bluuebunny/crossref_metadata_2025 huggingface dataset:
Neural-network-based observer for turbine engine parameter estimation
Authors: Shankar P , Yedavalli R K
Published: July 2009

Accurate estimation of unmeasurable engine parameters such as thrust and turbine inlet temperatures constitutes a significant challenge for the aircraft community. A solution to this problem is to estimate these parameters from the measured outputs using an observer. Currently existing technologies rely on Kalman and extended Kalman filters to achieve this estimation. This paper presents a neural-network-based observer that augments the linear Kalman filter with a neural network to compensate for any non-linearity that is not handled by the linear filter. The implemented neural network is a radial basis function network that is trained offline using a growing and pruning algorithm. The neural-network-based observer is trained and simulated to estimate the high-pressure turbine inlet temperature, thrust, and stall margins at different levels of engine degradation for a two-spool turbofan engine. Simulation results show the ability of the observer to accurately estimate the performance parameters. The advantage of this observer is that it does not need explicit estimation of health parameters to accurately estimate the performance parameters.
An L1 adaptive closed-loop guidance law for an orbital injection problem
Authors: Roshanian J , Zareh M , Afshari H H , Rezaei M
Published: July 2009

The current paper presents the determination of a closed-loop guidance law for an orbital injection problem using two different approaches and, considering the existing time-optimal open-loop trajectory as the nominal solution, compares the advantages of the two proposed strategies. In the first method, named neighbouring optimal control (NOC), the perturbation feedback method is utilized to determine the closed-loop trajectory in an analytical form for the non-linear system. This law, which produces feedback gains, is in general a function of small perturbations appearing in the states and constraints separately. The second method uses an L1 adaptive strategy in determination of the non-linear closed-loop guidance law. The main advantages of this method include characteristics such as improvement of asymptotic tracking, guaranteed time-delay margin, and smooth control input. The accuracy of the two methods is compared by introducing a high-frequency sinusoidal noise. The simulation results indicate that the L1 adaptive strategy has a better performance than the NOC method to track the nominal trajectory when the noise amplitude is increased. On the other hand, the main advantage of the NOC method is its ability to solve a non-linear, two-point, boundary-value problem in the minimum time.
H∞ model reduction for discrete singular Markovian jump systems
Authors: Wu Z , Su H , Chu J
Published: July 2009

The problem of H∞ model reduction is investigated for discrete singular systems with Markovian jump. A stochastic admissibility condition and bounded real lemma (BRL) are established for the discrete singular Markovian jump system in terms of the linear matrix inequality (LMI) approach. Under partial knowledge of the transition probabilities, the strict LMI-based sufficient condition is obtained for the existence of desired reduced-order model. The numerical example is proposed to show the validity of the developed result.
Impact of Workload on Service Time and Patient Safety: An Econometric Analysis of Hospital Operations
Authors: Kc Diwas S. , Terwiesch Christian
Published: July 2009

Much of prior work in the area of service operations management has assumed service rates to be exogenous to the level of load on the system. Using operational data from patient transport services and cardiothoracic surgery—two vastly different health-care delivery services—we show that the processing speed of service workers is influenced by the system load. We find that workers accelerate the service rate as load increases. In particular, a 10% increase in load reduces length of stay by two days for cardiothoracic surgery patients, whereas a 20% increase in the load for patient transporters reduces the transport time by 30 seconds. Moreover, we show that such acceleration may not be sustainable. Long periods of increased load (overwork) have the effect of decreasing the service rate. In cardiothoracic surgery, an increase in overwork by 1% increases length of stay by six hours. Consistent with prior studies in the medical literature, we also find that overwork is associated with a reduction in quality of care in cardiothoracic surgery—an increase in overwork by 10% is associated with an increase in likelihood of mortality by 2%. We also find that load is associated with an early discharge of patients, which is in turn correlated with a small increase in mortality rate.
The In Vivo Expression of Dipeptidyl Peptidases 8 and 9
Authors: Yu Denise M.T. , Ajami Katerina , Gall Margaret G. , Park Joohong , Lee C. Soon , Evans Kathryn A. , McLaughlin Eileen A. , Pitman Melissa R. , Abbott Catherine A. , McCaughan Geoffrey W. , Gorrell Mark D.
Published: July 2009

The dipeptidyl peptidase IV (DPIV) enzyme family contains both potential and proven therapeutic targets. Recent reports indicate the presence of DP8 and DP9 in peripheral blood lymphocytes, testis, lung, and brain. For a more comprehensive understanding of DP8 and DP9 tissue and cellular expression, mRNA and enzyme activity were examined. Many organs from C57BL/6 wild-type and DPIV gene-knockout mice were examined; DP8/9 enzyme activity was detected in the immune system, brain, testis, muscle, and epithelia. In situ hybridization localized DP8 and DP9 mRNA to lymphocytes and epithelial cells in liver, gastrointestinal tract, lymph node, spleen, and lung. DP8 and DP9 mRNA was detected in baboon and mouse testis, and DP9 expression was elevated in human testicular cancers. DP8 and DP9 mRNA were ubiquitous in day 17 mouse embryo, with greatest expression in epithelium (skin and gastrointestinal tract) and brain. Thus, DP8 and DP9 are widely expressed enzymes. Their expression in lymphocytes and epithelia indicates potential for roles in the digestive and immune systems. This manuscript contains online supplemental material at http://www.jhc.org . Please visit this article online to view these materials.
Association of AMP-activated Protein Kinase Subunits With Glycogen Particles as Revealed In Situ by Immunoelectron Microscopy
Authors: Bendayan Moise , London Irene , Kemp Bruce E. , Hardie Grahame D. , Ruderman Neil , Prentki Marc
Published: July 2009

Immunogold cytochemistry was applied to reveal the intracellular location of AMP-activated protein kinase (AMPK) subunits in liver tissue of normal rats fed ad libitum. AMPK α and β subunits were located both in the cytosol and in close association with rosettes of glycogen particles (α particles). To reveal their true in situ association with glycogen, particular tissue processing conditions that retain glycogen in the cells were required. These included fixation with a combination of glutaraldehyde and paraformaldehyde, followed by postfixation with osmium tetroxide and lead citrate and embedding in Epon. Processing by less-stringent fixation conditions and embedding in Lowicryl led to the extraction of the glycogen deposits, which in turn resulted in the absence of any labeling. This indicates that the loss of glycogen deposits leads to the loss of closely associated proteins. Labeling for the α1 and α2 subunits of AMPK was found to be about 2-fold greater over glycogen than over cytosol, whereas labeling for β1 was 8-fold higher over the glycogen particles than over the cytosol. Immunogold combined with morphometric analysis demonstrated that the β1 subunits are located at the periphery of the glycogen rosettes, consistent with a recent hypothesis developed via biochemical approaches.
Convex subspace closure of the point shadow of an apartment of a spherical building
Authors: Kasikova Anna
Published: July 2009

Let Σ be the point-line truncation of an augmented J-Grassmann geometry of a spherical building B. We show that if |J| = 1, or if |J| ≥ 2 and some additional conditions hold, then the convex subspace closure in Σ of the point shadow of an apartment of B is the entire space Σ.
The center conjecture for equifacetal simplices
Authors: Edmonds Allan L.
Published: July 2009

An equifacetal simplex, in which all facets are congruent, has a unique center. The center conjecture states that a simplex that has a unique center must be equifacetal. A strong version of the conjecture is proved in dimensions at most six by showing that there is an explicit list of centers, defined for all simplices, whose coinciding implies the simplex is equifacetal. It remains an open problem whether the conjecture is true in dimensions greater than six.
Polarities of shift planes
Authors: Knarr Norbert , Stroppel Markus
Published: July 2009

We construct polarities for arbitrary shift planes and develop criteria for conjugacy under the normalizer of the shift group. Under suitable assumptions (in particular, for finite or compact planes) we construct all shift groups on a given plane, and our constructions yield all conjugacy classes of polarities. We show that a translation plane admits an orthogonal polarity if, and only if, it is a shift plane. The corresponding planes are exactly those that can be coordinatized by commutative semifields. The orthogonal polarities form a single conjugacy class. Finally, we construct examples of compact connected shift planes with more conjugacy classes of polarities than the corresponding classical planes.
Irradiation-Induced Hardening and Embrittlement of High-Cr ODS Ferritic Steels
Authors: Lee J. H. , Kasada R. , Cho H. S. , Kimura A.
Published: July 2009

The dependence of irradiation temperature, neutron dose, and Cr content on irradiation hardening and embrittlement has been investigated for oxide dispersion strengthened (ODS) ferritic steels irradiated from 290 to 600°C up to the maximum neutron dose of 0.75 dpa. Irradiation hardening and embrittlement of the materials strongly depend on the irradiation temperature. While neutron dose increases from 0.01 to 0.21 dpa, the ODS steels with Al show a saturation of irradiation hardening but the no-Al ODS steel has an increase in the hardening. The higher the Cr content, the more significant the irradiation hardening and embrittlement of ODS steels irradiated below 420°C. Interestingly, the ODS ferritic steels exposed to neutrons show little change of tensile elongation, compared to 9Cr JLF-1. Furthermore the ductile-brittle transition temperature (DBTT) shift of ODS steels increases with the increasing irradiation hardening, indicating that the increase of yield strength due to radiation induced hardening increases the DBTT and thus a reduction of hardening is effective to reduce the DBTT shift.
Final Results from the Crack Initiation and Arrest of Irradiated Steel Materials Project on Fracture Mechanical Assessments of Pre-Irradiated RPV Steels Used in German PWR
Authors: Hein H. , Keim E. , Schnabel H. , Seibert T. , Gundermann A.
Published: July 2009

Pre-irradiated original reactor pressure vessel (RPV) materials covering all four German pressurized water reactors (PWR) construction lines were tested in the Crack Initiation and Arrest of Irradiated Steel Materials program to create a database of fracture toughness and arrest values for neutron fluences beyond the end of life range. The new database comprises data from both unirradiated and irradiated RPV base and weld materials generated by tensile, Charpy-V impact, fracture toughness KJc, and crack arrest KIa tests. The test matrix consists of materials with optimized chemical composition and with high Copper or high Nickel content, respectively. Based on the generated and already existing data the RTNDT and the RTT0 (Master Curve) concepts are applied with specific view on reference temperatures, transition temperature shifts, and on possible correlations between the criteria used in both concepts. In this context the consequences of some influencing factors like type and chemical composition of the RPV steel, its manufacturing conditions, and the specimen type and size on the reference temperatures are discussed. Moreover, the test results are assessed with respect to the American Society of Mechanical Engineers (ASME) code and German Nuclear Safety Standards Commission safety standards. The crack arrest characteristics for these typical RPV materials are also determined in a twofold way by testing Compact Crack Arrest specimens and by evaluation of instrumented Charpy-V impact test data. The available results made a good point that crack arrest is a reliable phenomenon that doubtless exists. It is also shown that the obtained KIa data can be enveloped by applying the ASME KIc lower bound curve indexed by different reference temperatures. Finally, the results show that the used RPV materials are well designed in terms of material behavior under irradiated conditions and that optimized manufacture specifications are of great benefit particularly after long operation times.
Buchbesprechungen
Authors: Woldt Claudia
Published: July 2009

PÖPPEL, LUDMILA, The Rhetoric of Pravda Editorials: A Diachronic Study of a Political Genre. Stockholm: Stockholm University, 2007. 306 S. (Acta Universitatis Stockholmiensis; Stockholm Slavic Studios; 33) ISBN 978-91-85445-61-5
Familial hypophosphatemic rickets caused by a large deletion in PHEX gene
Authors: Saito Tasuku , Nishii Yutaka , Yasuda Toshiyuki , Ito Nobuaki , Suzuki Hisanori , Igarashi Takashi , Fukumoto Seiji , Fujita Toshiro
Published: July 2009

Context

X-linked hypophosphatemic rickets/osteomalacia (XLH), autosomal dominant and recessive hypophosphatemic rickets/osteomalacia (ADHR and ARHR) share common clinical features including high fibroblast growth factor 23 (FGF23) levels. These diseases are caused by mutations in phosphate regulating endopeptidase homolog, X-linked (PHEX), FGF23, and dentin matrix acidic phosphoprotein 1 (DMP1) gene respectively. It remains unclear whether these diseases can be clinically discriminated.

Objective

To clarify the underlying mechanism of patients with hypophosphatemic rickets whose parents showed no physical findings suggesting rickets.

Design and patients

The proband is a 39-year-old woman. She and her 37-year-old brother show the same clinical features such as bowing of legs together with hypophosphatemia (sister: P 1.8 mg/dl, brother: P 1.6 mg/dl) and high FGF23 levels (sister: 542 pg/ml, brother: 96 pg/ml). Physical findings of their parents are normal and ARHR was suspected.

Results

Sequencing of all coding exons and exon–intron junctions of DMP1 and FGF23 genes showed no mutation. Subsequent analysis revealed that there is a deletion of 52 143 bp including exons 1–3 in PHEX gene in the brother. His sister was found to be a heterozygote for the same deletion indicating that they are suffering from XLH. The same deletion was detected in the mother. However, the amount of the wild-type allele was more and that of the mutant one was less in genomic DNA from the mother compared with those from the sister. Single nucleotide polymorphism (SNP) analysis indicated that the mother has three kinds of PHEX alleles suggesting a somatic mosaicism.

Conclusion

Careful genetic analysis is mandatory for correct differential diagnosis of hypophosphatemic rickets with high FGF23 levels.
Subclinical hyperthyroidism and blood pressure in a population-based prospective cohort study
Authors: Völzke Henry , Ittermann Till , Schmidt Carsten O , Dörr Marcus , John Ulrich , Wallaschofski Henri , Stricker Bruno H C , Felix Stephan B , Rettig Rainer
Published: July 2009

Objectives

There is current controversy on the association between subclinical hyperthyroidism and hypertension. Data from cohort studies have not been available yet. The present study was designed to longitudinally investigate possible associations of subclinical hyperthyroidism with blood pressure, pulse pressure and the risk of hypertension.

Methods

We used data from the population-based, prospective cohort Study of Health in Pomerania and included 2910 subjects (1469 women) aged 20–79 years with completed 5-year examination follow-up. Subjects with increased serum TSH levels or overt hyperthyroidism were excluded. Serum TSH levels below 0.25 mIU/l with free triiodothyronine and free thyroxine levels within the reference range were defined as subclinical hyperthyroidism. Blood pressure was measured according to standard methods.

Results

Multivariable analyses adjusted for age, sex, overweight, obesity, smoking status and time between the examinations did not reveal any statistically significant association between subclinical hyperthyroidism and any of the blood pressure-related variables in the whole study population. Although the 5-year hypertension incidence was higher in subjects with subclinical hyperthyroidism compared with those without (31.4 vs 19.2%; risk ratio 1.64; 95% confidence interval (CI) 1.17–2.28, P=0.006), both groups did not differ with respect to the risk of hypertension, after analyses were adjusted for confounders (relative risk 1.23, 95% CI 0.91–1.68, P=0.182). Analyses yielded similar results in subjects without thyroid disease and in those who took no antihypertensive medication.

Conclusion

Subclinical hyperthyroidism is not associated with changes in blood pressure, pulse pressure or incident hypertension.
Ancestral Population Genomics: The Coalescent Hidden Markov Model Approach
Authors: Dutheil Julien Y , Ganapathy Ganesh , Hobolth Asger , Mailund Thomas , Uyenoyama Marcy K , Schierup Mikkel H
Published: July 2009

With incomplete lineage sorting (ILS), the genealogy of closely related species differs along their genomes. The amount of ILS depends on population parameters such as the ancestral effective population sizes and the recombination rate, but also on the number of generations between speciation events. We use a hidden Markov model parameterized according to coalescent theory to infer the genealogy along a four-species genome alignment of closely related species and estimate population parameters. We analyze a basic, panmictic demographic model and study its properties using an extensive set of coalescent simulations. We assess the effect of the model assumptions and demonstrate that the Markov property provides a good approximation to the ancestral recombination graph. Using a too restricted set of possible genealogies, necessary to reduce the computational load, can bias parameter estimates. We propose a simple correction for this bias and suggest directions for future extensions of the model. We show that the patterns of ILS along a sequence alignment can be recovered efficiently together with the ancestral recombination rate. Finally, we introduce an extension of the basic model that allows for mutation rate heterogeneity and reanalyze human–chimpanzee–gorilla–orangutan alignments, using the new models. We expect that this framework will prove useful for population genomics and provide exciting insights into genome evolution.
Is There Variation in Crossover Interference Levels Among Chromosomes From Human Males?
Authors: Housworth E A , Stahl F W
Published: July 2009

We demonstrate that recent data from human males are consistent with constant interference levels among chromosomes under the two-pathway model, whereas inappropriately fitting shape parameters of Gamma distributions to immunofluorescent interfoci distances observed on finite chromosomes generates false interpretations of higher levels of interference on shorter chromosomes. We provide appropriate statistical methodology.
KlAft, the Kluyveromyces lactis Ortholog of Aft1 and Aft2, Mediates Activation of Iron-Responsive Transcription Through the PuCACCC Aft-Type Sequence
Authors: Conde e Silva Natalia , Gonçalves Isabelle R , Lemaire Marc , Lesuisse Emmanuel , Camadro Jean Michel , Blaiseau Pierre Louis
Published: July 2009

Iron homeostasis in fungi is regulated at the transcriptional level by two different mechanisms. It is mediated by a conserved GATA-type repressor in most fungi except in the yeast Saccharomyces cerevisiae, where it is controlled by the transcription activators Aft1 and Aft2. These activators are encoded by the paralogous genes AFT1 and AFT2, which result from the whole-genome duplication. Here, we explore regulation of iron homeostasis in the yeast Kluyveromyces lactis that diverged from S. cerevisiae before this event. We identify an ortholog of AFT1/AFT2, designated KlAFT, whose deletion leads to the inability to grow under iron limitation. We show with quantitative real-time PCR analysis that KlAft activates the transcription of all homologs of the Aft1-target genes involved in the iron transport at the cell surface in response to iron limitation. However, homologs of Aft2-specific target genes encoding intracellular iron transporters are regulated neither by KlAft nor by iron. Both bioinformatic and DNA binding and transcription analyses demonstrate that KlAft activates iron-responsive gene expression through the PuCACCC Aft-type sequence. Thus, K. lactis is the first documented species with a positive iron-transcriptional control mediated by only one copy of the Aft-type regulator. This indicates that this function was acquired before the whole-genome duplication and was then diversified into two regulators in S. cerevisiae.
Polymorphisms in Multiple Genes Contribute to the Spontaneous Mitochondrial Genome Instability ofSaccharomyces cerevisiaeS288C Strains
Authors: Dimitrov Lazar N , Brem Rachel B , Kruglyak Leonid , Gottschling Daniel E
Published: July 2009

The mitochondrial genome (mtDNA) is required for normal cellular function; inherited and somatic mutations in mtDNA lead to a variety of diseases. Saccharomyces cerevisiae has served as a model to study mtDNA integrity, in part because it can survive without mtDNA. A measure of defective mtDNA in S. cerevisiae is the formation of petite colonies. The frequency at which spontaneous petite colonies arise varies by ∼100-fold between laboratory and natural isolate strains. To determine the genetic basis of this difference, we applied quantitative trait locus (QTL) mapping to two strains at the opposite extremes of the phenotypic spectrum: the widely studied laboratory strain S288C and the vineyard isolate RM11-1a. Four main genetic determinants explained the phenotypic difference. Alleles of SAL1, CAT5, and MIP1 contributed to the high petite frequency of S288C and its derivatives by increasing the formation of petite colonies. By contrast, the S288C allele of MKT1 reduced the formation of petite colonies and compromised the growth of petite cells. The former three alleles were found in the EM93 strain, the founder that contributed ∼88% of the S288C genome. Nearly all of the phenotypic difference between S288C and RM11-1a was reconstituted by introducing the common alleles of these four genes into the S288C background. In addition to the nuclear gene contribution, the source of the mtDNA influenced its stability. These results demonstrate that a few rare genetic variants with individually small effects can have a profound phenotypic effect in combination. Moreover, the polymorphisms identified in this study open new lines of investigation into mtDNA maintenance.
Candidate Gene Association Mapping of Arabidopsis Flowering Time
Authors: Ehrenreich Ian M , Hanzawa Yoshie , Chou Lucy , Roe Judith L , Kover Paula X , Purugganan Michael D
Published: July 2009

The pathways responsible for flowering time in Arabidopsis thaliana comprise one of the best characterized genetic networks in plants. We harness this extensive molecular genetic knowledge to identify potential flowering time quantitative trait genes (QTGs) through candidate gene association mapping using 51 flowering time loci. We genotyped common single nucleotide polymorphisms (SNPs) at these genes in 275 A. thaliana accessions that were also phenotyped for flowering time and rosette leaf number in long and short days. Using structured association techniques, we find that haplotype-tagging SNPs in 27 flowering time genes show significant associations in various trait/environment combinations. After correction for multiple testing, between 2 and 10 genes remain significantly associated with flowering time, with CO arguably possessing the most promising associations. We also genotyped a subset of these flowering time gene SNPs in an independent recombinant inbred line population derived from the intercrossing of 19 accessions. Approximately one-third of significant polymorphisms that were associated with flowering time in the accessions and genotyped in the outbred population were replicated in both mapping populations, including SNPs at the CO, FLC, VIN3, PHYD, and GA1 loci, and coding region deletions at the FRI gene. We conservatively estimate that ∼4–14% of known flowering time genes may harbor common alleles that contribute to natural variation in this life history trait.
The Population Genomics of Trans-Specific Inversion Polymorphisms in Anopheles gambiae
Authors: White Bradley J , Cheng Changde , Sangaré Djibril , Lobo Neil F , Collins Frank H , Besansky Nora J
Published: July 2009

In the malaria mosquito Anopheles gambiae polymorphic chromosomal inversions may play an important role in adaptation to environmental variation. Recently, we used microarray-based divergence mapping combined with targeted resequencing to map nucleotide differentiation between alternative arrangements of the 2La inversion. Here, we applied the same technique to four different polymorphic inversions on the 2R chromosome of An. gambiae. Surprisingly, divergence was much lower between alternative arrangements for all 2R inversions when compared to the 2La inversion. For one of the rearrangements, 2Ru, we successfully mapped a very small region (∼100 kb) of elevated divergence. For the other three rearrangements, we did not identify any regions of significantly high divergence, despite ample independent evidence from natural populations of geographic clines and seasonal cycling, and stable heterotic polymorphisms in laboratory populations. If these inversions are the targets of selection as hypothesized, we suggest that divergence between rearrangements may have escaped detection due to retained ancestral polymorphism in the case of the youngest 2R rearrangements and to extensive gene flux in the older 2R inversion systems that segregate in both An. gambiae and its sibling species An. arabiensis.
Spp382p Interacts with Multiple Yeast Splicing Factors, Including Possible Regulators of Prp43 DExD/H-Box Protein Function
Authors: Pandit Shatakshi , Paul Sudakshina , Zhang Li , Chen Min , Durbin Nicole , Harrison Susan M W , Rymond Brian C
Published: July 2009

Prp43p catalyzes essential steps in pre-mRNA splicing and rRNA biogenesis. In splicing, Spp382p stimulates the Prp43p helicase to dissociate the postcatalytic spliceosome and, in some way, to maintain the integrity of the spliceosome assembly. Here we present a dosage interference assay to identify Spp382p-interacting factors by screening for genes that when overexpressed specifically inhibit the growth of a conditional lethal prp38-1 spliceosome assembly mutant in the spp382-1 suppressor background. Identified, among others, are genes encoding the established splicing factors Prp8p, Prp9p, Prp11p, Prp39p, and Yhc1p and two poorly characterized proteins with possible links to splicing, Sqs1p and Cwc23p. Sqs1p copurifies with Prp43p and is shown to bind Prp43p and Spp382p in the two-hybrid assay. Overexpression of Sqs1p blocks pre-mRNA splicing and inhibits Prp43p-dependent steps in rRNA processing. Increased Prp43p levels buffer Sqs1p cytotoxicity, providing strong evidence that the Prp43p DExD/H-box protein is a target of Sqs1p. Cwc23p is the only known yeast splicing factor with a DnaJ motif characteristic of Hsp40-like chaperones. We show that similar to SPP382, CWC23 activity is critical for efficient pre-mRNA splicing and intron metabolism yet, surprisingly, this activity does not require the canonical DnaJ/Hsp40 motif. These and related data establish the value of this dosage interference assay for finding genes that alter cellular splicing and define Sqs1p and Cwc23p as prospective modulators of Spp382p-stimuated Prp43p function.
Association of Family History of Autoimmune Diseases and Autism Spectrum Disorders
Authors: Atladóttir Hjördís Ó. , Pedersen Marianne G. , Thorsen Poul , Mortensen Preben Bo , Deleuran Bent , Eaton William W. , Parner Erik T.
Published: July 2009

OBJECTIVES: Recent studies suggest that familial autoimmunity plays a part in the pathogenesis of ASDs. In this study we investigated the association between family history of autoimmune diseases (ADs) and ASDs/infantile autism. We perform confirmatory analyses based on results from previous studies, as well as various explorative analyses.

METHODS: The study cohort consisted of all of the children born in Denmark from 1993 through 2004 (689 196 children). Outcome data consisted of both inpatient and outpatient diagnoses reported to the Danish National Psychiatric Registry. Information on ADs in parents and siblings of the cohort members was obtained from the Danish National Hospital Register. The incidence rate ratio of autism was estimated by using log-linear Poisson regression.

RESULTS: A total of 3325 children were diagnosed with ASDs, of which 1089 had an infantile autism diagnosis. Increased risk of ASDs was observed for children with a maternal history of rheumatoid arthritis and celiac disease. Also, increased risk of infantile autism was observed for children with a family history of type 1 diabetes.

CONCLUSIONS: Associations regarding family history of type 1 diabetes and infantile autism and maternal history of rheumatoid arthritis and ASDs were confirmed from previous studies. A significant association between maternal history of celiac disease and ASDs was observed for the first time. The observed associations between familial autoimmunity and ASDs/infantile autism are probably attributable to a combination of a common genetic background and a possible prenatal antibody exposure or alteration in fetal environment during pregnancy.
No Change in the Age of Diagnosis for Fragile X Syndrome: Findings From a National Parent Survey
Authors: Bailey Donald B. , Raspa Melissa , Bishop Ellen , Holiday David
Published: July 2009

OBJECTIVE: To determine recent trends in the diagnosis of children with fragile X syndrome (FXS) and identify factors associated with the timing of diagnosis.

METHODS: More than 1000 families of children with FXS participated in a national survey. Of these, 249 had their first child (213 boys, 36 girls) diagnosed between 2001 and 2007 and did not know about FXS in their family before diagnosis. These parents answered questions about the average age of first concerns, developmental delays, early intervention, and the FXS diagnosis. They also provided other information about their child and family, reported who made the diagnosis, and described ramifications for other children and extended family members.

RESULTS: The average age of FXS diagnosis of boys remained relatively stable across the 7-year period at ∼35 to 37 months. The 36 girls with full mutation were given the diagnosis at an average age of 41.6 months. A trend was noted in earlier diagnosis of developmental delay for boys in more recent years. Approximately 25% of the families of male children had a second child with the full mutation before the diagnosis was given to the first child; 14 (39%) of the 36 families of female children had a second child with the full mutation before the diagnosis.

CONCLUSIONS: Despite patient advocacy, professional recommendations regarding prompt referral for genetic testing, and increased exposure to information about FXS in the pediatric literature, no changes were detected in the age of diagnosis of FXS during the time period studied. Earlier identification in the absence of systematic screening will likely continue to be a challenge.
Decline and Change in Seasonality of US Rotavirus Activity After the Introduction of Rotavirus Vaccine
Authors: Tate Jacqueline E. , Panozzo Catherine A. , Payne Daniel C. , Patel Manish M. , Cortese Margaret M. , Fowlkes Ashley L. , Parashar Umesh D.
Published: July 2009

BACKGROUND: In 2006, routine immunization of US infants against rotavirus was initiated. We assessed national, regional, and local trends in rotavirus testing and detection before and after vaccine introduction.

METHODS: We examined data for July 2000 through June 2008 from a national network of ∼70 US laboratories to compare geographical and temporal aspects of rotavirus season timing and peak activity. To assess trends in rotavirus testing and detection, we restricted the analyses to 33 laboratories that reported for ≥26 weeks per season from 2000 to 2008.

RESULTS: Nationally, the onset and peak of the 2007–2008 rotavirus season were delayed 15 and 8 weeks, respectively, compared with prevaccine seasons from 2000–2006. Delays were observed in each region. The 2007–2008 rotavirus season lasted 14 weeks compared with a median of 26 weeks during the prevaccine era. Of 33 laboratories, 32 reported fewer positive results and a lower proportion of positive test results in 2007–2008 compared with the median in 2000–2006, with a 67% decline in the number and a 69% decline in the proportion of rotavirus-positive test results. The proportion of positive test results in 2007–2008 compared with the median in 2000–2006 declined >50% in 79% of the laboratories and >75% in 39% of the laboratories.

CONCLUSIONS: The 2007–2008 US rotavirus season seems substantially delayed, shorter, and diminished in magnitude compared with seasons before vaccine implementation. The extent of change seems greater than expected on the basis of estimated vaccine coverage, suggesting indirect benefits to unvaccinated individuals. Monitoring in future seasons is needed to confirm these trends.
Gender Differences in Research Grant Applications for Pediatric Residents
Authors: Gordon Mary Beth , Osganian Stavroula K. , Emans S. Jean , Lovejoy Frederick H.
Published: July 2009

OBJECTIVE: Recent studies have reported gender differences in research grant applications and funding outcomes for medical school faculty. Our goal was to determine whether similar patterns exist at the resident level and, if so, to explore possible explanations.

METHODS: We conducted a retrospective review of all applications to an internal, mentored research grant fund at a large academic pediatric residency program from 2003 to 2008. We determined whether gender differences existed for application characteristics and outcomes and defined significant predictors of success.

RESULTS: During the 5-year period, the fund supported 42 (66%) of 64 applications. Among all applicants, men were more likely than women to hold an advanced research degree. Men requested more money than women and obtained more favorable application scores. Funding success rates were not statistically different between male and female applicants. Among funded applicants, men received higher awards than women, although the percentage of requests funded was the same. In a multiple regression analysis, advanced degree was the significant independent predictor of successful funding outcome. Controlling for advanced degree attenuated the association between gender and timing of application, type of project, dollars requested, and dollars awarded; however, even after controlling for advanced degree, women had inferior grant scores compared with men.

CONCLUSIONS: Gender differences existed in research grant applications and funding among pediatric residents that mirrored faculty patterns. Among residents, these differences were explained in part by the correlation of male gender with holding an advanced research degree.
What Determines Nutritional Recovery in Malnourished Children After Correction of Congenital Heart Defects?
Authors: Vaidyanathan Balu , Radhakrishnan Reshma , Sarala Deepa Aravindakshan , Sundaram Karimassery Ramaiyar , Kumar Raman Krishna
Published: July 2009

BACKGROUND: Malnutrition is common in children with congenital heart disease (CHD), especially in developing countries.

OBJECTIVE: To examine the impact of corrective intervention on the nutritional status of children with CHD and identify factors associated with suboptimal recovery.

METHODS: Consecutive patients with CHD in a tertiary center in South India were evaluated for nutritional status before and 2 years after corrective intervention. Anthropometry was performed at presentation and every 6 months for 2 years, and z scores were compared. Malnutrition was defined as a weight-for-age, height-for-age, and weight/height z score <−2. Determinants of malnutrition were entered into a multivariate logistic regression analysis model.

RESULTS: Of 476 patients undergoing corrective intervention (surgical: 344; catheter-based: 132) z scores of less than −2 for weight for age, height for age, and weight/height were recorded in 59%, 26.3%, and 55.9% of patients, respectively, at presentation. On follow-up (425 patients [92.5% of survivors; 20.63 ± 13.1 months of age]), z scores for weight for age and weight/height improved significantly from the baseline (weight: −1.42 ± 1.03 vs −2.19 ± 1.16; P < .001; weight/height: −1.15 ± 1.25 vs −2.09 ± 1.3; P < .001). Height-for-age z scores were not significantly different. Malnutrition persisted in 116 (27.3%) patients on follow-up and was associated with a birth weight of ≤2.5 kg, nutritional status at presentation, and height of parents and not with type of cardiac lesion, dietary intake, or socioeconomic factors.

CONCLUSIONS: This study from South India demonstrates severe malnutrition in over half of the patients with CHD and is not always reversed by corrective surgery or intervention. Persistent malnutrition after corrective intervention is predicted by nutritional status at presentation, birth weight, and parental anthropometry.
Arquitetura multiprocessada e reconfigurável para a síntese de redes de Petri em hardware
Authors: Oliveira Tiago de , Marranghello Norian
Published: July 2009

Uma arquitetura reconfigurável e multiprocessada para a implementação física de Redes de Petri foi desenvolvida em VHDL e mapeada sobre um FPGA. Convencionalmente, as Redes de Petri são transformadas em uma linguagem de descrição de hardware no nível de transferências entre registradores e um processo de síntese de alto nível é utilizado para gerar as funções booleanas e tabelas de transição de estado para que se possa, finalmente, mapeá-las num FPGA (Morris et al., 2000) (Soto and Pereira, 2001). A arquitetura proposta possui blocos lógicos reconfiguráveis desenvolvidos exclusivamente para a implementação dos lugares e das transições da rede, não sendo necessária a descrição da rede em níveis de abstração intermediários e nem a utilização de um processo de síntese para realizar o mapeamento da rede na arquitetura. A arquitetura permite o mapeamento de modelos de Redes de Petri com diferenciação entre as marcas e associação de tempo no disparo das transições, sendo composta por um arranjo de processadores reconfiguráveis, cada um dos quais representando o comportamento de uma transição da Rede de Petri a ser mapeada e por um sistema de comunicação, implementado por um conjunto de roteadores que são capazes de enviar pacotes de dados de um processador reconfigurável a outro. A arquitetura proposta foi validada num FPGA de 10.570 elementos lógicos com uma topologia que permitiu a implementação de Redes de Petri de até 9 transições e 36 lugares, atingindo uma latência de 15,4ns e uma vazão de até 17,12GB/s com uma freqüência de operação de 64,58MHz.
Integração de uma descrição de dispositivos aberta e não-proprietária em sistemas fieldbus reais e simulados
Authors: Pantoni Rodrigo Palucci , Brandão Dennis
Published: July 2009

Os sistemas de automação industrial contam com a definição de arquiteturas abertas padronizadas, a maioria delas utilizando tecnologias proprietárias. Em sistemas fieldbus, a tecnologia normatizada que provê a descrição das características dos dispositivos para o software configurador (IHM - Interface Homem Máquina) é de natureza proprietária e de alto custo, chamada de EDD (Electronic Device Description). Alternativamente, a Open-EDD (Open Electronic Device Description) é uma tecnologia aberta e não-proprietária baseada em padrões de software. Este trabalho descreve a utilização e validação da Open-EDD em duas diferentes aplicações: num sistema fieldbus real e num ambiente fieldbus simulado. Os resultados validam a técnica e indicam que esta pode ser aplicada a demais sistemas de automação.
Projeto e implementação de um controlador de corrente robusto para inversores com filtro LCL conectados à rede com incertezas paramétricas
Authors: Gabe Ivan Jorge , Massing Jorge Rodrigo , Montagner Vinícius Foletto , Grigoletto Felipe Bovolini , Pinheiro Humberto
Published: July 2009

Este artigo trata do projeto e implementação de um controlador discreto de corrente para um inversor trifásico alimentado em tensão e conectado à rede através de um filtro LCL, geralmente encontrado em sistemas de geração eólica. Primeiramente, é desenvolvido um teorema que relaciona a controlabilidade da equação dinâmica discreta, que representa o comportamento do conversor conectado à rede, aos parâmetros do filtro e a freqüência de amostragem do sistema. Então é derivada uma condição para a obtenção dos ganhos de retroação parcial robusta de estados baseada em desigualdades matriciais lineares. Este controlador garante a estabilidade e o amortecimento ativo da ressonância do filtro LCL conectado à rede, mesmo com incertezas paramétricas no ponto de conexão sem a necessidade de procedimentos de auto-sintonia ou algoritmos adaptativos. Finalmente, um controlador com modelo interno é adicionado a fim de prover rastreamento assimptótico da referência e rejeição do distúrbio, diminuindo significativamente o impacto dos distúrbios harmônicos de baixa freqüência da tensão da rede nas correntes de saída. Resultados experimentais e de simulação são apresentados para dar suporte a análise teórica desenvolvida bem como para demonstrar o desempenho do sistema.
Serum α-Fetoprotein Response as a Surrogate for Clinical Outcome in Patients Receiving Systemic Therapy for Advanced Hepatocellular Carcinoma
Authors: Vora Sadhna R. , Zheng Hui , Stadler Zsofia K. , Fuchs Charles S. , Zhu Andrew X.
Published: July 2009

Background.

The role of serum α-fetoprotein (AFP) as a marker for treatment response in patients with hepatocellular carcinoma (HCC) receiving systemic therapy is poorly defined.

Methods.

A retrospective study was performed on patients with advanced HCC enrolled in five phase II clinical trials. Serum AFP was prospectively collected at baseline and at different time points through treatment in parallel with radiologic response and clinical outcome. Patients were separated into three groups based on a 50% change in serum AFP from baseline. Overall survival (OS), progression-free survival (PFS), and radiologic responses were compared between groups using log-rank and Wilcoxon tests.

Results.

Of 144 patients, 107 met the eligibility criteria. Eighteen patients experienced a >50% AFP decline, 57 patients had a >50% AFP increase, and 32 patients had a <50% change in serum AFP in either direction. Compared with patients with a <50% change in serum AFP (median PFS, 5.6 months), patients with a >50% AFP decrease had a longer PFS time (median, 16.9 months; p = .029), whereas those with a >50% increase had a shorter PFS time (median, 2.3 months; p = .038). Patients with a >50% rise in AFP had a shorter OS time than those with a <50% change (median, 6.3 months versus 11.1 months, respectively; p = .004), whereas a >50% AFP decrease was not associated with a significant difference in OS (median, 13.0 months; p = .87). AFP changes were significantly associated with radiologic response.

Conclusions.

Our study suggests that serum AFP change during treatment may serve as a useful surrogate marker for clinical outcome in patients with advanced HCC receiving systemic therapy.
Studying Genetic Variations in Cancer Prognosis (and Risk): A Primer for Clinicians
Authors: Savas Sevtap , Liu Geoffrey
Published: July 2009

Learning Objectives

Evaluate SNPs as genetic markers and functional genetic variations. Select candidate genes for cancer research based on knowledge of their biological function. Assess candidate gene and genome-wide association studies for their potential to improve translational research.

This article is available for continuing medical education credit at CME.TheOncologist.com
When Communicating with Diverse Audiences, Use Velcro to Make Science Stick
Authors: Reynolds Julie
Published: July 2009

Many people use Velcro, that two‐layer fabric with tiny loops on one side and hooks on the other, for everything from fastening shoes to bundling computer cords, but few would think of using it as a tool for communication. I have found, however, two distinct but related rhetorical uses for it. First, Velcro can be used as an analogy for how people learn, a useful insight for anyone whose goal is to teach or inform. Second, VELCRO can also be used as a mnemonic device for remembering six strategies that improve both written and oral communication. Together, these uses of VELCRO help address the challenges that scientists face when communicating about science with diverse audiences, including those we address in classrooms, scientific meetings, or public venues, and those we target in scientific, interdisciplinary, or popular writing.
Whole‐lake estimates of carbon flux through algae and bacteria in benthic and pelagic habitats of clear‐water lakes
Authors: Ask Jenny , Karlsson Jan , Persson Lennart , Ask Per , Byström Pär , Jansson Mats
Published: July 2009

This study quantified new biomass production of algae and bacteria in both benthic and pelagic habitats of clear‐water lakes to contrast how carbon from the atmosphere and terrestrial sources regulates whole‐lake metabolism. We studied four small unproductive lakes in subarctic northern Sweden during one summer season. The production of new biomass in both benthic and pelagic habitats was calculated as the sum of autotrophic production by algae and heterotrophic production by bacteria using allochthonous organic carbon (OC). Whole‐lake production of new biomass was dominated by the benthic habitat (86% ± 4% [mean ± SD]) and by primary production (77% ± 9%). Still, heterotrophic bacteria fueled by allochthonous OC constituted a significant portion of the new biomass production in both benthic (19% ± 11%) and pelagic habitats (51% ± 24%). In addition, overall net production (primary production minus respiration) was close to zero in the benthic habitats but highly negative (−163 ± 81 mg C·m−2·d−1) in pelagic regions of all lakes. We conclude (1) that allochthonous OC supported a significant part of total production of new biomass in both pelagic and benthic habitats, (2) that benthic habitats dominated the whole‐lake production of new biomass, and (3) that respiration and net CO2 production dominated the carbon flux of the pelagic habitats and biomass production dominated the benthic carbon flux. Taken together, these findings suggest that previous investigations have greatly underestimated the productivity of clear‐water lakes when benthic autotrophic production and metabolism of allochthonous OC have not been measured.