bluuebunny/crossref_metadata_2025 huggingface dataset:
Analytical solution for pulsatile viscous flow in a straight elliptic annulus and application to the motion of the cerebrospinal fluid
Authors: Gupta Sumeet , Poulikakos Dimos , Kurtcuoglu Vartan
Published: October 2008

We present here the analytical solution of transient, laminar, viscous flow of an incompressible, Newtonian fluid driven by a harmonically oscillating pressure gradient in a straight elliptic annulus. The analytical formulation is based on the exact solution of the governing fluid flow equations known as Navier–Stokes equations. We validate the analytical solution using a finite-volume computational fluid dynamics approach. As the analytical solution includes Mathieu and modified Mathieu functions, we also present a stepwise procedure for their evaluation for large complex arguments typically associated with viscous flows. We further outline the procedure for evaluating the associated Fourier coefficients and their eigenvalues. We finally apply the analytical solution to investigate the cerebrospinal fluid flow in the human spinal cavity, which features a shape similar to an elliptic annulus.
Evolution of linearly polarized electromagnetic pulses in laser plasmas
Authors: Borhanian J. , Sobhanian S. , Kourakis I. , Esfandyari-Kalejahi A.
Published: October 2008

An analytical and numerical investigation is presented of the behavior of a linearly polarized electromagnetic pulse as it propagates through a plasma. Considering a weakly relativistic regime, the system of one-dimensional fluid-Maxwell equations is reduced to a generalized nonlinear Schrödinger type equation, which is solved numerically using a split step Fourier method. The spatio-temporal evolution of an electromagnetic pulse is investigated. The evolution of the envelope amplitude of density harmonics is also studied. An electromagnetic pulse propagating through the plasma tends to broaden due to dispersion, while the nonlinear frequency shift is observed to slow down the pulse at a speed lower than the group velocity. Such nonlinear effects are more important for higher density plasmas. The pulse broadening factor is calculated numerically, and is shown to be related to the background plasma density. In particular, the broadening effect appears to be stronger for dense plasmas. The relation to existing results on electromagnetic pulses in laser plasmas is discussed.
Diffusive motions in liquid medium-chain n-alkanes as seen by quasielastic time-of-flight neutron spectroscopy
Authors: Unruh Tobias , Smuda Christoph , Busch Sebastian , Neuhaus Jürgen , Petry Winfried
Published: October 2008

Different diffusive motions in liquid C32H66 on a picosecond time scale could be disentangled by resolution resolved quasielastic time-of-flight neutron spectroscopy (QENS). It is demonstrated that at all observation times, the dominating motion causes a Q2 proportionality of the QENS signal, which indicates a Fickian diffusion mechanism. The observed motions can be characterized by an observation time dependent apparent diffusion coefficient Da(to), which is up to one order of magnitude larger than the molecular self-diffusion coefficient Ds. By comparison with molecular dynamics simulations, the identified motions are attributed to displacements of hydrogen atoms reflecting not only global but also local molecular trajectories. Despite the rodlike shape of the molecules, the center of mass diffusion was found to be essentially isotropic. A coherent picture of the diffusional processes ranging from the fast tumbling of CH2 groups to the slow long range molecular diffusion is presented.
Numerical study of an original device to generate compressible flow in microchannels
Authors: Giordano J. , Parisse J. D. , Perrier P.
Published: October 2008

This study is devoted to the design of an experimental device to generate shock waves in a micropipe. Indeed, the recent advances in the microfluidics of gas lead the scientific community to the question of scaling law in supersonic regime. Thus, in this paper, we simulate the flow induced by the opening of a small solenoid valve to know if it is able to generate a minishock wave. This shock wave moving in an intermediate pipe could be transmitted into a micro one. In this work, we focus on the flow in the intermediate pipe and on the properties of the transmitted wave into the microchannel. Three geometry of convergent between intermediate and micropipe are investigated. We have compared the results of our simulation to the classical analytical models dealing with shock tubes. After presenting the geometries of the study case, we give the characteristics of our numerical approach, and then we describe our main results. In a last section, the flow generated by the valve used in free jet regime is described.
Closed source experimental system for soft x-ray spectroscopy of radioactive materials
Authors: Modin A. , Butorin S. M. , Vegelius J. , Olsson A. , Englund C.-J. , Andersson J. , Werme L. , Nordgren J. , Käämbre T. , Skarnemark G. , Burakov B. E.
Published: October 2008

An instrumental and experimental setup for soft x-ray spectroscopy meeting the requirements of a closed source for radioactivity is described. The system consists of a vacuum sealed cell containing the sample, mounted on a tubing system to ensure compatibility with most standard manipulators. The soft x rays penetrate a thin x-ray window separating the interior of the cell from the vacuum in the experimental chamber. Our first results for single crystal PuO2 confirm the feasibility of experiments using the setup. The results are consistent with results of first principles calculations and previously recorded spectra obtained using a standard open source setup. The results show that the closed source experimental system can be used to collect valuable experimental data from radioactive materials.
Study tracks the changes in a vision protein as fish evolved
Authors: Day Charles
Published: October 2008

Genetic engineering, statistics, and spectroscopy are combined to address a fundamental question in biology.
US falters on commitments to international science projects
Authors: Kramer David
Published: October 2008

ITER and the ILC are the latest in a series of big-ticket science collaborations to fall victim to the US political process.
India revives neutrino research
Authors: Feder Toni
Published: October 2008

Some 45 years after the discovery in India of atmospheric neutrinos, a new lab and detector could put the country back on the international neutrino research scene.
Special report: Science issues are prominent in this year’s presidential race
Authors: Kramer David
Published: October 2008

Barack Obama responds to the quadrennial Physics Today questionnaire on science policy matters; John McCain declines invitations to participate.
The larger world of nano
Authors: Mody Cyrus C. M.
Published: October 2008

Research in the social sciences and humanities can help scientists and policymakers to better understand the nanotechnology enterprise and to make it more transparent to an enthusiastic but cautious public.
When fermions become bosons: Pairing in ultracold gases
Authors: Sá de Melo Carlos A. R.
Published: October 2008

The unprecedented control over the interactions and pairing of ultracold fermionic atoms provides insight into exotic strongly correlated phenomena and illuminates the physics of superfluidity in metals, nuclei, and neutron stars.
Histone deacetylase SIRT1 modulates neuronal differentiation by its nuclear translocation
Authors: Hisahara Shin , Chiba Susumu , Matsumoto Hiroyuki , Tanno Masaya , Yagi Hideshi , Shimohama Shun , Sato Makoto , Horio Yoshiyuki
Published: October 2008

Neural precursor cells (NPCs) differentiate into neurons, astrocytes, and oligodendrocytes in response to intrinsic and extrinsic changes. Notch signals maintain undifferentiated NPCs, but the mechanisms underlying the neuronal differentiation are largely unknown. We show that SIRT1, an NAD
+
-dependent histone deacetylase, modulates neuronal differentiation. SIRT1 was found in the cytoplasm of embryonic and adult NPCs and was transiently localized in the nucleus in response to differentiation stimulus. SIRT1 started to translocate into the nucleus within 10 min after the transfer of NPCs into differentiation conditions, stayed in the nucleus, and then gradually retranslocated to the cytoplasm after several hours. The number of neurospheres that generated Tuj1
+
neurons was significantly decreased by pharmacological inhibitors of SIRT1, dominant-negative SIRT1 and
SIRT1-siRNA
, whereas overexpression of SIRT1, but not that of cytoplasm-localized mutant SIRT1, enhanced neuronal differentiation and decreased Hes1 expression. Expression of
SIRT1-siRNA
impaired neuronal differentiation and migration of NPCs into the cortical plate in the embryonic brain. Nuclear receptor corepressor (N-CoR), which has been reported to bind SIRT1, promoted neuronal differentiation and synergistically increased the number of Tuj1
+
neurons with SIRT1, and both bound the
Hes1
promoter region in differentiating NPCs.
Hes1
transactivation by Notch1 was inhibited by SIRT1 and/or N-CoR. Our study indicated that SIRT1 is a player of repressing Notch1-Hes1 signaling pathway, and its transient translocation into the nucleus may have a role in the differentiation of NPCs.
The HDAC inhibitor 4b ameliorates the disease phenotype and transcriptional abnormalities in Huntington's disease transgenic mice
Authors: Thomas Elizabeth A. , Coppola Giovanni , Desplats Paula A. , Tang Bin , Soragni Elisabetta , Burnett Ryan , Gao Fuying , Fitzgerald Kelsey M. , Borok Jenna F. , Herman David , Geschwind Daniel H. , Gottesfeld Joel M.
Published: October 2008

Transcriptional dysregulation has emerged as a core pathologic feature of Huntington's disease (HD), one of several triplet-repeat disorders characterized by movement deficits and cognitive dysfunction. Although the mechanisms contributing to the gene expression deficits remain unknown, therapeutic strategies have aimed to improve transcriptional output via modulation of chromatin structure. Recent studies have demonstrated therapeutic effects of commercially available histone deacetylase (HDAC) inhibitors in several HD models; however, the therapeutic value of these compounds is limited by their toxic effects. Here, beneficial effects of a novel pimelic diphenylamide HDAC inhibitor, HDACi 4b, in an HD mouse model are reported. Chronic oral administration of HDACi 4b, beginning after the onset of motor deficits, significantly improved motor performance, overall appearance, and body weight of symptomatic R6/2
300Q
transgenic mice. These effects were associated with significant attenuation of gross brain-size decline and striatal atrophy. Microarray studies revealed that HDACi 4b treatment ameliorated, in part, alterations in gene expression caused by the presence of mutant huntingtin protein in the striatum, cortex, and cerebellum of R6/2
300Q
transgenic mice. For selected genes, HDACi 4b treatment reversed histone H3 hypoacetylation observed in the presence of mutant huntingtin, in association with correction of mRNA expression levels. These findings suggest that HDACi 4b, and possibly related HDAC inhibitors, may offer clinical benefit for HD patients and provide a novel set of potential biomarkers for clinical assessment.
Quantitative proteomic analysis of primary neurons reveals diverse changes in synaptic protein content infmr1knockout mice
Authors: Liao Lujian , Park Sung Kyu , Xu Tao , Vanderklish Peter , Yates John R.
Published: October 2008

Fragile X syndrome (FXS) is a common inherited form of mental retardation that is caused, in the vast majority of cases, by the transcriptional silencing of a single gene,fmr1. The encoded protein, FMRP, regulates mRNA translation in neuronal dendrites, and it is thought that changes in translation-dependent forms of synaptic plasticity lead to many symptoms of FXS. However, little is known about the potentially extensive changes in synaptic protein content that accompany loss of FMRP. Here, we describe the development of a high-throughput quantitative proteomic method to identify differences in synaptic protein expression between wild-type andfmr1−/− mouse cortical neurons. The method is based on stable isotope labeling by amino acids in cell culture (SILAC), which has been used to characterize differentially expressed proteins in dividing cells, but not in terminally differentiated cells because of reduced labeling efficiency. To address the issue of incomplete labeling, we developed a mathematical method to normalize protein ratios relative to a reference based on the labeling efficiency. Using this approach, in conjunction with multidimensional protein identification technology (MudPIT), we identified >100 proteins that are up- or down-regulated. These proteins fall into a variety of functional categories, including those regulating synaptic structure, neurotransmission, dendritic mRNA transport, and several proteins implicated in epilepsy and autism, two endophenotypes of FXS. These studies provide insights into the potential origins of synaptic abnormalities in FXS and a demonstration of a methodology that can be used to explore neuronal protein changes in neurological disorders.
Energetics of peptide (pHLIP) binding to and folding across a lipid bilayer membrane
Authors: Reshetnyak Yana K. , Andreev Oleg A. , Segala Michael , Markin Vladislav S. , Engelman Donald M.
Published: October 2008

The pH low-insertion peptide (pHLIP) serves as a model system for peptide insertion and folding across a lipid bilayer. It has three general states: (I) soluble in water or (II) bound to the surface of a lipid bilayer as an unstructured monomer, and (III) inserted across the bilayer as a monomeric α-helix. We used fluorescence spectroscopy and isothermal titration calorimetry to study the interactions of pHLIP with a palmitoyloleoylphosphatidylcholine (POPC) lipid bilayer and to calculate the transition energies between states. We found that the Gibbs free energy of binding to a POPC surface at low pHLIP concentration (state I–state II transition) at 37°C is approximately −7 kcal/mol near neutral pH and that the free energy of insertion and folding across a lipid bilayer at low pH (state II–state III transition) is nearly −2 kcal/mol. We discuss a number of related thermodynamic parameters from our measurements. Besides its fundamental interest as a model system for the study of membrane protein folding, pHLIP has utility as an agent to target diseased tissues and translocate molecules through the membrane into the cytoplasm of cells in environments with elevated levels of extracellular acidity, as in cancer and inflammation. The results give the amount of energy that might be used to move cargo molecules across a membrane.
The role of the C terminus of the SNARE protein SNAP-25 in fusion pore opening and a model for fusion pore mechanics
Authors: Fang Qinghua , Berberian Khajak , Gong Liang-Wei , Hafez Ismail , Sørensen Jakob B. , Lindau Manfred
Published: October 2008

Formation of a fusion pore between a vesicle and its target membrane is thought to involve the so-called SNARE protein complex. However, there is no mechanistic model explaining how the fusion pore is opened by conformational changes in the SNARE complex. It has been suggested that C-terminal zipping triggers fusion pore opening. A SNAP-25 mutant named SNAP-25Δ9 (lacking the last nine C-terminal residues) should lead to a less-tight C-terminal zipping. Single exocytotic events in chromaffin cells expressing this mutant were characterized by carbon fiber amperometry and cell-attached patch capacitance measurements. Cells expressing SNAP-25Δ9 displayed smaller amperometric “foot-current” currents, reduced fusion pore conductances, and lower fusion pore expansion rates. We propose that SNARE/lipid complexes form proteolipid fusion pores. Fusion pores involving the SNAP-25Δ9 mutant will be less tightly zipped and may lead to a longer fusion pore structure, consistent with the observed decrease of fusion pore conductance.
Single-particle kinetics of influenza virus membrane fusion
Authors: Floyd Daniel L. , Ragains Justin R. , Skehel John J. , Harrison Stephen C. , van Oijen Antoine M.
Published: October 2008

Membrane fusion is an essential step during entry of enveloped viruses into cells. Conventional fusion assays are generally limited to observation of ensembles of multiple fusion events, confounding more detailed analysis of the sequence of the molecular steps involved. We have developed an
in vitro
, two-color fluorescence assay to monitor kinetics of single virus particles fusing with a target bilayer on an essentially fluid support. Analysis of lipid- and content-mixing trajectories on a particle-by-particle basis provides evidence for multiple, long-lived kinetic intermediates leading to hemifusion, followed by a single, rate-limiting step to pore formation. We interpret the series of intermediates preceding hemifusion as a result of the requirement that multiple copies of the trimeric hemagglutinin fusion protein be activated to initiate the fusion process.
Treatment approaches for dual diagnosis clients in England
Authors: SCHULTE SABRINA J. , MEIER PETRA S. , STIRLING JOHN , BERRY MIKE
Published: October 2008

Introduction. Dual diagnosis (DD, co‐occurrence of substance use and mental health problems) prevalence data in England are limited to specific regions and reported rates vary widely. Reliable information on actual service provision for dual diagnosis clients has not been collated. Thus a national survey was carried out to estimate dual diagnosis prevalence in treatment populations and describe the service provision available for this client population in drug/alcohol (DAS) and mental health services (MHS). Design. A questionnaire was sent to managers of 706 DAS and 2374 MHS. Overall, 249 (39%) DAS and 493 (23%) MHS participated in the survey. Results. In both DAS and MHS, around 32% of clients were estimated to have dual diagnosis problems. However, fewer than 50% of services reported assessing clients for both problem areas. Regarding specific treatment approaches, most services (DAS: 88%, MHS: 87%) indicated working jointly with other agencies. Significantly fewer services used joint protocols (DAS: 55%, MHS: 48%) or shared care arrangements, including access to external drug/alcohol or mental health teams (DAS: 47%, MHS: 54%). Only 25% of DAS and 17% of MHS employed dual diagnosis specialists. Conclusions. Dual diagnosis clients constitute a substantial proportion of clients in both DAS and MHS in England. Despite recent policy initiatives, joint working approaches tend to remain unstructured.
Centrism in Italian politics
Authors: Donovan Mark , Newell James L.
Published: October 2008

Recent developments, especially the outcome of the 2008 election, appear to point to the definitive sidelining of centrism in Italian politics. In reality, it remains significant – not least because of the opportunities for influence all bipolar systems give to parties not of the left or right, and because of the possible consequences of reassessments of centrism's historical significance. The term itself has been used to denote a kind of political outlook or ideology and, consequently, a kind of political strategy. A number of party and elite-level strategies called centrist are identified; one of these – transformism – has roots that stretch back at least to the nineteenth century and is not specifically Italian. Transformism has been variously interpreted. Against this background, the articles in this special issue together evaluate the historical importance of centrism and its current significance for Italian politics. As a governing strategy, centrism is practiced differently now than in the past, but it continues to be practiced.
The ‘centre’ between structure and agency: The Italian case
Authors: Donovan Mark
Published: October 2008

It is widely accepted, among political scientists at least, that Italy's so-called ‘First Republic’ (c.1946–1994) had a tripolar party system while the ‘Second Republic’ has had, at least until 2008, a fragmented bipolar one. A superior conceptualisation of the party system of the ‘First Republic’ was provided by Paolo Farneti, and it remains relevant both for a better understanding of the current party system and for exploring party system dynamics, particularly the relationship between structure and agency in such dynamics. Farneti synthesised Sartori's 1976 analysis of tripolar mechanics with Galli's equally famous analysis of the party system (as one of ‘imperfect bipartism’) in terms of the coexistence of a subordinate bipolar dynamic and a dominant tripolar one. This article argues that the dynamics of the party system in the ‘Second Republic’, or at least the transition to it, can be conceptualised in terms of a dominant bipolar dynamic and a subordinate, tripolar one. This latter dynamic is significant, both empirically and theoretically, despite being subordinate.
From proportional representation to plurality and back: Post-Christian Democratic parties compared
Authors: Di Virgilio Aldo
Published: October 2008

This article analyses the competition strategies adopted by the Christian Democratic (DC) and post-Christian Democratic (post-DC) parties after the electoral reforms of 1993 and 2005. Four main aspects are considered: the significance of cultural (ideological and cognitive) factors in the DC's exit from the political stage; the need to adapt post-DC strategy to bipolarism and the nostalgia for an autonomous centre; the nature and geography of the post-DC vote; and the attitudes of the middle-level elites of the three principal post-DC parties (the DL, the UDEUR and the UDC) vis-à-vis the competitive and strategic decisions they had to make. The article reaches the following conclusions: the post-DC parties share the same cultural orientations and have similar politico-electoral characteristics (a confessional background, the relevance of patronage networks and personalistic vote mobilisation); all three parties adapted, in different ways and with different degrees of success, to the new structure of coalitional bipolarism in the decade 1996–2006; and both research data on the main post-DC parties’ national congress delegates and the evolution of their electoral strategies on the eve of the 2008 elections show that the post-Christian Democrats felt more at home in the centre-left alignment, together with the post-communist PDS-DS, than in the centre-right alignment led by Berlusconi.
From Democrazia Cristiana to Forza Italia and the Popolo della Libertà: Partisan change in Italy
Authors: Paolucci Caterina
Published: October 2008

The general question underlying this article is how much have parties changed in Italy in the transition from the First to the Second Republic? The disintegration of the Christian Democrats (DC) in the early 1990s created a large opening on the centre-right of the political spectrum, which was promptly occupied by Forza Italia (FI). A totally new party organisationally speaking, FI, with its centralisation, its personalisation and its charismatic leadership, marked a clear break with all that the DC had represented in terms of its unrestricted pluralism based on strong factions. However, the franchise model adopted by Berlusconi's party, characterised by the co-existence of unity of command at the top, and differentiated and quasi-autonomous bodies locally, may facilitate the convergence of the parties representing the various interests and outlooks on the centre-right in the newrassemblementparty that is the PdL. Through the latter, and given the new systemic conditions, Italy may achieve a transformation in the nature of the centre from Christian Democratic to conservative, enabling it to integrate most of the political right as well.
The spindle assembly checkpoint is satisfied in the absence of interkinetochore tension during mitosis with unreplicated genomes
Authors: O'Connell Christopher B. , Lončarek Jadranka , Hergert Polla , Kourtidis Antonis , Conklin Douglas S. , Khodjakov Alexey
Published: October 2008

The accuracy of chromosome segregation is enhanced by the spindle assembly checkpoint (SAC). The SAC is thought to monitor two distinct events: attachment of kinetochores to microtubules and the stretch of the centromere between the sister kinetochores that arises only when the chromosome becomes properly bioriented. We examined human cells undergoing mitosis with unreplicated genomes (MUG). Kinetochores in these cells are not paired, which implies that the centromere cannot be stretched; however, cells progress through mitosis. A SAC is present during MUG as cells arrest in response to nocodazole, taxol, or monastrol treatments. Mad2 is recruited to unattached MUG kinetochores and released upon their attachment. In contrast, BubR1 remains on attached kinetochores and exhibits a level of phosphorylation consistent with the inability of MUG spindles to establish normal levels of centromere tension. Thus, kinetochore attachment to microtubules is sufficient to satisfy the SAC even in the absence of interkinetochore tension.
Grapes(Chk1) prevents nuclear CDK1 activation by delaying cyclin B nuclear accumulation
Authors: Royou Anne , McCusker Derek , Kellogg Douglas R. , Sullivan William
Published: October 2008

Entry into mitosis is characterized by a dramatic remodeling of nuclear and cytoplasmic compartments. These changes are driven by cyclin-dependent kinase 1 (CDK1) activity, yet how cytoplasmic and nuclear CDK1 activities are coordinated is unclear. We injected cyclin B (CycB) into Drosophila melanogaster embryos during interphase of syncytial cycles and monitored effects on cytoplasmic and nuclear mitotic events. In untreated embryos or embryos arrested in interphase with a protein synthesis inhibitor, injection of CycB accelerates nuclear envelope breakdown and mitotic remodeling of the cytoskeleton. Upon activation of the Grapes(checkpoint kinase 1) (Grp(Chk1))-dependent S-phase checkpoint, increased levels of CycB drives cytoplasmic but not nuclear mitotic events. Grp(Chk1) prevents nuclear CDK1 activation by delaying CycB nuclear accumulation through Wee1-dependent and independent mechanisms.
The role of GTP binding and hydrolysis at the atToc159 preprotein receptor during protein import into chloroplasts
Authors: Wang Fei , Agne Birgit , Kessler Felix , Schnell Danny J.
Published: October 2008

The majority of nucleus-encoded chloroplast proteins are targeted to the organelle by direct binding to two membrane-bound GTPase receptors, Toc34 and Toc159. The GTPase activities of the receptors are implicated in two key import activities, preprotein binding and driving membrane translocation, but their precise functions have not been defined. We use a combination of in vivo and in vitro approaches to study the role of the Toc159 receptor in the import reaction. We show that atToc159-A864R, a receptor with reduced GTPase activity, can fully complement a lethal insertion mutation in the ATTOC159 gene. Surprisingly, the atToc159-A864R receptor increases the rate of protein import relative to wild-type receptor in isolated chloroplasts by stabilizing the formation of a GTP-dependent preprotein binding intermediate. These data favor a model in which the atToc159 receptor acts as part of a GTP-regulated switch for preprotein recognition at the TOC translocon.
Autonomy and robustness of translocation through the nuclear pore complex: a single-molecule study
Authors: Dange Thomas , Grünwald David , Grünwald Antje , Peters Reiner , Kubitscheck Ulrich
Published: October 2008

All molecular traffic between nucleus and cytoplasm occurs via the nuclear pore complex (NPC) within the nuclear envelope. In this study we analyzed the interactions of the nuclear transport receptors kapα2, kapβ1, kapβ1ΔN44, and kapβ2, and the model transport substrate, BSA-NLS, with NPCs to determine binding sites and kinetics using single-molecule microscopy in living cells. Recombinant transport receptors and BSA-NLS were fluorescently labeled by AlexaFluor 488, and microinjected into the cytoplasm of living HeLa cells expressing POM121-GFP as a nuclear pore marker. After bleaching the dominant GFP fluorescence the interactions of the microinjected molecules could be studied using video microscopy with a time resolution of 5 ms, achieving a colocalization precision of 30 nm. These measurements allowed defining the interaction sites with the NPCs with an unprecedented precision, and the comparison of the interaction kinetics with previous in vitro measurements revealed new insights into the translocation mechanism.
Tre1 GPCR initiates germ cell transepithelial migration by regulating Drosophila melanogaster E-cadherin
Authors: Kunwar Prabhat S. , Sano Hiroko , Renault Andrew D. , Barbosa Vitor , Fuse Naoyuki , Lehmann Ruth
Published: October 2008

Despite significant progress in identifying the guidance pathways that control cell migration, how a cell starts to move within an intact organism, acquires motility, and loses contact with its neighbors is poorly understood. We show that activation of the G protein–coupled receptor (GPCR) trapped in endoderm 1 (Tre1) directs the redistribution of the G protein Gβ as well as adherens junction proteins and Rho guanosine triphosphatase from the cell periphery to the lagging tail of germ cells at the onset of Drosophila melanogaster germ cell migration. Subsequently, Tre1 activity triggers germ cell dispersal and orients them toward the midgut for directed transepithelial migration. A transition toward invasive migration is also a prerequisite for metastasis formation, which often correlates with down-regulation of adhesion proteins. We show that uniform down-regulation of E-cadherin causes germ cell dispersal but is not sufficient for transepithelial migration in the absence of Tre1. Our findings therefore suggest a new mechanism for GPCR function that links cell polarity, modulation of cell adhesion, and invasion.
Ground-state cooling of a nanomechanical resonator via a Cooper-pair box qubit
Authors: Jaehne Konstanze , Hammerer Klemens , Wallquist Margareta
Published: October 2008

In this paper, we present a scheme for ground-state cooling of a flexural mode of a nanomechanical beam incorporated in a loop-shaped Cooper-pair box (CPB) circuit. Via the Lorentz force coupling of the beam motion to circulating CPB-circuit currents, energy is transferred to the CPB qubit which acts as a dissipative two-level system. The cooling process is driven by a detuned gate voltage drive acting on the CPB. We analyze the cooling force spectrum and present analytical expressions for the cooling rate and final occupation number for a wide parameter regime. In particular, we find that cooling is optimized in a strong drive regime, and we present the necessary conditions for ground-state cooling.
BNFinder: exact and efficient method for learning Bayesian networks
Authors: Wilczyński Bartek , Dojer Norbert
Published: October 2008

Motivation: Bayesian methods are widely used in many different areas of research. Recently, it has become a very popular tool for biological network reconstruction, due to its ability to handle noisy data. Even though there are many software packages allowing for Bayesian network reconstruction, only few of them are freely available to researchers. Moreover, they usually require at least basic programming abilities, which restricts their potential user base. Our goal was to provide software which would be freely available, efficient and usable to non-programmers.

Results: We present a BNFinder software, which allows for Bayesian network reconstruction from experimental data. It supports dynamic Bayesian networks and, if the variables are partially ordered, also static Bayesian networks. The main advantage of BNFinder is the use exact algorithm, which is at the same time very efficient (polynomial with respect to the number of observations).

Availability: The software, supplementary information and manual is available at http://bioputer.mimuw.edu.pl/software/bnf/. Besides the availability of the standalone application and the source code, we have developed a web interface to BNFinder application running on our servers. A web tutorial on different options of BNFinder is also available.

Contact:  dojer@mimuw.edu.pl
Smarter clustering methods for SNP genotype calling
Authors: Lin Yan , Tseng George C. , Cheong Soo Yeon , Bean Lora J. H. , Sherman Stephanie L. , Feingold Eleanor
Published: October 2008

Motivation: Most genotyping technologies for single nucleotide polymorphism (SNP) markers use standard clustering methods to ‘call’ the SNP genotypes. These methods are not always optimal in distinguishing the genotype clusters of a SNP because they do not take advantage of specific features of the genotype calling problem. In particular, when family data are available, pedigree information is ignored. Furthermore, prior information about the distribution of the measurements for each cluster can be used to choose an appropriate model-based clustering method and can significantly improve the genotype calls. One special genotyping problem that has never been discussed in the literature is that of genotyping of trisomic individuals, such as individuals with Down syndrome. Calling trisomic genotypes is a more complicated problem, and the addition of external information becomes very important.

Results: In this article, we discuss the impact of incorporating external information into clustering algorithms to call the genotypes for both disomic and trisomic data. We also propose two new methods to call genotypes using family data. One is a modification of the K-means method and uses the pedigree information by updating all members of a family together. The other is a likelihood-based method that combines the Gaussian or beta-mixture model with pedigree information. We compare the performance of these two methods and some other existing methods using simulation studies. We also compare the performance of these methods on a real dataset generated by the Illumina platform (www.illumina.com).

Availability: The R code for the family-based genotype calling methods (SNPCaller) is available to be downloaded from the following website: http://watson.hgen.pitt.edu/register.

Contact:  liny@upmc.edu

Supplementary information:  Supplementary data are available at Bioinformatics online.
When Wall Street Met Main Street: The Quest for an Investors' Democracy and the Emergence of the Retail Investor in the United States, 1890–1930
Authors: Ott Julia Cathleen
Published: October 2008

“When Wall Street met Main Street” recovers the lost history of the American investor and locates the origins of conservative belief in the ability of laissez-faire financialmarkets to provide economic security and justice for all. Bond and stock marketing by the federal government, corporations, and the financial industry is analyzed alongside emerging investor-centered theories of political economy and the relevant debates over economic reform. As early twentieth century securities marketers and their ideological allies promoted investment, they wrestled with the meaning of citizenship and democracy under industrial corporate capitalism. The ideas and institutions examined in this study endured the Crash of 1929, shaping the parameters of New Deal securities market regulation and sustaining opposition to modern liberalism until the present day.
Dynamics of conserved waters in human Hsp90: implications for drug design
Authors: Yan Aixia , Grant Guy H , Graham Richards W
Published: October 2008

The flexibility of a promising protein target, human heat shock protein 90 (Hsp90), is investigated by molecular dynamics simulations. These simulations focus on: (i) the interactions between the protein and conserved water molecules; and (ii) the interactions of the ligand PU3, the conserved water molecules and the protein. This is followed by a virtual screening docking study of the PU3 family of compounds and Hsp90 incorporating several conserved water molecules.
Introduction. Biomolecular simulation
Authors: Mulholland Adrian J
Published: October 2008

‘Everything that living things do can be understood in terms of the jigglings and wigglings of atoms’ as Richard Feynman provocatively stated nearly 50 years ago. But how can we ‘see’ this wiggling and jiggling and understand how it drives biology? Increasingly, computer simulations of biological macromolecules are helping to meet this challenge.
Bayesian coalescent inference of major human mitochondrial DNA haplogroup expansions in Africa
Authors: Atkinson Quentin D , Gray Russell D , Drummond Alexei J
Published: October 2008

Past population size can be estimated from modern genetic diversity using coalescent theory. Estimates of ancestral human population dynamics in sub-Saharan Africa can tell us about the timing and nature of our first steps towards colonizing the globe. Here, we combine Bayesian coalescent inference with a dataset of 224 complete human mitochondrial DNA (mtDNA) sequences to estimate effective population size through time for each of the four major African mtDNA haplogroups (L0–L3). We find evidence of three distinct demographic histories underlying the four haplogroups. Haplogroups L0 and L1 both show slow, steady exponential growth from 156 to 213 kyr ago. By contrast, haplogroups L2 and L3 show evidence of substantial growth beginning 12–20 and 61–86 kyr ago, respectively. These later expansions may be associated with contemporaneous environmental and/or cultural changes. The timing of the L3 expansion—8–12 kyr prior to the emergence of the first non-African mtDNA lineages—together with high L3 diversity in eastern Africa, strongly supports the proposal that the human exodus from Africa and subsequent colonization of the globe was prefaced by a major expansion within Africa, perhaps driven by some form of cultural innovation.
Of mice and (Viking?) men: phylogeography of British and Irish house mice
Authors: Searle Jeremy B , Jones Catherine S , Gündüz İslam , Scascitelli Moira , Jones Eleanor P , Herman Jeremy S , Rambau R. Victor , Noble Leslie R , Berry R.J , Giménez Mabel D , Jóhannesdóttir Fríða
Published: October 2008

The west European subspecies of house mouse (Mus musculus domesticus) has gained much of its current widespread distribution through commensalism with humans. This means that the phylogeography ofM. m. domesticusshould reflect patterns of human movements. We studied restriction fragment length polymorphism (RFLP) and DNA sequence variations in mouse mitochondrial (mt) DNA throughout the British Isles (328 mice from 105 localities, including previously published data). There is a major mtDNA lineage revealed by both RFLP and sequence analyses, which is restricted to the northern and western peripheries of the British Isles, and also occurs in Norway. This distribution of the ‘Orkney’ lineage fits well with the sphere of influence of the Norwegian Vikings and was probably generated through inadvertent transport by them. To form viable populations, house mice would have required large human settlements such as the Norwegian Vikings founded. The other parts of the British Isles (essentially most of mainland Britain) are characterized by house mice with different mtDNA sequences, some of which are also found in Germany, and which probably reflect both Iron Age movements of people and mice and earlier development of large human settlements. MtDNA studies on house mice have the potential to reveal novel aspects of human history.
Testosterone and paternal care in East African foragers and pastoralists
Authors: Muller Martin N , Marlowe Frank W , Bugumba Revocatus , Ellison Peter T
Published: October 2008

The ‘challenge hypothesis’ posits that testosterone facilitates reproductive effort (investment in male–male competition and mate-seeking) at the expense of parenting effort (investment in offspring and mates). Multiple studies, primarily in North America, have shown that men in committed relationships, fathers, or both maintain lower levels of testosterone than unpaired men. Data from non-western populations, however, show inconsistent results. We hypothesized that much of this cross-cultural variation can be attributed to differential investment in mating versus parenting effort, even among married fathers. Here, we directly test this idea by comparing two neighbouring Tanzanian groups that exhibit divergent styles of paternal involvement: Hadza foragers and Datoga pastoralists. We predicted that high levels of paternal care by Hadza fathers would be associated with decreased testosterone in comparison with non-fathers, and that no such difference between fathers and non-fathers would be evident in Datoga men, who provide minimal direct paternal care. Twenty-seven Hadza men and 80 Datoga men between the ages of 17 and 60 provided morning and afternoon saliva samples from which testosterone was assayed. Measurements in both populations confirmed these predictions, adding further support to the hypothesis that paternal care is associated with decreased testosterone production in men.
Between-group competition and human cooperation
Authors: Puurtinen Mikael , Mappes Tapio
Published: October 2008

A distinctive feature of human behaviour is the widespread occurrence of cooperation among unrelated individuals. Explaining the maintenance of costly within-group cooperation is a challenge because the incentive to free ride on the efforts of other group members is expected to lead to decay of cooperation. However, the costs of cooperation can be diminished or overcome when there is competition at a higher level of organizational hierarchy. Here we show that competition between groups resolves the paradigmatic ‘public goods’ social dilemma and increases within-group cooperation and overall productivity. Further, group competition intensifies the moral emotions of anger and guilt associated with violations of the cooperative norm. The results suggest an important role for group conflict in the evolution of human cooperation and moral emotions.
The hierarchy of directional interactions in visual motion processing
Authors: Curran William , Clifford Colin W.G , Benton Christopher P
Published: October 2008

It is well known that context influences our perception of visual motion direction. For example, spatial and temporal context manipulations can be used to induce two well-known motion illusions: direction repulsion and the direction after-effect (DAE). Both result in inaccurate perception of direction when a moving pattern is either superimposed on (direction repulsion), or presented following adaptation to (DAE), another pattern moving in a different direction. Remarkable similarities in tuning characteristics suggest that common processes underlie the two illusions. What is not clear, however, is whether the processes driving the two illusions are expressions of the same or different neural substrates. Here we report two experiments demonstrating that direction repulsion and the DAE are, in fact, expressions of different neural substrates. Our strategy was to use each of the illusions to create a distorted perceptual representation upon which the mechanisms generating the other illusion could potentially operate. We found that the processes mediating direction repulsion did indeed access the distorted perceptual representation induced by the DAE. Conversely, the DAE was unaffected by direction repulsion. Thus parallels in perceptual phenomenology do not necessarily imply common neural substrates. Our results also demonstrate that the neural processes driving the DAE occur at an earlier stage of motion processing than those underlying direction repulsion.
Human-mediated dispersal of seeds over long distances
Authors: Wichmann Matthias C , Alexander Matt J , Soons Merel B , Galsworthy Stephen , Dunne Laura , Gould Robert , Fairfax Christina , Niggemann Marc , Hails Rosie S , Bullock James M
Published: October 2008

Human activities have fundamental impacts on the distribution of species through altered land use, but also directly by dispersal of propagules. Rare long-distance dispersal events have a disproportionate importance for the spread of species including invasions. While it is widely accepted that humans may act as vectors of long-distance dispersal, there are few studies that quantify this process. We studied in detail a mechanism of human-mediated dispersal (HMD). For two plant species we measured, over a wide range of distances, how many seeds are carried by humans on shoes. While over half of the seeds fell off within 5 m, seeds were regularly still attached to shoes after 5 km. Semi-mechanistic models were fitted, and these suggested that long-distance dispersal on shoes is facilitated by decreasing seed detachment probability with distance. Mechanistic modelling showed that the primary vector, wind, was less important as an agent of long-distance dispersal, dispersing seeds less than 250 m. Full dispersal kernels were derived by combining the models for primary dispersal by wind and secondary dispersal by humans. These suggest that walking humans can disperse seeds to very long distances, up to at least 10 km, and provide some of the first quantified dispersal kernels for HMD.
Genomic evidence for a large-Z effect
Authors: Ellegren Hans
Published: October 2008

The ‘large-X effect’ suggests that sex chromosomes play a disproportionate role in adaptive evolution. Theoretical work indicates that this effect may be most pronounced in genetic systems with female heterogamety under both good-genes and Fisher's runaway models of sexual selection (males ZZ, females ZW). Here, I use a comparative genomic approach (alignments of several thousands of chicken–zebra finch–human–mouse–opossum orthologues) to show that avian Z-linked genes are highly overrepresented among those bird–mammalian orthologues that show evidence of accelerated rate of functional evolution in birds relative to mammals; the data suggest a twofold excess of such genes on the Z chromosome. A reciprocal analysis of genes accelerated in mammals found no evidence for an excess of X-linkage. This would be compatible with theoretical expectations for differential selection on sex-linked genes under male and female heterogamety, although the power in this case was not sufficient to statistically show that ‘large-Z’ was more pronounced than ‘large-X’. Accelerated Z-linked genes include a variety of functional categories and are characterized by higher non-synonymous to synonymous substitution rate ratios than both accelerated autosomal and non-accelerated genes. This points at a genomic ‘large-Z effect’, which is widespread and of general significance for adaptive divergence in birds.
Compressibility of water in magma and the prediction of density crossovers in mantle differentiation
Authors: Agee Carl B
Published: October 2008

Hydrous silicate melts appear to have greater compressibility relative to anhydrous melts of the same composition at low pressures (<2 GPa); however, at higher pressures, this difference is greatly reduced and becomes very small at pressures above 5 GPa. This implies that the pressure effect on the partial molar volume of water in silicate melt

is highly dependent on pressure regime. Thus, H
2
O can be thought of as the most compressible ‘liquid oxide’ component in silicate melt at low pressure, but at high pressure its compressibility resembles that of other liquid oxide components. A best-fit curve to the data on

from various studies allows calculation of hydrous melt compression curves relevant to high-pressure planetary differentiation. From these compression curves, crystal–liquid density crossovers are predicted for the mantles of the Earth and Mars. For the Earth, trapped dense hydrous melts may reside atop the 410 km discontinuity, and, although not required to be hydrous, atop the core–mantle boundary (CMB), in accord with seismic observations of low-velocity zones in these regions. For Mars, a density crossover at the base of the upper mantle is predicted, which would produce a low-velocity zone at a depth of approximately 1200 km. If perovskite is stable at the base of the Martian mantle, then density crossovers or trapped dense hydrous melts are unlikely to reside there, and long-lived, melt-induced, low-velocity regions atop the CMB are not predicted.