bluuebunny/crossref_metadata_2025 huggingface dataset:
Characterization of transient molecular vibration excited with shaped femtosecond pulses
Authors: Konorov Stanislav O. , Xu Xiaoji G. , Hepburn John W. , Milner Valery
Published: June 2009

We study vibrational dynamics of molecules interacting with spectrally shaped broadband laser pulses. After performing a single measurement based on cross-correlation frequency resolved optical gating of molecular vibration, complete evolution of the complex-valued quantum coherence between the vibrational states is reconstructed with variable time and frequency resolution. The ability to change the resolution in the analysis of the transient molecular dynamics without repeating the experiment or changing experimental parameters is useful in designing and understanding various schemes of controlling quantum states of molecules.
Full dimensional (15-dimensional) quantum-dynamical simulation of the protonated water-dimer III: Mixed Jacobi-valence parametrization and benchmark results for the zero point energy, vibrationally excited states, and infrared spectrum
Authors: Vendrell Oriol , Brill Michael , Gatti Fabien , Lauvergnat David , Meyer Hans-Dieter
Published: June 2009

Quantum dynamical calculations are reported for the zero point energy, several low-lying vibrational states, and the infrared spectrum of the H5O2+ cation. The calculations are performed by the multiconfiguration time-dependent Hartree (MCTDH) method. A new vector parametrization based on a mixed Jacobi-valence description of the system is presented. With this parametrization the potential energy surface coupling is reduced with respect to a full Jacobi description, providing a better convergence of the n-mode representation of the potential. However, new coupling terms appear in the kinetic energy operator. These terms are derived and discussed. A mode-combination scheme based on six combined coordinates is used, and the representation of the 15-dimensional potential in terms of a six-combined mode cluster expansion including up to some 7-dimensional grids is discussed. A statistical analysis of the accuracy of the n-mode representation of the potential at all orders is performed. Benchmark, fully converged results are reported for the zero point energy, which lie within the statistical uncertainty of the reference diffusion Monte Carlo result for this system. Some low-lying vibrationally excited eigenstates are computed by block improved relaxation, illustrating the applicability of the approach to large systems. Benchmark calculations of the linear infrared spectrum are provided, and convergence with increasing size of the time-dependent basis and as a function of the order of the n-mode representation is studied. The calculations presented here make use of recent developments in the parallel version of the MCTDH code, which are briefly discussed. We also show that the infrared spectrum can be computed, to a very good approximation, within D2d symmetry, instead of the G16 symmetry used before, in which the complete rotation of one water molecule with respect to the other is allowed, thus simplifying the dynamical problem.
Low-threshold organic laser based on an oligofluorene truxene with low optical losses
Authors: Tsiminis Georgios , Wang Yue , Shaw Paul E. , Kanibolotsky Alexander L. , Perepichka Igor F. , Dawson Martin D. , Skabara Peter J. , Turnbull Graham A. , Samuel Ifor D. W.
Published: June 2009

A blue-emitting distributed feedback laser based on a star-shaped oligofluorene truxene molecule is presented. The gain, loss, refractive index, and (lack of) anisotropy are measured by amplified spontaneous emission and variable-angle ellipsometry. The waveguide losses are very low for an organic semiconductor gain medium, particularly for a neat film. The results suggest that truxenes are promising for reducing loss, a key parameter in the operation of organic semiconductor lasers. Distributed feedback lasers fabricated from solution by spin-coating show a low lasing threshold of 270 W/cm2 and broad tunability across 25 nm in the blue part of the spectrum.
Thermal and daylighting evaluation of the effect of varying aspect ratios in urban canyons in Curitiba, Brazil
Authors: Krüger Eduardo , Suga Mauro
Published: June 2009

Urbanization is commonly associated with densification, which may lead to vertical growth or urban consolidation. The present study evaluates the daylighting potential as a function of urban morphology for the city of Curitiba (25°25′50″ S, 46°16′15″ W). It also presents a thermal analysis for a representative street axis orientation in this location, showing indoor conditions within a test office for different aspect ratios. In Curitiba, certain street axes were designated to allow densification (in the so-called structural sector of the city). As a consequence, there is a great risk of urban canyons being formed, as local legislation does not impose height restrictions to adjacent buildings. Daylight analysis was based on software simulations with LUZ DO SOL, DLN, ECOTECT, and RADIANCE. Thermal analysis was carried out by means of computer simulations with the IDA ICE software. It was verified that diagonal axial orientations relative to the north (rotated in 45°) provide higher daylighting potentials to buildings located in urban canyons. With regard to the thermal effect of varying the aspect ratio in an east-west street axis, results confirm daylighting simulations, showing the interrelation between both comfort parameters.
Disentangling strain effects in manganite heterostructures
Authors: Tebano A. , Orsini A. , Medaglia P. G. , Balestrino G.
Published: June 2009

Understanding the physical behavior of an interface between two different oxides is made difficult because of the many competing physical mechanisms such as epitaxial strain, broken symmetry, elemental interdiffusion, and polarity discontinuity, which may be at play simultaneously. We propose an approach, based on heterostructures engineering, to single out the effect of the epitaxial strain from the other physical-chemical effects at the interface between the substrate and the La07Sr0.3MnO3 film. It was found that the degradation of magnetotransport properties, reported for relatively thick films, is a consequence of epitaxial strain alone and is not affected by interface chemistry.
Negative capacitance in Wigner crystal forming polymer nanowires
Authors: Rahman Atikur , Sanyal Milan K.
Published: June 2009

Negative capacitance has been observed in conducting polymer nanowires. These nanowires exhibit features of one-dimensional Wigner crystals, such as switching transition that reduces resistance by several orders of magnitude, negative differential resistance, and enhancement of noise in the switched state. Negative capacitance is theoretically predicted characteristic feature of a Wigner crystal. The magnitude of negative capacitance increases with increasing bias voltage below the switching transition. Above switching transition the magnitude decreases with increasing current bias. The capacitance goes from negative to positive value as the features of Wigner crystal state disappear with increasing temperature.
Suppression of superconductivity in FeSe films under tensile strain
Authors: Nie Y. F. , Brahimi E. , Budnick J. I. , Hines W. A. , Jain M. , Wells B. O.
Published: June 2009

We have studied the effect of tensile strain on the superconductivity in FeSe films. 50, 100, and 200 nm FeSe films were grown on MgO, SrTiO3, and LaAlO3 substrates by using a pulsed laser deposition technique. X-ray diffraction analysis showed that the tetragonal phase is dominant in all of our FeSe films. The 50 nm FeSe films on MgO and SrTiO3 are under tensile strain, while the 50 nm FeSe film on LaAlO3 and the other thick FeSe films are unstrained. Superconducting transitions have been observed in unstrained FeSe films with Tonset≈8 K, which is close to the bulk value. However, no sign of superconductivity has been observed in FeSe films under tensile strain down to 5 K. This is evidence to show that tensile strain suppresses superconductivity in FeSe films.
Integration of (PbZr0.52Ti0.48O3) on single crystal diamond as metal-ferroelectric-insulator-semiconductor capacitor
Authors: Liao Meiyong , Imura Masataka , Fang Xiaosheng , Nakajima Kiyomi , Chen Guangchao , Koide Yasuo
Published: June 2009

The authors report the integration of ferroelectric Pb(Zr0.52,Ti0.48)O3 (PZT) thin film on single crystal diamond by using Al2O3 as a buffer layer and SrTiO3 as a seed layer. The PZT film exhibits a remanent in-plane polarization of 2Pr=31 μC/cm2 and a coercive field of 36 kV/cm. The electrical properties of the metal-ferroelectric-insulator-semiconductor (MFIS) capacitor using boron-doped single crystal diamond epilayer are investigated. The leakage current of the MFIS device is found to be greatly reduced as compared to that of the metal/diamond Schottky diode. Although the overall capacitance-voltage characteristic shows a trap dominated hysteresis behavior, the ferroelectric polarization induced voltage shift is demonstrated under positive gate voltage.
Targeting Tim-1 to overcome resistance to transplantation tolerance mediated by CD8 T17 cells
Authors: Yuan Xueli , Ansari M. Javeed , D'Addio Francesca , Paez-Cortez Jesus , Schmitt Isabella , Donnarumma Michela , Boenisch Olaf , Zhao Xiaozhi , Popoola Joyce , Clarkson Michael R. , Yagita Hideo , Akiba Hisaya , Freeman Gordon J. , Iacomini John , Turka Laurence A. , Glimcher Laurie H. , Sayegh Mohamed H.
Published: June 2009

The ability to induce durable transplantation tolerance predictably and consistently in the clinic is a highly desired but elusive goal. Progress is hampered by lack of appropriate experimental models in which to study resistance to transplantation tolerance. Here, we demonstrate that T helper 1-associated T box 21 transcription factor (Tbet) KO recipients exhibit allograft tolerance resistance specifically mediated by IL-17-producing CD8 T (T17) cells. Neutralization of IL-17 facilitates long-term cardiac allograft survival with combined T cell co-stimulation (CD28-CD80/86 and CD154-CD40) blockade in Tbet KO recipients. We have used this T17-biased Tbet KO model of allograft tolerance resistance to study the impact of targeting a T cell-co-stimulatory pathway, and demonstrate that targeting T cell Ig and mucin domain-1 (Tim-1) with anti-Tim-1 overcomes this resistance by specifically inhibiting the pathogenic IL-17-producing CD8 T17 cells. These data indicate that in the absence of Th1 immunity, CD8 T17 alloreactivity constitutes a barrier to transplantation tolerance. Targeting TIM-1 provides an approach to overcome resistance to tolerance in clinical transplantation.
The Darwinian revolution: Rethinking its meaning and significance
Authors: Ruse Michael
Published: June 2009

The Darwinian revolution is generally taken to be one of the key events in the history of Western science. In recent years, however, the very notion of a scientific revolution has come under attack, and in the specific case of Charles Darwin and hisOrigin of Speciesthere are serious questions about the nature of the change (if there was such) and the specifically Darwinian input. This article considers these issues by addressing these questions: Was there a Darwinianrevolution? That is, was there a revolution at all? Was there aDarwinianrevolution? That is, what was the specific contribution of Charles Darwin? Was there aDarwinian revolution? That is, what was the conceptual nature of what occurred on and around the publication of theOrigin? I argue that there was a major change, both scientifically and in a broader metaphysical sense; that Charles Darwin was the major player in the change, although one must qualify the nature and the extent of the change, looking particularly at things in a broader historical context than just as an immediate event; and that the revolution was complex and we need the insights of rather different philosophies of scientific change to capture the whole phenomenon. In some respects, indeed, the process of analysis is still ongoing and unresolved.
Did Darwin write theOriginbackwards?
Authors: Sober Elliott
Published: June 2009

After clarifying how Darwin understood natural selection and common ancestry, I consider how the two concepts are related in his theory. I argue that common ancestry has evidential priority. Arguments about natural selection often make use of the assumption of common ancestry, whereas arguments for common ancestry do not require the assumption that natural selection has been at work. In fact, Darwin held that the key evidence for common ancestry comes from characters whose evolution isnotcaused by natural selection. This raises the question of why Darwin puts natural selection first and foremost in theOrigin.
Tracking footprints of maize domestication and evidence for a massive selective sweep on chromosome 10
Authors: Tian Feng , Stevens Natalie M. , Buckler Edward S.
Published: June 2009

Maize domestication is one of the greatest feats of artificial selection and evolution, wherein a weedy plant in Central Mexico was converted through human-mediated selection into the most productive crop in the world. In fact, the changes were so astounding that it took much of the last century to identify modern maize's true ancestor. Through modern genetic studies, the molecular basis of this evolution is being unraveled. Maize's new morphology and adaptation to diverse environments required selection at thousands of loci, and we are beginning to understand the magnitude and rates of these genetic changes. Most of the known major genes have experienced strong selection, but only small regions surrounding the selected genes exhibit substantially reduced genetic diversity. Here, we report the discovery of a large region on chromosome 10 involved in adaptation or domestication that has been the target of strong selection during maize domestication. Unlike previously described regions in the maize genome, 1.1 Mb and >15 genes lost genetic diversity during selection at this region. Finally, the prospects of a detailed understanding of maize evolution are discussed with consideration of both top-down and bottom-up approaches.
Reproductive decisions under ecological constraints: It's about time
Authors: Gowaty Patricia Adair , Hubbell Stephen P.
Published: June 2009

The switch point theorem (SPT) is the quantitative statement of the hypothesis that stochastic effects on survival, mate encounter, and latency affect individuals' time available for mating, the mean and variance in fitness, and thus, originally favored the evolution of individuals able to make adaptively flexible reproductive decisions. The SPT says that demographic stochasticity acting through variation in (
i
) individual survival probability,
s
; (
ii
) individual encounter probability,
e
; (
iii
) latency,
l
; (
iv
) the number of potential mates in the population,
n
; and (
v
) the distribution of fitness conferred, the
w
distribution, together affect average lifetime fitness, and induce adaptive switches in individual reproductive decisions. The switch point is the rank of potential mates at which focal individuals switch from accepting to rejecting potential mates, a decision rule that the SPT proves maximizes the average lifetime fitness of a focal individual under given values of ecological constraints on time. The SPT makes many predictions, including that the shape of the distribution of fitness conferred affects individual switch points. All else equal, higher probabilities of individual survival and encounter decrease the fraction of acceptable potential mates, such that focal individuals achieve higher average lifetime fitness by rejecting more potential mates. The primary prediction of the SPT is that each decision a focal individual makes is determined jointly by
e
,
s
,
l
,
n
, and the
w
distribution.
Natural selection in action during speciation
Authors: Via Sara
Published: June 2009

The role of natural selection in speciation, first described by Darwin, has finally been widely accepted. Yet, the nature and time course of the genetic changes that result in speciation remain mysterious. To date, genetic analyses of speciation have focused almost exclusively on retrospective analyses of reproductive isolation between species or subspecies and on hybrid sterility or inviability rather than on ecologically based barriers to gene flow. However, if we are to fully understand the origin of species, we must analyze the process from additional vantage points. By studying the genetic causes of partial reproductive isolation between specialized ecological races, early barriers to gene flow can be identified before they become confounded with other species differences. This population-level approach can reveal patterns that become invisible over time, such as the mosaic nature of the genome early in speciation. Under divergent selection in sympatry, the genomes of incipient species become temporary genetic mosaics in which ecologically important genomic regions resist gene exchange, even as gene flow continues over most of the genome. Analysis of such mosaic genomes suggests that surprisingly large genomic regions around divergently selected quantitative trait loci can be protected from interrace recombination by “divergence hitchhiking.” Here, I describe the formation of the genetic mosaic during early ecological speciation, consider the establishment, effects, and transitory nature of divergence hitchhiking around key ecologically important genes, and describe a 2-stage model for genetic divergence during ecological speciation with gene flow.
Darwin and the scientific method
Authors: Ayala Francisco J.
Published: June 2009

There is a contradiction between Darwin's methodology and how he described it for public consumption. Darwin claimed that he proceeded “on true Baconian [inductive] principles and without any theory collected facts on a wholesale scale.” He also wrote, “How odd it is that anyone should not see that all observation must be for or against some view if it is to be of any service!” The scientific method includes 2 episodes. The first consists of formulating hypotheses; the second consists of experimentally testing them. What differentiates science from other knowledge is the second episode: subjecting hypotheses to empirical testing by observing whether or not predictions derived from a hypothesis are the case in relevant observations and experiments. A hypothesis is scientific only if it is consistent with some but not other possible states of affairs not yet observed, so that it is subject to the possibility of falsification by reference to experience. Darwin occupies an exalted place in the history of Western thought, deservedly receiving credit for the theory of evolution. InThe Origin of Species, he laid out the evidence demonstrating the evolution of organisms. More important yet is that he discovered natural selection, the process that accounts for the adaptations of organisms and their complexity and diversification. Natural selection and other causal processes of evolution are investigated by formulating and testing hypotheses. Darwin advanced hypotheses in multiple fields, including geology, plant morphology and physiology, psychology, and evolution, and subjected them to severe empirical tests.
In the light of directed evolution: Pathways of adaptive protein evolution
Authors: Bloom Jesse D. , Arnold Frances H.
Published: June 2009

Directed evolution is a widely-used engineering strategy for improving the stabilities or biochemical functions of proteins by repeated rounds of mutation and selection. These experiments offer empirical lessons about how proteins evolve in the face of clearly-defined laboratory selection pressures. Directed evolution has revealed that single amino acid mutations can enhance properties such as catalytic activity or stability and that adaptation can often occur through pathways consisting of sequential beneficial mutations. When there are no single mutations that improve a particular protein property experiments always find a wealth of mutations that are neutral with respect to the laboratory-defined measure of fitness. These neutral mutations can open new adaptive pathways by at least 2 different mechanisms. Functionally-neutral mutations can enhance a protein's stability, thereby increasing its tolerance for subsequent functionally beneficial but destabilizing mutations. They can also lead to changes in “promiscuous” functions that are not currently under selective pressure, but can subsequently become the starting points for the adaptive evolution of new functions. These lessons about the coupling between adaptive and neutral protein evolution in the laboratory offer insight into the evolution of proteins in nature.
From wild animals to domestic pets, an evolutionary view of domestication
Authors: Driscoll Carlos A. , Macdonald David W. , O'Brien Stephen J.
Published: June 2009

Artificial selection is the selection of advantageous natural variation for human ends and is the mechanism by which most domestic species evolved. Most domesticates have their origin in one of a few historic centers of domestication as farm animals. Two notable exceptions are cats and dogs. Wolf domestication was initiated late in the Mesolithic when humans were nomadic hunter-gatherers. Those wolves less afraid of humans scavenged nomadic hunting camps and over time developed utility, initially as guards warning of approaching animals or other nomadic bands and soon thereafter as hunters, an attribute tuned by artificial selection. The first domestic cats had limited utility and initiated their domestication among the earliest agricultural Neolithic settlements in the Near East. Wildcat domestication occurred through a self-selective process in which behavioral reproductive isolation evolved as a correlated character of assortative mating coupled to habitat choice for urban environments. Eurasian wildcats initiated domestication and their evolution to companion animals was initially a process of natural, rather than artificial, selection over time driven during their sympatry with forbear wildcats.
A mitochondria-targeted
S
-nitrosothiol modulates respiration, nitrosates thiols, and protects against ischemia-reperfusion injury
Authors: Prime Tracy A. , Blaikie Frances H. , Evans Cameron , Nadtochiy Sergiy M. , James Andrew M. , Dahm Christina C. , Vitturi Dario A. , Patel Rakesh P. , Hiley C. Robin , Abakumova Irina , Requejo Raquel , Chouchani Edward T. , Hurd Thomas R. , Garvey John F. , Taylor Cormac T. , Brookes Paul S. , Smith Robin A. J. , Murphy Michael P.
Published: June 2009

Nitric oxide (NO
•
) competitively inhibits oxygen consumption by mitochondria at cytochrome
c
oxidase and
S
-nitrosates thiol proteins. We developed mitochondria-targeted
S
-nitrosothiols (MitoSNOs) that selectively modulate and protect mitochondrial function. The exemplar MitoSNO1, produced by covalently linking an
S
-nitrosothiol to the lipophilic triphenylphosphonium cation, was rapidly and extensively accumulated within mitochondria, driven by the membrane potential, where it generated NO
•
and
S
-nitrosated thiol proteins. MitoSNO1-induced NO
•
production reversibly inhibited respiration at cytochrome
c
oxidase and increased extracellular oxygen concentration under hypoxic conditions. MitoSNO1 also caused vasorelaxation due to its NO
•
generation. Infusion of MitoSNO1 during reperfusion was protective against heart ischemia-reperfusion injury, consistent with a functional modification of mitochondrial proteins, such as complex I, following
S
-nitrosation. These results support the idea that selectively targeting NO
•
donors to mitochondria is an effective strategy to reversibly modulate respiration and to protect mitochondria against ischemia-reperfusion injury.
Pancreatic protease activation by alcohol metabolite depends on Ca
2+
release via acid store IP
3
receptors
Authors: Gerasimenko Julia V. , Lur György , Sherwood Mark W. , Ebisui Etsuko , Tepikin Alexei V. , Mikoshiba Katsuhiko , Gerasimenko Oleg V. , Petersen Ole H.
Published: June 2009

Toxic alcohol effects on pancreatic acinar cells, causing the often fatal human disease acute pancreatitis, are principally mediated by fatty acid ethyl esters (non-oxidative products of alcohol and fatty acids), emptying internal stores of Ca
2+
. This excessive Ca
2+
liberation induces Ca
2+
-dependent necrosis due to intracellular trypsin activation. Our aim was to identify the specific source of the Ca
2+
release linked to the fatal intracellular protease activation. In 2-photon permeabilized mouse pancreatic acinar cells, we monitored changes in the Ca
2+
concentration in the thapsigargin-sensitive endoplasmic reticulum (ER) as well as in a bafilomycin-sensitive acid compartment, localized exclusively in the apical granular pole. We also assessed trypsin activity in the apical granular region. Palmitoleic acid ethyl ester (POAEE) elicited Ca
2+
release from both the ER as well as the acid pool, but trypsin activation depended predominantly on Ca
2+
release from the acid pool, that was mainly mediated by functional inositol 1,4,5- trisphosphate receptors (IP
3
Rs) of types 2 and 3. POAEE evoked very little Ca
2+
release and trypsin activation when IP
3
Rs of both types 2 and 3 were knocked out. Antibodies against IP
3
Rs of types 2 and 3, but not type 1, markedly inhibited POAEE-elicited Ca
2+
release and trypsin activation. We conclude that Ca
2+
release through IP
3
Rs of types 2 and 3 in the acid granular Ca
2+
store induces intracellular protease activation, and propose that this is a critical process in the initiation of alcohol-related acute pancreatitis.
Peptide immunotherapy in allergic asthma generates IL-10–dependent immunological tolerance associated with linked epitope suppression
Authors: Campbell John D. , Buckland Karen F. , McMillan Sarah J. , Kearley Jennifer , Oldfield William L.G. , Stern Lawrence J. , Grönlund Hans , van Hage Marianne , Reynolds Catherine J. , Boyton Rosemary J. , Cobbold Stephen P. , Kay A. Barry , Altmann Daniel M. , Lloyd Clare M. , Larché Mark
Published: June 2009

Treatment of patients with allergic asthma using low doses of peptides containing T cell epitopes from Fel d 1, the major cat allergen, reduces allergic sensitization and improves surrogate markers of disease. Here, we demonstrate a key immunological mechanism, linked epitope suppression, associated with this therapeutic effect. Treatment with selected epitopes from a single allergen resulted in suppression of responses to other (“linked”) epitopes within the same molecule. This phenomenon was induced after peptide immunotherapy in human asthmatic subjects and in a novel HLA-DR1 transgenic mouse model of asthma. Tracking of allergen-specific T cells using DR1 tetramers determined that suppression was associated with the induction of interleukin (IL)-10+ T cells that were more abundant than T cells specific for the single-treatment peptide and was reversed by anti–IL-10 receptor administration. Resolution of airway pathophysiology in this model was associated with reduced recruitment, proliferation, and effector function of allergen-specific Th2 cells. Our results provide, for the first time, in vivo evidence of linked epitope suppression and IL-10 induction in both human allergic disease and a mouse model designed to closely mimic peptide therapy in humans.
The B7 family member B7-H6 is a tumor cell ligand for the activating natural killer cell receptor NKp30 in humans
Authors: Brandt Cameron S. , Baratin Myriam , Yi Eugene C. , Kennedy Jacob , Gao Zeren , Fox Brian , Haldeman Betty , Ostrander Craig D. , Kaifu Tomonori , Chabannon Christian , Moretta Alessandro , West Robert , Xu WenFeng , Vivier Eric , Levin Steven D.
Published: June 2009

Cancer development is often associated with the lack of specific and efficient recognition of tumor cells by the immune system. Natural killer (NK) cells are lymphocytes of the innate immune system that participate in the elimination of tumors. We report the identification of a tumor cell surface molecule that binds NKp30, a human receptor which triggers antitumor NK cell cytotoxicity and cytokine secretion. This previously unannotated gene belongs to the B7 family and, hence, was designated B7-H6. B7-H6 triggers NKp30-mediated activation of human NK cells. B7-H6 was not detected in normal human tissues but was expressed on human tumor cells, emphasizing that the expression of stress-induced self-molecules associated with cell transformation serves as a mode of cell recognition in innate immunity.
PROMISE: a tool to identify genomic features with a specific biologically interesting pattern of associations with multiple endpoint variables
Authors: Pounds Stan , Cheng Cheng , Cao Xueyuan , Crews Kristine R. , Plunkett William , Gandhi Varsha , Rubnitz Jeffrey , Ribeiro Raul C. , Downing James R. , Lamba Jatinder
Published: June 2009

Motivation: In some applications, prior biological knowledge can be used to define a specific pattern of association of multiple endpoint variables with a genomic variable that is biologically most interesting. However, to our knowledge, there is no statistical procedure designed to detect specific patterns of association with multiple endpoint variables.

Results: Projection onto the most interesting statistical evidence (PROMISE) is proposed as a general procedure to identify genomic variables that exhibit a specific biologically interesting pattern of association with multiple endpoint variables. Biological knowledge of the endpoint variables is used to define a vector that represents the biologically most interesting values for statistics that characterize the associations of the endpoint variables with a genomic variable. A test statistic is defined as the dot-product of the vector of the observed association statistics and the vector of the most interesting values of the association statistics. By definition, this test statistic is proportional to the length of the projection of the observed vector of correlations onto the vector of most interesting associations. Statistical significance is determined via permutation. In simulation studies and an example application, PROMISE shows greater statistical power to identify genes with the interesting pattern of associations than classical multivariate procedures, individual endpoint analyses or listing genes that have the pattern of interest and are significant in more than one individual endpoint analysis.

Availability: Documented R routines are freely available from www.stjuderesearch.org/depts/biostats and will soon be available as a Bioconductor package from www.bioconductor.org.

Contact:  stanley.pounds@stjude.org

Supplementary information:  Supplementary data are available at Bioinformatics online.
Inferring progression models for CGH data
Authors: Liu Jun , Bandyopadhyay Nirmalya , Ranka Sanjay , Baudis M. , Kahveci Tamer
Published: June 2009

Motivation: One of the mutational processes that has been monitored genome-wide is the occurrence of regional DNA copy number alterations (CNAs), which may lead to deletion or over-expression of tumor suppressors or oncogenes, respectively. Understanding the relationship between CNAs and different cancer types is a fundamental problem in cancer studies.

Results: This article develops an efficient method that can accurately model the progression of the cancer markers and reconstruct evolutionary relationship between multiple types of cancers using comparative genomic hybridization (CGH) data. Such modeling can lead to better understanding of the commonalities and differences between multiple cancer types and potential therapies. We have developed an automatic method to infer a graph model for the markers of multiple cancers from a large population of CGH data. Our method identifies highly related markers across different cancer types. It then builds a directed acyclic graph that shows the evolutionary history of these markers based on how common each marker is in different cancer types. We demonstrated the use of this model in determining the importance of markers in cancer evolution. We have also developed a new method to measure the evolutionary distance between different cancers based on their markers. This method employs the graph model we developed for the individual markers to measure the distance between pairs of cancers. We used this measure to create an evolutionary tree for multiple cancers. Our experiments on Progenetix database show that our markers are largely consistent to the reported hot-spot imbalances and most frequent imbalances. The results show that our distance measure can accurately reconstruct the evolutionary relationship between multiple cancer types.

Availability: All the code developed in this article are available at http://bioinformatics.cise.ufl.edu/phylogeny.html.

Contact:  nirmalya@cise.ufl.edu; tamer@cise.ufl.edu

Supplementary information:  Supplementary data are available at Bioinformatics online.
A CitationRank algorithm inheriting Google technology designed to highlight genes responsible for serious adverse drug reaction
Authors: Yang Lun , Xu Langlai , He Lin
Published: June 2009

Motivation: Serious adverse drug reaction (SADR) is an urgent, world-wide problem. In the absence of any well-organized gene-oriented SADR information pool, a database should be constructed. Since the importance of a gene to a particular SADR cannot simply be defined in terms of how frequently the two are cited together in the literature, an algorithm should be devised to sort genes according to their relevance to the SADR topics.

Results: The SADR-Gengle database, which is made up of gene–SADR relationships extracted from Pubmed, has been constructed, covering six major SADRs, namely cholestasis, deafness, muscle toxicity, QT prolongation, Stevens–Johnson syndrome and torsades de points. The CitationRank algorithm, which inherits the principle of the Google PageRank algorithm that a gene should be highly ranked when biologically related to other highly ranked genes, is devised. The algorithm performs robustly in recovering SADR-related genes in the presence of extraneous noise, and the use of the algorithm has been extended to sorting genes in our database. Users can browse genes in a Google-type system where genes are ordered according to their descending relevance to the SADR topic selected by the user. The database also provides users with visualized gene–gene knowledge chain networks, helping them to systematize their gene-oriented knowledge chain whilst navigating these networks.

Availability: The SADR-Gengle is freely available at http://Gengle.Bio-X.cn/SADR/.

Contact:  helinhelin@gmail.com

Supplementary information:  Supplementary data are available at Bioinformatics online.
Modelling the direct impact of bottom trawling on the North Sea fish community to derive estimates of fishing mortality for non-target fish species
Authors: Piet G. J. , van Hal R. , Greenstreet S. P. R.
Published: June 2009

Piet, G. J., van Hal, R., and Greenstreet, S. P. R. 2009. Modelling the direct impact of bottom trawling on the North Sea fish community to derive estimates of fishing mortality for non-target fish species. – ICES Journal of Marine Science, 66: 1985–1998. This study introduces a spatially explicit model that combines abundance data for all the main fish species in the demersal North Sea fish community with international effort data and estimates of gear-, species-, and size-dependent catch efficiency to determine the mortality of non-target fish species caused by bottom trawl fisheries and its spatial variation. Where necessary information was lacking, assumptions were made, and a sensitivity analysis performed to examine the impact of these issues on model results. Model outcomes were validated using international landings and discard data for five target species: cod, haddock, whiting, sole, and plaice. This showed that depending on its configuration, the model could reproduce recorded landings and discards of these species reasonably well. This suggests that the model could be used to simulate rates of fishing mortality for non-target fish species, for which few data are currently available. Sensitivity analyses revealed that model outcomes were most strongly influenced by the estimates of gear catch efficiency and the extent to which the distributions of fishing effort and each species overlapped. Better data for these processes would enhance the contribution that this type of model could make in supporting an ecosystem approach to fisheries management.
Ailanthus altissima Wilt and Mortality: Etiology
Authors: Schall Mark J. , Davis Donald D.
Published: June 2009

Extensive, unprecedented wilt and mortality of the highly invasive tree-of-heaven (Ailanthus altissima) occurred recently within mixed-hardwood forests in south-central Pennsylvania. Until this study, the cause of the epidemic was unknown. Verticillium albo-atrum was consistently isolated from symptomatic Ailanthus seedlings and trees in areas having high levels of mortality, whereas V. dahliae was isolated from small scattered patches of diseased Ailanthus. Inoculations of potted Ailanthus seedlings in the greenhouse, as well as canopy trees in the field, revealed that both V. albo-atrum and V. dahliae were capable of infecting Ailanthus, but V. albo-atrum was more pathogenic. All Ailanthus seedlings and canopy trees inoculated with V. albo-atrum died within 3 months. In contrast, Ailanthus seedlings and canopy trees inoculated with V. dahliae became symptomatic, but 84% were still living 1 year following inoculation. We conclude that the major cause of Ailanthus wilt within forests of south-central Pennsylvania is V. albo-atrum. Pending further studies, including risk analysis, V. albo-atrum may be considered as a possible biocontrol agent for invasive Ailanthus.
First Report of Dry Rot Caused by Fusarium oxysporum on Rose (Rosa spp.) in Brazil
Authors: Barguil B. M. , Viana F. M. P. , Anjos R. M. , Cardoso J. E.
Published: June 2009

Roses are a high-value niche crop in the higher altitudes of northeastern Brazil. From July of 2007 and throughout 2008, severe stem rot and wilting of rose seedlings were observed in commercial fields in the São Benedito District, Ceará State, Brazil. Although economic losses due to the disease are unknown, it poses a threat to the growing rose industry in that region. Symptoms included leaf yellowing and abscission followed by plant collapse. Symptoms appeared earlier when grafted seedlings were produced during periods of high relative humidity (80 to 98%) and warm temperatures (20 to 31°C). In the laboratory, symptomatic seedlings were rinsed with distilled water, surface sterilized with 0.5% NaOCl, and incubated on PDA at 26 ± 2°C. Fusarium oxysporum was consistently isolated from infected scions and rootstocks. Identification of F. oxysporum was based on colony and conidia morphology obtained from single-spore colonies. Five 4-week-old rose (‘Carola’) seedlings were inoculated with a culture of fungus by spraying the needle-wounded scion with a spore suspension (1 × 105 CFU/ml). The spore suspension was obtained from a 1-week-old PDA culture incubated at 26 ± 2°C. Control seedlings were sprayed with sterile water. Inoculated seedlings were incubated for the first 48 h in a saturated humidity chamber. After 20 days at room temperature, the scion tissue of inoculated seedlings turned necrotic. Two symptomatic seedlings were placed in a saturated humidity chamber for 24 h to determine if fungal sporulation could be observed on the surface of the tissue. After 5 to 7 days, a white mycelium was observed over the necrotic tissue. Seedlings sprayed with sterile water remained symptomless. F. oxysporum was reisolated from symptomatic tissue. An isolate of F. oxyporum (No. 1484) was deposited in the Mycology Collection of Lavras (Minas Gerais State, Brazil). To our knowledge, this is the first report of F. oxysporum causing a disease on rose seedlings in Brazil.
Large eddy simulation of the atmosphere on various scales
Authors: Cullen M.J.P. , Brown A.R.
Published: June 2009

Numerical simulations of the atmosphere are routinely carried out on various scales for purposes ranging from weather forecasts for local areas a few hours ahead to forecasts of climate change over periods of hundreds of years. Almost without exception, these forecasts are made with space/time-averaged versions of the governing Navier–Stokes equations and laws of thermodynamics, together with additional terms representing internal and boundary forcing. The calculations are a form of large eddy modelling, because the subgrid-scale processes have to be modelled. In the global atmospheric models used for long-term predictions, the primary method is implicit large eddy modelling, using discretization to perform the averaging, supplemented by specialized subgrid models, where there is organized small-scale activity, such as in the lower boundary layer and near active convection. Smaller scale models used for local or short-range forecasts can use a much smaller averaging scale. This allows some of the specialized subgrid models to be dropped in favour of direct simulations. In research mode, the same models can be run as a conventional large eddy simulation only a few orders of magnitude away from a direct simulation. These simulations can then be used in the development of the subgrid models for coarser resolution models.
Large eddy simulation modelling of combustion for propulsion applications
Authors: Fureby C.
Published: June 2009

Predictive modelling of turbulent combustion is important for the development of air-breathing engines, internal combustion engines, furnaces and for power generation. Significant advances in modelling non-reactive turbulent flows are now possible with the development of large eddy simulation (LES), in which the large energetic scales of the flow are resolved on the grid while modelling the effects of the small scales. Here, we discuss the use of combustion LES in predictive modelling of propulsion applications such as gas turbine, ramjet and scramjet engines. The LES models used are described in some detail and are validated against laboratory data—of which results from two cases are presented. These validated LES models are then applied to an annular multi-burner gas turbine combustor and a simplified scramjet combustor, for which some additional experimental data are available. For these cases, good agreement with the available reference data is obtained, and the LES predictions are used to elucidate the flow physics in such devices to further enhance our knowledge of these propulsion systems. Particular attention is focused on the influence of the combustion chemistry, turbulence–chemistry interaction, self-ignition, flame holding burner-to-burner interactions and combustion oscillations.
Developing large eddy simulation for turbomachinery applications
Authors: Eastwood Simon J. , Tucker Paul G. , Xia Hao , Klostermeier Christian
Published: June 2009

For jets, large eddy resolving simulations are compared for a range of numerical schemes with no subgrid scale (SGS) model and for a range of SGS models with the same scheme. There is little variation in results for the different SGS models, and it is shown that, for schemes which tend towards having dissipative elements, the SGS model can be abandoned, giving what can be termed numerical large eddy simulation (NLES). More complex geometries are investigated, including coaxial and chevron nozzle jets. A near-wall Reynolds-averaged Navier–Stokes (RANS) model is used to cover over streak-like structures that cannot be resolved. Compressor and turbine flows are also successfully computed using a similar NLES–RANS strategy. Upstream of the compressor leading edge, the RANS layer is helpful in preventing premature separation. Capturing the correct flow over the turbine is particularly challenging, but nonetheless the RANS layer is helpful. In relation to the SGS model, for the flows considered, evidence suggests issues such as inflow conditions, problem definition and transition are more influential.
Analysis of errors occurring in large eddy simulation
Authors: Geurts Bernard J.
Published: June 2009

We analyse the effect of second- and fourth-order accurate central finite-volume discretizations on the outcome of large eddy simulations of homogeneous, isotropic, decaying turbulence at an initial Taylor–Reynolds number
Re

λ

=100. We determine the implicit filter that is induced by the spatial discretization and show that a higher order discretization also induces a higher order filter, i.e. a low-pass filter that keeps a wider range of flow scales virtually unchanged. The effectiveness of the implicit filtering is correlated with the optimal refinement strategy as observed in an error-landscape analysis based on Smagorinsky's subfilter model. As a point of reference, a finite-volume method that is second-order accurate for both the convective and the viscous fluxes in the Navier–Stokes equations is used. We observe that changing to a fourth-order accurate convective discretization leads to a higher value of the Smagorinsky coefficient
C
S
required to achieve minimal total error at given resolution. Conversely, changing only the viscous flux discretization to fourth-order accuracy implies that optimal simulation results are obtained at lower values of
C
S
. Finally, a fully fourth-order discretization yields an optimal
C
S
that is slightly lower than the reference fully second-order method.
Large eddy simulation of flows around ground vehicles and other bluff bodies
Authors: Krajnović Siniša
Published: June 2009

A brief review of large eddy simulation (LES) applications for different bluff-body flows performed by the author and his co-workers is presented. Examples of flows range from simple cube flows characterized by sharp edge separation over a three-dimensional hill where LES relies on good near-wall resolution, to complex flows of a tall, finite cylinder that contains several flow regimes that cause different challenges to LES. The second part of the paper is devoted to flows around ground vehicles at moderate Reynolds numbers. Although the present review proves the applicability of LES for various bluff-body flows, an increase of the Reynolds number towards the operational speeds of ground vehicles requires accurate near-wall modelling for a successful LES.
On integrating large eddy simulation and laboratory turbulent flow experiments
Authors: Grinstein Fernando F.
Published: June 2009

Critical issues involved in large eddy simulation (LES) experiments relate to the treatment of unresolved subgrid scale flow features and required initial and boundary condition
supergrid
scale modelling. The inherently intrusive nature of both LES and laboratory experiments is noted in this context. Flow characterization issues becomes very challenging ones in validation and computational laboratory studies, where potential sources of discrepancies between predictions and measurements need to be clearly evaluated and controlled. A special focus of the discussion is devoted to turbulent initial condition issues.
Mind the gap: a guideline for large eddy simulation
Authors: George William K. , Tutkun Murat
Published: June 2009

This paper briefly reviews some of the fundamental ideas of turbulence as they relate to large eddy simulation (LES). Of special interest is how our thinking about the so-called ‘spectral gap’ has evolved over the past decade, and what this evolution implies for LES applications.