Sample records for molecular events basic
-
Huang, Wei Tao; Luo, Hong Qun; Li, Nian Bing
2014-05-06
The most serious, and yet unsolved, problem of constructing molecular computing devices consists in connecting all of these molecular events into a usable device. This report demonstrates the use of Boolean logic tree for analyzing the chemical event network based on graphene, organic dye, thrombin aptamer, and Fenton reaction, organizing and connecting these basic chemical events. And this chemical event network can be utilized to implement fluorescent combinatorial logic (including basic logic gates and complex integrated logic circuits) and fuzzy logic computing. On the basis of the Boolean logic tree analysis and logic computing, these basic chemical events can be considered as programmable "words" and chemical interactions as "syntax" logic rules to construct molecular search engine for performing intelligent molecular search query. Our approach is helpful in developing the advanced logic program based on molecules for application in biosensing, nanotechnology, and drug delivery.
-
NASA Astrophysics Data System (ADS)
Voter, Arthur
Many important materials processes take place on time scales that far exceed the roughly one microsecond accessible to molecular dynamics simulation. Typically, this long-time evolution is characterized by a succession of thermally activated infrequent events involving defects in the material. In the accelerated molecular dynamics (AMD) methodology, known characteristics of infrequent-event systems are exploited to make reactive events take place more frequently, in a dynamically correct way. For certain processes, this approach has been remarkably successful, offering a view of complex dynamical evolution on time scales of microseconds, milliseconds, and sometimes beyond. We have recently made advances in all three of the basic AMD methods (hyperdynamics, parallel replica dynamics, and temperature accelerated dynamics (TAD)), exploiting both algorithmic advances and novel parallelization approaches. I will describe these advances, present some examples of our latest results, and discuss what should be possible when exascale computing arrives in roughly five years. Funded by the U.S. Department of Energy, Office of Basic Energy Sciences, Materials Sciences and Engineering Division, and by the Los Alamos Laboratory Directed Research and Development program.
-
Pathophysiology of chest trauma.
Calhoon, J H; Trinkle, J K
1997-05-01
Recent information indicates that there is a complex cellular and molecular generic response to injury that can lead to multi-organ failure. For many years, basic physiology and biochemistry were considered to be the systemic mechanisms to injury, but now it is known that subcellular and molecular events are the keys to unlocking the secrets of the body's response to trauma. The interaction of the endothelial cell with neutrophils and platelets to produce cytokines, free radicals, and upregulating adhesion molecules is especially significant.
-
Stromal cells can contribute oncogenic signals
NASA Technical Reports Server (NTRS)
Tlsty, T. D.
2001-01-01
The majority of studies of neoplastic transformation have focused attention on events that occur within transformed cells. These cell autonomous events result in the disruption of molecular pathways that regulate basic activities of the cells such as proliferation, death, movement and genomic integrity. Other studies have addressed the microenvironment of tumor cells and documented its importance in supporting tumor progression. Recent work has begun to expand on these initial studies of tumor microenvironment and now provide novel insights into the possible initiation and progression of malignant cells. This review will address the transforming effect of stromal cells on epithelial components. Copyright 2001 Academic Press.
-
Cusimano, Natalie; Sousa, Aretuza; Renner, Susanne S.
2012-01-01
Background and Aims For 84 years, botanists have relied on calculating the highest common factor for series of haploid chromosome numbers to arrive at a so-called basic number, x. This was done without consistent (reproducible) reference to species relationships and frequencies of different numbers in a clade. Likelihood models that treat polyploidy, chromosome fusion and fission as events with particular probabilities now allow reconstruction of ancestral chromosome numbers in an explicit framework. We have used a modelling approach to reconstruct chromosome number change in the large monocot family Araceae and to test earlier hypotheses about basic numbers in the family. Methods Using a maximum likelihood approach and chromosome counts for 26 % of the 3300 species of Araceae and representative numbers for each of the other 13 families of Alismatales, polyploidization events and single chromosome changes were inferred on a genus-level phylogenetic tree for 113 of the 117 genera of Araceae. Key Results The previously inferred basic numbers x = 14 and x = 7 are rejected. Instead, maximum likelihood optimization revealed an ancestral haploid chromosome number of n = 16, Bayesian inference of n = 18. Chromosome fusion (loss) is the predominant inferred event, whereas polyploidization events occurred less frequently and mainly towards the tips of the tree. Conclusions The bias towards low basic numbers (x) introduced by the algebraic approach to inferring chromosome number changes, prevalent among botanists, may have contributed to an unrealistic picture of ancestral chromosome numbers in many plant clades. The availability of robust quantitative methods for reconstructing ancestral chromosome numbers on molecular phylogenetic trees (with or without branch length information), with confidence statistics, makes the calculation of x an obsolete approach, at least when applied to large clades. PMID:22210850
-
[Pathophysiology of sickle cell disease].
Elion, J; Laurance, S; Lapouméroulie, C
2010-12-01
It has been 100 years since Herrick published the first medical case report of sickle cell disease. In 1949, Pauling discovered hemoglobin S (HbS). As early as the 1960-70s, emerged a coherent detailed molecular-level description of pathophysiology of sickle disease. It involved polymerization of deoxyhemoglobin S with formation of long fibers inside red blood cells (RBC) causing a distorted sickle shape and shortened lifespan. These changes constitute the basic disease process and account for hemolytic anemia and for obstructive events underlying vasoocclusive crises (VOC). However, they do not explain the mechanisms that trigger VOC. The purpose of this review is to present recent data on dehydration of sickle cell RBC, abnormalities in RBC adhesion to the vascular endothelium, the role of inflammatory events and of activation of all cells in the vessel, and abnormalities of vascular tone and carbon monoxide metabolism. These data provide new insight into the pathophysiology of the first molecular disease.
-
Colombo, Jorge A
2018-06-01
Assertions regarding attempts to link glial and macrostructural brain events with cognitive performance regarding Albert Einstein, are critically reviewed. One basic problem arises from attempting to draw causal relationships regarding complex, delicately interactive functional processes involving finely tuned molecular and connectivity phenomena expressed in cognitive performance, based on highly variable brain structural events of a single, aged, formalin fixed brain. Data weaknesses and logical flaws are considered. In other instances, similar neuroanatomical observations received different interpretations and conclusions, as those drawn, e.g., from schizophrenic brains. Observations on white matter events also raise methodological queries. Additionally, neurocognitive considerations on other intellectual aptitudes of A. Einstein were simply ignored.
-
An ALuc-Based Molecular Tension Probe for Sensing Intramolecular Protein-Protein Interactions.
Kim, Sung-Bae; Nishihara, Ryo; Suzuki, Koji
2016-01-01
Optical imaging of protein-protein interactions (PPIs) facilitates comprehensive elucidation of intracellular molecular events. The present protocol demonstrates an optical measure for visualizing molecular tension triggered by any PPI in mammalian cells. A unique design of single-chain probes was fabricated, in which a full-length artificial luciferase (ALuc(®)) was sandwiched between two model proteins of interest, e.g., FKBP and FRB. A molecular tension probe comprising ALuc23 greatly enhances the bioluminescence in response to varying concentrations of rapamycin, and named "tension probe (TP)." The basic probe design can be further modified towards eliminating the C-terminal end of ALuc and was found to improve signal-to-background ratios, named "combinational probe." TPs may become an important addition to the tool box of bioassays in the determination of protein dynamics of interest in mammalian cells.
-
Loeza-Quintana, Tzitziki; Adamowicz, Sarah J
2018-02-01
During the past 50 years, the molecular clock has become one of the main tools for providing a time scale for the history of life. In the era of robust molecular evolutionary analysis, clock calibration is still one of the most basic steps needing attention. When fossil records are limited, well-dated geological events are the main resource for calibration. However, biogeographic calibrations have often been used in a simplistic manner, for example assuming simultaneous vicariant divergence of multiple sister lineages. Here, we propose a novel iterative calibration approach to define the most appropriate calibration date by seeking congruence between the dates assigned to multiple allopatric divergences and the geological history. Exploring patterns of molecular divergence in 16 trans-Bering sister clades of echinoderms, we demonstrate that the iterative calibration is predominantly advantageous when using complex geological or climatological events-such as the opening/reclosure of the Bering Strait-providing a powerful tool for clock dating that can be applied to other biogeographic calibration systems and further taxa. Using Bayesian analysis, we observed that evolutionary rate variability in the COI-5P gene is generally distributed in a clock-like fashion for Northern echinoderms. The results reveal a large range of genetic divergences, consistent with multiple pulses of trans-Bering migrations. A resulting rate of 2.8% pairwise Kimura-2-parameter sequence divergence per million years is suggested for the COI-5P gene in Northern echinoderms. Given that molecular rates may vary across latitudes and taxa, this study provides a new context for dating the evolutionary history of Arctic marine life.
-
Editorial overview: Molecular and genetic bases of disease: the double life of DNA.
McMurray, Cynthia T; Vijg, Jan
2014-06-01
This issue of Current Opinions focuses on the dual role of DNA in life and death. In ancient Roman religion and myth, Janus is the god who looks both to the past and to the future. He guides the beginnings of life, its progression from one condition to another, and he foresees distant events. The analogy to DNA could not be stronger. Closely interacting with the environment, our basic genetics provides the origin of life, guides the quality of health with age, predicts disease, and ultimately foresees our end. A shared and deep interest with the origin of life has long prompted our desire to define aging, and, ultimately, to understand whether it can be reversed. In this special issue, the authors collectively review concepts of normative aging, DNA instability, DNA repair, the genetic contribution of age and diet to disease, and how the basic molecular transactions of DNA guide both the transitions to life as well as the transitions to death. Published by Elsevier Ltd.
-
Gamo, Nao J.; Arnsten, Amy F.T.
2011-01-01
Dysfunction of the prefrontal cortex (PFC) is a central feature of many psychiatric disorders, such as attention deficit hyperactivity disorder (ADHD), post-traumatic stress disorder (PTSD), schizophrenia and bipolar disorder. Thus, understanding molecular influences on PFC function through basic research in animals is essential to rational drug development. In this review, we discuss the molecular signaling events initiated by norepinephrine and dopamine that strengthen working memory function mediated by the dorsolateral PFC under optimal conditions, and weaken working memory function during uncontrollable stress. We also discuss how these intracellular mechanisms can be compromised in psychiatric disorders, and how novel treatments based on these findings may restore a molecular environment conducive to PFC regulation of behavior, thought and emotion. Examples of successful translation from animals to humans include guanfacine for the treatment of ADHD and related PFC disorders, and prazosin for the treatment of PTSD. PMID:21480691
-
Yu, Victor L; Stout, Janet E
2009-12-01
Two nonsynchronous events have affected the management of community-acquired pneumonia (CAP): spiraling empiricism for CAP and the "golden era" of clinical microbiology. The development of broad-spectrum antibiotics has led to widespread empiric use without ascertaining the etiology of the infecting microbe. Unfortunately, this approach clashes with the second event, which is the advent of molecular-based microbiology that can identify the causative pathogen rapidly at the point of care. The urinary antigen is a most effective rapid test that has allowed targeted therapy for Legionnaire disease at the point of care. The high specificity (> 90%) allows the clinician to administer appropriate anti-Legionella therapy based on a single rapid test; however, its low sensitivity (76%) means that a notable number of cases of Legionnaire disease will go undiagnosed if other tests, especially culture, are not performed. Further, culture for Legionella is not readily available. If a culture is not performed, epidemiologic identification of the source of the bacterium cannot be ascertained by molecular fingerprinting of the patient and the putative source strain. We recommend resurrection of the basic principles of infectious disease, which are to identify the microbial etiology of the infection and to use narrow, targeted antimicrobial therapy. To reduce antimicrobial overuse with subsequent antimicrobial resistance, these basic principles must be applied in concert with traditional and newer tests in the clinical microbiology laboratory.
-
Statistical inference of the generation probability of T-cell receptors from sequence repertoires.
Murugan, Anand; Mora, Thierry; Walczak, Aleksandra M; Callan, Curtis G
2012-10-02
Stochastic rearrangement of germline V-, D-, and J-genes to create variable coding sequence for certain cell surface receptors is at the origin of immune system diversity. This process, known as "VDJ recombination", is implemented via a series of stochastic molecular events involving gene choices and random nucleotide insertions between, and deletions from, genes. We use large sequence repertoires of the variable CDR3 region of human CD4+ T-cell receptor beta chains to infer the statistical properties of these basic biochemical events. Because any given CDR3 sequence can be produced in multiple ways, the probability distribution of hidden recombination events cannot be inferred directly from the observed sequences; we therefore develop a maximum likelihood inference method to achieve this end. To separate the properties of the molecular rearrangement mechanism from the effects of selection, we focus on nonproductive CDR3 sequences in T-cell DNA. We infer the joint distribution of the various generative events that occur when a new T-cell receptor gene is created. We find a rich picture of correlation (and absence thereof), providing insight into the molecular mechanisms involved. The generative event statistics are consistent between individuals, suggesting a universal biochemical process. Our probabilistic model predicts the generation probability of any specific CDR3 sequence by the primitive recombination process, allowing us to quantify the potential diversity of the T-cell repertoire and to understand why some sequences are shared between individuals. We argue that the use of formal statistical inference methods, of the kind presented in this paper, will be essential for quantitative understanding of the generation and evolution of diversity in the adaptive immune system.
-
DOE Office of Scientific and Technical Information (OSTI.GOV)
Powell, Danny H; Elwood Jr, Robert H
2011-01-01
Analysis of the material protection, control, and accountability (MPC&A) system is necessary to understand the limits and vulnerabilities of the system to internal threats. A self-appraisal helps the facility be prepared to respond to internal threats and reduce the risk of theft or diversion of nuclear material. The material control and accountability (MC&A) system effectiveness tool (MSET) fault tree was developed to depict the failure of the MPC&A system as a result of poor practices and random failures in the MC&A system. It can also be employed as a basis for assessing deliberate threats against a facility. MSET uses faultmore » tree analysis, which is a top-down approach to examining system failure. The analysis starts with identifying a potential undesirable event called a 'top event' and then determining the ways it can occur (e.g., 'Fail To Maintain Nuclear Materials Under The Purview Of The MC&A System'). The analysis proceeds by determining how the top event can be caused by individual or combined lower level faults or failures. These faults, which are the causes of the top event, are 'connected' through logic gates. The MSET model uses AND-gates and OR-gates and propagates the effect of event failure using Boolean algebra. To enable the fault tree analysis calculations, the basic events in the fault tree are populated with probability risk values derived by conversion of questionnaire data to numeric values. The basic events are treated as independent variables. This assumption affects the Boolean algebraic calculations used to calculate results. All the necessary calculations are built into the fault tree codes, but it is often useful to estimate the probabilities manually as a check on code functioning. The probability of failure of a given basic event is the probability that the basic event primary question fails to meet the performance metric for that question. The failure probability is related to how well the facility performs the task identified in that basic event over time (not just one performance or exercise). Fault tree calculations provide a failure probability for the top event in the fault tree. The basic fault tree calculations establish a baseline relative risk value for the system. This probability depicts relative risk, not absolute risk. Subsequent calculations are made to evaluate the change in relative risk that would occur if system performance is improved or degraded. During the development effort of MSET, the fault tree analysis program used was SAPHIRE. SAPHIRE is an acronym for 'Systems Analysis Programs for Hands-on Integrated Reliability Evaluations.' Version 1 of the SAPHIRE code was sponsored by the Nuclear Regulatory Commission in 1987 as an innovative way to draw, edit, and analyze graphical fault trees primarily for safe operation of nuclear power reactors. When the fault tree calculations are performed, the fault tree analysis program will produce several reports that can be used to analyze the MPC&A system. SAPHIRE produces reports showing risk importance factors for all basic events in the operational MC&A system. The risk importance information is used to examine the potential impacts when performance of certain basic events increases or decreases. The initial results produced by the SAPHIRE program are considered relative risk values. None of the results can be interpreted as absolute risk values since the basic event probability values represent estimates of risk associated with the performance of MPC&A tasks throughout the material balance area (MBA). The RRR for a basic event represents the decrease in total system risk that would result from improvement of that one event to a perfect performance level. Improvement of the basic event with the greatest RRR value produces a greater decrease in total system risk than improvement of any other basic event. Basic events with the greatest potential for system risk reduction are assigned performance improvement values, and new fault tree calculations show the improvement in total system risk. The operational impact or cost-effectiveness from implementing the performance improvements can then be evaluated. The improvements being evaluated can be system performance improvements, or they can be potential, or actual, upgrades to the system. The RIR for a basic event represents the increase in total system risk that would result from failure of that one event. Failure of the basic event with the greatest RIR value produces a greater increase in total system risk than failure of any other basic event. Basic events with the greatest potential for system risk increase are assigned failure performance values, and new fault tree calculations show the increase in total system risk. This evaluation shows the importance of preventing performance degradation of the basic events. SAPHIRE identifies combinations of basic events where concurrent failure of the events results in failure of the top event.« less
-
DOE Office of Scientific and Technical Information (OSTI.GOV)
Sotomayor, Marcos
Hair cell mechanotransduction happens in tens of microseconds, involves forces of a few picoNewtons, and is mediated by nanometer-scale molecular conformational changes. As proteins involved in this process become identified and their high resolution structures become available, multiple tools are being used to explore their “single-molecule responses” to force. Optical tweezers and atomic force microscopy offer exquisite force and extension resolution, but cannot reach the high loading rates expected for high frequency auditory stimuli. Molecular dynamics (MD) simulations can reach these fast time scales, and also provide a unique view of the molecular events underlying protein mechanics, but its predictionsmore » must be experimentally verified. Thus a combination of simulations and experiments might be appropriate to study the molecular mechanics of hearing. Here I review the basics of MD simulations and the different methods used to apply force and study protein mechanics in silico. Simulations of tip link proteins are used to illustrate the advantages and limitations of this method.« less
-
Molecular mechanism of Mg2+-dependent gating in CorA
NASA Astrophysics Data System (ADS)
Dalmas, Olivier; Sompornpisut, Pornthep; Bezanilla, Francisco; Perozo, Eduardo
2014-04-01
CorA is the major transport system responsible for Mg2+ uptake in bacteria and can functionally substitute for its homologue Mrs2p in the yeast inner mitochondrial membrane. Although several CorA crystal structures are available, the molecular mechanism of Mg2+ uptake remains to be established. Here we use electron paramagnetic resonance spectroscopy, electrophysiology and molecular dynamic simulations to show that CorA is regulated by cytoplasmic Mg2+ acting as a ligand and elucidate the basic conformational rearrangements responsible for Mg2+-dependent gating. Mg2+ unbinding at the divalent cation sensor triggers a conformational change that leads to the inward motion of the stalk helix, which propagates to the pore-forming transmembrane helix TM1. Helical tilting and rotation in TM1 generates an iris-like motion that increases the diameter of the permeation pathway, triggering ion conduction. This work establishes the molecular basis of a Mg2+-driven negative feedback loop in CorA as the key physiological event controlling Mg2+ uptake and homeostasis in prokaryotes.
-
Fontanet, Pilar; Vicient, Carlos M
2008-01-01
Plant embryo development is a complex process that includes several coordinated events. Maize mature embryos consist of a well-differentiated embryonic axis surrounded by a single massive cotyledon called scutellum. Mature embryo axis also includes lateral roots and several developed leaves. In contrast to Arabidopsis, in which the orientation of cell divisions are perfectly established, only the first planes of cell division are predictable in maize embryos. These distinctive characteristics joined to the availability of a large collection of embryo mutants, well-developed molecular biology and tissue culture tools, an established genetics and its economical importance make maize a good model plant for grass embryogenesis. Here, we describe basic concepts and techniques necessary for studying maize embryo development: how to grow maize in greenhouses and basic techniques for in vitro embryo culture, somatic embryogenesis and in situ hybridization.
-
Molecular paleontology and complexity in the last eukaryotic common ancestor
Koumandou, V. Lila; Wickstead, Bill; Ginger, Michael L.; van der Giezen, Mark; Dacks, Joel B.
2013-01-01
Eukaryogenesis, the origin of the eukaryotic cell, represents one of the fundamental evolutionary transitions in the history of life on earth. This event, which is estimated to have occurred over one billion years ago, remains rather poorly understood. While some well-validated examples of fossil microbial eukaryotes for this time frame have been described, these can provide only basic morphology and the molecular machinery present in these organisms has remained unknown. Complete and partial genomic information has begun to fill this gap, and is being used to trace proteins and cellular traits to their roots and to provide unprecedented levels of resolution of structures, metabolic pathways and capabilities of organisms at these earliest points within the eukaryotic lineage. This is essentially allowing a molecular paleontology. What has emerged from these studies is spectacular cellular complexity prior to expansion of the eukaryotic lineages. Multiple reconstructed cellular systems indicate a very sophisticated biology, which by implication arose following the initial eukaryogenesis event but prior to eukaryotic radiation and provides a challenge in terms of explaining how these early eukaryotes arose and in understanding how they lived. Here, we provide brief overviews of several cellular systems and the major emerging conclusions, together with predictions for subsequent directions in evolution leading to extant taxa. We also consider what these reconstructions suggest about the life styles and capabilities of these earliest eukaryotes and the period of evolution between the radiation of eukaryotes and the eukaryogenesis event itself. PMID:23895660
-
Borysov, Sergiy; Bryant, Victoria L; Alexandrow, Mark G
2015-01-01
Of critical importance to many of the events underlying transcriptional control of gene expression are modifications to core and linker histones that regulate the accessibility of trans-acting factors to the DNA substrate within the context of chromatin. Likewise, control over the initiation of DNA replication, as well as the ability of the replication machinery to proceed during elongation through the multiple levels of chromatin condensation that are likely to be encountered, is known to involve the creation of chromatin accessibility. In the latter case, chromatin access will likely need to be a transient event so as to prevent total genomic unraveling of the chromatin that would be deleterious to cells. While there are many molecular and biochemical approaches in use to study histone changes and their relationship to transcription and chromatin accessibility, few techniques exist that allow a molecular dissection of the events underlying DNA replication control as it pertains to chromatin changes and accessibility. Here, we outline a novel experimental strategy for addressing the ability of specific proteins to induce large-scale chromatin unfolding (decondensation) in vivo upon site-specific targeting to an engineered locus. Our laboratory has used this powerful system in novel ways to directly address the ability of DNA replication proteins to create chromatin accessibility, and have incorporated modifications to the basic approach that allow for a molecular genetic analysis of the mechanisms and associated factors involved in causing chromatin decondensation by a protein of interest. Alternative approaches involving co-expression of other proteins (competitors or stimulators), concurrent drug treatments, and analysis of co-localizing histone modifications are also addressed, all of which are illustrative of the utility of this experimental system for extending basic findings to physiologically relevant mechanisms. Although used by our group to analyze mechanisms underlying DNA replication associated chromatin accessibility, this unique and powerful experimental system has the propensity to be a valuable tool for understanding chromatin remodeling mechanisms orchestrated by other cellular processes such as DNA repair, recombination, mitotic chromosome condensation, or other chromosome dynamics involving chromatin alterations and accessibility.
-
Application of FRET probes in the analysis of neuronal plasticity
Ueda, Yoshibumi; Kwok, Showming; Hayashi, Yasunori
2013-01-01
Breakthroughs in imaging techniques and optical probes in recent years have revolutionized the field of life sciences in ways that traditional methods could never match. The spatial and temporal regulation of molecular events can now be studied with great precision. There have been several key discoveries that have made this possible. Since green fluorescent protein (GFP) was cloned in 1992, it has become the dominant tracer of proteins in living cells. Then the evolution of color variants of GFP opened the door to the application of Förster resonance energy transfer (FRET), which is now widely recognized as a powerful tool to study complicated signal transduction events and interactions between molecules. Employment of fluorescent lifetime imaging microscopy (FLIM) allows the precise detection of FRET in small subcellular structures such as dendritic spines. In this review, we provide an overview of the basic and practical aspects of FRET imaging and discuss how different FRET probes have revealed insights into the molecular mechanisms of synaptic plasticity and enabled visualization of neuronal network activity both in vitro and in vivo. PMID:24133415
-
Marine biosurfaces research program
NASA Astrophysics Data System (ADS)
The Office of Naval Research (ONR) of the U.S. Navy is starting a basic research program to address the initial events that control colonization of surfaces by organisms in marine environments. The program “arises from the Navy's need to understand and ultimately control biofouling and biocorrosion in marine environments,” according to a Navy announcement.The program, “Biological Processes Controlling Surface Modification in the Marine Environment,” will emphasize the application of in situ techniques and modern molecular biological, biochemical, and biophysical approaches; it will also encourage the development of interdisciplinary projects. Specific areas of interest include sensing and response to environmental surface (physiology/physical chemistry), factors controlling movement to and retention at surfaces (behavior/hydrodynamics), genetic regulation of attachment (molecular genetics), and mechanisms of attachment (biochemistry/surface chemistry).
-
Rowe, Catherine A; Walker, Kristin L; Britton, Peter C; Hirsch, Jameson K
2013-01-01
Individuals who experience negative life events may be at increased risk for suicidal behavior. Intrapersonal characteristics, such as basic psychological needs, however, may buffer this association. To assess the potential moderating role of overall basic psychological needs, and the separate components of autonomy, competence, and relatedness, on the association between negative life events and suicidal behavior. Our sample of 439 college students (311 females, 71%) completed the following self-report surveys: Life Events Scale, Basic Psychological Needs Scale, Beck Depression Inventory - II, and the Suicide Behaviors Questionnaire-Revised. In support of our hypotheses, negative life events were associated with greater levels of suicidal ideation and attempts, and satisfaction of basic psychological needs, including autonomy, relatedness, and competence, significantly moderated this relationship, over and above the effects of the covariates of age, sex, and depressive symptoms. Suicidal behavior associated with the experience of negative life events is not inevitable. Therapeutically bolstering competence, autonomy, and relatedness may be an important suicide prevention strategy for individuals experiencing life stressors.
-
Guanidine: A Highly Efficient Stabilizer in Atmospheric New-Particle Formation.
Myllys, Nanna; Ponkkonen, Tuomo; Passananti, Monica; Elm, Jonas; Vehkamäki, Hanna; Olenius, Tinja
2018-05-24
The role of a strong organobase, guanidine, in sulfuric acid-driven new-particle formation is studied using state-of-the-art quantum chemical methods and molecular cluster formation simulations. Cluster formation mechanisms at the molecular level are resolved, and theoretical results on cluster stability are confirmed with mass spectrometer measurements. New-particle formation from guanidine and sulfuric acid molecules occurs without thermodynamic barriers under studied conditions, and clusters are growing close to a 1:1 composition of acid and base. Evaporation rates of the most stable clusters are extremely low, which can be explained by the proton transfers and symmetrical cluster structures. We compare the ability of guanidine and dimethylamine to enhance sulfuric acid-driven particle formation and show that more than 2000-fold concentration of dimethylamine is needed to yield as efficient particle formation as in the case of guanidine. At similar conditions, guanidine yields 8 orders of magnitude higher particle formation rates compared to dimethylamine. Highly basic compounds such as guanidine may explain experimentally observed particle formation events at low precursor vapor concentrations, whereas less basic and more abundant bases such as ammonia and amines are likely to explain measurements at high concentrations.
-
Contributions of basic immunology to human health.
Albright, J F; Oppenheim, J J
1991-03-01
The sixth symposium in the series "Contemporary Topics in Immunology" was held in New Orleans on June 3, 1990, at the joint meeting of The American Association of Immunologists and the American Society of Biochemistry and Molecular Biology. The symposium was sponsored jointly by The American Association of Immunologists, the Clinical Immunology Society, and and the National Institute of Allergy and Infectious Diseases, and was titled "The Contributions of Basic Immunology to Human Health." Five speakers, whose research has clear relevance to the treatment and prevention of major human diseases, discussed topics of great current interest: hematopoietic stem cells, cell adhesion and lymphocyte homing; the complexities of autoimmunity and approaches to diverting or depressing autoaggressive immunity; structure and functions of the interferons and the construction of designer and chimeric interferons; the varied functions of transforming growth factors and molecular events that regulate the synthesis of TGF beta; and the roles of cytokines in the expression of human immunodeficiency virus and the prospects for controlling HIV infections by regulating selected cytokines. This symposium will be remembered for the exceptional clarity with which each speaker illustrated how fundamental knowledge in immunology fuels advances in the treatment and prevention of those human disorders that involve the immune system.
-
Fault and event tree analyses for process systems risk analysis: uncertainty handling formulations.
Ferdous, Refaul; Khan, Faisal; Sadiq, Rehan; Amyotte, Paul; Veitch, Brian
2011-01-01
Quantitative risk analysis (QRA) is a systematic approach for evaluating likelihood, consequences, and risk of adverse events. QRA based on event (ETA) and fault tree analyses (FTA) employs two basic assumptions. The first assumption is related to likelihood values of input events, and the second assumption is regarding interdependence among the events (for ETA) or basic events (for FTA). Traditionally, FTA and ETA both use crisp probabilities; however, to deal with uncertainties, the probability distributions of input event likelihoods are assumed. These probability distributions are often hard to come by and even if available, they are subject to incompleteness (partial ignorance) and imprecision. Furthermore, both FTA and ETA assume that events (or basic events) are independent. In practice, these two assumptions are often unrealistic. This article focuses on handling uncertainty in a QRA framework of a process system. Fuzzy set theory and evidence theory are used to describe the uncertainties in the input event likelihoods. A method based on a dependency coefficient is used to express interdependencies of events (or basic events) in ETA and FTA. To demonstrate the approach, two case studies are discussed. © 2010 Society for Risk Analysis.
-
Convergent evolution of gene networks by single-gene duplications in higher eukaryotes.
Amoutzias, Gregory D; Robertson, David L; Oliver, Stephen G; Bornberg-Bauer, Erich
2004-03-01
By combining phylogenetic, proteomic and structural information, we have elucidated the evolutionary driving forces for the gene-regulatory interaction networks of basic helix-loop-helix transcription factors. We infer that recurrent events of single-gene duplication and domain rearrangement repeatedly gave rise to distinct networks with almost identical hub-based topologies, and multiple activators and repressors. We thus provide the first empirical evidence for scale-free protein networks emerging through single-gene duplications, the dominant importance of molecular modularity in the bottom-up construction of complex biological entities, and the convergent evolution of networks.
-
[HPV-associated head and neck cancer. The basics of molecular and translational research].
Wittekindt, C; Wagner, S; Klussmann, J P
2011-09-01
Translational research refers to the interfaces between preclinical research and targeted short- and medium-term developments through to clinical standards. There are two distinct groups of oropharyngeal malignancies: those caused by tobacco and alcohol abuse and those caused by HPV infection. Although the prognosis of patients in the latter group is significantly better, this is not taken into consideration in the choice of treatment. However, less intensive use of radiotherapy, chemotherapy, or surgery, as well as targeted multimodal therapeutic approaches, is under research. This article summarizes the main events in the HPV life cycle, with emphasis on carcinogenic mechanisms and potential new molecular targets. Identifying distinct tumor entities of the oropharynx enables the design and development of new preventive and therapeutic strategies to reduce the incidence and mortality of HPV-associated oropharyngeal cancers in the near future.
-
Jackson, Patricia L; Cao, Ligong; Blalock, J Edwin; Whitaker, John N
2003-10-15
Urinary myelin basic protein-like material (MBPLM), so designated because of its immunoreactivity with a polyclonal antibody directed against a cryptic epitope located in residues 83-89 of myelin basic protein (MBP), exists in humans normally but increases in concentration in patients with multiple sclerosis who have progressive disease. Given its possible role in reflecting events of neural tissue destruction occurring in multiple sclerosis, urinary MBPLM is a candidate surrogate marker for this phase of the disease. Previously, it has been demonstrated that p-cresol sulfate (PCS) is the dominant component of MBPLM; however, another component(s) was essential in enabling p-cresol sulfate to have molecular mimicry with MBP peptide 83-89 detected by immunoreactivity. In the present investigation, this remaining component(s) was characterized by a combination of high performance size exclusion chromatography followed by nuclear magnetic resonance spectroscopy and shown to be ammonium. The monovalent cation ammonium could be substituted in vitro by several different monovalent and divalent cations, most notably zinc, in restoring to deprotonated p-cresol sulfate its immunoreactivity as MBPLM. These findings indicate the basis for the unexpected molecular mimicry between an epitope of an encephalitogenic protein and a complex containing a small organic molecule, p-cresol sulfate. Furthermore, the reaction of either ammonium or other cations with p-cresol sulfate may represent an in vivo process directly related to damage of axonal membranes.
-
In vivo optical imaging and dynamic contrast methods for biomedical research
Hillman, Elizabeth M. C.; Amoozegar, Cyrus B.; Wang, Tracy; McCaslin, Addason F. H.; Bouchard, Matthew B.; Mansfield, James; Levenson, Richard M.
2011-01-01
This paper provides an overview of optical imaging methods commonly applied to basic research applications. Optical imaging is well suited for non-clinical use, since it can exploit an enormous range of endogenous and exogenous forms of contrast that provide information about the structure and function of tissues ranging from single cells to entire organisms. An additional benefit of optical imaging that is often under-exploited is its ability to acquire data at high speeds; a feature that enables it to not only observe static distributions of contrast, but to probe and characterize dynamic events related to physiology, disease progression and acute interventions in real time. The benefits and limitations of in vivo optical imaging for biomedical research applications are described, followed by a perspective on future applications of optical imaging for basic research centred on a recently introduced real-time imaging technique called dynamic contrast-enhanced small animal molecular imaging (DyCE). PMID:22006910
-
ERIC Educational Resources Information Center
Hayes, Joseph M.
2014-01-01
A 3D model visualization and basic molecular modeling laboratory suitable for first-year undergraduates studying introductory medicinal chemistry is presented. The 2 h practical is embedded within a series of lectures on drug design, target-drug interactions, enzymes, receptors, nucleic acids, and basic pharmacokinetics. Serving as a teaching aid…
-
Molecular sled sequences are common in mammalian proteins.
Xiong, Kan; Blainey, Paul C
2016-03-18
Recent work revealed a new class of molecular machines called molecular sleds, which are small basic molecules that bind and slide along DNA with the ability to carry cargo along DNA. Here, we performed biochemical and single-molecule flow stretching assays to investigate the basis of sliding activity in molecular sleds. In particular, we identified the functional core of pVIc, the first molecular sled characterized; peptide functional groups that control sliding activity; and propose a model for the sliding activity of molecular sleds. We also observed widespread DNA binding and sliding activity among basic polypeptide sequences that implicate mammalian nuclear localization sequences and many cell penetrating peptides as molecular sleds. These basic protein motifs exhibit weak but physiologically relevant sequence-nonspecific DNA affinity. Our findings indicate that many mammalian proteins contain molecular sled sequences and suggest the possibility that substantial undiscovered sliding activity exists among nuclear mammalian proteins. © The Author(s) 2016. Published by Oxford University Press on behalf of Nucleic Acids Research.
-
A Structural Basis for How Motile Cilia Beat
Satir, Peter; Heuser, Thomas; Sale, Winfield S.
2014-01-01
The motile cilium is a mechanical wonder, a cellular nanomachine that produces a high-speed beat based on a cycle of bends that move along an axoneme made of 9+2 microtubules. The molecular motors, dyneins, power the ciliary beat. The dyneins are compacted into inner and outer dynein arms, whose activity is highly regulated to produce microtubule sliding and axonemal bending. The switch point hypothesis was developed long ago to account for how sliding in the presence of axonemal radial spoke–central pair interactions causes the ciliary beat. Since then, a new genetic, biochemical, and structural complexity has been discovered, in part, with Chlamydomonas mutants, with high-speed, high-resolution analysis of movement and with cryoelectron tomography. We stand poised on the brink of new discoveries relating to the molecular control of motility that extend and refine our understanding of the basic events underlying the switching of arm activity and of bend formation and propagation. PMID:26955066
-
McCauslin, Christine Seitz; Gunn, Kathryn Elaine; Pirone, Dana; Staiger, Jennifer
2015-01-01
We describe a structured inquiry laboratory exercise that examines transcriptional regulation of the NOS2 gene under conditions that simulate the inflammatory response in macrophages. Using quantitative PCR and the comparative CT method, students are able determine whether transcriptional activation of NOS2 occurs and to what degree. The exercise is aimed at second year undergraduates who possess basic knowledge of gene expression events. It requires only 4-5 hr of dedicated laboratory time and focuses on use of the primary literature, data analysis, and interpretation. Importantly, this exercise provides a mechanism to introduce the concept of differential gene expression and provides a starting point for development of more complex guided or open inquiry projects for students moving into upper level molecular biology, immunology, and biochemistry course work. © 2015 The International Union of Biochemistry and Molecular Biology.
-
Molecular inflammation: underpinnings of aging and age-related diseases.
Chung, Hae Young; Cesari, Matteo; Anton, Stephen; Marzetti, Emanuele; Giovannini, Silvia; Seo, Arnold Young; Carter, Christy; Yu, Byung Pal; Leeuwenburgh, Christiaan
2009-01-01
Recent scientific studies have advanced the notion of chronic inflammation as a major risk factor underlying aging and age-related diseases. In this review, low-grade, unresolved, molecular inflammation is described as an underlying mechanism of aging and age-related diseases, which may serve as a bridge between normal aging and age-related pathological processes. Accumulated data strongly suggest that continuous (chronic) upregulation of pro-inflammatory mediators (e.g., TNF-alpha, IL-1beta, IL-6, COX-2, iNOS) are induced during the aging process due to an age-related redox imbalance that activates many pro-inflammatory signaling pathways, including the NF-kappaB signaling pathway. These pro-inflammatory molecular events are discussed in relation to their role as basic mechanisms underlying aging and age-related diseases. Further, the anti-inflammatory actions of aging-retarding caloric restriction and exercise are reviewed. Thus, the purpose of this review is to describe the molecular roles of age-related physiological functional declines and the accompanying chronic diseases associated with aging. This new view on the role of molecular inflammation as a mechanism of aging and age-related pathogenesis can provide insights into potential interventions that may affect the aging process and reduce age-related diseases, thereby promoting healthy longevity.
-
Molecular Inflammation: Underpinnings of Aging and Age-related Diseases
Chung, Hae Young; Cesari, Matteo; Anton, Stephen; Marzetti, Emanuele; Giovannini, Silvia; Seo, Arnold Young; Carter, Christy; Yu, Byung Pal; Leeuwenburgh, Christiaan
2013-01-01
Recent scientific studies have advanced the notion of chronic inflammation as a major risk factor underlying aging and age-related diseases. In this review, low-grade, unresolved, molecular inflammation is described as an underlying mechanism of aging and age-related diseases, which may serve as a bridge between normal aging and age-related pathological processes. Accumulated data strongly suggest that continuous (chronic) up-regulation of pro-inflammatory mediators (e.g., TNF-α, IL-1β, 6, COX-2, iNOS) are induced during the aging process due to an age-related redox imbalance that activates many pro-inflammatory signaling pathways, including the NF-κB signaling pathway. These pro-inflammatory molecular events are discussed in relation to their role as basic mechanisms underlying aging and age-related diseases. Further, the anti-inflammatory actions of aging-retarding caloric restriction and exercise are reviewed. Thus, the purpose of this review is to describe the molecular roles of age-related physiological functional declines and the accompanying chronic diseases associated with aging. This new view on the role of molecular inflammation as a mechanism of aging and age-related pathogenesis can provide insights into potential interventions that may affect the aging process and reduce age-related diseases, thereby promoting healthy longevity. PMID:18692159
-
[MUC4 research progress in tumor molecular markers].
Zhu, Hua; You, Jinhui
2014-02-01
Mucin antigen 4 (MUC4) is a molecular marker for some malignant tumors for early tumor diagnosis, prognosis and targeted therapy. It provides a new research direction in tumor diagnosis and treatment that will have a wide application prospect. In recent years, there has been a large number of research reports on the basic and clini-a wide application prospect. In recent years, there has been a large number of research reports on the basic and clinical studies about MUC4, but the molecular imaging study about MUC4 is seldom reported. In this paper the recentcal studies about MUC4, but the molecular imaging study about MUC4 is seldom reported. In this paper the recent research about MUC4 on basic and clinical studies is briefly reviewed, and it is expected to promote the development of tumor molecular imaging.
-
Evoli, Stefania; Guzzi, Rita; Rizzuti, Bruno
2013-10-01
The spectroscopic, thermal, and functional properties of blue copper proteins can be modulated by mutations in the metal binding loop. Molecular dynamics simulation was used to compare the conformational properties of azurin and two chimeric variants, which were obtained by inserting into the azurin scaffold the copper binding loop of amicyanin and plastocyanin, respectively. Simulations at room temperature show that the proteins retain their overall structure and exhibit concerted motions among specific inner regions, as revealed by principal component analysis. Molecular dynamics at high temperature indicates that the first events in the unfolding pathway are structurally similar in the three proteins and unfolding starts from the region of the α-helix that is far from the metal binding loop. The results provide details of the denaturation process that are consistent with experimental data and in close agreement with other computational approaches, suggesting a distinct mechanism of unfolding of azurin and its chimeric variants. Moreover, differences observed in the dynamics of specific regions in the three proteins correlate with their thermal behavior, contributing to the determination of the basic factors that influence the stability.
-
Genetic, genomic, and molecular tools for studying the protoploid yeast, L. waltii.
Di Rienzi, Sara C; Lindstrom, Kimberly C; Lancaster, Ragina; Rolczynski, Lisa; Raghuraman, M K; Brewer, Bonita J
2011-02-01
Sequencing of the yeast Kluyveromyces waltii (recently renamed Lachancea waltii) provided evidence of a whole genome duplication event in the lineage leading to the well-studied Saccharomyces cerevisiae. While comparative genomic analyses of these yeasts have proven to be extremely instructive in modeling the loss or maintenance of gene duplicates, experimental tests of the ramifications following such genome alterations remain difficult. To transform L. waltii from an organism of the computational comparative genomic literature into an organism of the functional comparative genomic literature, we have developed genetic, molecular and genomic tools for working with L. waltii. In particular, we have characterized basic properties of L. waltii (growth, ploidy, molecular karyotype, mating type and the sexual cycle), developed transformation, cell cycle arrest and synchronization protocols, and have created centromeric and non-centromeric vectors as well as a genome browser for L. waltii. We hope that these tools will be used by the community to follow up on the ideas generated by sequence data and lead to a greater understanding of eukaryotic biology and genome evolution. 2010 John Wiley & Sons, Ltd.
-
Genetic, genomic, and molecular tools for studying the protoploid yeast, L. waltii
Di Rienzi, Sara C.; Lindstrom, Kimberly C.; Lancaster, Ragina; Rolczynski, Lisa; Raghuraman, M. K.; Brewer, Bonita J.
2011-01-01
Sequencing of the yeast Kluyveromyces waltii (recently renamed Lachancea waltii) provided evidence of a whole genome duplication event in the lineage leading to the well-studied Saccharomyces cerevisiae. While comparative genomic analyses of these yeasts have proven to be extremely instructive in modeling the loss or maintenance of gene duplicates, experimental tests of the ramifications following such genome alterations remain difficult. To transform L. waltii from an organism of the computational comparative genomic literature into an organism of the functional comparative genomic literature, we have developed genetic, molecular and genomic tools for working with L. waltii. In particular, we have characterized basic properties of L. waltii (growth, ploidy, molecular karyotype, mating type and the sexual cycle), developed transformation, cell cycle arrest and synchronization protocols, and have created centromeric and non-centromeric vectors as well as a genome browser for L. waltii. We hope that these tools will be used by the community to follow up on the ideas generated by sequence data and lead to a greater understanding of eukaryotic biology and genome evolution. PMID:21246627
-
Molecular basis of angiosperm tree architecture
USDA-ARS?s Scientific Manuscript database
The shoot architecture of trees greatly impacts orchard and forest management methods. Amassing greater knowledge of the molecular genetics behind tree form can benefit these industries as well as contribute to basic knowledge of plant developmental biology. This review covers basic components of ...
-
The Basic Principles of FDG-PET/CT Imaging.
Basu, Sandip; Hess, Søren; Nielsen Braad, Poul-Erik; Olsen, Birgitte Brinkmann; Inglev, Signe; Høilund-Carlsen, Poul Flemming
2014-10-01
Positron emission tomography (PET) imaging with 2-[(18)F]fluoro-2-deoxy-D-glucose (FDG) forms the basis of molecular imaging. FDG-PET imaging is a multidisciplinary undertaking that requires close interdisciplinary collaboration in a broad team comprising physicians, technologists, secretaries, radio-chemists, hospital physicists, molecular biologists, engineers, and cyclotron technicians. The aim of this review is to provide a brief overview of important basic issues and considerations pivotal to successful patient examinations, including basic physics, instrumentation, radiochemistry, molecular and cell biology, patient preparation, normal distribution of tracer, and potential interpretive pitfalls. Copyright © 2014 Elsevier Inc. All rights reserved.
-
Poorly Understood Aspects of Striated Muscle Contraction
Månsson, Alf
2015-01-01
Muscle contraction results from cyclic interactions between the contractile proteins myosin and actin, driven by the turnover of adenosine triphosphate (ATP). Despite intense studies, several molecular events in the contraction process are poorly understood, including the relationship between force-generation and phosphate-release in the ATP-turnover. Different aspects of the force-generating transition are reflected in the changes in tension development by muscle cells, myofibrils and single molecules upon changes in temperature, altered phosphate concentration, or length perturbations. It has been notoriously difficult to explain all these events within a given theoretical framework and to unequivocally correlate observed events with the atomic structures of the myosin motor. Other incompletely understood issues include the role of the two heads of myosin II and structural changes in the actin filaments as well as the importance of the three-dimensional order. We here review these issues in relation to controversies regarding basic physiological properties of striated muscle. We also briefly consider actomyosin mutation effects in cardiac and skeletal muscle function and the possibility to treat these defects by drugs. PMID:25961006
-
Poorly understood aspects of striated muscle contraction.
Månsson, Alf; Rassier, Dilson; Tsiavaliaris, Georgios
2015-01-01
Muscle contraction results from cyclic interactions between the contractile proteins myosin and actin, driven by the turnover of adenosine triphosphate (ATP). Despite intense studies, several molecular events in the contraction process are poorly understood, including the relationship between force-generation and phosphate-release in the ATP-turnover. Different aspects of the force-generating transition are reflected in the changes in tension development by muscle cells, myofibrils and single molecules upon changes in temperature, altered phosphate concentration, or length perturbations. It has been notoriously difficult to explain all these events within a given theoretical framework and to unequivocally correlate observed events with the atomic structures of the myosin motor. Other incompletely understood issues include the role of the two heads of myosin II and structural changes in the actin filaments as well as the importance of the three-dimensional order. We here review these issues in relation to controversies regarding basic physiological properties of striated muscle. We also briefly consider actomyosin mutation effects in cardiac and skeletal muscle function and the possibility to treat these defects by drugs.
-
Electron and Ion Reactions in Molecular Solids: from water ice to DNA
NASA Astrophysics Data System (ADS)
Huels, Michael A.
2002-05-01
Wherever ionizing radiation interacts with matter, it initiates reaction cascades involving non-thermal ions, radicals, and ballistic secondary electrons, which in turn may lead to substantial physical and chemical modifications of a medium. The detailed study of the fundamental reaction mechanisms which occur on a molecular level aids our general understanding of radiation induced processes in a variety of contexts, ranging from radiobiology to astrochemistry. Here I present measurements of electron (1 - 80 eV) and some ion (1 - 8 eV) mediated reactions in molecular films that resemble biological model systems. These consist of cryogenic films (pure or mixed) of rare gases, oxygen, water, methane, or aromatic hydrocarbons of increasing complexity, including bases, sugars, single and double stranded DNA. Although the basic nature of the electron or ion reaction mechanisms are found to be similar to those in the gas phase, they are often modulated by the physico-chemical characteristics of the medium. Depending on the latter, some reaction channels may be strongly enhanced, some may be quenched, and new reaction pathways, unavailable in the gas phase, may open. Thus, a given reaction cascade may lead to different end-points even in the same target. Although the goal of these studies is to unravel some of the nascent secondary-electron and reactive-ion induced events that contribute to radiation damage in living tissue, the basic observed reactions relate to other areas of application which will be briefly discussed. This research is supported by the Canadian Institutes of Health Research (CIHR), the National Cancer Institutes of Canada, the Natural Science and Engineering Research Council, and NATO.
-
McMurray, Cynthia T.; Vijg, Jan
2015-01-01
This issue of Current Opinions focuses on the dual role of DNA in life and death. In ancient Roman religion and myth, Janus is the god who looks both to the past and to the future. He guides the beginnings of life, its progression from one condition to another, and he foresees distant events. The analogy to DNA could not be stronger. Closely interacting with the environment, our basic genetics provides the origin of life, guides the quality of health with age, predicts disease, and ultimately foresees our end. A shared and deep interest in the origin of life has long prompted our desire to define aging, and, ultimately, to understand whether it can be reversed. In this special issue, the authors collectively review concepts of normative aging, DNA instability, DNA repair, the genetic contribution of age and diet to disease, and how the basic molecular transactions of DNA give it a double life that guides health and survival, as well as the transitions to death. PMID:25282314
-
Adverse outcome pathway (AOP) development and evaluation ...
The Adverse Outcome Pathway provides a construct for assembling mechanistic information at different levels of biological organization in a form designed to support regulatory decision making. In particular, it frames the link between molecular and cellular events that can be measured in high throughput toxicity testing and the organism or population-level events that are commonly relevant in defining risk. Recognizing the importance of this emerging framework, the Organisation for Economic Co-operation and Development (OECD) launched a program to support the development, documentation and consideration of AOPs by the international community in 2012 (http://www.oecd.org/chemicalsafety/testing/adverse-outcome-pathways-molecular-screening-and-toxicogenomics.htm). In 2014, a handbook (https://aopkb.org/common/AOP_Handbook.pdf) was developed to guide users in the documentation and evaluation of AOPs and their entry into an official knowledgebase. The handbook draws on longstanding experience in consideration of mechanistic data (e.g., mode of action analysis) to inform risk assessment. To further assist users, a training program was developed by members of the OECD Extended Advisory Group to teach users the basic principles of AOP development and the best practices as outlined in the OECD AOP handbook. Training sessions began in early 2015, and this course will provide training for interested SOT scientists. Following this course, all participants will be familiar w
-
Current Events in Basic Business Education
ERIC Educational Resources Information Center
Van Hook, Barry L.
1974-01-01
The author suggests the use of current events to stimulate student interest in basic business courses. Suggested topics described are monetary devaluation, interest rate adjustments, Illinois no-fault automobile insurance, labor-management disputes, Dow-Jones average, Picasso's death, energy crisis, sale of surplus wheat, local consumer assistance…
-
DOE Office of Scientific and Technical Information (OSTI.GOV)
Knudsen, J.K.; Smith, C.L.
The steps involved to incorporate parameter uncertainty into the Nuclear Regulatory Commission (NRC) accident sequence precursor (ASP) models is covered in this paper. Three different uncertainty distributions (i.e., lognormal, beta, gamma) were evaluated to Determine the most appropriate distribution. From the evaluation, it was Determined that the lognormal distribution will be used for the ASP models uncertainty parameters. Selection of the uncertainty parameters for the basic events is also discussed. This paper covers the process of determining uncertainty parameters for the supercomponent basic events (i.e., basic events that are comprised of more than one component which can have more thanmore » one failure mode) that are utilized in the ASP models. Once this is completed, the ASP model is ready to be utilized to propagate parameter uncertainty for event assessments.« less
-
Building a Database for a Quantitative Model
NASA Technical Reports Server (NTRS)
Kahn, C. Joseph; Kleinhammer, Roger
2014-01-01
A database can greatly benefit a quantitative analysis. The defining characteristic of a quantitative risk, or reliability, model is the use of failure estimate data. Models can easily contain a thousand Basic Events, relying on hundreds of individual data sources. Obviously, entering so much data by hand will eventually lead to errors. Not so obviously entering data this way does not aid linking the Basic Events to the data sources. The best way to organize large amounts of data on a computer is with a database. But a model does not require a large, enterprise-level database with dedicated developers and administrators. A database built in Excel can be quite sufficient. A simple spreadsheet database can link every Basic Event to the individual data source selected for them. This database can also contain the manipulations appropriate for how the data is used in the model. These manipulations include stressing factors based on use and maintenance cycles, dormancy, unique failure modes, the modeling of multiple items as a single "Super component" Basic Event, and Bayesian Updating based on flight and testing experience. A simple, unique metadata field in both the model and database provides a link from any Basic Event in the model to its data source and all relevant calculations. The credibility for the entire model often rests on the credibility and traceability of the data.
-
Oxygen regulates molecular mechanisms of cancer progression and metastasis.
Gupta, Kartik; Madan, Esha; Sayyid, Muzzammil; Arias-Pulido, Hugo; Moreno, Eduardo; Kuppusamy, Periannan; Gogna, Rajan
2014-03-01
Oxygen is the basic molecule which supports life and it truly is "god's gift to life." Despite its immense importance, research on "oxygen biology" has never received the light of the day and has been limited to physiological and biochemical studies. It seems that in modern day biology, oxygen research is summarized in one word "hypoxia." Scientists have focused on hypoxia-induced transcriptomics and molecular-cellular alterations exclusively in disease models. Interestingly, the potential of oxygen to control the basic principles of biology like homeostatic maintenance, transcription, replication, and protein folding among many others, at the molecular level, has been completely ignored. Here, we present a perspective on the crucial role played by oxygen in regulation of basic biological phenomena. Our conclusion highlights the importance of establishing novel research areas like oxygen biology, as there is great potential in this field for basic science discoveries and clinical benefits to the society.
-
Li, Jie; Sun, Jin; Cui, Shengmiao; He, Zhonggui
2006-11-03
Linear solvation energy relationships (LSERs) amended by the introduction of a molecular electronic factor were employed to establish quantitative structure-retention relationships using immobilized artificial membrane (IAM) chromatography, in particular ionizable solutes. The chromatographic indices, log k(IAM), were determined by HPLC on an IAM.PC.DD2 column for 53 structurally diverse compounds, including neutral, acidic and basic compounds. Unlike neutral compounds, the IAM chromatographic retention of ionizable compounds was affected by their molecular charge state. When the mean net charge per molecule (delta) was introduced into the amended LSER as the sixth variable, the LSER regression coefficient was significantly improved for the test set including ionizable solutes. The delta coefficients of acidic and basic compounds were quite different indicating that the molecular electronic factor had a markedly different impact on the retention of acidic and basic compounds on IAM column. Ionization of acidic compounds containing a carboxylic group tended to impair their retention on IAM, while the ionization of basic compounds did not have such a marked effect. In addition, the extra-interaction with the polar head of phospholipids might cause a certain change in the retention of basic compounds. A comparison of calculated and experimental retention indices suggested that the semi-empirical LSER amended by the addition of a molecular electronic factor was able to reproduce adequately the experimental retention factors of the structurally diverse solutes investigated.
-
Translational bioinformatics: linking the molecular world to the clinical world.
Altman, R B
2012-06-01
Translational bioinformatics represents the union of translational medicine and bioinformatics. Translational medicine moves basic biological discoveries from the research bench into the patient-care setting and uses clinical observations to inform basic biology. It focuses on patient care, including the creation of new diagnostics, prognostics, prevention strategies, and therapies based on biological discoveries. Bioinformatics involves algorithms to represent, store, and analyze basic biological data, including DNA sequence, RNA expression, and protein and small-molecule abundance within cells. Translational bioinformatics spans these two fields; it involves the development of algorithms to analyze basic molecular and cellular data with an explicit goal of affecting clinical care.
-
Sexual polyploidization in plants – cytological mechanisms and molecular regulation
De Storme, Nico; Geelen, Danny
2013-01-01
In the plant kingdom, events of whole genome duplication or polyploidization are generally believed to occur via alterations of the sexual reproduction process. Thereby, diploid pollen and eggs are formed that contain the somatic number of chromosomes rather than the gametophytic number. By participating in fertilization, these so-called 2n gametes generate polyploid offspring and therefore constitute the basis for the establishment of polyploidy in plants. In addition, diplogamete formation, through meiotic restitution, is an essential component of apomixis and also serves as an important mechanism for the restoration of F1 hybrid fertility. Characterization of the cytological mechanisms and molecular factors underlying 2n gamete formation is therefore not only relevant for basic plant biology and evolution, but may also provide valuable cues for agricultural and biotechnological applications (e.g. reverse breeding, clonal seeds). Recent data have provided novel insights into the process of 2n pollen and egg formation and have revealed multiple means to the same end. Here, we summarize the cytological mechanisms and molecular regulatory networks underlying 2n gamete formation, and outline important mitotic and meiotic processes involved in the ectopic induction of sexual polyploidization. PMID:23421646
-
Sexual polyploidization in plants--cytological mechanisms and molecular regulation.
De Storme, Nico; Geelen, Danny
2013-05-01
In the plant kingdom, events of whole genome duplication or polyploidization are generally believed to occur via alterations of the sexual reproduction process. Thereby, diploid pollen and eggs are formed that contain the somatic number of chromosomes rather than the gametophytic number. By participating in fertilization, these so-called 2n gametes generate polyploid offspring and therefore constitute the basis for the establishment of polyploidy in plants. In addition, diplogamete formation, through meiotic restitution, is an essential component of apomixis and also serves as an important mechanism for the restoration of F1 hybrid fertility. Characterization of the cytological mechanisms and molecular factors underlying 2n gamete formation is therefore not only relevant for basic plant biology and evolution, but may also provide valuable cues for agricultural and biotechnological applications (e.g. reverse breeding, clonal seeds). Recent data have provided novel insights into the process of 2n pollen and egg formation and have revealed multiple means to the same end. Here, we summarize the cytological mechanisms and molecular regulatory networks underlying 2n gamete formation, and outline important mitotic and meiotic processes involved in the ectopic induction of sexual polyploidization. © 2013 Ghent University. New Phytologist © 2013 New Phytologist Trust.
-
Field Effect Sensors for Nucleic Acid Detection: Recent Advances and Future Perspectives
Veigas, Bruno; Fortunato, Elvira; Baptista, Pedro V.
2015-01-01
In the last decade the use of field-effect-based devices has become a basic structural element in a new generation of biosensors that allow label-free DNA analysis. In particular, ion sensitive field effect transistors (FET) are the basis for the development of radical new approaches for the specific detection and characterization of DNA due to FETs’ greater signal-to-noise ratio, fast measurement capabilities, and possibility to be included in portable instrumentation. Reliable molecular characterization of DNA and/or RNA is vital for disease diagnostics and to follow up alterations in gene expression profiles. FET biosensors may become a relevant tool for molecular diagnostics and at point-of-care. The development of these devices and strategies should be carefully designed, as biomolecular recognition and detection events must occur within the Debye length. This limitation is sometimes considered to be fundamental for FET devices and considerable efforts have been made to develop better architectures. Herein we review the use of field effect sensors for nucleic acid detection strategies—from production and functionalization to integration in molecular diagnostics platforms, with special focus on those that have made their way into the diagnostics lab. PMID:25946631
-
Seniors: Current Events and Consumer Awareness. Final Report.
ERIC Educational Resources Information Center
Molek, Carol
A project was conducted to design and implement a curriculum for older adults in the areas of consumer events and consumer awareness. The project aimed to improve the seniors' basic skills by providing relevant content in a basic education context. During the project a curriculum was developed and presented through workshops held in 2 senior…
-
Cataloging the biomedical world of pain through semi-automated curation of molecular interactions
Jamieson, Daniel G.; Roberts, Phoebe M.; Robertson, David L.; Sidders, Ben; Nenadic, Goran
2013-01-01
The vast collection of biomedical literature and its continued expansion has presented a number of challenges to researchers who require structured findings to stay abreast of and analyze molecular mechanisms relevant to their domain of interest. By structuring literature content into topic-specific machine-readable databases, the aggregate data from multiple articles can be used to infer trends that can be compared and contrasted with similar findings from topic-independent resources. Our study presents a generalized procedure for semi-automatically creating a custom topic-specific molecular interaction database through the use of text mining to assist manual curation. We apply the procedure to capture molecular events that underlie ‘pain’, a complex phenomenon with a large societal burden and unmet medical need. We describe how existing text mining solutions are used to build a pain-specific corpus, extract molecular events from it, add context to the extracted events and assess their relevance. The pain-specific corpus contains 765 692 documents from Medline and PubMed Central, from which we extracted 356 499 unique normalized molecular events, with 261 438 single protein events and 93 271 molecular interactions supplied by BioContext. Event chains are annotated with negation, speculation, anatomy, Gene Ontology terms, mutations, pain and disease relevance, which collectively provide detailed insight into how that event chain is associated with pain. The extracted relations are visualized in a wiki platform (wiki-pain.org) that enables efficient manual curation and exploration of the molecular mechanisms that underlie pain. Curation of 1500 grouped event chains ranked by pain relevance revealed 613 accurately extracted unique molecular interactions that in the future can be used to study the underlying mechanisms involved in pain. Our approach demonstrates that combining existing text mining tools with domain-specific terms and wiki-based visualization can facilitate rapid curation of molecular interactions to create a custom database. Database URL: ••• PMID:23707966
-
Cataloging the biomedical world of pain through semi-automated curation of molecular interactions.
Jamieson, Daniel G; Roberts, Phoebe M; Robertson, David L; Sidders, Ben; Nenadic, Goran
2013-01-01
The vast collection of biomedical literature and its continued expansion has presented a number of challenges to researchers who require structured findings to stay abreast of and analyze molecular mechanisms relevant to their domain of interest. By structuring literature content into topic-specific machine-readable databases, the aggregate data from multiple articles can be used to infer trends that can be compared and contrasted with similar findings from topic-independent resources. Our study presents a generalized procedure for semi-automatically creating a custom topic-specific molecular interaction database through the use of text mining to assist manual curation. We apply the procedure to capture molecular events that underlie 'pain', a complex phenomenon with a large societal burden and unmet medical need. We describe how existing text mining solutions are used to build a pain-specific corpus, extract molecular events from it, add context to the extracted events and assess their relevance. The pain-specific corpus contains 765 692 documents from Medline and PubMed Central, from which we extracted 356 499 unique normalized molecular events, with 261 438 single protein events and 93 271 molecular interactions supplied by BioContext. Event chains are annotated with negation, speculation, anatomy, Gene Ontology terms, mutations, pain and disease relevance, which collectively provide detailed insight into how that event chain is associated with pain. The extracted relations are visualized in a wiki platform (wiki-pain.org) that enables efficient manual curation and exploration of the molecular mechanisms that underlie pain. Curation of 1500 grouped event chains ranked by pain relevance revealed 613 accurately extracted unique molecular interactions that in the future can be used to study the underlying mechanisms involved in pain. Our approach demonstrates that combining existing text mining tools with domain-specific terms and wiki-based visualization can facilitate rapid curation of molecular interactions to create a custom database. Database URL: •••
-
What are the priorities in basic asthma research? A United Kingdom perspective.
Hallsworth, Matthew P; Major, Philippa J; Barnes, Jack; Lee, Tak H
2003-02-01
The National Asthma Campaign (in the United Kingdom) has recently completed a strategic review of priorities for basic asthma research over the next 5 to 10 years. Leading asthma experts and representatives of the main funding agencies were involved in a nationwide consultation. Discussions were carried out in 7 thematic areas: Genetics of asthma, early-life events, environmental influences, immunology and immunotherapy, inflammation and anti-inflammation, airway remodeling, and the interface between academia and industry. Discussions were not restricted by considerations of financial affordability but were driven by vision and science. The consultation highlighted a number of generic issues pertaining to the organization of basic asthma research. Phenotypes of asthma require more robust characterization, particularly for genetic studies. Emphasis on longitudinal studies should be encouraged, and more information can still be gained from existing well-characterized asthma cohorts, though this requires some coordination. Human research is particularly strong and should continue, and the use of human tissue is vital to our understanding of the disease at the cellular and molecular levels. Animal models of asthma remain an important tool with which to dissect disease mechanisms, but they must be improved and refined. The consultation covered a wide range of issues and highlighted the need for collaboration at all levels between research groups and with industry and also between funding agencies. The recommendations made have relevance to everyone involved in basic asthma research. This article describes the recommendations and reviews the specific research issues relating to each of the 7 thematic areas.
-
Centro de Biologia Molecular "Severo Ochoa": a center for basic research into Alzheimer's disease.
Avila, Jesus; Hernandez, Felix; Wandosell, Francisco; Lucas, Jose J; Esteban, Jose A; Ledesma, M Dolores; Bullido, Maria J
2010-01-01
One important aspect of studies carried out at the Center for Molecular Biology "Severo Ochoa" is focused on basic aspects of Alzheimer's disease, mainly the search for suitable therapeutic targets for this disorder. Several groups at the Center are involved in these studies, and, in this spotlight, the work they are carrying out will be described.
-
Ultrasensitive response motifs: basic amplifiers in molecular signalling networks
Zhang, Qiang; Bhattacharya, Sudin; Andersen, Melvin E.
2013-01-01
Multi-component signal transduction pathways and gene regulatory circuits underpin integrated cellular responses to perturbations. A recurring set of network motifs serve as the basic building blocks of these molecular signalling networks. This review focuses on ultrasensitive response motifs (URMs) that amplify small percentage changes in the input signal into larger percentage changes in the output response. URMs generally possess a sigmoid input–output relationship that is steeper than the Michaelis–Menten type of response and is often approximated by the Hill function. Six types of URMs can be commonly found in intracellular molecular networks and each has a distinct kinetic mechanism for signal amplification. These URMs are: (i) positive cooperative binding, (ii) homo-multimerization, (iii) multistep signalling, (iv) molecular titration, (v) zero-order covalent modification cycle and (vi) positive feedback. Multiple URMs can be combined to generate highly switch-like responses. Serving as basic signal amplifiers, these URMs are essential for molecular circuits to produce complex nonlinear dynamics, including multistability, robust adaptation and oscillation. These dynamic properties are in turn responsible for higher-level cellular behaviours, such as cell fate determination, homeostasis and biological rhythm. PMID:23615029
-
Propagating Molecular Recognition Events through Highly Integrated Sense-Response Chemical Systems
2017-08-01
Propagating Molecular Recognition Events through Highly Integrated Sense-Response Chemical Systems The views, opinions and/or findings contained in...University of California - San Diego Title: Propagating Molecular Recognition Events through Highly Integrated Sense-Response Chemical Systems Report Term...including enzymatic reactions , occurring at the aqueous interfaces of thermotropic LCs show promise as the basis of biomolecular triggers of LC
-
Normal and abnormal development of the kidney: a clinician's interpretation of current knowledge.
Glassberg, Kenneth I
2002-06-01
The recent basic science literature is replete with new discoveries in the molecular genetics of renal development. However, little of this information has filtered into urological textbooks and journals. An effort is made herein to integrate these new findings and propose a more sophisticated blueprint of renal development than the one traditionally taught in medical school and residency. To accomplish this goal the author offers simple definitions and interpretations of complicated terms and events, and points out how maldevelopment results when mutations take place. A review of recent advances in the molecular genetics of renal development and maldevelopment was done. Renal metanephric development results from the expression of many genes in the ureteral bud and metanephric blastema with each sending messages to the other to induce organogenesis. Currently an understanding of normal renal organogenesis stems from a study of disease states resulting from perturbations in molecular genetics. In turn, a better understanding of normal renal organogenesis facilitates an understanding of how dysplasia, hypoplasia, cystic disease and tumors develop when molecular genetics go awry. For each form of renal dysgenesis and for most renal tumors 1 or more gene defects are eventually identified. The young urologist based in these new discoveries would be better prepared to make the breakthroughs in the future that are necessary for advancing the prevention and management of these conditions.
-
Coutelle, C; Speer, A; Grade, K; Rosenthal, A; Hunger, H D
1989-01-01
The introduction of molecular human genetics has become a paradigma for the application of genetic engineering in medicine. The main principles of this technology are the isolation of molecular probes, their application in hybridization reactions, specific gene-amplification by the polymerase chain reaction, and DNA sequencing reactions. These methods are used for the analysis of monogenic diseases by linkage studies and the elucidation of the molecular defect causing these conditions, respectively. They are also the basis for genomic diagnosis of monogenic diseases, introduced into the health care system of the GDR by a national project on Duchenne/Becker muscular dystrophy, Cystic Fibrosis and Phenylketonuria. The rapid development of basic research on the molecular analysis of the human genome and genomic diagnosis indicates, that human molecular genetics is becoming a decisive basic discipline of modern medicine.
-
MOLECULAR DIAGNOSTICS - ANOTHER PIECE IN THE ENVIRONMENTAL PUZZLE
Molecular biology offers sensitive and expedient tools for the detection of exposure to environmental stressors. Molecular approaches provide the means for detection of the "first cellular event(s)" in response to environmental changes-specifically, immediate changes in gene expr...
-
Selli, Cigdem; Yıldırım, Gokce; Kaymak, Aysegul; Karacicek, Bilge; Ogut, Deniz; Gungor, Turkan; Erem, Erdem; Ege, Mehmet; Bümen, Nilay; Tosun, Metiner
2014-01-01
This study includes the results of a 2-day education project titled "Molecular Biology Laboratory Summer School, MoBiLYO." The project was held at a University Research Center by scientists from Department of Pharmacology and graduate students. The project was composed of introductory lectures, model construction, DNA isolation, polymerase chain reaction (PCR), and gel electrophoresis. The participants were 13-year-old eighth-graders attending primary schools affiliated with Ministry of National Education in urban and rural areas of Izmir, Turkey. The purpose of this study was to introduce basic molecular biology concepts through individually performed experiments such as PCR and gel electrophoresis integrated with creative drama. The students were assessed at the beginning and the end of each project day via mini-tests, experimental and presentation skills evaluation forms. Data showed that students' knowledge about DNA structure and basic molecular biology techniques significantly increased. On the basis of experimental and presentational skills, there was no significant difference between kids from urban and rural schools or between public and boarding public schools, whereas the average score of girls was significantly higher than that of boys. In conclusion, individually performed experiments integrated with creative drama significantly increased students' perception of complex experimental procedures on basic molecular biology concepts. Data suggests that integration of these concepts into the science and technology curriculum of Turkish primary education may support the recruitment of future scientists who can handle rapidly developing genomic techniques that will affect our everyday life. © 2014 by The International Union of Biochemistry and Molecular Biology.
-
ERIC Educational Resources Information Center
Hafner, Mathias
2008-01-01
Cell biology and molecular imaging technologies have made enormous progress in basic research. However, the transfer of this knowledge to the pharmaceutical drug discovery process, or even therapeutic improvements for disorders such as neuronal diseases, is still in its infancy. This transfer needs scientists who can integrate basic research with…
-
Bibliometric analysis of original molecular biology research in anaesthesia.
Schreiber, K; Girard, T; Kindler, C H
2004-10-01
Molecular biology has expanded the horizons of anaesthesia during the last 20 years and has led to an increase of basic science articles that are published in the specialised anaesthetic journals or originate in anaesthetic institutions. We searched for and analysed the specific features, such as year of publication, publishing journal, and country of origin, of all such molecular biology articles stored in the MEDLINE database during the period 1986-2002. We identified 1265 original articles that used molecular biology techniques; 223 (18%) of these articles were published in anaesthetic journals and 1042 (82%) articles in 556 other biomedical journals. While in the late 1980s only a few molecular biology articles were published each year by anaesthetic institutions, worldwide this number reached approximately 200 basic science articles by the end of 2002. The USA clearly dominates the field of anaesthesia with respect to molecular biology research with 839 (66%) such articles.
-
Introduction to molecular topology: basic concepts and application to drug design.
Gálvez, Jorge; Gálvez-Llompart, María; García-Domenech, Ramón
2012-09-01
In this review it is dealt the use of molecular topology (MT) in the selection and design of new drugs. After an introduction of the actual methods used for drug design, the basic concepts of MT are defined, including examples of calculation of topological indices, which are numerical descriptors of molecular structures. The goal is making this calculation familiar to the potential students and allowing a straightforward comprehension of the topic. Finally, the achievements obtained in this field are detailed, so that the reader can figure out the great interest of this approach.
-
NASA Astrophysics Data System (ADS)
Shirai, Yasuhiro; Minami, Kosuke; Nakanishi, Waka; Yonamine, Yusuke; Joachim, Christian; Ariga, Katsuhiko
2016-11-01
Nanomachine and molecular machines are state-of-the-art objects in current physics and chemistry. The operation and manufacturing of nanosize machines are top-level technologies that we have desired to accomplish for a long time. There have been extensive attempts to design and synthesize nanomachines. In this paper, we review the these attempts using the concept of nanoarchitectonics toward the design, synthesis, and testing of molecular machinery, especially at interfacial media. In the first half of this review, various historical attempts to design and prepare nanomachines are introduced as well as their operation mechanisms from their basic principles. Furthermore, in order to emphasize the importance and possibilities of this research field, we also give examples of two new challenging topics in the second half of this review: (i) a world wide nanocar race and (ii) new modes of nanomachine operation on water. The nanocar race event involves actual use of nanomachines and will take place in the near future, and nanomachine operation of a dynamic fluidic interface will enable future advances in nanomachine science and technology.
-
[ON THE ORIGIN OF HYPERVIRULENCE OF THE CAUSATIVE AGENT OF PLAGUE].
Anisimov, N V; Kislichkina, A A; Platonov, M E; Evseeva, V V; Kadnikova, L A; Lipatnikova, N A; Bogun, A G; Dentovskaya, S V; Anisimov, A P
2016-01-01
The attempt to combine Yersinia pseudotuberculosis and Yersinia pestis into one species has been unsupported by microbiologists due to the specific features of the epidemiology and clinical presentations of their induced diseases and to basic differences in their virulence. Pseudotuberculosis is predominantly a relatively mild human intestinal infection transmitted through contaminated food and plague is an acute generalized disease with high mortality, which is most frequently transmitted by the bites of infected fleas. Y. pestis hypervirulence, the ability of single bacteria to ensure the development of predagonal bacteriemia in rodents, which is sufficient to contaminate the fleas, is one of the main events during pathogen adaptation to a new ecological niche. By analyzing the data of molecular typing of the representative kits of naturally occurring Y. pestis isolates, the authois consider the issues of formation of intraspecies groups with universal hypervirulence, as well as biovars that are highly virulent only to their major host. A strategy for searching for selective virulence factors, the potential molecular targets for vaccination and etiotropic treatment of plague, is discussed.
-
Translational physiology: from molecules to public health.
Seals, Douglas R
2013-07-15
The term 'translational research' was coined 20 years ago and has become a guiding influence in biomedical research. It refers to a process by which the findings of basic research are extended to the clinical research setting (bench to bedside) and then to clinical practice and eventually health policy (bedside to community). It is a dynamic, multidisciplinary research approach. The concept of translational physiology applies the translational research model to the physiological sciences. It differs from the traditional areas of integrative and clinical physiology by its broad investigative scope of basic research to community health. Translational physiology offers exciting opportunities, but presently is under-developed and -utilized. A key challenge will be to expand physiological research by extending investigations to communities of patients and healthy (or at risk) individuals. This will allow bidirectional physiological investigation throughout the translational continuum: basic research observations can be studied up to the population level, and mechanisms can be assessed by 'reverse translation' in clinical research settings and preclinical models based on initial observations made in populations. Examples of translational physiology questions, experimental approaches, roadblocks and strategies for promotion are discussed. Translational physiology provides a novel framework for physiology programs and an investigational platform for physiologists to study function from molecular events to public health. It holds promise for enhancing the completeness and societal impact of our work, while further solidifying the critical role of physiology in the biomedical research enterprise.
-
Translational physiology: from molecules to public health
Seals, Douglas R
2013-01-01
The term ‘translational research’ was coined 20 years ago and has become a guiding influence in biomedical research. It refers to a process by which the findings of basic research are extended to the clinical research setting (bench to bedside) and then to clinical practice and eventually health policy (bedside to community). It is a dynamic, multidisciplinary research approach. The concept of translational physiology applies the translational research model to the physiological sciences. It differs from the traditional areas of integrative and clinical physiology by its broad investigative scope of basic research to community health. Translational physiology offers exciting opportunities, but presently is under-developed and -utilized. A key challenge will be to expand physiological research by extending investigations to communities of patients and healthy (or at risk) individuals. This will allow bidirectional physiological investigation throughout the translational continuum: basic research observations can be studied up to the population level, and mechanisms can be assessed by ‘reverse translation’ in clinical research settings and preclinical models based on initial observations made in populations. Examples of translational physiology questions, experimental approaches, roadblocks and strategies for promotion are discussed. Translational physiology provides a novel framework for physiology programs and an investigational platform for physiologists to study function from molecular events to public health. It holds promise for enhancing the completeness and societal impact of our work, while further solidifying the critical role of physiology in the biomedical research enterprise. PMID:23732641
-
Systems Toxicology: From Basic Research to Risk Assessment
2014-01-01
Systems Toxicology is the integration of classical toxicology with quantitative analysis of large networks of molecular and functional changes occurring across multiple levels of biological organization. Society demands increasingly close scrutiny of the potential health risks associated with exposure to chemicals present in our everyday life, leading to an increasing need for more predictive and accurate risk-assessment approaches. Developing such approaches requires a detailed mechanistic understanding of the ways in which xenobiotic substances perturb biological systems and lead to adverse outcomes. Thus, Systems Toxicology approaches offer modern strategies for gaining such mechanistic knowledge by combining advanced analytical and computational tools. Furthermore, Systems Toxicology is a means for the identification and application of biomarkers for improved safety assessments. In Systems Toxicology, quantitative systems-wide molecular changes in the context of an exposure are measured, and a causal chain of molecular events linking exposures with adverse outcomes (i.e., functional and apical end points) is deciphered. Mathematical models are then built to describe these processes in a quantitative manner. The integrated data analysis leads to the identification of how biological networks are perturbed by the exposure and enables the development of predictive mathematical models of toxicological processes. This perspective integrates current knowledge regarding bioanalytical approaches, computational analysis, and the potential for improved risk assessment. PMID:24446777
-
Systems toxicology: from basic research to risk assessment.
Sturla, Shana J; Boobis, Alan R; FitzGerald, Rex E; Hoeng, Julia; Kavlock, Robert J; Schirmer, Kristin; Whelan, Maurice; Wilks, Martin F; Peitsch, Manuel C
2014-03-17
Systems Toxicology is the integration of classical toxicology with quantitative analysis of large networks of molecular and functional changes occurring across multiple levels of biological organization. Society demands increasingly close scrutiny of the potential health risks associated with exposure to chemicals present in our everyday life, leading to an increasing need for more predictive and accurate risk-assessment approaches. Developing such approaches requires a detailed mechanistic understanding of the ways in which xenobiotic substances perturb biological systems and lead to adverse outcomes. Thus, Systems Toxicology approaches offer modern strategies for gaining such mechanistic knowledge by combining advanced analytical and computational tools. Furthermore, Systems Toxicology is a means for the identification and application of biomarkers for improved safety assessments. In Systems Toxicology, quantitative systems-wide molecular changes in the context of an exposure are measured, and a causal chain of molecular events linking exposures with adverse outcomes (i.e., functional and apical end points) is deciphered. Mathematical models are then built to describe these processes in a quantitative manner. The integrated data analysis leads to the identification of how biological networks are perturbed by the exposure and enables the development of predictive mathematical models of toxicological processes. This perspective integrates current knowledge regarding bioanalytical approaches, computational analysis, and the potential for improved risk assessment.
-
NASA Astrophysics Data System (ADS)
Siontorou, Christina G.
2012-12-01
Biosensors are analytic devices that incorporate a biochemical recognition system (biological, biologicalderived or biomimic: enzyme, antibody, DNA, receptor, etc.) in close contact with a physicochemical transducer (electrochemical, optical, piezoelectric, conductimetric, etc.) that converts the biochemical information, produced by the specific biological recognition reaction (analyte-biomolecule binding), into a chemical or physical output signal, related to the concentration of the analyte in the measuring sample. The biosensing concept is based on natural chemoreception mechanisms, which are feasible over/within/by means of a biological membrane, i.e., a structured lipid bilayer, incorporating or attached to proteinaceous moieties that regulate molecular recognition events which trigger ion flux changes (facilitated or passive) through the bilayer. The creation of functional structures that are similar to natural signal transduction systems, correlating and interrelating compatibly and successfully the physicochemical transducer with the lipid film that is self-assembled on its surface while embedding the reconstituted biological recognition system, and at the same time manage to satisfy the basic conditions for measuring device development (simplicity, easy handling, ease of fabrication) is far from trivial. The aim of the present work is to present a methodological framework for designing such molecular sensing interfaces, functioning within a knowledge-based system built on an ontological platform for supplying sub-systems options, compatibilities, and optimization parameters.
-
Kim, Jeong-Su; Khamoui, Andy V; Jo, Edward; Park, Bong-Sup; Lee, Won Jun
2013-10-01
Cancer cachexia is a life-threatening condition characterized by involuntary body weight loss and skeletal muscle wasting. In addition to being associated with poor prognosis and reduced survival, patients with cachexia exhibit a critical loss of physical function that impinges upon their ability to perform basic activities of daily living. Consequently, there is a loss of independence and a drastically reduced quality of life. Despite being a major unmet medical need of patients, very few treatment options exist. Maintaining muscle mass represents an important objective in the cancer patient trajectory not only because it relates to one's capacity to perform activities of daily living, but also because muscle preservation may be a critical determinant of survival while in a tumor-bearing state. In this regard, research has been directed towards identifying countermeasures effective in preserving muscle. With respect to nutritional approaches, administration of the leucine metabolite β-hydroxy-β-methylbutyrate (HMB) could be a viable component in multi-modal therapies targeting cancer cachexia. Evidence suggests that HMB treatment promotes regenerative events (i.e. myogenic program), suppresses protein degradation, and activates signaling pathways preceding protein synthesis and skeletal muscle growth. HMB therefore, could conceivably act on key regulatory events driving cancer cachexia, thereby favoring muscle growth/preservation. In this review, we take a mechanistic approach in making a case for the use of HMB provision as a possible therapeutic strategy for cancer cachexia by highlighting the cellular and molecular aspects of HMB function.
-
The chromatin-binding protein Smyd1 restricts adult mammalian heart growth
Kimball, Todd; Rasmussen, Tara L.; Rosa-Garrido, Manuel; Chen, Haodong; Tran, Tam; Miller, Mickey R.; Gray, Ricardo; Jiang, Shanxi; Ren, Shuxun; Wang, Yibin; Tucker, Haley O.; Vondriska, Thomas M.
2016-01-01
All terminally differentiated organs face two challenges, maintaining their cellular identity and restricting organ size. The molecular mechanisms responsible for these decisions are of critical importance to organismal development, and perturbations in their normal balance can lead to disease. A hallmark of heart failure, a condition affecting millions of people worldwide, is hypertrophic growth of cardiomyocytes. The various forms of heart failure in human and animal models share conserved transcriptome remodeling events that lead to expression of genes normally silenced in the healthy adult heart. However, the chromatin remodeling events that maintain cell and organ size are incompletely understood; insights into these mechanisms could provide new targets for heart failure therapy. Using a quantitative proteomics approach to identify muscle-specific chromatin regulators in a mouse model of hypertrophy and heart failure, we identified upregulation of the histone methyltransferase Smyd1 during disease. Inducible loss-of-function studies in vivo demonstrate that Smyd1 is responsible for restricting growth in the adult heart, with its absence leading to cellular hypertrophy, organ remodeling, and fulminate heart failure. Molecular studies reveal Smyd1 to be a muscle-specific regulator of gene expression and indicate that Smyd1 modulates expression of gene isoforms whose expression is associated with cardiac pathology. Importantly, activation of Smyd1 can prevent pathological cell growth. These findings have basic implications for our understanding of cardiac pathologies and open new avenues to the treatment of cardiac hypertrophy and failure by modulating Smyd1. PMID:27663768
-
The chromatin-binding protein Smyd1 restricts adult mammalian heart growth.
Franklin, Sarah; Kimball, Todd; Rasmussen, Tara L; Rosa-Garrido, Manuel; Chen, Haodong; Tran, Tam; Miller, Mickey R; Gray, Ricardo; Jiang, Shanxi; Ren, Shuxun; Wang, Yibin; Tucker, Haley O; Vondriska, Thomas M
2016-11-01
All terminally differentiated organs face two challenges, maintaining their cellular identity and restricting organ size. The molecular mechanisms responsible for these decisions are of critical importance to organismal development, and perturbations in their normal balance can lead to disease. A hallmark of heart failure, a condition affecting millions of people worldwide, is hypertrophic growth of cardiomyocytes. The various forms of heart failure in human and animal models share conserved transcriptome remodeling events that lead to expression of genes normally silenced in the healthy adult heart. However, the chromatin remodeling events that maintain cell and organ size are incompletely understood; insights into these mechanisms could provide new targets for heart failure therapy. Using a quantitative proteomics approach to identify muscle-specific chromatin regulators in a mouse model of hypertrophy and heart failure, we identified upregulation of the histone methyltransferase Smyd1 during disease. Inducible loss-of-function studies in vivo demonstrate that Smyd1 is responsible for restricting growth in the adult heart, with its absence leading to cellular hypertrophy, organ remodeling, and fulminate heart failure. Molecular studies reveal Smyd1 to be a muscle-specific regulator of gene expression and indicate that Smyd1 modulates expression of gene isoforms whose expression is associated with cardiac pathology. Importantly, activation of Smyd1 can prevent pathological cell growth. These findings have basic implications for our understanding of cardiac pathologies and open new avenues to the treatment of cardiac hypertrophy and failure by modulating Smyd1. Copyright © 2016 the American Physiological Society.
-
78 FR 32260 - Center For Scientific Review; Notice of Closed Meetings
Federal Register 2010, 2011, 2012, 2013, 2014
2013-05-29
... 20892, (301) 435-4445, [email protected] . Name of Committee: Oncology 1-Basic Translational... . Name of Committee: Oncology 1-Basic Translational Integrated Review Group Molecular Oncogenesis Study...
-
scientific understanding-of molecular, nanoscale, semiconductor, and biological materials, systems, and molecular, nanoscale, and semiconductor systems to capture, control, and convert solar radiation with high
-
Haneda, Kiyofumi; Umeda, Tokuo; Koyama, Tadashi; Harauchi, Hajime; Inamura, Kiyonari
2002-01-01
The target of our study is to establish the methodology for analyzing level of security requirements, for searching suitable security measures and for optimizing security distribution to every portion of medical practice. Quantitative expression must be introduced to our study as possible for the purpose of easy follow up of security procedures and easy evaluation of security outcomes or results. Results of system analysis by fault tree analysis (FTA) clarified that subdivided system elements in detail contribute to much more accurate analysis. Such subdivided composition factors very much depended on behavior of staff, interactive terminal devices, kinds of service, and routes of network. As conclusion, we found the methods to analyze levels of security requirements for each medical information systems employing FTA, basic events for each composition factor and combination of basic events. Methods for searching suitable security measures were found. Namely risk factors for each basic event, number of elements for each composition factor and candidates of security measure elements were found. Method to optimize the security measures for each medical information system was proposed. Namely optimum distribution of risk factors in terms of basic events were figured out, and comparison of them between each medical information systems became possible.
-
An adverse outcome pathway (AOP) conceptually links a molecular initiating event with measureable key events at higher levels of biological organization that ultimately result in an adverse outcome. Development of an AOP requires experimental data and scientific expertise to ide...
-
The FTA Method And A Possibility Of Its Application In The Area Of Road Freight Transport
NASA Astrophysics Data System (ADS)
Poliaková, Adela
2015-06-01
The Fault Tree process utilizes logic diagrams to portray and analyse potentially hazardous events. Three basic symbols (logic gates) are adequate for diagramming any fault tree. However, additional recently developed symbols can be used to reduce the time and effort required for analysis. A fault tree is a graphical representation of the relationship between certain specific events and the ultimate undesired event (2). This paper deals to method of Fault Tree Analysis basic description and provides a practical view on possibility of application by quality improvement in road freight transport company.
-
The Molecular Architecture of Cell Adhesion: Dynamic Remodeling Revealed by Videonanoscopy.
Sergé, Arnauld
2016-01-01
The plasma membrane delimits the cell, which is the basic unit of living organisms, and is also a privileged site for cell communication with the environment. Cell adhesion can occur through cell-cell and cell-matrix contacts. Adhesion proteins such as integrins and cadherins also constitute receptors for inside-out and outside-in signaling within proteolipidic platforms. Adhesion molecule targeting and stabilization relies on specific features such as preferential segregation by the sub-membrane cytoskeleton meshwork and within membrane proteolipidic microdomains. This review presents an overview of the recent insights brought by the latest developments in microscopy, to unravel the molecular remodeling occurring at cell contacts. The dynamic aspect of cell adhesion was recently highlighted by super-resolution videomicroscopy, also named videonanoscopy. By circumventing the diffraction limit of light, nanoscopy has allowed the monitoring of molecular localization and behavior at the single-molecule level, on fixed and living cells. Accessing molecular-resolution details such as quantitatively monitoring components entering and leaving cell contacts by lateral diffusion and reversible association has revealed an unexpected plasticity. Adhesion structures can be highly specialized, such as focal adhesion in motile cells, as well as immune and neuronal synapses. Spatiotemporal reorganization of adhesion molecules, receptors, and adaptors directly relates to structure/function modulation. Assembly of these supramolecular complexes is continuously balanced by dynamic events, remodeling adhesions on various timescales, notably by molecular conformation switches, lateral diffusion within the membrane and endo/exocytosis. Pathological alterations in cell adhesion are involved in cancer evolution, through cancer stem cell interaction with stromal niches, growth, extravasation, and metastasis.
-
SIGPI. Fault Tree Cut Set System Performance
DOE Office of Scientific and Technical Information (OSTI.GOV)
Patenaude, C.J.
1992-01-13
SIGPI computes the probabilistic performance of complex systems by combining cut set or other binary product data with probability information on each basic event. SIGPI is designed to work with either coherent systems, where the system fails when certain combinations of components fail, or noncoherent systems, where at least one cut set occurs only if at least one component of the system is operating properly. The program can handle conditionally independent components, dependent components, or a combination of component types and has been used to evaluate responses to environmental threats and seismic events. The three data types that can bemore » input are cut set data in disjoint normal form, basic component probabilities for independent basic components, and mean and covariance data for statistically dependent basic components.« less
-
SIGPI. Fault Tree Cut Set System Performance
DOE Office of Scientific and Technical Information (OSTI.GOV)
Patenaude, C.J.
1992-01-14
SIGPI computes the probabilistic performance of complex systems by combining cut set or other binary product data with probability information on each basic event. SIGPI is designed to work with either coherent systems, where the system fails when certain combinations of components fail, or noncoherent systems, where at least one cut set occurs only if at least one component of the system is operating properly. The program can handle conditionally independent components, dependent components, or a combination of component types and has been used to evaluate responses to environmental threats and seismic events. The three data types that can bemore » input are cut set data in disjoint normal form, basic component probabilities for independent basic components, and mean and covariance data for statistically dependent basic components.« less
-
NEW MOLECULAR MEDICINE-BASED SCAR MANAGEMENT STRATEGIES
Arno, Anna I; Gauglitz, Gerd G; Barret, Juan P; Jeschke, Marc G
2014-01-01
Keloids and hypertrophic scars are prevalent disabling conditions with still suboptimal treatments. Basic science and molecular-based medicine research has contributed to unravel new bench-to-bedside scar therapies, and to dissect the complex signaling pathways involved. Peptides such as transforming growth factor beta (TGF-β) superfamily, with SMADs, Ski, SnoN, Fussels, endoglin, DS-Sily, Cav-1p, AZX100, thymosin-β4 and other related molecules may emerge as targets to prevent and treat keloids and hypertrophic scars. The aim of this review is to describe the basic complexity of these new molecular scar management strategies, and point out new fibrosis research lines. PMID:24438742
-
Axis of evil: molecular mechanisms of cancer metastasis.
Bogenrieder, Thomas; Herlyn, Meenhard
2003-09-29
Although the genetic basis of tumorigenesis may vary greatly between different cancer types, the cellular and molecular steps required for metastasis are similar for all cancer cells. Not surprisingly, the molecular mechanisms that propel invasive growth and metastasis are also found in embryonic development, and to a less perpetual extent, in adult tissue repair processes. It is increasingly apparent that the stromal microenvironment, in which neoplastic cells develop, profoundly influences many steps of cancer progression, including the ability of tumor cells to metastasize. In carcinomas, the influences of the microenvironment are mediated, in large part, by bidirectional interactions (adhesion, survival, proteolysis, migration, immune escape mechanisms lymph-/angiogenesis, and homing on target organs) between epithelial tumor cells and neighboring stromal cells, such as fibroblasts as well as endothelial and immune cells. In this review, we summarize recent advances in understanding the molecular mechanisms that govern this frequently lethal metastatic progression along an axis from primary tumor to regional lymph nodes to distant organ sites. Affected proteins include growth factor signaling molecules, chemokines, cell-cell adhesion molecules (cadherins, integrins) as well as extracellular proteases (matrix metalloproteinases). We then discuss promising new therapeutic approaches targeting the microenvironment. We note, however, that there is still too little knowledge of how the many events are coordinated and integrated by the cancer cell, with conspiratorial help by the stromal component of the host. Before drug development can proceed with a legitimate chance of success, significant gaps in basic knowledge need to be filled.
-
Kiontke, Andreas; Oliveira-Birkmeier, Ariana; Opitz, Andreas
2016-01-01
Over the past decades, electrospray ionization for mass spectrometry (ESI-MS) has become one of the most commonly employed techniques in analytical chemistry, mainly due to its broad applicability to polar and semipolar compounds and the superior selectivity which is achieved in combination with high resolution separation techniques. However, responsiveness of an analytical method also determines its suitability for the quantitation of chemical compounds; and in electrospray ionization for mass spectrometry, it can vary significantly among different analytes with identical solution concentrations. Therefore, we investigated the ESI-response behavior of 56 nitrogen-containing compounds including aromatic amines and pyridines, two compound classes of high importance to both, synthetic organic chemistry as well as to pharmaceutical sciences. These compounds are increasingly analyzed employing ESI mass spectrometry detection due to their polar, basic character. Signal intensities of the peaks from the protonated molecular ion (MH+) were acquired under different conditions and related to compound properties such as basicity, polarity, volatility and molecular size exploring their quantitative impact on ionization efficiency. As a result, we found that though solution basicity of a compound is the main factor initially determining the ESI response of the protonated molecular ion, other factors such as polarity and vaporability become more important under acidic solvent conditions and may nearly outweigh the importance of basicity under these conditions. Moreover, we show that different molecular descriptors may become important when using different types of instruments for such investigations, a fact not detailed so far in the available literature. PMID:27907110
-
Medical management of youth baseball and softball tournaments.
Kanaan, Matthew; Ray, Tracy R
2013-01-01
The medical management of youth baseball and softball tournaments requires both proper planning and a basic awareness of commonly seen sport-specific injuries. While youth sporting events are designed to be a fun experience for all, injuries and emergencies will occur. With proper planning, and supplies, the impact of these issues can be minimized. This article will outline some basic principles for the medical personnel that may be involved in youth baseball and softball events.
-
75 FR 25273 - Center for Scientific Review; Notice of Closed Meetings
Federal Register 2010, 2011, 2012, 2013, 2014
2010-05-07
... Genetics Integrated Review Group, Molecular Genetics C Study Section. Date: June 3-4, 2010. Time: 8 a.m. to... Committee: Oncology 1-Basic Translational Integrated Review Group, Cancer Molecular Pathobiology Study... Committee: Molecular, Cellular and Developmental Neuroscience Integrated Review Group, Cellular and...
-
[Biometric bases: basic concepts of probability calculation].
Dinya, E
1998-04-26
The author gives or outline of the basic concepts of probability theory. The bases of the event algebra, definition of the probability, the classical probability model and the random variable are presented.
-
Krishnan, Ranjani; Walton, Emily B; Van Vliet, Krystyn J
2009-11-01
As computational resources increase, molecular dynamics simulations of biomolecules are becoming an increasingly informative complement to experimental studies. In particular, it has now become feasible to use multiple initial molecular configurations to generate an ensemble of replicate production-run simulations that allows for more complete characterization of rare events such as ligand-receptor unbinding. However, there are currently no explicit guidelines for selecting an ensemble of initial configurations for replicate simulations. Here, we use clustering analysis and steered molecular dynamics simulations to demonstrate that the configurational changes accessible in molecular dynamics simulations of biomolecules do not necessarily correlate with observed rare-event properties. This informs selection of a representative set of initial configurations. We also employ statistical analysis to identify the minimum number of replicate simulations required to sufficiently sample a given biomolecular property distribution. Together, these results suggest a general procedure for generating an ensemble of replicate simulations that will maximize accurate characterization of rare-event property distributions in biomolecules.
-
Lognormal Approximations of Fault Tree Uncertainty Distributions.
El-Shanawany, Ashraf Ben; Ardron, Keith H; Walker, Simon P
2018-01-26
Fault trees are used in reliability modeling to create logical models of fault combinations that can lead to undesirable events. The output of a fault tree analysis (the top event probability) is expressed in terms of the failure probabilities of basic events that are input to the model. Typically, the basic event probabilities are not known exactly, but are modeled as probability distributions: therefore, the top event probability is also represented as an uncertainty distribution. Monte Carlo methods are generally used for evaluating the uncertainty distribution, but such calculations are computationally intensive and do not readily reveal the dominant contributors to the uncertainty. In this article, a closed-form approximation for the fault tree top event uncertainty distribution is developed, which is applicable when the uncertainties in the basic events of the model are lognormally distributed. The results of the approximate method are compared with results from two sampling-based methods: namely, the Monte Carlo method and the Wilks method based on order statistics. It is shown that the closed-form expression can provide a reasonable approximation to results obtained by Monte Carlo sampling, without incurring the computational expense. The Wilks method is found to be a useful means of providing an upper bound for the percentiles of the uncertainty distribution while being computationally inexpensive compared with full Monte Carlo sampling. The lognormal approximation method and Wilks's method appear attractive, practical alternatives for the evaluation of uncertainty in the output of fault trees and similar multilinear models. © 2018 Society for Risk Analysis.
-
Visualizing protein interactions and dynamics: evolving a visual language for molecular animation.
Jenkinson, Jodie; McGill, Gaël
2012-01-01
Undergraduate biology education provides students with a number of learning challenges. Subject areas that are particularly difficult to understand include protein conformational change and stability, diffusion and random molecular motion, and molecular crowding. In this study, we examined the relative effectiveness of three-dimensional visualization techniques for learning about protein conformation and molecular motion in association with a ligand-receptor binding event. Increasingly complex versions of the same binding event were depicted in each of four animated treatments. Students (n = 131) were recruited from the undergraduate biology program at University of Toronto, Mississauga. Visualization media were developed in the Center for Molecular and Cellular Dynamics at Harvard Medical School. Stem cell factor ligand and cKit receptor tyrosine kinase were used as a classical example of a ligand-induced receptor dimerization and activation event. Each group completed a pretest, viewed one of four variants of the animation, and completed a posttest and, at 2 wk following the assessment, a delayed posttest. Overall, the most complex animation was the most effective at fostering students' understanding of the events depicted. These results suggest that, in select learning contexts, increasingly complex representations may be more desirable for conveying the dynamic nature of cell binding events.
-
Teaching Molecular Biology with Microcomputers.
ERIC Educational Resources Information Center
Reiss, Rebecca; Jameson, David
1984-01-01
Describes a series of computer programs that use simulation and gaming techniques to present the basic principles of the central dogma of molecular genetics, mutation, and the genetic code. A history of discoveries in molecular biology is presented and the evolution of these computer assisted instructional programs is described. (MBR)
-
NASA Astrophysics Data System (ADS)
Xie, Yihui; Ma, Yajuan; Bai, Wenting; Zhu, Xiaofang; Liu, Min; Huang, Liping
2017-08-01
A mixed imprinted polymer which can rapidly adsorb all flavonoids from raspberry extract was prepared and recycled. The hybrid molecular surface imprinted polymers were prepared by using quercetin as the template molecule and Fe3O4 magnetic nanospheres as the carrier. The molecular imprinting polymer was prepared by using the "initial template molecule, molecularly imprinted polymer, mixed template molecule, molecularly imprint ted polymers (MIPS)". The adsorption performance and durability of the hybrid molecularly imprinted polymers were investigated by using the fingerprints of the ethyl acetate fraction of raspberry as an index. The adsorption of flavonoids from raspberry extract, lindenoside, cis-lindenin, quercetin, kaempferol and other flavonoids was completely adsorbed by mixed molecular-imprinted polymer, and the other components were basically adsorbed. When Mix-IMPs were repeatedly used 10 times, the fingerprints showed that the content and content of flavonoids were basically the same. The experimental results show that Mix-IMPs has good adsorption performance, can be recycled and used for rapid enrichment of flavonoids in raspberry.
-
Bernardi, Paolo; Di Lisa, Fabio
2015-01-01
The mitochondrial permeability transition (PT) – an abrupt increase permeability of the inner membrane to solutes – is a causative event in ischemia–reperfusion injury of the heart, and the focus of intense research in cardioprotection. The PT is due to opening of the PT pore (PTP), a high conductance channel that is critically regulated by a variety of pathophysiological effectors. Very recent work indicates that the PTP forms from the F-ATP synthase, which would switch from an energy-conserving to an energy-dissipating device. This review provides an update on the current debate on how this transition is achieved, and on the PTP as a target for therapeutic intervention. This article is part of a Special Issue entitled "Mitochondria: from basic mitochondrial biology to cardiovascular disease". PMID:25268651
-
Common-Cause Failure Treatment in Event Assessment: Basis for a Proposed New Model
DOE Office of Scientific and Technical Information (OSTI.GOV)
Dana Kelly; Song-Hua Shen; Gary DeMoss
2010-06-01
Event assessment is an application of probabilistic risk assessment in which observed equipment failures and outages are mapped into the risk model to obtain a numerical estimate of the event’s risk significance. In this paper, we focus on retrospective assessments to estimate the risk significance of degraded conditions such as equipment failure accompanied by a deficiency in a process such as maintenance practices. In modeling such events, the basic events in the risk model that are associated with observed failures and other off-normal situations are typically configured to be failed, while those associated with observed successes and unchallenged components aremore » assumed capable of failing, typically with their baseline probabilities. This is referred to as the failure memory approach to event assessment. The conditioning of common-cause failure probabilities for the common cause component group associated with the observed component failure is particularly important, as it is insufficient to simply leave these probabilities at their baseline values, and doing so may result in a significant underestimate of risk significance for the event. Past work in this area has focused on the mathematics of the adjustment. In this paper, we review the Basic Parameter Model for common-cause failure, which underlies most current risk modelling, discuss the limitations of this model with respect to event assessment, and introduce a proposed new framework for common-cause failure, which uses a Bayesian network to model underlying causes of failure, and which has the potential to overcome the limitations of the Basic Parameter Model with respect to event assessment.« less
-
Characterization of GM events by insert knowledge adapted re-sequencing approaches
Yang, Litao; Wang, Congmao; Holst-Jensen, Arne; Morisset, Dany; Lin, Yongjun; Zhang, Dabing
2013-01-01
Detection methods and data from molecular characterization of genetically modified (GM) events are needed by stakeholders of public risk assessors and regulators. Generally, the molecular characteristics of GM events are incomprehensively revealed by current approaches and biased towards detecting transformation vector derived sequences. GM events are classified based on available knowledge of the sequences of vectors and inserts (insert knowledge). Herein we present three insert knowledge-adapted approaches for characterization GM events (TT51-1 and T1c-19 rice as examples) based on paired-end re-sequencing with the advantages of comprehensiveness, accuracy, and automation. The comprehensive molecular characteristics of two rice events were revealed with additional unintended insertions comparing with the results from PCR and Southern blotting. Comprehensive transgene characterization of TT51-1 and T1c-19 is shown to be independent of a priori knowledge of the insert and vector sequences employing the developed approaches. This provides an opportunity to identify and characterize also unknown GM events. PMID:24088728
-
Characterization of GM events by insert knowledge adapted re-sequencing approaches.
Yang, Litao; Wang, Congmao; Holst-Jensen, Arne; Morisset, Dany; Lin, Yongjun; Zhang, Dabing
2013-10-03
Detection methods and data from molecular characterization of genetically modified (GM) events are needed by stakeholders of public risk assessors and regulators. Generally, the molecular characteristics of GM events are incomprehensively revealed by current approaches and biased towards detecting transformation vector derived sequences. GM events are classified based on available knowledge of the sequences of vectors and inserts (insert knowledge). Herein we present three insert knowledge-adapted approaches for characterization GM events (TT51-1 and T1c-19 rice as examples) based on paired-end re-sequencing with the advantages of comprehensiveness, accuracy, and automation. The comprehensive molecular characteristics of two rice events were revealed with additional unintended insertions comparing with the results from PCR and Southern blotting. Comprehensive transgene characterization of TT51-1 and T1c-19 is shown to be independent of a priori knowledge of the insert and vector sequences employing the developed approaches. This provides an opportunity to identify and characterize also unknown GM events.
-
A Diagnostic Assessment for Introductory Molecular and Cell Biology
ERIC Educational Resources Information Center
Shi, Jia; Wood, William B.; Martin, Jennifer M.; Guild, Nancy A.; Vicens, Quentin; Knight, Jennifer K.
2010-01-01
We have developed and validated a tool for assessing understanding of a selection of fundamental concepts and basic knowledge in undergraduate introductory molecular and cell biology, focusing on areas in which students often have misconceptions. This multiple-choice Introductory Molecular and Cell Biology Assessment (IMCA) instrument is designed…
-
Molecular Mechanics: The Method and Its Underlying Philosophy.
ERIC Educational Resources Information Center
Boyd, Donald B.; Lipkowitz, Kenny B.
1982-01-01
Molecular mechanics is a nonquantum mechanical method for solving problems concerning molecular geometries and energy. Methodology based on: the principle of combining potential energy functions of all structural features of a particular molecule into a total force field; derivation of basic equations; and use of available computer programs is…
-
Education M.S., Biomedical Basic Science, Department of Biochemistry and Molecular Genetics, University of Interaction with Histones H3 and H4," Molecular and Cellular Biology (2013) "The Lysine 48 and Cerevisiae," Molecular and Cellular Biology (2007) View all NREL Publications for Seth M. Noone
-
Learning and Memory, Part II: Molecular Mechanisms of Synaptic Plasticity
ERIC Educational Resources Information Center
Lombroso, Paul; Ogren, Marilee
2009-01-01
The molecular events that are responsible for strengthening synaptic connections and how these are linked to memory and learning are discussed. The laboratory preparations that allow the investigation of these events are also described.
-
Language learning impairments: integrating basic science, technology, and remediation.
Tallal, P; Merzenich, M M; Miller, S; Jenkins, W
1998-11-01
One of the fundamental goals of the modern field of neuroscience is to understand how neuronal activity gives rise to higher cortical function. However, to bridge the gap between neurobiology and behavior, we must understand higher cortical functions at the behavioral level at least as well as we have come to understand neurobiological processes at the cellular and molecular levels. This is certainly the case in the study of speech processing, where critical studies of behavioral dysfunction have provided key insights into the basic neurobiological mechanisms relevant to speech perception and production. Much of this progress derives from a detailed analysis of the sensory, perceptual, cognitive, and motor abilities of children who fail to acquire speech, language, and reading skills normally within the context of otherwise normal development. Current research now shows that a dysfunction in normal phonological processing, which is critical to the development of oral and written language, may derive, at least in part, from difficulties in perceiving and producing basic sensory-motor information in rapid succession--within tens of ms (see Tallal et al. 1993a for a review). There is now substantial evidence supporting the hypothesis that basic temporal integration processes play a fundamental role in establishing neural representations for the units of speech (phonemes), which must be segmented from the (continuous) speech stream and combined to form words, in order for the normal development of oral and written language to proceed. Results from magnetic resonance imaging (MRI) and positron emission tomography (PET) studies, as well as studies of behavioral performance in normal and language impaired children and adults, will be reviewed to support the view that the integration of rapidly changing successive acoustic events plays a primary role in phonological development and disorders. Finally, remediation studies based on this research, coupled with neuroplasticity research, will be presented.
-
MicroRNAs in Neurocognitive Dysfunctions: New Molecular Targets for Pharmacological Treatments?
Nadim, Wissem Deraredj; Simion, Viorel; Bénédetti, Hélène; Pichon, Chantal; Baril, Patrick; Morisset-Lopez, Séverine
2017-01-01
Background Neurodegenerative and cognitive disorders are multifactorial diseases (i.e., involving neurodevelopmental, genetic, age or environmental factors) characterized by an abnormal development that affects neuronal function and integrity. Recently, an increasing number of studies revealed that the dysregulation of microRNAs (miRNAs) may be involved in the etiology of cognitive disorders as Alzheimer, Parkinson, and Huntington‘s diseases, Schizophrenia and Autism spectrum disorders. Methods From an extensive search in bibliographic databases of peer-reviewed research literature, we identified relevant published studies related to specific key words such as memory, cognition, neurodegenerative disorders, neurogenesis and miRNA. We then analysed, evaluated and summerized scientific evidences derived from these studies. Results We first briefly summarize the basic molecular events involved in memory, a process inherent to cognitive disease, and then describe the role of miRNAs in neurodevelopment, synaptic plasticity and memory. Secondly, we provide an overview of the impact of miRNA dysregulation in the pathogenesis of different neurocognitive disorders, and lastly discuss the feasibility of miRNA-based therapeutics in the treatment of these disorders. Conclusion This review highlights the molecular basis of neurodegenerative and cognitive disorders by focusing on the impact of miRNAs dysregulation in these pathological phenotypes. Altogether, the published reports suggest that miRNAs-based therapy could be a viable therapeutic alternative to current treatment options in the future. PMID:27396304
-
Discovering the intelligence in molecular biology.
Uberbacher, E
1995-12-01
The Third International Conference on Intelligent Systems in Molecular Biology was truly an outstanding event. Computational methods in molecular biology have reached a new level of maturity and utility, resulting in many high-impact applications. The success of this meeting bodes well for the rapid and continuing development of computational methods, intelligent systems and information-based approaches for the biosciences. The basic technology, originally most often applied to 'feasibility' problems, is now dealing effectively with the most difficult real-world problems. Significant progress has been made in understanding protein-structure information, structural classification, and how functional information and the relevant features of active-site geometry can be gleaned from structures by automated computational approaches. The value and limits of homology-based methods, and the ability to classify proteins by structure in the absence of homology, have reached a new level of sophistication. New methods for covariation analysis in the folding of large structures such as RNAs have shown remarkably good results, indicating the long-term potential to understand very complicated molecules and multimolecular complexes using computational means. Novel methods, such as HMMs, context-free grammars and the uses of mutual information theory, have taken center stage as highly valuable tools in our quest to represent and characterize biological information. A focus on creative uses of intelligent systems technologies and the trend toward biological application will undoubtedly continue and grow at the 1996 ISMB meeting in St Louis.
-
29 CFR 5.32 - Overtime payments.
Code of Federal Regulations, 2014 CFR
2014-07-01
....25 an hour to a mechanic as his basic cash wage plus 50 cents an hour as a contribution to a welfare... prevailing wage statutes. It is clear from the legislative history that in no event can the regular or basic... less than the amount determined by the Secretary of Labor as the basic hourly rate (i.e. cash rate...
-
29 CFR 5.32 - Overtime payments.
Code of Federal Regulations, 2013 CFR
2013-07-01
....25 an hour to a mechanic as his basic cash wage plus 50 cents an hour as a contribution to a welfare... prevailing wage statutes. It is clear from the legislative history that in no event can the regular or basic... less than the amount determined by the Secretary of Labor as the basic hourly rate (i.e. cash rate...
-
29 CFR 5.32 - Overtime payments.
Code of Federal Regulations, 2012 CFR
2012-07-01
....25 an hour to a mechanic as his basic cash wage plus 50 cents an hour as a contribution to a welfare... prevailing wage statutes. It is clear from the legislative history that in no event can the regular or basic... less than the amount determined by the Secretary of Labor as the basic hourly rate (i.e. cash rate...
-
Lan, Daoliang; Xiong, Xianrong; Huang, Cai; Mipam, Tserang Donko; Li, Jian
2016-01-01
Yaks (Bos grunniens) are endemic species that can adapt well to thin air, cold temperatures, and high altitude. These species can survive in harsh plateau environments and are major source of animal production for local residents, being an important breed in the Qinghai-Tibet Plateau. However, compared with ordinary cattle that live in the plains, yaks generally have lower fertility. Investigating the basic physiological molecular features of yak ovary and identifying the biological events underlying the differences between the ovaries of yak and plain cattle is necessary to understand the specificity of yak reproduction. Therefore, RNA-seq technology was applied to analyze transcriptome data comparatively between the yak and plain cattle estrous ovaries. After deep sequencing, 3,653,032 clean reads with a total of 4,828,772,880 base pairs were obtained from yak ovary library. Alignment analysis showed that 16992 yak genes mapped to the yak genome, among which, 12,731 and 14,631 genes were assigned to Gene Ontology (GO) categories and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways. Furthermore, comparison of yak and cattle ovary transcriptome data revealed that 1307 genes were significantly and differentially expressed between the two libraries, wherein 661 genes were upregulated and 646 genes were downregulated in yak ovary. Functional analysis showed that the differentially expressed genes were involved in various Gene Ontology (GO) categories and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways. GO annotations indicated that the genes related to "cell adhesion," "hormonal" biological processes, and "calcium ion binding," "cation transmembrane transport" molecular events were significantly active. KEGG pathway analysis showed that the "complement and coagulation cascade" pathway was the most enriched in yak ovary transcriptome data, followed by the "cytochrome P450" related and "ECM-receptor interaction" pathways. Moreover, several novel pathways, such as "circadian rhythm," were significantly enriched despite having no evident associations with the reproductive function. Our findings provide a molecular resource for further investigation of the general molecular mechanism of yak ovary and offer new insights to understand comprehensively the specificity of yak reproduction.
-
A Symphony of Regulations Centered on p63 to Control Development of Ectoderm-Derived Structures
Guerrini, Luisa; Costanzo, Antonio; Merlo, Giorgio R.
2011-01-01
The p53-related transcription factor p63 is critically important for basic cellular functions during development of the ectoderm and derived structure and tissues, including skin, limb, palate, and hair. On the one side, p63 is required to sustain the proliferation of keratinocyte progenitors, while on the other side it is required for cell stratification, commitment to differentiate, cell adhesion, and epithelial-mesenchymal signaling. Molecules that are components or regulators of the p63 pathway(s) are rapidly being identified, and it comes with no surprise that alterations in the p63 pathway lead to congenital conditions in which the skin and other ectoderm-derived structures are affected. In this paper, we summarize the current knowledge of the molecular and cellular regulations centered on p63, derived from the comprehension of p63-linked human diseases and the corresponding animal models, as well as from cellular models and high-throughput molecular approaches. We point out common themes and features, that allow to speculate on the possible role of p63 downstream events and their potential exploitation in future attempts to correct the congenital defect in preclinical studies. PMID:21716671
-
Lactic acid bacterial extract as a biogenic mineral growth modifier
NASA Astrophysics Data System (ADS)
Borah, Ballav M.; Singh, Atul K.; Ramesh, Aiyagari; Das, Gopal
2009-04-01
The formation of minerals and mechanisms by which bacteria could control their formation in natural habitats is now of current interest for material scientists to have an insight of the mechanism of in vivo mineralization, as well as to seek industrial and technological applications. Crystalline uniform structures of calcium and barium minerals formed micron-sized building blocks when synthesized in the presence of an organic matrix consisting of secreted protein extracts from three different lactic acid bacteria (LAB) viz.: Lactobacillus plantarum MTCC 1325, Lactobacillus acidophilus NRRL B4495 and Pediococcus acidilactici CFR K7. LABs are not known to form organic matrix in biological materialization processes. The influence of these bacterial extracts on the crystallization behavior was investigated in details to test the basic coordination behavior of the acidic protein. In this report, varied architecture of the mineral crystals obtained in presence of high molecular weight protein extracts of three different LAB strains has been discussed. The role of native form of high molecular weight bacterial protein extracts in the generation of nucleation centers for crystal growth was clearly established. A model for the formation of organic matrix-cation complex and the subsequent events leading to crystal growth is proposed.
-
Visualizing Protein Interactions and Dynamics: Evolving a Visual Language for Molecular Animation
Jenkinson, Jodie; McGill, Gaël
2012-01-01
Undergraduate biology education provides students with a number of learning challenges. Subject areas that are particularly difficult to understand include protein conformational change and stability, diffusion and random molecular motion, and molecular crowding. In this study, we examined the relative effectiveness of three-dimensional visualization techniques for learning about protein conformation and molecular motion in association with a ligand–receptor binding event. Increasingly complex versions of the same binding event were depicted in each of four animated treatments. Students (n = 131) were recruited from the undergraduate biology program at University of Toronto, Mississauga. Visualization media were developed in the Center for Molecular and Cellular Dynamics at Harvard Medical School. Stem cell factor ligand and cKit receptor tyrosine kinase were used as a classical example of a ligand-induced receptor dimerization and activation event. Each group completed a pretest, viewed one of four variants of the animation, and completed a posttest and, at 2 wk following the assessment, a delayed posttest. Overall, the most complex animation was the most effective at fostering students' understanding of the events depicted. These results suggest that, in select learning contexts, increasingly complex representations may be more desirable for conveying the dynamic nature of cell binding events. PMID:22383622
-
Data science approaches to pharmacogenetics.
Penrod, N M; Moore, J H
2014-01-01
Pharmacogenetic studies rely on applied statistics to evaluate genetic data describing natural variation in response to pharmacotherapeutics such as drugs and vaccines. In the beginning, these studies were based on candidate gene approaches that specifically focused on efficacy or adverse events correlated with variants of single genes. This hypothesis driven method required the researcher to have a priori knowledge of which genes or gene sets to investigate. According to rational design, the focus of these studies has been on drug metabolizing enzymes, drug transporters, and drug targets. As technology has progressed, these studies have transitioned to hypothesis-free explorations where markers across the entire genome can be measured in large scale, population based, genome-wide association studies (GWAS). This enables identification of novel genetic biomarkers, therapeutic targets, and analysis of gene-gene interactions, which may reveal molecular mechanisms of drug activities. Ultimately, the challenge is to utilize gene-drug associations to create dosing algorithms based individual genotypes, which will guide physicians and ensure they prescribe the correct dose of the correct drug the first time eliminating trial-and-error and adverse events. We review here basic concepts and applications of data science to the genetic analysis of pharmacologic outcomes.
-
Molecular Cloning and Analysis of a DNA Repetitive Element from the Mouse Genome
ERIC Educational Resources Information Center
Geisinger, Adriana; Cossio, Gabriela; Wettstein, Rodolfo
2006-01-01
We report the development of a 3-week laboratory activity for an undergraduate molecular biology course. This activity introduces students to the practice of basic molecular techniques such as restriction enzyme digestion, agarose gel electrophoresis, cloning, plasmid DNA purification, Southern blotting, and sequencing. Students learn how to carry…
-
ERIC Educational Resources Information Center
Yisau, J. I.; Adagbada, A. O.; Bamidele, T.; Fowora, M.; Brai, B. I. C.; Adebesin, O.; Bamidele, M.; Fesobi, T.; Nwaokorie, F. O.; Ajayi, A.; Smith, S. I.
2017-01-01
The deployment of molecular biology techniques for diagnosis and research in Nigeria is faced with a number of challenges, including the cost of equipment and reagents coupled with the dearth of personnel skilled in the procedures and handling of equipment. Short molecular biology training workshops were conducted at the Nigerian Institute of…
-
ERIC Educational Resources Information Center
Zhang, Xu; Shao, Meng; Gao, Lu; Zhao, Yuanyuan; Sun, Zixuan; Zhou, Liping; Yan, Yongmin; Shao, Qixiang; Xu, Wenrong; Qian, Hui
2017-01-01
Laboratory exercise is helpful for medical students to understand the basic principles of molecular biology and to learn about the practical applications of molecular biology. We have designed a lab course on molecular biology about the determination of single nucleotide polymorphism (SNP) in human REV3 gene, the product of which is a subunit of…
-
Interactions between spontaneous instantiations to the basic level and post-event suggestions.
Pansky, Ainat; Tenenboim, Einat
2011-11-01
Extensive research shows that post-event suggestions can distort the memory for a target event. In this study we examined the effect of such suggestions as they interact with the products of a spontaneous memory process: instantiation of abstract information to an intermediate level of abstractness, the basic level (Pansky & Koriat, 2004 ). Participants read a narrative containing items presented at the superordinate level (e.g., FRUIT), were exposed to suggestions that referred to these items at the basic level (e.g., APPLE), and were finally asked to recall the original items. We found that the tendency to instantiate spontaneously in the control (non-misleading) condition, particularly over time, increased following exposure to suggestions that were likely to coincide with those instantiations. Exposure to such suggestions, either immediately or following a 24-hour delay, reduced subsequent correct recall of the original items only if the suggested information coincided with the information one tends to instantiate spontaneously in a given context. Suggestibility, in this case, was particularly pronounced and phenomenologically compelling in terms of remember/know judgements. The findings are taken to imply that effects of post-event suggestions can be understood in terms of the constructive processes that set the stage for their occurrence.
-
Molecular evolution of the polyamine oxidase gene family in Metazoa
2012-01-01
Background Polyamine oxidase enzymes catalyze the oxidation of polyamines and acetylpolyamines. Since polyamines are basic regulators of cell growth and proliferation, their homeostasis is crucial for cell life. Members of the polyamine oxidase gene family have been identified in a wide variety of animals, including vertebrates, arthropodes, nematodes, placozoa, as well as in plants and fungi. Polyamine oxidases (PAOs) from yeast can oxidize spermine, N1-acetylspermine, and N1-acetylspermidine, however, in vertebrates two different enzymes, namely spermine oxidase (SMO) and acetylpolyamine oxidase (APAO), specifically catalyze the oxidation of spermine, and N1-acetylspermine/N1-acetylspermidine, respectively. Little is known about the molecular evolutionary history of these enzymes. However, since the yeast PAO is able to catalyze the oxidation of both acetylated and non acetylated polyamines, and in vertebrates these functions are addressed by two specialized polyamine oxidase subfamilies (APAO and SMO), it can be hypothesized an ancestral reference for the former enzyme from which the latter would have been derived. Results We analysed 36 SMO, 26 APAO, and 14 PAO homologue protein sequences from 54 taxa including various vertebrates and invertebrates. The analysis of the full-length sequences and the principal domains of vertebrate and invertebrate PAOs yielded consensus primary protein sequences for vertebrate SMOs and APAOs, and invertebrate PAOs. This analysis, coupled to molecular modeling techniques, also unveiled sequence regions that confer specific structural and functional properties, including substrate specificity, by the different PAO subfamilies. Molecular phylogenetic trees revealed a basal position of all the invertebrates PAO enzymes relative to vertebrate SMOs and APAOs. PAOs from insects constitute a monophyletic clade. Two PAO variants sampled in the amphioxus are basal to the dichotomy between two well supported monophyletic clades including, respectively, all the SMOs and APAOs from vertebrates. The two vertebrate monophyletic clades clustered strictly mirroring the organismal phylogeny of fishes, amphibians, reptiles, birds, and mammals. Evidences from comparative genomic analysis, structural evolution and functional divergence in a phylogenetic framework across Metazoa suggested an evolutionary scenario where the ancestor PAO coding sequence, present in invertebrates as an orthologous gene, has been duplicated in the vertebrate branch to originate the paralogous SMO and APAO genes. A further genome evolution event concerns the SMO gene of placental, but not marsupial and monotremate, mammals which increased its functional variation following an alternative splicing (AS) mechanism. Conclusions In this study the explicit integration in a phylogenomic framework of phylogenetic tree construction, structure prediction, and biochemical function data/prediction, allowed inferring the molecular evolutionary history of the PAO gene family and to disambiguate paralogous genes related by duplication event (SMO and APAO) and orthologous genes related by speciation events (PAOs, SMOs/APAOs). Further, while in vertebrates experimental data corroborate SMO and APAO molecular function predictions, in invertebrates the finding of a supported phylogenetic clusters of insect PAOs and the co-occurrence of two PAO variants in the amphioxus urgently claim the need for future structure-function studies. PMID:22716069
-
Molecular evolution of the polyamine oxidase gene family in Metazoa.
Polticelli, Fabio; Salvi, Daniele; Mariottini, Paolo; Amendola, Roberto; Cervelli, Manuela
2012-06-20
Polyamine oxidase enzymes catalyze the oxidation of polyamines and acetylpolyamines. Since polyamines are basic regulators of cell growth and proliferation, their homeostasis is crucial for cell life. Members of the polyamine oxidase gene family have been identified in a wide variety of animals, including vertebrates, arthropodes, nematodes, placozoa, as well as in plants and fungi. Polyamine oxidases (PAOs) from yeast can oxidize spermine, N1-acetylspermine, and N1-acetylspermidine, however, in vertebrates two different enzymes, namely spermine oxidase (SMO) and acetylpolyamine oxidase (APAO), specifically catalyze the oxidation of spermine, and N1-acetylspermine/N1-acetylspermidine, respectively. Little is known about the molecular evolutionary history of these enzymes. However, since the yeast PAO is able to catalyze the oxidation of both acetylated and non acetylated polyamines, and in vertebrates these functions are addressed by two specialized polyamine oxidase subfamilies (APAO and SMO), it can be hypothesized an ancestral reference for the former enzyme from which the latter would have been derived. We analysed 36 SMO, 26 APAO, and 14 PAO homologue protein sequences from 54 taxa including various vertebrates and invertebrates. The analysis of the full-length sequences and the principal domains of vertebrate and invertebrate PAOs yielded consensus primary protein sequences for vertebrate SMOs and APAOs, and invertebrate PAOs. This analysis, coupled to molecular modeling techniques, also unveiled sequence regions that confer specific structural and functional properties, including substrate specificity, by the different PAO subfamilies. Molecular phylogenetic trees revealed a basal position of all the invertebrates PAO enzymes relative to vertebrate SMOs and APAOs. PAOs from insects constitute a monophyletic clade. Two PAO variants sampled in the amphioxus are basal to the dichotomy between two well supported monophyletic clades including, respectively, all the SMOs and APAOs from vertebrates. The two vertebrate monophyletic clades clustered strictly mirroring the organismal phylogeny of fishes, amphibians, reptiles, birds, and mammals. Evidences from comparative genomic analysis, structural evolution and functional divergence in a phylogenetic framework across Metazoa suggested an evolutionary scenario where the ancestor PAO coding sequence, present in invertebrates as an orthologous gene, has been duplicated in the vertebrate branch to originate the paralogous SMO and APAO genes. A further genome evolution event concerns the SMO gene of placental, but not marsupial and monotremate, mammals which increased its functional variation following an alternative splicing (AS) mechanism. In this study the explicit integration in a phylogenomic framework of phylogenetic tree construction, structure prediction, and biochemical function data/prediction, allowed inferring the molecular evolutionary history of the PAO gene family and to disambiguate paralogous genes related by duplication event (SMO and APAO) and orthologous genes related by speciation events (PAOs, SMOs/APAOs). Further, while in vertebrates experimental data corroborate SMO and APAO molecular function predictions, in invertebrates the finding of a supported phylogenetic clusters of insect PAOs and the co-occurrence of two PAO variants in the amphioxus urgently claim the need for future structure-function studies.
-
Summary of speakers and events from the 2006 ICMAOI conference, focused on presenting basic, epidemiologic, and clinical aspects of research on malignancies in HIV-infected and other immunosuppressed individuals.
-
Summary of speakers and events from the 2005 ICMAOI conference, focused on presenting basic, epidemiologic, and clinical aspects of research on malignancies in HIV-infected and other immunosuppressed individuals.
-
Summary of speakers and events from the 2002 ICMAOI conference, focused on presenting basic, epidemiologic, and clinical aspects of research on malignancies in HIV-infected and other immunosuppressed individuals.
-
Summary of speakers and events from the 2005 ICMAOI conference, focused on presenting basic, epidemiologic, and clinical aspects of research on malignancies in HIV-infected and other immunosuppressed individuals.
-
Summary of speakers and events from the 2003 ICMAOI conference, focused on presenting basic, epidemiologic, and clinical aspects of research on malignancies in HIV-infected and other immunosuppressed individuals.
-
Summary of speakers and events from the 2000 ICMAOI conference, focused on presenting basic, epidemiologic, and clinical aspects of research on malignancies in HIV-infected and other immunosuppressed individuals.
-
Summary of speakers and events from the 1999 ICMAOI conference, focused on presenting basic, epidemiologic, and clinical aspects of research on malignancies in HIV-infected and other immunosuppressed individuals.
-
ERIC Educational Resources Information Center
Barrow, Gordon M.
1970-01-01
Presents the basic ideas of modern spectroscopy. Both the angular momenta and wave-nature approaches to the determination of energy level patterns for atomic and molecular systems are discussed. The interpretation of spectra, based on atomic and molecular models, is considered. (LC)
-
Training New Technologists in the Basics of Molecular Pathology.
ERIC Educational Resources Information Center
Matta, Nahida
1993-01-01
Outlines a training model designed to help senior technologists ensure that the newly hired technologists in the clinical molecular pathology laboratory achieve the minimum level of knowledge needed to perform and progress on the job. (Author)
-
Related Factors of the Influence on Mental Symptoms of the Recruits in the Basic Military Training
ERIC Educational Resources Information Center
Hong-zheng, Li; Mei-ying, Lei; Dong-hai Zhao; Li-qiong, Zhao; Geng, Liu; Hong-kui, Zhou; Mei, Qin; Jie-feng, Li; Jian, Wen; Pin-de, Huang; Yi, Li; Chuang, Wang; Zhou-ran, Wang
2012-01-01
The objective of the study is to explore the psychosocial characteristics of recruits for mental health education during the basic military training. A total of 1,366 male recruits were assessed during the basic military training. The psychosocial characteristics, such as effects of LE (life events), mental symptoms, personality trait coping style…
-
SU-F-J-200: An Improved Method for Event Selection in Compton Camera Imaging for Particle Therapy
DOE Office of Scientific and Technical Information (OSTI.GOV)
Mackin, D; Beddar, S; Polf, J
2016-06-15
Purpose: The uncertainty in the beam range in particle therapy limits the conformality of the dose distributions. Compton scatter cameras (CC), which measure the prompt gamma rays produced by nuclear interactions in the patient tissue, can reduce this uncertainty by producing 3D images confirming the particle beam range and dose delivery. However, the high intensity and short time windows of the particle beams limit the number of gammas detected. We attempt to address this problem by developing a method for filtering gamma ray scattering events from the background by applying the known gamma ray spectrum. Methods: We used a 4more » stage Compton camera to record in list mode the energy deposition and scatter positions of gammas from a Co-60 source. Each CC stage contained a 4×4 array of CdZnTe crystal. To produce images, we used a back-projection algorithm and four filtering Methods: basic, energy windowing, delta energy (ΔE), or delta scattering angle (Δθ). Basic filtering requires events to be physically consistent. Energy windowing requires event energy to fall within a defined range. ΔE filtering selects events with the minimum difference between the measured and a known gamma energy (1.17 and 1.33 MeV for Co-60). Δθ filtering selects events with the minimum difference between the measured scattering angle and the angle corresponding to a known gamma energy. Results: Energy window filtering reduced the FWHM from 197.8 mm for basic filtering to 78.3 mm. ΔE and Δθ filtering achieved the best results, FWHMs of 64.3 and 55.6 mm, respectively. In general, Δθ filtering selected events with scattering angles < 40°, while ΔE filtering selected events with angles > 60°. Conclusion: Filtering CC events improved the quality and resolution of the corresponding images. ΔE and Δθ filtering produced similar results but each favored different events.« less
-
NASA Astrophysics Data System (ADS)
Arnal, L.; Longo, G.; Stupar, P.; Castez, M. F.; Cattelan, N.; Salvarezza, R. C.; Yantorno, O. M.; Kasas, S.; Vela, M. E.
2015-10-01
Bacterial adhesion is the first and a significant step in establishing infection. This adhesion normally occurs in the presence of flow of fluids. Therefore, bacterial adhesins must be able to provide high strength interactions with their target surface in order to maintain the adhered bacteria under hydromechanical stressing conditions. In the case of B. pertussis, a Gram-negative bacterium responsible for pertussis, a highly contagious human respiratory tract infection, an important protein participating in the adhesion process is a 220 kDa adhesin named filamentous haemagglutinin (FHA), an outer membrane and also secreted protein that contains recognition domains to adhere to ciliated respiratory epithelial cells and macrophages. In this work, we obtained information on the cell-surface localization and distribution of the B. pertussis adhesin FHA using an antibody-functionalized AFM tip. Through the analysis of specific molecular recognition events we built a map of the spatial distribution of the adhesin which revealed a non-homogeneous pattern. Moreover, our experiments showed a force induced reorganization of the adhesin on the surface of the cells, which could explain a reinforced adhesive response under external forces. This single-molecule information contributes to the understanding of basic molecular mechanisms used by bacterial pathogens to cause infectious disease and to gain insights into the structural features by which adhesins can act as force sensors under mechanical shear conditions.Bacterial adhesion is the first and a significant step in establishing infection. This adhesion normally occurs in the presence of flow of fluids. Therefore, bacterial adhesins must be able to provide high strength interactions with their target surface in order to maintain the adhered bacteria under hydromechanical stressing conditions. In the case of B. pertussis, a Gram-negative bacterium responsible for pertussis, a highly contagious human respiratory tract infection, an important protein participating in the adhesion process is a 220 kDa adhesin named filamentous haemagglutinin (FHA), an outer membrane and also secreted protein that contains recognition domains to adhere to ciliated respiratory epithelial cells and macrophages. In this work, we obtained information on the cell-surface localization and distribution of the B. pertussis adhesin FHA using an antibody-functionalized AFM tip. Through the analysis of specific molecular recognition events we built a map of the spatial distribution of the adhesin which revealed a non-homogeneous pattern. Moreover, our experiments showed a force induced reorganization of the adhesin on the surface of the cells, which could explain a reinforced adhesive response under external forces. This single-molecule information contributes to the understanding of basic molecular mechanisms used by bacterial pathogens to cause infectious disease and to gain insights into the structural features by which adhesins can act as force sensors under mechanical shear conditions. Electronic supplementary information (ESI) available. See DOI: 10.1039/c5nr04644k
-
Understanding molecular structure from molecular mechanics.
Allinger, Norman L
2011-04-01
Molecular mechanics gives us a well known model of molecular structure. It is less widely recognized that valence bond theory gives us structures which offer a direct interpretation of molecular mechanics formulations and parameters. The electronic effects well-known in physical organic chemistry can be directly interpreted in terms of valence bond structures, and hence quantitatively calculated and understood. The basic theory is outlined in this paper, and examples of the effects, and their interpretation in illustrative examples is presented.
-
Contains basic information on the role and origins of the Selected Analytical Methods including the formation of the Homeland Security Laboratory Capacity Work Group and the Environmental Evaluation Analytical Process Roadmap for Homeland Security Events
-
Rescue strategies against non-steroidal anti-inflammatory drug-induced gastroduodenal damage.
Lim, Yun Jeong; Lee, Jeong Sang; Ku, Yang Suh; Hahm, Ki-Baik
2009-07-01
Non-steroidal anti-inflammatory drugs (NSAIDs) are the most commonly prescribed drugs worldwide, which attests to their efficacy as analgesic, antipyretic and anti-inflammatory agents as well as anticancer drugs. However, NSAID use also carries a risk of major gastroduodenal events, including symptomatic ulcers and their serious complications that can lead to fatal outcomes. The development of "coxibs" (selective cyclooxygenase-2 [COX-2] inhibitors) offered similar efficacy with reduced toxicity, but this promise of gastroduodenal safety has only partially been fulfilled, and is now dented with associated risks of cardiovascular or intestinal complications. Recent advances in basic science and biotechnology have given insights into molecular mechanisms of NSAID-induced gastroduodenal damage beyond COX-2 inhibition. The emergence of newer kinds of NSAIDs should alleviate gastroduodenal toxicity without compromising innate drug efficacy. In this review, novel strategies for avoiding NSAID-associated gastroduodenal damage will be described.
-
Pre-implantation Development of Domestic Animals.
Piliszek, Anna; Madeja, Zofia E
2018-01-01
During the first days following fertilization, cells of mammalian embryo gradually lose totipotency, acquiring distinct identity. The first three lineages specified in the mammalian embryo are pluripotent epiblast, which later gives rise to the embryo proper, and two extraembryonic lineages, hypoblast (also known as primitive endoderm) and trophectoderm, which form tissues supporting development of the fetus in utero. Most of our knowledge regarding the mechanisms of early lineage specification in mammals comes from studies in the mouse. However, the growing body of evidence points to both similarities and species-specific differences. Understanding molecular and cellular mechanisms of early embryonic development in nonrodent mammals expands our understanding of basic mechanisms of differentiation and is essential for the development of effective protocols for assisted reproduction in agriculture, veterinary medicine, and for biomedical research. This review summarizes the current state of knowledge on key events in epiblast, hypoblast, and trophoblast differentiation in domestic mammals. © 2018 Elsevier Inc. All rights reserved.
-
Coccini, Teresa; Manzo, Luigi; De Simone, Uliana; Acerbi, Davide; Roda, Elisa
2012-01-01
There is strong epidemiological evidence that air pollution exposure (short- and long-term, i.e. < 24 hr to 3 weeks, and year/s) is related to exacerbation of cardiovascular and respiratory diseases. Data from toxicological and basic science/molecular studies, controlled animal and human exposures and human panel studies have demonstrated several mechanisms by which particle exposure may both trigger acute events as well as prompt the chronic development of cardiovascular diseases. These pollutant-mediated biological mechanisms are supporting the potential use of haematic (inflammation/coagulation/oxidative stress) markers of effects in cardio-respiratory diseases. Various examples from in vitro, in vivo and epidemiological investigations are reported, together with some novel technologies that should provide with new tools for research in these diseases and improve the knowledge about any linkage of local and systemic inflammation and clinical features of these diseases (in particular COPD), including lung function, exacerbations, disease progression, and mortality.
-
Bioenergetics of Mammalian Sperm Capacitation
Ferramosca, Alessandra; Zara, Vincenzo
2014-01-01
After ejaculation, the mammalian male gamete must undergo the capacitation process, which is a prerequisite for egg fertilization. The bioenergetics of sperm capacitation is poorly understood despite its fundamental role in sustaining the biochemical and molecular events occurring during gamete activation. Glycolysis and mitochondrial oxidative phosphorylation (OXPHOS) are the two major metabolic pathways producing ATP which is the primary source of energy for spermatozoa. Since recent data suggest that spermatozoa have the ability to use different metabolic substrates, the main aim of this work is to present a broad overview of the current knowledge on the energy-producing metabolic pathways operating inside sperm mitochondria during capacitation in different mammalian species. Metabolism of glucose and of other energetic substrates, such as pyruvate, lactate, and citrate, is critically analyzed. Such knowledge, besides its obvious importance for basic science, could eventually translate into the development of novel strategies for treatment of male infertility, artificial reproduction, and sperm selection methods. PMID:24791005
-
Bioenergetics of mammalian sperm capacitation.
Ferramosca, Alessandra; Zara, Vincenzo
2014-01-01
After ejaculation, the mammalian male gamete must undergo the capacitation process, which is a prerequisite for egg fertilization. The bioenergetics of sperm capacitation is poorly understood despite its fundamental role in sustaining the biochemical and molecular events occurring during gamete activation. Glycolysis and mitochondrial oxidative phosphorylation (OXPHOS) are the two major metabolic pathways producing ATP which is the primary source of energy for spermatozoa. Since recent data suggest that spermatozoa have the ability to use different metabolic substrates, the main aim of this work is to present a broad overview of the current knowledge on the energy-producing metabolic pathways operating inside sperm mitochondria during capacitation in different mammalian species. Metabolism of glucose and of other energetic substrates, such as pyruvate, lactate, and citrate, is critically analyzed. Such knowledge, besides its obvious importance for basic science, could eventually translate into the development of novel strategies for treatment of male infertility, artificial reproduction, and sperm selection methods.
-
Low dosages: new chemotherapeutic weapons on the battlefield of immune-related disease
Liu, Jing; Zhao, Jie; Hu, Liang; Cao, Yuchun; Huang, Bo
2011-01-01
Chemotherapeutic drugs eliminate tumor cells at relatively high doses and are considered weapons against tumors in clinics and hospitals. However, despite their ability to induce cellular apoptosis, chemotherapeutic drugs should probably be regarded more as a class of cell regulators than cell killers, if the dosage used and the fact that their targets are involved in basic molecular events are considered. Unfortunately, the regulatory properties of chemotherapeutic drugs are usually hidden or masked by the massive cell death induced by high doses. Recent evidence has begun to suggest that low dosages of chemotherapeutic drugs might profoundly regulate various intracellular aspects of normal cells, especially immune cells. Here, we discuss the immune regulatory roles of three kinds of chemotherapeutic drugs under low-dose conditions and propose low dosages as potential new chemotherapeutic weapons on the battlefield of immune-related disease. PMID:21423201
-
Inflammation--a lifelong companion. Attempt at a non-analytical holistic view.
Ferencík, M; Stvrtinová, V; Hulín, I; Novák, M
2007-01-01
Inflammation is a key component of the immune system. It has important functions in both defense and pathophysiological events maintaining the dynamic homeostasis of a host organism including its tissues, organs and individual cells. On the cellular level it is controlled by more than 400 currently known genes. Their polymorphisms and environmental conditions give rise to different genotypes in human population. Pro-inflammatory genotype, which dominates in the present population, may be advantageous in childhood but not in elderly people because it is characterized by an increased vulnerability to, and intensity of, inflammatory reactions. These reactions may be the possible reasons of chronic inflammatory diseases, especially in old age. Better understanding of complex molecular and cellular inflammatory mechanisms is indispensable for detailed knowledge of pathogenesis of many diseases, their prevention and directed drug therapy. Here we summarize the basic current knowledge on these mechanisms.
-
The volatile composition of comets
NASA Technical Reports Server (NTRS)
Weaver, H. A.
1988-01-01
Comets may be our best probes of the physical and chemical conditions in the outer regions of the solar nebula during that crucial period when the planets formed. The volatile composition of cometary nuclei can be used to decide whether comets are the product of a condensation sequence similar to that invoked to explain the compositions of the planets and asteroids, or if comets are simply agglomerations of interstellar grains which have been insignificantly modified by the events that shaped the other bodies in the solar system. Although cometary nuclei are not generally accessible to observation, observations of cometary comae can illuminate at least some of the mysteries of the nuclei provided one has a detailed knowledge of the excitation conditions in the coma and also has access to basic atomic and molecular data on the many species present in comets. Examined here is the status of our knowledge of the volatile composition of cometary nuclei and how these data are obtained.
-
Meiotic recombination and male infertility: from basic science to clinical reality?
Hann, Michael C; Lau, Patricio E; Tempest, Helen G
2011-01-01
Infertility is a common problem that affects approximately 15% of the population. Although many advances have been made in the treatment of infertility, the molecular and genetic causes of male infertility remain largely elusive. This review will present a summary of our current knowledge on the genetic origin of male infertility and the key events of male meiosis. It focuses on chromosome synapsis and meiotic recombination and the problems that arise when errors in these processes occur, specifically meiotic arrest and chromosome aneuploidy, the leading cause of pregnancy loss in humans. In addition, meiosis-specific candidate genes will be discussed, including a discussion on why we have been largely unsuccessful at identifying disease-causing mutations in infertile men. Finally clinical applications of sperm aneuploidy screening will be touched upon along with future prospective clinical tests to better characterize male infertility in a move towards personalized medicine. PMID:21297654
-
Meiotic recombination and male infertility: from basic science to clinical reality?
Hann, Michael C; Lau, Patricio E; Tempest, Helen G
2011-03-01
Infertility is a common problem that affects approximately 15% of the population. Although many advances have been made in the treatment of infertility, the molecular and genetic causes of male infertility remain largely elusive. This review will present a summary of our current knowledge on the genetic origin of male infertility and the key events of male meiosis. It focuses on chromosome synapsis and meiotic recombination and the problems that arise when errors in these processes occur, specifically meiotic arrest and chromosome aneuploidy, the leading cause of pregnancy loss in humans. In addition, meiosis-specific candidate genes will be discussed, including a discussion on why we have been largely unsuccessful at identifying disease-causing mutations in infertile men. Finally clinical applications of sperm aneuploidy screening will be touched upon along with future prospective clinical tests to better characterize male infertility in a move towards personalized medicine.
-
Structure and Function of Caltrin (Calcium Transport Inhibitor) Proteins
Grasso, Ernesto Javier; Coronel, Carlos Enrique
2017-01-01
Caltrin (calcium transport inhibitor) is a family of small and basic proteins of the mammalian seminal plasma which bind to sperm cells during ejaculation and inhibit the extracellular Ca2+ uptake, preventing the premature acrosomal exocytosis and hyperactivation when sperm cells ascend through the female reproductive tract. The binding of caltrin proteins to specific areas of the sperm surface suggests the existence of caltrin receptors, or precise protein-phospholipid arrangements in the sperm membrane, distributed in the regions where Ca2+ influx may take place. However, the molecular mechanisms of recognition and interaction between caltrin and spermatozoa have not been elucidated. Therefore, the aim of this article is to describe in depth the known structural features and functional properties of caltrin proteins, to find out how they may possibly interact with the sperm membranes to control the intracellular signaling that trigger physiological events required for fertilization. PMID:29308010
-
The Transition from Mathematician to Astrophysicist
NASA Astrophysics Data System (ADS)
Flannery, M. R.
Various landmarks in the evolution of Alexander Dalgarno from a gifted mathematician to becoming the acknowledged Father of Molecular Astrophysics are noted. His researches in basic atomic and molecular physics, aeronomy (the study of the upper atmosphere) and astrophysics are highlighted.
-
PyRETIS: A well-done, medium-sized python library for rare events.
Lervik, Anders; Riccardi, Enrico; van Erp, Titus S
2017-10-30
Transition path sampling techniques are becoming common approaches in the study of rare events at the molecular scale. More efficient methods, such as transition interface sampling (TIS) and replica exchange transition interface sampling (RETIS), allow the investigation of rare events, for example, chemical reactions and structural/morphological transitions, in a reasonable computational time. Here, we present PyRETIS, a Python library for performing TIS and RETIS simulations. PyRETIS directs molecular dynamics (MD) simulations in order to sample rare events with unbiased dynamics. PyRETIS is designed to be easily interfaced with any molecular simulation package and in the present release, it has been interfaced with GROMACS and CP2K, for classical and ab initio MD simulations, respectively. © 2017 Wiley Periodicals, Inc. © 2017 Wiley Periodicals, Inc.
-
ERIC Educational Resources Information Center
Sharma, Prince; D'Souza, David R.; Bhandari, Deepali; Parashar, Vijay; Capalash, Neena
2003-01-01
Restriction enzymes are basic tools in recombinant DNA technology. To shape the molecular biology experiments, the students must know how to work with these molecular scissors. Here, we describe an integrated set of experiments, introduced in the "Advances in Molecular Biology and Biotechnology" postgraduate course, which covers the important…
-
Huang, Johnny X.; Cooper, Matthew A.; Baker, Mark A.; Azad, Mohammad A.K.; Nation, Roger L.; Li, Jian; Velkov, Tony
2012-01-01
This study utilizes sensitive, modern isothermal titration calorimetric (ITC) methods to characterize the microscopic thermodynamic parameters that drive the binding of basic drugs to α-1-acid glycoprotein (AGP) and thereby rationalize the thermodynamic data in relation to docking models and crystallographic structures of the drug-AGP complexes. The binding of basic compounds from the tricyclic antidepressant series, together with miaserine, chlorpromazine, disopyramide and cimetidine all displayed an exothermically driven binding interaction with AGP. The impact of protonation/deprotonation events, ionic strength, temperature and the individual selectivity of the A and F1*S AGP variants on drug-binding thermodynamics were characterized. A correlation plot of the thermodynamic parameters for all of the test compounds revealed enthalpy-entropy compensation is in effect. The exothermic binding energetics of the test compounds were driven by a combination of favorable (negative) enthalpic (ΔH°) and favorable (positive) entropic (ΔS°) contributions to the Gibbs free energy (ΔG°). Collectively, the data imply that the free energies that drive drug binding to AGP and its relationship to drug-serum residency evolve from the complex interplay of enthalpic and entropic forces from interactions with explicit combinations of hydrophobic and polar side-chain sub-domains within the multi-lobed AGP ligand binding cavity. PMID:23192962
-
Mechanism of polyphosphate kinase from Propionibacterium shermanii
DOE Office of Scientific and Technical Information (OSTI.GOV)
Robinson, N.A.
1986-01-01
Polyphosphate kinase, which catalyzes the reaction shown below, is one of two enzymes which have been reported to catalyze the synthesis of polyphosphate. Purification performed by ammonium sulfate precipitation (0-40% fraction) was followed by chromatography. The enzyme represents 70% of the protein in the hydroxylapatite pool and is stable at this level of purity. The subunit molecular weight was determined by SDS polyacrylamide gel analysis, (83,000 +/- 3000), nondenaturing polyacrylamide gel electrophoresis, (80,000 and 86,000 daltons), gel filtration (Biogel A 0.5m column was 85,000 +/- 4000.) Polyphosphate kinase appears to be a monomeric enzyme of approx.83,000 daltons. Four assays weremore » developed for polyphosphate kinase. Basic proteins such as polylysine stimulate the synthesis of polyphosphate, these proteins cause precipitation of polyphosphate kinase from relatively impure enzyme extracts: Synthesized polyphosphate interacts noncovalently with the basic protein-enzyme precipitate. Efficient synthesis of polyphosphate requires the addition of either phosphate or short chain polyphosphate. Synthesis did occur at 1/10 the rate when neither of these two compounds were included. Initiation, elongation, and termination events of polyphosphate synthesis were examined. Short chain polyphosphate acts as a primer, with (/sup 32/P) short-chain polyphosphate incorporation into long chain polyphosphate by the kinase.« less
-
DOE Office of Scientific and Technical Information (OSTI.GOV)
Le, Hai D.
2017-03-02
SimEngine provides the core functionalities and components that are key to the development of discrete event simulation tools. These include events, activities, event queues, random number generators, and basic result tracking classes. SimEngine was designed for high performance, integrates seamlessly into any Microsoft .Net development environment, and provides a flexible API for simulation developers.
-
Li, Jia; Wang, Deming; Huang, Zonghou
2017-01-01
Coal dust explosions (CDE) are one of the main threats to the occupational safety of coal miners. Aiming to identify and assess the risk of CDE, this paper proposes a novel method of fuzzy fault tree analysis combined with the Visual Basic (VB) program. In this methodology, various potential causes of the CDE are identified and a CDE fault tree is constructed. To overcome drawbacks from the lack of exact probability data for the basic events, fuzzy set theory is employed and the probability data of each basic event is treated as intuitionistic trapezoidal fuzzy numbers. In addition, a new approach for calculating the weighting of each expert is also introduced in this paper to reduce the error during the expert elicitation process. Specifically, an in-depth quantitative analysis of the fuzzy fault tree, such as the importance measure of the basic events and the cut sets, and the CDE occurrence probability is given to assess the explosion risk and acquire more details of the CDE. The VB program is applied to simplify the analysis process. A case study and analysis is provided to illustrate the effectiveness of this proposed method, and some suggestions are given to take preventive measures in advance and avoid CDE accidents. PMID:28793348
-
Syncope among U.S. Air Force basic military trainees, August 2012-July 2013.
Webber, Bryant J; Cropper, Thomas L; Federinko, Susan P
2013-11-01
Syncope is a common event with many possible etiologies, ranging from benign to severe. Syncopal episodes of any origin, however, may result in traumatic injury due to postural collapse. Based on the prevalence of internal and external stressors during training, basic military trainees may be at increased risk for syncope. Between 1 August 2012 and 31 July 2013, there were 112 unique individuals who experienced syncopal or pre-syncopal events among basic military trainees at Joint Base San Antonio-Lackland, Texas, the only basic training site in the U.S. Air Force. The overall rate was 19.6 cases per 1,000 person-years (18.4 and 36.1 per 1,000 person-years in males and females, respectively). Based upon the findings of electronic chart review of the 112 cases, a majority of events occurred either during or immediately after exercise (n=38) or during a blood draw, immunization, or laceration repair (n=22). The most common etiologies were judged to be neurocardiogenic (n=54) and orthostatic hypotension (n=40), and two cases were attributed to cardiovascular disease. These findings support current preventive measures, including anemia screening during medical in-processing, an emphasis on hydration throughout training, and a padded floor in the trainee vaccination bay.
-
Wang, Hetang; Li, Jia; Wang, Deming; Huang, Zonghou
2017-01-01
Coal dust explosions (CDE) are one of the main threats to the occupational safety of coal miners. Aiming to identify and assess the risk of CDE, this paper proposes a novel method of fuzzy fault tree analysis combined with the Visual Basic (VB) program. In this methodology, various potential causes of the CDE are identified and a CDE fault tree is constructed. To overcome drawbacks from the lack of exact probability data for the basic events, fuzzy set theory is employed and the probability data of each basic event is treated as intuitionistic trapezoidal fuzzy numbers. In addition, a new approach for calculating the weighting of each expert is also introduced in this paper to reduce the error during the expert elicitation process. Specifically, an in-depth quantitative analysis of the fuzzy fault tree, such as the importance measure of the basic events and the cut sets, and the CDE occurrence probability is given to assess the explosion risk and acquire more details of the CDE. The VB program is applied to simplify the analysis process. A case study and analysis is provided to illustrate the effectiveness of this proposed method, and some suggestions are given to take preventive measures in advance and avoid CDE accidents.
-
Toxicology is increasingly focused on molecular events comprising adverse outcome pathways. Atrazine activates the hypothalamic-pituitary adrenal axis, but relationships to gonadal alterations are unknown. We characterized hormone profiles and adrenal (intact and castrate) and te...
-
Adverse outcome pathway (AOP) analyses illustrate that some molecular-initiating events (MIEs) for thyroid disruption, including thyroperoxidase (TPO) inhibition, are not evaluated by current ToxCast/Tox21 high-throughput screening (HTS) assays. A novel HTS assay for TPO inhibiti...
-
Lincoln, Barron L.; Alabsi, Sahar H.; Frendo, Nicholas; Freund, Robert; Keller, Lani C.
2015-01-01
Neurodegenerative diseases affect millions of people worldwide, and as the global population ages, there is a critical need to improve our understanding of the molecular and cellular mechanisms that drive neurodegeneration. At the molecular level, neurodegeneration involves the activation of complex signaling pathways that drive the active destruction of neurons and their intracellular components. Here, we use an in vivo motor neuron injury assay to acutely induce neurodegeneration in order to follow the temporal order of events that occur following injury in Drosophila melanogaster. We find that sites of injury can be rapidly identified based on structural defects to the neuronal cytoskeleton that result in disrupted axonal transport. Additionally, the neuromuscular junction accumulates ubiquitinated proteins prior to the neurodegenerative events, occurring at 24 hours post injury. Our data provide insights into the early molecular events that occur during axonal and neuromuscular degeneration in a genetically tractable model organism. Importantly, the mechanisms that mediate neurodegeneration in flies are conserved in humans. Thus, these studies have implications for our understanding of the cellular and molecular events that occur in humans and will facilitate the identification of biomedically relevant targets for future treatments. PMID:26512206
-
High-altitude electrical discharges associated with thunderstorms and lightning
NASA Astrophysics Data System (ADS)
Liu, Ningyu; McHarg, Matthew G.; Stenbaek-Nielsen, Hans C.
2015-12-01
The purpose of this paper is to introduce electrical discharge phenomena known as transient luminous events above thunderstorms to the lightning protection community. Transient luminous events include the upward electrical discharges from thunderstorms known as starters, jets, and gigantic jets, and electrical discharges initiated in the lower ionosphere such as sprites, halos, and elves. We give an overview of these phenomena with a focus on starters, jets, gigantic jets, and sprites, because similar to ordinary lightning, streamers and leaders are basic components of these four types of transient luminous events. We present a few recent observations to illustrate their main properties and briefly review the theories. The research in transient luminous events has not only advanced our understanding of the effects of thunderstorms and lightning in the middle and upper atmosphere, but also improved our knowledge of basic electrical discharge processes critical for sparks and lightning.
-
Catchment scale molecular composition of hydrologically mobilized dissolved organic matter
NASA Astrophysics Data System (ADS)
Raeke, Julia; Lechtenfeld, Oliver J.; Oosterwoud, Marieke R.; Bornmann, Katrin; Tittel, Jörg; Reemtsma, Thorsten
2016-04-01
Increasing concentrations of dissolved organic matter (DOM) in rivers of temperate catchments in Europe and North Amerika impose new technical challenges for drinking water production. The driving factors for this decadal increase in DOM concentration are not conclusive and changes in annual temperatures, precipitation and atmospheric deposition are intensely discussed. It is known that the majority of DOM is released by few but large hydrologic events, mobilizing DOM from riparian wetlands for export by rivers and streams. The mechanisms of this mobilization and the resulting molecular composition of the released DOM may be used to infer long-term changes in the biogeochemistry of the respective catchment. Event-based samples collected over two years from streams in three temperate catchments in the German mid-range mountains were analyzed after solid-phase extraction of DOM for their molecular composition by ultra-high resolution mass spectrometry (FT-ICR MS). Hydrologic conditions, land use and water chemistry parameters were used to complement the molecular analysis. The molecular composition of the riverine DOM was strongly dependent on the magnitude of the hydrologic events, with unsaturated, oxygen-enriched compounds being preferentially mobilized by large events. This pattern is consistent with an increase in dissolved iron and aluminum concentrations. In contrast, the relative proportions of nitrogen and sulfur bearing compounds increased with an increased agricultural land use but were less affected by the mobilization events. Co-precipitation experiments with colloidal aluminum showed that unsaturated and oxygen-rich compounds are preferentially removed from the dissolved phase. The precipitated compounds thus had similar chemical characteristics as compared to the mobilized DOM from heavy rain events. Radiocarbon analyses also indicated that this precipitated fraction of DOM was of comparably young radiocarbon age. DOM radiocarbon from field samples showed that also the event-mobilized DOM had higher radiocarbon content. Overall, hydrology not only controls the quantity of exported carbon from temperate catchments but also strongly influences the molecular composition by mobilizing distinct compound classes in conjunction with dissolved iron and aluminum. From these results future compositional changes in temperate river DOM can be assessed, given an expected increase in the magnitude of hydrologic events, and technical advice for drinking water production may be inferred.
-
From bedside to blackboard: the benefits of teaching molecular biology within a medical context.
Sitaraman, Ramakrishnan
2012-01-01
Courses in molecular biology are part of practically every degree program in medicine and the life sciences. Historically, many basic discoveries in this field have resulted from investigations by doctors into the nature of diseases. This essay suggests that medical educators deliberately incorporate such material, whether historical or contemporaneous, into their molecular and cell biology courses. An example of such usage, an early report of the detection of bacteriophage activity on pathogenic bacteria, is discussed in detail. Such an approach can potentially narrow the perceived gap between "basic" and "applied" science. As medicine is so intimately and obviously linked with human welfare, this also provides an avenue for educators to discuss issues of scientific integrity and ethics within a "pure science" course.
-
Teaching microbiology to undergraduate students in the humanities and the social sciences.
Oren, Aharon
2015-10-01
This paper summarizes my experiences teaching a 28-hour course on the bacterial world for undergraduate students in the humanities and the social sciences at the Hebrew University of Jerusalem. This course was offered in the framework of a program in which students must obtain credit points for courses offered by other faculties to broaden their education. Most students had little biology in high school and had never been exposed to the basics of chemistry. Using a historical approach, highlighting the work of pioneers such as van Leeuwenhoek, Koch, Fleming, Pasteur, Winogradsky and Woese, I covered a broad area of general, medical, environmental and evolutionary microbiology. The lectures included basic concepts of organic and inorganic chemistry necessary to understand the principles of fermentations and chemoautotrophy, and basic molecular biology to explain biotechnology using transgenic microorganisms and molecular phylogeny. Teaching the basics of microbiology to intelligent students lacking any background in the natural sciences was a rewarding experience. Some students complained that, in spite of my efforts, basic concepts of chemistry remained beyond their understanding. But overall the students' evaluation showed that the course had achieved its goal. © FEMS 2015. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.
-
NASA Astrophysics Data System (ADS)
Haneda, Kiyofumi; Kajima, Toshio; Koyama, Tadashi; Muranaka, Hiroyuki; Dojo, Hirofumi; Aratani, Yasuhiko
2002-05-01
The target of our study is to analyze the level of necessary security requirements, to search for suitable security measures and to optimize security distribution to every portion of the medical practice. Quantitative expression must be introduced to our study, if possible, to enable simplified follow-up security procedures and easy evaluation of security outcomes or results. Using fault tree analysis (FTA), system analysis showed that system elements subdivided into groups by details result in a much more accurate analysis. Such subdivided composition factors greatly depend on behavior of staff, interactive terminal devices, kinds of services provided, and network routes. Security measures were then implemented based on the analysis results. In conclusion, we identified the methods needed to determine the required level of security and proposed security measures for each medical information system, and the basic events and combinations of events that comprise the threat composition factors. Methods for identifying suitable security measures were found and implemented. Risk factors for each basic event, a number of elements for each composition factor, and potential security measures were found. Methods to optimize the security measures for each medical information system were proposed, developing the most efficient distribution of risk factors for basic events.
-
The molecular biology of soft-tissue sarcomas and current trends in therapy.
Quesada, Jorge; Amato, Robert
2012-01-01
Basic research in sarcoma models has been fundamental in the discovery of scientific milestones leading to a better understanding of the molecular biology of cancer. Yet, clinical research in sarcoma has lagged behind other cancers because of the multiple clinical and pathological entities that characterize sarcomas and their rarity. Sarcomas encompass a very heterogeneous group of tumors with diverse pathological and clinical overlapping characteristics. Molecular testing has been fundamental in the identification and better definition of more specific entities among this vast array of malignancies. A group of sarcomas are distinguished by specific molecular aberrations such as somatic mutations, intergene deletions, gene amplifications, reciprocal translocations, and complex karyotypes. These and other discoveries have led to a better understanding of the growth signals and the molecular pathways involved in the development of these tumors. These findings are leading to treatment strategies currently under intense investigation. Disruption of the growth signals is being targeted with antagonistic antibodies, tyrosine kinase inhibitors, and inhibitors of several downstream molecules in diverse molecular pathways. Preliminary clinical trials, supported by solid basic research and strong preclinical evidence, promises a new era in the clinical management of these broad spectrum of malignant tumors.
-
Integration of Basic Sciences in Health's Courses
ERIC Educational Resources Information Center
Azzalis, L. A.; Giavarotti, L.; Sato, S. N.; Barros, N. M. T.; Junqueira, V. B. C.; Fonseca, F. L. A.
2012-01-01
Concepts from disciplines such as Biochemistry, Genetics, Cellular and Molecular Biology are essential to the understanding and treatment of an elevated number of illnesses, but often they are studied separately, with no integration between them. This article proposes a model for basic sciences integration based on problem-based learning (PBL) and…
-
Senior Computational Scientist | Center for Cancer Research
The Basic Science Program (BSP) pursues independent, multidisciplinary research in basic and applied molecular biology, immunology, retrovirology, cancer biology, and human genetics. Research efforts and support are an integral part of the Center for Cancer Research (CCR) at the Frederick National Laboratory for Cancer Research (FNLCR). The Cancer & Inflammation Program (CIP),
-
Secretary | Center for Cancer Research
The Basic Science Program (BSP) pursues independent, multidisciplinary research programs in basic or applied molecular biology, immunology, retrovirology, cancer biology, or human genetics. Research efforts and support are an integral part of the Center for Cancer Research (CCR) at the Frederick national Laboratory for Cancer Research (FNLCR). The BSP Office provides
-
ERIC Educational Resources Information Center
Stefani, Christina; Tsaparlis, Georgios
2009-01-01
We investigated students' knowledge constructions of basic quantum chemistry concepts, namely atomic orbitals, the Schrodinger equation, molecular orbitals, hybridization, and chemical bonding. Ausubel's theory of meaningful learning provided the theoretical framework and phenomenography the method of analysis. The semi-structured interview with…
-
How Expert Pilots Think Cognitive Processes in Expert Decision Making
1993-02-01
Management (CRM) This document is available to the public Advanced Qualification Program (AQP) through the National Technical Information Cognitive Task Analysis (CTA...8217 Selecting realistic EDM scenarios with critical events and performing a cognitive task analysis of novice vs. expert decision making for these events...scenarios with critical events and performing a cognitive task analysis of novice vs. expert decision making for these events is a basic requirement for
-
Orchestrating change: The thyroid hormones and GI-tract development in flatfish metamorphosis.
Gomes, A S; Alves, R N; Rønnestad, I; Power, D M
2015-09-01
Metamorphosis in flatfish (Pleuronectiformes) is a late post-embryonic developmental event that prepares the organism for the larval-to-juvenile transition. Thyroid hormones (THs) play a central role in flatfish metamorphosis and the basic elements that constitute the thyroid axis in vertebrates are all present at this stage. The advantage of using flatfish to study the larval-to-juvenile transition is the profound change in external morphology that accompanies metamorphosis making it easy to track progression to climax. This important lifecycle transition is underpinned by molecular, cellular, structural and functional modifications of organs and tissues that prepare larvae for a successful transition to the adult habitat and lifestyle. Understanding the role of THs in the maturation of organs and tissues with diverse functions during metamorphosis is a major challenge. The change in diet that accompanies the transition from a pelagic larvae to a benthic juvenile in flatfish is associated with structural and functional modifications in the gastrointestinal tract (GI-tract). The present review will focus on the maturation of the GI-tract during metamorphosis giving particular attention to organogenesis of the stomach a TH triggered event. Gene transcripts and biological processes that are associated with GI-tract maturation during Atlantic halibut metamorphosis are identified. Gene ontology analysis reveals core biological functions and putative TH-responsive genes that underpin TH-driven metamorphosis of the GI-tract in Atlantic halibut. Deciphering the specific role remains a challenge. Recent advances in characterizing the molecular, structural and functional modifications that accompany the appearance of a functional stomach in Atlantic halibut are considered and future research challenges identified. Copyright © 2014 Elsevier Inc. All rights reserved.
-
Risk Importance Measures in the Designand Operation of Nuclear Power Plants
DOE Office of Scientific and Technical Information (OSTI.GOV)
Vrbanic I.; Samanta P.; Basic, I
This monograph presents and discusses risk importance measures as quantified by the probabilistic risk assessment (PRA) models of nuclear power plants (NPPs) developed according to the current standards and practices. Usually, PRA tools calculate risk importance measures related to a single ?basic event? representing particular failure mode. This is, then, reflected in many current PRA applications. The monograph focuses on the concept of ?component-level? importance measures that take into account different failure modes of the component including common-cause failures (CCFs). In opening sections the roleof risk assessment in safety analysis of an NPP is introduced and discussion given of ?traditional?,more » mainly deterministic, design principles which have been established to assign a level of importance to a particular system, structure or component. This is followed by an overview of main risk importance measures for risk increase and risk decrease from current PRAs. Basic relations which exist among the measures are shown. Some of the current practical applications of risk importancemeasures from the field of NPP design, operation and regulation are discussed. The core of the monograph provides a discussion on theoreticalbackground and practical aspects of main risk importance measures at the level of ?component? as modeled in a PRA, starting from the simplest case, single basic event, and going toward more complexcases with multiple basic events and involvements in CCF groups. The intent is to express the component-level importance measures via theimportance measures and probabilities of the underlying single basic events, which are the inputs readily available from a PRA model andits results. Formulas are derived and discussed for some typical cases. The formulas and their results are demonstrated through some practicalexamples, done by means of a simplified PRA model developed in and run by RiskSpectrum? tool, which are presented in the appendices. The monograph concludes with discussion of limitations of the use of risk importance measures and a summary of component-level importance cases evaluated.« less
-
Advances in molecular biological methods are continually being brought to bear on human health research, from a basic understanding of systems biology to identification of toxicity pathways for environmental stressors and to correlations of molecular indicators with physiological...
-
75 FR 26970 - Center for Scientific Review; Notice of Closed Meetings
Federal Register 2010, 2011, 2012, 2013, 2014
2010-05-13
...-496-8551, [email protected] . Name of Committee: Molecular, Cellular and Developmental...: Oncology 1--Basic Translational Integrated Review Group, Cancer Genetics Study Section. Date: June 3-4... 20892, (301) 435-1154, [email protected] . Name of Committee: Molecular, Cellular and Developmental...
-
Molecular spectroscopy and collisional excitation. [in astrophysics
NASA Technical Reports Server (NTRS)
Green, S.
1975-01-01
The paper examines the basic principles underlying the molecular transitions responsible for interstellar molecular spectra. The energy levels of molecules are discussed in detail with special attention given to the Born-Oppenheimer approximation, the electronic Hamiltonian, and the parameters of vibrational and rotational energy. The probabilities for radiative and collisional transitions are calculated. A brief review of techniques for molecular spectroscopy is presented along with methods used to determine collision cross sections on both an experimental and a theoretical basis.
-
Molecular aspects of magnetic resonance imaging and spectroscopy.
Boesch, C
1999-01-01
Magnetic resonance imaging (MRI) is a well known diagnostic tool in radiology that produces unsurpassed images of the human body, in particular of soft tissue. However, the medical community is often not aware that MRI is an important yet limited segment of magnetic resonance (MR) or nuclear magnetic resonance (NMR) as this method is called in basic science. The tremendous morphological information of MR images sometimes conceal the fact that MR signals in general contain much more information, especially on processes on the molecular level. NMR is successfully used in physics, chemistry, and biology to explore and characterize chemical reactions, molecular conformations, biochemical pathways, solid state material, and many other applications that elucidate invisible characteristics of matter and tissue. In medical applications, knowledge of the molecular background of MRI and in particular MR spectroscopy (MRS) is an inevitable basis to understand molecular phenomenon leading to macroscopic effects visible in diagnostic images or spectra. This review shall provide the necessary background to comprehend molecular aspects of magnetic resonance applications in medicine. An introduction into the physical basics aims at an understanding of some of the molecular mechanisms without extended mathematical treatment. The MR typical terminology is explained such that reading of original MR publications could be facilitated for non-MR experts. Applications in MRI and MRS are intended to illustrate the consequences of molecular effects on images and spectra.
-
Developing and applying the adverse outcome pathway ...
To support a paradigm shift in regulatory toxicology testing and risk assessment, the Adverse Outcome Pathway (AOP) concept has recently been proposed. This concept is similar to that for Mode of Action (MOA), describing a sequence of measurable key events triggered by a molecular initiating event in which a stressor interacts with a biological target. The resulting cascade of key events includes molecular, cellular, structural and functional changes in biological systems, resulting in a measurable adverse outcome. Thereby, an AOP ideally provides information relevant to chemical structure-activity relationships as a basis to predict effects for structurally similar compounds. AOPs could potentially also form the basis for qualitative and quantitative predictive modeling of the human adverse outcome resulting from molecular initiating or other key events for which higher-throughput testing methods are available or can be developed.A variety of cellular and molecular processes are known to be critical to normal function of the central (CNS) and peripheral nervous systems (PNS). Because of the biological and functional complexity of the CNS and PNS, it has been challenging to establish causative links and quantitative relationships between key events that comprise the pathways leading from chemical exposure to an adverse outcome in the nervous system. Following introduction of principles of the description and assessment of MOA and AOPs, examples of adverse out
-
Fritzsch, Bernd; Jahan, Israt; Pan, Ning; Elliott, Karen L.
2014-01-01
Understanding the evolution of the neurosensory system of man, able to reflect on its own origin, is one of the major goals of comparative neurobiology. Details of the origin of neurosensory cells, their aggregation into central nervous systems and associated sensory organs, their localized patterning into remarkably different cell types aggregated into variably sized parts of the central nervous system begin to emerge. Insights at the cellular and molecular level begin to shed some light on the evolution of neurosensory cells, partially covered in this review. Molecular evidence suggests that high mobility group (HMG) proteins of pre-metazoans evolved into the definitive Sox [SRY (sex determining region Y)-box] genes used for neurosensory precursor specification in metazoans. Likewise, pre-metazoan basic helix-loop-helix (bHLH) genes evolved in metazoans into the group A bHLH genes dedicated to neurosensory differentiation in bilaterians. Available evidence suggests that the Sox and bHLH genes evolved a cross-regulatory network able to synchronize expansion of precursor populations and their subsequent differentiation into novel parts of the brain or sensory organs. Molecular evidence suggests metazoans evolved patterning gene networks early and not dedicated to neuronal development. Only later in evolution were these patterning gene networks tied into the increasing complexity of diffusible factors, many of which were already present in pre-metazoans, to drive local patterning events. It appears that the evolving molecular basis of neurosensory cell development may have led, in interaction with differentially expressed patterning genes, to local network modifications guiding unique specializations of neurosensory cells into sensory organs and various areas of the central nervous system. PMID:25416504
-
Fritzsch, Bernd; Jahan, Israt; Pan, Ning; Elliott, Karen L
2015-01-01
Understanding the evolution of the neurosensory system of man, able to reflect on its own origin, is one of the major goals of comparative neurobiology. Details of the origin of neurosensory cells, their aggregation into central nervous systems and associated sensory organs and their localized patterning leading to remarkably different cell types aggregated into variably sized parts of the central nervous system have begun to emerge. Insights at the cellular and molecular level have begun to shed some light on the evolution of neurosensory cells, partially covered in this review. Molecular evidence suggests that high mobility group (HMG) proteins of pre-metazoans evolved into the definitive Sox [SRY (sex determining region Y)-box] genes used for neurosensory precursor specification in metazoans. Likewise, pre-metazoan basic helix-loop-helix (bHLH) genes evolved in metazoans into the group A bHLH genes dedicated to neurosensory differentiation in bilaterians. Available evidence suggests that the Sox and bHLH genes evolved a cross-regulatory network able to synchronize expansion of precursor populations and their subsequent differentiation into novel parts of the brain or sensory organs. Molecular evidence suggests metazoans evolved patterning gene networks early, which were not dedicated to neuronal development. Only later in evolution were these patterning gene networks tied into the increasing complexity of diffusible factors, many of which were already present in pre-metazoans, to drive local patterning events. It appears that the evolving molecular basis of neurosensory cell development may have led, in interaction with differentially expressed patterning genes, to local network modifications guiding unique specializations of neurosensory cells into sensory organs and various areas of the central nervous system.
-
Single-molecule force-conductance spectroscopy of hydrogen-bonded complexes
NASA Astrophysics Data System (ADS)
Pirrotta, Alessandro; De Vico, Luca; Solomon, Gemma C.; Franco, Ignacio
2017-03-01
The emerging ability to study physical properties at the single-molecule limit highlights the disparity between what is observable in an ensemble of molecules and the heterogeneous contributions of its constituent parts. A particularly convenient platform for single-molecule studies are molecular junctions where forces and voltages can be applied to individual molecules, giving access to a series of electromechanical observables that can form the basis of highly discriminating multidimensional single-molecule spectroscopies. Here, we computationally examine the ability of force and conductance to inform about molecular recognition events at the single-molecule limit. For this, we consider the force-conductance characteristics of a prototypical class of hydrogen bonded bimolecular complexes sandwiched between gold electrodes. The complexes consist of derivatives of a barbituric acid and a Hamilton receptor that can form up to six simultaneous hydrogen bonds. The simulations combine classical molecular dynamics of the mechanical deformation of the junction with non-equilibrium Green's function computations of the electronic transport. As shown, in these complexes hydrogen bonds mediate transport either by directly participating as a possible transport pathway or by stabilizing molecular conformations with enhanced conductance properties. Further, we observe that force-conductance correlations can be very sensitive to small changes in the chemical structure of the complexes and provide detailed information about the behavior of single molecules that cannot be gleaned from either measurement alone. In fact, there are regions during the elongation that are only mechanically active, others that are only conductance active, and regions where both force and conductance changes as the complex is mechanically manipulated. The implication is that force and conductance provide complementary information about the evolution of molecules in junctions that can be used to interrogate basic structure-transport relations at the single-molecule limit.
-
Adults Learning Mathematics: What We Should Know about Betting and Bookkeeping?
ERIC Educational Resources Information Center
Maasz, Juergen; Siller, Hans-Stefan
2010-01-01
A lot of people risk money with bets on sport events or other events. Bookkeepers that offer such bets earn a lot of money. We are making a proposal (more exactly: a concept for a part of a basic mathematics course) for learning mathematics behind the screen (internet bets are very popular). Learners should organize a "sports event"…
-
Kida, S; Kato, T
2015-01-01
Psychiatric disorders are caused not only by genetic factors but also by complicated factors such as environmental ones. Moreover, environmental factors are rarely quantitated as biological and biochemical indicators, making it extremely difficult to understand the pathological conditions of psychiatric disorders as well as their underlying pathogenic mechanisms. Additionally, we have actually no other option but to perform biological studies on postmortem human brains that display features of psychiatric disorders, thereby resulting in a lack of experimental materials to characterize the basic biology of these disorders. From these backgrounds, animal, tissue, or cell models that can be used in basic research are indispensable to understand biologically the pathogenic mechanisms of psychiatric disorders. In this review, we discuss the importance of microendophenotypes of psychiatric disorders, i.e., phenotypes at the level of molecular dynamics, neurons, synapses, and neural circuits, as targets of basic research on these disorders.
-
Auer, Timo A; Renovanz, Mirjam; Marini, Federico; Brockmann, Marc A; Tanyildizi, Yasemin
2017-07-01
Bevacizumab (BVZ), a monoclonal antibody directed against vascular endothelial growth factor (VEGF), has been suspected to increase the incidence of ischemic stroke (IS) and intracranial hemorrhage (ICH) in GBM patients. Intracranial vascular events, such as IS and ICH, were retrospectively analyzed in 364 MRI scans of 82 patients with recurrent GBM (1st/2nd/3rd relapse). Out of these 82 patients, 40 were treated with BVZ (178 scans) in addition to basic treatment, whereas 42 patients matching for age and gender received basic treatment (186 scans). Distribution of typical vascular risk factors between both groups was analyzed retrospectively. In seven out of 82 patients (8%) vascular events were detected in MRI. Four vascular events were recorded in the BVZ-group (3 IS and 1 ICH), and 3 vascular events were found in the Control-group (1 IS and 2 ICH; p > 0.05 between both groups). Likewise, vascular risk factors (arterial hypertension, diabetes mellitus, obesity, former vascular event, hyperlipidemia, tobacco consumption and/or hypercholesterolemia) did not differ significantly between both groups. BVZ treatment does not seem to be associated with an increased risk for vascular events in patients with GBM in recurrence.
-
A mathematical model for the occurrence of historical events
NASA Astrophysics Data System (ADS)
Ohnishi, Teruaki
2017-12-01
A mathematical model was proposed for the frequency distribution of historical inter-event time τ. A basic ingredient was constructed by assuming the significance of a newly occurring historical event depending on the magnitude of a preceding event, the decrease of its significance by oblivion during the successive events, and an independent Poisson process for the occurrence of the event. The frequency distribution of τ was derived by integrating the basic ingredient with respect to all social fields and to all stake holders. The function of such a distribution was revealed as the forms of an exponential type, a power law type or an exponential-with-a-tail type depending on the values of constants appearing in the ingredient. The validity of this model was studied by applying it to the two cases of Modern China and Northern Ireland Troubles, where the τ-distribution varies depending on the different countries interacting with China and on the different stage of history of the Troubles, respectively. This indicates that history is consisted from many components with such different types of τ-distribution, which are the similar situation to the cases of other general human activities.
-
78 FR 60296 - Center for Scientific Review; Notice of Closed Meetings
Federal Register 2010, 2011, 2012, 2013, 2014
2013-10-01
... 20892, 301-435-1501, [email protected] . Name of Committee: Genes, Genomes, and Genetics Integrated Review Group; Prokaryotic Cell and Molecular Biology Study Section. Date: October 25, 2013. Time: 8:00 a... Committee: Oncology 1-Basic Translational Integrated Review Group; Cancer Molecular Pathobiology Study...
-
The Molecular Basis of Development.
ERIC Educational Resources Information Center
Gehring, Walter J.
1985-01-01
Basic architecture of embryo development appears to be under homeobox control (a short stretch of DNA). Outlines research on this genetic segment in fruit flies which led to identification of this control on the embryo's spatial organization. Indicates that molecular mechanisms underlying development may be much more universal than previously…
-
From basics to clinical: a comprehensive review on spinal cord injury.
Silva, Nuno A; Sousa, Nuno; Reis, Rui L; Salgado, António J
2014-03-01
Spinal cord injury (SCI) is a devastating neurological disorder that affects thousands of individuals each year. Over the past decades an enormous progress has been made in our understanding of the molecular and cellular events generated by SCI, providing insights into crucial mechanisms that contribute to tissue damage and regenerative failure of injured neurons. Current treatment options for SCI include the use of high dose methylprednisolone, surgical interventions to stabilize and decompress the spinal cord, and rehabilitative care. Nonetheless, SCI is still a harmful condition for which there is yet no cure. Cellular, molecular, rehabilitative training and combinatorial therapies have shown promising results in animal models. Nevertheless, work remains to be done to ascertain whether any of these therapies can safely improve patient's condition after human SCI. This review provides an extensive overview of SCI research, as well as its clinical component. It starts covering areas from physiology and anatomy of the spinal cord, neuropathology of the SCI, current clinical options, neuronal plasticity after SCI, animal models and techniques to assess recovery, focusing the subsequent discussion on a variety of promising neuroprotective, cell-based and combinatorial therapeutic approaches that have recently moved, or are close, to clinical testing. Copyright © 2013 Elsevier Ltd. All rights reserved.
-
NASA Astrophysics Data System (ADS)
Masoumi, Massoud; Raissi, Farshid; Ahmadian, Mahmoud; Keshavarzi, Parviz
2006-01-01
We are proposing that the recently proposed semiconductor-nanowire-molecular architecture (CMOL) is an optimum platform to realize encryption algorithms. The basic modules for the advanced encryption standard algorithm (Rijndael) have been designed using CMOL architecture. The performance of this design has been evaluated with respect to chip area and speed. It is observed that CMOL provides considerable improvement over implementation with regular CMOS architecture even with a 20% defect rate. Pseudo-optimum gate placement and routing are provided for Rijndael building blocks and the possibility of designing high speed, attack tolerant and long key encryptions are discussed.
-
This collection of 3 AOPs describe varying outcomes of adversity dependent upon species in response to inhibition of thyroperoxidase (TPO) during development. Chemical inhibition of TPO, the molecular-initiating event (MIE), results in decreased thyroid hormone (TH) synthesis, a...
-
The power of the adverse outcome pathway (AOP) framework arises from its utilization of pathway-based data to describe the initial interaction of a chemical with a molecular target (molecular initiating event; (MIE), followed by a progression through a series of key events that l...
-
Lu, Zhenghui; Zhou, Yuling; Zhang, Xiaozhou; Zhang, Guimin
2015-11-01
Bacillus subtilis is a generally recognized as safe (GRAS) strain that has been widely used in industries including fodder, food, and biological control. In addition, B. subtilis expression system also plays a significant role in the production of industrial enzymes. However, its application is limited by its low sporulation frequency and transformation efficiency. Immense studies have been done on interpreting the molecular mechanisms of sporulation and competence development, whereas only few of them were focused on improving sporulation frequency and transformation efficiency of B. subtilis by genetic modification. The main challenge is that sporulation and competence development, as the two major developmental events in the stationary phase of B. subtilis, are regulated by the complicated intracellular genetic regulatory systems. In addition, mutual regulatory mechanisms also exist in these two developmental events. With the development of genetic and metabolic engineering, constructing genetic regulatory networks is currently one of the most attractive research fields, together with the genetic information of cell growth, metabolism, and development, to guide the industrial application. In this review, the mechanisms of sporulation and competence development of B. subtilis, their interactions, and the genetic regulation of cell growth were interpreted. In addition, the roles of these regulatory networks in guiding basic and applied research of B. subtilis and its related species were discussed.
-
Rates and impact of trauma and current stressors among Darfuri refugees in Eastern Chad.
Rasmussen, Andrew; Nguyen, Leanh; Wilkinson, John; Vundla, Sikhumbuzo; Raghavan, Sumithra; Miller, Kenneth E; Keller, Allen S
2010-04-01
Darfur refugees face hardships associated with chronic displacement, including lack of basic needs and safety concerns. Psychiatric research on refugees has focused on trauma, but daily stressors may contribute more to variance in distress. This article reports rates of past trauma and current stressors among Darfur refugees and gauges the contribution of each to psychological distress and functional impairment. A representative sample of 848 Darfuris in 2 refugee camps were interviewed about traumatic events, stressors faced in the camps, psychological distress, and functional impairment. Basic needs and safety concerns were more strongly correlated with measures of distress (rs = .19-.31) than were war-related traumatic events (rs = .09-.20). Hierarchical regression supported models in which effects of trauma on distress were mediated by current stressors. Although war-related traumatic events are the initial causes of refugees' hardship, findings suggest that the day-to-day challenges and concerns in camps mediate psychological distress associated with these events.
-
Rates and Impact of Trauma and Current Stressors Among Darfuri Refugees in Eastern Chad
Rasmussen, Andrew; Nguyen, Leanh; Wilkinson, John; Vundla, Sikhumbuzo; Raghavan, Sumithra; Miller, Kenneth E.; Keller, Allen S.
2010-01-01
Darfur refugees face hardships associated with chronic displacement, including lack of basic needs and safety concerns. Psychiatric research on refugees has focused on trauma, but daily stressors may contribute more to variance in distress. In this article we report rates of past trauma and current stressors among Darfur refugees and gauge the contribution of each to psychological distress and functional impairment. A representative sample of 848 Darfuris in two refugee camps were interviewed about traumatic events, stressors faced in the camps, psychological distress and functional impairment. Basic needs and safety concerns were more strongly correlated with measures of distress (r's = .19–.31) than were war-related traumatic events (r's = .09–.20). Hierarchical regression supported models in which effects of trauma on distress were mediated by current stressors. Although war-related traumatic events are the initial causes of refugees' hardship, findings suggest that the day-to-day challenges and concerns in camps mediate psychological distress associated with these events. PMID:20553516
-
Using Restriction Mapping to Teach Basic Skills in the Molecular Biology Lab
ERIC Educational Resources Information Center
Walsh, Lauren; Shaker, Elizabeth; De Stasio, Elizabeth A.
2007-01-01
Digestion of DNA with restriction enzymes, calculation of volumes and concentrations of reagents for reactions, and the separation of DNA fragments by agarose gel electrophoresis are common molecular biology techniques that are best taught through repetition. The following open-ended, investigative laboratory exercise in plasmid restriction…
-
Molecular Recognition: Detection of Colorless Compounds Based on Color Change
ERIC Educational Resources Information Center
Khalafi, Lida; Kashani, Samira; Karimi, Javad
2016-01-01
A laboratory experiment is described in which students measure the amount of cetirizine in allergy-treatment tablets based on molecular recognition. The basis of recognition is competition of cetirizine with phenolphthalein to form an inclusion complex with ß-cyclodextrin. Phenolphthalein is pinkish under basic condition, whereas it's complex form…
-
The Use of Molecular Modeling Programs in Medicinal Chemistry Instruction.
ERIC Educational Resources Information Center
Harrold, Marc W.
1992-01-01
This paper describes and evaluates the use of a molecular modeling computer program (Alchemy II) in a pharmaceutical education program. Provided are the hardware requirements and basic program features as well as several examples of how this program and its features have been applied in the classroom. (GLR)
-
The impact of culture collections on molecular identification, taxonomy, and solving real problems
USDA-ARS?s Scientific Manuscript database
Among the fungi, Fusarium has stood out as a major focus for culture collection resource development over the last century. This has facilitated unprecedented molecular taxonomic advancements, which in turn has led to problem solving in plant pathology, mycotoxicology, medical mycology, and basic re...
-
Huang, Cai; Mipam, Tserang Donko; Li, Jian
2016-01-01
Background Yaks (Bos grunniens) are endemic species that can adapt well to thin air, cold temperatures, and high altitude. These species can survive in harsh plateau environments and are major source of animal production for local residents, being an important breed in the Qinghai–Tibet Plateau. However, compared with ordinary cattle that live in the plains, yaks generally have lower fertility. Investigating the basic physiological molecular features of yak ovary and identifying the biological events underlying the differences between the ovaries of yak and plain cattle is necessary to understand the specificity of yak reproduction. Therefore, RNA-seq technology was applied to analyze transcriptome data comparatively between the yak and plain cattle estrous ovaries. Results After deep sequencing, 3,653,032 clean reads with a total of 4,828,772,880 base pairs were obtained from yak ovary library. Alignment analysis showed that 16992 yak genes mapped to the yak genome, among which, 12,731 and 14,631 genes were assigned to Gene Ontology (GO) categories and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways. Furthermore, comparison of yak and cattle ovary transcriptome data revealed that 1307 genes were significantly and differentially expressed between the two libraries, wherein 661 genes were upregulated and 646 genes were downregulated in yak ovary. Functional analysis showed that the differentially expressed genes were involved in various Gene Ontology (GO) categories and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways. GO annotations indicated that the genes related to “cell adhesion,” “hormonal” biological processes, and “calcium ion binding,” “cation transmembrane transport” molecular events were significantly active. KEGG pathway analysis showed that the “complement and coagulation cascade” pathway was the most enriched in yak ovary transcriptome data, followed by the “cytochrome P450” related and “ECM–receptor interaction” pathways. Moreover, several novel pathways, such as “circadian rhythm,” were significantly enriched despite having no evident associations with the reproductive function. Conclusion Our findings provide a molecular resource for further investigation of the general molecular mechanism of yak ovary and offer new insights to understand comprehensively the specificity of yak reproduction. PMID:27044040
-
HCV Core Residues Critical for Infectivity Are Also Involved in Core-NS5A Complex Formation
Gawlik, Katarzyna; Baugh, James; Chatterji, Udayan; Lim, Precious J.; Bobardt, Michael D.; Gallay, Philippe A.
2014-01-01
Hepatitis C virus (HCV) infection is a major cause of liver disease. The molecular machinery of HCV assembly and particle release remains obscure. A better understanding of the assembly events might reveal new potential antiviral strategies. It was suggested that the nonstructural protein 5A (NS5A), an attractive recent drug target, participates in the production of infectious particles as a result of its interaction with the HCV core protein. However, prior to the present study, the NS5A-binding site in the viral core remained unknown. We found that the D1 domain of core contains the NS5A-binding site with the strongest interacting capacity in the basic P38-K74 cluster. We also demonstrated that the N-terminal basic residues of core at positions 50, 51, 59 and 62 were required for NS5A binding. Analysis of all substitution combinations of R50A, K51A, R59A, and R62A, in the context of the HCVcc system, showed that single, double, triple, and quadruple mutants were fully competent for viral RNA replication, but deficient in secretion of viral particles. Furthermore, we found that the extracellular and intracellular infectivity of all the mutants was abolished, suggesting a defect in the formation of infectious particles. Importantly, we showed that the interaction between the single and quadruple core mutants and NS5A was impaired in cells expressing full-length HCV genome. Interestingly, mutations of the four basic residues of core did not alter the association of core or NS5A with lipid droplets. This study showed for the first time that basic residues in the D1 domain of core that are critical for the formation of infectious extracellular and intracellular particles also play a role in core-NS5A interactions. PMID:24533158
-
2017-10-01
pancreatic cancer cells. 3. Sequoyah Bennett Sequoyah worked in the lab of Dr. Surinder Batra, Department of Biochemistry and Molecular Biology , College...the lab of Dr. Kaustubh Datta, Department of Biochemistry and Molecular Biology at the University of Nebraska Medical Center. During that time, Ciera...following the therapeutic intervention or prostate cancer. Furthermore, she learned the basic cell culture and molecular biology techniques. (2016) 1
-
Motivation: Molecular pathways and networks play a key role in basic and disease biology. An emerging notion is that networks encoding patterns of molecular interplay may themselves differ between contexts, such as cell type, tissue or disease (sub)type. However, while statistical testing of differences in mean expression levels has been extensively studied, testing of network differences remains challenging.
-
Quality Assurance Program for Molecular Medicine Laboratories
Hajia, M; Safadel, N; Samiee, S Mirab; Dahim, P; Anjarani, S; Nafisi, N; Sohrabi, A; Rafiee, M; Sabzavi, F; Entekhabi, B
2013-01-01
Background: Molecular diagnostic methods have played and continuing to have a critical role in clinical laboratories in recent years. Therefore, standardization is an evolutionary process that needs to be upgrade with increasing scientific knowledge, improvement of the instruments and techniques. The aim of this study was to design a quality assurance program in order to have similar conditions for all medical laboratories engaging with molecular tests. Methods: We had to design a plan for all four elements; required space conditions, equipments, training, and basic guidelines. Necessary guidelines was prepared and confirmed by the launched specific committee at the Health Reference Laboratory. Results: Several workshops were also held for medical laboratories directors and staffs, quality control manager of molecular companies, directors and nominees from universities. Accreditation of equipments and molecular material was followed parallel with rest of program. Now we are going to accredit medical laboratories and to evaluate the success of the program. Conclusion: Accreditation of medical laboratory will be succeeding if its basic elements are provided in advance. Professional practice guidelines, holding training and performing accreditation the molecular materials and equipments ensured us that laboratories are aware of best practices, proper interpretation, limitations of techniques, and technical issues. Now, active external auditing can improve the applied laboratory conditions toward the defined standard level. PMID:23865028
-
Quality assurance program for molecular medicine laboratories.
Hajia, M; Safadel, N; Samiee, S Mirab; Dahim, P; Anjarani, S; Nafisi, N; Sohrabi, A; Rafiee, M; Sabzavi, F; Entekhabi, B
2013-01-01
Molecular diagnostic methods have played and continuing to have a critical role in clinical laboratories in recent years. Therefore, standardization is an evolutionary process that needs to be upgrade with increasing scientific knowledge, improvement of the instruments and techniques. The aim of this study was to design a quality assurance program in order to have similar conditions for all medical laboratories engaging with molecular tests. We had to design a plan for all four elements; required space conditions, equipments, training, and basic guidelines. Necessary guidelines was prepared and confirmed by the launched specific committee at the Health Reference Laboratory. Several workshops were also held for medical laboratories directors and staffs, quality control manager of molecular companies, directors and nominees from universities. Accreditation of equipments and molecular material was followed parallel with rest of program. Now we are going to accredit medical laboratories and to evaluate the success of the program. Accreditation of medical laboratory will be succeeding if its basic elements are provided in advance. Professional practice guidelines, holding training and performing accreditation the molecular materials and equipments ensured us that laboratories are aware of best practices, proper interpretation, limitations of techniques, and technical issues. Now, active external auditing can improve the applied laboratory conditions toward the defined standard level.
-
NASA Astrophysics Data System (ADS)
Kosov, Daniel S.
2017-09-01
Quantum transport of electrons through a molecule is a series of individual electron tunneling events separated by stochastic waiting time intervals. We study the emergence of temporal correlations between successive waiting times for the electron transport in a vibrating molecular junction. Using the master equation approach, we compute the joint probability distribution for waiting times of two successive tunneling events. We show that the probability distribution is completely reset after each tunneling event if molecular vibrations are thermally equilibrated. If we treat vibrational dynamics exactly without imposing the equilibration constraint, the statistics of electron tunneling events become non-renewal. Non-renewal statistics between two waiting times τ1 and τ2 means that the density matrix of the molecule is not fully renewed after time τ1 and the probability of observing waiting time τ2 for the second electron transfer depends on the previous electron waiting time τ1. The strong electron-vibration coupling is required for the emergence of the non-renewal statistics. We show that in the Franck-Condon blockade regime, extremely rare tunneling events become positively correlated.
-
2012 National Policy Seminar Wrap-Up
ERIC Educational Resources Information Center
Blandford, Ayoka
2012-01-01
CTE works! That was the recurring theme that attendees heard at the 2012 National Policy Seminar (NPS) hosted by ACTE. For those new to the event and lobbying, a pre-conference workshop, "Learning the Ropes of Washington CTE Advocacy," laid out the basics of Hill advocacy. Veteran CTE advocates were offered a basics-plus session,…
-
Counterfactual Reasoning: Developing a sense of “nearest possible world”
Rafetseder, Eva; Cristi-Vargas, Renate; Perner, Josef
2011-01-01
We investigated at what point in development 3- to 6-year-old children begin to demonstrate counterfactual reasoning by controlling for fortuitously correct answers that result from basic conditional reasoning. Basic conditional reasoning occurs when one applies typical regularities (such as “If
it doesn’t rain the street is dry”) to counterfactual questions (such as “If it had not rained, would the street be wet or dry?”) without regard to actual events (for example, if street cleaners had just been washing the street). In counterfactual reasoning, however, the conditional reasoning must be constrained by actual events (according to the “nearest possible world”). In situations when counterfactual reasoning and basic conditional reasoning would yield the same answers, even the youngest children gave mostly correct answers. However, tasks in which the two reasoning strategies resulted in different answers proved unusually difficult even for the older children. PMID:20331674 -
A cascade reaction network mimicking the basic functional steps of adaptive immune response
NASA Astrophysics Data System (ADS)
Han, Da; Wu, Cuichen; You, Mingxu; Zhang, Tao; Wan, Shuo; Chen, Tao; Qiu, Liping; Zheng, Zheng; Liang, Hao; Tan, Weihong
2015-10-01
Biological systems use complex ‘information-processing cores’ composed of molecular networks to coordinate their external environment and internal states. An example of this is the acquired, or adaptive, immune system (AIS), which is composed of both humoral and cell-mediated components. Here we report the step-by-step construction of a prototype mimic of the AIS that we call an adaptive immune response simulator (AIRS). DNA and enzymes are used as simple artificial analogues of the components of the AIS to create a system that responds to specific molecular stimuli in vitro. We show that this network of reactions can function in a manner that is superficially similar to the most basic responses of the vertebrate AIS, including reaction sequences that mimic both humoral and cellular responses. As such, AIRS provides guidelines for the design and engineering of artificial reaction networks and molecular devices.
-
Synergy between Molecular and Contextual Views of Coping among Four Ethnic Groups of Older Adults
ERIC Educational Resources Information Center
Conway, Francine; Magai, Carol; McPherson-Salandy, Renee; Milano, Kate
2010-01-01
The coping styles of four ethnic groups of older adults in response to negative life events were analyzed in a population-based study of 1118 residents of Brooklyn, New York. Using a molecular approach, data regarding the context of events and the corresponding coping responses was obtained. Open-ended semi-structured interviews allowed…
-
Geological dates and molecular rates: rapid divergence of rivers and their biotas.
Waters, Jonathan M; Rowe, Diane L; Apte, Smita; King, Tania M; Wallis, Graham P; Anderson, Leigh; Norris, Richard J; Craw, Dave; Burridge, Christopher P
2007-04-01
We highlight a novel molecular clock calibration system based on geologically dated river reversal and river capture events. Changes in drainage pattern may effect vicariant isolation of freshwater taxa, and thus provide a predictive framework for associated phylogeographic study. As a case in point, New Zealand's Pelorus and Kaituna rivers became geologically isolated from the larger Wairau River system 70 to 130 kyr BP. We conducted mitochondrial DNA phylogeographic analyses of two unrelated freshwater-limited fish taxa native to these river systems (Gobiomorphus breviceps, n = 63; Galaxias divergens, n = 95). Phylogenetic analysis of combined control region and cytochrome b sequences yielded reciprocally monophyletic clades of Pelorus-Kaituna and Wairau haplotypes for each species. Calibrated rates of molecular change based on this freshwater vicariant event are substantially faster than traditionally accepted rates for fishes but consistent with other recent inferences based on geologically young calibration points. A survey of freshwater phylogeographic literature reveals numerous examples in which the ages of recent evolutionary events may have been substantially overestimated through the use of "accepted" calibrations. We recommend that--wherever possible--biologists should start to reassess the conclusions of such studies by using more appropriate molecular calibrations derived from recent geological events.
-
Implementing system simulation of C3 systems using autonomous objects
NASA Technical Reports Server (NTRS)
Rogers, Ralph V.
1987-01-01
The basis of all conflict recognition in simulation is a common frame of reference. Synchronous discrete-event simulation relies on the fixed points in time as the basic frame of reference. Asynchronous discrete-event simulation relies on fixed-points in the model space as the basic frame of reference. Neither approach provides sufficient support for autonomous objects. The use of a spatial template as a frame of reference is proposed to address these insufficiencies. The concept of a spatial template is defined and an implementation approach offered. Discussed are the uses of this approach to analyze the integration of sensor data associated with Command, Control, and Communication systems.
-
PET Imaging: Basics and New Trends
NASA Astrophysics Data System (ADS)
Dahlbom, Magnus
Positron Emission Tomography or PET is a noninvasive molecular imaging method used both in research to study biology and disease, and clinically as a routine diagnostic imaging tool. In PET imaging, the subject is injected with a tracer labeled with a positron-emitting isotope and is then placed in a scanner to localize the radioactive tracer in the body. The localization of the tracer utilizes the unique decay characteristics of isotopes decaying by positron emission. In the PET scanner, a large number of scintillation detectors use coincidence detection of the annihilation radiation that is emitted as a result of the positron decay. By collecting a large number of these coincidence events, together with tomographic image reconstruction methods, the 3-D distribution of the radioactive tracer in the body can be reconstructed. Depending on the type of tracer used, the distribution will reflect a particular biological process, such as glucose metabolism when fluoro-deoxyglucose is used. PET has evolved from a relatively inefficient single-slice imaging system with relatively poor spatial resolution to an efficient, high-resolution imaging modality which can acquire a whole-body scan in a few minutes. This chapter will describe the basic physics and instrumentation used in PET. The various corrections that are necessary to apply to the acquired data in order to produce quantitative images are also described. Finally, some of the latest trends in instrumentation development are also discussed.
-
2012-01-01
Background F1 hybrid clones of Eucalyptus grandis and E. urophylla are widely grown for pulp and paper production in tropical and subtropical regions. Volume growth and wood quality are priority objectives in Eucalyptus tree improvement. The molecular basis of quantitative variation and trait expression in eucalypt hybrids, however, remains largely unknown. The recent availability of a draft genome sequence (http://www.phytozome.net) and genome-wide genotyping platforms, combined with high levels of genetic variation and high linkage disequilibrium in hybrid crosses, greatly facilitate the detection of quantitative trait loci (QTLs) as well as underlying candidate genes for growth and wood property traits. In this study, we used Diversity Arrays Technology markers to assess the genetic architecture of volume growth (diameter at breast height, DBH) and wood basic density in four-year-old progeny of an interspecific backcross pedigree of E. grandis and E. urophylla. In addition, we used Illumina RNA-Seq expression profiling in the E. urophylla backcross family to identify cis- and trans-acting polymorphisms (eQTLs) affecting transcript abundance of genes underlying QTLs for wood basic density. Results A total of five QTLs for DBH and 12 for wood basic density were identified in the two backcross families. Individual QTLs for DBH and wood basic density explained 3.1 to 12.2% of phenotypic variation. Candidate genes underlying QTLs for wood basic density on linkage groups 8 and 9 were found to share trans-acting eQTLs located on linkage groups 4 and 10, which in turn coincided with QTLs for wood basic density suggesting that these QTLs represent segregating components of an underlying transcriptional network. Conclusion This is the first demonstration of the use of next-generation expression profiling to quantify transcript abundance in a segregating tree population and identify candidate genes potentially affecting wood property variation. The QTLs identified in this study provide a resource for identifying candidate genes and developing molecular markers for marker-assisted breeding of volume growth and wood basic density. Our results suggest that integrated analysis of transcript and trait variation in eucalypt hybrids can be used to dissect the molecular basis of quantitative variation in wood property traits. PMID:22817272
-
Blennow, Kaj; Zetterberg, Henrik
2015-01-01
This paper gives a short review on cerebrospinal fluid (CSF) biomarkers for Alzheimer's disease (AD), from early developments to high-precision validated assays on fully automated lab analyzers. We also discuss developments on novel biomarkers, such as synaptic proteins and Aβ oligomers. Our vision for the future is that assaying a set of biomarkers in a single CSF tube can monitor the whole spectrum of AD molecular pathogenic events. CSF biomarkers will have a central position not only for clinical diagnosis, but also for the understanding of the sequence of molecular events in the pathogenic process underlying AD and as tools to monitor the effects of novel drug candidates targeting these different mechanisms.
-
Human papillomavirus molecular biology.
Harden, Mallory E; Munger, Karl
Human papillomaviruses are small DNA viruses with a tropism for squamous epithelia. A unique aspect of human papillomavirus molecular biology involves dependence on the differentiation status of the host epithelial cell to complete the viral lifecycle. A small group of these viruses are the etiologic agents of several types of human cancers, including oral and anogenital tract carcinomas. This review focuses on the basic molecular biology of human papillomaviruses. Copyright © 2016 Elsevier B.V. All rights reserved.
-
Introducing Disjoint and Independent Events in Probability.
ERIC Educational Resources Information Center
Kelly, I. W.; Zwiers, F. W.
Two central concepts in probability theory are those of independence and mutually exclusive events. This document is intended to provide suggestions to teachers that can be used to equip students with an intuitive, comprehensive understanding of these basic concepts in probability. The first section of the paper delineates mutually exclusive and…
-
ERIC Educational Resources Information Center
Birnbaum, Mark J.; Picco, Jenna; Clements, Meghan; Witwicka, Hanna; Yang, Meiheng; Hoey, Margaret T.; Odgren, Paul R.
2010-01-01
A key goal of molecular/cell biology/biotechnology is to identify essential genes in virtually every physiological process to uncover basic mechanisms of cell function and to establish potential targets of drug therapy combating human disease. This article describes a semester-long, project-oriented molecular/cellular/biotechnology laboratory…
-
Code of Federal Regulations, 2013 CFR
2013-04-01
...) INDIRECT FOOD ADDITIVES: POLYMERS Substances for Use as Basic Components of Single and Repeated Use Food Contact Surfaces § 177.1440 4,4′-Isopropylidenediphenol-epichlorohydrin resins minimum molecular weight 10... may be safely used as articles or components of articles intended for use in producing, manufacturing...
-
Code of Federal Regulations, 2012 CFR
2012-04-01
...) INDIRECT FOOD ADDITIVES: POLYMERS Substances for Use as Basic Components of Single and Repeated Use Food Contact Surfaces § 177.1440 4,4′-Isopropylidenediphenol-epichlorohydrin resins minimum molecular weight 10... may be safely used as articles or components of articles intended for use in producing, manufacturing...
-
A Cartoon in One Dimension of the Hydrogen Molecular Ion
ERIC Educational Resources Information Center
Dutta, Sourav; Ganguly, Shreemoyee; Dutta-Roy, Binayak
2008-01-01
To illustrate the basic methodology involved in the quantum mechanics of molecules, a one-dimensional caricature of the hydrogen molecular ion (H[superscript +][subscript 2]) is presented, which is exactly solvable, in the Born-Oppenheimer approximation, in terms of elementary functions. The purpose of the exercise is to elucidate in a simple…
-
BIOPS Interactive: An e-Learning Platform Focused on Protein Structure and DNA
ERIC Educational Resources Information Center
Pontelli, Enrico; Pinto, Jorge; Qin, Xiaoxiao; He, Jing; Bevan, David; MacCuish, Norah; MacCuish, John; Chapman, Mitch; Moreland, David
2009-01-01
One of the difficulties in teaching basic molecular biology concepts to the students with little biological background is the lack of hands-on exercises that combines the challenges of the concepts with visualization and immediate feedback. BIOPS Interactive is a web-based interactive learning environment for molecular biology that complements…
-
Datta, Subimal; MacLean, Robert Ross
2007-01-01
At its most basic level, the function of mammalian sleep can be described as a restorative process of the brain and body; recently, however, progressive research has revealed a host of vital functions to which sleep is essential. Although many excellent reviews on sleep behavior have been published, none have incorporated contemporary studies examining the molecular mechanisms that govern the various stages of sleep. Utilizing a holistic approach, this review is focused on the basic mechanisms involved in the transition from wakefulness, initiation of sleep and the subsequent generation of slow-wave sleep and rapid eye movement (REM) sleep. Additionally, using recent molecular studies and experimental evidence that provides a direct link to sleep as a behavior, we have developed a new model, the Cellular-Molecular-Network model, explaining the mechanisms responsible for regulating REM sleep. By analyzing the fundamental neurobiological mechanisms responsible for the generation and maintenance of sleep-wake behavior in mammals, we intend to provide a broader understanding of our present knowledge in the field of sleep research. PMID:17445891
-
Chemical and Biochemical Approaches in the Study of Histone Methylation and Demethylation
Li, Keqin Kathy; Luo, Cheng; Wang, Dongxia; Jiang, Hualiang; Zheng, Y. George
2014-01-01
Histone methylation represents one of the most critical epigenetic events in DNA function regulation in eukaryotic organisms. Classic molecular biology and genetics tools provide significant knowledge about mechanisms and physiological roles of histone methyltransferases and demethylases in various cellular processes. In addition to this stream line, development and application of chemistry and chemistry-related techniques are increasingly involved in biological study, and provide information otherwise difficulty to obtain by standard molecular biology methods. Herein, we review recent achievements and progress in developing and applying chemical and biochemical approaches in the study of histone methylation, including chromatin immunoprecipitation (ChIP), chemical ligation, mass spectrometry (MS), biochemical assays, and inhibitor development. These technological advances allow histone methylation to be studied from genome-wide level to molecular and atomic levels. With ChIP technology, information can be obtained about precise mapping of histone methylation patterns at specific promoters, genes or other genomic regions. MS is particularly useful in detecting and analyzing methylation marks in histone and nonhistone protein substrates. Chemical approaches that permit site-specific incorporation of methyl groups into histone proteins greatly facilitate the investigation of the biological impacts of methylation at individual modification sites. Discovery and design of selective organic inhibitors of histone methyltransferases and demethylases provide chemical probes to interrogate methylation-mediated cellular pathways. Overall, these chemistry-related technological advances have greatly improved our understanding of the biological functions of histone methylation in normal physiology and diseased states, and also are of great potential to translate basic epigenetics research into diagnostic and therapeutic application in the clinic. PMID:22777714
-
Folding and Homodimerization of Wheat Germ Agglutinin
Portillo-Téllez, María del Carmen; Bello, Martiniano; Salcedo, Guillermo; Gutiérrez, Gabriel; Gómez-Vidales, Virginia; García-Hernández, Enrique
2011-01-01
Wheat germ agglutinin (WGA) is emblematic of proteins that specialize in the recognition of carbohydrates. It was the first lectin reported to have a capacity for discriminating between normal and malignant cells. Since then, it has become a preferred model for basic research and is frequently considered in the development of biomedical and biotechnological applications. However, the molecular basis for the structural stability of this homodimeric lectin remains largely unknown, a situation that limits the rational manipulation and modification of its function. In this work we performed a thermodynamic characterization of WGA folding and self-association processes as a function of pH and temperature by using differential scanning and isothermal dilution calorimetry. WGA is monomeric at pH 2, and one of its four hevein-like domains is unfolded at room temperature. Under such conditions, the agglutinin exhibits a fully reversible thermal unfolding that consists of three two-state transitions. At higher pH values, the protein forms weak, nonobligate dimers. This behavior contrasts with that observed for the other plant lectins studied thus far, which form strong, obligate oligomers, indicating a distinctly different molecular basis for WGA function. For dimer formation, the four domains must be properly folded. Nevertheless, depending on the solution conditions, self-association may be coupled with folding of the labile domain. Therefore, dimerization may proceed as a rigid-body-like association or a folding-by-binding event. This hybrid behavior is not seen in other plant lectins. The emerging molecular picture for the WGA assembly highlights the need for a reexamination of existing ligand-binding data in the literature. PMID:21943423
-
Targeting inflammatory pathways in myocardial infarction
Christia, Panagiota; Frangogiannis, Nikolaos G
2013-01-01
Acute cardiomyocyte necrosis in the infarcted heart generates Damage-Associated Molecular Patterns (DAMPs), activating complement and Toll-Like Receptor (TLR)/Interleukin (IL)-1 signaling, and triggering an intense inflammatory reaction. Infiltrating leukocytes clear the infarct from dead cells, while activating reparative pathways that lead to formation of a scar. As the infarct heals the ventricle remodels; the geometric, functional and molecular alterations associated with post-infarction remodeling are driven by the inflammatory cascade and are involved in the development of heart failure. Because unrestrained inflammation in the infarcted heart induces matrix degradation and cardiomyocyte apoptosis, timely suppression of the post-infarction inflammatory reaction may be crucial to protect the myocardium from dilative remodeling and progressive dysfunction. Inhibition and resolution of post-infarction inflammation involves mobilization of inhibitory mononuclear cell subsets and requires activation of endogenous STOP signals. Our manuscript discusses the basic cellular and molecular events involved in initiation, activation and resolution of the post-infarction inflammatory response, focusing on identification of therapeutic targets. The failure of anti-integrin approaches in patients with myocardial infarction and a growing body of experimental evidence suggest that inflammation may not increase ischemic cardiomyocyte death, but accentuates matrix degradation causing dilative remodeling. Given the pathophysiologic complexity of post-infarction remodeling, personalized biomarker-based approaches are needed to target patient subpopulations with dysregulated inflammatory and reparative responses. Inhibition of pro-inflammatory signals (such as IL-1 and Monocyte Chemoattractant Protein-1) may be effective in patients with defective resolution of post-infarction inflammation who exhibit progressive dilative remodeling. In contrast, patients with predominant hypertrophic/fibrotic responses may benefit from anti-TGF strategies. PMID:23772948
-
Mucin-Type O-Glycosylation in Invertebrates.
Staudacher, Erika
2015-06-09
O-Glycosylation is one of the most important posttranslational modifications of proteins. It takes part in protein conformation, protein sorting, developmental processes and the modulation of enzymatic activities. In vertebrates, the basics of the biosynthetic pathway of O-glycans are already well understood. However, the regulation of the processes and the molecular aspects of defects, especially in correlation with cancer or developmental abnormalities, are still under investigation. The knowledge of the correlating invertebrate systems and evolutionary aspects of these highly conserved biosynthetic events may help improve the understanding of the regulatory factors of this pathway. Invertebrates display a broad spectrum of glycosylation varieties, providing an enormous potential for glycan modifications which may be used for the design of new pharmaceutically active substances. Here, overviews of the present knowledge of invertebrate mucin-type O-glycan structures and the currently identified enzymes responsible for the biosynthesis of these oligosaccharides are presented, and the few data dealing with functional aspects of O-glycans are summarised.
-
Bottleneck limitations for microRNA-based therapeutics from bench to the bedside.
Chen, Yan; Zhao, Hongliang; Tan, Zhijun; Zhang, Cuiping; Fu, Xiaobing
2015-03-01
MicroRNAs are endogenous non-coding small RNAs that repress expression of a broad array of target genes. Research into the role and underlying molecular events of microRNAs in disease processes and the potential of microRNAs as drug targets has expanded rapidly. Significant advances have been made in identifying the associations of microRNAs with cancers, viral infections, immune diseases, cardiovascular diseases, wound healing, biological development and other areas of medicine. However, because of intense competition and financial risks, there is a series of stringent criteria and conditions that must be met before microRNA-based therapeutics could be pursued as new drug candidates. In this review, we specifically emphasized the obstacles for bench-based microRNA to the bedside, including common barriers in basic research, application limitations while moving to the clinic at the aspects of vector delivery, off-target effects, toxicity mediation, immunological activation and dosage determination, which should be overcome before microRNA-based therapeutics take their place in the clinic.
-
Alternans Arrhythmias: From Cell to Heart
Weiss, James N.; Nivala, Michael; Garfinkel, Alan; Qu, Zhilin
2010-01-01
The goal of systems biology is to relate events at the molecular level to more integrated scales from organelle to cell, tissue and living organism. Here we review how normal and abnormal excitation-contraction (EC) coupling properties emerge from the protein scale, where behaviors are dominated by randomness, to the cell and tissue scales, where heart has to beat with reliable regularity for a life-time. Beginning with the fundamental unit of EC coupling, the couplon where L-type Ca channels in the sarcolemmal membrane adjoin ryanodine receptors in the sarcoplasmic reticulum membrane, we show how a network of couplons with three basic properties (random activation, refractoriness, and recruitment) produces the classical physiological properties of excitation-contraction (EC) coupling and, under pathophysiological conditions, leads to Ca alternans and Ca waves. Moving to the tissue scale, we discuss how cellular Ca alternans and Ca waves promote both reentrant and focal arrhythmias in the heart. Throughout, we emphasize the qualitatively novel properties which emerge at each new scale of integration. PMID:21212392
-
Uncertainty analysis in fault tree models with dependent basic events.
Pedroni, Nicola; Zio, Enrico
2013-06-01
In general, two types of dependence need to be considered when estimating the probability of the top event (TE) of a fault tree (FT): "objective" dependence between the (random) occurrences of different basic events (BEs) in the FT and "state-of-knowledge" (epistemic) dependence between estimates of the epistemically uncertain probabilities of some BEs of the FT model. In this article, we study the effects on the TE probability of objective and epistemic dependences. The well-known Frèchet bounds and the distribution envelope determination (DEnv) method are used to model all kinds of (possibly unknown) objective and epistemic dependences, respectively. For exemplification, the analyses are carried out on a FT with six BEs. Results show that both types of dependence significantly affect the TE probability; however, the effects of epistemic dependence are likely to be overwhelmed by those of objective dependence (if present). © 2012 Society for Risk Analysis.
-
Balaur, Irina; Saqi, Mansoor; Barat, Ana; Lysenko, Artem; Mazein, Alexander; Rawlings, Christopher J; Ruskin, Heather J; Auffray, Charles
2017-10-01
The development of colorectal cancer (CRC)-the third most common cancer type-has been associated with deregulations of cellular mechanisms stimulated by both genetic and epigenetic events. StatEpigen is a manually curated and annotated database, containing information on interdependencies between genetic and epigenetic signals, and specialized currently for CRC research. Although StatEpigen provides a well-developed graphical user interface for information retrieval, advanced queries involving associations between multiple concepts can benefit from more detailed graph representation of the integrated data. This can be achieved by using a graph database (NoSQL) approach. Data were extracted from StatEpigen and imported to our newly developed EpiGeNet, a graph database for storage and querying of conditional relationships between molecular (genetic and epigenetic) events observed at different stages of colorectal oncogenesis. We illustrate the enhanced capability of EpiGeNet for exploration of different queries related to colorectal tumor progression; specifically, we demonstrate the query process for (i) stage-specific molecular events, (ii) most frequently observed genetic and epigenetic interdependencies in colon adenoma, and (iii) paths connecting key genes reported in CRC and associated events. The EpiGeNet framework offers improved capability for management and visualization of data on molecular events specific to CRC initiation and progression.
-
NASA Astrophysics Data System (ADS)
Dandouras, Iannis; Poppe, Andrew R.; Fillingim, Matt O.; Kistler, Lynn M.; Mouikis, Christopher G.; Rème, Henri
2017-04-01
Heavy molecular ions escaping from a planetary atmosphere can contribute to the long-term evolution of its composition. The ARTEMIS (Acceleration, Reconnection, Turbulence, and Electrodynamics of the Moon's Interaction with the Sun) spacecraft has recently observed outflowing molecular ions at lunar distances in the terrestrial magnetotail (Poppe et al., 2016). Backward particle tracing indicated that these ions should originate from the terrestrial inner magnetosphere. Here we have examined Cluster data acquired by the CIS-CODIF (Cluster Ion Spectrometry-Composition Distribution Function) ion mass spectrometer, obtained in the terrestrial magnetosphere. An event was selected where the orbital conditions were favourable and the Cluster spacecraft were in the high-latitude inner magnetosphere a few hours before the ARTEMIS molecular ion detection. Analysis shows that the CIS-CODIF instrument detected a series of energetic ion species, including not only O+ but also a group of molecular ions around 30 amu. Given the 5-7 m/Δm mass resolution of the instrument, these could include N2+, NO+, or O2+. These ions were detected by Cluster about 14 hours before the ARTEMIS observation in the lunar environment, a time which is compatible with the transfer to lunar distances. The event was during an active period followed by a northward rotation of the IMF. Although energetic heavy molecular ions have been detected in the storm time magnetosphere in the past (e.g. Klecker et al., 1986; Christon et al., 1994), this event constitutes the first coordinated observation in the Earth's inner magnetosphere and at the Moon. Additional events of coordinated outflowing molecular ion observations are currently under analysis. Future missions, as the proposed ESCAPE mission, should investigate in detail the mechanisms of molecular ion acceleration and escape, their link to the solar and magnetospheric activity, and their role in the magnetospheric dynamics and in the long-term evolution of the atmospheric composition.
-
Iwamoto, Noriko; Shimada, Takashi
2018-05-01
Since the turn of the century, mass spectrometry (MS) technologies have continued to improve dramatically, and advanced strategies that were impossible a decade ago are increasingly becoming available. The basic characteristics behind these advancements are MS resolution, quantitative accuracy, and information science for appropriate data processing. The spectral data from MS contain various types of information. The benefits of improving the resolution of MS data include accurate molecular structural-derived information, and as a result, we can obtain a refined biomolecular structure determination in a sequential and large-scale manner. Moreover, in MS data, not only accurate structural information but also the generated ion amount plays an important rule. This progress has greatly contributed a research field that captures biological events as a system by comprehensively tracing the various changes in biomolecular dynamics. The sequential changes of proteome expression in biological pathways are very essential, and the amounts of the changes often directly become the targets of drug discovery or indicators of clinical efficacy. To take this proteomic approach, it is necessary to separate the individual MS spectra derived from each biomolecule in the complexed biological samples. MS itself is not so infinite to perform the all peak separation, and we should consider improving the methods for sample processing and purification to make them suitable for injection into MS. The above-described characteristics can only be achieved using MS with any analytical instrument. Moreover, MS is expected to be applied and expand into many fields, not only basic life sciences but also forensic medicine, plant sciences, materials, and natural products. In this review, we focus on the technical fundamentals and future aspects of the strategies for accurate structural identification, structure-indicated quantitation, and on the challenges for pharmacokinetics of high-molecular-weight protein biopharmaceuticals. Copyright © 2017 The Authors. Published by Elsevier Inc. All rights reserved.
-
NASA Astrophysics Data System (ADS)
2008-01-01
Evaluation of Projects for Basic Research of Scientific Instruments in 2008 Completed NSFC Former President Tang Ao-qing Passed Away Professor Tang Aoqing and NSFC Carbon Nanotube Film-Based Speaker Developed in Tsinghua University Dinosaur Footprint Fossils Discovered in Xinjiang New Method for Early Cancer Diagnosis New Progress Achieved by NSFC Project in Basic Research of Black Hole Physics New progress in Organic FET 67 NSFC-RFBR Cooperative Projects Approved for 2008 Spin Configuration and Super-exchange Mechanism in Molecular Magnets Observed NSFC Strengthens its Funding in Wenchuan Concerns Go to Disaster's Impact on Economy and Emergency Response Thirty-seven NSFC-KOSEF Cooperative Projects Approved
-
Efficient method for events detection in phonocardiographic signals
NASA Astrophysics Data System (ADS)
Martinez-Alajarin, Juan; Ruiz-Merino, Ramon
2005-06-01
The auscultation of the heart is still the first basic analysis tool used to evaluate the functional state of the heart, as well as the first indicator used to submit the patient to a cardiologist. In order to improve the diagnosis capabilities of auscultation, signal processing algorithms are currently being developed to assist the physician at primary care centers for adult and pediatric population. A basic task for the diagnosis from the phonocardiogram is to detect the events (main and additional sounds, murmurs and clicks) present in the cardiac cycle. This is usually made by applying a threshold and detecting the events that are bigger than the threshold. However, this method usually does not allow the detection of the main sounds when additional sounds and murmurs exist, or it may join several events into a unique one. In this paper we present a reliable method to detect the events present in the phonocardiogram, even in the presence of heart murmurs or additional sounds. The method detects relative maxima peaks in the amplitude envelope of the phonocardiogram, and computes a set of parameters associated with each event. Finally, a set of characteristics is extracted from each event to aid in the identification of the events. Besides, the morphology of the murmurs is also detected, which aids in the differentiation of different diseases that can occur in the same temporal localization. The algorithms have been applied to real normal heart sounds and murmurs, achieving satisfactory results.
-
Wilf, Peter; Escapa, Ignacio H
2015-07-01
Evolutionary divergence-age estimates derived from molecular 'clocks' are frequently correlated with paleogeographic, paleoclimatic and extinction events. One prominent hypothesis based on molecular data states that the dominant pattern of Southern Hemisphere biogeography is post-Gondwanan clade origins and subsequent dispersal across the oceans in a metaphoric 'Green Web'. We tested this idea against well-dated Patagonian fossils of 19 plant lineages, representing organisms that actually lived on Gondwana. Most of these occurrences are substantially older than their respective, often post-Gondwanan molecular dates. The Green Web interpretation probably results from directional bias in molecular results. Gondwanan history remains fundamental to understanding Southern Hemisphere plant radiations, and we urge significantly greater caution when using molecular dating to interpret the biological impacts of geological events. © 2014 The Authors. New Phytologist © 2014 New Phytologist Trust.
-
Directly observable optical properties of sprites in Central Europe
NASA Astrophysics Data System (ADS)
Bór, József
2013-04-01
Luminous optical emissions accompanying streamer-based natural electric breakdown processes initiating in the mesosphere are called sprites. 489 sprite events have been observed with a TV frame rate video system in Central Europe from Sopron (47.68N, 16.58E, 230 m MSL), Hungary between 2007 and 2009. On the basis of these observations, characteristic morphological properties of sprites, i.e. basic forms (e.g. column, carrot, angel, etc.) as well as common morphological features (e.g. tendrils, glows, puffs, beads, etc.), have been identified. Probable time sequences of streamer propagation directions were associated with each of the basic sprite forms. It is speculated that different sequences of streamer propagation directions can result in very similar final sprite shapes. The number and type variety of sprite elements appearing in an event as well as the total optical duration of an event was analyzed statistically. Jellyfish and dancing sprite events were considered as special subsets of sprite clusters. It was found that more than 90% of the recorded sprite elements appeared in clusters rather than alone and more than half of the clusters contained more than one basic sprite forms. The analysis showed that jellyfish sprites and clusters of column sprites featuring glows and tendrils do not tend to have optical lifetimes longer than 80 ms. Such very long optical lifetimes have not been observed in sprite clusters containing more than 25 elements of any type, either. In contrast to clusters containing sprite entities of only one form, sprite events showing more sprite forms seem to have extended optical durations more likely. The need for further investigation and for finding theoretical concepts to link these observations to electric conditions ambient for sprite formation is emphasized.
-
Sampling of Protein Folding Transitions: Multicanonical Versus Replica Exchange Molecular Dynamics.
Jiang, Ping; Yaşar, Fatih; Hansmann, Ulrich H E
2013-08-13
We compare the efficiency of multicanonical and replica exchange molecular dynamics for the sampling of folding/unfolding events in simulations of proteins with end-to-end β -sheet. In Go-model simulations of the 75-residue MNK6, we observe improvement factors of 30 in the number of folding/unfolding events of multicanonical molecular dynamics over replica exchange molecular dynamics. As an application, we use this enhanced sampling to study the folding landscape of the 36-residue DS119 with an all-atom physical force field and implicit solvent. Here, we find that the rate-limiting step is the formation of the central helix that then provides a scaffold for the parallel β -sheet formed by the two chain ends.
-
Burkhart, Keith K; Abernethy, Darrell; Jackson, David
2015-06-01
Drug features that are associated with Stevens-Johnson syndrome (SJS) have not been fully characterized. A molecular target analysis of the drugs associated with SJS in the FDA Adverse Event Reporting System (FAERS) may contribute to mechanistic insights into SJS pathophysiology. The publicly available version of FAERS was analyzed to identify disproportionality among the molecular targets, metabolizing enzymes, and transporters for drugs associated with SJS. The FAERS in-house version was also analyzed for an internal comparison of the drugs most highly associated with SJS. Cyclooxygenases 1 and 2, carbonic anhydrase 2, and sodium channel 2 alpha were identified as disproportionately associated with SJS. Cytochrome P450 (CYPs) 3A4 and 2C9 are disproportionately represented as metabolizing enzymes of the drugs associated with SJS adverse event reports. Multidrug resistance protein 1 (MRP-1), organic anion transporter 1 (OAT1), and PEPT2 were also identified and are highly associated with the transport of these drugs. A detailed review of the molecular targets identifies important roles for these targets in immune response. The association with CYP metabolizing enzymes suggests that reactive metabolites and oxidative stress may have a contributory role. Drug transporters may enhance intracellular tissue concentrations and also have vital physiologic roles that impact keratinocyte proliferation and survival. Data mining FAERS may be used to hypothesize mechanisms for adverse drug events by identifying molecular targets that are highly associated with drug-induced adverse events. The information gained may contribute to systems biology disease models.
-
A three-tiered approach for linking pharmacokinetic ...
The power of the adverse outcome pathway (AOP) framework arises from its utilization of pathway-based data to describe the initial interaction of a chemical with a molecular target (molecular initiating event; (MIE), followed by a progression through a series of key events that lead to an adverse outcome relevant for regulatory purposes. The AOP itself is not chemical specific, thus providing the biological context necessary for interpreting high throughput (HT) toxicity screening results. Application of the AOP framework and HT predictions in ecological and human health risk assessment, however, requires the consideration of chemical-specific properties that influence external exposure doses and target tissue doses. To address this requirement, a three-tiered approach was developed to provide a workflow for connecting biology-based AOPs to biochemical-based pharmacokinetic properties (absorption, distribution, metabolism, excretion; ADME), and then to chemical/human activity-based exposure pathways. This approach included: (1) The power of the adverse outcome pathway (AOP) framework arisesfrom its utilization of pathway-based data to describe the initial interaction of a chemical with a molecular target (molecular initiating event; (MIE), followed by a progression through a series of key events that lead to an adverse outcome relevant for regulatory purposes. The AOP itself is not chemical specific, thus providing the biological context necessary for interpreti
-
Students' Engaging School Experiences: A Precondition for Functional Inclusive Practice
ERIC Educational Resources Information Center
Palmgren, Marina Helena; Pyhältö, Kirsi; Soini, Tiina; Pietarinen, Janne
2017-01-01
Basic education strives to provide an equal education for all students, whether the students attend regular or special education. In this study, we explore seventh grade comprehensive school students' (N = 119) experiences of engaging and disengaging events at school and the points at which these events occur in their school career. The students…
-
Ratings of Severity of Life Events by Ninth-Grade Students.
ERIC Educational Resources Information Center
Hutton, Jerry B.; And Others
1987-01-01
Special education, basic, and honors ninth-grade students (n=60) rated the severity of stress for each of the life events on the Source of Stress Inventory (Chandler, 1981). There was a significant positive relationship between the Chandler rankings (teachers and mental health workers) and the student rankings. (Author/NB)
-
Mei, Lin; Cho, Kei; Lee, C Justin; Li, Xiao-Jiang; Zhuo, Min; Kaang, Bong-Kiun
2008-01-01
We are delighted to announce the arrival of a brand new journal dedicated to the ever-expanding field of neuroscience. Molecular Brain is a peer-reviewed, open-access online journal that aims at publishing high quality articles as rapidly as possible. The journal will cover a broad spectrum of neuroscience ranging from molecular/cellular to behavioral/cognitive neuroscience and from basic to clinical research. Molecular Brain will publish not only research articles, but also methodology articles, editorials, reviews, and short reports. It will be a premier platform for neuroscientists to exchange their ideas with researchers from around the world to help improve our understanding of the molecular mechanisms of the brain and mind. PMID:18803854
-
Positron Emission Tomography Molecular Imaging in Late-Life Depression
Hirao, Kentaro; Smith, Gwenn S.
2017-01-01
Molecular imaging represents a bridge between basic and clinical neuroscience observations and provides many opportunities for translation and identifying mechanisms that may inform prevention and intervention strategies in late-life depression (LLD). Substantial advances in instrumentation and radiotracer chemistry have resulted in improved sensitivity and spatial resolution and the ability to study in vivo an increasing number of neurotransmitters, neuromodulators, and, importantly, neuropathological processes. Molecular brain imaging studies in LLD will be reviewed, with a primary focus on positron emission tomography. Future directions for the field of molecular imaging in LLD will be discussed, including integrating molecular imaging with genetic, neuropsychiatric, and cognitive outcomes and multimodality neuroimaging. PMID:24394152
-
Random Amplified Polymorphic DNA PCR in the Teaching of Molecular Epidemiology
ERIC Educational Resources Information Center
Reinoso, Elina B.; Bettera, Susana G.
2016-01-01
In this article, we describe a basic practical laboratory designed for fifth-year undergraduate students of Microbiology as part of the Epidemiology course. This practice provides the students with the tools for molecular epidemiological analysis of pathogenic microorganisms using a rapid and simple PCR technique. The aim of this work was to assay…
-
The Fragile X Syndrome: From Molecular Genetics to Neurobiology
ERIC Educational Resources Information Center
Willemsen, Rob; Oostra, Ben A.; Bassell, Gary J.; Dictenberg, Jason
2004-01-01
Since the identification of the FMR1 gene basic research has been focused on the molecular characterization of the FMR1 gene product, the fragile X mental retardation protein (FMRP). Recent developments in fragile X research have provided new insights and knowledge about the physiological function of FMRP in the cell and the nerve cell in…
-
Th1/Th2 Cytokines: An Easy Model to Study Gene Expression in Immune Cells
ERIC Educational Resources Information Center
Moran, Jose M.; Gonzalez-Polo, Rosa A.; Soler, German; Fuentes, Jose M.
2006-01-01
This report describes a laboratory exercise that was incorporated into a Cell Biology and Molecular Biology advanced course. The exercise was made for a class size with eight students and was designed to reinforce the understanding of basic molecular biology techniques. Students used the techniques of reverse transcription and arginase activity…
-
Modeling and simulation of count data.
Plan, E L
2014-08-13
Count data, or number of events per time interval, are discrete data arising from repeated time to event observations. Their mean count, or piecewise constant event rate, can be evaluated by discrete probability distributions from the Poisson model family. Clinical trial data characterization often involves population count analysis. This tutorial presents the basics and diagnostics of count modeling and simulation in the context of pharmacometrics. Consideration is given to overdispersion, underdispersion, autocorrelation, and inhomogeneity.
-
NASA Astrophysics Data System (ADS)
Salazar Valencia, P. J.; Bolívar Marinez, L. E.; Pérez Merchancano, S. T.
2015-12-01
Lignosulphonates (LS), also known as lignin sulfonates or sulfite lignin, are lignins in sulfonated forms, obtained from the "sulfite liquors," a residue of the wood pulp extraction process. Their main utility lies in its wide range of properties, they can be used as additives, dispersants, binders, fluxing, binder agents, etc. in fields ranging from food to fertilizer manufacture and even as agents in the preparation of ion exchange membranes. Since they can be manufactured relatively easy and quickly, and that its molecular size can be manipulated to obtain fragments of very low molecular weight, they are used as transport agents in the food industry, cosmetics, pharmaceutical and drug development, and as molecular elements for the treatment of health problems. In this paper, we study the electronic structural and optical characteristics of LS incorporating ammonium, sulfur, calcium, and sodium ions in acidic and basic aqueous media in order to gain a better understanding of their behavior and the very interesting properties exhibit. The studies were performed using the molecular modeling program HyperChem 5 using the semiempirical method PM3 of the NDO Family (neglect of differential overlap), to calculate the structural properties. We calculated the electronic and optical properties using the semiempirical method ZINDO / CI.
-
Best Practices in the Evaluation of Large-scale STEM-focused Events: A Review of Recent Literature
NASA Astrophysics Data System (ADS)
Shebby, S.; Cobb, W. H.; Buxner, S.; Shipp, S. S.
2015-12-01
Each year, the National Aeronautics and Space Administration (NASA) sponsors a variety of educational events to share information with educators, students, and the general public. Intended outcomes of these events include increased interest in and awareness of the mission and goals of NASA. Events range in size from relatively small family science nights at a local school to large-scale mission and celestial event celebrations involving thousands of members of the general public. To support community members in designing event evaluations, the Science Mission Directorate (SMD) Planetary Science Forum sponsored the creation of a Best Practices Guide. The guide was generated by reviewing published large-scale event evaluation reports; however, the best practices described within are pertinent for all event organizers and evaluators regardless of event size. Each source included in the guide identified numerous challenges to conducting their event evaluation. These included difficulty in identifying extant instruments or items, collecting representative data, and disaggregating data to inform different evaluation questions. Overall, the guide demonstrates that evaluations of the large-scale events are generally done at a very basic level, with the types of data collected limited to observable demographic information and participant reactions collected via online survey. In addition to these findings, this presentation will describe evaluation best practices that will help practitioners move beyond these basic indicators and examine how to make the evaluation process an integral—and valuable—element of event planning, ultimately informing event outcomes and impacts. It will provide detailed information on five recommendations presented in the guide: 1) consider evaluation methodology, including data analysis, in advance; 2) design data collection instruments well in advance of the event; 3) collect data at different times and from multiple sources; 4) use technology to make the job easier; and 5) be aware of how challenging it is to measure impact.
-
Basic Residues of β-Sheet A Contribute to Heparin Binding and Activation of Vaspin (Serpin A12).
Ulbricht, David; Oertwig, Kathrin; Arnsburg, Kristin; Saalbach, Anja; Pippel, Jan; Sträter, Norbert; Heiker, John T
2017-01-20
Many members of the serine protease inhibitor (serpin) family are activated by glycosaminoglycans (GAGs). Visceral adipose tissue-derived serpin (vaspin), serpin A12 of the serpin family, and its target protease kallikrein 7 (KLK7) are heparin-binding proteins, and inhibition of KLK7 by vaspin is accelerated by heparin. However, the nature of GAG binding to vaspin is not known. Here, we measured vaspin binding of various glycosaminoglycans and low molecular weight heparins by microscale thermophoresis and analyzed acceleration of protease inhibition by these molecules. In addition, basic residues contributing to heparin binding and heparin activation were identified by a selective labeling approach. Together, these data show that vaspin binds heparin with high affinity (K D = 21 ± 2 nm) and that binding takes place at a basic patch on top of β-sheet A and is different from other heparin-binding serpins. Mutation of basic residues decreased heparin binding and activation of vaspin. Similarly, reactive center loop insertion into sheet A decreased heparin binding because it disturbs the basic cluster. Finally, using vaspin-overexpressing keratinocyte cells, we show that a significant part of secreted vaspin is bound in the extracellular matrix on the cell surface. Together, basic residues of central β-sheet A contribute to heparin binding and activation of vaspin. Thus, binding to GAGs in the extracellular matrix can direct and regulate vaspin interaction with target proteases or other proteins and may play an important role in the various beneficial functions of vaspin in different tissues. © 2017 by The American Society for Biochemistry and Molecular Biology, Inc.
-
Amanullah, Ayeman; Upadhyay, Arun; Joshi, Vibhuti; Mishra, Ribhav; Jana, Nihar Ranjan; Mishra, Amit
2017-12-01
Proteins are ordered useful cellular entities, required for normal health and organism's survival. The proteome is the absolute set of cellular expressed proteins, which regulates a wide range of physiological functions linked with all domains of life. In aging cells or under unfavorable cellular conditions, misfolding of proteins generates common pathological events linked with neurodegenerative diseases and aging. Current advances of proteome studies systematically generates some progress in our knowledge that how misfolding of proteins or their accumulation can contribute to the impairment or depletion of proteome functions. Still, the underlying causes of this unrecoverable loss are not clear that how such unsolved transitions give rise to multifactorial challengeable degenerative pathological conditions in neurodegeneration. In this review, we specifically focus and systematically summarize various molecular mechanisms of proteostasis maintenance, as well as discuss progressing neurobiological strategies, promising natural and pharmacological candidates, which can be useful to counteract the problem of proteopathies. Our article emphasizes an urgent need that now it is important for us to recognize the fundamentals of proteostasis to design a new molecular framework and fruitful strategies to uncover how the proteome defects are associated with aging and neurodegenerative diseases. A enhance understanding of progress link with proteome and neurobiological challenges may provide new basic concepts in the near future, based on pharmacological agents, linked with impaired proteostasis and neurodegenerative diseases. Copyright © 2017 Elsevier Ltd. All rights reserved.
-
New approaches for managing preeclampsia: clues from clinical and basic research.
George, Eric M
2014-12-01
One of the most common, and most vexing, obstetric complications is preeclampsia-a major cause of maternal and perinatal morbidity. Hallmarked by new-onset hypertension and a myriad of other symptoms, the underlying cause of the disorder remains obscure despite intensive research into its etiology. Although the initiating events are not clear, one common finding in preeclamptic patients is failure to remodel the maternal arteries that supply the placenta, with resulting hypoxia/ischemia. Intensive research over the past 2 decades has identified several categories of molecular dysfunction resulting from placental hypoxia, which, when released into the maternal circulation, are involved in the spectrum of symptoms seen in these patients-in particular, angiogenic imbalance and the activation of innate and adaptive immune responses. Despite these new insights, little in the way of new treatments for the management of these patients has been advanced into clinical practice. Indeed, few therapeutic options exist for the obstetrician treating a case of preeclampsia. Pharmacologic management is typically seizure prophylaxis, and, in severe cases, antihypertensive agents for controlling worsening hypertension. Ultimately, the induction of labor is indicated, making preeclampsia a leading cause of premature birth. Here, the molecular mechanisms linking placental ischemia to the maternal symptoms of preeclampsia are reviewed, and several areas of recent research suggesting new potential therapeutic approaches to the management of preeclampsia are identified. Copyright © 2014 Elsevier HS Journals, Inc. All rights reserved.
-
An Easily Constructed and Versatile Molecular Model
NASA Astrophysics Data System (ADS)
Hernandez, Sandra A.; Rodriguez, Nora M.; Quinzani, Oscar
1996-08-01
Three-dimensional molecular models are powerful tools used in basic courses of general and organic chemistry when the students must visualize the spatial distributions of atoms in molecules and relate them to the physical and chemical properties of such molecules. This article discusses inexpensive, easily carried, and semipermanent molecular models that the students may build by themselves. These models are based upon two different types of arrays of thin flexible wires, like telephone hook-up wires, which may be bent easily but keep their shapes.
-
Molecular Mechanisms of Neuroplasticity: An Expanding Universe.
Gulyaeva, N V
2017-03-01
Biochemical processes in synapses and other neuronal compartments underlie neuroplasticity (functional and structural alterations in the brain enabling adaptation to the environment, learning, memory, as well as rehabilitation after brain injury). This basic molecular level of brain plasticity covers numerous specific proteins (enzymes, receptors, structural proteins, etc.) participating in many coordinated and interacting signal and metabolic processes, their modulation forming a molecular basis for brain plasticity. The articles in this issue are focused on different "hot points" in the research area of biochemical mechanisms supporting neuroplasticity.
-
Pathology of the human pituitary adenomas
Kajiya, Hanako; Takei, Mao; Egashira, Noboru; Tobita, Maya; Takekoshi, Susumu; Teramoto, Akira
2008-01-01
This article describes pertinent aspects of histochemical and molecular changes of the human pituitary adenomas. The article outlines individual tumor groups with general, specific and molecular findings. The discussion further extends to the unusual adenomas or carcinomas. The description in this article are pertinent not only for the practicing pathologists who are in the position of making proper diagnosis, but also for the pituitary research scientists who engage in solving basic problems in pituitary neoplasms by histochemistry and molecular biology. PMID:18688636
-
The circadian clock of Neurospora crassa.
Baker, Christopher L; Loros, Jennifer J; Dunlap, Jay C
2012-01-01
Circadian clocks organize our inner physiology with respect to the external world, providing life with the ability to anticipate and thereby better prepare for major fluctuations in its environment. Circadian systems are widely represented in nearly all major branches of life, except archaebacteria, and within the eukaryotes, the filamentous fungus Neurospora crassa has served for nearly half a century as a durable model organism for uncovering the basic circadian physiology and molecular biology. Studies using Neurospora have clarified our fundamental understanding of the clock as nested positive and negative feedback loops regulated through transcriptional and post-transcriptional processes. These feedback loops are centered on a limited number of proteins that form molecular complexes, and their regulation provides a physical explanation for nearly all clock properties. This review will introduce the basics of circadian rhythms, the model filamentous fungus N. crassa, and provide an overview of the molecular components and regulation of the circadian clock. © 2011 Federation of European Microbiological Societies. Published by Blackwell Publishing Ltd. All rights reserved.
-
ACOG Technology Assessment No. 11: Genetics and molecular diagnostic testing.
2014-02-01
Human genetics and molecular testing are playing an increasingly important role in medicine, including obstetric and gynecologic practice. As the genetic basis for reproductive disorders, common diseases, and cancer is elucidated with improved molecular technology, genetic testing opportunities are expanding and influencing treatment options and prevention strategies. It is essential that obstetrician-gynecologists be aware of advances in the understanding of genetic disease and the fundamental principles of genetic screening and molecular testing as genetics becomes a more integral part of routine medical practice. This document reviews the basics of genetic transmission and genetic technologies in current use.
-
Physiological and molecular determinants of embryo implantation
Zhang, Shuang; Lin, Haiyan; Kong, Shuangbo; Wang, Shumin; Wang, Hongmei; Wang, Haibin; Armant, D. Randall
2014-01-01
Embryo implantation involves the intimate interaction between an implantation-competent blastocyst and a receptive uterus, which occurs in a limited time period known as the window of implantation. Emerging evidence shows that defects originating during embryo implantation induce ripple effects with adverse consequences on later gestation events, highlighting the significance of this event for pregnancy success. Although a multitude of cellular events and molecular pathways involved in embryo-uterine crosstalk during implantation have been identified through gene expression studies and genetically engineered mouse models, a comprehensive understanding of the nature of embryo implantation is still missing. This review focuses on recent progress with particular attention to physiological and molecular determinants of blastocyst activation, uterine receptivity, blastocyst attachment and uterine decidualization. A better understanding of underlying mechanisms governing embryo implantation should generate new strategies to rectify implantation failure and improve pregnancy rates in women. PMID:23290997
-
STRIDE: Species Tree Root Inference from Gene Duplication Events.
Emms, David M; Kelly, Steven
2017-12-01
The correct interpretation of any phylogenetic tree is dependent on that tree being correctly rooted. We present STRIDE, a fast, effective, and outgroup-free method for identification of gene duplication events and species tree root inference in large-scale molecular phylogenetic analyses. STRIDE identifies sets of well-supported in-group gene duplication events from a set of unrooted gene trees, and analyses these events to infer a probability distribution over an unrooted species tree for the location of its root. We show that STRIDE correctly identifies the root of the species tree in multiple large-scale molecular phylogenetic data sets spanning a wide range of timescales and taxonomic groups. We demonstrate that the novel probability model implemented in STRIDE can accurately represent the ambiguity in species tree root assignment for data sets where information is limited. Furthermore, application of STRIDE to outgroup-free inference of the origin of the eukaryotic tree resulted in a root probability distribution that provides additional support for leading hypotheses for the origin of the eukaryotes. © The Author 2017. Published by Oxford University Press on behalf of the Society for Molecular Biology and Evolution.
-
Anthology of the Development of Radiation Transport Tools as Applied to Single Event Effects
NASA Astrophysics Data System (ADS)
Reed, R. A.; Weller, R. A.; Akkerman, A.; Barak, J.; Culpepper, W.; Duzellier, S.; Foster, C.; Gaillardin, M.; Hubert, G.; Jordan, T.; Jun, I.; Koontz, S.; Lei, F.; McNulty, P.; Mendenhall, M. H.; Murat, M.; Nieminen, P.; O'Neill, P.; Raine, M.; Reddell, B.; Saigné, F.; Santin, G.; Sihver, L.; Tang, H. H. K.; Truscott, P. R.; Wrobel, F.
2013-06-01
This anthology contains contributions from eleven different groups, each developing and/or applying Monte Carlo-based radiation transport tools to simulate a variety of effects that result from energy transferred to a semiconductor material by a single particle event. The topics span from basic mechanisms for single-particle induced failures to applied tasks like developing websites to predict on-orbit single event failure rates using Monte Carlo radiation transport tools.
-
[Injury mechanisms in extreme violence settings].
Arcaute-Velazquez, Fernando Federico; García-Núñez, Luis Manuel; Noyola-Vilallobos, Héctor Faustino; Espinoza-Mercado, Fernando; Rodríguez-Vega, Carlos Eynar
2016-01-01
Extreme violence events are consequence of current world-wide economic, political and social conditions. Injury patterns found among victims of extreme violence events are very complex, obeying several high-energy injury mechanisms. In this article, we present the basic concepts of trauma kinematics that regulate the clinical approach to victims of extreme violence events, in the hope that clinicians increase their theoretical armamentarium, and reflecting on obtaining better outcomes. Copyright © 2016. Published by Masson Doyma México S.A.
-
Molecular Diode Studies Based on a Highly Sensitive Molecular Measurement Technique.
Iwane, Madoka; Fujii, Shintaro; Kiguchi, Manabu
2017-04-26
In 1974, molecular electronics pioneers Mark Ratner and Arieh Aviram predicted that a single molecule could act as a diode, in which electronic current can be rectified. The electronic rectification property of the diode is one of basic functions of electronic components and since then, the molecular diode has been investigated as a first single-molecule device that would have a practical application. In this review, we first describe the experimental fabrication and electronic characterization techniques of molecular diodes consisting of a small number of molecules or a single molecule. Then, two main mechanisms of the rectification property of the molecular diode are discussed. Finally, representative results for the molecular diode are reviewed and a brief outlook on crucial issues that need to be addressed in future research is discussed.
-
Molecular Diode Studies Based on a Highly Sensitive Molecular Measurement Technique
Iwane, Madoka; Fujii, Shintaro; Kiguchi, Manabu
2017-01-01
In 1974, molecular electronics pioneers Mark Ratner and Arieh Aviram predicted that a single molecule could act as a diode, in which electronic current can be rectified. The electronic rectification property of the diode is one of basic functions of electronic components and since then, the molecular diode has been investigated as a first single-molecule device that would have a practical application. In this review, we first describe the experimental fabrication and electronic characterization techniques of molecular diodes consisting of a small number of molecules or a single molecule. Then, two main mechanisms of the rectification property of the molecular diode are discussed. Finally, representative results for the molecular diode are reviewed and a brief outlook on crucial issues that need to be addressed in future research is discussed. PMID:28445393
-
ERIC Educational Resources Information Center
Selli, Cigdem; Yildirim, Gokce; Kaymak, Aysegul; Karacicek, Bilge; Ogut, Deniz; Gungor, Turkan; Erem, Erdem; Ege, Mehmet; Bümen, Nilay; Tosun, Metiner
2014-01-01
This study includes the results of a 2-day education project titled "Molecular Biology Laboratory Summer School, MoBiLYO." The project was held at a University Research Center by scientists from Department of Pharmacology and graduate students. The project was composed of introductory lectures, model construction, DNA isolation,…
-
77 FR 56855 - Center For Scientific Review; Notice of Closed Meetings
Federal Register 2010, 2011, 2012, 2013, 2014
2012-09-14
... Review Group; Molecular Genetics A Study Section. Date: October 15-16, 2012. Time: 8:00 a.m. to 6:00 p.m... Genetics Study Section. Date: October 15, 2012. Time: 8:00 a.m. to 5:00 p.m. Agenda: To review and evaluate...: Oncology 1--Basic Translational Integrated Review Group; Cancer Molecular Pathobiology Study Section. Date...
-
ERIC Educational Resources Information Center
Hooley, Paul; Cooper, Phillippa; Skidmore, Nick
2008-01-01
A one day practical course in molecular biology skills suitable for year 12/13 students is described. Colleagues from partner schools and colleges were trained by university staff in basic techniques and then collaborated in the design of a course suitable for their own students. Participants carried out a transformation of "E.coli"…
-
Valerie Rapp
2002-01-01
Pacific Northwest forests and all their species evolved with fires, floods, windstorms, landslides, and other disturbances. The dynamics of disturbance were basic to how forests changed and renewed. Disturbance regimes, as scientists call the long-term patterns of these eventsâwhat kind of event, how often, how large, and how severeâcreated the landscape patterns seen...
-
Valerie Rapp
2003-01-01
Pacific Northwest forests and all their species evolved with fires, floods, windstorms, landslides, and other disturbances. The dynamics of disturbance were basic to how forests changed and renewed. Disturbance regimes, as scientists call the long-term patterns of these eventsâwhat kind of event, how often, how large, and how severeâcreated the landscape patterns seen...
-
Code of Federal Regulations, 2010 CFR
2010-04-01
... 27 Alcohol, Tobacco Products and Firearms 1 2010-04-01 2010-04-01 false Change of name. 1.40... Amendment and Duration of Basic Permits § 1.40 Change of name. In the event of any change in the name (trade or corporate name) of a permittee, or, in the event a permittee desires to engage in operations under...
-
Code of Federal Regulations, 2013 CFR
2013-04-01
... 27 Alcohol, Tobacco Products and Firearms 1 2013-04-01 2013-04-01 false Change of name. 1.40... Amendment and Duration of Basic Permits § 1.40 Change of name. In the event of any change in the name (trade or corporate name) of a permittee, or, in the event a permittee desires to engage in operations under...
-
Code of Federal Regulations, 2012 CFR
2012-04-01
... 27 Alcohol, Tobacco Products and Firearms 1 2012-04-01 2012-04-01 false Change of name. 1.40... Amendment and Duration of Basic Permits § 1.40 Change of name. In the event of any change in the name (trade or corporate name) of a permittee, or, in the event a permittee desires to engage in operations under...
-
Code of Federal Regulations, 2011 CFR
2011-04-01
... 27 Alcohol, Tobacco Products and Firearms 1 2011-04-01 2011-04-01 false Change of name. 1.40... Amendment and Duration of Basic Permits § 1.40 Change of name. In the event of any change in the name (trade or corporate name) of a permittee, or, in the event a permittee desires to engage in operations under...
-
Code of Federal Regulations, 2014 CFR
2014-04-01
... 27 Alcohol, Tobacco Products and Firearms 1 2014-04-01 2014-04-01 false Change of name. 1.40... Amendment and Duration of Basic Permits § 1.40 Change of name. In the event of any change in the name (trade or corporate name) of a permittee, or, in the event a permittee desires to engage in operations under...
-
A molecular quantum spin network controlled by a single qubit.
Schlipf, Lukas; Oeckinghaus, Thomas; Xu, Kebiao; Dasari, Durga Bhaktavatsala Rao; Zappe, Andrea; de Oliveira, Felipe Fávaro; Kern, Bastian; Azarkh, Mykhailo; Drescher, Malte; Ternes, Markus; Kern, Klaus; Wrachtrup, Jörg; Finkler, Amit
2017-08-01
Scalable quantum technologies require an unprecedented combination of precision and complexity for designing stable structures of well-controllable quantum systems on the nanoscale. It is a challenging task to find a suitable elementary building block, of which a quantum network can be comprised in a scalable way. We present the working principle of such a basic unit, engineered using molecular chemistry, whose collective control and readout are executed using a nitrogen vacancy (NV) center in diamond. The basic unit we investigate is a synthetic polyproline with electron spins localized on attached molecular side groups separated by a few nanometers. We demonstrate the collective readout and coherent manipulation of very few (≤ 6) of these S = 1/2 electronic spin systems and access their direct dipolar coupling tensor. Our results show that it is feasible to use spin-labeled peptides as a resource for a molecular qubit-based network, while at the same time providing simple optical readout of single quantum states through NV magnetometry. This work lays the foundation for building arbitrary quantum networks using well-established chemistry methods, which has many applications ranging from mapping distances in single molecules to quantum information processing.
-
Problem Reframing: Intelligence Professionals’ Role in Design
2010-04-01
The idea of differences exists in intelligence analyst’s Don McDowell’s book Strategic Intelligence, when he explains that covering all events...Complexity, (New York, Basic Books , 2000), 7. 57 Gharajedaghi, 107. 20 intelligence community with an end result of increasing the potential for greater...Avoiding Error in Complex Situations, (New York: Basic Books , 1996), 164. 79 Ibid. 26 understanding the operational environment to planning the
-
The chemistry side of AOP: implications for toxicity ...
An adverse outcome pathway (AOP) is a structured representation of the biological events that lead to adverse impacts following a molecular initiating event caused by chemical interaction with a macromolecule. AOPs have been proposed to facilitate toxicity extrapolation across species through understanding of species similarity in the sequence of molecular, cellular, organ and organismal level responses. However, AOPs are non-specific regarding the identity of the chemical initiators, and the range of structures for which an AOP is considered applicable has generally been poorly defined. Applicability domain has been widely understood in the field of QSAR as the response and chemical structure space in which the model makes predictions with a given reliability, and has been traditionally applied to define the similarity of query molecules within the training set. Three dimensional (3D) receptor modeling offers an approach to better define the applicability domain for selected AOPs through determination of the chemical space of the molecular initiating event. Universal 3D-QSAR models were developed for acetylcholinesterase inhibitors and estrogen receptor agonists and antagonists using a combination of fingerprint, molecular docking and structure-based pharmacophore approaches. The models were based on the critical molecular interactions within each receptor ligand binding domain, and included the key amino acid residues responsible for high binding affinity. T
-
King, C. Judson; Tung, Lisa A.
1992-01-01
Carboxylic acids are sorbed from aqueous feedstocks at pHs close to or above the acids' pH.sub.a into a strongly basic organic liquid phase or onto a basic solid adsorbent or moderately basic ion exchange resin. the acids are freed from the sorbent phase by treating it with aqueous alkylamine or ammonia thus forming an alkylammonium or ammonium carobxylate which dewatered and decomposed to the desired carboxylic acid and the alkylamine or ammonia.
-
The East German Research Landscape in Transition. Part B. Non-University Institutes
1993-03-02
struc- tures and metal ions: Basic research of the biosorption , bioaccumulation and metal desorption mechanisms Influence and increase of the sorption...microbial corrosion problems - Investigation of che interaction between microbial structures and metal ions: Basic research of the biosorption ...Additional work has been undertaken on the response of the cell at the molecular level to various stresses, including heat and heavy metals . In both cases
-
DOE Office of Scientific and Technical Information (OSTI.GOV)
Mitchell, R.
1992-01-01
This book covers issues ranging from global climate changes to biocontrol of plant diseases. Many of its contributions stress how new technologies in areas such as molecular biology and environmental engineering expand understanding and applications of basic concepts in environmental microbiology. Articles in the book are in three basic subject areas: effects of environmental contamination on the role of microbes in geochemical cycling of the major elements, pathogens in the environment, and microbial activities in environmental management.
-
Storm loads of culturable and molecular fecal indicators in an inland urban stream.
Liao, Hehuan; Krometis, Leigh-Anne H; Cully Hession, W; Benitez, Romina; Sawyer, Richard; Schaberg, Erin; von Wagoner, Emily; Badgley, Brian D
2015-10-15
Elevated concentrations of fecal indicator bacteria in receiving waters during wet-weather flows are a considerable public health concern that is likely to be exacerbated by future climate change and urbanization. Knowledge of factors driving the fate and transport of fecal indicator bacteria in stormwater is limited, and even less is known about molecular fecal indicators, which may eventually supplant traditional culturable indicators. In this study, concentrations and loading rates of both culturable and molecular fecal indicators were quantified throughout six storm events in an instrumented inland urban stream. While both concentrations and loading rates of each fecal indicator increased rapidly during the rising limb of the storm hydrographs, it is the loading rates rather than instantaneous concentrations that provide a better estimate of transport through the stream during the entire storm. Concentrations of general fecal indicators (both culturable and molecular) correlated most highly with each other during storm events but not with the human-associated HF183 Bacteroides marker. Event loads of general fecal indicators most strongly correlated with total runoff volume, maximum discharge, and maximum turbidity, while event loads of HF183 most strongly correlated with the time to peak flow in a hydrograph. These observations suggest that collection of multiple samples during a storm event is critical for accurate predictions of fecal indicator loading rates and total loads during wet-weather flows, which are required for effective watershed management. In addition, existing predictive models based on general fecal indicators may not be sufficient to predict source-specific genetic markers of fecal contamination. Copyright © 2015 Elsevier B.V. All rights reserved.
-
Bal-Price, Anna; Lein, Pamela J.; Keil, Kimberly P.; Sethi, Sunjay; Shafer, Timothy; Barenys, Marta; Fritsche, Ellen; Sachana, Magdalini; Meek, M.E. (Bette)
2016-01-01
The Adverse Outcome Pathway (AOP) concept has recently been proposed to support a paradigm shift in regulatory toxicology testing and risk assessment. This concept is similar to the Mode of Action (MOA), in that it describes a sequence of measurable key events triggered by a molecular initiating event in which a stressor interacts with a biological target. The resulting cascade of key events includes molecular, cellular, structural and functional changes in biological systems, resulting in a measurable adverse outcome. Thereby, an AOP ideally provides information relevant to chemical structure-activity relationships as a basis for predicting effects of structurally similar compounds. AOPs could potentially also form the basis for qualitative and quantitative predictive modeling of the human adverse outcome resulting from molecular initiating or other key events for which higher-throughput testing methods are available or can be developed. A variety of cellular and molecular processes are known to be critical for normal function of the central (CNS) and peripheral nervous systems (PNS). Because of the biological and functional complexity of the CNS and PNS, it has been challenging to establish causative links and quantitative relationships between key events that comprise the pathways leading from chemical exposure to an adverse outcome in the nervous system. Following introduction of the principles of MOA and AOPs, examples of potential or putative adverse outcome pathways specific for developmental or adult neurotoxicity are summarized and aspects of their assessment considered. Their possible application in developing mechanistically informed Integrated Approaches to Testing and Assessment (IATA) is also discussed. PMID:27212452
-
Structural Biology and Molecular Applications Research
Part of NCI's Division of Cancer Biology's research portfolio, research and development in this area focuses on enabling technologies, models, and methodologies to support basic and applied cancer research.
-
Hall, S; Poller, B; Bailey, C; Gregory, S; Clark, R; Roberts, P; Tunbridge, A; Poran, V; Evans, C; Crook, B
2018-06-01
Variations currently exist across the UK in the choice of personal protective equipment (PPE) used by healthcare workers when caring for patients with suspected high-consequence infectious diseases (HCIDs). To test the protection afforded to healthcare workers by current PPE ensembles during assessment of a suspected HCID case, and to provide an evidence base to justify proposal of a unified PPE ensemble for healthcare workers across the UK. One 'basic level' (enhanced precautions) PPE ensemble and five 'suspected case' PPE ensembles were evaluated in volunteer trials using 'Violet'; an ultraviolet-fluorescence-based simulation exercise to visualize exposure/contamination events. Contamination was photographed and mapped. There were 147 post-simulation and 31 post-doffing contamination events, from a maximum of 980, when evaluating the basic level of PPE. Therefore, this PPE ensemble did not afford adequate protection, primarily due to direct contamination of exposed areas of the skin. For the five suspected case ensembles, 1584 post-simulation contamination events were recorded, from a maximum of 5110. Twelve post-doffing contamination events were also observed (face, two events; neck, one event; forearm, one event; lower legs, eight events). All suspected case PPE ensembles either had post-doffing contamination events or other significant disadvantages to their use. This identified the need to design a unified PPE ensemble and doffing procedure, incorporating the most protective PPE considered for each body area. This work has been presented to, and reviewed by, key stakeholders to decide on a proposed unified ensemble, subject to further evaluation. Crown Copyright © 2018. Published by Elsevier Ltd. All rights reserved.
-
NASA Astrophysics Data System (ADS)
Guan, Yifeng; Zhao, Jie; Shi, Tengfei; Zhu, Peipei
2016-09-01
In recent years, China's increased interest in environmental protection has led to a promotion of energy-efficient dual fuel (diesel/natural gas) ships in Chinese inland rivers. A natural gas as ship fuel may pose dangers of fire and explosion if a gas leak occurs. If explosions or fires occur in the engine rooms of a ship, heavy damage and losses will be incurred. In this paper, a fault tree model is presented that considers both fires and explosions in a dual fuel ship; in this model, dual fuel engine rooms are the top events. All the basic events along with the minimum cut sets are obtained through the analysis. The primary factors that affect accidents involving fires and explosions are determined by calculating the degree of structure importance of the basic events. According to these results, corresponding measures are proposed to ensure and improve the safety and reliability of Chinese inland dual fuel ships.
-
Macken, W L; Clarke, N; Nadeem, M; Coghlan, D
2017-05-10
Apparent Life-Threatening Events (ALTEs) are a common presentation to paediatric hospitals and represent a significant cause of parental anxiety. Basic Life Support (BLS) training is recommended for all caregivers following ALTEs. This study aimed to assess the rate of caregiver BLS training and reviewed parents experience following discharge. Parents were interviewed by phone following discharge. Over the study period 25 children attended the Emergency Department with ALTE, 17/25 (68%) were trained and 13/17 (76%) were contactable for interview. All parents found training decreased their anxiety level and were interested in attending for re-training. BLS resuscitation was subsequently required by 2/13 (15%) of children. Non-medical grade monitors were in use by 10/13 (77%) of caregivers following discharge. Caregivers are eager to engage in BLS training and it effectively reduces their caregiver anxiety. We recommend an increase in instructor staff and use of group re-training post discharge.
-
Uncertainty in the Timing of Origin of Animals and the Limits of Precision in Molecular Timescales
dos Reis, Mario; Thawornwattana, Yuttapong; Angelis, Konstantinos; Telford, Maximilian J.; Donoghue, Philip C.J.; Yang, Ziheng
2015-01-01
Summary The timing of divergences among metazoan lineages is integral to understanding the processes of animal evolution, placing the biological events of species divergences into the correct geological timeframe. Recent fossil discoveries and molecular clock dating studies have suggested a divergence of bilaterian phyla >100 million years before the Cambrian, when the first definite crown-bilaterian fossils occur. Most previous molecular clock dating studies, however, have suffered from limited data and biases in methodologies, and virtually all have failed to acknowledge the large uncertainties associated with the fossil record of early animals, leading to inconsistent estimates among studies. Here we use an unprecedented amount of molecular data, combined with four fossil calibration strategies (reflecting disparate and controversial interpretations of the metazoan fossil record) to obtain Bayesian estimates of metazoan divergence times. Our results indicate that the uncertain nature of ancient fossils and violations of the molecular clock impose a limit on the precision that can be achieved in estimates of ancient molecular timescales. For example, although we can assert that crown Metazoa originated during the Cryogenian (with most crown-bilaterian phyla diversifying during the Ediacaran), it is not possible with current data to pinpoint the divergence events with sufficient accuracy to test for correlations between geological and biological events in the history of animals. Although a Cryogenian origin of crown Metazoa agrees with current geological interpretations, the divergence dates of the bilaterians remain controversial. Thus, attempts to build evolutionary narratives of early animal evolution based on molecular clock timescales appear to be premature. PMID:26603774
-
Li, Yafeng; Song, Delu; Song, Ying; Zhao, Liangliang; Wolkow, Natalie; Tobias, John W; Song, Wenchao; Dunaief, Joshua L
2015-05-08
Dysregulation of iron homeostasis may be a pathogenic factor in age-related macular degeneration (AMD). Meanwhile, the formation of complement-containing deposits under the retinal pigment epithelial (RPE) cell layer is a pathognomonic feature of AMD. In this study, we investigated the molecular mechanisms by which complement component 3 (C3), a central protein in the complement cascade, is up-regulated by iron in RPE cells. Modulation of TGF-β signaling, involving ERK1/2, SMAD3, and CCAAT/enhancer-binding protein-δ, is responsible for iron-induced C3 expression. The differential effects of spatially distinct SMAD3 phosphorylation sites at the linker region and at the C terminus determined the up-regulation of C3. Pharmacologic inhibition of either ERK1/2 or SMAD3 phosphorylation decreased iron-induced C3 expression levels. Knockdown of SMAD3 blocked the iron-induced up-regulation and nuclear accumulation of CCAAT/enhancer-binding protein-δ, a transcription factor that has been shown previously to bind the basic leucine zipper 1 domain in the C3 promoter. We show herein that mutation of this domain reduced iron-induced C3 promoter activity. In vivo studies support our in vitro finding of iron-induced C3 up-regulation. Mice with a mosaic pattern of RPE-specific iron overload demonstrated co-localization of iron-induced ferritin and C3d deposits. Humans with aceruloplasminemia causing RPE iron overload had increased RPE C3d deposition. The molecular events in the iron-C3 pathway represent therapeutic targets for AMD or other diseases exacerbated by iron-induced local complement dysregulation. © 2015 by The American Society for Biochemistry and Molecular Biology, Inc.
-
Epithelial ovarian cancer: the molecular genetics of epithelial ovarian cancer.
Krzystyniak, J; Ceppi, L; Dizon, D S; Birrer, M J
2016-04-01
Epithelial ovarian cancer (EOC) remains one of the leading causes of cancer-related deaths among women worldwide, despite gains in diagnostics and treatments made over the last three decades. Existing markers of ovarian cancer possess very limited clinical relevance highlighting the emerging need for identification of novel prognostic biomarkers as well as better predictive factors that might allow the stratification of patients who could benefit from a more targeted approach. A summary of molecular genetics of EOC. Large-scale high-throughput genomic technologies appear to be powerful tools for investigations into the genetic abnormalities in ovarian tumors, including studies on dysregulated genes and aberrantly activated signaling pathways. Such technologies can complement well-established clinical histopathology analysis and tumor grading and will hope to result in better, more tailored treatments in the future. Genomic signatures obtained by gene expression profiling of EOC may be able to predict survival outcomes and other important clinical outcomes, such as the success of surgical treatment. Finally, genomic analyses may allow for the identification of novel predictive biomarkers for purposes of treatment planning. These data combined suggest a pathway to progress in the treatment of advanced ovarian cancer and the promise of fulfilling the objective of providing personalized medicine to women with ovarian cancer. The understanding of basic molecular events in the tumorigenesis and chemoresistance of EOC together with discovery of potential biomarkers may be greatly enhanced through large-scale genomic studies. In order to maximize the impact of these technologies, however, extensive validation studies are required. © The Author 2016. Published by Oxford University Press on behalf of the European Society for Medical Oncology. All rights reserved. For permissions, please email: journals.permissions@oup.com.
-
Engram formation in psychiatric disorders.
Gebicke-Haerter, Peter J
2014-01-01
Environmental factors substantially influence beginning and progression of mental illness, reinforcing or reducing the consequences of genetic vulnerability. Often initiated by early traumatic events, "engrams" or memories are formed that may give rise to a slow and subtle progression of psychiatric disorders. The large delay between beginning and time of onset (diagnosis) may be explained by efficient compensatory mechanisms observed in brain metabolism that use optional pathways in highly redundant molecular interactions. To this end, research has to deal with mechanisms of learning and long-term memory formation, which involves (a) epigenetic changes, (b) altered neuronal activities, and (c) changes in neuron-glia communication. On the epigenetic level, apparently DNA-methylations are more stable than histone modifications, although both closely interact. Neuronal activities basically deliver digital information, which clearly can serve as basis for memory formation (LTP). However, research in this respect has long time neglected the importance of glia. They are more actively involved in the control of neuronal activities than thought before. They can both reinforce and inhibit neuronal activities by transducing neuronal information from frequency-encoded to amplitude and frequency-modulated calcium wave patterns spreading in the glial syncytium by use of gap junctions. In this way, they serve integrative functions. In conclusion, we are dealing with two concepts of encoding information that mutually control each other and synergize: a digital (neuronal) and a wave-like (glial) computing, forming neuron-glia functional units with inbuilt feedback loops to maintain balance of excitation and inhibition. To better understand mental illness, we have to gain more insight into the dynamics of adverse environmental impact on those cellular and molecular systems. This report summarizes existing knowledge and draws some outline about further research in molecular psychiatry.
-
Engram formation in psychiatric disorders
Gebicke-Haerter, Peter J.
2014-01-01
Environmental factors substantially influence beginning and progression of mental illness, reinforcing or reducing the consequences of genetic vulnerability. Often initiated by early traumatic events, “engrams” or memories are formed that may give rise to a slow and subtle progression of psychiatric disorders. The large delay between beginning and time of onset (diagnosis) may be explained by efficient compensatory mechanisms observed in brain metabolism that use optional pathways in highly redundant molecular interactions. To this end, research has to deal with mechanisms of learning and long-term memory formation, which involves (a) epigenetic changes, (b) altered neuronal activities, and (c) changes in neuron-glia communication. On the epigenetic level, apparently DNA-methylations are more stable than histone modifications, although both closely interact. Neuronal activities basically deliver digital information, which clearly can serve as basis for memory formation (LTP). However, research in this respect has long time neglected the importance of glia. They are more actively involved in the control of neuronal activities than thought before. They can both reinforce and inhibit neuronal activities by transducing neuronal information from frequency-encoded to amplitude and frequency-modulated calcium wave patterns spreading in the glial syncytium by use of gap junctions. In this way, they serve integrative functions. In conclusion, we are dealing with two concepts of encoding information that mutually control each other and synergize: a digital (neuronal) and a wave-like (glial) computing, forming neuron-glia functional units with inbuilt feedback loops to maintain balance of excitation and inhibition. To better understand mental illness, we have to gain more insight into the dynamics of adverse environmental impact on those cellular and molecular systems. This report summarizes existing knowledge and draws some outline about further research in molecular psychiatry. PMID:24904262
-
Basic Beaches for the Classroom.
ERIC Educational Resources Information Center
McLaren, J. Philip
1986-01-01
Lists and explains the major characteristics of water. Compares water's molecular structure and its temperature-related properties with four other lightweight molecules. Discusses why water is considered the universal solvent. (ML)
-
... Century-Old Evolutionary Puzzle Computing Genetics Model Organisms RNA Interference The New Genetics is a science education ... the basics of DNA and its molecular cousin RNA, and new directions in genetic research. The New ...
-
Soft matter food physics--the physics of food and cooking.
Vilgis, Thomas A
2015-12-01
This review discusses the (soft matter) physics of food. Although food is generally not considered as a typical model system for fundamental (soft matter) physics, a number of basic principles can be found in the interplay between the basic components of foods, water, oil/fat, proteins and carbohydrates. The review starts with the introduction and behavior of food-relevant molecules and discusses food-relevant properties and applications from their fundamental (multiscale) behavior. Typical food aspects from 'hard matter systems', such as chocolates or crystalline fats, to 'soft matter' in emulsions, dough, pasta and meat are covered and can be explained on a molecular basis. An important conclusion is the point that the macroscopic properties and the perception are defined by the molecular interplay on all length and time scales.
-
A micromotor based on polymer single crystals and nanoparticles: toward functional versatility
NASA Astrophysics Data System (ADS)
Liu, Mei; Liu, Limei; Gao, Wenlong; Su, Miaoda; Ge, Ya; Shi, Lili; Zhang, Hui; Dong, Bin; Li, Christopher Y.
2014-07-01
We report a multifunctional micromotor fabricated by the self-assembly technique using multifunctional materials, i.e. polymer single crystals and nanoparticles, as basic building blocks. Not only can this micromotor achieve autonomous and directed movement, it also possesses unprecedented functions, including enzymatic degradation-induced micromotor disassembly, sustained release and molecular detection.We report a multifunctional micromotor fabricated by the self-assembly technique using multifunctional materials, i.e. polymer single crystals and nanoparticles, as basic building blocks. Not only can this micromotor achieve autonomous and directed movement, it also possesses unprecedented functions, including enzymatic degradation-induced micromotor disassembly, sustained release and molecular detection. Electronic supplementary information (ESI) available: Experimental section, Fig. S1-S8 and Video S1-S4. See DOI: 10.1039/c4nr02593h
-
Soft matter food physics—the physics of food and cooking
NASA Astrophysics Data System (ADS)
Vilgis, Thomas A.
2015-12-01
This review discusses the (soft matter) physics of food. Although food is generally not considered as a typical model system for fundamental (soft matter) physics, a number of basic principles can be found in the interplay between the basic components of foods, water, oil/fat, proteins and carbohydrates. The review starts with the introduction and behavior of food-relevant molecules and discusses food-relevant properties and applications from their fundamental (multiscale) behavior. Typical food aspects from ‘hard matter systems’, such as chocolates or crystalline fats, to ‘soft matter’ in emulsions, dough, pasta and meat are covered and can be explained on a molecular basis. An important conclusion is the point that the macroscopic properties and the perception are defined by the molecular interplay on all length and time scales.
-
Information resources at the National Center for Biotechnology Information.
Woodsmall, R M; Benson, D A
1993-01-01
The National Center for Biotechnology Information (NCBI), part of the National Library of Medicine, was established in 1988 to perform basic research in the field of computational molecular biology as well as build and distribute molecular biology databases. The basic research has led to new algorithms and analysis tools for interpreting genomic data and has been instrumental in the discovery of human disease genes for neurofibromatosis and Kallmann syndrome. The principal database responsibility is the National Institutes of Health (NIH) genetic sequence database, GenBank. NCBI, in collaboration with international partners, builds, distributes, and provides online and CD-ROM access to over 112,000 DNA sequences. Another major program is the integration of multiple sequences databases and related bibliographic information and the development of network-based retrieval systems for Internet access. PMID:8374583
-
NASA Technical Reports Server (NTRS)
Embleton, Tony F. W.; Daigle, Gilles A.
1991-01-01
Reviewed here is the current state of knowledge with respect to each basic mechanism of sound propagation in the atmosphere and how each mechanism changes the spectral or temporal characteristics of the sound received at a distance from the source. Some of the basic processes affecting sound wave propagation which are present in any situation are discussed. They are geometrical spreading, molecular absorption, and turbulent scattering. In geometrical spreading, sound levels decrease with increasing distance from the source; there is no frequency dependence. In molecular absorption, sound energy is converted into heat as the sound wave propagates through the air; there is a strong dependence on frequency. In turbulent scattering, local variations in wind velocity and temperature induce fluctuations in phase and amplitude of the sound waves as they propagate through an inhomogeneous medium; there is a moderate dependence on frequency.
-
Physiological, Molecular and Genetic Mechanisms of Long-Term Habituation
DOE Office of Scientific and Technical Information (OSTI.GOV)
Calin-Jageman, Robert J
Work funded on this grant has explored the mechanisms of long-term habituation, a ubiquitous form of learning that plays a key role in basic cognitive functioning. Specifically, behavioral, physiological, and molecular mechanisms of habituation have been explored using a simple model system, the tail-elicited siphon-withdrawal reflex (T-SWR) in the marine mollusk Aplysia californica. Substantial progress has been made on the first and third aims, providing some fundamental insights into the mechanisms by which memories are stored. We have characterized the physiological correlates of short- and long-term habituation. We found that short-term habituation is accompanied by a robust sensory adaptation, whereasmore » long-term habituation is accompanied by alterations in sensory and interneuron synaptic efficacy. Thus, our data indicates memories can be shifted between different sites in a neural network as they are consolidated from short to long term. At the molecular level, we have accomplished microarray analysis comparing gene expression in both habituated and control ganglia. We have identified a network of putatively regulated transcripts that seems particularly targeted towards synaptic changes (e.g. SNAP25, calmodulin) . We are now beginning additional work to confirm regulation of these transcripts and build a more detailed understanding of the cascade of molecular events leading to the permanent storage of long-term memories. On the third aim, we have fostered a nascent neuroscience program via a variety of successful initiatives. We have funded over 11 undergraduate neuroscience scholars, several of whom have been recognized at national and regional levels for their research. We have also conducted a pioneering summer research program for community college students which is helping enhance access of underrepresented groups to life science careers. Despite minimal progress on the second aim, this project has provided a) novel insight into the network mechanisms by which short-term memories are permanently stored, and b) a strong foundation for continued growth of an excellent undergraduate neuroscience program.« less
-
Survey of critical failure events in on-chip interconnect by fault tree analysis
NASA Astrophysics Data System (ADS)
Yokogawa, Shinji; Kunii, Kyousuke
2018-07-01
In this paper, a framework based on reliability physics is proposed for adopting fault tree analysis (FTA) to the on-chip interconnect system of a semiconductor. By integrating expert knowledge and experience regarding the possibilities of failure on basic events, critical issues of on-chip interconnect reliability will be evaluated by FTA. In particular, FTA is used to identify the minimal cut sets with high risk priority. Critical events affecting the on-chip interconnect reliability are identified and discussed from the viewpoint of long-term reliability assessment. The moisture impact is evaluated as an external event.
-
An Overview of Recent Advances in Event-Triggered Consensus of Multiagent Systems.
Ding, Lei; Han, Qing-Long; Ge, Xiaohua; Zhang, Xian-Ming
2018-04-01
Event-triggered consensus of multiagent systems (MASs) has attracted tremendous attention from both theoretical and practical perspectives due to the fact that it enables all agents eventually to reach an agreement upon a common quantity of interest while significantly alleviating utilization of communication and computation resources. This paper aims to provide an overview of recent advances in event-triggered consensus of MASs. First, a basic framework of multiagent event-triggered operational mechanisms is established. Second, representative results and methodologies reported in the literature are reviewed and some in-depth analysis is made on several event-triggered schemes, including event-based sampling schemes, model-based event-triggered schemes, sampled-data-based event-triggered schemes, and self-triggered sampling schemes. Third, two examples are outlined to show applicability of event-triggered consensus in power sharing of microgrids and formation control of multirobot systems, respectively. Finally, some challenging issues on event-triggered consensus are proposed for future research.
-
Molecular diversity of the faecal microbiota of Toy Poodles in Japan.
Omatsu, Tsutomu; Omura, Miki; Katayama, Yukie; Kimura, Toru; Okumura, Maho; Okumura, Atsushi; Murata, Yoshiteru; Mizutani, Tetsuya
2018-05-18
The intestinal microbiota was revealed with the recent advances in molecular techniques, such as high-throughput sequencing analysis. As a result, the microbial changes are thought to influence the health of humans and animals and such changes are affected by several factors including diet, genetics, age, sex, and diseases. Similar studies are being conducted in dogs, and the knowledge of intestinal microbiota in dogs is expanding. Nonetheless, basic information on intestinal microbiota in dogs is less than that of humans. Our aim was to study toy poodles (n=21), a popular companion dog, in terms of basic characteristics of the faecal microbiota by 16S rRNA gene barcoding analysis. In the faecal microbiota, Firmicutes, Bacteroidetes, Proteobacteria, and Fusobacteria were the dominant phyla (over 93.4% of faecal microbiota) regardless of the attributes of the dogs. In family level, Enterobacteriaceae, Bacteroidaceae, and Lachnospiraceae were most prevalent. In case of a dog with protein-losing enteropathy, the diversity of faecal microbiota was different between before and after treatment. This study provides basic information for studying on faecal microbiota in toy poodles.
-
Yusuf, Kareem; Badjah-Hadj-Ahmed, Ahmed Yacine; Aqel, Ahmad; Aouak, Taieb; ALOthman, Zeid Abdullah
2016-04-22
Thermodynamic characterization of butyl methacrylate-co-ethylene dimethacrylate neat monolith and zeolitic imidazolate framework-8 incorporated with butyl methacrylate-co-ethylene dimethacrylate composite monolith were studied using inverse gas chromatography at infinite dilution under 1MPa column pressure and various column temperatures. The free energy of adsorption (ΔGA), enthalpy of adsorption (ΔHA) and entropy of adsorption (ΔSA) were determined using a series of n-alkanes. The dispersive component of surface energy (γS(D)) was estimated by Dorris-Gray and Schultz et al. The composite monolith showed a more energetic surface than the neat monolith. The acidic, KA, and basic, KD, parameters for both materials were estimated using a group of polar probes. A basic character was concluded with more basic behavior for the neat monolith. Flory-Huggins parameter, χ, was taken as a measure of miscibility between the probes with the low molecular weight and the high molecular weight monolith. Inverse gas chromatography provides a better understanding of the role of incorporated zeolitic imidazolate framework (ZIF-8) into the polymer matrix in its monolithic form. Copyright © 2016 Elsevier B.V. All rights reserved.
-
2010-01-01
Background The challenge today is to develop a modeling and simulation paradigm that integrates structural, molecular and genetic data for a quantitative understanding of physiology and behavior of biological processes at multiple scales. This modeling method requires techniques that maintain a reasonable accuracy of the biological process and also reduces the computational overhead. This objective motivates the use of new methods that can transform the problem from energy and affinity based modeling to information theory based modeling. To achieve this, we transform all dynamics within the cell into a random event time, which is specified through an information domain measure like probability distribution. This allows us to use the “in silico” stochastic event based modeling approach to find the molecular dynamics of the system. Results In this paper, we present the discrete event simulation concept using the example of the signal transduction cascade triggered by extra-cellular Mg2+ concentration in the two component PhoPQ regulatory system of Salmonella Typhimurium. We also present a model to compute the information domain measure of the molecular transport process by estimating the statistical parameters of inter-arrival time between molecules/ions coming to a cell receptor as external signal. This model transforms the diffusion process into the information theory measure of stochastic event completion time to get the distribution of the Mg2+ departure events. Using these molecular transport models, we next study the in-silico effects of this external trigger on the PhoPQ system. Conclusions Our results illustrate the accuracy of the proposed diffusion models in explaining the molecular/ionic transport processes inside the cell. Also, the proposed simulation framework can incorporate the stochasticity in cellular environments to a certain degree of accuracy. We expect that this scalable simulation platform will be able to model more complex biological systems with reasonable accuracy to understand their temporal dynamics. PMID:21143785
-
Ghosh, Preetam; Ghosh, Samik; Basu, Kalyan; Das, Sajal K; Zhang, Chaoyang
2010-12-01
The challenge today is to develop a modeling and simulation paradigm that integrates structural, molecular and genetic data for a quantitative understanding of physiology and behavior of biological processes at multiple scales. This modeling method requires techniques that maintain a reasonable accuracy of the biological process and also reduces the computational overhead. This objective motivates the use of new methods that can transform the problem from energy and affinity based modeling to information theory based modeling. To achieve this, we transform all dynamics within the cell into a random event time, which is specified through an information domain measure like probability distribution. This allows us to use the "in silico" stochastic event based modeling approach to find the molecular dynamics of the system. In this paper, we present the discrete event simulation concept using the example of the signal transduction cascade triggered by extra-cellular Mg2+ concentration in the two component PhoPQ regulatory system of Salmonella Typhimurium. We also present a model to compute the information domain measure of the molecular transport process by estimating the statistical parameters of inter-arrival time between molecules/ions coming to a cell receptor as external signal. This model transforms the diffusion process into the information theory measure of stochastic event completion time to get the distribution of the Mg2+ departure events. Using these molecular transport models, we next study the in-silico effects of this external trigger on the PhoPQ system. Our results illustrate the accuracy of the proposed diffusion models in explaining the molecular/ionic transport processes inside the cell. Also, the proposed simulation framework can incorporate the stochasticity in cellular environments to a certain degree of accuracy. We expect that this scalable simulation platform will be able to model more complex biological systems with reasonable accuracy to understand their temporal dynamics.
-
Molecular toolbox for the identification of unknown genetically modified organisms.
Ruttink, Tom; Demeyer, Rolinde; Van Gulck, Elke; Van Droogenbroeck, Bart; Querci, Maddalena; Taverniers, Isabel; De Loose, Marc
2010-03-01
Competent laboratories monitor genetically modified organisms (GMOs) and products derived thereof in the food and feed chain in the framework of labeling and traceability legislation. In addition, screening is performed to detect the unauthorized presence of GMOs including asynchronously authorized GMOs or GMOs that are not officially registered for commercialization (unknown GMOs). Currently, unauthorized or unknown events are detected by screening blind samples for commonly used transgenic elements, such as p35S or t-nos. If (1) positive detection of such screening elements shows the presence of transgenic material and (2) all known GMOs are tested by event-specific methods but are not detected, then the presence of an unknown GMO is inferred. However, such evidence is indirect because it is based on negative observations and inconclusive because the procedure does not identify the causative event per se. In addition, detection of unknown events is hampered in products that also contain known authorized events. Here, we outline alternative approaches for analytical detection and GMO identification and develop new methods to complement the existing routine screening procedure. We developed a fluorescent anchor-polymerase chain reaction (PCR) method for the identification of the sequences flanking the p35S and t-nos screening elements. Thus, anchor-PCR fingerprinting allows the detection of unique discriminative signals per event. In addition, we established a collection of in silico calculated fingerprints of known events to support interpretation of experimentally generated anchor-PCR GM fingerprints of blind samples. Here, we first describe the molecular characterization of a novel GMO, which expresses recombinant human intrinsic factor in Arabidopsis thaliana. Next, we purposefully treated the novel GMO as a blind sample to simulate how the new methods lead to the molecular identification of a novel unknown event without prior knowledge of its transgene sequence. The results demonstrate that the new methods complement routine screening procedures by providing direct conclusive evidence and may also be useful to resolve masking of unknown events by known events.
-
General morphological and biological features of neoplasms: integration of molecular findings.
Diaz-Cano, S J
2008-07-01
This review highlights the importance of morphology-molecular correlations for a proper implementation of new markers. It covers both general aspects of tumorigenesis (which are normally omitted in papers analysing molecular pathways) and the general mechanisms for the acquired capabilities of neoplasms. The mechanisms are also supported by appropriate diagrams for each acquired capability that include overlooked features such as mobilization of cellular resources and changes in chromatin, transcription and epigenetics; fully accepted oncogenes and tumour suppressor genes are highlighted, while the pathways are also presented as activating or inactivating with appropriate colour coding. Finally, the concepts and mechanisms presented enable us to understand the basic requirements for the appropriate implementation of molecular tests in clinical practice. In summary, the basic findings are presented to serve as a bridge to clinical applications. The current definition of neoplasm is descriptive and difficult to apply routinely. Biologically, neoplasms develop through acquisition of capabilities that involve tumour cell aspects and modified microenvironment interactions, resulting in unrestricted growth due to a stepwise accumulation of cooperative genetic alterations that affect key molecular pathways. The correlation of these molecular aspects with morphological changes is essential for better understanding of essential concepts as early neoplasms/precancerous lesions, progression/dedifferentiation, and intratumour heterogeneity. The acquired capabilities include self-maintained replication (cell cycle dysregulation), extended cell survival (cell cycle arrest, apoptosis dysregulation, and replicative lifespan), genetic instability (chromosomal and microsatellite), changes of chromatin, transcription and epigenetics, mobilization of cellular resources, and modified microenvironment interactions (tumour cells, stromal cells, extracellular, endothelium). The acquired capabilities defining neoplasms are the hallmarks of cancer, but they also comprise useful tools to improve diagnosis and prognosis, as well as potential therapeutic targets. The application of these concepts in oncological pathology leads to consideration of the molecular test requirements (Molecular Test Score System) for reliable implementation; these requirements should cover biological effects, molecular pathway, biological validation, and technical validation. Sensible application of molecular markers in tumour pathology always needs solid morphological support.
-
Pressure-induced orientational glass phase in molecular para-hydrogen.
Schelkacheva, T I; Tareyeva, E E; Chtchelkatchev, N M
2009-02-01
We propose a theoretical description of a possible orientational glass transition in solid molecular para-hydrogen and ortho-deuterium under pressure supposing that they are mixtures of J=0 and J=2 states of molecules. The theory uses the basic concepts and methods of standard spin-glass theory. We expect our orientational glass to correspond to the II' phase of the high-pressure hydrogen phase diagram.
-
Primer on Molecular Genetics; DOE Human Genome Program
DOE R&D Accomplishments Database
1992-04-01
This report is taken from the April 1992 draft of the DOE Human Genome 1991--1992 Program Report, which is expected to be published in May 1992. The primer is intended to be an introduction to basic principles of molecular genetics pertaining to the genome project. The material contained herein is not final and may be incomplete. Techniques of genetic mapping and DNA sequencing are described.
-
Fashion, Paper Dolls and Multiplicatives
ERIC Educational Resources Information Center
Ura, Suzana Kaori; Stein-Barana, Alzira C. M.; Munhoz, Deisy P.
2011-01-01
The multiplicative principle is the tool allowing the counting of groups that can be described by a sequence of events. An event is a subset of sample space, i.e. a collection of possible outcomes, which may be equal to or smaller than the sample space as a whole. It is important that students understand this basic principle early on and know how…
-
Validation of the Impact of Event Scale for Psychological Sequelae of Combat.
ERIC Educational Resources Information Center
Schwarzwald, Joseph; And Others
1987-01-01
Attempted to validate the Impact of Event Scale (IES) with a large sample of males who had been exposed to combat trauma. The IES was shown to be sensitive to differences between and within the three subject groups (combat stress reaction group, combat control group, noncombat control group). Four basic patterns of intrusion and avoidance were…
-
A Studio Project Based on the Events of September 11
ERIC Educational Resources Information Center
Ruby, Nell
2004-01-01
A week after the 9/11 WTC event, the collage project that Nell Ruby and her class had been working on in a basic design classroom lacked relevance. They had been working from master works, analyzing hue and value relationships, color schemes, shape, and composition. The master works seemed unimportant because of the immense emotional impact of the…
-
Cundy, Thomas P; Mayer, Erik K; Camps, Juan I; Olsen, Lars H; Pelizzo, Gloria; Yang, Guang-Zhong; Darzi, Ara; Najmaldin, Azad S
2015-03-01
The introduction of robotic surgery into clinical practice brings new and specific needs for education and training. Application to the pediatric setting comes with unique considerations, warranting dedicated training resources that are accessible. A pediatric robotic surgery workshop was convened to address initial education and training requirements. The event was designed to offer an exposure rich environment for delegates to familiarize and learn basic principles in a maximally efficient manner. Pre- and post-workshop survey responses were evaluated to reflect on the quality of the educational experience and scope for improvement. Feasibility and sustainability of such events was further evaluated by reviewing various challenges encountered. A total of 29 surgeons participated in the workshop, with 7 countries represented. The majority of delegates (94 %) indicated they were "very satisfied" with the overall program. Delegates almost unanimously expressed preference and satisfaction for hands-on content. Qualitative feedback favored a stepwise and modular workshop structure, transitioning from didactic teaching to progressively more advanced training. At the basic and intermediate level, this style of event is able to satisfy initial training and educational needs. Feasibility and sustainability of such events is highly dependent on infrastructure resources that have numerous barriers to accessibility.
-
Molecular Characterization of Macrophage-Biomaterial Interactions
Moore, Laura Beth; Kyriakides, Themis R.
2015-01-01
Implantation of biomaterials in vascularized tissues elicits the sequential engagement of molecular and cellular elements that constitute the foreign body response. Initial events include the non-specific adsorption of proteins to the biomaterial surface that render it adhesive for cells such as neutrophils and macrophages. The latter undergo unique activation and in some cases undergo cell-cell fusion to form foreign body giant cells that contribute to implant damage and fibrotic encapsulation. In this review, we discuss the molecular events that contribute to macrophage activation and fusion with a focus on the role of the inflammasome, signaling pathways such as JAK/STAT and NF-κB, and the putative involvement of micro RNAs in the regulation of these processes. PMID:26306446
-
Molecular Characterization of Macrophage-Biomaterial Interactions.
Moore, Laura Beth; Kyriakides, Themis R
2015-01-01
Implantation of biomaterials in vascularized tissues elicits the sequential engagement of molecular and cellular elements that constitute the foreign body response. Initial events include the non-specific adsorption of proteins to the biomaterial surface that render it adhesive for cells such as neutrophils and macrophages. The latter undergo unique activation and in some cases undergo cell-cell fusion to form foreign body giant cells that contribute to implant damage and fibrotic encapsulation. In this review, we discuss the molecular events that contribute to macrophage activation and fusion with a focus on the role of the inflammasome, signaling pathways such as JAK/STAT and NF-κB, and the putative involvement of micro RNAs in the regulation of these processes.
-
Strategic placement of stereogenic centers in molecular materials for second harmonic generation.
Gangopadhyay, P; Rao, D Narayana; Agranat, Israel; Radhakrishnan, T P
2002-01-01
Basic aspects of the nonlinear optical phenomenon of second harmonic generation (SHG) and the assembly of molecular materials for SHG are reviewed. Extensive use of chirality as a convenient tool to generate noncentrosymmetricity in molecular lattices, an essential requirement for the development of quadratic nonlinear optical materials, is noted. An overview of our investigations of chiral diaminodicyanoquinodimethanes is presented, which provides insight into a systematic approach to the effective deployment of chirality to achieve optimal molecular orientations for enhanced solid state SHG. Extension of these ideas to the realization of strong SHG in materials based on helical superstructures is outlined.
-
1999-11-01
Increasing knowledge of the molecular basis of disease and advances in technology for analyzing nucleic acids and gene products are changing pathology practice. The explosion of information regarding inherited susceptibility to disease is an important aspect of this transformation. Pathology residency programs are incorporating molecular pathology education into their curricula to prepare newly trained pathologists for the future, yet little guidance has been available regarding the important components of molecular pathology training. We present general goals for pathology training programs for molecular pathology education. These include recommendations to pathology residents for the acquisition of both basic knowledge in human genetics and molecular biology and specific skills relevant to microbiology, molecular oncology, genetics, histocompatibility, and identity determination. The importance of residents gaining facility in integrating data gained via nucleic acid based-technology with other laboratory and clinical information available in the care of patients is emphasized.
-
Molecular Force Spectroscopy on Cells
NASA Astrophysics Data System (ADS)
Liu, Baoyu; Chen, Wei; Zhu, Cheng
2015-04-01
Molecular force spectroscopy has become a powerful tool to study how mechanics regulates biology, especially the mechanical regulation of molecular interactions and its impact on cellular functions. This force-driven methodology has uncovered a wealth of new information of the physical chemistry of molecular bonds for various biological systems. The new concepts, qualitative and quantitative measures describing bond behavior under force, and structural bases underlying these phenomena have substantially advanced our fundamental understanding of the inner workings of biological systems from the nanoscale (molecule) to the microscale (cell), elucidated basic molecular mechanisms of a wide range of important biological processes, and provided opportunities for engineering applications. Here, we review major force spectroscopic assays, conceptual developments of mechanically regulated kinetics of molecular interactions, and their biological relevance. We also present current challenges and highlight future directions.
-
DOE Office of Scientific and Technical Information (OSTI.GOV)
Elber, Ron
Atomically detailed computer simulations of complex molecular events attracted the imagination of many researchers in the field as providing comprehensive information on chemical, biological, and physical processes. However, one of the greatest limitations of these simulations is of time scales. The physical time scales accessible to straightforward simulations are too short to address many interesting and important molecular events. In the last decade significant advances were made in different directions (theory, software, and hardware) that significantly expand the capabilities and accuracies of these techniques. This perspective describes and critically examines some of these advances.
-
Nanotechnology Review: Molecular Electronics to Molecular Motors
NASA Technical Reports Server (NTRS)
Srivastava, Deepak; Saini, Subhash (Technical Monitor)
1998-01-01
Reviewing the status of current approaches and future projections, as already published in scientific journals and books, the talk will summarize the direction in which computational and experimental nanotechnologies are progressing. Examples of nanotechnological approaches to the concepts of design and simulation of carbon nanotube based molecular electronic and mechanical devices will be presented. The concepts of nanotube based gears and motors will be discussed. The above is a non-technical review talk which covers long term precompetitive basic research in already published material that has been presented before many US scientific meeting audiences.
-
Molecular Foundry Workshop draws overflow crowd to BerkeleyLab
DOE Office of Scientific and Technical Information (OSTI.GOV)
Robinson, Art
2002-11-27
Nanoscale science and technology is now one of the top research priorities in the United States. With this background, it is no surprise that an overflow crowd or more than 350 registrants filled two auditoriums to hear about and contribute ideas for the new Molecular Foundry during a two-day workshop at the Lawrence Berkeley National Laboratory (Berkeley Lab). Scheduled to open for business at Berkeley Labin early 2006, the Molecular Foundry is one of three Nanoscale Science Research Centers (NSRCs) put forward for funding by the DOE's Office of Basic Energy Sciences (BES).
-
Mondieig, Denise; Rajabalee, Fazil; Laprie, Alain; Oonk, Harry A J; Calvet, Thereza; Cuevas-Diarte, Miguel Angel
2003-04-01
In this paper we present an example of the application of molecular alloys for thermal protection of biomedical products during transport or storage. Particularly, thermal protection of blood elements have been considered at different temperatures. All steps from basic research to marketing have been addressed. The high latent heat of fusion of the components allows us to propose molecular alloys as materials for thermal energy storage and also for thermal protection over a large range of temperatures, which can be used in many industrial sectors.
-
Event segmentation ability uniquely predicts event memory.
Sargent, Jesse Q; Zacks, Jeffrey M; Hambrick, David Z; Zacks, Rose T; Kurby, Christopher A; Bailey, Heather R; Eisenberg, Michelle L; Beck, Taylor M
2013-11-01
Memory for everyday events plays a central role in tasks of daily living, autobiographical memory, and planning. Event memory depends in part on segmenting ongoing activity into meaningful units. This study examined the relationship between event segmentation and memory in a lifespan sample to answer the following question: Is the ability to segment activity into meaningful events a unique predictor of subsequent memory, or is the relationship between event perception and memory accounted for by general cognitive abilities? Two hundred and eight adults ranging from 20 to 79years old segmented movies of everyday events and attempted to remember the events afterwards. They also completed psychometric ability tests and tests measuring script knowledge for everyday events. Event segmentation and script knowledge both explained unique variance in event memory above and beyond the psychometric measures, and did so as strongly in older as in younger adults. These results suggest that event segmentation is a basic cognitive mechanism, important for memory across the lifespan. Copyright © 2013 Elsevier B.V. All rights reserved.
-
Event Segmentation Ability Uniquely Predicts Event Memory
Sargent, Jesse Q.; Zacks, Jeffrey M.; Hambrick, David Z.; Zacks, Rose T.; Kurby, Christopher A.; Bailey, Heather R.; Eisenberg, Michelle L.; Beck, Taylor M.
2013-01-01
Memory for everyday events plays a central role in tasks of daily living, autobiographical memory, and planning. Event memory depends in part on segmenting ongoing activity into meaningful units. This study examined the relationship between event segmentation and memory in a lifespan sample to answer the following question: Is the ability to segment activity into meaningful events a unique predictor of subsequent memory, or is the relationship between event perception and memory accounted for by general cognitive abilities? Two hundred and eight adults ranging from 20 to 79 years old segmented movies of everyday events and attempted to remember the events afterwards. They also completed psychometric ability tests and tests measuring script knowledge for everyday events. Event segmentation and script knowledge both explained unique variance in event memory above and beyond the psychometric measures, and did so as strongly in older as in younger adults. These results suggest that event segmentation is a basic cognitive mechanism, important for memory across the lifespan. PMID:23942350
-
Molecular Thresholds for Early Key Events in Liver Tumorgensis: PhthalateCase StudyTriangleShort-term changes in molecular profiles are a central component of strategies to model health effects of environmental chemicals such as phthalates, for which there is widespread human exp...
-
Jurchenko, Carol
2015-01-01
The ability of cells to sense the physical nature of their surroundings is critical to the survival of multicellular organisms. Cellular response to physical cues from adjacent cells and the extracellular matrix leads to a dynamic cycle in which cells respond by remodeling their local microenvironment, fine-tuning cell stiffness, polarity, and shape. Mechanical regulation is important in cellular development, normal morphogenesis, and wound healing. The mechanisms by which these finely balanced mechanotransduction events occur, however, are not well understood. In large part, this is due to the limited availability of tools to study molecular mechanotransduction events in live cells. Several classes of molecular tension probes have been recently developed which are rapidly transforming the study of mechanotransduction. Molecular tension probes are primarily based on fluorescence resonance energy transfer (FRET) and report on piconewton scale tension events in live cells. In this minireview, we describe the two main classes of tension probes, genetically encoded tension sensors and immobilized tension sensors, and discuss the advantages and limitations of each type. We discuss future opportunities to address major biological questions and outline the challenges facing the next generation of molecular tension probes. PMID:26031334
-
NASA Astrophysics Data System (ADS)
Kobayashi, Takashi; Komoda, Norihisa
The traditional business process design methods, in which the usecase is the most typical, have no useful framework to design the activity sequence with. Therefore, the design efficiency and quality vary widely according to the designer’s experience and skill. In this paper, to solve this problem, we propose the business events and their state transition model (a basic business event model) based on the language/action perspective, which is the result in the cognitive science domain. In the business process design, using this model, we decide event occurrence conditions so that every event synchronizes with each other. We also propose the design pattern to decide the event occurrence condition (a business event improvement strategy). Lastly, we apply the business process design method based on the business event model and the business event improvement strategy to the credit card issue process and estimate its effect.
-
Unveiling molecular events in the brain by noninvasive imaging.
Klohs, Jan; Rudin, Markus
2011-10-01
Neuroimaging allows researchers and clinicians to noninvasively assess structure and function of the brain. With the advances of imaging modalities such as magnetic resonance, nuclear, and optical imaging; the design of target-specific probes; and/or the introduction of reporter gene assays, these technologies are now capable of visualizing cellular and molecular processes in vivo. Undoubtedly, the system biological character of molecular neuroimaging, which allows for the study of molecular events in the intact organism, will enhance our understanding of physiology and pathophysiology of the brain and improve our ability to diagnose and treat diseases more specifically. Technical/scientific challenges to be faced are the development of highly sensitive imaging modalities, the design of specific imaging probe molecules capable of penetrating the CNS and reporting on endogenous cellular and molecular processes, and the development of tools for extracting quantitative, biologically relevant information from imaging data. Today, molecular neuroimaging is still an experimental approach with limited clinical impact; this is expected to change within the next decade. This article provides an overview of molecular neuroimaging approaches with a focus on rodent studies documenting the exploratory state of the field. Concepts are illustrated by discussing applications related to the pathophysiology of Alzheimer's disease.
-
Etienne, Gabriel; Dulucq, Stéphanie; Nicolini, Franck-Emmanuel; Morisset, Stéphane; Fort, Marie-Pierre; Schmitt, Anna; Etienne, Madeleine; Hayette, Sandrine; Lippert, Eric; Bureau, Caroline; Tigaud, Isabelle; Adiko, Didier; Marit, Gérald; Reiffers, Josy; Mahon, François-Xavier
2014-01-01
Sustained imatinib treatment in chronic myeloid leukemia patients can result in complete molecular response allowing discontinuation without relapse. We set out to evaluate the frequency of complete molecular response in imatinib de novo chronic phase chronic myeloid leukemia patients, to identify base-line and under-treatment predictive factors of complete molecular response in patients achieving complete cytogenetic response, and to assess if complete molecular response is associated with a better outcome. A random selection of patients on front-line imatinib therapy (n=266) were considered for inclusion. Complete molecular response was confirmed and defined as MR 4.5 with undetectable BCR-ABL transcript levels. Median follow up was 4.43 years (range 0.79–10.8 years). Sixty-five patients (24%) achieved complete molecular response within a median time of 32.7 months. Absence of spleen enlargement at diagnosis, achieving complete cytogenetic response before 12 months of therapy, and major molecular response during the year following complete cytogenetic response was predictive of achieving further complete molecular response. Patients who achieved complete molecular response had better event-free and failure-free survivals than those with complete cytogenetic response irrespective of major molecular response status (95.2% vs. 64.7% vs. 27.7%, P=0.00124; 98.4% vs. 82.3% vs. 56%, P=0.0335), respectively. Overall survival was identical in the 3 groups. In addition to complete cytogenetic response and major molecular response, further deeper molecular response is associated with better event-free and failure-free survivals, and complete molecular response confers the best outcome. PMID:24362549
-
Brooks, Antone L.; Hoel, David G.; Preston, R. Julian
2016-01-01
Abstract Purpose: This review evaluates the role of dose rate on cell and molecular responses. It focuses on the influence of dose rate on key events in critical pathways in the development of cancer. This approach is similar to that used by the U.S. EPA and others to evaluate risk from chemicals. It provides a mechanistic method to account for the influence of the dose rate from low-LET radiation, especially in the low-dose region on cancer risk assessment. Molecular, cellular, and tissues changes are observed in many key events and change as a function of dose rate. The magnitude and direction of change can be used to help establish an appropriate dose rate effectiveness factor (DREF). Conclusions: Extensive data on key events suggest that exposure to low dose-rates are less effective in producing changes than high dose rates. Most of these data at the molecular and cellular level support a large (2–30) DREF. In addition, some evidence suggests that doses delivered at a low dose rate decrease damage to levels below that observed in the controls. However, there are some data human and mechanistic data that support a dose-rate effectiveness factor of 1. In summary, a review of the available molecular, cellular and tissue data indicates that not only is dose rate an important variable in understanding radiation risk but it also supports the selection of a DREF greater than one as currently recommended by ICRP (2007) and BEIR VII (NRC/NAS 2006). PMID:27266588
-
Kernel approach to molecular similarity based on iterative graph similarity.
Rupp, Matthias; Proschak, Ewgenij; Schneider, Gisbert
2007-01-01
Similarity measures for molecules are of basic importance in chemical, biological, and pharmaceutical applications. We introduce a molecular similarity measure defined directly on the annotated molecular graph, based on iterative graph similarity and optimal assignments. We give an iterative algorithm for the computation of the proposed molecular similarity measure, prove its convergence and the uniqueness of the solution, and provide an upper bound on the required number of iterations necessary to achieve a desired precision. Empirical evidence for the positive semidefiniteness of certain parametrizations of our function is presented. We evaluated our molecular similarity measure by using it as a kernel in support vector machine classification and regression applied to several pharmaceutical and toxicological data sets, with encouraging results.
-
Molecular Contrast Optical Coherence Tomography: A Review¶
Yang, Changhuei
2005-01-01
This article reviews the current state of research on the use of molecular contrast agents in optical coherence tomography (OCT) imaging techniques. After a brief discussion of the basic principle of OCT and the importance of incorporating molecular contrast agent usage into this imaging modality, we shall present an overview of the different molecular contrast OCT (MCOCT) methods that have been developed thus far. We will then discuss several important practical issues that define the possible range of contrast agent choice, the design criteria for engineered molecular contrast agent and the implementability of a given MCOCT method for clinical or biological applications. We will conclude by outlining a few areas of pursuit that deserve a greater degree of research and development. PMID:15588122
-
Possibility designing half-wave and full-wave molecular rectifiers by using single benzene molecule
NASA Astrophysics Data System (ADS)
Abbas, Mohammed A.; Hanoon, Falah H.; Al-Badry, Lafy F.
2018-02-01
This work focused on possibility designing half-wave and full-wave molecular rectifiers by using single and two benzene rings, respectively. The benzene rings were threaded by a magnetic flux that changes over time. The quantum interference effect was considered as the basic idea in the rectification action, the para and meta configurations were investigated. All the calculations are performed by using steady-state theoretical model, which is based on the time-dependent Hamiltonian model. The electrical conductance and the electric current are considered as DC output signals of half-wave and full-wave molecular rectifiers. The finding in this work opens up the exciting potential to use these molecular rectifiers in molecular electronics.
-
NASA Technical Reports Server (NTRS)
Christon, S. P.; Gloeckler, G.; Williams, D. J.; Mukai, T.; Mcentire, R. W.; Jacquey, C.; Angelopoulos, V.; Lui, A. T. Y.; Kokubun, S.; Fairfield, D. H.
1994-01-01
Energetic atomic (O(+1) and N(+1)) and molecular (O2(+1), NO(+1), and N2(+1)) ions of ionospheric origin were observed in Earth's magnetotail at X approximately -146 R(sub E) during two plasma sheet sunward/tailward flow-reversal events measured by instruments on the GEOTAIL spacecraft. These events were associated with concurrent ground-measured geomagnetic disturbance intensification at auroral-and mid-latitudes (Kp = 7(-)). Energetic ions in the sunward-component and tailward flows were from both the solar wind and ionosphere. Plasma and energetic ions participated in the flows. During tailward flow, ionospheric origin ion abundance ratios at approximately 200-900 km/s in the rest frame were N(+1)/O(+1) = approximately 25-30% and ((O2(+1), NO(+1), and N2(+1))/O(+1) = approximately 1-2%. We argue that tailward flow most likely initiated approximately 80-100 R(sub E) tailward of Earth and molecular ions were in the plasma sheet prior to geomagnetic intensification onset.
-
Procession to pediatric bacteremia and sepsis: covert operations and failures in diplomacy.
Bateman, Stacey L; Seed, Patrick C
2010-07-01
Despite advances in diagnosis and treatment, bacterial sepsis remains a major cause of pediatric morbidity and mortality, particularly among neonates, the critically ill, and the growing immunocompromised patient population. Sepsis is the end point of a complex and dynamic series of events in which both host and microbial factors drive high morbidity and potentially lethal physiologic alterations. In this article we provide a succinct overview of the events that lead to pediatric bloodstream infections (BSIs) and sepsis, with a focus on the molecular mechanisms used by bacteria to subvert host barriers and local immunity to gain access to and persist within the systemic circulation. In the events preceding and during BSI and sepsis, Gram-positive and Gram-negative pathogens use a battery of factors for translocation, inhibition of immunity, molecular mimicry, intracellular survival, and nutrient scavenging. Gaps in understanding the molecular pathogenesis of bacterial BSIs and sepsis are highlighted as opportunities to identify and develop new therapeutics.
-
King, C.J.; Tung, L.A.
1992-07-21
Carboxylic acids are sorbed from aqueous feedstocks at pHs close to or above the acids' pH[sub a] into a strongly basic organic liquid phase or onto a basic solid adsorbent or moderately basic ion exchange resin. The acids are freed from the sorbent phase by treating it with aqueous alkylamine or ammonia thus forming an alkylammonium or ammonium carboxylate which dewatered and decomposed to the desired carboxylic acid and the alkylamine or ammonia. 8 figs.
-
Raeke, Julia; Lechtenfeld, Oliver J; Tittel, Jörg; Oosterwoud, Marieke R; Bornmann, Katrin; Reemtsma, Thorsten
2017-04-15
Drinking water reservoirs in the Northern Hemisphere are largely affected by the decadal-long increase in riverine dissolved organic carbon (DOC) concentrations. The removal of DOC in drinking water treatment is costly and predictions are needed to link DOC removal efficiency to its mobilization in catchments, both of which are determined by the molecular composition. To study the effect of hydrological events and land use on the molecular characteristics of dissolved organic matter (DOM), 36 samples from three different catchment areas in the German low mountain ranges, with DOC concentrations ranging from 3 to 32 mg L -1 , were examined. Additionally, nine pairs of samples from downstream drinking water reservoirs were analyzed before and after flocculation. The molecular composition and the age of DOM were analyzed using ultrahigh resolution Fourier transform ion cyclotron resonance mass spectrometry (FTICR-MS) and radiocarbon ( 14 C) analysis. At elevated discharge in a forested catchment comparatively younger, more oxygenated and unsaturated molecules of higher molecular weight were preferentially mobilized, likely linked to the reductive mobilization of iron. DOM with highly similar molecular characteristics (O/C ratio > 0.5, m/z > 500) could also be efficiently removed through flocculation in drinking water treatment. The proportion of DOM removed through flocculation ranged between 43% and 73% of DOC and was highest at elevated discharge. In catchment areas with a higher percentage of grassland and agriculture a higher proportion of DOM molecules containing sulfur and nitrogen was detected, which in turn could be less efficiently flocculated. Altogether, it was shown that DOM that is released during large hydrological events can be efficiently flocculated again, suggesting a reversal of similar chemical mechanisms in both processes. Since the occurrence of heavy rainfall events is predicted to increase in the future, event-driven mobilization of DOC may continue to challenge drinking water production. Copyright © 2017 Elsevier Ltd. All rights reserved.
-
Luque, Raúl M; Ibáñez-Costa, Alejandro; Sánchez-Tejada, Laura; Rivero-Cortés, Esther; Robledo, Mercedes; Madrazo-Atutxa, Ainara; Mora, Mireia; Álvarez, Clara V; Lucas-Morante, Tomás; Álvarez-Escolá, Cristina; Fajardo, Carmen; Castaño, Luis; Gaztambide, Sonia; Venegas-Moreno, Eva; Soto-Moreno, Alfonso; Gálvez, María Ángeles; Salvador, Javier; Valassi, Elena; Webb, Susan M; Picó, Antonio; Puig-Domingo, Manel; Gilabert, Montserrat; Bernabéu, Ignacio; Marazuela, Mónica; Leal-Cerro, Alfonso; Castaño, Justo P
2016-01-01
Pituitary adenomas are uncommon, difficult to diagnose tumors whose heterogeneity and low incidence complicate large-scale studies. The Molecular Registry of Pituitary Adenomas (REMAH) was promoted by the Andalusian Society of Endocrinology and Nutrition (SAEN) in 2008 as a cooperative clinical-basic multicenter strategy aimed at improving diagnosis and treatment of pituitary adenomas by combining clinical, pathological, and molecular information. In 2010, the Spanish Society of Endocrinology and Nutrition (SEEN) extended this project to national level and established 6 nodes with common protocols and methods for sample and clinical data collection, molecular analysis, and data recording in a common registry (www.remahnacional.com). The registry combines clinical data with molecular phenotyping of the resected pituitary adenoma using quantitative real-time PCR of expression of 26 genes: Pituitary hormones (GH-PRL-LH-FSH-PRL-ACTH-CGA), receptors (somatostatin, dopamine, GHRH, GnRH, CRH, arginine-vasopressin, ghrelin), other markers (Ki67, PTTG1), and control genes. Until 2015, molecular information has been collected from 704 adenomas, out of 1179 patients registered. This strategy allows for comparative and relational analysis between the molecular profile of the different types of adenoma and the clinical phenotype of patients, which may provide a better understanding of the condition and potentially help in treatment selection. The REMAH is therefore a unique multicenter, interdisciplinary network founded on a shared database that provides a far-reaching translational approach for management of pituitary adenomas, and paves the way for the conduct of combined clinical-basic innovative studies on large patient samples. Copyright © 2016 SEEN. Published by Elsevier España, S.L.U. All rights reserved.
-
Yu, Yingyan
2014-01-01
Histopathological classification is in a pivotal position in both basic research and clinical diagnosis and treatment of gastric cancer. Currently, there are different classification systems in basic science and clinical application. In medical literatures, different classifications are used including Lauren and WHO systems, which have confused many researchers. Lauren classification has been proposed for half a century, but is still used worldwide. It shows many advantages of simple, easy handling with prognostic significance. The WHO classification scheme is better than Lauren classification in that it is continuously being revised according to the progress of gastric cancer, and is always used in the clinical and pathological diagnosis of common scenarios. Along with the progression of genomics, transcriptomics, proteomics, metabolomics researches, molecular classification of gastric cancer becomes the current hot topics. The traditional therapeutic approach based on phenotypic characteristics of gastric cancer will most likely be replaced with a gene variation mode. The gene-targeted therapy against the same molecular variation seems more reasonable than traditional chemical treatment based on the same morphological change.
-
Akata, Takashi
2007-01-01
General anesthetics cause hemodynamic instability and alter blood flow to various organs. There is mounting evidence that most general anesthetics, at clinical concentrations, influence a wide variety of cellular and molecular mechanisms regulating the contractile state of vascular smooth muscle cells (i.e., vascular tone). In addition, in current anesthetic practice, various types of vasoactive agents are often used to control vascular reactivity and to sustain tissue blood flow in high-risk surgical patients with impaired vital organ function and/or hemodynamic instability. Understanding the physiological mechanisms involved in the regulation of vascular tone thus would be beneficial for anesthesiologists. This review, in two parts, provides an overview of current knowledge about the cellular and molecular mechanisms regulating vascular tone-i.e., targets for general anesthetics, as well as for vasoactive drugs that are used in intraoperative circulatory management. This first part of the two-part review focuses on basic mechanisms regulating cytosolic Ca2+ concentration and the Ca2+-dependent regulation of vascular tone.
-
Modeling the Mechanism of Action of a DGAT1 Inhibitor Using a Causal Reasoning Platform
Enayetallah, Ahmed E.; Ziemek, Daniel; Leininger, Michael T.; Randhawa, Ranjit; Yang, Jianxin; Manion, Tara B.; Mather, Dawn E.; Zavadoski, William J.; Kuhn, Max; Treadway, Judith L.; des Etages, Shelly Ann G.; Gibbs, E. Michael; Greene, Nigel; Steppan, Claire M.
2011-01-01
Triglyceride accumulation is associated with obesity and type 2 diabetes. Genetic disruption of diacylglycerol acyltransferase 1 (DGAT1), which catalyzes the final reaction of triglyceride synthesis, confers dramatic resistance to high-fat diet induced obesity. Hence, DGAT1 is considered a potential therapeutic target for treating obesity and related metabolic disorders. However, the molecular events shaping the mechanism of action of DGAT1 pharmacological inhibition have not been fully explored yet. Here, we investigate the metabolic molecular mechanisms induced in response to pharmacological inhibition of DGAT1 using a recently developed computational systems biology approach, the Causal Reasoning Engine (CRE). The CRE algorithm utilizes microarray transcriptomic data and causal statements derived from the biomedical literature to infer upstream molecular events driving these transcriptional changes. The inferred upstream events (also called hypotheses) are aggregated into biological models using a set of analytical tools that allow for evaluation and integration of the hypotheses in context of their supporting evidence. In comparison to gene ontology enrichment analysis which pointed to high-level changes in metabolic processes, the CRE results provide detailed molecular hypotheses to explain the measured transcriptional changes. CRE analysis of gene expression changes in high fat habituated rats treated with a potent and selective DGAT1 inhibitor demonstrate that the majority of transcriptomic changes support a metabolic network indicative of reversal of high fat diet effects that includes a number of molecular hypotheses such as PPARG, HNF4A and SREBPs. Finally, the CRE-generated molecular hypotheses from DGAT1 inhibitor treated rats were found to capture the major molecular characteristics of DGAT1 deficient mice, supporting a phenotype of decreased lipid and increased insulin sensitivity. PMID:22073239
-
Hughes, Timothy P; Munhoz, Eduardo; Aurelio Salvino, Marco; Ong, Tee Chuan; Elhaddad, Alaa; Shortt, Jake; Quach, Hang; Pavlovsky, Carolina; Louw, Vernon J; Shih, Lee-Yung; Turkina, Anna G; Meillon, Luis; Jin, Yu; Acharya, Sandip; Dalal, Darshan; Lipton, Jeffrey H
2017-10-01
The Evaluating Nilotinib Efficacy and Safety in Clinical Trials-Extending Molecular Responses (ENESTxtnd) study was conducted to evaluate the kinetics of molecular response to nilotinib in patients with newly diagnosed chronic myeloid leukaemia in chronic phase and the impact of novel dose-optimization strategies on patient outcomes. The ENESTxtnd protocol allowed nilotinib dose escalation (from 300 to 400 mg twice daily) in the case of suboptimal response or treatment failure as well as dose re-escalation for patients with nilotinib dose reductions due to adverse events. Among 421 patients enrolled in ENESTxtnd, 70·8% (95% confidence interval, 66·2-75·1%) achieved major molecular response (BCR-ABL1 ≤ 0·1% on the International Scale) by 12 months (primary endpoint). By 24 months, 81·0% of patients achieved major molecular response, including 63·6% (56 of 88) of those with dose escalations for lack of efficacy and 74·3% (55 of 74) of those with dose reductions due to adverse events (including 43 of 54 patients with successful re-escalation). The safety profile of nilotinib was consistent with prior studies. The most common non-haematological adverse events were headache, rash, and nausea; cardiovascular events were reported in 4·5% of patients (grade 3/4, 3·1%). The study was registered at clinicaltrials.gov (NCT01254188). © 2017 The Authors. British Journal of Haematology published by John Wiley & Sons Ltd.
-
ERIC Educational Resources Information Center
Edmondson, Katherine M.
A new problem-based course in molecular biology, genetics, and cancer for first-year veterinary students was developed at the College of Veterinary Medicine at Cornell University (New York). The course was developed out of a desire to foster student-centered and lifelong learning and to integrate basic and clinical science knowledge despite a lack…
-
Stöver, Timo; Diensthuber, Marc
2012-01-01
The inner ear is our most sensitive sensory organ and can be subdivided into three functional units: organ of Corti, stria vascularis and spiral ganglion. The appropriate stimulus for the organ of hearing is sound, which travels through the external auditory canal to the middle ear where it is transmitted to the inner ear. The inner ear houses the hair cells, the sensory cells of hearing. The inner hair cells are capable of mechanotransduction, the transformation of mechanical force into an electrical signal, which is the basic principle of hearing. The stria vascularis generates the endocochlear potential and maintains the ionic homeostasis of the endolymph. The dendrites of the spiral ganglion form synaptic contacts with the hair cells. The spiral ganglion is composed of neurons that transmit the electrical signals from the cochlea to the central nervous system. In recent years there has been significant progress in research on the molecular basis of hearing. An increasing number of genes and proteins related to hearing are being identified and characterized. The growing knowledge of these genes contributes not only to greater appreciation of the mechanism of hearing but also to a deeper understanding of the molecular basis of hereditary hearing loss. This basic research is a prerequisite for the development of molecular diagnostics and novel therapies for hearing loss. PMID:22558056
-
Forward hadron calorimeter at MPD/NICA
NASA Astrophysics Data System (ADS)
Golubeva, M.; Guber, F.; Ivashkin, A.; Izvestnyy, A.; Kurepin, A.; Morozov, S.; Parfenov, P.; Petukhov, O.; Taranenko, A.; Selyuzhenkov, I.; Svintsov, I.
2017-01-01
Forward hadron calorimeter (FHCAL) at MPD/NICA experimental setup is described. The main purpose of the FHCAL is to provide an experimental measurement of a heavy-ion collision centrality (impact parameter) and orientation of its reaction plane. Precise event-by-event estimate of these basic observables is crucial for many physics phenomena studies to be performed by the MPD experiment. The simulation results of FHCAL performance are presented.
-
Thanks-a-Latte, Seniors: The Library Hosts an Election Day Event
ERIC Educational Resources Information Center
Repp, Anne
2009-01-01
This article presents the Louisa County High School Library's annual Thanks-a-Latte Day, an event that introduces the American political process to LCHS seniors in a real way. Thanks-a-Latte Day was born from an idea found in a "School Library Journal" article by Charli O'Dell published in 1999. Her basic idea was to promote the school library by…
-
Timing the Random and Anomalous Arrival of Particles in a Geiger Counter with GPS Devices
ERIC Educational Resources Information Center
Blanco, F.; La Rocca, P.; Riggi, F.; Riggi, S.
2008-01-01
The properties of the arrival time distribution of particles in a detector have been studied by the use of a small Geiger counter, with a GPS device to tag the event time. The experiment is intended to check the basic properties of the random arrival time distribution between successive events and to simulate the investigations carried out by…
-
Unfolding of globular polymers by external force
DOE Office of Scientific and Technical Information (OSTI.GOV)
Bell, Samuel; Terentjev, Eugene M., E-mail: emt1000@cam.ac.uk
2015-11-14
We examine the problem of a polymer chain, folded into a globule in poor solvent, subjected to a constant tensile force. Such a situation represents a Gibbs thermodynamic ensemble and is useful for analysing force-clamp atomic force microscopy measurements, now very common in molecular biophysics. Using a basic Flory mean-field theory, we account for surface interactions of monomers with solvent. Under an increasing tensile force, a first-order phase transition occurs from a compact globule to a fully extended chain, in an “all-or-nothing” unfolding event. This contrasts with the regime of imposed extension, first studied by Halperin and Zhulina [Europhys. Lett.more » 15, 417 (1991)], where there is a regime of coexistence of a partial globule with an extended chain segment. We relate the transition forces in this problem to the solvent quality and degree of polymerisation, and also find analytical expressions for the energy barriers present in the problem. Using these expressions, we analyse the kinetic problem of a force-ramp experiment and show that the force at which a globule ruptures depends on the rate of loading.« less
-
Chang, Rui; You, Jiacong; Zhou, Qinghua
2013-04-01
Lung cancer is one of the most common diseases that endanger health and life of people domestically. A number of recurrence and death of lung cancer originated from metastasis. As a key step in metastasis of lung cancer, epithelial to mesenchymal transition involved down-regulation of E-cadherin, as well as regulated by EMT transcription factors. HATs and HDACs is a protein family that catalyzes acetylation and deacetylation of histones. Not only they have vital functions in tumor pathogenesis, but also participate in the EMT of lung cancer. HATs and HDACs interact with certain EMT transcription factors. Moreover, the function of these EMT transcription factors may be regulated by acetylation, which has influence on EMT program in lung cancer. Therefore, this review introduces the event of HATs and HDACs function in EMT of lung cancer, and investigate the molecular mechanism of their interaction. Then, the potential of HDAC inhibitor utilization in the inhibition of EMT and lung cancer therapy were discussed, as to pave the way for the related basic research and clinical practice.
-
Sandrock, Björn
2012-10-09
Phosphorylation is a key event in many cellular processes like cell cycle, transformation of environmental signals to transcriptional activation or polar growth. The chemical genetics approach can be used to analyse the effect of highly specific inhibition in vivo and is a promising method to screen for kinase targets. We have used this approach to study the role of the germinal centre kinase Don3 during the cell division in the phytopathogenic fungus Ustilago maydis. Due to the easy determination of the don3 phenotype we have chosen this approach for a genetic course for M.Sc. students and for IMPRS (International Max-Planck research school) students. According to the principle of "problem-based learning" the aim of this two-week course is to transfer knowledge about the broad spectrum of kinases to the students and that the students acquire the ability to design their own analog-sensitive kinase of interest. In addition to these training goals, we benefit from these annual courses the synthesis of basic constructs for genetic modification of several kinases in our model system U. maydis.
-
Heterogeneous Structure of Stem Cells Dynamics: Statistical Models and Quantitative Predictions
Bogdan, Paul; Deasy, Bridget M.; Gharaibeh, Burhan; Roehrs, Timo; Marculescu, Radu
2014-01-01
Understanding stem cell (SC) population dynamics is essential for developing models that can be used in basic science and medicine, to aid in predicting cells fate. These models can be used as tools e.g. in studying patho-physiological events at the cellular and tissue level, predicting (mal)functions along the developmental course, and personalized regenerative medicine. Using time-lapsed imaging and statistical tools, we show that the dynamics of SC populations involve a heterogeneous structure consisting of multiple sub-population behaviors. Using non-Gaussian statistical approaches, we identify the co-existence of fast and slow dividing subpopulations, and quiescent cells, in stem cells from three species. The mathematical analysis also shows that, instead of developing independently, SCs exhibit a time-dependent fractal behavior as they interact with each other through molecular and tactile signals. These findings suggest that more sophisticated models of SC dynamics should view SC populations as a collective and avoid the simplifying homogeneity assumption by accounting for the presence of more than one dividing sub-population, and their multi-fractal characteristics. PMID:24769917
-
Heutink, Rene; Bergervoet, Saskia A.; Harders, Frank; Bossers, Alex; Koch, Guus
2017-01-01
In 2016, an epidemic of highly pathogenic avian influenza A virus subtype H5N8 in the Netherlands caused mass deaths among wild birds, and several commercial poultry farms and captive bird holdings were affected. We performed complete genome sequencing to study the relationship between the wild bird and poultry viruses. Phylogenetic analysis showed that the viruses are related to H5 clade 2.3.4.4 viruses detected in Russia in May 2016 but contained novel polymerase basic 2 and nucleoprotein gene segments and 2 different variants of the polymerase acidic segment. Molecular dating suggests that the reassortment events most likely occurred in wild birds in Russia or Mongolia. Furthermore, 2 genetically distinct H5N5 reassortant viruses were detected in wild birds in the Netherlands. Our study provides evidence for fast and continuing reassortment of H5 clade 2.3.4.4 viruses, which might lead to rapid changes in virus characteristics, such as pathogenicity, infectivity, transmission, and zoonotic potential. PMID:29148396
-
Beerens, Nancy; Heutink, Rene; Bergervoet, Saskia A; Harders, Frank; Bossers, Alex; Koch, Guus
2017-12-01
In 2016, an epidemic of highly pathogenic avian influenza A virus subtype H5N8 in the Netherlands caused mass deaths among wild birds, and several commercial poultry farms and captive bird holdings were affected. We performed complete genome sequencing to study the relationship between the wild bird and poultry viruses. Phylogenetic analysis showed that the viruses are related to H5 clade 2.3.4.4 viruses detected in Russia in May 2016 but contained novel polymerase basic 2 and nucleoprotein gene segments and 2 different variants of the polymerase acidic segment. Molecular dating suggests that the reassortment events most likely occurred in wild birds in Russia or Mongolia. Furthermore, 2 genetically distinct H5N5 reassortant viruses were detected in wild birds in the Netherlands. Our study provides evidence for fast and continuing reassortment of H5 clade 2.3.4.4 viruses, which might lead to rapid changes in virus characteristics, such as pathogenicity, infectivity, transmission, and zoonotic potential.
-
Mouse Models for Investigating the Developmental Bases of Human Birth Defects
MOON, ANNE M.
2006-01-01
Clinicians and basic scientists share an interest in discovering how genetic or environmental factors interact to perturb normal development and cause birth defects and human disease. Given the complexity of such interactions, it is not surprising that 4% of human infants are born with a congenital malformation, and cardiovascular defects occur in nearly 1%. Our research is based on the fundamental hypothesis that an understanding of normal and abnormal development will permit us to generate effective strategies for both prevention and treatment of human birth defects. Animal models are invaluable in these efforts because they allow one to interrogate the genetic, molecular and cellular events that distinguish normal from abnormal development. Several features of the mouse make it a particularly powerful experimental model: it is a mammalian system with similar embryology, anatomy and physiology to humans; genes, proteins and regulatory programs are largely conserved between human and mouse; and finally, gene targeting in murine embryonic stem cells has made the mouse genome amenable to sophisticated genetic manipulation currently unavailable in any other model organism. PMID:16641221
-
'Sex and crime' in evolution - why sexuality was so successful.
Schubert, Ingo
2011-01-01
Components of sexuality have fore-runners already in prokaryotes, for instance conjugation, recombination- repair and the molecular constituents needed for nuclear division. For eukaryotes, the basic and predominant mode of propagation is via sexuality, although it is highly complex and costly. Many interactions between individual cells are detrimental for one partner and might be considered as a 'criminal' act performed by the active partner. For instance, the irreversible and non-reciprocal processes of phagocytosis or endocellular parasitism but also the irreversible, asymmetric and sustainable endosymbiosis with a benefit bias in favour of the active partner represent such events. Contrary to this, sexuality in general represents an indirectly reversible, reciprocal, sustainable (by reiteration) and mutually beneficial interaction between equal-ranking cells. After fertilization, a doubled set of genetic information protects against loss of essential genes, while the haplophase allows ridding lethal mutations. Resorting of parental chromosome sets, recombination between homologous chromosomes during meiosis, and new combination of alleles during fertilization, mediate a high genetic variability at a minimum risk of deleterious variants, thus promoting evolutionary adaptability.
-
The Impact of Sleep Deprivation on the Brain
Trošt Bobić, Tatjana; Šečić, Ana; Zavoreo, Iris; Matijević, Valentina; Filipović, Branimir; Kolak, Željka; Bašić Kes, Vanja; Ciliga, Dubravka; Sajković, Dubravka
2016-09-01
Each sleep phase is characterized by specific chemical, cellular and anatomic events of vital importance for normal neural functioning. Different forms of sleep deprivation may lead to a decline of cognitive functions in individuals. Studies in this field make a distinction between total sleep deprivation, chronic sleep restriction, and the situation of sleep disruption. Investigations covering the acute effects of sleep deprivation on the brain show that the discovered behavioral deficits in most cases regenerate after two nights of complete sleep. However, some studies done on mice emphasize the possible chronic effects of long-term sleep deprivation or chronic restriction on the occurrence of neurodegenerative diseases such as Alzheimer’s disease and dementia. In order to better understand the acute and chronic effects of sleep loss, the mechanisms of neural adaptation in the situations of insufficient sleep need to be further investigated. Future integrative research on the impact of sleep deprivation on neural functioning measured through the macro level of cognitive functions and the micro molecular and cell level could contribute to more accurate conclusions about the basic cellular mechanisms responsible for the detected behavioral deficits occurring due to sleep deprivation.
-
Generation of Mouse Lung Epithelial Cells.
Kasinski, Andrea L; Slack, Frank J
2013-08-05
Although in vivo models are excellent for assessing various facets of whole organism physiology, pathology, and overall response to treatments, evaluating basic cellular functions, and molecular events in mammalian model systems is challenging. It is therefore advantageous to perform these studies in a refined and less costly setting. One approach involves utilizing cells derived from the model under evaluation. The approach to generate such cells varies based on the cell of origin and often the genetics of the cell. Here we describe the steps involved in generating epithelial cells from the lungs of Kras LSL-G12D/+ ; p53 LSL-R172/+ mice (Kasinski and Slack, 2012). These mice develop aggressive lung adenocarcinoma following cre-recombinase dependent removal of a stop cassette in the transgenes and subsequent expression of Kra -G12D and p53 R172 . While this protocol may be useful for the generation of epithelial lines from other genetic backgrounds, it should be noted that the Kras; p53 cell line generated here is capable of proliferating in culture without any additional genetic manipulation that is often needed for less aggressive backgrounds.
-
Molecular dynamics simulation of low-energy recoil events in titanate pyrochlores
DOE Office of Scientific and Technical Information (OSTI.GOV)
Dong, Liyuan; Setyawan, Wahyu; Li, Yuhong
2017-01-01
Molecular dynamics simulations of low-energy displacements in titanate pyrochlores have been carried out along three main directions, to determineE dfor A, Ti and O, corresponding defect configurations, and defect formation dynamics.
-
HPV: Molecular pathways and targets.
Gupta, Shilpi; Kumar, Prabhat; Das, Bhudev C
2018-04-05
Infection of high-risk human papillomaviruses (HPVs) is a prerequisite for the development of cervical carcinoma. HPV infections are also implicated in the development of other types of carcinomas. Chronic or persistent infection of HPV is essential but HPV alone is inadequate, additional endogenous or exogenous cues are needed along with HPV to induce cervical carcinogenesis. The strategies that high-risk HPVs have developed in differentiating epithelial cells to reach a DNA-synthesis competent state leading to tumorigenic transformation are basically due to overexpression of the E6 and E7 oncoproteins and the activation of diverse cellular regulatory or signaling pathways that are targeted by them. Moreover, the Wnt/β-catenin/Notch and phosphoinositide 3-kinase (PI3K)/protein kinase B (Akt) pathways are deregulated in various cancers, and have also been implicated in HPV-induced cancers. These are basically related to the "cancer hallmarks," and include sustaining proliferative signals, the evasion of growth suppression and immune destruction, replicative immortality, inflammation, invasion, metastasis and angiogenesis, as well as genome instability, resisting cell death, and deregulation of cellular energetics. These information could eventually aid in identifying or developing new diagnostic, prognostic biomarkers, and may contribute to design more effective targeted therapeutics and treatment strategies. Although surgery, chemotherapy and radiotherapy can cure more than 90% of women with early stage cervical cancer, the recurrent and metastatic disease remains a major cause of cancer mortality. Numerous efforts have been made to design new drugs and develop gene therapies to treat cervical cancer. In recent years, research on treatment strategies has proposed several options, including the role of HPV E5, E6, and E7 oncogenes, which are retained and overexpressed in most of the cervical cancers and whose respective oncoproteins are critical to the induction and maintenance of the malignant phenotype. Other efforts have been focused on antitumor immunotherapy strategies. It is known that during the development of cervical cancer, a cascade of abnormal events is induced, including disruption of cell cycle control, perturbation of antitumor immune response, alteration of gene expression, deregulation of microRNA and cancer stem cell and stemness related markers expression could serve as novel molecular targets for reliable diagnosis and treatment of HPV-positive cancers. However, the search for new proposals for disease control and prevention has brought new findings and approaches in the context of molecular biology indicating innovations and perspectives in the early detection and prevention of the disease. Thus, in this article, we discuss molecular signaling pathways activated by HPV and potential targets or biomarkers for early detection or prevention and the treatment of HPV-associated cancers. Copyright © 2018 Elsevier Inc. All rights reserved.
-
A Web interface generator for molecular biology programs in Unix.
Letondal, C
2001-01-01
Almost all users encounter problems using sequence analysis programs. Not only are they difficult to learn because of the parameters, syntax and semantic, but many are different. That is why we have developed a Web interface generator for more than 150 molecular biology command-line driven programs, including: phylogeny, gene prediction, alignment, RNA, DNA and protein analysis, motif discovery, structure analysis and database searching programs. The generator uses XML as a high-level description language of the legacy software parameters. Its aim is to provide users with the equivalent of a basic Unix environment, with program combination, customization and basic scripting through macro registration. The program has been used for three years by about 15000 users throughout the world; it has recently been installed on other sites and evaluated as a standard user interface for EMBOSS programs.
-
NASA Technical Reports Server (NTRS)
Jalufka, N. W.
1983-01-01
The development of direct nuclear pumped lasers is reviewed. Theoretical and experimental investigations of various methods of converting the energy of nuclear fission fragments to laser power are summarized. The development of direct nuclear pumped lasers was achieved. The basic processes involved in the production of a plasma by nuclear radiation were studied. Significant progress was accomplished in this area and a large amount of basic data on plasma formation and atomic and molecular processes leading to population inversions is available.
-
Electrocardiography: A Technologist's Guide to Interpretation.
Tso, Colin; Currie, Geoffrey M; Gilmore, David; Kiat, Hosen
2015-12-01
The nuclear medicine technologist works with electrocardiography when performing cardiac stress testing and gated cardiac imaging and when monitoring critical patients. To enhance patient care, basic electrocardiogram interpretation skills and recognition of key arrhythmias are essential for the nuclear medicine technologist. This article provides insight into the anatomy of an electrocardiogram trace, covers basic electrocardiogram interpretation methods, and describes an example case typical in the nuclear medicine environment. © 2015 by the Society of Nuclear Medicine and Molecular Imaging, Inc.
-
1988-11-01
rates.6 The Hammet equation , also called the Linear Free Energy Relationship (LFER) because of the relationship of the Gibb’s Free Energy to the... equations for numerous biological and physicochemical properties. Linear Solvation Enery Relationship (LSER), a sub-set of QSAR have been used by...originates from thermodynamics, where Hammet recognized the relationship of structure to the Gibb’s Free Energy, and ultimately to equilibria and reaction
-
Deep Learning in Nuclear Medicine and Molecular Imaging: Current Perspectives and Future Directions.
Choi, Hongyoon
2018-04-01
Recent advances in deep learning have impacted various scientific and industrial fields. Due to the rapid application of deep learning in biomedical data, molecular imaging has also started to adopt this technique. In this regard, it is expected that deep learning will potentially affect the roles of molecular imaging experts as well as clinical decision making. This review firstly offers a basic overview of deep learning particularly for image data analysis to give knowledge to nuclear medicine physicians and researchers. Because of the unique characteristics and distinctive aims of various types of molecular imaging, deep learning applications can be different from other fields. In this context, the review deals with current perspectives of deep learning in molecular imaging particularly in terms of development of biomarkers. Finally, future challenges of deep learning application for molecular imaging and future roles of experts in molecular imaging will be discussed.
-
Molecular chirality: language, history, and significance.
Gal, Joseph
2013-01-01
In this chapter some background material concerning molecular chirality and enantiomerism is presented. First some basic chemical-molecular aspects of chirality are reviewed, after which certain relevant terminology whose use in the literature has been problematic is discussed. Then an overview is provided of some of the early discoveries that laid the foundations of the science of molecular chirality in chemistry and biology, including the discovery of the phenomenon of molecular chirality by L. Pasteur, the proposals for the asymmetric carbon atom by J.H. van 't Hoff and J.A. Lebel, Pasteur's discovery of biological enantioselectivity, the discovery of enantioselectivity at biological receptors by A. Piutti, the studies of enzymatic stereoselectivity by E. Fischer, and the work on enantioselectivity in pharmacology by A. Cushny. Finally, the role of molecular chirality in pharmacotherapy and new-drug development, arguably one of the main driving forces for the current intense interest in the phenomenon of molecular chirality, is discussed.
-
Goals and Objectives for Molecular Pathology Education in Residency Programs
1999-01-01
Increasing knowledge of the molecular basis of disease and advances in technology for analyzing nucleic acids and gene products are changing pathology practice. The explosion of information regarding inherited susceptibility to disease is an important aspect of this transformation. Pathology residency programs are incorporating molecular pathology education into their curricula to prepare newly trained pathologists for the future, yet little guidance has been available regarding the important components of molecular pathology training. We present general goals for pathology training programs for molecular pathology education. These include recommendations to pathology residents for the acquisition of both basic knowledge in human genetics and molecular biology and specific skills relevant to microbiology, molecular oncology, genetics, histocompatibility, and identity determination. The importance of residents gaining facility in integrating data gained via nucleic acid based-technology with other laboratory and clinical information available in the care of patients is emphasized. PMID:11272908
-
Tiny Hiccups To Titanic Explosions: Tackling Transients in Anomalous X-ray Pulsars
NASA Astrophysics Data System (ADS)
Kaspi, Victoria
2006-09-01
Recently discovered transient events in Anomalous X-ray Pulsars (AXPs) may be a Rosetta Stone for understanding the persistent emission from magnetars. They also may hold the key to quantifying the number of magnetars in the Galaxy. Here we request Chandra TOO time to observe any AXP following a rare transient event, including a major outburst or a long-duration flare. Specifically, the requested observations will determine the pulsed fraction and spectral evolution of a transient AXP event as the source relaxes back to quiescence, in order to quantitatively test the "twisted magnetosphere" model for magnetars, and establish the basic phenomenology of transient AXP events.
-
TINY HICCUPS TO TITANIC EXPLOSIONS: Tackling Transients in Anomalous X-ray Pulsars
NASA Astrophysics Data System (ADS)
Kaspi, Victoria
2007-09-01
Recently discovered transient events in Anomalous X-ray Pulsars (AXPs) may be a Rosetta Stone for understanding the persistent emission from magnetars. They also may hold the key to quantifying the number of magnetars in the Galaxy. Here we request Chandra TOO time to observe any AXP following a rare transient event, including a major outburst or a long-duration flare. Specifically, the requested observations will determine the pulsed fraction and spectral evolution of a transient AXP event as the source relaxes back to quiescence, in order to quantitatively test the "twisted magnetosphere" model for magnetars, and establish the basic phenomenology of transient AXP events.
-
ERIC Educational Resources Information Center
Kelly, Resa M.
2014-01-01
Molecular visualizations have been widely endorsed by many chemical educators as an efficient way to convey the dynamic and atomic-level details of chemistry events. Research indicates that students who use molecular visualizations are able to incorporate most of the intended features of the animations into their explanations. However, studies…
-
ERIC Educational Resources Information Center
Hubler, Tina; Adams, Patti; Scammell, Jonathan
2015-01-01
The molecular basis of evolution is an important and challenging concept for students to understand. In a previous article, we provided some of the scientific background necessary to teach this topic. This article features a series of laboratory activities demonstrating that molecular events can alter the genomes of organisms. These activities are…
-
ERIC Educational Resources Information Center
Valenzuela-Harrington, Mauricio; Delgado-Garcia, Jose M.; Minichiello, Liliana; Gruart, Agnes; Sciarretta, Carla
2007-01-01
Previous in vitro studies have characterized the electrophysiological properties and molecular events associated with long-term potentiation (LTP), but as yet there are no in vivo data from molecular-level dissection that directly identify LTP as the biological substrate for learning and memory. Understanding whether the molecular pathways…
-
78 FR 34101 - Agency Information Collection Activities: Proposed Collection; Comment Request
Federal Register 2010, 2011, 2012, 2013, 2014
2013-06-06
... and basic descriptive statistics on the quantity and type of consumer-reported patient safety events... conduct correlations, cross tabulations of responses and other statistical analysis. Estimated Annual...
-
Increasing Student Engagement and Enthusiasm: A Projectile Motion Crime Scene
NASA Astrophysics Data System (ADS)
Bonner, David
2010-05-01
Connecting physics concepts with real-world events allows students to establish a strong conceptual foundation. When such events are particularly interesting to students, it can greatly impact their engagement and enthusiasm in an activity. Activities that involve studying real-world events of high interest can provide students a long-lasting understanding and positive memorable experiences, both of which heighten the learning experiences of those students. One such activity, described in depth in this paper, utilizes a murder mystery and crime scene investigation as an application of basic projectile motion.
-
Jo, Ick Hyun; Kim, Young Chang; Kim, Dong Hwi; Kim, Kee Hong; Hyun, Tae Kyung; Ryu, Hojin; Bang, Kyong Hwan
2017-10-01
The development of molecular markers is one of the most useful methods for molecular breeding and marker-based molecular associated selections. Even though there is less information on the reference genome, molecular markers are indispensable tools for determination of genetic variation and identification of species with high levels of accuracy and reproducibility. The demand for molecular approaches for marker-based breeding and genetic discriminations in Panax species has greatly increased in recent times and has been successfully applied for various purposes. However, owing to the existence of diverse molecular techniques and differences in their principles and applications, there should be careful consideration while selecting appropriate marker types. In this review, we outline the recent status of different molecular marker applications in ginseng research and industrial fields. In addition, we discuss the basic principles, requirements, and advantages and disadvantages of the most widely used molecular markers, including restriction fragment length polymorphism, random amplified polymorphic DNA, sequence tag sites, simple sequence repeats, and single nucleotide polymorphisms.
-
Fundamental approaches in molecular biology for communication sciences and disorders.
Bartlett, Rebecca S; Jetté, Marie E; King, Suzanne N; Schaser, Allison; Thibeault, Susan L
2012-08-01
This contemporary tutorial will introduce general principles of molecular biology, common deoxyribonucleic acid (DNA), ribonucleic acid (RNA), and protein assays and their relevance in the field of communication sciences and disorders. Over the past 2 decades, knowledge of the molecular pathophysiology of human disease has increased at a remarkable pace. Most of this progress can be attributed to concomitant advances in basic molecular biology and, specifically, the development of an ever-expanding armamentarium of technologies for analysis of DNA, RNA, and protein structure and function. Details of these methodologies, their limitations, and examples from the communication sciences and disorders literature are presented. Results/Conclusions The use of molecular biology techniques in the fields of speech, language, and hearing sciences is increasing, facilitating the need for an understanding of molecular biology fundamentals and common experimental assays.
-
Dreyer, Chantal; Afchain, Pauline; Trouilloud, Isabelle; André, Thierry
2016-01-01
This review reports 3 of recently published molecular classifications of the 3 main gastro-intestinal cancers: gastric, pancreatic and colorectal adenocarcinoma. In colorectal adenocarcinoma, 6 independent classifications were combined to finally hold 4 molecular sub-groups, Consensus Molecular Subtypes (CMS 1-4), linked to various clinical, molecular and survival data. CMS1 (14% MSI with immune activation); CMS2 (37%: canonical with epithelial differentiation and activation of the WNT/MYC pathway); CMS3 (13% metabolic with epithelial differentiation and RAS mutation); CMS4 (23%: mesenchymal with activation of TGFβ pathway and angiogenesis with stromal invasion). In gastric adenocarcinoma, 4 groups were established: subtype "EBV" (9%, high frequency of PIK3CA mutations, hypermetylation and amplification of JAK2, PD-L1 and PD-L2), subtype "MSI" (22%, high rate of mutation), subtype "genomically stable tumor" (20%, diffuse histology type and mutations of RAS and genes encoding integrins and adhesion proteins including CDH1) and subtype "tumors with chromosomal instability" (50%, intestinal type, aneuploidy and receptor tyrosine kinase amplification). In pancreatic adenocarcinomas, a classification in four sub-groups has been proposed, stable subtype (20%, aneuploidy), locally rearranged subtype (30%, focal event on one or two chromosoms), scattered subtype (36%,<200 structural variation events), and unstable subtype (14%,>200 structural variation events, defects in DNA maintenance). Although currently away from the care of patients, these classifications open the way to "à la carte" treatment depending on molecular biology. Copyright © 2016 Société Française du Cancer. Published by Elsevier Masson SAS. All rights reserved.
-
Mares, Joise Hander; Gramacho, Karina Peres; Santos, Everton Cruz; da Silva Santiago, André; Santana, Juliano Oliveira; de Sousa, Aurizângela Oliveira; Alvim, Fátima Cerqueira; Pirovani, Carlos Priminho
2017-08-17
Moniliophthora perniciosa is a phytopathogenic fungus responsible for witches' broom disease of cacao trees (Theobroma cacao L.). Understanding the molecular events during germination of the pathogen may enable the development of strategies for disease control in these economically important plants. In this study, we determined a comparative proteomic profile of M. perniciosa basidiospores during germination by two-dimensional SDS-PAGE and mass spectrometry. A total of 316 proteins were identified. Molecular changes during the development of the germinative tube were identified by a hierarchical clustering analysis based on the differential accumulation of proteins. Proteins associated with fungal filamentation, such as septin and kinesin, were detected only 4 h after germination (hag). A transcription factor related to biosynthesis of the secondary metabolite fumagillin, which can form hybrids with polyketides, was induced 2 hag, and polyketide synthase was observed 4 hag. The accumulation of ATP synthase, binding immunoglobulin protein (BiP), and catalase was validated by western blotting. In this study, we showed variations in protein expression during the early germination stages of fungus M. perniciosa. Proteins associated with fungal filamentation, and consequently with virulence, were detected in basidiospores 4 hag., for example, septin and kinesin. We discuss these results and propose a model of the germination of fungus M. perniciosa. This research can help elucidate the mechanisms underlying basic processes of host invasion and to develop strategies for control of the disease.
-
Evolution of neuronal signalling: transmitters and receptors.
Hoyle, Charles H V
2011-11-16
Evolution is a dynamic process during which the genome should not be regarded as a static entity. Molecular and morphological information yield insights into the evolution of species and their phylogenetic relationships, and molecular information in particular provides information into the evolution of signalling processes. Many signalling systems have their origin in primitive, even unicellular, organisms. Through time, and as organismal complexity increased, certain molecules were employed as intercellular signal molecules. In the autonomic nervous system the basic unit of chemical transmission is a ligand and its cognate receptor. The general mechanisms underlying evolution of signal molecules and their cognate receptors have their basis in the alteration of the genome. In the past this has occurred in large-scale events, represented by two or more doublings of the whole genome, or large segments of the genome, early in the deuterostome lineage, after the emergence of urochordates and cephalochordates, and before the emergence of vertebrates. These duplications were followed by extensive remodelling involving subsequent small-scale changes, ranging from point mutations to exon duplication. Concurrent with these processes was multiple gene loss so that the modern genome contains roughly the same number of genes as in early deuterostomes despite the large-scale genomic duplications. In this review, the principles that underlie evolution that have led to large and small families of autonomic neurotransmitters and their receptors are discussed, with emphasis on G protein-coupled receptors. Copyright © 2010 Elsevier B.V. All rights reserved.
-
Molecular genetic approaches to the study of cellular senescence.
Goletz, T J; Smith, J R; Pereira-Smith, O M
1994-01-01
Cellular senescence is an inability of cells to synthesize DNA and divide, which results in a terminal loss of proliferation despite the maintenance of basic metabolic processes. Senescence has been proposed as a model for the study of aging at the cellular level, and the basis for this model system and its features have been summarized. Although strong experimental evidence exists to support the hypothesis that cellular senescence is a dominant active process, the mechanisms responsible for this phenomenon remain a mystery. Investigators have taken several approaches to gain a better understanding of senescence. Several groups have documented the differences between young and senescent cells, and others have identified changes that occur during the course of a cell's in vitro life span. Using molecular and biochemical approaches, important changes in gene expression and function of cell-cycle-associated products have been identified. The active production of an inhibitor of DNA synthesis has been demonstrated. This may represent the final step in a cascade of events governing senescence. The study of immortal cells which have escaped senescence has also provided useful information, particularly with regard to the genes governing the senescence program. These studies have identified four complementation groups for indefinite division, which suggests that there are at least four genes or gene pathways in the senescence program. Through the use of microcell-mediated chromosome transfer, chromosomes encoding senescence genes have been identified; efforts to clone these genes are ongoing.(ABSTRACT TRUNCATED AT 250 WORDS)
-
Chen, Junhua; Pan, Jiafeng; Chen, Shu
2018-01-14
A complete set of binary basic logic gates (OR, AND, NOR, NAND, INHIBT, IMPLICATION, XOR and XNOR) is realized on a label-free and enzyme-free sensing platform using caged G-quadruplex as the signal transducer. In the presence of an appropriate input, the temporarily blocked G-rich sequence in the hairpin DNA is released through cleavage by the synergetically-stabilized Mg 2+ -dependent DNAzyme which can be made to function via the input-guided cooperative conjunction of the DNAzyme subunits. In the presence of hemin, the unblocked G-quadruplex DNAzyme catalyzes the oxidation of 3,3',5,5'-tetramethylbenzidine (TMB) by H 2 O 2 to generate a colored readout signal which can be readily distinguished by the naked eye. This strategy is quite versatile and straightforward for logic operations. Two combinatorial gates (XOR + AND and XOR + NOR) are also successfully fabricated to demonstrate the modularity and scalability of the computing elements. The distinctive advantage of this logic system is that molecular events in aqueous solution could be translated into a color change which can be directly observed by the naked eye without resorting to any analytical instrumentation. Moreover, this work reveals a new route for the design of molecular logic gates that can be executed without any labeling and immobilization procedure or separation and washing step, which holds great promise for intelligent point-of-care diagnostics and in-field applications.
-
NASA Space Radiation Program Integrative Risk Model Toolkit
NASA Technical Reports Server (NTRS)
Kim, Myung-Hee Y.; Hu, Shaowen; Plante, Ianik; Ponomarev, Artem L.; Sandridge, Chris
2015-01-01
NASA Space Radiation Program Element scientists have been actively involved in development of an integrative risk models toolkit that includes models for acute radiation risk and organ dose projection (ARRBOD), NASA space radiation cancer risk projection (NSCR), hemocyte dose estimation (HemoDose), GCR event-based risk model code (GERMcode), and relativistic ion tracks (RITRACKS), NASA radiation track image (NASARTI), and the On-Line Tool for the Assessment of Radiation in Space (OLTARIS). This session will introduce the components of the risk toolkit with opportunity for hands on demonstrations. The brief descriptions of each tools are: ARRBOD for Organ dose projection and acute radiation risk calculation from exposure to solar particle event; NSCR for Projection of cancer risk from exposure to space radiation; HemoDose for retrospective dose estimation by using multi-type blood cell counts; GERMcode for basic physical and biophysical properties for an ion beam, and biophysical and radiobiological properties for a beam transport to the target in the NASA Space Radiation Laboratory beam line; RITRACKS for simulation of heavy ion and delta-ray track structure, radiation chemistry, DNA structure and DNA damage at the molecular scale; NASARTI for modeling of the effects of space radiation on human cells and tissue by incorporating a physical model of tracks, cell nucleus, and DNA damage foci with image segmentation for the automated count; and OLTARIS, an integrated tool set utilizing HZETRN (High Charge and Energy Transport) intended to help scientists and engineers study the effects of space radiation on shielding materials, electronics, and biological systems.
-
Bone remodelling: its local regulation and the emergence of bone fragility.
Martin, T John; Seeman, Ego
2008-10-01
Bone modelling prevents the occurrence of damage by adapting bone structure - and hence bone strength - to its loading circumstances. Bone remodelling removes damage, when it inevitably occurs, in order to maintain bone strength. This cellular machinery is successful during growth, but fails during advancing age because of the development of a negative balance between the volumes of bone resorbed and formed during remodelling by the basic multicellular unit (BMU), high rates of remodelling during midlife in women and late in life in both sexes, and a decline in periosteal bone formation. together resulting in bone loss and structural decay each time a remodelling event occurs. The two steps in remodelling - resorption of a volume of bone by osteoclasts and formation of a comparable volume by osteoblasts - are sequential, but the regulatory events leading to these two fully differentiated functions are not. Reparative remodelling is initiated by damage producing osteocyte apoptosis, which signals the location of damage via the osteocyte canalicular system to endosteal lining cells which forms the canopy of a bone-remodelling compartment (BRC). Within the BRC, local recruitment of osteoblast precursors from the lining cells, the marrow and circulation, direct contact with osteoclast precursors, osteoclastogenesis and molecular cross-talk between precursors, mature cells, cells of the immune system, and products of the resorbed matrix, titrate the birth, work and lifespan of the cells of this multicellular remodelling machinery to either remove or form a net volume of bone appropriate to the mechanical requirements.
-
Amplifying Electrochemical Indicators
NASA Technical Reports Server (NTRS)
Fan, Wenhong; Li, Jun; Han, Jie
2004-01-01
Dendrimeric reporter compounds have been invented for use in sensing and amplifying electrochemical signals from molecular recognition events that involve many chemical and biological entities. These reporter compounds can be formulated to target specific molecules or molecular recognition events. They can also be formulated to be, variously, hydrophilic or amphiphilic so that they are suitable for use at interfaces between (1) aqueous solutions and (2) electrodes connected to external signal-processing electronic circuits. The invention of these reporter compounds is expected to enable the development of highly miniaturized, low-power-consumption, relatively inexpensive, mass-producible sensor units for diverse applications.
-
NASA Astrophysics Data System (ADS)
Heshmat, Mojgan; Privalov, Timofei
2017-09-01
Using Born-Oppenheimer molecular dynamics (BOMD), we explore the nature of interactions between H2 and the activated carbonyl carbon, C(carbonyl), of the acetone-B(C6F5)3 adduct surrounded by an explicit solvent (1,4-dioxane). BOMD simulations at finite (non-zero) temperature with an explicit solvent produced long-lasting instances of significant vibrational perturbation of the H—H bond and H2-polarization at C(carbonyl). As far as the characteristics of H2 are concerned, the dynamical transient state approximates the transition-state of the heterolytic H2-cleavage. The culprit is the concerted interactions of H2 with C(carbonyl) and a number of Lewis basic solvent molecules—i.e., the concerted C(carbonyl)⋯H2⋯solvent interactions. On one hand, the results presented herein complement the mechanistic insight gained from our recent transition-state calculations, reported separately from this article. But on the other hand, we now indicate that an idea of the sufficiency of just one simple reaction coordinate in solution-phase reactions can be too simplistic and misleading. This article goes in the footsteps of the rapidly strengthening approach of investigating molecular interactions in large molecular systems via "computational experimentation" employing, primarily, ab initio molecular dynamics describing reactants-interaction without constraints of the preordained reaction coordinate and/or foreknowledge of the sampling order parameters.
-
USDA-ARS?s Scientific Manuscript database
The genus Capsicum represents one of several well characterized Solanaceous genera. A wealth of classical and molecular genetics research is available for the genus. Information gleaned from its cultivated relatives, tomato and potato, provide further insight for basic and applied studies. Early ...
-
A decade of molecular cell biology: achievements and challenges.
Akhtar, Asifa; Fuchs, Elaine; Mitchison, Tim; Shaw, Reuben J; St Johnston, Daniel; Strasser, Andreas; Taylor, Susan; Walczak, Claire; Zerial, Marino
2011-09-23
Nature Reviews Molecular Cell Biology celebrated its 10-year anniversary during this past year with a series of specially commissioned articles. To complement this, here we have asked researchers from across the field for their insights into how molecular cell biology research has evolved during this past decade, the key concepts that have emerged and the most promising interfaces that have developed. Their comments highlight the broad impact that particular advances have had, some of the basic understanding that we still require, and the collaborative approaches that will be essential for driving the field forward.
-
A decade of molecular cell biology: achievements and challenges
Akhtar, Asifa; Fuchs, Elaine; Mitchison, Tim; Shaw, Reuben J.; St Johnston, Daniel; Strasser, Andreas; Taylor, Susan; Walczak, Claire; Zerial, Marino
2012-01-01
Nature Reviews Molecular Cell Biology celebrated its 10-year anniversary during this past year with a series of specially commissioned articles. To complement this, here we have asked researchers from across the field for their insights into how molecular cell biology research has evolved during this past decade, the key concepts that have emerged and the most promising interfaces that have developed. Their comments highlight the broad impact that particular advances have had, some of the basic understanding that we still require, and the collaborative approaches that will be essential for driving the field forward. PMID:21941276
-
NASA Astrophysics Data System (ADS)
Ascenso, Joana
The past decade has seen an increase of star formation studies made at the molecular cloud scale, motivated mostly by the deployment of a wealth of sensitive infrared telescopes and instruments. Embedded clusters, long recognised as the basic units of coherent star formation in molecular clouds, are now seen to inhabit preferentially cluster complexes tens of parsecs across. This chapter gives an overview of some important properties of the embedded clusters in these complexes and of the complexes themselves, along with the implications of viewing star formation as a molecular-cloud scale process rather than an isolated process at the scale of clusters.
-
Ueno, Yutaka; Ito, Shuntaro; Konagaya, Akihiko
2014-12-01
To better understand the behaviors and structural dynamics of proteins within a cell, novel software tools are being developed that can create molecular animations based on the findings of structural biology. This study proposes our method developed based on our prototypes to detect collisions and examine the soft-body dynamics of molecular models. The code was implemented with a software development toolkit for rigid-body dynamics simulation and a three-dimensional graphics library. The essential functions of the target software system included the basic molecular modeling environment, collision detection in the molecular models, and physical simulations of the movement of the model. Taking advantage of recent software technologies such as physics simulation modules and interpreted scripting language, the functions required for accurate and meaningful molecular animation were implemented efficiently.
-
Random amplified polymorphic DNA PCR in the teaching of molecular epidemiology.
Reinoso, Elina B; Bettera, Susana G
2016-07-08
In this article, we describe a basic practical laboratory designed for fifth-year undergraduate students of Microbiology as part of the Epidemiology course. This practice provides the students with the tools for molecular epidemiological analysis of pathogenic microorganisms using a rapid and simple PCR technique. The aim of this work was to assay RAPD-PCR technique in order to infer possible epidemiological relationships. The activity gives students an appreciation of the value of applying a simple molecular biological method as RAPD-PCR to a discipline-specific question. It comprises a three-session laboratory module to genetically assay DNAs from strains isolated from a food outbreak. © 2016 by The International Union of Biochemistry and Molecular Biology, 44(4):391-396, 2016. © 2016 The International Union of Biochemistry and Molecular Biology.
-
Cheminformatics Research at the Unilever Centre for Molecular Science Informatics Cambridge.
Fuchs, Julian E; Bender, Andreas; Glen, Robert C
2015-09-01
The Centre for Molecular Informatics, formerly Unilever Centre for Molecular Science Informatics (UCMSI), at the University of Cambridge is a world-leading driving force in the field of cheminformatics. Since its opening in 2000 more than 300 scientific articles have fundamentally changed the field of molecular informatics. The Centre has been a key player in promoting open chemical data and semantic access. Though mainly focussing on basic research, close collaborations with industrial partners ensured real world feedback and access to high quality molecular data. A variety of tools and standard protocols have been developed and are ubiquitous in the daily practice of cheminformatics. Here, we present a retrospective of cheminformatics research performed at the UCMSI, thereby highlighting historical and recent trends in the field as well as indicating future directions.
-
NASA Technical Reports Server (NTRS)
Etters, R. D.
1985-01-01
Work directed toward understanding the high pressure properties of molecular solids and molecular surfaces deposited on hetrogeneous substrates is reported. The motivation, apart from expanding our basic knowledge about these systems, was to understand and predict the properties of new materials synthesized at high pressure, including pressure induced metallic and superconducting states. As a consequence, information about the states of matter of the Jovian planets and their satellites, which are natural high pressure laboratories was also provided. The work on molecular surfaces and finite two and three dimensional clusters of atoms and molecules was connected with the composition and behavior of planetary atmospheres and on the processes involved in forming surface layers, which is vital to the development of composite materials and microcircuitry.
-
Recent advances in targeted endoscopic imaging: Early detection of gastrointestinal neoplasms
Kwon, Yong-Soo; Cho, Young-Seok; Yoon, Tae-Jong; Kim, Ho-Shik; Choi, Myung-Gyu
2012-01-01
Molecular imaging has emerged as a new discipline in gastrointestinal endoscopy. This technology encompasses modalities that can visualize disease-specific morphological or functional tissue changes based on the molecular signature of individual cells. Molecular imaging has several advantages including minimal damage to tissues, repetitive visualization, and utility for conducting quantitative analyses. Advancements in basic science coupled with endoscopy have made early detection of gastrointestinal cancer possible. Molecular imaging during gastrointestinal endoscopy requires the development of safe biomarkers and exogenous probes to detect molecular changes in cells with high specificity anda high signal-to-background ratio. Additionally, a high-resolution endoscope with an accurate wide-field viewing capability must be developed. Targeted endoscopic imaging is expected to improve early diagnosis and individual therapy of gastrointestinal cancer. PMID:22442742
-
Cheminformatics Research at the Unilever Centre for Molecular Science Informatics Cambridge
Fuchs, Julian E; Bender, Andreas; Glen, Robert C
2015-01-01
The Centre for Molecular Informatics, formerly Unilever Centre for Molecular Science Informatics (UCMSI), at the University of Cambridge is a world-leading driving force in the field of cheminformatics. Since its opening in 2000 more than 300 scientific articles have fundamentally changed the field of molecular informatics. The Centre has been a key player in promoting open chemical data and semantic access. Though mainly focussing on basic research, close collaborations with industrial partners ensured real world feedback and access to high quality molecular data. A variety of tools and standard protocols have been developed and are ubiquitous in the daily practice of cheminformatics. Here, we present a retrospective of cheminformatics research performed at the UCMSI, thereby highlighting historical and recent trends in the field as well as indicating future directions. PMID:26435758
-
Operations analysis (study 2.1): Program manual and users guide for the LOVES computer code
NASA Technical Reports Server (NTRS)
Wray, S. T., Jr.
1975-01-01
Information is provided necessary to use the LOVES Computer Program in its existing state, or to modify the program to include studies not properly handled by the basic model. The Users Guide defines the basic elements assembled together to form the model for servicing satellites in orbit. As the program is a simulation, the method of attack is to disassemble the problem into a sequence of events, each occurring instantaneously and each creating one or more other events in the future. The main driving force of the simulation is the deterministic launch schedule of satellites and the subsequent failure of the various modules which make up the satellites. The LOVES Computer Program uses a random number generator to simulate the failure of module elements and therefore operates over a long span of time typically 10 to 15 years. The sequence of events is varied by making several runs in succession with different random numbers resulting in a Monte Carlo technique to determine statistical parameters of minimum value, average value, and maximum value.
-
NASA Technical Reports Server (NTRS)
Wong, Willy
2009-01-01
This slide presentation reviews the basics of biosafety and the importance of assuring proper biosafety practices. The objectives of the presentation are to review regulations about biosafety, and the different biosafety levels; the biosafety facilities at Johnson Space Center; the usage and maintenance of the biosafety cabinet, the proper methods to handle biologically hazardous materials upon exposure, and the methods of cleanup in the event of a spill, and the training requirements that are mandated for personnel handling biologically hazardous materials.
-
Molecular pathogenesis and clinical management of Fanconi anemia
Kee, Younghoon; D’Andrea, Alan D.
2012-01-01
Fanconi anemia (FA) is a rare genetic disorder associated with a high frequency of hematological abnormalities and congenital anomalies. Based on multilateral efforts from basic scientists and clinicians, significant advances in our knowledge of FA have been made in recent years. Here we review the clinical features, the diagnostic criteria, and the current and future therapies of FA and describe the current understanding of the molecular basis of the disease. PMID:23114602
-
Neural correlates of processing "self-conscious" vs. "basic" emotions.
Gilead, Michael; Katzir, Maayan; Eyal, Tal; Liberman, Nira
2016-01-29
Self-conscious emotions are prevalent in our daily lives and play an important role in both normal and pathological behavior. Despite their immense significance, the neural substrates that are involved in the processing of such emotions are surprisingly under-studied. In light of this, we conducted an fMRI study in which participants thought of various personal events which elicited feelings of negative and positive self-conscious (i.e., guilt, pride) or basic (i.e., anger, joy) emotions. We performed a conjunction analysis to investigate the neural correlates associated with processing events that are related to self-conscious vs. basic emotions, irrespective of valence. The results show that processing self-conscious emotions resulted in activation within frontal areas associated with self-processing and self-control, namely, the mPFC extending to the dACC, and within the lateral-dorsal prefrontal cortex. Processing basic emotions resulted in activation throughout relatively phylogenetically-ancient regions of the cortex, namely in visual and tactile processing areas and in the insular cortex. Furthermore, self-conscious emotions differentially activated the mPFC such that the negative self-conscious emotion (guilt) was associated with a more dorsal activation, and the positive self-conscious emotion (pride) was associated with a more ventral activation. We discuss how these results shed light on the nature of mental representations and neural systems involved in self-reflective and affective processing. Copyright © 2015 Elsevier Ltd. All rights reserved.
-
Practical Development of Modern Mass Media Education in Poland
ERIC Educational Resources Information Center
Fedorov, Alexander
2012-01-01
Practical development of modern mass media education in Poland. The paper analyzes the main ways of practical development of modern media education (1992-2012 years) in Poland: basic technologies, main events, etc.
-
12th International Conference on Malignancies in AIDS and Other Acquired Immunodeficiencies
Summary of speakers and events from the 2010 ICMAOI conference, focused on presenting basic, epidemiologic, and clinical aspects of research on malignancies in HIV-infected and other immunosuppressed individuals.
-
8th International Conference on Malignancies in AIDS and Other Immunodeficiencies
Program guide of speakers and events from the 2004 ICMAOI conference, focused on presenting basic, epidemiologic, and clinical aspects of research on malignancies in HIV-infected and other immunosuppressed individuals.
-
13th International Conference on Malignancies in AIDS and Other Acquired Immunodeficiencies
Summary of speakers and events from the 2011 ICMAOI conference, focused on presenting basic, epidemiologic, and clinical aspects of research on malignancies in HIV-infected and other immunosuppressed individuals.
-
Basic Research on Seismic and Infrasonic Monitoring of the European Arctic
2008-09-01
characteristics as well as the inherent variability among these signals . We have used available recordings both from the Apatity infrasound array and from...experimentally attempt to generate an infrasonic event bulletin using only the estimated azimuths and detection times of infrasound phases recorded by... detection . Our studies have shown a remarkably efficient wave propagation from events near Novaya Zemlya across the Barents Sea. Significant signal
-
Educating medical staff about responding to a radiological or nuclear emergency.
McCurley, M Carol; Miller, Charles W; Tucker, Florie E; Guinn, Amy; Donnelly, Elizabeth; Ansari, Armin; Holcombe, Maire; Nemhauser, Jeffrey B; Whitcomb, Robert C
2009-05-01
A growing body of audience research reveals medical personnel in hospitals are unprepared for a large-scale radiological emergency such as a terrorist event involving radioactive or nuclear materials. Also, medical personnel in hospitals lack a basic understanding of radiation principles, as well as diagnostic and treatment guidelines for radiation exposure. Clinicians have indicated that they lack sufficient training on radiological emergency preparedness; they are potentially unwilling to treat patients if those patients are perceived to be radiologically contaminated; and they have major concerns about public panic and overloading of clinical systems. In response to these findings, the Centers for Disease Control and Prevention (CDC) has developed a tool kit for use by hospital medical personnel who may be called on to respond to unintentional or intentional mass-casualty radiological and nuclear events. This tool kit includes clinician fact sheets, a clinician pocket guide, a digital video disc (DVD) of just-in-time basic skills training, a CD-ROM training on mass-casualty management, and a satellite broadcast dealing with medical management of radiological events. CDC training information emphasizes the key role that medical health physicists can play in the education and support of emergency department activities following a radiological or nuclear mass-casualty event.
-
Manifestations Of Mine-induced Seismicity At Large-scale Mining Operations In Khibiny Massive
NASA Astrophysics Data System (ADS)
Fedotova, I. V.; Kozyrev, A. A.; Yunga, S. L.
The focal mechanisms of seismic events in the Khibiny massive and their interrelation with spent mining operations were investigated. As a result it is detected, that redistri- bution of stresses stipulated by structural features of a rock mass and ore technology, is the basic reason of origin of dynamic rock pressure manifestations. On the basis of the available plan tectonic disturbances of an investigated lease of a massif and anal- ysis of seismic activity, in view of events with the detected focal mechanism, some bands, various on a degree of potential seismic activity are chosen. For each band the calculations of mechanisms of rock bumps with separation of planes of adjustments with engaging of the geologic data are held. As a result of this analysis it is approved, that the basic forerunner of cracking of a separation at a roof fall of the cantilever of hanging wall (on decryption of focal mechanisms) is the reorientation of axes of prin- cipal stresses. And, at conducting coal-face works in a trailing side of ore deposits, at cracking a separation in the cantilever of hanging wall there are seismic events pre- dominantly to a fault type of the focal mechanism. In a massif of soils of the working excavation, located in limits, and under it, most typical focal mechanisms are mainly strike-slip and normal faults. The researches are executed at support of the Russian foundation for basic research, - projects 00-05-64758, 01-05-65340.
-
2016-11-01
2015;6:7505. doi: 10.1038/ncomms8505. PubMed PMID: 26106036; PubMed Central PMCID: PMC4491827. 19. Kalluri R, Weinberg RA. The basics of epithelial...Gupta PB, Evans KW, Hollier BG, Ram PT, Lander ES, Rosen JM, Weinberg RA, Mani SA. Core epithelial-to- mesenchymal transition interactome gene...Molecular analysis reveals heterogeneity of mouse mammary tumors conditionally mutant for Brca1. Mol Cancer 2008;7:29. 14. Kalluri R, Weinberg RA. The basics
-
Proton transfer in organic scaffolds
NASA Astrophysics Data System (ADS)
Basak, Dipankar
This dissertation focuses on the fundamental understanding of the proton transfer process and translating the knowledge into design/development of new organic materials for efficient non-aqueous proton transport. For example, what controls the shuttling of a proton between two basic sites? a) Distance between two groups? or b) the basicity? c) What is the impact of protonation on molecular conformation when the basic sites are attached to rigid scaffolds? For this purpose, we developed several tunable proton sponges and studied proton transfer in these scaffolds theoretically as well as experimentally. Next we moved our attention to understand long-range proton conduction or proton transport. We introduced liquid crystalline (LC) proton conductor based on triphenylene molecule and established that activation energy barrier for proton transport is lower in the LC phase compared to the crystalline phase. Furthermore, we investigated the impact of several critical factors: the choice of the proton transferring groups, mobility of the charge carriers, intrinsic vs. extrinsic charge carrier concentrations and the molecular architectures on long-range proton transport. The outcome of this research will lead to a deeper understanding of non-aqueous proton transfer process and aid the design of next generation proton exchange membrane (PEM) for fuel cell.
-
A molecular trigger for intercontinental epidemics of group A Streptococcus
Zhu, Luchang; Olsen, Randall J.; Nasser, Waleed; Beres, Stephen B.; Vuopio, Jaana; Kristinsson, Karl G.; Gottfredsson, Magnus; Porter, Adeline R.; DeLeo, Frank R.; Musser, James M.
2015-01-01
The identification of the molecular events responsible for strain emergence, enhanced virulence, and epidemicity has been a long-pursued goal in infectious diseases research. A recent analysis of 3,615 genomes of serotype M1 group A Streptococcus strains (the so-called “flesh-eating” bacterium) identified a recombination event that coincides with the global M1 pandemic beginning in the early 1980s. Here, we have shown that the allelic variation that results from this recombination event, which replaces the chromosomal region encoding secreted NADase and streptolysin O, is the key driver of increased toxin production and enhanced infection severity of the M1 pandemic strains. Using isoallelic mutant strains, we found that 3 polymorphisms in this toxin gene region increase resistance to killing by human polymorphonuclear leukocytes, increase bacterial proliferation, and increase virulence in animal models of pharyngitis and necrotizing fasciitis. Genome sequencing of an additional 1,125 streptococcal strains and virulence studies revealed that a highly similar recombinational replacement event underlies an ongoing intercontinental epidemic of serotype M89 group A Streptococcus infections. By identifying the molecular changes that enhance upper respiratory tract fitness, increased resistance to innate immunity, and increased tissue destruction, we describe a mechanism that underpins epidemic streptococcal infections, which have affected many millions of people. PMID:26258415
-
Vilar, Santiago; Harpaz, Rave; Chase, Herbert S; Costanzi, Stefano; Rabadan, Raul
2011-01-01
Background Adverse drug events (ADE) cause considerable harm to patients, and consequently their detection is critical for patient safety. The US Food and Drug Administration maintains an adverse event reporting system (AERS) to facilitate the detection of ADE in drugs. Various data mining approaches have been developed that use AERS to detect signals identifying associations between drugs and ADE. The signals must then be monitored further by domain experts, which is a time-consuming task. Objective To develop a new methodology that combines existing data mining algorithms with chemical information by analysis of molecular fingerprints to enhance initial ADE signals generated from AERS, and to provide a decision support mechanism to facilitate the identification of novel adverse events. Results The method achieved a significant improvement in precision in identifying known ADE, and a more than twofold signal enhancement when applied to the ADE rhabdomyolysis. The simplicity of the method assists in highlighting the etiology of the ADE by identifying structurally similar drugs. A set of drugs with strong evidence from both AERS and molecular fingerprint-based modeling is constructed for further analysis. Conclusion The results demonstrate that the proposed methodology could be used as a pharmacovigilance decision support tool to facilitate ADE detection. PMID:21946238
-
Pérez Zapata, A I; Gutiérrez Samaniego, M; Rodríguez Cuéllar, E; Gómez de la Cámara, A; Ruiz López, P
Surgery is a high risk for the occurrence of adverse events (AE). The main objective of this study is to compare the effectiveness of the Trigger tool with the Hospital National Health System registration of Discharges, the minimum basic data set (MBDS), in detecting adverse events in patients admitted to General Surgery and undergoing surgery. Observational and descriptive retrospective study of patients admitted to general surgery of a tertiary hospital, and undergoing surgery in 2012. The identification of adverse events was made by reviewing the medical records, using an adaptation of "Global Trigger Tool" methodology, as well as the (MBDS) registered on the same patients. Once the AE were identified, they were classified according to damage and to the extent to which these could have been avoided. The area under the curve (ROC) were used to determine the discriminatory power of the tools. The Hanley and Mcneil test was used to compare both tools. AE prevalence was 36.8%. The TT detected 89.9% of all AE, while the MBDS detected 28.48%. The TT provides more information on the nature and characteristics of the AE. The area under the curve was 0.89 for the TT and 0.66 for the MBDS. These differences were statistically significant (P<.001). The Trigger tool detects three times more adverse events than the MBDS registry. The prevalence of adverse events in General Surgery is higher than that estimated in other studies. Copyright © 2017 SECA. Publicado por Elsevier España, S.L.U. All rights reserved.
-
NASA Astrophysics Data System (ADS)
Valberg, Arne
2005-04-01
Light Vision Color takes a well-balanced, interdisciplinary approach to our most important sensory system. The book successfully combines basics in vision sciences with recent developments from different areas such as neuroscience, biophysics, sensory psychology and philosophy. Originally published in 1998 this edition has been extensively revised and updated to include new chapters on clinical problems and eye diseases, low vision rehabilitation and the basic molecular biology and genetics of colour vision. Takes a broad interdisciplinary approach combining basics in vision sciences with the most recent developments in the area Includes an extensive list of technical terms and explanations to encourage student understanding Successfully brings together the most important areas of the subject in to one volume
-
The evolutionary origin of the vertebrate body plan: the problem of head segmentation.
Onai, Takayuki; Irie, Naoki; Kuratani, Shigeru
2014-01-01
The basic body plan of vertebrates, as typified by the complex head structure, evolved from the last common ancestor approximately 530 Mya. In this review, we present a brief overview of historical discussions to disentangle the various concepts and arguments regarding the evolutionary development of the vertebrate body plan. We then explain the historical transition of the arguments about the vertebrate body plan from merely epistemological comparative morphology to comparative embryology as a scientific treatment on this topic. Finally, we review the current progress of molecular evidence regarding the basic vertebrate body plan, focusing on the link between the basic vertebrate body plan and the evolutionarily conserved developmental stages (phylotypic stages).
-
The Development of a Post-Baccalaureate Certificate Program in Molecular Diagnostics
Williams, Gail S.; Brown, Judith D.; Keagle, Martha B.
2000-01-01
A post-baccalaureate certificate program in diagnostic molecular sciences was created in 1995 by the Diagnostic Genetic Sciences Program in the School of Allied Health at the University of Connecticut. The required on-campus lecture and laboratory courses include basic laboratory techniques, health care issues, cell biology, immunology, human genetics, research, management, and molecular diagnostic techniques and laboratory in molecular diagnostics. These courses precede a 6-month, full-time practicum at an affiliated full-service molecular laboratory. The practicum includes amplification and blotting methods, a research project, and a choice of specialized electives including DNA sequencing, mutagenesis, in situ hybridization methods, or molecular diagnostic applications in microbiology. Graduates of the program are immediately eligible to sit for the National Credentialing Agency examination in molecular biology to obtain the credential Clinical Laboratory Specialist in Molecular Biology (CLSp(MB). This description of the University of Connecticut program may assist other laboratory science programs in creating similar curricula. PMID:11232107
-
Luker, Gary D
2002-04-01
The AACR Special Conference on Molecular Imaging in Cancer: Linking Biology, Function, and Clinical Applications In Vivo, was held January 23-27, 2002, at the Contemporary Hotel, Walt Disney World, Orlando, FL. Co-Chairs David Piwnica-Worms, Patricia Price and Thomas Meade brought together researchers with diverse expertise in molecular biology, gene therapy, chemistry, engineering, pharmacology, and imaging to accelerate progress in developing and applying technologies for imaging specific cellular and molecular signals in living animals and humans. The format of the conference was the presentation of research that focused on basic and translational biology of cancer and current state-of-the-art techniques for molecular imaging in animal models and humans. This report summarizes the special conference on molecular imaging, highlighting the interfaces of molecular biology with animal models, instrumentation, chemistry, and pharmacology that are essential to convert the dreams and promise of molecular imaging into improved understanding, diagnosis, and management of cancer.
-
Kedrov, Alexej; Janovjak, Harald; Sapra, K Tanuj; Müller, Daniel J
2007-01-01
Molecular interactions are the basic language of biological processes. They establish the forces interacting between the building blocks of proteins and other macromolecules, thus determining their functional roles. Because molecular interactions trigger virtually every biological process, approaches to decipher their language are needed. Single-molecule force spectroscopy (SMFS) has been used to detect and characterize different types of molecular interactions that occur between and within native membrane proteins. The first experiments detected and localized molecular interactions that stabilized membrane proteins, including how these interactions were established during folding of alpha-helical secondary structure elements into the native protein and how they changed with oligomerization, temperature, and mutations. SMFS also enables investigators to detect and locate molecular interactions established during ligand and inhibitor binding. These exciting applications provide opportunities for studying the molecular forces of life. Further developments will elucidate the origins of molecular interactions encoded in their lifetimes, interaction ranges, interplay, and dynamics characteristic of biological systems.
-
Lectindb: a plant lectin database.
Chandra, Nagasuma R; Kumar, Nirmal; Jeyakani, Justin; Singh, Desh Deepak; Gowda, Sharan B; Prathima, M N
2006-10-01
Lectins, a class of carbohydrate-binding proteins, are now widely recognized to play a range of crucial roles in many cell-cell recognition events triggering several important cellular processes. They encompass different members that are diverse in their sequences, structures, binding site architectures, quaternary structures, carbohydrate affinities, and specificities as well as their larger biological roles and potential applications. It is not surprising, therefore, that the vast amount of experimental data on lectins available in the literature is so diverse, that it becomes difficult and time consuming, if not impossible to comprehend the advances in various areas and obtain the maximum benefit. To achieve an effective use of all the data toward understanding the function and their possible applications, an organization of these seemingly independent data into a common framework is essential. An integrated knowledge base ( Lectindb, http://nscdb.bic.physics.iisc.ernet.in ) together with appropriate analytical tools has therefore been developed initially for plant lectins by collating and integrating diverse data. The database has been implemented using MySQL on a Linux platform and web-enabled using PERL-CGI and Java tools. Data for each lectin pertain to taxonomic, biochemical, domain architecture, molecular sequence, and structural details as well as carbohydrate and hence blood group specificities. Extensive links have also been provided for relevant bioinformatics resources and analytical tools. Availability of diverse data integrated into a common framework is expected to be of high value not only for basic studies in lectin biology but also for basic studies in pursuing several applications in biotechnology, immunology, and clinical practice, using these molecules.
-
Neurotrophins Role in Depression Neurobiology: A Review of Basic and Clinical Evidence
Neto, Fani L; Borges, Gisela; Torres-Sanchez, Sonia; Mico, Juan A; Berrocoso, Esther
2011-01-01
Depression is a neuropsychiatric disorder affecting a huge percentage of the active population especially in developed countries. Research has devoted much of its attention to this problematic and many drugs have been developed and are currently prescribed to treat this pathology. Yet, many patients are refractory to the available therapeutic drugs, which mainly act by increasing the levels of the monoamines serotonin and noradrenaline in the synaptic cleft. Even in the cases antidepressants are effective, it is usually observed a delay of a few weeks between the onset of treatment and remission of the clinical symptoms. Additionally, many of these patients who show remission with antidepressant therapy present a relapse of depression upon treatment cessation. Thus research has focused on other possible molecular targets, besides monoamines, underlying depression. Both basic and clinical evidence indicates that depression is associated with several structural and neurochemical changes where the levels of neurotrophins, particularly of brain-derived neurotrophic factor (BDNF), are altered. Antidepressants, as well as other therapeutic strategies, seem to restore these levels. Neuronal atrophy, mostly detected in limbic structures that regulate mood and cognition, like the hippocampus, is observed in depressed patients and in animal behavioural paradigms for depression. Moreover, chronic antidepressant treatment enhances adult hippocampal neurogenesis, supporting the notion that this event underlies antidepressants effects. Here we review some of the preclinical and clinical studies, aimed at disclosing the role of neurotrophins in the pathophysiological mechanisms of depression and the mode of action of antidepressants, which favour the neurotrophic/neurogenic hypothesis. PMID:22654714
-
The chemistry side of AOP: implications for toxicity extrapolation
An adverse outcome pathway (AOP) is a structured representation of the biological events that lead to adverse impacts following a molecular initiating event caused by chemical interaction with a macromolecule. AOPs have been proposed to facilitate toxicity extrapolation across s...
-
Identification of Potential Chemical Carcinogens in Compendia of Gene Expression Profiles
Chemicals induce cancer through partially characterized adverse outcome pathways (AOPs) that include molecular initiating events (MIEs) and downstream key events (KEs). Microarray profiling of chemical-induced effects is being increasingly used in medium- and high-throughput form...
-
Pilla, Giulia; McVicker, Gareth; Tang, Christoph M
2017-09-01
Acquisition of a single copy, large virulence plasmid, pINV, led to the emergence of Shigella spp. from Escherichia coli. The plasmid encodes a Type III secretion system (T3SS) on a 30 kb pathogenicity island (PAI), and is maintained in a bacterial population through a series of toxin:antitoxin (TA) systems which mediate post-segregational killing (PSK). The T3SS imposes a significant cost on the bacterium, and strains which have lost the plasmid and/or genes encoding the T3SS grow faster than wild-type strains in the laboratory, and fail to bind the indicator dye Congo Red (CR). Our aim was to define the molecular events in Shigella flexneri that cause loss of Type III secretion (T3S), and to examine whether TA systems exert positional effects on pINV. During growth at 37°C, we found that deletions of regions of the plasmid including the PAI lead to the emergence of CR-negative colonies; deletions occur through intra-molecular recombination events between insertion sequences (ISs) flanking the PAI. Furthermore, by repositioning MvpAT (which belongs to the VapBC family of TA systems) near the PAI, we demonstrate that the location of this TA system alters the rearrangements that lead to loss of T3S, indicating that MvpAT acts both globally (by reducing loss of pINV through PSK) as well as locally (by preventing loss of adjacent sequences). During growth at environmental temperatures, we show for the first time that pINV spontaneously integrates into different sites in the chromosome, and this is mediated by inter-molecular events involving IS1294. Integration leads to reduced PAI gene expression and impaired secretion through the T3SS, while excision of pINV from the chromosome restores T3SS function. Therefore, pINV integration provides a reversible mechanism for Shigella to circumvent the metabolic burden imposed by pINV. Intra- and inter-molecular events between ISs, which are abundant in Shigella spp., mediate plasticity of S. flexneri pINV.
-
Engineered Aptamers to Probe Molecular Interactions on the Cell Surface
Batool, Sana; Bhandari, Sanam; George, Shanell; Okeoma, Precious; Van, Nabeela; Zümrüt, Hazan E.; Mallikaratchy, Prabodhika
2017-01-01
Significant progress has been made in understanding the nature of molecular interactions on the cell membrane. To decipher such interactions, molecular scaffolds can be engineered as a tool to modulate these events as they occur on the cell membrane. To guarantee reliability, scaffolds that function as modulators of cell membrane events must be coupled to a targeting moiety with superior chemical versatility. In this regard, nucleic acid aptamers are a suitable class of targeting moieties. Aptamers are inherently chemical in nature, allowing extensive site-specific chemical modification to engineer sensing molecules. Aptamers can be easily selected using a simple laboratory-based in vitro evolution method enabling the design and development of aptamer-based functional molecular scaffolds against wide range of cell surface molecules. This article reviews the application of aptamers as monitors and modulators of molecular interactions on the mammalian cell surface with the aim of increasing our understanding of cell-surface receptor response to external stimuli. The information gained from these types of studies could eventually prove useful in engineering improved medical diagnostics and therapeutics. PMID:28850067
-
There are multiple molecular initiating events (MIEs) that can disrupt male sexual differentiation including AR antagonism and inhibition of synthesis, and metabolism of fetal testosterone. Disruption of this event by pesticides like vinclozolin that act as AR antagonists and ph...
-
Oxidative Stress, Redox Signaling, and Autophagy: Cell Death Versus Survival
Navarro-Yepes, Juliana; Burns, Michaela; Anandhan, Annadurai; Khalimonchuk, Oleh; del Razo, Luz Maria; Quintanilla-Vega, Betzabet; Pappa, Aglaia; Panayiotidis, Mihalis I.
2014-01-01
Abstract Significance: The molecular machinery regulating autophagy has started becoming elucidated, and a number of studies have undertaken the task to determine the role of autophagy in cell fate determination within the context of human disease progression. Oxidative stress and redox signaling are also largely involved in the etiology of human diseases, where both survival and cell death signaling cascades have been reported to be modulated by reactive oxygen species (ROS) and reactive nitrogen species (RNS). Recent Advances: To date, there is a good understanding of the signaling events regulating autophagy, as well as the signaling processes by which alterations in redox homeostasis are transduced to the activation/regulation of signaling cascades. However, very little is known about the molecular events linking them to the regulation of autophagy. This lack of information has hampered the understanding of the role of oxidative stress and autophagy in human disease progression. Critical Issues: In this review, we will focus on (i) the molecular mechanism by which ROS/RNS generation, redox signaling, and/or oxidative stress/damage alter autophagic flux rates; (ii) the role of autophagy as a cell death process or survival mechanism in response to oxidative stress; and (iii) alternative mechanisms by which autophagy-related signaling regulate mitochondrial function and antioxidant response. Future Directions: Our research efforts should now focus on understanding the molecular basis of events by which autophagy is fine tuned by oxidation/reduction events. This knowledge will enable us to understand the mechanisms by which oxidative stress and autophagy regulate human diseases such as cancer and neurodegenerative disorders. Antioxid. Redox Signal. 21, 66–85. PMID:24483238
-
ERIC Educational Resources Information Center
Munoz, Karen E.; Hyde, Luke W.; Hariri, Ahmad R.
2009-01-01
Imaging genetics is an experimental strategy that integrates molecular genetics and neuroimaging technology to examine biological mechanisms that mediate differences in behavior and the risks for psychiatric disorder. The basic principles in imaging genetics and the development of the field are discussed.
-
The basics of thiols and cysteines in redox biology and chemistry.
Poole, Leslie B
2015-03-01
Cysteine is one of the least abundant amino acids, yet it is frequently found as a highly conserved residue within functional (regulatory, catalytic, or binding) sites in proteins. It is the unique chemistry of the thiol or thiolate group of cysteine that imparts to functional sites their specialized properties (e.g., nucleophilicity, high-affinity metal binding, and/or ability to form disulfide bonds). Highlighted in this review are some of the basic biophysical and biochemical properties of cysteine groups and the equations that apply to them, particularly with respect to pKa and redox potential. Also summarized are the types of low-molecular-weight thiols present in high concentrations in most cells, as well as the ways in which modifications of cysteinyl residues can impart or regulate molecular functions important to cellular processes, including signal transduction. Copyright © 2014 Elsevier Inc. All rights reserved.
-
Steinberg, Benjamin E; Goldenberg, Neil M; Fairn, Gregory D; Kuebler, Wolfgang M; Slutsky, Arthur S; Lee, Warren L
2016-02-01
Explosive growth in our understanding of genomics and molecular biology have fueled calls for the pursuit of personalized medicine, the notion of harnessing biologic variability to provide patient-specific care. This vision will necessitate a deep understanding of the underlying pathophysiology in each patient. Medical journals play a pivotal role in the education of trainees and clinicians, yet we suspected that the amount of basic science in the top medical journals has been in decline. We conducted an automated search strategy in PubMed to identify basic science articles and calculated the proportion of articles dealing with basic science in the highest impact journals for 8 different medical specialties from 1994 to 2013. We observed a steep decline (40-60%) in such articles over time in almost all of the journals examined. This rapid decline in basic science from medical journals is likely to affect practitioners' understanding of and interest in the basic mechanisms of disease and therapy. In this Life Sciences Forum, we discuss why this decline may be occurring and what it means for the future of science and medicine. © FASEB.
-
NASA Astrophysics Data System (ADS)
Isobe, Masaharu
Hard sphere/disk systems are among the simplest models and have been used to address numerous fundamental problems in the field of statistical physics. The pioneering numerical works on the solid-fluid phase transition based on Monte Carlo (MC) and molecular dynamics (MD) methods published in 1957 represent historical milestones, which have had a significant influence on the development of computer algorithms and novel tools to obtain physical insights. This chapter addresses the works of Alder's breakthrough regarding hard sphere/disk simulation: (i) event-driven molecular dynamics, (ii) long-time tail, (iii) molasses tail, and (iv) two-dimensional melting/crystallization. From a numerical viewpoint, there are serious issues that must be overcome for further breakthrough. Here, we present a brief review of recent progress in this area.
-
Current concepts of molecular events during bovine and porcine spermatozoa capacitation.
Vadnais, Melissa L; Galantino-Homer, Hannah L; Althouse, Gary C
2007-01-01
Spermatozoa are required to undergo the processes of capacitation before they obtain fertilizing ability. The molecular changes of capacitation are still not fully understood. However, it is accepted that capacitation is a sequential process involving numerous physiological changes including destabilization of the plasma membrane, alterations of intracellular ion concentrations and membrane potential, and protein phosphorylation. There are no known morphological changes that occur to the spermatozoon during capacitation. The purpose of this review is to summarize current evidence on the molecular aspects of capacitation both in vivo and in vitro in bovine and porcine spermatozoa. For the purpose of this review, the process of sperm capacitation will encompass maturational events that occur following ejaculation up to binding to the zona pellucida, that triggers acrosomal exocytosis and initiates fertilization.
-
Metamorphosis in solitary ascidians.
Karaiskou, Anthi; Swalla, Billie J; Sasakura, Yasunori; Chambon, Jean-Philippe
2015-01-01
Embryonic and postembryonic development in ascidians have been studied for over a century, but it is only in the last 10 years that the complex molecular network involved in coordinating postlarval development and metamorphosis has started to emerge. In most ascidians, the transition from the larval to the sessile juvenile/adult stage, or metamorphosis, requires a combination of environmental and endogenous signals and is characterized by coordinated global morphogenetic changes that are initiated by the adhesion of the larvae. Cloney was the first to describe cellular events of ascidians' metamorphosis in 1978 and only recently elements of the molecular regulation of this crucial developmental step have been revealed. This review aims to present a thorough view of this crucial developmental step by combining recent molecular data to the already established cellular events. © 2014 Wiley Periodicals, Inc.
-
Binder, Elisabeth B.
2017-01-01
ABSTRACT Epidemiological studies indicate a combined contribution of genetic and environmental factors, mainly exposure to adverse life events, in the risk for psychiatric disease. Understanding how adverse life events interact with genetic predisposition on the molecular level to shape risk and resilience to psychiatric disorders may yield important insight into disease mechanism. Using the example of the molecular mechanisms of interaction of functional genetic variants within the stress-regulating gene FKBP5 and early adversity, it is delineated how this interaction could contribute to transdiagnostic disease risk via a combined genetic and epigenetic disinhibition of FKBP5 transcription. This knowledge may now allow to develop biomarkers for a transdiagnostic subset of psychiatric patients and to personalize treatment. PMID:29372006
-
Master Logic Diagram: An Approach to Identify Initiating Events of HTGRs
NASA Astrophysics Data System (ADS)
Purba, J. H.
2018-02-01
Initiating events of a nuclear power plant being evaluated need to be firstly identified prior to applying probabilistic safety assessment on that plant. Various types of master logic diagrams (MLDs) have been proposedforsearching initiating events of the next generation of nuclear power plants, which have limited data and operating experiences. Those MLDs are different in the number of steps or levels and different in the basis for developing them. This study proposed another type of MLD approach to find high temperature gas cooled reactor (HTGR) initiating events. It consists of five functional steps starting from the top event representing the final objective of the safety functions to the basic event representing the goal of the MLD development, which is an initiating event. The application of the proposed approach to search for two HTGR initiating events, i.e. power turbine generator trip and loss of offsite power, is provided. The results confirmed that the proposed MLD is feasiblefor finding HTGR initiating events.
-
Three-body dissociation of OCS3+: Separating sequential and concerted pathways
NASA Astrophysics Data System (ADS)
Kumar, Herendra; Bhatt, Pragya; Safvan, C. P.; Rajput, Jyoti
2018-02-01
Events from the sequential and concerted modes of the fragmentation of OCS3+ that result in coincident detection of fragments C+, O+, and S+ have been separated using a newly proposed representation. An ion beam of 1.8 MeV Xe9+ is used to make the triply charged molecular ion, with the fragments being detected by a recoil ion momentum spectrometer. By separating events belonging exclusively to the sequential mode of breakup, the electronic states of the intermediate molecular ion (CO2+ or CS2+) involved are determined, and from the kinetic energy release spectra, it is shown that the low lying excited states of the parent OCS3+ are responsible for this mechanism. An estimate of branching ratios of events coming from sequential versus concerted mode is presented.
-
Update of KDBI: Kinetic Data of Bio-molecular Interaction database
Kumar, Pankaj; Han, B. C.; Shi, Z.; Jia, J.; Wang, Y. P.; Zhang, Y. T.; Liang, L.; Liu, Q. F.; Ji, Z. L.; Chen, Y. Z.
2009-01-01
Knowledge of the kinetics of biomolecular interactions is important for facilitating the study of cellular processes and underlying molecular events, and is essential for quantitative study and simulation of biological systems. Kinetic Data of Bio-molecular Interaction database (KDBI) has been developed to provide information about experimentally determined kinetic data of protein–protein, protein–nucleic acid, protein–ligand, nucleic acid–ligand binding or reaction events described in the literature. To accommodate increasing demand for studying and simulating biological systems, numerous improvements and updates have been made to KDBI, including new ways to access data by pathway and molecule names, data file in System Biology Markup Language format, more efficient search engine, access to published parameter sets of simulation models of 63 pathways, and 2.3-fold increase of data (19 263 entries of 10 532 distinctive biomolecular binding and 11 954 interaction events, involving 2635 proteins/protein complexes, 847 nucleic acids, 1603 small molecules and 45 multi-step processes). KDBI is publically available at http://bidd.nus.edu.sg/group/kdbi/kdbi.asp. PMID:18971255
-
Hall, Claire E; Yao, Zhi; Choi, Minee; Tyzack, Giulia E; Serio, Andrea; Luisier, Raphaelle; Harley, Jasmine; Preza, Elisavet; Arber, Charlie; Crisp, Sarah J; Watson, P Marc D; Kullmann, Dimitri M; Abramov, Andrey Y; Wray, Selina; Burley, Russell; Loh, Samantha H Y; Martins, L Miguel; Stevens, Molly M; Luscombe, Nicholas M; Sibley, Christopher R; Lakatos, Andras; Ule, Jernej; Gandhi, Sonia; Patani, Rickie
2017-05-30
Motor neurons (MNs) and astrocytes (ACs) are implicated in the pathogenesis of amyotrophic lateral sclerosis (ALS), but their interaction and the sequence of molecular events leading to MN death remain unresolved. Here, we optimized directed differentiation of induced pluripotent stem cells (iPSCs) into highly enriched (> 85%) functional populations of spinal cord MNs and ACs. We identify significantly increased cytoplasmic TDP-43 and ER stress as primary pathogenic events in patient-specific valosin-containing protein (VCP)-mutant MNs, with secondary mitochondrial dysfunction and oxidative stress. Cumulatively, these cellular stresses result in synaptic pathology and cell death in VCP-mutant MNs. We additionally identify a cell-autonomous VCP-mutant AC survival phenotype, which is not attributable to the same molecular pathology occurring in VCP-mutant MNs. Finally, through iterative co-culture experiments, we uncover non-cell-autonomous effects of VCP-mutant ACs on both control and mutant MNs. This work elucidates molecular events and cellular interplay that could guide future therapeutic strategies in ALS. Copyright © 2017 The Authors. Published by Elsevier Inc. All rights reserved.
-
Schiff, Hillary C; Johansen, Joshua P; Hou, Mian; Bush, David E A; Smith, Emily K; Klein, JoAnna E; LeDoux, Joseph E; Sears, Robert M
2017-01-01
Memory formation requires the temporal coordination of molecular events and cellular processes following a learned event. During Pavlovian threat (fear) conditioning (PTC), sensory and neuromodulatory inputs converge on post-synaptic neurons within the lateral nucleus of the amygdala (LA). By activating an intracellular cascade of signaling molecules, these G-protein-coupled neuromodulatory receptors are capable of recruiting a diverse profile of plasticity-related proteins. Here we report that norepinephrine, through its actions on β-adrenergic receptors (βARs), modulates aversive memory formation following PTC through two molecularly and temporally distinct signaling mechanisms. Specifically, using behavioral pharmacology and biochemistry in adult rats, we determined that βAR activity during, but not after PTC training initiates the activation of two plasticity-related targets: AMPA receptors (AMPARs) for memory acquisition and short-term memory and extracellular regulated kinase (ERK) for consolidating the learned association into a long-term memory. These findings reveal that βAR activity during, but not following PTC sets in motion cascading molecular events for the acquisition (AMPARs) and subsequent consolidation (ERK) of learned associations. PMID:27762270
-
Schiff, Hillary C; Johansen, Joshua P; Hou, Mian; Bush, David E A; Smith, Emily K; Klein, JoAnna E; LeDoux, Joseph E; Sears, Robert M
2017-03-01
Memory formation requires the temporal coordination of molecular events and cellular processes following a learned event. During Pavlovian threat (fear) conditioning (PTC), sensory and neuromodulatory inputs converge on post-synaptic neurons within the lateral nucleus of the amygdala (LA). By activating an intracellular cascade of signaling molecules, these G-protein-coupled neuromodulatory receptors are capable of recruiting a diverse profile of plasticity-related proteins. Here we report that norepinephrine, through its actions on β-adrenergic receptors (βARs), modulates aversive memory formation following PTC through two molecularly and temporally distinct signaling mechanisms. Specifically, using behavioral pharmacology and biochemistry in adult rats, we determined that βAR activity during, but not after PTC training initiates the activation of two plasticity-related targets: AMPA receptors (AMPARs) for memory acquisition and short-term memory and extracellular regulated kinase (ERK) for consolidating the learned association into a long-term memory. These findings reveal that βAR activity during, but not following PTC sets in motion cascading molecular events for the acquisition (AMPARs) and subsequent consolidation (ERK) of learned associations.
-
The detection and analysis of point processes in biological signals
NASA Technical Reports Server (NTRS)
Anderson, D. J.; Correia, M. J.
1977-01-01
A pragmatic approach to the detection and analysis of discrete events in biomedical signals is taken. Examples from both clinical and basic research are provided. Introductory sections discuss not only discrete events which are easily extracted from recordings by conventional threshold detectors but also events embedded in other information carrying signals. The primary considerations are factors governing event-time resolution and the effects limits to this resolution have on the subsequent analysis of the underlying process. The analysis portion describes tests for qualifying the records as stationary point processes and procedures for providing meaningful information about the biological signals under investigation. All of these procedures are designed to be implemented on laboratory computers of modest computational capacity.
-
11th International Conference on Malignancies in AIDS and Other Acquired Immunodeficiencies (ICMAOI)
Summary of speakers and events from the 2008 ICMAOI conference, focused on presenting basic, epidemiologic, and clinical aspects of research on malignancies in HIV-infected and other immunosuppressed individuals.
-
77 FR 55475 - Agency Information Collection Activities: Proposed Collection; Comment Request
Federal Register 2010, 2011, 2012, 2013, 2014
2012-09-10
... collected will be analyzed to produce estimates and basic descriptive statistics on the quantity and type of... mode of data collection by event types, and conduct correlations, cross tabulations of responses and...
-
Chaudhari, Mangesh I; Muralidharan, Ajay; Pratt, Lawrence R; Rempe, Susan B
2018-02-12
Progress in understanding liquid ethylene carbonate (EC) and propylene carbonate (PC) on the basis of molecular simulation, emphasizing simple models of interatomic forces, is reviewed. Results on the bulk liquids are examined from the perspective of anticipated applications to materials for electrical energy storage devices. Preliminary results on electrochemical double-layer capacitors based on carbon nanotube forests and on model solid-electrolyte interphase (SEI) layers of lithium ion batteries are considered as examples. The basic results discussed suggest that an empirically parameterized, non-polarizable force field can reproduce experimental structural, thermodynamic, and dielectric properties of EC and PC liquids with acceptable accuracy. More sophisticated force fields might include molecular polarizability and Buckingham-model description of inter-atomic overlap repulsions as extensions to Lennard-Jones models of van der Waals interactions. Simple approaches should be similarly successful also for applications to organic molecular ions in EC/PC solutions, but the important case of Li[Formula: see text] deserves special attention because of the particularly strong interactions of that small ion with neighboring solvent molecules. To treat the Li[Formula: see text] ions in liquid EC/PC solutions, we identify interaction models defined by empirically scaled partial charges for ion-solvent interactions. The empirical adjustments use more basic inputs, electronic structure calculations and ab initio molecular dynamics simulations, and also experimental results on Li[Formula: see text] thermodynamics and transport in EC/PC solutions. Application of such models to the mechanism of Li[Formula: see text] transport in glassy SEI models emphasizes the advantage of long time-scale molecular dynamics studies of these non-equilibrium materials.
-
Adverse outcome pathways (AOPs) are conceptual frameworks that portray causal and predictive linkages between key events at multiple scales of biological organization that connect molecular initiating events and early cellular perturbations (e.g., initiation of toxicity pathways)...
-
Monitoring intracellular oxidative events using dynamic spectral unmixing microscopy
There is increasing interest in using live-cell imaging to monitor not just individual intracellular endpoints, but to investigate the interplay between multiple molecular events as they unfold in real time within the cell. A major impediment to simultaneous acquisition of multip...
-
Adverse Outcome Pathways: From Research to Regulation - Scientific Workshop Report
An adverse outcome pathway (AOP) organizes existing knowledge on chemical mode of action, starting with a molecular initiating event such as receptor binding, continuing through key events, and ending with an adverse outcome such as reproductive impairment. AOPs can help identify...
-
Quantitative Adverse Outcome Pathways and Their Application to Predictive Toxicology
A quantitative adverse outcome pathway (qAOP) consists of one or more biologically based, computational models describing key event relationships linking a molecular initiating event (MIE) to an adverse outcome. A qAOP provides quantitative, dose–response, and time-course p...
-
Motivation, cognition and pseudoscience.
Lindeman, M
1998-12-01
The article proposes a framework that views pseudoscientific beliefs as a joint function of the basic social motives and the default way of processing everyday information. The interplay between the basic motives and experiential thinking is illustrated with three examples. The first concerns comprehension of self via astrology and graphology, and the second involves the comprehension of unexpected events (one domain of the motive to comprehend the world). The last example describes health control by alternative medicine, as a modern way of controlling future outcomes.
-
[A group of new experiments on molecular evolution].
Zhu, Xin-Yu; Xie, Xiao-Ling; Chen, Pei-Lin
2004-07-01
This paper presents a group of new experiments on molecular evolution. It allows students to get acquaint with the basic process of the reconstruction of phylogenetic tree using DNA or protein sequences, and to acquire the correct viewpoint how to affect the result of reconstruction when different tree-building methods, materials and parameters were used. This group of experiments are also characteristic of the opening and exploring, which accords with the direction and demand of experimental teaching reform.
-
Molecular catchers for pharmacologically active substances in wastewaters, a theoretical study
NASA Astrophysics Data System (ADS)
Salazar Valencia, P. J.; Pérez Merchancano, S. T.; Paredes, H.; Bolívar Marinez, L. E.
2016-08-01
A basic and pressing need in the treatment of residual waste waters for urban and rural centers is the removal of pharmacological active residues from them, these resides are originated in a wide array of domestic, agricultural and industrial sources and can't be removed in the residual waters treatment plants by conventional methods, the result is the incorporation of them into the ecosystem altering the physiology and behavior of living organisms. Among the most active pharmacological substances found in very high concentration in residual waters is paracetamol, an analgesic of very wide excessive use due to its ease of access and low cost [1]. No pharmacological substance is entirely absorbed by the human organism and therefore a wide family of molecular residues is excreted by the urinary tract. In this work we have used the AM1 (Austin Model 1), PM3 (Parametric Method 3) and ZINDO/CI semiempirical methods, from the NDO (Neglect Differential Overlap) family [2] to study and observe the structural, electronic and optical characteristics of paracetamol while immersed in different basic and acidic aqueous environments, either alone or interacting with lignosulphonates. We have previously found that lignosulphonates, a lignin derivatives of wide industrial applications, can be engineered as a binding and flocculant agent and acts as molecular catchers therefore showing the potential to be used as a mean to filter and eliminate molecular residues from the residual waters [3].
-
Logic circuits based on molecular spider systems.
Mo, Dandan; Lakin, Matthew R; Stefanovic, Darko
2016-08-01
Spatial locality brings the advantages of computation speed-up and sequence reuse to molecular computing. In particular, molecular walkers that undergo localized reactions are of interest for implementing logic computations at the nanoscale. We use molecular spider walkers to implement logic circuits. We develop an extended multi-spider model with a dynamic environment wherein signal transmission is triggered via localized reactions, and use this model to implement three basic gates (AND, OR, NOT) and a cascading mechanism. We develop an algorithm to automatically generate the layout of the circuit. We use a kinetic Monte Carlo algorithm to simulate circuit computations, and we analyze circuit complexity: our design scales linearly with formula size and has a logarithmic time complexity. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.
-
Conversion of Questionnaire Data
DOE Office of Scientific and Technical Information (OSTI.GOV)
Powell, Danny H; Elwood Jr, Robert H
During the survey, respondents are asked to provide qualitative answers (well, adequate, needs improvement) on how well material control and accountability (MC&A) functions are being performed. These responses can be used to develop failure probabilities for basic events performed during routine operation of the MC&A systems. The failure frequencies for individual events may be used to estimate total system effectiveness using a fault tree in a probabilistic risk analysis (PRA). Numeric risk values are required for the PRA fault tree calculations that are performed to evaluate system effectiveness. So, the performance ratings in the questionnaire must be converted to relativemore » risk values for all of the basic MC&A tasks performed in the facility. If a specific material protection, control, and accountability (MPC&A) task is being performed at the 'perfect' level, the task is considered to have a near zero risk of failure. If the task is performed at a less than perfect level, the deficiency in performance represents some risk of failure for the event. As the degree of deficiency in performance increases, the risk of failure increases. If a task that should be performed is not being performed, that task is in a state of failure. The failure probabilities of all basic events contribute to the total system risk. Conversion of questionnaire MPC&A system performance data to numeric values is a separate function from the process of completing the questionnaire. When specific questions in the questionnaire are answered, the focus is on correctly assessing and reporting, in an adjectival manner, the actual performance of the related MC&A function. Prior to conversion, consideration should not be given to the numeric value that will be assigned during the conversion process. In the conversion process, adjectival responses to questions on system performance are quantified based on a log normal scale typically used in human error analysis (see A.D. Swain and H.E. Guttmann, 'Handbook of Human Reliability Analysis with Emphasis on Nuclear Power Plant Applications,' NUREG/CR-1278). This conversion produces the basic event risk of failure values required for the fault tree calculations. The fault tree is a deductive logic structure that corresponds to the operational nuclear MC&A system at a nuclear facility. The conventional Delphi process is a time-honored approach commonly used in the risk assessment field to extract numerical values for the failure rates of actions or activities when statistically significant data is absent.« less
-
The veto system of the DarkSide-50 experiment
Agnes, P.
2016-03-16
Here, nuclear recoil events produced by neutron scatters form one of the most important classes of background in WIMP direct detection experiments, as they may produce nuclear recoils that look exactly like WIMP interactions. In DarkSide-50, we both actively suppress and measure the rate of neutron-induced background events using our neutron veto, composed of a boron-loaded liquid scintillator detector within a water Cherenkov detector. This paper is devoted to the description of the neutron veto system of DarkSide-50, including the detector structure, the fundamentals of event reconstruction and data analysis, and basic performance parameters.
-
The veto system of the DarkSide-50 experiment
NASA Astrophysics Data System (ADS)
Agnes, P.; Agostino, L.; Albuquerque, I. F. M.; Alexander, T.; Alton, A. K.; Arisaka, K.; Back, H. O.; Baldin, B.; Biery, K.; Bonfini, G.; Bossa, M.; Bottino, B.; Brigatti, A.; Brodsky, J.; Budano, F.; Bussino, S.; Cadeddu, M.; Cadonati, L.; Cadoni, M.; Calaprice, F.; Canci, N.; Candela, A.; Cao, H.; Cariello, M.; Carlini, M.; Catalanotti, S.; Cavalcante, P.; Chepurnov, A.; Cocco, A. G.; Covone, G.; Crippa, L.; D'Angelo, D.; D'Incecco, M.; Davini, S.; De Cecco, S.; De Deo, M.; De Vincenzi, M.; Derbin, A.; Devoto, A.; Di Eusanio, F.; Di Pietro, G.; Edkins, E.; Empl, A.; Fan, A.; Fiorillo, G.; Fomenko, K.; Foster, G.; Franco, D.; Gabriele, F.; Galbiati, C.; Giganti, C.; Goretti, A. M.; Granato, F.; Grandi, L.; Gromov, M.; Guan, M.; Guardincerri, Y.; Hackett, B. R.; Herner, K. R.; Hungerford, E. V.; Ianni, Aldo; Ianni, Andrea; James, I.; Johnson, T.; Jollet, C.; Keeter, K.; Kendziora, C. L.; Kobychev, V.; Koh, G.; Korablev, D.; Korga, G.; Kubankin, A.; Li, X.; Lissia, M.; Lombardi, P.; Luitz, S.; Ma, Y.; Machulin, I. N.; Mandarano, A.; Mari, S. M.; Maricic, J.; Marini, L.; Martoff, C. J.; Meregaglia, A.; Meyers, P. D.; Miletic, T.; Milincic, R.; Montanari, D.; Monte, A.; Montuschi, M.; Monzani, M. E.; Mosteiro, P.; Mount, B. J.; Muratova, V. N.; Musico, P.; Napolitano, J.; Nelson, A.; Odrowski, S.; Orsini, M.; Ortica, F.; Pagani, L.; Pallavicini, M.; Pantic, E.; Parmeggiano, S.; Pelczar, K.; Pelliccia, N.; Perasso, S.; Pocar, A.; Pordes, S.; Pugachev, D. A.; Qian, H.; Randle, K.; Ranucci, G.; Razeto, A.; Reinhold, B.; Renshaw, A. L.; Romani, A.; Rossi, B.; Rossi, N.; Rountree, S. D.; Sablone, D.; Saggese, P.; Saldanha, R.; Sands, W.; Sangiorgio, S.; Savarese, C.; Segreto, E.; Semenov, D. A.; Shields, E.; Singh, P. N.; Skorokhvatov, M. D.; Smirnov, O.; Sotnikov, A.; Stanford, C.; Suvorov, Y.; Tartaglia, R.; Tatarowicz, J.; Testera, G.; Tonazzo, A.; Trinchese, P.; Unzhakov, E. V.; Vishneva, A.; Vogelaar, R. B.; Wada, M.; Walker, S.; Wang, H.; Wang, Y.; Watson, A. W.; Westerdale, S.; Wilhelmi, J.; Wojcik, M. M.; Xiang, X.; Xu, J.; Yang, C.; Yoo, J.; Zavatarelli, S.; Zec, A.; Zhong, W.; Zhu, C.; Zuzel, G.
2016-03-01
Nuclear recoil events produced by neutron scatters form one of the most important classes of background in WIMP direct detection experiments, as they may produce nuclear recoils that look exactly like WIMP interactions. In DarkSide-50, we both actively suppress and measure the rate of neutron-induced background events using our neutron veto, composed of a boron-loaded liquid scintillator detector within a water Cherenkov detector. This paper is devoted to the description of the neutron veto system of DarkSide-50, including the detector structure, the fundamentals of event reconstruction and data analysis, and basic performance parameters.
-
Minicomputer Hardware Monitor Design.
1980-06-01
detected signals. Both the COMTEN and TESDATA systems rely on a " plugboard " arrangement where sensor inputs may be combined by means of standard gate logic...systems. A further use of the plugboard "patch panels" is to direct the measured "event" to collection and/or distribution circuitry, where the event...are plugboard and sensor hookup configurations. The available T-PACs are: o Basic System Profile o Regional Mapping o Advanced System Management
-
DOE Office of Scientific and Technical Information (OSTI.GOV)
Mumpower, J.L.
There are strong structural similarities between risks from technological hazards and big-purse state lottery games. Risks from technological hazards are often described as low-probability, high-consequence negative events. State lotteries could be equally well characterized as low-probability, high-consequence positive events. Typical communications about state lotteries provide a virtual strategic textbook for opponents of risky technologies. The same techniques can be used to sell lottery tickets or sell opposition to risky technologies. Eight basic principles are enumerated.
-
[Analysis of after-vacination side-effects occurred in Teresina].
de Araújo, Telma Maria Evangelista; de Carvalho, Patrícia Maria Gomes; Vieira, Raimunda Damasceno Ferreira
2007-01-01
This study focuses the profile of the adverse events after-vaccine occurrences in Teresina in 2006. The data had been collected by means of the form application with 73 participants in 18 Basic Units of Health. The results show that the vaccines that had more produced events adverse had been tetravalente, BCG and DPT The events most frequent had been: fever, hiporresponsivo hipotonic episode, moderate irritability and local manifestations. Amongst the behaviors adopted for the health professionals, 80% had been approximately adjusted. The year minors had been accomitted by the events. All the events had evolved for the cure. It was concluded that the action of vaccination still continues requiring constant qualification of the professionals of the area. It is suggested to deepen the knowledge with relation to the handling, diagnosis, inquiry and treatment.
-
REVIEWS OF TOPICAL PROBLEMS: Physical aspects of cryobiology
NASA Astrophysics Data System (ADS)
Zhmakin, A. I.
2008-03-01
Physical phenomena during biological freezing and thawing processes at the molecular, cellular, tissue, and organ levels are examined. The basics of cryosurgery and cryopreservation of cells and tissues are presented. Existing cryobiological models, including numerical ones, are reviewed.
-
Molecular Identification and Databases in Fusarium
USDA-ARS?s Scientific Manuscript database
DNA sequence-based methods for identifying pathogenic and mycotoxigenic Fusarium isolates have become the gold standard worldwide. Moreover, fusarial DNA sequence data are increasing rapidly in several web-accessible databases for comparative purposes. Unfortunately, the use of Basic Alignment Sea...
-
Quantum Dots: An Experiment for Physical or Materials Chemistry
ERIC Educational Resources Information Center
Winkler, L. D.; Arceo, J. F.; Hughes, W. C.; DeGraff, B. A.; Augustine, B. H.
2005-01-01
An experiment is conducted for obtaining quantum dots for physical or materials chemistry. This experiment serves to both reinforce the basic concept of quantum confinement and providing a useful bridge between the molecular and solid-state world.
-
Proteomics for Adverse Outcome Pathway Discovery using Human Kidney Cells?
An Adverse Outcome Pathway (AOP) is a conceptual framework that applies molecular-based data for use in risk assessment and regulatory decision support. AOP development is based on effects data of chemicals on biological processes (i.e., molecular initiating events, key intermedi...
-
The whole-genome landscape of medulloblastoma subtypes.
Northcott, Paul A; Buchhalter, Ivo; Morrissy, A Sorana; Hovestadt, Volker; Weischenfeldt, Joachim; Ehrenberger, Tobias; Gröbner, Susanne; Segura-Wang, Maia; Zichner, Thomas; Rudneva, Vasilisa A; Warnatz, Hans-Jörg; Sidiropoulos, Nikos; Phillips, Aaron H; Schumacher, Steven; Kleinheinz, Kortine; Waszak, Sebastian M; Erkek, Serap; Jones, David T W; Worst, Barbara C; Kool, Marcel; Zapatka, Marc; Jäger, Natalie; Chavez, Lukas; Hutter, Barbara; Bieg, Matthias; Paramasivam, Nagarajan; Heinold, Michael; Gu, Zuguang; Ishaque, Naveed; Jäger-Schmidt, Christina; Imbusch, Charles D; Jugold, Alke; Hübschmann, Daniel; Risch, Thomas; Amstislavskiy, Vyacheslav; Gonzalez, Francisco German Rodriguez; Weber, Ursula D; Wolf, Stephan; Robinson, Giles W; Zhou, Xin; Wu, Gang; Finkelstein, David; Liu, Yanling; Cavalli, Florence M G; Luu, Betty; Ramaswamy, Vijay; Wu, Xiaochong; Koster, Jan; Ryzhova, Marina; Cho, Yoon-Jae; Pomeroy, Scott L; Herold-Mende, Christel; Schuhmann, Martin; Ebinger, Martin; Liau, Linda M; Mora, Jaume; McLendon, Roger E; Jabado, Nada; Kumabe, Toshihiro; Chuah, Eric; Ma, Yussanne; Moore, Richard A; Mungall, Andrew J; Mungall, Karen L; Thiessen, Nina; Tse, Kane; Wong, Tina; Jones, Steven J M; Witt, Olaf; Milde, Till; Von Deimling, Andreas; Capper, David; Korshunov, Andrey; Yaspo, Marie-Laure; Kriwacki, Richard; Gajjar, Amar; Zhang, Jinghui; Beroukhim, Rameen; Fraenkel, Ernest; Korbel, Jan O; Brors, Benedikt; Schlesner, Matthias; Eils, Roland; Marra, Marco A; Pfister, Stefan M; Taylor, Michael D; Lichter, Peter
2017-07-19
Current therapies for medulloblastoma, a highly malignant childhood brain tumour, impose debilitating effects on the developing child, and highlight the need for molecularly targeted treatments with reduced toxicity. Previous studies have been unable to identify the full spectrum of driver genes and molecular processes that operate in medulloblastoma subgroups. Here we analyse the somatic landscape across 491 sequenced medulloblastoma samples and the molecular heterogeneity among 1,256 epigenetically analysed cases, and identify subgroup-specific driver alterations that include previously undiscovered actionable targets. Driver mutations were confidently assigned to most patients belonging to Group 3 and Group 4 medulloblastoma subgroups, greatly enhancing previous knowledge. New molecular subtypes were differentially enriched for specific driver events, including hotspot in-frame insertions that target KBTBD4 and 'enhancer hijacking' events that activate PRDM6. Thus, the application of integrative genomics to an extensive cohort of clinical samples derived from a single childhood cancer entity revealed a series of cancer genes and biologically relevant subtype diversity that represent attractive therapeutic targets for the treatment of patients with medulloblastoma.
-
The Extracellular Surface of the GLP-1 Receptor Is a Molecular Trigger for Biased Agonism.
Wootten, Denise; Reynolds, Christopher A; Smith, Kevin J; Mobarec, Juan C; Koole, Cassandra; Savage, Emilia E; Pabreja, Kavita; Simms, John; Sridhar, Rohan; Furness, Sebastian G B; Liu, Mengjie; Thompson, Philip E; Miller, Laurence J; Christopoulos, Arthur; Sexton, Patrick M
2016-06-16
Ligand-directed signal bias offers opportunities for sculpting molecular events, with the promise of better, safer therapeutics. Critical to the exploitation of signal bias is an understanding of the molecular events coupling ligand binding to intracellular signaling. Activation of class B G protein-coupled receptors is driven by interaction of the peptide N terminus with the receptor core. To understand how this drives signaling, we have used advanced analytical methods that enable separation of effects on pathway-specific signaling from those that modify agonist affinity and mapped the functional consequence of receptor modification onto three-dimensional models of a receptor-ligand complex. This yields molecular insights into the initiation of receptor activation and the mechanistic basis for biased agonism. Our data reveal that peptide agonists can engage different elements of the receptor extracellular face to achieve effector coupling and biased signaling providing a foundation for rational design of biased agonists. Copyright © 2016 The Authors. Published by Elsevier Inc. All rights reserved.
-
Towards a high sensitivity small animal PET system based on CZT detectors (Conference Presentation)
NASA Astrophysics Data System (ADS)
Abbaszadeh, Shiva; Levin, Craig
2017-03-01
Small animal positron emission tomography (PET) is a biological imaging technology that allows non-invasive interrogation of internal molecular and cellular processes and mechanisms of disease. New PET molecular probes with high specificity are under development to target, detect, visualize, and quantify subtle molecular and cellular processes associated with cancer, heart disease, and neurological disorders. However, the limited uptake of these targeted probes leads to significant reduction in signal. There is a need to advance the performance of small animal PET system technology to reach its full potential for molecular imaging. Our goal is to assemble a small animal PET system based on CZT detectors and to explore methods to enhance its photon sensitivity. In this work, we reconstruct an image from a phantom using a two-panel subsystem consisting of six CZT crystals in each panel. For image reconstruction, coincidence events with energy between 450 and 570 keV were included. We are developing an algorithm to improve sensitivity of the system by including multiple interaction events.
-
Identifying Candidate Chemical-Disease Linkages ...
Presentation at meeting on Environmental and Epigenetic Determinants of IBD in New York, NY on identifying candidate chemical-disease linkages by using AOPs to identify molecular initiating events and using relevant high throughput assays to screen for candidate chemicals. This hazard information is combined with exposure models to inform risk assessment. Presentation at meeting on Environmental and Epigenetic Determinants of IBD in New York, NY on identifying candidate chemical-disease linkages by using AOPs to identify molecular initiating events and using relevant high throughput assays to screen for candidate chemicals. This hazard information is combined with exposure models to inform risk assessment.
-
The Development of Adult Innate Lymphoid Cells
Yang, Qi; Bhandoola, Avinash
2016-01-01
Innate lymphoid cells (ILC) are a specialized family of effector lymphocytes that transcriptionally and functionally mirror effector subsets of T cells, but differ from T cells in that they lack clonally-distributed adaptive antigen receptors. Our understanding of this family of lymphocytes is still in its infancy. In this review, we summarize current understanding and discuss recent insights into the cellular and molecular events that occur during early ILC development in adult mice. We discuss how these events overlap and diverge with the early development of adaptive T cells, and how they may influence the molecular and functional properties of mature ILC. PMID:26871595
-
Vibrational Heat Transport in Molecular Junctions
NASA Astrophysics Data System (ADS)
Segal, Dvira; Agarwalla, Bijay Kumar
2016-05-01
We review studies of vibrational energy transfer in a molecular junction geometry, consisting of a molecule bridging two heat reservoirs, solids or large chemical compounds. This setup is of interest for applications in molecular electronics, thermoelectrics, and nanophononics, and for addressing basic questions in the theory of classical and quantum transport. Calculations show that system size, disorder, structure, dimensionality, internal anharmonicities, contact interaction, and quantum coherent effects are factors that combine to determine the predominant mechanism (ballistic/diffusive), effectiveness (poor/good), and functionality (linear/nonlinear) of thermal conduction at the nanoscale. We review recent experiments and relevant calculations of quantum heat transfer in molecular junctions. We recount the Landauer approach, appropriate for the study of elastic (harmonic) phononic transport, and outline techniques that incorporate molecular anharmonicities. Theoretical methods are described along with examples illustrating the challenge of reaching control over vibrational heat conduction in molecules.
-
[Precision medicine: new opportunities and challenges for molecular epidemiology].
Song, Jing; Hu, Yonghua
2016-04-01
Since the completion of the Human Genome Project in 2003 and the announcement of the Precision Medicine Initiative by U.S. President Barack Obama in January 2015, human beings have initially completed the " three steps" of " genomics to biology, genomics to health as well as genomics to society". As a new inter-discipline, the emergence and development of precision medicine have relied on the support and promotion from biological science, basic medicine, clinical medicine, epidemiology, statistics, sociology and information science, etc. Meanwhile, molecular epidemiology is considered to be the core power to promote precision medical as a cross discipline of epidemiology and molecular biology. This article is based on the characteristics and research progress of medicine and molecular epidemiology respectively, focusing on the contribution and significance of molecular epidemiology to precision medicine, and exploring the possible opportunities and challenges in the future.
-
Molecular plant breeding: methodology and achievements.
Varshney, Rajeev K; Hoisington, Dave A; Nayak, Spurthi N; Graner, Andreas
2009-01-01
The progress made in DNA marker technology has been remarkable and exciting in recent years. DNA markers have proved valuable tools in various analyses in plant breeding, for example, early generation selection, enrichment of complex F(1)s, choice of donor parent in backcrossing, recovery of recurrent parent genotype in backcrossing, linkage block analysis and selection. Other main areas of applications of molecular markers in plant breeding include germplasm characterization/fingerprinting, determining seed purity, systematic sampling of germplasm, and phylogenetic analysis. Molecular markers, thus, have proved powerful tools in replacing the bioassays and there are now many examples available to show the efficacy of such markers. We have illustrated some basic concepts and methodology of applying molecular markers for enhancing the selection efficiency in plant breeding. Some successful examples of product developments of molecular breeding have also been presented.
-
Modelling of Cosmic Molecular Masers: Introduction to a Computation Cookbook
NASA Astrophysics Data System (ADS)
Sobolev, Andrej M.; Gray, Malcolm D.
2012-07-01
Numerical modeling of molecular masers is necessary in order to understand their nature and diagnostic capabilities. Model construction requires elaboration of a basic description which allows computation, that is a definition of the parameter space and basic physical relations. Usually, this requires additional thorough studies that can consist of the following stages/parts: relevant molecular spectroscopy and collisional rate coefficients; conditions in and around the masing region (that part of space where population inversion is realized); geometry and size of the masing region (including the question of whether maser spots are discrete clumps or line-of-sight correlations in a much bigger region) and propagation of maser radiation. Output of the maser computer modeling can have the following forms: exploration of parameter space (where do inversions appear in particular maser transitions and their combinations, which parameter values describe a `typical' source, and so on); modeling of individual sources (line flux ratios, spectra, images and their variability); analysis of the pumping mechanism; predictions (new maser transitions, correlations in variability of different maser transitions, and the like). Described schemes (constituents and hierarchy) of the model input and output are based mainly on the experience of the authors and make no claim to be dogmatic.
-
Huang, Ying; Li, Cao; Liu, Linhai; Jia, Xianbo; Lai, Song-Jia
2016-01-01
Although various computer tools have been elaborately developed to calculate a series of statistics in molecular population genetics for both small- and large-scale DNA data, there is no efficient and easy-to-use toolkit available yet for exclusively focusing on the steps of mathematical calculation. Here, we present PopSc, a bioinformatic toolkit for calculating 45 basic statistics in molecular population genetics, which could be categorized into three classes, including (i) genetic diversity of DNA sequences, (ii) statistical tests for neutral evolution, and (iii) measures of genetic differentiation among populations. In contrast to the existing computer tools, PopSc was designed to directly accept the intermediate metadata, such as allele frequencies, rather than the raw DNA sequences or genotyping results. PopSc is first implemented as the web-based calculator with user-friendly interface, which greatly facilitates the teaching of population genetics in class and also promotes the convenient and straightforward calculation of statistics in research. Additionally, we also provide the Python library and R package of PopSc, which can be flexibly integrated into other advanced bioinformatic packages of population genetics analysis. PMID:27792763
-
Alam, Mahboob; Lee, Dong-Ung
2015-01-01
The aim of this study was to report the synthesis of biologically active compounds; 7-(2′-aminoethoxyimino)-cholest-5-ene (4), a steroidal oxime-ether and its derivatives (5, 6) via a facile microwave assisted solvent free reaction methodology. This new synthetic, eco-friendly, sustainable protocol resulted in a remarkable improvement in the synthetic efficiency (85-93 % yield) and high purity using basic alumina. The synthesized compounds were screened for their antibacterial against six bacterial strains by disc diffusion method and antioxidant potential by DPPH assay. The binding capabilities of a compound 6 exhibiting good antibacterial potential were assessed on the basis of molecular docking studies and four types of three-dimensional molecular field descriptors. Moreover the structure-antimicrobial activity relationships were studied using some physicochemical and quantum-chemical parameters with GAMESS interface as well as WebMO Job Manager by using the basic level of theory. Hence, this synthetic approach is believed to provide a better scope for the synthesis of steroidal oxime-ether analogues and will be a more practical alternative to the presently existing procedures. Moreover, detailed in silico docking studies suggested the plausible mechanism of steroidal oxime-ethers as effective antimicrobial agents. PMID:27330525
-
Fundamental Studies of Crystal Growth of Microporous Materials
NASA Technical Reports Server (NTRS)
Singh, Ramsharan; Doolittle, John, Jr.; Payra, Pramatha; Dutta, Prabir K.; George, Michael A.; Ramachandran, Narayanan; Schoeman, Brian J.
2003-01-01
Microporous materials are framework structures with well-defined porosity, often of molecular dimensions. Zeolites contain aluminum and silicon atoms in their framework and are the most extensively studied amongst all microporous materials. Framework structures with P, Ga, Fe, Co, Zn, B, Ti and a host of other elements have also been made. Typical synthesis of microporous materials involve mixing the framework elements (or compounds, thereof) in a basic solution, followed by aging in some cases and then heating at elevated temperatures. This process is termed hydrothermal synthesis, and involves complex chemical and physical changes. Because of a limited understanding of this process, most synthesis advancements happen by a trial and error approach. There is considerable interest in understanding the synthesis process at a molecular level with the expectation that eventually new framework structures will be built by design. The basic issues in the microporous materials crystallization process include: (a) Nature of the molecular units responsible for the crystal nuclei formation; (b) Nature of the nuclei and nucleation process; (c) Growth process of the nuclei into crystal; (d) Morphological control and size of the resulting crystal; (e) Surface structure of the resulting crystals; and (f) Transformation of frameworks into other frameworks or condensed structures.
-
Chen, Shi-Yi; Deng, Feilong; Huang, Ying; Li, Cao; Liu, Linhai; Jia, Xianbo; Lai, Song-Jia
2016-01-01
Although various computer tools have been elaborately developed to calculate a series of statistics in molecular population genetics for both small- and large-scale DNA data, there is no efficient and easy-to-use toolkit available yet for exclusively focusing on the steps of mathematical calculation. Here, we present PopSc, a bioinformatic toolkit for calculating 45 basic statistics in molecular population genetics, which could be categorized into three classes, including (i) genetic diversity of DNA sequences, (ii) statistical tests for neutral evolution, and (iii) measures of genetic differentiation among populations. In contrast to the existing computer tools, PopSc was designed to directly accept the intermediate metadata, such as allele frequencies, rather than the raw DNA sequences or genotyping results. PopSc is first implemented as the web-based calculator with user-friendly interface, which greatly facilitates the teaching of population genetics in class and also promotes the convenient and straightforward calculation of statistics in research. Additionally, we also provide the Python library and R package of PopSc, which can be flexibly integrated into other advanced bioinformatic packages of population genetics analysis.
-
Singh, Itu; Yadav, Asha Ram; Mohanty, Keshar Kunja; Katoch, Kiran; Sharma, Prashant; Mishra, Bishal; Bisht, Deepa; Gupta, U D; Sengupta, Utpal
2015-04-01
Autoantibodies against various components of host are known to occur in leprosy. Nerve damage is the primary cause of disability associated with leprosy. The aim of this study was to detect the level of autoantibodies and lympho-proliferative response against myelin basic protein (MBP) in leprosy patients (LPs) and their correlation with clinical phenotypes of LPs. Further, probable role of molecular mimicry in nerve damage of LPs was investigated. We observed significantly high level of anti-MBP antibodies in LPs across the spectrum and a positive significant correlation between the level of anti-MBP antibodies and the number of nerves involved in LPs. We report here that 4 B cell epitopes of myelin A1 and Mycobacterium leprae proteins, 50S ribosomal L2 and lysyl tRNA synthetase are cross-reactive. Further, M. leprae sonicated antigen hyperimmunization was responsible for induction of autoantibody response in mice which could be adoptively transferred to naive mice. For the first time our findings suggest the role of molecular mimicry in nerve damage in leprosy. Copyright © 2015 Institut Pasteur. Published by Elsevier Masson SAS. All rights reserved.
-
2012-01-01
Background Particulate air pollution in lung epithelial cells induces pathogenic endpoints like proliferation, apoptosis, and pro-inflammatory reactions. The activation of the epidermal growth factor receptor (EGFR) is a key event responsible for signalling events involving mitogen activated protein kinases specific for these endpoints. The molecular events leading to receptor activation however are not well understood. These events are relevant for the toxicological evaluation of inhalable particles as well as for potential preventive strategies in situations when particulate air pollution cannot be avoided. The current study therefore had the objective to elucidate membrane-coupled events leading to EGFR activation and the subsequent signalling cascade in lung epithelial cells. Furthermore, we aimed to identify the molecular target of ectoine, a biophysical active substance which we described to prevent carbon nanoparticle-induced lung inflammation. Methods Membrane signalling events were investigated in isolated lipid rafts from lung epithelial cells with regard to lipid and protein content of the signalling platforms. Using positive and negative intervention approaches, lipid raft changes, subsequent signalling events, and lung inflammation were investigated in vitro in lung epithelial cells (RLE-6TN) and in vivo in exposed animals. Results Carbon nanoparticle treatment specifically led to an accumulation of ceramides in lipid rafts. Detailed analyses demonstrated a causal link of ceramides and subsequent EGFR activation coupled with a loss of the receptor in the lipid raft fractions. In vitro and in vivo investigations demonstrate the relevance of these events for carbon nanoparticle-induced lung inflammation. Moreover, the compatible solute ectoine was able to prevent ceramide-mediated EGFR phosphorylation and subsequent signalling as well as lung inflammation in vivo. Conclusion The data identify a so far unknown event in pro-inflammatory signalling and contribute to the understanding of particle cell interaction and therefore to risk identification and risk assessment of inhalable xenobiotics. Moreover, as this cellular reaction can be prevented by the well tolerated substance ectoine, a molecular preventive strategy for susceptible persons against airway inflammation is proposed. PMID:23228165
-
Beres, Stephen B; Kachroo, Priyanka; Nasser, Waleed; Olsen, Randall J; Zhu, Luchang; Flores, Anthony R; de la Riva, Ivan; Paez-Mayorga, Jesus; Jimenez, Francisco E; Cantu, Concepcion; Vuopio, Jaana; Jalava, Jari; Kristinsson, Karl G; Gottfredsson, Magnus; Corander, Jukka; Fittipaldi, Nahuel; Di Luca, Maria Chiara; Petrelli, Dezemona; Vitali, Luca A; Raiford, Annessa; Jenkins, Leslie; Musser, James M
2016-05-31
For over a century, a fundamental objective in infection biology research has been to understand the molecular processes contributing to the origin and perpetuation of epidemics. Divergent hypotheses have emerged concerning the extent to which environmental events or pathogen evolution dominates in these processes. Remarkably few studies bear on this important issue. Based on population pathogenomic analysis of 1,200 Streptococcus pyogenes type emm89 infection isolates, we report that a series of horizontal gene transfer events produced a new pathogenic genotype with increased ability to cause infection, leading to an epidemic wave of disease on at least two continents. In the aggregate, these and other genetic changes substantially remodeled the transcriptomes of the evolved progeny, causing extensive differential expression of virulence genes and altered pathogen-host interaction, including enhanced immune evasion. Our findings delineate the precise molecular genetic changes that occurred and enhance our understanding of the evolutionary processes that contribute to the emergence and persistence of epidemically successful pathogen clones. The data have significant implications for understanding bacterial epidemics and for translational research efforts to blunt their detrimental effects. The confluence of studies of molecular events underlying pathogen strain emergence, evolutionary genetic processes mediating altered virulence, and epidemics is in its infancy. Although understanding these events is necessary to develop new or improved strategies to protect health, surprisingly few studies have addressed this issue, in particular, at the comprehensive population genomic level. Herein we establish that substantial remodeling of the transcriptome of the human-specific pathogen Streptococcus pyogenes by horizontal gene flow and other evolutionary genetic changes is a central factor in precipitating and perpetuating epidemic disease. The data unambiguously show that the key outcome of these molecular events is evolution of a new, more virulent pathogenic genotype. Our findings provide new understanding of epidemic disease. Copyright © 2016 Beres et al.
-
A Quantitative Adverse Outcome Pathway Linking Aromatase Inhibition in Fathead Minnows with Population DynamicsAn adverse outcome pathway (AOP) is a qualitative description linking a molecular initiating event (MIE) with measureable key events leading to an adverse outcome (AO). ...
-
Adverse outcome pathways (AOPs) are designed to describe linkages of key events (KEs) within a biological pathway that result in an adverse outcome associated with chemical perturbation of a well-defined molecular initiating event (MIE). Risk assessors have traditionally relied ...
-
Tipping the Balance: Hepatotoxicity and the Four Apical Key Events of Hepatic Steatosis
Adverse outcome pathways (AOPs) are descriptive biological sequences that start from a molecular initiating event (MIE) and end with an adverse health outcome. AOPs provide biological context for high throughput chemical testing and further prioritize environmental health risk r...
-
Molecular dynamics study on the microscopic details of the evaporation of water.
Mason, Phillip E
2011-06-16
Molecular dynamics simulations were conducted on a drop of water (containing 4890 TIP3P waters) at 350 K. About 70 evaporation events were found and characterized in enough detail to determine significant patterns relating to the mechanism of evaporation. It was found that in almost all evaporation events that a single, high-energy state immediately preceded the evaporation event. In ∼50% of the cases, this high-energy state involved a short oxygen-oxygen distance, suggesting a van der Waals collision, whereas in the remaining cases, a short hydrogen-hydrogen distance was found, suggesting an electrostatic "collision". Of the high-energy states that led to evaporation, about half occurred when the coordination number of water was 1, and about half, when the coordination number was 2. It was found that the 1-coordinated waters (∼1% of the surface waters) and 2-coordinated waters (6% of the surface waters) were responsible for almost all the evaporation events. © 2011 American Chemical Society
-
Parallel Discrete Molecular Dynamics Simulation With Speculation and In-Order Commitment*†
Khan, Md. Ashfaquzzaman; Herbordt, Martin C.
2011-01-01
Discrete molecular dynamics simulation (DMD) uses simplified and discretized models enabling simulations to advance by event rather than by timestep. DMD is an instance of discrete event simulation and so is difficult to scale: even in this multi-core era, all reported DMD codes are serial. In this paper we discuss the inherent difficulties of scaling DMD and present our method of parallelizing DMD through event-based decomposition. Our method is microarchitecture inspired: speculative processing of events exposes parallelism, while in-order commitment ensures correctness. We analyze the potential of this parallelization method for shared-memory multiprocessors. Achieving scalability required extensive experimentation with scheduling and synchronization methods to mitigate serialization. The speed-up achieved for a variety of system sizes and complexities is nearly 6× on an 8-core and over 9× on a 12-core processor. We present and verify analytical models that account for the achieved performance as a function of available concurrency and architectural limitations. PMID:21822327
-
Parallel Discrete Molecular Dynamics Simulation With Speculation and In-Order Commitment.
Khan, Md Ashfaquzzaman; Herbordt, Martin C
2011-07-20
Discrete molecular dynamics simulation (DMD) uses simplified and discretized models enabling simulations to advance by event rather than by timestep. DMD is an instance of discrete event simulation and so is difficult to scale: even in this multi-core era, all reported DMD codes are serial. In this paper we discuss the inherent difficulties of scaling DMD and present our method of parallelizing DMD through event-based decomposition. Our method is microarchitecture inspired: speculative processing of events exposes parallelism, while in-order commitment ensures correctness. We analyze the potential of this parallelization method for shared-memory multiprocessors. Achieving scalability required extensive experimentation with scheduling and synchronization methods to mitigate serialization. The speed-up achieved for a variety of system sizes and complexities is nearly 6× on an 8-core and over 9× on a 12-core processor. We present and verify analytical models that account for the achieved performance as a function of available concurrency and architectural limitations.
-
A functional comparison of basic restraint systems.
DOT National Transportation Integrated Search
1967-06-01
The availability of information necessary to provide realistic solutions for personal safety problems in public and private transportation systems is found to be inadequate and incomplete. The problem of body restraint during the accident event is pu...
-
ERIC Educational Resources Information Center
Classroom Computer Learning, 1984
1984-01-01
Presents five activities suitable for middle grades. These include listings for a car race (BASIC) and poetry (Pilot) programs, and activities on graphics without programing, new meanings (related to computers) of old words, and developing a list of historical events. (JN)
-
Patient Safety—Incorporating Drawing Software into Root Cause Analysis Software
Williams, Linda; Grayson, Diana; Gosbee, John
2001-01-01
Drawing software from Lassalle Technologies1 (France) designed for Visual Basic is the tool we used to standardize the creation, storage, and retrieval of flow diagrams containing information about adverse events and close calls.
-
Patient Safety—Incorporating Drawing Software into Root Cause Analysis Software
Williams, Linda; Grayson, Diana; Gosbee, John
2002-01-01
Drawing software from Lassalle Technologies1 (France) designed for Visual Basic is the tool we used to standardize the creation, storage, and retrieval of flow diagrams containing information about adverse events and close calls.
-
Li, Jun; Zhang, Hong; Han, Yinshan; Wang, Baodong
2016-01-01
Focusing on the diversity, complexity and uncertainty of the third-party damage accident, the failure probability of third-party damage to urban gas pipeline was evaluated on the theory of analytic hierarchy process and fuzzy mathematics. The fault tree of third-party damage containing 56 basic events was built by hazard identification of third-party damage. The fuzzy evaluation of basic event probabilities were conducted by the expert judgment method and using membership function of fuzzy set. The determination of the weight of each expert and the modification of the evaluation opinions were accomplished using the improved analytic hierarchy process, and the failure possibility of the third-party to urban gas pipeline was calculated. Taking gas pipelines of a certain large provincial capital city as an example, the risk assessment structure of the method was proved to conform to the actual situation, which provides the basis for the safety risk prevention.
-
Quality Improvement With Discrete Event Simulation: A Primer for Radiologists.
Booker, Michael T; O'Connell, Ryan J; Desai, Bhushan; Duddalwar, Vinay A
2016-04-01
The application of simulation software in health care has transformed quality and process improvement. Specifically, software based on discrete-event simulation (DES) has shown the ability to improve radiology workflows and systems. Nevertheless, despite the successful application of DES in the medical literature, the power and value of simulation remains underutilized. For this reason, the basics of DES modeling are introduced, with specific attention to medical imaging. In an effort to provide readers with the tools necessary to begin their own DES analyses, the practical steps of choosing a software package and building a basic radiology model are discussed. In addition, three radiology system examples are presented, with accompanying DES models that assist in analysis and decision making. Through these simulations, we provide readers with an understanding of the theory, requirements, and benefits of implementing DES in their own radiology practices. Copyright © 2016 American College of Radiology. All rights reserved.
-
Modeling a maintenance simulation of the geosynchronous platform
NASA Technical Reports Server (NTRS)
Kleiner, A. F., Jr.
1980-01-01
A modeling technique used to conduct a simulation study comparing various maintenance routines for a space platform is dicussed. A system model is described and illustrated, the basic concepts of a simulation pass are detailed, and sections on failures and maintenance are included. The operation of the system across time is best modeled by a discrete event approach with two basic events - failure and maintenance of the system. Each overall simulation run consists of introducing a particular model of the physical system, together with a maintenance policy, demand function, and mission lifetime. The system is then run through many passes, each pass corresponding to one mission and the model is re-initialized before each pass. Statistics are compiled at the end of each pass and after the last pass a report is printed. Items of interest typically include the time to first maintenance, total number of maintenance trips for each pass, average capability of the system, etc.
-
The Astrocentric Hypothesis: proposed role of astrocytes in consciousness and memory formation.
Robertson, James M
2002-01-01
Consciousness is self-awareness. This process is closely associated with attention and working memory, a special form of short-term memory, which is vital when solving explicit task. Edelman has equated consciousness as the "remembered present" to highlight the importance of this form of memory (G.M. Edelman, Bright Air, Brilliant Fire, Basic Books, New York, 1992). The majority of other memories are recollections of past events that are encoded, stored, and brought back into consciousness if appropriate for solving new problems. Encoding prior experiences into memories is based on the salience of each event (A.R. Damasio, Descartes' Error, G.P. Putnam's Sons, New York, 1994; G.M. Edelman, Bright Air, Brilliant Fire, Basic Books, New York, 1992). It is proposed that protoplasmic astrocytes bind attended sensory information into consciousness and store encoded memories. This conclusion is supported by research conducted by gliobiologist over the past 15 years. Copyright 2002 Elsevier Science Ltd.
-
Renal amyloidosis: current views on pathogenesis and impact on diagnosis.
Herrera, Guillermo A; Teng, Jiamin; Turbat-Herrera, Elba A
2011-01-01
The amyloidoses constitute a group of diseases in which misfolding of extracellular proteins plays a fundamental role. The aggregation of normally soluble proteins into insoluble unbranching fibrils is the basic underlying pathology in amyloidosis. The process of amyloid formation generates toxic insoluble (in saline) protein aggregates that are deposited in tissues in the form of β- pleated sheets of fibrillary material. The amyloidoses are considered to be part of the so-called protein storage diseases (protein thesauroses). In addition, due to the unusual protein folding associated with amyloid, this group of diseases has been referred to as conformational and protein folding disorders. For many years amyloidosis was considered an extremely rare, somewhat mysterious disease. However, in recent years its pathogenesis, particularly that of renal amyloidosis, has been carefully dissected in the research laboratory using in vitro and, to a lesser extent, in vivo models. These have provided a molecular understanding of sequential events that take place in the renal mesangium leading to the formation of amyloid fibrils and eventual extrusion into the mesangial matrix, which itself becomes seriously damaged and, in due time, replaced by the fibrillary material. Amyloid, once considered to be an 'inert' substance, has been proven to be involved in crucial biological processes that result in the destruction and eventual replacement of normal renal constituents. Although there are more than two dozen recognized amyloid precursor proteins (and new ones being added to the list) that can be involved in the genesis of amyloid fibrils, the pathophysiologic mechanisms that occur in the renal mesangium are likely to be very similar, if not the same, regardless of the type of amyloidosis. Likewise, the same is true of amyloid formation in the renal vasculature. Mesangial cells are essentially smooth muscle cells and the events that take place in the mesangium and vasculature (where smooth muscle cells and/or pericytes are present) in the entire body responsible for the formation of amyloid are the same. In the renal interstitium, fibroblasts likely participate in the formation of amyloid, following a similar sequence of events as smooth muscle cells. Although much of the information gathered has been from in vitro systems, an in vivo model of renal amyloidosis has recently been designed to study renal amyloidogenesis. Crucial steps in the cascade of events that result in the formation of amyloid fibrils have been elucidated in the laboratory. The information that has been gathered regarding the pathogenesis of amyloidosis has been translated to the clinical arena where implementation of new therapeutic approaches is beginning to occur. Additional molecular-based therapies will be implemented in the near future. Copyright © 2011 S. Karger AG, Basel.
-
Bayse, Craig A; Merz, Kenneth M
2014-08-05
Understanding the mechanism of prenyltransferases is important to the design of engineered proteins capable of synthesizing derivatives of naturally occurring therapeutic agents. CloQ is a Mg(2+)-independent aromatic prenyltransferase (APTase) that transfers a dimethylallyl group to 4-hydroxyphenylpyruvate in the biosynthetic pathway for clorobiocin. APTases consist of a common ABBA fold that defines a β-barrel containing the reaction cavity. Positively charged basic residues line the inside of the β-barrel of CloQ to activate the pyrophosphate leaving group to replace the function of the Mg(2+) cofactor in other APTases. Classical molecular dynamics simulations of CloQ, its E281G and F68S mutants, and the related NovQ were used to explore the binding of the 4-hydroxyphenylpyruvate (4HPP) and dimethylallyl diphosphate substrates in the reactive cavity and the role of various conserved residues. Hybrid quantum mechanics/molecular mechanics potential of mean force (PMF) calculations show that the effect of the replacement of the Mg(2+) cofactor with basic residues yields a similar activation barrier for prenylation to Mg(2+)-dependent APTases like NphB. The topology of the binding pocket for 4HPP is important for selective prenylation at the ortho position of the ring. Methylation at this position alters the conformation of the substrate for O-prenylation at the phenol group. Further, a two-dimensional PMF scan shows that a "reverse" prenylation product may be a possible target for protein engineering.
-
Molecular pathology of adamantinomatous craniopharyngioma: review and opportunities for practice.
Apps, John Richard; Martinez-Barbera, Juan Pedro
2016-12-01
Since the first identification of CTNNB1 mutations in adamantinomatous craniopharyngioma (ACP), much has been learned about the molecular pathways and processes that are disrupted in ACP pathogenesis. To date this understanding has not translated into tangible patient benefit. The recent development of novel techniques and a range of preclinical models now provides an opportunity to begin to support treatment decisions and develop new therapeutics based on molecular pathology. In this review the authors summarize many of the key findings and pathways implicated in ACP pathogenesis and discuss the challenges that need to be tackled to translate these basic science findings for the benefit of patients.
-
Stochastic computing with biomolecular automata
Adar, Rivka; Benenson, Yaakov; Linshiz, Gregory; Rosner, Amit; Tishby, Naftali; Shapiro, Ehud
2004-01-01
Stochastic computing has a broad range of applications, yet electronic computers realize its basic step, stochastic choice between alternative computation paths, in a cumbersome way. Biomolecular computers use a different computational paradigm and hence afford novel designs. We constructed a stochastic molecular automaton in which stochastic choice is realized by means of competition between alternative biochemical pathways, and choice probabilities are programmed by the relative molar concentrations of the software molecules coding for the alternatives. Programmable and autonomous stochastic molecular automata have been shown to perform direct analysis of disease-related molecular indicators in vitro and may have the potential to provide in situ medical diagnosis and cure. PMID:15215499
-
DNA under Force: Mechanics, Electrostatics, and Hydration.
Li, Jingqiang; Wijeratne, Sithara S; Qiu, Xiangyun; Kiang, Ching-Hwa
2015-02-25
Quantifying the basic intra- and inter-molecular forces of DNA has helped us to better understand and further predict the behavior of DNA. Single molecule technique elucidates the mechanics of DNA under applied external forces, sometimes under extreme forces. On the other hand, ensemble studies of DNA molecular force allow us to extend our understanding of DNA molecules under other forces such as electrostatic and hydration forces. Using a variety of techniques, we can have a comprehensive understanding of DNA molecular forces, which is crucial in unraveling the complex DNA functions in living cells as well as in designing a system that utilizes the unique properties of DNA in nanotechnology.
-
Development of design information for molecular-sieve type regenerative CO2-removal systems
NASA Technical Reports Server (NTRS)
Wright, R. M.; Ruder, J. M.; Dunn, V. B.; Hwang, K. C.
1973-01-01
Experimental and analytic studies were conducted with molecular sieve sorbents to provide basic design information, and to develop a system design technique for regenerable CO2-removal systems for manned spacecraft. Single sorbate equilibrium data were obtained over a wide range of conditions for CO2, water, nitrogen, and oxygen on several molecular sieve and silica gel sorbents. The coadsorption of CO2 with water preloads, and with oxygen and nitrogen was experimentally evaluated. Mass-transfer, and some limited heat-transfer performance evaluations were accomplished under representative operating conditions, including the coadsorption of CO2 and water. CO2-removal system performance prediction capability was derived.
-
Hybrid quantum processors: molecular ensembles as quantum memory for solid state circuits.
Rabl, P; DeMille, D; Doyle, J M; Lukin, M D; Schoelkopf, R J; Zoller, P
2006-07-21
We investigate a hybrid quantum circuit where ensembles of cold polar molecules serve as long-lived quantum memories and optical interfaces for solid state quantum processors. The quantum memory realized by collective spin states (ensemble qubit) is coupled to a high-Q stripline cavity via microwave Raman processes. We show that, for convenient trap-surface distances of a few microm, strong coupling between the cavity and ensemble qubit can be achieved. We discuss basic quantum information protocols, including a swap from the cavity photon bus to the molecular quantum memory, and a deterministic two qubit gate. Finally, we investigate coherence properties of molecular ensemble quantum bits.
-
Resuscitation and Obstetrical Care to Reduce Intrapartum-Related Neonatal Deaths: A MANDATE Study.
Kamath-Rayne, Beena D; Griffin, Jennifer B; Moran, Katelin; Jones, Bonnie; Downs, Allan; McClure, Elizabeth M; Goldenberg, Robert L; Rouse, Doris; Jobe, Alan H
2015-08-01
To evaluate the impact of neonatal resuscitation and basic obstetric care on intrapartum-related neonatal mortality in low and middle-income countries, using the mathematical model, Maternal and Neonatal Directed Assessment of Technology (MANDATE). Using MANDATE, we evaluated the impact of interventions for intrapartum-related events causing birth asphyxia (basic neonatal resuscitation, advanced neonatal care, increasing facility birth, and emergency obstetric care) when implemented in home, clinic, and hospital settings of sub-Saharan African and India for 2008. Total intrapartum-related neonatal mortality (IRNM) was acute neonatal deaths from intrapartum-related events plus late neonatal deaths from ongoing intrapartum-related injury. Introducing basic neonatal resuscitation in all settings had a large impact on decreasing IRNM. Increasing facility births and scaling up emergency obstetric care in clinics and hospitals also had a large impact on decreasing IRNM. Increasing prevalence and utilization of advanced neonatal care in hospital settings had limited impact on IRNM. The greatest improvement in IRNM was seen with widespread advanced neonatal care and basic neonatal resuscitation, scaled-up emergency obstetric care in clinics and hospitals, and increased facility deliveries, resulting in an estimated decrease in IRNM to 2.0 per 1,000 live births in India and 2.5 per 1,000 live births in sub-Saharan Africa. With more deliveries occurring in clinics and hospitals, the scale-up of obstetric care can have a greater effect than if modeled individually. Use of MANDATE enables health leaders to direct resources towards interventions that could prevent intrapartum-related deaths. A lack of widespread implementation of basic neonatal resuscitation, increased facility births, and emergency obstetric care are missed opportunities to save newborn lives.
-
Synthetic Foveal Imaging Technology
NASA Technical Reports Server (NTRS)
Hoenk, Michael; Monacos, Steve; Nikzad, Shouleh
2009-01-01
Synthetic Foveal imaging Technology (SyFT) is an emerging discipline of image capture and image-data processing that offers the prospect of greatly increased capabilities for real-time processing of large, high-resolution images (including mosaic images) for such purposes as automated recognition and tracking of moving objects of interest. SyFT offers a solution to the image-data processing problem arising from the proposed development of gigapixel mosaic focal-plane image-detector assemblies for very wide field-of-view imaging with high resolution for detecting and tracking sparse objects or events within narrow subfields of view. In order to identify and track the objects or events without the means of dynamic adaptation to be afforded by SyFT, it would be necessary to post-process data from an image-data space consisting of terabytes of data. Such post-processing would be time-consuming and, as a consequence, could result in missing significant events that could not be observed at all due to the time evolution of such events or could not be observed at required levels of fidelity without such real-time adaptations as adjusting focal-plane operating conditions or aiming of the focal plane in different directions to track such events. The basic concept of foveal imaging is straightforward: In imitation of a natural eye, a foveal-vision image sensor is designed to offer higher resolution in a small region of interest (ROI) within its field of view. Foveal vision reduces the amount of unwanted information that must be transferred from the image sensor to external image-data-processing circuitry. The aforementioned basic concept is not new in itself: indeed, image sensors based on these concepts have been described in several previous NASA Tech Briefs articles. Active-pixel integrated-circuit image sensors that can be programmed in real time to effect foveal artificial vision on demand are one such example. What is new in SyFT is a synergistic combination of recent advances in foveal imaging, computing, and related fields, along with a generalization of the basic foveal-vision concept to admit a synthetic fovea that is not restricted to one contiguous region of an image.
-
The adverse outcome pathway (AOP) framework has been developed as a means for assembling scientifically defensible descriptions of how particular molecular perturbations, termed molecular initiating events (MIEs), can evoke a set of predictable responses at different levels of bi...
-
Design and construction of functional AAV vectors.
Gray, John T; Zolotukhin, Serge
2011-01-01
Using the basic principles of molecular biology and laboratory techniques presented in this chapter, researchers should be able to create a wide variety of AAV vectors for both clinical and basic research applications. Basic vector design concepts are covered for both protein coding gene expression and small non-coding RNA gene expression cassettes. AAV plasmid vector backbones (available via AddGene) are described, along with critical sequence details for a variety of modular expression components that can be inserted as needed for specific applications. Protocols are provided for assembling the various DNA components into AAV vector plasmids in Escherichia coli, as well as for transferring these vector sequences into baculovirus genomes for large-scale production of AAV in the insect cell production system.
-
Back to the Basics: Cnidarians Start to Fire
Bosch, Thomas C. G.; Klimovich, Alexander; Domazet-Lošo, Tomislav; Gründer, Stefan; Holstein, Thomas W.; Jékely, Gáspár; Miller, David J.; Murillo-Rincon, Andrea P.; Rentzsch, Fabian; Richards, Gemma S.; Schröder, Katja; Technau, Ulrich; Yuste, Rafael
2016-01-01
The nervous systems of cnidarians, pre-bilaterian animals that diverged close to the base of the metazoan radiation, are structurally simple and thus have great potential to inform us about basic structural and functional principles of neural circuits. Unfortunately, cnidarians have thus far been relatively intractable to electrophysiological and genetic techniques and consequently have been largely passed over by neurobiologists. However, recent advances in molecular and imaging methods are fueling a renaissance of interest in and research into cnidarians nervous systems. Here, we review current knowledge on the nervous systems of some cnidarian species and propose that researchers should seize this opportunity and undertake the study of this phylum as strategic experimental systems with great basic and translational relevance for neuroscience. PMID:28041633
-
Tamura, Koichi; Hayashi, Shigehiko
2015-07-14
Molecular functions of proteins are often fulfilled by global conformational changes that couple with local events such as the binding of ligand molecules. High molecular complexity of proteins has, however, been an obstacle to obtain an atomistic view of the global conformational transitions, imposing a limitation on the mechanistic understanding of the functional processes. In this study, we developed a new method of molecular dynamics (MD) simulation called the linear response path following (LRPF) to simulate a protein's global conformational changes upon ligand binding. The method introduces a biasing force based on a linear response theory, which determines a local reaction coordinate in the configuration space that represents linear coupling between local events of ligand binding and global conformational changes and thus provides one with fully atomistic models undergoing large conformational changes without knowledge of a target structure. The overall transition process involving nonlinear conformational changes is simulated through iterative cycles consisting of a biased MD simulation with an updated linear response force and a following unbiased MD simulation for relaxation. We applied the method to the simulation of global conformational changes of the yeast calmodulin N-terminal domain and successfully searched out the end conformation. The atomistically detailed trajectories revealed a sequence of molecular events that properly lead to the global conformational changes and identified key steps of local-global coupling that induce the conformational transitions. The LRPF method provides one with a powerful means to model conformational changes of proteins such as motors and transporters where local-global coupling plays a pivotal role in their functional processes.