bluuebunny/crossref_metadata_2025_split huggingface dataset:
Improving NMR protein structure quality by Rosetta refinement: A molecular replacement study
Authors: Ramelot Theresa A. , Raman Srivatsan , Kuzin Alexandre P. , Xiao Rong , Ma Li‐Chung , Acton Thomas B. , Hunt John F. , Montelione Gaetano T. , Baker David , Kennedy Michael A. 
Published: September 2008

AbstractThe structure of human protein HSPC034 has been determined by both solution nuclear magnetic resonance (NMR) spectroscopy and X‐ray crystallography. Refinement of the NMR structure ensemble, using a Rosetta protocol in the absence of NMR restraints, resulted in significant improvements not only in structure quality, but also in molecular replacement (MR) performance with the raw X‐ray diffraction data using MOLREP and Phaser. This method has recently been shown to be generally applicable with improved MR performance demonstrated for eight NMR structures refined using Rosetta (Qian et al., Nature 2007;450:259–264). Additionally, NMR structures of HSPC034 calculated by standard methods that include NMR restraints have improvements in the RMSD to the crystal structure and MR performance in the order DYANA, CYANA, XPLOR‐NIH, and CNS with explicit water refinement (CNSw). Further Rosetta refinement of the CNSw structures, perhaps due to more thorough conformational sampling and/or a superior force field, was capable of finding alternative low energy protein conformations that were equally consistent with the NMR data according to the Recall, Precision, and F‐measure (RPF) scores. On further examination, the additional MR‐performance shortfall for NMR refined structures as compared with the X‐ray structure were attributed, in part, to crystal‐packing effects, real structural differences, and inferior hydrogen bonding in the NMR structures. A good correlation between a decrease in the number of buried unsatisfied hydrogen‐bond donors and improved MR performance demonstrates the importance of hydrogen‐bond terms in the force field for improving NMR structures. The superior hydrogen‐bond network in Rosetta‐refined structures demonstrates that correct identification of hydrogen bonds should be a critical goal of NMR structure refinement. Inclusion of nonbivalent hydrogen bonds identified from Rosetta structures as additional restraints in the structure calculation results in NMR structures with improved MR performance. Proteins 2009. © 2008 Wiley‐Liss, Inc.
A case study of a severe winter storm in the Middle East
Authors: Lee Tiros Pei‐Jiun , Silberberg Steven R. , Bosart Lance F. 
Published: September 2008

AbstractA detailed synoptic and mesoscale analysis is conducted of an intense convective outbreak which struck much of Israel, Jordan, Lebanon and Syria in early March 1980. Severe winter weather caused considerable personal hardship and economic disruption over a wide area.The planetary‐scale circulation featured a confluent flow pattern across North Africa and southern Europe downstream of a block just west of the Greenwich meridian. A strong subtropical jet stream was maintained across North Africa in the confluent flow regime. Synoptic‐scale disturbances from the Atlantic were diverted northward across Scandinavia from where they plunged south‐eastward toward the Mediterranean to the west of the Black Sea. A series of three disturbances, the last being the most powerful, swept through the eastern Mediterranean as the vortex settled south‐eastward toward the Middle East.Our analysis of the available evidence has established that three physical mechanisms contributed primarily to the extreme nature of the event. First, the steady south‐eastward movement of mobile short wave troughs resulted in the progressive cooling of the lower and middle troposphere over the eastern Mediterranean Sea and the Middle East. Second, sea surface heat and moisture fluxes contributed to destabilization and the generation of extreme instability where the cold air from higher latitudes had a long overwater fetch. Third, exceptionally heavy precipitation fell where a strong low‐level moist, unstable westerly air stream impinged on the coastal mountains. The strong westerly flow was generated to the south of an intense subsynoptic‐scale vortex that formed in the lower and mid troposphere as the updraught region of a powerful short‐wave‐trough/ jet‐streak system aloft ingested air that had been destabilized below.
Large‐eddy simulation and parametrization of the baroclinic boundary‐layer
Authors: Brown A. R. 
Published: September 2008

AbstractLarge‐eddy simulations of the non‐entraining dry boundary‐layer, in which the geostrophic wind varies with height, are described. Results are presented for various turbulence statistics, and the large‐eddy model results are used to evaluate the performance of two simple closure‐models. It is shown that the performance of these models is not significantly degraded, in either neutral or convective conditions, by the presence of shear in the geostrophic wind.
A parametrization of the ice water content observed in frontal and convective clouds
Authors: Bower Keith N. , Moss S. J. , Johnson D. W. , Choularton T. W. , Latham J. , Brown P. R. A. , Blyth A. M. , Cardwell J. 
Published: September 2008

AbstractThe properties of the ice phase in a number of cloud types are investigated to improve the ice phase parametrization in atmospheric global‐climate models. Frontal clouds over southern England and the sea areas around the British Isles, maritime convective clouds over the North Atlantic, and continental convective clouds over New Mexico and Montana in the USA are studied.Ice concentrations are seen to be several orders of magnitude higher than those which could be attributed to primary nucleation of ice nuclei at cloud‐top temperatures. Thus secondary ice multiplication processes must be operating in each cloud type. Evidence suggests that the process of ice splinter production during riming, the Hallett–Mossop process which operates at temperatures around −6°C, is the dominant mechanism operating.The data analysed are parametrized as phase ratios, the fraction of cloud condensed water found in the liquid phase, and the variation of this phase ratio with temperature is examined. The greatest differences are observed between frontal and convective clouds, although smaller differences between continental and maritime clouds of the same type are also seen. In general, frontal clouds possess very high fractions of ice across a wide range of temperature. In contrast, convective clouds exhibit a wide range of phase ratio across the whole temperature range observed. These differences are attributed to the greater vertical wind velocities present in convective clouds.These parametrizations have been used in the UK Meteorological Office Global Climate Model. They are valid for clouds which span the Hallett‐Mossop splinter‐production temperature range.
A method to determine the amounts of cloud‐top radiative and evaporative cooling in a stratocumulus‐topped boundary layer
Authors: Shao Qingqiu , Randall David A. , Moeng Chin‐Hoh , Dickinson Robert E. 
Published: September 2008

AbstractThe turbulent processes of a stratocumulus‐topped marine boundary layer are not yet fully understood. Among the issues is the relative importance of the effects of cloud‐top radiative and evaporative cooling in driving the stratocumulus‐topped marine boundary layer turbulence, and in producing cloud break‐up. A better way to analyse the relevant observations is needed.Based on the concepts of mixing fraction and mixing‐line analysis, a new method to quantitatively determine the radiative and evaporative cooling of the entrained air parcels near cloud top is proposed. Quantities δ(Sv,)R, which includes evaporative cooling and entrainment mixing warming, and δ(Sv,)R,which includes both radiative cooling and the condensation warming due to radiative cooling, are defined to measure the relative importance of entrainment and radiation effects on parcel buoyancy. Provided that radiative cooling does not depend on mixing fraction for a solid cloud, slopes of the mixing lines from the linear regression of aircraft data, rather than the jumps from soundings, can be used to determine δ(Sv,)E, and δ(Sv,)R. In this way, the information from an extra level above cloud is not needed to determine δ(Sv,)E and δ(Sv,)R, and thus the ambiguities associated with the jumps are by‐passed.The applications of the method to a large‐eddy simulation case and an aircraft data set suggest that radiative cooling is the dominant contributor to the negative buoyancy of the entrained parcels for both cases. They also raise the question as to how much a single sounding can be trusted quantitatively to determine the jumps across the inversion.
Mapping surface‐cover parameters using aggregation rules and remotely sensed cover classes
Authors: Arain Altaf M. , James Shuttleworth W. , Yang Z.‐Liang , Michaud Jené , Dolman Johannes 
Published: September 2008

AbstractA coupled model, which combines the Biosphere—Atmosphere Transfer Scheme (BATS) with an advanced atmospheric boundary‐layer model, is used to validate hypothetical aggregation rules for BATS‐specific surfacecover parameters. the model is initialized and tested with observations from the Anglo—Brazilian Amazonian Climate Observational Study and is used to simulate surface fluxes for rain forest and pasture mixes at a site near Manaus in Brazil. the aggregation rules are shown to estimate parameters which give area‐average surface fluxes similar to those calculated, with explicit representation of forest and pasture patches for a range of meteorological and surface conditions relevant to this site, but the agreement deteriorates somewhat when there are large patchto‐patch differences in soil moisture. the aggregation rules, validated as above, are then applied to a remotely sensed 1 km land‐cover data set to obtain grid‐average values of BATS vegetation parameters for 2.8° x 2.8° and 1° x 1° grids within the conterminous United States. There are significant differences in key vegetation parameters (aerodynamic roughness length, albedo, leaf‐area index, and stomatal resistance) when aggregate parameters are compared with parameters for the single, dominant cover within the grid. However, the surface energy fluxes calculated by stand‐alone BATS with the 2‐year forcing data from the International Satellite Land Surface Climatology Pogramme CD‐ROM are reasonably similar using aggregate‐vegetation parameters and dominant‐cover parameters, but there are some significant differences, particularly in the western USA.
An explicit flux‐form semi‐lagrangian shallow‐water model on the sphere
Authors: Lin Shian‐Jiann , Rood Richard B. 
Published: September 2008

AbstractA global shallow‐water model based on the flux‐form semi‐lagrangian scheme is described. the mass‐conserving flux‐form semi‐Lagrangian scheme is a multidimensional semi‐Lagrangian extension of the higher order Godunov‐type finite‐volume schemes (e.g., the piece‐wise parabolic method). Unlike the piece‐wise parabolic methodology, neither directional splitting nor a Riemann solver is involved. A reverse engineering procedure is introduced to achieve the goal of consistent transport of the absolute vorticity and the mass, and hence, the potential vorticity. Gravity waves are treated explicitly, in a manner that is consistent with the forward‐in‐time flux‐form semi‐Lagrangian transport scheme. Due to the finite‐volume nature of the flux‐form semi‐lagrangian scheme and the application of the monotonicity constraint, which can be regarded as a subgrid‐scale flux parametrization, essentially noise‐free solutions are obtained without additional diffusion. Two selected shallow‐water test cases proposed by Williamson et al. (1992) and a stratospheric vortex erosion simulation are presented. Discussions on the accuracy and computational efficiency are given based on the comparisons with a Eulerian spectral model and two advective‐form semi‐implicit semi‐Lagrangian models.
Travelling wave ion mobility mass spectrometry studies of protein structure: biological significance and comparison with X‐ray crystallography and nuclear magnetic resonance spectroscopy measurements
Authors: Scarff Charlotte A. , Thalassinos Konstantinos , Hilton Gillian R. , Scrivens James H. 
Published: September 2008

AbstractThe three‐dimensional conformation of a protein is central to its biological function. The characterisation of aspects of three‐dimensional protein structure by mass spectrometry is an area of much interest as the gas‐phase conformation, in many instances, can be related to that of the solution phase. Travelling wave ion mobility mass spectrometry (TWIMS) was used to investigate the biological significance of gas‐phase protein structure. Protein standards were analysed by TWIMS under denaturing and near‐physiological solvent conditions and cross‐sections estimated for the charge states observed. Estimates of collision cross‐sections were obtained with reference to known standards with published cross‐sections. Estimated cross‐sections were compared with values from published X‐ray crystallography and nuclear magnetic resonance (NMR) spectroscopy structures. The cross‐section measured by ion mobility mass spectrometry varies with charge state, allowing the unfolding transition of proteins in the gas phase to be studied. Cross‐sections estimated experimentally for proteins studied, for charge states most indicative of native structure, are in good agreement with measurements calculated from published X‐ray and NMR structures. The relative stability of gas‐phase structures has been investigated, for the proteins studied, based on their change in cross‐section with increase in charge. These results illustrate that the TWIMS approach can provide data on three‐dimensional protein structures of biological relevance. Copyright © 2008 John Wiley & Sons, Ltd.
Hepatitis B and liver transplantation: 2008 update
Authors: Beckebaum Susanne , Sotiropoulos Georgios C. , Gerken Guido , Cicinnati Vito R. 
Published: September 2008

AbstractThe ultimate goal of treatment is suppression of viral replication to undetectable HBV‐DNA levels prior to and after liver transplantation (LT) to prevent infection of the newly transplanted liver. Most published data are available from therapy with lamivudine (LAM) in pre‐ and post‐transplant HBV patients. Add‐on therapy with adefovir dipivoxil (ADV) in pre‐transplant LAM‐resistant patients has been shown to represent an effective antiviral strategy leading to hepatic recompensation in many cases and, eventually, removal from the waiting list. Newer nucleos(t)ide analogues such as entecavir, tenofovir and telbivudine have shown lower resistance rates than LAM and more antiviral potency in studies in the non‐transplant setting. Combined hepatitis B immune globulin (HBIG) and nucleos(t)ide analogue therapy have been widely adopted as the most effective treatment strategy against recurrent HBV disease after LT. Many programs have evaluated lower doses or a shorter duration of HBIG and intramuscular versus intravenous routes of administration. Active immunisation using recombinant HBV vaccines, including the S, pre‐S1 and pre‐S2 regions, and those with immunostimulatory adjuvants, seem to be more immunogenic than the currently available vaccines and have been used in studies to replace HBIG. Furthermore, it has been shown that immune memory against HBV can be adoptively transferred from organ donors to transplant recipients. Nucleos(t)ide analogue combination therapies might provide an alternative to the current treatment paradigm with costly HBIG; however, experience with this new treatment regimen is very limited and controlled clinical studies are urgently warranted to investigate its safety and efficacy and to determine which nucleos(t)ide analogue combinations will be the most promising in the long term after LT. Copyright © 2008 John Wiley & Sons, Ltd.
Multiple choice tries and distributed hash tables
Authors: Devroye Luc , Lugosi Gábor , Park Gahyun , Szpankowski Wojciech 
Published: September 2008

AbstractIn this article we consider tries built fromnstrings such that each string can be chosen from a pool ofkstrings, each of them generated by a discrete i.i.d. source. Three cases are considered:k= 2,kis large but fixed, andk˜clogn. The goal in each case is to obtain tries as balanced as possible. Various parameters such as height and fill‐up level are analyzed. It is shown that for two‐choice tries a 50% reduction in height is achieved when compared with ordinary tries. In a greedy online construction when the string that minimizes the depth of insertion for every pair is inserted, the height is only reduced by 25%. To further reduce the height by another 25%, we design a more refined online algorithm. The total computation time of the algorithm isO(nlogn). Furthermore, when we choose the best amongk≥ 2 strings, then for large but fixedkthe height is asymptotically equal to the typical depth in a trie. Finally, we show that further improvement can be achieved if the number of choices for each string is proportional to logn. In this case highly balanced trees can be constructed by a simple greedy algorithm for which the difference between the height and the fill‐up level is bounded by a constant with high probability. This, in turn, has implications for distributed hash tables, leading to a randomized ID management algorithm in peer‐to‐peer networks such that, with high probability, the ratio between the maximum and the minimum load of a processor is O(1). © 2008 Wiley Periodicals, Inc. Random Struct. Alg., 2009
Network risk management using attacker profiling
Authors: Dantu Ram , Kolan Prakash , Cangussu João 
Published: September 2008

AbstractRisk management refers to the process of making decisions that minimize the effects of vulnerabilities on the network hosts. This can be a difficult task in the context of high‐exploit probability and the difficult to identify new exploits and vulnerabilities. For many years, security engineers have performed risk analysis using economic models for the design and operation of risk‐prone, technological systems using attack profiles. Based on the type of attacker identified, security administrators can formulate effective risk management policies for a network. We hypothesize that sequence of network actions by an attacker depends on the social behavior (e.g., skill level, tenacity, financial ability). We extended this and formulated a mechanism to estimate the risk level of critical resources that may be compromised based on attacker behavior. This estimation is accomplished using behavior based attack graphs representing all the possible attack paths to all the critical resources. The risk level is computed based on these graphs and are used as a measure of the vulnerability of the resource and forming an effective basis for a system administrator to perform suitable changes to network configuration. Copyright © 2008 John Wiley & Sons, Ltd.
Avoiding infinite estimates of time‐dependent effects in small‐sample survival studies
Authors: Heinze Georg , Dunkler Daniela 
Published: September 2008

AbstractWe address the phenomenon of monotone likelihood in Cox regression with time‐dependent effects. Monotone likelihood occurs in the fitting process of a Cox model if at least one parameter estimate diverges to ± infinity. We show that the probability of monotone likelihood is increased by the inclusion of time‐dependent effects, particularly in small samples with several unbalanced and highly predictive covariates, and with a high percentage of censoring. Firth's bias reduction procedure was shown to provide an ideal solution to monotone likelihood. Here we extend his idea to Cox regression with time‐dependent effects. By penalized maximum likelihood estimation, finite hazard ratio estimates of constant and time‐dependent effects can be obtained. Penalized likelihood ratio tests and profile penalized likelihood confidence intervals are proposed as tools for inference. A Monte Carlo study of Cox regression with time‐dependent effects confirms advantages of Firth‐corrected (FC) over standard Cox analysis in terms of average bias and median absolute deviation. We also compare the FC and standard Cox approaches by means of analyses of two studies with time‐dependent effects. An SAS macro and an R package for FC Cox regression with time‐varying covariates and time‐dependent effects are available at:http://www.muw.ac.at/msi/biometrie/programs. Copyright © 2008 John Wiley & Sons, Ltd.
Curtailed two‐stage designs in Phase II clinical trials
Authors: Chi Yunchan , Chen Chia‐Min 
Published: September 2008

AbstractWhen the accrual rate is low and the treatment period is long, a long observational period is required before information concerning the primary end point, such as binary response, becomes available in the study. Simon's two‐stage designs are often employed in Phase II clinical trials to avoid giving patient an ineffective drug. Thus, if the new drug is ineffective then this design would certainly accelerate the process of drug discovery and development. However, for a promising new drug this design may still require a long observational period. Therefore, when drug safety is not a primary concern, this paper proposes curtailed two‐stage designs to shorten the drug development process as soon as the treatment either shows lack of efficacy or is very effective. The proposed design is superior to Simon's two‐stage designs in terms of savings in expected sample size and is much easier to implement in practice than stochastically curtailed Simon's designs. Copyright © 2008 John Wiley & Sons, Ltd.
An R2 statistic for fixed effects in the linear mixed model
Authors: Edwards Lloyd J. , Muller Keith E. , Wolfinger Russell D. , Qaqish Bahjat F. , Schabenberger Oliver 
Published: September 2008

AbstractStatisticians most often use the linear mixed model to analyze Gaussian longitudinal data. The value and familiarity of the R2 statistic in the linear univariate model naturally creates great interest in extending it to the linear mixed model. We define and describe how to compute a model R2 statistic for the linear mixed model by using only a single model. The proposed R2 statistic measures multivariate association between the repeated outcomes and the fixed effects in the linear mixed model. The R2 statistic arises as a 1–1 function of an appropriate F statistic for testing all fixed effects (except typically the intercept) in a full model. The statistic compares the full model with a null model with all fixed effects deleted (except typically the intercept) while retaining exactly the same covariance structure. Furthermore, the R2 statistic leads immediately to a natural definition of a partial R2 statistic. A mixed model in which ethnicity gives a very small p‐value as a longitudinal predictor of blood pressure (BP) compellingly illustrates the value of the statistic. In sharp contrast to the extreme p‐value, a very small R2 , a measure of statistical and scientific importance, indicates that ethnicity has an almost negligible association with the repeated BP outcomes for the study. Copyright © 2008 John Wiley & Sons, Ltd.