bluuebunny/crossref_metadata_2025_split huggingface dataset:
CD4+ CD25+ regulatory T cells control the induction of antigen-specific CD4+ helper T cell responses in cancer patients
Authors: Nishikawa Hiroyoshi , Jäger Elke , Ritter Gerd , Old Lloyd J. , Gnjatic Sacha 
Published: April 2005

AbstractA proportion of cancer patients naturally develop CD4+ T-helper type 1 (Th1) cell responses to NY-ESO-1 that correlate with anti–NY-ESO-1 serum antibodies. To address the role of T-cell regulation in the control of spontaneous tumor immunity, we analyzed NY-ESO-1–specific Th1 cell induction before or after depletion of CD4+CD25+ T cells in vitro. While Th1 cells were generated in the presence of CD25+ T cells in cancer patients seropositive for NY-ESO-1, seronegative cancer patients and healthy donors required CD25+ T-cell depletion for in vitro induction of NY-ESO-1–specific Th1 cells. In vitro, newly generated NY-ESO-1–specific Th1 cells were derived from naive precursors, whereas preexisting memory populations were detectable exclusively in patients with NY-ESO-1 antibody. Memory populations were less sensitive than naive populations to CD4+CD25+ regulatory T cells. We propose that CD4+CD25+ regulatory T cells are involved in the generation and regulation of NY-ESO-1–specific antitumor immunity.
Development of hemophagocytic lymphohistiocytosis in triplets infected with HHV-8
Authors: Grossman William J. , Radhi Mohammed , Schauer Dennis , Gerday Erick , Grose Charles , Goldman Frederick D. 
Published: April 2005

AbstractHemophagocytic lymphohistiocytosis (HLH) is a rare disorder of immune dysregulation, characterized by end-organ damage from lymphocytic infiltration and macrophage activation. All known mutations associated with the HLH occur in genes critical in the perforin-granzyme pathway. Herein, we report HLH occurring in 2 female triplet infants who also had associated human herpesvirus type 8 (HHV-8) infections. The subjects had identical novel compound-heterozygous mutations in the Perforin alleles, resulting in undetectable perforin expression and NK-cell cytotoxicity. Both infants also had evidence of infection with HHV-8. These reports are, to our knowledge, the first cases of HLH in triplets and the first reported cases of HHV-8 infection associated with HLH in non–renal transplant and non–HIV-infected subjects.
Historical Perspective: The social determinants of disease – some roots of the movement
Authors: Syme S Leonard 
Published: April 2005

AbstractThis is an account of the early days of research on social determinants as I experienced them. I describe my time as one of four Fellows in a new training program in Medical Sociology at Yale University and how I came to be the first Sociologist employed in the U.S. Public Health Service. I then became the first Executive Secretary of a new Study Section at NIH dealing with a small number of research grant proposals in the field of Epidemiology. My account deals with some of my experiences in this developing field, culminating with my appointment as the first Sociologist to become a Professor of Epidemiology in a School of Public Health.
Coastal winds and low‐level jets: Simulations for sea gulfs
Authors: SavijÄRvi Hannu , NiemelÄ Sami , Tisler Priit 
Published: April 2005

AbstractThe reasons for the relatively strong coastal afternoon surface winds observed along the Gulf of Finland were studied by using a high‐resolution two‐dimensional numerical model in typical summertime conditions. Sea breeze effects were included by defining a clear sky, whereas they were minimized by alternatively defining a thick cloud cover. The geostrophic wind was varied both in speed and direction. A case‐study was made with a three‐dimensional operational forecast model with results that agreed with the two‐dimensional experiments and observations.Strongish afternoon surface winds nearly parallel with the coastline were obtained in the overcast gulf experiments. In these cases, well‐mixed air entering the smooth sea slantwise from over land commenced an inertial oscillation downstream such that the emerging low‐level jet maximum was located just above the opposite coast, causing the strong winds there. If the sky was clear, sea breezes and strong convective mixing further enhanced the coastal surface winds to supergeostrophic speeds.In contrast, weak coastal winds occurred when the sea breeze and the basic flow were nearly opposite. Given the gulf geometry, the sea breeze cell from the opposite coast could be advected over the gulf in a suitable basic flow, which resulted in another minimum in the coastal wind speed as a function of geostrophic wind direction. Copyright © 2005 Royal Meteorological Society.
Observational synthesis of mesoscale structures within an explosively developing cyclone
Authors: Browning K. A. 
Published: April 2005

AbstractAn observational case‐study is presented of a rapidly developing UK cyclone on 30 October 2000 to reveal the rich diversity of coexisting mesoscale structures in the vicinity of the cloud head, dry slot and polar‐front cloud band. The mesoscale structures include: multiple rain bands, due to upright convection originating in the boundary layer; stacked slantwise convective circulations at middle levels; cloud‐top striations, due to upright convection originating at high levels above the polar‐front cloud band; multiple sub‐structure within the cloud head; and inertia–gravity waves in the region of the tropopause fold. The emphasis of the analysis (synthesis) is on the inter‐relationships between the various mesoscale structures. Issues raised by this study include: (i) the interaction between upright and slantwise convection, including the effects of evaporation in the dry slot; (ii) the possible roles of inertia–gravity waves and conditional symmetric instability in triggering/organizing the dry‐slot convective rain bands and the sub‐structure within the cloud head; and (iii) the relationship between the dry‐slot rain bands and the multiple structures within the cloud head. This study is limited to documenting these relationships; controlled experiments with high‐resolution mesoscale models will be required to establish cause and effect and to assess their importance. Copyright © 2005 Royal Meteorological Society.
Upward and downward injection of Rossby wave activity across the tropopause: A new aspect of the troposphere–stratosphere dynamical linkage
Authors: Nishii Kazuaki , Nakamura Hisashi 
Published: April 2005

AbstractPropagation of zonally confined Rossby wave activity between the troposphere and lower stratosphere of the southern hemisphere during austral winter and spring of 1997 is studied, by using a wave‐activity flux and refractive index, both defined for stationary Rossby waves on a zonally asymmetric time‐mean flow. A particular event of large‐scale quasi‐stationary cyclogenesis in the troposphere is discussed, to which downward wave‐activity injection from anticyclonic anomalies upstream that had developed in the exit region of the lower‐stratospheric polar‐night jet (PNJ) contributed substantially. Consistent with that downward injection, phase lines of observed stream‐function anomalies exhibited a distinct eastward tilt with height. The development of the anticyclonic anomalies occurred at the leading edge of a quasi‐stationary Rossby wave train propagating along the PNJ, that had originated from a tropospheric blocking ridge farther upstream. Though less common than upward wave‐activity injection across the tropopause, similar events of downward wave‐activity injection occurred several times during that season, primarily in the regions south of Australia and over the central South Pacific, over each of which the PNJ exit overlapped with a tropospheric subpolar jet to form a vertical waveguide locally. It is argued that the downward wave‐activity propagation is essentially due to refraction in the vertically sheared westerlies, and the zonal asymmetries in the time‐mean flow are a likely factor for the observed geographical preference of the downward wave‐activity injection. Copyright © 2005 Royal Meteorological Society.
The assimilation of SSM/I and TMI rainfall rates in the ECMWF 4D‐Var system
Authors: Mahfouf Jean‐françois , Bauer Peter , Marécal Virginie 
Published: April 2005

AbstractA recent version of the European Centre for Medium‐Range Weather Forecasts four‐dimensional variational (4D‐Var) assimilation system (40 km horizontal resolution with a 12‐hour window) is used to examine the comparative impact of including satellite‐derived rainfall rates from SSM/I and TMI radiometers within the tropics. The methodology is similar to the one proposed by Marécal and Mahfouf (2002) where Total Column Water Vapour (TCWV) retrievals in rainy areas from a simplified 1D‐Var assimilation are introduced in the 4D‐Var system. An improved methodology for the estimation of rain rate retrieval errors proposed by Bauer et al. (2002) is used. Three one‐month experiments are undertaken: a control run (no rain rate assimilation), a TMI run (assimilation of TMI‐derived rain rates) and a SSM/I run (assimilation of SSM/I‐derived rain rates). The corrections of TCWV in rainy areas introduced in the 4D‐Var are very similar between SSM/I and TMI because they are dominated by the ‘no rain’ information. The impact of TMI and SSM/I assimilations is positive on forecast scores, both in the extratropics and in the tropics. Results from the SSM/I run show a larger positive impact which tends to demonstrate the benefit of the increased number of data from the SSM/I with respect to TMI. Copyright © 2005 Royal Meteorological Society.
Comparison of Point-of-Care HbA1c Test versus Standardized Laboratory Testing
Authors: Sicard Devin A , Taylor James R 
Published: April 2005

BACKGROUND: Glycosylated hemoglobin (HbA1c) evaluation is an accepted standard of care for assessing diabetes control. Point-of-care HbA1c monitors are relatively new, and there are few published data on their accuracy. OBJECTIVE: To compare a point-of-care HbA1c monitor with standardized laboratory testing. METHODS: Twenty-three patients who had type 1 or 2 diabetes were identified from our pharmacy-run diabetes clinic at a primary care clinic as needing HbA1c evaluation based on the American Diabetes Association guidelines. All patients with diabetes who attended our clinic were invited to participate in the study. Patients were required to obtain both a standardized laboratory HbA1c evaluation and a point-of-care A1c Now value within a week of each other. An analysis evaluating both clinical and statistical significance was completed at the end of the study. RESULTS: The A1c Now monitor showed good correlation (r = 0.758) to the standardized laboratory test. We found that the most accurate A1c Now values were within a range of 6–8%. One patient's value would have resulted in a different clinical decision if the decision were based on the A1c Now value. CONCLUSIONS: It appears that A1c Now may provide adequate accuracy and be useful for some patients. The monitor would be most beneficial for patients who cannot obtain standardized laboratory values secondary to either financial or transportation constraints. However, the decision to make adjustments in therapy should not be based solely on the A1c Now point-of-care result.
Effect of Indapamide on Urinary Calcium Excretion in Patients with and without Urinary Stone Disease
Authors: Ceylan Kadir , Topal Cevat , Erkoc Reha , Sayarlioglu Hayriye , Can Saban , Yilmaz Yuksel , Dogan Ekrem , Algun Ekrem , Gonulalan Hasan 
Published: April 2005

BACKGROUND: Indapamide is an antihypertensive agent similar to thiazides, but with some different effects. Thiazide and thiazide-like diuretics are useful in preventing recurrent urinary stone formation due to their hypocalciuric effects. OBJECTIVE: To determine the hypocalciuric and other effects on certain laboratory parameters of indapamide 1.5 mg in different patient groups. METHODS: Four groups of patients recruited from urology and nephrology outpatient departments were experiencing non-hypercalciuric urinary stone disease (group 1), idiopathic hypercalciuria (group 2), urinary stone disease with hypercalciuria (group 3), and essential hypertension (group 4). In all patients, fasting serum uric acid, calcium, sodium, potassium, cholesterol, triglyceride, parathyroid hormone (PTH) values, and morning second-spot urine calcium and creatinine levels were assessed before and 8 weeks after treatment with indapamide. RESULTS: Urinary calcium excretion was reduced significantly in all groups: group 1 from 0.10 ± 0.02 to 0.07 ± 0.03 (mean ± SD; 30% reduction; p < 0.001), group 2 from 0.30 ± 0.15 to 0.15 ± 0.10 (50% reduction; p < 0.001), group 3 from 0.35 ± 0.15 to 0.20 ± 0.10 (43% reduction; p < 0.001), and group 4 from 0.10 ± 0.03 to 0.08 ± 0.02 (20% reduction; p < 0.0010). These results should be interpreted with caution since no control group was included in this study. Mean serum uric acid and triglyceride levels were significantly increased, and mean PTH and potassium levels and diastolic and systolic blood pressure were significantly decreased in all groups. Few temporary adverse effects, such as dizziness and fatigue, were noticed and none of them caused discontinuation of treatment. CONCLUSIONS: Indapamide 1.5 mg/day is effective in decreasing calciuria in patients with non-hypercalciuric urinary stone disease, idiopathic hypercalciuria, urinary stone disease with hypercalciuria, and essential hypertension. This could be achieved with few adverse effects similar to those of thiazides and indapamide 2.5 mg. Indapamide decreased the PTH levels in all groups. Long-term clinical benefits of these effects should be evaluated prospectively with further randomized studies.
Population genomics: patterns of genetic variation within populations
Authors: Gibson Greg 
Published: April 2005

AbstractPopulation genomics is the study of the forces that shape the distribution of molecular variation within and among populations, on a genome‐wide scale (Luikartet al.,). Throughout the twentieth century, the mathematical theory of the history and fate of alleles became increasingly sophisticated, to the point where it was recognized that multiple gene sequences are required to describe the history or demography of a species (Hey and Machado,) and that properties of single genes must be interpreted in light of other sequences (Chakravati,; Bamshad and Wooding,). While robust evolutionary theory from first principles is essential for the interpretation of the distribution of genetic variation (Kimura,; Hartl and Clark,), it must be supplemented by empirical data that places confidence limits on key parameters. That these vary widely among species is one of the important insights from genomic analysis, which is thus ushering in a dramatic new phase in the discipline of population genetics.
The role of gene regulation in evolution
Authors: Rockman Matthew V. 
Published: April 2005

Abstract
Regulatory mutations that alter gene expression are likely to play key roles in phenotypic evolution. Because of the modular nature of cis‐regulatory DNA, mutations can alter phenotypes without pleiotropic side effects, yet because regulatory mutations often result in systemic transformations of complex phenotypes, they can result in radical but functionally integrated changes to organismal form. Empirical evidence supports the importance of regulatory mutations with restricted pleiotropic effects in phenotypic evolution. Moreover, data suggest that more mutations affect gene expression than gene structure, so such mutations are likely to be a major source of the heritable phenotypic variation on which selection acts.
Modeling protein evolution
Authors: Pollock David D. , Goldstein Richard A. 
Published: April 2005

Abstract
Modeling protein evolution has been frustratingly simplistic in the past, but new methodologies and approaches have been rapidly changing this situation. Increased computational power, improved phylogeny‐based maximum likelihood and Bayesian approaches, larger data sets, and better protein structure prediction methods are jointly improving the outlook and allowing researchers to improve the biological realism of protein models. They are also allowing more detailed analysis of differences in processes among sequence positions over space and time, of selection and adaptation, coevolution, and functional divergence, and of ancestral changes in function. The future is expected to bring improved integration of models of protein evolution with protein structure prediction, with the potential to dramatically improve the accuracy and power of both.
Studies of human genetic history using mt
DNA
variation
Authors: Torroni Antonio , Rengo Chiara 
Published: April 2005

Abstract
Current studies of human mitochondrial DNA have revealed that the dissection of its variation into smaller and younger subhaplogroups is an essential step in the identification of spatial frequency patterns, and that mass screening of a limited number of markers identified using complete mtDNA sequences is a very efficient strategy for inferring features of human genetic history.
Advances in cytogenetic diagnosis
Authors: Wolff Daynna J. 
Published: April 2005

AbstractClinical cytogenetic diagnosis became established in medical practice when the original genome screen, a karyotype, identified the numerical chromosome abnormalities associated with Down, Turner, and Klinefelter syndromes. Since then, technological advances have propelled the field from the basics of identifying duplications and deletions of large portions of chromosomes to delineating submicroscopic aberrations. Innovations involving fluorescence in situ hybridization (FISH), multicolor chromosome “painting” and comparative genomic hybridization (CGH) have linked the study of chromosomes and molecular sequence data, allowing for a detailed understanding of cytogenetic abnormalities and the associated phenotypes.
The clinical and economic implications of pharmacogenomics
Authors: Veenstra David L. 
Published: April 2005

AbstractThe rapid advance of the Human Genome Project and the development of new genetic analysis technologies promise to bring a new era of genomics to medicine. Among the applications of genetics to medicine, pharmacogenomics will likely be one of the first tangible benefits from the Human Genome Project. It has been suggested that the use of pharmacogenomics will be widespread and lead to lower health care costs, but there has been little outcomes research on pharmacogenomics.The objective of this article is to present a cost‐effectiveness framework for evaluating the incremental clinical and economic benefits of pharmacogenomic‐based therapies, apply this framework to noted pharmacogenomic examples, and evaluate the potential impact of pharmacogenomics on research and development in the pharmaceutical industry and the delivery of health care.The use of pharmacogenomics to individualize drug therapy will offer clinical and economic benefits. However, these benefits must be weighed against the additional cost of genotyping all patients in order to adjust the therapy in a few. Our analysis suggests that pharmacogenomics will likely be cost‐effective only for certain combinations of disease, drug, gene, and test characteristics, and that the cost‐effectiveness of pharmacogenomic‐based therapies needs to be evaluated on a case‐by‐case basis. Cost‐effectiveness analysis can help scientists, clinicians, and decision makers invest in technologies and develop drug utilization guidelines that will benefit patients in an economically viable fashion.
Molecular dysmorphology
Authors: Biesecker Leslie G. 
Published: April 2005

AbstractClinical dysmorphology includes the diagnosis and management of patients with multiple malformation syndromes. When this clinical practice is merged with the research disciplines of genomics and developmental biology, it is called molecular dysmorphology. The goals of this scientific discipline are the delineation of the molecular basis of normal and abnormal development and the improvement of the care of patients affected by these disorders through increased knowledge. The development of the field is reviewed and examples are presented to demonstrate the power and excitement of this discipline.
Changing paradigms of genetic counseling
Authors: Schneider Katherine A. , Venne Vickie 
Published: April 2005

Abstract
Genetic counseling, as a formal medical specialty, has been around since the 1970s. This article provides an overview of current genetic counseling providers and services while weaving in an historical perspective to illustrate how much the profession has evolved since then. We describe the current qualifications and work settings of genetic counseling providers and detail the components of genetic counseling sessions; collecting family history information, assessing risk, arranging genetic testing, and providing counseling. Lastly, we describe some family dilemmas and ethical issues that are unique or more intense in genetics and ponder the possible impact of increased genetic testing opportunities on future medical practices.
Genetic testing and genotype–phenotype correlations
Authors: De Baere Elfride , Messiaen Ludwine 
Published: April 2005

Abstract
In the postgenome era, the study of genotype–phenotype correlations has come to the front. Insight into genotype–phenotype correlations would move clinical genetics toward predictive medicine. However, it has become clear that the correlation between genotype and phenotype is often incomplete. The frequent lack of correlations supports the notion that a mutant gene product is part of a complex system in which tissue‐specific alternative splicing, intragenic SNPs, epigenetic changes, protein–gene and protein–protein interactions, modifying genes, and environmental factors play a role. The insight that “simple” Mendelian traits are in fact complex traits has consequences for families and their physicians, and is a challenge for the scientific community. Hence, there is a strong clinical and scientific motivation to identify factors playing a role in genotype–phenotype correlations. Examples of diseases and disease genes where genotype–phenotype correlations have been observed to some extent are described below.
Uses of databases
Authors: Pagon Roberta A. 
Published: April 2005

Abstract
Databases are used by clinicians practicing genetic medicine and clinical genetics to determine the molecular basis of inherited disorders, establish diagnoses, identify sources and uses of molecular genetic testing, assess and manage inherited cancer risk, provide consumer‐health‐oriented information to patients, and identify clinical genetic services for geographically dispersed family members. Those databases that are freely available on the Internet are discussed. They include OMIM, GeneTests, PDQ Cancer Genetics, The Genetics and Rare Conditions Site, Family Village, Genetic Home Reference, and the Genetic Alliance.
Eukaryotic genomics
Authors: Adams Mark D. 
Published: April 2005

Abstract
The human genome is perhaps the most famous to be sequenced, but genomes from a diverse array of other eukaryotes are now being compiled. In a few years, genome sequences will be available from all widely studied model organisms and many relatives to facilitate comparative and functional studies. This chapter introduces the strategies that have been used to sequence eukaryotic genomes and some of the issues that affect the choice of strategy.
Genome sequencing of microbial species
Authors: Ravel Jacques , Fraser Claire M. 
Published: April 2005

Abstract

Since the publication of the first complete genome sequence in 1995, of a free‐living organism, the bacterium

Haemophilus influenzae

, more than 220 microbial genomes have been completed and at least another 650 are in progress. Whole‐genome shotgun sequencing remains the industry standard and combined with the current state of sequencing technologies, it is expected that the rate at which genomic data is generated is only going to increase. The major challenge is to decipher this wealth of information and link genes to function. In this chapter, the impact of genome sequencing technologies in the field of microbiology is being explored.