bluuebunny/crossref_metadata_2025 huggingface dataset:
Isolation and detection of Mycobacterium avium subsp. paratuberculosis (MAP) from cattle in Ireland using both traditional culture and molecular based methods
Authors: Douarre Pierre E , Cashman William , Buckley Jim , Coffey Aidan , O'Mahony Jim M
Published: September 2010

Background

Mycobacterium avium subsp. paratuberculosis (MAP) causes a chronic gastroenteritis affecting many species. Johne's disease is one of the most widespread and economically important disease of ruminants. Since 1992 and the opening of the European market, the exposure and the transmission of MAP in cattle herds considerably increased. Improvements in diagnostic strategies for Ireland and elsewhere are urgently required. In total, 290 cattle from seven Irish herds with either a history or a strong likelihood of paratuberculosis infection were selected by a veterinary team over 2 years. Faecal samples (290) were collected and screened for MAP by a conventional culture method and two PCR assays. In order to further evaluate the usefulness of molecular testing, a nested PCR was also assessed.

Results

M. paratuberculosis was isolated and cultured from 23 faecal samples (7.9%) on solid medium. From a molecular perspective, 105 faecal samples (36%) were PCR positive for MAP specific DNA. A complete correlation (100%) was observed between the results of both molecular targets (IS900 and ISMAP02). Sensitivity was increased by ~10% with the inclusion of a nested PCR for ISMAP02 (29 further samples were positive). When culturing and PCR were retrospectively compared, every culture positive faecal sample also yielded a PCR positive result for both targets. Alternatively, however not every PCR positive sample (n = 105, 36%) produced a corresponding culture isolate. Interestingly though when analysed collectively at the herd level, the correlation between culture and PCR results was 100% (ie every herd which recorded at least 1 early PCR +ve result later yielded culture positive samples within that herd).

Conclusion

PCR on bovine faecal samples is a fast reliable test and should be applied routinely when screening for MAP within herds suspected of paratuberculosis. Nested PCR increases the threshold limit of detection for MAP DNA by approximately 10% but proved to be problematic in this study. Although slow and impractical, culturing is still regarded as one of the most reliable methods for detecting MAP among infected cattle.
Validity of clinical associations of biomarkers in translational research studies: the case of systemic autoimmune diseases
Authors: Tektonidou Maria G , Ward Michael M
Published: September 2010

Introduction

Validity of biomarkers may be affected if studies do not include certain features in their design. We evaluated whether translational research studies of potential biomarkers incorporated design features important for valid clinical associations.

Methods

We searched 10 journals for translational studies in six systemic autoimmune diseases published in 2004 through 2009. We included studies that reported associations between laboratory markers and the presence of disease, measures of disease activity, or prognosis. We examined the following design features: age, sex, and race matching; control for effects of treatment on expression of the biomarker; inclusion of patients with both early and late disease, or both active and inactive disease; longitudinal or cross-sectional design; and use of validated activity and damage measures.

Results

Among 170 articles, 156 articles examined potential biomarkers for diagnosis, 37 for disease activity assessment, and nine for prognosis; 67 were studies of rheumatoid arthritis (RA); 48, of systemic lupus erythematosus; and 41, of other diseases. Gene-expression profiles were the most commonly examined potential biomarkers (n = 51). Fewer than one half of studies incorporated study-design features important for valid clinical associations. Only 47.4% of studies of biomarkers for diagnosis had groups that were age-matched, 45.5% were sex-matched, and 35.3% controlled for treatment. Studies that examined biomarkers in histologic samples and studies of RA were less likely to include important design features.

Conclusions

Fewer than one half of translational studies of potential biomarkers incorporated design features needed for valid interpretation of clinical associations. Attention to these features could reduce false-positive and false-negative associations.
Sublingual microcirculatory changes during high-volume hemofiltration in hyperdynamic septic shock patients
Authors: Ruiz Carolina , Hernandez Glenn , Godoy Cristian , Downey Patricio , Andresen Max , Bruhn Alejandro
Published: September 2010

Introduction

Previous studies have suggested that high volume hemofiltration (HVHF) may contribute to revert hypotension in severe hyperdynamic septic shock patients. However, arterial pressure stabilization occurs due to an increase in systemic vascular resistance, which could eventually compromise microcirculatory blood flow and perfusion. The goal of this study was to determine if HVHF deteriorates sublingual microcirculation in severe hyperdynamic septic shock patients.

Methods

This was a prospective, non-randomized study at a 16-bed, medical-surgical intensive care unit of a university hospital. We included 12 severe hyperdynamic septic shock patients (norepinephrine requirements > 0.3 μg/kg/min and cardiac index > 3.0 L/min/m2) who underwent a 12-hour HVHF as a rescue therapy according to a predefined algorithm. Sublingual microcirculation (Microscan for NTSC, Microvision Medical), systemic hemodynamics and perfusion parameters were assessed at baseline, at 12 hours of HVHF, and 6 hours after stopping HVHF.

Results

Microcirculatory flow index increased after 12 hours of HVHF and this increase persisted 6 hours after stopping HVHF. A similar trend was observed for the proportion of perfused microvessels. The increase in microcirculatory blood flow was inversely correlated with baseline levels. There was no significant change in microvascular density or heterogeneity during or after HVHF. Mean arterial pressure and systemic vascular resistance increased while lactate levels decreased after the 12-hour HVHF.

Conclusions

The use of HVHF as a rescue therapy in patients with severe hyperdynamic septic shock does not deteriorate sublingual microcirculatory blood flow despite the increase in systemic vascular resistance.
Delirium as a predictor of sepsis in post-coronary artery bypass grafting patients: a retrospective cohort study
Authors: Martin Billie-Jean , Buth Karen J , Arora Rakesh C , Baskett Roger JF
Published: September 2010

Introduction

Delirium is the most common neurological complication following cardiac surgery. Much research has focused on potential causes of delirium; however, the sequelae of delirium have not been well investigated. The objective of this study was to investigate the relationship between delirium and sepsis post coronary artery bypass grafting (CABG) and to determine if delirium is a predictor of sepsis.

Methods

Peri-operative data were collected prospectively on all patients. Subjects were identified as having agitated delirium if they experienced a short-term mental disturbance marked by confusion, illusions and cerebral excitement. Patient characteristics were compared between those who became delirious and those who did not. The primary outcome of interest was post-operative sepsis. The association of delirium with sepsis was assessed by logistic regression, adjusting for differences in age, acuity, and co-morbidities.

Results

Among 14,301 patients, 981 became delirious and 227 developed sepsis post-operatively. Rates of delirium increased over the years of the study from 4.8 to 8.0% (P = 0.0003). A total of 70 patients of the 227 with sepsis, were delirious. In 30.8% of patients delirium preceded the development of overt sepsis by at least 48 hours. Multivariate analysis identified several factors associated with sepsis, (receiver operating characteristic (ROC) 79.3%): delirium (odds ratio (OR) 2.3, 95% confidence interval (CI) 1.6 to 3.4), emergent surgery (OR 3.3, CI 2.2 to 5.1), age (OR 1.2, CI 1.0 to 1.3), pre-operative length of stay (LOS) more than seven days (OR 1.6, CI 1.1 to 2.3), pre-operative renal insufficiency (OR 1.9, CI 1.2 to 2.9) and complex coronary disease (OR 3.1, CI 1.8 to 5.3).

Conclusions

These data demonstrate an association between delirium and post-operative sepsis in the CABG population. Delirium emerged as an independent predictor of sepsis, along with traditional risk factors including age, pre-operative renal failure and peripheral vascular disease. Given the advancing age and increasing rates of delirium in the CABG population, the prevention and management of delirium need to be addressed.
Clinical Outcome of Children With Newly Diagnosed Philadelphia Chromosome–Positive Acute Lymphoblastic Leukemia Treated Between 1995 and 2005
Authors: Aricò Maurizio , Schrappe Martin , Hunger Stephen P. , Carroll William L. , Conter Valentino , Galimberti Stefania , Manabe Atsushi , Saha Vaskar , Baruchel André , Vettenranta Kim , Horibe Keizo , Benoit Yves , Pieters Rob , Escherich Gabriele , Silverman Lewis B. , Pui Ching-Hon , Valsecchi Maria Grazia
Published: September 2010

Purpose

In a previous analysis of 326 children with Philadelphia chromosome (Ph) –positive acute lymphoblastic leukemia (ALL) treated between 1986 and 1996, hematopoietic stem-cell transplantation from HLA-matched related donors, but not from unrelated donors, offered a superior outcome than chemotherapy alone. To evaluate the impact of recent improvements in chemotherapy and transplantation, we performed a similar analysis on patients treated in the following decade.

Patients and Methods

We analyzed 610 patients with Ph-positive ALL treated between 1995 and 2005 without tyrosine kinase inhibitor therapy. The median follow-up duration was 6.3 years.

Results

Complete remission was achieved in 89% of patients. The 7-year event-free survival and overall survival rates were superior in the present cohort compared with the previous cohort (32.0% ± 2.0% v 25.0% ± 3.0, respectively, P = .007; and 44.9% ± 2.2% v 36.0% ± 3.0%, respectively, P = .017). Compared with chemotherapy alone, transplantation with matched related donors or unrelated donors in first remission (325 patients) showed an advantage with increasing follow-up, suggesting greater protection against late relapses (hazard ratio at 5 years, 0.37; P < .001). In the multivariate Cox regression analysis accounting for treatment (transplantation v no transplantation), age, leukocyte count, and early response had independent impact on treatment outcome.

Conclusion

Clinical outcome of children and adolescents with Ph-positive ALL has improved with advances in transplantation and chemotherapy. Transplantations with matched related donors and unrelated donors were equivalent and offered better disease control compared with chemotherapy alone. Age, leukocyte count, and early treatment response were independent prognostic indicators. The results of this study will serve as a historical reference to evaluate the therapeutic impact of tyrosine kinase inhibitors on the outcome of Ph-positive ALL.
Mouse models of cancer as biological filters for complex genomic data
Authors: Oricchio Elisa , Wolfe Andrew L. , Schatz Jonathan H. , Mavrakis Konstantinos J. , Wendel Hans-Guido
Published: September 2010

Genetically and pathologically accurate mouse models of leukemia and lymphoma have been developed in recent years. Adoptive transfer of genetically modified hematopoietic progenitor cells enables rapid and highly controlled gain- and loss-of-function studies for these types of cancer. In this Commentary, we discuss how these highly versatile experimental approaches can be used as biological filters to pinpoint transformation-relevant activities from complex cancer genome data. We anticipate that the functional identification of genetic ‘drivers’ using mouse models of leukemia and lymphoma will facilitate the development of molecular diagnostics and mechanism-based therapies for patients that suffer from these diseases.
The zebrafish embryo as a model for assessing off-target drug effects
Authors: Strähle Uwe , Grabher Clemens
Published: September 2010

Although first used experimentally for the genetic analysis of vertebrate development and neurobiology, the zebrafish has been adapted as a model for many human diseases. In recent years, the zebrafish embryo has increasingly attracted the attention of chemists and pharmacologists for its utility in identifying chemicals with pharmacological activity in a whole-animal context. Its experimental virtues make it an ideal system with which to identify new bioactive molecules, and to assess their toxicity and teratogenicity at medium-to-high throughput. More recently, the zebrafish embryo has been applied to identify off-target effects of drug candidates. Here, we discuss the value of the zebrafish embryo for detecting off-target effects, and propose that this model could be useful for improving the efficiency of the drug-development pipeline.
A Variational Monte Carlo Study of Positronic Compounds Using Inhomogeneous Backflow Transformations
Authors: Kita Yukiumi , Tachikawa Masanori , Drummond Neil D , Needs Richard J
Published: September 2010

A variational Monte Carlo study using inhomogeneous backflow transformations is reported for the [H−;e+] and [Li−;e+] positronic compounds. The backflow transformations greatly improve the total energies, positron affinities, and two-photon annihilation rates. The Slater–Jastrow-backflow trial wave function is well suited to the theoretical analysis of positronic compounds.
Electrocatalytic O2 Evolution from Water at an ITO Electrode Modified with [Ru(terpy){4,4′-(CH2PO3H2)2-2,2′-bpy}(OH2)]2+: Evidence for a Unimolecular Pathway
Authors: Kiyota Josaku , Yokoyama Junpei , Yoshida Masaki , Masaoka Shigeyuki , Sakai Ken
Published: September 2010

An ITO (indium tin oxide) electrode modified with [Ru(terpy){4,4′-(CH2PO3H2)2-2,2′-bpy}(OH2)]2+ was prepared to gain insight into the mechanism of O2 evolution from water catalyzed by a series of mononuclear aquaruthenium complexes, such as [Ru(terpy)(bpy)(OH2)]2+. The modified ITO electrode showed a clear decrease in overpotential for O2 evolution (1.35 V in an aqueous 0.1 M Na2SO4/H2SO4 solution, pH 4.0), indicating that the O2 evolution proceeds in a unimolecular fashion without having any intermolecular associations.
Molecular recognition and switching via radical dimerization
Authors: Spruell Jason M.
Published: September 2010

This article highlights the emerging use of the interactions of radical π-dimers to drive both molecular recognition and switching processes within supramolecular systems and mechanically interlocked molecular architectures. The enhanced stability experienced by dimers of radical cation species when encapsulated, as compared to when they are free in solution, is driving their useful incorporation into functional systems. The redox stimulation used in the production of radical cation species provides the ideal trigger for molecular switching events. Moreover, the nature and strength of the radical dimerization events introduces a completely novel recognition motif within supramolecular and mechanically interlocked molecular systems, complementing well-established techniques and enabling new research opportunities to blossom.
Efficient Single Muscle Fiber Isolation from Alcohol-Fixed Adult Muscle following β-Galactosidase Staining for Satellite Cell Detection
Authors: Verma Mayank , Asakura Atsushi
Published: September 2010

Staining for β-galactosidase activity for whole tissues, sections, and cells is a common method to detect expression of β- galactosidase reporter transgene as well as senescence-dependent β-galactosidase activity. Choice of fixatives is a critical step for detection of β-galactosidase activity, subsequent immunostaining, and enzymatic digestion of tissue to dissociate cells. In this report, the authors examined several aldehyde and alcohol fixatives in mouse skeletal muscle tissues for their efficiency at improving detection of β-galactosidase activity as well as detection by immunostaining. In addition, fixatives were also analyzed for their efficiency for collagenase digestion to isolate single muscle fibers on postfixed β-galactosidase-stained whole skeletal muscle tissues. The results show that fixing cells with isopropanol yields the greatest reliability and intensity in both β-galactosidase staining as well as double staining for β-galactosidase activity and antibodies. In addition, isopropanol and ethanol, but not glutaraldehyde or paraformaldehyde, allow for the isolation of single muscle fibers from the diaphragm and tibialis anterior muscles following postfixed β-galactosidase staining. Using this method, it is possible to identify the amount of cells that occupy the satellite cell compartment in single muscle fibers prepared from any muscle tissues, including tibialis anterior muscle and diaphragm.
A Novel Approach to Genetic and Environmental Analysis of Cross-Lagged Associations Over Time: The Cross-Lagged Relationship Between Self-Perceived Abilities and School Achievement is Mediated by Genes as Well as the Environment
Authors: Luo Yu L. L. , Haworth Claire M. A. , Plomin Robert
Published: September 2010

Using longitudinal cross-lagged analysis to infer causal directions of reciprocal effects is one of the most important tools in the developmental armamentarium. The strength of these analyses can be enhanced by analyzing the genetic and environmental aetiology underlying cross-lagged relationships, for which we present a novel approach here. Our approach is based on standard Cholesky decomposition. Standardized path coefficients are employed to assess genetic and environmental contributions to cross-lagged associations. We indicate how our model differs importantly from another approach that does not in fact analyze genetic and environmental contributions to cross-lagged associations. As an illustration, we apply our approach to the analysis of the cross-lagged relationships between self-perceived abilities and school achievement from age 9 to age 12. Self-perceived abilities of 3852 pairs of twins from the UK Twins Early Development Study were assessed using a self-report scale. School achievement was assessed by teachers based on UK National Curriculum criteria. The key cross-lagged association between self-perceived abilities at age 9 and school achievement at age 12 was mediated by genetic influences (28%) as well as shared (55%) and non-shared (16%) environment. The reverse cross-lagged association from school achievement at 9 to self-perceived abilities at 12 was primarily genetically mediated (73%). Unlike the approach to cross-lagged genetic analysis used in recent research, our approach assesses genetic and environmental contributions to cross-lagged associations per se. We discuss implications of finding that genetic factors contribute to the cross-lag between self-perceived abilities at age 9 and school achievement at age 12.
Are There Sex Differences in the Genetic and Environmental Effects on Mental Rotation Ability?
Authors: Vuoksimaa Eero , Viken Richard J. , Hokkanen Laura , Tuulio-Henriksson Annamari , Rose Richard J. , Kaprio Jaakko
Published: September 2010

Probably the most robust sex difference in cognitive abilities is that on average males outperform females in tests of mental rotation. Using twin data we tested whether there are sex differences in the magnitude of genetic and environmental effects on mental rotation test performance and whether the same or different genetic effects operate in females and males. The present study replicated the well-known male advantage in mental rotation ability. The relative proportion of variance explained by genetic effects did not differ between females and males, but interestingly, absolute additive genetic and unique environmental variances were greater in males reflecting significantly greater phenotypic variance in mental rotation test performance in males. Over half of the variance in mental rotation test performance was explained by genetic effects, which suggest that mental rotation ability is a good phenotype for studies finding genes underlying spatial abilities. Results indicate that females and males could be combined for such genetic studies, because the same genetic effects affected mental rotation test performance in females and males.
Failure to Confirm CNVs as of Aetiological Significance in Twin Pairs Discordant for Schizophrenia
Authors: Ono Shinji , Imamura Akira , Tasaki Shinya , Kurotaki Naohiro , Ozawa Hiroki , Yoshiura Koh-ichiro , Okazaki Yuji
Published: September 2010

Copy number variations (CNVs) are common structural variations in the human genome that strongly affect genomic diversity and can play a role in the development of several diseases, including neurodevelopmental disorders. Recent reports indicate that monozygotic twins can show differential CNV profiles. We searched CNVs in monozygotic twins discordant for schizophrenia to identify susceptible loci for schizophrenia. Three pairs of monozygotic twins discordant for schizophrenia were subjected to analysis. Genomic DNA samples were extracted from peripheral blood lymphocytes. We adopted the Affymetrix Genome-Wide Human SNP (Single Nucleotide Polymorphism) Array 6.0 to detect copy number discordance using Partek Genomics Suite 6.5 beta. In three twin pairs, however, validations by quantitative PCR and DNA sequencing revealed that none of the regions had any discordance between the three twin pairs. Our results support the hypothesis that epigenetic changes or fluctuation in developmental process triggered by environmental factors mainly contribute to the pathogenesis of schizophrenia. Schizophrenia caused by strong genetics factors including copy number alteration or gene mutation may be a small subset of the clinical population.
A Longitudinal Study on Genetic and Environmental Influences on Leisure Time Physical Activity in the Finnish Twin Cohort
Authors: Aaltonen Sari , Ortega-Alonso Alfredo , Kujala Urho M. , Kaprio Jaakko
Published: September 2010

The purpose of this study was to examine changes in the contribution of genetic and environmental influences to leisure time physical activity among male and female twins over a 6-year follow-up. At baseline the sample comprised 4,280 monozygotic and 9,276 dizygotic twin individuals, and at follow-up 4,383 monozygotic and 9,439 dizygotic twin individuals. Participants were aged 18–54 years at baseline. Genetic modeling results showed that genetic influences on leisure time physical activity declined from baseline (44%) to follow-up (34%). Most of the genetic influences identified at baseline were present at followup (rg= 0.72). Specific environmental influences increased from baseline (56%) to follow-up (66%) while at follow-up new environmental time-specific influences were observed (re= 0.23). The model with sex differences showed a higher estimate of genetic influences for men than women both at baseline (men 47% vs. women 42%) and at follow-up (men 38% vs. women 31%). The additive genetic correlation for this phenotype was greater for men (rg= 0.79) than women (rg= 0.64). The specific environmental influences were corresponding; at baseline men 53% and women 56% and at follow-up men 62 % and women 69%. The environmental correlations between the two time points were similar for men (re= 0.21) and for women (re= 0.24). In conclusion, in a sample of healthy twins most of the genetic influences on leisure time physical activity expressed at baseline were present at 6 years of follow-up. New specific environmental factors underlying follow-up leisure time physical activity were observed.
Digital Dermatoglyphic Heritability Differences as Evidenced by a Female Twin Study
Authors: Machado João Felipe , Fernandes Paula Roquetti , Roquetti Ricardo Wagner , Filho José Fernandes
Published: September 2010

The genetic and environmental contributions to determine digital dermatoglyphic traits were investigated by using female dizygotic and monozygotic twin pairs to estimate heritability indexes (h2). The evaluated sample was composed by 20 monozygotic twin pairs and 13 dizygotic twin pairs. A significant heritability (h2= 0.65 to 0.96) was observed for 12 dermatoglyphic characteristics (delta indexes and ridge counts for right hand, left hand and both hands, and ridge counts for most individual fingers). A negative correlation between the ridge counts and heritability indexes from individual fingers was found for the left hand, which appears to be associated to a higher arch pattern frequency in most left-hand fingers, since this frequency was negatively correlated with ridge counts and positively correlated with heritability indexes. Heritability indexes of right-hand fingers were positively correlated with loop pattern frequency and negatively correlated with whorl pattern frequency. The low heritability of ridge counts from left thumb, ring and little fingers (h2= 0.11 to 0.32) indicates a higher chance that the chorion type had an influence in the intra-pair variance of monozygotic twins. Results confirmed the predominant genetic influence on the total ridge count. The heritability indexes varied in up to 8 times between different fingers and its association to ridge counts and pattern frequency was very variable between hands, evidencing that the use of dermatoglyphic traits from individual fingers as indicators of genetic influences to other human traits should consider this variability.
Birthweight Discordance, Risk Factors and its Impact on Perinatal Mortality Among Japanese Twins: Data From a National Project During 2001–2005
Authors: Tobe Ruoyan Gai , Mori Rintaro , Shinozuka Norio , Kubo Takahiko , Itabashi Kazuo
Published: September 2010

Our aims were to assess the incidence of birthweight discordance of twins, to explore risk factors and its impact on perinatal mortality, and to quantify the risks at different severity of birthweight discordance in Japan, by using a nationwide obstetric database. There were 10,828 pairs of twins, born from 2001 to 2005 recorded in the database of the national Perinatal Health Care Project, fully enrolled. The overall incidence of birthweight discordance was 47.34%. The incidence of mild, severe and extremely severe discordance was 19.26%, 10.21% and 17.87%, respectively. The incidence of birthweight discordance in Japan is much higher than that in other countries, particularly at higher severity level. By linear regression model, our study added independent factors of primiparity (p < .001), sex composition (p < .001), chorionicity (p < .001), gestational age (p < .001), and delivery mode (p < .001) in determining birthweight discordance percentage. Maternal age and application of assisted reproduction technologies (ART) didn't significantly influence the birthweight discordance. The birthweight discordance is closely associated with gestational age and affected discharge mortality. From 25% of birthweight discordance, risk to discharge mortality tended to significantly increase, suggesting it should be added as a reference for clinical practices.
Twin Pregnancies Complicated by a Single Malformed Fetus: Chorionicity, Outcome and Management
Authors: Gedikbasi Ali , Akyol Alpaslan , Yildirim Gokhan , Ekiz Ali , Gul Ahmet , Ceylan Yavuz
Published: September 2010

The objective of this study was to evaluate the impact of one abnormal fetus in a twin pregnancy, to compare impact of chorionicity and clinical outcome of intervention and expectant management. Thirty-seven dichorionic (DC) twins and 18 monochorionic (MC) twins complicated with one malformed fetus were evaluated for gestational age, birthweight and perinatal outcome. Six hundred and forty-two twin pregnancies were evaluated in the database. The control groups consisted of 429 DC and 86 MC twins without anomalous fetus. Mean birthweight and gestational age at birth for DC control group were (n= 429; 2137g and 34.71 weeks), DC study group,n= 37; 2117g (p= .338) and 33.97 weeks (p= .311), and DC study group with major malformations,n= 30; 2019g (p= .289) and 33.3 weeks (p= .01), and showed only significance for gestational age. There was no statistical significance between MC control group,n= 86; 2097g and 34.93 weeks, and MC study group,n= 18; 2237g (p= .338), and 34.42 weeks (p= .502). Because of limited data, the preliminary evaluation for expectant management and intervention, and survival of at least one normal fetus showed no impact. We conclude that, although, all DC twin pregnancies have a risk for preterm delivery, DC twins complicated with major malformation of one twin, have a lower mean gestational age at birth. Preliminary results for intervention does not improve fetal outcome for DC and MC twins and needs further evaluation with greater studies of impact or review.
Ein modellbasiertes Konzept zur Antriebsstrangregelung für ein Parallelhybridfahrzeug
Authors: Alt Benedikt , Antritter Felix , Svaricek Ferdinand , Schultalbers Matthias
Published: September 2010

In diesem Beitrag wird ein modellbasierter Ansatz zur Antriebsstrangregelung für ein Parallelhybridfahrzeug vorgestellt. Dabei wird eine Antriebsstrangkonfiguration betrachtet, bei der kein eigener elektrischer Startermotor für den Verbrennungsmotor verwendet wird. Der Synchronisationsvorgang des Verbrennungsmotors erfolgt stattdessen über den Elektromotor der Antriebswelle sowie über eine Ansteuerung der Trennkupplung. Für diese Konfiguration wird ein flachheitsbasiertes Steuerungskonzept vorgestellt, mit dem die Drehzahlen des Verbrennungsmotors und des Elektromotors unabhängig voneinander eingestellt werden können. Im Zusammenspiel mit zwei entkoppelten Folgereglern ergibt sich zudem ein Regelungskonzept, das hervorragende Robustheitseigenschaften gegenüber Modellunsicherheiten besitzt.
Powermanagement eines hybridelektrischen Antriebs — Auslegung, Optimierung und Leistungsregelung
Authors: Söffker Dirk , Özbek Markus , Marx Matthias
Published: September 2010

Dieser Beitrag diskutiert verschiedene Aspekte zur Bewertung hybridelektrischer Antriebe. Anhand eines brennstoffzellenbasierten Hybridsystems wird der Einfluss des Powermanagements auf Kenngrößen wie z. B. System- und Komponenteneffizienz und -verfügbarkeit erörtert. Durch experimentelle Untersuchungen wird für einen gegebenen Fahrzyklus anhand einfacher Betriebsstrategien ein Optimierungsansatz dargestellt, wobei mit verschiedenen Kennwerten das Systemverhalten bewertet und nachfolgende Iterationsschritte bestimmt werden. Dabei kann bereits mit wenigen Iterationen ein Optimum erzielt werden.
Anthropology in Policy and Practice in India
Authors: Mahapatra L. K.
Published: September 2010

Anthropology was introduced into India as an early colonial concern. In these early years, controversy surrounded the development of anthropology because of its application in the colonial/nationalist juxtaposition. Later theoretical and applied studies in anthropology were framed in nationalist terms not based on a value‐neutral approach. This chapter examines the work of applied anthropologists from these early times to the present with an emphasis how global issues are increasing anthropological work. It will also discuss the structure of applied anthropology in the country and present examples of anthropologists working for government and international agencies, Universities, NGOs, and for tribal and vulnerable sections of India.
Fibroblast growth factor 10 enhances bovine oocyte maturation and developmental competence in vitro
Authors: Zhang Kun , Hansen Peter J , Ealy Alan D
Published: September 2010

The ability of oocytes to resume meiosis, become fertilized, and generate viable pregnancies is controlled during folliculogenesis by several endocrine and paracrine factors. The aim of this work is to determine whether fibroblast growth factor 10 (FGF10) is an oocyte competent factor. Transcripts for each of the four FGF receptor types (FGFR) were present in cumulus and oocytes after their extraction from the follicles. FGFR1 transcripts predominated in cumulus cells whereas FGFR2 was most abundant in oocytes. Exposing the cumulus–oocyte complexes to FGF10 duringin vitromaturation did not affect cleavage rates, but increases (P<0.05) in the percentage of embryos at the 8–16-cell stage on day 3 and at the blastocyst stage on day 7, which were evident in FGF10-supplemented oocytes. The progression of oocytes through meiosis and cumulus expansion was increased (P<0.05) by FGF10. The importance of the endogenous sources of FGFs was examined by adding anti-FGF10 IgG during oocyte maturation. Blocking endogenous FGF10 activity decreased (P<0.05) the percentage of oocytes developing into blastocysts and limited (P<0.05) cumulus expansion. Expression profiles of putative cumulus and oocyte competency markers were examined for their involvement in FGF10-mediated responses. FGF10 influenced the expression ofCTSBandSPRY2in cumulus cells andBMP15in oocytes. In summary, this work provides new insight into the importance of FGFRs and locally derived FGF10 during oocyte maturation in cattle. Its subsequent impact onin vitroembryo development implicates it as a noteworthy oocyte competent factor.
The sperm nucleus: chromatin, RNA, and the nuclear matrix
Authors: Johnson Graham D , Lalancette Claudia , Linnemann Amelia K , Leduc Frédéric , Boissonneault Guylain , Krawetz Stephen A
Published: September 2010

Within the sperm nucleus, the paternal genome remains functionally inert and protected following protamination. This is marked by a structural morphogenesis that is heralded by a striking reduction in nuclear volume. Despite these changes, both human and mouse spermatozoa maintain low levels of nucleosomes that appear non-randomly distributed throughout the genome. These regions may be necessary for organizing higher order genomic structure through interactions with the nuclear matrix. The promoters of this transcriptionally quiescent genome are differentially marked by modified histones that may poise downstream epigenetic effects. This notion is supported by increasing evidence that the embryo inherits these differing levels of chromatin organization. In concert with the suite of RNAs retained in the mature sperm, they may synergistically interact to direct early embryonic gene expression. Irrespective, these features reflect the transcriptional history of spermatogenic differentiation. As such, they may soon be utilized as clinical markers of male fertility. In this review, we explore and discuss how this may be orchestrated.
Phenotypic Consequences of Aneuploidy inArabidopsis thaliana
Authors: Henry Isabelle M , Dilkes Brian P , Miller Eric S , Burkart-Waco Diana , Comai Luca
Published: September 2010

Aneuploid cells are characterized by incomplete chromosome sets. The resulting imbalance in gene dosage has phenotypic consequences that are specific to each karyotype. Even in the case of Down syndrome, the most viable and studied form of human aneuploidy, the mechanisms underlying the connected phenotypes remain mostly unclear. Because of their tolerance to aneuploidy, plants provide a powerful system for a genome-wide investigation of aneuploid syndromes, an approach that is not feasible in animal systems. Indeed, in many plant species, populations of aneuploid individuals can be easily obtained from triploid individuals. We phenotyped a population of Arabidopsis thaliana aneuploid individuals containing 25 different karyotypes. Even in this highly heterogeneous population, we demonstrate that certain traits are strongly associated with the dosage of specific chromosome types and that chromosomal effects can be additive. Further, we identified subtle developmental phenotypes expressed in the diploid progeny of aneuploid parent(s) but not in euploid controls from diploid lineages. These results indicate long-term phenotypic consequences of aneuploidy that can persist after chromosomal balance has been restored. We verified the diploid nature of these individuals by whole-genome sequencing and discuss the possibility that trans-generational phenotypic effects stem from epigenetic modifications passed from aneuploid parents to their diploid progeny.
Antagonistic Roles of PP2A-Pab1 and Etd1 in the Control of Cytokinesis in Fission Yeast
Authors: Lahoz Aurelia , Alcaide-Gavilán María , Daga Rafael R , Jimenez Juan
Published: September 2010

In Schizosaccharomyces pombe, Etd1 is a positive regulator of the septation initiation network (SIN), a conserved GTPase-regulated kinase cascade that triggers cytokinesis. Here we show that a mutation in the pab1 gene, which encodes the B-regulatory subunit of the protein phosphatase 2A (PP2A), suppresses mutations in the etd1 gene. Etd1 is required for the function of the GTPase Spg1, a key regulator of SIN signaling. Interestingly, the loss of Pab1 function restored the activity of Spg1 in Etd1-deficient cells. This result suggests that PP2A-Pab1–mediated dephosphorylation inhibits Spg1, thus antagonizing Etd1 function. The loss of pab1 function also rescues the lethality of mutants of other genes in the SIN cascade such as mob1, sid1, and cdc11. Two-hybrid assays indicate that Pab1 physically interacts with Mob1, Sid1, Sid2, and Cdc11, suggesting that the phosphatase 2A B-subunit is a component of the SIN complex. Together, our results indicate that PP2A-Pab1 plays a novel role in cytokinesis, regulating SIN activity at different levels. Pab1 is also required to activate polarized cell growth. Thus, PP2A-Pab1 may be involved in coordinating polar growth and cytokinesis.
Temporal and Spatial Regulation of Gene Expression During Asexual Development ofNeurospora crassa
Authors: Greenwald Charles J , Kasuga Takao , Glass N Louise , Shaw Brian D , Ebbole Daniel J , Wilkinson Heather H
Published: September 2010

In this study we profiled spatial and temporal transcriptional changes during asexual sporulation in the filamentous fungus Neurospora crassa. Aerial tissue was separated from the mycelium to allow detection of genes specific to each tissue. We identified 2641 genes that were differentially expressed during development, which represents ∼25% of the predicted genes in the genome of this model fungus. On the basis of the distribution of functional annotations of 1102 of these genes, we identified gene expression patterns that define key physiological events during conidial development. Not surprisingly, genes encoding transcription factors, cell wall remodeling proteins, and proteins involved in signal transduction were differentially regulated during asexual development. Among the genes differentially expressed in aerial tissues the majority were unclassified and tended to be unique to ascomycete genomes. This finding is consistent with the view that these genes evolved for asexual development in the Pezizomycotina. Strains containing deletions of several differentially expressed genes encoding transcription factors exhibited asexual development-associated phenotypes. Gene expression patterns during asexual development suggested that cAMP signaling plays a critical role in the transition from aerial growth to proconidial chain formation. This observation prompted us to characterize a deletion of the gene encoding a high-affinity cAMP phosphodiesterase (NCU00478). NCU00478 was determined to be allelic to aconidiate-2, a previously identified genetic locus controlling conidiation.
H2B- and H3-Specific Histone Deacetylases Are Required for DNA Methylation in Neurospora crassa
Authors: Smith Kristina M , Dobosy Joseph R , Reifsnyder Jennifer E , Rountree Michael R , Anderson D C , Green George R , Selker Eric U
Published: September 2010

Neurospora crassa utilizes DNA methylation to inhibit transcription of heterochromatin. DNA methylation is controlled by the histone methyltransferase DIM-5, which trimethylates histone H3 lysine 9, leading to recruitment of the DNA methyltransferase DIM-2. Previous work demonstrated that the histone deacetylase (HDAC) inhibitor trichostatin A caused a reduction in DNA methylation, suggesting involvement of histone deacetylation in DNA methylation. We therefore created mutants of each of the four classical N. crassa HDAC genes and tested their effect on histone acetylation levels and DNA methylation. Global increases in H3 and H4 acetylation levels were observed in both the hda-3 and the hda-4 mutants. Mutation of two of the genes, hda-1 and hda-3, caused partial loss of DNA methylation. The site-specific loss of DNA methylation in hda-1 correlated with loss of H3 lysine 9 trimethylation and increased H3 acetylation. In addition, an increase in H2B acetylation was observed by two-dimensional gel electrophoresis of histones of the hda-1 mutant. We found a similar increase in the Schizosaccharomyces pombe Clr3 mutant, suggesting that this HDAC has a previously unrecognized substrate and raising the possibility that the acetylation state of H2B may play a role in the regulation of DNA methylation and heterochromatin formation.
Rescue of a Dominant Mutant With RNA Interference
Authors: Wu Yongrui , Messing Joachim
Published: September 2010

Maize Mucronate1 is a dominant floury mutant based on a misfolded 16-kDa γ-zein protein. To prove its function, we applied RNA interference (RNAi) as a dominant suppressor of the mutant seed phenotype. A γ-zein RNAi transgene was able to rescue the mutation and restore normal seed phenotype. RNA interference prevents gene expression. In most cases, this is used to study gene function by creating a new phenotype. Here, we use it for the opposite purpose. We use it to reverse the creation of a mutant phenotype by restoring the normal phenotype. In the case of the maize Mucronate1 (Mc1) phenotype, interaction of a misfolded protein with other proteins is believed to be the basis for the Mc1 phenotype. If no misfolded protein is present, we can reverse the mutant to the normal phenotype. One can envision using this approach to study complex traits and in gene therapy.
Long-term Outcomes of Acute Encephalitis in Childhood
Authors: Fowler Åsa , Stödberg Tommy , Eriksson Margareta , Wickström Ronny
Published: September 2010

OBJECTIVES:

The aims of this study were to investigate the long-term outcomes of childhood encephalitis and to examine possible prognostic factors.

METHODS:

Of 93 children who were treated for acute encephalitis in 2000–2004, 71 were eligible for follow-up evaluations. A structured interview, using 2 questionnaires, was conducted with the parents. Fifteen of the children with the most-severe symptoms at the time of discharge also underwent electroencephalographic recording and tests of reaction times and working memory.

RESULTS:

Persisting symptoms were reported by 54% of children. The predominant symptoms were personality changes and cognitive problems. Children who made a complete recovery did so within 6 to 12 months. The only significant risk factor for sequelae was disease severity leading to admission to the ICU. The risk of subsequent epilepsy was increased for children with seizures at presentation. Most follow-up electroencephalograms showed improvement, but results had not normalized for 9 of 15 children. Children with encephalitis had slower reaction times, compared with control subjects, but no difference in working memory could be seen.

CONCLUSION:

Persisting symptoms after childhood encephalitis were present for a substantial number of children. Seizures increased the risk of subsequent epilepsy; the only other prognostic marker was admission to the ICU. Even children who were considered fully recovered at discharge reported persisting symptoms at follow-up evaluations. Children who made a full recovery did so within 6 to 12 months, which suggests that all children with encephalitis should be monitored for 1 year after the acute illness.
Noonan Syndrome: Clinical Features, Diagnosis, and Management Guidelines
Authors: Romano Alicia A. , Allanson Judith E. , Dahlgren Jovanna , Gelb Bruce D. , Hall Bryan , Pierpont Mary Ella , Roberts Amy E. , Robinson Wanda , Takemoto Clifford M. , Noonan Jacqueline A.
Published: September 2010

Noonan syndrome (NS) is a common, clinically and genetically heterogeneous condition characterized by distinctive facial features, short stature, chest deformity, congenital heart disease, and other comorbidities. Gene mutations identified in individuals with the NS phenotype are involved in the Ras/MAPK (mitogen-activated protein kinase) signal transduction pathway and currently explain ∼61% of NS cases. Thus, NS frequently remains a clinical diagnosis. Because of the variability in presentation and the need for multidisciplinary care, it is essential that the condition be identified and managed comprehensively. The Noonan Syndrome Support Group (NSSG) is a nonprofit organization committed to providing support, current information, and understanding to those affected by NS. The NSSG convened a conference of health care providers, all involved in various aspects of NS, to develop these guidelines for use by pediatricians in the diagnosis and management of individuals with NS and to provide updated genetic findings.
Trends in Admissions for Pediatric Status Asthmaticus in New Jersey Over a 15-Year Period
Authors: Hartman Mary E. , Linde-Zwirble Walter T. , Angus Derek C. , Watson R. Scott
Published: September 2010

OBJECTIVE:

Status asthmaticus accounts for a large portion of the morbidity and mortality associated with asthma, but we know little about its epidemiology. We describe here the hospitalization characteristics of children with status asthmaticus, how they changed over time, and how they differed between hospitals with and without PICUs.

PATIENTS AND METHODS:

We used administrative data from New Jersey that included all hospitalizations in the state from 1992, 1995, and 1999–2006. We identified children with status asthmaticus by using International Classification of Diseases, Ninth Revision, diagnosis codes that indicate status asthmaticus and the use of mechanical ventilation by using procedure codes. We designated hospitals with a PICU as “PICU hospitals” and those without as “adult hospitals.”

RESULTS:

We identified 28 309 admissions of children with status asthmaticus (22.8% of all asthma hospitalizations). From 1992 to 2006, the rate of hospital admissions decreased by half (from 1.98 in 1000 to 0.93 in 1000 children), and there was a 70% decrease in the number of children admitted to adult hospitals. The rate of ICU care in PICU hospitals more than tripled. However, the rate of mechanical ventilation remained low, and the number of deaths was small and unchanged (n = 14 total). Hospital costs climbed from $6.6 million to $9.5 million.

CONCLUSIONS:

Although fewer children are being admitted with status asthmaticus, the proportion of patients managed in PICUs is climbing. There has been no substantial change in rates of mechanical ventilation or death. Additional research is needed to better understand how patients and physicians decide on the appropriate site for hospital care and how that choice affects outcome.