bluuebunny/crossref_metadata_2025 huggingface dataset:
Enabling intelligent unmanned vehicles through XMOS Technology
Authors: Martins Goncalo , Moses Allistair , Rutherford Matthew J , Valavanis Kimon P
Published: January 2011

In this paper we describe a new design for intelligent unmanned vehicles using the XMOS processor and related technology. The current unmanned system design paradigm generally uses widely available microcontroller platforms such as PIC from Microchip, ARM microcontrollers, x86 architectures, among others. These technologies have pros and cons, but one common disadvantage is the complexity of handling multiple I/O streams while simultaneously engaging in complex computational tasks required for intelligent behavior. The conventional approach combines several types of microprocessors together to achieve simultaneous processing at different levels, a design choice that increases the overall complexity of the system by requiring glue logic and more off-chip communication. The proposed platform overcomes this limitation by unifying the high-level processing with the low-level, real-time control required for vehicle control using the XMOS technology, a new event-driven parallel processor for embedded systems. In this paper, we describe the overall design of our ground and aerial vehicles built around the XMOS processor, and present case-study analyses of the systems.
Strategic leadership: The accomplishment of strategy as a ‘perennially unfinished project’
Authors: Iszatt-White Marian
Published: January 2011

Based on an ethnomethodologically informed ethnography of further education college principals, this paper explores the nature and accomplishment of strategic leadership work as an ongoing, processual activity. In particular, the paper focuses on the ‘pre-implementation’ phase of the strategizing process, and suggests how the practices of clarifying, rehearsing, upholding, adapting and elaborating are integral to maintaining the spirit of the strategy in the face of unforeseen events. In so doing, it adopts the notion of strategy as a ‘perennially unfinished project’ (Knights and Mueller, 2004: 55), and explicates the constant need for improvisation and adjustment in order to successfully implement, not the letter of a strategic plan, but its intent. It also echoes Suchman’s seminal thesis on plans as ‘resources for situated action [that] do not in any strong sense determine its course’ (Suchman, 1987: 52).
An empirical evaluation of imputation accuracy for association statistics reveals increased type-I error rates in genome-wide associations
Authors: Almeida Marcio AA , Oliveira Paulo SL , Pereira Tiago V , Krieger José E , Pereira Alexandre C
Published: January 2011

Background

Genome wide association studies (GWAS) are becoming the approach of choice to identify genetic determinants of complex phenotypes and common diseases. The astonishing amount of generated data and the use of distinct genotyping platforms with variable genomic coverage are still analytical challenges. Imputation algorithms combine directly genotyped markers information with haplotypic structure for the population of interest for the inference of a badly genotyped or missing marker and are considered a near zero cost approach to allow the comparison and combination of data generated in different studies. Several reports stated that imputed markers have an overall acceptable accuracy but no published report has performed a pair wise comparison of imputed and empiric association statistics of a complete set of GWAS markers.

Results

In this report we identified a total of 73 imputed markers that yielded a nominally statistically significant association at P < 10 -5 for type 2 Diabetes Mellitus and compared them with results obtained based on empirical allelic frequencies. Interestingly, despite their overall high correlation, association statistics based on imputed frequencies were discordant in 35 of the 73 (47%) associated markers, considerably inflating the type I error rate of imputed markers. We comprehensively tested several quality thresholds, the haplotypic structure underlying imputed markers and the use of flanking markers as predictors of inaccurate association statistics derived from imputed markers.

Conclusions

Our results suggest that association statistics from imputed markers showing specific MAF (Minor Allele Frequencies) range, located in weak linkage disequilibrium blocks or strongly deviating from local patterns of association are prone to have inflated false positive association signals. The present study highlights the potential of imputation procedures and proposes simple procedures for selecting the best imputed markers for follow-up genotyping studies.
False negative rates in Drosophila cell-based RNAi screens: a case study
Authors: Booker Matthew , Samsonova Anastasia A , Kwon Young , Flockhart Ian , Mohr Stephanie E , Perrimon Norbert
Published: January 2011

Background

High-throughput screening using RNAi is a powerful gene discovery method but is often complicated by false positive and false negative results. Whereas false positive results associated with RNAi reagents has been a matter of extensive study, the issue of false negatives has received less attention.

Results

We performed a meta-analysis of several genome-wide, cell-based Drosophila RNAi screens, together with a more focused RNAi screen, and conclude that the rate of false negative results is at least 8%. Further, we demonstrate how knowledge of the cell transcriptome can be used to resolve ambiguous results and how the number of false negative results can be reduced by using multiple, independently-tested RNAi reagents per gene.

Conclusions

RNAi reagents that target the same gene do not always yield consistent results due to false positives and weak or ineffective reagents. False positive results can be partially minimized by filtering with transcriptome data. RNAi libraries with multiple reagents per gene also reduce false positive and false negative outcomes when inconsistent results are disambiguated carefully.
Development of genic-SSR markers by deep transcriptome sequencing in pigeonpea [Cajanus cajan (L.) Millspaugh]
Authors: Dutta Sutapa , Kumawat Giriraj , Singh Bikram P , Gupta Deepak K , Singh Sangeeta , Dogra Vivek , Gaikwad Kishor , Sharma Tilak R , Raje Ranjeet S , Bandhopadhya Tapas K , Datta Subhojit , Singh Mahendra N , Bashasab Fakrudin , Kulwal Pawan , Wanjari KB , K Varshney Rajeev , Cook Douglas R , Singh Nagendra K
Published: January 2011

Background

Pigeonpea [Cajanus cajan (L.) Millspaugh], one of the most important food legumes of semi-arid tropical and subtropical regions, has limited genomic resources, particularly expressed sequence based (genic) markers. We report a comprehensive set of validated genic simple sequence repeat (SSR) markers using deep transcriptome sequencing, and its application in genetic diversity analysis and mapping.

Results

In this study, 43,324 transcriptome shotgun assembly unigene contigs were assembled from 1.696 million 454 GS-FLX sequence reads of separate pooled cDNA libraries prepared from leaf, root, stem and immature seed of two pigeonpea varieties, Asha and UPAS 120. A total of 3,771 genic-SSR loci, excluding homopolymeric and compound repeats, were identified; of which 2,877 PCR primer pairs were designed for marker development. Dinucleotide was the most common repeat motif with a frequency of 60.41%, followed by tri- (34.52%), hexa- (2.62%), tetra- (1.67%) and pentanucleotide (0.76%) repeat motifs. Primers were synthesized and tested for 772 of these loci with repeat lengths of ≥18 bp. Of these, 550 markers were validated for consistent amplification in eight diverse pigeonpea varieties; 71 were found to be polymorphic on agarose gel electrophoresis. Genetic diversity analysis was done on 22 pigeonpea varieties and eight wild species using 20 highly polymorphic genic-SSR markers. The number of alleles at these loci ranged from 4-10 and the polymorphism information content values ranged from 0.46 to 0.72. Neighbor-joining dendrogram showed distinct separation of the different groups of pigeonpea cultivars and wild species. Deep transcriptome sequencing of the two parental lines helped in silico identification of polymorphic genic-SSR loci to facilitate the rapid development of an intra-species reference genetic map, a subset of which was validated for expected allelic segregation in the reference mapping population.

Conclusion

We developed 550 validated genic-SSR markers in pigeonpea using deep transcriptome sequencing. From these, 20 highly polymorphic markers were used to evaluate the genetic relationship among species of the genus Cajanus. A comprehensive set of genic-SSR markers was developed as an important genomic resource for diversity analysis and genetic mapping in pigeonpea.
Enhanced genetic maps from family-based disease studies: population-specific comparisons
Authors: He Chunsheng , Weeks Daniel E , Buyske Steven , Abecasis Goncalo R , Stewart William C , Matise Tara C ,   The Enhanced Map Consortium
Published: January 2011

Background

Accurate genetic maps are required for successful and efficient linkage mapping of disease genes. However, most available genome-wide genetic maps were built using only small collections of pedigrees, and therefore have large sampling errors. A large set of genetic studies genotyped by the NHLBI Mammalian Genotyping Service (MGS) provide appropriate data for generating more accurate maps.

Results

We collected a large sample of uncleaned genotype data for 461 markers generated by the MGS using the Weber screening sets 9 and 10. This collection includes genotypes for over 4,400 pedigrees containing over 17,000 genotyped individuals from different populations. We identified and cleaned numerous relationship and genotyping errors, as well as verified the marker orders. We used this dataset to test for population-specific genetic maps, and to re-estimate the genetic map distances with greater precision; standard errors for all intervals are provided. The map-interval sizes from the European (or European descent), Chinese, and Hispanic samples are in quite good agreement with each other. We found one map interval on chromosome 8p with a statistically significant size difference between the European and Chinese samples, and several map intervals with significant size differences between the African American and Chinese samples. When comparing Palauan with European samples, a statistically significant difference was detected at the telomeric region of chromosome 11p. Several significant differences were also identified between populations in chromosomal and genome lengths.

Conclusions

Our new population-specific screening set maps can be used to improve the accuracy of disease-mapping studies. As a result of the large sample size, the average length of the 95% confidence interval (CI) for a 10 cM map interval is only 2.4 cM, which is considerably smaller than on previously published maps.
Breast cancer and human papillomavirus infection: No evidence of HPV etiology of breast cancer in Indian women
Authors: Hedau Suresh , Kumar Umesh , Hussain Showket , Shukla Shirish , Pande Shailja , Jain Neeraj , Tyagi Abhishek , Deshpande Trivikram , Bhat Dilafroze , Mir Mohammad Muzaffar , Chakraborty Sekhar , Singh Y Mohan , Kumar Rakesh , Somasundaram Kumaravel , Bharti Alok C , Das Bhudev C
Published: January 2011

Background

Two clinically relevant high-risk HPV (HR-HPV) types 16 and 18 are etiologically associated with the development of cervical carcinoma and are also reported to be present in many other carcinomas in extra-genital organ sites. Presence of HPV has been reported in breast carcinoma which is the second most common cancer in India and is showing a fast rising trend in urban population. The two early genes E6 and E7 of HPV type 16 have been shown to immortalize breast epithelial cells in vitro, but the role of HPV infection in breast carcinogenesis is highly controversial. Present study has therefore been undertaken to analyze the prevalence of HPV infection in both breast cancer tissues and blood samples from a large number of Indian women with breast cancer from different geographic regions.

Methods

The presence of all mucosal HPVs and the most common high-risk HPV types 16 and 18 DNA was detected by two different PCR methods - (i) conventional PCR assays using consensus primers (MY09/11, or GP5+/GP6+) or HPV16 E6/E7 primers and (ii) highly sensitive Real-Time PCR. A total of 228 biopsies and corresponding 142 blood samples collected prospectively from 252 patients from four different regions of India with significant socio-cultural, ethnic and demographic variations were tested.

Results

All biopsies and blood samples of breast cancer patients tested by PCR methods did not show positivity for HPV DNA sequences in conventional PCRs either by MY09/11 or by GP5+/GP6+/HPV16 E6/E7 primers. Further testing of these samples by real time PCR also failed to detect HPV DNA sequences.

Conclusions

Lack of detection of HPV DNA either in the tumor or in the blood DNA of breast cancer patients by both conventional and real time PCR does not support a role of genital HPV in the pathogenesis of breast cancer in Indian women.
Dual induction of caspase 3- and transglutaminase-dependent apoptosis by acyclic retinoid in hepatocellular carcinoma cells
Authors: Tatsukawa Hideki , Sano Tetsuro , Fukaya Yayoi , Ishibashi Naoto , Watanabe Makiko , Okuno Masataka , Moriwaki Hisataka , Kojima Soichi
Published: January 2011

Background

Hepatocellular carcinoma has a high mortality rate due to its rate of recurrence. Acyclic retinoid prevents recurrence of hepatocellular carcinoma in patients after surgical removal of their primary tumors by inducing apoptosis in hepatocellular carcinoma cells, although the molecular mechanisms of action are not understood.

Methods

Human hepatocellular carcinoma cells in culture, as well as nude mice transplanted with hepatocellular carcinoma cells and rats given with N-diethylnitrosamine were treated with acyclic retinoid. Changes in activated caspase 3 and transglutaminase 2 (TG2) levels, Sp1 cross-linking and its activities, expression of epidermal growth factor receptor, and apoptotic levels were measured.

Results

Acyclic retinoid simultaneously stimulated the activation of caspase 3, and the expression, nuclear localization and crosslinking activity of TG2, resulting in crosslinking and inactivation of the transcription factor, Sp1, thereby reducing expression of epidermal growth factor receptor and cell death in three hepatocellular carcinoma cell lines. These effects were partially restored by a caspase inhibitor, transfection of antisense TG2, restoration of functional Sp1, or an excess of epidermal growth factor. Nuclear expression of TG2 and crosslinked Sp1, as also activated caspase 3 were found in both hepatocellular carcinoma cells transplanted into nude mice and cancerous regions within the liver in N-diethylnitrosamine-induced hepatocarcinogenesis model in rats, following treatment of animals with acyclic retinoid.

Conclusions

Treatment with acyclic retinoid produces a dual activation of caspase 3 and TG2 induced apoptosis of hepatocellular carcinoma cells via modification and inactivation of Sp1, resulting in reduced expression of epidermal growth factor receptor.
Analysis of the proteome of human airway epithelial secretions
Authors: Ali Mehboob , Lillehoj Erik P , Park Yongsung , Kyo Yoshiyuki , Kim K Chul
Published: January 2011

Background

Airway surface liquid, often referred to as mucus, is a thin layer of fluid covering the luminal surface that plays an important defensive role against foreign particles and chemicals entering the lungs. Airway mucus contains various macromolecules, the most abundant being mucin glycoproteins, which contribute to its defensive function. Airway epithelial cells cultured in vitro secrete mucins and nonmucin proteins from their apical surface that mimics mucus production in vivo. The current study was undertaken to identify the polypeptide constituents of human airway epithelial cell secretions to gain a better understanding of the protein composition of respiratory mucus.

Results

Fifty-five proteins were identified in the high molecular weight fraction of apical secretions collected from in vitro cultures of well-differentiated primary human airway epithelial cells and isolated under physiological conditions. Among these were MUC1, MUC4, MUC5B, and MUC16 mucins. By proteomic analysis, the nonmucin proteins could be classified as inflammatory, anti-inflammatory, anti-oxidative, and/or anti-microbial.

Conclusions

Because the majority of the nonmucin proteins possess molecular weights less than that selected for analysis, it is theoretically possible that they may associate with the high molecular weight and negatively charged mucins to form a highly ordered structural organization that is likely to be important for maintaining the proper defensive function of airway mucus.
Hepatic accumulation of intestinal cholesterol is decreased and fecal cholesterol excretion is increased in mice fed a high-fat diet supplemented with milk phospholipids
Authors: Kamili Alvin , Wat Elaine , Chung Rosanna WS , Tandy Sally , Weir Jacquelyn M , Meikle Peter J , Cohn Jeffrey S
Published: January 2011

Background

Milk phospholipids (PLs) reduce liver lipid levels when given as a dietary supplement to mice fed a high-fat diet. We have speculated that this might be due to reduced intestinal cholesterol uptake.

Methods

Mice were given a high-fat diet for 3 or 5 weeks that had no added PL or that were supplemented with 1.2% by wt PL from cow's milk. Two milk PL preparations were investigated: a) a PL-rich dairy milk extract (PLRDME), and b) a commercially-available milk PL concentrate (PC-700). Intestinal cholesterol uptake was assessed by measuring fecal and hepatic radioactivity after intragastric administration of [14C]cholesterol and [3H]sitostanol. Fecal and hepatic lipids were measured enzymatically and by ESI-MS/MS.

Results

Both PL preparations led to significant decreases in total liver cholesterol and triglyceride (-20% to -60%, P < 0.05). Hepatic accumulation of intragastrically-administered [14C]cholesterol was significantly less (-30% to -60%, P < 0.05) and fecal excretion of [14C]cholesterol and unlabeled cholesterol was significantly higher in PL-supplemented mice (+15% to +30%, P < 0.05). Liver cholesterol and triglyceride levels were positively correlated with hepatic accumulation of intragastrically-administered [14C]cholesterol (P < 0.001) and negatively correlated with fecal excretion of [14C]cholesterol (P < 0.05). Increased PL and ceramide levels in the diet of mice supplemented with milk PL were associated with significantly higher levels of fecal PL and ceramide excretion, but reduced levels of hepatic PL and ceramide, specifically, phosphatidylcholine (-21%, P < 0.05) and monohexosylceramide (-33%, P < 0.01).

Conclusion

These results indicate that milk PL extracts reduce hepatic accumulation of intestinal cholesterol and increase fecal cholesterol excretion when given to mice fed a high-fat diet.
Involvement of Spinal NR2B-Containing NMDA Receptors in Oxaliplatin-Induced Mechanical Allodynia in Rats
Authors: Mihara Yuki , Egashira Nobuaki , Sada Hikaru , Kawashiri Takehiro , Ushio Soichiro , Yano Takahisa , Ikesue Hiroaki , Oishi Ryozo
Published: January 2011

Background:

Oxaliplatin is a platinum-based chemotherapy drug characterized by the development of acute and chronic peripheral neuropathies. The chronic neuropathy is a dose-limiting toxicity. We previously reported that repeated administration of oxaliplatin induced cold hyperalgesia in the early phase and mechanical allodynia in the late phase in rats. In the present study, we investigated the involvement of NR2B-containing N-methyl-D-aspartate (NMDA) receptors in oxaliplatin-induced mechanical allodynia in rats.

Results:

Repeated administration of oxaliplatin (4 mg/kg, i.p., twice a week) caused mechanical allodynia in the fourth week, which was reversed by intrathecal injection of MK-801 (10 nmol) and memantine (1 μmol), NMDA receptor antagonists. Similarly, selective NR2B antagonists Ro25-6981 (300 nmol, i.t.) and ifenprodil (50 mg/kg, p.o.) significantly attenuated the oxaliplatin-induced pain behavior. In addition, the expression of NR2B protein and mRNA in the rat spinal cord was increased by oxaliplatin on Day 25 (late phase) but not on Day 5 (early phase). Moreover, we examined the involvement of nitric oxide synthase (NOS) as a downstream target of NMDA receptor. L-NAME, a non-selective NOS inhibitor, and 7-nitroindazole, a neuronal NOS (nNOS) inhibitor, significantly suppressed the oxaliplatin-induced pain behavior. The intensity of NADPH diaphorase staining, a histochemical marker for NOS, in the superficial layer of spinal dorsal horn was obviously increased by oxaliplatin, and this increased intensity was reversed by intrathecal injection of Ro25-6981.

Conclusion:

These results indicated that spinal NR2B-containing NMDA receptors are involved in the oxaliplatin-induced mechanical allodynia.
Osteoid osteoma near the intervertebral foramen may induce radiculopathy through tumorous inflammation
Authors: Zenmyo Michihisa , Yamamoto Takuya , Ishidou Yasuhiro , Komiya Setsuro , Ijiri Kosei
Published: January 2011

Osteoid osteoma of the spine is a relatively rare bone-forming tumor. Pain that is worse at night and relieved by aspirin and muscle contracture are the most characteristic symptoms of spinal osteoid osteoma. Although radicular pain occasionally occurs in spinal osteoid osteoma, spinal cord and nerve root compression is absent in most cases. Although radicular pain appears to be associated with tumorous inflammation, there have been no presentations of histological findings of inflammation around the nerve root. We present here two rare cases of spinal osteoid osteoma causing radiculopathy and the first histological evidence of tumorous inflammation as a cause of radiculopathy in osteoid osteoma near the intervertebral foramen.
Progressive multifocal cerebral infarction from intravascular large B cell lymphoma presenting in a man: a case report
Authors: Jitpratoom Pornpong , Yuckpan Patcharawan , Sitthinamsuwan Panitta , Chotinaiwattarakul Wattanachai , Chinthammitr Yingyong
Published: January 2011

Introduction

Intravascular lymphoma is rare, and may present as ischemic stroke. Diagnosis is difficult due to the non-specific presentation and lack of lymphadenopathy, thus leading to frequent instances of autopsy-proven diagnosis. To the best of our knowledge, this is the first report of progressive stroke from intravascular lymphoma diagnosed antemortem by random skin biopsy.

Case presentation

A 42-year-old Thai man presented to our hospital with progressive multifocal cerebral infarction. Despite taking aspirin (300 mg/day), his neurological symptoms worsened. During admission, he developed an unexplained fever and hypoxemia. Magnetic resonance angiography clearly showed patency of all cerebral arteries including the internal carotid and vertebrobasilar arteries. Echocardiography, an antiphospholipid antibody test, cerebrospinal fluid cytology and a bone marrow study were normal. Other laboratory test results showed an elevated lactate dehydrogenase level, nephrotic range proteinuria (3.91 g/day), hypoalbuminemia (1.9 g/dL), a very low high-density lipoprotein level (7 mg/dL) and hypertriglyceridemia (353 mg/dL). Because of suspected vasculitis, pulse methylprednisolone was given with transiently minimal improvement. A random skin biopsy from both thighs revealed intravascular large B cell lymphoma. Chemotherapy was not given due to our patient having ventilator associated pneumonia. He died 10 days after the definite diagnosis was established.

Conclusion

One etiology of stroke is intravascular lymphoma, in which random skin biopsy can be helpful for antemortem diagnosis.
Reverse transcription of the pFOXC mitochondrial retroplasmids of Fusarium oxysporum is protein primed
Authors: Galligan Jeffrey T , Marchetti Sarah E , Kennell John C
Published: January 2011

Background

The pFOXC retroplasmids are small, autonomously replicating DNA molecules found in mitochondria of certain strains of the filamentous fungus Fusarium oxysporum and are among the first linear genetic elements shown to replicate via reverse transcription. The plasmids have a unique clothespin structure that includes a 5'-linked protein and telomere-like terminal repeats, with pFOXC2 and pFOXC3 having iterative copies of a 5 bp sequence. The plasmids contain a single large open reading frame (ORF) encoding an active reverse transcriptase (RT). The pFOXC-RT is associated with the plasmid transcript in a ribonucleoprotein (RNP) complex and can synthesize full-length (-) strand cDNA products. In reactions containing partially purified RT preparations with exogenous RNAs, the pFOXC3-RT has been shown to initiate cDNA synthesis by use of snapped-back RNAs, as well as loosely associated DNA primers.

Results

The complete sequence of the distantly related pFOXC1 plasmid was determined and found to terminate in 3-5 copies of a 3 bp sequence. Unexpectedly, the majority of (-) strand cDNA molecules produced from endogenous pFOXC1 transcripts were attached to protein. In vitro experiments using partially purified pFOXC3-RT preparations having a single radiolabeled deoxyribonucleotide triphosphate (dNTP) generated a nucleotide-labeled protein that migrated at the size of the pFOXC-RT. The nucleotide preference of deoxynucleotidylation differed between pFOXC3 and pFOXC1 and showed complementarity to the respective 3' terminal repeats. In reactions that include exogenous RNA templates corresponding to the 3' end of pFOXC1, a protein-linked cDNA product was generated following deoxynucleotidylation, suggesting that reverse transcription initiates with a protein primer.

Conclusions

The finding that reverse transcription is protein primed suggests the pFOXC retroplasmids may have an evolutionary relationship with hepadnaviruses, the only other retroelement family known to initiate reverse transcription via a protein primer. Moreover, the similarity to protein-primed linear DNA elements supports models in which the terminal repeats are generated and maintained by a DNA slideback mechanism. The ability of the pFOXC-RT to utilize RNA, DNA and protein primers is unique among polymerases and suggests that the pFOXC plasmids may be evolutionary precursors of a broad range of retroelements, including hepadnaviruses, non-long terminal repeat (non-LTR) retrotransposons and telomerase.
Ancestral and derived attributes of the dlx gene repertoire, cluster structure and expression patterns in an African cichlid fish
Authors: Renz Adina J , Gunter Helen M , Fischer Jan MF , Qiu Huan , Meyer Axel , Kuraku Shigehiro
Published: January 2011

Background

Cichlid fishes have undergone rapid, expansive evolutionary radiations that are manifested in the diversification of their trophic morphologies, tooth patterning and coloration. Understanding the molecular mechanisms that underlie the cichlids' unique patterns of evolution requires a thorough examination of genes that pattern the neural crest, from which these diverse phenotypes are derived. Among those genes, the homeobox-containing Dlx gene family is of particular interest since it is involved in the patterning of the brain, jaws and teeth.

Results

In this study, we characterized the dlx genes of an African cichlid fish, Astatotilapia burtoni, to provide a baseline to later allow cross-species comparison within Cichlidae. We identified seven dlx paralogs (dlx1a, -2a, -4a, -3b, -4b, -5a and -6a), whose orthologies were validated with molecular phylogenetic trees. The intergenic regions of three dlx gene clusters (dlx1a-2a, dlx3b-4b, and dlx5a-6a) were amplified with long PCR. Intensive cross-species comparison revealed a number of conserved non-coding elements (CNEs) that are shared with other percomorph fishes. This analysis highlighted additional lineage-specific gains/losses of CNEs in different teleost fish lineages and a novel CNE that had previously not been identified. Our gene expression analyses revealed overlapping but distinct expression of dlx orthologs in the developing brain and pharyngeal arches. Notably, four of the seven A. burtoni dlx genes, dlx2a, dlx3b, dlx4a and dlx5a, were expressed in the developing pharyngeal teeth.

Conclusion

This comparative study of the dlx genes of A. burtoni has deepened our knowledge of the diversity of the Dlx gene family, in terms of gene repertoire, expression patterns and non-coding elements. We have identified possible cichlid lineage-specific changes, including losses of a subset of dlx expression domains in the pharyngeal teeth, which will be the targets of future functional studies.
p53 mutant breast cancer patients expressing p53γ have as good a prognosis as wild-type p53 breast cancer patients
Authors: Bourdon Jean-Christophe , Khoury Marie P , Diot Alexandra , Baker Lee , Fernandes Kenneth , Aoubala Mustapha , Quinlan Philip , Purdie Colin A , Jordan Lee B , Prats Anne-Catherine , Lane David P , Thompson Alastair M
Published: January 2011

Introduction

Normal function of the p53 network is lost in most cancers, often through p53 mutation. The clinical impact of p53 mutations in breast cancer remains uncertain, especially where p53 isoforms may modify the effects of these p53 mutations.

Methods

Expression of p53β and p53γ isoforms, the isoforms identified in normal breast tissue, was detected by reverse transcription polymerase chain reaction from a cohort of 127 primary breast tumours. Expression of p53β and p53γ isoforms was analysed in relation to clinical markers and clinical outcomes (5 years) by binary logistic regression, Cox proportional hazards regression and Kaplan-Meier survival analyses.

Results

p53β and p53γ were not randomly expressed in breast cancer. p53β was associated with tumour oestrogen receptor (ER) expression, and p53γ was associated with mutation of the p53 gene. The patient group with the mutant p53 breast tumour-expressing p53γ isoform had low cancer recurrence and an overall survival as good as that of patients with wild-type p53 breast cancer. Conversely, patients expressing only mutant p53, without p53γ isoform expression, had a particularly poor prognosis.

Conclusions

The determination of p53γ expression may allow the identification, independently of the ER status, of two subpopulations of mutant p53 breast cancer patients, one expressing p53γ with a prognosis as good as the wild-type p53 breast cancer patients and a second one not expressing p53γ with a particularly poor prognosis. The p53γ isoform may provide an explanation of the hitherto inconsistent relationship between p53 mutation, treatment response and outcome in breast cancer.
G6PD Up-Regulation Promotes Pancreatic β-Cell Dysfunction
Authors: Lee Joo-Won , Choi A Hyun , Ham Mira , Kim Ji-Won , Choe Sung Sik , Park Jiyoung , Lee Gha Young , Yoon Kun-Ho , Kim Jae Bum
Published: January 2011

Increased reactive oxygen species (ROS) induce pancreatic β-cell dysfunction during progressive type 2 diabetes. Glucose-6-phosphate dehydrogenase (G6PD) is a reduced nicotinamide adenine dinucleotide phosphate-producing enzyme that plays a key role in cellular reduction/oxidation regulation. We have investigated whether variations in G6PD contribute to β-cell dysfunction through regulation of ROS accumulation and β-cell gene expression. When the level of G6PD expression in pancreatic islets was examined in several diabetic animal models, such as db/db mice and OLEFT rats, G6PD expression was evidently up-regulated in pancreatic islets in diabetic animals. To investigate the effect of G6PD on β-cell dysfunction, we assessed the levels of cellular ROS, glucose-stimulated insulin secretion and β-cell apoptosis in G6PD-overexpressing pancreatic β-cells. In INS-1 cells, G6PD overexpression augmented ROS accumulation associated with increased expression of prooxidative enzymes, such as inducible nitric oxide synthase and reduced nicotinamide adenine dinucleotide phosphate oxidase. G6PD up-regulation also caused decrease in glucose-stimulated insulin secretion in INS-1 cells and primary pancreatic islets. Moreover, elevated G6PD expression led to β-cell apoptosis, concomitant with the increase in proapoptotic gene expression. On the contrary, suppression of G6PD with small interference RNA attenuated palmitate-induced β-cell apoptosis. Together, these data suggest that up-regulation of G6PD in pancreatic β-cells would induce β-cell dysregulation through ROS accumulation in the development of type 2 diabetes.
Effect of Animal Facility Construction on Basal Hypothalamic-Pituitary-Adrenal and Renin-Aldosterone Activity in the Rat
Authors: Raff Hershel , Bruder Eric D. , Cullinan William E. , Ziegler Dana R. , Cohen Eric P.
Published: January 2011

Although loud noise and intense vibration are known to alter the behavior and phenotype of laboratory animals, little is known about the effects of nearby construction. We studied the effect of a nearby construction project on the classic stress hormones ACTH, corticosterone, renin, and aldosterone in rats residing in a barrier animal facility before, for the first 3 months of a construction project, and at 1 month after all construction was completed. During some of the construction, noise and vibrations were not obvious to investigators inside the animal rooms. Body weight matched for age was not altered by nearby construction. During nearby construction, plasma ACTH, corticosterone, and aldosterone were approximately doubled compared with those of pre- and postconstruction levels. Expression of CRH mRNA in the paraventricular nucleus of the hypothalamus, CRH receptor and POMC mRNA in the anterior pituitary, and most mRNAs for steroidogenic genes in the adrenal gland were not significantly changed during construction. We conclude that nearby construction can cause a stress response without long-term effects on hypothalamic-pituitary-adrenal axis gene expression and body weight.
Improvement of Pharmaceutical near Infrared Calibrations by Empirical Target Distribution Optimisation
Authors: Igne Benoît , Talwar Sameer , Drennen James K. , Anderson Carl A.
Published: January 2011

Using process samples to develop near infrared prediction models can generate artefacts in the calibration set, potentially reducing model performance. Due to the inherent variability of manufacturing processes, the assumption that all samples from a given batch have the same concentration for the compound of interest is incorrect. A tablet press will produce compacts with different drug concentrations, distributed around a nominal value, due to mechanical effects, vibrations and powder segregation that occur in the hopper. Differences in tablet crushing strength may also be observed for those same reasons. Consequently, using such samples and their associated nominal concentrations for the development of a calibration model for the prediction of content uniformity of tablets might produce models with rather high error while able to cope with a large range of process variability. The objective of this work was to investigate empirical approaches for optimising the target (reference) concentrations of prediction samples to best match the underlying spectral variance in an attempt to mitigate interferences that may be responsible for select portions of calibration error. Three approaches were developed. The first used samples presenting a low residual from an original model to re-predict high residual samples. The second approach was an iterative search of the best target value for each sample. The third method used target values generated from a normal distribution. These approaches were compared with the classical slope and bias correction methods on their ability to predict two independent validation sets. While several methods showed significant over-fitting and a high validation error, the iterative search routine enhanced calibration performance compared to post-regression correction methods and was proven to be a viable alternative to current industry practices.
The Relationship Between Physical Fitness and Work Integration Following Stroke
Authors: Schönberger Michael , Hansen Niels R. , Pedersen Daniel T. , Zeeman Peter , Jørgensen Jørgen Roed
Published: January 2011

Objective:To investigate the relationship between physical fitness and work integration following stroke.Design:Single-group study, measurement of physical fitness pre and post physical training, measurement of employment status in a follow-up assessment 2 to 36 months after rehabilitation.Setting:Interdisciplinary outpatient rehabilitation program.Participants:58 stroke survivors (62% male, mean age at program start 46.7 years, mean time since stroke 1.1 years) who were consecutively referred to the program.Intervention:1½ hours of intensive training of cardiorespiratory fitness and muscle strength 1–3 times weekly as part of the 3-month program.Measures:Physical fitness was measured with a modified Harvard Step Test, the Åstrand Cycling Test, and walking/running speed. The type of participants' employment as well as the amount of working hours was registered.Results:Good physical fitness as measured by the Harvard Step test, but not the Åstrand Cycling Test and walking/running speed, was related to return to competitive, full-time employment. Test results from training tended to predict work reintegration better than test results from training start. Improvement of physical fitness as measured by the Harvard Step Test was also related to follow-up employment.Conclusions:The results imply a relationship between physical fitness and work integration following stroke and should be confirmed with a randomised controlled study design.
Autobiographical Event Memory in Patients With Mesial Temporal Lobe Lesions: Impact of Test Methodology and Aetiology of Lesion
Authors: Gray Kathryn , Lah Suncica , Batchelor Samantha , Thompson Elizabeth , Miller Laurie
Published: January 2011

There is some evidence that in patients with temporal lobe lesions, the presence and temporal pattern of deficits in autobiographical event memory depends on aetiology and the methodology used. In this study, 19 patients with mesial temporal lesions that involved the hippocampus (14 temporal lobectomy [TL] and 5 cerebral vascular accident [CVA]) were compared to 20 normal control [NC] subjects on the Autobiographical Memory Interview, Autobiographical Fluency Test for Events (AFT-Events) and a modified Crovitz Cue Technique. All three measures revealed impairments in autobiographical event recall for the TL patients, but only the Crovitz Cue Technique detected a deficit for the CVA group. No temporal gradients in retrograde recall were found. The findings indicate that test methodology and aetiology of lesion influence the likelihood of finding deficits in recall of autobiographical events but not the temporal pattern of deficits.
EU state aid rules, public service broadcasters' online media engagement and Public Value Tests: the German and UK cases compared
Authors: Humphreys Peter
Published: January 2011

The article examines how the competition issues raised by the public service broadcasters' (PSBs) new media engagement have been handled in Germany and the United Kingdom. Private communications interests, and certain political actors, have sought to restrict the scope of public service
broadcasting, particularly with regard to their online media operations. EU state aid rules have been called into play by complaints from the private media sector about unfair competition and market distortion. The article looks at how the PSBs and media policy-makers have handled the competition
issues raised by the PSBs' online media engagement, and explains how they have met the requirements of EU state aid rules. To be precise, the article examines the development of the Public Value Test in the United Kingdom and its equivalent in Germany, the Three-Step-Test (Drei Stufen Test).
The article considers the issues surrounding implementation of these tests and the implications of the new procedures for the future organization, accountability and output of the PSBs.
Is the public interest under threat? Public service broadcasting, market failure and new technologies: the view from the European Union
Authors: Michalis Maria
Published: January 2011

This article examines the status of public service broadcasting in the European Union, focusing on the extent to which State aid rules prescribe its scope in particular in the new media environment. Although its substantive policy output is centred on economic and competition priorities, the European Union has been increasingly sensitive to public interest considerations. Moreover, it is argued that the European Commission has generally supported public service broadcasters in its decisions and, even if critical at times, has overall respected the balance between economic and sociocultural aims struck at the national level.

The revised Broadcasting Communication (2009) endorses market arguments, but at the same time it rejects some potentially restrictive approaches implied in earlier investigations and strengthens subsidiarity in the field of public service broadcasting. The Communication reaffirms that the member states are primarily responsible for promoting democratic and public interest objectives, but, and here lies the tension, the European Union has effectively a vetting power in ensuring that these objectives do not unduly distort competition. The precise impact of the Communication on the public interest now hangs on how member states will implement it.
Media ownership policy in a recession: redefining the public interest
Authors: Barnett Steven
Published: January 2011

As media enterprises steer a path through unprecedented economic upheaval, many are looking to consolidation as a means of achieving economies of scale that would, they argue, shore up their investment in journalism. There is therefore growing pressure on policy-makers to relax traditional
ownership rules preventing undue concentration of media conglomerates. This poses a challenge to critical scholars traditionally opposed to such relaxation on the grounds of promoting pluralism and diversity in a democracy. This article argues that, rather than risk the rapid emasculation
of original journalism, we should be thinking more creatively about how the public interest and journalistic diversity might be protected within a policy of consolidation. Drawing on recent legislative initiatives in the United Kingdom, it proposes two possible approaches: first, inserting
into merger legislation detailed public interest provisions rooted in normative values of professional journalism; and second, on the basis of clear evidence that ownership structures influence content, fostering different forms of ownership that move beyond the traditional privatepublic dichotomy
to exploit online and not-for-profit opportunities.
Review
Authors: Scifo Salvatore
Published: January 2011

Narrating Media History, Michael Bailey (2009) Abingdon: Routledge, 256 pages ISBN 978-0-415-41916-1 Paperback, 19.99
Lessons from an “Oops” at Consumer Reports: Consumers Follow Experts and Ignore Invalid Information
Authors: Simonsohn Uri
Published: January 2011

In 2007, Consumer Reports released, and two weeks later retracted, a flawed report on the safety of infant car seats. Analyzing data from 5471 online auctions for car seats ending before, during, and after the information was considered valid, this article shows that (1) consumers responded to the new information and, more surprisingly, (2) they promptly ceased to do so when it was retracted. Because of the random nature of the flawed ratings, this first finding demonstrates that expert advice has a causal effect on consumer demand. The second finding suggests that people's inability to willfully ignore information is not as extreme as the experimental evidence in the psychological literature suggests.
Product Line Design for Consumer Durables: An Integrated Marketing and Engineering Approach
Authors: Luo Lan
Published: January 2011

Product line design for consumer durables often relies on close coordination between marketing and engineering domains. Product lines that evolve as optimal from marketers’ perspective may not be optimal from an engineering viewpoint, and vice versa. Although extant research has proposed sophisticated techniques to handle problems that characterize each individual domain, the majority of these developments have not addressed the interdependent issues across marketing and engineering. The author presents a product line optimization method that enables managers to simultaneously consider factors deemed important from both marketing and engineering domains. One major advantage of this method is that it takes into account the strategic reactions from the incumbent manufacturers and the retailer in the design of the product line. The author demonstrates in a simulation study that this method is applicable to problems with a reasonably large scale. Using data collected in a power tool development project undertaken by a major U.S. manufacturer, the study illustrates that the proposed method leads to a more profitable product line than alternative approaches that consider requirements from these two domains separately.
Answering the Unasked Question: Response Substitution in Consumer Surveys
Authors: Gal David , Rucker Derek D.
Published: January 2011

Researchers and practitioners alike frequently survey consumers to gain insights into their attitudes, preferences, and beliefs. The authors propose a potentially pervasive, but as of yet unidentified, source of bias in survey responding. Specifically, they propose that respondents’ answers to questions might sometimes reflect attitudes that respondents want to convey but that the researcher has not asked about, a phenomenon termed “response substitution.” The authors examine this proposition in a series of three experiments that demonstrate the phenomenon, provide support for the process account, and identify boundary conditions. They also discuss general theoretical, methodological, and practical implications as well as specific implications for research on attitudes and contingent valuation.
Measuring Contagion in the Diffusion of Consumer Packaged Goods
Authors: Du Rex Yuxing , Kamakura Wagner A.
Published: January 2011

This study measures the degree of contagion or interpersonal influence in the diffusion of new consumer packaged goods (CPGs). The authors demonstrate that when an individual-level trial hazard model is properly specified to account for potential sources of biases, substantial contagion effects may be detected in the diffusion of many CPGs. Using longitudinal panel data on individual-level trial and repeat purchases of 67 newly introduced CPGs, they show that standard diffusion models fail to detect contagion. However, after extending the model to allow for spatial and temporal heterogeneity in contagion and controlling for various cross-sectional and temporal confounds, they find statistically significant contagion effects in 33 to 40 of the 67 sample products. The empirical evidence of contagion in the diffusion of many CPGs has important implications because most new product trial models for CPGs have assumed a priori that there is no contagion in the diffusion of these products. Moreover, the individual-level simultaneous analysis of the diffusion of 67 newly introduced CPGs provides useful insights into the unobservable network of influences among consumers. Such analysis allows a vendor to identify the most influential early adopters among its customers, who could help diffuse a new product more effectively in the market.