bluuebunny/crossref_metadata_2025 huggingface dataset:
Estimating Haplotype Relative Risks on Human Survival in Population-Based Association Studies
Authors: Tan Qihua , Christiansen Lene , Bathum Lise , Zhao Jing Hua , Yashin Anatoli I. , Vaupel James W. , Christensen Kaare , Kruse Torben A.
Published: April 2005

Association-based linkage disequilibrium (LD) mapping is an increasingly important tool for localizing genes that show potential influence on human aging and longevity. As haplotypes contain more LD information than single markers, a haplotype-based LD approach can have increased power in detecting associations as well as increased robustness in statistical testing. In this paper, we develop a new statistical model to estimate haplotype relative risks (HRRs) on human survival using unphased multilocus genotype data from unrelated individuals in cross-sectional studies. Based on the proportional hazard assumption, the model can estimate haplotype risk and frequency parameters, incorporate observed covariates, assess interactions between haplotypes and the covariates, and investigate the modes of gene function. By introducing population survival information available from population statistics, we are able to develop a procedure that carries out the parameter estimation using a nonparametric baseline hazard function and estimates sex-specific HRRs to infer gene-sex interaction. We also evaluate the haplotype effects on human survival while taking into account individual heterogeneity in the unobserved genetic and nongenetic factors or frailty by introducing the gamma-distributed frailty into the survival function. After model validation by computer simulation, we apply our method to an empirical data set to measure haplotype effects on human survival and to estimate haplotype frequencies at birth and over the observed ages. Results from both simulation and model application indicate that our survival analysis model is an efficient method for inferring haplotype effects on human survival in population-based association studies.
Metamorphoses of Power: From Coercion to Cooperation?
Authors: Nederveen Pieterse Jan
Published: April 2005

In probing metamorphoses of power and changing understandings of power, this treatment examines the question of whether there is a general trend from coercive towards cooperative and consensual forms of power over time. This reflection unpacks power in its various dimensions, considers the contributions of Gramsci and Foucault, and then examines the hypothesis of a growing trend towards cooperative forms of power in domestic politics and civil society, and in international politics.
An assessment of the reliability of growth rings counts for age determination in the Hermann's Tortoise Testudo hermanni
Authors: Bertolero Albert , Carretero Miguel , Llorente Gustavo
Published: April 2005

Growth ring counts on the shell have been widely used for age estimation in Chelonians. However, as stated by Wilson et al. (2003), most studies have applied this method without assessing its reliability by proving that 1 : 1 ratio between number of rings and real age exists. In the present study, the reliability of this method is analysed for a population of Hermann's Tortoise, Testudo hermanni introduced in the Ebro Delta (NE Spain). Age estimations were obtained from direct observations of tortoises in the field in 2000 (n = 82) together with those from photographs of the same and other individuals of the population taken between 1991 and 2001 (n= 356). A second photograph was taken at one or more years after the first one for 101 individuals. Results of Model II linear regression analysis indicated that the method was reliable only for tortoises between 0 and 7 years old, whereas tended to underestimate age for those between 8 and 11 years. Since, sexual maturity in this population is attained around 8 years (mean for both sexes), ring counts are only reliable for juveniles and subadults. Finally, it is noteworthy that the results coming for photographs were equivalent to those coming from direct observations in the field.
The specialized reproductive mode of the treefrog Aplastodiscus perviridis (Anura: Hylidae)
Authors: Faivovich Julian , Garcia Paulo , Haddad Célio
Published: April 2005

Males of the South American treefrog Aplastodiscus perviridis construct concealed subterranean nests. Using a complex courtship behavior that involves tactile stimuli and vocalizations, males guide the females to the subterranean nests where eggs are laid. Embryos and facultatively oophagous tadpoles (at least in stage 25) stay in subterranean nests until flooding transports them to ponds or streams. This is a rare reproductive mode previously known for few species in the Hyla albosignata and H. albofrenata complexes. Based on similarities of reproductive mode we suggest a monophyletic origin for Aplastodiscus and these complexes of Hyla.
Diet and habitat use of two sympatric species of Philodryas (Colubridae), in south Brazil
Authors: Marques Otávio , Hartmann Paulo
Published: April 2005

Feeding habits and habitat use of the colubrid snakes Philodryas olfersii and P. patagoniensis in southern Brazil are presented here. Philodryas olfersii and P. patagoniensis are sympatric in the study area and both dwell in open and forested areas. Specimens preserved in collections and observations of snakes in the field yielded the data. Both species are diet generalists, feeding on small vertebrates, mainly frogs. Philodryas patagoniensis has a broader diet, a less variable frequency of food items, and fed on heavier prey than P. olfersii. Seasonal variation in diet occurs in both species. The semiarboreal Philodryas olfersii is more slender and has a longer tail than the terrestrial P. patagoniensis, characters that may reflect differences in microhabitat use. There are a strong relationship between habitat use and frequency of a given food type. Differences in the use of food resources between P. olfersii and P. patagoniensis seem to reflect differences in foraging microhabitats used by each species.
Effect of TC–Trough Interaction on the Intensity Change of Two Typhoons
Authors: Yu Hui , Kwon H. Joe
Published: April 2005

Using large-scale analyses, the effect of tropical cyclone–trough interaction on tropical cyclone (TC) intensity change is readdressed by studying the evolution of upper-level eddy flux convergence (EFC) of angular momentum and vertical wind shear for two TCs in the western North Pacific [Typhoons Prapiroon (2000) and Olga (1999)]. Major findings include the following: 1) In spite of decreasing SST, the cyclonic inflow associated with a midlatitude trough should have played an important role in Prapiroon’s intensification to its maximum intensity and the maintenance after recurvature through an increase in EFC. The accompanied large vertical wind shear is concentrated in a shallow layer in the upper troposphere. 2) Although Olga also recurved downstream of a midlatitude trough, its development and maintenance were not strongly influenced by the trough. A TC could maintain itself in an environment with or without upper-level eddy momentum forcing. 3) Both TCs started to decay over cold SST in a large EFC and vertical wind shear environment imposed by the trough. 4) Uncertainty of input adds difficulties in quantitative TC intensity forecasting.
A Four-Season Impact Study of Rawinsonde, GOES, and POES Data in the Eta Data Assimilation System. Part I: The Total Contribution
Authors: Zapotocny Tom H. , Menzel W. Paul , Jung James A. , Nelson James P.
Published: April 2005

The impact of in situ rawinsonde (raob) data, remotely sensed Geostationary Operational Environmental Satellite (GOES), and Polar Operational Environmental Satellite (POES) data routinely used in NCEP’s Eta Data Assimilation/Forecast System (EDAS) is studied for extended-length time periods during four seasons. The work described in this paper is relevant for users of the Eta Model trying to compare and contrast the overall forecast impact of traditional, mostly land-based rawinsonde data with remotely sensed data that are available domainwide.

The case studies chosen consist of 15-day periods during fall 2001, winter 2001/02, spring 2002, and summer 2002. During these periods, a 32-km/60-layer November 2001 version of the EDAS is run four times at both 0000 and 1200 UTC. The four runs include a control run, which utilizes all data types routinely used in the EDAS, and three experimental runs in which either all rawinsonde, GOES, or POES data are denied. Differences between the experimental and control runs are then accumulated over the 15-day periods and analyzed to demonstrate the 24- and 48-h forecast impact of these data types in the EDAS. Conventional meteorological terms evaluated include mean sea level pressure as well as temperature, both components of the wind, and relative humidity. Comparisons are made on seven pressure levels extending from near the earth’s surface to the lower stratosphere. The diagnostics are computed over both the entire horizontal model domain, and within a subsection covering the continental United States and adjacent coastal waters (extended CONUS).

The 24-h domainwide results show that a positive forecast impact is achieved from all three data sources during all four seasons. Cumulatively, the rawinsonde data have the largest positive impact over both the entire model domain and extended CONUS. However, GOES data have the largest contribution for several fields, especially moisture during summer and fall 2001. In general, GOES data also provide larger forecast impacts than POES data, especially for the wind components. All three data types demonstrate comparable forecast impact in terms of relative humidity. Finally, raob and POES data display a “spike” in positive forecast impact in the lower stratosphere during three of the four seasons.

Two additional findings from this study are also important. The first is that the forecast impact of all data types drops by at least a factor of 2 during all seasons between 24 and 48 h. The second is that GOES data show a preference for providing nearly equal improvement to the 0000 and 1200 UTC forecast cycles, while rawinsonde and especially POES data provide consistently larger forecast impacts at 1200 than at 0000 UTC.
A Four-Season Impact Study of Rawinsonde, GOES, and POES Data in the Eta Data Assimilation System. Part II: Contribution of the Components
Authors: Zapotocny Tom H. , Menzel W. Paul , Jung James A. , Nelson James P.
Published: April 2005

The impact of in situ rawinsonde observations (raob), remotely sensed Geostationary Operational Environmental Satellite (GOES), and Polar-Orbiting Operational Environmental Satellite (POES) observations routinely used in NCEP’s Eta Data Assimilation/Forecast System (EDAS) is studied for extended-length time periods during four seasons. This work examines the contribution of nine individual components of the total observing system. The nine data types examined include rawinsonde mass and wind observations, GOES mass and wind observations, POES observations from the Microwave Sounding Unit (MSU), the Advanced Microwave Sounding Unit (AMSU-A and AMSU-B), the High Resolution Infrared Radiation Sounder (HIRS), and column total precipitable water and low-level wind observations from the Special Sensor Microwave Imager (SSM/I). The results are relevant for users of the Eta Model trying to compare/contrast the overall forecast impact of traditional, largely land-based rawinsonde observations against remotely sensed satellite observations, which are available domainwide.

The case studies chosen consist of 15-day periods during fall 2001, winter 2001/02, spring 2002, and summer 2002. Throughout these periods, a November 2001 32-km version of the EDAS is run 10 times at both 0000 and 1200 UTC. The 10 runs include a control run, which utilizes all data types routinely used in the EDAS, and 9 experimental runs in which one of the component data types noted above is denied. Differences between the experimental and control runs are then accumulated over the 15-day periods and analyzed to demonstrate the 00-h sensitivity and 24-h forecast impact of these individual data types in the EDAS. The diagnostics are computed over the entire horizontal model domain and a subsection covering the continental United States (CONUS) and adjacent coastal waters on isobaric surfaces extending into the lower stratosphere.

The 24-h forecast impact results show that a positive forecast impact is achieved from most of the nine component data sources during all four time periods. HIRS, MSU, and SSM/I wind observations yield only a slight positive forecast impact to all fields. Rawinsonde and GOES wind observations have the largest positive forecast impact for temperature over both the entire model domain and the extended CONUS. The same data types also provide the largest forecast impact to the u component of the wind, while GOES wind observations provide the largest forecast impact to moisture.
Where Is the Real Cloud-to-Ground Lightning Maximum in North America?
Authors: Murphy Martin J. , Holle Ronald L.
Published: April 2005

A local maximum in cloud-to-ground (CG) lightning flash density over northwestern Mexico as measured by the U.S. National Lightning Detection Network is examined in detail. Corrections are derived for the relative detection efficiency of the network in this region that is outside the perimeter of the sensors. The need to adjust the parameters of the signal normalization model used for the network is also documented. New propagation model parameters are employed to derive relative detection efficiency corrections for northwestern Mexico and these are then used to show that the actual CG flash density over the region significantly exceeds that observed in Florida, the area with the highest flash density within the perimeter of the network.
LDL receptor cooperates with LDL receptor–related protein in regulating plasma levels of coagulation factor VIII in vivo
Authors: Bovenschen Niels , Mertens Koen , Hu Lihui , Havekes Louis M. , van Vlijmen Bart J. M.
Published: April 2005

Low-density lipoprotein (LDL) receptor (LDLR) and LDLR-related protein (LRP) are members of the LDLR family of endocytic receptors. LRP recognizes a wide spectrum of structurally and functionally unrelated ligands, including coagulation factor VIII (FVIII). In contrast, the ligand specificity of LDLR is restricted to apolipoproteins E and B-100. Ligand binding to the LDLR family is inhibited by receptor-associated protein (RAP). We have previously reported that, apart from LRP, other RAP-sensitive mechanisms contribute to the regulation of FVIII in vivo. In the present study, we showed that the extracellular ligand-binding domain of LDLR interacts with FVIII in vitro and that binding was inhibited by RAP. The physiologic relevance of the FVIII–LDLR interaction was addressed using mouse models of LDLR or hepatic LRP deficiency. In the absence of hepatic LRP, LDLR played a dominant role in the regulation and clearance of FVIII in vivo. Furthermore, FVIII clearance was accelerated after adenovirus-mediated gene transfer of LDLR. The role of LDLR in FVIII catabolism was not secondary to increased plasma lipoproteins or to changes in lipoprotein profiles. We propose that LDLR acts in concert with LRP in regulating plasma levels of FVIII in vivo. This represents a previously unrecognized link between LDLR and hemostasis.
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

A 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

Hemophagocytic 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

This 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.
Time delay and data loss compensation for Internet-based process control systems
Authors: Yang S. H. , Chen X. , Tan L. S. , Yang L.
Published: April 2005

Introducing the Internet into process control systems has brought a lot of benefits and some difficulties to control engineers as well. The major challenge of Internet-based process control systems is how to deal with Internet time delay and data loss. This paper analyses Internet communication features and proposes a control structure with a variable sampling time to overcome the Internet transmission delay. In order to take advantage of the structure fully and attack the major difficulties, two compensation elements have been designed and implemented in the system. These two compensators are located in the feedback and feedforward channels in the architecture respectively. Our simulation and experimental results illustrate that the control structure and two compensation elements can efficiently deal with the Internet time delay and data loss. Our simulation results also show that the time delay and data loss in the feedforward channel seem to cause more serious influence on the control performance and is more difficult to be compensated for.
Automated inspection system for colour and shape grading of starfruit (Averrhoa carambola L.) using machine vision sensor
Authors: Abdullah M. Z. , Fathinul-Syahir A. S. , Mohd-Azemi B. M.N.
Published: April 2005

A prototype machine vision station was developed for quality grading of the unique star shape and rich golden colour carambola fruits (Averrhoa carambola L.). The grading criteria were based on the Malaysia’s Federal Agriculture Marketing Authority standards for starfruits export. A Fourier-based shape separations method was developed for shape grading, whereas colour recognition was established using multivariate discriminant analysis. The Wilks’ lambda analysis was invoked to transform and compress the data set comprising of large number of interconnected variates to a reduced set of variates. A robust scaling normalization was introduced in order to achieve invariant to geometrical transformations. Over 200 starfruit samples were inspected by the machine vision system and the results were compared to human judgement. Overall, the vision system was able to classify correctly 100% of the starfruits for shape and 92% for colour. Since the algorithms were implemented in software, the system could be programmed to inspect other fruits and agriculture commodities.
Compatibility and stability of the novel anti-cancer agent C1311 in infusion devices and its in vitro biocompatibility
Authors: den Brok Monique WJ , Nuijen Bastiaan , Harms Remko , Buluran Josie N , Harvey Michael D , Grieshaber Charles K , Beijnen Jos H
Published: April 2005

C1311 is the lead compound from the imidazoacridinones, a novel group of rationally designed anti-cancer agents. The compound is pharmaceutically formulated as a lyophilized product containing 100 mg C1311 (anhydrous free base) per dosage unit and requires reconstitution before intravenous administration. The aim of this study was to determine the stability of C1311 in the reconstituted solution and infusion solution and its compatibility with infusion devices. Moreover, the buffer capacity and haemolytic potential of C1311 infusion solutions, which exhibit a relatively low pH of 2-3, were evaluated in vitro. C1311 was shown to be stable in the reconstituted solution for at least 48 h and for at least 96 h after subsequent dilution in 0.9% sodium chloride and 5% dextrose. In vitro infusion simulation studies showed C1311 infusion solutions to be compatible with a low-density polyethylene administration set. Furthermore, the buffer capacity and haemolysis studies showed no indications for haemolysis or potential for vascular irritation upon continuous infusion of C1311. In conclusion, C1311 lyophilized product is adequately stable and compatible after reconstitution and in infusion fluids to be used in the clinic and is not expected to cause formulation-associated side effects in the intended administration schedule in the forthcoming Phase I clinical study.
Secretory carrier membrane proteins interact and regulate trafficking of the organellar (Na+,K+)/H+ exchanger NHE7
Authors: Lin Paulo J. C. , Williams Warren P. , Luu Yvonne , Molday Robert S. , Orlowski John , Numata Masayuki
Published: April 2005

The mammalian (Na+,K+)/H+ exchanger NHE7 resides chiefly in the trans-Golgi network (TGN) and post-Golgi vesicles where it is thought to contribute to organellar pH homeostasis. However, the mechanisms that underlie the targeting and regulation of NHE7 are unknown. To gain insight into these processes, yeast two-hybrid methodology was used to screen a human brain cDNA library for proteins that interact with the cytoplasmic C-terminus of NHE7. One binding partner we identified was SCAMP2, a member of the secretory carrier membrane protein (SCAMP) gene family. Direct association of these two proteins was further supported by co-immunolocalization and co-immunoprecipitation analyses using transfected cells, by their co-sedimentation in membrane fractions resolved on sucrose density gradients, and by in vitro protein binding assays. Other members of the SCAMP family, such as SCAMP1 and SCAMP5, also associated with NHE7. The majority of the NHE7-SCAMP complexes accumulated at the TGN, but a minor fraction also resided in recycling vesicles. Biochemical analyses indicated that the C-terminal cytoplasmic tail of NHE7 bound preferentially to a highly conserved cytoplasmic loop between the second and the third transmembrane segments (TM2-TM3 loop) of SCAMP2. A deletion mutant of SCAMP2 lacking this region (SCAMP2/Δ184-208) bound weakly to NHE7, but caused a significant fraction of NHE7 and wild-type SCAMP2 to redistribute to a pool of scattered recycling vesicles without noticeably affecting the location of other resident TGN (syntaxin 6) or Golgi cisternae (GM130) proteins. Conversely, a GFP-tagged TM2-TM3 construct of SCAMP2 interacted with NHE7, but also led to the redistribution of NHE7 to dispersed vesicular structures. We propose a model wherein SCAMPs participate in the shuttling of NHE7 between recycling vesicles and the TGN.
Evidence of the presence of calcium/calmodulin-dependent protein kinase IV in human sperm and its involvement in motility regulation
Authors: Marín-Briggiler Clara I. , Jha Kula N. , Chertihin Olga , Buffone Mariano G. , Herr John C. , Vazquez-Levin Mónica H. , Visconti Pablo E.
Published: April 2005

The mechanisms involved in the regulation of mammalian sperm motility are not well understood. Calcium ions (Ca2+) have been suggested to play a key role in the maintenance of motility; nevertheless, how Ca2+ modulates this process has not yet been completely characterized. Ca2+ can bind to calmodulin and this complex regulates the activity of multiple enzymes, including Ca2+/calmodulin-dependent protein kinases (CaM kinases). Results from this study confirmed that the presence of Ca2+ in the incubation medium is essential for maintaining human sperm motility. The involvement of CaM kinases in Ca2+ regulation of human sperm motility was evaluated using specific inhibitors (KN62 and KN93) or their inactive analogues (KN04 and KN92 respectively). Sperm incubation in the presence of KN62 or KN93 led to a progressive decrease in the percentage of motile cells; in particular, incubation with KN62 also reduced sperm motility parameters. These inhibitors did not alter sperm viability, protein tyrosine phosphorylation or the follicular fluid-induced acrosome reaction; however, KN62 decreased the total amount of ATP in human sperm. Immunological studies showed that Ca2+/calmodulin-dependent protein kinase IV (CaMKIV) is present and localizes to the human sperm flagellum. Moreover, CaMKIV activity increases during capacitation and is inhibited in the presence of KN62. This report is the first to demonstrate the presence of CaMKIV in mammalian sperm and suggests the involvement of this kinase in the regulation of human sperm motility.
Theory and practice: Requirements for adhesive bonding in marine structures
Authors: Wacker G , Brügge D , Fach K , Franzelius W
Published: April 2005

The use of adhesive bonding in ship structures has been slow compared to other industries. For high-speed craft adhesives are used for the panes, seat rails, the rudder bearings in the housing and propulsion shafts. Adhesives are used for the connection of rotor blades of a wind turbine. This paper describes specialities of the design of adhesive bonds, rules and guidelines as well as approval aspects for adhesives and manufacturing requirements. For panes of a cruise vessel a calculation method is compared with full-scale test results and finite element results. The authors of this paper want to show that adhesive bonding is a suitable way of joining elements, assuming that all relevant pre-conditions are fulfilled.
Coastal winds and low‐level jets: Simulations for sea gulfs
Authors: SavijÄRvi Hannu , NiemelÄ Sami , Tisler Priit
Published: April 2005

The 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

An 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

Propagation 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

A 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.
The Wake-Promoting Hypocretin/Orexin Neurons Change Their Response to Noradrenaline after Sleep Deprivation
Authors: Grivel Jeremy , Cvetkovic Vesna , Bayer Laurence , Machard Danièle , Tobler Irene , Mühlethaler Michel , Serafin Mauro
Published: April 2005

Sleep deprivation is accompanied by the progressive development of an irresistible need to sleep, a phenomenon whose mechanism has remained elusive. Here, we identified for the first time a reflection of that phenomenonin vitroby showing that, after a short 2 h period of total sleep deprivation, the action of noradrenaline on the wake-promoting hypocretin/orexin neurons changes from an excitation to an inhibition. We propose that such a conspicuous modification of responsiveness should contribute to the growing sleepiness that accompanies sleep deprivation.
Diminished Neuronal Activity Increases Neuron-Neuron Connectivity Underlying Silent Synapse Formation and the Rapid Conversion of Silent to Functional Synapses
Authors: Nakayama Kimiko , Kiyosue Kazuyuki , Taguchi Takahisa
Published: April 2005

Neuronal activity regulates the synaptic strength of neuronal networks. However, it is still unclear how diminished activity changes connection patterns in neuronal circuits. To address this issue, we analyzed neuronal connectivity and relevant mechanisms using hippocampal cultures in which developmental synaptogenesis had occurred. We show that diminution of network activity in mature neuronal circuit promotes reorganization of neuronal circuits via NR2B subunit-containing NMDA-type glutamate receptors (NR2B-NMDARs), which mediate silent synapse formation. Simultaneous double whole-cell recordings revealed that diminishing neuronal circuit activity for 48 h increased the number of synaptically connected neuron pairs with both silent and functional synapses. This increase was accompanied by the specific expression of NR2B-NMDARs at synaptic sites. Analysis of miniature EPSCs (mEPSCs) showed that the frequency of NMDAR-mediated, but not AMPAR-mediated, mEPSCs increased, indicating that diminished neuronal activity promotes silent synapse formation via the surface delivering NR2B-NMDARs in mature neurons. After activation of neuronal circuit by releasing from TTX blockade (referred as circuit reactivation), the frequency of AMPAR-mediated mEPSCs increased instead, and this increase was prevented by ifenprodil. The circuit reactivation also caused an increased colocalization of glutamate receptor 1-specfic and synaptic NR2B-specific puncta. These results indicate that the circuit reactivation converts rapidly silent synapses formed during activity suppression to functional synapses. These data may provide a new example of homeostatic circuit plasticity that entails the modulation of neuron-neuron connectivity by synaptic activity.
Thrombin-Induced Oxidative Stress Contributes to the Death of Hippocampal NeuronsIn Vivo: Role of Microglial NADPH Oxidase
Authors: Choi Sang-Ho , Lee Da Yong , Kim Seung Up , Jin Byung Kwan
Published: April 2005

The present study investigated whether thrombin, a potent microglial activator, can induce reactive oxygen species (ROS) generation through activation of microglial NADPH oxidase and if this may contribute to oxidative damage and consequent neurodegeneration. Seven days after intrahippocampal injection of thrombin, Nissl staining and immunohistochemistry using the neuronal-specific nuclear protein NeuN revealed a significant loss in hippocampal CA1 neurons. In parallel, thrombin-activated microglia, assessed by OX-42 and OX-6 immunohistochemistry, and ROS production, assessed by hydroethidine histochemistry, were observed in the hippocampal CA1 area in which degeneration of hippocampal neurons occurred. Reverse transcription-PCR at various time points after thrombin administration demonstrated an early and transient expression of inducible nitric oxide synthase (iNOS) and several proinflammatory cytokines. Western blot analysis and double-label immunohistochemistry showed an increase in the expression of and the localization of iNOS within microglia. Additional studies demonstrated that thrombin induced the upregulation of membrane (gp91phox) and cytosolic (p47phoxand p67phox) components, translocation of cytosolic proteins (p47phox, p67phox, and Rac1) to the membrane, and p67phoxexpression of the NADPH oxidase in microglia in the hippocampusin vivo, indicating the activation of NADPH oxidase. The thrombin-induced oxidation of proteins and loss of hippocampal CA1 neurons were partially inhibited by an NADPH oxidase inhibitor and by an antioxidant. To our knowledge, the present study is the first to demonstrate that thrombin-induced neurotoxicity in the hippocampusin vivois caused by microglial NADPH oxidase-mediated oxidative stress. This suggests that thrombin inhibition or enhancing antioxidants may be beneficial for the treatment of neurodegenerative diseases, such as Alzheimer's disease, that are associated with microglial-derived oxidative damage.
Brain-Specific Knock-Out of Hypoxia-Inducible Factor-1α Reduces Rather Than Increases Hypoxic-Ischemic Damage
Authors: Helton Rob , Cui Jiankun , Scheel John R. , Ellison Julie A. , Ames Chris , Gibson Claire , Blouw Barbara , Ouyang Ling , Dragatsis Ioannis , Zeitlin Scott , Johnson Randall S. , Lipton Stuart A. , Barlow Carrolee
Published: April 2005

Hypoxia-inducible factor-1α (HIF-1α) plays an essential role in cellular and systemic O2homeostasis by regulating the expression of genes important in glycolysis, erythropoiesis, angiogenesis, and catecholamine metabolism. It is also believed to be a key component of the cellular response to hypoxia and ischemia under pathophysiological conditions, such as stroke. To clarify the function of HIF-1α in the brain, we exposed adult mice with late-stage brain deletion of HIF-1α to hypoxic injuries. Contrary to expectations, the brains from theHIF-1α-deficient mice were protected from hypoxia-induced cell death. These surprising findings suggest that decreasing the level of HIF-1α can be neuroprotective. Gene chip expression analysis revealed that, contrary to expectations, the majority of hypoxia-dependent gene-expression changes were unaltered, whereas a specific downregulation of apoptotic genes was observed in theHIF-1α-deficient mice. Although the role of HIF-1α has been extensively characterizedin vitro, in cancer models, and in chronic preconditioning paradigms, this is the first study to evaluate the role of HIF-1αin vivoin the brain in response to acute hypoxia/ischemia. Our data suggest, that in acute hypoxia, the neuroprotection found in theHIF-1α-deficient mice is mechanistically consistent with a predominant role of HIF-1α as proapoptotic and loss of function leads to neuroprotection. Furthermore, our data suggest that functional redundancy develops after excluding HIF-1α, leading to the preservation of gene expression regulating the majority of other previously characterized HIF-dependent genes.
Proton-Mediated Feedback Inhibition of Presynaptic Calcium Channels at the Cone Photoreceptor Synapse
Authors: Vessey John P. , Stratis Anna K. , Daniels Bryan A. , Da Silva Noel , Jonz Michael G. , Lalonde Melanie R. , Baldridge William H. , Barnes Steven
Published: April 2005

Generation of center-surround antagonistic receptive fields in the outer retina occurs via inhibitory feedback modulation of presynaptic voltage-gated calcium channels in cone photoreceptor synaptic terminals. Both conventional and unconventional neurotransmitters, as well as an ephaptic effect, have been proposed, but the intercellular messaging that mediates the inhibitory feedback signal from postsynaptic horizontal cells (HCs) to cones remains unknown. We examined the possibility that proton concentration in the synaptic cleft is regulated by HCs and that it carries the feedback signal to cones. In isolated, dark-adapted goldfish retina, we assessed feedback in the responses of HCs to light and found that strengthened pH buffering reduced both rollback and the depolarization to red light. In zebrafish retinal slices loaded with Fluo-4, depolarization with elevated K+increased Ca signals in the synaptic terminals of cone photoreceptors. Kainic acid, which depolarizes HCs but has no direct effect on cones, depressed the K+-induced Ca signal, whereas CNQX, which hyperpolarizes HCs, increased the Ca signals, suggesting that polarization of HCs alters inhibitory feedback to cones. We found that these feedback signals were blocked by elevated extracellular pH buffering, as well as amiloride and divalent cations. Voltage clamp of isolated HCs revealed an amiloride-sensitive conductance that could mediate modulation of cleft pH dependent on the membrane potential of these postsynaptic cells.
Gonadal Steroid Attenuation of Developing Hamster Facial Motoneuron Loss by Axotomy: Equal Efficacy of Testosterone, Dihydrotestosterone, and 17-β Estradiol
Authors: Huppenbauer Christopher B. , Tanzer Lisa , DonCarlos Lydia L. , Jones Kathryn J.
Published: April 2005

In the hamster facial nerve injury paradigm, we have established that androgens enhance both functional recovery from facial nerve paralysis and the rate of regeneration in the adult, through intrinsic effects on the nerve cell body response to injury and via an androgen receptor (AR)-mediated mechanism. Whether these therapeutic effects of gonadal steroids encompass neuroprotection from axotomy-induced cell death is the focus of the present study. Virtually 100% of adult hamster facial motoneurons (FMNs) survive axotomy at the stylomastoid foramen (SMF), whereas, before postnatal day 15 (P15), developing FMNs undergo substantial axotomy-induced cell death. The first part of the present study focuses on determining when ARs are first expressed in developing hamster FMNs. Using AR immunocytochemistry, it was found that males express ARs by P2 and females by P4, which is the earliest demonstration of AR expression in mammalian motoneurons reported thus far in the literature. The second half examines the neuroprotective effects of testosterone propionate, 17-β estradiol, and dihydrotestosterone on FMNs of P7 hamsters after facial nerve transection at the SMF. The results demonstrate that androgens and estrogens are equally able to rescue ∼20% of FMNs from axotomy-induced cell death, with the effects permanent. This study is the first to investigate the effects of both androgens and estrogens on axotomy-induced cell death in one system and, with our previously published work, to validate the hamster FMN injury paradigm as a model of choice in the investigation of both neurotherapeutic and neuroprotective actions of gonadal steroids.