bluuebunny/crossref_metadata_2025_split huggingface dataset:
How to parameterize models with bursty workloads
Authors: Casale Giuliano , Mi Ningfang , Cherkasova Ludmila , Smirni Evgenia 
Published: October 2008

Although recent advances in theory indicate that burstiness in the service time process can be handled effectively by queueing models (e.g.,MAP queueing networks [2]), there is a lack of understanding and of practical results on how to perform model parameterization, especially when this parameterization must be derived from limited coarse measurements.
We propose a new parameterization methodology based on the index of dispersion of the service process at a server, which is inferred by observing the number of completions within the concatenated busy periods of that server. The index of dispersion together with other measurements that reflect the "estimated" mean and the 95th percentile of service times are used to derive a MAP process that captures well burstiness of the true service process.
Detailed experimentation on a TPC-W testbed where all measurements are obtained via a commercially available tool, the HP (Mercury) Diagnostics, shows that the proposed technique offers a simple yet powerful solution to the difficult problem of inferring accurate descriptors of the service time process from coarse measurements. Experimental and model prediction results are in excellent agreement and argue strongly for the effectiveness of the proposed methodology under bursty or simply variable workloads.
Power management in the EPOS system
Authors: Wiedenhoft Geovani Ricardo , Wanner Lucas Francisco , Gracioli Giovani , Fröhlich Antônio Augusto 
Published: October 2008

Power management strategies for embedded systems typically rely on static, application driven deactivation of components (e.g. sleep, suspend), or on dynamic voltage and frequency scaling. However, the design and implementation of these strategies in embedded operating system often fail to deal with real-time and quality-of-service (QoS) requirements.
The EPOS system implements an infra-structure that supports both static (application-driven) and dynamic (system-driven) power management. In this work, this infrastructure is used to explore energy as a parameter for QoS in embedded systems, with the goal of guaranteeing energy consumption metrics, while preserving the deadlines of essential (hard real-time) tasks. Given a set of real-time tasks and their associated energy consumption, we provide equations to check schedulability in project-time. At runtime, a preemptive scheduler for imprecise tasks prevents the execution of optional subtasks whenever there is the possibility of deadline loss or depletion of the energy source. We show that this mechanism is effective in controlling energy consumption and ensuring "best-effort" computation without deadline loss.
Electrochemical Immunoassay Detection of Bacillus Anthracis Protective Antigen
Authors: Aguilar Zoraida , Yoga Narasimhan Padma , Wansapura Chamika , Henrichs Andrea , Aday Julie , Aguilar Ysmael , Estorninos Leo 
Published: October 2008

A self-contained microelectrochemical immunoassay detection of Bacillus anthracis protective antigen (PA) has been developed. A microcavity array (VEG4x1{trade mark, serif}) of 50-mm diameter cavities with self-contained microelectrodes were used for the detection of as low as 2.5 pg of B. anthracis Protective Antigen in a less than 12 min total assay time from capture to signal generation.	The micro-electrochemical sandwich enzyme-linked immunoassay involved covalent immobilization of the capture antibody on the free end of mercaptoundecanol self-assembled monolayers at the bottom Au-microdisk electrode that also serves as the bottom of the microcavities. Signal generation involved alkaline phosphatase hydrolysis of the enzyme substrate p-aminophenyl phosphate to p-aminophenol that is detected with the wall middle layer gold as the detecting electrode and the top layer gold as the pseudoreference/auxiliary electrodes. The microelectrodes in the cavity exhibited background signals lower than signal for the lowest concentration detected that was 2.5 pg.
Sampling Uncertainty and Confidence Intervals for the Brier Score and Brier Skill Score
Authors: Bradley A. Allen , Schwartz Stuart S. , Hashino Tempei 
Published: October 2008

Abstract
For probability forecasts, the Brier score and Brier skill score are commonly used verification measures of forecast accuracy and skill. Using sampling theory, analytical expressions are derived to estimate their sampling uncertainties. The Brier score is an unbiased estimator of the accuracy, and an exact expression defines its sampling variance. The Brier skill score (with climatology as a reference forecast) is a biased estimator, and approximations are needed to estimate its bias and sampling variance. The uncertainty estimators depend only on the moments of the forecasts and observations, so it is easy to routinely compute them at the same time as the Brier score and skill score. The resulting uncertainty estimates can be used to construct error bars or confidence intervals for the verification measures, or perform hypothesis testing.
Monte Carlo experiments using synthetic forecasting examples illustrate the performance of the expressions. In general, the estimates provide very reliable information on uncertainty. However, the quality of an estimate depends on both the sample size and the occurrence frequency of the forecast event. The examples also illustrate that with infrequently occurring events, verification sample sizes of a few hundred forecast–observation pairs are needed to establish that a forecast is skillful because of the large uncertainties that exist.
The Atlantic Multidecadal Oscillation Inferred from the Forced Climate Response in Coupled General Circulation Models
Authors: Knight Jeff R. 
Published: October 2008

Abstract
Instrumental sea surface temperature records in the North Atlantic Ocean are characterized by large multidecadal variability known as the Atlantic multidecadal oscillation (AMO). The lack of strong oscillatory forcing of the climate system at multidecadal time scales and the results of long unforced climate simulations have led to the widespread, although not ubiquitous, view that the AMO is an internal mode of climate variability. Here, a more objective examination of this hypothesis is performed using simulations with natural and anthropogenic forcings from the Coupled Model Intercomparison Project phase 3 (CMIP3) database. Ensemble means derived from these data allow an estimate of the response of models to forcings, as averaging leads to cancellation of the internal variability between ensemble members. In general, the means of individual model ensembles appear to be inconsistent with observed temperatures, although small ensemble sizes result in uncertainty in this conclusion. Combining the ensembles from different models creates a multimodel ensemble of sufficient size to allow for a good estimate of the forced response. This shows that the variability in observed North Atlantic temperatures possess a clearly distinct signature to the climate response expected from forcings. The reliability of this finding is confirmed by sampling those models with low decadal internal variability and by comparing simulated and observed trends. In contrast to the inconsistency with the ensemble mean, the observations are consistent with the spread of responses in the ensemble members, suggesting they can be accounted for by the combined effects of forcings and internal variability. In the most recent period, the results suggest that the North Atlantic is warming faster than expected, and that the AMO entered a positive phase in the 1990s. The differences found between observed and ensemble mean temperatures could arise through errors in the observational data, errors in the models’ response to forcings or in the forcings themselves, or as a result of genuine internal variability. Each of these possibilities is discussed, and it is concluded that internal variability within the natural climate system is the most likely origin of the differences. Finally, the estimate of internal variability obtained using the model-derived ensemble mean is proposed as a new way of defining the AMO, which has important advantages over previous definitions.
Some Practical Considerations Regarding Horizontal Resolution in the First Generation of Operational Convection-Allowing NWP
Authors: Kain John S. , Weiss Steven J. , Bright David R. , Baldwin Michael E. , Levit Jason J. , Carbin Gregory W. , Schwartz Craig S. , Weisman Morris L. , Droegemeier Kelvin K. , Weber Daniel B. , Thomas Kevin W. 
Published: October 2008

Abstract
During the 2005 NOAA Hazardous Weather Testbed Spring Experiment two different high-resolution configurations of the Weather Research and Forecasting-Advanced Research WRF (WRF-ARW) model were used to produce 30-h forecasts 5 days a week for a total of 7 weeks. These configurations used the same physical parameterizations and the same input dataset for the initial and boundary conditions, differing primarily in their spatial resolution. The first set of runs used 4-km horizontal grid spacing with 35 vertical levels while the second used 2-km grid spacing and 51 vertical levels.
Output from these daily forecasts is analyzed to assess the numerical forecast sensitivity to spatial resolution in the upper end of the convection-allowing range of grid spacing. The focus is on the central United States and the time period 18–30 h after model initialization. The analysis is based on a combination of visual comparison, systematic subjective verification conducted during the Spring Experiment, and objective metrics based largely on the mean diurnal cycle of the simulated reflectivity and precipitation fields. Additional insight is gained by examining the size distributions of the individual reflectivity and precipitation entities, and by comparing forecasts of mesocyclone occurrence in the two sets of forecasts.
In general, the 2-km forecasts provide more detailed presentations of convective activity, but there appears to be little, if any, forecast skill on the scales where the added details emerge. On the scales where both model configurations show higher levels of skill—the scale of mesoscale convective features—the numerical forecasts appear to provide comparable utility as guidance for severe weather forecasters. These results suggest that, for the geographical, phenomenological, and temporal parameters of this study, any added value provided by decreasing the grid increment from 4 to 2 km (with commensurate adjustments to the vertical resolution) may not be worth the considerable increases in computational expense.
Ligand-engaged urokinase-type plasminogen activator receptor and activation of the CD11b/CD18 integrin inhibit late events of HIV expression in monocytic cells
Authors: Alfano Massimo , Mariani Samanta A. , Elia Chiara , Pardi Ruggero , Blasi Francesco , Poli Guido 
Published: October 2008

AbstractUrokinase-type plasminogen activator (uPA) signaling via its receptor uPAR inhibits late events in HIV-1 replication in acutely infected primary monocyte-derived macrophages (MDMs) and promonocytic U937 cells. Here we show that U937-derived, chronically infected U1 cells stimulated with phorbol 12-myristate 13-acetate (PMA) express integrins, uPA, and soluble uPAR at levels similar to those of MDMs. uPA inhibited HIV expression in U1 cells incubated with either PMA or tumor necrosis factor-α (TNF-α), but not with other HIV-inductive cytokines or lipopolysaccharide. Of interest, only PMA and TNF-α, but not other HIV-inductive stimuli, induced surface expression of the αM chain CD11b in U1 cells constitutively expressing CD18, the β2 chain of the Mac-1 integrin. Like uPA, fibrinogen, a Mac-1 (CD11b/CD18) ligand, and M25, a peptide homologous to a portion of the β-propeller region of CD11b preventing its association with uPAR, inhibited HIV virion release in PMA-stimulated U1 cells. Both uPAR small-interference RNA (siRNA) and soluble anti-β1/-β2 monoclonal antibodies abolished the anti-HIV effects of uPA, whereas CD11b siRNA reversed the anti-HIV effect of M25, but not that induced by uPA. Thus, either uPA/uPAR interaction, Mac-1 activation, or prevention of its association with uPAR triggers a signaling pathway leading to the inefficient release of HIV from monocytic cells.
CD49d provides access to “untouched” human Foxp3+ Treg free of contaminating effector cells
Authors: Kleinewietfeld Markus , Starke Mireille , Di Mitri Diletta , Borsellino Giovanna , Battistini Luca , Rötzschke Olaf , Falk Kirsten 
Published: October 2008

AbstractThe adoptive transfer of regulatory Foxp3+ T (Treg) cells has been shown in various animal models to prevent inflammatory immune and autoimmune diseases. Translation into therapeutic applications, however, is hindered by the lack of suitable techniques and markers. CD25, commonly used to isolate Treg cells from mice, has only limited value in humans as it is also present on proinflammatory CD4+ effector cells. Here we show that clean populations of human Foxp3+ Treg cells can be obtained with antibodies directed against CD49d. The marker is present on proinflammatory peripheral blood mononuclear cells but is absent on immune-suppressive Treg cells. Depletion with α-CD49d removes contaminating interferon-γ (IFN-γ)– and interleukin-17 (IL-17)–secreting cells from Treg preparations of CD4+CD25high cells. More importantly, in combination with α-CD127 it allows the isolation of “untouched” Foxp3+ Treg (ie, cells that have not been targeted by an antibody during purification). The removal of CD49d+/CD127+ cells leaves a population of Foxp3+ Treg virtually free of contaminating CD25+ effector cells. The cells can be expanded in vitro and are effective suppressors both in vitro and in vivo. Thus, CD49d provides access to highly pure populations of untouched Foxp3+ Treg cells conferring maximal safety for future clinical applications.
Properties and structure-function relationships of veltuzumab (hA20), a humanized anti-CD20 monoclonal antibody
Authors: Goldenberg David M. , Rossi Edmund A. , Stein Rhona , Cardillo Thomas M. , Czuczman Myron S. , Hernandez-Ilizaliturri Francisco J. , Hansen Hans J. , Chang Chien-Hsing 
Published: October 2008

AbstractVeltuzumab is a humanized anti-CD20 monoclonal antibody with complementarity-determining regions (CDRs) identical to rituximab, except for one residue at the 101st position (Kabat numbering) in CDR3 of the variable heavy chain (VH), having aspartic acid (Asp) instead of asparagine (Asn), with framework regions of epratuzumab, a humanized anti-CD22 antibody. When compared with rituximab, veltuzumab has significantly reduced off-rates in 3 human lymphoma cell lines tested, aswell as increased complement-dependent cytotoxicity in 1 of 3 cell lines, but no other in vitro differences. Mutation studies confirmed that the differentiation of the off-rate between veltuzumab and rituximab is related to the single amino acid change in CDR3-VH. Studies of intraperitoneal and subcutaneous doses in mouse models of human lymphoma and in normal cynomolgus monkeys disclosed that low doses of veltuzumab control tumor growth or deplete circulating or sessile B cells. Low- and high-dose veltuzumab were significantly more effective in vivo than rituximab in 3 lymphoma models. These findings are consistent with activity in patients with non-Hodgkin lymphoma given low intravenous or subcutaneous doses of veltuzumab. Thus, changing Asn101 to Asp101 in CDR3-VH of rituximab is responsible for veltuzumab's lower off-rate and apparent improved potency in preclinical models that could translate into advantages in patients.
T-cell modulation combined with intratumoral CpG cures lymphoma in a mouse model without the need for chemotherapy
Authors: Houot Roch , Levy Ronald 
Published: October 2008

Abstract
We have previously shown that intratumoral injection of CpG oligodeoxynucleotide plus systemic chemotherapy can induce a T-cell immune response against lymphoma and serve as a therapeutic vaccine to cure tumors in a murine model. Here, we demonstrate that antibody-mediated modulation of T cells increases the efficacy of CpG vaccination, thereby eliminating the need for chemotherapy. T-cell modulation was accomplished by targeting both effector and regulatory T-cell populations using systemic administration of monoclonal antibodies against OX40, CTLA4, GITR, and folate receptor 4 (FR4). Each of these antibodies enhanced the effect of intratumoral CpG. Some pairwise combinations of these antibodies potentiated T-cell modulation and further enhanced the efficacy of CpG vaccination. Specifically, the combination of anti-OX40 and anti-CTLA4 which enhance activation and block cell-intrinsic negative regulatory circuits in T cells, respectively, was especially potent. When combined with intratumoral CpG, it induced antitumor CD4 and CD8 T-cell immunity, cured large and systemic lymphoma tumors without chemotherapy, and provided long-lasting immunity against tumor rechallenge. Our results show that the combination of intratumoral CpG and immunomodulatory T-cell antibodies has promise for therapeutic vaccination against lymphoma. These reagents are becoming available for human clinical trials.
Donors with group B KIR haplotypes improve relapse-free survival after unrelated hematopoietic cell transplantation for acute myelogenous leukemia
Authors: Cooley Sarah , Trachtenberg Elizabeth , Bergemann Tracy L. , Saeteurn Koy , Klein John , Le Chap T. , Marsh Steven G. E. , Guethlein Lisbeth A. , Parham Peter , Miller Jeffrey S. , Weisdorf Daniel J. 
Published: October 2008

Abstract
Survival for patients with acute myeloid leukemia (AML) is limited by treatment-related mortality (TRM) and relapse after unrelated donor (URD) hematopoietic cell transplantation (HCT). Natural killer (NK)–cell alloreactivity, determined by donor killer-cell immunoglobulin-like receptors (KIRs) and recipient HLA, correlates with successful HCT for AML. Hypothesizing that donor KIR genotype (A/A: 2 A KIR haplotypes; B/x: at least 1 B haplotype) would affect outcomes, we genotyped donors and recipients from 209 HLA-matched and 239 mismatched T-replete URD transplantations for AML. Three-year overall survival was significantly higher after transplantation from a KIR B/x donor (31% [95% CI: 26-36] vs 20% [95% CI: 13-27]; P = .007). Multivariate analysis demonstrated a 30% improvement in the relative risk of relapse-free survival with B/x donors compared with A/A donors (RR: 0.70 [95% CI: 0.55-0.88]; P = .002). B/x donors were associated with a higher incidence of chronic graft-versus-host disease (GVHD; RR: 1.51 [95% CI: 1.01-2.18]; P = .03), but not of acute GVHD, relapse, or TRM. This analysis demonstrates that unrelated donors with KIR B haplotypes confer significant survival benefit to patients undergoing T-replete HCT for AML. KIR genotyping of prospective donors, in addition to HLA typing, should be performed to identify HLA-matched donors with B KIR haplotypes.
AccPbFRET: An ImageJ plugin for semi-automatic, fully corrected analysis of acceptor photobleaching FRET images
Authors: Roszik János , Szöllősi János , Vereb György 
Published: October 2008

Abstract

Background
The acceptor photobleaching fluorescence resonance energy transfer (FRET) method is widely used for monitoring molecular interactions in cells. This method of FRET, while among those with the simplest mathematics, is robust, self-controlled and independent of fluorophore amounts and ratios.

Results
AccPbFRET is a user-friendly, efficient ImageJ plugin which allows fully corrected, pixel-wise calculation and detailed, ROI (region of interest)-based analysis of FRET efficiencies in microscopic images. Furthermore, automatic registration and semi-automatic analysis of large image sets is provided, which are not available in any existing FRET evaluation software.

Conclusion
Despite of the widespread applicability of the acceptor photobleaching FRET technique, this is the first paper where all possible sources of major errors of the measurement and analysis are considered, and AccPbFRET is the only program which provides the complete suite of corrections – for registering image pairs, for unwanted photobleaching of the donor, for cross-talk of the acceptor and/or its photoproduct to the donor channel and for partial photobleaching of the acceptor. The program efficiently speeds up the analysis of large image sets even for novice users and is freely available.
Canine fibroblast growth factor receptor 3 sequence is conserved across dogs of divergent skeletal size
Authors: Smith Logan B , Bannasch Danika L , Young Amy E , Grossman Deborah I , Belanger Janelle M , Oberbauer Anita M 
Published: October 2008

Abstract

Background
Fibroblast growth factor receptor 3 (FGFR3) is expressed in the growth plate of endochondral bones and serves as a negative regulator of linear bone elongation. Activating mutations severely limit bone growth, resulting in dwarfism, while inactivating mutations significantly enhance bone elongation and overall skeletal size. Domesticated dogs exhibit the greatest skeletal size diversity of any species and, given the regulatory role of FGFR3 on growth plate proliferation, we asked whether sequence differences in FGFR3 could account for some of the size differences.

Methods
All exons, the promoter region, and 60 bp of the 3' flanking region of the canine FGFR3 gene were sequenced for nine different dog breeds representing a spectrum of skeletal size. The resultant sequences were compared to the reference Boxer genome sequence.

Results
There was no variation in sequence for any FGFR3 exons, promoter region, or 3' flanking sequence across all breeds evaluated.

Conclusion
The results suggest that, regardless of domestication selection pressure to develop breeds having extreme differences in skeletal size, the FGFR3 gene is conserved. This implies a critical role for this gene in normal skeletal integrity and indicates that other genes account for size variability in dogs.
Lack of association between the CALM1 core promoter polymorphism (-16C/T) and susceptibility to knee osteoarthritis in a Chinese Han population
Authors: Shi Dongquan , Ni Haijian , Dai Jin , Qin Jianghui , Xu Yong , Zhu Lunqing , Yao Chen , Shao Zhenxing , Chen Dongyang , Xu Zhihong , Yi Long , Ikegawa Shiro , Jiang Qing 
Published: October 2008

Abstract

Background

CALM1 gene encodes calmodulin (CaM), an important and ubiquitous eukaryotic Ca2+-binding protein. Several studies have indicated that a deficient CaM function is likely to be involved in the pathogenesis of osteoarthritis (OA). Using a convincing genome-wide association study, a Japanese group has recently demonstrated a genetic association between the CALM1 core promoter polymorphism (-16C/T transition SNP, rs12885713) and OA susceptibility. However, the subsequent association studies failed to provide consistent results in OA patients of differently selected populations. The present study is to evaluate the association of the -16C/T polymorphism with knee OA in a Chinese Han population.

Methods
A case-control association study was conducted. The polymorphism was genotyped in 183 patients who had primary symptomatic knee OA with radiographic confirmation and in 210 matched controls. Allelic and genotypic frequencies were compared between patients and control subjects.

Results
No significant difference was detected in genotype or allele distribution between knee OA and control groups (all P > 0.05). The association was also negative even after stratification by sex. Furthermore, no association between the -16C/T SNP genotype and the clinical variables age, sex, BMI (body mass index) and K/L (Kellgren/Lawrence) score was observed in OA patients.

Conclusion
The present study suggests that the CALM1 core promoter polymorphism -16C/T is not a risk factor for knee OA susceptibility in the Chinese Han population. Further studies are needed to give a global view of this polymorphism in pathogenesis of OA.