bluuebunny/crossref_metadata_2025 huggingface dataset:
Antiangiogenesis therapy in the treatment of metastatic colorectal cancer
Authors: Grothey Axel , Allegra Carmen
Published: August 2012

The process of new blood vessel formation, or angiogenesis, has become an important target for therapeutic intervention in many cancers, including metastatic colorectal cancer (mCRC). The growth and metastasis of primary tumors is dependent upon their ability to acquire and maintain an adequate blood supply; however, angiogenesis in tumors is an irregular process leading to chaotic and hyperpermeable vessels that may result in increased intratumoral pressure and poor exchange of macromolecules and oxygen. It has been hypothesized that inhibition of angiogenesis in tumors can both impair the formation of new tumor blood vessels and possibly ‘normalize’ the existing tumor vasculature, causing a more efficient delivery of cytotoxic chemotherapies (CTs). Over the last decade, therapies that target vascular endothelial growth factor (VEGF) have become a component of treatment for several cancers. In particular, the combination of bevacizumab with established chemotherapeutic regimens for mCRC has been shown to improve overall and progression-free survival, as well as response rates, over CT alone. Agents that target various members of the VEGF family, as well as signaling by the VEGF receptors and their tyrosine kinase components, are currently under development and evaluation in clinical trials. Integration of these new therapies into the treatment of mCRC will ultimately increase the available therapeutic options for patients. Still, many challenges remain, including identifying and validating relevant biomarkers to guide the optimal use of antiangiogenesis agents.
New agents on the horizon in hepatocellular carcinoma
Authors: Zhu Andrew X.
Published: August 2012

Despite the successful approval and extensive application of sorafenib, the prognosis for patients with advanced hepatocellular carcinoma (HCC) remains poor. Fortunately, there have been renewed and continued interests and active research in developing other molecularly targeted agents in HCC during the past few years. While there is early evidence of antitumor activity of several agents in phase I/II studies, phase III efforts with a few targeted agents have failed, highlighting the challenges of new drug development in HCC. This review summarizes the current status of other molecularly targeted agents under development in advanced HCC.
Sickle cell pain: a critical reappraisal
Authors: Ballas Samir K. , Gupta Kalpna , Adams-Graves Patricia
Published: August 2012

Sickle cell pain includes 3 types: acute recurrent painful crises, chronic pain syndromes, and neuropathic pain. The acute painful crisis is the hallmark of the disease and the most common cause of hospitalization and treatment in the emergency department. It evolves through 4 phases: prodromal, initial, established, and resolving. Each acute painful episode is associated with inflammation that worsens with recurrent episodes, often culminating in serious complications and organ damage, such as acute chest syndrome, multiorgan failure, and sudden death. Three pathophysiologic events operate in unison during the prodromal phase of the crisis: vaso-occlusion, inflammation, and nociception. Aborting the acute painful episode at the prodromal phase could potentially prevent or minimize tissue damage. Our hypothesis is that managing these events with hydration, anti-inflammatory drugs, aggressive analgesia, and possibly vasodilators could abort the crisis and prevent or minimize further damage. Chronic pain syndromes are associated with or accompany avascular necrosis and leg ulcers. Neuropathic pain is not well studied in patients with sickle cell disease but has been modeled in the transgenic sickle mouse. Management of sickle cell pain should be based on its own pathophysiologic mechanisms rather than borrowing guidelines from other nonsickle pain syndromes.
How I treat transfusional iron overload
Authors: Hoffbrand A. Victor , Taher Ali , Cappellini Maria Domenica
Published: August 2012

Patients with β-thalassemia major (TM) and other refractory anemias requiring regular blood transfusions accumulate iron that damages the liver, endocrine system, and most importantly the heart. The prognosis in TM has improved remarkably over the past 10 years. This improvement has resulted from the development of magnetic resonance imaging (MRI) techniques, especially T2*, to accurately measure cardiac and liver iron, and from the availability of 3 iron-chelating drugs. In this article we describe the use of MRI to determine which adult and pediatric patients need to begin iron chelation therapy and to monitor their progress. We summarize the properties of each of the 3 drugs, deferoxamine (DFO), deferiprone (DFP), and deferasirox (DFX), including their efficacy, patient acceptability, and side effects. We describe when to initiate or intensify therapy, switch to another drug, or use combined therapy. We also discuss the management of refractory anemias other than TM that may require multiple blood transfusions, including sickle cell anemia and myelodysplasia. The development of a potential fourth chelator FBS 0701 and the combined use of oral chelators may further improve the quality of life and survival in patients with TM and other transfusion-dependent patients.
Sampling issues in quantitative analysis of dendritic spines morphology
Authors: Ruszczycki Błażej , Szepesi Zsuzsanna , Wilczynski Grzegorz M , Bijata Monika , Kalita Katarzyna , Kaczmarek Leszek , Wlodarczyk Jakub
Published: August 2012

Background

Quantitative analysis of changes in dendritic spine morphology has become an interesting issue in contemporary neuroscience. However, the diversity in dendritic spine population might seriously influence the result of measurements in which their morphology is studied. The detection of differences in spine morphology between control and test group is often compromised by the number of dendritic spines taken for analysis. In order to estimate the impact of dendritic spine diversity we performed Monte Carlo simulations examining various experimental setups and statistical approaches. The confocal images of dendritic spines from hippocampal dissociated cultures have been used to create a set of variables exploited as the simulation resources.

Results

The tabulated results of simulations given in this article, provide the number of dendritic spines required for the detection of hidden morphological differences between control and test groups in terms of spine head-width, length and area. It turns out that this is the head-width among these three variables, where the changes are most easily detected. Simulation of changes occurring in a subpopulation of spines reveal the strong dependence of detectability on the statistical approach applied. The analysis based on comparison of percentage of spines in subclasses is less sensitive than the direct comparison of relevant variables describing spines morphology.

Conclusions

We evaluated the sampling aspect and effect of systematic morphological variation on detecting the differences in spine morphology. The results provided here may serve as a guideline in selecting the number of samples to be studied in a planned experiment. Our simulations might be a step towards the development of a standardized method of quantitative comparison of dendritic spines morphology, in which different sources of errors are considered.
Yellow lupin (Lupinus luteus L.) transcriptome sequencing: molecular marker development and comparative studies
Authors: Parra-González Lorena B , Aravena-Abarzúa Gabriela A , Navarro-Navarro Cristell S , Udall Joshua , Maughan Jeff , Peterson Louis M , Salvo-Garrido Haroldo E , Maureira-Butler Iván J
Published: August 2012

Background

Yellow lupin (Lupinus luteusL.) is a minor legume crop characterized by its high seed protein content. Although grown in several temperate countries, its orphan condition has limited the generation of genomic tools to aid breeding efforts to improve yield and nutritional quality. In this study, we report the construction of 454-expresed sequence tag (EST) libraries, carried out comparative studies betweenL. luteusand model legume species, developed a comprehensive set of EST-simple sequence repeat (SSR) markers, and validated their utility on diversity studies and transferability to related species.

Results

Two runs of 454 pyrosequencing yielded 205 Mb and 530 Mb of sequence data for L1 (young leaves, buds and flowers) and L2 (immature seeds) EST- libraries. A combined assembly (L1L2) yielded 71,655 contigs with an average contig length of 632 nucleotides. L1L2 contigs were clustered into 55,309 isotigs. 38,200 isotigs translated into proteins and 8,741 of them were full length. Around 57% ofL. luteussequences had significant similarity with at least one sequence ofMedicago,Lotus,Arabidopsis, orGlycine, and 40.17% showed positive matches with all of these species.L. luteusisotigs were also screened for the presence of SSR sequences. A total of 2,572 isotigs contained at least one EST-SSR, with a frequency of one SSR per 17.75 kbp. Empirical evaluation of the EST-SSR candidate markers resulted in 222 polymorphic EST-SSRs. Two hundred and fifty four (65.7%) and 113 (30%) SSR primer pairs were able to amplify fragments fromL. hispanicusandL. mutabilisDNA, respectively. Fifty polymorphic EST-SSRs were used to genotype a sample of 64 L. luteusaccessions. Neighbor-joining distance analysis detected the existence of several clusters amongL. luteusaccessions, strongly suggesting the existence of population subdivisions. However, no clear clustering patterns followed the accession’s origin.

Conclusion

L. luteusdeep transcriptome sequencing will facilitate the further development of genomic tools and lupin germplasm. Massive sequencing of cDNA libraries will continue to produce raw materials for gene discovery, identification of polymorphisms (SNPs, EST-SSRs, INDELs, etc.) for marker development, anchoring sequences for genome comparisons and putative gene candidates for QTL detection.
Chagasic patients are able to respond against a viral antigen from influenza virus
Authors: Lasso Paola , Mesa Diana , Bolaños Natalia , Cuéllar Adriana , Guzmán Fanny , Cucunuba Zulma , Rosas Fernando , Velasco Víctor , Thomas Maria C , López Manuel Carlos , González John Mario , Puerta Concepción Judith
Published: August 2012

Background

Trypanosoma cruzi,the etiological agent of Chagas’ disease,is an obligate intracellular parasite which induces a CD8+T cell immune response with secretion of cytokines and release of cytotoxic granules. Although an immune-suppressive effect ofT. cruzion the acute phase of the disease has been described, little is known about the capacity of CD8+T cell from chronic chagasic patients to respond to a non-T. cruzimicrobial antigen.

Methods

In the present paper, the frequency, phenotype and the functional activity of the CD8+T cells specific from Flu-MP*, an influenza virus epitope, were determined in 13 chagasic patients and 5 healthy donors.

Results

The results show that Flu-MP* peptide specific CD8+T cells were found with similar frequencies in both groups. In addition, Flu-MP* specific CD8+T cells were distributed in the early or intermediate/late differentiation stages without showing enrichment of a specific sub-population. The mentioned Flu-MP* specific CD8+T cells from chagasic patients were predominately TEM(CCR7- CD62L-), producing IL-2, IFNγ, CD107a/b and perforin, and did not present significant differences when compared with those from healthy donors.

Conclusions

Our results support the hypothesis that there is no CD8+T cell nonspecific immune-suppression during chronic Chagas disease infection. Nonetheless, other viral antigens must be studied in order to confirm our findings.
Stromal proteome expression profile and muscle-invasive bladder cancer research
Authors: Niu Haitao , Jiang Haiping , Cheng Bo , Li Xinhui , Dong Qian , Shao Leping , Liu Shiguo , Wang Xinsheng
Published: August 2012

Background

To globally characterize the cancer stroma expression profile of muscle-invasive transitional cell carcinoma and to discuss the cancer biology as well as biomarker discovery from stroma. Laser capture micro dissection was used to harvest purified muscle-invasive bladder cancer stromal cells and normal urothelial stromal cells from 4 paired samples. Two-dimensional liquid chromatography tandem mass spectrometry was used to identify the proteome expression profile. The differential proteins were further analyzed using bioinformatics tools and compared with the published literature.

Results

We identified 868/872 commonly expressed proteins and 978 differential proteins from 4 paired cancer and normal stromal samples using laser capture micro dissection coupled with two-dimensional liquid chromatography tandem mass spectrometry. 487/491 proteins uniquely expressed in cancer/normal stroma. Differential proteins were compared with the entire list of the international protein index (IPI), and there were 42/42 gene ontology (GO) terms exhibited as enriched and 8/5 exhibited as depleted in cellular Component, respectively. Significantly altered pathways between cancer/normal stroma mainly include metabolic pathways, ribosome, focal adhesion, etc. Finally, descriptive statistics show that the stromal proteins with extremes of PI and MW have the same probability to be a biomarker.

Conclusions

Based on our results, stromal cells are essential component of the cancer, biomarker discovery and network based multi target therapy should consider neoplastic cells itself and corresponding stroma as whole one.
Dichotomy effects of Akt signaling in breast cancer
Authors: Peng Zhengang , Weber Jennifer Chao , Han Zhaosheng , Shen Rulong , Zhou Wenchao , Scott James R , Chan Michael WY , Lin Huey-Jen L
Published: August 2012

Background

The oncogenic roles contributed by the Akt/PKB kinase family remain controversial and presumably depend on cell context, but are perceived to be modulated by an interplay and net balance between various isoforms. This study is intended to decipher whether distinct Akt kinase isoforms exert either redundant or unique functions in regulating neoplastic features of breast cancer cells, including epithelial-mesenchymal transition (EMT), cell motility, and stem/progenitor cell expansion.

Results

We demonstrate that overactivation of Akt signaling in nonmalignant MCF10A cells and in primary cultures of normal human mammary epithelial tissue results in previously unreported inhibitory effects on EMT, cell motility and stem/progenitor cell expansion. Importantly, this effect is largely redundant and independent of Akt isoform types. However, using a series of isogenic cell lines derived from MCF-10A cells but exhibiting varying stages of progressive tumorigenesis, we observe that this inhibition of neoplastic behavior can be reversed in epithelial cells that have advanced to a highly malignant state. In contrast to the tumor suppressive properties of Akt, activated Akt signaling in MCF10A cells can rescue cell viability upon treatment with cytotoxic agents. This feature is regarded as tumor-promoting.

Conclusion

We demonstrate that Akt signaling conveys novel dichotomy effects in which its oncogenic properties contributes mainly to sustaining cell viability, as opposed to the its tumor suppressing effects, which are mediated by repressing EMT, cell motility, and stem/progenitor cell expansion. While the former exerts a tumor-enhancing effect, the latter merely acts as a safeguard by restraining epithelial cells at the primary sites until metastatic spread can be moved forward, a process that is presumably dictated by the permissive tumor microenvironment or additional oncogenic insults.
An explicit construction of fast cocyclic jacket transform on the finite field with any size
Authors: Guo Ying , Lee Moon Ho , Kim Kyeong Jin
Published: August 2012

An orthogonal cocyclic framework of the block-wise inverse Jacket transform (BIJT) is proposed over the finite field. Instead of the conventional block-wise inverse Jacket matrix (BIJM), we investigate the cocyclic block-wise inverse Jacket matrix (CBIJM), where the high-order CBIJM can be factorized into the low-order sparse CBIJMs with a successive block architecture. It has a recursive fashion that leads to a fast algorithm concerned for reducing computational load. The fast transforms are also developed for the two-dimensional cocyclic block-wise inverse Jacket transform (CBIJT). The present CBIJM may be used for many matrix-based applications, such as the DFT signal processing, combinatorics, and the Reed-Muller code design.
Exosomal cell-to-cell transmission of alpha synuclein oligomers
Authors: Danzer Karin M , Kranich Lisa R , Ruf Wolfgang P , Cagsal-Getkin Ozge , Winslow Ashley R , Zhu Liya , Vanderburg Charles R , McLean Pamela J
Published: August 2012

Background

Aggregation of alpha-synuclein (αsyn) and resulting cytotoxicity is a hallmark of sporadic and familial Parkinson’s disease (PD) as well as dementia with Lewy bodies, with recent evidence implicating oligomeric and pre-fibrillar forms of αsyn as the pathogenic species. Recentin vitrostudies support the idea of transcellular spread of extracellular, secreted αsyn across membranes. The aim of this study is to characterize the transcellular spread of αsyn oligomers and determine their extracellular location.

Results

Using a novel protein fragment complementation assay where αsyn is fused to non-bioluminescent amino-or carboxy-terminus fragments of humanized Gaussia Luciferase we demonstrate here that αsyn oligomers can be found in at least two extracellular fractions: either associated with exosomes or free. Exosome-associated αsyn oligomers are more likely to be taken up by recipient cells and can induce more toxicity compared tofreeαsyn oligomers. Specifically, we determine that αsyn oligomers are present on both the outside as well as inside of exosomes. Notably, the pathway of secretion of αsyn oligomers is strongly influenced by autophagic activity.

Conclusions

Our data suggest that αsyn may be secreted via different secretory pathways. We hypothesize that exosome-mediated release of αsyn oligomers is a mechanism whereby cells clear toxic αsyn oligomers when autophagic mechanisms fail to be sufficient. Preventing the early events in αsyn exosomal release and uptake by inducing autophagy may be a novel approach to halt disease spreading in PD and other synucleinopathies.
Potentially preventable incidence of diabetes due to risk factor modification
Authors: Motamedi Seyed Mohammad Kalantar , Majdzadeh Reza , Larijani Fatemeh Ardeshir , Raheem Fakher , Koleini Zahra , Larijani Bagher
Published: August 2012

Background

Increasing diabetes incidence demands investigation of risk factors, prioritization and designing modification interventions. We calculated the potential modifiable incidence of diabetes due to reduction in risk factors.

Methods

We used counterfactual analysis model to estimate avoidable burden of incident diabetes related to each risk factor. The potential impact fraction (PIF) index calculated utilizing the data of current prevalence, magnitude of impact and counterfactual status of risk factors. We considered the levels of evidence while giving higher priority to domestic data.

Results

The estimated PIF regarding minimum feasible risk for the impaired fasting glucose (IFG), impaired glucose tolerance (IGT), combined IFG/IGT, low HDL, high triglyceride, high total cholesterol, hypertension, general obesity, central obesity and physical inactivity were 0.13, 0.10, 0.18, 0.01, 0.12, 0.03, 0.13, 0.03, 0.02 and 0.10, respectively.

Conclusion

While the combined risk factors of IFG and IGT should be noticed as the most important potential factor in prevention of diabetes and reducing its incidence burden, among the other risk factors, modification of hypertension, high triglyceride, and physical inactivity could have more impact.
Platelets: key players in vascular inflammation
Authors: Projahn Delia , Koenen Rory R
Published: August 2012

Review on platelet function in inflammation and atherosclerosis.

Platelets play a crucial role in the physiology of the primary hemostasis and in the pathophysiological activity of arterial thrombosis, provide rapid protection against bleeding, and catalyze the formation of stable blood clots via the coagulation cascade. Over the past years, it has become clear that platelets are important, not only in hemostasis and thrombosis but also in inflammation and in distinct aspects of atherosclerosis. Nowadays, platelets are known to have a large variety of functions. Platelets are able to interact with a large variety of cell types, such as leukocytes, endothelial cells, and SMCs, and these interactions have been implicated in the pathophysiology of vascular inflammation. In addition, platelets carry a highly inflammatory payload and are able to transport, synthesize, and deposit cytokines, chemokines, and lipid mediators, thereby initiating and propagating atherosclerotic disease. In this review, the current state of the art of the proinflammatory functions in the context of atherosclerotic cardiovascular disease will be outlined.
Tomography of diffraction-based focusing operators
Authors: Santos Luiz Alberto , Mansur Webe Joao , McMechan George A.
Published: August 2012

Diffractions carry the same kinematic information provided by common focus point operators (CFPOs). Thus CFPO and diffraction time trajectories may be used separately, or combined into a single unified tomography for velocity analysis. Velocity estimation by tomography of CFPOs reduces the depth-velocity ambiguity compared to two-way time tomography. CFPO estimation is complicated where there are event discontinuities and diffractions. This problem is overcome by using the kinematic information in diffractions in near-offset common-offset gathers. The procedure is illustrated using synthetic data, and a single-channel field seismic profile from the Blake Ridge (off the east coast of the United States). The results show the effectiveness of the proposed method for estimation of velocity from single channel seismic data, and for refinement of the velocity field from multichannel data. Both applications are cost-competitive.
Homozygous and heterozygous GH transgenesis alters fatty acid composition and content in the liver of Amago salmon (Oncorhynchus masou ishikawae)
Authors: Sugiyama Manabu , Takenaga Fumio , Kitani Yoichiro , Yamamoto Goshi , Okamoto Hiroyuki , Masaoka Tetsuji , Araki Kazuo , Nagoya Hiroyuki , Mori Tsukasa
Published: August 2012

Growth hormone (GH) transgenic Amago (Oncorhynchus masou ishikawae), containing the sockeye GH1 gene fused with metallothionein-B promoter from the same species, were generated and the physiological condition through lipid metabolism compared among homozygous (Tg/Tg) and heterozygous GH transgenic (Tg/+) Amago and the wild type control (+/+). Previously, we have reported that the adipose tissue was generally smaller in GH transgenic fish compared to the control, and that the Δ-6 fatty acyl desaturase gene was down-regulated in the Tg/+ fish. However, fatty acid (FA) compositions have not been measured previously in these fish. In this study we compared the FAs composition and content in the liver using gas chromatography. Eleven kinds of FA were detected. The composition of saturated and monounsaturated fatty acids (SFA and MUFA) such as myristic acid (14:0), palmitoleic acid (16:1n-7), and cis-vaccenic acid (cis-18:1n-7) was significantly (P<0.05) decreased in GH transgenic Amago. On the other hand, the composition of polyunsaturated fatty acids (PUFAs) such as linoleic acid (18:2n-6), arachidonic acid (20:4n-6), and docosapentaenoic acid (22:5n-3) was significantly (P<0.05) increased. Levels of serum glucose and triacylglycerol were significantly (P<0.05) decreased in the GH transgenics compared with +/+ fish. Furthermore, 3′-tag digital gene expression profiling was performed using liver tissues from Tg/Tg and +/+ fish, and showed that Mid1 interacting protein 1 (Mid1ip1), which is an important factor to activate Acetyl-CoA carboxylase (ACC), was down-regulated in Tg/Tg fish, while genes involved in FA catabolism were up-regulated, including long-chain-fatty-acid–CoA ligase 1 (ACSL1) and acyl-coenzyme A oxidase 3 (ACOX3). These data suggest that liver tissue from GH transgenic Amago showed starvation by alteration in glucose and lipid metabolism due to GH overexpression. The decrease of serum glucose suppressed Mid1ip1, and caused a decrease of de novo FA synthesis, resulting in a decrease of SFA and MUFA. This induced expression of ACSL1 and ACOX3 to produce energy through β-oxidation in the GH transgenic Amago.
vasa is expressed in somatic cells of the embryonic gonad in a sex-specific manner in Drosophila melanogaster
Authors: Renault Andrew D.
Published: August 2012

Vasa is a DEAD box helicase expressed in the Drosophila germline at all stages of development. vasa homologs are found widely in animals and vasa has become the gene of choice in identifying germ cells. I now show that Drosophila vasa expression is not restricted to the germline but is also expressed in a somatic lineage, the embryonic somatic gonadal precursor cells. This expression is sexually dimorphic, being maintained specifically in males, and is regulated post-transcriptionally. Although somatic Vasa expression is not required for gonad coalescence, these data support the notion that Vasa is not solely a germline factor.
Acute hemodynamic effects of erythropoietin do not mediate its cardioprotective properties
Authors: Ahmet Ismayil , Lakatta Edward G. , Talan Mark I.
Published: August 2012

Activation of nitric oxide (NO) signaling is considered, at list partially, a mechanistic basis for EPO-induced cardioprotection. Surprisingly, hemodynamic response subsequent to NO activation after EPO administration has never been reported. The objectives of this study were to evaluate the acute hemodynamic and cardiovascular responses to EPO administration, to confirm their NO genesis, and to test the hypothesis that EPO-induced cardioprotection is mediated through cardiovascular changes related to NO activation. In Experiment 1, after 3000 U/kg of rhEPO was administered intravenously to Wistar rats, arterial blood pressure, monitored via indwelling catheter, progressively declined almost immediately until it leveled off 90 minutes after injection at 20% below control level. In Experiment 2 the 25% reduction of mean blood pressure, compared to control group, was observed 2 hours after intravenous injection of either 3000 or 150 U/kg of rhEPO. Detailed pressure–volume loop analyses of cardiac performance (Experiment 3) 2 hours after intravenous injection of human or rat recombinant EPO (3000 U/kg) revealed a significant reduction of systolic function (PRSW was 33% less than control). Reduction of arterial blood pressure and systolic cardiac function in response to rhEPO were blocked in rats pretreated with a non-selective inhibitor of nitric oxide synthase (L-NAME). In Experiment 4, 24 hours after a permanent ligation of a coronary artery, myocardial infarction (MI) measured 26±3.5% of left ventricle in untreated rats. MI in rats treated with 3000 U/kg of rhEPO immediately after coronary ligation was 56% smaller. Pretreatment with L-NAME did not attenuate the beneficial effect of rhEPO on MI size, while MI size in rats treated with L-NAME alone did not differ from control. Therefore, a single injection of rhEPO resulted in a significant, NO-mediated reduction of systemic blood pressure and corresponding reduction of cardiac systolic function. However, EPO-induced protection of myocardium from ischemic damage is not associated with NO activation or NO-mediated hemodynamic responses.
A cell-based fascin bioassay identifies compounds with potential anti-metastasis or cognition-enhancing functions
Authors: Kraft Robert , Kahn Allon , Medina-Franco José L. , Orlowski Mikayla L. , Baynes Cayla , López-Vallejo Fabian , Barnard Kobus , Maggiora Gerald M. , Restifo Linda L.
Published: August 2012

The actin-bundling protein fascin is a key mediator of tumor invasion and metastasis whose activity drives filopodia formation, cell-shape changes, and cell migration. Small-molecule inhibitors of fascin block tumor metastasis in animal models. Conversely, fascin deficiency may underlie the pathogenesis of some developmental brain disorders. To identify fascin-pathway modulators we devised a cell-based assay for fascin function and used it in a bi-directional drug screen. The screen utilized cultured fascin-deficient mutant Drosophila neurons, whose neurite arbors manifest the "filagree" phenotype. Taking a repurposing approach, we screened a library of 1,040 known compounds, many of them FDA-approved drugs, for filagree modifiers. Based on scaffold distribution, molecular-fingerprint similarities, and chemical-space distribution, this library has high structural diversity, supporting its utility as a screening tool. We identified 34 fascin-pathway blockers (with potential anti-metastasis activity) and 48 fascin-pathway enhancers (with potential cognitive-enhancer activity). The structural diversity of the active compounds suggests multiple molecular targets. Comparisons of active and inactive compounds provided preliminary structure-activity relationship information. The screen also revealed diverse neurotoxic effects of other drugs, notably "Beads-on-a-String" induced solely by statins. Statin-induced neurotoxicity is enhanced by fascin deficiency. In summary, we provide evidence that primary neuron culture using a genetic model organism can be valuable for early-stage drug discovery and developmental neurotoxicity testing. Furthermore, we propose that, given an appropriate assay for target-pathway function, bi-directional screening for brain-development disorders and invasive cancers represents an efficient, multipurpose drug-discovery strategy.
The Preparation of Nanostructured ZrO2 Microspheres
Authors: Chang Ying , Dong Shijie , Wang Huihu , Du Kuanhe
Published: August 2012

Spherical reunion powders composed of tetragonal and cubic phase ZrO2 have been prepared for the first time via a coupling route of w/o (water in oil) emulsion with dimethyl oxalate homogenous precipitation. The as-prepared ZrO2 microspheres and the precursor powders were analyzed and characterized by TG-DTA, XRD, and SEM. The formation mechanism of these powders is discussed in detail. Experimental results indicate that the coupling route may accomplish the one-step synthesis of ZrO2 microspheres possessing well-rounded spherical shape and narrow size distribution, which consists of closely attached nanoparticles, the microspheres are approximately 5–10 µm in size.
One-path and Selective Conversion of Ethanol to Propene on Scandium-modified Indium Oxide Catalysts
Authors: Mizuno Shouta , Kurosawa Mika , Tanaka Masashi , Iwamoto Masakazu
Published: August 2012

The direct and stable conversion of ethanol to propene with yields up to 60 mol % was achieved on scandium-modified indium oxide catalysts at 823 K in the presence of water and hydrogen. The reaction pathways are also suggested, ethanol → acetaldehyde → acetone → propene, which is quite different from those on zeolites and on nickel ion-loaded silica catalysts.
Synthesis of Novel pH-Responsive Magnetic Nanocomposites as Highly Efficient Heterogeneous Fenton Catalysts
Authors: Wang Wei , Wang Yuan , Liu Ying , Li Tielong
Published: August 2012

Intelligent polymer was extendedly applied to fabricate a novel environmentally responsive Fenton catalyst in this study. The obtained magnetite/sodium carboxymethyl cellulose-graft-poly(acrylic acid) (Fe3O4/CMC-g-PAA) nanocomposites showed perfect superparamagnetism, pH response, and superior catalytic activity. In a wide range of pH (3–9), the highly swollen polymer coating not only favored the dispersion of Fe3O4 nanoparticles and protected them from leaching but also promoted interface mass transfer with large amounts of hydrophilic ingredients.
Electrophilic Aromatic Substitution of Arenes with CO2 Mediated by R3SiB(C6F5)4
Authors: Konno Megumi , Chiba Masafumi , Nemoto Koji , Hattori Tetsutaro
Published: August 2012

The Friedel–Crafts-type carboxylation of arenes has been achieved by activating CO2 with silylium borates. The reaction exhibits broader substrate applicability than does our previously reported AlX3/R3SiX-mediated carboxylation.
Paying the price for an incentive: An exploratory study of smokers’ reasons for failing to complete an incentive based smoking cessation scheme
Authors: Allan Caroline , Radley Andrew , Williams Brian
Published: August 2012

Objectives:

In 2009, one Scottish region launched a smoking cessation programme offering a weekly financial incentive of £12.50 over a 12-week period. However, a significant proportion of registered participants dropped out of the programme, some even failing to collect the financial reward they were owed. We explore reasons for disengagement and failure to re-engage within this group.

Method:

Individuals (n =14) were interviewed in depth. Transcripts from recorded interviews formed the dataset and were analysed using the “Framework” method.

Results:

Incentives appeared to introduce a potential change/reversal in the felt contractual relationship between service provider and client: the client was now the provider and being paid to quit. This led to an increased sense of obligation towards the service, and enhanced feelings of failure, guilt and shame post-relapse, and reluctance to continue engagement or re-engagement. Other service factors promoting disengagement included issues of practical delivery through location, timing, administrative burden and incentive preference.

Conclusion:

The future design of incentive-based schemes should be cognisant of the potential impact on the client-professional relationship. Increasing the value of the incentive may overcome clients’ antipathy towards bureaucracy and monitoring, but may simultaneously exacerbate the sense of failure and resultant stigma associated with relapse. It may be more cost-effective to reduce barriers/costs such as inconvenience, lack of privacy, timing and embarrassment of association of attendance at the pharmacy with methadone use. Alternatively, risks may be managed by reframing weekly rewards as three separate month-long stages, increasing a sense of achievement that a particular stage has been achieved before any relapse.
The fetal origins of adult disease: a narrative review of the epidemiological literature
Authors: Skogen Jens Christoffer , Øverland Simon
Published: August 2012

The fetal origins of adult disease (FOAD) hypothesis suggests that risk factors from intrauterine environmental exposures affect the fetus’ development during sensitive periods, and increases the risk of specific diseases in adult life. This link was initially observed between prenatal exposures and adult coronary heart disease, but corresponding observations have later been published for a range of chronic conditions. Although the hypothesis has been praised as an essential shift in our understanding of determinants for health, the hypothesis has also been criticized on a number of accounts, both methodologically and theoretically. The aim of this paper is to critically discuss the FOAD-hypothesis, in relation to the epidemiological evidence. We conclude that much of the research literature on the FOAD-hypothesis finds support for the hypothesis. Despite this, it is still unclear if the effects are independent and what the public health relevance is. Notwithstanding the heart of the hypothesis - that environmental influences during gestation have an effect on later development - should be considered a major insight and constitutes a complement to a focus on genetic and more proximal factors (such as adult lifestyle) as causes of adult disease. As the search for determinants for disease and health continues, the FOAD-hypothesis is likely to remain an important perspective. It may however be better positioned as part of a broader life course perspective, rather than as an independent hypothesis.
Air proteins control differential TRAMP substrate specificity for nuclear RNA surveillance
Authors: Schmidt Karyn , Xu Zhenjiang , Mathews David H. , Butler J. Scott
Published: August 2012

RNA surveillance systems function at critical steps during the formation and function of RNA molecules in all organisms. The RNA exosome plays a central role in RNA surveillance by processing and degrading RNA molecules in the nucleus and cytoplasm of eukaryotic cells. The exosome functions as a complex of proteins composed of a nine-member core and two ribonucleases. The identity of the molecular determinants of exosome RNA substrate specificity remains an important unsolved aspect of RNA surveillance. In the nucleus of Saccharomyces cerevisiae, TRAMP complexes recognize and polyadenylate RNAs, which enhances RNA degradation by the exosome and may contribute to its specificity. TRAMPs contain either of two putative RNA-binding factors called Air proteins. Previous studies suggested that these proteins function interchangeably in targeting the poly(A)-polymerase activity of TRAMPs to RNAs. Experiments reported here show that the Air proteins govern separable functions. Phenotypic analysis and RNA deep-sequencing results from air mutants reveal specific requirements for each Air protein in the regulation of the levels of noncoding and coding RNAs. Loss of these regulatory functions results in specific metabolic and plasmid inheritance defects. These findings reveal differential functions for Air proteins in RNA metabolism and indicate that they control the substrate specificity of the RNA exosome.
HP Enterprise Services Uses Optimization for Resource Planning
Authors: Santos Cipriano , Gonzalez Tere , Li Haitao , Chen Kay-Yut , Beyer Dirk , Biligi Sundaresh , Feng Qi , Kumar Ravindra , Jain Shelen , Ramanujam Ranga , Zhang Alex
Published: August 2012

The main responsibility of resource and delivery managers at Hewlett-Packard (HP) Enterprise Services (HPES) involves matching resources (skilled professionals) with jobs that project opportunities require. The previous Solution Opportunity Approval and Review (SOAR) process at HPES addressed uncertainty by producing decentralized project staffing decisions. This often led to many last-minute subjective, sometimes costly, resource allocation decisions. Based on our research, we developed a decision support tool for resource planning (RP) to enhance the SOAR process. It optimizes matching professionals who have diverse delivery roles and skills to jobs and projects across geographical locations while explicitly accounting for both demand and supply uncertainties. It also embeds capabilities for managers to incorporate tacit human knowledge and judgment information into the decision-making process. With its 2009 deployment in Best Shore, Bangalore operations of HPES, the RP tool’s significant benefits include reduced service delivery costs, increased workforce utilization, and profitability.
Digital Divide Initiative Success in Developing Countries: A Longitudinal Field Study in a Village in India
Authors: Venkatesh Viswanath , Sykes Tracy Ann
Published: August 2012

Digital divide initiatives in developing countries are an important avenue for the socioeconomic advancement of those countries. Yet little research has focused on understanding the success of such initiatives. We develop a model of technology use and economic outcomes of digital divide initiatives in developing countries. We use social networks as the guiding theoretical lens because it is well suited to this context, given the low literacy, high poverty, high collectivism, and an oral tradition of information dissemination in developing countries. We test our model with longitudinal data gathered from 210 families in a rural village in India in the context of a digital divide initiative. As theorized, we found that the social network constructs contributed significantly to the explanation of technology use (R2= 0.39). Also as we predicted, technology use partially mediated the effect of social network constructs on economic outcomes (R2= 0.47). We discuss implications for theory and practice.
Effects of the Presence of Organic Listing in Search Advertising
Authors: Xu Lizhen , Chen Jianqing , Whinston Andrew
Published: August 2012

This paper analyzes how the presence of organic listing as a competing information source affects advertisers' sponsored bidding and the equilibrium outcomes in search advertising. We consider a game-theoretic model in which two firms bid for sponsored advertising slots provided by a monopolistic search engine and then compete for consumers in price in the product market. Firms are asymmetrically differentiated in market preference and are given different exposure in organic listing aligned with their market appeal. We identify two aspects of a firm's sponsored bidding incentive, namely, the promotive and the preventive incentives. The presence of organic listing alters firms' sponsored bidding incentives such that the stronger firm has primarily preventive incentive, whereas the weaker has mainly promotive incentive. We show that the preventive incentive decreases and the promotive incentive increases as the difference in firms' market appeal decreases, and as a result, even the weaker firm may outbid the stronger competitor under such a co-listing setting. We further examine how the presence of organic listing affects the equilibrium outcomes by comparing it with a benchmark case in which there is only a sponsored list. We show that the differentiated exposure in the organic list gives the weaker advertiser chances to win a better sponsored position, which improves the overall information structure the search engine provides. As a result, the equilibrium social welfare, sales diversity, and consumer surplus increase. Although the presence of the free exposure from the organic list may reduce advertisers' sponsored bidding incentive per se, the overall effect benefits the search engine's growth in the long run.
Governance of Interorganizational Information Systems: A Resource Dependence Perspective
Authors: Chatterjee Dipanjan , Ravichandran T.
Published: August 2012

In this paper we examine why firms seek to control and own interorganizational information systems, or IOS. Practitioners have largely cited the issues related to control and ownership of IOS, referred to as IOS governance in this paper, as the key reason behind the failure of many IOS initiatives. We distinguish between two IOS governance modes, transactional and financial, and develop a mediated-moderation model to explain the factors influencing the governance choices. In our model, the key motivators of IOS governance are the criticality and the replaceability of the resources that firms procure, which affect IOS governance through their influence on the degree of operational integration existing between partners. We hypothesize that while resource criticality will increase the needs for financial and transactional governance because of its positive impact on operational integration, resource replaceability will negatively influence governance needs because of its negative impact on operational integration. Furthermore, technological uncertainty associated with the resources is argued to negatively impact the extent of IOS governance exercised by firms by weakening the positive impact of resource criticality and strengthening the negative impact of resource replaceability on operational integration respectively. We empirically test our model using data gathered from a survey of 159 United States manufacturing firms. Results show that resource criticality positively affects the extent of financial and transactional IOS governance by increasing the need for operational integration, whereas resource replaceability negatively affects them by reducing the need for operational integration. Furthermore, technological uncertainty creates disincentives for IOS governance primarily by weakening the positive influence of resource criticality on operational integration, while no statistically significant effect of technological uncertainty on the relationship between resource replaceability and operational integration was discerned.
Research Note—An Investigation of the Appropriation of Technology-Mediated Training Methods Incorporating Enactive and Collaborative Learning
Authors: Gupta Saurabh , Bostrom Robert
Published: August 2012

The growth in the application of information technology to student and employee learning underscores the need to understand the impact of technology-mediated learning (TML) methods. Using previous developed TML models, based on social cognitive theory and adaptive structuration meta-theory, the effectiveness of three training methods were examined in this study: technology mediated (using both vicarious and enactive learning), and collaborative and combined (collaborative plus technology mediated). The study also focused on the learning process. The experimental study results showed a significant positive influence of enactive learning enabled TML and collaborative training on specific training outcomes, and the combined training method shows positive results on all training outcomes. The study results also showed that faithful appropriation of the training methods during the learning process has a moderator effect on training outcomes. The study provides important research implications for theory and practice.
The Effects of Diversity in Global, Distributed Collectives: A Study of Open Source Project Success
Authors: Daniel Sherae , Agarwal Ritu , Stewart Katherine J.
Published: August 2012

Diversity is a defining characteristic of global collectives facilitated by the Internet. Though substantial evidence suggests that diversity has profound implications for a variety of outcomes including performance, member engagement, and withdrawal behavior, the effects of diversity have been predominantly investigated in the context of organizational workgroups or virtual teams. We use a diversity lens to study the success of nontraditional virtual work groups exemplified by open source software (OSS) projects. Building on the diversity literature, we propose that three types of diversity (separation, variety, and disparity) influence two critical outcomes for OSS projects: community engagement and market success. We draw on the OSS literature to further suggest that the effects of diversity on market success are moderated by the application development stage. We instantiate the operational definitions of three forms of diversity to the unique context of open source projects. Using archival data from 357 projects hosted on SourceForge, we find that disparity diversity, reflecting variation in participants' contribution-based reputation, is positively associated with success. The impact of separation diversity, conceptualized as culture and measured as diversity in the spoken language and country of participants, has a negative impact on community engagement but an unexpected positive effect on market success. Variety diversity, reflected in dispersion in project participant roles, positively influences community engagement and market success. The impact of diversity on market success is conditional on the development stage of the project. We discuss how the study's findings advance the literature on antecedents of OSS success, expand our theoretical understanding of diversity, and present the practical implications of the results for managers of distributed collectives.