bluuebunny/crossref_metadata_2025 huggingface dataset:
Learning by Doing, Knowledge Spillovers, and Technological and Organizational Change in High-Altitude Mountaineering
Authors: Boyce John R. , Bischak Diane P.
Published: December 2009

We present an analysis of microlevel data from mountaineering on the 14 peaks over 8,000 m in height during the period 1895-1998. Prior to 1950, no expedition was successful in making an ascent and almost half of expeditions experienced a death, frostbite, or altitude sickness. By the 1990s, however, over half of the expeditions would successfully make an ascent and only about one in seven would experience an adverse outcome. Our objective is to distinguish between the effects of learning by doing and knowledge spillovers versus the effects of changes in technology or economic organization in explaining these results. As we can identify each climber by name and nationality, as well as each expedition team's methods and outcomes, we are able to disentangle the effects of learning at the individual, national, and international levels from effects due to improvements in climbing technology or changes in organizational methods and objectives. We find evidence that both individual learning by doing and learning through knowledge spillovers have contributed to the observed increase in ascent rates and to the decrease in death, frostbite, and altitude sickness rates.
Incorporating 3D Multiplanar Reconstructed Images for Endovaginal Endometrial Assessment
Authors: Chouinard Nancy Teresa , Fix Catherine , Swan Hans
Published: December 2009

A study was undertaken to evaluate the use of 3D multiplanar reconstructed (MPR) images to reduce the scan time for endovaginal studies, thereby potentially reducing sonographer strain and possibly improving patient workflow. The scope of the study was limited to evaluation of the endometrium. A group of 42 patients with dysfunctional uterine bleeding was selected for the study. After initial transabdominal examination on each patient, an endovaginal study of the endometrium was performed using 3D data collection; this was followed by a complete conventional 2D endovaginal scan. The scan times and endometrial measurements for 3D and 2D methods were compared. Staff members were interviewed for feedback on the experience and for future protocol recommendations.
A highly efficient short hairpin RNA potently down-regulates CCR5 expression in systemic lymphoid organs in the hu-BLT mouse model
Authors: Shimizu Saki , Hong Patrick , Arumugam Balamurugan , Pokomo Lauren , Boyer Joshua , Koizumi Naoya , Kittipongdaja Panyamol , Chen Angela , Bristol Greg , Galic Zoran , Zack Jerome A. , Yang Otto , Chen Irvin S. Y. , Lee Benhur , An Dong Sung
Published: December 2009

Inhibiting the expression of the HIV-1 coreceptor CCR5 holds great promise for controlling HIV-1 infection in patients. Here we report stable knockdown of human CCR5 by a short hairpin RNA (shRNA) in a humanized bone marrow/liver/thymus (BLT) mouse model. We delivered a potent shRNA against CCR5 into human fetal liver-derived CD34+ hematopoietic progenitor/stem cells (HPSCs) by lentiviral vector transduction. We transplanted vector-transduced HPSCs solidified with Matrigel and a thymus segment under the mouse kidney capsule. Vector-transduced autologous CD34+ cells were subsequently injected in the irradiated mouse, intended to create systemic reconstitution. CCR5 expression was down-regulated in human T cells and monocytes/macrophages in systemic lymphoid tissues, including gut-associated lymphoid tissue, the major site of HIV-1 replication. The shRNA-mediated CCR5 knockdown had no apparent adverse effects on T-cell development as assessed by polyclonal T-cell receptor Vβ family development and naive/memory T-cell differentiation. CCR5 knockdown in the secondary transplanted mice suggested the potential of long-term hematopoietic reconstitution by the shRNA-transduced HPSCs. CCR5 tropic HIV-1 infection was effectively inhibited in mouse-derived human splenocytes ex vivo. These results demonstrate that lentiviral vector delivery of shRNA into human HPSCs could stably down-regulate CCR5 in systemic lymphoid organs in vivo.
Very long-term outcome of acute promyelocytic leukemia after treatment with all-trans retinoic acid and chemotherapy: the European APL Group experience
Authors: Adès Lionel , Guerci Agnes , Raffoux Emmanuel , Sanz Miguel , Chevallier Patrice , Lapusan Simona , Recher Christian , Thomas Xavier , Rayon Consuelo , Castaigne Sylvie , Tournilhac Olivier , de Botton Stephane , Ifrah Norbert , Cahn Jean-Yves , Solary Eric , Gardin Claude , Fegeux Nathalie , Bordessoule Dominique , Ferrant Augustin , Meyer-Monard Sandrine , Vey Norbert , Dombret Herve , Degos Laurent , Chevret Sylvie , Fenaux Pierre ,   for the European APL Group
Published: December 2009

Acute promyelocytic leukemia (APL) is highly curable with the combination of all-trans retinoic acid (ATRA) and anthracycline-based chemotherapy (CT), but very long-term results of this treatment, when CT should be added to ATRA and the role of maintenance treatment, remain uncertain. In our APL93 trial that included 576 newly diagnosed APL patients, with a median follow-up of 10 years, 10-year survival was 77%. Maintenance treatment significantly reduced 10-year cumulative incidence of relapses, from 43.2% to 33%, 23.4%, and 13.4% with no maintenance, maintenance using intermittent ATRA, continuous 6 mercaptopurine plus methotrexate, and both treatments, respectively (P < .001). Maintenance particularly benefited patients with white blood cell (WBC) count higher than 5 × 109/L (5000/μL). Early addition of CT to ATRA significantly improved 10-year event-free survival (EFS), but without significant effect on overall survival (OS). The 10-year cumulative incidence of deaths in complete response (CR), resulting mainly from myelosuppression, was 5.7%, 15.4%, and 21.7% in patients younger than 55, 55 to 65, and older than 65 years, respectively, supporting the need for less myelosuppressive treatments, particularly for consolidation therapy. This study is registered at http://clinicaltrials.gov as NCT00599937.
DDIT3/CHOP and the sarcoma fusion oncoprotein FUS-DDIT3/TLS-CHOP bind cyclin-dependent kinase 2
Authors: Bento Christoffer , Andersson Mattias K , Åman Pierre
Published: December 2009

Background

The DDIT3 gene encodes a transcription factor belonging to the CCAAT/enhancer binding protein (C/EBP) family. It is normally expressed at very low levels but is activated by cellular stress conditions and induces G1 arrest and, in some cell types, apoptosis. DDIT3 is found as a part of the fusion oncogene FUS-DDIT3 that is causal for the development of myxoid/round-cell liposarcomas (MLS/RCLS).

Results

In the present study, we searched for putative interaction partners of DDIT3 and the oncogenic FUS-DDIT3 among G1 cyclins and cyclin-dependent kinases. We found that FUS-DDIT3 and the normal DDIT3 bind CDK2. In addition, CDK2 showed an increased affinity for cytoskeletal proteins in cells expressing FUS-DDIT3 and DDIT3.

Conclusions

We conclude that DDIT3 binds CDK2 and that many of the observed biological effects of DDIT3 may involve interaction with CDK2.
Whole genome transcript profiling from fingerstick blood samples: a comparison and feasibility study
Authors: Robison Elizabeth H , Mondala Tony S , Williams Adam R , Head Steven R , Salomon Daniel R , Kurian Sunil M
Published: December 2009

Background

Whole genome gene expression profiling has revolutionized research in the past decade especially with the advent of microarrays. Recently, there have been significant improvements in whole blood RNA isolation techniques which, through stabilization of RNA at the time of sample collection, avoid bias and artifacts introduced during sample handling. Despite these improvements, current human whole blood RNA stabilization/isolation kits are limited by the requirement of a venous blood sample of at least 2.5 mL. While fingerstick blood collection has been used for many different assays, there has yet to be a kit developed to isolate high quality RNA for use in gene expression studies from such small human samples. The clinical and field testing advantages of obtaining reliable and reproducible gene expression data from a fingerstick are many; it is less invasive, time saving, more mobile, and eliminates the need of a trained phlebotomist. Furthermore, this method could also be employed in small animal studies, i.e. mice, where larger sample collections often require sacrificing the animal. In this study, we offer a rapid and simple method to extract sufficient amounts of high quality total RNA from approximately 70 μl of whole blood collected via a fingerstick using a modified protocol of the commercially available Qiagen PAXgene RNA Blood Kit.

Results

From two sets of fingerstick collections, about 70 uL whole blood collected via finger lancet and capillary tube, we recovered an average of 252.6 ng total RNA with an average RIN of 9.3. The post-amplification yields for 50 ng of total RNA averaged at 7.0 ug cDNA. The cDNA hybridized to Affymetrix HG-U133 Plus 2.0 GeneChips had an average % Present call of 52.5%. Both fingerstick collections were highly correlated with r2values ranging from 0.94 to 0.97. Similarly both fingerstick collections were highly correlated to the venous collection with r2values ranging from 0.88 to 0.96 for fingerstick collection 1 and 0.94 to 0.96 for fingerstick collection 2.

Conclusions

Our comparisons of RNA quality and gene expression data of the fingerstick method with traditionally processed sample workflows demonstrate excellent RNA quality from the capillary collection as well as very high correlations of gene expression data.
A novel anti-mycobacterial function of mitogen-activated protein kinase phosphatase-1
Authors: Cheung Benny KW , Yim Howard CH , Lee Norris CM , Lau Allan SY
Published: December 2009

Background

Mycobacterium tuberculosis (MTB) is a major cause of morbidity and mortality in the world. To combat against this pathogen, immune cells release cytokines including tumor necrosis factor-α (TNF-α), which is pivotal in the development of protective granulomas. Our previous results showed that Bacillus Calmette Guerin (BCG), a mycobacterium used as a model to investigate the immune response against MTB, stimulates the induction of TNF-α via mitogen-activated protein kinase (MAPK) in human blood monocytes. Since MAPK phosphatase-1 (MKP-1) is known to regulate MAPK activities, we examined whether MKP-1 plays a role in BCG-induced MAPK activation and cytokine expression.

Results

Primary human blood monocytes were treated with BCG and assayed for MKP-1 expression. Our results demonstrated that following exposure to BCG, there was an increase in the expression of MKP-1. Additionally, the induction of MKP-1 was regulated by p38 MAPK and extracellular signal-regulated kinase 1 and 2 (ERK1/2). Surprisingly, when MKP-1 expression was blocked by its specific siRNA, there was a significant decrease in the levels of phospho-MAPK (p38 MAPK and ERK1/2) and TNF-α inducible by BCG.

Conclusions

Since TNF-α is pivotal in granuloma formation, the results indicated an unexpected positive function of MKP-1 against mycobacterial infection as opposed to its usual phosphatase activity.
Burkholderia thailandensis harbors two identical rhl gene clusters responsible for the biosynthesis of rhamnolipids
Authors: Dubeau Danielle , Déziel Eric , Woods Donald E , Lépine François
Published: December 2009

Background

Rhamnolipids are surface active molecules composed of rhamnose and β-hydroxydecanoic acid. These biosurfactants are produced mainly by Pseudomonas aeruginosa and have been thoroughly investigated since their early discovery. Recently, they have attracted renewed attention because of their involvement in various multicellular behaviors. Despite this high interest, only very few studies have focused on the production of rhamnolipids by Burkholderia species.

Results

Orthologs of rhlA, rhlB and rhlC, which are responsible for the biosynthesis of rhamnolipids in P. aeruginosa, have been found in the non-infectious Burkholderia thailandensis, as well as in the genetically similar important pathogen B. pseudomallei. In contrast to P. aeruginosa, both Burkholderia species contain these three genes necessary for rhamnolipid production within a single gene cluster. Furthermore, two identical, paralogous copies of this gene cluster are found on the second chromosome of these bacteria. Both Burkholderia spp. produce rhamnolipids containing 3-hydroxy fatty acid moieties with longer side chains than those described for P. aeruginosa. Additionally, the rhamnolipids produced by B. thailandensis contain a much larger proportion of dirhamnolipids versus monorhamnolipids when compared to P. aeruginosa. The rhamnolipids produced by B. thailandensis reduce the surface tension of water to 42 mN/m while displaying a critical micelle concentration value of 225 mg/L. Separate mutations in both rhlA alleles, which are responsible for the synthesis of the rhamnolipid precursor 3-(3-hydroxyalkanoyloxy)alkanoic acid, prove that both copies of the rhl gene cluster are functional, but one contributes more to the total production than the other. Finally, a double ΔrhlA mutant that is completely devoid of rhamnolipid production is incapable of swarming motility, showing that both gene clusters contribute to this phenotype.

Conclusions

Collectively, these results add another Burkholderia species to the list of bacteria able to produce rhamnolipids and this, by the means of two identical functional gene clusters. Our results also demonstrate the very impressive tensio-active properties these long-chain rhamnolipids possess in comparison to the well-studied short-chain ones from P. aeruginosa.
Genetic tools for the investigation of Roseobacter clade bacteria
Authors: Piekarski Tanja , Buchholz Ina , Drepper Thomas , Schobert Max , Wagner-Doebler Irene , Tielen Petra , Jahn Dieter
Published: December 2009

Background

TheRoseobacterclade represents one of the most abundant, metabolically versatile and ecologically important bacterial groups found in marine habitats. A detailed molecular investigation of the regulatory and metabolic networks of these organisms is currently limited for many strains by missing suitable genetic tools.

Results

Conjugation and electroporation methods for the efficient and stable genetic transformation of selectedRoseobacterclade bacteria includingDinoroseobacter shibae,Oceanibulbus indolifex,Phaeobacter gallaeciensis,Phaeobacter inhibens,Roseobacter denitrificansandRoseobacter litoraliswere tested. For this purpose an antibiotic resistance screening was performed and suitable genetic markers were selected. Based on these transformation protocols stably maintained plasmids were identified. A plasmid encoded oxygen-independent fluorescent system was established using the flavin mononucleotide-based fluorescent protein FbFP. Finally, a chromosomal gene knockout strategy was successfully employed for the inactivation of the anaerobic metabolism regulatory genednrfromD. shibaeDFL12T.

Conclusion

A genetic toolbox for members of theRoseobacterclade was established. This provides a solid methodical basis for the detailed elucidation of gene regulatory and metabolic networks underlying the ecological success of this group of marine bacteria.
Melusin gene (ITGB1BP2) nucleotide variations study in hypertensive and cardiopathic patients
Authors: Palumbo Valeria , Segat Ludovica , Padovan Lara , Amoroso Antonio , Trimarco Bruno , Izzo Raffaele , Lembo Giuseppe , Regitz–Zagrosek Vera , Knoll Ralph , Brancaccio Mara , Tarone Guido , Crovella Sergio
Published: December 2009

Background

Melusin is a muscle specific signaling protein, required for compensatory hypertrophy response in pressure-overloaded heart. The role of Melusin in heart function has been established both by loss and gain of function experiments in murine models. With the aim of verifying the hypothesis of a potential role of the Melusin encoding gene, ITGB1BP2, in the modification of the clinical phenotype of human cardiomyopathies, we screened the ITGB1BP2 gene looking for genetic variations possibly associated to the pathological phenotype in three selected groups of patients affected by hypertension and dilated or hypertrophic cardiomyopathy

Methods

We analyzed ITGB1BP2 by direct sequencing of the 11 coding exons and intron flanking sequences in 928 subjects, including 656 hypertensive or cardiopathic patients and 272 healthy individuals.

Results

Only three nucleotide variations were found in patients of three distinct families: a C>T missense substitution at position 37 of exon 1 causing an amino acid change from His-13 to Tyr in the protein primary sequence, a duplication (IVS6+12_18dupTTTTGAG) near the 5'donor splice site of intron 6, and a silent 843C>T substitution in exon 11.

Conclusions

The three variations of the ITGB1BP2 gene have been detected in families of patients affected either by hypertension or primary hypertrophic cardiomyopathy; however, a clear genotype/phenotype correlation was not evident. Preliminary functional results and bioinformatic analysis seem to exclude a role for IVS6+12_18dupTTTTGAG and 843C>T in affecting splicing mechanism.

Our analysis revealed an extremely low number of variations in the ITGB1BP2 gene in nearly 1000 hypertensive/cardiopathic and healthy individuals, thus suggesting a high degree of conservation of the melusin gene within the populations analyzed.
Primary ciliogenesis defects are associated with human astrocytoma/glioblastoma cells
Authors: Moser Joanna J , Fritzler Marvin J , Rattner Jerome B
Published: December 2009

Background

Primary cilia are non-motile sensory cytoplasmic organelles that have been implicated in signal transduction, cell to cell communication, left and right pattern embryonic development, sensation of fluid flow, regulation of calcium levels, mechanosensation, growth factor signaling and cell cycle progression. Defects in the formation and/or function of these structures underlie a variety of human diseases such as Alström, Bardet-Biedl, Joubert, Meckel-Gruber and oral-facial-digital type 1 syndromes. The expression and function of primary cilia in cancer cells has now become a focus of attention but has not been studied in astrocytomas/glioblastomas. To begin to address this issue, we compared the structure and expression of primary cilia in a normal human astrocyte cell line with five human astrocytoma/glioblastoma cell lines.

Methods

Cultured normal human astrocytes and five human astrocytoma/glioblastoma cell lines were examined for primary cilia expression and structure using indirect immunofluorescence and electron microscopy. Monospecific antibodies were used to detect primary cilia and map the relationship between the primary cilia region and sites of endocytosis.

Results

We show that expression of primary cilia in normal astrocytes is cell cycle related and the primary cilium extends through the cell within a unique structure which we show to be a site of endocytosis. Importantly, we document that in each of the five astrocytoma/glioblastoma cell lines fully formed primary cilia are either expressed at a very low level, are completely absent or have aberrant forms, due to incomplete ciliogenesis.

Conclusions

The recent discovery of the importance of primary cilia in a variety of cell functions raises the possibility that this structure may have a role in a variety of cancers. Our finding that the formation of the primary cilium is disrupted in cells derived from astrocytoma/glioblastoma tumors provides the first evidence that altered primary cilium expression and function may be part of some malignant phenotypes. Further, we provide the first evidence that ciliogenesis is not an all or none process; rather defects can arrest this process at various points, particularly at the stage subsequent to basal body association with the plasma membrane.
Compound K, a metabolite of ginseng saponin, induces apoptosis via caspase-8-dependent pathway in HL-60 human leukemia cells
Authors: Cho Sung-Hee , Chung Kyung-Sook , Choi Jung-Hye , Kim Dong-Hyun , Lee Kyung-Tae
Published: December 2009

Background

Compound K [20-O-β-(D-glucopyranosyl)-20(S)-protopanaxadiol], a metabolite of the protopanaxadiol-type saponins of Panax ginseng C.A. Meyer, has been reported to possess anti-tumor properties to inhibit angiogenesis and to induce tumor apoptosis. In the present study, we investigated the effect of Compound K on apoptosis and explored the underlying mechanisms involved in HL-60 human leukemia cells.

Methods

We examined the effect of Compound K on the viabilities of various cancer cell lines using MTT assays. DAPI assay, Annexin V and PI double staining, Western blot assay and immunoprecipitation were used to determine the effect of Compound K on the induction of apoptosis.

Results

Compound K was found to inhibit the viability of HL-60 cells in a dose- and time-dependent manner with an IC50 of 14 μM. Moreover, this cell death had typical features of apoptosis, that is, DNA fragmentation, DNA ladder formation, and the externalization of Annexin V targeted phosphatidylserine residues in HL-60 cells. In addition, compound-K induced a series of intracellular events associated with both the mitochondrial- and death receptor-dependent apoptotic pathways, namely, (1) the activation of caspases-3, -8, and -9; (2) the loss of mitochondrial membrane potential; (3) the release of cytochrome c and Smac/DIABLO to the cytosol; (4) the translocation of Bid and Bax to mitochondria; and (5) the downregulations of Bcl-2 and Bcl-xL. Furthermore, a caspase-8 inhibitor completely abolished caspase-3 activation, Bid cleavage, and subsequent DNA fragmentation by Compound K. Interestingly, the activation of caspase-3 and -8 and DNA fragmentation were significantly prevented in the presence of cycloheximide, suggesting that Compound K-induced apoptosis is dependent on de novo protein synthesis.

Conclusions

The results indicate that caspase-8 plays a key role in Compound K-stimulated apoptosis via the activation of caspase-3 directly or indirectly through Bid cleavage, cytochrome c release, and caspase-9 activation.
Eukaryotic large nucleo-cytoplasmic DNA viruses: Clusters of orthologous genes and reconstruction of viral genome evolution
Authors: Yutin Natalya , Wolf Yuri I , Raoult Didier , Koonin Eugene V
Published: December 2009

Background

The Nucleo-Cytoplasmic Large DNA Viruses (NCLDV) comprise an apparently monophyletic class of viruses that infect a broad variety of eukaryotic hosts. Recent progress in isolation of new viruses and genome sequencing resulted in a substantial expansion of the NCLDV diversity, resulting in additional opportunities for comparative genomic analysis, and a demand for a comprehensive classification of viral genes.

Results

A comprehensive comparison of the protein sequences encoded in the genomes of 45 NCLDV belonging to 6 families was performed in order to delineate cluster of orthologous viral genes. Using previously developed computational methods for orthology identification, 1445 Nucleo-Cytoplasmic Virus Orthologous Groups (NCVOGs) were identified of which 177 are represented in more than one NCLDV family. The NCVOGs were manually curated and annotated and can be used as a computational platform for functional annotation and evolutionary analysis of new NCLDV genomes. A maximum-likelihood reconstruction of the NCLDV evolution yielded a set of 47 conserved genes that were probably present in the genome of the common ancestor of this class of eukaryotic viruses. This reconstructed ancestral gene set is robust to the parameters of the reconstruction procedure and so is likely to accurately reflect the gene core of the ancestral NCLDV, indicating that this virus encoded a complex machinery of replication, expression and morphogenesis that made it relatively independent from host cell functions.

Conclusions

The NCVOGs are a flexible and expandable platform for genome analysis and functional annotation of newly characterized NCLDV. Evolutionary reconstructions employing NCVOGs point to complex ancestral viruses.
Oral benign fibrous histiocytoma: two case reports
Authors: Menditti Dardo , Laino Luigi , Mezzogiorno Antonio , Sava Sara , Bianchi Alexander , Caruso Giovanni , Di Maio Luigi , Baldi Alfonso
Published: December 2009

Fibrous histiocytoma is a benign soft tissue tumour arising as a fibrous mass everywhere in the human body. The involvement of the oral cavity is rare. We report two cases of benign fibrous histiocytoma that localized in the oral cavity. The clinical and histological features of the lesion are reported. Finally, a literature revision of this pathology at the level of the oral cavity is reported.
Basaloid squamous cell carcinoma: two case reports
Authors: Vasudev Pooja , Boutross-Tadross Odette , Radhi Jasim
Published: December 2009

Basaloid squamous cell carcinoma (BSCC) is a rare and aggressive variant of squamous cell carcinoma (SCC) that occurs preferentially in the upper aerodigestive tract. We present two cases of BSCC, one arising in the conjunctiva and the other arising in a paranasal sinus. Clinical and pathological findings in these two cases, including immunohistochemistry is presented along with brief discussion of literature. To the best of our knowledge, this is the first report of BSCC of the conjunctiva. BSCC of the head and neck should be distinguished from adenoid cystic carcinoma, small cell neuroendocrine carcinoma, basal cell adenocarcinoma, adenosquamous carcinoma, squamous cell carcinoma, spindle cell squamous carcinoma, mucoepidermoid carcinoma, and adenoid cystic carcinoma.
Introduction to the Year In Basic Science Series . . . 2009
Authors: Shupnik Margaret A.
Published: December 2009

This year represents the second, of what we expect to be an annual series, of articles based on The Endocrine Society annual meeting presentations that highlight recent advances in vibrant basic science areas in endocrinology. For ENDO 09, two general areas with broad appeal and significance to our members were chosen: neuroendocrinology and G protein-coupled receptors. The invited participants were charged with presenting and discussing important papers that were published approximately during the year leading up to the most recent annual meetings (June 2009) and to put them into broad perspective for the greater endocrine community. Two distinguished members, Jeffrey Blaustein and Robert Millar, continued on last year’s successful features by synthesizing the top findings in their fields, and these articles are based on their annual meeting presentations. Interestingly, there were several points of intersection in these topics and chosen papers, as advances in the neuroendocrinology of reproduction have been coupled to identification and/or characterization of additional novel G protein-coupled receptors. In both presentations, fundamental basic science findings deriving from structural studies and signaling pathways are linked to broad endocrine physiology issues and to potential use in clinical treatment and therapeutics.
G protein-coupled receptor 48 upregulates estrogen receptor α expression via cAMP/PKA signaling in the male reproductive tract
Authors: Li Xiao-Ying , Lu Yan , Sun Hai-Yan , Wang Ji-Qiu , Yang Jun , Zhang Hui-Jie , Fan Neng-Guang , Xu Jia , Jiang Jing-Jing , Liu Ru-Ya , Li Da-Li , Liu Ming-Yao , Ning Guang
Published: December 2009

The epididymis and efferent ducts play major roles in sperm maturation, transport, concentration and storage by reabsorbing water, ions and proteins produced from seminiferous tubules. Gpr48-null male mice demonstrate reproductive tract defects and infertility. In the present study, we found that estrogen receptor α (ERα) was dramatically reduced in the epididymis and efferent ducts in Gpr48-null male mice. We further revealed that ERα could be upregulated by Gpr48 activation via the cAMP/PKA signaling pathway. Moreover, we identified a cAMP responsive element (Cre) motif located at −1307 to −1300 bp in the ERα promoter that is able to interact with Cre binding protein (Creb). In conclusion, Gpr48 participates in the development of the male epididymis and efferent ducts through regulation of ERα expression via the cAMP/PKA signaling pathway.
The Drosophila nuclear receptors DHR3 and βFTZ-F1 control overlapping developmental responses in late embryos
Authors: Ruaud Anne-Françoise , Lam Geanette , Thummel Carl S.
Published: December 2009

Studies of the onset of metamorphosis have identified an ecdysone-triggered transcriptional cascade that consists of the sequential expression of the transcription-factor-encoding genes DHR3, βFTZ-F1, E74A and E75A. Although the regulatory interactions between these genes have been well characterized by genetic and molecular studies over the past 20 years, their developmental functions have remained more poorly understood. In addition, a transcriptional sequence similar to that observed in prepupae is repeated before each developmental transition in the life cycle, including mid-embryogenesis and the larval molts. Whether the regulatory interactions between DHR3, βFTZ-F1, E74A and E75A at these earlier stages are similar to those defined at the onset of metamorphosis, however, is unknown. In this study, we turn to embryonic development to address these two issues. We show that mid-embryonic expression of DHR3 and βFTZ-F1 is part of a 20-hydroxyecdysone (20E)-triggered transcriptional cascade similar to that seen in mid-prepupae, directing maximal expression of E74A and E75A during late embryogenesis. In addition, DHR3 and βFTZ-F1 exert overlapping developmental functions at the end of embryogenesis. Both genes are required for tracheal air filling, whereas DHR3 is required for ventral nerve cord condensation and βFTZ-F1 is required for proper maturation of the cuticular denticles. Rescue experiments support these observations, indicating that DHR3 has essential functions independent from those of βFTZ-F1. DHR3 and βFTZ-F1 also contribute to overlapping transcriptional responses during embryogenesis. Taken together, these studies define the lethal phenotypes of DHR3 and βFTZ-F1 mutants, and provide evidence for functional bifurcation in the 20E-responsive transcriptional cascade.
Control of cell proliferation in Arabidopsis thaliana by microRNA miR396
Authors: Rodriguez Ramiro E. , Mecchia Martin A. , Debernardi Juan M. , Schommer Carla , Weigel Detlef , Palatnik Javier F.
Published: December 2009

Cell proliferation is an important determinant of plant form, but little is known about how developmental programs control cell division. Here, we describe the role of microRNA miR396 in the coordination of cell proliferation in Arabidopsis leaves. In leaf primordia, miR396 is expressed at low levels that steadily increase during organ development. We found that miR396 antagonizes the expression pattern of its targets, the GROWTH-REGULATING FACTOR (GRF) transcription factors. miR396 accumulates preferentially in the distal part of young developing leaves, restricting the expression of GRF2 to the proximal part of the organ. This, in turn, coincides with the activity of the cell proliferation marker CYCLINB1;1. We show that miR396 attenuates cell proliferation in developing leaves, through the repression of GRF activity and a decrease in the expression of cell cycle genes. We observed that the balance between miR396 and the GRFs controls the final number of cells in leaves. Furthermore, overexpression of miR396 in a mutant lacking GRF-INTERACTING FACTOR 1 severely compromises the shoot meristem. We found that miR396 is expressed at low levels throughout the meristem, overlapping with the expression of its target, GRF2. In addition, we show that miR396 can regulate cell proliferation and the size of the meristem. Arabidopsis plants with an increased activity of the transcription factor TCP4, which reduces cell proliferation in leaves, have higher miR396 and lower GRF levels. These results implicate miR396 as a significant module in the regulation of cell proliferation in plants.
The MED12-MED13 module of Mediator regulates the timing of embryo patterning in Arabidopsis
Authors: Gillmor C. Stewart , Park Mee Yeon , Smith Michael R. , Pepitone Robert , Kerstetter Randall A. , Poethig R. Scott
Published: December 2009

The Arabidopsis embryo becomes patterned into central and peripheral domains during the first few days after fertilization. A screen for mutants that affect this process identified two genes, GRAND CENTRAL (GCT)and CENTER CITY (CCT). Mutations in GCT and CCT delay the specification of central and peripheral identity and the globular-to-heart transition, but have little or no effect on the initial growth rate of the embryo. Mutant embryos eventually recover and undergo relatively normal patterning, albeit at an inappropriate size. GCT and CCT were identified as the Arabidopsis orthologs of MED13 and MED12 — evolutionarily conserved proteins that act in association with the Mediator complex to negatively regulate transcription. The predicted function of these proteins combined with the effect of gct and cct on embryo development suggests that MED13 and MED12 regulate pattern formation during Arabidopsis embryogenesis by transiently repressing a transcriptional program that interferes with this process. Their mutant phenotype reveals the existence of a previously unknown temporal regulatory mechanism in plant embryogenesis.
Evidence for a role of vertebrate Disp1 in long-range Shh signaling
Authors: Etheridge L. Alton , Crawford T. Quinn , Zhang Shile , Roelink Henk
Published: December 2009

Dispatched 1 (Disp1) encodes a twelve transmembrane domain protein that is required for long-range sonic hedgehog (Shh) signaling. Inhibition of Disp1 function, both by RNAi or dominant-negative constructs, prevents secretion and results in the accumulation of Shh in source cells. Measuring the Shh response in neuralized embryoid bodies (EBs) derived from embryonic stem (ES) cells, with or without Disp1 function, demonstrates an additional role for Disp1 in cells transporting Shh. Co-cultures with Shh-expressing cells revealed a significant reduction in the range of the contact-dependent Shh response in Disp1−/− neuralized EBs. These observations support a dual role for Disp1, not only in the secretion of Shh from the source cells, but also in the subsequent transport of Shh through tissue.
Dynamics of Delta/Notch signaling on endomesoderm segregation in the sea urchin embryo
Authors: Croce Jenifer C. , McClay David R.
Published: December 2009

Endomesoderm is the common progenitor of endoderm and mesoderm early in the development of many animals. In the sea urchin embryo, the Delta/Notch pathway is necessary for the diversification of this tissue, as are two early transcription factors, Gcm and FoxA, which are expressed in mesoderm and endoderm, respectively. Here, we provide a detailed lineage analysis of the cleavages leading to endomesoderm segregation, and examine the expression patterns and the regulatory relationships of three known regulators of this cell fate dichotomy in the context of the lineages. We observed that endomesoderm segregation first occurs at hatched blastula stage. Prior to this stage, Gcm and FoxA are co-expressed in the same cells, whereas at hatching these genes are detected in two distinct cell populations. Gcm remains expressed in the most vegetal endomesoderm descendant cells, while FoxA is downregulated in those cells and activated in the above neighboring cells. Initially, Delta is expressed exclusively in the micromeres, where it is necessary for the most vegetal endomesoderm cell descendants to express Gcm and become mesoderm. Our experiments show a requirement for a continuous Delta input for more than two cleavages (or about 2.5 hours) before Gcm expression continues in those cells independently of further Delta input. Thus, this study provides new insights into the timing mechanisms and the molecular dynamics of endomesoderm segregation during sea urchin embryogenesis and into the mode of action of the Delta/Notch pathway in mediating mesoderm fate.
The application of disturbance observer-based sliding mode control for magnetic levitation systems
Authors: Sun Z G , Cheung N C , Zhao S W , Gan W C
Published: December 2009

A control algorithm for the position tracking of a magnetic levitation system is presented in this article. The magnetic levitation system is well known for its non-linear dynamic characteristics and open-loop instability. The external disturbances will deteriorate the dynamic performance of the magnetic levitation system, and may give rise to system instability. This problem triggers enormous interests in designing various controllers for the non-linear dynamic system. In this article, a magnetic levitation system is first modelled. Then, a sliding mode controller is proposed, with a simple yet effective disturbance observer to perform disturbance rejection. Both the simulation results and the experimental results verify the validity of the robust controller.
The effect of rotation in a magneto-micropolar thermoelastic layer with one relaxation time
Authors: Kumar R
Published: December 2009

The present investigation deals with the propagation of waves in a rotating micropolar generalized thermoelastic layer in the presence of a transverse magnetic field. The generalized theory of thermoelasticity (Lord and Shulman theory) is employed to study the problem. Secular equations for symmetric and skew-symmetric modes of wave propagation in completely separate terms are derived. The amplitudes of displacement, microrotation, and temperature distribution were also obtained. The dispersion curves (of phase velocity and attenuation coefficient) for symmetric and skew-symmetric modes are presented graphically to illustrate and compare the results to study the magnetic effect and the effect of rotation.
Numerical investigation of the Lorentz force effect on the vortex transfiguration in a two-dimensional lid-driven cavity
Authors: Farahbakhsh I , Ghassemi H
Published: December 2009

Numerical calculations of the two-dimensional unsteady incompressible driven cavity flow in the presence of the Lorentz body force are presented. The Navier—Stokes equations in vorticity-stream function formulation are solved numerically using a uniform grid mesh of 201×201. A second-order central difference approximation is used for spatial derivatives and the solutions march in time with a fourth-order Runge—Kutta method. The unsteady driven cavity flow solution is computed for a Reynolds number of Re=1000. The effects of the Stuart number (ratio of the electromagnetic forces to inertial forces) and penetration depth of the Lorentz force on the lid-driven cavity vortices are investigated. Two new quaternary vortices at the bottom corners of the cavity are observed in the flow field as the Stuart number and penetration depth increase. The primary vortex size also dwindles and eventually breaks down into two tertiary vortices as these parameters increase. The velocity component profiles are also considerably sensitive with respect to these parameters.

It should be emphasized that on the basis of extensive comparisons and validations, which are made with benchmark solutions found in the literature, the numerical computations are repeated considering the Lorentz body force effect in the lid-driven cavity. Detailed results are presented in the article.
Engineering value recovery from municipal solid waste
Authors: Griffiths A J , Williams K P , Owen N
Published: December 2009

As world population and industrialization increase, the consequence has been an increase in waste generation. In an attempt to curb this increase and recover value from the waste streams, the European Union (EU) and UK have introduced a wide range of legislation, focusing to a large extent on the biodegradable component of municipal solid waste (MSW). Although by no means the largest component of the total waste generated, it is a significant contributor to greenhouse gas emissions if left unmanaged. Strict targets for its diversion from landfill have been set and these will become increasingly challenging between 2010 and 2020. Despite the raft of legislation, this article demonstrates that the definitions and properties of MSW and its management strategies can vary considerably across the EU. Variations also exist across the UK, making it difficult to compare one region and its management strategies to another. The generic role of the materials recovery facility (MRF) is seen as crucial by the authors and this article examines its place across the management spectrum. Data are presented to demonstrate the effectiveness of one such MRF operating in both ‘clean’ and ‘dirty’ modes. Its ability to recover product streams such as ferrous metal, aluminium, plastic containers, paper, and card is reported along with a brief economic assessment.
An analytical solution for the Marangoni mixed convection boundary layer flow
Authors: Moghimi M A , Kimiaeifar A , Rahimpour M , Bagheri G H
Published: December 2009

In this article, an analytical solution for a Marangoni mixed convection boundary layer flow is presented. A similarity transform reduces the Navier—Stokes equations to a set of non-linear ordinary differential equations, which are solved analytically by means of the homotopy analysis method (HAM). The results obtained in this study are compared with the numerical results released in the literature. A close agreement of the two sets of results indicates the accuracy of the HAM. The method can obtain an expression that is acceptable for all values of effective parameters and is also able to control the convergence of the solution. The numerical solution of the similarity equations is developed and the results are in good agreement with the analytical results based on the HAM.
Developing an auto-tracking automated guided vehicle carrier using a wave-varied detecting method
Authors: Chiu M-C , Yeh L-J , Lai G-J , Huang B-M
Published: December 2009

Robots are widely used in modern industrial manufacturing, in households, in the entertainment sector, and in the security sector. In recent times, because of the increasing lifetime for old people, the concept of lifestyles of health and sustainability is prevailing. To facilitate a heavily loaded hand-carrier when aged people are travelling or working outside, an intelligent automated guided vehicle (AGV) is necessary.

In this article, an intelligent and interactive AGV is developed. In order to develop the auto-tracking carrier for an AGV within an unlimited working space, a dynamic distance measuring system using the speed variation between a radio wave and an ultrasonic wave propagating in the air is adopted. The microchip PIC 18F452 is used as the control core. To facilitate the targeted functions, interactivity in conjunction with high quality sensors plays an essential role. By using a wireless transmitter (radio ray) and an ultrasonic transmitter on the user's waist angled towards the sensors at the front of the AGV, the distance between the user and the AGV can be calculated. To avoid colliding with a barrier, an ultrasonic transmitter is installed on both sides of the AGV. Subsequently, a controller based on fuzzy thinking will actuate the motor's motion enabling it to follow and dodge barriers.

Consequently, a prototype AGV has been manufactured and successfully tested in the laboratory.
The effects of circular sawblade diamond segment characteristics on marble processing performance
Authors: Buyuksagis I S
Published: December 2009

Utilizing a fully instrumented block-cutter, an experimental study was carried out to investigate the effects of diamond/metal matrix properties on the sawing performance of segmented circular sawblades. Six commercially available sawblades differing in segment compositions were used in the sawing experiments of Afyon Tiger Skin Marble. Bond compositions of the tested sawblades were determined by carrying out energy dispersive X-ray spectrometer analysis. The sawing tests were performed in the down-cutting mode. The sawing performances of the sawblades were evaluated in terms of cutting specific energy (SE), cutting force, axial force, and force ratio (ratio of tangential to normal force). The worn surfaces of the diamond segments were examined by scanning electron microscope micrographs.

Upon evaluation of the experimental data, it was concluded that the determined performance criteria from laboratory sawing tests can aid manufacturers in the design of appropriate sawblades for specific rock types. Valid for the employed machining parameters, tested sawblade types, and workpiece properties, the results of a multiple linear regression analysis have indicated that the Sn percentage of the segment matrix, the diamond concentration, and the matrix hardness are the common dominant variables that affect cutting SE, axial force, and cutting force.
Modifications to the response of a parametrically excited cantilever beam by means of smart active elements
Authors: Su X , Cartmell M P
Published: December 2009

This article is concerned with applying active smart material elements for modifying parametric vibration in a flexible composite beam structure. The glass epoxy beam is bonded to two theoretically prestrained shape memory alloy (SMA) strips and fitted with a lumped end mass. In this study, the components of the recovery force generated during the SMA activation are derived with respect to a three-dimensional frame when the structure is undergoing combined bending and torsional motions. In order to employ Lagrangian dynamics, the generalized forces are formulated and the equations of motion are then derived. Three different parametric resonances for the structure are predicted by using the multiple scales perturbation method. In addition, the effects of the SMA strips on the natural frequencies, the mode shapes, and the instability regions of the structure are all investigated. It is shown that the different thresholds of instability for parametric resonances within a composite structure of this sort may be influenced by smart active elements.
Study of a permanent magnet spring mechanism and its application to hydraulic valves
Authors: Wang Q , Yang F , Yang Q , Guan H , Chen J
Published: December 2009

Through study on structure, mechanism, and the calculation method of the magnetic force of a permanent-magnet spring, it can be known that rare-earth permanent-magnet springs can be used for replacing springs used in mechanical equipment, especially in hydraulic valves. The use of magnetic springs can decrease the size of the device and can also reduce noise and vibration. Meanwhile, magnetic springs are more sensitive to load and have a long useful time without fatigue wear.
Wave propagation in composite structures
Authors: Bareille O , Ichchou M N
Published: December 2009

Dynamic behaviour of honeycomb-core composite structures forms the framework of this article. The wave numbers of propagative waves are the elements of comparison between a numerical method (wave finite-element method) and an experimental identification technique (inhomogeneous wave correlation). The numerical method is based on the description of the dynamics of periodic waveguides. The experimental technique uses a matching criterion with the measured displacement field to obtain the corresponding wave numbers for a wave-based description of the displacement. Both approaches are applied to a sandwich composite beam with a honeycomb core. They seem to be in quite good accordance with analytical results for the flexural wave number.
On Fast Modal Frequency Response Analysis of Large Structural System with Gyroscopic Effect
Authors: Kim C-W
Published: December 2009

A new algorithm, fast frequency response analysis (FFRA), for the modal frequency response analysis (FRA) with gyroscopic effects is presented for a large and complex structural system. Because the modal gyroscopic matrix is low rank matrix compared to other modal matrices, the FFRA algorithm uses the Sherman-Morrison-Woodbury formula for computing the inverse of coefficient matrix efficiently. The new method, FFRA algorithm, dramatically improve the performance of the modal frequency response analysis with gyroscopic matrix compared to conventional methods in industry with the same accuracy.