lambda transition temperature are on the same order of magnitude as experimental values, while the agreement of shear viscosity is better. Above 2.3 K the CMD well reproduces the temperature dependences of isochoric shear viscosity and of the time integral of the energy current and off-diagonal stress tensor correlation functions. The calculated bulk viscosity, not known in experiments, is several times larger than shear viscosity.

  13. Modern Aspects of Halophilism: The Edmond de Rothschild School in Molecular Biophysics (12th) Held in Israel on March 26-April 5, 1989. Program and Abstracts

    DTIC Science & Technology

    1989-04-01

    THE HALOPHILIC ARCHAEBACTERIUM Haloferax mediterranei Paola Londei, Ricardo Amils 1 and M.Emma Sancheza Dpt.Biopatologia Umana, Sez. Biologia ...Copy THE TWELFTH EDMOND DE ROTHSCHILD SCHOOL IN MOLECULAR BIOPHYSICS MODERN ASPECTS I CRAMSDTIC TAB 1 OF HALOPHILISM u .............. PROGRAM Dist...special ABSTRACTS A- 1 MARCH 26 to APRIL 5, 1989 ISRAEL SPONSORED BY THE INSTITUT DE BIOLOGIE PHYSICO-CHIMIQUE (Fondation Edmond do Rothschild, Paris) THE

  14. 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.

  15. Potential molecular consequences of transgene integration: The R6/2 mouse example

    PubMed Central

    Jacobsen, Jessie C.; Erdin, Serkan; Chiang, Colby; Hanscom, Carrie; Handley, Renee R.; Barker, Douglas D.; Stortchevoi, Alex; Blumenthal, Ian; Reid, Suzanne J.; Snell, Russell G.; MacDonald, Marcy E.; Morton, A. Jennifer; Ernst, Carl; Gusella, James F.; Talkowski, Michael E.

    2017-01-01

    Integration of exogenous DNA into a host genome represents an important route to generate animal and cellular models for exploration into human disease and therapeutic development. In most models, little is known concerning structural integrity of the transgene, precise site of integration, or its impact on the host genome. We previously used whole-genome and targeted sequencing approaches to reconstruct transgene structure and integration sites in models of Huntington’s disease, revealing complex structural rearrangements that can result from transgenesis. Here, we demonstrate in the R6/2 mouse, a widely used Huntington’s disease model, that integration of a rearranged transgene with coincident deletion of 5,444 bp of host genome within the gene Gm12695 has striking molecular consequences. Gm12695, the function of which is unknown, is normally expressed at negligible levels in mouse brain, but transgene integration has resulted in cortical expression of a partial fragment (exons 8–11) 3’ to the transgene integration site in R6/2. This transcript shows significant expression among the extensive network of differentially expressed genes associated with this model, including synaptic transmission, cell signalling and transcription. These data illustrate the value of sequence-level resolution of transgene insertions and transcription analysis to inform phenotypic characterization of transgenic models utilized in therapeutic research. PMID:28120936

  16. High throughput gene expression profiling: a molecular approach to integrative physiology

    PubMed Central

    Liang, Mingyu; Cowley, Allen W; Greene, Andrew S

    2004-01-01

    Integrative physiology emphasizes the importance of understanding multiple pathways with overlapping, complementary, or opposing effects and their interactions in the context of intact organisms. The DNA microarray technology, the most commonly used method for high-throughput gene expression profiling, has been touted as an integrative tool that provides insights into regulatory pathways. However, the physiology community has been slow in acceptance of these techniques because of early failure in generating useful data and the lack of a cohesive theoretical framework in which experiments can be analysed. With recent advances in both technology and analysis, we propose a concept of multidimensional integration of physiology that incorporates data generated by DNA microarray and other functional, genomic, and proteomic approaches to achieve a truly integrative understanding of physiology. Analysis of several studies performed in simpler organisms or in mammalian model animals supports the feasibility of such multidimensional integration and demonstrates the power of DNA microarray as an indispensable molecular tool for such integration. Evaluation of DNA microarray techniques indicates that these techniques, despite limitations, have advanced to a point where the question-driven profiling research has become a feasible complement to the conventional, hypothesis-driven research. With a keen sense of homeostasis, global regulation, and quantitative analysis, integrative physiologists are uniquely positioned to apply these techniques to enhance the understanding of complex physiological functions. PMID:14678487

  17. Integrating multiple molecular sources into a clinical risk prediction signature by extracting complementary information.

    PubMed

    Hieke, Stefanie; Benner, Axel; Schlenl, Richard F; Schumacher, Martin; Bullinger, Lars; Binder, Harald

    2016-08-30

    High-throughput technology allows for genome-wide measurements at different molecular levels for the same patient, e.g. single nucleotide polymorphisms (SNPs) and gene expression. Correspondingly, it might be beneficial to also integrate complementary information from different molecular levels when building multivariable risk prediction models for a clinical endpoint, such as treatment response or survival. Unfortunately, such a high-dimensional modeling task will often be complicated by a limited overlap of molecular measurements at different levels between patients, i.e. measurements from all molecular levels are available only for a smaller proportion of patients. We propose a sequential strategy for building clinical risk prediction models that integrate genome-wide measurements from two molecular levels in a complementary way. To deal with partial overlap, we develop an imputation approach that allows us to use all available data. This approach is investigated in two acute myeloid leukemia applications combining gene expression with either SNP or DNA methylation data. After obtaining a sparse risk prediction signature e.g. from SNP data, an automatically selected set of prognostic SNPs, by componentwise likelihood-based boosting, imputation is performed for the corresponding linear predictor by a linking model that incorporates e.g. gene expression measurements. The imputed linear predictor is then used for adjustment when building a prognostic signature from the gene expression data. For evaluation, we consider stability, as quantified by inclusion frequencies across resampling data sets. Despite an extremely small overlap in the application example with gene expression and SNPs, several genes are seen to be more stably identified when taking the (imputed) linear predictor from the SNP data into account. In the application with gene expression and DNA methylation, prediction performance with respect to survival also indicates that the proposed approach might

  18. 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

  19. Vertical resonant tunneling transistors with molecular quantum dots for large-scale integration.

    PubMed

    Hayakawa, Ryoma; Chikyow, Toyohiro; Wakayama, Yutaka

    2017-08-10

    Quantum molecular devices have a potential for the construction of new data processing architectures that cannot be achieved using current complementary metal-oxide-semiconductor (CMOS) technology. The relevant basic quantum transport properties have been examined by specific methods such as scanning probe and break-junction techniques. However, these methodologies are not compatible with current CMOS applications, and the development of practical molecular devices remains a persistent challenge. Here, we demonstrate a new vertical resonant tunneling transistor for large-scale integration. The transistor channel is comprised of a MOS structure with C60 molecules as quantum dots, and the structure behaves like a double tunnel junction. Notably, the transistors enabled the observation of stepwise drain currents, which originated from resonant tunneling via the discrete molecular orbitals. Applying side-gate voltages produced depletion layers in Si substrates, to achieve effective modulation of the drain currents and obvious peak shifts in the differential conductance curves. Our device configuration thus provides a promising means of integrating molecular functions into future CMOS applications.

  20. 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

  1. Adaptive Splitting Integrators for Enhancing Sampling Efficiency of Modified Hamiltonian Monte Carlo Methods in Molecular Simulation.

    PubMed

    Akhmatskaya, Elena; Fernández-Pendás, Mario; Radivojević, Tijana; Sanz-Serna, J M

    2017-08-02

    The modified Hamiltonian Monte Carlo (MHMC) methods, i.e., importance sampling methods that use modified Hamiltonians within a Hybrid Monte Carlo (HMC) framework, often outperform in sampling efficiency standard techniques such as molecular dynamics (MD) and HMC. The performance of MHMC may be enhanced further through the rational choice of the simulation parameters and by replacing the standard Verlet integrator with more sophisticated splitting algorithms. Unfortunately, it is not easy to identify the appropriate values of the parameters that appear in those algorithms. We propose a technique, that we call MAIA (Modified Adaptive Integration Approach), which, for a given simulation system and a given time step, automatically selects the optimal integrator within a useful family of two-stage splitting formulas. Extended MAIA (or e-MAIA) is an enhanced version of MAIA, which additionally supplies a value of the method-specific parameter that, for the problem under consideration, keeps the momentum acceptance rate at a user-desired level. The MAIA and e-MAIA algorithms have been implemented, with no computational overhead during simulations, in MultiHMC-GROMACS, a modified version of the popular software package GROMACS. Tests performed on well-known molecular models demonstrate the superiority of the suggested approaches over a range of integrators (both standard and recently developed), as well as their capacity to improve the sampling efficiency of GSHMC, a noticeable method for molecular simulation in the MHMC family. GSHMC combined with e-MAIA shows a remarkably good performance when compared to MD and HMC coupled with the appropriate adaptive integrators.

  2. Integral Equation Theory of Molecular Solvation Coupled with Quantum Mechanical/Molecular Mechanics Method in NWChem Package

    SciTech Connect

    Chuev, Gennady N.; Valiev, Marat; Fedotova, Marina V.

    2012-04-10

    We have developed a hybrid approach based on a combination of integral equation theory of molecular liquids and QM/MM methodology in NorthWest computational Chemistry (NWChem) software package. We have split the evaluations into conse- quent QM/MM and statistical mechanics calculations based on the one-dimensional reference interaction site model, which allows us to reduce signicantly the time of computation. The method complements QM/MM capabilities existing in the NWChem package. The accuracy of the presented method was tested through com- putation of water structure around several organic solutes and their hydration free energies. We have also evaluated the solvent effect on the conformational equilibria. The applicability and limitations of the developed approach are discussed.

  3. 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.

  4. Integrated genomics and molecular breeding approaches for dissecting the complex quantitative traits in crop plants.

    PubMed

    Kujur, Alice; Saxena, Maneesha S; Bajaj, Deepak; Laxmi; Parida, Swarup K

    2013-12-01

    The enormous population growth, climate change and global warming are now considered major threats to agriculture and world's food security. To improve the productivity and sustainability of agriculture, the development of highyielding and durable abiotic and biotic stress-tolerant cultivars and/climate resilient crops is essential. Henceforth, understanding the molecular mechanism and dissection of complex quantitative yield and stress tolerance traits is the prime objective in current agricultural biotechnology research. In recent years, tremendous progress has been made in plant genomics and molecular breeding research pertaining to conventional and next-generation whole genome, transcriptome and epigenome sequencing efforts, generation of huge genomic, transcriptomic and epigenomic resources and development of modern genomics-assisted breeding approaches in diverse crop genotypes with contrasting yield and abiotic stress tolerance traits. Unfortunately, the detailed molecular mechanism and gene regulatory networks controlling such complex quantitative traits is not yet well understood in crop plants. Therefore, we propose an integrated strategies involving available enormous and diverse traditional and modern -omics (structural, functional, comparative and epigenomics) approaches/resources and genomics-assisted breeding methods which agricultural biotechnologist can adopt/utilize to dissect and decode the molecular and gene regulatory networks involved in the complex quantitative yield and stress tolerance traits in crop plants. This would provide clues and much needed inputs for rapid selection of novel functionally relevant molecular tags regulating such complex traits to expedite traditional and modern marker-assisted genetic enhancement studies in target crop species for developing high-yielding stress-tolerant varieties.

  5. Integrating molecular design resources within modern drug discovery research: the Roche experience.

    PubMed

    Stahl, Martin; Guba, Wolfgang; Kansy, Manfred

    2006-04-01

    Various computational disciplines, such as cheminformatics, ADME modeling, virtual screening, chemogenomics search strategies and classic structure-based design, should be seen as one multifaceted discipline contributing to the early drug discovery process. Although significant resources enabling these activities have been established, their true integration into daily research should not be taken for granted. This article reviews value-adding activities from target assessment to lead optimization, and highlights the technical and process-related aspects that can be considered essential for performance and alignment within the research organization.

  6. Molecular signals that shape the integrative responses of the heat-acclimated phenotype.

    PubMed

    Horowitz, Michal; Kodesh, Einat

    2010-12-01

    The introduction of molecular biology to thermoregulation was delayed compared with its application in other research fields pertinent to human health and disease. Using principles from molecular biology, we revisited fundamental problems in integrative and environmental physiology and were able to explore new research horizons. Global genomic responses in tandem with an appropriate physiological experimental model are a good experimental design strategy that can unravel the molecular mechanisms underlying integrative thermoregulatory responses. In this way, dynamic adaptation models, with accentuated or diminished regulatory circuits, triggered by superimposition of novel stressors sharing similar protective pathways, have significant benefits. On the basis of this approach, we will discuss the molecular physiological linkage of heat acclimation alone or combined with exercise training and decipher stress-specific genes in the thermoregulatory circuits in the heart and skeletal muscles. Opposing/competing adaptive features are required for each of the above-mentioned physiological conditions. Aerobic training increases the capacity to store/use ATP. In contrast, the acclimated phenotype attempts to counteract excessive heat production. Nevertheless, both treatments augment muscle force generation. These changes are tissue-specific; in the exercise-trained rat heart, there is up-regulation of Ca2+-induced Ca2+ release mechanism genes, whereas in the skeletal muscle (soleus), the enrichment is found in genes involved in metabolism. The final issue discussed in this review is the possibility that heat shock proteins serve as consensus markers of heat stress. The role of the autonomic nervous system in their induction during heat stress and how they affect integrative body systems are described.

  7. 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.

  8. An integrated microfluidic platform for rapid tumor cell isolation, counting and molecular diagnosis.

    PubMed

    Hung, Lien-Yu; Chuang, Ying-Hsin; Kuo, Hsin-Tzu; Wang, Chih-Hung; Hsu, Keng-Fu; Chou, Cheng-Yang; Lee, Gwo-Bin

    2013-04-01

    Ovarian cancer is the second most common of the gynecological cancers in Taiwan. It is challenging to diagnose at an early stage when proper treatment is the most effective. It is well recognized that the detection of tumor cells (TCs) is critical for determining cancer growth stages and may provide important information for accurate diagnosis and even prognosis. In this study, a new microfluidic platform integrated with a moving-wall micro-incubator, a micro flow cytometer and a molecular diagnosis module performed automated identification of ovarian cancer cells. By efficiently mixing the cells and immunomagnetic beads coated with specific antibodies, the target TCs were successfully isolated from the clinical samples. Then counting of the target cells was achieved by a combination of the micro flow cytometer and an optical detection module and showed a counting accuracy as high as 92.5 %. Finally, cancer-associated genes were amplified and detected by the downstream molecular diagnosis module. The fluorescence intensity of specific genes (CD24 and HE4) associated with ovarian cancer was amplified by the molecular diagnosis module and the results were comparable to traditional slab-gel electrophoresis analysis, with a limit of detection around 10 TCs. This integrated microfluidic platform realized the concept of a "lab-on-a-chip" and had advantages which included automation, disposability, lower cost and rapid diagnosis and, therefore, may provide a promising approach for the fast and accurate detection of cancer cells.

  9. Error and timing analysis of multiple time-step integration methods for molecular dynamics

    NASA Astrophysics Data System (ADS)

    Han, Guowen; Deng, Yuefan; Glimm, James; Martyna, Glenn

    2007-02-01

    Molecular dynamics simulations of biomolecules performed using multiple time-step integration methods are hampered by resonance instabilities. We analyze the properties of a simple 1D linear system integrated with the symplectic reference system propagator MTS (r-RESPA) technique following earlier work by others. A closed form expression for the time step dependent Hamiltonian which corresponds to r-RESPA integration of the model is derived. This permits us to present an analytic formula for the dependence of the integration accuracy on short-range force cutoff range. A detailed analysis of the force decomposition for the standard Ewald summation method is then given as the Ewald method is a good candidate to achieve high scaling on modern massively parallel machines. We test the new analysis on a realistic system, a protein in water. Under Langevin dynamics with a weak friction coefficient ( ζ=1 ps) to maintain temperature control and using the SHAKE algorithm to freeze out high frequency vibrations, we show that the 5 fs resonance barrier present when all degrees of freedom are unconstrained is postponed to ≈12 fs. An iso-error boundary with respect to the short-range cutoff range and multiple time step size agrees well with the analytical results which are valid due to dominance of the high frequency modes in determining integrator accuracy. Using r-RESPA to treat the long range interactions results in a 6× increase in efficiency for the decomposition described in the text.

  10. 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.

  11. NCI Thesaurus: a semantic model integrating cancer-related clinical and molecular information.

    PubMed

    Sioutos, Nicholas; de Coronado, Sherri; Haber, Margaret W; Hartel, Frank W; Shaiu, Wen-Ling; Wright, Lawrence W

    2007-02-01

    Over the last 8 years, the National Cancer Institute (NCI) has launched a major effort to integrate molecular and clinical cancer-related information within a unified biomedical informatics framework, with controlled terminology as its foundational layer. The NCI Thesaurus is the reference terminology underpinning these efforts. It is designed to meet the growing need for accurate, comprehensive, and shared terminology, covering topics including: cancers, findings, drugs, therapies, anatomy, genes, pathways, cellular and subcellular processes, proteins, and experimental organisms. The NCI Thesaurus provides a partial model of how these things relate to each other, responding to actual user needs and implemented in a deductive logic framework that can help maintain the integrity and extend the informational power of what is provided. This paper presents the semantic model for cancer diseases and its uses in integrating clinical and molecular knowledge, more briefly examines the models and uses for drug, biochemical pathway, and mouse terminology, and discusses limits of the current approach and directions for future work.

  12. Optimized acoustic biochip integrated with microfluidics for biomarkers detection in molecular diagnostics.

    PubMed

    Papadakis, G; Friedt, J M; Eck, M; Rabus, D; Jobst, G; Gizeli, E

    2017-09-01

    The development of integrated platforms incorporating an acoustic device as the detection element requires addressing simultaneously several challenges of technological and scientific nature. The present work was focused on the design of a microfluidic module, which, combined with a dual or array type Love wave acoustic chip could be applied to biomedical applications and molecular diagnostics. Based on a systematic study we optimized the mechanics of the flow cell attachment and the sealing material so that fluidic interfacing/encapsulation would impose minimal losses to the acoustic wave. We have also investigated combinations of operating frequencies with waveguide materials and thicknesses for maximum sensitivity during the detection of protein and DNA biomarkers. Within our investigations neutravidin was used as a model protein biomarker and unpurified PCR amplified Salmonella DNA as the model genetic target. Our results clearly indicate the need for experimental verification of the optimum engineering and analytical parameters, in order to develop commercially viable systems for integrated analysis. The good reproducibility of the signal together with the ability of the array biochip to detect multiple samples hold promise for the future use of the integrated system in a Lab-on-a-Chip platform for application to molecular diagnostics.

  13. An integro-differential transform to analytically reduce H2 molecular integrals

    NASA Astrophysics Data System (ADS)

    Straton, Jack

    2012-06-01

    Molecular integrals that have a coordinate dependence akin to the bonding H2 wave function are often carried out one-by-one, using hyper-spherical coordinates [1], Jacobi coordinates or bond-length coordinates [2], or confocal ellipsoidal coordinates [3]. An alternative strategy is to extend the general result developed by the author [4] for evaluating integrals of any number of products of multicenter ground-state or excited [5] atomic wave functions, Coulomb or Yukawa potentials, and Coulomb-waves [6] to include the H2 molecular wave function. Modifications for semi-infinite integrals that terminate on a surface such as a Scanning Tunneling Microscope sample are also discussed. [4pt] [1] Y. Zhou, C. D. Lin and J. Shertzer, J. Phys. B: At. Mol. Opt. Phys. 26, 3937-3949 (1993).[0pt] [2] J. M. Hutson and P. Soldan, International Reviews in Physical Chemistry, 26(1) 1 - 28 (January 2007).[0pt] [3] J. P. Grivet, J. Chem. Educ., 79(1), 127 (2002).[0pt] [4] Jack C. Straton, Phys. Rev. A 39, 1676-84 (1989); Erratum Phys. Rev. A 40, 2819 (1989).[0pt] [5] Jack C. Straton, Phys. Rev. A 41, 71-7 (1990).[0pt] [6] Jack C. Straton, Phys. Rev. A 42, 307-10 (1990).

  14. Integrated molecular analysis reveals complex interactions between genomic and epigenomic alterations in esophageal adenocarcinomas

    PubMed Central

    Peng, DunFa; Guo, Yan; Chen, Heidi; Zhao, Shilin; Washington, Kay; Hu, TianLing; Shyr, Yu; El-Rifai, Wael

    2017-01-01

    The incidence of esophageal adenocarcinoma (EAC) is rapidly rising in the United States and Western countries. In this study, we carried out an integrative molecular analysis to identify interactions between genomic and epigenomic alterations in regulating gene expression networks in EAC. We detected significant alterations in DNA copy numbers (CN), gene expression levels, and DNA methylation profiles. The integrative analysis demonstrated that altered expression of 1,755 genes was associated with changes in CN or methylation. We found that expression alterations in 84 genes were associated with changes in both CN and methylation. These data suggest a strong interaction between genetic and epigenetic events to modulate gene expression in EAC. Of note, bioinformatics analysis detected a prominent K-RAS signature and predicted activation of several important transcription factor networks, including β-catenin, MYB, TWIST1, SOX7, GATA3 and GATA6. Notably, we detected hypomethylation and overexpression of several pro-inflammatory genes such as COX2, IL8 and IL23R, suggesting an important role of epigenetic regulation of these genes in the inflammatory cascade associated with EAC. In summary, this integrative analysis demonstrates a complex interaction between genetic and epigenetic mechanisms providing several novel insights for our understanding of molecular events in EAC. PMID:28102292

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

    PubMed

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

    2013-10-01

    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. 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. 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 parameters and their standard

  17. 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.

  18. 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.

    PubMed

    Ji, Cuiying; Zhang, Xuewei; Yu, Peiqiang

    2016-03-05

    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.

  19. Integration of Chinese medicine with Western medicine could lead to future medicine: molecular module medicine.

    PubMed

    Zhang, Chi; Zhang, Ge; Chen, Ke-ji; Lu, Ai-ping

    2016-04-01

    The development of an effective classification method for human health conditions is essential for precise diagnosis and delivery of tailored therapy to individuals. Contemporary classification of disease systems has properties that limit its information content and usability. Chinese medicine pattern classification has been incorporated with disease classification, and this integrated classification method became more precise because of the increased understanding of the molecular mechanisms. However, we are still facing the complexity of diseases and patterns in the classification of health conditions. With continuing advances in omics methodologies and instrumentation, we are proposing a new classification approach: molecular module classification, which is applying molecular modules to classifying human health status. The initiative would be precisely defining the health status, providing accurate diagnoses, optimizing the therapeutics and improving new drug discovery strategy. Therefore, there would be no current disease diagnosis, no disease pattern classification, and in the future, a new medicine based on this classification, molecular module medicine, could redefine health statuses and reshape the clinical practice.

  20. Logic integration of mRNA signals by an RNAi-based molecular computer.

    PubMed

    Xie, Zhen; Liu, Siyuan John; Bleris, Leonidas; Benenson, Yaakov

    2010-05-01

    Synthetic in vivo molecular 'computers' could rewire biological processes by establishing programmable, non-native pathways between molecular signals and biological responses. Multiple molecular computer prototypes have been shown to work in simple buffered solutions. Many of those prototypes were made of DNA strands and performed computations using cycles of annealing-digestion or strand displacement. We have previously introduced RNA interference (RNAi)-based computing as a way of implementing complex molecular logic in vivo. Because it also relies on nucleic acids for its operation, RNAi computing could benefit from the tools developed for DNA systems. However, these tools must be harnessed to produce bioactive components and be adapted for harsh operating environments that reflect in vivo conditions. In a step toward this goal, we report the construction and implementation of biosensors that 'transduce' mRNA levels into bioactive, small interfering RNA molecules via RNA strand exchange in a cell-free Drosophila embryo lysate, a step beyond simple buffered environments. We further integrate the sensors with our RNAi 'computational' module to evaluate two-input logic functions on mRNA concentrations. Our results show how RNA strand exchange can expand the utility of RNAi computing and point toward the possibility of using strand exchange in a native biological setting.

  1. Integrated residency training pathways of the future: diagnostic radiology, nuclear radiology, nuclear medicine, and molecular imaging.

    PubMed

    Oates, M Elizabeth

    2012-04-01

    Following up on the recommendations of the ACR/SNM Task Force on Nuclear Medicine Training, the respective leaderships convened Task Force II. Its charge is to develop realistic residency training pathways integrating diagnostic radiology, nuclear radiology, nuclear medicine, and molecular imaging. The diagnostic radiology participants offer these "pathways of the future" that are built on a foundation of training in diagnostic radiology. It is hoped that these pathways will ensure that the traditional and emerging clinical, educational, and research domains of nuclear radiology, nuclear medicine, and molecular imaging will be sustained and will indeed flourish in the decades to come. Copyright © 2012 American College of Radiology. Published by Elsevier Inc. All rights reserved.

  2. Future Directions in Pain Management: Integrating Anatomically Selective Delivery Techniques With Novel Molecularly Selective Agents.

    PubMed

    Pleticha, Josef; Maus, Timothy P; Beutler, Andreas S

    2016-04-01

    Treatment for chronic, locoregional pain ranks among the most prevalent unmet medical needs. The failure of systemic analgesic drugs, such as opioids, is often due to their off-target toxicity, development of tolerance, and abuse potential. Interventional pain procedures provide target specificity but lack pharmacologically selective agents with long-term efficacy. Gene therapy vectors are a new tool for the development of molecularly selective pain therapies, which have already been proved to provide durable analgesia in preclinical models. Taken together, advances in image-guided delivery and gene therapy may lead to a new class of dual selective analgesic treatments integrating the molecular selectivity of analgesic genes with the anatomic selectivity of interventional delivery techniques.

  3. Low-temperature metallic liquid hydrogen: an ab-initio path-integral molecular dynamics perspective

    NASA Astrophysics Data System (ADS)

    Chen, Ji; Li, Xin-Zheng; Zhang, Qianfan; Probert, Matthew; Pickard, Chris; Needs, Richard; Michaelides, Angelos; Wang, Enge

    2013-03-01

    Experiments and computer simulations have shown that the melting temperature of solid hydrogen drops with pressure above about 65 GPa, suggesting that a low temperature liquid state might exist. It has also been suggested that this liquid state might be non-molecular and metallic, although evidence for such behaviour is lacking. Using a combination of ab initio path-integral molecular dynamics and the two-phase methods, we have simulated the melting of solid hydrogen under finite temperatures. We found an atomic solid phase from 500 to 800 GPa which melts at < 200 K. Beyond this and up to pressures of 1,200 GPa a metallic atomic liquid is stable at temperatures as low as 50 K. The quantum motion of the protons is critical to the low melting temperature in this system as ab initio simulations with classical nuclei lead to a considerably higher melting temperature of ~300 K across the entire pressure range considered.

  4. Molecular pathological epidemiology of epigenetics: emerging integrative science to analyze environment, host, and disease.

    PubMed

    Ogino, Shuji; Lochhead, Paul; Chan, Andrew T; Nishihara, Reiko; Cho, Eunyoung; Wolpin, Brian M; Meyerhardt, Jeffrey A; Meissner, Alexander; Schernhammer, Eva S; Fuchs, Charles S; Giovannucci, Edward

    2013-04-01

    Epigenetics acts as an interface between environmental/exogenous factors, cellular responses, and pathological processes. Aberrant epigenetic signatures are a hallmark of complex multifactorial diseases (including neoplasms and malignancies such as leukemias, lymphomas, sarcomas, and breast, lung, prostate, liver, and colorectal cancers). Epigenetic signatures (DNA methylation, mRNA and microRNA expression, etc) may serve as biomarkers for risk stratification, early detection, and disease classification, as well as targets for therapy and chemoprevention. In particular, DNA methylation assays are widely applied to formalin-fixed, paraffin-embedded archival tissue specimens as clinical pathology tests. To better understand the interplay between etiological factors, cellular molecular characteristics, and disease evolution, the field of 'molecular pathological epidemiology (MPE)' has emerged as an interdisciplinary integration of 'molecular pathology' and 'epidemiology'. In contrast to traditional epidemiological research including genome-wide association studies (GWAS), MPE is founded on the unique disease principle, that is, each disease process results from unique profiles of exposomes, epigenomes, transcriptomes, proteomes, metabolomes, microbiomes, and interactomes in relation to the macroenvironment and tissue microenvironment. MPE may represent a logical evolution of GWAS, termed 'GWAS-MPE approach'. Although epigenome-wide association study attracts increasing attention, currently, it has a fundamental problem in that each cell within one individual has a unique, time-varying epigenome. Having a similar conceptual framework to systems biology, the holistic MPE approach enables us to link potential etiological factors to specific molecular pathology, and gain novel pathogenic insights on causality. The widespread application of epigenome (eg, methylome) analyses will enhance our understanding of disease heterogeneity, epigenotypes (CpG island methylator

  5. 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.

  6. Formation of bound states in expanded metal studied via path integral molecular dynamics

    NASA Astrophysics Data System (ADS)

    Deymier, P. A.; Oh, Ki-Dong

    2004-03-01

    The usefulness of the restricted path integral molecular dynamics method for the study of strongly correlated electrons is demonstrated by studying the formation of bound electronic states in a half-filled expanded three-dimensional hydrogenoid body-centred cubic lattice at finite temperature. Starting from a metallic state with one-component plasma character, we find that bound electrons form upon expansion of the lattice. The bound electrons are spatially localized with their centre for the motion of gyration located at ionic positions. The number of bound electrons increases monotonically with decreasing density.

  7. Many-body quantum dynamics by adiabatic path-integral molecular dynamics: Disordered Frenkel Kontorova models

    NASA Astrophysics Data System (ADS)

    Krajewski, Florian R.; Müser, Martin H.

    2005-07-01

    The spectral density of quantum mechanical Frenkel Kontorova chains moving in disordered, external potentials is investigated by means of path-integral molecular dynamics. If the second moment of the embedding potential is well defined (roughness exponent H=0), there is one regime in which the chain is pinned (large masses m of chain particles) and one in which it is unpinned (small m). If the embedding potential can be classified as a random walk on large length scales ( H=1/2), then the chain is always pinned irrespective of the value of m. For H=1/2, two phonon-like branches appear in the spectra.

  8. Path-integral molecular dynamics simulations for water anion clusters (HO)5- and (DO)5-

    NASA Astrophysics Data System (ADS)

    Takayanagi, Toshiyuki; Yoshikawa, Takehiro; Motegi, Haruki; Shiga, Motoyuki

    2009-11-01

    Quantum path-integral molecular dynamics simulations have been performed for the (HO)5- and (DO)5- anion clusters on the basis of a semiempirical one-electron pseudopotential-polarization model. Due to larger zero-point vibrational amplitudes for H atoms than that of D atoms, hydrogen-bond lengths in the (HO)5- cluster are slightly larger than those in (DO)5-. The distribution of the vertical detachment energies for (HO)5- also show a broader feature than that for (DO)5-. The present PIMD simulations thus demonstrate the importance of nuclear quantum effects in water anion clusters.

  9. Restricted Path-Integral Molecular Dynamics for Simulating the Correlated Electron Plasma in Warm Dense Matter

    NASA Astrophysics Data System (ADS)

    Kapila, Vivek; Deymier, Pierre; Runge, Keith

    2011-10-01

    Several areas of study including heavy ion beam, large scale laser, and high pressure or Thomson scattering studies necessitate a fundamental understanding of warm dense matter (WDM) i.e. matter at high temperature and high density. The WDM regime, however, lacks any adequate highly developed class of simulation methods. Recent progress to address this deficit has been the development of orbital-free Density Functional Theory (ofDFT). However, scant benchmark information is available on temperature and pressure dependence of simple but realistic models in WDM regime. The present work aims to fill this critical gap using the restricted path-integral molecular dynamics (rPIMD) method. Within the discrete path integral representation, electrons are described as harmonic necklaces. Quantum exchange takes the form of cross linking between electron necklaces. The fermion sign problem is addressed by restricting the density matrix to positive values. The molecular dynamics algorithm is employed to sample phase space. Here, we focus on the behavior of strongly correlated electron plasmas under WDM conditions. We compute the kinetic and potential energies and compare them to those obtained with the ofDFT method. Several areas of study including heavy ion beam, large scale laser, and high pressure or Thomson scattering studies necessitate a fundamental understanding of warm dense matter (WDM) i.e. matter at high temperature and high density. The WDM regime, however, lacks any adequate highly developed class of simulation methods. Recent progress to address this deficit has been the development of orbital-free Density Functional Theory (ofDFT). However, scant benchmark information is available on temperature and pressure dependence of simple but realistic models in WDM regime. The present work aims to fill this critical gap using the restricted path-integral molecular dynamics (rPIMD) method. Within the discrete path integral representation, electrons are described as

  10. Path Integral Molecular Dynamics for Hydrogen with Orbital-Free Density Functional Theory

    NASA Astrophysics Data System (ADS)

    Runge, Keith; Karasiev, Valentin; Deymier, Pierre

    2014-03-01

    The computational bottleneck for performing path-integral molecular dynamics (PIMD) for nuclei on a first principles electronic potential energy surface has been the speed with which forces from the electrons can be generated. Recent advances in orbital-free density functional theory (OF-DFT) not only allow for faster generation of first principles forces but also include the effects of temperature on the electron density. We will present results of calculations on hydrogen in warm dense matter conditions where the protons are described by PIMD and the electrons by OF-DFT. Work supported by U.S. Dept. of Energy, grant DE-SC0002139.

  11. Outbreak Control and Clinical, Pathological, and Epidemiological Aspects and Molecular Characterization of a Bovine Herpesvirus Type 5 on a Feedlot Farm in São Paulo State

    PubMed Central

    Ferreira Vicente, Acácia; Appolinario, Camila Michele; Allendorf, Susan Dora; Gasparini Baraldi, Thaís; Cortez, Adriana; Bryan Heinemann, Marcos; Reinaldo Silva Fonseca, Clovis; Cristina Pelícia, Vanessa; Devidé Ribeiro, Bruna Leticia; Hiromi Okuda, Liria; Pituco, Edviges Maristela

    2015-01-01

    This paper describes the control, epidemiological, pathological, and molecular aspects of an outbreak of meningoencephalitis in calves due to bovine herpesvirus 5 at a feedlot with 540 animals in São Paulo State, Brazil. The introduction of new animals and contact between the resident animals and the introduced ones were most likely responsible for virus transmission. Bovine herpesvirus 1 vaccine was used, resulting in the efficacy of the outbreak control, although two bovine herpesvirus 1 positive animals, vaccinated and revaccinated, presented meningoencephalitis, thereby characterizing vaccinal failure. PMID:26090469

  12. Advances on the interaction between tea catechins and plasma proteins: structure-affinity relationship, influence on antioxidant activity, and molecular docking aspects.

    PubMed

    Cao, Hui; Shi, Yujun; Chen, Xiaoqing

    2013-05-01

    Tea materials are widely consumed beverages in the world and are a rich source of dietary polyphenols. Catechins found in tea show excellent antioxidant potential, which is beneficial for many diseases such as cancers and cardiovascular diseases. These Tea catechins can interact with plasma proteins to form soluble or insoluble complexes, which are responsible for their bioactivities in vivo. However, there is little review published recently which focused on tea catechins-plasma protein interaction (TcPI), despite numerous articles have appeared in this field. This review summarizes the recent trend in TcPI studies focusing on metabolism, structure-affinity relationship, influence on antioxidant activity, and molecular docking aspects.

  13. Outbreak Control and Clinical, Pathological, and Epidemiological Aspects and Molecular Characterization of a Bovine Herpesvirus Type 5 on a Feedlot Farm in São Paulo State.

    PubMed

    Megid, Jane; Ferreira Vicente, Acácia; Appolinario, Camila Michele; Allendorf, Susan Dora; de Souza Ribeiro Mioni, Mateus; Gasparini Baraldi, Thaís; Cortez, Adriana; Bryan Heinemann, Marcos; Reinaldo Silva Fonseca, Clovis; Cristina Pelícia, Vanessa; Devidé Ribeiro, Bruna Leticia; Hiromi Okuda, Liria; Pituco, Edviges Maristela

    2015-01-01

    This paper describes the control, epidemiological, pathological, and molecular aspects of an outbreak of meningoencephalitis in calves due to bovine herpesvirus 5 at a feedlot with 540 animals in São Paulo State, Brazil. The introduction of new animals and contact between the resident animals and the introduced ones were most likely responsible for virus transmission. Bovine herpesvirus 1 vaccine was used, resulting in the efficacy of the outbreak control, although two bovine herpesvirus 1 positive animals, vaccinated and revaccinated, presented meningoencephalitis, thereby characterizing vaccinal failure.

  14. Echinococcus oligarthrus in the subtropical region of Argentina: First integration of morphological and molecular analyses determines two distinct populations.

    PubMed

    Arrabal, Juan Pablo; Avila, Hector Gabriel; Rivero, Maria Romina; Camicia, Federico; Salas, Martin Miguel; Costa, Sebastián A; Nocera, Carlos G; Rosenzvit, Mara C; Kamenetzky, Laura

    2017-06-15

    Echinococcosis is a parasitic zoonosis that is considered as a neglected disease by the World Health Organization. The species Echinococcus oligarthrus is one of the causative agents of Neotropical echinococcosis, which is a poorly understood disease that requires a complex medical examination, may threaten human life, and is frequently associated with a low socioeconomic status. Morphological and genetic diversity in E. oligarthrus remains unknown. The aim of this work is to identify and characterize E. oligarthrus infections in sylvatic animals from the Upper Paraná Atlantic Forest in the province of Misiones, Argentina, by following an integrative approach that links morphological, genetic and ecological aspects. This study demonstrates, for the first time, one of the complete life cycles of E. oligarthrus in an important ecoregion. The Upper Paraná Atlantic Forest constitutes the largest remnant continuous forest of the Atlantic Forest, representing 7% of the world's biodiversity. This is the first molecular determination of E. oligarthrus in Argentina. In addition, the agouti (Dasyprocta azarae), the ocelot (Leopardus pardalis) and the puma (Puma concolor) were identified as sylvatic hosts of Neotropical echinococcosis caused by E. oligarthrus. Mitochondrial and nuclear molecular marker analyses showed a high genetic diversity in E. oligarthrus. Moreover, the genetic distance found among E. oligarthrus isolates is higher than the one observed among Echinococcus granulosus genotypes, which clearly indicates that there are at least two different E. oligarthrus populations in Argentina. This study provides valuable information to understand the underlying conditions that favour the maintenance of E. oligarthrus in sylvatic cycles and to evaluate its zoonotic significance for devising preventive measures for human and animal wellbeing. Copyright © 2017 Elsevier B.V. All rights reserved.

  15. Proton momentum distribution in water: an open path integral molecular dynamics study.

    PubMed

    Morrone, Joseph A; Srinivasan, Varadharajan; Sebastiani, Daniel; Car, Roberto

    2007-06-21

    Recent neutron Compton scattering experiments have detected the proton momentum distribution in water. The theoretical calculation of this property can be carried out via "open" path integral expressions. In this work, present an extension of the staging path integral molecular dynamics method, which is then employed to calculate the proton momentum distributions of water in the solid, liquid, and supercritical phases. We utilize a flexible, single point charge empirical force field to model the system's interactions. The calculated momentum distributions depict both agreement and discrepancies with experiment. The differences may be explained by the deviation of the force field from the true interactions. These distributions provide an abundance of information about the environment and interactions surrounding the proton.

  16. 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

  17. 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

  18. Efficient molecular dynamics using geodesic integration and solvent-solute splitting.

    PubMed

    Leimkuhler, Benedict; Matthews, Charles

    2016-05-01

    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.

  19. Integrating open-source software applications to build molecular dynamics systems.

    PubMed

    Allen, Bruce M; Predecki, Paul K; Kumosa, Maciej

    2014-04-05

    Three open-source applications, NanoEngineer-1, packmol, and mis2lmp are integrated using an open-source file format to quickly create molecular dynamics (MD) cells for simulation. The three software applications collectively make up the open-source software (OSS) suite known as MD Studio (MDS). The software is validated through software engineering practices and is verified through simulation of the diglycidyl ether of bisphenol-a and isophorone diamine (DGEBA/IPD) system. Multiple simulations are run using the MDS software to create MD cells, and the data generated are used to calculate density, bulk modulus, and glass transition temperature of the DGEBA/IPD system. Simulation results compare well with published experimental and numerical results. The MDS software prototype confirms that OSS applications can be analyzed against real-world research requirements and integrated to create a new capability. Copyright © 2014 Wiley Periodicals, Inc.

  20. Proton momentum distributions in water: A path integral molecular dynamics study

    NASA Astrophysics Data System (ADS)

    Srinivasan, Varadharajan; Morrone, Joseph A.; Sebastiani, Daniel; Car, Roberto

    2007-03-01

    Recent neutron Compton scattering experiments have detected the proton momentum distributions of water. This density in momentum space is a quantum mechanical property of the proton, due to the confining anharmonic potential from covalent and hydrogen bonds. The theoretical calculation of this property can be carried out via ``open'' path integral expressions. In this work, we present an extension of the staging path integral molecular dynamics method, which is then employed to calculate the proton momentum distributions of water in the solid, liquid, and supercritical phases. We utilize the SPC/F2 empirical force field to model the system's interactions. The calculated momentum distributions depict both agreement and discrepancies with experiment. The differences may be explained by the deviation of the force field from the true interactions. These distributions provide an abundance of information about the environment and interactions surrounding the proton.

  1. Proton momentum distribution in water: an open path integral molecular dynamics study

    NASA Astrophysics Data System (ADS)

    Morrone, Joseph A.; Srinivasan, Varadharajan; Sebastiani, Daniel; Car, Roberto

    2007-06-01

    Recent neutron Compton scattering experiments have detected the proton momentum distribution in water. The theoretical calculation of this property can be carried out via "open" path integral expressions. In this work, present an extension of the staging path integral molecular dynamics method, which is then employed to calculate the proton momentum distributions of water in the solid, liquid, and supercritical phases. We utilize a flexible, single point charge empirical force field to model the system's interactions. The calculated momentum distributions depict both agreement and discrepancies with experiment. The differences may be explained by the deviation of the force field from the true interactions. These distributions provide an abundance of information about the environment and interactions surrounding the proton.

  2. Ab Initio Path Integral Molecular Dynamics Simulation of Hydrogen in Silicon

    NASA Astrophysics Data System (ADS)

    Probert, M. I. J.; Glover, M. J.

    2006-05-01

    We report results of a first-principles theoretical study of an isolated neutral hydrogen atom in crystalline silicon. Spin-polarised density functional theory is used to treat the electrons, and the path-integral molecular dynamics method is used to describe the quantum properties of the nucleus at finite temperature. This is necessary as the hydrogen atom has sufficiently low mass that it exhibits significant nuclear quantum delocalisation and zero-point motion even at room temperature. Unlike post-hoc treatments, such as calculating a static potential energy surface, the path-integral treatment enables such effects to be included "on-the-fly". This is found to be significant, as a coupling is found between the structure of the host silicon lattice and the quantum delocalisation of the hydrogen defect.

  3. Molecular, Cellular and Pharmaceutical Aspects of bone grafting materials and membranes during maxillary sinus-lift procedures. Part 2: detailed characteristics of the materials.

    PubMed

    Iezzi, Giovanna; Piatelli, Adriano; Giuliani, Alessandra; Mangano, Carlo; Barone, Antonio; Manzon, Licia; Degidi, Marco; Scarano, Antonio; Filippone, Antonella; Perrotti, Vittoria

    2016-12-01

    Various grafts or combination of bone substitute materials have been used in sinus lift procedures. Currently, ongoing developments in several disciplines, from molecular biology and chemistry to computer science and engineering, have contributed to the understanding of biological processes leading to bone healing after the use of bone substitute materials (BSBs) and therefore of the behavior of BSBs. The understanding of the properties of each graft enables individual treatment concepts and therefore allows shift from a simple replacement material to the modern concept of an individually created composite biomaterial. Indeed, the choice of the best BSB still remains crucial for success in maxillary sinus augmentation procedures. The present article provides an overview of most of the materials currently available for sinus lift, with a specific focus on their histological, molecular, cellular and pharmaceutical aspects.

  4. Legal Aspects in Quebec of Integration of Students with Handicaps, Social Maladjustments or Learning Disabilities: A Changing Situation.

    ERIC Educational Resources Information Center

    Dore, Robert; Wagner, Serge; Dore, Isabelle

    2001-01-01

    This article examines the current situation and evolution of school integration policies in Quebec and the influence of court decisions on these policies. Variations across Canada are discussed, particularly the differences between English-language school boards, who integrate many more students with intellectual disability, and French-speaking…

  5. Preparation, Purification, and Secondary Structure Determination of Bacillus Circulans Xylanase. A Molecular Laboratory Incorporating Aspects of Molecular Biology, Biochemistry, and Biophysical Chemistry

    ERIC Educational Resources Information Center

    Russo, Sal; Gentile, Lisa

    2006-01-01

    A project module designed for biochemistry or cellular and molecular biology student which involves determining the secondary structure of Bacillus circulans xylanase (BCX) by circular dichroism (CD) spectroscopy under conditions that compromise its stabilizing intramolecular forces is described. The lab model enhanced students knowledge of the…

  6. Preparation, Purification, and Secondary Structure Determination of Bacillus Circulans Xylanase. A Molecular Laboratory Incorporating Aspects of Molecular Biology, Biochemistry, and Biophysical Chemistry

    ERIC Educational Resources Information Center

    Russo, Sal; Gentile, Lisa

    2006-01-01

    A project module designed for biochemistry or cellular and molecular biology student which involves determining the secondary structure of Bacillus circulans xylanase (BCX) by circular dichroism (CD) spectroscopy under conditions that compromise its stabilizing intramolecular forces is described. The lab model enhanced students knowledge of the…

  7. Lambda Red recombinase-mediated integration of the high molecular weight DNA into the Escherichia coli chromosome.

    PubMed

    Juhas, Mario; Ajioka, James W

    2016-10-05

    Escherichia coli K-12 is a frequently used host for a number of synthetic biology and biotechnology applications and chassis for the development of the minimal cell factories. Novel approaches for integrating high molecular weight DNA into the E. coli chromosome would therefore greatly facilitate engineering efforts in this bacterium. We developed a reliable and flexible lambda Red recombinase-based system, which utilizes overlapping DNA fragments for integration of the high molecular weight DNA into the E. coli chromosome. Our chromosomal integration strategy can be used to integrate high molecular weight DNA of variable length into any non-essential locus in the E. coli chromosome. Using this approach we integrated 15 kb DNA encoding sucrose catabolism and lactose metabolism and transport operons into the fliK locus of the flagellar region 3b in the E. coli K12 MG1655 chromosome. Furthermore, with this system we integrated 50 kb of Bacillus subtilis 168 DNA into two target sites in the E. coli K12 MG1655 chromosome. The chromosomal integrations into the fliK locus occurred with high efficiency, inhibited motility, and did not have a negative effect on the growth of E. coli. In addition to the rational design of synthetic biology devices, our high molecular weight DNA chromosomal integration system will facilitate metabolic and genome-scale engineering of E. coli.

  8. Structural aspects of the solvation shell of lysine and acetylated lysine: A Car-Parrinello and classical molecular dynamics investigation.

    PubMed

    Carnevale, V; Raugei, S

    2009-12-14

    Lysine acetylation is a post-translational modification, which modulates the affinity of protein-protein and/or protein-DNA complexes. Its crucial role as a switch in signaling pathways highlights the relevance of charged chemical groups in determining the interactions between water and biomolecules. A great effort has been recently devoted to assess the reliability of classical molecular dynamics simulations in describing the solvation properties of charged moieties. In the spirit of these investigations, we performed classical and Car-Parrinello molecular dynamics simulations on lysine and acetylated-lysine in aqueous solution. A comparative analysis between the two computational schemes is presented with a focus on the first solvation shell of the charged groups. An accurate structural analysis unveils subtle, yet statistically significant, differences which are discussed in connection to the significant electronic density charge transfer occurring between the solute and the surrounding water molecules.

  9. Structural aspects of the solvation shell of lysine and acetylated lysine: A Car-Parrinello and classical molecular dynamics investigation

    SciTech Connect

    Carnevale, V.; Raugei, S.

    2009-12-14

    Lysine acetylation is a post-translational modification, which modulates the affinity of protein-protein and/or protein-DNA complexes. Its crucial role as a switch in signaling pathways highlights the relevance of charged chemical groups in determining the interactions between water and biomolecules. A great effort has been recently devoted to assess the reliability of classical molecular dynamics simulations in describing the solvation properties of charged moieties. In the spirit of these investigations, we performed classical and Car-Parrinello molecular dynamics simulations on lysine and acetylated-lysine in aqueous solution. A comparative analysis between the two computational schemes is presented with a focus on the first solvation shell of the charged groups. An accurate structural analysis unveils subtle, yet statistically significant, differences which are discussed in connection to the significant electronic density charge transfer occurring between the solute and the surrounding water molecules.

  10. Translational toxicology and rescue strategies of the hERG channel dysfunction: biochemical and molecular mechanistic aspects

    PubMed Central

    Zhang, Kai-ping; Yang, Bao-feng; Li, Bao-xin

    2014-01-01

    The human ether-à-go-go related gene (hERG) potassium channel is an obligatory anti-target for drug development on account of its essential role in cardiac repolarization and its close association with arrhythmia. Diverse drugs have been removed from the market owing to their inhibitory activity on the hERG channel and their contribution to acquired long QT syndrome (LQTS). Moreover, mutations that cause hERG channel dysfunction may induce congenital LQTS. Recently, an increasing number of biochemical and molecular mechanisms underlying hERG-associated LQTS have been reported. In fact, numerous potential biochemical and molecular rescue strategies are hidden within the biogenesis and regulating network. So far, rescue strategies of hERG channel dysfunction and LQTS mainly include activators, blockers, and molecules that interfere with specific links and other mechanisms. The aim of this review is to discuss the rescue strategies based on hERG channel toxicology from the biochemical and molecular perspectives. PMID:25418379

  11. Evaluation of the OPLS-AA force field for the study of structural and energetic aspects of molecular organic crystals.

    PubMed

    Bernardes, Carlos E S; Joseph, Abhinav

    2015-03-26

    Motivated by the need for reliable experimental data for the assessment of theoretical predictions, this work proposes a data set of enthalpies of sublimation determined for specific crystalline structures, for the validation of molecular force fields (FF). The selected data were used to explore the ability of the OPLS-AA parametrization to investigate the properties of solid materials in molecular dynamics simulations. Furthermore, several approaches to improve this parametrization were also considered. These modifications consisted in replacing the original FF atomic point charges (APC), by values calculated using quantum chemical methods, and by the implementation of a polarizable FF. The obtained results indicated that, in general, the best agreement between theoretical and experimental data is found when the OPLS-AA force field is used with the original APC or when these are replaced by ChelpG charges, computed at the MP2/aug-cc-pVDZ level of theory, for isolated molecules in the gaseous phase. If a good description of the energetic relations between the polymorphs of a compound is required then either the use of polarizable FF or the use of charges determined taking into account the vicinity of the molecules in the crystal (combining the ChelpG and MP2/cc-pVDZ methods) is recommended. Finally, it was concluded that density functional theory methods, like B3LYP or B3PW91, are not advisable for the evaluation of APC of organic compounds for molecular dynamic simulations. Instead, the MP2 method should be considered.

  12. SalmoBase: an integrated molecular data resource for Salmonid species.

    PubMed

    Samy, Jeevan Karloss Antony; Mulugeta, Teshome Dagne; Nome, Torfinn; Sandve, Simen Rød; Grammes, Fabian; Kent, Matthew Peter; Lien, Sigbjørn; Våge, Dag Inge

    2017-06-26

    Salmonids are ray-finned fishes which constitute 11 genera and at least 70 species including Atlantic salmon, whitefishes, graylings, rainbow trout, and char. The common ancestor of all Salmonidae experienced a whole genome duplication (WGD) ~80 million years ago, resulting in an autotetraploid genome. Genomic rediplodization is still going on in salmonid species, providing an unique system for studying evolutionary consequences of whole genome duplication. In recent years, high quality genome sequences of Atlantic salmon and Rainbow trout has been established, due to their scientific and commercial values. In this paper we introduce SalmoBase ( http://www.salmobase.org/ ), a tool for making molecular resources for salmonids public available in a framework of visualizations and analytic tools. SalmoBase has been developed as a part of the ELIXIR.NO project. Currently, SalmoBase contains molecular resources for Atlantic salmon and Rainbow trout. Data can be accessed through BLAST, Genome Browser (GBrowse), Genetic Variation Browser (GVBrowse) and Gene Expression Browser (GEBrowse). To the best of our knowledge, SalmoBase is the first database which integrates salmonids data and allow users to study salmonids in an integrated framework. The database and its tools (e.g., comparative genomics tools, synteny browsers) will be expanded as additional public resources describing other Salmonidae genomes become available.

  13. 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

  14. CytoSolve: A Scalable Computational Method for Dynamic Integration of Multiple Molecular Pathway Models.

    PubMed

    Ayyadurai, V A Shiva; Dewey, C Forbes

    2011-03-01

    A grand challenge of computational systems biology is to create a molecular pathway model of the whole cell. Current approaches involve merging smaller molecular pathway models' source codes to create a large monolithic model (computer program) that runs on a single computer. Such a larger model is difficult, if not impossible, to maintain given ongoing updates to the source codes of the smaller models. This paper describes a new system called CytoSolve that dynamically integrates computations of smaller models that can run in parallel across different machines without the need to merge the source codes of the individual models. This approach is demonstrated on the classic Epidermal Growth Factor Receptor (EGFR) model of Kholodenko. The EGFR model is split into four smaller models and each smaller model is distributed on a different machine. Results from four smaller models are dynamically integrated to generate identical results to the monolithic EGFR model running on a single machine. The overhead for parallel and dynamic computation is approximately twice that of a monolithic model running on a single machine. The CytoSolve approach provides a scalable method since smaller models may reside on any computer worldwide, where the source code of each model can be independently maintained and updated.

  15. Transport properties of liquid para-hydrogen: The path integral centroid molecular dynamics approach

    NASA Astrophysics Data System (ADS)

    Yonetani, Yoshiteru; Kinugawa, Kenichi

    2003-11-01

    Several fundamental transport properties of a quantum liquid para-hydrogen (p-H2) at 17 K have been numerically evaluated by means of the quantum dynamics simulation called the path integral centroid molecular dynamics (CMD). For comparison, classical molecular dynamics (MD) simulations have also been performed under the same condition. In accordance with the previous path integral simulations, the calculated static properties of the liquid agree well with the experimental results. For the diffusion coefficient, thermal conductivity, and shear viscosity, the CMD predicts the values closer to the experimental ones though the classical MD results are far from the reality. The agreement of the CMD result with the experimental one is especially good for the shear viscosity with the difference less than 5%. The calculated diffusion coefficient and the thermal conductivity agree with the experimental values at least in the same order. We predict that the ratio of bulk viscosity to shear viscosity for liquid p-H2 is much larger than classical van der Waals simple liquids such as rare gas liquids.

  16. Evaluation and molecular characterization of human adenovirus in drinking water supplies: viral integrity and viability assays.

    PubMed

    Fongaro, Gislaine; Nascimento, Mariana A do; Rigotto, Caroline; Ritterbusch, Giseli; da Silva, Alessandra D' A; Esteves, Paulo A; Barardi, Célia R M

    2013-05-28

    Human adenoviruses (HAdVs) are the second-leading cause of childhood gastroenteritis worldwide. This virus is commonly found in environmental waters and is very resistant to water disinfection and environmental stressors, especially UV light inactivation. Molecular techniques, such as PCR-based methods (Polymerase Chain Reaction), are commonly used to detect and identify viral contamination in water, although PCR alone does not allow the discrimination between infectious and non-infectious viral particles. A combination of cell culture and PCR has allowed detection of infectious viruses that grow slowly or fail to produce cytopathic effects (CPE) in cell culture. This study aimed to assess the integrity and viability of human adenovirus (HAdV) in environmental water and evaluate circulating strains by molecular characterization in three sites of the water supply in Florianópolis, Santa Catarina Island, Brazil: Peri Lagoon water, spring source water, and water from the public water supply system. Water samples were collected, concentrated and HAdV quantified by real-time PCR. Viral integrity was evaluated by enzymatic assay (DNase I) and infectivity by plaque assay (PA) and integrated cell culture using transcribed mRNA (ICC-RT-qPCR). Samples containing particles of infectious HAdV were selected for sequencing and molecular characterization. The analyzed sites contained 83, 66 and 58% undamaged HAdV particles (defined as those in which the genetic material is protected by the viral capsid) at Peri Lagoon, spring source water and public supply system water, respectively. Of these, 66% of the particles (by PA) and 75% (by ICC-RT-qPCR) HAdV were shown to be infectious, due to being undamaged in Peri Lagoon, 33% (by PA) and 58% (by ICC-RT-qPCR) in spring source water and 8% (by PA) and 25% (by ICC-RT-qPCR) in the public water supply system. ICC-RT-qPCR, a very sensitive and rapid technique, was able to detect as low as 1 × 102 HAdV genome copies per milliliter of

  17. Evaluation and molecular characterization of human adenovirus in drinking water supplies: viral integrity and viability assays

    PubMed Central

    2013-01-01

    Background Human adenoviruses (HAdVs) are the second-leading cause of childhood gastroenteritis worldwide. This virus is commonly found in environmental waters and is very resistant to water disinfection and environmental stressors, especially UV light inactivation. Molecular techniques, such as PCR-based methods (Polymerase Chain Reaction), are commonly used to detect and identify viral contamination in water, although PCR alone does not allow the discrimination between infectious and non-infectious viral particles. A combination of cell culture and PCR has allowed detection of infectious viruses that grow slowly or fail to produce cytopathic effects (CPE) in cell culture. This study aimed to assess the integrity and viability of human adenovirus (HAdV) in environmental water and evaluate circulating strains by molecular characterization in three sites of the water supply in Florianópolis, Santa Catarina Island, Brazil: Peri Lagoon water, spring source water, and water from the public water supply system. Methods Water samples were collected, concentrated and HAdV quantified by real-time PCR. Viral integrity was evaluated by enzymatic assay (DNase I) and infectivity by plaque assay (PA) and integrated cell culture using transcribed mRNA (ICC-RT-qPCR). Samples containing particles of infectious HAdV were selected for sequencing and molecular characterization. Results The analyzed sites contained 83, 66 and 58% undamaged HAdV particles (defined as those in which the genetic material is protected by the viral capsid) at Peri Lagoon, spring source water and public supply system water, respectively. Of these, 66% of the particles (by PA) and 75% (by ICC-RT-qPCR) HAdV were shown to be infectious, due to being undamaged in Peri Lagoon, 33% (by PA) and 58% (by ICC-RT-qPCR) in spring source water and 8% (by PA) and 25% (by ICC-RT-qPCR) in the public water supply system. ICC-RT-qPCR, a very sensitive and rapid technique, was able to detect as low as 1 × 102 HAd

  18. inTB - a data integration platform for molecular and clinical epidemiological analysis of tuberculosis

    PubMed Central

    2013-01-01

    Background Tuberculosis is currently the second highest cause of death from infectious diseases worldwide. The emergence of multi and extensive drug resistance is threatening to make tuberculosis incurable. There is growing evidence that the genetic diversity of Mycobacterium tuberculosis may have important clinical consequences. Therefore, combining genetic, clinical and socio-demographic data is critical to understand the epidemiology of this infectious disease, and how virulence and other phenotypic traits evolve over time. This requires dedicated bioinformatics platforms, capable of integrating and enabling analyses of this heterogeneous data. Results We developed inTB, a web-based system for integrated warehousing and analysis of clinical, socio-demographic and molecular data for Mycobacterium sp. isolates. As a database it can organize and display data from any of the standard genotyping methods (SNP, MIRU-VNTR, RFLP and spoligotype), as well as an extensive array of clinical and socio-demographic variables that are used in multiple countries to characterize the disease. Through the inTB interface it is possible to insert and download data, browse the database and search specific parameters. New isolates are automatically classified into strains according to an internal reference, and data uploaded or typed in is checked for internal consistency. As an analysis framework, the system provides simple, point and click analysis tools that allow multiple types of data plotting, as well as simple ways to download data for external analysis. Individual trees for each genotyping method are available, as well as a super tree combining all of them. The integrative nature of inTB grants the user the ability to generate trees for filtered subsets of data crossing molecular and clinical/socio-demografic information. inTB is built on open source software, can be easily installed locally and easily adapted to other diseases. Its design allows for use by research

  19. inTB - a data integration platform for molecular and clinical epidemiological analysis of tuberculosis.

    PubMed

    Soares, Patrícia; Alves, Renato J; Abecasis, Ana B; Penha-Gonçalves, Carlos; Gomes, M Gabriela M; Pereira-Leal, José B

    2013-08-30

    Tuberculosis is currently the second highest cause of death from infectious diseases worldwide. The emergence of multi and extensive drug resistance is threatening to make tuberculosis incurable. There is growing evidence that the genetic diversity of Mycobacterium tuberculosis may have important clinical consequences. Therefore, combining genetic, clinical and socio-demographic data is critical to understand the epidemiology of this infectious disease, and how virulence and other phenotypic traits evolve over time. This requires dedicated bioinformatics platforms, capable of integrating and enabling analyses of this heterogeneous data. We developed inTB, a web-based system for integrated warehousing and analysis of clinical, socio-demographic and molecular data for Mycobacterium sp. isolates. As a database it can organize and display data from any of the standard genotyping methods (SNP, MIRU-VNTR, RFLP and spoligotype), as well as an extensive array of clinical and socio-demographic variables that are used in multiple countries to characterize the disease. Through the inTB interface it is possible to insert and download data, browse the database and search specific parameters. New isolates are automatically classified into strains according to an internal reference, and data uploaded or typed in is checked for internal consistency. As an analysis framework, the system provides simple, point and click analysis tools that allow multiple types of data plotting, as well as simple ways to download data for external analysis. Individual trees for each genotyping method are available, as well as a super tree combining all of them. The integrative nature of inTB grants the user the ability to generate trees for filtered subsets of data crossing molecular and clinical/socio-demografic information. inTB is built on open source software, can be easily installed locally and easily adapted to other diseases. Its design allows for use by research laboratories, hospitals or

  20. SpectraPlot.com: Integrated spectroscopic modeling of atomic and molecular gases

    NASA Astrophysics Data System (ADS)

    Goldenstein, Christopher S.; Miller, Victor A.; Mitchell Spearrin, R.; Strand, Christopher L.

    2017-10-01

    SpectraPlot is a web-based application for simulating spectra of atomic and molecular gases. At the time this manuscript was written, SpectraPlot consisted of four primary tools for calculating: (1) atomic and molecular absorption spectra, (2) atomic and molecular emission spectra, (3) transition linestrengths, and (4) blackbody emission spectra. These tools currently employ the NIST ASD, HITRAN2012, and HITEMP2010 databases to perform line-by-line simulations of spectra. SpectraPlot employs a modular, integrated architecture, enabling multiple simulations across multiple databases and/or thermodynamic conditions to be visualized in an interactive plot window. The primary objective of this paper is to describe the architecture and spectroscopic models employed by SpectraPlot in order to provide its users with the knowledge required to understand the capabilities and limitations of simulations performed using SpectraPlot. Further, this manuscript discusses the accuracy of several underlying approximations used to decrease computational time, in particular, the use of far-wing cutoff criteria.

  1. Molecular Basis of the Mechanical Hierarchy in Myomesin Dimers for Sarcomere Integrity

    PubMed Central

    Xiao, Senbo; Gräter, Frauke

    2014-01-01

    Myomesin is one of the most important structural molecules constructing the M-band in the force-generating unit of striated muscle, and a critical structural maintainer of the sarcomere. Using molecular dynamics simulations, we here dissect the mechanical properties of the structurally known building blocks of myomesin, namely α-helices, immunglobulin (Ig) domains, and the dimer interface at myomesin’s 13th Ig domain, covering the mechanically important C-terminal part of the molecule. We find the interdomain α-helices to be stabilized by the hydrophobic interface formed between the N-terminal half of these helices and adjacent Ig domains, and, interestingly, to show a rapid unfolding and refolding equilibrium especially under low axial forces up to ∼15 pN. These results support and yield atomic details for the notion of recent atomic-force microscopy experiments, namely, that the unique helices inserted between Ig domains in myomesin function as elastomers and force buffers. Our results also explain how the C-terminal dimer of two myomesin molecules is mechanically outperforming the helices and Ig domains in myomesin and elsewhere, explaining former experimental findings. This study provides a fresh view onto how myomesin integrates elastic helices, rigid immunoglobulin domains, and an extraordinarily resistant dimer into a molecular structure, to feature a mechanical hierarchy that represents a firm and yet extensible molecular anchor to guard the stability of the sarcomere. PMID:25140432

  2. All-optical integrated logic operations based on chemical communication between molecular switches.

    PubMed

    Silvi, Serena; Constable, Edwin C; Housecroft, Catherine E; Beves, Jonathon E; Dunphy, Emma L; Tomasulo, Massimiliano; Raymo, Françisco M; Credi, Alberto

    2009-01-01

    Molecular logic gates process physical or chemical "inputs" to generate "outputs" based on a set of logical operators. We report the design and operation of a chemical ensemble in solution that behaves as integrated AND, OR, and XNOR gates with optical input and output signals. The ensemble is composed of a reversible merocyanine-type photoacid and a ruthenium polypyridine complex that functions as a pH-controlled three-state luminescent switch. The light-triggered release of protons from the photoacid is used to control the state of the transition-metal complex. Therefore, the two molecular switching devices communicate with one another through the exchange of ionic signals. By means of such a double (optical-chemical-optical) signal-transduction mechanism, inputs of violet light modulate a luminescence output in the red/far-red region of the visible spectrum. Nondestructive reading is guaranteed because the green light used for excitation in the photoluminescence experiments does not affect the state of the gate. The reset is thermally driven and, thus, does not involve the addition of chemicals and accumulation of byproducts. Owing to its reversibility and stability, this molecular device can afford many cycles of digital operation.

  3. 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

  4. Multiple-Time Step Ab Initio Molecular Dynamics Based on Two-Electron Integral Screening.

    PubMed

    Fatehi, Shervin; Steele, Ryan P

    2015-03-10

    A multiple-timestep ab initio molecular dynamics scheme based on varying the two-electron integral screening method used in Hartree-Fock or density functional theory calculations is presented. Although screening is motivated by numerical considerations, it is also related to separations in the length- and timescales characterizing forces in a molecular system: Loose thresholds are sufficient to describe fast motions over short distances, while tight thresholds may be employed for larger length scales and longer times, leading to a practical acceleration of ab initio molecular dynamics simulations. Standard screening approaches can lead, however, to significant discontinuities in (and inconsistencies between) the energy and gradient when the screening threshold is loose, making them inappropriate for use in dynamics. To remedy this problem, a consistent window-screening method that smooths these discontinuities is devised. Further algorithmic improvements reuse electronic-structure information within the dynamics step and enhance efficiency relative to a naı̈ve multiple-timestepping protocol. The resulting scheme is shown to realize meaningful reductions in the cost of Hartree-Fock and B3LYP simulations of a moderately large system, the protonated sarcosine/glycine dipeptide embedded in a 19-water cluster.

  5. 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

    2016-06-15

    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.

  6. Integration of molecular genetics and proteomics with cell metabolism: how to proceed; how not to proceed!

    PubMed

    Costello, Leslie C; Franklin, Renty B

    2011-10-15

    There now exists a resurgence of interest in the role of intermediary metabolism in medicine; especially in relation to medical disorders. Coupled with this is the contemporary focus on molecular biology, genetics and proteomics and their integration into studies of regulation and alterations in cellular metabolism in health and disease. This is a marriage that has vast potential for elucidation of the factors and conditions that are involved in cellular metabolic and functional changes, which heretofore could not be addressed by the earlier generations of biochemists who established the major pathways of intermediary metabolism. The achievement of this present potential requires the appropriate application and interpretation of genetic and proteomic studies relating to cell metabolism and cell function. This requires knowledge and understanding of the principles, relationships, and methodology, such as biochemistry and enzymology, which are involved in the elucidation of cellular regulatory enzymes and metabolic pathways. Unfortunately, many and possibly most contemporary molecular biologists are not adequately trained and knowledgeable in these areas of cell metabolism. This has resulted in much too common inappropriate application and misinformation from genetic/proteomic studies of cell metabolism and function. This presentation describes important relationships of cellular intermediary metabolism, and provides examples of the appropriate and inappropriate application of genetics and proteomics. It calls for the inclusion of biochemistry, enzymology, cell metabolism and cell physiology in the graduate and postgraduate training of molecular biology and other biomedical researchers.

  7. 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.

  8. Integrating molecular and morphological approaches for characterizing parasite cryptic species: implications for parasitology.

    PubMed

    Nadler, Steven A; DE León, Gerardo Pérez-Ponce

    2011-11-01

    Herein we review theoretical and methodological considerations important for finding and delimiting cryptic species of parasites (species that are difficult to recognize using traditional systematic methods). Applications of molecular data in empirical investigations of cryptic species are discussed from an historical perspective, and we evaluate advantages and disadvantages of approaches that have been used to date. Developments concerning the theory and practice of species delimitation are emphasized because theory is critical to interpretation of data. The advantages and disadvantages of different molecular methodologies, including the number and kind of loci, are discussed relative to tree-based approaches for detecting and delimiting cryptic species. We conclude by discussing some implications that cryptic species have for research programmes in parasitology, emphasizing that careful attention to the theory and operational practices involved in finding, delimiting, and describing new species (including cryptic species) is essential, not only for fully characterizing parasite biodiversity and broader aspects of comparative biology such as systematics, evolution, ecology and biogeography, but to applied research efforts that strive to improve development and understanding of epidemiology, diagnostics, control and potential eradication of parasitic diseases.

  9. Molecular Pathological Epidemiology of Epigenetics: Emerging Integrative Science to Analyze Environment, Host, and Disease

    PubMed Central

    Ogino, Shuji; Lochhead, Paul; Chan, Andrew T.; Nishihara, Reiko; Cho, Eunyoung; Wolpin, Brian M.; Meyerhardt, Jeffrey A.; Meissner, Alexander; Schernhammer, Eva S.; Fuchs, Charles S.; Giovannucci, Edward

    2013-01-01

    Epigenetics acts as an interface between environmental / exogenous factors, cellular responses and pathological processes. Aberrant epigenetic signatures are a hallmark of complex multifactorial diseases, including non-neoplastic disorders (e.g., cardiovascular diseases, hypertension, diabetes mellitus, autoimmune diseases, and some infectious diseases) and neoplasms (e.g., leukemias, lymphomas, sarcomas, and breast, lung, prostate, liver and colorectal cancers). Epigenetic signatures (DNA methylation, mRNA and microRNA expression, etc.) may serve as biomarkers for risk stratification, early detection, and disease classification, as well as targets for therapy and chemoprevention. DNA methylation assays are widely applied to formalin-fixed paraffin-embedded archival tissue specimens as clinical pathology tests. To better understand the interplay between etiologic factors, cellular molecular characteristics, and disease evolution, the field of “Molecular Pathological Epidemiology (MPE)” has emerged as an interdisciplinary integration of “molecular pathology” and “epidemiology”, with a similar conceptual framework to systems biology and network medicine. In contrast to traditional epidemiologic research including genome-wide association studies (GWAS), MPE is founded on the unique disease principle; that is, each disease process results from unique profiles of exposomes, epigenomes, transcriptomes, proteomes, metabolomes, microbiomes, and interactomes in relation to the macro-environment and tissue microenvironment. The widespread application of epigenomics (e.g., methylome) analyses will enhance our understanding of disease heterogeneity, epigenotypes (CpG island methylator phenotype, LINE-1 hypomethylation, etc.), and host-disease interactions. MPE may represent a logical evolution of GWAS, termed “GWAS-MPE approach”. Though epigenome-wide association study attracts increasing attention, currently, it has a fundamental problem in that each cell

  10. VitisNet: “Omics” Integration through Grapevine Molecular Networks

    PubMed Central

    Grimplet, Jérôme; Cramer, Grant R.; Dickerson, Julie A.; Mathiason, Kathy; Van Hemert, John; Fennell, Anne Y.

    2009-01-01

    Background Genomic data release for the grapevine has increased exponentially in the last five years. The Vitis vinifera genome has been sequenced and Vitis EST, transcriptomic, proteomic, and metabolomic tools and data sets continue to be developed. The next critical challenge is to provide biological meaning to this tremendous amount of data by annotating genes and integrating them within their biological context. We have developed and validated a system of Grapevine Molecular Networks (VitisNet). Methodology/Principal Findings The sequences from the Vitis vinifera (cv. Pinot Noir PN40024) genome sequencing project and ESTs from the Vitis genus have been paired and the 39,424 resulting unique sequences have been manually annotated. Among these, 13,145 genes have been assigned to 219 networks. The pathway sets include 88 “Metabolic”, 15 “Genetic Information Processing”, 12 “Environmental Information Processing”, 3 “Cellular Processes”, 21 “Transport”, and 80 “Transcription Factors”. The quantitative data is loaded onto molecular networks, allowing the simultaneous visualization of changes in the transcriptome, proteome, and metabolome for a given experiment. Conclusions/Significance VitisNet uses manually annotated networks in SBML or XML format, enabling the integration of large datasets, streamlining biological functional processing, and improving the understanding of dynamic processes in systems biology experiments. VitisNet is grounded in the Vitis vinifera genome (currently at 8x coverage) and can be readily updated with subsequent updates of the genome or biochemical discoveries. The molecular network files can be dynamically searched by pathway name or individual genes, proteins, or metabolites through the MetNet Pathway database and web-portal at http://metnet3.vrac.iastate.edu/. All VitisNet files including the manual annotation of the grape genome encompassing pathway names, individual genes, their genome identifier, and

  11. Integrative Taxonomy and Molecular Phylogeny of Genus Aplysina (Demospongiae: Verongida) from Mexican Pacific

    PubMed Central

    Cruz-Barraza, José Antonio; Carballo, José Luis; Rocha-Olivares, Axayacatl; Ehrlich, Hermann; Hog, Martin

    2012-01-01

    Integrative taxonomy provides a major approximation to species delimitation based on integration of different perspectives (e.g. morphology, biochemistry and DNA sequences). The aim of this study was to assess the relationships and boundaries among Eastern Pacific Aplysina species using morphological, biochemical and molecular data. For this, a collection of sponges of the genus Aplysina from the Mexican Pacific was studied on the basis of their morphological, chemical (chitin composition), and molecular markers (mitochondrial COI and nuclear ribosomal rDNA: ITS1-5.8-ITS2). Three morphological species were identified, two of which are new to science. A. clathrata sp. nov. is a yellow to yellow-reddish or -brownish sponge, characterized by external clathrate-like morphology; A. revillagigedi sp. nov. is a lemon yellow to green, cushion-shaped sometimes lobate sponge, characterized by conspicuous oscules, which are slightly elevated and usually linearly distributed on rims; and A. gerardogreeni a known species distributed along the Mexican Pacific coast. Chitin was identified as the main structural component within skeletons of the three species using FTIR, confirming that it is shared among Verongida sponges. Morphological differences were confirmed by DNA sequences from nuclear ITS1-5.8-ITS2. Mitochondrial COI sequences showed extremely low but diagnostic variability for Aplysina revillagigedi sp. nov., thus our results corroborate that COI has limited power for DNA-barcoding of sponges and should be complemented with other markers (e.g. rDNA). Phylogenetic analyses of Aplysina sequences from the Eastern Pacific and Caribbean, resolved two allopatric and reciprocally monophyletic groups for each region. Eastern Pacific species were grouped in general accordance with the taxonomic hypothesis based on morphological characters. An identification key of Eastern Pacific Aplysina species is presented. Our results constitute one of the first approximations to integrative

  12. Integrative taxonomy and molecular phylogeny of genus Aplysina (Demospongiae: Verongida) from Mexican Pacific.

    PubMed

    Cruz-Barraza, José Antonio; Carballo, José Luis; Rocha-Olivares, Axayacatl; Ehrlich, Hermann; Hog, Martin

    2012-01-01

    Integrative taxonomy provides a major approximation to species delimitation based on integration of different perspectives (e.g. morphology, biochemistry and DNA sequences). The aim of this study was to assess the relationships and boundaries among Eastern Pacific Aplysina species using morphological, biochemical and molecular data. For this, a collection of sponges of the genus Aplysina from the Mexican Pacific was studied on the basis of their morphological, chemical (chitin composition), and molecular markers (mitochondrial COI and nuclear ribosomal rDNA: ITS1-5.8-ITS2). Three morphological species were identified, two of which are new to science. A. clathrata sp. nov. is a yellow to yellow-reddish or -brownish sponge, characterized by external clathrate-like morphology; A. revillagigedi sp. nov. is a lemon yellow to green, cushion-shaped sometimes lobate sponge, characterized by conspicuous oscules, which are slightly elevated and usually linearly distributed on rims; and A. gerardogreeni a known species distributed along the Mexican Pacific coast. Chitin was identified as the main structural component within skeletons of the three species using FTIR, confirming that it is shared among Verongida sponges. Morphological differences were confirmed by DNA sequences from nuclear ITS1-5.8-ITS2. Mitochondrial COI sequences showed extremely low but diagnostic variability for Aplysina revillagigedi sp. nov., thus our results corroborate that COI has limited power for DNA-barcoding of sponges and should be complemented with other markers (e.g. rDNA). Phylogenetic analyses of Aplysina sequences from the Eastern Pacific and Caribbean, resolved two allopatric and reciprocally monophyletic groups for each region. Eastern Pacific species were grouped in general accordance with the taxonomic hypothesis based on morphological characters. An identification key of Eastern Pacific Aplysina species is presented. Our results constitute one of the first approximations to integrative

  13. From Research to Operations: Integrating Components of an Advanced Diagnostic System with an Aspect-Oriented Framework

    NASA Technical Reports Server (NTRS)

    Fletcher, Daryl P.; Alena, Richard L.; Akkawi, Faisal; Duncavage, Daniel P.

    2004-01-01

    This paper presents some of the challenges associated with bringing software projects from the research world into an operationa1 environment. While the core functional components of research-oriented software applications can have great utility in an operational setting, these applications often lack aspects important in an operational environment such as logging and security. Furthermore, these stand-alone applications, sometimes developed in isolation from one another, can produce data products useful to other applications in a software ecosystem.

  14. Differential amplicons (ΔAmp)—a new molecular method to assess RNA integrity

    PubMed Central

    Björkman, J.; Švec, D.; Lott, E.; Kubista, M.; Sjöback, R.

    2015-01-01

    Integrity of the mRNA in clinical samples has major impact on the quality of measured expression levels. This is independent of the measurement technique being next generation sequencing (NGS), Quantitative real-time PCR (qPCR) or microarray profiling. If mRNA is highly degraded or damaged, measured data will be very unreliable and the whole study is likely a waste of time and money. It is therefore common strategy to test the quality of RNA in samples before conducting large and costly studies. Most methods today to assess the quality of RNA are ignorant to the nature of the RNA and, therefore, reflect the integrity of ribosomal RNA, which is the dominant species, rather than of mRNAs, microRNAs and long non-coding RNAs, which usually are the species of interest. Here, we present a novel molecular approach to assess the quality of the targeted RNA species by measuring the differential amplification (ΔAmp) of an Endogenous RNase Resistant (ERR) marker relative to a reference gene, optionally combined with the measurement of two amplicons of different lengths. The combination reveals any mRNA degradation caused by ribonucleases as well as physical, chemical or UV damage. ΔAmp has superior sensitivity to common microfluidic electrophoretic methods, senses the integrity of the actual targeted RNA species, and allows for a smoother and more cost efficient workflow. PMID:27077042

  15. Accelerating ab initio path integral molecular dynamics with multilevel sampling of potential surface

    SciTech Connect

    Geng, Hua Y.

    2015-02-15

    A multilevel approach to sample the potential energy surface in a path integral formalism is proposed. The purpose is to reduce the required number of ab initio evaluations of energy and forces in ab initio path integral molecular dynamics (AI-PIMD) simulation, without compromising the overall accuracy. To validate the method, the internal energy and free energy of an Einstein crystal are calculated and compared with the analytical solutions. As a preliminary application, we assess the performance of the method in a realistic model—the FCC phase of dense atomic hydrogen, in which the calculated result shows that the acceleration rate is about 3 to 4-fold for a two-level implementation, and can be increased up to 10 times if extrapolation is used. With only 16 beads used for the ab initio potential sampling, this method gives a well converged internal energy. The residual error in pressure is just about 3 GPa, whereas it is about 20 GPa for a plain AI-PIMD calculation with the same number of beads. The vibrational free energy of the FCC phase of dense hydrogen at 300 K is also calculated with an AI-PIMD thermodynamic integration method, which gives a result of about 0.51 eV/proton at a density of r{sub s}=0.912.

  16. Accelerating ab initio path integral molecular dynamics with multilevel sampling of potential surface

    NASA Astrophysics Data System (ADS)

    Geng, Hua Y.

    2015-02-01

    A multilevel approach to sample the potential energy surface in a path integral formalism is proposed. The purpose is to reduce the required number of ab initio evaluations of energy and forces in ab initio path integral molecular dynamics (AI-PIMD) simulation, without compromising the overall accuracy. To validate the method, the internal energy and free energy of an Einstein crystal are calculated and compared with the analytical solutions. As a preliminary application, we assess the performance of the method in a realistic model-the FCC phase of dense atomic hydrogen, in which the calculated result shows that the acceleration rate is about 3 to 4-fold for a two-level implementation, and can be increased up to 10 times if extrapolation is used. With only 16 beads used for the ab initio potential sampling, this method gives a well converged internal energy. The residual error in pressure is just about 3 GPa, whereas it is about 20 GPa for a plain AI-PIMD calculation with the same number of beads. The vibrational free energy of the FCC phase of dense hydrogen at 300 K is also calculated with an AI-PIMD thermodynamic integration method, which gives a result of about 0.51 eV/proton at a density of rs = 0.912.

  17. Molecular characterization and morphological aspects of Myxobolus parvus (Myxozoa) from Liza saliens (Mugilidae) off the Turkish Black Sea coasts.

    PubMed

    Özer, A; Gürkanlı, C T; Özkan, H; Acar, G; Çiftçi, Y; Yurakhno, V

    2016-09-01

    Members of the phylum Myxozoa are among the most cosmopolitan parasites of fish, and the genus Myxobolus is the largest within the class Myxosporea in freshwater and marine environment from all over the world. Myxobolus parvus has been reported from mainly mugilid fishes from different localities including the Black Sea. Leaping mullet Liza saliens collected by fishermen off Sinop coasts of the Black Sea in the period between September 2014 and December 2015 was investigated for myxosporean parasites using conventional methods. M. parvus Schulman, 1962 was the only Myxobolus species identified and it was found in the gills, gall bladder, kidney tubules, and inside several cysts located on the lower jaw of examined fish in the present study. Morphometric data and all details of parasitic infection were determined and presented in tables and illustrated in figures. Molecular characterization was also conducted to reveal its position within Myxosporea. Two M. parvus samples from gills and kidney showed the same haplotype and appeared in the same sub-lineage with marine Myxobolus species. The closest haplotypes to M. parvus were Triactinomyxon sp. and Endocapsa sp. which are the actinosporeans forms of unknown myxozoan species. These data are the first in molecular characterization of M. parvus, its occurrence in lower jaw of leaping mullet along with its infection prevalence values off the Turkish Black Sea coasts.

  18. The Epidemiological and Molecular Aspects of Influenza H5N1 Viruses at the Human-Animal Interface in Egypt

    PubMed Central

    Kayali, Ghazi; Webby, Richard J.; Ducatez, Mariette F.; El Shesheny, Rabeh A.; Kandeil, Ahmed M.; Govorkova, Elena A.; Mostafa, Ahmed; Ali, Mohamed A.

    2011-01-01

    With 119 confirmed cases between March 2006 and December 2010, Egypt ranks second among countries reporting human H5N1 influenza virus infections. In 2009–2010, Egypt reported 68 new human cases and became the new epicenter for H5N1 infections. We conducted an epidemiological and molecular analysis in order to better understand the situation in Egypt. The onset of new cases peaked annually during the winter and spring months, with majority of cases reported in the Nile Delta region. Most cases were less than 18 years old (62%) and females (60%). The overall case-fatality rate was 34% and significantly increased by age. There was a significant difference between the case-fatality rates among females and males. We observed a significant drop (p = 0.004) in case fatality rate in 2009 (10%) as compared to higher rates (36%–56%) in other years. Hospitalization within 2 or 3 days after onset of symptoms significantly decreased mortality. Molecular analysis showed that variations do occur among viruses isolated from birds as well as from humans in Egypt, and these mutations were especially noted in 2009 viruses. As the epidemiological profile of Egyptian cases differs from other countries, there is an urgent need to conduct prospective studies to enhance our understanding of incidence, prevalence, and determinants of virulence of human infections with avian H5N1 influenza viruses. PMID:21445292

  19. Exploring the biophysical aspects and binding mechanism of thionine with bovine hemoglobin by optical spectroscopic and molecular docking methods.

    PubMed

    Shanmugaraj, Krishnamoorthy; Anandakumar, Shanmugam; Ilanchelian, Malaichamy

    2014-02-05

    In the present investigation, we have elucidated the interaction between thionine (TH) and bovine hemoglobin (BHb) under physiological conditions by using absorption, emission, time resolved fluorescence, synchronous fluorescence, circular dichroism (CD) and three dimensional emission (3D) spectral studies. Molecular docking experiment was also carried out to establish the possible binding site of TH on BHb. The emission spectral studies revealed that, TH have the ability to bind with BHb and form a ground state complex via static quenching process. The calculated binding constant and the number of binding sites was found to be 3.65×10(4)dm(3)mol(-1) and 1.04, respectively. Förster Resonance Energy Transfer (FRET) theory was employed to calculate the distance (r) between donor (BHb) and acceptor (TH) as 3.64nm. Furthermore, the conformational changes of BHb induced by TH complexation showed some degree of structural unfolding. In addition, molecular docking study confirmed that the most probable binding site of TH was located within the active cavity constituted by α1 and α2 subunits of BHb.

  20. Mechanistic aspects of the low-molecular-weight phosphatase activity of the calmodulin-activated phosphatase, calcineurin.

    PubMed

    Martin, B L; Graves, D J

    1986-11-05

    Product and substrate analogs have been employed as inhibitors of the low-molecular-weight phosphatase activity of calcineurin, a calmodulin-activated protein phosphatase. Product inhibition kinetics demonstrate that both products, para-nitrophenol and inorganic phosphate, inhibit para-nitrophenyl phosphate hydrolysis in a competitive manner. Inorganic phosphate is a linear competitive inhibitor, whereas the inhibition by para-nitrophenol is more complex. An analog of para-nitrophenol, pentafluorophenol, was found to be a linear competitive inhibitor. These patterns indicate a rapid equilibrium random kinetic mechanism for calcineurin. This mechanism suggests that calcineurin does not generate a phosphoryl enzyme during its catalytic reaction. Application of sulfate analogs indicates that binding of substrate occurs via the phosphoryl moiety. It is suggested that binding is a function of the affinity of ligand for the metal ion involved in calcineurin action. The dependence of the kinetic parameters of calcineurin upon pH was examined to provide information concerning the role of protonation in the activity and specificity of calcineurin. Log (VM) versus pH data for two low-molecular-weight substrates, para-nitrophenyl phosphate and tyrosine-O-phosphate, reveal a pKa value for the enzyme-substrate complex. Analysis of log (VM/KM) data yields a pKa value for the free enzyme of 8.0. Protonation of the phenolic leaving group during hydrolysis is not the rate-limiting step in calcineurin catalysis.

  1. Molecular aspects of structure, gating, and physiology of pH-sensitive background K2P and Kir K+-transport channels.

    PubMed

    Sepúlveda, Francisco V; Pablo Cid, L; Teulon, Jacques; Niemeyer, María Isabel

    2015-01-01

    K(+) channels fulfill roles spanning from the control of excitability to the regulation of transepithelial transport. Here we review two groups of K(+) channels, pH-regulated K2P channels and the transport group of Kir channels. After considering advances in the molecular aspects of their gating based on structural and functional studies, we examine their participation in certain chosen physiological and pathophysiological scenarios. Crystal structures of K2P and Kir channels reveal rather unique features with important consequences for the gating mechanisms. Important tasks of these channels are discussed in kidney physiology and disease, K(+) homeostasis in the brain by Kir channel-equipped glia, and central functions in the hearing mechanism in the inner ear and in acid secretion by parietal cells in the stomach. K2P channels fulfill a crucial part in central chemoreception probably by virtue of their pH sensitivity and are central to adrenal secretion of aldosterone. Finally, some unorthodox behaviors of the selectivity filters of K2P channels might explain their normal and pathological functions. Although a great deal has been learned about structure, molecular details of gating, and physiological functions of K2P and Kir K(+)-transport channels, this has been only scratching at the surface. More molecular and animal studies are clearly needed to deepen our knowledge.

  2. Molecular Aspects of Structure, Gating, and Physiology of pH-Sensitive Background K2P and Kir K+-Transport Channels

    PubMed Central

    Sepúlveda, Francisco V.; Pablo Cid, L.; Teulon, Jacques; Niemeyer, María Isabel

    2015-01-01

    K+ channels fulfill roles spanning from the control of excitability to the regulation of transepithelial transport. Here we review two groups of K+ channels, pH-regulated K2P channels and the transport group of Kir channels. After considering advances in the molecular aspects of their gating based on structural and functional studies, we examine their participation in certain chosen physiological and pathophysiological scenarios. Crystal structures of K2P and Kir channels reveal rather unique features with important consequences for the gating mechanisms. Important tasks of these channels are discussed in kidney physiology and disease, K+ homeostasis in the brain by Kir channel-equipped glia, and central functions in the hearing mechanism in the inner ear and in acid secretion by parietal cells in the stomach. K2P channels fulfill a crucial part in central chemoreception probably by virtue of their pH sensitivity and are central to adrenal secretion of aldosterone. Finally, some unorthodox behaviors of the selectivity filters of K2P channels might explain their normal and pathological functions. Although a great deal has been learned about structure, molecular details of gating, and physiological functions of K2P and Kir K+-transport channels, this has been only scratching at the surface. More molecular and animal studies are clearly needed to deepen our knowledge. PMID:25540142

  3. Ab initio molecular dynamics investigation of structural, dynamic and spectroscopic aspects of Se(vi) species in the aqueous environment.

    PubMed

    Borah, Sangkha; Padma Kumar, P

    2016-06-07

    Microscopic investigation of solvation of selenic acid (H2SeO4) in the aqueous environment has been carried out using the Car-Parrinello molecular dynamics simulation technique. The species deprotonates to HSeO4(-) in a few picoseconds owing to its low pKa1 value of -3.0. A dynamic equilibrium between HSeO4(-) and SeO4(2-), is observed in qualitative agreement with the reported pKa2 value of 1.70. The governing deprotonation mechanism and the structural and dynamic evolutions of the system, particularly the nature of hydrogen bonding, their strengths and lifetimes are investigated comprehensively. A comparison of the vibrational spectra of the species recorded in the gas phase and in the aqueous environment provides further insights on the nature of the interaction between the solute species and water. The results are in good agreement with the available experimental data and other recent computational studies.

  4. A Critical Analysis of Rejection in Vascularized Composite Allotransplantation: Clinical, Cellular and Molecular Aspects, Current Challenges, and Novel Concepts

    PubMed Central

    Sarhane, Karim A.; Tuffaha, Sami H.; Broyles, Justin M.; Ibrahim, Amir E.; Khalifian, Saami; Baltodano, Pablo; Santiago, Gabriel F.; Alrakan, Mohammed; Ibrahim, Zuhaib

    2013-01-01

    Advances in microsurgical techniques and immunomodulatory protocols have contributed to the expansion of vascularized composite allotransplantation (VCA) with very encouraging immunological, functional, and cosmetic results. Rejection remains however a major hurdle that portends serious threats to recipients. Rejection features in VCA have been described in a number of studies, and an international consensus on the classification of rejection was established. Unfortunately, current available diagnostic methods carry many shortcomings that, in certain cases, pose a great diagnostic challenge to physicians especially in borderline rejection cases. In this review, we revisit the features of acute skin rejection in hand and face transplantation at the clinical, cellular, and molecular levels. The multiple challenges in diagnosing rejection and in defining chronic and antibody-mediated rejection in VCA are then presented, and we finish by analyzing current research directions and novel concepts aiming at improving available diagnostic measures. PMID:24324470

  5. The Integration of Select Aspects of Educational Foundations as Applied to Health Care Education: A Religious Perspective

    ERIC Educational Resources Information Center

    Fredericks, Marcel; Kondellas, Bill; Fredericks, Janet; Langer, Michael; Ross, Michael W. V.

    2013-01-01

    The purpose of this paper is to establish the necessity to fully and effectively integrate the sub-disciplines of educational foundations, such as psychology and philosophy, in addition to the natural and social sciences, within medical and health-related educational programs. This is particularly pertinent in Catholic and other religiously…

  6. The Integration of Select Aspects of Educational Foundations as Applied to Health Care Education: A Religious Perspective

    ERIC Educational Resources Information Center

    Fredericks, Marcel; Kondellas, Bill; Fredericks, Janet; Langer, Michael; Ross, Michael W. V.

    2013-01-01

    The purpose of this paper is to establish the necessity to fully and effectively integrate the sub-disciplines of educational foundations, such as psychology and philosophy, in addition to the natural and social sciences, within medical and health-related educational programs. This is particularly pertinent in Catholic and other religiously…

  7. Harnessing Integrative Omics to Facilitate Molecular Imaging of the Human Epidermal Growth Factor Receptor Family for Precision Medicine.

    PubMed

    Pool, Martin; de Boer, H Rudolf; Hooge, Marjolijn N Lub-de; van Vugt, Marcel A T M; de Vries, Elisabeth G E

    2017-01-01

    Cancer is a growing problem worldwide. The cause of death in cancer patients is often due to treatment-resistant metastatic disease. Many molecularly targeted anticancer drugs have been developed against 'oncogenic driver' pathways. However, these treatments are usually only effective in properly selected patients. Resistance to molecularly targeted drugs through selective pressure on acquired mutations or molecular rewiring can hinder their effectiveness. This review summarizes how molecular imaging techniques can potentially facilitate the optimal implementation of targeted agents. Using the human epidermal growth factor receptor (HER) family as a model in (pre)clinical studies, we illustrate how molecular imaging may be employed to characterize whole body target expression as well as monitor drug effectiveness and the emergence of tumor resistance. We further discuss how an integrative omics discovery platform could guide the selection of 'effect sensors' - new molecular imaging targets - which are dynamic markers that indicate treatment effectiveness or resistance.

  8. Harnessing Integrative Omics to Facilitate Molecular Imaging of the Human Epidermal Growth Factor Receptor Family for Precision Medicine

    PubMed Central

    Pool, Martin; de Boer, H. Rudolf; Hooge, Marjolijn N. Lub-de; van Vugt, Marcel A.T.M.; de Vries, Elisabeth G.E.

    2017-01-01

    Cancer is a growing problem worldwide. The cause of death in cancer patients is often due to treatment-resistant metastatic disease. Many molecularly targeted anticancer drugs have been developed against 'oncogenic driver' pathways. However, these treatments are usually only effective in properly selected patients. Resistance to molecularly targeted drugs through selective pressure on acquired mutations or molecular rewiring can hinder their effectiveness. This review summarizes how molecular imaging techniques can potentially facilitate the optimal implementation of targeted agents. Using the human epidermal growth factor receptor (HER) family as a model in (pre)clinical studies, we illustrate how molecular imaging may be employed to characterize whole body target expression as well as monitor drug effectiveness and the emergence of tumor resistance. We further discuss how an integrative omics discovery platform could guide the selection of 'effect sensors' - new molecular imaging targets - which are dynamic markers that indicate treatment effectiveness or resistance. PMID:28638489

  9. Diversity in recognition of glycans by F-type lectins and galectins: molecular, structural, and biophysical aspects

    PubMed Central

    Vasta, Gerardo R.; Ahmed, Hafiz; Bianchet, Mario A.; Fernández-Robledo, José A.; Amzel, L. Mario

    2013-01-01

    Although lectins are “hard-wired” in the germline, the presence of tandemly arrayed carbohydrate recognition domains (CRDs), of chimeric structures displaying distinct CRDs, of polymorphic genes resulting in multiple isoforms, and in some cases, of a considerable recognition plasticity of their carbohydrate binding sites, significantly expand the lectin ligand-recognition spectrum and lectin functional diversification. Analysis of structural/functional aspects of galectins and F-lectins—the most recently identified lectin family characterized by a unique CRD sequence motif (a distinctive structural fold) and nominal specificity for l-Fuc—has led to a greater understanding of self/nonself recognition by proteins with tandemly arrayed CRDs. For lectins with a single CRD, however, recognition of self and nonself glycans can only be rationalized in terms of protein oligomerization and ligand clustering and presentation. Spatial and temporal changes in lectin expression, secretion, and local concentrations in extracellular microenvironments, as well as structural diversity and spatial display of their carbohydrate ligands on the host or microbial cell surface, are suggestive of a dynamic interplay of their recognition and effector functions in development and immunity. PMID:22973821

  10. Practical Aspects of Molecular Spectroscopy in Plasmas 4. The Role of Molecular Spectroscopy in the Vacuum Ultraviolet Region for the Development of a Negative Ion Source

    NASA Astrophysics Data System (ADS)

    Nishiura, Masaki

    Fundamental plasma processes of negative ions in a low pressure region (a gas pressure Pg < 1.5 Pa) have been studied using the photodetachment technique and vacuum ultraviolet (VUV) spectroscopic measurements in the spectral range from 100 to 180 nm. Understanding the behavior of a plasma with negative ions, in particular, the correlation between H- density and vibrationally excited H2 density, is of great interest in the field of atomic-molecular physics and ion source developments. The volume and the surface effects of negative ions are discussed taking into account the e-V, the E-V, and the RD processes, and the measured VUV spectrum is compared with the synthetic one. The cascade transition to the B1Σ+u state by the electron excitation contributes to the production of the highly vibrationally excited levels of the X1Σ+g ground electronic state.

  11. [Psychological features of body integrity identity disorder (BIID): personality traits, interpersonal aspects, coping mechanisms regarding stress and conflicts, body perception].

    PubMed

    Oddo, S; Möller, J; Skoruppa, S; Stirn, A

    2014-05-01

    In BIID a disorder of body identity, concerned subjects desire an amputation of a healthy limb. So far, no psychiatric comorbidity was found in the few studies on BIID-subjects. This study explored clinical symptoms, personality characteristics, interpersonal aspects and coping strategies in 15 BIID persons. Psychometric testing on the topics (1) clinical symptoms, (2) personality and interpersonal aspects, (3) coping strategies, (4) attitudes towards the body were used and statistically evaluated with the T-test for one sample. Some psychopathologies such as depression, anxiety and obsessive-compulsive disorders (OCD) could be excluded although an increased tendency of depressiveness was found. BIID subjects showed specific personality and interpersonal characteristics: high agreeableness, autonomy, autarky and restrained behaviour towards others. Stress and conflicts are managed by self-control and self-affirmation. Their subjective physical attractiveness was low. BIID persons do not exhibit psychopathological characteristics (such as anxiety, depression or OCD), but do show specifics in personality, relationships and coping mechanisms. In the future, further personality traits and personality disorders should be investigated to shed more light on the categorisation and treatment of BIID. © Georg Thieme Verlag KG Stuttgart · New York.

  12. Vapor-solid-solid grown Ge nanowires at integrated circuit compatible temperature by molecular beam epitaxy

    NASA Astrophysics Data System (ADS)

    Zhu, Zhongyunshen; Song, Yuxin; Zhang, Zhenpu; Sun, Hao; Han, Yi; Li, Yaoyao; Zhang, Liyao; Xue, Zhongying; Di, Zengfeng; Wang, Shumin

    2017-09-01

    We demonstrate Au-assisted vapor-solid-solid (VSS) growth of Ge nanowires (NWs) by molecular beam epitaxy at the substrate temperature of ˜180 °C, which is compatible with the temperature window for Si-based integrated circuit. Low temperature grown Ge NWs hold a smaller size, similar uniformity, and better fit with Au tips in diameter, in contrast to Ge NWs grown at around or above the eutectic temperature of Au-Ge alloy in the vapor-liquid-solid (VLS) growth. Six ⟨110⟩ growth orientations were observed on Ge (110) by the VSS growth at ˜180 °C, differing from only one vertical growth direction of Ge NWs by the VLS growth at a high temperature. The evolution of NWs dimension and morphology from the VLS growth to the VSS growth is qualitatively explained by analyzing the mechanism of the two growth modes.

  13. Path integral centroid molecular dynamics simulation of para-hydrogen sandwiched by graphene sheets

    NASA Astrophysics Data System (ADS)

    Minamino, Yuki; Kinugawa, Kenichi

    2016-11-01

    The carbon-hydrogen composite systems of para-hydrogen (p-H2) sandwiched by a couple of graphene sheets have been investigated by means of path integral centroid molecular dynamics simulations at 17 K. It has been shown that sandwiched hydrogen is liquid-like but p-H2 molecules are preferably adsorbed onto the graphene sheets because of attractive graphene-hydrogen interaction. The diffusion coefficient of p-H2 molecules in the direction parallel to the graphene sheets is comparable to that in pure liquid p-H2. There exists a characteristic mode of 140 cm-1 of the p-H2 molecules, attributed to adsorption-binding motion perpendicular to the graphene sheets.