Major Interest (major + interest)

Distribution by Scientific Domains
Distribution within Life Sciences

Selected Abstracts

Acute exercise reverses TRB3 expression in the skeletal muscle and ameliorates whole body insulin sensitivity in diabetic mice

A. Matos
Abstract Aim:, TRB3 became of major interest in diabetes research when it was shown to interact with and inhibit the activity of Akt. Conversely, physical exercise has been linked to improved glucose homeostasis. Thus, the current study was designed to investigate the effects of acute exercise on TRB3 expression and whole body insulin sensitivity in obese diabetic mice. Methods:, Male leptin-deficient (ob/ob) mice swam for two 3-h-long bouts, separated by a 45-min rest period. After the second bout of exercise, food was withdrawn 6 h before antibody analysis. Eight hours after the exercise protocol, the mice were submitted to an insulin tolerance test (ITT). Gastrocnemius muscle samples were evaluated for insulin receptor (IR) and IRS-1 tyrosine phosphorylation, Akt serine phosphorylation, TRB3/Akt association and membrane GLUT4 expression. Results:, Western blot analysis showed that TRB3 expression was reduced in the gastrocnemius of leptin-deficient (ob/ob) mice submitted to exercise when compared with respective ob/ob mice at rest. In parallel, there was an increase in the insulin-signalling pathway in skeletal muscle from leptin-deficient mice after exercise. Furthermore, the GLUT4 membrane expression was increased in the muscle after the exercise protocol. Finally, a single session of exercise improved the glucose disappearance (KITT) rate in ob/ob mice. Conclusion:, Our results demonstrate that acute exercise reverses TRB3 expression and insulin signalling restoration in muscle. Thus, these results provide new insights into the mechanism by which physical activity ameliorates whole body insulin sensitivity in type 2 diabetes. [source]

Investigating Academic Success Factors for Undergraduate Business Students

Mehdi Kaighobadi
ABSTRACT Student academic performance is of major interest to all stakeholders of higher education institutions. This study questions whether or not statistical analysis of information that is readily available in most universities' official records system can be used to predict overall academic success. In particular, this study is an attempt to understand factors that affect academic success for business students by examining gender, age, ethnicity, and performance in two required core knowledge courses as predictors of academic success for a large sample of undergraduate students at a Association to Advance Collegiate Schools of Business,accredited business school. The results suggest that student performance is significantly related to some basic demographic variables, but the strongest predictors of overall academic success are the grades the students receive in core knowledge courses that are typically taken in the earlier semesters of business students' plans of study. [source]

Effect of sialic acid content on glycoprotein pI analyzed by two-dimensional electrophoresis

Sílvia Barrabés
Abstract 2-DE is broadly used for quantitative analysis of differential protein expression in complex mixtures such as serum samples or cell lysates. PTMs directly influence the 2-DE pattern, and knowledge of the rules of protein separation is required in order to understand the protein distribution in a 2-DE gel. Glycosylation is the most common PTM and can modify both the molecular weight and the pI of a protein. In particular, the effect of charged monosaccharides (mainly sialic acids, SAs) on the 2-DE pattern of a protein is of major interest since changes in sialylation are regularly observed in comparative studies. Little is known about the pI shift of a glycoprotein induced by the presence of SAs, or whether this shift is the same for all glycoproteins. To address this issue, this study examined the influence of SA on the 2-DE pattern of three serum glycoproteins (haptoglobin, ,1-antitrypsin and ribonuclease 1), which N -glycan chains had been previously characterised, and reviewed existing bibliographic data. The SA content of the different glycoforms of a glycoprotein showed a negative linear correlation with the pI, although the slope varied among the studied glycoproteins. We also described a positive correlation between the protein pI and the pI decrease per SA molecule. [source]

The imbalance between Bim and Mcl-1 expression controls the survival of human myeloma cells

Patricia Gomez-Bougie
Abstract Multiple myeloma is a fatal B,cell malignancy characterized by the accumulation of plasma cells within the bone marrow. IL-6 is a major survival factor for myeloma cells. Bcl-2 protein family regulates pathways to apoptosis that are activated upon growth factor deprivation. Pro-apoptotic proteins that have only a single Bcl-2 homology domain, BH3-only, are potent inducers of apoptosis. In myeloma cells, Mcl-1 has been shown to be a major anti-apoptotic protein that appears to regulate cell survival through the JAK/STAT pathway. In this study, we examined the regulation of the BH3-only protein Bim and its interaction with Mcl-1. The three major Bim isoforms are expressed in myeloma cells and are negatively regulated by IL-6. Blockade of IL-6 signaling induces an up-regulation of Bim concomitant to Mcl-1 down-regulation. Of major interest, Bim is found strongly associated with Mcl-1 in viable myeloma cells while this interaction is disrupted under apoptosis induction. Of note, while Bim is also found strongly associated to Bcl-2, this interaction is not changed under apoptosis induction. Thus, in myeloma cells, Mcl-1 neutralizes Bim through complex formation and therefore prevents apoptosis. Under apoptosis induction, the disappearance of Mcl-1 allows Bim to exercise its pro-apoptotic function and to activate Bax. [source]

UMD-predictor, a new prediction tool for nucleotide substitution pathogenicity,application to four genes: FBN1, FBN2, TGFBR1, and TGFBR2,

HUMAN MUTATION, Issue 6 2009
Mélissa Yana Frédéric
Abstract Approximately half of gene lesions responsible for human inherited diseases are due to an amino acid substitution, showing that this mutational mechanism plays a large role in diseases. Distinguishing neutral sequence variations from those responsible for the phenotype is of major interest in human genetics. Because in vitro validation of mutations is not always possible in diagnostic settings, indirect arguments must be accumulated to define whether a missense variation is causative. To further differentiate neutral variants from pathogenic nucleotide substitutions, we developed a new tool, UMD-Predictor®. This tool provides a combinatorial approach that associates the following data: localization within the protein, conservation, biochemical properties of the mutant and wild-type residues, and the potential impact of the variation on mRNA. To evaluate this new tool, we compared it to the SIFT, PolyPhen, and SNAP software, the BLOSUM62 and Yu's Biochemical Matrices. All tools were evaluated using variations from well-validated datasets extracted from four UMD,LSDB databases (UMD,FBN1, UMD,FBN2, UMD,TGFBR1, and UMD,TGFBR2) that contain all published mutations of the corresponding genes, that is, 1,945 mutations, among which 796 different substitutions corresponding to missense mutations. Our results show that the UMD-Predictor® algorithm is the most efficient tool to predict pathogenic mutations in this context with a positive predictive value of 99.4%, a sensitivity of 95.4%, and a specificity of 92.2%. It can thus enhance the interpretation of variations in these genes, and could easily be applied to any other disease gene through the freely available UMD® generic software ( Hum Mutat 30:1,8, 2009. © 2009 Wiley-Liss, Inc. [source]

Nonlinear model predictive control for the polymorphic transformation of L -glutamic acid crystals

AICHE JOURNAL, Issue 10 2009
Martin Wijaya Hermanto
Abstract Polymorphism, a phenomenon where a substance can have more than one crystal forms, has recently become a major interest to the food, speciality chemical, and pharmaceutical industries. The different physical properties for polymorphs such as solubility, morphology, and dissolution rate may jeopardize operability or product quality, resulting in significant effort in controlling crystallization processes to ensure consistent production of the desired polymorph. Here, a nonlinear model predictive control (NMPC) strategy is developed for the polymorphic transformation of L -glutamic acid from the metastable ,-form to the stable ,-form crystals. The robustness of the proposed NMPC strategy to parameter perturbations is compared with temperature control (T-control), concentration control (C-control), and quadratic matrix control with successive linearization (SL-QDMC). Simulation studies show that T-control is the least robust, whereas C-control performs very robustly but long batch times may be required. SL-QDMC performs rather poorly even when there is no plant-model mismatch due to the high process nonlinearity, rendering successive linearization inaccurate. The NMPC strategy shows good overall robustness for two different control objectives, which were both within 7% of their optimal values, while satisfying all constraints on manipulated and state variables within the specified batch time. © 2009 American Institute of Chemical Engineers AIChE J, 2009 [source]

Functional ,glial' GLYT1 glycine transporters expressed in neurons

Luca Raiteri
J. Neurochem. (2010) 114, 647,653. Abstract Glycine transporter 1 (GLYT1) and GLYT2 are the glycine transporters in CNS. While GLYT2 is largely expressed in glycinergic neurons, GLYT1 has long been considered to be exclusively present in glial cells. There is increasing evidence that significant amounts of the ,glial' transporter also exist on neurons, particularly on pre-synaptic nerve endings of glutamatergic neurons. The functions of ,neuronal GLYT1' may be manifold and are discussed in this review. Of major interest are the interactions between neuronal GLYT1 and glutamatergic receptors of the NMDA type the activity of which is modulated not only by astrocytic GLYT1 but also by neuronal GLYT1. Pathophysiological roles and therapeutic implications of neuronal GLYT1 are emerging from recent studies with genetically modified mice, particularly with animals lacking forebrain neuron-specific GLYT1 transporters. These mutant mice exhibit promnesic phenotypes reflecting enhancement of NMDA receptor function, as it occurs following administration of GLYT1 inhibitors. Inactivation of neuronal GLYT1 in the forebrain may represent an effective therapeutic intervention for the treatment of schizophrenia. [source]

Adult human spinal cord harbors neural precursor cells that generate neurons and glial cells in vitro

C. Dromard
Abstract Adult human and rodent brains contain neural stem and progenitor cells, and the presence of neural stem cells in the adult rodent spinal cord has also been described. Here, using electron microscopy, expression of neural precursor cell markers, and cell culture, we investigated whether neural precursor cells are also present in adult human spinal cord. In well-preserved nonpathological post-mortem human adult spinal cord, nestin, Sox2, GFAP, CD15, Nkx6.1, and PSA-NCAM were found to be expressed heterogeneously by cells located around the central canal. Ultrastructural analysis revealed the existence of immature cells close to the ependymal cells, which display characteristics of type B and C cells found in the adult rodent brain subventricular region, which are considered to be stem and progenitor cells, respectively. Completely dissociated spinal cord cells reproducibly formed Sox2+ nestin+ neurospheres containing proliferative precursor cells. On differentiation, these generate glial cells and ,-aminobutyric acid (GABA)-ergic neurons. These results provide the first evidence for the existence in the adult human spinal cord of neural precursors with the potential to differentiate into neurons and glia. They represent a major interest for endogenous regeneration of spinal cord after trauma and in degenerative diseases. © 2008 Wiley-Liss, Inc. [source]

Performance of Atraumatic Restorative Treatment (ART) depending on operator-experience

Rainer A. Jordan MSc
Abstract Objectives: Oral health care is not of major interest in developing countries because of lack of infrastructure and professional manpower. Therefore, atraumatic restorative treatment (ART) was introduced by the World Health Organization to be performed by dental auxiliary personnel. The aim of this study was to evaluate the performance of ART depending on operator-experience in The Republic of The Gambia. Methods: One hundred twenty-eight newly inserted restorations were followed up for 12 months using the clinical ART index in a prospective and blinded study design. The patients were randomly assigned to operators. The clinical performance was compared among three groups: trainees, experienced Community Oral Health Workers (COHW), and professional dentists. The difference in success rates was calculated at a 95 percent confidence interval. Results: There was a statistically significant difference between trainees and dentists in performing leakage/gap-free one-surface restorations (P < 0.05). No significant differences were found between the two groups of auxiliaries (trainees versus experienced COHWs, P > 0.05). Finally, both groups , experienced COHWs and dentists , performed restorations not showing statistically significant differences (P > 0.05). Conclusions: For The Republic of The Gambia , especially for areas with underdeveloped medical infrastructure , training and assignment to perform ART can be recommended for auxiliary dental staff of Community Oral Health Workers. [source]

Regression analysis based on semicompeting risks data

Jin-Jian Hsieh
Summary., Semicompeting risks data are commonly seen in biomedical applications in which a terminal event censors a non-terminal event. Possible dependent censoring complicates statistical analysis. We consider regression analysis based on a non-terminal event, say disease progression, which is subject to censoring by death. The methodology proposed is developed for discrete covariates under two types of assumption. First, separate copula models are assumed for each covariate group and then a flexible regression model is imposed on the progression time which is of major interest. Model checking procedures are also proposed to help to choose a best-fitted model. Under a two-sample setting, Lin and co-workers proposed a competing method which requires an additional marginal assumption on the terminal event and implicitly assumes that the dependence structures in the two groups are the same. Using simulations, we compare the two approaches on the basis of their finite sample performances and robustness properties under model misspecification. The method proposed is applied to a bone marrow transplant data set. [source]

How to modulate inflammatory cytokines in liver diseases

Herbert Tilg
Abstract: Most acute and chronic liver diseases are characterized by inflammatory processes with enhanced expression of various pro- and anti-inflammatory cytokines in the liver. These cytokines are the driving force of many inflammatory liver disorders often resulting in fibrosis and cirrhosis. Severe alcoholic hepatitis is a prototypic tumor necrosis factor-, (TNF-,)-associated disease. This knowledge has recently led to pilot studies with promising results investigating specific anti-TNF drugs such as infliximab or etanercept in the treatment of this disease, although a recently performed controlled French study did show a potential detrimental effect of this approach. Anti-TNF treatment strategies might also improve chronic hepatitis C infection as shown by one controlled trial using etanercept administered subcutaneously for 24 weeks. Furthermore, several case reports suggest that TNF-, neutralization is not harmful to patients chronically infected with this virus. In contrast, neutralization of TNF-, worsens and might even be associated with fatalities in chronic hepatitis B infection. Anti-inflammatory cytokines such as interleukin-10 (IL-10) have also been tried in patients with chronic liver diseases. Whereas IL-10 administered to patients with chronic hepatitis C virus infection shows indeed anti-inflammatory effects in the liver, it seems to act as a proviral agent thereby limiting its clinical utility. Another cytokine with major anti-inflammatory potential is the adipokine adiponectin, as its administration is beneficial in many experimental models of liver injury. Interference with cytokine pathways and/or administration of anti-inflammatory cytokines will be of major interest in the future therapy of many liver diseases. [source]

Correlation of visinin-like-protein-1 expression with clinicopathological features in squamous cell carcinoma of the esophagus

Carla Wickborn
Abstract EF-hand Ca2+ -sensor proteins are key molecules for transducing Ca2+ signals into physiological answers and changes in cytosolic Ca2+ concentration control a variety of cellular responses, including proliferation, migration, and differentiation, which are relevant for tumor progression. The Ca2+ -sensor visinin-like protein-1 (VILIP-1) has recently attracted major interest due to its putative tumor suppressor function. Whereas VILIP-1 is expressed in normal skin, it is downregulated in skin tumors in a murine tumor model. The aim of this study was to investigate the expression of the Ca2+ -sensor VILIP-1 in squamous cell carcinoma of the esophagus and to correlate expression levels with clinicopathological features of the tumor. We examined VILIP-1 expression in 54 specimens of esophageal squamous cell carcinomas and 24 normal esophagus tissues, with immunohistochemical staining and immunofluorescence co-staining techniques. VILIP-1 expression was completely lost or significantly reduced in esophageal tumor tissue compared with normal squamous epithelium. Correlation with clinicopathological features indicated that there was significantly less VILIP-1 expression in lymph node positive (N,=,1) versus lymph node negative (N,=,0) tumors (P,=,0.002). Although there was no significant difference between highly (G1), moderately (G2) and poorly differentiated (G3) tumors (P,=,0.177), VILIP-1 expression in tumors is significantly correlated with the depth of tumor invasion (P,=,0.028 between T1, T2, T3, and T4). In contrast, co-staining with the proliferation marker Ki-67 indicated no significant correlation with proliferation rates in tumors (Ki-67 index of the tumor). In summary, the expression of the Ca2+ -sensor VILIP-1 was found to be lost during development of squamous cell carcinoma of the esophagus. The protein expression level significantly correlates with invasive features, such as depth of tumor invasion and local lymph node metastasis, but not with proliferation rate of tumor cells. © 2006 Wiley-Liss, Inc. [source]

Fine-scale genetic pattern and evidence for sex-biased dispersal in the túngara frog, Physalaemus pustulosus

Kathrin P. Lampert
Abstract Túngara frogs (Physalaemus pustulosus) are a model system for sexual selection and communication. Population dynamics and gene flow are of major interest in this species because they influence speciation processes and microevolution, and could consequently provide a deeper understanding of the evolutionary processes involved in mate recognition. Although earlier studies have documented genetic variation across the species' range, attempts to investigate dispersal on a local level have been limited to mark,recapture studies. These behavioural studies indicated high mobility at a scale of several hundred metres. In this study we used seven highly polymorphic microsatellite loci to investigate fine-scaled genetic variation in the túngara frog. We analysed the influence of geographical distance on observed genetic patterns, examined the influence of a river on gene flow, and tested for sex-biased dispersal. Data for 668 individuals from 17 populations ranging in distance from 0.26 to 11.8 km revealed significant levels of genetic differentiation among populations. Genetic differentiation was significantly correlated with geographic distance. A river acted as an efficient barrier to gene flow. Several tests of sex-biased dispersal were conducted. Most of them showed no difference between the sexes, but variance of Assignment Indices exhibited a statistically significant male bias in dispersal. [source]

Assessment of blood volume, vessel size, and the expression of angiogenic factors in two rat glioma models: a longitudinal in vivo and ex vivo study

Samuel Valable
Abstract Assessment of angiogenesis may help to determine tumor grade and therapy follow-up. In vivo imaging methods for non-invasively monitoring microvasculature evolution are therefore of major interest for tumor management. MRI evaluation of blood volume fraction (BVf) and vessel size index (VSI) was applied to assess the evolution of tumor microvasculature in two rat models of glioma (C6 and RG2). The results show that repeated MRI of BVf and VSI , which involves repeated injection of an iron-based MR contrast agent , does not affect either the physiological status of the animals or the accuracy of the MR estimates of the microvascular parameters. The MR measurements were found to correlate well with those obtained from histology. They indicate that microvascular evolution differs significantly between the two glioma models, in good agreement with expression of angiogenic factors (vascular endothelial growth factor, angiopoietin-2) and with activities of matrix metalloproteinases, also assessed in this study. These MRI methods thus provide considerable potential for assessing the response of gliomas to anti-angiogenic and anti-vascular agents, in preclinical studies as well as in the clinic. Furthermore, as differences between the fate of tumor microvasculature may underlie differences in therapeutic response, there is a need for preclinical study of several tumor models. Copyright © 2008 John Wiley & Sons, Ltd. [source]

Eisenhower, King Utopus, and the Fifties Decade in America

Philip Abbott
Assessment of presidential performance across time has become a major interest of students of the office. This article examines the reassessments of Dwight D. Eisenhower as a function of contested appraisals of the 1950s. The author shows that disagreements about the normative character of the decade are so starkly drawn that the fifties mimic the basic features of Utopian discourse. As such, assessments of Eisenhower's presidency parallel, admittedly in a secluded fashion, assessments of King Utopus, the founder of Utopia, as well as other founding figures in Utopian fiction. Of course, Eisenhower was not a Utopian founder; nor was his career identical to that of King Utopus. Nevertheless, we can profitably understand the differences and fluctuations in assessments of the Eisenhower presidency by utilizing this Utopian format. Not all decades are cast in this particular framework, but the case of Eisenhower illustrates the cultural complexity of assessments of presidential leadership. [source]

Synapses on NG2-expressing progenitors in the brain: multiple functions?

Vittorio Gallo
Progenitor cells expressing the proteoglycan NG2 represent approximately 5% of the total cells in the adult brain, and are found both in grey and white matter regions where they give rise to oligodendrocytes. The finding that these cells receive synaptic contacts from excitatory and inhibitory neurons has not only raised major interest in the possible roles of these synapses, but also stimulated further research on the developmental and cellular functions of NG2-expressing (NG2+) progenitors themselves in the context of neural circuit physiology. Here we review recent findings on the functional properties of the synapses on NG2+ cells in grey and white matter regions of the brain. In this review article we make an attempt to integrate current knowledge on the cellular and developmental properties of NG2+ progenitors with the functional attributes of their synapses, in order to understand the physiological relevance of neuron,NG2+ progenitor signal transmission. We propose that, although NG2+ progenitors receive synaptic contact in all brain regions where they are found, their synapses might have different developmental and functional roles, probably reflecting the distinct functions of NG2+ progenitors in the brain. [source]

Numerische Modellierungen mit einem zyklisch-viskoplastischen Stoffansatz für granulare Böden

BAUTECHNIK, Issue 1 2005
vormals Universität Kassel Tim Stöcker Dr.-Ing.
In der Geotechnik, insbesondere aber im Verkehrswegebau, gewinnt die Frage der Boden-Bauwerk-Interaktion bei nichtruhenden Lasteinwirkungen zunehmend an Bedeutung. Dabei stehen neben sicherheitsrelevanten Aspekten besonders Fragen zur Gebrauchstauglichkeit sowie wirtschaftliche Aspekte im Vordergrund. Ziel einer anwendungsorientierten Forschung muß daher die Entwicklung eines praxisorientierten Verfahrens zur ingenieurmäßigen Modellierung der Langzeitverformungen bzw. des Langzeitverhaltens des Baugrundes unter nichtruhender Belastung sein. Die dargestellten Arbeiten beschäftigen sich daher mit der Implementierung, Validierung und Anwendung eines neuen, im folgenden als "zyklisch-viskoplastisch" bezeichneten Stoffansatzes für granulare Böden unter nichtruhender Lasteinwirkung. Die wesentlichen Grundlagen dieses Ansatzes sind dabei im Heft 4, 2004, dieser Zeitschrift beschrieben, [1]. Das erreichte Ziel war, den Stoffansatz für numerische Berechnungsmodelle ingenieurmäßig aufzubereiten, zu implementieren, sowie das Berechnungsmodell zu verifizieren und auf reale Problemstellungen anzuwenden. Numerical modelling with a cyclic viscoplastic constitutive approach for granular soils. In modern Geotechnics, especially in track engineering, research for soil-structure interaction under cyclic loading has been gaining importance over the past decades. Next to states of system/structure failure, the long-term (deformation) behaviour is of major interest, as it has a major impact on e.g. maintenance costs in track engineering. Hence, the objective of this work is to be seen in the necessity of investigations on the long-term deformation behaviour of granular soils and ballast under cyclic loading. In the present paper the validation and implementation of a cyclic viscoplastic constitutive approach for granular under cyclic dynamic loading, [1], into a numerical model is carried out. The investigation and set up of a theoretical and physical complete model has not been intended. The objective rather is the development of an engineering type model, appropriate for practical tasks. Some modelling examples are given to illustrate modelling capacities. [source]

Die Grippe-Pandemie 1918,20 in der medizinischen Debatte,

Wilfried Witte Dr. med.
Abstract The Influenza Pandemic of 1918,20 in medical debate. The history of the so called Spanish Influenza 1918,1920 is summarized especially in regard to the developments in medical debate. In Germany, Richard Pfeiffer, who had discovered Haemophilus influenzae after the previous pandemic 1890 / 91, managed it to defend his thesis that his "bacillus" was the causative agent of the flu, by modifying his theory moderately. The Early Virology of influenza in postwar times was still fixed to bacteriology and did not yet have the force of school-building. Aggressive therapy, e.g. with derivatives of chinine, were used in a concept of polypragmasy. The connection between influenza in animals and influenza in mankind was unknown or of no major interest till the rise of virology as an academic discipline in the 1950s. Since the outbreak of avian influenza in Asia 1997 virological archaeology is challenged to fill the historical part in the attempt to fight the threat of the highly pathogenic bird flu. In the beginning of the "short 20. century" politicians and doctors had no interest to build a "monument" of influenza. Today, virological reductionism does not have the power to (re-)construct such a monument. [source]

Long-distance signals influence assessment of close range mating displays in the field cricket, Gryllus integer

Male sexual displays often include components detected across long distances, and those perceived only at close range. Understanding what information females gain from each component of a complex display and how they use these signals to make decisions are questions of major interest in sexual selection research. We evaluated content-based hypotheses (,redundant signals' and ,multiple messages') for the courtship displays of field crickets (Gryllus integer) by measuring female responses to males' long-distance calling song (calls) and close-range chemical cues. Females' responses to a male's calls and chemical cues were uncorrelated, supporting the ,multiple messages' hypothesis. We also tested the ,inter-signal interaction' hypothesis by investigating how long-distance calls influence evaluation of close-range courtship. The relationship between long- and close-range signals was complex and conditional: females accepted close-range courtship more quickly after exposure to attractive calling song than they did after exposure to either unattractive calling song or silence, and unattractive calls were no more or less effective than silence. This inter-signal interaction could affect our understanding of mate choice in species with multiple mating signals because it implies that females may save time and energy by not assessing the close-range signals of attractive long-distance signalers. © 2010 The Linnean Society of London, Biological Journal of the Linnean Society, 2010, 100, 856,865. [source]

Some contributions to the analysis of multivariate data

Arne C. Bathke
Abstract In this paper, we provide an overview of recently developed methods for the analysis of multivariate data that do not necessarily emanate from a normal universe. Multivariate data occur naturally in the life sciences and in other research fields. When drawing inference, it is generally recommended to take the multivariate nature of the data into account, and not merely analyze each variable separately. Furthermore, it is often of major interest to select an appropriate set of important variables. We present contributions in three different, but closely related, research areas: first, a general approach to the comparison of mean vectors, which allows for profile analysis and tests of dimensionality; second, non-parametric and parametric methods for the comparison of independent samples of multivariate observations; and third, methods for the situation where the experimental units are observed repeatedly, for example, over time, and the main focus is on analyzing different time profiles when the number p of repeated observations per subject is larger than the number n of subjects. [source]

Semiparametric Regression in Size-Biased Sampling

BIOMETRICS, Issue 1 2010
Ying Qing Chen
Summary Size-biased sampling arises when a positive-valued outcome variable is sampled with selection probability proportional to its size. In this article, we propose a semiparametric linear regression model to analyze size-biased outcomes. In our proposed model, the regression parameters of covariates are of major interest, while the distribution of random errors is unspecified. Under the proposed model, we discover that regression parameters are invariant regardless of size-biased sampling. Following this invariance property, we develop a simple estimation procedure for inferences. Our proposed methods are evaluated in simulation studies and applied to two real data analyses. [source]

In this issue: Biotechnology Journal 11/2009

Article first published online: 13 NOV 200
Forensic identification on chips Choi and Seo et al., Biotechnol. J. 2009, 4, 1530,1541 Short tandem repeat (STR) analysis can be used for genetic fingerprinting of individuals as it is done for forensic human identification. However, the current state-of-the-art STR genotyping processes and instruments are labor intensive, expensive, time consuming, and lack portability. Micro-total-analysis systems or lab-on-a-chip platforms based on microfabrication technologies have the capability to miniaturize and integrate bioanalysis steps in a single format and have already been successfully applied for forensic STR typing. Researchers from Daejeon, Korea, highlight up-to-date work on advanced microdevices for high-throughput STR genotyping, and a portable integrated microsystem for on-site forensic DNA analysis. Surface plasmon resonance on chips Maynard et al., Biotechnol. J. 2009, 4, 1542,1558 Technologies based on surface plasmon resonance (SPR) have allowed rapid, label-free characterization of protein-protein and protein-small molecule interactions. SPR has become the gold standard in industrial and academic settings, in which the interaction between a pair of soluble binding partners is characterized in detail or a library of molecules is screened for binding against a single soluble protein. In spite of these successes, SPR is only beginning to be adapted to the needs of membrane-bound proteins which are promising targets for drug and biomarker development. This team of authors from Austin, Minneapolis and Rochester (all USA) describe current SPR instrumentation and the potential for SPR nanopore arrays to enable quantitative, high-throughput screening of G-protein coupled receptor ligands and applications in cellular biology. Nucleotide immobilization on chips Sethi et al., Biotechnol. J. 2009, 4, 1513,1529 The development of oligonucleotide-based microarrays (biochips) is of major interest in science and biotechnology industry and has applications in a wide range of research areas including genomics, proteomics, computational biology and pharmaceuticals. Especially microarrays have proven to be a unique method for time and cost efficient analysis of thousands of genes at one. Authors from Delhi and Lucknow, India discuss currently used chemical strategies for immobilization of oligonucleotides and put a special emphasis on post-synthetic immobilization on glass surfaces. Recent advances on these synthesis pathways are presented in detail. [source]

Using information technology to improve surgical safety

D. W. Bates
Patient Safety Leading Article Series, 2004 Dr David W Bates of Harvard Medical School, and Brigham and Women's Hospital, Boston, has for some years had a major interest in information technology in healthcare. Here, he continues our ,Patient Safety' series of leading articles, exploring how the tools of the modern era can help avoid harm in the surgical arena. Copyright © 2004 British Journal of Surgery Society Ltd. Published by John Wiley & Sons, Ltd. [source]

Synthesis of S -Adenosyl- L -homocysteine Capture Compounds for Selective Photoinduced Isolation of Methyltransferases

CHEMBIOCHEM, Issue 2 2010
Christian Dalhoff Dr.
Abstract Understanding the interplay of different cellular proteins and their substrates is of major interest in the postgenomic era. For this purpose, selective isolation and identification of proteins from complex biological samples is necessary and targeted isolation of enzyme families is a challenging task. Over the last years, methods like activity-based protein profiling (ABPP) and capture compound mass spectrometry (CCMS) have been developed to reduce the complexity of the proteome by means of protein function in contrast to standard approaches, which utilize differences in physical properties for protein separation. To isolate and identify the subproteome consisting of S -adenosyl- L -methionine (SAM or AdoMet)-dependent methyltransferases (methylome), we developed and synthesized trifunctional capture compounds containing the chemically stable cofactor product S -adenosyl- L -homocysteine (SAH or AdoHcy) as selectivity function. SAH analogues with amino linkers at the N6 or C8 positions were synthesized and attached to scaffolds containing different photocrosslinking groups for covalent protein modification and biotin for affinity isolation. The utility of these SAH capture compounds for selective photoinduced protein isolation is demonstrated for various methyltransferases (MTases) acting on DNA, RNA and proteins as well as with Escherichia coli cell lysate. In addition, they can be used to determine dissociation constants for MTase,cofactor complexes. [source]

Development of H1e histone linker-specific antibodies by means of synthetic peptides

K. Foulon
Abstract:, A large body of data suggests that the linker histones family (H1) affects gene expression. Investigation of the linker histones role is then of a major interest in cell cycle studies with implications in gene therapy. Indeed, it has been shown that in most tissues a switch of histone subtypes occurs when the cells cease to divide. To investigate linker histone role in gene or transgene expression, an antibody against subtypes of H1 would be useful for immunoprecipitation experiments and further assays measuring H1subtypes,DNA interactions in living cells. In order to produce an antibody against the H1e subtype of linker histones, two synthetic peptides derived from two regions of the H1e mouse histone protein were examined for their potential, [as keyhole limpet hemocyanin (KLH) conjugates] to elicit polyclonal anti-H1e antibodies in New Zealand white rabbits. Selection of the peptide sequences was based on amino acid differences within the different classes of histones and between mice and rabbit histones as well. The evaluation of their potential immunogenic properties was based on examination of peptide hydropathy using predicting algorithms. Immunoglobulins (IgG) obtained from immunized and nonimmunized rabbits were tested using enzyme-linked immunosorbent assay (ELISA) procedures, Western immunoblot, and immunofluorescence experiments. Results showed that the selected synthetic peptides gave rise to a high-titer polyclonal antibody able to recognize the H1e histone under various conditions. This polyclonal antibody did not cross-react with other histones. To our knowledge, this is the first antibody produced against the mouse H1e linker histone. [source]

Oncogenes in thyroid cancer

D.S. Kim
There have been significant advances in our understanding of carcinogenesis at the molecular level over the last 25 years. Oncogenes are of major interest as part of our search for knowledge surrounding the aetiology of cancer. There are several oncogenes associated with thyroid cancer. Detailed investigation of the nature and function of these tumour genes has provided important insights into both the tumour biology and the complex biochemical pathways of normal cellular functioning. Our knowledge of oncogene biology offers the hope of better diagnostic, therapeutic and prognostic modalities in our fight against this and other common cancers. Development of specific thyroid tumour markers and gene therapy is now a realistic prospect to supplement our present armamentarium of surgery and radiotherapy. This review aims to outline the pertinent information gained so far from studies of these oncogenes and provides both clinical relevance and fuel for further interest amongst the ENT thyroid community in this exciting area of research. [source]


James D. Marshall
In this essay, James D. Marshall aims to present Beauvoir, not as a mere entry in the history of French philosophy, nor as an under-laborer to Jean-Paul Sartre, but as someone who has important philosophical insights to contribute to ongoing debates on the human condition, including those concerned with education. Central to these debates are issues such as what does it mean to be an individual human being and what characterizes the relations between individuals and others and between individuals and society. Marshall argues that Beauvoir can participate in such philosophical and educational debates, for philosophy of education has major interests in such questions as who or what is this "person" whom we profess to be educating, what kind of person or outcome of education is desirable, and in what kind of society should these individuals take part? [source]