bluuebunny/crossref_metadata_2025 huggingface dataset:
Improved configuration space sampling: Langevin dynamics with alternative mobility
Authors: Chau C. D. , Sevink G. J. A. , Fraaije J. G. E. M.
Published: June 2008

We present a new and efficient method for determining optimal configurations of a large number (N) of interacting particles. We use a coarse-grained stochastic Langevin equation in the overdamped limit to describe the dynamics of this system and replace the standard mobility by an effective space dependent inverse Hessian correlation matrix. Due to the analogy of the drift term in the Langevin equation and the update scheme in Newton’s method, we expect accelerated dynamics or improved convergence in the convex part of the potential energy surface Φ. The stochastic noise term, however, is not only essential for proper thermodynamic sampling but also allows the system to access transition states in the concave parts of Φ. We employ a Broyden–Fletcher–Goldfarb–Shannon method for updating the local mobility matrix. Quantitative analysis for one and two dimensional systems shows that the new method is indeed more efficient than standard methods with constant effective friction. Due to the construction, our effective mobility adapts high values/low friction in configurations which are less optimal and low values/high friction in configurations that are more optimal.
Two-dimensional nonlinear plane Poiseuille–Couette flow homotopy revisited
Authors: Ehrenstein Uwe , Nagata Masato , Rincon François
Published: June 2008

A recent paper by Rincon [Phys. Fluids 19, 074105 (2007)] readdressed the question of the existence of two-dimensional steady nonlinear states in plane Couette flow, coming to the conclusion that it is not possible to obtain the nonlinear plane Couette flow solutions reported by Cherhabili and Ehrenstein [Eur. J. Mech. B/Fluids 14, 667 (1995)] using their Poiseuille–Couette homotopy. Exploring the multiparameter space by performing several consecutive and distinct continuations, we show that it is possible to find a complex numerical path from plane Poiseuille streamwise periodic waves to two-dimensional nonlinear steady states for the plane Couette flow limit. The nonlinear Couette flow states are retrieved using three independent solution procedures and the disturbance flow structure is shown to be localized in the streamwise periodic box. Numerical evidence is provided that the width of the nonlinear plane Couette flow disturbance decreases with increasing resolution at fixed boxlength. This singular-type behavior of the solution structure for increasing resolution suggests that the pseudospectral solutions do not converge to smooth two-dimensional physical solutions of the continuous nonlinear system, the existence of which remains an open question.
On the holonomy of the Coulomb connection over manifolds with boundary
Authors: Gryc William E.
Published: June 2008

Narasimhan and Ramadas [Commun. Math. Phys. 67, 121 (1979)] showed that the restricted holonomy group of the Coulomb connection is dense in the connected component of the identity of the gauge group when one considers the product principal bundle S3×SU(2)→S3. Instead of a base manifold S3, we consider here a base manifold of dimension n≥2 with a boundary and use Dirichlet boundary conditions on connections as defined by Marini [Commun. Pure Appl. Math. 45, 1015 (1992)]. A key step in the method of Narasimhan and Ramadas consisted in showing that the linear space spanned by the curvature form at one specially chosen connection is dense in the holonomy Lie algebra with respect to an appropriate Sobolev norm. Our objective is to explore the effect of the presence of a boundary on this construction of the holonomy Lie algebra. Fixing appropriate Sobolev norms, it will be shown that the space spanned, linearly, by the curvature form at any one connection is never dense in the holonomy Lie algebra. In contrast, the linear space spanned by the curvature form and its first commutators at the flat connection is dense and, in the C∞ category, is in fact the entire holonomy Lie algebra. The former, negative, theorem is proven for a general principle bundle over M, while the latter, positive, theorem is proven only for a product bundle over the closure of a bounded open subset of Rn. Our technique for proving the absence of density consists in showing that the linear space spanned by the curvature form at one point is contained in the kernel of a linear map consisting of a third order differential operator, followed by a restriction operation at the boundary; this mapping is determined by the mean curvature of the boundary.
Feed-forward compensation of surface potential in atomic force microscopy
Authors: Ziegler Dominik , Naujoks Nicola , Stemmer Andreas
Published: June 2008

We introduce a feed-forward technique for lift-mode Kelvin probe force microscopy to minimize electrostatically induced errors in topography scans. Such errors typically occur when a grounded tip is scanned over a heterogeneous sample with differences in local work function or areas of local surface charging. To minimize electrostatic forces during the topography scan we bias the tip with the surface potential recorded in the previous Kelvin probe scan line. With this method we achieve an error free topography on samples with large variations in local surface potential. Compared to conventional tapping mode, we further observe a significant reduction of tip-induced surface charge modifications on charge patterns written in electret films.
Technique for designing and evaluating probe caps used in optical topography of infants using a real head model based on three dimensional magnetic resonance images
Authors: Hirabayashi Yukiko , Sato Hiroki , Uchida-Ota Mariko , Nakai Akio , Maki Atsushi
Published: June 2008

We have developed an effective technique for aiding the design and evaluating the performance of the probe caps used to perform optical topography (OT) on infants. To design and evaluate a probe cap, it is necessary to determine the measurement positions for conducting OT on the brain surface of subjects. One technique for determining these positions on the brain surface is to find their three-dimensional (3D) coordinates using a 3D magnetic space digitizer, which consists of a 3D magnetic source and a 3D magnetic sensor. The problem with this technique is that it takes a long time to determine all the measurement points on the subject’s head and it is difficult to use with infants. It is a particular problem with infants who cannot support their own heads. Therefore, we have developed a real model of an infant subject’s head based on 3D magnetic resonance (MR) images. The model is made from an optical-curable resin using 3D computer-aided-format coordinate data taken from 3D MR image-format coordinate data. We have determined the measurement positions on the surface of the model corresponding to a scalp using a 3D magnetic space digitizer and displayed the positions on a 3D MR image of the infant’s brain. Using this technique, we then determined the actual 72 measurement positions located over the entire brain surface area for use with our new whole-head probe cap for neonates and infants. This method is useful for evaluating the performance of and designing probe caps.
Extraction of ultraviolet emitting silicon species from strongly hydrogenated nanoporous silicon
Authors: Lysenko V. , Onyskevych V. , Marty O. , Skryshevsky V. A. , Chevolot Y. , Bru-Chevallier C.
Published: June 2008

Ultraviolet emitting silicon species were extracted from strongly hydrogenated porous silicon nanostructures. Their photoluminescence spectra depend on size distribution of the species and can be tuned by centrifugation. Molecular structure of the extracted Si species is assumed to be very similar to some kinds of polysilanes which were theoretically described earlier by Allan et al. [Phys. Rev. B 48, 7951 (1993)]. Absence of photoluminescence signal coming from the polysilanes in the initial porous nanostructures is supposed to be due to the competitive absorption and to the energy transfer between the polysilanes and Si red emitting porous nanoparticles.
Logic circuits using solution-processed single-walled carbon nanotube transistors
Authors: Nouchi Ryo , Tomita Haruo , Ogura Akio , Kataura Hiromichi , Shiraishi Masashi
Published: June 2008

This letter reports on the realization of logic circuits employing solution-processed networks of single-walled carbon nanotubes. We constructed basic logic gates (inverter and NAND) with n- and p-type field-effect transistors fabricated by solution-based chemical doping. Complementary metal-oxide-semiconductor inverters exhibited voltage gains of up to 20, which illustrates the great potential of carbon nanotube networks for printable flexible electronics.
Size-selective optical forces for microspheres using evanescent wave excitation of whispering gallery modes
Authors: Ng Jack , Chan C. T.
Published: June 2008

We show that when a microsphere is illuminated by an evanescent wave, the optical forces on- and off-whispering gallery mode (WGM) resonance can differ by several orders of magnitude. Such size-selective force allows one to selectively manipulate the resonating particles, while leaving those particles at off-resonance untouched. As WGM resonances have very high-Q’s, this kind of force could be deployed for size-selective manipulation with a very high accuracy (∼1∕Q), as well as simultaneous particle-sorting according to their size or resonant frequency.
Pockel’s effect and optical rectification in (111)-cut near-intrinsic silicon crystals
Authors: Chen Zhanguo , Zhao Jianxun , Zhang Yuhong , Jia Gang , Liu Xiuhuan , Ren Ce , Wu Wenqing , Sun Jianbo , Cao Kun , Wang Shuang , Shi Bao
Published: June 2008

Pockel’s effect and optical rectification are demonstrated in the charge space region of a (111)-cut near-intrinsic silicon crystal by the use of a planar metal-insulator-semiconductor structure. The results show that both Pockel’s effect and optical rectification are so considerable that these effects should be taken into account for designing silicon-based photonic devices. The anisotropy of optical rectification is measured too, and experimental results are in good accordance with the theoretical analysis. These effects can also be used as a tool to investigate the properties of the charge space region of silicon devices in future.
Electric-field switching of exciton spin splitting in coupled quantum dots
Authors: Li Xiaojing , Chang Kai
Published: June 2008

We investigate theoretically the spin splitting of the exciton states in semiconductor coupled quantum dots (CQDs) containing a single magnetic ion. We find that the spin splitting can be switched on/off in the CQDs via the sp-d exchange interaction using the electric field. An interesting bright-to-dark exciton transition can be found and it significantly affects the photoluminescence spectrum. This phenomenon is induced by the transition of the ground exciton state, arising from the hole mixing effect, between the bonding and antibonding states.
Horizontally aligned Cu5Si polycrystalline nanorods on Si
Authors: Wu Wei , Yu Qingkai , Zhang Jiaming , Lian Jie , Liang Gang , Ewing Rodney C. , Pei Shin-Shem
Published: June 2008

In this letter, we report a method for the growth of copper silicide (Cu5Si) nanorods with a horizontal alignment via chemical vapor deposition. The Cu5Si nanorods with an oxygen-rich shell grew in the [110] direction of Si on a (001) Si substrate. A growth model that explains the formation mechanism of the horizontally aligned, polycrystalline nanorods is proposed.
Photochemistry of retinal chromophore in mouse melanopsin
Authors: Walker Marquis T. , Brown R. Lane , Cronin Thomas W. , Robinson Phyllis R.
Published: June 2008

In mammals, melanopsin is exclusively expressed in intrinsically photosensitive retinal ganglion cells (ipRGCs), which play an important role in circadian photoentrainment and other nonimage-forming functions. These ipRGCs reside in the inner retina, far removed from the pigment epithelium, which synthesizes the 11-
cis
retinal chromophore used by rod and cone photoreceptors to regenerate opsin for light detection. There has been considerable interest in the identification of the melanopsin chromophore and in understanding the process of photopigment regeneration in photoreceptors that are not in proximity to the classical visual cycle. We have devised an immuno-magnetic purification protocol that allows melanopsin-expressing retinal ganglion cells to be isolated and collected from multiple mouse retinas. Using this technique, we have demonstrated that native melanopsin
in vivo
exclusively binds 11-
cis
retinal in the dark and that illumination causes isomerization to the all-
trans
isoform. Furthermore, spectral analysis of the melanopsin photoproduct shows the formation of a protonated metarhodopsin with a maximum absorbance between 520 and 540 nm. These results indicate that even if melanopsin functions as a bistable photopigment with photo-regenerative activity native melanopsin must also use some other light-independent retinoid regeneration mechanism to return to the dark state, where all of the retinal is observed to be in the 11-
cis
form.
The mechanism of micro-RNA-mediated translation repression is determined by the promoter of the target gene
Authors: Kong Yi Wen , Cannell Ian G. , de Moor Cornelia H. , Hill Kirsti , Garside Paul G. , Hamilton Tiffany L. , Meijer Hedda A. , Dobbyn Helen C. , Stoneley Mark , Spriggs Keith A. , Willis Anne E. , Bushell Martin
Published: June 2008

MicroRNAs (miRNAs) are noncoding RNAs that base pair imperfectly to homologous regions in target mRNAs and negatively influence the synthesis of the corresponding proteins. Repression is mediated by a number of mechanisms, one of which is the direct inhibition of protein synthesis. Surprisingly, previous studies have suggested that two mutually exclusive mechanisms exist, one acting at the initiation phase of protein synthesis and the other at a postinitiation event. Here, we resolve this apparent dichotomy by demonstrating that the promoter used to transcribe the mRNA influences the type of miRNA-mediated translational repression. Transcripts derived from the SV40 promoter that contain let-7 target sites in their 3′ UTRs are repressed at the initiation stage of translation, whereas essentially identical mRNAs derived from the TK promoter are repressed at a postinitiation step. We also show that there is a miR-34 target site within the 3′ UTR of c-
myc
mRNA and that promoter dependency is also true for this endogenous 3′ UTR. Overall, these data establish a link between the nuclear history of an mRNA and the mechanism of miRNA-mediated translational regulation in the cytoplasm.
Congenital disease SNPs target lineage specific structural elements in protein kinases
Authors: Torkamani Ali , Kannan Natarajan , Taylor Susan S. , Schork Nicholas J.
Published: June 2008

The catalytic domain of protein kinases harbors a large number of disease-causing single nucleotide polymorphisms (SNPs) and common or neutral SNPs that are not known or hypothesized to be associated with any disease. Distinguishing these two types of polymorphisms is critical in accurately predicting the causative role of SNPs in both candidate gene and genome-wide association studies. In this study, we have analyzed the structural location of common and disease-associated SNPs in the catalytic domain of protein kinases and find that, although common SNPs are randomly distributed within the catalytic core, known disease SNPs consistently map to regulatory and substrate binding regions. In particular, a buried side-chain network that anchors the flexible activation loop to the catalytic core is frequently mutated in disease patients. This network was recently shown to be absent in distantly related eukaryotic-like kinases, which lack an exaggerated activation loop and, presumably, are not regulated by phosphorylation.
In silicoactivity profiling reveals the mechanism of action of antimalarials discovered in a high-throughput screen
Authors: Plouffe David , Brinker Achim , McNamara Case , Henson Kerstin , Kato Nobutaka , Kuhen Kelli , Nagle Advait , Adrián Francisco , Matzen Jason T. , Anderson Paul , Nam Tae-gyu , Gray Nathanael S. , Chatterjee Arnab , Janes Jeff , Yan S. Frank , Trager Richard , Caldwell Jeremy S. , Schultz Peter G. , Zhou Yingyao , Winzeler Elizabeth A.
Published: June 2008

The growing resistance to current first-line antimalarial drugs represents a major health challenge. To facilitate the discovery of new antimalarials, we have implemented an efficient and robust high-throughput cell-based screen (1,536-well format) based on proliferation ofPlasmodium falciparum(Pf) in erythrocytes. From a screen of ≈1.7 million compounds, we identified a diverse collection of ≈6,000 small molecules comprised of >530 distinct scaffolds, all of which show potent antimalarial activity (<1.25 μM). Most known antimalarials were identified in this screen, thus validating our approach. In addition, we identified many novel chemical scaffolds, which likely act through both known and novel pathways. We further show that in some cases the mechanism of action of these antimalarials can be determined byin silicocompound activity profiling. This method uses large datasets from unrelated cellular and biochemical screens and the guilt-by-association principle to predict which cellular pathway and/or protein target is being inhibited by select compounds. In addition, the screening method has the potential to provide the malaria community with many new starting points for the development of biological probes and drugs with novel antiparasitic activities.
Structurally different alleles of the ath-
MIR824
microRNA precursor are maintained at high frequency in
Arabidopsis thaliana
Authors: de Meaux Juliette , Hu Jin-Yong , Tartler Ute , Goebel Ulrike
Published: June 2008

In plants and animals, gene expression can be down-regulated at the posttranscriptional level by microRNAs (miRNAs), a class of small endogenous RNA. Comparative analysis of miRNA content across species indicates continuous birth and death of these loci in the course of evolution. However, little is known about the microevolutionary dynamics of these genetic elements, especially in plants. In this article we examine polymorphism at two miRNA-encoding loci in
Arabidopsis thaliana
, miR856 and miR824, which are not found in rice or poplar. We compare their diversity to other miRNA-encoding loci conserved across distant taxa. We find that levels of variation vary significantly across loci and that the two recently derived loci harbor patterns of diversity deviating from neutrality. miRNA miR856 shows a weak signature of a selective sweep whereas miR824 displays signs of balancing selection. A detailed examination of structural variation among alleles found at the miR824-encoding locus suggests nonrandom evolution of a thermoresistant substructure in the precursor. Expression analysis of pre-miR824 and its target, AGL16, indicates that these structural differences likely impact the processing of mature miR824. Our work highlights the relevance of RNA structure in precursor sequence evolution, suggesting that the evolutionary dynamics of miRNA-encoding loci is more complex than suggested by the constraints exerted on the interaction between mature miRNA fragments and their target exon.
The kinesin-1 motor protein is regulated by a direct interaction of its head and tail
Authors: Dietrich Kristen A. , Sindelar Charles V. , Brewer Paul D. , Downing Kenneth H. , Cremo Christine R. , Rice Sarah E.
Published: June 2008

Kinesin-1 is a molecular motor protein that transports cargo along microtubules. Inside cells, the vast majority of kinesin-1 is regulated to conserve ATP and to ensure its proper intracellular distribution and coordination with other molecular motors. Regulated kinesin-1 folds in half at a hinge in its coiled-coil stalk. Interactions between coiled-coil regions near the enzymatically active heads at the N terminus and the regulatory tails at the C terminus bring these globular elements in proximity and stabilize the folded conformation. However, it has remained a mystery how kinesin-1's microtubule-stimulated ATPase activity is regulated in this folded conformation. Here, we present evidence for a direct interaction between the kinesin-1 head and tail. We photochemically cross-linked heads and tails and produced an 8-Å cryoEM reconstruction of the cross-linked head–tail complex on microtubules. These data demonstrate that a conserved essential regulatory element in the kinesin-1 tail interacts directly and specifically with the enzymatically critical Switch I region of the head. This interaction suggests a mechanism for tail-mediated regulation of the ATPase activity of kinesin-1. In our structure, the tail makes simultaneous contacts with the kinesin-1 head and the microtubule, suggesting the tail may both regulate kinesin-1 in solution and hold it in a paused state with high ADP affinity on microtubules. The interaction of the Switch I region of the kinesin-1 head with the tail is strikingly similar to the interactions of small GTPases with their regulators, indicating that other kinesin motors may share similar regulatory mechanisms.
The Management of Encephalitis: Clinical Practice Guidelines by the Infectious Diseases Society of America
Authors: Tunkel Allan R. , Glaser Carol A. , Bloch Karen C. , Sejvar James J. , Marra Christina M. , Roos Karen L. , Hartman Barry J. , Kaplan Sheldon L. , Scheld W. Michael , Whitley Richard J.
Published: June 2008

Guidelines for the diagnosis and treatment of patients with encephalitis were prepared by an Expert Panel of the Infectious Diseases Society of America. The guidelines are intended for use by health care providers who care for patients with encephalitis. The guideline includes data on the epidemiology, clinical features, diagnosis, and treatment of many viral, bacterial, fungal, protozoal, and helminthic etiologies of encephalitis and provides information on when specific etiologic agents should be considered in individual patients with encephalitis.
Is an Increased Dwell Time of a Peripherally Inserted Catheter Associated With an Increased Risk of Bloodstream Infection in Infants?
Authors: Smith P. Brian , Benjamin Daniel K. , Cotten C. Michael , Schultz Eric , Guo Rose , Nowell Lisa , Smithwick Mary Laura , Thornburg Courtney D.
Published: June 2008

Objective.

To estimate the risk of bloodstream infection associated with catheter dwell time in infants.

Design.

Retrospective study.

Setting.

Duke University Medical Center neonatal intensive care unit, an academic, level 3 nursery in Durham, North Carolina.

Methods.

A case of catheter-associated bloodstream infection was defined as one that occurred in an infant whose culture-positive blood sample was collected more than 24 hours after catheter insertion or within 72 hours after catheter removal. We used multivariable logistic regression to control for the catheter's position and dwell time as well as the infant's sex, gestational age, age at time of catheter insertion, birth weight, and weight at time of catheter insertion.

Results.

We identified 135 cases of catheter-associated bloodstream infection. The mean catheter dwell time was 12.2 days (range, 0–113 days), and the mean time to bloodstream infection was 10.8 days (range, 1–57 days). An increase in catheter dwell time was associated with a lower risk of bloodstream infection (odds ratio, 0.975 [95% confidence interval, 0.954–0.996]; P = .02).

Conclusion. No

increased risk of catheter-associated bloodstream infection was observed with increased catheter dwell time. This may have been due to the infant's improved nutrition, decreased need for other invasive devices, and maturing skin and immune system as catheter dwell time increased.
The SNAP-25 Linker as an Adaptation Toward Fast Exocytosis
Authors: Nagy Gábor , Milosevic Ira , Mohrmann Ralf , Wiederhold Katrin , Walter Alexander M. , Sørensen Jakob B.
Published: June 2008

The assembly of four soluble N-ethylmaleimide-sensitive factor attachment protein receptor domains into a complex is essential for membrane fusion. In most cases, the four SNARE-domains are encoded by separate membrane-targeted proteins. However, in the exocytotic pathway, two SNARE-domains are present in one protein, connected by a flexible linker. The significance of this arrangement is unknown. We characterized the role of the linker in SNAP-25, a neuronal SNARE, by using overexpression techniques in synaptosomal-associated protein of 25 kDa (SNAP-25) null mouse chromaffin cells and fast electrophysiological techniques. We confirm that the palmitoylated linker-cysteines are important for membrane association. A SNAP-25 mutant without cysteines supported exocytosis, but the fusion rate was slowed down and the fusion pore duration prolonged. Using chimeric proteins between SNAP-25 and its ubiquitous homologue SNAP-23, we show that the cysteine-containing part of the linkers is interchangeable. However, a stretch of 10 hydrophobic and charged amino acids in the C-terminal half of the SNAP-25 linker is required for fast exocytosis and in its absence the calcium dependence of exocytosis is shifted toward higher concentrations. The SNAP-25 linker therefore might have evolved as an adaptation toward calcium triggering and a high rate of execution of the fusion process, those features that distinguish exocytosis from other membrane fusion pathways.
Global Gene Expression Analysis Identifies PDEF Transcriptional Networks Regulating Cell Migration during Cancer Progression
Authors: Turner David P. , Findlay Victoria J. , Kirven A. Darby , Moussa Omar , Watson Dennis K.
Published: June 2008

Prostate derived ETS factor (PDEF) is an ETS (epithelial-specific E26 transforming sequence) family member that has been identified as a potential tumor suppressor. In multiple invasive breast cancer cells, PDEF expression inhibits cell migration by preventing the acquisition of directional morphological polarity conferred by changes in cytoskeleton organization. In this study, microarray analysis was used to identify >200 human genes that displayed a common differential expression pattern in three invasive breast cancer cell lines after expression of exogenous PDEF protein. Gene ontology associations and data mining analysis identified focal adhesion, adherens junctions, cell adhesion, and actin cytoskeleton regulation as cell migration-associated interaction pathways significantly impacted by PDEF expression. Validation experiments confirmed the differential expression of four cytoskeleton-associated genes with known functional associations with these pathways: uPA, uPAR, LASP1, and VASP. Significantly, chromatin immunoprecipitation studies identified PDEF as a direct negative regulator of the metastasis-associated gene uPA and phenotypic rescue experiments demonstrate that exogenous urokinase plasminogen activator (uPA) expression can restore the migratory ability of invasive breast cancer cells expressing PDEF. Furthermore, immunofluorescence studies identify the subcellular relocalization of urokinase plasminogen activator receptor (uPAR), LIM and SH3 protein (LASP1), and vasodilator-stimulated protein (VASP) as a possible mechanism accounting for the loss of morphological polarity observed upon PDEF expression.
Comparing simulation results of SBML capable simulators
Authors: Bergmann Frank T. , Sauro Herbert M.
Published: June 2008

Motivation: Simulations are an essential tool when analyzing biochemical networks. Researchers and developers seeking to refine simulation tools or develop new ones would benefit greatly from being able to compare their simulation results.

Summary: We present an approach to compare simulation results between several SBML capable simulators and provide a website for the community to share simulation results.

Availability: The website with simulation results and additional material can be found under: http://sys-bio.org/sbwWiki/compare. The software used to generate the simulation results is available on the website for download.

Contact:  fbergman@u.washington.edu
PRIMEGENS-v2: genome-wide primer design for analyzing DNA methylation patterns of CpG islands
Authors: Srivastava Gyan P. , Guo Juyuan , Shi Huidong , Xu Dong
Published: June 2008

Motivation: DNA methylation plays important roles in biological processes and human diseases, especially cancers. High-throughput bisulfite genomic sequencing based on new generation of sequencers, such as the 454-sequencing system provides an efficient method for analyzing DNA methylation patterns. The successful implementation of this approach depends on the use of primer design software capable of performing genome-wide scan for optimal primers from in silico bisulfite-treated genome sequences. We have developed a method, which fulfills this requirement and conduct primer design for sequences including regions of given promoter CpG islands.

Results: The developed method has been implemented using the C and JAVA programming languages. The primer design results were tested in the PCR experiments of 96 selected human DNA sequences containing CpG islands in the promoter regions. The results indicate that this method is efficient and reliable for designing sequence-specific primers.

Availability: The sequence-specific primer design for DNA meth-ylated sequences including CpG islands has been integrated into the second version of PRIMEGENS as one of the primer design features. The software is freely available for academic use at http://digbio.missouri.edu/primegens/.

Contact:  xudong@missouri.edu
Population biology of monkfish Lophius americanus
Authors: Richards R. Anne , Nitschke Paul C. , Sosebee Katherine A.
Published: June 2008

Richards, R. A., Nitschke, P. C., and Sosebee, K. A. 2008. Population biology of monkfish Lophius americanus. – ICES Journal of Marine Science, 65: 1291–1305. This paper provides an overview of the biology of monkfish in US waters of the Northwest Atlantic Ocean using data from resource surveys spanning the period 1948–2007. Monkfish exhibited seasonal onshore–offshore shifts in distribution, migrated out of the southern Mid-Atlantic Bight (MAB) in mid-spring, and re-appeared there in autumn. Sex ratios at length for fish 40–65-cm long were skewed towards males in the southern MAB, but approximated unity elsewhere, suggesting that a portion of the population resides outside sampled areas. Growth was linear at 9.9 cm year−1 and did not differ by region or sex. Maximum observed size was 138 cm for females and 85 cm for males. Length at 50% maturity for males was 35.6 cm (4.1 years old) in the north and 37.9 cm (4.3 years old) in the south; for females 38.8 cm (4.6 years old) in the north and 43.8 cm (4.9 years old) in the south. Ripe females were found in shallow (<50 m) and deep (>200 m) water in the south, and in shallow water (<50 m) in the north.
Wouldn't It Be Nice …? The Automatic Unbiasedness of OLS (and GLS)
Authors: Luskin Robert C.
Published: June 2008

In a recent issue of this journal, Larocca (2005) makes two notable claims about the best linear unbiasedness of ordinary least squares (OLS) estimation of the linear regression model. The first, drawn from McElroy (1967), is that OLS remains best linear unbiased in the face of a particular kind of autocorrelation (constant for all pairs of observations). The second, much larger and more heterodox, is that the disturbance need not be assumed uncorrelated with the regressors for OLS to be best linear unbiased. The assumption is unnecessary, Larocca says, because “orthogonality [of disturbance and regressors] is a property of all OLS estimates” (p. 192). Of course OLS's being best linear unbiased still requires that the disturbance be homoskedastic and (McElroy's loophole aside) nonautocorrelated, but Larocca also adds that the same automatic orthogonality obtains for generalized least squares (GLS), which is also therefore best linear unbiased, when the disturbance is heteroskedastic or autocorrelated.
Hybrid trait speciation andHeliconiusbutterflies
Authors: Jiggins Chris D , Salazar Camilo , Linares Mauricio , Mavarez Jesus
Published: June 2008

Homoploid hybrid speciation (HHS) is the establishment of a novel species through introgressive hybridization without a change in chromosome number. We discuss different routes by which this might occur and propose a novel term, ‘hybrid trait speciation’, which combines the idea that hybridization can generate adaptive novelty with the ‘magic trait’ model of ecological speciation.Heliconiusbutterflies contain many putative examples of hybrid colour patterns, but only recently has the HHS hypothesis been tested explicitly in this group. Molecular data has shown evidence for gene flow between many distinct species. Furthermore, the colour pattern ofHeliconius heurippacan be recreated in laboratory crosses betweenHeliconius melpomeneandHeliconius cydnoand, crucially, plays a role in assortative mating between the three species. Nonetheless, although the genome ofH. heurippashows evidence for hybridization, it is not a mosaic of the two parental species. Instead, ongoing hybridization has likely blurred any signal of the original speciation event. We argue that where hybridization leads to novel adaptive traits that also cause reproductive isolation, it is likely to trigger speciation.
Hybridization, ecological races and the nature of species: empirical evidence for the ease of speciation
Authors: Mallet James
Published: June 2008

Species are generally viewed by evolutionists as ‘real’ distinct entities in nature, making speciation appear difficult. Charles Darwin had originally promoted a very different uniformitarian view that biological species were continuous with ‘varieties’ below the level of species and became distinguishable from them only when divergent natural selection led to gaps in the distribution of morphology. This Darwinian view on species came under immediate attack, and the consensus among evolutionary biologists today appears to side more with the ideas of Ernst Mayr and Theodosius Dobzhansky, who argued 70 years ago that Darwin was wrong about species. Here, I show how recent genetic studies of supposedly well-behaved animals, such as insects and vertebrates, including our own species, have supported the existence of the Darwinian continuum between varieties and species. Below the level of species, there are well-defined ecological races, while above the level of species, hybridization still occurs, and may often lead to introgression and, sometimes, hybrid speciation. This continuum is evident, not only across vast geographical regions, but also locally in sympatry. The existence of this continuum provides good evidence for gradual evolution of species from ecological races and biotypes, to hybridizing species and, ultimately, to species that no longer cross. Continuity between varieties and species not only provides an excellent argument against creationism, but also gives insight into the process of speciation. The lack of a hiatus between species and ecological races suggests that speciation may occur, perhaps frequently, in sympatry, and the abundant intermediate stages suggest that it is happening all around us. Speciation is easy!
Polarization of the
C. elegans
Embryo by RhoGAP-Mediated Exclusion of PAR-6 from Cell Contacts
Authors: Anderson Dorian C. , Gill Jason S. , Cinalli Ryan M. , Nance Jeremy
Published: June 2008

Early embryos of some metazoans polarize radially to facilitate critical patterning events such as gastrulation and asymmetric cell division; however, little is known about how radial polarity is established. Early embryos of
Caenorhabditis elegans
polarize radially when cell contacts restrict the polarity protein PAR-6 to contact-free cell surfaces, where PAR-6 regulates gastrulation movements. We have identified a Rho guanosine triphosphatase activating protein (RhoGAP), PAC-1, which mediates
C. elegans
radial polarity and gastrulation by excluding PAR-6 from contacted cell surfaces. We show that PAC-1 is recruited to cell contacts, and we suggest that PAC-1 controls radial polarity by restricting active CDC-42 to contact-free surfaces, where CDC-42 binds and recruits PAR-6. Thus, PAC-1 provides a dynamic molecular link between cell contacts and PAR proteins that polarizes embryos radially.
Dislocation Mean Free Paths and Strain Hardening of Crystals
Authors: Devincre B. , Hoc T. , Kubin L.
Published: June 2008

Predicting the strain hardening properties of crystals constitutes a long-standing challenge for dislocation theory. The main difficulty resides in the integration of dislocation processes through a wide range of time and length scales, up to macroscopic dimensions. In the present multiscale approach, dislocation dynamics simulations are used to establish a dislocation-based continuum model incorporating discrete and intermittent aspects of plastic flow. This is performed through the modeling of a key quantity, the mean free path of dislocations. The model is then integrated at the scale of bulk crystals, which allows for the detailed reproduction of the complex deformation curves of face-centered cubic crystals. Because of its predictive ability, the proposed framework has a large potential for further applications.
FGF-Dependent Mechanosensory Organ Patterning in Zebrafish
Authors: Nechiporuk Alex , Raible David W.
Published: June 2008

During development, organ primordia reorganize to form repeated functional units. In zebrafish (
Danio rerio
), mechanosensory organs called neuromasts are deposited at regular intervals by the migrating posterior lateral line (pLL) primordium. The pLL primordium is organized into polarized rosettes representing proto-neuromasts, each with a central
atoh1a
-positive focus of mechanosensory precursors. We show that rosettes form cyclically from a progenitor pool at the leading zone of the primordium as neuromasts are deposited from the trailing region.
fgf3/10
signals localized to the leading zone are required for rosette formation,
atoh1a
expression, and primordium migration. We propose that the fibroblast growth factor (FGF) source controls primordium organization, which, in turn, regulates the periodicity of neuromast deposition. This previously unrecognized mechanism may be applicable to understanding segmentation and morphogenesis in other organ systems.
Both Catalytic Steps of Nuclear Pre-mRNA Splicing Are Reversible
Authors: Tseng Chi-Kang , Cheng Soo-Chen
Published: June 2008

Nuclear pre–messenger RNA (pre-mRNA) splicing is an essential processing step for the production of mature mRNAs from most eukaryotic genes. Splicing is catalyzed by a large ribonucleoprotein complex, the spliceosome, which is composed of five small nuclear RNAs and more than 100 protein factors. Despite the complexity of the spliceosome, the chemistry of the splicing reaction is simple, consisting of two consecutive transesterification reactions. The presence of introns in spliceosomal RNAs of certain fungi has suggested that splicing may be reversible; however, this has never been demonstrated experimentally. By using affinity-purified spliceosomes, we have shown that both catalytic steps of splicing can be efficiently reversed under appropriate conditions. These results provide considerable insight into the catalytic flexibility of the spliceosome.
Expression and Secretion of Cathelicidin LL-37 in Human Epithelial Cells after Infection byMycobacterium bovisBacillus Calmette-Guérin
Authors: Méndez-Samperio Patricia , Miranda Elena , Trejo Artemisa
Published: June 2008

The antimicrobial cathelicidin LL-37 is considered to play an important role in the innate immune response to tuberculosis infection. However, little is known about the induction and secretion of this antimicrobial peptide in A549 epithelial cells after infection withMycobacterium bovisbacillus Calmette-Guérin (BCG), the world's most widely used tuberculosis vaccine. In this study, we investigated the effect ofM. bovisBCG on LL-37 mRNA levels in A549 cells by real-time PCR and on protein levels by Western blotting. Treatment of cells withM. bovisBCG upregulates LL-37 mRNA expression in a dose- and time-dependent manner. The quantitative analysis of LL-37 gene expression correlated with our Western blotting results. Moreover, our results demonstrated that treatment of cells with the transcriptional inhibitor actinomycin D effectively inhibited in a concentration-dependent manner the ability ofM. bovisBCG to induce LL-37 mRNA expression. Finally, inhibition of the MEK1/2 and p38 mitogen-activated protein kinase (MAPK) signaling pathways reducedM. bovisBCG-mediated LL-37 mRNA expression, a reduction that correlated with the observed high level of downregulation of LL-37 protein induction. Thus, these results indicate that the MEK1/2 and p38 MAPK signaling pathways play a critical role in the regulation of inducible LL-37 gene expression in A549 cells infected withM. bovisBCG.
In Vitro Cell-Mediated Immune Responses of Human Immunodeficiency Virus-Infected and -Uninfected Individuals to Whole Cytomegalovirus Antigens and Their Subunits
Authors: Weinberg A. , Spritzler J. , Nokta M. , Schrier R. , Landay A. , Brown D. , Pollard R.
Published: June 2008

The aim of this study was to optimize the ability to detect cytomegalovirus (CMV)-specfic cell-mediated immunity (CMI) in human immunodeficiency virus (HIV)-infected individuals by comparing different assays (the lymphocyte proliferation assay [LPA] and assays for gamma interferon [IFN-γ] and interleukin-2 [IL-2] production) and CMV antigenic preparations. Thresholds discriminating positive from negative CMI results were developed with specimens from 36 CMV-seropositive and 21 CMV-seronegative healthy individuals. The analysis showed that the CMI elicited by any of the four CMV whole lysates tested in this study tended to be more robust and sensitive than the responses to the subunit antigens gB and pp65. LPA and inducible IFN-γ but not IL-2 were highly sensitive measures of CMV-specific CMI in HIV-infected and -uninfected individuals. The ability to detect CMV-specific LPA or IFN-γ responses in HIV-infected individuals significantly increased with higher CD4 cell numbers. Nevertheless, the proportion of HIV-infected subjects with CD4 counts of ≥500 cells/μl who had a detectable CMV-specific CMI remained significantly lower than that of healthy adults. The ability to detect CMV-specific CMI in HIV-infected individuals decreased with higher levels of HIV replication, with discriminative thresholds of 10
3
to 10
4
HIV RNA copies/ml of plasma, for LPA or inducible IFN-γ production elicited by different antigens. The LPA responses obtained with CMV whole lysate and phytohemagglutinin were significantly correlated in HIV-infected subjects but not uninfected controls, indicating a novel characteristic of the CMI defect caused by HIV. The intrasubject variabilities of the CMV-specific CMI were similar in HIV-infected and -uninfected individuals. These data show that LPA and the inducible IFN-γ production elicited by CMV whole lysates may be used to assess modifications of the immune competency of HIV-infected individuals.
Randomized Clinical Trial Assessing the Safety and Immunogenicity of Oral Microencapsulated Enterotoxigenic
Escherichia coli
Surface Antigen 6 with or without Heat-Labile Enterotoxin with Mutation R192G
Authors: Lapa Joyce A. , Sincock Stephanie A. , Ananthakrishnan Madhumita , Porter Chad K. , Cassels Frederick J. , Brinkley Carl , Hall Eric R. , van Hamont John , Gramling Joseph D. , Carpenter Colleen M. , Baqar S. , Tribble David R.
Published: June 2008

An oral, microencapsulated anti-colonization factor 6 antigen (meCS6) vaccine, with or without heat-labile enterotoxin with mutation R192G (LT
R192G
) (mucosal adjuvant), against enterotoxigenic
Escherichia coli
(ETEC) was evaluated for regimen and adjuvant effects on safety and immunogenicity. Sixty subjects were enrolled into a three-dose, 2-week interval or four-dose, 2-day interval regimen. Each regimen was randomized into two equal groups of meCS6 alone (1 mg) or meCS6 with adjuvant (2 μg of LT
R192G
). The vaccine was well tolerated and no serious adverse events were reported. Serologic response to CS6 was low in all regimens (0 to 27%). CS6-immunogloublin A (IgA) antibody-secreting cell (ASC) responses ranged from 36 to 86%, with the highest level in the three-dose adjuvanted regimen; however, the magnitude was low. As expected, serologic and ASC LT responses were limited to adjuvanted regimens, with the exception of fecal IgA, which appeared to be nonspecific to LT administration. Further modifications to the delivery strategy and CS6 and adjuvant dose optimization will be needed before conducting further clinical trials with this epidemiologically important class of ETEC.
Sensitive and Broadly Reactive Reverse Transcription-PCR Assays To Detect Novel Paramyxoviruses
Authors: Tong Suxiang , Chern Shur-Wern Wang , Li Yan , Pallansch Mark A. , Anderson Larry J.
Published: June 2008

We have developed a set of reverse transcription-PCR assays for the detection and identification of known and novel paramyxoviruses in clinical specimens. Primers were designed from the conserved motifs of the polymerase
pol
gene sequences to detect members of the
Paramyxovirinae
or
Pneumovirinae
subfamily or groups of genera within the
Paramyxovirinae
subfamily. The consensus-degenerate hybrid oligonucleotide primer design and seminested or nested PCR assay design were used to enhance the breadth of reactivity and sensitivity of the respective assays. Using expressed RNA and 10-fold dilution series of virus-infected tissue culture isolates from different members of the family or genera, these assays were able to detect on average between 100 and 500 copies of template RNA. The assays were specific to the respective group of genera or subfamily viruses. This set of primers enhances our ability to look for novel viruses in outbreaks and diseases of unknown etiology.
Cord Formation in a Clinical Isolate of
Mycobacterium marinum
Authors: Staropoli John F. , Branda John A.
Published: June 2008

Cord formation is a characteristic property of the cultured
Mycobacterium tuberculosis
complex species. We describe a case of
Mycobacterium marinum
demonstrating robust cord formation. Nontuberculous mycobacteria can form true cords in broth culture but do so rarely, despite the fact that many species contain the cell wall glycolipid that mediates cord formation.