bluuebunny/crossref_metadata_2025 huggingface dataset:
Autophagy: Basic Principles and Relevance to Disease
Authors: Kundu Mondira , Thompson Craig B.
Published: January 2008

Autophagy is a process by which cytoplasmic components are sequestered in double membrane vesicles and degraded upon fusion with lysosomal compartments. In yeast, autophagy is activated in response to changes in the extracellular milieu. Depending upon the stimulus, autophagy can degrade cytoplasmic contents nonspecifically or can target the degradation of specific cellular components. Both of these have been adopted in higher eukaryotes and account for the expanding role of autophagy in various cellular processes, as well as contribute to the variation in cellular outcomes after induction of autophagy. In some cases, autophagy appears to be an adaptive response, whereas under other circumstances it is involved in cell death. In mammals, autophagy has been implicated in either the pathogenesis or response to a wide variety of diseases, including neurodegenerative disease, chronic bacterial and viral infections, atherosclerosis, and cancer. As the basic molecular pathways that regulate autophagy are elucidated, the relationship of autophagy to the pathogenesis of various disease states emerges.
Gene Expression Profiling of Breast Cancer
Authors: Cheang Maggie C.U. , van de Rijn Matt , Nielsen Torsten O.
Published: January 2008

DNA microarray platforms for gene expression profiling were invented relatively recently, and breast cancer has been among the earliest and most intensely studied diseases using this technology. The molecular signatures so identified help reveal the biologic spectrum of breast cancers, provide diagnostic tools as well as prognostic and predictive gene signatures, and may identify new therapeutic targets. Data are best presented in an open access format to facilitate external validation, the most crucial step in identifying robust, reproducible gene signatures suitable for clinical translation. Clinically practical applications derived from full expression profile studies already in use include reduced versions of microarrays representing key discriminatory genes and therapeutic targets, quantitative polymerase chain reaction assays, or immunohistochemical surrogate panels (suitable for application to standard pathology blocks). Prospective trials are now underway to determine the value of such tools for clinical decision making in breast cancer; these efforts may serve as a model for using such approaches in other tumor types.
Kidney Transplantation: Mechanisms of Rejection and Acceptance
Authors: Cornell Lynn D. , Smith R. Neal , Colvin Robert B.
Published: January 2008

We describe the molecular and cellular mechanisms believed to be responsible for the rejection of renal allografts, including acute T cell–mediated rejection, acute antibody-mediated (humoral) rejection, rejection mediated by the innate immune system, and chronic rejection. We present mechanisms of graft acceptance, including accommodation, regulation, and tolerance. Studies in animals have replicated many pathologic features of acute and chronic rejection. We illuminate the pathogenesis of human pathology by reflection from experimental models.
Molecular Biology and Pathology of Lymphangiogenesis
Authors: Karpanen Terhi , Alitalo Kari
Published: January 2008

The lymphatic vasculature is essential for the maintenance of tissue fluid balance, immune surveillance, and adsorption fatty acids in the gut. The lymphatic vessels are also crucially involved in the pathogenesis of diseases such as tumor metastasis, lymphedema, and various inflammatory conditions. Attempts to control or treat these diseases have drawn a lot of interest to lymphatic vascular research during the past few years. Recently, several markers specific for lymphatic endothelium and models for lymphatic vascular research have been characterized, enabling great technical progress in lymphatic vascular biology, and many critical regulators of lymphatic vessel growth have been identified. Despite these significant achievements, our understanding of the lymphatic vessel development and pathogenesis is still rather limited. Several key questions remain to be resolved, including the relative contributions of different pathways targeting lymphatic vasculature, the molecular and cellular processes of lymphatic maturation, and the detailed mechanisms of tumor metastasis via the lymphatic system.
The Origins of Medulloblastoma Subtypes
Authors: Gilbertson Richard J. , Ellison David W.
Published: January 2008

Childhood tumors containing cells that are morphologically and functionally similar to normal progenitor cells provide fertile ground for investigating the links between development and cancer. In this respect, integrated studies of normal cerebellar development and the medulloblastoma, a malignant embryonal tumor of the cerebellum, have proven especially fruitful. Emerging evidence indicates that the different precursor cell populations that form the cerebellum and the cell signaling pathways that regulate its development likely represent distinct compartments from which the various subtypes of medulloblastoma arise. Definitive characterization of each medulloblastoma subtype will undoubtedly improve treatment of this disease and provide important insights to the origins of cancer.
Metastatic Cancer Cell
Authors: Bacac Marina , Stamenkovic Ivan
Published: January 2008

Metastasis is the result of cancer cell adaptation to a tissue microenvironment at a distance from the primary tumor. Metastatic cancer cells require properties that allow them not only to adapt to a foreign microenvironment but to subvert it in a way that is conducive to their continued proliferation and survival. Recent conceptual and technological advances have contributed to our understanding of the role of the host tissue stroma in promoting tumor cell growth and dissemination and have provided new insight into the genetic makeup of cancers with high metastatic proclivity.
The Relevance of Research on Red Cell Membranes to the Understanding of Complex Human Disease: A Personal Perspective
Authors: Marchesi Vincent T.
Published: January 2008

Molecular analysis in the service of research on human disease has finally come of age, as the chapters within this volume testify. Many technical advances, among them the development of recombinant DNA and its many applications, opened the way to study cells and processes that were unapproachable in the 1960s, when I first began my research career. The state of molecular biological studies at that time limited studies of human cell membrane proteins to experimental material most available and accessible, making the human erythrocyte membrane the favored target. I describe here how studies of red blood cell membrane proteins evolved and how results from those studies still inform present-day research.
Neonatal dexamethasone administration causes progressive renal damage due to induction of an early inflammatory response
Authors: Liu Yan , van Goor Harry , Havinga Rick , Baller Julius F. W. , Bloks Vincent W. , van der Leij Feike R. , Sauer Pieter J. J. , Kuipers Folkert , Navis Gerjan , de Borst Martin H.
Published: January 2008

Glucocorticoids (GCs) are widely used to prevent chronic lung disease in immature newborns. Emerging evidence indicates that GC exposure in early life may interfere with kidney function and is associated with hypertension in later life. In this study, we have investigated the effect of neonatal dexamethasone (DEX) administration on renal function in rats. Male rats were treated with DEX in the first 3 days after birth, controls received saline (SAL). Severe renal damage associated with premature death was found at 50 wks upon DEX treatment, while renal function and morphology were normal in controls. A subsequent time-course study was performed from 2 days to 32 wks. Compared with controls, neonatal DEX administration led to significant and persistent growth retardation. Progressive proteinuria and increased systolic blood pressure were found from 8 wks onwards in DEX-treated animals. Renal α-SMA gene expression was elevated from wk 24 onwards and morphological fibrosis was noted at 32 wks of age following DEX treatment. Markedly increased renal gene expression of TNF-α and MCP-1 in DEX -treated rats was observed at day 7, probably contributing to the permanent increase in interstitial macrophage numbers that started at 14 days. Permanently elevated renal TGF-β gene expression was induced by DEX administration from 4 wks onwards. Our data indicate that neonatal DEX administration in rats leads to renal failure in later life, presumably due to an early inflammatory trigger that elicits a persistent pro-fibrotic process that eventually results in progressive renal deterioration.
N-Arachidonoyl l-Serine, a Putative Endocannabinoid, Alters the Activation of N-Type Ca2+ Channels in Sympathetic Neurons
Authors: Guo Juan , Williams Damian J. , Ikeda Stephen R.
Published: January 2008

The effect of N-arachidonoyl l-serine (ARA-S), a recently discovered lipoamino acid found in the CNS, on N-type Ca2+ channels of rat sympathetic ganglion neurons was determined using whole cell patch clamp. Application of ARA-S produced a rapid and reversible augmentation of Ca2+ current that was voltage dependent and resulted from a hyperpolarizing shift in the activation curve. ARA-S did not influence G protein modulation of Ca2+ channels and appeared to act independently of G-protein-coupled receptors. These findings provide a foundation for investigating possible roles for ARA-S in nervous system function.
Down-Regulation of Mcl-1 by Small Interfering RNA Sensitizes Resistant Melanoma Cells to Fas-Mediated Apoptosis
Authors: Chetoui Nizar , Sylla Khaoussou , Gagnon-Houde Jean-Vincent , Alcaide-Loridan Catherine , Charron Dominique , Al-Daccak Reem , Aoudjit Fawzi
Published: January 2008

Resistance of malignant melanoma cells to Fas-mediated apoptosis is among the mechanisms by which they escape immune surveillance. However, the mechanisms contributing to their resistance are not completely understood, and it is still unclear whether antiapoptotic Bcl-2–related family proteins play a role in this resistance. In this study, we report that treatment of Fas-resistant melanoma cell lines with cycloheximide, a general inhibitor of de novo protein synthesis, sensitizes them to anti-Fas monoclonal antibody (mAb)–induced apoptosis. The cycloheximide-induced sensitization to Fas-induced apoptosis is associated with a rapid down-regulation of Mcl-1 protein levels, but not that of Bcl-2 or Bcl-xL. Targeting Mcl-1 in these melanoma cell lines with specific small interfering RNA was sufficient to sensitize them to both anti-Fas mAb-induced apoptosis and activation of caspase-9. Furthermore, ectopic expression of Mcl-1 in a Fas-sensitive melanoma cell line rescues the cells from Fas-mediated apoptosis. Our results further show that the expression of Mcl-1 in melanoma cells is regulated by the mitogen-activated protein kinase/extracellular signal-regulated kinase (ERK) and not by phosphatidylinositol 3-kinase/AKT signaling pathway. Inhibition of ERK signaling with the mitogen-activated protein/ERK kinase-1 inhibitor or by expressing a dominant negative form of mitogen-activated protein/ERK kinase-1 also sensitizes resistant melanoma cells to anti-Fas mAb-induced apoptosis. Thus, our study identifies mitogen-activated protein kinase/ERK/Mcl-1 as an important survival signaling pathway in the resistance of melanoma cells to Fas-mediated apoptosis and suggests that its targeting may contribute to the elimination of melanoma tumors by the immune system. (Mol Cancer Res 2008;6(1):42–52)
The Osterix Transcription Factor Down-Regulates Interleukin-1α Expression in Mouse Osteosarcoma Cells
Authors: Cao Ying , Jia Shu-Fang , Chakravarty Geetika , de Crombrugghe Benoit , Kleinerman Eugenie S.
Published: January 2008

K7M2 mouse osteosarcoma cells form lytic tumors and are deficient in osterix (Osx), a zinc finger–containing transcription factor required for osteoblast differentiation and bone formation. Our previous studies showed that replacement of Osx suppresses lytic bone destruction. Cytokines, including interleukin (IL)-1α, IL-6, IL-11, and prostaglandin E2, have been shown to stimulate osteoclast activity. We showed that IL-1α production by K7M2 cells was significantly suppressed following Osx transfection through a transcription-mediated mechanism. Osx had no effect on IL-6, IL-11, or prostaglandin E2. Site-directed mutagenesis and chromatin immunoprecipitation indicated that Osx down-regulated IL-1α through an Sp1-binding site on the IL-1α promoter. Inhibiting Osx by small interfering RNA in two cell lines (Dunn and DLM8) that expressed high levels of Osx led to enhanced IL-1α promoter activity and protein production and altered the phenotype from blastic to lytic. These data suggest that Osx down-regulates IL-1α expression in mouse osteosarcoma cells via transcriptional repression of IL-1α and this may in turn affect the lytic activity of the tumor cells. (Mol Cancer Res 2008;6(1):119–26)
Sustained VEGF Blockade Results in Microenvironmental Sequestration of VEGF by Tumors and Persistent VEGF Receptor-2 Activation
Authors: Kadenhe-Chiweshe Angela , Papa Joey , McCrudden Kimberly W. , Frischer Jason , Bae Jae-O , Huang Jianzhong , Fisher Jason , Lefkowitch Jay H. , Feirt Nikki , Rudge John , Holash Jocelyn , Yancopoulos George D. , Kandel Jessica J. , Yamashiro Darrell J.
Published: January 2008

Vascular endothelial growth factor (VEGF) blockade has been validated clinically as a treatment for human cancers, yet virtually all patients eventually develop progressive disease during therapy. In order to dissect this phenomenon, we examined the effect of sustained VEGF blockade in a model of advanced pediatric cancer. Treatment of late-stage hepatoblastoma xenografts resulted in the initial collapse of the vasculature and significant tumor regression. However, during sustained treatment, vessels recovered, concurrent with a striking increase in tumor expression of perlecan, a heparan sulfate proteoglycan. Whereas VEGF mRNA was expressed at the periphery of surviving clusters of tumor cells, both secreted VEGF and perlecan accumulated circumferential to central vessels. Vascular expression of heparanase, VEGF receptor-2 ligand binding, and receptor activation were concurrently maintained despite circulating unbound VEGF Trap. Endothelial survival signaling via Akt persisted. These findings provide a novel mechanism for vascular survival during sustained VEGF blockade and indicate a role for extracellular matrix molecules that sequester and release biologically active VEGF. (Mol Cancer Res 2008;6(1):1–9)
A JNK1/AP-1–Dependent, COX-2 Induction Is Implicated in 12-O-Tetradecanoylphorbol-13-Acetate–Induced Cell Transformation through Regulating Cell Cycle Progression
Authors: Zhang Dongyun , Li Jingxia , Song Lun , Ouyang Weiming , Gao Jimin , Huang Chuanshu
Published: January 2008

Cyclooxygenase-2 (COX-2) is reported to be one of the early-response gene products induced by 12-O-tetradecanoylphorbol-13-acetate (TPA). However, the relevance of COX-2 in TPA-induced cell transformation and the underlying mechanisms remains to be explored. Initially, we verified COX-2 induction after TPA treatment in mouse embryonic fibroblasts (MEF) and mouse epidermal cells Cl 41. More importantly, introduction of COX-2 small interfering RNA in MEFs or Cl 41 cells suppressed the cell transformation caused by TPA treatment. This inhibition could be reversed by overexpression of human full-length COX-2, indicating that COX-2 is at least one of the critical molecules involved in TPA-induced cell transformation. We further showed that TPA-promoted cell cycle progression was partially suppressed by COX-2 small interfering RNA, indicating that COX-2 also participated in TPA-associated cell cycle progression. Investigation of the upstream signaling pathways revealed that c-Jun-NH2-kinase 1 (JNK1), but not JNK2, played important roles in COX-2 induction, because knockout of JNK1 gene rather than JNK2 gene markedly impaired COX-2 induction. Furthermore, inhibition of c-Jun/activator protein 1 pathway or JNKs/c-Jun pathway by overexpression of dominant negative mutants of c-Jun, or MKK4 and MKK7 together, resulted in impairment of COX-2 induction, suggesting that JNK1/c-Jun/activator protein 1 pathway is involved in TPA-associated COX-2 induction. In contrast, IKK/p65 nuclear factor-κB pathway was not implicated because knockout of IKKα, IKKβ, or p65 gene did not affect COX-2 induction although nuclear factor-κB was activated by TPA. In addition, the TPA-promoted cell cycle progression was found impaired in JNK1-deficient, but not in JNK2-deficient, MEFs. Our results show that JNK1-associated COX-2 induction is implicated in TPA-associated cell transformation and cell cycle progression. (Mol Cancer Res 2008;6(1):165–74)
Cutaneous Graft-versus-Host Disease: A Guide for the Dermatologist
Authors: Häusermann Peter , Walter Roland B. , Halter Jörg , Biedermann Barbara C. , Tichelli André , Itin Peter , Gratwohl Alois
Published: January 2008

Graft-versus-host disease (GVHD) is defined by the aggregation of clinical and pathological manifestations in a recipient of allogeneic stem cells or bone marrow transplantation in which specific immunological as well as nonspecific phenomena lead to characteristic features. GVHD is one of the major complications after hematopoietic stem cell transplantations and responsible for posttherapeutic morbidity, mortality and decrease in quality of life of those patients. GVHD is critically induced and maintained by donor immunocompetent cells that particularly attack epithelia of fast proliferating tissues such as those from the liver, gastrointestinal tract and skin. On the basis of the time of presentation, cutaneous GVHD has been originally divided into an acute and chronic disease. The latter has traditionally been further subclassified into a more epithelial or lichenoid and a predominantly dermal or sclerodermoid form. With respect to the growing importance of this therapeutic procedure and increasing numbers of outpatients presenting with chronic GVHD, this article summarizes the updated knowledge on this disease focused for the dermatologist, and additionally it emphasizes the recent consensus documents on the various aspects of chronic GVHD of the National Institute of Health.
A Novel Frameshift Mutation (+A) at Codon 18 of the β-Globin Gene Associated with High Persistence of Fetal Hemoglobin Phenotype and δβ-Thalassemia
Authors: Feriotto Giordana , Salvatori Francesca , Finotti Alessia , Breveglieri Giulia , Venturi Marina , Zuccato Cristina , Bianchi Nicoletta , Borgatti Monica , Lampronti Ilaria , Mancini Irene , Massei Francesco , Favre Claudio , Gambari Roberto
Published: January 2008

We report in this paper a novel thalassemia mutation (insertion of a single A nucleotide within the exon 1, at codon 18, of the β-globin gene) associated with a deletion of the δβ-globin gene region, in a patient exhibiting high persistence of fetal hemoglobin. The novel mutation causes a frameshift with the generation of a UGA stop codon. Analysis of the parent’s DNA demonstrates that the A insertion and frameshift mutation are inherited from the father, while the δβ-globin gene deletion is inherited from the mother. Gene dosage analysis and deletion-specific PCR demonstrate that the deletion is the (δβ)⁰ Sicilian deletion, involving a 13.4-kb δβ-globin gene region.
Decreased Cytokine and Chemokine mRNA Expression in Bronchoalveolar Lavage in Asymptomatic Smoking Subjects
Authors: Meuronen Anna , Majuri Marja-Leena , Alenius Harri , Mäntylä Timo , Wolff Henrik , Piirilä Päivi , Laitinen Annika
Published: January 2008

Background: Smoking alters the inflammatory cell balance in the airways, often leading to repeated respiratory infections and, eventually, chronic obstructive pulmonary disease (COPD) in susceptible individuals. Objective: It was the aim of this study to evaluate alterations in the airway inflammatory balance caused by chronic cigarette smoke exposure. Methods: We compared results of biopsy and bronchoalveolar lavage (BAL) samples from non-smoking (n = 8) and smoking (n = 5; pack years 25.06 ± 11.75, range 7.13–36.8) subjects without COPD. Results: In BAL samples, we found a significantly higher number of total cells (353 ± 96 million vs. 114 ± 52 million; p = 0.003) and macrophages (331 ± 100 million vs. 84 ± 36 million; p = 0.002) in asymptomatic smoking subjects in comparison with never-smokers. Macrophages correlated negatively with the forced expiratory volume in 1 s as percent of the predicted value (ρ = –0.75, p = 0.003). Of 23 mediators examined, mRNA expression of cytokines interleukin (IL)-6, interferon-γ, tumor necrosis factor-β, IL-13 and chemokines CCL5, CCL3, CCL4 and CCL20 was significantly lowered in BAL cells of smokers compared with never-smokers and was negatively correlated with macrophages and positively correlated with the forced expiratory volume in 1 s as percent of the predicted value. Differential cell counts were similar between smokers and never-smokers in the bronchial biopsies. Conclusion: We conclude that in a susceptible population, smoking suppresses inflammatory defense by inhibiting expression of inflammatory mediators in the airways on a large scale.
Cloud Detection with MODIS. Part II: Validation
Authors: Ackerman S. A. , Holz R. E. , Frey R. , Eloranta E. W. , Maddux B. C. , McGill M.
Published: January 2008

An assessment of the performance of the Moderate Resolution Imaging Spectroradiometer (MODIS) cloud mask algorithm for Terra and Aqua satellites is presented. The MODIS cloud mask algorithm output is compared with lidar observations from ground [Arctic High-Spectral Resolution Lidar (AHSRL)], aircraft [Cloud Physics Lidar (CPL)], and satellite-borne [Geoscience Laser Altimeter System (GLAS)] platforms. The comparison with 3 yr of coincident observations of MODIS and combined radar and lidar cloud product from the Department of Energy (DOE) Atmospheric Radiation Measurement (ARM) Program Southern Great Plains (SGP) site in Lamont, Oklahoma, indicates that the MODIS algorithm agrees with the lidar about 85% of the time. A comparison with the CPL and AHSRL indicates that the optical depth limitation of the MODIS cloud mask is approximately 0.4. While MODIS algorithm flags scenes with a cloud optical depth of 0.4 as cloudy, approximately 90% of the mislabeled scenes have optical depths less than 0.4. A comparison with the GLAS cloud dataset indicates that cloud detection in polar regions at night remains challenging with the passive infrared imager approach.

In anticipation of comparisons with other satellite instruments, the sensitivity of the cloud mask algorithm to instrument characteristics (e.g., instantaneous field of view and viewing geometry) and thresholds is demonstrated. As expected, cloud amount generally increases with scan angle and instantaneous field of view (IFOV). Nadir sampling represents zonal monthly mean cloud amounts but can have large differences for regional studies when compared to full-swath-width analysis.
The Slope of Moist Symmetric Instability with Water Loading
Authors: Fantini Maurizio , Malguzzi Piero
Published: January 2008

Idealized numerical experiments, supported by analytic considerations, are performed to determine the preferred direction of symmetric instability when water loading is considered. It is concluded that the most unstable direction is tangent to a surface of neutral buoyancy, which can be defined numerically from the water content of lifted air, and coincides with the tangent to saturated isentropes only when all condensed water is precipitated out, consistent with the thermodynamic approximations made in the definition of equivalent potential temperature.

In more common situations, when part or all of the condensed water is retained in the cloud, the orientation of symmetrically unstable normal modes is much more slanted toward the horizontal, to the point that regions of the atmosphere, diagnosed as unstable from the consideration of equivalent potential temperature and vorticity, can in fact be stable.
Tropical and Stratospheric Influences on Extratropical Short-Term Climate Variability
Authors: Newman Matthew , Sardeshmukh Prashant D.
Published: January 2008

The relative impacts of tropical diabatic heating and stratospheric circulation anomalies on wintertime extratropical tropospheric variability are investigated in a linear inverse model (LIM) derived from the observed zero lag and 5-day lag covariances of 7-day running mean departures from the annual cycle. The model predicts the covariances at all other lags. The predicted and observed lag covariances are generally found to be in excellent agreement, even at the much longer lag of 21 days. This validates the LIM’s basic premise that the dynamics of weekly averages are effectively linear and stochastically driven, which justifies further linear diagnosis of the system.

Analysis of interactions among the LIM’s variables shows that tropical diabatic heating greatly enhances persistent variability over most of the Northern Hemisphere, especially over the Pacific Ocean and North America. Stratospheric effects are largely confined to the polar region, where they ensure that the dominant pattern of sea level pressure variability is the annular Arctic Oscillation rather than the more localized North Atlantic Oscillation. Over the North Atlantic, both effects are important, although some of the stratospheric influence is ultimately traceable to tropical forcing. In general, the tropically forced anomalies extend through the depth of the troposphere and into the stratosphere, whereas stratospherically generated anomalies tend to be largest at the surface and relatively weak at midtropospheric levels. Some persistent variability is, however, found even in the absence of these “external” forcings, especially near the amplitude maxima of the leading eigenmodes of the internal extratropical tropospheric evolution operator. One of these eigenmodes has a circumglobal zonal wavenumber-5 structure with maxima over the Arabian Sea and the central Pacific, and two others are associated with north–south dipole variations across the North Atlantic jet. Overall, tropical influences are generally found to be larger than stratospheric influences on extratropical tropospheric variability and have a pronounced impact on the persistent, and therefore the potentially predictable, portion of that variability.
Evaluation of the NOHRSC Snow Model (NSM) in a One-Dimensional Mode
Authors: Rutter Nick , Cline Don , Li Long
Published: January 2008

The National Operational Hydrologic Remote Sensing Center (NOHRSC) Snow Model (NSM) is an energy- and mass-balance model used by the National Oceanic and Atmospheric Administration’s National Weather Service for moderate-resolution spatially distributed snow analysis and data assimilation over the United States. The NSM was evaluated in a one-dimensional mode using meteorological and snowpit observations from five sites in Colorado collected during 2002–03. Four parameters estimated by the NSM [snow water equivalent (SWE), snow depth, average snowpack temperature, and snow surface temperature] were compared with snowpit observations and with estimates from another snow energy and mass-balance model, SNTHERM. Root-mean-squared differences (RMSDs) between snowpit SWE observations (January–June) at all sites and estimates from the NSM were about 11% (RMSD = 0.073 m) of the average maximum observed SWE from all sites of 0.694 m. SNTHERM exhibited only a slightly better agreement (RMSD = 0.066 m). During the winter and early spring period before snowpacks became isothermal at 273.15 K, both NSM and SNTHERM simulated significantly cooler average snowpack temperatures than observed (RMSD = 3 and 2 K, respectively). During this snow accumulation period estimates of SWE by both models were very similar. Differences in modeled SWE were traced to short periods (5–21 days) during isothermal conditions in early spring when the two models diverged. These events caused SWE differences that persisted throughout the ablation period and resulted in a range in melt-out times of 0.2–7.2 days between depth observations and modeled estimates. The divergence in SWE resulted from differences in snowmelt fluxes estimated by the two models, which are suggested to result from 1) liquid water fractions within a snowpack being estimated by the NSM using an internal energy method and by SNTHERM using a semiempirical temperature-based approach, and 2) SNTHERM, but not the NSM, accounting for the small liquid water fraction that coexists in equilibrium with snow when the snowpack surface is dry (<273.15 K).
Model Performance of Downscaling 1999–2004 Hydrometeorological Fields to the Upper Rio Grande Basin Using Different Forcing Datasets
Authors: Li J. , Gao X. , Sorooshian S.
Published: January 2008

This study downscaled more than five years of data (1999–2004) for hydrometeorological fields over the upper Rio Grande basin (URGB) to a 4-km resolution using a regional model [fifth-generation Pennsylvania State University–National Center for Atmospheric Research (NCAR) Mesoscale Model (MM5, version 3)] and two forcing datasets that include National Centers for Environmental Prediction (NCEP)–NCAR reanalysis-1 (R1) and North America Regional Reanalysis (NARR) data. The long-term high-resolution simulation results show detailed patterns of hydroclimatological fields that are highly related to the characteristics of the regional terrain; the most important of these patterns are precipitation localization features caused by the complex topography. In comparison with station observational data, the downscaling processing, on whichever forcing field is used, generated more accurate surface temperature and humidity fields than the Eta Model and NARR data, although it still included marked errors, such as a negative (positive) bias toward the daily maximum (minimum) temperature and overestimated precipitation, especially in the cold season.

Comparing the downscaling results forced by the NARR and R1 with both the gridded and station observational data shows that under the NARR forcing, the MM5 model produced generally better results for precipitation, temperature, and humidity than it did under the R1 forcing. These improvements were more apparent in winter and spring. During the warm season, although the use of NARR improved the precipitation estimates statistically at the regional (basin) scale, it substantially underestimated them over the southern upper Rio Grande basin, partly because the NARR forcing data exhibited warm and dry biases in the monsoon-active region during the simulation period and improper domain selection. Analyses also indicate that over mountainous regions, both the Climate Prediction Center’s (CPC’s) gridded (0.25°) and NARR forcings underestimate precipitation in comparison with station gauge data.
Normal-Mode Instabilities of a Time-Dependent Coastal Upwelling Jet
Authors: Durski S. M. , Samelson R. M. , Allen J. S. , Egbert G. D.
Published: January 2008

The linear stability of a nearly time-periodic, nonlinear, coastal upwelling–downwelling circulation, over alongshore-uniform topography, driven by a time-periodic wind stress is investigated using numerical methods. The near-periodic alongshore-uniform basic flow is obtained by forcing a primitive equation numerical model of coastal ocean circulation with periodic wind stress. Disturbance growth on this near-periodic flow is explored in linear and nonlinear model simulations. Numerous growing normal modes are found in the linear analyses at alongshore scales between 4 and 24 km. These modes vary in cross-shore structure and timing of maximum disturbance growth rate. One group of modes, in the 6.5–8.5-km alongshore-scale range, bears strong resemblance to the ensemble average disturbance structures observed in perturbed nonlinear model simulations. These modes are of a mixed type, exhibiting both strong baroclinic and barotropic energy exchange mechanisms, with maximum disturbance growth occurring during the transition from upwelling favorable to downwelling favorable winds. Nonlinear disturbance growth is characterized by similar structures at these same scales, but with significant exchange of energy between disturbances at different alongshore scales, such that overall disturbance energy accumulates at the longest (domain) scales, and gradually propagates offshore mainly in the pycnocline over numerous forcing cycles.
Predictability Associated with the Downstream Impacts of the Extratropical Transition of Tropical Cyclones: Methodology and a Case Study of Typhoon Nabi (2005)
Authors: Harr Patrick A. , Anwender Doris , Jones Sarah C.
Published: January 2008

Measures of the variability among ensemble members from the National Centers for Environmental Prediction ensemble prediction system are examined with respect to forecasts of the extratropical transition (ET) of Typhoon Nabi over the western North Pacific during September 2005. In this study, variability among ensemble members is used as a proxy for predictability. The time–longitude distribution of standard deviations among 500-hPa height fields from the ensemble members is found to increase across the North Pacific following the completion of the extratropical transition. Furthermore, the increase in ensemble standard deviation is organized such that an increase is associated with the extratropical transition and another increase extends downstream from the ET event. The organization and amplitude of the standard deviations increase from 144 h until approximately 72–48 h prior to the completion of the extratropical transition, and then decrease as the forecast interval decreases.

An empirical orthogonal function analysis of potential temperature on the dynamic tropopause is applied to ensemble members to identify the spatial and temporal organization of centers of variability related to the extratropical transition. The principal components are then used in a fuzzy cluster analysis to examine the grouping of forecast sequences in the collection of ensemble members. The number of forecast groups decreases as the forecast interval to the completion of the ET decreases. However, there is a systematic progression of centers of variability downstream of the ET event. Once the variability associated with the ET begins to decrease, the variability downstream of the ET event also begins to decrease.
Synoptic Control of Mesoscale Precipitating Systems in the Pacific Northwest
Authors: Roebber Paul J. , Swanson Kyle L. , Ghorai Jugal K.
Published: January 2008

This research examines whether an adequate representation of flow features on the synoptic scale allows for the skillful inference of mesoscale precipitating systems. The focus is on the specific problem of landfalling systems on the west coast of the United States for a variety of synoptic types that lead to significant rainfall. The methodology emphasizes rigorous hypothesis testing within a controlled hindcast setting to quantify the significance of the results. The role of lateral boundary conditions is explicitly accounted for by the study.

The hypotheses that (a) uncertainty in the large-scale analysis and (b) upstream buffer size have no impact on the skill of precipitation simulations are each rejected at a high level of confidence, with the results showing that mean precipitation skill is higher where low analysis uncertainty exists and for small nested grids. This indicates that an important connection exists between the quality of the synoptic information and predictability at the mesoscale in this environment, despite the absence of such information in the initialization or boundary conditions. Further, the flow-through of synoptic information strongly constrains the evolution of the mesoscale such that a small upstream buffer produces superior results consistent with the higher quality of the information crossing the boundary. Some preliminary evidence that synoptic type has an influence on precipitation skill is also found. The implications of these results for data assimilation, forecasting, and climate modeling are discussed.
Systematic Error Correction of Dynamical Seasonal Prediction of Sea Surface Temperature Using a Stepwise Pattern Project Method
Authors: Kug Jong-Seong , Lee June-Yi , Kang In-Sik
Published: January 2008

Every dynamical climate prediction model has significant errors in its mean state and anomaly field, thus degrading its performance in climate prediction. In addition to correcting the model’s systematic errors in the mean state, it is also possible to correct systematic errors in the predicted anomalies by means of dynamical or statistical postprocessing. In this study, a new statistical model has been developed based on the pattern projection method in order to empirically correct the dynamical seasonal climate prediction. The strength of the present model lies in the objective and automatic selection of optimal predictor grid points. The statistical model was applied to systematic error correction of SST anomalies predicted by Seoul National University’s (SNU) coupled GCM and evaluated in terms of temporal correlation skill and standardized root-mean-square error. It turns out that the statistical error correction improves the SST prediction over most regions of the global ocean with most forecast lead times up to 6 months. In particular, the SST predictions over the western Pacific and Indian Ocean are improved significantly, where the SNU coupled GCM shows a large error.
An Ensemble-Based Four-Dimensional Variational Data Assimilation Scheme. Part I: Technical Formulation and Preliminary Test
Authors: Liu Chengsi , Xiao Qingnong , Wang Bin
Published: January 2008

Applying a flow-dependent background error covariance (𝗕 matrix) in variational data assimilation has been a topic of interest among researchers in recent years. In this paper, an ensemble-based four-dimensional variational (En4DVAR) algorithm, designed by the authors, is presented that uses a flow-dependent background error covariance matrix constructed by ensemble forecasts and performs 4DVAR optimization to produce a balanced analysis. A great advantage of this En4DVAR design over standard 4DVAR methods is that the tangent linear and adjoint models can be avoided in its formulation and implementation. In addition, it can be easily incorporated into variational data assimilation systems that are already in use at operational centers and among the research community.

A one-dimensional shallow water model was used for preliminary tests of the En4DVAR scheme. Compared with standard 4DVAR, the En4DVAR converges well and can produce results that are as good as those with 4DVAR but with far less computation cost in its minimization. In addition, a comparison of the results from En4DVAR with those from other data assimilation schemes [e.g., 3DVAR and ensemble Kalman filter (EnKF)] is made. The results show that the En4DVAR yields an analysis that is comparable to the widely used variational or ensemble data assimilation schemes and can be a promising approach for real-time applications.

In addition, experiments were carried out to test the sensitivities of EnKF and En4DVAR, whose background error covariance is estimated from the same ensemble forecasts. The experiments indicated that En4DVAR obtained reasonably sound analysis even with larger observation error, higher observation frequency, and more unbalanced background field.
School Performance Measurement
Authors: Miller William H. , Kerr Brinck , Ritter Gary
Published: January 2008

Growing political pressure for increased efficiency in government has led many to support the use of performance measurement schemes. Such schemes are never neutral and frequently influence the allocation of resources and power. The increased use of performance measures in the public sector raises questions regarding the fairness of the measures and the justness of the accompanying sanctions and rewards. Focusing on public schools, this study demonstrates the need to assess governmental performance measurement schemes for their impact on equity. Three measurement schemes (No Child Left Behind, value added, and adjusted performance measures) are evaluated and compared regarding their impact on majority African American public schools in the state of Arkansas.
Preventing Mother-to-Child HIV Transmission Among South African Adolescents
Authors: Varga Christine , Brookes Heather
Published: January 2008

Although prevention of mother-to-child HIV transmission (PMTCT) programs are predicated on maternal behavior change, little is known about sociocultural factors affecting maternal—child care practices in this arena. The authors used narrative methods (key informant workshops, questionnaires, focus groups, and case study analysis) to explore how sociocultural context shapes adolescent mothers' ability to adhere to programmatic recommendations in rural and urban South Africa. The study aims were to understand the extent to which mothers' decisions are borne out in PMTCT-related practices and to identify contextual elements that affect the link between individual resolutions and action. The results revealed rural adolescents as less likely than urbanites to successfully implement most PMTCT-related practices. HIV stigma, family decision making, and cultural norms surrounding infant feeding hampered mothers' efforts to implement practices that would decrease the risk for infant infection. Barriers to behavior change were analyzed along four domains: history, culture, gender, and power. Methodological aspects and programmatic implications are discussed.
Late Relapse of Herpes Simplex Virus Encephalitis in a Child Due to Reactivation of Latent Virus: Clinicopathological Report and Review
Authors: Spiegel Ronen , Miron Dan , Yodko Helena , Lumelsky Dmitry , Habib Adib , Horovitz Yoseph
Published: January 2008

A child suffered from herpes simplex virus encephalitis at the age of 6 months; a late relapse occurred 8.5 years after the initial episode, the longest latency period reported. Radiologic and autopsy findings suggest local reactivation of latent herpes simplex virus as the cause of relapse. All cases of late relapse of herpes simplex virus encephalitis in the last 15 years are reviewed, with emphasis on clinical characteristics and possible mechanisms.
A Case of Congenital Glycogen Storage Disease Type IV With a Novel GBE1 Mutation
Authors: Raju G. Praveen , Li Hsin-Chang , Bali Deeksha S. , Chen Yuan-Tsong , Urion David K. , Lidov Hart G. W. , Kang Peter B.
Published: January 2008

Glycogen storage disease type IV (Andersen disease) is a rare metabolic disorder characterized by deficient glycogen branching enzyme activity resulting in abnormal, amylopectin-like glycogen deposition in multiple organs. This article reports on an infant with the congenital neuromuscular subtype of glycogen storage disease type IV who presented with polyhydramnios, hydrops fetalis, bilateral ankle contractures, biventricular cardiac dysfunction, and severe facial and extremity weakness. A muscle biopsy showed the presence of material with histochemical and ultrastructural characteristics consistent with amylopectin. Biochemical analysis demonstrated severely reduced branching enzyme activity in muscle tissue and fibroblasts. Genetic analysis demonstrated a novel deletion of exon 16 within GBE1 , the gene associated with glycogen storage disease type IV. Continued genetic characterization of glycogen storage disease type IV patients may aid in predicting clinical outcomes in these patients and may also help in identifying treatment strategies for this potentially devastating metabolic disorder.
Clinical Presentation and Diagnosis of Tuberous Sclerosis Complex in Infancy
Authors: Datta Anita N. , Hahn Cecil D. , Sahin Mustafa
Published: January 2008

The age-dependent nature of the characteristic features of tuberous sclerosis complex has historically presented challenges for the diagnosis in infancy. Although the increasing availability of neuroimaging and genetic testing has facilitated the diagnosis in neonates and infants, there are few reports describing how tuberous sclerosis complex presents in this age group. We performed a retrospective review of children diagnosed with tuberous sclerosis complex during the first year of life, compiling their clinical features at presentation and diagnosis, seizure history, and imaging findings. We identified 41 infants diagnosed with tuberous sclerosis complex before age 1 year. Their age at initial presentation ranged from antenatal to 9 months of age. Twenty-three patients (56%) initially presented with a cardiac rhabdomyoma, of which 15 were identified antenatally. Fourteen patients (34%) initially presented with seizures, and 6 (15%) initially presented with hypomelanotic macules. Five infants (12%) had a family history of tuberous sclerosis complex. A definitive diagnosis of tuberous sclerosis complex was accomplished antenatally in 4 patients, whereas the rest were diagnosed at a median age of 2 months. All 41 patients underwent neuroimaging during infancy; 36 (88%) had radiographic evidence of cortical tubers, and 38 (93%) had subependymal nodules. Neuroimaging resulted in a definitive diagnosis of tuberous sclerosis complex in 95% of patients. The diagnosis of tuberous sclerosis complex in infancy is aided by a high index of suspicion and timely access to neuroimaging. Early diagnosis of tuberous sclerosis complex may be essential to the success of future therapies by providing a window of opportunity for their use.
Assessing the Extent of Nonresponse Bias on NIBRS Estimates of Violent Crime
Authors: Addington Lynn A.
Published: January 2008

More than two decades ago, the U.S. Department of Justice released its recommendations for a new data collection method for the Uniform Crime Reporting Program that would become the National Incident-Based Reporting System (NIBRS). The full potential of NIBRS data has not been realized based on assumptions that these data are inherently biased due to a lack of national coverage and overrepresentation by law enforcement agencies serving smaller populations. To date, no research has assessed the amount of nonresponse or the degree to which NIBRS data are biased for generating crime estimates. Although this study confirms an overall low response rate for NIBRS reporting, higher rates are found for particular subnational population groups. An examination of violent crime rates and change estimates suggests that the amount of bias in NIBRS is not so small as to be ignorable but is not so considerable as to warrant abandoning these data altogether.
The Impact of Population Density on Municipal Government Expenditures
Authors: Holcombe Randall G. , Williams DeEdgra W.
Published: January 2008

Data from 487 municipal governments with populations greater than 50,000 are examined to see the relationship between population density and per capita government expenditures. There is no statistically significant relationship between per capita total government expenditures and operational expenditures for cities smaller than 500,000, and for larger cities, higher population density is associated with higher per capita government expenditures. Infrastructure expenditures tend to decline with increases in population density for cities smaller than 500,000, whereas expenditures on services tend to increase with population density for cities larger than 500,000. The relationship between per capita total expenditures and population density has policy relevance because it indicates that when all government expenditures are taken into account, policies that increase population density will not reduce per capita government expenditures and, in larger cities, will lead to higher per capita government expenditures.