bluuebunny/crossref_metadata_2025 huggingface dataset:
Corridors of Warm Season Precipitation in the Central United States
Authors: Tuttle John D. , Davis Chris A.
Published: September 2006

During the warm season in the central United States there often exists a corridor of precipitation where a succession of mesoscale convective systems (MCSs) follow similar paths lasting several days. The total cumulative rainfall within a corridor can be substantial while precipitation at nearby regions may be below normal. Understanding the nature of the corridors and the environmental factors important for their formation thus has important implications for quantitative precipitation forecasting and hydrological studies. In this study a U.S. national composite radar dataset and model-analyzed fields are used for the 1998–2002 warm seasons (July–August) to understand the properties of corridors and what environmental factors are important for determining when and where they develop. The analysis is restricted to a relatively narrow longitudinal band in the central United States (95°–100°W), a region where convection often intensifies and becomes highly organized. It is found that ∼68% of MCSs were members of a series and that corridors typically persist for 2–7 days with an extreme case lasting 13 days. Cumulative radar-derived maximum rainfall ranges from 8 to 50 cm, underscoring the fact that corridors can experience excessive rainfall. Combining radar with Rapid Update Cycle model kinematic and thermodynamic fields, 5-yr composites are presented and stratified according to the environmental conditions. While the corridors show the expected association with areas of enhanced CAPE and relatively strong northwesterly/westerly shear, the strongest association is with the northern terminus region of the nocturnal low-level jet (LLJ). Furthermore, the relative intensity of the rainfall is positively correlated with the strength of the LLJ. The LLJ is thought to play a role through enhanced convergence and lifting, moisture transport, and frontogenesis. In the five years analyzed, the large-scale environment varied considerably, but the role of the LLJ in the formation of corridors remained persistent.
The Use of an Ensemble Approach to Study the Background Error Covariances in a Global NWP Model
Authors: Pereira Margarida Belo , Berre Loïk
Published: September 2006

The estimation of the background error statistics is a key issue for data assimilation. Their time average is estimated here using an analysis ensemble method. The experiments are performed with the nonstretched version of the Action de Recherche Petite Echelle Grande Echelle global model, in a perfect-model context. The global (spatially averaged) correlation functions are sharper in the ensemble method than in the so-called National Meteorological Center (NMC) method. This is shown to be closely related to the differences in the analysis step representation. The local (spatially varying) variances appear to reflect some effects of the data density and of the atmospheric variability. The resulting geographical contrasts are found to be partly different from those that are visible in the operational variances and in the NMC method. An economical estimate is also introduced to calculate and compare the local correlation length scales. This allows for the diagnosis of some existing heterogeneities and anisotropies. This information can also be useful for the modeling of heterogeneous covariances based, for example, on wavelets. The implementation of the global covariances and of the local variances, which are provided by the ensemble method, appears moreover to have a positive impact on the forecast quality.
Assessing the Skill of Yes/No Forecasts for Markov Observations
Authors: Briggs William , Ruppert David
Published: September 2006

Briggs and Ruppert recently introduced a new, easy-to-calculate economic skill/value score for use in yes/no forecast decisions, of which precipitation forecast decisions are an example. The advantage of this new skill/value score is that the sampling distribution is known, which allows one to perform hypothesis tests on collections of forecasts and to say whether a given skill/value score is significant or not. Here, the climate skill/value score is taken and extended to the case where the predicted series is first-order Markov in nature, of which, again, precipitation occurrence series can be an example. It is shown that, in general, Markov skill/value is different and more demanding than is persistence skill. Persistence skill is defined as improvement over forecasts that state that the next value in a series will equal the present value. It is also shown that any naive forecasts based solely on the Markov parameters is always at least as skillful/valuable as are persistence forecasts; in general, persistence forecasts should not be used. The distribution for the Markov skill score is presented, and examples of hypothesis testing for precipitation forecasts are given. These skill scores are graphed for a wide range of forecast/user loss functions, a process that makes their interpretation simple.
Impacts of Waves and Sea Spray on Midlatitude Storm Structure and Intensity
Authors: Zhang Weiqing , Perrie William , Li Weibiao
Published: September 2006

A coupled atmosphere–wave–sea spray model system is used to evaluate the combined impacts of spray evaporation and wave drag on midlatitude storms. The focus of this paper is on the role of air–sea fluxes on storm intensity and development, and related impacts on the structure of the atmospheric boundary layer. The composite model system consists of the Canadian Mesoscale Compressible Community atmospheric model coupled to the operational wave model WAVEWATCH III, and a recent bulk parameterization for heat fluxes due to sea spray. The case studies are extratropical Hurricane Earl (in 1998) and two intense winter storms from 2000 and 2002, hereafter denoted “superbomb” and “bomb,” respectively. The results show that sea spray tends to intensify storms, whereas wave-related drag tends to weaken storms. The mechanisms by which spray and wave-related drag can influence storm intensity are quite different. When wind speeds are high and sea surface temperatures warm, spray can significantly increase the surface heat fluxes. By comparison, momentum fluxes related to wave drag are important over regions of the storm where young, newly generated waves are prevalent, for example during the rapid development phase of the storm. These momentum fluxes decrease in areas where the storm waves reach maturity. The collective influence of spray and waves on storm intensity depends on their occurrence in the early stages of a storm’s rapid intensification phase, and their spatial distribution with respect to the storm center. Moreover, for the case of the superbomb, a potential vorticity framework is used to show the relative importance of these surface flux impacts compared with baroclinic processes.
A Comparison of Adaptive Observing Guidance for Atlantic Tropical Cyclones
Authors: Majumdar S. J. , Aberson S. D. , Bishop C. H. , Buizza R. , Peng M. S. , Reynolds C. A.
Published: September 2006

Airborne adaptive observations have been collected for more than two decades in the neighborhood of tropical cyclones, to attempt to improve short-range forecasts of cyclone track. However, only simple subjective strategies for adaptive observations have been used, and the utility of objective strategies to improve tropical cyclone forecasts remains unexplored. Two objective techniques that have been used extensively for midlatitude adaptive observing programs, and the current strategy based on the ensemble deep-layer mean (DLM) wind variance, are compared quantitatively using two metrics. The ensemble transform Kalman filter (ETKF) uses ensembles from NCEP and the ECMWF. Total-energy singular vectors (TESVs) are computed by the ECMWF and the Naval Research Laboratory, using their respective global models. Comparisons of 78 guidance products for 2-day forecasts during the 2004 Atlantic hurricane season are made, on both continental and localized scales relevant to synoptic surveillance missions. The ECMWF and NRL TESV guidance identifies similar large-scale target regions in 90% of the cases, but are less similar to each other in the local tropical cyclone environment (56% of the cases) with a more stringent criterion for similarity. For major hurricanes, all techniques usually indicate targets close to the storm center. For weaker tropical cyclones, the TESV guidance selects similar targets to those from the ETKF (DLM wind variance) in only 30% (20%) of the cases. ETKF guidance using the ECMWF ensemble is more like that provided by the NCEP ensemble (and DLM wind variance) for major hurricanes than for weaker tropical cyclones. Minor differences in these results occur when a different metric based on the ranking of fixed storm-relative regions is used.
A New Vertical Diffusion Package with an Explicit Treatment of Entrainment Processes
Authors: Hong Song-You , Noh Yign , Dudhia Jimy
Published: September 2006

This paper proposes a revised vertical diffusion package with a nonlocal turbulent mixing coefficient in the planetary boundary layer (PBL). Based on the study of Noh et al. and accumulated results of the behavior of the Hong and Pan algorithm, a revised vertical diffusion algorithm that is suitable for weather forecasting and climate prediction models is developed. The major ingredient of the revision is the inclusion of an explicit treatment of entrainment processes at the top of the PBL. The new diffusion package is called the Yonsei University PBL (YSU PBL). In a one-dimensional offline test framework, the revised scheme is found to improve several features compared with the Hong and Pan implementation. The YSU PBL increases boundary layer mixing in the thermally induced free convection regime and decreases it in the mechanically induced forced convection regime, which alleviates the well-known problems in the Medium-Range Forecast (MRF) PBL. Excessive mixing in the mixed layer in the presence of strong winds is resolved. Overly rapid growth of the PBL in the case of the Hong and Pan is also rectified. The scheme has been successfully implemented in the Weather Research and Forecast model producing a more realistic structure of the PBL and its development. In a case study of a frontal tornado outbreak, it is found that some systematic biases of the large-scale features such as an afternoon cold bias at 850 hPa in the MRF PBL are resolved. Consequently, the new scheme does a better job in reproducing the convective inhibition. Because the convective inhibition is accurately predicted, widespread light precipitation ahead of a front, in the case of the MRF PBL, is reduced. In the frontal region, the YSU PBL scheme improves some characteristics, such as a double line of intense convection. This is because the boundary layer from the YSU PBL scheme remains less diluted by entrainment leaving more fuel for severe convection when the front triggers it.
Cloud-to-Ground Lightning Flash Parameters Associated with Heavy Rainfall Alarms in the Denver, Colorado, Urban Drainage and Flood Control District ALERT Network
Authors: Underwood S. Jeffrey
Published: September 2006

Rainfall data from the Denver, Colorado, Urban Drainage and Flood Control District Automated Local Evaluation in Real Time (ALERT) network were used to identify heavy rainfall alarms for the period 1999–2003. Twenty-nine heavy rainfall-rate alarms were identified. Cloud-to-ground (CG) lightning flash data from the National Lightning Detection Network (NLDN) were analyzed for the 90 min prior to each heavy rainfall alarm. Spatial patterns from NLDN data were extracted using a point-polygon topology developed with basic Geographic Information System procedures. The information extracted from the polygons was used to calculated summary statistics for rainfall rates, CG flash rates, and CG flash duration. Heavy rainfall episodes were divided into two groups based on latitude, longitude, and elevation. Heavy rainfall episodes in the higher elevations of the study area produced an average of 29 mm of rainfall per episode and 1095 CG flashes in the 90 min prior to the rainfall-rate alarm. Only five polygons, all closely proximal to the alarm sites, produced significant CG flash rates prior to the rainfall alarms, and areas with CG flash durations greater than 25 min were clustered near the rainfall-rate alarm sites. In the second group (the lower elevation stations) the mean event produced a total of 33 mm of rainfall and 1182 CG flashes during the 90 min prior to the rainfall alarm. Four polygons saw consistent CG flash rates in the 90 min prior to the heavy rainfall alarms and CG flash duration was at its greatest in areas just west of the ALERT stations.
The Diabatic Contour Advective Semi-Lagrangian Model
Authors: Dritschel David G. , Ambaum Maarten H. P.
Published: September 2006

This article describes a novel algorithmic development extending the contour advective semi-Lagrangian model to include nonconservative effects. The Lagrangian contour representation of finescale tracer fields, such as potential vorticity, allows for conservative, nondiffusive treatment of sharp gradients allowing very high numerical Reynolds numbers. It has been widely employed in accurate geostrophic turbulence and tracer advection simulations. In the present, diabatic version of the model the constraint of conservative dynamics is overcome by including a parallel Eulerian field that absorbs the nonconservative (diabatic) tendencies. The diabatic buildup in this Eulerian field is limited through regular, controlled transfers of this field to the contour representation. This transfer is done with a fast newly developed contouring algorithm. This model has been implemented for several idealized geometries. In this paper a single-layer doubly periodic geometry is used to demonstrate the validity of the model. The present model converges faster than the analogous semi-Lagrangian models at increased resolutions. At the same nominal spatial resolution the new model is 40 times faster than the analogous semi-Lagrangian model. Results of an orographically forced idealized storm track show nontrivial dependency of storm-track statistics on resolution and on the numerical model employed. If this result is more generally applicable, this may have important consequences for future high-resolution climate modeling.
The Role of Tropical Waves in Tropical Cyclogenesis
Authors: Frank William M. , Roundy Paul E.
Published: September 2006

This paper analyzes relationships between tropical wave activity and tropical cyclogenesis in all of the earth’s major tropical cyclone basins. Twenty-nine years of outgoing longwave radiation data and global reanalysis winds are filtered and analyzed to determine statistical relationships between wave activity in each basin and the corresponding cyclogenesis. Composite analyses relative to the storm genesis locations show the structures of the waves and their preferred phase relationships with genesis. Five wave types are examined in this study, including mixed Rossby–gravity waves, tropical-depression-type or easterly waves, equatorial Rossby waves, Kelvin waves, and the Madden–Julian oscillation. The latter is not one of the classical tropical wave types, but is a wavelike phenomenon known to have a strong impact on tropical cyclogenesis. Tropical cyclone formation is strongly related to enhanced activity in all of the wave filter bands except for the Kelvin band. In each basin the structure of each composite wave and the phase relationship between the wave and cyclogenesis are similar, suggesting consistent forcing mechanisms. The waves appear to enhance the local circulations by increasing the forced upward vertical motion, increasing the low-level vorticity at the genesis location, and by modulating the vertical shear. Convective anomalies of waves associated with genesis are detectable in the analyses as long as 1 month prior to genesis. This opens up the possibility of developing statistically based genesis forecasts.
Assimilation of SSM/I Radiances in the NCEP Global Data Assimilation System
Authors: Okamoto Kozo , Derber John C.
Published: September 2006

A technique for the assimilation of Special Sensor Microwave Imager (SSM/I) data in the National Centers for Environmental Prediction (NCEP) global data assimilation and forecast system is described. Because the radiative transfer model used does not yet allow for cloud/rain effects, it is crucial to properly identify and exclude (or correct) cloud/rain-contaminated radiances using quality control (QC) and bias correction procedures. The assimilation technique is unique in that both procedures take into account the effect of the liquid cloud on the difference between observed and simulated brightness temperature for each SSM/I channel. The estimate of the total column cloud liquid water from observed radiances is used in a frequency-dependent cloud detection component of the QC and as a predictor in the bias correction algorithm. Also, a microwave emissivity Jacobian model with respect to wind speed is developed for oceanic radiances. It was found that the surface wind information in the radiance data can be extracted through the emissivity model Jacobian rather than producing and including a separate SSM/I wind speed retrieval.

A two-month-long data assimilation experiment from July to August 2004 using NCEP’s Gridpoint Statistical Interpolation analysis system and the NCEP operational forecast model was performed. In general, the assimilation of SSM/I radiance has a significant positive impact on the analyses and forecasts. Moisture is added in the Northern Hemisphere and Tropics and is slightly reduced in the Southern Hemisphere. The moisture added appears to be slightly excessive in the Tropics verified against rawinsonde observations. Nevertheless, the assimilation of SSM/I radiance data reduces model spinup of precipitation and substantially improves the dynamic fields, especially in measures of the vector wind error at 200 hPa in the Tropics. In terms of hurricane tracks, SSM/I radiance assimilation produces more cases with smaller errors and reduces the average error. No disruption of the Hadley circulation is found from the introduction of the SSM/I radiance data.
The Thermal Circulation of a Grand Plateau: Sensitivity to the Height, Width, and Shape of the Plateau
Authors: Zängl Günther , Chico Silvia Gonzalez
Published: September 2006

Idealized numerical simulations are presented to investigate the sensitivity of the thermal plateau circulation to the plateau height, width, and the presence of a mountain ridge encompassing the plateau. The study concentrates on plateaus surrounded by land with the same surface properties so that the topography is the only source of differential heating. For low plateaus, it is found that the strength of the plateau circulation increases with the plateau height because the excess heating of the plateau increases with its height. The plateau circulation reaches its maximum strength for plateau heights similar to the mixed-layer depth over the surrounding lowlands. For even higher plateaus, the depth of the circulation decreases whereas the peak intensity exhibits little change. The plateau height also controls the temporal evolution of the plateau circulation. For low plateaus, low-level inflow is primarily found during the night because convection cells forming over the lateral slopes prevent an inward mass flux during the day. With increasing plateau height, the phases of the plateau circulation shift toward earlier times. If the plateau height exceeds the mixed-layer depth over the surrounding lowlands, inflow occurs from afternoon until the late evening. After sunset, the inflow layer tends to assume the characteristics of a density current. The convergence of the density currents propagating from each side of the plateau toward the center helps to fill the heat low formed during the day. Moreover gravity waves are triggered that propagate away from the plateau center and terminate the inflow. The propagation speed of the density currents is found to increase with the plateau height, so that their convergence occurs earlier for high plateaus than for low plateaus. For the parameter range considered in this study, the plateau width is found to have only a minor impact on the mass fluxes associated with the plateau circulation. However, the convergence of the density currents over the plateau center occurs later for a wider plateau, implying that the heat low is more persistent. Substantial changes are obtained when the plateau is surrounded by a mountain ridge. In this case, the inflow toward the plateau gets delayed because a slope wind circulation forms over the mountain ridge. Moreover, the mass fluxes toward the plateau are reduced so that the heat low that formed over the plateau during the day is filled only slowly. As a consequence, the inflow lasts throughout the night in the presence of a high mountain ridge surrounding the plateau.
Tissue factor deficiency and PAR-1 deficiency are protective against renal ischemia reperfusion injury
Authors: Sevastos Jacob , Kennedy Sean E. , Davis Darren R. , Sam Melissa , Peake Philip W. , Charlesworth John A. , Mackman Nigel , Erlich Jonathan H.
Published: September 2006

Ischemia/reperfusion (IR) injury is a leading cause of acute renal failure and an important contributor to allograft damage. Tissue factor (TF) is up-regulated during IR, and TF inhibition reduces renal injury. However, the underlying mechanisms by which TF contributes to injury have not been elucidated. We postulated that TF contributes to IR injury by production of coagulation proteases and subsequent signaling by protease activated receptor (PARs). We compared renal injury after 25 minutes of bilateral renal ischemia and varying periods of reperfusion in C57BL/6 mice, those expressing low levels of TF (low-TF), hirudin-treated C57BL/6, and mice lacking either PAR-1 or PAR-2. C57BL/6 mice developed severe renal failure and died within 48 hours of reperfusion. In contrast, low-TF, hirudin-treated C57BL/6, and PAR-1−/− mice were protected from renal failure and had reduced mortality, tubular injury, neutrophil accumulation, and lower levels of the chemokines KC and MIP-2. Importantly, PAR-1−/− mice had lower chemokine levels despite up-regulation of TF and fibrin deposition. In addition, treating PAR-1−/− mice with hirudin conferred no additional benefit. Somewhat surprisingly, PAR-2 deficiency did not protect from renal failure. These experiments indicate that increased TF activity after renal IR leads to increased CXC chemokine expression and subsequent neutrophil-mediated injury predominantly by thrombin-dependent PAR-1 signaling.
Rho GTPase Rac1 is critical for neutrophil migration into the lung
Authors: Filippi Marie-Dominique , Szczur Kathleen , Harris Chad E. , Berclaz Pierre-Yves
Published: September 2006

Neutrophils are critical in the inflammatory process by moving rapidly to tissue sites of inflammation. Members of the small Rho GTPase family, Rac1, Rac2, CDC42, and RhoA, are central regulators of cell migration by cytoskeleton rearrangement. The role of Rac1 in neutrophil migration related to inflammatory processes has remained elusive and has yet to be determined in physiologic in vivo models. We previously demonstrated a role for Rac1 in tail retraction. Here, we present evidence that Rac1-mediated uropod formation may be due to crosstalk with a related Rho GTPase RhoA. To assess the physiologic relevance of these findings, we used adoptive transfer of Rac1flox/flox bone marrow cells which allows postengraftment in vivo deletion of Rac1 only in blood cells. We examined the specific role of Rac1 in neutrophil migration into the lung during the inflammatory process induced by formyl-methionyl-leucyl-phenylalanine exposure. The loss of Rac1 activity in neutrophils is associated with a significant decreased neutrophil recruitment into lung alveolar and attenuation of emphysematous lesions. Overall, this study suggests that Rac1 is a physiologic integrator of signals for neutrophil recruitment into lung tissue during an inflammatory response.
A randomized comparison of bypassing agents in hemophilia complicated by an inhibitor: the FEIBA NovoSeven Comparative (FENOC) Study
Authors: Astermark Jan , Donfield Sharyne M. , DiMichele Donna M. , Gringeri Alessandro , Gilbert Steven A. , Waters Jennifer , Berntorp Erik ,   for the FENOC Study Group
Published: September 2006

The development of inhibitory antibodies to factor VIII is a serious complication of hemophilia. FEIBA (factor VIII inhibitor-bypassing activity), an activated prothrombin complex concentrate (aPCC), and NovoSeven, recombinant factor VIIa (rFVIIa), are used as hemostatic bypassing agents in treating patients with inhibitors. The FENOC study was designed to test equivalence of the products in the treatment of ankle, knee, and elbow joint bleeding. A prospective, open-label, randomized, crossover, equivalency design was used. The parameters of interest were the percentage of patients who reported efficacy in response to FEIBA and the percentage that reported efficacy in response to NovoSeven. A difference in these percentages of no more than 15% was determined to be a clinically acceptable magnitude for equivalence of the 2 products. The primary outcome was evaluation 6 hours after treatment. Data for 96 bleeding episodes contributed by 48 participants were analyzed. The criterion for declaring the 2 products equivalent at 6 hours was not met; however, the confidence interval of the difference in percentages of efficacy reported for each product only slightly exceeded the 15% boundary (−11.4%-15.7%), P = .059. FEIBA and NovoSeven appear to exhibit a similar effect on joint bleeds, although the efficacy between products is rated differently by a substantial proportion of patients. This trial was registered at www.clinicaltrials.gov as #NCT00166309.
Solenopsin, the alkaloidal component of the fire ant (Solenopsis invicta), is a naturally occurring inhibitor of phosphatidylinositol-3-kinase signaling and angiogenesis
Authors: Arbiser Jack L. , Kau Tweeny , Konar Martha , Narra Krishna , Ramchandran Ramani , Summers Scott A. , Vlahos Chris J. , Ye Keqiang , Perry Betsy N. , Matter William , Fischl Anthony , Cook James , Silver Pamela A. , Bain Jenny , Cohen Philip , Whitmire David , Furness Scott , Govindarajan Baskaran , Bowen J. Phillip
Published: September 2006

Phosphatidylinositol-3-kinase (PI3K), and its downstream effector Akt, or protein kinase Bα (PKBα), play a major regulatory role in control of apoptosis, proliferation, and angiogenesis. PI3K and Akt are amplified or overexpressed in a number of malignancies, including sarcomas, ovarian cancer, multiple myeloma, and melanoma. This pathway regulates production of the potent angiogenic factor vascular endothelial growth factor (VEGF), and protects tumor cells against both chemotherapy and reactive oxygen–induced apoptosis through phosphorylation of substrates such as apoptotic peptidase–activating factor-1 (APAF-1), forkhead proteins, and caspase 9. Given its diverse actions, compounds that suppress the PI3K/Akt pathway have potential pharmacologic utility as angiogenesis inhibitors and antineoplastic agents. Using the SVR angiogenesis assay, a screen of natural products, we isolated the alkaloid solenopsin, and found that it is a potent angiogenesis inhibitor. We also found that solenopsin inhibits the PI3K signaling pathway in cells upstream of PI3K, which may underlie its affects on angiogenesis. Consistent with inhibition of the activation of PI3K, solenopsin prevented the phosphorylation of Akt and the phosphorylation of its substrate forkhead box 01a (FOXO1a), a member of the forkhead family of transcription factors. Interestingly, solenopsin also inhibited Akt-1 activity in an ATP-competitive manner in vitro without affecting 27 of 28 other protein kinases tested.
Functional characterization of natural telomerase mutations found in patients with hematologic disorders
Authors: Xin Zhong-Tao , Beauchamp Adam D. , Calado Rodrigo T. , Bradford Jennifer W. , Regal Joshua A. , Shenoy Aarthi , Liang Yuying , Lansdorp Peter M. , Young Neal S. , Ly Hinh
Published: September 2006

Human telomerase hTERC RNA serves as a template for the catalytic hTERT protein to synthesize telomere repeats at chromosome ends. We have recently shown that some patients with bone marrow failure syndromes are heterozygous carriers for hTERC or hTERT mutations. These sequence variations usually lead to a compromised telomerase function by haploinsufficiency. Here, we provide functional characterization of an additional 8 distinct hTERT sequence variants and 5 hTERC variants that have recently been identified in patients with dyskeratosis congenita (DC) or aplastic anemia (AA). Among the mutations, 2 are novel telomerase variants that were identified in our cohort of patients. Whereas most of the sequence variants modulate telomerase function by haploinsufficiency, 2 hTERC variants with sequence changes located within the template region appear to act in a dominant-negative fashion. Inherited telomerase gene mutations, therefore, operate by various mechanisms to shorten telomere lengths, leading to limited marrow stem cell reserve and renewal capacity in patients with hematologic disorders.
Somatic revertant mosaicism in a patient with leukocyte adhesion deficiency type 1
Authors: Tone Yumi , Wada Taizo , Shibata Fumie , Toma Tomoko , Hashida Yoko , Kasahara Yoshihito , Koizumi Shoichi , Yachie Akihiro
Published: September 2006

Leukocyte adhesion deficiency type 1 (LAD-1) is an autosomal recessive disorder caused by mutations in the ITGB2 (CD18) gene and characterized by recurrent severe infections, impaired pus formation, and defective wound healing. We describe an unusual case of severe phenotypic LAD-1 presenting with somatic mosaicism. The patient is a compound heterozygote bearing 2 different frameshift mutations that abrogate protein expression. However, CD18 expression was detected in a small proportion of T cells but was undetectable in granulocytes, monocytes, B cells, and natural killer (NK) cells. The T cells were not of maternal origin, lacked the paternal mutation, and showed a selective advantage in vivo. Molecular analysis using sorted CD18+ cells revealed them to be derived from a single CD8+ T cell carrying T-cell receptor VB22. These findings suggest that spontaneous in vivo reversion was responsible for the somatic mosaicism in our patient.
The complete mitochondrial genome of a basal teleost, the Asian arowana (Scleropages formosus, Osteoglossidae)
Authors: Yue Gen Hua , Liew Woei Chang , Orban Laszlo
Published: September 2006

Background

Mitochondrial DNA-derived sequences have become popular markers for evolutionary studies, as their comparison may yield significant insights into the evolution of both the organisms and their genomes. From the more than 24,000 teleost species, only 254 complete mtDNA sequences are available (GenBank status on 06 Sep 2006). In this paper, we report the complete mitochondrial genome sequence of Asian arowana, a basal bonytongue fish species, which belongs to the order of Osteoglossiformes.

Results

The complete mitochondrial genomic sequence (mtDNA) of Asian arowana (Scleropages formosus) was determined by using shotgun sequencing method. The length of Asian arowana mtDNA is ca. 16,650 bp (its variation is due to polymorphic repeats in the control region), containing 13 protein-coding genes, 22 tRNA and 2 rRNA genes. Twelve of the thirteen protein coding genes were found to be encoded by the heavy strand in the order typically observed for vertebrate mitochondrial genomes, whereas only nad6 was located on the light strand. An interesting feature of Asian arowana mitogenome is that two different repeat arrays were identified in the control region: a 37 bp tandem repeat at the 5' end and an AT-type dinucleotide microsatellite at the 3' end. Both repeats show polymorphism among the six individuals tested; moreover the former one is present in the mitochondrial genomes of several other teleost groups. The TACAT motif described earlier only from mammals and lungfish was found in the tandem repeat of several osteoglossid and eel species. Phylogenetic analysis of fish species representing Actinopterygii and Sarcopterygii taxa has shown that the Asian arowana is located near the baseline of the teleost tree, confirming its status among the ancestral teleost lineages.

Conclusion

The mitogenome of Asian arowana is very similar to the typical vertebrate mitochondrial genome in terms of gene arrangements, codon usage and base composition. However its control region contains two different types of repeat units at both ends, an interesting feature that to our knowledge has never been reported before for other vertebrate mitochondrial control regions. Phylogenetic analysis using the complete mtDNA sequence of Asian arowana confirmed that it belongs to an ancestral teleost lineage.
Brain-derived proteins in the CSF, do they correlate with brain pathology in CJD?
Authors: Boesenberg-Grosse Constanze , Schulz-Schaeffer Walter J , Bodemer Monika , Ciesielczyk Barbara , Meissner Bettina , Krasnianski Anna , Bartl Mario , Heinemann Uta , Varges Daniela , Eigenbrod Sabina , Kretzschmar Hans A , Green Alison , Zerr Inga
Published: September 2006

Background

Brain derived proteins such as 14-3-3, neuron-specific enolase (NSE), S 100b, tau, phosphorylated tau and Aβ1–42 were found to be altered in the cerebrospinal fluid (CSF) in Creutzfeldt-Jakob disease (CJD) patients. The pathogenic mechanisms leading to these abnormalities are not known, but a relation to rapid neuronal damage is assumed. No systematic analysis on brain-derived proteins in the CSF and neuropathological lesion profiles has been performed.

Methods

CSF protein levels of brain-derived proteins and the degree of spongiform changes, neuronal loss and gliosis in various brain areas were analyzed in 57 CJD patients.

Results

We observed three different patterns of CSF alteration associated with the degree of cortical and subcortical changes. NSE levels increased with lesion severity of subcortical areas. Tau and 14-3-3 levels increased with minor pathological changes, a negative correlation was observed with severity of cortical lesions. Levels of the physiological form of the prion protein (PrPc) and Aβ1–42 levels correlated negatively with cortical pathology, most clearly with temporal and occipital lesions.

Conclusion

Our results indicate that the alteration of levels of brain-derived proteins in the CSF does not only reflect the degree of neuronal damage, but it is also modified by the localization on the brain pathology. Brain specific lesion patterns have to be considered when analyzing CSF neuronal proteins.
Adenoid cystic carcinoma of the lacrimal gland metastasising to the liver: report of a case
Authors: Zeidan Bashar A , Hilal Mohammed Abu , Al-Gholmy Mohammed , El-Mahallawi Hanan , Pearce Neil W , Primrose John N
Published: September 2006

Background

Adenoid Cystic Carcinoma of the lacrimal gland is a rare tumour. Their aggressive behaviour, with a high-risk of local recurrence, and late distant spread of the tumour even after aggressive management has been reported. Metastasis to the liver is rare and when it occurs, it is usually part of widespread metastasis, and therefore surgical treatment is seldom considered.

Case presentation

We report a rare case of an isolated liver metastasis from a lacrimal gland adenoid cystic carcinoma 20 years after resection of the primary tumour. The patient presented with right upper quadrant pain radiating to the back and shortness of breath of 3 months duration. No local recurrence was detected during a 15 year follow-up with computerized tomography (CT) of the head. Abdominal CT scan demonstrated a solitary liver tumour with no other primary source, and the bone scan was normal. The patient was treated with an extended right hemihepatectomy. The histology revealed a predominantly cribriform tumour with focal areas of basaloid type metastatic lacrimal gland adenoid cystic carcinoma.

Conclusion

This case illustrates the unpredictable behaviour of adenoid cystic carcinoma and the need for a life long follow up for these patients after treatment. The possibility of surgical resection for liver metastasis from adenoid cystic carcinoma should always be considered.
Identification of a human peripheral blood monocyte subset that differentiates into osteoclasts
Authors: Komano Yukiko , Nanki Toshihiro , Hayashida Kenji , Taniguchi Ken , Miyasaka Nobuyuki
Published: September 2006

Increased bone resorption mediated by osteoclasts causes various diseases such as osteoporosis and bone erosion in rheumatoid arthritis (RA). Osteoclasts are derived from the monocyte/macrophage lineage, but the precise origin remains unclear. In the present study, we show that the purified CD16- human peripheral blood monocyte subset, but not the CD16+ monocyte subset, differentiates into osteoclast by stimulation with receptor activator of NF-κB ligand (RANKL) in combination with macrophage colony-stimulating factor (M-CSF). Integrin-β3 mRNA and the integrin-αvβ3 heterodimer were only expressed on CD16- monocytes, when they were stimulated with RANKL + M-CSF. Downregulation of β3-subunit expression by small interfering RNA targeting β3 abrogated osteoclastogenesis from the CD16- monocyte subset. In contrast, the CD16+ monocyte subset expressed larger amounts of tumor necrosis factor alpha and IL-6 than the CD16- subset, which was further enhanced by RANKL stimulation. Examination of RA synovial tissue showed accumulation of both CD16+ and CD16- macrophages. Our results suggest that peripheral blood monocytes consist of two functionally heterogeneous subsets with distinct responses to RANKL. Osteoclasts seem to originate from CD16- monocytes, and integrin β3 is necessary for osteoclastogenesis. Blockade of accumulation and activation of CD16- monocytes could therefore be a beneficial approach as an anti-bone resorptive therapy, especially for RA.
Activin A Decreases glucagon and arx Gene Expression in α-Cell Lines
Authors: Mamin Aline , Philippe Jacques
Published: September 2006

Activin A is a potent growth and differentiation factor involved in development, differentiation, and physiological functions of the endocrine pancreas; it increases insulin and pax4 gene expression in β-cells and can induce transdifferentiation of the exocrine acinar cell line AR42J into insulin-producing cells. We show here that Activin A decreases glucagon gene expression in the α-cell lines InR1G9 and αTC1 in a dose- and time-dependent manner and that the effect is blocked by Follistatin. This effect is also observed in adult human islets. Glucagon gene expression is inhibited at the transcriptional level by the Smad signaling pathway through the G3 DNA control element. Furthermore, Activin A decreases cell proliferation of InR1G9 and αTC1 cells as well as cyclin D2 and arx gene expression, whose protein product Arx has been shown to be critical for α-cell differentiation. Overexpression of Arx in Activin A-treated InR1G9 cells does not prevent the decrease in glucagon gene expression but corrects the inhibition of cell proliferation, indicating that Arx mediates the Activin A effects on the cell cycle. We conclude that Activin A has opposite effects on α-cells compared with β-cells, a finding that may have relevance during pancreatic endocrine lineage specification and physiological function of the adult islets.
Parathyroid-Specific Double Knockout of Gq and G11 α-Subunits Leads to a Phenotype Resembling Germline Knockout of the Extracellular Ca2+-Sensing Receptor
Authors: Wettschureck Nina , Lee EunAh , Libutti Steven K. , Offermanns Stefan , Robey Pamela G. , Spiegel Allen M.
Published: September 2006

Germline knockout of the extracellular Ca2+-sensing receptor (CaR) leads to a phenotype that includes severe hypercalcemia, hyperparathyroidism, relative hypocalciuria, skeletal abnormalities, retarded growth, and early postnatal death. To investigate the role of heterotrimeric G proteins in CaR signaling, we used cre/lox technology to delete the respective α-subunits of Gq and G11 selectively in parathyroid cells. Mice that were PTH-Cre+/−; Gnaqflox/flox; Gna11−/− (PTH-Gαq/Gα11-double knockouts) were viable, but showed all the features of germline knockout of the CaR except hypocalcuria. Our results demonstrate the critical role of both Gq and G11 in mediating inhibition of PTH secretion by extracellular Ca2+.
An analysis of transient Markov decision processes
Authors: James Huw W. , Collins E. J.
Published: September 2006

This paper is concerned with the analysis of Markov decision processes in which a natural form of termination ensures that the expected future costs are bounded, at least under some policies. Whereas most previous analyses have restricted attention to the case where the set of states is finite, this paper analyses the case where the set of states is not necessarily finite or even countable. It is shown that all the existence, uniqueness, and convergence results of the finite-state case hold when the set of states is a general Borel space, provided we make the additional assumption that the optimal value function is bounded below. We give a sufficient condition for the optimal value function to be bounded below which holds, in particular, if the set of states is countable.
Monotone utility convergence
Authors: Ankirchner Stefan
Published: September 2006

We show that the maximal expected utility satisfies a monotone continuity property with respect to increasing information. Let be a sequence of increasing filtrations converging to , and let un(x) and u∞(x) be the maximal expected utilities when investing in a financial market according to strategies adapted to and , respectively. We give sufficient conditions for the convergence un(x) → u∞(x) as n → ∞. We provide examples in which convergence does not hold. Then we consider the respective utility-based prices, πn and π∞, of contingent claims under (Gtn) and (Gt∞). We analyse to what extent πn → π∞ as n → ∞.
Derivatives pricing viap-optimal martingale measures: some extreme cases
Authors: Santacroce Marina
Published: September 2006

In an incomplete financial market in which the dynamics of the asset prices is driven by ad-dimensional continuous semimartingaleX, we consider the problem of pricing European contingent claims embedded in a power utility framework. This problem reduces to identifying thep-optimal martingale measure, which can be given in terms of the solution to a semimartingale backward equation. We use this characterization to examine two extreme cases. In particular, we find a necessary and sufficient condition, written in terms of the mean-variance trade-off, for thep-optimal martingale measure to coincide with the minimal martingale measure. Moreover, if and only if an exponential function of the mean-variance trade-off is a martingale strongly orthogonal to the asset price process, thep-optimal martingale measure can be simply expressed in terms of a Doléans-Dade exponential involvingX.
Ultra-small scale-free geometric networks
Authors: Yukich J. E.
Published: September 2006

We consider a family of long-range percolation models (Gp)p>0on ℤdthat allow dependence between edges and have the following connectivity properties forp∈ (1/d, ∞): (i) the degree distribution of vertices inGphas a power-law distribution; (ii) the graph distance between pointsxandyis bounded by a multiple of logpdlogpd|x-y| with probability 1 -o(1); and (iii) an adversary can delete a relatively small number of nodes fromGp(ℤd∩ [0,n]d), resulting in two large, disconnected subgraphs.
Efficient routeing in Poisson small-world networks
Authors: Draief M. , Ganesh A.
Published: September 2006

In a recent paper, Kleinberg (2000) considered a small-world network model consisting of ad-dimensional lattice augmented with shortcuts. The probability of a shortcut being present between two points decays as a power,r-α, of the distance,r, between them. Kleinberg showed that greedy routeing is efficient if α =dand that there is no efficient decentralised routeing algorithm if α ≠d. The results were extended to a continuum model by Franceschetti and Meester (2003). In our work, we extend the result to more realistic models constructed from a Poisson point process wherein each point is connected to all its neighbours within some fixed radius, and possesses random shortcuts to more distant nodes as described above.
Large deviations for risk processes with reinsurance
Authors: Macci Claudio , Stabile Gabriele
Published: September 2006

We consider risk processes with reinsurance. A general family of reinsurance contracts is allowed, including proportional and excess-of-loss policies. Claim occurrence is regulated by a classical compound Poisson process or by a Markov-modulated compound Poisson process. We provide some large deviation results concerning these two risk processes in the small-claim case. Finally, we derive the so-called Lundberg estimate for the ruin probabilities and present a numerical example.
On-line selection of an acceptable pair
Authors: Preater J.
Published: September 2006

A sequence of objects with independent, identically distributed qualities is presented to a selector who must choose two on-line, i.e. without anticipation or recall. The selector's aim is to obtain a satisfactory pair as quickly as possible. Two versions of the problem are considered, and optimal selection rules are derived and compared. An investigation is also made of a heuristic rule suitable for a selector who has no prior knowledge of the nature of the object sequence.
Ergodicity and mixing properties of the northeast model
Authors: Kordzakhia George , Lalley Steven P.
Published: September 2006

The northeast model is a spin system on the two-dimensional integer lattice that evolves according to the following rule: whenever a site's southerly and westerly nearest neighbors have spin 1, it may reset its own spin by tossing a p-coin; at all other times, its spin remains frozen. It is proved that the northeast model has a phase transition at pc = 1 - βc, where βc is the critical parameter for oriented percolation. For p < pc, the trivial measure, δ0, that puts mass one on the configuration with all spins set at 0 is the unique ergodic, translation-invariant, stationary measure. For p ≥ pc, the product Bernoulli-p measure on configuration space is the unique nontrivial, ergodic, translation-invariant, stationary measure for the system, and it is mixing. For p > ⅔, it is shown that there is exponential decay of correlations.
Bounds for perpetual American option prices in a jump diffusion model
Authors: Ekström Erik
Published: September 2006

We provide bounds for perpetual American option prices in a jump diffusion model in terms of American option prices in the standard Black–Scholes model. We also investigate the dependence of the bounds on different parameters of the model.
Asymptotics of the density of the supremum of a random walk with heavy-tailed increments
Authors: Wang Yuebao , Wang Kaiyong
Published: September 2006

Under some relaxed conditions, in this paper we obtain some equivalent conditions on the asymptotics of the density of the supremum of a random walk with heavy-tailed increments. To do this, we investigate the asymptotics of the first ascending ladder height of a random walk with heavy-tailed increments. The results obtained improve and extend the corresponding classical results.
Critical scaling for the SIS stochastic epidemic
Authors: Dolgoarshinnykh R. G. , Lalley Steven P.
Published: September 2006

We exhibit a scaling law for the criticalSISstochastic epidemic. If at time 0 the population consists ofinfected andsusceptible individuals, then when the time and the number currently infected are both scaled by, the resulting process converges, asN→ ∞, to a diffusion process related to the Feller diffusion by a change of drift. As a consequence, the rescaled size of the epidemic has a limit law that coincides with that of a first passage time for the standard Ornstein-Uhlenbeck process. These results are the analogs for the SIS epidemic of results of Martin-Löf (1998) and Aldous (1997) for the simple SIR epidemic.