bluuebunny/crossref_metadata_2025 huggingface dataset:
Mobile communication and social capital: an analysis of geographically differentiated usage patterns
Authors: Campbell Scott W. , Kwak Nojin
Published: February 2010

Drawing from a representative sample of adults in the USA, this study explored the links between mobile communication and select indicators of social capital, while also accounting for usage patterns regarding the proximity of mobile contact. Overall, the findings show that mobile phone use intersects with proximity in distinctive ways that are related to spending leisure time with others in a face-to-face context and being active in organized groups and clubs. For individuals with primarily local usage patterns, both voice calling and text messaging were positively associated with social leisure activity. For those who primarily used the mobile phone to contact others from a distance, text messaging was positively related to social leisure activity, and for those whose mobile contacts were balanced between local and distant, voice calling was positively associated with active membership in organizations. Interpretation of these findings and directions for future research are offered in the discussion.
Hard news, soft news, ‘general’ news: The necessity and utility of an intermediate classification
Authors: Lehman-Wilzig Sam N. , Seletzky Michal
Published: February 2010

For at least the past three decades journalism scholars have focused on two types of news — soft and hard — without reassessing these categories or adding to them. The present article investigates whether such neglect is warranted, through a questionnaire and in-depth interviews with 32 journalists and editors from the three main Israeli dailies: Yediot Ahronot, Maariv and Haaretz. The findings argue strongly for a third, intermediate category of news — ‘general news’ — as well as for more rigorous and comprehensive definitions of ‘hard’ news and ‘soft’ news that are here supplied. These three news categories were then tested on 465 news items of the above dailies which led to the categorization of a new newspaper type, lying somewhere between the elite and populist press. Methodological and substantive ramifications of this addition are discussed.
High-dose cyclophosphamide as single-agent, short-course prophylaxis of graft-versus-host disease
Authors: Luznik Leo , Bolaños-Meade Javier , Zahurak Marianna , Chen Allen R. , Smith B. Douglas , Brodsky Robert , Huff Carol Ann , Borrello Ivan , Matsui William , Powell Jonathan D. , Kasamon Yvette , Goodman Steven N. , Hess Allan , Levitsky Hyam I. , Ambinder Richard F. , Jones Richard J. , Fuchs Ephraim J.
Published: February 2010

Because of its potent immunosuppressive yet stem cell–sparing activity, high-dose cyclophosphamide was tested as sole prophylaxis of graft-versus-host disease (GVHD) after myeloablative allogeneic bone marrow transplantation (alloBMT). We treated 117 patients (median age, 50 years; range, 21-66 years) with advanced hematologic malignancies; 78 had human leukocyte antigen (HLA)–matched related donors and 39 had HLA-matched unrelated donors. All patients received conventional myeloablation with busulfan/cyclophosphamide (BuCy) and T cell–replete bone marrow followed by 50 mg/kg/d of cyclophosphamide on days 3 and 4 after transplantation. The incidences of acute grades II through IV and grades III through IV GVHD for all patients were 43% and 10%, respectively. The nonrelapse mortality at day 100 and 2 years after transplantation were 9% and 17%, respectively. The actuarial overall survival and event-free survivals at 2 years after transplantation were 55% and 39%, respectively, for all patients and 63% and 54%, respectively, for patients who underwent transplantation while in remission. With a median follow-up of 26.3 months among surviving patients, the cumulative incidence of chronic GVHD is 10%. These results suggest that high-dose posttransplantation cyclophosphamide is an effective single-agent prophylaxis of acute and chronic GVHD after BuCy conditioning and HLA-matched BMT (clinicaltrials.gov no. NCT00134017).
FUNGIpath: a tool to assess fungal metabolic pathways predicted by orthology
Authors: Grossetête Sandrine , Labedan Bernard , Lespinet Olivier
Published: February 2010

Background

More and more completely sequenced fungal genomes are becoming available and many more sequencing projects are in progress. This deluge of data should improve our knowledge of the various primary and secondary metabolisms of Fungi, including their synthesis of useful compounds such as antibiotics or toxic molecules such as mycotoxins. Functional annotation of many fungal genomes is imperfect, especially of genes encoding enzymes, so we need dedicated tools to analyze their metabolic pathways in depth.

Description

FUNGIpath is a new tool built using a two-stage approach. Groups of orthologous proteins predicted using complementary methods of detection were collected in a relational database. Each group was further mapped on to steps in the metabolic pathways published in the public databases KEGG and MetaCyc. As a result, FUNGIpath allows the primary and secondary metabolisms of the different fungal species represented in the database to be compared easily, making it possible to assess the level of specificity of various pathways at different taxonomic distances. It is freely accessible at http://www.fungipath.u-psud.fr.

Conclusions

As more and more fungal genomes are expected to be sequenced during the coming years, FUNGIpath should help progressively to reconstruct the ancestral primary and secondary metabolisms of the main branches of the fungal tree of life and to elucidate the evolution of these ancestral fungal metabolisms to various specific derived metabolisms.
Gene prioritization in Type 2 Diabetes using domain interactions and network analysis
Authors: Sharma Amitabh , Chavali Sreenivas , Tabassum Rubina , Tandon Nikhil , Bharadwaj Dwaipayan
Published: February 2010

Background

Identification of disease genes for Type 2 Diabetes (T2D) by traditional methods has yielded limited success. Based on our previous observation that T2D may result from disturbed protein-protein interactions affected through disrupting modular domain interactions, here we have designed an approach to rank the candidates in the T2D linked genomic regions as plausible disease genes.

Results

Our approach integrates Weight value (Wv) method followed by prioritization using clustering coefficients derived from domain interaction network. Wv for each candidate is calculated based on the assumption that disease genes might be functionally related, mainly facilitated by interactions among domains of the interacting proteins. The benchmarking using a test dataset comprising of both known T2D genes and non-T2D genes revealed that Wv method had a sensitivity and specificity of 0.74 and 0.96 respectively with 9 fold enrichment. The candidate genes having a Wv > 0.5 were called High Weight Elements (HWEs). Further, we ranked HWEs by using the network property-the clustering coefficient (Ci). Each HWE with a Ci < 0.015 was prioritized as plausible disease candidates (HWEc) as previous studies indicate that disease genes tend to avoid dense clustering (with an average Ci of 0.015). This method further prioritized the identified disease genes with a sensitivity of 0.32 and a specificity of 0.98 and enriched the candidate list by 6.8 fold. Thus, from the dataset of 4052 positional candidates the method ranked 435 to be most likely disease candidates. The gene ontology sharing for the candidates showed higher representation of metabolic and signaling processes. The approach also captured genes with unknown functions which were characterized by network motif analysis.

Conclusions

Prioritization of positional candidates is essential for cost-effective and an expedited discovery of disease genes. Here, we demonstrate a novel approach for disease candidate prioritization from numerous loci linked to T2D.
Reduced blood brain barrier breakdown in P-selectin deficient mice following transient ischemic stroke: a future therapeutic target for treatment of stroke
Authors: Jin Albert Y , Tuor Ursula I , Rushforth David , Kaur Jaspreet , Muller Robert N , Petterson Jodie Lee , Boutry Sébastien , Barber Philip A
Published: February 2010

Background

The link between early blood- brain barrier (BBB) breakdown and endothelial cell activation in acute stroke remain poorly defined. We hypothesized that P-selectin, a mediator of the early phase of leukocyte recruitment in acute ischemia is also a major contributor to early BBB dysfunction following stroke. This was investigated by examining the relationship between BBB alterations following transient ischemic stroke and expression of cellular adhesion molecule P-selectin using a combination of magnetic resonance molecular imaging (MRMI), intravital microscopy and immunohistochemistry. MRMI was performed using the contrast, gadolinium diethylenetriaminepentaacetic acid (Gd-DTPA) conjugated to Sialyl Lewis X (Slex) where the latter is known to bind to activated endothelium via E- or P selectins. Middle cerebral artery occlusion was induced in male C57/BL 6 wild-type (WT) mice and P-selectin-knockout (KO) mice. At 24 hours following middle cerebral artery occlusion, T1 maps were acquired prior to and following contrast injection. In addition to measuring P- and E-selectin expression in brain homogenates, alterations in BBB function were determined immunohistochemically by assessing the extravasation of immunoglobulin G (IgG) or staining for polymorphonuclear (PMN) leukocytes. In vivo assessment of BBB dysfunction was also investigated optically using intravital microscopy of the pial circulation following the injection of Fluorescein Isothiocyanate (FITC)-dextran (MW 2000 kDa).

Results

MRI confirmed similar infarct sizes and T1 values at 24 hours following stroke for both WT and KO animals. However, the blood to brain transfer constant for Gd DTPA (Kgd) demonstrated greater tissue extravasation of Gd DTPA in WT animals than KO mice (P < 0.03). In the P selectin KO mice, Δ T1 stroke -Δ T1 contralateral control cortex, decreased significantly in the Gd-DTPA(sLeX) group compared to Gd-DTPA, indicative of sLeX mediated accumulation of the targeted contrast agent. Regarding BBB function, in the P-selectin KO mice compared to WT control mice, there was an attenuation in the extravasation of IgG (P < 0.001), a trend for decreased FITC extravasation and less infiltration of PMN leukocytes (P < 0.001) thereby supporting the observed increase in Kgd permeability in stroke brain of WT compared to KO mice.

Conclusion

P-selectin expression contributes to enhanced BBB dysfunction at 24 hours after transient focal cerebral ischemia.
A novel germline PALB2 deletion in Polish breast and ovarian cancer patients
Authors: Dansonka-Mieszkowska Agnieszka , Kluska Anna , Moes Joanna , Dabrowska Michalina , Nowakowska Dorota , Niwinska Anna , Derlatka Pawel , Cendrowski Krzysztof , Kupryjanczyk Jolanta
Published: February 2010

Background

PALB2 protein was recently identified as a partner of BRCA1 and BRCA2 which determines their proper function in DNA repair.

Methods

Initially, the entire coding sequence of the PALB2 gene with exon/intron boundaries was evaluated by the PCR-SSCP and direct sequencing methods on 70 ovarian carcinomas. Sequence variants of interest were further studied on enlarged groups of ovarian carcinomas (total 339 non-consecutive ovarian carcinomas), blood samples from 334 consecutive sporadic and 648 consecutive familial breast cancer patients, and 1310 healthy controls from central Poland.

Results

Ten types of sequence variants were detected, and among them four novel polymorphisms: c.2996+58T>C in intron 9; c.505C>A (p.L169I), c.618T>G (p.L206L), both in exon 4; and c.2135C>T (A712V) in exon 5 of the PALB2 gene. Another two polymorphisms, c.212-58A>C and c.2014G>C (E672Q) were always detected together, both in cancer (7.5% of patients) and control samples (4.9% of controls, p = 0.2). A novel germline truncating mutation, c.509_510delGA (p.R170fs) was found in exon 4: in 2 of 339 (0.6%) unrelated ovarian cancer patients, in 4 of 648 (0.6%) unrelated familial breast cancer patients, and in 1 of 1310 controls (0.08%, p = 0.1, p = 0.044, respectively). One ovarian cancer patient with the PALB2 mutation had also a germline nonsense mutation of the BRCA2 gene.

Conclusions

The c.509_510delGA is a novel PALB2 mutation that increases the risk of familial breast cancer. Occurrence of the same PALB2 alteration in seven unrelated women suggests that c.509_510delGA (p.R170fs) is a recurrent mutation for Polish population.
Should we use closed or open infusion containers for prevention of bloodstream infections?
Authors: Rangel-Frausto Manuel S , Higuera-Ramirez Francisco , Martinez-Soto Jose , Rosenthal Victor D
Published: February 2010

Background

Hospitalized patients in critical care settings are at risk for bloodstream infections (BSI). Most BSIs originate from a central line (CL), and they increase length of stay, cost, and mortality. Open infusion containers may increase the risk of contamination and administration-related (CLAB) because they allow the entry of air into the system, thereby also providing an opportunity for microbial entry. Closed infusion containers were designed to overcome this flaw. However, open infusion containers are still widely used throughout the world.

The objective of the study was to determine the effect of switching from open (glass, burettes, and semi-rigid) infusion containers to closed, fully collapsible, plastic infusion containers (Viaflex®) on the rate and time to onset of central line-associated bloodstream infections CLABs.

Methods

An open label, prospective cohort, active healthcare-associated infection surveillance, sequential study was conducted in four ICUs in Mexico. Centers for Disease Control National Nosocomial Infections Surveillance Systems definitions were used to define device-associated infections.

Results

A total of 1,096 adult patients who had a central line in place for >24 hours were enrolled. The CLAB rate was significantly higher during the open versus the closed container period (16.1 versus 3.2 CLAB/1000 central line days; RR = 0.20, 95% CI = 0.11-0.36, P < 0.0001). The probability of developing CLAB remained relatively constant in the closed container period (1.4% Days 2-4 to 0.5% Days 8-10), but increased in the open container period (4.9% Days 2-4 to 5.4% Days 8-10). The chance of acquiring a CLAB was significantly decreased (81%) in the closed container period (Cox proportional hazard ratio 0.19, P < 0.0001). Mortality was statistically significantly lower during the closed versus the open container period (23.4% versus 16.1%; RR = 0.69, 95% CI = 0.54-0.88, P < 0.01).

Conclusions

Closed infusion containers significantly reduced CLAB rate, the probability of acquiring CLAB, and mortality.
Role of platelets in neuroinflammation: a wide-angle perspective
Authors: Horstman Lawrence L , Jy Wenche , Ahn Yeon S , Zivadinov Robert , Maghzi Amir H , Etemadifar Masoud , Steven Alexander J , Minagar Alireza
Published: February 2010

Objectives

This review summarizes recent developments in platelet biology relevant to neuroinflammatory disorders. Multiple sclerosis (MS) is taken as the "Poster Child" of these disorders but the implications are wide. The role of platelets in inflammation is well appreciated in the cardiovascular and cancer research communities but appears to be relatively neglected in neurological research.

Organization

After a brief introduction to platelets, topics covered include the matrix metalloproteinases, platelet chemokines, cytokines and growth factors, the recent finding of platelet PPAR receptors and Toll-like receptors, complement, bioactive lipids, and other agents/functions likely to be relevant in neuroinflammatory diseases. Each section cites literature linking the topic to areas of active research in MS or other disorders, including especially Alzheimer's disease.

Conclusion

The final section summarizes evidence of platelet involvement in MS. The general conclusion is that platelets may be key players in MS and related disorders, and warrant more attention in neurological research.
Jane: a new tool for the cophylogeny reconstruction problem
Authors: Conow Chris , Fielder Daniel , Ovadia Yaniv , Libeskind-Hadas Ran
Published: February 2010

Background

This paper describes the theory and implementation of a new software tool, called Jane, for the study of historical associations. This problem arises in parasitology (associations of hosts and parasites), molecular systematics (associations of orderings and genes), and biogeography (associations of regions and orderings). The underlying problem is that of reconciling pairs of trees subject to biologically plausible events and costs associated with these events. Existing software tools for this problem have strengths and limitations, and the new Jane tool described here provides functionality that complements existing tools.

Results

The Jane software tool uses a polynomial time dynamic programming algorithm in conjunction with a genetic algorithm to find very good, and often optimal, solutions even for relatively large pairs of trees. The tool allows the user to provide rich timing information on both the host and parasite trees. In addition the user can limit host switch distance and specify multiple host switch costs by specifying regions in the host tree and costs for host switches between pairs of regions. Jane also provides a graphical user interface that allows the user to interactively experiment with modifications to the solutions found by the program.

Conclusions

Jane is shown to be a useful tool for cophylogenetic reconstruction. Its functionality complements existing tools and it is therefore likely to be of use to researchers in the areas of parasitology, molecular systematics, and biogeography.
Temporal Trends in Cause-Specific Late Mortality Among 5-Year Survivors of Childhood Cancer
Authors: Armstrong Gregory T. , Pan Zhenyu , Ness Kirsten K. , Srivastava Deokumar , Robison Leslie L.
Published: February 2010

Purpose

Five-year survival rates for childhood cancer have improved over the past four decades. However, it is unknown whether changes in primary cancer therapy have improved rates of long-term (> 5 years from diagnosis) durable remissions and reduced treatment-related deaths. We investigated changes in patterns of late mortality over time and cause-specific attribution of late-mortality among 5-year survivors.

Patients and Methods

Using data from the Surveillance, Epidemiology and End Results (SEER) population-based registry, we assessed all-cause and cause-specific (recurrence/progression of primary disease, external cause, and nonrecurrence/nonexternal cause) late mortality during four consecutive time periods from 1974 through 2000 among 26,643 5-year survivors of childhood cancer.

Results

All-cause late mortality improved during more recent eras, dropping from 7.1% (95% CI, 6.4% to 7.8%) among children diagnosed during 1974 to 1980 to 3.9% (95% CI, 3.3% to 4.4%) among children diagnosed during 1995 to 2000 (P < .001), largely because of reduced mortality from recurrence or progression. While there was no significant reduction in mortality attributable to other health conditions (including treatment-related health conditions), analysis controlling for demographic characteristics identified a trend toward reduced risk during more recent eras (P = .007). Disparity by race/ethnicity was identified, with higher mortality among non-Hispanic blacks than among non-Hispanic whites for all-cause and nonrecurrence/nonexternal -cause late mortality.

Conclusion

While overall patterns of mortality from other health conditions do not differ over time, adjustment for demographic characteristics provides evidence that risk of treatment-related mortality may be lower in more recent eras. Disparities in health care utilization among survivors should be explored.
Compose, Condense, Constrain
Authors: Roubaud Jacques
Published: February 2010

An elaboration of the Oulipian practice of writing under constraint, this lecture illuminates select philosophical arguments in a manner that exposes François Le Lionnais's conception of universal potentiality. To illustrate the advised position to adopt with respect to composition, the initial discussion of Nelson Goodman's paradox of induction (the “grue” paradox) demonstrates, on the one hand, the utility of the future-in-the-past of moment t, and, on the other hand, how this paradox exercises an abolition of time: all composition is now. The ensuing discussion of condensation aligns composition with atemporal conception, where the composition reveals itself to the mind as a full object, all of it graspable through inner vision, even anticipating its end prior to beginning. Granted, then, that, as a hypothesis for precision, composition requires an internal and external memory, it is an exception to the Dummettian rule of the publicity of meaning. In the final discussion, the activity of constraint is considered simultaneous to that of composition and condensation. Comparing Le Lionnais's inventions to those of his friend and fellow Oulipian, Marcel Duchamp, the lecture concludes by evoking horizons for potentiality that outstrip ordinary ideas of literature.
Human Timeless and Tipin stabilize replication forks and facilitate sister-chromatid cohesion
Authors: Leman Adam R. , Noguchi Chiaki , Lee Candice Y. , Noguchi Eishi
Published: February 2010

The Timeless-Tipin protein complex has been reported to be important for replication checkpoint and normal DNA replication processes. However, the precise mechanisms by which Timeless-Tipin preserves genomic integrity are largely unclear. Here, we describe the roles of Timeless-Tipin in replication fork stabilization and sister chromatid cohesion. We show in human cells that Timeless is recruited to replication origin regions and dissociate from them as replication proceeds. Cdc45, which is known to be required for replication fork progression, shows similar patterns of origin association to those of Timeless. Depletion of Timeless-Tipin causes chromosome fragmentation and defects in damage repair in response to fork collapse, suggesting that it is required for replication fork maintenance under stress. We also demonstrate that depletion of Timeless-Tipin impairs sister chromatid cohesion and causes a defect in mitotic progression. Consistently, Timeless-Tipin co-purifies with cohesin subunits and is required for their stable association with chromatin during S phase. Timeless associates with the cohesion-promoting DNA helicase ChlR1, which, when overexpressed, partially alleviates the cohesion defect of cells depleted of Timeless-Tipin. These results suggest that Timeless-Tipin functions as a replication fork stabilizer that couples DNA replication with sister chromatid cohesion established at replication forks.
The RNA helicase DHH1 is central to the correct expression of many developmentally regulated mRNAs in trypanosomes
Authors: Kramer Susanne , Queiroz Rafael , Ellis Louise , Hoheisel Jörg D. , Clayton Christine , Carrington Mark
Published: February 2010

In trypanosomes, the predominant mechanisms of regulation of gene expression are post-transcriptional. The DEAD-box RNA helicase DHH1 was identified in a screen for gene products that are necessary for the instability of the GPI-PLC mRNA in insect-stage trypanosomes. Expression of an ATPase-deficient dhh1 mutant caused a rapid growth arrest associated with a decrease in polysomes, an increase in P-bodies and a slight decrease in average mRNA levels. However, the effect of dhh1 mutant expression on both turnover and translational repression of mRNAs was selective. Whereas there was little effect on the stability of constitutive mRNAs, the control of a large cohort of developmentally regulated mRNAs was reversed; many mRNAs normally downregulated in insect-stage trypanosomes were stabilized and many mRNAs normally upregulated decreased in level. One stabilised mRNA, ISG75, was characterised further. Despite the overall decrease in polysomes, the proportion of the ISG75 mRNA in polysomes was unchanged and the result was ISG75 protein accumulation. Our data show that specific mRNAs can escape DHH1-mediated translational repression. In trypanosomes, DHH1 has a selective role in determining the levels of developmentally regulated mRNAs.
Dynamic organisation of prolactin gene expression in living pituitary tissue
Authors: Harper Claire V. , Featherstone Karen , Semprini Sabrina , Friedrichsen Sönke , McNeilly Judith , Paszek Pawel , Spiller David G. , McNeilly Alan S. , Mullins John J. , Davis Julian R. E. , White Michael R. H.
Published: February 2010

Gene expression in living cells is highly dynamic, but temporal patterns of gene expression in intact tissues are largely unknown. The mammalian pituitary gland comprises several intermingled cell types, organised as interdigitated networks that interact functionally to generate co-ordinated hormone secretion. Live-cell imaging was used to quantify patterns of reporter gene expression in dispersed lactotrophic cells or intact pituitary tissue from bacterial artificial chromosome (BAC) transgenic rats in which a large prolactin genomic fragment directed expression of luciferase or destabilised enhanced green fluorescent protein (d2EGFP). Prolactin promoter activity in transgenic pituitaries varied with time across different regions of the gland. Although amplitude of transcriptional responses differed, all regions of the gland displayed similar overall patterns of reporter gene expression over a 50-hour period, implying overall co-ordination of cellular behaviour. By contrast, enzymatically dispersed pituitary cell cultures showed unsynchronised fluctuations of promoter activity amongst different cells, suggesting that transcriptional patterns were constrained by tissue architecture. Short-term, high resolution, single cell analyses in prolactin-d2EGFP transgenic pituitary slice preparations showed varying transcriptional patterns with little correlation between adjacent cells. Together, these data suggest that pituitary tissue comprises a series of cell ensembles, which individually display a variety of patterns of short-term stochastic behaviour, but together yield long-range and long-term coordinated behaviour.
Signalling complexes and clusters: functional advantages and methodological hurdles
Authors: Cebecauer Marek , Spitaler Martin , Sergé Arnauld , Magee Anthony I.
Published: February 2010

Signalling molecules integrate, codify and transport information in cells. Organisation of these molecules in complexes and clusters improves the efficiency, fidelity and robustness of cellular signalling. Here, we summarise current views on how signalling molecules assemble into macromolecular complexes and clusters and how they use their physical properties to transduce environmental information into a variety of cellular processes. In addition, we discuss recent innovations in live-cell imaging at the sub-micrometer scale and the challenges of object (particle) tracking, both of which help us to observe signalling complexes and clusters and to examine their dynamic character.
A Theory of Deception
Authors: Ettinger David , Jehiel Philippe
Published: February 2010

This paper proposes an equilibrium approach to belief manipulation and deception in which agents only have coarse knowledge of their opponent's strategy. Equilibrium requires the coarse knowledge available to agents to be correct, and the inferences and optimizations to be made on the basis of the simplest theories compatible with the available knowledge. The approach can be viewed as formalizing into a game theoretic setting a well documented bias in social psychology, the fundamental attribution error. It is applied to a bargaining problem, thereby revealing a deceptive tactic that is hard to explain in the full rationality paradigm. (JEL C78, D83, D84)
A multi-strand approach to promoting equalities and human rights in policy making
Authors: Parken Alison
Published: February 2010

New European Union policy is to be subject to equality impact assessment for all strands of inequality and multiple discrimination (European Commission, 2006). This article discusses research that tested a gender mainstreaming model for its ability to reveal intersectional inequalities. The resulting collaborative multi-strand model situates intersectional enquiry at a structural level, enables the integration of equalities and human rights approaches and supports prioritisation without reductively homogenising ‘strand’ specific inequalities. This is a step towards intersectional working. Gaining satisfactory intersectional evidence will require improved quantitative data collection, the revaluing of qualitative data, and collaborative working between ‘equality makers and policy makers’.
Area-based regeneration partnerships and the role of central government: the New Deal for Communities programme in England
Authors: Beatty Christina , Foden Mike , Lawless Paul , Wilson Ian
Published: February 2010

The New Deal for Communities (NDC) is an ambitious English area-based initiative (ABI) designed to transform 39 deprived areas in relation to five outcomes: crime, education, health, worklessness, and housing and the physical environment. Change data are now available for 2002–08. NDC areas continue to see positive change, but show only modest improvements against other benchmarks, notably similarly deprived comparator areas. Regeneration has been complex because of a range of ‘barrier sets’ of which the most insistent has been the relationship between NDC Partnerships and central government. This relationship informs wider debates surrounding interpretations of the programme.
Functional intersection of the kallikrein-related peptidases (KLKs) and thrombostasis axis
Authors: Blaber Michael , Yoon Hyesook , Juliano Maria A. , Scarisbrick Isobel A. , Blaber Sachiko I.
Published: February 2010

A large body of emerging evidence indicates a functional interaction between the kallikrein-related peptidases (KLKs) and proteases of the thrombostasis axis. These interactions appear relevant for both normal health as well as pathologies associated with inflammation, tissue injury, and remodeling. Regulatory interactions between the KLKs and thrombostasis proteases could impact several serious human diseases, including neurodegeneration and cancer. The emerging network of specific interactions between these two protease families appears to be complex, and much work remains to elucidate it. Complete understanding how this functional network resolves over time, given specific initial conditions, and how it might be controllably manipulated, will probably contribute to the emergence of novel diagnostics and therapeutic agents for major diseases.
KLK5 gene expression is severely upregulated in androgen-independent prostate cancer cells after treatment with the chemotherapeutic agents docetaxel and mitoxantrone
Authors: Mavridis Konstantinos , Talieri Maroulio , Scorilas Andreas
Published: February 2010

Kallikrein-related peptidases (KLKs), includingKLK5, have been proposed as promising biomarkers for prostate cancer diagnosis and prognosis. In the present study, we report that distinct augmentations (up to 6.4-fold) ofKLK5mRNA expressional levels, calculated via quantitative real-time PCR, occur after treatment of DU145 cells with appropriate concentrations, determined by the MTT method, of docetaxel and mitoxantrone. Our data reveal the endogenous need of prostate cancer cells for modifiedKLK5expression to cope with the administration of chemotherapeutic drugs. Furthermore, it is proposed that the expression profile ofKLK5could serve as a putative biomarker for monitoring the treatment response in hormone refractory prostate cancer patients.
12-Lipoxygenase Regulates Hippocampal Long-Term Potentiation by Modulating L-Type Ca2+Channels
Authors: DeCostanzo Anthony J. , Voloshyna Iryna , Rosen Zev B. , Feinmark Steven J. , Siegelbaum Steven A.
Published: February 2010

Although long-term potentiation (LTP) has been intensively studied, there is disagreement as to which molecules mediate and modulate LTP. This is partly attributable to the presence of mechanistically distinct forms of LTP that are induced by different patterns of stimulation and that depend on distinct Ca2+sources. Here, we report a novel role for the arachidonic acid-metabolizing enzyme 12-lipoxygenase (12-LO) in LTP at CA3–CA1 hippocampal synapses that is dependent on the pattern of tetanic stimulation. We find that 12-LO activity is required for the induction of LTP in response to a theta burst stimulation protocol that depends on Ca2+influx through both NMDA receptors and L-type voltage-gated Ca2+channels. In contrast, LTP induced by 100 Hz tetanic stimulation, which requires Ca2+influx through NMDA receptors but not L-type channels, does not require 12-LO. We find that 12-LO regulates LTP by enhancing postsynaptic somatodendritic Ca2+influx through L-type channels during theta burst stimulation, an action exerted via 12(S)-HPETE [12(S)-hydroperoxyeicosa-5Z,8Z,10E,14Z-tetraenoic acid], a downstream metabolite of 12-LO. These results help define the role of a long-disputed signaling enzyme in LTP.
Dopamine and Memory: Modulation of the Persistence of Memory for Novel Hippocampal NMDA Receptor-Dependent Paired Associates
Authors: Bethus Ingrid , Tse Dorothy , Morris Richard G. M.
Published: February 2010

Three experiments investigated the role in memory processing of dopamine (DA) afferents to the hippocampus (HPC) that arise from the ventral tegmental area. One hypothesis is that D1/D5receptor activation in HPC is necessary for the encoding of novel, episodic-like information; the other is that DA activation ensures the greater temporal persistence of transient hippocampal memory traces. Rats (n= 35) were trained, in separate experiments using an episodic-like memory task, to learn six paired associates (PAs) in an “event arena” involving a repeated association between specific flavors of food and locations in space. After 6 weeks of training, rats had learned a “schema” such that two new paired associates could be acquired in a single trial in one session (episodic-like memory). We show that encoding of novel PAs is sensitive to intrahippocampal microinfusion of the NMDA antagonistd-AP-5. Experiment 1 established that intrahippocampal infusion of the D1/D5dopaminergic antagonist SCH23390 [R(+)-7-chloro-8-hydroxy-3-methyl-1-phenyl-2,3,4,5-tetrahydro-1H-3-benzazepine hydrochloride] before encoding of new PAs caused impaired memory 24 h later but that SCH23390 had no effect on the later memory of previously established PAs. Experiment 2 established that SCH23390 modulated the persistence of new memories over time (30 min vs 24 h) rather than affecting initial encoding. Experiment 3 revealed that the impact of SCH23390 was not mediated by state dependence nor had an effect on memory retrieval. These findings support the second hypothesis and establish that persistent, long-term memory of rapid, hippocampal-mediated acquisition of new paired associates requires activation of D1/D5receptors in HPC at or around the time of encoding.
Ca2+Influx through NMDA-Gated Channels Activates ATP-Sensitive K+Currents through a Nitric Oxide–cGMP Pathway in Subthalamic Neurons
Authors: Shen Ke-Zhong , Johnson Steven W.
Published: February 2010

Excessive burst firing of action potentials in subthalamic nucleus (STN) neurons has been correlated with the bradykinesia and rigidity seen in Parkinson's disease. Consequently, there is much interest in characterizing mechanisms that promote burst firing, such as the regulation of NMDA receptor function. Using whole-cell recording techniques in rat brain slices, we report that inward currents evoked by NMDA are greatly potentiated by ATP-sensitive K+(K-ATP) channel blocking agents in STN neurons but not in dopamine neurons in the substantia nigra. Moreover, we found that the ability of NMDA to evoke K-ATP current was blocked by inhibitors of nitric oxide synthase, guanylyl cyclase, and calcium/calmodulin. By altering firing patterns of STN neurons, this NMDA/K-ATP interaction may exert an important influence on basal ganglia output and thereby affect the clinical expression of Parkinson's disease.
Global Inhibition and Stimulus Competition in the Owl Optic Tectum
Authors: Mysore Shreesh P. , Asadollahi Ali , Knudsen Eric I.
Published: February 2010

Stimulus selection for gaze and spatial attention involves competition among stimuli across sensory modalities and across all of space. We demonstrate that such cross-modal, global competition takes place in the intermediate and deep layers of the optic tectum, a structure known to be involved in gaze control and attention. A variety of either visual or auditory stimuli located anywhere outside of a neuron's receptive field (RF) were shown to suppress or completely eliminate responses to a visual stimulus located inside the RF in nitrous oxide sedated owls. The essential mechanism underlying this stimulus competition is global, divisive inhibition. Unlike the effect of the classical inhibitory surround, which decreases with distance from the RF center and shapes neuronal responses to individual stimuli, global inhibition acts across the entirety of space and modulates responses primarily in the context of multiple stimuli. Whereas the source of this global inhibition is as yet unknown, our data indicate that different networks mediate the classical surround and global inhibition. We hypothesize that this global, cross-modal inhibition, which acts automatically in a bottom-up manner even in sedated animals, is critical to the creation of a map of stimulus salience in the optic tectum.
Nitric Oxide Acts as a Volume Transmitter to Modulate Electrical Properties of Spontaneously Firing Neurons via Apamin-Sensitive Potassium Channels
Authors: Artinian Liana , Tornieri Karine , Zhong Lei , Baro Deborah , Rehder Vincent
Published: February 2010

Nitric oxide (NO) is a radical and a gas, properties that allow NO to diffuse through membranes and potentially enable it to function as a “volume messenger.” This study had two goals: first, to investigate the mechanisms by which NO functions as a modulator of neuronal excitability, and second, to compare NO effects produced by NO release from chemical NO donors with those elicited by physiological NO release from single neurons. We demonstrate that NO depolarizes the membrane potential of B5 neurons of the molluskHelisoma trivolvis, initially increasing their firing rate and later causing neuronal silencing. Both effects of NO were mediated by inhibition of Ca-activated iberiotoxin- and apamin-sensitive K channels, but only inhibition of apamin-sensitive K channels fully mimicked all effects of NO on firing activity, suggesting that the majority of electrical effects of NO are mediated via inhibition of apamin-sensitive K channels. We further show that single neurons release sufficient amounts of NO to affect the electrical activity of B5 neurons located nearby. These effects are similar to NO release from the chemical NO donor NOC-7 [3-(2-hydroxy-1-methyl-2-nitrosohydazino)-N-methyl-1-propyanamine], validating the use of NO donors in studies of neuronal excitability. Together with previous findings demonstrating a role for NO in neurite outgrowth and growth cone motility, the results suggest that NO has the potential to shape the development of the nervous system by modulating both electrical activity and neurite outgrowth in neurons located in the vicinity of NO-producing cells, supporting the notion of NO functioning as a volume messenger.
Distinct Representations and Theta Dynamics in Dorsal and Ventral Hippocampus
Authors: Royer Sébastien , Sirota Anton , Patel Jagdish , Buzsáki György
Published: February 2010

Although anatomical, lesion, and imaging studies of the hippocampus indicate qualitatively different information processing along its septo-temporal axis, physiological mechanisms supporting such distinction are missing. We found fundamental differences between the dorsal (dCA3) and the ventral-most parts (vCA3) of the hippocampus in both environmental representation and temporal dynamics. Discrete place fields of dCA3 neurons evenly covered all parts of the testing environments. In contrast, vCA3 neurons (1) rarely showed continuous two-dimensional place fields, (2) differentiated open and closed arms of a radial maze, and (3) discharged similar firing patterns with respect to the goals, both on multiple arms of a radial maze and during opposite journeys in a zigzag maze. In addition, theta power and the fraction of theta-rhythmic neurons were substantially reduced in the ventral compared with dorsal hippocampus. We hypothesize that the spatial representation in the septo-temporal axis of the hippocampus is progressively decreased. This change is paralleled with a reduction of theta rhythm and an increased representation of nonspatial information.
Using Cartesian Space in Motion Planning for 7 DoF ManipulatorNutzung des kartesischen Raums in der Bewegungsplannung für Manipulatoren mit 7 Freiheitsgraden
Authors: Ojdanic Darko , Gräser Axel
Published: February 2010

This paper introduces motion planning algorithms that are suitable for real-time applications with dexterous manipulators. Developed motion planner obtains needed efficiency by using the Cartesian space information, and therefore avoids the dimensionality problem of the configuration space. In this work, a skillful planner is developed together with a post-processing path-smoothing technique, which is independent from the planner. A comparison with the state-of-the-art planners emphasises the advantages of this approach. Described algorithms successfully operate on a rehabilitation robotic system FRIEND.
Bahnplanung und Regelung unteraktuierter Manipulatoren mittels nichtlinearer zeitdiskreter AnsätzePath-planning and Control of Underactuated Manipulators by Nonlinear Discrete-time Approaches
Authors: Weidemann Dirk , Scherm Norbert , Heimann Bodo
Published: February 2010

In der Klasse der unteraktuierten Systeme stellen horizontal bewegte Manipulatoren mit passiven Gelenken eine besondere Herausforderung dar, weil die Linearisierung in einer Ruhelage zu einem nicht vollständig steuerbaren Modell führt. Für Bewegungen, die in Ruhelagen beginnen und enden, sind lineare Ansätze zum Reglerentwurf ungeeignet. Auch bei Wahl eines nichtlinearen Modells liegt in der Umgebung einer Ruhelage ein schlecht konditioniertes Regelungsproblem vor. Zeitkontinuierliche Ansätze, die ein asymptotisches Annähern an die Ruhelage fordern, führen daher selten auf ein zufriedenstellendes Systemverhalten. Die vorgestellten zeitdiskreten Ansätze ermöglichen dieses Problem mittels Bahnplanung auf endlichem Zeitintervall und Dead-Beat-Regelung zu umgehen. Neben Bahnplanungsansätzen, die schnelle Konvergenz und systematische Berechnung der Bewegungsdauer gewährleisten, werden zwei Regler präsentiert und verifiziert.
Vollständige Modale Synthese regulärer DeskriptorsystemeParametric Feedback Design of Regular Descriptor Systems
Authors: Manderla Maximilian , Konigorski Ulrich
Published: February 2010

Der Beitrag beschreibt ein neues Verfahren zur Synthese konstanter Zustandsrückführungen für lineare, zeitinvariante Deskriptorsysteme. Ausgehend von bekannten parametrischen Entwurfsmethoden für gewöhnliche Zustandsraumbeschreibungen wird eine Synthesevorschrift angegeben, welche sämtliche Freiheitsgrade beim Entwurf regulärer Deskriptorsysteme und deren Auswirkungen auf die Dynamik des geschlossenen Regelkreises sichtbar macht. Insbesondere lassen sich alle steuerbaren endlichen sowie unendlichen Eigenwerte explizit vorgeben.
Die Bedeutung der Materialentwicklung für elektrochemische SensorenMaterials Research and Development for Electrochemical Sensors
Authors: Vonau Winfried , Oelßner Wolfram , Zosel Jens , Kohler Heinz
Published: February 2010

Elektrochemische Sensoren werden in verschiedenen Ausführungsformen in einem weiten Temperaturbereich von ca. -30°C bis über 1500°C in festen, flüssigen und gasförmigen Medien eingesetzt. Die Erschließung neuer Anwendungsgebiete sowie die Erweiterung des Temperatureinsatzbereiches, die Erhöhung von Sensitivität, Selektivität und Stabilität und die Optimierung von Fertigungstechnologien der Sensoren beruhen fast immer auf Neu- und Weiter-entwicklungen von Sensormaterialien und Verfahren zu deren Herstellung. Der Übersichtsartikel zeigt die Vielfalt dieser Bemühungen anhand von Beispielen zu Materialentwicklungen für elektrochemische Referenzelektroden, Metalloxidelektroden, Metalloxid-Gassensoren sowie YSZ-basierten Festelektrolytsensoren.
Die kombinierte Standardunsicherheit als Variationsproblem am Beispiel eines TurbinenradzählersThe Combined Standard Uncertainty as Variation Problem Using the Example of a Turbine Meter
Authors: Riedel Jörg
Published: February 2010

Die Verifizierung der Unsicherheit, die einem ermittelten Wert einer Messgröße anhaftet, ist mit Hilfe der kombinierten Standardunsicherheit möglich. Ebenfalls ist eine Unsicherheitsanalyse zur Planung einer Messaufgabe nützlich, um die richtige Auswahl der Messgeräte und eines geeigneten Messverfahrens treffen zu können. Dazu wird in diesem Beitrag die relative kombinierte Standardunsicherheit als Variationsproblem beteiligter Unsicherheitskomponenten aufgefasst und am Beispiel eines Turbinenradzählers für Flüssigkeitsmessungen behandelt.
Thermoelektrische Dünnschicht-Generatoren. Energieautarke Versorgung für KleinleistungsverbraucherThin Film Thermoelectric Generators. Autonomous Power Supply for Low-Power Devices
Authors: Nurnus Joachim , Habbe Burkhard
Published: February 2010

Thermoelektrische Bauteile zur Erzeugung von elektrischer Energie aus Verlustwärme lassen sich mittels Halbleitertechnologien extrem miniaturiesieren. Mithilfe eines waferbasierten, MEMS-ähnlichen Herstellungsprozesses können Bauteile mit Gesamtdicken zwischen 0,5 mm und 1 mm sowie Grundflächen von weniger als 1 mm2 bis zu 25 mm2 hergestellt werden. Die Herstellung der Bauteile erfolgt auf Standard-Halbleiterequipment. Daher sind von anderen chipbasierten Produkten bekannte Expansionsszenarien und die daraus resultierenden Skaleneffekte bei großen Stückzahlen (“economy-of-scale”) auch auf diese Bauteile anwendbar. Dass aufgrund der verwendeten Dünnschicht-Technologie zusätzlich ca. 1000 Mal weniger thermoelektrisches Material als bei konventionellen Modulen benötigt wird, ist ein weiterer Garant für langfristig kostengünstige Bauteile. In diesem Artikel wird neben dem Herstellverfahren für Micropelt-Thermogeneratoren auch deren Einsatz in thermischen Harvesting-Modulen anhand des Evaluationsmoduls TE-Power NODE beschrieben.
DMR1 (CCM1/YGR150C) of Saccharomyces cerevisiae Encodes an RNA-Binding Protein from the Pentatricopeptide Repeat Family Required for the Maintenance of the Mitochondrial 15S Ribosomal RNA
Authors: Puchta Olga , Lubas Michal , Lipinski Kamil A , Piatkowski Jakub , Malecki Michal , Golik Pawel
Published: February 2010

Pentatricopeptide repeat (PPR) proteins form the largest known RNA-binding protein family and are found in all eukaryotes, being particularly abundant in higher plants. PPR proteins localize mostly in mitochondria and chloroplasts, where they modulate organellar genome expression on the post-transcriptional level. The Saccharomyces cerevisiae DMR1 (CCM1, YGR150C) encodes a PPR protein that localizes to mitochondria. Deletion of DMR1 results in a complete and irreversible loss of respiratory capacity and loss of wild-type mtDNA by conversion to ρ−/ρ0 petites, regardless of the presence of introns in mtDNA. The phenotype of the dmr1Δ mitochondria is characterized by fragmentation of the small subunit mitochondrial rRNA (15S rRNA), that can be reversed by wild-type Dmr1p. Other mitochondrial transcripts, including the large subunit mitochondrial rRNA (21S rRNA), are not affected by the lack of Dmr1p. The purified Dmr1 protein specifically binds to different regions of 15S rRNA in vitro, consistent with the deletion phenotype. Dmr1p is therefore the first yeast PPR protein, which has an rRNA target and is probably involved in the biogenesis of mitochondrial ribosomes and translation.