bluuebunny/crossref_metadata_2025 huggingface dataset:
Generalized Orthogonality Condition for Beams with Intermediate Lumped Masses Subjected to Axial Force
Authors: Hassanpour P.A. , Esmailzadeh E. , Cleghorn W.L. , Mills J.K.
Published: March 2010

The orthogonality of the modes of vibration of a distributed parameter system plays an important role in the study of the dynamic behavior of that system. The definition of orthogonality for beams with classical boundary conditions is well known. However, it has been shown that the exact mode shapes of beams that carry one or more attached lumped masses are not orthogonal to each other under the classic condition. In this paper, the effect of axial force on the orthogonality condition of the exact mode shapes of beams with several attached lumped masses, as well as translational and rotational springs, is investigated. It has been shown that, in contrast to the mode shapes themselves, the orthogonality condition remains unchanged when an axial force is applied. Furthermore, the generalized orthogonality condition is employed to study the dynamic behavior of a beam—mass system under different boundary conditions. It has been shown that for the precise investigation of the dynamic response, application of exact mode shapes is not adequate enough, and the orthogonality condition associated with the problem must also be used. Finally, a discussion of the effect of the orthogonality condition on the damping matrices is presented. It has been shown that using the exact mode shapes and generalized orthogonality condition may result in non-modal and non-diagonal damping matrices, which, in turn, may increase the computation time.
Developing a Psychometrically Sound Assessment of School Leadership: The VAL-ED as a Case Study
Authors: Porter Andrew C. , Polikoff Morgan S. , Goldring Ellen , Murphy Joseph , Elliott Stephen N. , May Henry
Published: March 2010

Research has consistently shown that principal leadership matters for successful schools. Evaluating principals on the behaviors shown to improve student learning should be an important leverage point for raising leadership quality. Yet principals are often evaluated with the use of instruments with no theoretical background and little, if any, documented psychometric properties. To address this need, a team of researchers in principal leadership, assessment development, and psychometrics developed the Vanderbilt Assessment of Leadership in Education (VAL-ED). The purpose here is to report on iterative development work where the instrument was tested and revised across several cycles. Future work to investigate the instrument’s psychometric properties is identified. After an extensive item writing and instrument development phase, the authors embarked on a series of studies designed to guide improvements to the instrument. These studies include a sorting study, two rounds of cognitive interviews, a bias review, and two rounds of small- scale pilot tests. Results and implications from each study are discussed. The iterative development process helped improve the clarity of instructions and items while building a growing collection of preliminary validity and reliability evidence. At the end of the development process, the VAL-ED represents a promising instrument for assessing principal instructional leadership.The VAL- ED also represents a tool for possible use by principal leadership researchers in measuring the effectiveness of school principals.
Effect of La content on microstructure evolution of 20Ag–Cu–Zn–Sn–P–La filler metals and properties of joints
Authors: Li Z. R. , Cao J. , Liu B. , Feng J. C.
Published: March 2010

The influence of La content on the microstructure evolution of 20Ag–Cu–Zn–Sn–P (wt-%) filler metals and the mechanical properties of joint was investigated in this study. The typical microstructure of filler metal was analysed by means of scanning electron microscopy, optical microscopy and X-ray diffraction. Microstructural observation indicated that the growth of crystal grains in filler metals was prohibited with increasing the La content. It was found that 0·1–0·3 wt-%La improved the wettability of filler metals on 321 stainless steel and Cu substrates. From mechanical properties tests, the shear strength increased with increasing the La content in the range of 0·1 to 0·5 wt-%. When the La content reached 0·5 wt-%, the maximum of the joint shear strength was achieved. When the content is proper, the La addition had a positive effect on wettability by reducing surface tension of liquid alloys.
Study of friction stir joining of thin aluminium sheets in lap joint configuration
Authors: Yadava M. K. , Mishra R. S. , Chen Y. L. , Carlson B. , Grant G. J.
Published: March 2010

Thinning in friction stir lap joints and its relation with the process variables was investigated. Friction stir welds were made on 1 mm thick AA6111 aluminium alloy sheets in order to study the effects of rotation rate, traverse speed, plunge depth, tilt angle and pin height on faying surface defects. Sheet thinning on the advancing and retreating sides was quantified and the lap shear strength of the joints was evaluated. A decrease in the pitch of the runs at constant rotation rate increased the sheet thinning and reduced the joint strength in a linear manner. Process pitch and pin height were found to be the most critical factors in determining the faying surface lift up. A pin of the same height as the sheet thickness resulted in maximum lap shear strength. Tool tilt did not show a significant effect on the sheet thinning.
Dual inhibition of PI3K and mTOR inhibits autocrine and paracrine proliferative loops in PI3K/Akt/mTOR-addicted lymphomas
Authors: Bhatt Aadra P. , Bhende Prasanna M. , Sin Sang-Hoon , Roy Debasmita , Dittmer Dirk P. , Damania Blossom
Published: March 2010

Primary effusion lymphoma (PEL) constitutes a subset of non-Hodgkin lymphoma whose incidence is highly increased in the context of HIV infection. Kaposi sarcoma–associated herpesvirus is the causative agent of PEL. The phosphatidylinositol 3-kinase (PI3K) signaling pathway plays a critical role in cell proliferation and survival, and this pathway is dysregulated in many different cancers, including PEL, which display activated PI3K, Akt, and mammalian target of rapamycin (mTOR) kinases. PELs rely heavily on PI3K/Akt/mTOR signaling, are dependent on autocrine and paracrine growth factors, and also have a poor prognosis with reported median survival times of less than 6 months. We compared different compounds that inhibit the PI3K/Akt/mTOR pathway in PEL. Although compounds that modulated activity of only a single pathway member inhibited PEL proliferation, the use of a novel compound, NVP-BEZ235, that dually inhibits both PI3K and mTOR kinases was significantly more efficacious in culture and in a PEL xenograft tumor model. NVP-BEZ235 was effective at low nanomolar concentrations and has oral bioavailability. We also report a novel mechanism for NVP-BEZ235 involving the suppression of multiple autocrine and paracrine growth factors required for lymphoma survival. Our data have broad applicability for the treatment of cytokine-dependent tumors with PI3K/mTOR dual inhibitors.
Particle size and activation threshold: a new dimension of danger signaling
Authors: Rettig Lorna , Haen Sebastian P. , Bittermann Anne Greet , von Boehmer Lotta , Curioni Alessandra , Krämer Stefanie D. , Knuth Alexander , Pascolo Steve
Published: March 2010

Previous studies have shown that single-stranded RNA (ssRNA) mixed with protamine forms particles and activates immune cells through Toll-like receptors (TLRs). We have found that the size of protamine-RNA particles generated depends on the electrolyte content when mixing the 2 components. Moreover, we have evidenced that (1) nanometric particles induce production of interferon-α, whereas (2) micrometric particles mainly induce production of tumor necrosis factor-α (TNF-α) in human immune cells. We found that the mechanisms underlying these observations are (1) nanoparticles but not microparticles are selectively phagocytosed by plasmacytoid dendritic cells (pDCs), which produce interferon-α and (2) monocytes that produce TNF-α have a higher activation threshold than that of pDCs. Thus, at the same time as sensing pathogen-associated molecular patterns such as ssRNA, the immune system distinguishes the size of the associated structure in such a way as to trigger the adapted antivirus (nanometric) or antibacterial/antifungal (micrometric) immune response. Our results introduce a new dimension in danger signaling—how size qualitatively affects innate response.
G-CSF and its receptor in myeloid malignancy
Authors: Beekman Renée , Touw Ivo P.
Published: March 2010

Granulocyte colony-stimulating factor (G-CSF) has been used in the clinic for more than 2 decades to treat congenital and acquired neutropenias and to reduce febrile neutropenia before or during courses of intensive cytoreductive therapy. In addition, healthy stem cell donors receive short-term treatment with G-CSF for mobilization of hematopoietic stem cells. G-CSF has also been applied in priming strategies designed to enhance the sensitivity of leukemia stem cells to cytotoxic agents, in protocols aimed to induce their differentiation and accompanying growth arrest and cell death, and in severe aplastic anemia and myelodysplastic syndrome (MDS) to alleviate anemia. The potential adverse effects of G-CSF administration, particularly the risk of malignant transformation, have fueled ongoing debates, some of which can only be settled in follow-up studies extending over several decades. This specifically applies to children with severe congenital neutropenia who receive lifelong treatment with G-CSF and in which the high susceptibility to develop MDS and acute myeloid leukemia (AML) has now become a major clinical concern. Here, we will highlight some of the controversies and challenges regarding the clinical application of G-CSF and discuss a possible role of G-CSF in malignant transformation, particularly in patients with neutropenia harboring mutations in the gene encoding the G-CSF receptor.
IRF5 is required for late-phase TNF secretion by human dendritic cells
Authors: Krausgruber Thomas , Saliba David , Ryzhakov Grigory , Lanfrancotti Alessandra , Blazek Katrina , Udalova Irina A.
Published: March 2010

Spatially and temporally controlled expression of inflammatory mediators is critical for an appropriate immune response. In this study, we define the role for interferon regulatory factor 5 (IRF5) in secretion of tumor necrosis factor (TNF) by human dendritic cells (DCs). We demonstrate that DCs but not macrophages have high levels of IRF5 protein, and that IRF5 is responsible for the late-phase expression of TNF, which is absent in macrophages. Sustained TNF secretion is essential for robust T-cell activation by DCs. Systematic bioinformatic and biochemical analyses of the TNF gene locus map 2 sites of IRF5 recruitment: 5′ upstream and 3′ downstream of the TNF gene. Remarkably, while IRF5 can directly bind to DNA in the upstream region, its recruitment to the downstream region depends on the protein-protein interactions with NF-κB RelA. This study provides new insights into diverse molecular mechanisms employed by IRF5 to regulate gene expression and implicates RelA-IRF5 interactions as a putative target for cell-specific modulation of TNF expression.
Members of the microRNA-17-92 cluster exhibit a cell-intrinsic antiangiogenic function in endothelial cells
Authors: Doebele Carmen , Bonauer Angelika , Fischer Ariane , Scholz Alexander , Reiss Yvonne , Urbich Carmen , Hofmann Wolf-Karsten , Zeiher Andreas M. , Dimmeler Stefanie
Published: March 2010

MicroRNAs are endogenously expressed small noncoding RNAs that regulate gene expression on the posttranscriptional level. The miR-17-92 cluster (encoding miR-17, -18a, -19a/b, -20a, and miR-92a) is highly expressed in tumor cells and is up-regulated by ischemia. Whereas miR-92a was recently identified as negative regulator of angiogenesis, the specific functions of the other members of the cluster are less clear. Here we demonstrate that overexpression of miR-17, -18a, -19a, and -20a significantly inhibited 3-dimensional spheroid sprouting in vitro, whereas inhibition of miR-17, -18a, and -20a augmented endothelial cell sprout formation. Inhibition of miR-17 and miR-20a in vivo using antagomirs significantly increased the number of perfused vessels in Matrigel plugs, whereas antagomirs that specifically target miR-18a and miR-19a were less effective. However, systemic inhibition of miR-17/20 did not affect tumor angiogenesis. Further mechanistic studies showed that miR-17/20 targets several proangiogenic genes. Specifically, Janus kinase 1 was shown to be a direct target of miR-17. In summary, we show that miR-17/20 exhibit a cell-intrinsic antiangiogenic activity in endothelial cells. Inhibition of miR-17/20 specifically augmented neovascularization of Matrigel plugs but did not affect tumor angiogenesis indicating a context-dependent regulation of angiogenesis by miR-17/20 in vivo.
Evolutionary history and stress regulation of the lectin superfamily in higher plants
Authors: Jiang Shu-Ye , Ma Zhigang , Ramachandran Srinivasan
Published: March 2010

Background

Lectins are a class of carbohydrate-binding proteins. They play roles in various biological processes. However, little is known about their evolutionary history and their functions in plant stress regulation. The availability of full genome sequences from various plant species makes it possible to perform a whole-genome exploration for further understanding their biological functions.

Results

Higher plant genomes encode large numbers of lectin proteins. Based on their domain structures and phylogenetic analyses, a new classification system has been proposed. In this system, 12 different families have been classified and four of them consist of recently identified plant lectin members. Further analyses show that some of lectin families exhibit species-specific expansion and rapid birth-and-death evolution. Tandem and segmental duplications have been regarded as the major mechanisms to drive lectin expansion although retrogenes also significantly contributed to the birth of new lectin genes in soybean and rice. Evidence shows that lectin genes have been involved in biotic/abiotic stress regulations and tandem/segmental duplications may be regarded as drivers for plants to adapt various environmental stresses through duplication followed by expression divergence. Each member of this gene superfamily may play specialized roles in a specific stress condition and function as a regulator of various environmental factors such as cold, drought and high salinity as well as biotic stresses.

Conclusions

Our studies provide a new outline of the plant lectin gene superfamily and advance the understanding of plant lectin genes in lineage-specific expansion and their functions in biotic/abiotic stress-related developmental processes.
Gene-specific FACS sorting method for target selection in high-throughput amplicon sequencing
Authors: Sandberg Julia , Neiman Marten , Ahmadian Afshin , Lundeberg Joakim
Published: March 2010

Background

In addition to shotgun sequencing, next generation sequencing has been shown to be suitable for deep sequencing of many specific PCR-amplified target genes in parallel. However, unspecific product formation is a common problem in amplicon sequencing since these fragments are difficult to fully remove by gel purification, and their presence inevitably reduces the number of mappable sequence reads that can be obtained in each sequencing run.

Results

We have used a novel flow cytometric sorting approach to specifically enrich Roche/454 DNA Capture beads carrying target DNA sequences on their surface, and reject beads carrying unspecific sequences. This procedure gives a nearly three-fold increase in the fraction of informative sequences obtained. Presented results also show that there are no significant differences in the distribution or presence of different genotypes between a FACS-enriched sample and a standard-enriched control sample.

Conclusions

Target-specific FACS enrichment prior to Roche/454 sequencing provides a quick, inexpensive way of increasing the amount of high quality data obtained in a single sequencing run, without introducing any sequence bias.
Antimicrobial peptide-like genes in Nasonia vitripennis: a genomic perspective
Authors: Tian Caihuan , Gao Bin , Fang Qi , Ye Gongyin , Zhu Shunyi
Published: March 2010

Background

Antimicrobial peptides (AMPs) are an essential component of innate immunity which can rapidly respond to diverse microbial pathogens. Insects, as a rich source of AMPs, attract great attention of scientists in both understanding of the basic biology of the immune system and searching molecular templates for anti-infective drug design. Despite a large number of AMPs have been identified from different insect species, little information in terms of these peptides is available from parasitic insects.

Results

By using integrated computational approaches to systemically mining the Hymenopteran parasitic waspNasonia vitripennisgenome, we establish the first AMP repertoire whose members exhibit extensive sequence and structural diversity and can be distinguished into multiple molecular types, including insect and fungal defensin-like peptides (DLPs) with the cysteine-stabilized α-helical and β-sheet (CSαβ) fold; Pro- or Gly-rich abaecins and hymenoptaecins; horseshoe crab tachystatin-type AMPs with the inhibitor cystine knot (ICK) fold; and a linear α-helical peptide. Inducible expression pattern of sevenN. vitripennisAMP genes were verified, and two representative peptides were synthesized and functionally identified to be antibacterial. In comparison withApis mellifera(Hymenoptera) and several non-Hymenopteran model insects,N. vitripennishas evolved a complex antimicrobial immune system with more genes and larger protein precursors. Three classical strategies that are likely responsible for the complexity increase have been recognized:1) Gene duplication;2) Exon duplication; and3) Exon-shuffling.

Conclusion

The present study established theN. vitripennispeptidome associated with antimicrobial immunity by using a combined computational and experimental strategy. As the first AMP repertoire of a parasitic wasp, our results offer a basic platform for further studying the immunological and evolutionary significances of these newly discovered AMP-like genes in this class of insects.
Regulation of TFIIIB during F9 cell differentiation
Authors: Athineos Dimitris , Marshall Lynne , White Robert J
Published: March 2010

Background

Differentiation of F9 embryonal carcinoma (EC) cells into parietal endoderm (PE) provides a tractable model system for studying molecular events during early and inaccessible stages of murine development. PE formation is accompanied by extensive changes in gene expression both in vivo and in culture. One of the most dramatic is the ~10-fold decrease in transcriptional output by RNA polymerase (pol) III. This has been attributed to changes in activity of TFIIIB, a factor that is necessary and sufficient to recruit pol III to promoters. The goal of this study was to identify molecular changes that can account for the low activity of TFIIIB following F9 cell differentiation.

Results

Three essential subunits of TFIIIB decrease in abundance as F9 cells differentiate; these are Brf1 and Bdp1, which are pol III-specific, and TBP, which is also used by pols I and II. The decreased levels of Brf1 and Bdp1 proteins can be explained by reduced expression of the corresponding mRNAs. However, this is not the case for TBP, which is regulated post-transcriptionally. In proliferating cells, pol III transcription is stimulated by the proto-oncogene product c-Myc and the mitogen-activated protein kinase Erk, both of which bind to TFIIIB. However, c-Myc levels fall during differentiation and Erk becomes inactive through dephosphorylation. The diminished abundance of TFIIIB is therefore likely to be compounded by changes to these positive regulators that are required for its full activity. In addition, PE cells have elevated levels of the retinoblastoma protein RB, which is known to bind and repress TFIIIB.

Conclusion

The low activity of TFIIIB in PE can be attributed to a combination of changes, any one of which could be sufficient to inhibit pol III transcription. Declining levels of essential TFIIIB subunits and of activators that are required for maximal TFIIIB activity are accompanied by an increase in a potent repressor of TFIIIB. These events provide fail-safe guarantees to ensure that pol III output is appropriate to the diminished metabolic requirements of terminally differentiated cells.
Alterations of the extracellular matrix in ovarian cancer studied by Second Harmonic Generation imaging microscopy
Authors: Nadiarnykh Oleg , LaComb Ronald B , Brewer Molly A , Campagnola Paul J
Published: March 2010

Background

Remodeling of the extracellular matrix (ECM) has been implicated in ovarian cancer, and we hypothesize that these alterations may provide a better optical marker of early disease than currently available imaging/screening methods and that understanding their physical manifestations will provide insight into invasion.

Methods

For this investigation we use Second Harmonic Generation (SHG) imaging microcopy to study changes in the structure of the ovarian ECM in human normal and malignant ex vivo biopsies. This method directly visualizes the type I collagen in the ECM and provides quantitative metrics of the fibrillar assembly. To quantify these changes in collagen morphology we utilized an integrated approach combining 3D SHG imaging measurements and bulk optical parameter measurements in conjunction with Monte Carlo simulations of the experimental data to extract tissue structural properties.

Results

We find the SHG emission attributes (directionality and relative intensity) and bulk optical parameters, both of which are related to the tissue structure, are significantly different in the tumors in a manner that is consistent with the change in collagen assembly. The normal and malignant tissues have highly different collagen fiber assemblies, where collectively, our findings show that the malignant ovaries are characterized by lower cell density, denser collagen, as well as higher regularity at both the fibril and fiber levels. This further suggests that the assembly in cancer may be comprised of newly synthesized collagen as opposed to modification of existing collagen.

Conclusions

Due to the large structural changes in tissue assembly and the SHG sensitivity to these collagen alterations, quantitative discrimination is achieved using small patient data sets. Ultimately these measurements may be developed as intrinsic biomarkers for use in clinical applications.
Effect of hyperbaric oxygen on mesenchymal stem cells for lumbar fusion in vivo
Authors: Fu Tsai-Sheng , Ueng Steve WN , Tsai Tsung-Ting , Chen Lih-Huei , Lin Song-Shu , Chen Wen-Jer
Published: March 2010

Background

Hyperbaric oxygen (HBO) therapy has been proved in improving bone healing, but its effects on mesenchymal stem cells (MSCs) in vivo is not clear. The aims of this study are to clarify whether the HBO therapy has the same enhancing effect on MSCs with regard to bone formation and maturation and to ascertain whether the transplanted MSCs survive in the grafted area and contribute to new bone formation.

Methods

Twenty-three adult rabbits underwent posterolateral fusion at L4-L5 level. The animals were divided into three groups according to the material implanted and subsequent treatment: (1) Alginate carrier (n = 6); (2) Alginate-MSCs composite (n = 11); and (3) Alginate-MSCs composite with HBO therapy (n = 6). After 12 weeks, spine fusion was examined using radiographic examination, manual testing, and histological examination. Using a PKH fluorescence labeling system, whether the transplanted MSCs survived and contributed to new bone formation in the grafted area after HBO therapy was also examined.

Results

The bilateral fusion areas in each animal were evaluated independently. By radiographic examination and manual palpation, union for the Alginate, Alginate-MSCs, and Alginate-MSCs-HBO groups was 0 of 12, 10 of 22, and 6 of 12 respectively. The difference between the Alginate-MSCs and Alginate-MSCs-HBO groups was not significant (P = 0.7997). The fluorescence microscopy histological analysis indicated that the transplanted PKH67-labeled MSCs survived and partly contributed to new bone formation in the grafted area.

Conclusions

This study demonstrated that the preconditioned MSCs could survive and yield bone formation in the grafted area. HBO therapy did not enhance the osteogenic ability of MSCs and improve the success of spine fusion in the rabbit model. Although there was no significant effect of HBO therapy on MSCs for spine fusion, the study encourages us to research a more basic approach for determining the optimal oxygen tension and pressure that are required to maintain and enhance the osteogenic ability of preconditioned MSCs. Further controlled in vivo and in vitro studies are required for achieving a better understanding of the effect of HBO treatment on MSCs.
Evolving thermostability in mutant libraries of ligninolytic oxidoreductases expressed in yeast
Authors: García-Ruiz Eva , Maté Diana , Ballesteros Antonio , Martinez Angel T , Alcalde Miguel
Published: March 2010

Background

In the picture of a laboratory evolution experiment, to improve the thermostability whilst maintaining the activity requires of suitable procedures to generate diversity in combination with robust high-throughput protocols. The current work describes how to achieve this goal by engineering ligninolytic oxidoreductases (a high-redox potential laccase -HRPL- and a versatile peroxidase, -VP-) functionally expressed in Saccharomyces cerevisiae.

Results

Taking advantage of the eukaryotic machinery, complex mutant libraries were constructed by different in vivo recombination approaches and explored for improved stabilities and activities. A reliable high-throughput assay based on the analysis of T50 was employed for discovering thermostable oxidases from mutant libraries in yeast. Both VP and HRPL libraries contained variants with shifts in the T50 values. Stabilizing mutations were found at the surface of the protein establishing new interactions with the surrounding residues.

Conclusions

The existing tradeoff between activity and stability determined from many point mutations discovered by directed evolution and other protein engineering means can be circumvented combining different tools of in vitro evolution.
Krüppel-like factor 5 is a crucial mediator of intestinal tumorigenesis in mice harboring combined Apc
Min
and KRASV 12mutations
Authors: Nandan Mandayam O. , Ghaleb Amr M. , McConnell Beth B. , Patel Nilesh V. , Robine Sylvie , Yang Vincent W.
Published: March 2010

Background

Both mutational inactivation of the adenomatous polyposis coli (APC) tumor suppressor gene and activation of the KRAS oncogene are implicated in the pathogenesis of colorectal cancer. Mice harboring a germline Apc

Min
mutation or intestine-specific expression of the KRAS

V 12gene have been developed. Both mouse strains develop spontaneous intestinal tumors, including adenoma and carcinoma, though at a different age. The zinc finger transcription factor Krüppel-like factor 5 (KLF5) has previously been shown to promote proliferation of intestinal epithelial cells and modulate intestinal tumorigenesis. Here we investigated the in vivo effect of Klf5 heterozygosity on the propensity of Apc

Min
/KRAS

V 12double transgenic mice to develop intestinal tumors.

Results

At 12 weeks of age, Apc

Min
/KRAS

V 12mice had three times as many intestinal tumors as Apc

Min
mice. This increase in tumor number was reduced by 92% in triple transgenic Apc

Min
/KRAS

V 12/Klf5
+/- mice. The reduction in tumor number in Apc

Min
/KRAS

V 12/Klf5
+/- mice was also statistically significant compared to Apc

Min
mice alone, with a 75% decrease. Compared with Apc

Min
/KRAS

V 12, tumors from both Apc

Min
/KRAS

V 12/Klf5
+/- and Apc

Min
mice were smaller. In addition, tumors from Apc

Min
mice were more distally distributed in the intestine as contrasted by the more proximal distribution in Apc

Min
/KRAS

V 12and Apc

Min
/KRAS

V 12/Klf5
+/- mice. Klf5 levels in the normal-appearing intestinal mucosa were higher in both Apc

Min
and Apc

Min
/KRAS

V 12mice but were attenuated in Apc

Min
/KRAS

V 12/Klf5
+/- mice. The levels of β-catenin, cyclin D1 and Ki-67 were also reduced in the normal-appearing intestinal mucosa of Apc

Min
/KRAS

V 12/Klf5
+/- mice when compared to Apc

Min
/KRAS

V 12mice. Levels of pMek and pErk1/2 were elevated in the normal-appearing mucosa of Apc

Min
/KRAS

V 12mice and modestly reduced in ApcMin/KRAS

V 12/Klf5
+/- mice. Tumor tissues displayed higher levels of both Klf5 and β-catenin, irrespective of the mouse genotype from which tumors were derived.

Conclusions

Results of the current study confirm the cumulative effect of Apc loss and oncogenic KRAS activation on intestinal tumorigenesis. The drastic reduction in tumor number and size due to Klf5 heterozygosity in Apc

Min
/KRAS

V 12mice indicate a critical function of KLF5 in modulating intestinal tumor initiation and progression.
Genotype networks in metabolic reaction spaces
Authors: Samal Areejit , Matias Rodrigues João F , Jost Jürgen , Martin Olivier C , Wagner Andreas
Published: March 2010

Background

A metabolic genotype comprises all chemical reactions an organism can catalyze via enzymes encoded in its genome. A genotype is viable in a given environment if it is capable of producing all biomass components the organism needs to survive and reproduce. Previous work has focused on the properties of individual genotypes while little is known about how genome-scale metabolic networks with a given function can vary in their reaction content.

Results

We here characterize spaces of such genotypes. Specifically, we study metabolic genotypes whose phenotype is viability in minimal chemical environments that differ in their sole carbon sources. We show that regardless of the number of reactions in a metabolic genotype, the genotypes of a given phenotype typically form vast, connected, and unstructured sets -- genotype networks -- that nearly span the whole of genotype space. The robustness of metabolic phenotypes to random reaction removal in such spaces has a narrow distribution with a high mean. Different carbon sources differ in the number of metabolic genotypes in their genotype network; this number decreases as a genotype is required to be viable on increasing numbers of carbon sources, but much less than if metabolic reactions were used independently across different chemical environments.

Conclusions

Our work shows that phenotype-preserving genotype networks have generic organizational properties and that these properties are insensitive to the number of reactions in metabolic genotypes.
B-lymphocyte stimulator/a proliferation-inducing ligand heterotrimers are elevated in the sera of patients with autoimmune disease and are neutralized by atacicept and B-cell maturation antigen-immunoglobulin
Authors: Dillon Stacey R , Harder Brandon , Lewis Kenneth B , Moore Margaret D , Liu Hong , Bukowski Thomas R , Hamacher Nels B , Lantry Megan M , Maurer Mark , Krejsa Cecile M , Ellsworth Jeff L , Pederson Susan , Elkon Keith B , Wener Mark H , Dall'Era Maria , Gross Jane A
Published: March 2010

Introduction

B-lymphocyte stimulator (BLyS) and a proliferation-inducing ligand (APRIL) are members of the tumor necrosis factor (TNF) family that regulate B-cell maturation, survival, and function. They are overexpressed in a variety of autoimmune diseases and reportedly exist in vivo not only as homotrimers, but also as BLyS/APRIL heterotrimers.

Methods

A proprietary N-terminal trimerization domain was used to produce recombinant BLyS/APRIL heterotrimers. Heterotrimer biologic activity was compared with that of BLyS and APRIL in a 4-hour signaling assay by using transmembrane activator and CAML interactor (TACI)-transfected Jurkat cells and in a 4-day primary human B-cell proliferation assay. A bead-based immunoassay was developed to quantify native heterotrimers in human sera from healthy donors (n = 89) and patients with systemic lupus erythematosus (SLE; n = 89) or rheumatoid arthritis (RA; n = 30). Heterotrimer levels were compared with BLyS and APRIL homotrimer levels in a subset of these samples.

Results

The recombinant heterotrimers consisted mostly of one BLyS and two APRIL molecules. Heterotrimer signaling did not show any significant difference compared with APRIL in the TACI-Jurkat assay. Heterotrimers were less-potent inducers of B-cell proliferation than were homotrimeric BLyS or APRIL (EC50, nMol/L: BLyS, 0.02; APRIL, 0.17; heterotrimers, 4.06). The soluble receptor fusion proteins atacicept and B-cell maturation antigen (BCMA)-immunoglobulin (Ig) neutralized the activity of BLyS, APRIL, and heterotrimers in both cellular assays, whereas B-cell activating factor belonging to the TNF family receptor (BAFF-R)-Ig neutralized only the activity of BLyS. In human sera, significantly more patients with SLE had detectable BLyS (67% versus 18%; P < 0.0001), APRIL (38% versus 3%; P < 0.0002), and heterotrimer (27% versus 8%; P = 0.0013) levels compared with healthy donors. Significantly more patients with RA had detectable APRIL, but not BLyS or heterotrimer, levels compared with healthy donors (83% versus 3%; P < 0.0001). Heterotrimer levels weakly correlated with BLyS, but not APRIL, levels.

Conclusions

Recombinant BLyS/APRIL heterotrimers have biologic activity and are inhibited by atacicept and BCMA-Ig, but not by BAFF-R-Ig. A novel immunoassay demonstrated that native BLyS/APRIL heterotrimers, as well as BLyS and APRIL homotrimers, are elevated in patients with autoimmune diseases.
Race, Labor, and the City in the Obama Era: King's Unfinished Agenda
Authors: Honey Michael
Published: March 2010

In “Race, Labor and the City in the Obama Era: King's Unfinished Agenda,” Honey surveys what has happened in Memphis since the King assassination. He argues that King's phase one of civil rights has largely succeeded but that King's phase two of economic justice has not. As is the case all over the nation, the black working class has suffered disproportionately from deindustrialization, loss of unions, and the trickle-down economics of racial capitalism. Honey argues that the election of Barack Obama as president forty years after King's death provides unprecedented opportunity but only if a movement counters diluted proposals for “bipartisan” reform with demands that government implement King's unfinished agenda of ending racism, poverty, and war.
Inertia effects in textured hydrodynamic contacts
Authors: Cupillard S , Glavatskih S , Cervantes M J
Published: March 2010

A flow analysis is carried out for a parallel textured slider to investigate the role of fluid inertia. Numerical simulations are performed for a laminar, two-dimensional, steady and isothermal flow. Stokes solutions are compared with Navier—Stokes solutions at the same Reynolds number. A range of texture depths is analysed. It is shown that there is an optimum value of texture depth that provides maximum load-carrying capacity. It is also shown that there is a critical depth value. Inertia has a negative effect on the load-carrying capacity for depths higher than the critical value, whereas it has a positive effect for lower depths. For a given texture depth, these effects are amplified as the Reynolds number increases. The global effect of inertia is positive when a realistic configuration of a parallel textured slider with a fore-region is considered.
Investigating the effect of surface coatings on the wear behaviour of the friction contact in ultrasonic motors
Authors: Cheung C K , Shi B , Lau C S , Shum P W , Zhou Z F , Li K Y
Published: March 2010

Nowadays, ultrasonic motors (USMs) are used widely in a large variety of applications such as camera auto-focus mechanisms, devices in automobiles, industrial servo control in precision positioning, intelligent robotics, ultra-precision measuring, and medical equipment. USM is driven by traction force at high-frequency oscillations (>40 kHz) and the characteristics and life of the motor are strongly related to the friction material used in the tribological contact. In this study, two purposely built test rigs, including a USM and a high-frequency (up to 4000 r/min) reciprocating machine (HFRM), were developed. The reciprocating machine ran with a small amplitude and a high-frequency motion was used to examine the wear behaviour of the friction pairs. Different materials such as advanced surface coating (chromium titanium aluminium nitride, and diamond-like coating) on stainless steel substrates were used to investigate their combined tribological performance with the aim to be used in the USM context. A matrix screening test for material selection purpose were also carried out using the HFRM and the tribological performance of the chosen material pairs were subsequently investigated using the USM. The ranking results of the material pairs from the USM tests agreed with those from the HFRM tests. HFRM results could correlate well with the USM results by considering energy input into the wear system. Thus, HFRM can be used as a screening tool for selecting materials using in USMs.
Compound-archery-bow nocking-point locus in the vertical plane
Authors: Park J L
Published: March 2010

In general, the path taken by the nocking point of an archery bow in the vertical plane is not a straight line perpendicular to the rest position of the string; it may vary significantly from that. Any deviation from a straight line at a draw length around the full-draw position will potentially lead to significant inaccuracy if the draw length varies by small amounts from arrow to arrow. This can occur for a compound bow if the cams do not come to their full-draw position simultaneously.

The path taken by the nocking point over the length of the bow's draw, and especially near the bow's brace height, can be expected to influence significantly the way that the arrow flexes and rotates about its centre of mass as it leaves the bow and enters the airstream. Hence it is of importance in relation to the arrow's position on the string relative to the bow's launcher (or arrow rest) at the brace height.

This paper provides a model for the nocking-point locus in the vertical plane. While examples are provided for several configurations of compound bow, it is generally applicable to longbows and recurve bows as well. It is noted that asymmetric degrees of freedom in the cam configuration of a compound bow are required if the nocking-point locus is to be both straight and perpendicular to the rest position of the string, and that this cannot be achieved for some compound-bow configurations or for a longbow or recurve bow unless the arrow pass is in the geometric centre of the string.
Hospital-based injury data in Malawi: strategies for data collection and feasibility of trauma scoring tools
Authors: Samuel Jonathan C , Akinkuotu Adesola , Baloyi Paul , Villaveces Andres , Charles Anthony , Lee Clara N , Miller William , Hoffman Irving F , Muyco Arturo P
Published: March 2010

Injury is a major cause of morbidity and mortality in developing countries. Utilizing a partnership between Kamuzu Central Hospital (KCH) and the University of North Carolina Departments of Surgery, we describe an approach to injury surveillance, examine the utility of trauma scoring systems, and outline steps necessary before such scoring systems can be reliably instituted in a resource-constrained setting.
Postmortem findings in HIV/AIDS patients in a tertiary care hospital in rural South Africa
Authors: Garcia-Jardon Mirta , Bhat Vivek G , Blanco-Blanco E , Stepian Andrez
Published: March 2010

South Africa has the largest number of people living with HIV/AIDS, and various associated infectious and noninfectious conditions contribute towards mortality. The objective of this study was to determine the important post-mortem findings in HIV-infected individuals in a high HIV burden rural area in South Africa. The patient population included HIV patients who died at the tertiary care hospital, from 2000–2008. Autopsies were performed according to standard protocols and diagnoses were made with additional laboratory investigations wherever required. A total of 86 patients were autopsied (30 males, 56 females). The major postmortem findings were related to infections, with 38% of the patients having had some form of tuberculosis, followed by pyogenic infections – pneumonias (21.5%), meningitis (10.1%) and septicemias (5.1%). Other important infections included opportunistic fungi like cryptococcosis (7.6%) and pneumocystis pneumonia (8.9%). Among the noninfectious conditions, the findings seen were predominantly related to liver (10.1%) and cardiac involvement (10.1%).
Periodic Wellbore-Water Accumulation and Off-Take
Authors: Appah Dulu
Published: March 2010

Reliable representations of the accumulation and release of water from oil and condensate wellbores remain elusive due to the complexity of this random phenomenon. In this paper, spectral analysis is applied to strings of oilwell production rates to estimate the optimum flow regime and consequently predict its performance. The temporal rates of growth of fluid production are also calculated from wave theory. The dominant peaks of the spectral density curves calculated from flow-rate data correspond with calculated periods of the most unstable oscillation frequency of the instability theory. Observed well water-cut fluctuations, during fluid rate measurements, may therefore be explained by the periodic accumulation and off-take of water from the region around the wellbore. The frequency distribution of field data fluctuation is therefore used to identify the source of fluctuation generated by the flow mechanism. The present study reveals further information on the mechanism of production rate fluctuations and surging.
Selection and Use of CaO-Expanding Cements
Authors: Appah Dulu , Reichetseder Peter
Published: March 2010

With the rapid drilling of deep wells, cementing operations encounter new and more complex challenges due to harsh environments. To improve the use and selection of CaO-type expanding cements, a series of measurements have been made. Calcium oxide is used as an expanding agent to overcome contraction as cement slurry sets. Cement systems selection was based on their performances indicated by expansion tendency, consistency behaviour, lime reactivity at 60°C and atmospheric pressure, and autoclave-cured cement paste properties. Slurries were prepared using different mixing methods (API standards and an in-house procedure) to help choose appropriate slurry designs for wide field applications. Expansion and consistency tests were carried out in High Pressure-High Temperature devices at 60, 80, 90 and 120°C and 120 MPa. Mix waters of different salinities and sulphur contents were used to prepare cement slurries. It is shown that the expanding influence of CaO becomes significant when the temperature is higher than 60°C, but less than 80°C; salt content of 20–30% by weight of water; lime concentration of 12.5%. Gel and shear strengths of 150 Pa and 4 MPa, respectively and cement expansion greater than 4 % give sufficient tightness and seal, to stop gas migration in boreholes.
Renewable Energy: Power for a Sustainable Future
Authors: Kaygusuz Kamil
Published: March 2010

By the end of the 21st century, according to United Nations projections, the number of people on the earth is likely to have approximately doubled. How can a world of 10 to 12 billion people be provided with adequate supplies of energy, cleanly, safely and substantially? There is a growing consensus that renewable energy sources will be a very important part of the answer. The growing interest in “renewables” has been prompted in part, by increasing concern over the pollution, resource depletion and possible climate change implications of our continuing use of conventional fossil and nuclear fuels. But recent technological developments have also improved the cost-effectiveness of many of the renewables, making their economic prospects look increasingly attractive. It describes the achievement and progress made in hydropower, biomass conversion, geothermal, solar thermal technology, wind energy conversion and the increasing usage of photovoltaics. It is evident that global warming is setting in and is going to change the climate as well as the terrain of many countries unless drastic measures are taken. The Kyoto meeting emphasized the importance of limiting CO2 emissions and to abide by some form of agreement to reduce emissions. Present study concludes that renewable energy penetration into the energy market is much faster than was expected in recent years and by 2030, 15–20 percent of our prime energy will be met by renewable energy.
Underpressured and Overpressured Tight Gas Sands: I. Flow, Buoyancy and Limiting Conditions
Authors: Lerche Ian
Published: March 2010

This paper explores the steady-state flow situation through a uniform aquifer of gas being supplied from the lower end of the aquifer, with the gas subject to buoyancy and also a pressure drive. Two groups of situations arise. Either the ratio of the buoyancy pressure to the permeable flow pressure is greater or less than unity. For low permeability (“tight” gas sands) it is shown that both underpressured and overpressured situations can occur, depending on the precise values of updip and downdip pressures. For highly permeable flows such is not the case. Limitations at the moment are the simplifications of constant cross-section for the aquifer, as well as constant permeability and constant aquifer temperature, together with the steady-state assumption. These restrictions will be lifted in the next paper in the series. Perhaps the salient point is that one can account for underpressured tight gas sands, but the extreme sensitivity of the system to the ratio of buoyancy pressure to permeable flow pressure means that it is currently extremely difficult to predict, ahead of the drill, which situation will prevail in a given basin.
The Use of Supercritical Fluid Extraction in Carrier Recovery from a Spent Active Carbon–Zinc Acetate Catalyst
Authors: Dąbek Lidia
Published: March 2010

The present paper is aimed at showing the usefulness of supercritical fluid extraction in the removal of organic substances and zinc from the surface of a dangerous waste product, i.e. spent catalyst employed in the manufacture of vinyl acetate. The possibility of recovering active carbon (the carrier support for the catalyst concerned) so that it may be used in subsequent processes by combining supercritical fluid extraction with hydrochloric acid leaching has been demonstrated.
The Separation of Chloromethane Mixtures and the Recovery of Dichloromethane, Chloroform and Carbon Tetrachloride by Activated Carbon Fibre
Authors: Wu Jufang , Ma Lan , Zhao Hongyang , Wang Zijiu
Published: March 2010

One type of activated carbon fibre with a high micropore content was used to separate chloromethane mixtures and recover dichloromethane, chloroform and carbon tetrachloride. The adsorption process (which was accompanied by a temperature change of the activated carbon fibre bed) and the desorption process were investigated by the application of fixed-bed techniques. Two interesting and important phenomena were observed: (i) displacement between the adsorbates; and (ii) agreement in time between the breakthrough of the adsorbate and the temperature change of the activated carbon fibre bed. The recovery rate was greater than 96% and the cyclic process took ca. ½ h to complete, both being satisfactory from an industrial viewpoint. The effect of the current blank velocity on the adsorption capacity and obstruction of the activated carbon fibre bed were also investigated in order to provide fundamental data for industrial application.