bluuebunny/crossref_metadata_2025 huggingface dataset:
Diagnosis of adenocarcinoma in prostate needle biopsy tissue
Authors: Humphrey P A
Published: January 2007

Prostate cancer is a major public health problem throughout the developed world. For patients with clinically localised prostate cancer, the diagnosis is typically established by histopathological examination of prostate needle biopsy samples. Major and minor criteria are used to establish the diagnosis, based on the microscopic appearance of slides stained using haematoxylin and eosin. Major criteria include an infiltrative glandular growth pattern, an absence of basal cells and nuclear atypia in the form of nucleomegaly and nucleolomegaly. In difficult cases, basal cell absence may be confirmed by immunohistochemical stains for high-molecular-weight cytokeratins (marked with antibody 34βE12) or p63, which are basal cell markers. Minor criteria include intraluminal wispy blue mucin, pink amorphous secretions, mitotic figures, intraluminal crystalloids, adjacent high-grade prostatic intraepithelial neoplasia, amphophilic cytoplasm and nuclear hyperchromasia. Another useful diagnostic marker detectable by immunohistochemistry is α-methylacyl coenzyme A racemase (AMACR), an enzyme selectively expressed in neoplastic glandular epithelium. Cocktails of antibodies directed against basal cell markers and AMACR are particularly useful in evaluating small foci of atypical glands, and in substantiating a diagnosis of a minimal adenocarcinoma. Reporting of adenocarcinoma in needle biopsy specimens should always include the Gleason grade and measures of tumour extent in the needle core tissue. Measures of tumour extent are (1) number of cores positive for cancer in the number of cores examined, (2) percentage of needle core tissue affected by carcinoma and (3) linear millimetres of carcinoma present.
Aberrant gene methylation implicated in the progression of monoclonal gammopathy of undetermined significance to multiple myeloma
Authors: Chim Chor-Sang , Liang Raymond , Leung Man-Hin , Kwong Yok-Lam
Published: January 2007

Malignant transformation is a multistep process that may involve dysregulation of oncogenes and tumour suppressor genes, and monoclonal gammopathy of undetermined significance (MGUS) is believed to be a precursor of multiple myeloma. To investigate whether aberrant promoter methylation might be involved in the evolution of MGUS to multiple myeloma, we examined thep16,protein tyrosine phosphatase, non-receptor type 6(SHP1),death-associated protein(DAP)kinase,E-cadherinandoestrogen receptorgenes, most being tumour suppressor genes, by methylation-specific polymerase chain reaction. In 32 cases of multiple myeloma and 19 cases of MGUS, significantly more frequent methylation ofp16(p = 0.001),SHP1(p⩽0.001) andE-cadherin(p⩽0.001) genes was found in multiple myeloma than in MGUS. Methylation ofDAP kinaseandoestrogen receptorgenes was comparable in multiple myeloma and MGUS. In conclusion, methylation ofp16,SHP1andE-cadheringenes might be involved in the progression of MGUS to multiple myeloma.
Dietary protein for athletes: from requirements to metabolic advantage
Authors: Phillips Stuart M.
Published: January 2007

The Dietary Reference Intakes (DRI) specify that the requirement for dietary protein for all individuals aged 19 y and older is 0.8 g protein·kg–1·d–1. This Recommended Dietary Allowance (RDA) is cited as adequate for all persons. This amount of protein would be considered by many athletes as the amount to be consumed in a single meal, particularly for strength-training athletes. There does exist, however, published data to suggest that individuals habitually performing resistance and (or) endurance exercise require more protein than their sedentary counterparts. The RDA values for protein are clearly set at “…the level of protein judged to be adequate... to meet the known nutrient needs for practically all healthy people…”. The RDA covers protein losses with margins for inter-individual variability and protein quality; the notion of consumption of excess protein above these levels to cover increased needs owing to physical activity is not, however, given any credence. Notwithstanding, diet programs (i.e., energy restriction) espousing the virtue of high protein enjoy continued popularity. A number of well-controlled studies are now published in which “higher” protein diets have been shown to be effective in promoting weight reduction, particularly fat loss. The term “higher” refers to a diet that has people consuming more than the general populations’ average intake of ~15% of energy from protein, e.g., as much as 30%–35%, which is within an Acceptable Macronutrient Distribution Range (AMDR) as laid out in the DRIs. Of relevance to athletes and those in clinical practice is the fact that higher protein diets have quite consistently been shown to result in greater weight loss, greater fat loss, and preservation of lean mass as compared with “lower” protein diets. A framework for understanding dietary protein intake within the context of weight loss and athletic performance is laid out.
Mitochondrial oxidative function and type 2 diabetes
Authors: Rabøl Rasmus , Boushel Robert , Dela Flemming
Published: January 2007

The cause of insulin resistance and type 2 diabetes is unknown. The major part of insulin-mediated glucose disposal takes place in the skeletal muscle, and increased amounts of intramyocellular lipid has been associated with insulin resistance and linked to decreased activity of mitochondrial oxidative phosphorylation. This review will cover the present knowledge and literature on the topics of the activity of oxidative enzymes and the electron transport chain (ETC) in skeletal muscle of patients with type 2 diabetes. Different methods of studying mitochondrial function are described, including biochemical measurements of oxidative enzyme and electron transport activity, isolation of mitochondria for measurements of respiration, and ATP production and indirect measurements of ATP production using nuclear magnetic resonance (NMR) - spectroscopy. Biochemical markers of mitochondrial content are also discussed. Several studies show reduced activity of oxidative enzymes in skeletal muscle of type 2 diabetics. The reductions are independent of muscle fiber type, and are accompanied by visual evidence of damaged mitochondria. In most studies, the reduced oxidative enzyme activity is explained by decreases in mitochondrial content; thus, evidence of a functional impairment in mitochondria in type 2 diabetes is not convincing. These impairments in oxidative function and mitochondrial morphology could reflect the sedentary lifestyle of the diabetic subjects, and the influence of physical activity on oxidative activity and mitochondrial function is discussed. The studies on insulin-resistant offspring of type 2 diabetic parents have provided important insights in the earliest metabolic defects in type 2 diabetes. These defects include reductions in basal ATP production and an attenuated response to insulin stimulation. The decreased basal ATP production does not affect overall lipid or glucose oxidation, and no studies linking changes in oxidative activity and insulin sensitivity in type 2 diabetes have been published. It is concluded that evidence of a functional impairment in mitochondria in type 2 diabetes is not convincing, and that intervention studies describing the correlation between changes in insulin resistance and mitochondrial function in type 2 diabetes are lacking. Specific effects of regular physical training and muscular work on mitochondrial function and plasticity in type 2 diabetes remain an important area of research.
Stratégie optimale d’amaigrissement dans les sports à catégories de poids
Authors: Paillard Thierry
Published: January 2007

Weight-class sports incite the sportsmen to loose weight to change class and increase their chance of success in competition. Although these sports are very demanding on the physiological level (high intensity), most of the competitors undertake caloric restrictions that are likely to induce physiological disorders detrimental to their health and sport performances. Two strategies allow to loose bodyweight. The first is maintained over a very short time (less than 1 week), the second is maintained over a longer period (several weeks). Managing weight reduction, food intake, and physical activities over several weeks is a particularly efficient way to conserve the sportsman’s performance abilities. On the other hand, the transgression of certain principles in only one of these fields is enough to deteriorate the sportsman's capacities of performance and (or) his health, whatever the duration of the period of the loss of weight. During food restriction, the carbohydrate and protein rations must be increased to prevent the unavoidable involutions of body composition and performance. In spite of food restriction, the training intensity must be high, and only the training volume must decrease to remain competitive.
Physicochemical analysis of acid–base responses to prolonged moderate exercise in late gestation
Authors: Charlesworth Sarah A. , Wolfe Larry A. , Davies Gregory A.L.
Published: January 2007

Stewart’s physicochemical approach was employed to investigate the safety of an average recreational and occupational activity (prolonged moderate exercise) on maternal acid–base homeostasis. The responses of 10 healthy, physically active pregnant women (PG, gestational age 34–38 weeks) were compared with those of 10 non-pregnant female controls (CG). Subjects cycled for 40 min at 85% of their measured ventilatory threshold (VT). During the transition from rest to exercise, hydrogen ion concentration ([H+]) increased significantly and bicarbonate concentration ([HCO3–]) decreased significantly in both groups. Total weak acid ([Atot]) increased significantly with exercise in both groups, whereas the strong ion difference ([SID]) and CO2 tension (PaCO2) did not change significantly with exercise. Values for [H+], [HCO3–], PaCO2, [Atot] and [SID] were significantly lower in the PG vs. CG under all experimental conditions. Acid–base responses to prolonged moderate exercise are quantitatively similar in the pregnant vs. non-pregnant state. However, pregnant women maintain a lower plasma [H+] (approximately 3 neq/L (1 neq/L = 1 nmol/L)) throughout rest, exercise, and recovery, as a result of lower values for PaCO2 and [Atot], which is partly offset by a lower [SID]. The results indicate that prolonged moderate exercise appears to be well tolerated by healthy recreationally and occupationally active pregnant women.
Cigarette smoke-induced proinflammatory alterations in the endothelial phenotype: role of NAD(P)H oxidase activation
Authors: Orosz Zsuzsanna , Csiszar Anna , Labinskyy Nazar , Smith Kira , Kaminski Pawel M. , Ferdinandy Peter , Wolin Michael S. , Rivera Aracelie , Ungvari Zoltan
Published: January 2007

Although the cardiovascular morbidity and mortality induced by cigarette smoking exceed those attributable to lung cancer, the molecular basis of smoking-induced vascular injury remains unclear. To test the link between cigarette smoke, oxidative stress, and vascular inflammation, rats were exposed to the smoke of five cigarettes per day (for 1 wk). Also, isolated arteries were exposed to cigarette smoke extract (CSE; 0 to 40 μg/ml, for 6 h) in organoid culture. We found that smoking impaired acetylcholine-induced relaxations of carotid arteries, which could be improved by the NAD(P)H oxidase inhibitor apocynin. Lucigenin chemiluminescence measurements showed that both smoking and in vitro CSE exposure significantly increased vascular O2•− production. Dihydroethidine staining showed that increased O2•− generation was present both in endothelial and smooth muscle cells. CSE also increased vascular H2O2 production (dichlorofluorescein fluorescence). Vascular mRNA expression of the proinflammatory cytokines IL-1β, IL-6, and TNF-α and that of inducible nitric oxide synthase was significantly increased by both smoking and CSE exposure, which could be prevented by inhibition of NAD(P)H oxidase (diphenyleneiodonium and apocynin) or scavenging of H2O2. In cultured endothelial cells, CSE elicited NF-κB activation and increased monocyte adhesiveness, which were prevented by apocynin and catalase. Thus we propose that water-soluble components of cigarette smoke (which are likely to be present in the bloodstream in vivo in smokers) activate the vascular NAD(P)H oxidase. NAD(P)H oxidase-derived H2O2 activates NF-κB, leading to proinflammatory alterations in vascular phenotype, which likely promotes development of atherosclerosis, especially if other risk factors are also present.
Mitochondrial c-Jun NH2-Terminal Kinase Prevents the Accumulation of Reactive Oxygen Species and Reduces Necrotic Damage in Neural Tumor Cells that Lack Trophic Support
Authors: López-Sánchez Noelia , Rodríguez José-Rodrigo , Frade José María
Published: January 2007

In response to different stress signals, the c-Jun NH2-terminal kinase (JNK) can trigger cell death. However, JNK also facilitates the survival and cell cycle progression of tumor cells by mechanisms that are poorly defined. Here, we show that schwannoma RN22 cells can survive and proliferate under serum-free conditions although serum withdrawal rapidly induces mitochondrial fission and swelling. Although the morphologic changes observed in the mitochondria did not trigger cytochrome c release, they were accompanied by an increase in the mitochondrial membrane potential (ΔΨM) and of immunoreactivity for active JNK in these organelles. Pharmacologic inhibition of JNK provoked a further increase of the ΔΨM, an increase in reactive oxygen species (ROS) production, and a sustained decrease in cell viability due to necrosis. This increase in necrosis was prevented by the presence of ROS scavengers. Immunoreactivity for active JNK was also observed in the mitochondria of neuroblastoma 1E-115 and neuroblastoma 2a neuroblastoma cell lines on serum withdrawal, whereas active JNK was barely detected in serum-deprived fibroblasts. Accordingly, the reduction in neural tumor cell viability induced by JNK inhibition was largely attenuated in serum-deprived fibroblasts. These data indicate that local activation of JNK in the mitochondria can protect against necrotic cell death associated with ROS production, facilitating the growth of neural tumor cells subjected to serum deprivation. (Mol Cancer Res 2007;5(1):47–60)
Gene Transfer of Neuronal Nitric Oxide Synthase into Intracardiac Ganglia Reverses Vagal Impairment in Hypertensive Rats
Authors: Heaton Daniel A. , Li Dan , Almond Susanna C. , Dawson Tom A. , Wang Lijun , Channon Keith M. , Paterson David J.
Published: January 2007

Hypertension is associated with reduced cardiac vagal activity and decreased atrial guanylate cyclase and cGMP levels. Neuronal production of NO facilitates cardiac parasympathetic transmission, although oxidative stress caused by hypertension may disrupt this pathway. We tested the hypothesis that peripheral vagal responsiveness is attenuated in the spontaneously hypertensive rat (SHR) because of impaired NO-cGMP signaling and that gene transfer of neuronal NO synthase (nNOS) into cholinergic intracardiac ganglia can restore neural function. Cardiac vagal heart rate responses in the isolated SHR atrial/right vagus preparation were significantly attenuated compared with age-matched normotensive Wistar–Kyoto rats. [
3
H] acetylcholine release was also significantly lower in the SHR. The NO donor, sodium nitroprusside, augmented vagal responses to nerve stimulation and [
3
H] acetylcholine release in the Wistar–Kyoto rat, whereas the soluble guanylate cyclase inhibitor 1H-(1,2,4)oxadiazolo(4,3-a)quinoxaline-1-one attenuated [
3
H] acetylcholine release in Wistar–Kyoto atria. No effects of sodium nitroprusside or 1H-(1,2,4)oxadiazolo(4,3-a)quinoxaline-1-one were seen in the SHR during nerve stimulation. In contrast, SHR atria were hyperresponsive to carbachol-induced bradycardia, with elevated production of atrial cGMP. After gene transfer of adenoviral nNOS into the right atrium, vagal responsiveness in vivo was significantly increased in the SHR compared with transfection with adenoviral enhanced green fluorescent protein. Atrial nNOS activity was increased after gene transfer of adenoviral nNOS, as was expression of α
1
-soluble guanylate cyclase in both groups compared with adenoviral enhanced green fluorescent protein. In conclusion, a significant component of cardiac vagal dysfunction in hypertension is attributed to an impairment of the postganglionic presynaptic NO-cGMP pathway and that overexpression of nNOS can reverse this neural phenotype.
Excessive Sympathetic Activation in Heart Failure With Obesity and Metabolic Syndrome
Authors: Grassi Guido , Seravalle Gino , Quarti-Trevano Fosca , Scopelliti Francesco , Dell’Oro Raffaella , Bolla Gianbattista , Mancia Giuseppe
Published: January 2007

Congestive heart failure is characterized by sympathetic activation, which has also been described in the metabolic syndrome. No information exists, however, as to whether the sympathostimulating effects of these 2 conditions summate when heart failure is complicated by the metabolic syndrome, leading to an exceedingly high adrenergic drive. This is clinically relevant, because in heart failure sympathetic activation is closely related to mortality. We studied 48 control subjects (age: 58.4±1.6 years, mean±SEM) and 89 age-matched heart failure patients (New York Heart Association class II), of whom 47 were without and 42 were with metabolic syndrome. Measurements included blood pressure (Finapres), heart rate (ECG), and sympathetic nerve traffic (microneurography) at rest and during baroreceptor manipulation. Waist circumference, blood pressure, and metabolic variables were greater in heart failure with metabolic syndrome than in heart failure without metabolic syndrome and in control subjects. Left ventricular ejection fraction and end-diastolic diameter were similarly altered in the 2 heart failure groups. Compared with control subjects, sympathetic nerve activity was greater in heart failure patients without metabolic syndrome (64.7±3.2 versus 45.8±2.9 bursts/100 heartbeats;
P
<0.01), a further pronounced increase being detected in those with metabolic syndrome (80.9±3.2 bursts/100 heartbeats;
P
<0.01). In the multivariate analysis, waist circumference and body mass index were the variables most closely related to sympathetic activation. Compared with control subjects, baroreflex responses were significantly attenuated in the 2 heart failure groups, the impairment being more marked in the group with than without metabolic syndrome. Thus, obesity and metabolic syndrome potentiate the sympathetic activation characterizing heart failure. This potentiation is likely to mainly depend on metabolic and baroreflex mechanisms.
Agonistic Angiotensin II Type 1 Receptor Autoantibodies in Postpartum Women With a History of Preeclampsia
Authors: Hubel Carl A. , Wallukat Gerd , Wolf Myles , Herse Florian , Rajakumar Augustine , Roberts James M. , Markovic Nina , Thadhani Ravi , Luft Friedrich C. , Dechend Ralf
Published: January 2007

Activating angiotensin II type 1 autoantibodies (AT1-AAs) develop in women with preeclampsia and may contribute to the disorder. Insulin resistance and serum concentrations of the antiangiogenic soluble fms-like tyrosine kinase 1 (sFlt-1) are also increased in women with preeclampsia compared with normal pregnancy. sFlt-1 and insulin resistance decrease substantially after delivery; however, significant group differences persist postpartum. Women who have had preeclampsia are at increased cardiovascular risk later in life. We measured AT1-AAs in groups of women with previous preeclampsia (n=29) and previous normal pregnancies (n=35) 18±9 months after the first completed pregnancy. These women had had sFlt-1, insulin resistance homeostasis model assessment score, and related cardiovascular risk factors measured. Activating antibodies were detected by the chronotropic response of cultured neonatal rat cardiomyocytes coupled with receptor-specific antagonists (losartan and prazosin). AT1-AAs were detected in 17.2% of women with previous preeclampsia versus 2.9% of women with previous uncomplicated pregnancies (
P
<0.05). In contrast, there was no difference in the prevalence of autoantibodies against the α1-adrenoceptor (10% of previous preeclamptic versus 14% of previous normal pregnant). Women with activating autoantibodies had significantly increased sFlt-1, reduced free vascular endothelial growth factor, and higher insulin resistance homeostasis model assessment values compared with autoantibody-negative women. These data suggest that, as with sFlt-1 and insulin resistance, the AT1-AA does not regress completely after delivery and, secondarily, that correlations exist among these variables. The impact of AT1-AA after preeclampsia, especially in the context of cardiovascular risk, remains to be determined.
Congenital Heart Disease in the General Population
Authors: Marelli Ariane J. , Mackie Andrew S. , Ionescu-Ittu Raluca , Rahme Elham , Pilote Louise
Published: January 2007

Background—

Empirical data on the changing epidemiology of congenital heart disease (CHD) are scant. We determined the prevalence, age distribution, and proportion of adults and children with severe and other forms of CHD in the general population from 1985 to 2000.

Methods and Results—

Where healthcare access is universal, we used administrative databases that systematically recorded all diagnoses and claims. Diagnostic codes conformed to the
International Classification of Disease
, ninth revision. Severe CHD was defined as tetralogy of Fallot, truncus arteriosus, transposition complexes, endocardial cushion defects, and univentricular heart. Prevalence of severe and other CHD lesions was determined in l985, 1990, 1995, and 2000 using population numbers in Quebec. Children were subjects <18 years of age. The prevalence was 4.09 per 1000 adults in the year 2000 for all CHD and 0.38 per 1000 (9%) for those with severe lesions. Female subjects accounted for 57% of the adult CHD population. The median age of all patients with severe CHD was 11 years (interquartile range, 4 to 22 years) in 1985 and 17 years (interquartile range, 10 to 28 years) in 2000 (
P
<0.0001). The prevalence of severe CHD increased from 1985 to 2000, but the increase in adults was significantly higher than that observed in children. In the year 2000, 49% of those alive with severe CHD were adults.

Conclusions—

The prevalence in adults and median age of patients with severe CHD increased in the general population from 1985 to 2000. In 2000, there were nearly equal numbers of adults and children with severe CHD.
The Search for Reconciliation in E. L. Doctorow's City of God
Authors: Wilde Lawrence
Published: January 2007

E. L. Doctorow's novel City of God is constructed around a crisis of faith experienced by an Episcopalian minister who eventually converts to Judaism. Within and around this personal story unfolds a fascinating array of moral and spiritual dilemmas which raise provocative questions about the role of religion in modern society and its relationship to secular ethical thought. It is argued here that the novel can be understood as an appeal for reconciliation in a number of different but related ways. The 'religious' characters strive to preserve the relevance of religion by emphasizing the pre-eminence of ethical commitments to love and justice and to the open interpretation of scriptural messages rather than to rigorous adherence to doctrine. The novel tests the possibilities of reconciliation to the limit by revisiting the Holocaust and touching on other horrors, but implicitly it conveys a faith in the oneness of humanity which may yet prevail through a renewal of ethical dialog.
Provisional Measures and Provisional Arrangements in Maritime Boundary Disputes
Authors: Klein Natalie
Published: January 2007

This article examines the interaction under LOSC of the powers of international courts and tribunals to order binding provisional measures and the obligation of states to make every effort to enter into provisional arrangements pending the delimitation of a maritime boundary. The importance of provisional measures or arrangements in delimiting maritime boundaries, previous state and judicial practice related to provisional arrangements and measures, and the relevant substantive and procedural rules under LOSC are all explored as a means of explaining how courts and tribunals should exercise their powers of ordering provisional measures when provisional arrangements are required. It is argued here that an international court or tribunal should exercise caution in order to ensure that the procedural mechanism complements, rather than conflicts with, the substantive obligation. To this end, provisional measures entailing recommendations, duties of cooperation and obligations of non-aggravation are to be preferred.
Dispute Settlement under the UN Convention on the Law of the Sea: Survey for 2005
Authors: Churchill Robin
Published: January 2007

This is the second of a projected series of annual surveys reviewing dispute settlement under the UN Convention on the Law of the Sea (LOSC), which replaces the previous Annual. The main developments during 2005 were the settlement of the Land Reclamation case and the election of seven members of the International Tribunal for the Law of the Sea. No new cases were brought during the year.
Spring Thaw and Its Effect on Terrestrial Vegetation Productivity in the Western Arctic Observed from Satellite Microwave and Optical Remote Sensing
Authors: Kimball J. S. , McDonald K. C. , Zhao M.
Published: January 2007

Global satellite remote sensing records show evidence of recent vegetation greening and an advancing growing season at high latitudes. Satellite remote sensing–derived measures of photosynthetic leaf area index (LAI) and vegetation gross and net primary productivity (GPP and NPP) from the NOAA Advanced Very High Resolution Radiometer (AVHRR) Pathfinder record are utilized to assess annual variability in vegetation productivity for Alaska and northwest Canada in association with the Western Arctic Linkage Experiment (WALE). These results are compared with satellite microwave remote sensing measurements of springtime thaw from the Special Sensor Microwave Imager (SSM/I). The SSM/I-derived timing of the primary springtime thaw event was well correlated with annual anomalies in maximum LAI in spring and summer (P ≤ 0.009; n = 13), and GPP and NPP (P ≤ 0.0002) for the region. Mean annual variability in springtime thaw was on the order of ±7 days, with corresponding impacts to annual productivity of approximately 1% day−1. Years with relatively early seasonal thawing showed generally greater LAI and annual productivity, while years with delayed seasonal thawing showed corresponding reductions in canopy cover and productivity. The apparent sensitivity of LAI and vegetation productivity to springtime thaw indicates that a recent advance in the seasonal thaw cycle and associated lengthening of the potential period of photosynthesis in spring is sufficient to account for the sign and magnitude of an estimated positive vegetation productivity trend for the western Arctic from 1982 to 2000.
Uncertainty in Temperature and Precipitation Datasets over Terrestrial Regions of the Western Arctic
Authors: Drobot Sheldon , Maslanik James , Herzfeld Ute Christina , Fowler Charles , Wu Wanli
Published: January 2007

A better understanding of the interannual variability in temperature and precipitation datasets used as forcing fields for hydrologic models will lead to a more complete description of hydrologic model uncertainty, in turn helping scientists study the larger goal of how the Arctic terrestrial system is responding to global change. Accordingly, this paper investigates temporal and spatial variability in monthly mean (1992–2000) temperature and precipitation datasets over the Western Arctic Linkage Experiment (WALE) study region. The six temperature datasets include 1) the fifth-generation Pennsylvania State University–National Center for Atmospheric Research Mesoscale Model (MM5); 2) the 40-yr European Centre for Medium-Range Weather Forecasts (ECMWF) Re-Analysis (ERA-40); 3) the Advanced Polar Pathfinder all-sky temperatures (APP); 4) National Centers for Environmental Prediction– National Center for Atmospheric Research (NCEP–NCAR) reanalyses (NCEP1); 5) the Climatic Research Unit/University of East Anglia CRUTEM2v (CRU); and 6) the Matsuura and Wilmott 0.5° × 0.5° Global Surface Air Temperature and Precipitation (MW). Comparisons of monthly precipitation are examined for MM5, ERA-40, NCEP1, CRU, and MW. Results of the temporal analyses indicate significant differences between at least two datasets (for either temperature or precipitation) in almost every month. The largest number of significant differences for temperature occurs in October, when there are five separate groupings; for precipitation, there are four significantly different groupings from March through June, and again in December. Spatial analyses of June temperatures indicate that the greatest dissimilarity is concentrated in the central portion of the study region, with the NCEP1 and APP datasets showing the greatest differences. In comparison, the spatial analysis of June precipitation datasets suggests that the largest dissimilarity is concentrated in the eastern portion of the study region. These results indicate that the choice of forcing datasets likely will have a significant effect on the output from hydrologic models, and several different datasets should be used for a robust hydrologic assessment.
Functional status measured by walking impairment questionnaire and cardiovascular risk prediction in peripheral arterial disease: results of the Peripheral Arteriopathy and Cardiovascular Events (PACE) study
Authors: Schiano Vittorio , Brevetti Gregorio , Sirico Giusy , Silvestro Antonio , Giugliano Giuseppe , Chiariello Massimo
Published: January 2007

The prognostic impact of the functional status of patients with intermittent claudication is still obscure. From the lists of seven general practitioners, we identified all subjects aged 40-80 years (n = 4352). Of those reporting leg symptoms while walking on the Rose questionnaire (n = 760), 60 had a qualifying diagnosis of peripheral arterial disease (PAD). All of them received the Walking Impairment Questionnaire (WIQ). For each patient affected by PAD, three sex- and age-matched controls were selected randomly. After a 24-month follow-up, survival curves showed that PAD patients with WIQ scores > median had a higher cardiovascular risk than controls, and patients with WIQ scores < median had an even poorer prognosis (p < 0.001 for all WIQ domains). In PAD, after adjustment for age, sex, ankle-brachial index and comorbidity, two WIQ domains (ie walking speed and stairclimbing) were associated with cardiovascular events. The cardiovascular risk of claudicants who had a score > median for at least three WIQ domains was intermediate versus the risk of controls and PAD patients with a WIQ score < median, also when adjusted for the covariates indicated above (RR = 3.26, p = 0.019). In intermittent claudication, a worse functional status entails a greater risk of ischemic events versus low functional impairment.
The Health-e-AME Faith-Based Physical Activity Initiative: Description and Baseline Findings
Authors: Wilcox Sara , Laken Marilyn , Anderson Thaje , Bopp Melissa , Bryant Deborah , Carter Rickey , Gethers Octavia , Jordan Jeannette , McClorin Lottie , O'Rourke Kathleen , Parrott Allen W. , Swinton Rosetta , Yancey Antronette
Published: January 2007

This article provides an overview of the development, implementation, and baseline findings from a statewide faith-based physical activity (PA) initiative. The 3-year program is training African Methodist Episcopal volunteers across South Carolina to implement programs to increase PA in their congregations. To date, 98 churches have been trained. Interviews done with a random sample (n = 39) indicated that 54% are implementing at least one PA program. The baseline telephone survey (N = 571) estimates that 27.8% of the population is regularly active, 54.9% underactive, and 17.3% sedentary. Baseline rates of regular PA were higher in those who were younger, healthier, and nonsmokers. Challenges to date have included obtaining rosters and implementing a large-scale program with limited resources. Interest in the program has been strong and supported by church leaders. Current efforts are on training additional churches and working with those already trained to support sustainability.
TAMGeS: a Three-Array Method for Genotyping of SNPs by a dual-colour approach
Authors: Cozza Arianna , Morandin Francesco , Galfrè Silvia Giulia , Mariotti Veronica , Marangoni Roberto , Pellegrini Silvia
Published: January 2007

Background

Many of the most effective high-throughput protocols for SNP genotyping employ microarrays. Genotypes are assessed by comparing the signal intensities that derive from the hybridization of different allele-specific probes labelled either by using four fluorescent dyes, one for each base, or by using only two dyes and investigating the polymorphic alleles two by two on separate arrays. The employment of only two dyes makes it possible to use a dual-laser scanner, which has the advantage of being present in every microarray laboratory. However, this protocol may present some drawbacks. To infer all the six possible genotypes it is necessary to compare signals from two arrays, but this comparison not always is successful. A number of systematic errors in the experimental protocol, in fact, may differently affect signal intensities on separate arrays. Here we present TAMGeS (Three-Array Method for Genotyping of SNPs), an exhaustive method for SNP genotyping through SBE (Single Base Extension) and dual-colour microarrays, which makes the comparison of signals on distinct arrays reliable by using a third array and a data handling method for signal normalization based on bilinear regression theory.

Results

We tested the effectiveness of the proposed method by evaluating the results obtained from the direct comparison of the two arrays or by applying TAMGeS, both on experimental and synthetic data. With synthetic data, TAMGeS reduced the frequency of errors by an order of magnitude, when the incidence of systematic errors was not negligible. With the experimental data, produced by genotyping 25 SNPs in 437 subjects, TAMGeS reduced the percentage of missing genotypes from 54% (Two-Array Method) to 14.5%. Allelic and genotypic call rates were 99.3% and 99.5%, respectively. The normalization procedure takes into account also systematic errors, which can be generated by a time-delayed assay, thus making the protocol more flexible.

Conclusion

TAMGeS represents an innovative method, which proved to be very effective in producing reliable SNP genotyping data by dual-colour microarrays. The requirement of a third array is well balanced by the strong enhancement in data quality and by the greater flexibility of the experimental protocol.
The effects of second-hand smoke on biological processes important in atherogenesis
Authors: Yuan Hongwei , Wong Lina S , Bhattacharya Monideepa , Ma Chongze , Zafarani Mohammed , Yao Min , Schneider Matthias , Pitas Robert E , Martins-Green Manuela
Published: January 2007

Background

Atherosclerosis is the leading cause of death in western societies and cigarette smoke is among the factors that strongly contribute to the development of this disease. The early events in atherogenesis are stimulated on the one hand by cytokines that chemoattract leukocytes and on the other hand by decrease in circulating molecules that protect endothelial cells (ECs) from injury. Here we focus our studies on the effects of "second-hand" smoke on atherogenesis.

Methods

To perform these studies, a smoking system that closely simulates exposure of humans to second-hand smoke was developed and a mouse model system transgenic for human apoB100 was used. These mice have moderate lipid levels that closely mimic human conditions that lead to atherosclerotic plaque formation.

Results

"Second-hand" cigarette smoke decreases plasma high density lipoprotein levels in the blood and also decreases the ratios between high density lipoprotein and low density lipoprotein, high density lipoprotein and triglyceride, and high density lipoprotein and total cholesterol. This change in lipid profiles causes not only more lipid accumulation in the aorta but also lipid deposition in many of the smaller vessels of the heart and in hepatocytes. In addition, mice exposed to smoke have increased levels of Monocyte Chemoattractant Protein–1 in circulation and in the heart/aorta tissue, have increased macrophages in the arterial walls, and have decreased levels of adiponectin, an EC-protective protein. Also, cytokine arrays revealed that mice exposed to smoke do not undergo the switch from the pro-inflammatory cytokine profile (that develops when the mice are initially exposed to second-hand smoke) to the adaptive response. Furthermore, triglyceride levels increase significantly in the liver of smoke-exposed mice.

Conclusion

Long-term exposure to "second-hand" smoke creates a state of permanent inflammation and an imbalance in the lipid profile that leads to lipid accumulation in the liver and in the blood vessels of the heart and aorta. The former potentially can lead to non-alcoholic fatty liver disease and the latter to heart attacks.
A generalized analysis of hydrophobic and loop clusters within globular protein sequences
Authors: Eudes Richard , Le Tuan Khanh , Delettré Jean , Mornon Jean-Paul , Callebaut Isabelle
Published: January 2007

Background

Hydrophobic Cluster Analysis (HCA) is an efficient way to compare highly divergent sequences through the implicit secondary structure information directly derived from hydrophobic clusters. However, its efficiency and application are currently limited by the need of user expertise. In order to help the analysis of HCA plots, we report here the structural preferences of hydrophobic cluster species, which are frequently encountered in globular domains of proteins. These species are characterized only by their hydrophobic/non-hydrophobic dichotomy. This analysis has been extended to loop-forming clusters, using an appropriate loop alphabet.

Results

The structural behavior of hydrophobic cluster species, which are typical of protein globular domains, was investigated within banks of experimental structures, considered at different levels of sequence redundancy. The 294 more frequent hydrophobic cluster species were analyzed with regard to their association with the different secondary structures (frequencies of association with secondary structures and secondary structure propensities). Hydrophobic cluster species are predominantly associated with regular secondary structures, and a large part (60 %) reveals preferences for α-helices or β-strands. Moreover, the analysis of the hydrophobic cluster amino acid composition generally allows for finer prediction of the regular secondary structure associated with the considered cluster within a cluster species. We also investigated the behavior of loop forming clusters, using a "PGDNS" alphabet. These loop clusters do not overlap with hydrophobic clusters and are highly associated with coils. Finally, the structural information contained in the hydrophobic structural words, as deduced from experimental structures, was compared to the PSI-PRED predictions, revealing that β-strands and especially α-helices are generally over-predicted within the limits of typical β and α hydrophobic clusters.

Conclusion

The dictionary of hydrophobic clusters described here can help the HCA user to interpret and compare the HCA plots of globular protein sequences, as well as provides an original fundamental insight into the structural bricks of protein folds. Moreover, the novel loop cluster analysis brings additional information for secondary structure prediction on the whole sequence through a generalized cluster analysis (GCA), and not only on regular secondary structures. Such information lays the foundations for developing a new and original tool for secondary structure prediction.
Crystal structure of an FIV/HIV chimeric protease complexed with the broad-based inhibitor, TL-3
Authors: Heaslet Holly , Lin Ying-Chuan , Tam Karen , Torbett Bruce E , Elder John H , Stout C David
Published: January 2007

We have obtained the 1.7 Å crystal structure of FIV protease (PR) in which 12 critical residues around the active site have been substituted with the structurally equivalent residues of HIV PR (12X FIV PR). The chimeric PR was crystallized in complex with the broad-based inhibitor TL-3, which inhibits wild type FIV and HIV PRs, as well as 12X FIV PR and several drug-resistant HIV mutants [1–4]. Biochemical analyses have demonstrated that TL-3 inhibits these PRs in the order HIV PR > 12X FIV PR > FIV PR, with Ki values of 1.5 nM, 10 nM, and 41 nM, respectively [2–4]. Comparison of the crystal structures of the TL-3 complexes of 12X FIV and wild-typeFIV PR revealed theformation of additinal van der Waals interactions between the enzyme inhibitor in the mutant PR. The 12X FIV PR retained the hydrogen bonding interactions between residues in the flap regions and active site involving the enzyme and the TL-3 inhibitor in comparison to both FIV PR and HIV PR. However, the flap regions of the 12X FIV PR more closely resemble those of HIV PR, having gained several stabilizing intra-flap interactions not present in wild type FIV PR. These findings offer a structural explanation for the observed inhibitor/substrate binding properties of the chimeric PR.
The cation-independent mannose 6-phosphate receptor is involved in lysosomal delivery of serglycin
Authors: Lemansky Peter , Fester Ines , Smolenova Eva , Uhländer Christoph , Hasilik Andrej
Published: January 2007

To clarify the sorting mechanism of the lysosomal/granular proteoglycan serglycin, we treated human promonocytic U937 cells with p-nitrophenyl-β-D-xyloside (PNP-xyl) and cycloheximide. In the absence of protein synthesis, the carbohydrate moiety of serglycin was synthesized as PNP-xyl-chondroitin sulfate (CS), and most of it was delivered to lysosomes and degraded. Further, an augmented lysosomal targeting of serglycin in the presence of tunicamycin suggested that a sorting/lectin receptor with multiple specificity was involved with an increased capacity for serglycin in the absence of N-glycosylation. Correspondingly, the cation-independent mannose 6-phosphate receptor (CI-MPR) and sortilin were observed to bind to immobilized CS. These receptors were eluted in the presence of 200–400 mM and 100–250 mM NaCl, respectively. After treating the cells with a cross-linking reagent, a portion of the sulfated proteoglycan was coimmunoprecipitated with the CI-MPR but not with sortilin. In the presence of phorbol ester, lysosomal targeting of serglycin and to a lesser extent, of cathepsin D was inhibited. We conclude that the CI-MPR participates in lysosomal and granular targeting of serglycin and basic proteins such as lysozyme associated with the proteoglycan in hematopoietic cells.
Lipoteichoic acid and muramyl dipeptide synergistically induce maturation of human dendritic cells and concurrent expression of proinflammatory cytokines
Authors: Kim Hye Jin , Yang Jae Seung , Woo Sang Su , Kim Sun Kyung , Yun Cheol-Heui , Kim Kack Kyun , Han Seung Hyun
Published: January 2007

Maturation is an important process by which dendritic cells (DC) develop the potent antigen-presentation capacity necessary for efficient activation of adaptive immunity. Here, we have investigated the ability of lipoteichoic acid (LTA) and muramyl dipeptide (MDP; the minimal structural unit of peptidoglycan with immunostimulating activity) to induce maturation of human immature DC (iDC), derived from peripheral blood CD14-positive cells, and the production of proinflammatory cytokines. Exposure of iDC to staphylococcal LTA (StLTA) at 1 or 10 μg/ml or MDP at 0.1 or 1 μg/ml alone had little effect on the expression of CD80 and CD83, with a minor increase in expression of CD86, all of which are indicative of cell surface markers for maturation. However, there was a synergistic expression of these molecules when iDC were stimulated with StLTA and MDP together. It is interesting that selective induction of MHC Class II expression was observed during the DC maturation, only when costimulated with LTA plus MDP, and Escherichia coli LPS induced dramatic expression of MHC Classes I and II. Endocytosis assay using Dextran-FITC showed that costimulation with StLTA and MDP attenuated the endocytic capacity of the DC, which is a typical phenomenon of DC maturation. Concomitantly, increased expression of DEC-205, but decreased expression of CD206, was observed under the same costimulating condition. Furthermore, ELISA showed that secretions of TNF-α and IL-12 p40, but not IL-10, were induced in iDC by the costimulation. These results suggest that StLTA and MDP synergistically induce maturation and activation of human DC.
High-resolution wave-equation amplitude-variation-with-ray-parameter (AVP) imaging with sparseness constraints
Authors: Wang Juefu , Sacchi Mauricio D.
Published: January 2007

We propose a new scheme for high-resolution amplitude-variation-with-ray-parameter (AVP) imaging that uses nonquadratic regularization. We pose migration as an inverse problem and propose a cost function that uses a priori information about common-image gathers (CIGs). In particular, we introduce two regularization constraints: smoothness along the offset-ray-parameter axis and sparseness in depth. The two-step regularization yields high-resolution CIGs with robust estimates of AVP. We use an iterative reweighted least-squares conjugate gradient algorithm to minimize the cost function of the problem. We test the algorithm with synthetic data (a wedge model and the Marmousi data set) and a real data set (Erskine area, Alberta). Tests show our method helps to enhance the vertical resolution of CIGs and improves amplitude accuracy along the ray-parameter direction.
AVO as a fluid indicator: A physical modeling study
Authors: Wandler Aaron , Evans Brian , Link Curtis
Published: January 2007

Information on time-lapse changes in seismic amplitude variation with offset (AVO) from a reservoir can be used to optimize production. We designed a scaled physical model experiment to study the AVO response of mixtures of brine, oil, and carbon dioxide at pressures of 0, 1.03, and [Formula: see text]. The small changes in density and velocity for each fluid because of increasing pressure were not detectable and were assumed to lie within the error of the experiment. However, AVO analysis was able to detect changes in the elastic properties between fluids that contained oil and those that did not. When the AVO response was plotted in the AVO intercept-gradient domain, fluids containing oil were clearly separated from fluids not containing oil. This was observed in the AVO response from both the top and base of the fluids in the physical model. We then compared the measured AVO response with the theoretical AVO response given by the Zoeppritz equations. The measured and theoretical AVO intercept responses for the top fluid reflection agree well, although the AVO gradients disagree slightly. For the fluid base reflection, the measured and theoretical responses are in close agreement.