bluuebunny/crossref_metadata_2025 huggingface dataset:
A multiscale strength model for extreme loading conditions
Authors: Barton N. R. , Bernier J. V. , Becker R. , Arsenlis A. , Cavallo R. , Marian J. , Rhee M. , Park H.-S. , Remington B. A. , Olson R. T.
Published: April 2011

We present a multiscale strength model in which strength depends on pressure, strain rate, temperature, and evolving dislocation density. Model construction employs an information passing paradigm to span from the atomistic level to the continuum level. Simulation methods in the overall hierarchy include density functional theory, molecular statics, molecular dynamics, dislocation dynamics, and continuum based approaches. Given the nature of the subcontinuum simulations upon which the strength model is based, the model is particularly appropriate to strain rates in excess of 104 s−1. Strength model parameters are obtained entirely from the hierarchy of simulation methods to obtain a full strength model in a range of loading conditions that so far has been inaccessible to direct measurement of material strength. Model predictions compare favorably with relevant high energy density physics (HEDP) experiments that have bearing on material strength. The model is used to provide insight into HEDP experimental observations and to make predictions of what might be observable using dynamic x-ray diffraction based experimental methods.
Investigating the use of magnonic crystals as extremely sensitive magnetic field sensors at room temperature
Authors: Inoue Mitsuteru , Baryshev Alexander , Takagi Hiroyuki , Lim Pang Boey , Hatafuku Kohei , Noda Josho , Togo Kenji
Published: April 2011

We have experimentally demonstrated that a magnonic crystal—an artificial magnetic structure for controlling propagation of magnetostatic waves—can be used as an extremely sensitive sensor for detecting magnetic fields. Functional characteristics of the sensor were studied at room temperature and in a normal noisy space without considering any magnetic shielding.
A Dialectics of Encounter
Authors: Ruddick Susan M
Published: March 2011

What forms of knowledge and nonknowledge continue to haunt contemporary debates, and in what ways were they ‘known too well’ in the aftermath of 1968 to precipitate the falling out of favor of Marx and Marxism and the recasting of Macherey along with the rest of Althusser's circle as ‘structuralist dinosaurs’? And what might we learn from the staging of this encounter between Hegel and Spinoza, both in terms of the specific points of application and the method of enquiry? Macherey offers an answer to these questions not only in Hegel or Spinoza but also in a series of papers addressing Hegel's prior uptake in France—an engagement that had solidified tendencies in Hegel that were also, not coincidentally, the points of Hegel's misreading of Spinoza. Read together, they offer us a fuller picture of the long shadow—cast initially in Hegel's misinterpretation of Spinoza and amplified subsequently in the uptake of Hegel in France. To return explicitly to Hegel in 1979—even if to ‘surpass’ him—was in part to exhume a corpse, to demonstrate the ways that Hegel continued to haunt philosophy. Hegel or Spinoza was a response to the long and still active legacy of what we might call (borrowing from Macherey) Hegel à la Française.
Beyond Imaginative Geographies? Critique, Co-Optation, and Imagination in the Aftermath of the War on Terror
Authors: Stephens Angharad Closs
Published: March 2011

This paper considers the question of what it might mean to resist the ‘imaginative geographies’ of the War on Terror through a reading of the bestselling novel The Reluctant Fundamentalist by Mohsin Hamid. Reading this novel against the claim that we are now at the ‘end’ of the War on Terror, the paper engages with how we might move beyond what Derek Gregory described as the split geographies of ‘us’ and ‘them’, ‘civilization’ and ‘barbarism’ that represent the violent return of the colonial past. The paper argues that critical attempts at resisting the imaginative geographies of the War on Terror, such as we find in this particular novel, often assume and reproduce an understanding of time as linear and progressive, an idea of time which Gregory points out makes these imaginative geographies possible. The paper argues that this becomes problematic when critical interventions risk reproducing the very understanding of political life that they set out to confront. Whilst it is an important political move to reveal the imaginative geographies at work in the War on Terror, the paper suggests that this approach also risks operating by confirming to a critical readership that which it already knows. We are too easily led to the conclusion that what is needed is better representations of ‘others’ in the world, as just as enlightened, cultured, reasoned as ‘us’. The contention of this paper is that such critical responses fail to do anything to disrupt or trouble the split geographies of ‘us’ and ‘them’; rather, they keep them firmly in place and entrench them further. The paper argues that we need to revisit and unsettle the concept of imagination at work in the idea of ‘imaginative geographies’ to explore a way of thinking coexistence in world politics that cannot be understood within a unifying temporal framework. It is suggested that, despite the closures identified in this novel, postcolonial urban literatures also provide many openings for thinking the “possibility that the field of the political is constitutively not singular” [Chakrabarty, 2000, Provincializing Europe (Princeton University Press, Princeton, NJ) page 148].
Solid-phase synthesis and chemical space analysis of a 190-membered alkaloid/terpenoid-like library
Authors: Moura-Letts Gustavo , DiBlasi Christine M. , Bauer Renato A. , Tan Derek S.
Published: March 2011

Alkaloid and terpenoid natural products display an extensive array of chemical frameworks and biological activities. However such scaffolds remain underrepresented in current screening collections and are, thus, attractive targets for the synthesis of natural product-based libraries that access underexploited regions of chemical space. Recently, we reported a systematic approach to the stereoselective synthesis of multiple alkaloid/terpenoid-like scaffolds using transition metal-mediated cycloaddition and cyclization reactions of enyne and diyne substrates assembled on a
tert
-butylsulfinamide lynchpin. We report herein the synthesis of a 190-membered library of alkaloid/terpenoid-like molecules using this synthetic approach. Translation to solid-phase synthesis was facilitated by the use of a
tert
-butyldiarylsilyl (TBDAS) linker that closely mimics the
tert
-butyldiphenysilyl protecting group used in the original solution-phase route development work. Unexpected differences in stereoselectivity and regioselectivity were observed in some reactions when carried out on solid support. Further, the sulfinamide moiety could be hydrolyzed or oxidized efficiently without compromising the TBDAS linker to provide additional amine and sulfonamide functionalities. Principal component analysis of the structural and physicochemical properties of these molecules confirmed that they access regions of chemical space that overlap with bona fide natural products and are distinct from areas addressed by conventional synthetic drugs and drug-like molecules. The influences of scaffolds and substituents were also evaluated, with both found to have significant impacts on location in chemical space and three-dimensional shape. Broad biological evaluation of this library will provide valuable insights into the abilities of natural product-based libraries to access similarly underexploited regions of biological space.
Questioning Implicit Motor Learning as Instantiated by the Pursuit-Tracking Task
Authors: Lang Alexandre , Gapenne Olivier , Rovira Katia
Published: April 2011

The effect of concurrent visual feedback on the implicit learning of repeated segments in a task of pursuit tracking has been tested. Although this feedback makes it possible to regulate the positional error during the movement, it could also induce negative guidance effects. To test this hypothesis, a first set of participants ( N = 42) were assigned to two groups, which performed either the standard pursuit-tracking task based on the experimental paradigm of Pew (1974; group F-ST), or a task called “movement reproduction” in which the feedback was suppressed (group noF-ST). A second set of participants ( N = 26) performed in the same feedback condition groups but in a dual-task situation (F-DT and noF-DT; Experiment 2). The results appear to confirm our predictions since the participants in groups without feedback, contrary to those in groups with feedback, succeeded with practice in differentiating their performances as a function of the nature of the segments (repeated or nonrepeated) both in simple (Experiment 1) and in dual-task (Experiment 2) situations. These experiments indicate that the feedback in the pursuit-tracking task induces a guidance function potentially resulting in an easiness tracking that prevents the participants from learning the repetition.
Jordan-Chevalley decomposition in finite dimensional Lie algebras
Authors: Cagliero Leandro , Szechtman Fernando
Published: March 2011

Let

g

\mathfrak {g}

be a finite dimensional Lie algebra over a field

k
k

of characteristic zero. An element

x
x

of

g

\mathfrak {g}

is said to have an abstract Jordan-Chevalley decomposition if there exist unique

s
,
n
∈

g

s,n\in \mathfrak {g}

such that

x
=
s
+
n

x=s+n

,

[
s
,
n
]
=
0

[s,n]=0

and given any finite dimensional representation

π
:

g

→

g
l

(
V
)

\pi :\mathfrak {g}\to \mathfrak {gl}(V)

the Jordan-Chevalley decomposition of

π
(
x
)

\pi (x)

in

g
l

(
V
)

\mathfrak {gl}(V)

is

π
(
x
)
=
π
(
s
)
+
π
(
n
)

\pi (x)=\pi (s)+\pi (n)

.

In this paper we prove that

x
∈

g

x\in \mathfrak {g}

has an abstract Jordan-Chevalley decomposition if and only if

x
∈
[

g

,

g

]

x\in [\mathfrak {g},\mathfrak {g}]

, in which case its semisimple and nilpotent parts are also in

[

g

,

g

]

[\mathfrak {g},\mathfrak {g}]

and are explicitly determined. We derive two immediate consequences: (1) every element of

g

\mathfrak {g}

has an abstract Jordan-Chevalley decomposition if and only if

g

\mathfrak {g}

is perfect; (2) if

g

\mathfrak {g}

is a Lie subalgebra of

g
l

(
n
,
k
)

\mathfrak {gl}(n,k)

, then

[

g

,

g

]

[\mathfrak {g},\mathfrak {g}]

contains the semisimple and nilpotent parts of all its elements. The last result was first proved by Bourbaki using different methods.

Our proof uses only elementary linear algebra and basic results on the representation theory of Lie algebras, such as the Invariance Lemma and Lie’s Theorem, in addition to the fundamental theorems of Ado and Levi.
A polynomial interpolation process at quasi-Chebyshev nodes with the FFT
Authors: Sugiura Hiroshi , Hasegawa Takemitsu
Published: March 2011

Interpolation polynomial

p
n

p_n

at the Chebyshev nodes

cos
⁡
π
j

/

n

\cos \pi j/n

(

0
≤
j
≤
n

0\le j\le n

) for smooth functions is known to converge fast as

n
→
∞

n\to \infty

. The sequence

{

p
n

}

\{p_n\}

is constructed recursively and efficiently in

O
(
n

log
2

⁡
n
)

O(n\log _2n)

flops for each

p
n

p_n

by using the FFT, where

n
n

is increased geometrically,

n
=

2
i

n=2^i

(

i
=
2
,
3
,
…

i=2,3,\dots

), until an estimated error is within a given tolerance of

ε
\varepsilon

. This sequence

{

2
j

}

\{2^j\}

, however, grows too fast to get

p
n

p_n

of proper

n
n

, often a much higher accuracy than

ε
\varepsilon

being achieved. To cope with this problem we present quasi-Chebyshev nodes (QCN) at which

{

p
n

}

\{p_n\}

can be constructed efficiently in the same order of flops as in the Chebyshev nodes by using the FFT, but with

n
n

increasing at a slower rate. We search for the optimum set in the QCN that minimizes the maximum error of

{

p
n

}

\{p_n\}

. Numerical examples illustrate the error behavior of

{

p
n

}

\{p_n\}

with the optimum nodes set obtained.
The caBIG® Life Science Business Architecture Model
Authors: Boyd Lauren Becnel , Hunicke-Smith Scott P. , Stafford Grace A. , Freund Elaine T. , Ehlman Michele , Chandran Uma , Dennis Robert , Fernandez Anna T. , Goldstein Stephen , Steffen David , Tycko Benjamin , Klemm Juli D.
Published: March 2011

Motivation: Business Architecture Models (BAMs) describe what a business does, who performs the activities, where and when activities are performed, how activities are accomplished and which data are present. The purpose of a BAM is to provide a common resource for understanding business functions and requirements and to guide software development. The cancer Biomedical Informatics Grid (caBIG®) Life Science BAM (LS BAM) provides a shared understanding of the vocabulary, goals and processes that are common in the business of LS research.

Results: LS BAM 1.1 includes 90 goals and 61 people and groups within Use Case and Activity Unified Modeling Language (UML) Diagrams. Here we report on the model's current release, LS BAM 1.1, its utility and usage, and plans for future use and continuing development for future releases.

Availability and Implementation: The LS BAM is freely available as UML, PDF and HTML (https://wiki.nci.nih.gov/x/OFNyAQ).

Contact:  lbboyd@bcm.edu; laurenbboyd@gmail.com

Supplementary information:  Supplementary data) are avaliable at Bioinformatics online.
pathClass: an R-package for integration of pathway knowledge into support vector machines for biomarker discovery
Authors: Johannes Marc , Fröhlich Holger , Sültmann Holger , Beißbarth Tim
Published: March 2011

Summary: Prognostic and diagnostic biomarker discovery is one of the key issues for a successful stratification of patients according to clinical risk factors. For this purpose, statistical classification methods, such as support vector machines (SVM), are frequently used tools. Different groups have recently shown that the usage of prior biological knowledge significantly improves the classification results in terms of accuracy as well as reproducibility and interpretability of gene lists. Here, we introduce pathClass, a collection of different SVM-based classification methods for improved gene selection and classfication performance. The methods contained in pathClass do not merely rely on gene expression data but also exploit the information that is carried in gene network data.

Availability:  pathClass is open source and freely available as an R-Package on the CRAN repository at http://cran.r-project.org

Contact:  m.johannes@dkfz-heidelberg.de; tim.beissbarth@ams.med.uni-goettingen.de
A qualitative continuous model of cellular auxin and brassinosteroid signaling and their crosstalk
Authors: Sankar Martial , Osmont Karen S. , Rolcik Jakub , Gujas Bojan , Tarkowska Danuse , Strnad Miroslav , Xenarios Ioannis , Hardtke Christian S.
Published: March 2011

Motivation: Hormone pathway interactions are crucial in shaping plant development, such as synergism between the auxin and brassinosteroid pathways in cell elongation. Both hormone pathways have been characterized in detail, revealing several feedback loops. The complexity of this network, combined with a shortage of kinetic data, renders its quantitative analysis virtually impossible at present.

Results: As a first step towards overcoming these obstacles, we analyzed the network using a Boolean logic approach to build models of auxin and brassinosteroid signaling, and their interaction. To compare these discrete dynamic models across conditions, we transformed them into qualitative continuous systems, which predict network component states more accurately and can accommodate kinetic data as they become available. To this end, we developed an extension for the SQUAD software, allowing semi-quantitative analysis of network states. Contrasting the developmental output depending on cell type-specific modulators enabled us to identify a most parsimonious model, which explains initially paradoxical mutant phenotypes and revealed a novel physiological feature.

Availability: The package SQUADD is freely available via the Bioconductor repository at http://www.bioconductor.org/help/bioc-views/release/bioc/html/SQUADD.html.

Contact:  martial.sankar@unil.ch; christian.hardtke@unil.ch

Supplementary information:  Supplementary data are available at Bioinformatics online.
High-dimensional pharmacogenetic prediction of a continuous trait using machine learning techniques with application to warfarin dose prediction in African Americans
Authors: Cosgun Erdal , Limdi Nita A. , Duarte Christine W.
Published: March 2011

Motivation: With complex traits and diseases having potential genetic contributions of thousands of genetic factors, and with current genotyping arrays consisting of millions of single nucleotide polymorphisms (SNPs), powerful high-dimensional statistical techniques are needed to comprehensively model the genetic variance. Machine learning techniques have many advantages including lack of parametric assumptions, and high power and flexibility.

Results: We have applied three machine learning approaches: Random Forest Regression (RFR), Boosted Regression Tree (BRT) and Support Vector Regression (SVR) to the prediction of warfarin maintenance dose in a cohort of African Americans. We have developed a multi-step approach that selects SNPs, builds prediction models with different subsets of selected SNPs along with known associated genetic and environmental variables and tests the discovered models in a cross-validation framework. Preliminary results indicate that our modeling approach gives much higher accuracy than previous models for warfarin dose prediction. A model size of 200 SNPs (in addition to the known genetic and environmental variables) gives the best accuracy. The R2 between the predicted and actual square root of warfarin dose in this model was on average 66.4% for RFR, 57.8% for SVR and 56.9% for BRT. Thus RFR had the best accuracy, but all three techniques achieved better performance than the current published R2 of 43% in a sample of mixed ethnicity, and 27% in an African American sample. In summary, machine learning approaches for high-dimensional pharmacogenetic prediction, and for prediction of clinical continuous traits of interest, hold great promise and warrant further research.

Contact:  cduarte@uab.edu

Supplementary information:  Supplementary data are available at Bioinformatics online.
MRSD: a web server for Metabolic Route Search and Design
Authors: Xia Deguo , Zheng Haoran , Liu Zhiqiang , Li Guisheng , Li Jinlong , Hong Jiong , Zhao Kai
Published: March 2011

Summary: We present a tool called MRSD (Metabolic Route Search and Design) to search and design routes based on the weighted compound transform diagraph. The search submodule returns routes between a source and product compound within seconds in the network of one or multiple organisms based on data from KEGG. The design submodule designs a route from an appointed compound in an interactive mode. The two complementary functions, Metabolic Route Search and Design, can be broadly used in biosynthesis, bio-pharmaceuticals and the other related fields.

Availability:  bioinfo.ustc.edu.cn/softwares/MRSD/

Contact:  hrzheng@ustc.edu.cn

Supplementary information:  Supplementary data are available at the Bioinformatics online.
Polymorphism in the Interleukin-1 Receptor Antagonist Gene Is Associated with Serum Interleukin-1 Receptor Antagonist Concentrations and Postoperative Opioid Consumption
Authors: Candiotti Keith A. , Yang Zongqi , Morris Richard , Yang Jinfeng , Crescimone Nicolas A. , Sanchez Greys C. , Bird Vincent , Leveillee Raymond , Rodriguez Yiliam , Liu Huanliang , Zhang Yu Dana , Bethea John R. , Gitlin Melvin C.
Published: March 2011

Background

The interleukin-1 receptor antagonist (IL-1Ra) is the principal determinant of IL-1β bioactivity within the IL-1 gene cluster, regulating IL-1α and IL-1β release. This study was designed to determine whether polymorphisms of the IL-1Ra gene (IL1RN) produce clinically measurable differences in serum IL-1Ra concentrations and opioid consumption in the postoperative period.

Methods

Opioid consumption and pain scores were evaluated in 96 patients undergoing a nephrectomy. DNA was extracted from all patients, and the genotypes of IL1RN were determined by polymerase chain reaction amplification of the variable number of tandem repeats of 86 base pairs in intron 2 of IL1RN. The concentrations of serum IL-1Ra concentrations at baseline and at 24 h postoperatively in 58 subjects were measured.

Results

Differences in opioid consumption among the three genotype groups (IL1RN*1 homozygotes and *2 and *3 carriers) were statistically significant in the first and second 12-h postoperative periods (P = 0.010). The IL1RN*2 carrier group consumed 43% (95% CI, 38-48%) less opioids in the first 24 h after surgery than the IL1RN*1 homozygote group (P = 0.003). Differences in the serum IL-1Ra concentration among the three genotype groups were statistically significant at 24 h postoperatively (P = 0.003), with IL1RN*2 carriers having the highest serum IL-1Ra concentrations.

Conclusions

The variable number of tandem repeats in intron 2 of IL1RN may contribute to interindividual variations in opioid consumption in the first 24 h after surgery. Patients homozygous for the IL1RN*1 allele have lower concentrations of IL-1Ra and require higher doses of opioids postoperatively than patients carrying at least one IL1RN*2 allele.
Skin as a potential source of infectious foot and mouth disease aerosols
Authors: Dillon Michael B.
Published: March 2011

This review examines whether exfoliated, virus-infected animal skin cells could be an important source of infectious foot and mouth disease virus (FMDV) aerosols. Infectious material rafting on skin cell aerosols is an established means of transmitting other diseases. The evidence for a similar mechanism for FMDV is: (i) FMDV is trophic for animal skin and FMDV epidermis titres are high, even in macroscopically normal skin; (ii) estimates for FMDV skin cell aerosol emissions appear consistent with measured aerosol emission rates and are orders of magnitude larger than the minimum infectious dose; (iii) the timing of infectious FMDV aerosol emissions is consistent with the timing of high FMDV skin concentrations; (iv) measured FMDV aerosol sizes are consistent with skin cell aerosols; and (v) FMDV stability in natural aerosols is consistent with that expected for skin cell aerosols. While these findings support the hypothesis, this review is insufficient, in and of itself, to prove the hypothesis and specific follow-on experiments are proposed. If this hypothesis is validated, (i) new FMDV detection, management and decontamination approaches could be developed and (ii) the relevance of skin cells to the spread of viral disease may need to be reassessed as skin cells may protect viruses against otherwise adverse environmental conditions.
Costly punishment prevails in intergroup conflict
Authors: Sääksvuori Lauri , Mappes Tapio , Puurtinen Mikael
Published: March 2011

Understanding how societies resolve conflicts between individual and common interests remains one of the most fundamental issues across disciplines. The observation that humans readily incur costs to sanction uncooperative individuals without tangible individual benefits has attracted considerable attention as a proximate cause as to why cooperative behaviours might evolve. However, the proliferation of individually costly punishment has been difficult to explain. Several studies over the last decade employing experimental designs with isolated groups have found clear evidence that the costs of punishment often nullify the benefits of increased cooperation, rendering the strong human tendency to punish a thorny evolutionary puzzle. Here, we show that group competition enhances the effectiveness of punishment so that when groups are in direct competition, individuals belonging to a group with punishment opportunity prevail over individuals in a group without this opportunity. In addition to competitive superiority in between-group competition, punishment reduces within-group variation in success, creating circumstances that are highly favourable for the evolution of accompanying group-functional behaviours. We find that the individual willingness to engage in costly punishment increases with tightening competitive pressure between groups. Our results suggest the importance of intergroup conflict behind the emergence of costly punishment and human cooperation.
Genotypic characterization of two bacterial artificial chromosome clones derived from a single DNA source of the very virulent gallid herpesvirus-2 strain C12/130
Authors: Spatz Stephen J. , Smith Lorraine P. , Baigent Susan J. , Petherbridge Lawrence , Nair Venugopal
Published: March 2011

The identification of specific genetic changes associated with differences in the pathogenicity of Marek's disease virus strains (GaHV-2) has been a formidable task due to the large number of mutations in mixed-genotype populations within DNA preparations. Very virulent UK isolate C12/130 induces extensive lymphoid atrophy, neurological manifestations and early mortality in young birds. We have recently reported the construction of several independent full-length bacterial artificial chromosome (BAC) clones of C12/130 capable of generating fully infectious viruses with significant differences in their pathogenicity profiles. Two of these clones (vC12/130-10 and vC12/130-15), which showed differences in virulence relative to each other and to the parental strain, had similar replication kinetics both in vitro and in
vivo in spite of the fact that vC12/130-15 was attenuated. To investigate the possible reasons for this, the nucleotide sequences of both clones were determined. Sequence analysis of the two genomes identified mutations within eight genes. A single 494 bp insertion was identified within the genome of the virulent vC12/130-10 clone. Seven non-synonymous substitutions distinguished virulent vC12/130-10 from that of attenuated vC12/130-15. By sequencing regions of parental DNA that differed between the two BAC clones, we confirmed that C12/130 does contain these mutations in varying proportions. Since the individual reconstituted BAC clones were functionally attenuated in vivo and derived from a single DNA source of phenotypically very virulent C12/130, this suggests that the C12/130 virus population exists as a collection of mixed genotypes.
High-resolution phylogenetics and phylogeography of human immunodeficiency virus type 1 subtype C epidemic in South America
Authors: Véras Nazle Mendonca Collaço , Gray Rebecca R. , de Macedo Brígido Luis Fernando , Rodrigues Rosângela , Salemi Marco
Published: March 2011

Human immunodeficiency virus type 1 subtype C (HIV-1C) represents 30–65 % of HIV infections in southern Brazil, and isolated cases of HIV-1C infection have also been reported in Argentina, Uruguay, Paraguay and Venezuela. Phylogenetic studies have suggested that the Brazilian subtype C epidemic was initiated by the introduction of closely related strains. Nevertheless, because of sampling limitations, the point of entry and the timing of subtype C introduction into Brazil, as well as the origin of the founder lineage, remain controversial. The present study investigated the origin, spread and phylogeography of HIV-1C in South America. Phylogenetic analysis showed a well-supported monophyletic clade including all available strains from Brazil, Uruguay and Argentina. Only one lineage from Venezuela was unrelated to the epidemic involving the other three countries. Molecular clock and likelihood mapping analysis showed that HIV-1C introduction in Brazil dated back to the period 1960–1970, much earlier than previously thought, and was followed by a nearly simultaneous star-like outburst of viral lineages, indicating a subsequent rapid spread. Phylogeographic patterns suggested Paraná or Rio Grande do Sul as the possible entrance points of subtype C and an asymmetrical gene flow from Paraná to Sao Paulo, Santa Catarina and Rio Grande do Sul, as well as from Rio Grande do Sul to Sao Paulo fostered by the strong inter-connectivity between population centres in southern Brazil. The study illustrates how coupling phylogeography inference with geographical information system data is critical to understand the origin and dissemination of viral pathogens and potentially predict their future spread.
DNA-dependent protein kinase interacts functionally with the RNA polymerase II complex recruited at the human immunodeficiency virus (HIV) long terminal repeat and plays an important role in HIV gene expression
Authors: Tyagi Shilpi , Ochem Alex , Tyagi Mudit
Published: March 2011

DNA-dependent protein kinase (DNA-PK), a nuclear protein kinase that specifically requires association with DNA for its kinase activity, plays important roles in the regulation of different DNA transactions, including transcription, replication and DNA repair, as well as in the maintenance of telomeres. Due to its large size, DNA-PK is also known to facilitate the activities of other factors by providing the docking platform at their site of action. In this study, by running several chromatin immunoprecipitation assays, we demonstrate the parallel distribution of DNA-PK with RNA polymerase II (RNAP II) along the human immunodeficiency virus (HIV) provirus before and after activation with tumour necrosis factor alpha. The association between DNA-PK and RNAP II is also long-lasting, at least for up to 4 h (the duration analysed in this study). Knockdown of endogenous DNA-PK using specific small hairpin RNAs expressed from lentiviral vectors resulted in significant reduction in HIV gene expression and replication, demonstrating the importance of DNA-PK for HIV gene expression. Sequence analysis of the HIV-1 Tat protein revealed three potential target sites for phosphorylation by DNA-PK and, by using kinase assays, we confirmed that Tat is an effective substrate of DNA-PK. Through peptide mapping, we found that two of these three potential phosphorylation sites are recognized and phosphorylated by DNA-PK. Mutational studies on the DNA-PK target sites of Tat further demonstrated the functional significance of the Tat–DNA-PK interaction. Thus, overall our results clearly demonstrate the functional interaction between DNA-PK and RNAP II during HIV transcription.
Effects of N-linked glycosylation of the fusion protein on replication of human metapneumovirus in vitro and in mouse lungs
Authors: Zhang Jinhui , Dou Ying , Wu Junfeng , She Weiwei , Luo Lizhong , Zhao Yao , Liu Ping , Zhao Xiaodong
Published: March 2011

The fusion (F) protein is an important membrane glycoprotein necessary for cellular entry and replication of human metapneumovirus (hMPV). Selective prevention of N-linked glycosylation may compromise the catalytic and fusion functions of the F protein. By using site-directed mutagenesis and reverse genetics, recombinant mutant viruses lacking one or two N-linked glycosylation sites in the F protein were constructed. M1, which lacked glycosylation at position 57 of the F protein, had slightly compromised replication, whereas M2 and M4, which lacked glycosylation at position(s) 172 or 57 and 172, respectively, showed profound impairment of replication when compared with wild-type (WT) NL/1/00–GFP virus in both Vero E6 cells and mouse lungs. M2 was less fit than WT virus in vitro and in immunocompromised mouse lungs. The F proteins of WT and mutant viruses were similarly expressed on the infected cell membrane, while the activated fusion protein subunits, F1 of M2 and M4, were produced in lower quantities compared with those of WT and M1 virus. The mutated viruses lacking N-linked glycosylation at position 353, either individually or together with other sites, could not be recovered. Thus, N-linked glycosylation may be involved in the catalysis of the fusion protein from F0 to F1 and F2, which is critical for fusion function. Strategies targeting N-linked glycosylation may be helpful for developing attenuated live vaccines or antiviral drugs for hMPV.
Recruitment of cyclin-dependent kinase 9 to nuclear compartments during cytomegalovirus late replication: importance of an interaction between viral pUL69 and cyclin T1
Authors: Feichtinger Sabine , Stamminger Thomas , Müller Regina , Graf Laura , Klebl Bert , Eickhoff Jan , Marschall Manfred
Published: March 2011

Cyclin-dependent protein kinases (CDKs) are important regulators of cellular processes and are functionally integrated into the replication of human cytomegalovirus (HCMV). Recently, a regulatory impact of CDK activity on the viral mRNA export factor pUL69 was shown. Here, specific aspects of the mode of interaction between CDK9/cyclin T1 and pUL69 are described. Intracellular localization was studied in the presence of a novel selective CDK9 inhibitor, R22, which exerts anti-cytomegaloviral activity in vitro. A pronounced R22-induced formation of nuclear speckled aggregation of pUL69 was demonstrated. Multi-labelling confocal laser-scanning microscopy revealed that CDK9 and cyclin T1 co-localized perfectly with pUL69 in individual speckles. The effects were similar to those described recently for the broad CDK inhibitor roscovitine. Co-immunoprecipitation and yeast two-hybrid analyses showed that cyclin T1 interacted with both CDK9 and pUL69. The interaction region of pUL69 for cyclin T1 could be attributed to aa 269–487. Moreover, another component of CDK inhibitor-induced speckled aggregates was identified with RNA polymerase II, supporting earlier reports that strongly suggested an association of pUL69 with transcription complexes. Interestingly, when using a UL69-deleted recombinant HCMV, no speckled aggregates were formed by CDK inhibitor treatment. This indicated that pUL69 is the defining component of aggregates and generally may represent a crucial viral interactor of cyclin T1. In conclusion, these data emphasize that HCMV inter-regulation with CDK9/cyclin T1 is at least partly based on a pUL69–cylin T1 interaction, thus contributing to the importance of CDK9 for HCMV replication.
The PI3K/Akt pathway is involved in early infection of some exogenous avian leukosis viruses
Authors: Feng Shao-zhen , Cao Wei-sheng , Liao Ming
Published: March 2011

Avian leukosis virus (ALV) is an enveloped and oncogenic retrovirus. Avian leukosis caused by the members of ALV subgroups A, B and J has become one of the major problems challenging the poultry industry in China. However, the cellular factors such as signal transduction pathways involved in ALV infection are not well defined. In this study, our data demonstrated that ALV-J strain NX0101 infection in primary chicken embryo fibroblasts or DF-1 cells was correlated with the activity and phosphorylation of Akt. Akt activation was initiated at a very early stage of infection independently of NX0101 replication. The specific phosphatidylinositol 3-kinase (PI3K) inhibitors LY294002 or wortmannin could suppress Akt phosphorylation, indicating that NX0101-induced Akt phosphorylation is PI3K-dependent. ALV-A strain GD08 or ALV-B strain CD08 infection also demonstrated a similar profile of PI3K/Akt activation. Treatment of DF-1 cells with the drug 5-(N, N-hexamethylene) amiloride that inhibits the activity of chicken Na+/H+ exchanger type 1 significantly reduced Akt activation induced by NX0101, but not by GD08 and CD08. Akt activation triggered by GD08 or CD08 was abolished by clathrin-mediated endocytosis inhibitor chlorpromazine. Receptor-mediated endocytosis inhibitor dansylcadaverine had a negligible effect on all ALV-induced Akt phosphorylation. Moreover, viral replication of ALV was suppressed by LY294002 in a dose-dependent manner, which was due to the inhibition of virus infection by LY294002. These data suggest that the activation of the PI3K/Akt signalling pathway by exogenous ALV infection plays an important role in viral entry, yet the precise mechanism remains under further investigation.
MicroRNA programs in normal and aberrant stem and progenitor cells
Authors: Arnold Christopher P. , Tan Ruoying , Zhou Baiyu , Yue Si-Biao , Schaffert Steven , Biggs Joseph R. , Doyonnas Regis , Lo Miao-Chia , Perry John M. , Renault Valérie M. , Sacco Alessandra , Somervaille Tim , Viatour Patrick , Brunet Anne , Cleary Michael L. , Li Linheng , Sage Julien , Zhang Dong-Er , Blau Helen M. , Chen Caifu , Chen Chang-Zheng
Published: March 2011

Emerging evidence suggests that microRNAs (miRNAs), an abundant class of ∼22-nucleotide small regulatory RNAs, play key roles in controlling the post-transcriptional genetic programs in stem and progenitor cells. Here we systematically examined miRNA expression profiles in various adult tissue-specific stem cells and their differentiated counterparts. These analyses revealed miRNA programs that are common or unique to blood, muscle, and neural stem cell populations and miRNA signatures that mark the transitions from self-renewing and quiescent stem cells to proliferative and differentiating progenitor cells. Moreover, we identified a stem/progenitor transition miRNA (SPT-miRNA) signature that predicts the effects of genetic perturbations, such as loss of PTEN and the Rb family, AML1-ETO9a expression, and MLL-AF10 transformation, on self-renewal and proliferation potentials of mutant stem/progenitor cells. We showed that some of the SPT-miRNAs control the self-renewal of embryonic stem cells and the reconstitution potential of hematopoietic stem cells (HSCs). Finally, we demonstrated that SPT-miRNAs coordinately regulate genes that are known to play roles in controlling HSC self-renewal, such as Hoxb6 and Hoxa4. Together, these analyses reveal the miRNA programs that may control key processes in normal and aberrant stem and progenitor cells, setting the foundations for dissecting post-transcriptional regulatory networks in stem cells.
HR outsourcing and service quality: theoretical framework and empirical evidence
Authors: Braun Irene , Pull Kerstin , Alewell Dorothea , Störmer Susi , Thommes Kirsten
Published: April 2011

Purpose

The purpose of this article is to analyse the relationship between HR outsourcing and service quality by focusing on motivational and incentive aspects.

Design/methodology/approach

The paper applies a game‐theoretic model of procurement decisions allowing for variable degrees of vertical integration and confronts the implications of its analysis with HR outsourcing data on a large sample of German firms.

Findings

The paper presents evidence for HR service quality being generally higher when procured from an external instead of an in‐house provider. Furthermore, the relationship between HR outsourcing and service quality is considerably stronger if the provided services are complex and if the potential for monitoring an internal provider is low.

Practical implications

The findings have immediate practical implications concerning the make‐or‐buy decision of HR services: the more complex the HR service under consideration and the lower the potential to monitor its in‐house provision, the more attractive is the external provision of HR services.

Originality/value

While most of the literature on HR outsourcing is based on transaction cost theory or follows a resource‐based approach, this paper uses a game‐theoretic model to analyse the make‐or‐buy decision of HR services, allowing the incentives of an internal or external provider to deliver high‐quality services to be focused on. Furthermore, for the empirical analysis the paper uses an original data set comprising more than 1,000 German firms.
An off‐line programming system for flexible drilling of aircraft wing structures
Authors: Zou Cheng , Liu Jihong
Published: April 2011

Purpose

Drilling is an important operation in aircraft wing assembly. In order to enhance this operation, automated machines are used. The purpose of this paper is to propose an off‐line programming system to generate NC code effectively and accurately for a five‐axis NC drilling machine applied in aircraft wing flexible assembly.

Design/methodology/approach

The NC program is divided into three hierarchical parts to correspond, respectively, to the whole wing, single rib and single hole. The programming procedure for such three‐layer wing structures is detailed, which includes product model modification, NC program generation and post‐processing.

Findings

By demonstration, the implemented system is proved to increase the efficiency and correctness of NC programming, and the generated program performed well on a flexible wing drilling system.

Research limitations/implications

The system can only program for automated drilling machine at present, however with further development both automated drilling and riveting machine in aircraft wing assembly can be programmed by this system. Another development might make this system universal for different machineries and other aircraft components.

Originality/value

The paper indicates a new way to program for rapid wing flexible drilling, and the generated NC program is more adaptable and easier to update for various aircraft wing structures.
Mapping the spatial patterns of public procurement
Authors: Cabras Ignazio
Published: April 2011

Purpose

The purpose of this paper is to investigate public procurement activity within the Cumbria County Council and its effects on the local supply chain. The paper seeks to identify the role of public procurement within the county, in relation to the propensity for income retention (or leakage) at local level. In addition, the paper seeks to consider issues related to public procurement in peripheral and rural areas, with particular reference to small and medium businesses operating in Cumbria, and to provide a spatial analysis of money flows at regional and national level.

Design/methodology/approach

Quantitative data, from primary and secondary sources, were obtained from a survey questionnaire conducted among the Council's suppliers and from SpikesCavell, an agency specializing in collecting procurement data, respectively. The study focuses on public sector suppliers. It analyses suppliers' attributes and characteristics such as size, location and sector of activity are used in order to explore suppliers' patterns of spend in relation to inward and outward cash‐flows within the County. Additionally, the paper explores the effects of the local authority's procurement in terms of advantages/disadvantages for the local supply chain.

Findings

The paper highlights the ability of competitive tendering systems to achieve cash saving and reduce wastage; but questions whether the adoption of such systems in the public sector produces positive economic effects on the local supply chain in peripheral and remote areas.

Originality/value

There is a lack of research on the impact of public procurement at regional and sub‐regional level and its significance as a source of income and businesses operating within local supply chains. This paper seeks to contribute to filling this research gap by presenting and analysing data associated with procurement activity within a peripheral local authority.
Public sector reform in Kazakhstan: issues and perspectives
Authors: Bhuiyan Shahjahan H. , Amagoh Francis
Published: April 2011

Purpose

This paper aims to investigate public sector reform (PSR) initiatives in Kazakhstan, and how such reform efforts have helped the government to be more responsive to the needs and demands of the citizens.

Design/methodology/approach

The paper examined four key PSR initiatives: decentralization, Civil Service reform, e‐governance, and civil society in improving governance in post‐Soviet Kazakhstan.

Findings

In light of Kazakhstan government's efforts to reform the public sector, the study finds that substantial progress has been made in improving its service delivery systems and enhancing good governance.

Research limitations/implications

The study is an investigation of four out of several PSR initiatives aimed at improving good governance.

Originality/value

The study provides insights into how aspects of PSR can be fundamentally useful in promoting good governance.
Establishing ex ante public construction supply chain guidelines in the public procurement of schools' estate
Authors: McAdam Rodney , Hazlett Shirley‐Ann , Johnston Sean
Published: April 2011

Purpose

The purpose of this study is to explore the formative development of construction supply chain guidelines or proposals in a UK region's schools' estates procurement process to more effectively address a forthcoming increase in investment.

Design/methodology/approach

The research approach is interpretive. Using an action research approach, repeated semi‐structured interviews and focus groups with a range of stakeholders are conducted.

Findings

The current construction supply chain in schools' estate procurement has many difficulties, not least given the highly fragmented and disconnected nature of the projects. Synergies are being missed and there is little or no continuous improvement. Drawing on these findings, the research iteratively develops a range of proposals and guidelines to address this situation.

Research limitations/implications

This research adds weight to the current focus on pressing for change in the construction industry. It presents potentially valuable insights into the benefits of partnering arrangements and how these might usefully be incorporated into schools' estate supply chain.

Practical implications

A set of guidelines is developed to guide the public procurement of schools' estate in a UK region. These guidelines are set within the context of the Modernising and Rethinking Construction agenda.

Originality/value

The action research approach enabled the researchers to gain a unique insight into how public procurement and contractor personnel interact and to establish effective practical guidelines.
Ready for the future? Universities' capabilities to strategically manage their intellectual capital
Authors: Elena‐Pérez Susana , Saritas Ozcan , Pook Katja , Warden Campbell
Published: April 2011

Purpose

This paper aims to explore the possibilities of combining foresight techniques and intellectual capital management, as two approaches of participatory strategic management, in higher education institutions. The objective is to generate concrete benefits for prospective strategic management in the academic sector. It also aims to focus on how it may be possible for universities to address the challenges of major change management programmes by implementing foresight and intellectual capital management models.

Design/methodology/approach

The paper reviews recent literature both on conceptual issues and experiences in relation to foresight and intellectual capital. The paper presents an ongoing project focused on the development of a vision for the future of the higher education system in Romania and a frame to differentiate Romanian universities.

Findings

A proposal of an integrated use of foresight and intellectual capital management for universities is suggested. The case study presented illustrates how foresight provides an excellent approach to address the question of how to develop a shared vision of the future and jointly define a strategy to best adapt an organization to the new context, and intellectual capital management models play a role in strategic management, resource allocation and monitoring of objectives and organization performance.

Practical implications

The issues addressed in the paper could provide the starting point for better integration of strategic management in higher education institutions.

Originality/value

The paper explores two concepts closely related but that have not been analysed together: the relationship between Intellectual capital approaches and foresight.