bluuebunny/crossref_metadata_2025 huggingface dataset:
Cystic colon duplication causing intussusception in a 25-year-old man: report of a case and review of the literature
Authors: Reiser-Erkan Carolin , Erkan Mert , Ulbrich Erika , Nährig Jörg , Kleeff Jörg
Published: June 2010

Background

Colonic intussusception is a rare congenital abnormality, mostly manifesting before the age of two with abdominal pain and acute intestinal obstruction with or without bleeding. In adults it may occur idiopathically or due to an intraluminal tumor mass.

Case presentation

A 25-year-old man presented with an acute abdomen and severe crampy abdominal pain. The clinical picture mimicked acute appendicitis. Transabdominal ultrasound examination revealed a 5 cm circular mass in the right upper abdomen. The ensuing computed tomography suggested an intussusception in the ascending colon. Intraoperatively, no full thickness invagination was detected. Due to a hard, intraluminal tumor a standard right hemicolectomy with ileotransversostomy was performed. The histopathological analysis revealed a cystic colon duplication leading to mucosal invagination and obstruction.

Conclusions

In adults, colon intussusception is a rare event causing approximately 1% of all acute intestinal obstructions. Unlike its preferentially nonsurgical management in children, a bowel intussusception in adults should be operated because an organic, often malignant lesion is present in most cases.
WHO policy development processes for a new vaccine: case study of malaria vaccines
Authors: Milstien Julie , Cárdenas Vicky , Cheyne James , Brooks Alan
Published: June 2010

Background

Recommendations from the World Health Organization (WHO) are crucial to inform developing country decisions to use, or not, a new intervention. This article analysed the WHO policy development process to predict its course for a malaria vaccine.

Methods

The decision-making processes for one malaria intervention and four vaccines were classified through (1) consultations with staff and expert advisors to WHO's Global Malaria Programme (GMP) and Immunization, Vaccines and Biologicals Department (IVB); (2) analysis of the procedures and recommendations of the major policy-making bodies of these groups; (3) interviews with staff of partnerships working toward new vaccine availability; and (4) review and analyses of evidence informing key policy decisions.

Case description

WHO policy formulation related to use of intermittent preventive treatment in infancy (IPTi) and the following vaccine interventions: Haemophilus influenzae type b conjugate vaccine (Hib), pneumococcal conjugate vaccine (PCV), rotavirus vaccine (RV), and human papillomavirus vaccine (HPV), five interventions which had relatively recently been through systematic WHO policy development processes as currently constituted, was analysed. Required information was categorized in three areas defined by a recent WHO publication on development of guidelines: safety and efficacy in relevant populations, implications for costs and population health, and localization of data to specific epidemiological situations.

Discussion and evaluation

Data needs for a malaria vaccine include safety; the demonstration of efficacy in a range of epidemiological settings in the context of other malaria prevention interventions; and information on potential rebound in which disease increases subsequent to the intervention. In addition, a malaria vaccine would require attention to additional factors, such as costs and cost-effectiveness, supply and demand, impact of use on other interventions, and distribution issues.

Conclusions

Although policy issues may be more complex for future vaccines, the lead-time between the date of product regulatory approval and a recommendation for its use in developing countries is decreasing. This study presents approaches to define in advance core data needs to support evidence-based decisions, to further decrease this lead-time, accelerating the availability of a malaria vaccine. Specific policy areas for which information should be collected are defined, including studying its use within the context of other malaria interventions.
The Wnt inhibitory factor 1 restoration in prostate cancer cells was associated with reduced tumor growth, decreased capacity of cell migration and invasion and a reversal of epithelial to mesenchymal transition
Authors: Yee David S. , Tang Yaxiong , Li Xuesen , Liu Zhongbo , Guo Yi , Ghaffar Samia , McQueen Peter , Atreya Dash , Xie Jun , Simoneau Anne R. , Hoang Bang H. , Zi Xiaolin
Published: June 2010

Background

Aberrations in the Wnt pathway have been reported to be involved in the metastasis of prostate cancer (PCa) to bone. We investigated the effect and underlying mechanism of a naturally-occurring Wnt inhibitor, WIF1, on the growth and cellular invasiveness of a bone metastatic PCa cell line, PC3.

Results

The WIF1 gene promoter was hypermethylated and its expression down-regulated in the majority (7 of 8) of PCa cell lines. Restoration of WIF1 expression in PC-3 cells resulted in a decreased cell motility and invasiveness via up-regulation of epithelial markers (E-cadherin, Keratin-8 and-18), down-regulation of mesenchymal markers (N-cadherin, Fibronectin and Vimentin) and decreased activity of MMP-2 and -9. PC3 cells transfected with WIF1 consistently demonstrated reduced expression of Epithelial-to-Mesenchymal Transition (EMT) transcription factors, Slug and Twist, and a change in morphology from mesenchymal to epithelial. Moreover, WIF1 expression significantly reduced tumor growth by approximately 63% in a xenograft mouse model. This was accompanied by an increased expression of E-cadherin and Keratin-18 and a decreased expression of vimentin in tumor tissues.

Conclusion

These data suggest that WIF1 regulates tumor invasion through EMT process and thus, may play an important role in controlling metastatic disease in PCa patients. Blocking Wnt signaling in PCa by WIF1 may represent a novel strategy in the future to reduce metastatic disease burden in PCa patients.
The role of Qa-2, the functional homolog of HLA-G, in a Behcet's disease-like mouse model induced by the herpes virus simplex
Authors: Lee Meeyoung , Choi Bunsoon , Kwon Hyuk Jae , Shim Ju A , Park Kyung Sook , Lee Eun-So , Sohn Seonghyang
Published: June 2010

Background

It has been suggested that the HLA-G molecule is a genetic risk factor for Behcet's disease (BD). In this study, we evaluated the level of Qa-2, a murine nonclassical class I MHC molecule and possible functional homolog of HLA-G, to determine if it was associated with various symptoms of BD-like mice. In addition, we investigated siRNA (small interfering RNA) treatment to determine if it inhibited Qa-2 expression, thereby changing the symptoms of mice.

Methods

RNA interference (RNAi) and vector transfection were employed to manipulate gene expressionin vivoin mice. siRNA (small interfering RNA) or Qa-2 expression vector was applied to inhibit or up-regulate Qa-2 expression, respectively.

Results

The Qa-2 levels in granulocytes were lower in BD-like mice than in normal controls. The silencing of Qa-2 by intravenous injection of siRNA (500 nmol/mouse, 4 times at 3-day intervals) specifically reduced the Qa-2 levels and worsened the BD-like symptoms.

Conclusions

Silencing Qa-2 by injecting siRNA into mice resulted in deterioration of symptoms in BD-like mice.
Different levels of overnutrition and weight gain during pregnancy have differential effects on fetal growth and organ development
Authors: George Lindsey A , Uthlaut Adam B , Long Nathan M , Zhang Liren , Ma Yan , Smith Derek T , Nathanielsz Peter W , Ford Stephen P
Published: June 2010

Background

Nearly 50% of U.S. women of child-bearing age are overweight or obese, conditions linked to offspring obesity and diabetes.

Methods

Utilizing the sheep, females were fed a highly palatable diet at two levels of overfeeding designed to induce different levels of maternal body weight increase and adiposity at conception, and from conception to midgestation. Fetal growth and organ development were then evaluated at midgestation in response to these two different levels of overfeeding. Ewes were fed to achieve: 1) normal weight gain (control, C), 2) overweight (125% of National Research Council [NRC] recommendations, OW125) or 3) obesity (150% of NRC recommendations, OB150) beginning 10 wks prior to breeding and through midgestation. Body fat % and insulin sensitivity were assessed at three points during the study: 1) diet initiation, 2) conception and 3) mid-gestation. Ewes were necropsied and fetuses recovered at mid-gestation (day 78).

Results

OB150 ewes had a higher % body fat than OW125 ewes prior to breeding (P = 0.03), but not at mid-gestation (P = 0.37). Insulin sensitivity decreased from diet initiation to mid-gestation (P = 0.04), and acute insulin response to glucose tended to be greater in OB150 ewes than C ewes (P = 0.09) and was greater than in OW125 ewes (P = 0.02). Fetal crown-rump length, thoracic and abdominal girths, and fetal perirenal fat were increased in the OW125 and OB150 versus C ewes at mid-gestation. However, only fetal heart, pancreas, and liver weights, as well as lipid content of fetal liver, were increased (P < 0.05) in OB150 ewes versus both C and OW125 ewes at midgestation.

Conclusions

These data demonstrate that different levels of overfeeding, resulting in differing levels of maternal weight gain and adiposity prior to and during pregnancy, lead to differential effects on fetal overgrowth and organ development.
Larval trematode communities in Radix auricularia and Lymnaea stagnalis in a reservoir system of the Ruhr River
Authors: Soldánová Miroslava , Selbach Christian , Sures Bernd , Kostadinova Aneta , Pérez-del-Olmo Ana
Published: June 2010

Background

Analysis of the data available from traditional faunistic approaches to mollusc-trematode systems covering large spatial and/or temporal scales in Europe convinced us that a parasite community approach in well-defined aquatic ecosystems is essential for the substantial advancement of our understanding of the parasite response to anthropogenic pressures in urbanised areas which are typical on a European scale. Here we describe communities of larval trematodes in two lymnaeid species, Radix auricularia and Lymnaea stagnalis in four man-made interconnected reservoirs of the Ruhr River (Germany) focusing on among- and within-reservoir variations in parasite prevalence and component community composition and structure.

Results

The mature reservoir system on the Ruhr River provides an excellent environment for the development of species-rich and abundant trematode communities in Radix auricularia (12 species) and Lymnaea stagnalis (6 species). The lake-adapted R. auricularia dominated numerically over L. stagnalis and played a major role in the trematode transmission in the reservoir system. Both host-parasite systems were dominated by bird parasites (13 out of 15 species) characteristic for eutrophic water bodies. In addition to snail size, two environmental variables, the oxygen content and pH of the water, were identified as important determinants of the probability of infection. Between-reservoir comparisons indicated an advanced eutrophication at Baldeneysee and Hengsteysee and the small-scale within-reservoir variations of component communities provided evidence that larval trematodes may have reflected spatial bird aggregations (infection 'hot spots'). Two life history groupings of dominant species, the 'cyprinid' and 'anatid' parasites, that depict two aspects of progressive eutrophication in this mature reservoir system, were identified.

Conclusions

We conclude that trematode communities in the lake-adapted R. auricularia are better suited for monitoring the effect of environmental change on host-parasite associations in the reservoir system on the Ruhr River and other similar systems due to the important role of this host in trematode transmission in lakes. Whereas variations in trematode community diversity and abundance may indicate the degree of eutrophication on a larger scale (among reservoirs), the infection rates of the two life history groups of dominant species, the 'cyprinid' and 'anatid' assemblages, may be particularly useful in depicting environmental variability, eutrophication effects and infection 'hot spots' on smaller spatial scales.
Low levels of ATM in breast cancer patients with clinical radiosensitivity
Authors: Fang Zhiming , Kozlov Sergei , McKay Michael J , Woods Rick , Birrell Geoff , Sprung Carl N , Murrell Dédée F , Wangoo Kiran , Teng Linda , Kearsley John H , Lavin Martin F , Graham Peter H , Clarke Raymond A
Published: June 2010

Background and Purpose

Adjuvant radiotherapy for cancer can result in severe adverse side effects for normal tissues. In this respect, individuals with anomalies of the ATM (ataxia telangiectasia) protein/gene are of particular interest as they may be at risk of both breast cancer and clinical radiosensitivity. The association of specific ATM gene mutations with these pathologies has been well documented, however, there is uncertainty regarding pathological thresholds for the ATM protein.

Results

Semi-quantitative immuno-blotting provided a reliable and reproducible method to compare levels of the ATM protein for a rare cohort of 20 cancer patients selected on the basis of their severe adverse normal tissue reactions to radiotherapy. We found that 4/12 (33%) of the breast cancer patients with severe adverse normal tissue reactions following radiotherapy had ATM protein levels < 55% compared to the mean for non-reactor controls.

Conclusions

ATM mutations are generally considered low risk alleles for breast cancer and clinical radiosensitivity. From results reported here we propose a tentative ATM protein threshold of ~55% for high-risk of clinical radiosensitivity for breast cancer patients.
Genomic subtypes of breast cancer identified by array-comparative genomic hybridization display distinct molecular and clinical characteristics
Authors: Jönsson Göran , Staaf Johan , Vallon-Christersson Johan , Ringnér Markus , Holm Karolina , Hegardt Cecilia , Gunnarsson Haukur , Fagerholm Rainer , Strand Carina , Agnarsson Bjarni A , Kilpivaara Outi , Luts Lena , Heikkilä Päivi , Aittomäki Kristiina , Blomqvist Carl , Loman Niklas , Malmström Per , Olsson Håkan , Th Johannsson Oskar , Arason Adalgeir , Nevanlinna Heli , Barkardottir Rosa B , Borg Åke
Published: June 2010

Introduction

Breast cancer is a profoundly heterogeneous disease with respect to biologic and clinical behavior. Gene-expression profiling has been used to dissect this complexity and to stratify tumors into intrinsic gene-expression subtypes, associated with distinct biology, patient outcome, and genomic alterations. Additionally, breast tumors occurring in individuals with germline BRCA1 or BRCA2 mutations typically fall into distinct subtypes.

Methods

We applied global DNA copy number and gene-expression profiling in 359 breast tumors. All tumors were classified according to intrinsic gene-expression subtypes and included cases from genetically predisposed women. The Genomic Identification of Significant Targets in Cancer (GISTIC) algorithm was used to identify significant DNA copy-number aberrations and genomic subgroups of breast cancer.

Results

We identified 31 genomic regions that were highly amplified in > 1% of the 359 breast tumors. Several amplicons were found to co-occur, the 8p12 and 11q13.3 regions being the most frequent combination besides amplicons on the same chromosomal arm. Unsupervised hierarchical clustering with 133 significant GISTIC regions revealed six genomic subtypes, termed 17q12, basal-complex, luminal-simple, luminal-complex, amplifier, and mixed subtypes. Four of them had striking similarity to intrinsic gene-expression subtypes and showed associations to conventional tumor biomarkers and clinical outcome. However, luminal A-classified tumors were distributed in two main genomic subtypes, luminal-simple and luminal-complex, the former group having a better prognosis, whereas the latter group included also luminal B and the majority of BRCA2-mutated tumors. The basal-complex subtype displayed extensive genomic homogeneity and harbored the majority of BRCA1-mutated tumors. The 17q12 subtype comprised mostly HER2-amplified and HER2-enriched subtype tumors and had the worst prognosis. The amplifier and mixed subtypes contained tumors from all gene-expression subtypes, the former being enriched for 8p12-amplified cases, whereas the mixed subtype included many tumors with predominantly DNA copy-number losses and poor prognosis.

Conclusions

Global DNA copy-number analysis integrated with gene-expression data can be used to dissect the complexity of breast cancer. This revealed six genomic subtypes with different clinical behavior and a striking concordance to the intrinsic subtypes. These genomic subtypes may prove useful for understanding the mechanisms of tumor development and for prognostic and treatment prediction purposes.
Pulse pressure variation and volume responsiveness during acutely increased pulmonary artery pressure: an experimental study
Authors: Daudel Fritz , Tüller David , Krähenbühl Stefanie , Jakob Stephan M , Takala Jukka
Published: June 2010

Introduction

We found that pulse pressure variation (PPV) did not predict volume responsiveness in patients with increased pulmonary artery pressure. This study tests the hypothesis that PPV does not predict fluid responsiveness during an endotoxin-induced acute increase in pulmonary artery pressure and right ventricular loading.

Methods

Pigs were subjected to endotoxemia (0.4 μg/kg/hour lipopolysaccharide), followed by volume expansion, subsequent hemorrhage (20% of estimated blood volume), retransfusion, and additional stepwise volume loading until cardiac output did not increase further (n = 5). A separate control group (n = 7) was subjected to bleeding, retransfusion, and volume expansion without endotoxemia. Systemic hemodynamics were measured at baseline and after each intervention, and PPV was calculated offline. Prediction of fluid-challenge-induced stroke volume increase by PPV was analyzed using receiver operating characteristic (ROC) curves.

Results

Sixty-eight volume challenges were performed in endotoxemic animals (22 before and 46 after hemorrhage), and 51 volume challenges in the controls. Endotoxin infusion resulted in an acute increase in pulmonary artery and central venous pressure and a decrease in stroke volume (all P < 0.05). In endotoxemia, 68% of volume challenges before hemorrhage increased the stroke volume by > 10%, but PPV did not predict fluid responsiveness (area under the ROC curve = 0.604, P = 0.461). After hemorrhage in endotoxemia, stroke volume increased in 48% and the predictive value of PPV improved (area under the ROC curve for PPV = 0.699, P = 0.021). In controls after hemorrhage, stroke volume increased in 67% of volume challenges and PPV was a predictor of fluid responsiveness (area under the ROC curve = 0.790, P = 0.001).

Conclusions

Fluid responsiveness cannot be predicted with PPV during acute pulmonary hypertension in porcine endotoxemia. Even following severe hemorrhage during endotoxemia, the predictive value of PPV is marginal.
NF-κB as a central regulator of macrophage function in tumors
Authors: Biswas Subhra K , Lewis Claire E
Published: June 2010

Review discusses the integral role of NF-κB signaling in regulating the macrophage function during tumor progression.

TAMs are usually abundant in the tumor microenvironment and are now known to play an essential role in tumor progression. For example, TAMs influence many aspects of tumorigenesis, such as the growth, survival, invasion, and metastasis of tumor cells, tumor angiogenesis, and the suppression of other tumor-infiltrating immune effector cells. The molecular pathways that regulate these tumor-promoting functions of TAMs are currently under intense investigation. Several recent studies about transgenic murine tumor models have shown that the transcription factor NF-κB is a key player in tumor progression with distinct roles in regulating the functions of macrophages and tumor cells in malignant tumors. Here, we outline the evidence for classical and noncanonical NF-κB signaling pathways driving the tumor-promoting repertoire of TAMs.
A Soluble Activin Receptor Type IIB Prevents the Effects of Androgen Deprivation on Body Composition and Bone Health
Authors: Koncarevic Alan , Cornwall-Brady Milton , Pullen Abigail , Davies Monique , Sako Dianne , Liu June , Kumar Ravindra , Tomkinson Kathleen , Baker Theresa , Umiker Ben , Monnell Travis , Grinberg Asya V. , Liharska Katia , Underwood Kathryn W. , Ucran Jeffrey A. , Howard Elizabeth , Barberio Joseph , Spaits Matthew , Pearsall Scott , Seehra Jasbir , Lachey Jennifer
Published: June 2010

Androgen deprivation, a consequence of hypogonadism, certain cancer treatments, or normal aging in men, leads to loss of muscle mass, increased adiposity, and osteoporosis. In the present study, using a soluble chimeric form of activin receptor type IIB (ActRIIB) we sought to offset the adverse effects of androgen deprivation on muscle, adipose tissue, and bone. Castrated (ORX) or sham-operated (SHAM) mice received either TBS [vehicle-treated (VEH)] or systemic administration of ActRIIB-mFc, a soluble fusion protein comprised of a form of the extracellular domain of ActRIIB fused to a murine IgG2aFc subunit. In vivo body composition imaging demonstrated that ActRIIB-mFc treatment results in increased lean tissue mass of 23% in SHAM mice [19.02 ± 0.42 g (VEH) versus 23.43 ± 0.35 g (ActRIIB-mFc), P < 0.00001] and 26% in ORX mice [15.59 ± 0.26 g (VEH) versus 19.78 ± 0.26 g (ActRIIB-mFc), P < 0.00001]. Treatment also caused a decrease in adiposity of 30% in SHAM mice [5.03 ± 0.48 g (VEH) versus 3.53 ± 0.19 g (ActRIIB-mFc), NS] and 36% in ORX mice [7.12 ± 0.53 g (VEH) versus 4.57 ± 0.28 g (ActRIIB-mFc), P < 0.001]. These changes were also accompanied by altered serum levels of leptin, adiponectin, and insulin, as well as by prevention of steatosis (fatty liver) in ActRIIB-mFc-treated ORX mice. Finally, ActRIIB-mFc prevented loss of bone mass in ORX mice as assessed by whole body dual x-ray absorptiometry and micro-computed tomography of proximal tibias. The data demonstrate that treatment with ActRIIB-mFc restored muscle mass, adiposity, and bone quality to normal levels in a mouse model of androgen deprivation, thereby alleviating multiple adverse consequences of such therapy.
Perinatal Iron and Copper Deficiencies Alter Neonatal Rat Circulating and Brain Thyroid Hormone Concentrations
Authors: Bastian Thomas W. , Prohaska Joseph R. , Georgieff Michael K. , Anderson Grant W.
Published: June 2010

Copper (Cu), iron (Fe), and iodine/thyroid hormone (TH) deficiencies lead to similar defects in late brain development, suggesting that these micronutrient deficiencies share a common mechanism contributing to the observed derangements. Previous studies in rodents (postweanling and adult) and humans (adolescent and adult) indicate that Cu and Fe deficiencies affect the hypothalamic-pituitary-thyroid axis, leading to altered TH status. Importantly, however, relationships between Fe and Cu deficiencies and thyroidal status have not been assessed in the most vulnerable population, the developing fetus/neonate. We hypothesized that Cu and Fe deficiencies reduce circulating and brain TH levels during development, contributing to the defects in brain development associated with these deficiencies. To test this hypothesis, pregnant rat dams were rendered Cu deficient (CuD), FeD, or TH deficient from early gestation through weaning. Serum thyroxine (T4) and triiodothyronine (T3), and brain T3 levels, were subsequently measured in postnatal d 12 (P12) pups. Cu deficiency reduced serum total T3 by 48%, serum total T4 by 21%, and whole-brain T3 by 10% at P12. Fe deficiency reduced serum total T3 by 43%, serum total T4 by 67%, and whole-brain T3 by 25% at P12. Brain mRNA analysis revealed that expression of several TH-responsive genes were altered in CuD or FeD neonates, suggesting that reduced TH concentrations were sensed by the FeD and CuD neonatal brain. These results indicate that at least some of the brain defects associated with neonatal Fe and Cu deficiencies are mediated through reductions in circulating and brain TH levels.
Kcnq1ot1 noncoding RNA mediates transcriptional gene silencing by interacting with Dnmt1
Authors: Mohammad Faizaan , Mondal Tanmoy , Guseva Natalia , Pandey Gaurav Kumar , Kanduri Chandrasekhar
Published: June 2010

A long noncoding RNA, Kcnq1ot1, regulates the expression of both ubiquitously and tissue-specific imprinted genes within the Kcnq1 domain. However, the functional sequences of the Kcnq1ot1 RNA that mediate lineage-specific imprinting are unknown. Here, we have generated a knockout mouse with a deletion encompassing an 890-bp silencing domain (Δ890) downstream of the Kcnq1ot1 promoter. Maternal transmission of the Δ890 allele has no effect on imprinting, whereas paternal inheritance of the deletion leads to selective relaxation of the imprinting of ubiquitously imprinted genes to a variable extent in a tissue-specific manner. Interestingly, the deletion affects DNA methylation at somatically acquired differentially methylated regions (DMRs), but does not affect the histone modifications of the ubiquitously imprinted genes. Importantly, we found that Kcnq1ot1 recruits Dnmt1 to somatic DMRs by interacting with Dnmt1, and that this interaction was significantly reduced in the Δ890 mice. Thus, the ubiquitous and placental-specific imprinting of genes within the Kcnq1 domain might be mediated by distinct mechanisms, and Kcnq1ot1 RNA might mediate the silencing of ubiquitously imprinted genes by maintaining allele-specific methylation through its interactions with Dnmt1.
Ring1B and Suv39h1 delineate distinct chromatin states at bivalent genes during early mouse lineage commitment
Authors: Alder Olivia , Lavial Fabrice , Helness Anne , Brookes Emily , Pinho Sandra , Chandrashekran Anil , Arnaud Philippe , Pombo Ana , O'Neill Laura , Azuara Véronique
Published: June 2010

Pluripotent cells develop within the inner cell mass of blastocysts, a mosaic of cells surrounded by an extra-embryonic layer, the trophectoderm. We show that a set of somatic lineage regulators (including Hox, Gata and Sox factors) that carry bivalent chromatin enriched in H3K27me3 and H3K4me2 are selectively targeted by Suv39h1-mediated H3K9me3 and de novo DNA methylation in extra-embryonic versus embryonic (pluripotent) lineages, as assessed both in blastocyst-derived stem cells and in vivo. This stably repressed state is linked with a loss of gene priming for transcription through the exclusion of PRC1 (Ring1B) and RNA polymerase II complexes at bivalent, lineage-inappropriate genes upon trophoblast lineage commitment. Collectively, our results suggest a mutually exclusive role for Ring1B and Suv39h1 in regulating distinct chromatin states at key developmental genes and propose a novel mechanism by which lineage specification can be reinforced during early development.
Proliferative and transcriptional identity of distinct classes of neural precursors in the mammalian olfactory epithelium
Authors: Tucker Eric S. , Lehtinen Maria K. , Maynard Tom , Zirlinger Mariela , Dulac Catherine , Rawson Nancy , Pevny Larysa , LaMantia Anthony-Samuel
Published: June 2010

Neural precursors in the developing olfactory epithelium (OE) give rise to three major neuronal classes – olfactory receptor (ORNs), vomeronasal (VRNs) and gonadotropin releasing hormone (GnRH) neurons. Nevertheless, the molecular and proliferative identities of these precursors are largely unknown. We characterized two precursor classes in the olfactory epithelium (OE) shortly after it becomes a distinct tissue at midgestation in the mouse: slowly dividing self-renewing precursors that express Meis1/2 at high levels, and rapidly dividing neurogenic precursors that express high levels of Sox2 and Ascl1. Precursors expressing high levels of Meis genes primarily reside in the lateral OE, whereas precursors expressing high levels of Sox2 and Ascl1 primarily reside in the medial OE. Fgf8 maintains these expression signatures and proliferative identities. Using electroporation in the wild-type embryonic OE in vitro as well as Fgf8, Sox2 and Ascl1 mutant mice in vivo, we found that Sox2 dose and Meis1 – independent of Pbx co-factors – regulate Ascl1 expression and the transition from lateral to medial precursor state. Thus, we have identified proliferative characteristics and a dose-dependent transcriptional network that define distinct OE precursors: medial precursors that are most probably transit amplifying neurogenic progenitors for ORNs, VRNs and GnRH neurons, and lateral precursors that include multi-potent self-renewing OE neural stem cells.
Negative control of Smad activity by ectodermin/Tif1γ patterns the mammalian embryo
Authors: Morsut Leonardo , Yan Kai-Ping , Enzo Elena , Aragona Mariaceleste , Soligo Sandra M. , Wendling Olivia , Mark Manuel , Khetchoumian Konstantin , Bressan Giorgio , Chambon Pierre , Dupont Sirio , Losson Régine , Piccolo Stefano
Published: June 2010

The definition of embryonic potency and induction of specific cell fates are intimately linked to the tight control over TGFβ signaling. Although extracellular regulation of ligand availability has received considerable attention in recent years, surprisingly little is known about the intracellular factors that negatively control Smad activity in mammalian tissues. By means of genetic ablation, we show that the Smad4 inhibitor ectodermin (Ecto, also known as Trim33 or Tif1γ) is required to limit Nodal responsiveness in vivo. New phenotypes, which are linked to excessive Nodal activity, emerge from such a modified landscape of Smad responsiveness in both embryonic and extra-embryonic territories. In extra-embryonic endoderm, Ecto is required to confine expression of Nodal antagonists to the anterior visceral endoderm. In trophoblast cells, Ecto precisely doses Nodal activity, balancing stem cell self-renewal and differentiation. Epiblast-specific Ecto deficiency shifts mesoderm fates towards node/organizer fates, revealing the requirement of Smad inhibition for the precise allocation of cells along the primitive streak. This study unveils that intracellular negative control of Smad function by ectodermin/Tif1γ is a crucial element in the cellular response to TGFβ signals in mammalian tissues.
Literature review of past and present performance of the Nigerian manufacturing sector
Authors: Ku H S-L , Mustapha U , Goh S
Published: June 2010

This paper attempts to examine the past and present performance of the Nigerian manufacturing sector. The major problems and limitations that impede the growth of the sector are analysed. In the 1960s and 1970s after the country's independence, the Nigerian manufacturing sector had been developing positively as a result of direct foreign investment. Foreign companies had introduced new manufacturing technology that saved time and cost, and improved the quality of the products manufactured. However, despite this initial flourishing growth phase, the sector was not able successfully to meet local demand and the costs to the country for imported manufactured goods were high. From the end of 1980s to date, many problems were found that were responsible for low growth and development in the manufacturing sector. Some of these problems were dependency on oil for income, weak infrastructure, shortage of skilled labour, lack of adequate financial resources, lack of proper management and planning, and so on. The paper concludes that it is essential to work towards resolving all of these problems in order to rejuvenate the Nigerian manufacturing establishments so that the manufacturing sector can play an important role in the country's economic development.
Experimental study of cooling during the temper-free induction bending of thick-walled super-duplex pipework to tight bend radii
Authors: Collie G J , Black I
Published: June 2010

Temper-free (TF) induction bending has been proven to produce complex pipework in a cost-effective manner. Super-duplex is eminently suitable for induction bending as it retains only a fraction of its ambient yield stress when exposed to elevated temperatures. Previous research has shown that metallurgical problems, namely the precipitation of chromium nitride (Cr2N) and α′, may be encountered when bending thick-walled super-duplex pipe to radii of less than 2.5 × nominal pipe diameter. This paper uses evidence obtained from thermocouple testing to demonstrate that the typical cooling strategy employed for TF induction is insufficiently rigorous to guarantee the complete cooling of thick-walled pipe bent to tight radii. It goes on to show that, at the intrados, a reservoir of heat remains which may be sufficient to sustain the pipe within key critical temperature ranges long enough to allow the formation of Cr2N and α′, as well as γ2.
Approach to evaluate the rolling mill capacity in a plate rolling process
Authors: Moon C-H , Lee Y
Published: June 2010

This study presents an approach to evaluating the rolling mill capacity from the viewpoints of productivity and revamping cost when a plate mill is upgraded. In this light, a concept is proposed of a ‘characteristic length’, defined as the ratio of the design torque of the drive motor over the design force of the rolling equipment (structure of the rolling mill). A draft schedule algorithm for the plate rolling process is also presented, which consists of a force–thickness relation at each pass, and a roll force and torque prediction model.

Using the draft schedule algorithm linked with the characteristic length, a series of plate rolling analyses was performed to examine the productivity of a plate mill while varying: (i) the design force of the rolling equipment; (ii) the design torque of the drive motor; (iii) both its design force and torque; and (iv) the strength of the slab. In addition, as a practical example, the proposed approach has been applied to three actual plate mills in Korea, China, and Russia.

The results reveal that upgrading the design torque is the most efficient method from the viewpoint of productivity and revamping cost. It was also found that a critical characteristic length exists in which productivity cannot be increased any further, even though the rolling mill capacity has been upgraded further. Hence, this critical characteristic length can be used as an index to avoid the overcapacity problem of a plate mill when it is revamped.
Error analysis of the cutting coefficients and optimization of calibration procedure for cutting force prediction
Authors: Ahn I H , Hwang J H , Choi W C
Published: June 2010

Cutting force prediction is very important because phenomena occurring during cutting and their resulting outcomes can be predicted and controlled by knowing the cutting forces. The accuracy of predicted cutting forces depends on that of calibration data. Therefore, the accuracy of calibration data needs to be known to estimate the prediction accuracy for cutting forces. In the present study, it is experimentally shown that calibration data used for mechanistic models have a specific probability distribution. A number of calibration data are generated through Monte-Carlo simulation using this probability distribution, resulting in an error index of calibration data ( MPE) and the relationship between error of the predicted cutting forces and the error index. The results from this error analysis are utilized to estimate the prediction accuracy of the cutting forces and to optimize the calibration procedure that ensures the error in the cutting forces is within a given tolerance. The error analysis made in the present study is very practical because the calibration data accumulated in industry for various cutting processes can be directly utilized for the analysis without any additional experiments.
Vibration isolation of a symmetric and asymmetric rigid bar using struts subject to axial static and dynamic excitation
Authors: El-Kafrawy A E , Kandil A , Omar A
Published: June 2010

Many developed modern machineries such as compressors, engines, and presses represent a serious source of undesirable, uncomfortable, and uncontrollable vibrations leading to harmful failure and loss of machine availability. Therefore, research of mechanical engineers in maintenance sections in the industry has been devoted to the control, isolation, and minimi-zation of harmful effects of such vibrations. The objective of the present paper is to study the influence of using a specific type of vibration isolator based on using post-buckled elastic clamped—clamped struts as an effective solution tool to relieve vibrating machines from these harmful effects. A model that consists of post-buckled struts acting as vibration isolators used to support symmetric and asymmetric rigid bars is introduced. The proposed clamped—clamped struts are subject to axial harmonic excitation at the base. The isolated bar is allowed to displace laterally. Displacement transmissibility is selected as the governing optimization variable of the isolator's effectiveness with the main objective to minimize vibrations transmitted from the base to the rigid bar. The transmissibility is calculated over a wide range of frequencies and plotted in the form of design charts to determine its effect on the vibration behaviour of struts. The lateral motion of the bar is considered. These plots are used to recognize the range of frequencies, for which full isolation is maintained. The frequencies at which resonance occurs in the system can then be depicted from the design graphs. The study reveals that at resonance frequencies, the most effective transmissibility is well below unity. Vibration characteristics are determined at specific frequencies, such that the physical performance of the vibrating system can be studied. All variables used in the analysis are normalized, such that the results are not dependent on any geometric of material property, such as the modulus of elasticity of the material, the section modulus of the profile used, or the length of the strut. In this way, the obtained results can be applied over a wide range of elastic materials, regardless of the type of material or section properties.
Study on evaluation method of tube—fin thermal contact conductance
Authors: Tang D , Li D , Peng Y , Du Z
Published: June 2010

The thermal contact conductance (TCC) is one of the principal parameter in heat transfer mechanism of tube—fin heat exchangers. Because of the difficulties in experimental measurements, the tube—fin TCC has not been focused deeply. This article presents a novel method in evaluating the TCC of tube—fin heatexchanger. First, the tube—fin contact status is investigated with a finite-element model of tube expansion process. Distribution of contact pressure along the tube—fin interface is obtained from the simulation results. Then, experiments are carried out for the relationship between the contact pressure and the TCC. Combining the experiment result with the contact pressure distribution, the tube—fin TCC can be evaluated. Based on the method, effect of processing factors of the expansion forming process, such as expanding ratio and die geometry, are examined.
The effect of aspherical geometry and surface texturing on the elastohydrodynamic lubrication of metal-on-metal hip prostheses under physiological loading and motions
Authors: Gao L M , Meng Q E , Liu F , Fisher J , Jin Z M
Published: June 2010

As an alternative material combination, metal-on-metal (MOM) hip replacement has attracted a revived interest due to its very low wear rates. In this article, an elastohydrodynamic lubrication analysis is performed for an MOM hip replacement with specific geometrical designs: a macro Alpharabola geometry of the cup bearing surface and micro-dimples on the head surface. The corresponding numerical methodology is presented and full numerical solutions are obtained. The effect of the macro- and micro-geometrical designs on the lubrication performance is investigated, under both simplified and physiological walking conditions. The real physiological loading and motion conditions are important to be considered when optimizing the conformity-associated geometry of hip bearings. The Alpharabola geometry of cup bearing surface is found to significantly improve the lubricating film thickness and reduce hydrodynamic pressure of MOM hip implants, when the Alpharabola minimum radius is aligned with the loading direction.

Dimpled surface texturing has an adverse effect in a fluid film lubrication regime under the conditions considered in this study.
Shape functions associated with inverse element formulations
Authors: Faroughi S , Ahmadian H
Published: June 2010

Super-convergent element formulations in local co-ordinates are obtained using inverse strategies. In the inverse approach discretization errors of the element formulation are minimized leading to super-convergent solutions. In the development of the inverse element model, no shape functions are introduced and therefore the task of element transformation from local to global co-ordinates system remains a challenge. In this paper, a procedure is proposed to produce shape functions associated with the inverse element formulations via hierarchical polynomials. A membrane element formulation is developed using inverse strategy as an example and its associated shape functions are determined using hierarchical polynomials. Numerical results indicate higher accuracy of the developed model in global co-ordinates compared to the reported models in the literature for the same element.
Simulation of the material behaviour of metal powder during compaction
Authors: Schmidt I , Trondl A , Kraft T , Wonisch A
Published: June 2010

This article describes a direct numerical homogenization method for investigating the deformation mechanisms in, and the material behaviour of metal powder during and after compaction. An assembly of elasto-plastic spherical particles in frictional contact with one another is considered, and the stress response to some prescribed deformation history as well as the resulting yield surface of the aggregate is computed with the finite-element method. This is done by applying periodic boundary conditions to the assembly, in a manner that allows arbitrary stress or strain control, and by monitoring the dissipated energies during re-loading simulations with prescribed stress space directions. Closed die and isostatic compaction are considered in particular; the resulting yield surfaces are compared and the role of plastic deformation and frictional sliding on the micro-scale is investigated. Significant deviations from isotropic phenomenological models are found and the development of anisotropy is demonstrated.
Energy analysis of a coupled power—refrigeration cycle
Authors: Dubey M , Rajput S P S , Nag P K , Misra R D
Published: June 2010

This article presents the energy analysis of a coupled power—refrigeration cycle which eliminates the requirement of electrical power for driving the compressor of the vapour compression refrigeration cycle. The coupled cycle which uses pentafluropropane R-245ca as the working fluid in top power loop and bottom refrigeration loop have been assessed with different combinations such as cycle with recuperator, reheater, and economizer with a view to augment its performance. In the condenser temperature range of 30–42 °C and recuperator effectiveness range of 0.7–0.9, the overall coefficient of performance (COP) of the coupled cycle with the introduction of the recuperator, increased by 19.5–50.7 per cent and in the cycle with recuperator, reheater and economizer, it increased by 41.6–59.3 per cent. Overall COP at a constant turbine inlet temperature remains almost invariant with boiler pressure in the condenser temperature range of 30–42 °C for a coupled power–refrigeration base cycle and cycle with recuperator, reheater, and economizer. Significant decrease in overall COP is observed for boiler pressure greater than 5 MPa at constant turbine inlet temperature and recuperator effectiveness for the coupled cycle with recuperator.
Development and validation of a new universal through flow method for axial compressors
Authors: Petrovic M V , Wiedermann A , Banjac M B
Published: June 2010

This article describes the development of a new through flow method for the analysis of axial multi-stage compressors. The method is based on a stream function approach and a finite-element solution procedure. It includes a high-fidelity loss and deviation model with improved correlations and end-wall boundary layer calculation. A radial distribution model of losses and a new spanwise mixing model are applied to simulate three-dimensional flow effects. The calibration of the models is made by calculating a number of test cases with different configurations with the aim of achieving high accuracy and optimum robustness for each of the test cases considered.

The code was applied to flow analysis and performance prediction of a newly developed gas turbine compressor. Comparison of the predicted results and measured test data for the overall compressor performance and a number of parameters under different operating conditions showed good agreement. The results of the validation confirm that this method based on cali-brated correlations can be applied as a reliable tool for flow analysis and parameter variation during the design phase for a wide range of compressor configurations.
A micro gas turbine for UK domestic combined heat and power
Authors: Clay A , Tansley G D
Published: June 2010

Various micro-radial compressor configurations were investigated using one-dimensional meanline and computational fluid dynamics (CFD) techniques for use in a micro gas turbine (MGT) domestic combined heat and power (DCHP) application. Blade backsweep, shaft speed, and blade height were varied at a constant pressure ratio. Shaft speeds were limited to 220 000 r/min, to enable the use of a turbocharger bearing platform. Off-design compressor performance was established and used to determine the MGT performance envelope; this in turn was used to assess potential cost and environmental savings in a heat-led DCHP operating scenario within the target market of a detached family home. A low target-stage pressure ratio provided an opportunity to reduce diffusion within the impeller. Critically for DCHP, this produced very regular flow, which improved impeller performance for a wider operating envelope. The best performing impeller was a low-speed, 170 000 r/min, low-backsweep, 15° configuration producing 71.76 per cent stage efficiency at a pressure ratio of 2.20. This produced an MGT design point system efficiency of 14.85 per cent at 993 W, matching prime movers in the latest commercial DCHP units.

Cost and CO2 savings were 10.7 per cent and 6.3 per cent, respectively, for annual power demands of 17.4 MWht and 6.1 MWhe compared to a standard condensing boiler (with grid) installation. The maximum cost saving (on design point) was 14.2 per cent for annual power demands of 22.62 MWht and 6.1 MWhe corresponding to an 8.1 per cent CO2 saving. When sizing, maximum savings were found with larger heat demands. When sized, maximum savings could be made by encouraging more electricity export either by reducing household electricity consumption or by increasing machine efficiency.
Modelling of neurofuzzy control of a flexible link
Authors: Tinkir M , Önen Ü , Kalyoncu M
Published: June 2010

A modelling approach for neuro-fuzzy control of a single-link flexible robot manipulator that uses a computer-aided design (CAD) program is proposed. Initially, a CAD model of the flexible link is created using experimentally determined values of system parameters. This CAD model is then exported to MATLAB software and the Simulink/SimMechanics toolbox. An adaptive-network-based fuzzy logic controller is used for position and vibration control of the flexible link.

Experimental and simulation results are presented that validate the proposed approach.