bluuebunny/crossref_metadata_2025 huggingface dataset:
When workplace interventions lead to negative effects: Learning from failures
Authors: Aust Birgit , Rugulies Reiner , Finken Annett , Jensen Chris
Published: December 2009

Aims: To investigate if workplace interventions resulted in changes in the psychosocial work environment. Process evaluation was conducted to study the implementation process and to use this knowledge to understand the results. Methods: Seven intervention units (n = 128) and seven non-randomized reference units (n = 103) of a large hospital in Denmark participated in an intervention project with the goal of improving the psychosocial working conditions. The intervention consisted of discussion days for all staff, employee working groups, leader coaching, and activities to improve communication and cooperation. Measures of the psychosocial work environment were conducted before the start of the intervention and again after 16 months using 13 scales from the Copenhagen Psychosocial Questionnaire, version I (COPSOQ I). Results: In the intervention units there was a statistically significant worsening in six out of 13 work environment scales. The decrease was most pronounced for three scales that measure aspects of interpersonal relations and leadership. In addition, all three scales that measure aspects of work organization and job content decreased. In comparison, the reference group showed statistically significant changes in only two scales. Process evaluation revealed that a large part of the implementation failed and that different implicit theories were at play. Conclusions: Without the insights gained from process data the negative effects of this intervention could not be understood. Sometimes — as it seems happened in this study — more harm can be done by disappointing expectations than by not conducting an intervention.
Postcards From Pigtown
Authors: Silk Michael
Published: December 2009

Within this article, the author draws upon his (lived) reflexive autoethnographic experiences within the city of Baltimore. Focusing on the pathways, decisions, and negotiations the author has taken through the city, the author offers a case study framed by a series of “picture postcards” that—despite official rhetoric centered on an urban glamour zone and a civic administration who panegyrically espouse the market logics of neoliberalism—emphasize the polarized nature of the polis. In particular, through these postcards, the brutal demarcation of winners and losers in Baltimore is discussed in an effort to elucidate, and expose, the practices and processes of social governance, through which both valorized and pathologized urban bodies are made visible (and are effectively regulated) as they contribute toward materializing the differentiated (and indeed differentiating) new urban landscape.
The Ambulatist: A Health Care Professional Specializing in Lifestyle Medicine for Chronic Disease Care Coordination
Authors: Lenz Thomas L.
Published: December 2009

Chronic diseases such as heart disease, diabetes, and obesity pose a significant burden on the US health care system. The Centers for Disease Control and Prevention (CDC) estimate that 70% of American deaths are a direct result of chronic diseases. Recently, discussions about care coordination in the health care system have been more frequent. However, there is still much to learn about providing effective health care coordination. A new model for care coordination is being developed and is focused on lifestyle medicine through the use of an ambulatist. An ambulatist is a health care provider who specializes in the prevention, management, and care coordination of ambulatory patients with chronic diseases by using lifestyle medicine and drug therapy. This article discusses how an ambulatist is being used in one chronic disease management program and the applicability for use in other settings.
IL-6 and MYC collaborate in plasma cell tumor formation in mice
Authors: Rutsch Sebastian , Neppalli Vishala T. , Shin Dong-Mi , DuBois Wendy , Morse Herbert C. , Goldschmidt Hartmut , Janz Siegfried
Published: December 2009

Interleukin-6 (IL-6) plays a critical role in the natural history of human plasma cell neoplasms (PCNs), such as plasma cell myeloma and plasmacytoma (PCT). IL-6 is also at the center of neoplastic plasma cell transformation in BALB/c (C) mice carrying a transgene, H2-Ld-IL6, that encodes human IL-6 under control of the major histocompatibility complex H2-Ld promoter: strain C.H2-Ld-IL6. These mice are prone to PCT, but tumor development is incomplete with long latencies (∼ 40% PCT at 12 months of age). To generate a more robust mouse model of IL-6–dependent PCN, we intercrossed strain C.H2-Ld-IL6 with strains C.iMycEμ or C.iMycCα, 2 interrelated gene-insertion models of the chromosomal T(12;15) translocation causing deregulated expression of Myc in mouse PCT. Deregulation of MYC is also a prominent feature of human PCN. We found that double-transgenic C.H2-Ld-IL6/iMycEμ and C.H2-Ld-IL6/iMycCα mice develop PCT with full penetrance (100% tumor incidence) and short latencies (3-6 months). The mouse tumors mimic molecular hallmarks of their human tumor counterparts, including elevated IL-6/Stat3/Bcl-XL signaling. The newly developed mouse strains may provide a good preclinical research tool for the design and testing of new approaches to target IL-6 in treatment and prevention of human PCNs.
The protein C pathway in tissue inflammation and injury: pathogenic role and therapeutic implications
Authors: Danese Silvio , Vetrano Stefania , Zhang Li , Poplis Victoria A. , Castellino Francis J.
Published: December 2009

Inflammation and coagulation are closely linked interdependent processes. Under physiologic conditions, the tissue microcirculation functions in anticoagulant and anti-inflammatory fashions. However, when inflammation occurs, coagulation is also set in motion and actively participates in enhancing inflammation. Recently, novel and unexpected roles of hemostasis in the humoral and cellular components of innate immunity have been described. In particular, the protein C system, besides its well-recognized role in anticoagulation, plays a crucial role in inflammation. Indeed, the protein C system is now emerging as a novel participant in the pathogenesis of acute and chronic inflammatory diseases, such as sepsis, asthma, inflammatory bowel disease, atherosclerosis, and lung and heart inflammation, and may emerge as unexpected therapeutic targets for intervention.
Circulating microvesicles in B-cell chronic lymphocytic leukemia can stimulate marrow stromal cells: implications for disease progression
Authors: Ghosh Asish K. , Secreto Charla R. , Knox Traci R. , Ding Wei , Mukhopadhyay Debabrata , Kay Neil E.
Published: December 2009

Microvesicles (MVs) released by malignant cancer cells constitute an important part of the tumor microenvironment. They can transfer various messages to target cells and may be critical to disease progression. Here, we demonstrate that MVs circulating in plasma of B-cell chronic lymphocytic leukemia (CLL) patients exhibit a phenotypic shift from predominantly platelet derived in early stage to leukemic B-cell derived at advanced stage. Furthermore, the total MV level in CLL was significantly greater compared with healthy subjects. To understand the functional implication, we examined whether MVs can interact and modulate CLL bone marrow stromal cells (BMSCs) known to provide a “homing and nurturing” environment for CLL B cells. We found that CLL-MV can activate the AKT/mammalian target of rapamycin/p70S6K/hypoxia-inducible factor-1α axis in CLL-BMSCs with production of vascular endothelial growth factor, a survival factor for CLL B cells. Moreover, MV-mediated AKT activation led to modulation of the β-catenin pathway and increased expression of cyclin D1 and c-myc in BMSCs. We found MV delivered phospho-receptor tyrosine kinase Axl directly to the BMSCs in association with AKT activation. This study demonstrates the existence of separate MV phenotypes during leukemic disease progression and underscores the important role of MVs in activation of the tumor microenvironment.
Inhibiting toll-like receptor 4 signaling ameliorates pulmonary fibrosis during acute lung injury induced by lipopolysaccharide: an experimental study
Authors: He ZhengYu , Zhu YeSen , Jiang Hong
Published: December 2009

Background

Toll-like receptor 4 (TLR4) is essential in lipopolysaccharide (LPS)-induced fibroblast activation and collagen secretion in vitro. However, its effects on the process of lung fibroblast activation and fibrosis initiation during LPS induced acute lung injury (ALI) remain unknown. The goal of the present study was to determine the effect of inhibiting TLR4 on LPS-induced ALI and fibrosis in vivo.

Methods

The ALI model was established by intraperitoneal injection of LPS in mice. TLR4-small hairpin RNA (shRNA) lentivirus was injected intravenously into the mice to inhibit TLR4 expression. mRNA and protein levels were detected by real-time PCR and Western-blot analysis, respectively. The contents of the C-terminal propeptide of type I procollagen (PICP) in bronchoalveolar lavage fluid (BALF) were detected by ELISA, and the degree of fibrosis was detected by van Gieson collagen staining, the hydroxyproline assay, and alpha smooth muscle actin (α-SMA) immunohistochemical staining.

Results

Overexpression of TLR4, type I procollagen, alpha-SMA, and p-AKT in murine pulmonary tissue after intraperitoneal injection of LPS at 72 hours and 28 days were detected. Moreover, the degree of fibrosis was shown to increase by ELISA analysis of PICP in BALF, van Gieson collagen staining, the hydroxyproline assay, and α-SMA immunohistochemical staining. All of these changes were alleviated by intravenous infection with TLR4-shRNA lentivirus.

Conclusions

Inhibiting TLR4 signaling could ameliorate fibrosis at the early stage of ALI induced by LPS.
Comparison of the receptor FGFRL1 from sea urchins and humans illustrates evolution of a zinc binding motif in the intracellular domain
Authors: Zhuang Lei , Karotki Andrei V , Bruecker Philip , Trueb Beat
Published: December 2009

Background

FGFRL1, the gene for the fifth member of the fibroblast growth factor receptor (FGFR) family, is found in all vertebrates from fish to man and in the cephalochordate amphioxus. Since it does not occur in more distantly related invertebrates such as insects and nematodes, we have speculated that FGFRL1 might have evolved just before branching of the vertebrate lineage from the other invertebrates (Beyeler and Trueb, 2006).

Results

We identified the gene for FGFRL1 also in the sea urchin Strongylocentrotus purpuratus and cloned its mRNA. The deduced amino acid sequence shares 62% sequence similarity with the human protein and shows conservation of all disulfides and N-linked carbohydrate attachment sites. Similar to the human protein, the S. purpuratus protein contains a histidine-rich motif at the C-terminus, but this motif is much shorter than the human counterpart. To analyze the function of the novel motif, recombinant fusion proteins were prepared in a bacterial expression system. The human fusion protein bound to nickel and zinc affinity columns, whereas the sea urchin protein barely interacted with such columns. Direct determination of metal ions by atomic absorption revealed 2.6 mole zinc/mole protein for human FGFRL1 and 1.7 mole zinc/mole protein for sea urchin FGFRL1.

Conclusion

The FGFRL1 gene has evolved much earlier than previously assumed. A comparison of the intracellular domain between sea urchin and human FGFRL1 provides interesting insights into the shaping of a novel zinc binding domain.
Characterization of the stem cell system of the acoel Isodiametra pulchra
Authors: De Mulder Katrien , Kuales Georg , Pfister Daniela , Willems Maxime , Egger Bernhard , Salvenmoser Willi , Thaler Marlene , Gorny Anne-Kathrin , Hrouda Martina , Borgonie Gaëtan , Ladurner Peter
Published: December 2009

Background

Tissue plasticity and a substantial regeneration capacity based on stem cells are the hallmark of several invertebrate groups such as sponges, cnidarians and Platyhelminthes. Traditionally, Acoela were seen as an early branching clade within the Platyhelminthes, but became recently positioned at the base of the Bilateria. However, little is known on how the stem cell system in this new phylum is organized. In this study, we wanted to examine if Acoela possess a neoblast-like stem cell system that is responsible for development, growth, homeostasis and regeneration.

Results

We established enduring laboratory cultures of the acoel Isodiametra pulchra (Acoela, Acoelomorpha) and implemented in situ hybridization and RNA interference (RNAi) for this species. We used BrdU labelling, morphology, ultrastructure and molecular tools to illuminate the morphology, distribution and plasticity of acoel stem cells under different developmental conditions. We demonstrate that neoblasts are the only proliferating cells which are solely mesodermally located within the organism. By means of in situ hybridisation and protein localisation we could demonstrate that the piwi-like gene ipiwi1 is expressed in testes, ovaries as well as in a subpopulation of somatic stem cells. In addition, we show that germ cell progenitors are present in freshly hatched worms, suggesting an embryonic formation of the germline. We identified a potent stem cell system that is responsible for development, homeostasis, regeneration and regrowth upon starvation.

Conclusions

We introduce the acoel Isodiametra pulchra as potential new model organism, suitable to address developmental questions in this understudied phylum. We show that neoblasts in I. pulchra are crucial for tissue homeostasis, development and regeneration. Notably, epidermal cells were found to be renewed exclusively from parenchymally located stem cells, a situation known only from rhabditophoran flatworms so far. For further comparison, it will be important to analyse the stem cell systems of other key-positioned understudied taxa.
A practical comparison of methods for detecting transcription factor binding sites in ChIP-seq experiments
Authors: Laajala Teemu D , Raghav Sunil , Tuomela Soile , Lahesmaa Riitta , Aittokallio Tero , Elo Laura L
Published: December 2009

Background

Chromatin immunoprecipitation coupled with massively parallel sequencing (ChIP-seq) is increasingly being applied to study transcriptional regulation on a genome-wide scale. While numerous algorithms have recently been proposed for analysing the large ChIP-seq datasets, their relative merits and potential limitations remain unclear in practical applications.

Results

The present study compares the state-of-the-art algorithms for detecting transcription factor binding sites in four diverse ChIP-seq datasets under a variety of practical research settings. First, we demonstrate how the biological conclusions may change dramatically when the different algorithms are applied. The reproducibility across biological replicates is then investigated as an internal validation of the detections. Finally, the predicted binding sites with each method are compared to high-scoring binding motifs as well as binding regions confirmed in independent qPCR experiments.

Conclusions

In general, our results indicate that the optimal choice of the computational approach depends heavily on the dataset under analysis. In addition to revealing valuable information to the users of this technology about the characteristics of the binding site detection approaches, the systematic evaluation framework provides also a useful reference to the developers of improved algorithms for ChIP-seq data.
Developmental iodine deficiency resulting in hypothyroidism reduces hippocampal ERK1/2 and CREB in lactational and adolescent rats
Authors: Dong Jing , Liu Wanyang , Wang Yi , Hou Yi , Xi Qi , Chen Jie
Published: December 2009

Background

Developmental iodine deficiency (ID) leads to inadequate thyroid hormone that impairs learning and memory with an unclear mechanism. Here, we show that hippocampal extracellular signal-regulated kinase (ERK1/2) and cAMP response element-binding protein (CREB) are implicated in the impaired learning and memory in lactational and adolescent rat hippocampus following developmental ID and hypothyroidism.

Methods

Three developmental rat models were created by administrating dam rats with either iodine-deficient diet or propylthiouracil (PTU, 5 ppm or 15 ppm)-added drinking water from gestational day (GD) 6 till postnatal day (PN) 28. Then, the total and phorsporylated ERK1/2 and total and phorsporylated CREB in the hippocampus were detected with western blot on PN14, PN21, PN28 and PN42.

Results

The iodine-deficient and hypothyroid pups showed lower serum FT3 and FT4 levels, smaller body size, and delayed eyes opening. The mean number of surviving cells in the hippocampus of the iodine-deficient and 15 ppm PTU-treated rats was significantly reduced compared to controls (P < 0.05). Iodine-deficient and 15 ppm PTU-treatment groups demonstrated significantly lower level of total and phosphorylated ERK1/2 and CREB than the controls on PN14, PN21 and PN28 (P < 0.05, respectively). The reduction of ERK1/2 and CREB was not reversible with the restoration of serum thyroid hormone concentrations on PN42.

Conclusions

Developmental ID and hypothyroidism down-regulate hippocampal ERK1/2 and CREB in lactational and adolescent rats.
Over-expression of miR172 causes loss of spikelet determinacy and floral organ abnormalities in rice (Oryza sativa)
Authors: Zhu Qian-Hao , Upadhyaya Narayana M , Gubler Frank , Helliwell Chris A
Published: December 2009

Background

Regulation of gene expression by microRNAs (miRNAs) plays a crucial role in many developmental and physiological processes in plants. miRNAs act to repress expression of their target genes via mRNA cleavage or translational repression. Dozens of miRNA families have been identified in rice, 21 of which are conserved between rice and Arabidopsis. miR172 is a conserved miRNA family which has been shown to regulate expression of APETALA2 (AP2)-like transcription factors in Arabidopsis and maize. The rice genome encodes five AP2-like genes predicted to be targets of miR172. To determine whether these rice AP2-like genes are regulated by miR172 and investigate the function of the target genes, we studied the effect of over-expressing two members of the miR172 family on rice plant development.

Results

Analysis of miR172 expression showed that it is most highly expressed in late vegetative stages and developing panicles. Analyses of expression of three miR172 targets showed that SUPERNUMERARY BRACT (SNB) and Os03g60430 have high expression in developing panicles. Expression of miR172 was not inversely correlated with expression of its targets although miR172-mediated cleavage of SNB was detected by 5' rapid amplification of cDNA ends (RACE). Over-expression of miR172b in rice delayed the transition from spikelet meristem to floral meristem, and resulted in floral and seed developmental defects, including changes to the number and identity of floral organs, lower fertility and reduced seed weight. Plants over-expressing miR172b not only phenocopied the T-DNA insertion mutant of SNB but showed additional defects in floret development not seen in the snb mutant. However SNB expression was not reduced in the miR172b over-expression plants.

Conclusions

The phenotypes resulting from over-expression of miR172b suggests it represses SNB and at least one of the other miR172 targets, most likely Os03g60430, indicating roles for other AP2-like genes in rice floret development. miR172 and the AP2-like genes had overlapping expression patterns in rice and their expression did not show an obvious negative correlation. There was not a uniform decrease in the expression of the AP2-like miR172 target mRNAs in the miR172b over-expression plants. These observations are consistent with miR172 functioning via translational repression or with expression of the AP2-like genes being regulated by a negative feedback loop.
Gene expression relationship between prostate cancer cells of Gleason 3, 4 and normal epithelial cells as revealed by cell type-specific transcriptomes
Authors: Pascal Laura E , Vêncio Ricardo ZN , Page Laura S , Liebeskind Emily S , Shadle Christina P , Troisch Pamela , Marzolf Bruz , True Lawrence D , Hood Leroy E , Liu Alvin Y
Published: December 2009

Background

Prostate cancer cells in primary tumors have been typed CD10-/CD13-/CD24hi/CD26+/CD38lo/CD44-/CD104-. This CD phenotype suggests a lineage relationship between cancer cells and luminal cells. The Gleason grade of tumors is a descriptive of tumor glandular differentiation. Higher Gleason scores are associated with treatment failure.

Methods

CD26+ cancer cells were isolated from Gleason 3+3 (G3) and Gleason 4+4 (G4) tumors by cell sorting, and their gene expression or transcriptome was determined by Affymetrix DNA array analysis. Dataset analysis was used to determine gene expression similarities and differences between G3 and G4 as well as to prostate cancer cell lines and histologically normal prostate luminal cells.

Results

The G3 and G4 transcriptomes were compared to those of prostatic cell types of non-cancer, which included luminal, basal, stromal fibromuscular, and endothelial. A principal components analysis of the various transcriptome datasets indicated a closer relationship between luminal and G3 than luminal and G4. Dataset comparison also showed that the cancer transcriptomes differed substantially from those of prostate cancer cell lines.

Conclusions

Genes differentially expressed in cancer are potential biomarkers for cancer detection, and those differentially expressed between G3 and G4 are potential biomarkers for disease stratification given that G4 cancer is associated with poor outcomes. Differentially expressed genes likely contribute to the prostate cancer phenotype and constitute the signatures of these particular cancer cell types.
Comparing methods for identifying patients with heart failure using electronic data sources
Authors: Alqaisi Fadi , Williams L Keoki , Peterson Edward L , Lanfear David E
Published: December 2009

Background

Accurately indentifying heart failure (HF) patients from administrative claims data is useful for both research and quality of care efforts. Yet, there are few comparisons of the various claims data criteria (also known as claims signatures) for identifying HF patients. We compared various HF claim signatures to assess their relative accuracy.

Methods

In this retrospective study, we identified 4174 patients who received care from a large health system in southeast Michigan and who had ≥1 HF encounter between January 1, 2004 and December 31, 2005. Four hundred patients were chosen at random and a detailed chart review was performed to assess which met the Framingham HF criteria. The sample was divided into 300 subjects for derivation and 100 subjects for validation. Sensitivity, specificity,, and area under the curve (AUC) were determined for the various claim signatures. The criteria with the highest AUC were retested in the validation set.

Results

Of the 400 patients sampled, 65% met Framingham HF criteria, and 56% had at least one B-type Natriuretic Peptide (BNP) measurement. There was substantial variation between claims signatures in terms of sensitivity (range 15%-77%) and specificity (range 69%-100%). The best performing criteria in the derivation set was if patients met any one of the following: ≥2 HF encounters, any hospital discharge diagnosis of HF, or a BNP ≥200 pg/ml. These criteria showed a sensitivity of 76%, specificity of 75%, and AUC of 0.754 for meeting the Framingham HF criteria. This claims signature performed similarly in the validation set.

Conclusion

Claim signatures for HF vary greatly in their relative sensitivity and specificity. These findings may facilitate efforts to identify HF patients for research and quality improvement efforts.
Population pharmacokinetics of artesunate and dihydroartemisinin following single- and multiple-dosing of oral artesunate in healthy subjects
Authors: Tan Beesan , Naik Himanshu , Jang In-Jin , Yu Kyung-Sang , Kirsch Lee E , Shin Chang-Sik , Craft J Carl , Fleckenstein Lawrence
Published: December 2009

Background

The population pharmacokinetics of artesunate (AS) and its active metabolite dihydroartemisinin (DHA) were studied in healthy subjects receiving single- or multiple-dosing of AS orally either in combination with pyronaridine (PYR) or as a monotherapy with or without food.

Methods

Data from 118 concentration-time profiles arising from 91 healthy Korean subjects were pooled from four Phase I clinical studies. Subjects received 2-5 mg/kg of single- and multiple-dosing of oral AS either in combination with PYR or as a monotherapy with or without food. Plasma AS and DHA were measured simultaneously using a validated liquid chromatography- mass spectrometric method with a lower limit of quantification of 1 ng/mL for both AS and DHA. Nonlinear mixed-effect modelling was used to obtain the pharmacokinetic and variability (inter-individual and residual variability) parameter estimates.

Results

A novel parent-metabolite pharmacokinetic model consisting of a dosing compartment, a central compartment for AS, a central compartment and a peripheral compartment for DHA was developed. AS and DHA data were modelled simultaneously assuming stoichiometric conversion to DHA. AS was rapidly absorbed with a population estimate of absorption rate constant (Ka) of 3.85 h-1. The population estimates of apparent clearance (CL/F) and volume of distribution (V2/F) for AS were 1190 L/h with 36.2% inter-individual variability (IIV) and 1210 L with 57.4% IIV, respectively. For DHA, the population estimates of apparent clearance (CLM/F) and central volume of distribution (V3/F) were 93.7 L/h with 28% IIV and 97.1 L with 30% IIV, respectively. The population estimates of apparent inter-compartmental clearance (Q/F) and peripheral volume of distribution (V4/F) for DHA were 5.74 L/h and 18.5 L, respectively. Intake of high-fat and high-caloric meal prior to the drug administration resulted in 84% reduction in Ka. Body weight impacted CLM/F, such that a unit change in weight resulted in 1.9-unit change in CLM/F in the same direction.

Conclusions

A novel simultaneous parent-metabolite pharmacokinetic model with good predictive power was developed to study the population pharmacokinetics of AS and DHA in healthy subjects following single- and multiple-dosing of AS with or without the presence of food. Food intake and weight were significant covariates for Ka and CLM/F, respectively.
Autistic disorder associated with a paternally derived unbalanced translocation leading to duplication of chromosome 15pter-q13.2: a case report
Authors: Wu David J , Wang Nicholas J , Driscoll Jennette , Dorrani Naghmeh , Liu Dahai , Sigman Marian , Schanen N Carolyn
Published: December 2009

Autism spectrum disorders have been associated with maternally derived duplications that involve the imprinted region on the proximal long arm of chromosome 15. Here we describe a boy with a chromosome 15 duplication arising from a 3:1 segregation error of a paternally derived translocation between chromosome 15q13.2 and chromosome 9q34.12, which led to trisomy of chromosome 15pter-q13.2 and 9q34.12-qter. Using array comparative genome hybridization, we localized the breakpoints on both chromosomes and sequence homology suggests that the translocation arose from non-allelic homologous recombination involving the low copy repeats on chromosome 15. The child manifests many characteristics of the maternally-derived duplication chromosome 15 phenotype including developmental delays with cognitive impairment, autism, hypotonia and facial dysmorphisms with nominal overlap of the most general symptoms found in duplications of chromosome 9q34. This case suggests that biallelically expressed genes on proximal 15q contribute to the idic(15) autism phenotype.
A rare case of isolated duodenal metastases from hepatocellular carcinoma associated with p53 and ki-67 expression: a case report
Authors: Chung Caroline , Al Ali Jaber , Owen David A , Weiss Alan A , Yoshida Eric M , Tai Isabella T
Published: December 2009

Hepatocellular carcinoma (HCC) is the most common primary tumor of the liver worldwide. The incidence of HCC is increasing in North America secondary to rises in chronic liver disease from alcohol abuse and viral hepatitis. HCC most commonly metastasizes hematogenously or through lymphatics to the lungs and regional lymph nodes. Involvement of small bowel is rare and typically results from direct invasion and extension. We examined the molecular features related to this extremely rare case of isolated duodenal metastasis of HCC and noted p53 and Ki-67 positive staining. Here, we review the possible molecular and immunohistochemical studies that may aid definitive diagnosis and the evidence for the management of metastatic hepatocellular carcinoma.
The Human Gene Mutation Database: 2008 update
Authors: Stenson Peter D , Mort Matthew , Ball Edward V , Howells Katy , Phillips Andrew D , Thomas Nick ST , Cooper David N
Published: December 2009

The Human Gene Mutation Database (HGMD®) is a comprehensive core collection of germline mutations in nuclear genes that underlie or are associated with human inherited disease. Here, we summarize the history of the database and its current resources. By December 2008, the database contained over 85,000 different lesions detected in 3,253 different genes, with new entries currently accumulating at a rate exceeding 9,000 per annum. Although originally established for the scientific study of mutational mechanisms in human genes, HGMD has since acquired a much broader utility for researchers, physicians, clinicians and genetic counselors as well as for companies specializing in biopharmaceuticals, bioinformatics and personalized genomics. HGMD was first made publicly available in April 1996, and a collaboration was initiated in 2006 between HGMD and BIOBASE GmbH. This cooperative agreement covers the exclusive worldwide marketing of the most up-to-date (subscription) version of HGMD, HGMD Professional, to academic, clinical and commercial users.
Promoting developmental transcription
Authors: Ohler Uwe , Wassarman David A.
Published: December 2009

Animal growth and development depend on the precise control of gene expression at the level of transcription. A central role in the regulation of developmental transcription is attributed to transcription factors that bind DNA enhancer elements, which are often located far from gene transcription start sites. Here, we review recent studies that have uncovered significant regulatory functions in developmental transcription for the TFIID basal transcription factors and for the DNA core promoter elements that are located close to transcription start sites.
FGF-receptor signalling controls neural cell diversity in the zebrafish hindbrain by regulating olig2 and sox9
Authors: Esain Virginie , Postlethwait John H. , Charnay Patrick , Ghislain Julien
Published: December 2009

The mechanisms underlying the generation of neural cell diversity are the subject of intense investigation, which has highlighted the involvement of different signalling molecules including Shh, BMP and Wnt. By contrast, relatively little is known about FGF in this process. In this report we identify an FGF-receptor-dependent pathway in zebrafish hindbrain neural progenitors that give rise to somatic motoneurons, oligodendrocyte progenitors and differentiating astroglia. Using a combination of chemical and genetic approaches to conditionally inactivate FGF-receptor signalling, we investigate the role of this pathway. We show that FGF-receptor signalling is not essential for the survival or maintenance of hindbrain neural progenitors but controls their fate by coordinately regulating key transcription factors. First, by cooperating with Shh, FGF-receptor signalling controls the expression of olig2, a patterning gene essential for the specification of somatic motoneurons and oligodendrocytes. Second, FGF-receptor signalling controls the development of both oligodendrocyte progenitors and astroglia through the regulation of sox9, a gliogenic transcription factor the function of which we show to be conserved in the zebrafish hindbrain. Overall, for the first time in vivo, our results reveal a mechanism of FGF in the control of neural cell diversity.
DNA LIGASE I exerts a maternal effect on seed development inArabidopsis thaliana
Authors: Andreuzza Sebastien , Li Jing , Guitton Anne-Elisabeth , Faure Jean-Emmanuel , Casanova Sandrine , Park Jin-Sup , Choi Yeonhee , Chen Zhong , Berger Frédéric
Published: December 2009

Maternal effects are defined by mutations that affect the next generation when they are maternally inherited. To date, most indepth studies of maternal effects in plants have attributed their origin to genomic imprinting that restricts expression to the maternal allele. The DNA glycosylase DEMETER (DME) removes methylated cytosine residues, causing transcriptional activation of the maternal allele of imprinted genes. In this study, we show that loss-of-function of the major DNA LIGASE I (AtLIG1) in Arabidopsis thaliana causes maternal effects in the endosperm, which is the seed tissue that nurtures embryo development. AtLIG1 expression is not imprinted and has a limited impact on imprinted gene expression. Genetic interaction analyses further indicate that AtLIG1 acts downstream of DME. The removal of methylated cytosine residues by DME involves the creation of DNA single-strand breaks and our results suggest that AtLIG1 repairs these breaks.
A novel regulatory mechanism for Fgf18 signaling involving cysteine-rich FGF receptor (Cfr) and delta-like protein (Dlk)
Authors: Miyaoka Yuichiro , Tanaka Minoru , Imamura Toru , Takada Shinji , Miyajima Atsushi
Published: December 2009

Fibroblast growth factors (FGFs) transduce signals through FGF receptors (FGFRs) and have pleiotropic functions. Besides signal-transducing FGFRs, cysteine-rich FGF receptor (Cfr; Glg1) is also known to bind some FGFs, although its physiological functions remain unknown. In this study, we generated Cfr-deficient mice and found that some of them die perinatally, and show growth retardation, tail malformation and cleft palate. These phenotypes are strikingly similar to those of Fgf18-deficient mice, and we revealed interaction between Cfr and Fgf18 both genetically and physically, suggesting functional cooperation. Consistently, introduction of Cfr facilitated Fgf18-dependent proliferation of Ba/F3 cells expressing Fgfr3c. In addition, we uncovered binding between Cfr and delta-like protein (Dlk), and noticed that Cfr-deficient mice are also similar to Dlk-transgenic mice, indicating that Cfr and Dlk function in opposite ways. Interestingly, we also found that Dlk interrupts the binding between Cfr and Fgf18. Thus, the Fgf18 signaling pathway seems to be finely tuned by Cfr and Dlk for skeletal development. This study reveals a novel regulatory mechanism for Fgf18 signaling involving Cfr and Dlk.
A new transmissive-type tilting actuator for a smooth projected television image
Authors: Im H , Kim W , Chung J
Published: December 2009

In this article, a new transmissive-type tilting actuator is presented for smooth projected television images. In order to implement the transmissive-type tilting actuator, a basic structure of the tilting actuator is proposed, which is composed of a voice coil motor, a transmissive glass plate, and frames. After designing and analysing the actuator electromagnetically and mechanically, a prototype of the actuator is built. With the manufactured prototype, the performances and design requirements of the actuator are experimentally verified by the modal test and response measurements.
Investigations of a two-stage pulse tube cryocooler operating down to 2.5 K
Authors: Shafi K A , Mohammed Sajid N K , Kasthurirengan S , Upendra B
Published: December 2009

A two-stage pulse tube cryocooler (PTC) which produces a no-load temperature of ∼2.5 K in its second stage at an operating frequency of 1.6 Hz has been designed and fabricated. The second stage of the system provides a refrigeration power of ∼250 mW at 5.0 K. The system uses stainless steel meshes (mesh size 200) along with lead (Pb) granules and combinations of Pb, Er3Ni, and HoCu2 as the first and second stage regenerator materials, respectively. Experimental studies have been carried out on different pulse tube configurations by varying the dimensions of the pulse tubes and regenerators to arrive at the best one, which leads to the lowest no-load second stage cold head temperature. Using this configuration, detailed experimental studies have been conducted by varying the volume percentage ratios of the second stage regenerator materials such as HoCu2, Er3Ni, and Pb (with an average grain size of ∼250 μm). This article presents the results of our experimental studies on cryocoolers with the regenerator material arranged in layered structures. Comparative studies have also been presented for specific cases where the regenerator materials are arranged as a homogeneous mixture in the second stage. The experimental results clearly indicate that the design of PTCs should use only layered structures of regenerator materials and not homogenous mixtures.
Decrease in uric acid in acute ischemic stroke correlates with stroke severity, evolution and outcome
Authors: Brouns Raf , Wauters Annick , Van De Vijver Gerda , De Surgeloose Didier , Sheorajpanday Rishi , De Deyn Peter P.
Published: December 2009

Background: Although uric acid (UA) is one of the most important antioxidants in plasma and appears to be neuroprotective in animal models, results from human studies are controversial. In this study, we investigated the kinetics of serum UA concentrations in the acute, subacute and chronic phase of ischemic stroke and its relation with initial stroke severity, stroke evolution in the subacute phase and long-term stroke outcome.

Methods: Serum concentrations of UA were measured in 199 stroke patients at admission (median, 2.8 h after stroke onset), at 24 h, 72 h, day 7, month 1 and month 3 after onset of stroke. We evaluated the relationship between changes in UA concentrations and (a) stroke severity [patients with transient ischemic attack (TIA) vs. stroke patients, National Institutes of Health Stroke Scale (NIHSS) score at admission], (b) stroke evolution (stroke progression, infarct volume at 72 h), and (c) stroke outcome [modified Rankin scale (mRS) score at month 3, mortality].

Results: UA concentrations decreased significantly during the first 7 days after stroke onset before returning to baseline (p<0.001). Mean plasma UA concentrations decreased from 336.66±113.01 μmol/L at admission to 300.37±110.04 μmol/L at day 7 (p<0.001) in patients with stroke, but did not change significantly in patients with TIA. Changes in UA concentrations from admission to day 7 (ΔUAday 7) correlated with the NIHSS score (ρ=0.32; p<0.001), stroke progression (ρ=0.29; p=0.001), infarct volume (ρ=0.37; p<0.001), mRS score (ρ=0.28; p=0.001) and mortality (p=0.010).

Conclusions: Decreases in UA during the first week after onset of stroke correlates with more severe stroke, unfavorable stroke evolution, and poor long-term stroke outcome.

Clin Chem Lab Med 2010;48:383–90.
Simulation und Optimierung eines Trinkwasserversorgungssystems im Rahmen eines IWRMSimulation and Optimisation of a Drinking Water Supply System within the Framework of an IWRM
Authors: Scharaw Buren , Röll Stefan , Westerhoff Thomas , Hopfgarten Siegbert
Published: December 2009

Im Beitrag wird die Modellierung, Simulation und Optimierung eines Trinkwasserversorgungssystems mit seinen beiden gekoppelten Teilsystemen Trinkwassergewinnung und -verteilung dargestellt. Die praktische Anwendung erfolgt im Rahmen eines integrierten Wasserressourcen-Managements (IWRM) für die semi-aride Modellregion Darkhan in der Mongolei.
Wandler für energieautarke Mikrosysteme. Stand der Technik kommerzieller EnergiewandlerMicro Energy Harvesting Converters. State of the Art of Commercially Available Energy Converters
Authors: Müller Monika , Freunek Michael , Ungan Tolgay , Reindl Leonhard M.
Published: December 2009

Dieser Bericht untersucht den Stand der Technik kommerziell verfügbarer Mikroenergiewandler. Typischerweise liegt die Größe der Wandler im Zentimeterbereich bei erzielten Leistungen von einigen Mikro- bis Milliwatt. Charakteristika, Kenngrößen und Forschungsbedarf der einzelnen Wandlertechnologien werden anhand der ersten kommerziellen Wandler diskutiert. Die Charakterisierung der Wandler weist Standardisierungsbedarf auf.
Mikrostrukturierte Energiewandler für energieautonome SensorenMicrostructured Energy Harvesters for Energy Autonomous Sensors
Authors: Hohlfeld Dennis , Kamel Talal , Altena Geert , Su Jiale , Elfrink René , Vullers Ruud , van Schaijk Rob
Published: December 2009

Diese Arbeit präsentiert mikrostrukturierte Energiewandler zur Stromversorgung energieautarker Sensoren. Vibrationsbasierte Energiewandler mit Betriebsfrequenzen von 100 bis 1000 Hz nutzen den piezoelektrischen oder den elektrostatischen Effekt. Wir beschreiben außerdem ein drahtloses energieautonomes Sensorsystem, welches von einem Vibrationswandler gespeist wird und alle 15 Sekunden Temperaturmessungen drahtlos überträgt. Mikrostrukturierte Thermoelemente werden darüber hinaus als kostengünstige Lösung für thermoelektrische Generatoren angesehen. Diese sollen bei geringen Temperaturunterschieden und schwachen Wärmeströmen arbeiten, die z. B. für menschliche Körperwärme typisch sind.
Ereignisbasierte Messwerterfassung in drahtlosen Sensornetzwerken für die StrukturüberwachungEvent-based Data Acquisition in Wireless Sensor Networks for Structural Health Monitoring
Authors: Krüger Markus , Große Christian U.
Published: December 2009

Durch die Verwendung von intelligenten, drahtlosen Sensornetzwerken wird zukünftig ein breites Anwendungsfeld erschlossen, da derartige Monitoringsysteme gegenüber konventionellen Messsystemen einfacher zu applizieren und deutlich kostengünstiger sind. Derzeit wird an der MPA Universität Stuttgart an den Grundlagen für eine praxisnahe Bauwerksüberwachung auf der Basis von kabelungebundenen Systemen gearbeitet, die preiswert und flexibel einsetzbar sind und eine gezielte Datenerfassung ermöglichen. Dazu sind Arbeiten im Bereich der Sensortechnik, der Mikrointegration und der analogen wie auch digitalen Datenanalyse notwendig. Der vorliegende Beitrag beschreibt die hier verfolgten Lösungsansätze und hierbei insbesondere die ereignisbasierte Messwerterfassung, die aufgrund der beschränkten Ressourcen für manche Messaufgaben unerlässlich ist. Anhand beispielhafter Anwendungen wie der Dehnungs- und Verformungsmessung unter dynamischer Beanspruchung oder auch der Schallemissionsanalyse zur Analyse von Schädigungsprozessen werden zudem konkrete Lösungen beschrieben.
Characterization and DFT Research of Nd/TiO2: Photocatalyst for Synthesis of Methanol from CO2 and H2O
Authors: Luo Dongmei , Chen Chao , Zhang Ning , Hong Sanguo , Wu Huanwen , Liu Zhihua
Published: December 2009

Nd3+–doped TiO2 synthesized via the sol-gel method, was used as catalyst for photoreduction of carbon dioxide into methanol in an aqueous solution under UV irradiation. The catalysts were characterized by XRD, IR, UV-vis etc. The maximum photocatalytic activity corresponds to the 0.2 wt.% Nd3+–doped TiO2 nanopowders. In that case, the methanol yield is 184.8μmol/g by 8h UV irradiation, indicating that the Nd/TiO2 can obviously enhance the efficiency of photocatalytic reduction comparing to pure TiO2. Furthermore, the adsorption properties of Nd atom on the regular (110) surface of rutile and (101) surface of anatase were studied by density functional calculations under the B3LYP level. H2O molecule catches the photo-induced hole in the reaction system forming H2O+ which dissociates further into H+ and OH radical on the catalyst surface. The transition state was found by DFT calculation, and the amount of the OH radicals has effects on the selectivity of CH3OH.
Conflict in the Chittagong Hill Tracts of Bangladesh: An Unimplemented Accord and Continued Violence
Authors: Panday Pranab Kumar , Jamil Ishtiaq
Published: December 2009

This article analyzes the dynamics of the conflict in the Chittagong Hill Tracts region of Bangladesh. This study argues that violations of human rights by law enforcement agencies and Bangali settlers against indigenous people continue even after the signing of the 1997 peace accord. Furthermore, peace remains elusive because of the "top-down" nature of that accord.
Renewed Ethnonationalist Insurgency in Balochistan, Pakistan: The Militarized State and Continuing Economic Deprivation
Authors: Khan Adeel
Published: December 2009

A mini-war is going on between the military and ethnic nationalists in Balochistan, Pakistan's territorially largest province. The military claims that violence is the result of tribal chiefs' opposition to the Pakistani government's development projects, whereas the militants believe that the Punjabi-dominated military is colonizing their land and exploiting its resources. This article argues that the violence is unlikely to subside, absent a comprehensive change in the government's approach to the conflict.
Separatist Militants and Contentious Politics in Assam, India: The Limits of Counterinsurgency
Authors: Baruah Sanjib
Published: December 2009

Insurgency-related violence continues in the northeast Indian state of Assam. Even though the fortunes of the United Liberation Front of Assam have declined significantly, a political settlement remains elusive. Unresolved tensions between regional patriotism and pan-Indianism explain the insurgent organization's resilience and the continuing appeal of its political ideology.
The Khalistan Movement in Punjab, India, and the Post-Militancy Era: Structural Change and New Political Compulsions
Authors: Van Dyke Virginia
Published: December 2009

A Sikh militant movement in Punjab is unlikely to reemerge in the near future because of exhaustion from the militant era, the shift toward federalism in the Indian political system, the increased importance of state level parties, the rise of the Bharatiya Janata Party, and the emergence of coalition politics.