bluuebunny/crossref_metadata_2025_split huggingface dataset:
CIRA/CSU Four-Dimensional Variational Data Assimilation System
Authors: Zupanski Milija , Zupanski Dusanka , Vukicevic Tomislava , Eis Kenneth , Haar Thomas Vonder 
Published: April 2005

A new four-dimensional variational data assimilation (4DVAR) system is developed at the Cooperative Institute for Research in the Atmosphere (CIRA)/Colorado State University (CSU). The system is also called the Regional Atmospheric Modeling Data Assimilation System (RAMDAS). In its present form, the 4DVAR system is employing the CSU/Regional Atmospheric Modeling System (RAMS) nonhydrostatic primitive equation model. The Weather Research and Forecasting (WRF) observation operator is used to access the observations, adopted from the WRF three-dimensional variational data assimilation (3DVAR) algorithm. In addition to the initial conditions adjustment, the RAMDAS includes the adjustment of model error (bias) and lateral boundary conditions through an augmented control variable definition. Also, the control variable is defined in terms of the velocity potential and streamfunction instead of the horizontal winds. The RAMDAS is developed after the National Centers for Environmental Prediction (NCEP) Eta 4DVAR system, however with added improvements addressing its use in a research environment. Preliminary results with RAMDAS are presented, focusing on the minimization performance and the impact of vertical correlations in error covariance modeling. A three-dimensional formulation of the background error correlation is introduced and evaluated. The Hessian preconditioning is revisited, and an alternate algebraic formulation is presented. The results indicate a robust minimization performance.
Dropsonde Observations in Low-Level Jets over the Northeastern Pacific Ocean from CALJET-1998 and PACJET-2001: Mean Vertical-Profile and Atmospheric-River Characteristics
Authors: Ralph F. Martin , Neiman Paul J. , Rotunno Richard 
Published: April 2005

Dropsonde observations are used to document the mean vertical profiles of kinematic and thermodynamic conditions in the pre-cold-frontal low-level-jet (LLJ) region of extratropical cyclones over the eastern Pacific Ocean. This is the region within storms that is responsible not only for the majority of heavy rainfall induced by orography when such storms strike the coast, but also for almost all meridional water vapor transport at midlatitudes. The data were collected from NOAA’s P-3 aircraft in 10 storms during the California Land-falling Jets Experiment (CALJET) of 1998 and in 7 storms during the Pacific Land-falling Jets Experiment (PACJET) of 2001. The mean position of the dropsondes was 500 km offshore, well upstream of orographic influences. The availability of data from two winters that were characterized by very different synoptic regimes and by differing phases of ENSO—that is, El Niño in 1998 and La Niña in 2001—allowed examination of interannual variability. The composite pre-cold-frontal profiles reveal a well-defined LLJ at 1.0-km altitude with a wind speed of 23.4 m s−1 and a wind direction of 216.7°, as well as vertical shear characteristic of warm advection. The composite thermodynamic conditions were also documented, with special attention given to moist static stability due to the nearly saturated conditions that were prevalent. Although the dry static stability indicated very stable conditions (4.5 K km−1), the moist static stability was approximately zero up to 2.8-km altitude. Although the composite winds, temperatures, and water vapor mixing ratios in 2001 differed markedly from 1998, the moist static stability remained near zero from the surface up to 2.8–3.0-km altitude for both seasons. Hence, orographic precipitation enhancement is favored in this sector of the storm, regardless of the phase of ENSO. The dropsonde data were also used to characterize the depth and strength of atmospheric rivers, which are responsible for most of the meridional water vapor transport at midlatitudes. The vertically integrated along-river water vapor fluxes averaged 525 × 105 kg s−1 (assuming a 100-km-wide swath), while the meridional and zonal components were 387 × 105 kg s−1 and 302 × 105 kg s−1, respectively. Although the composite meridional transport in 2001 was less than half that in 1998 (230 × 105 kg s−1 versus 497 × 105 kg s−1), the characteristic scale height of the meridional water vapor transport remained constant; that is, 75% of the transport occurred below 2.25-km altitude.
Redefinition of Affymetrix probe sets by sequence overlap with cDNA microarray probes reduces cross-platform inconsistencies in cancer-associated gene expression measurements
Authors: Carter Scott L , Eklund Aron C , Mecham Brigham H , Kohane Isaac S , Szallasi Zoltan 
Published: April 2005

Abstract
Background
Comparison of data produced on different microarray platforms often shows surprising discordance. It is not clear whether this discrepancy is caused by noisy data or by improper probe matching between platforms. We investigated whether the significant level of inconsistency between results produced by alternative gene expression microarray platforms could be reduced by stringent sequence matching of microarray probes. We mapped the short oligo probes of the Affymetrix platform onto cDNA clones of the Stanford microarray platform. Affymetrix probes were reassigned to redefined probe sets if they mapped to the same cDNA clone sequence, regardless of the original manufacturer-defined grouping. The NCI-60 gene expression profiles produced by Affymetrix HuFL platform were recalculated using these redefined probe sets and compared to previously published cDNA measurements of the same panel of RNA samples.

Results
The redefined probe sets displayed a substantially higher level of cross-platform consistency at the level of gene correlation, cell line correlation and unsupervised hierarchical clustering. The same strategy allowed an almost complete correspondence of breast cancer subtype classification between Affymetrix gene chip and cDNA microarray derived gene expression data, and gave an increased level of similarity between normal lung derived gene expression profiles using the two technologies. In total, two Affymetrix gene-chip platforms were remapped to three cDNA platforms in the various cross-platform analyses, resulting in improved concordance in each case.

Conclusion
We have shown that probes which target overlapping transcript sequence regions on cDNA microarrays and Affymetrix gene-chips exhibit a greater level of concordance than the corresponding Unigene or sequence matched features. This method will be useful for the integrated analysis of gene expression data generated by multiple disparate measurement platforms.
GABAAreceptor γ2 subunit knockdown mice have enhanced anxiety-like behavior but unaltered hypnotic response to benzodiazepines
Authors: Chandra Dev , Korpi Esa R , Miralles Celia P , De Blas Angel L , Homanics Gregg E 
Published: April 2005

Abstract

Background
Gamma-aminobutyric acid type A receptors (GABAA-Rs) are the major inhibitory receptors in the mammalian brain and are modulated by a number of sedative/hypnotic drugs including benzodiazepines and anesthetics. The significance of specific GABAA-Rs subunits with respect to behavior and in vivo drug responses is incompletely understood. The γ2 subunit is highly expressed throughout the brain. Global γ2 knockout mice are insensitive to the hypnotic effects of diazepam and die perinatally. Heterozygous γ2 global knockout mice are viable and have increased anxiety-like behaviors. To further investigate the role of the γ2 subunit in behavior and whole animal drug action, we used gene targeting to create a novel mouse line with attenuated γ2 expression, i.e., γ2 knockdown mice.

Results
Knockdown mice were created by inserting a neomycin resistance cassette into intron 8 of the γ2 gene. Knockdown mice, on average, showed a 65% reduction of γ2 subunit mRNA compared to controls; however γ2 gene expression was highly variable in these mice, ranging from 10–95% of normal. Immunohistochemical studies demonstrated that γ2 protein levels were also variably reduced. Pharmacological studies using autoradiography on frozen brain sections demonstrated that binding of the benzodiazepine site ligand Ro15-4513 was decreased in mutant mice compared to controls. Behaviorally, knockdown mice displayed enhanced anxiety-like behaviors on the elevated plus maze and forced novelty exploration tests. Surprisingly, mutant mice had an unaltered response to hypnotic doses of the benzodiazepine site ligands diazepam, midazolam and zolpidem as well as ethanol and pentobarbital. Lastly, we demonstrated that the γ2 knockdown mouse line can be used to create γ2 global knockout mice by crossing to a general deleter cre-expressing mouse line.

Conclusion
We conclude that: 1) insertion of a neomycin resistance gene into intron 8 of the γ2 gene variably reduced the amount of γ2, and that 2) attenuated expression of γ2 increased anxiety-like behaviors but did not lead to differences in the hypnotic response to benzodiazepine site ligands. This suggests that reduced synaptic inhibition can lead to a phenotype of increased anxiety-like behavior. In contrast, normal drug effects can be maintained despite a dramatic reduction in GABAA-R targets.
Time course study of oxidative and nitrosative stress and antioxidant enzymes in K2Cr2O7-induced nephrotoxicity
Authors: Pedraza-Chaverrí José , Barrera Diana , Medina-Campos Omar N , Carvajal Raymundo C , Hernández-Pando Rogelio , Macías-Ruvalcaba Norma A , Maldonado Perla D , Salcedo Marcos I , Tapia Edilia , Saldívar Liliana , Castilla María E , Ibarra-Rubio María E 
Published: April 2005

Abstract
Background
Potassium dichromate (K2Cr2O7)-induced nephrotoxicity is associated with oxidative and nitrosative stress. In this study we investigated the relation between the time course of the oxidative and nitrosative stress with kidney damage and alterations in the following antioxidant enzymes: Cu, Zn superoxide dismutase (Cu, Zn-SOD), Mn-SOD, glutathione peroxidase (GPx), glutathione reductase (GR), and catalase (CAT).

Methods
Nephrotoxicity was induced in rats by a single injection of K2Cr2O7. Groups of animals were sacrificed on days 1,2,3,4,6,8,10, and 12. Nephrotoxicity was evaluated by histological studies and by measuring creatinine clearance, serum creatinine, blood urea nitrogen (BUN), and urinary excretion of N-acetyl-β-D-glucosaminidase (NAG) and total protein. Oxidative and nitrosative stress were measured by immunohistochemical localization of protein carbonyls and 3-nitrotyrosine, respectively. Cu, Zn-SOD, Mn-SOD, and CAT were studied by immunohistochemical localization. The activity of total SOD, CAT, GPx, and GR was also measured as well as serum and kidney content of chromium and urinary excretion of NO2-/NO3-. Data were compared by two-way analysis of variance followed by a post hoc test.

Results
Serum and kidney chromium content increased reaching the highest value on day 1. Nephrotoxicity was made evident by the decrease in creatinine clearance (days 1–4) and by the increase in serum creatinine (days 1–4), BUN (days 1–6), urinary excretion of NAG (days 1–4), and total protein (day 1–6) and by the structural damage to the proximal tubules (days 1–6). Oxidative and nitrosative stress were clearly evident on days 1–8. Urinary excretion of NO2-/NO3- decreased on days 2–6. Mn-SOD and Cu, Zn-SOD, estimated by immunohistochemistry, and total SOD activity remained unchanged. Activity of GPx decreased on days 3–12 and those of GR and CAT on days 2–10. Similar findings were observed by immunohistochemistry of CAT.

Conclusion
These data show the association between oxidative and nitrosative stress with functional and structural renal damage induced by K2Cr2O7. Renal antioxidant enzymes were regulated differentially and were not closely associated with oxidative or nitrosative stress or with kidney damage. In addition, the decrease in the urinary excretion of NO2-/NO3- was associated with the renal nitrosative stress suggesting that nitric oxide was derived to the formation of reactive nitrogen species involved in protein nitration.
Identification of children who may benefit from self-hypnosis at a pediatric pulmonary center
Authors: Anbar Ran D , Geisler Susan C 
Published: April 2005

Abstract
Background
Emotional difficulties can trigger respiratory symptoms. Thus, children presenting with respiratory complaints may benefit from a psychological intervention. The purpose of this study was to define the proportion of patients referred to a Pediatric Pulmonary Center who may benefit from instruction in self-hypnosis, as a psychological intervention.

Methods
A retrospective chart review was conducted for all newly referred patients to the SUNY Upstate Medical University Pediatric Pulmonary Center during an 18 month period beginning January 1, 2000. Patients were offered hypnosis if they presented with symptoms or signs suggestive of psychological difficulties. Hypnosis was taught in one or two 15–45 minute sessions by a pediatric pulmonologist.

Results
Of 725 new referrals, 424 were 0–5 years old, 193 were 6–11 years old, and 108 were 12–18 years old. Diagnoses of anxiety, habit cough, or vocal cord dysfunction accounted for 1% of the 0–5 year olds, 20% of the 6–11 year olds, and 31% of the 12–18 year olds. Hypnotherapy was offered to 1% of 0–5 year olds, 36% of 6–11 year olds, and 55% of 12–18 year olds. Of 81 patients who received instruction in self-hypnosis for anxiety, cough, chest pain, dyspnea, or inspiratory difficulties, 75% returned for follow-up, and among the returning patients 95% reported improvement or resolution of their symptoms.

Conclusion
A large number of patients referred to a Pediatric Pulmonary Center appeared to benefit from instruction in self-hypnosis, which can be taught easily as a psychological intervention.
The effect of glucosamine sulphate on osteoarthritis: design of a long-term randomised clinical trial [ISRCTN54513166]
Authors: Rozendaal Rianne M , Koes Bart W , Weinans Harrie , Uitterlinden Elian J , van Osch Gerjo JVM , Ginai Abida Z , Verhaar Jan AN , Bierma-Zeinstra Sita MA 
Published: April 2005

Abstract

Background
Pharmacological treatment for osteoarthritis (OA) can be divided into two groups: symptom-modifying drugs and disease-modifying drugs. Symptom-modifying drugs are currently the prescription of choice for patients with OA, as disease-modifying drugs are not yet available in usual care. However, there has recently been a lot of debate about glucosamine sulphate (GS), a biological agent that is thought to have both symptom-modifying and disease-modifying properties. This assumption has yet to be proved.
The objective of this article is to present the design of a blind randomised clinical trial that examines the long-term symptom-modifying and disease-modifying effectiveness of GS in patients with hip OA. This trial is ongoing and will finish in March 2006.

Methods/design
Patients with hip OA meeting the ACR-criteria are randomly allocated to either 1500 mg of oral GS or placebo for the duration of two years. The primary outcome measures, which are joint space narrowing (JSN), and change in the pain and function score of the Western Ontario McMaster Universities Osteoarthritis index (WOMAC), are determined at baseline and after two years of follow-up during the final assessment. Intermediate measures at three-month intervals throughout the trial are used to study secondary outcome measures. Secondary outcome measures are changes in WOMAC stiffness score, quality of life, medical consumption, side effects and differences in biomarker CTX-II.
Promiscuous drugs compared to selective drugs (promiscuity can be a virtue)
Authors: Mencher Simon K , Wang Long G 
Published: April 2005

Abstract
Background
The word selectivity describes a drug's ability to affect a particular cell population in preference to others. As part of the current state of art in the search for new therapeutic agents, the property of selectivity is a mode of action thought to have a high degree of desirability. Consequently there is a growing activity in this area of research.
Selectivity is generally a worthy property in a drug because a drug having high selectivity may have a dramatic effect when there is a single agent that can be targeted against the appropriate molecular-driver involved in the pathogenesis of a disease. An example is chronic myeloid leukemia (CML). CML has a specific chromosomal abnormality, the Philadelphia chromosome, that results in a single gene that produces an abnormal protein

Discussion
There is a burgeoning understanding of the cellular mechanisms that control the etiology and pathogeneses of diseases. This understanding both enables and motivates the development of drugs that induce a specific action in a selected cell population; i.e., a targeted treatment. Consequently, drugs that can target distinct molecular targets involved in pathologic/pathogenetic processes, or signal-transduction pathways, are being developed.
However, in most cases, diseases involve multiple abnormalities. A disease may be associated with more than one dysfunctional protein and these may be out-of-balance with each other. Likewise a drug might strongly target a protein that shares a similar active domain with other proteins. A drug may also target pleiotropic cytokines, or other proteins that have multi-physiological functions. In this way multiple normal cellular pathways can be simultaneously influenced. Long term experience with drugs supposedly designed for only a single target, but which unavoidably involve other functional effects, is uncovering the fact that molecular targeting is not medically flawless.

Summary
We contend that an ideal drug may be one whose efficacy is based not on the inhibition of a single target, but rather on the rebalancing of the several proteins or events, that contribute to the etiology, pathogeneses, and progression of diseases, i.e., in effect a promiscuous drug. Ideally, if this could be done at minimum drug concentration, side effects could be minimized. Corollaries to this argument are that the growing fervor for researching truly selective drugs may be imprudent when considering the totality of responses; and that the expensive screening techniques used to discover these, may be both medically and financially inefficient.
Good governance and good health: The role of societal structures in the human immunodeficiency virus pandemic
Authors: Menon-Johansson Anatole S 
Published: April 2005

Abstract
Background
Only governments sensitive to the demands of their citizens appropriately respond to needs of their nation. Based on Professor Amartya Sen's analysis of the link between famine and democracy, the following null hypothesis was tested: "Human Immunodeficiency Virus (HIV) prevalence is not associated with governance".

Methods
Governance has been divided by a recent World Bank paper into six dimensions. These include Voice and Accountability, Political Stability and Absence of Violence, Government Effectiveness, Regulatory Quality, Rule of Law and the Control of Corruption. The 2002 adult HIV prevalence estimates were obtained from UNAIDS. Additional health and economic variables were collected from multiple sources to illustrate the development needs of countries.

Results
The null hypothesis was rejected for each dimension of governance for all 149 countries with UNAIDS HIV prevalence estimates. When these nations were divided into three groups, the median (range) HIV prevalence estimates remained constant at 0.7% (0.05 – 33.7%) and 0.75% (0.05% – 33.4%) for the lower and middle mean governance groups respectively despite improvements in other health and economic indices. The median HIV prevalence estimates in the higher mean governance group was 0.2% (0.05 – 38.8%).

Conclusion
HIV prevalence is significantly associated with poor governance. International public health programs need to address societal structures in order to create strong foundations upon which effective healthcare interventions can be implemented.
Fluorescent proteins as tools to aid protein production
Authors: Su Wei Wen 
Published: April 2005

Abstract
Fluorescent proteins are genetically encoded, highly versatile reporters useful for monitoring various aspects of recombinant protein production. In addition to the widely popular green fluorescent protein (GFP) from Aequorea victoria, a variety of other fluorescent proteins have been discovered that display a wide range of spectral properties. Synthetic variants have also been developed to overcome limitations associated with their wild-type counterparts. Having a large repertoire of fluorescent proteins with diverse traits opens new opportunities for rapid monitoring and optimization of recombinant protein production.
The role of mutation in the new cancer paradigm
Authors: Prehn Richmond T 
Published: April 2005

AbstractThe almost universal belief that cancer is caused by mutation may gradually be giving way to the belief that cancer begins as a cellular adaptation that involves the local epigenetic silencing of various genes. In my own interpretation of the new epigenetic paradigm, the genes epigenetically suppressed are genes that normally serve in post-embryonic life to suppress and keep suppressed those other genes upon which embryonic development depends. Those other genes, if not silenced or suppressed in the post-embryonic animal, become, I suggest, the oncogenes that are the basis of neoplasia.Mutations that occur in silenced genes supposedly go unrepaired and are, therefore, postulated to accumulate, but such mutations probably play little or no causative role in neoplasia because they occur in already epigenetically silenced genes. These mutations probably often serve to make the silencing, and therefore the cancer, epigenetically irreversible.
Prevalence and burden of self-reported blindness and low vision for individuals living in institutions: a nationwide survey
Authors: Brézin Antoine Pierre , Lafuma Antoine , Fagnani Francis , Mesbah Mounir , Berdeaux Gilles 
Published: April 2005

Abstract

Background
The prevalence of self-reported low vision (LV) and blindness, and their associated disabilities, handicaps and socio-economic consequences for individuals living in institutions are poorly documented.

Methods
2,075 institutions were selected at random and eight individuals were picked at random from the list of residents. Three groups of individuals were defined: blind, LV, and a control group (CG). These were compared after adjustment for age and co-morbidities. Of the 15,403 individuals, 14,603 interviews (94.9%) were completed.

Results
The prevalence of blindness was 1.6% and the LV 13.4%. Blind individuals needed assistance more often (OR: 2.65 to 11.35) than CG members while the assistance required by LV individuals was similar to that for the CG. Blind individuals required institution adaptation (building and furniture changes) more often than the CG. Blind (57.9%) and LV individuals (35.4%) were more often registered for social allowances. Monthly social allowances were EUR 86 higher for blind than LV individuals. Monthly family incomes were found to be similar between the three groups (from EUR 782 to 797). Social and demographic data, institution description, income, handicaps, disabilities, social allowances and details of daily activities were collected interviews

Conclusion
The results demonstrate the impact of self-reported blindness and LV on daily life for patients living in institutions.