bluuebunny/crossref_metadata_2025 huggingface dataset:
Mechanisms of protease‐activated receptor 2‐evoked hyperexcitability of nociceptive neurons innervating the mouse colon
Authors: Kayssi Ahmed , Amadesi Silvia , Bautista Francisco , Bunnett Nigel W. , Vanner Stephen
Published: February 2007

Agonists of protease‐activated receptor 2 (PAR2) evoke hyperexcitability of dorsal root ganglia (DRG) neurons by unknown mechanisms. We examined the cellular mechanisms underlying PAR2‐evoked hyperexcitability of mouse colonic DRG neurons to determine their potential role in pain syndromes such as visceral hyperalgesia. Colonic DRG neurons were identified by injecting Fast Blue and DiI retrograde tracers into the mouse colon. Using immunofluorescence, we found that DiI‐labelled neurons contained PAR2 immunoreactivity, confirming the presence of receptors on colonic neurons. Whole‐cell current‐clamp recordings of acutely dissociated neurons demonstrated that PAR2 activation with a brief application (3 min) of PAR2 agonists, SLIGRL‐NH2 and trypsin, evoked sustained depolarizations (up to 60 min) which were associated with increased input resistance and a marked reduction in rheobase (50% at 30 min). In voltage clamp, SLIGRL‐NH2 markedly suppressed delayed rectifier IK currents (55% at 10 min), but had no effect on the transient IA current or TTX‐resistant Na+ currents. In whole‐cell current‐clamp recordings, the sustained excitability evoked by PAR2 activation was blocked by the PKC inhibitor, calphostin, and the ERK1/2 inhibitor PD98059. Studies of ERK1/2 phosphorylation using confocal microscopy demonstrated that SLIGRL‐NH2 increased levels of immunoreactive pERK1/2 in DRG neurons, particularly in proximity to the plasma membrane. Thus, activation of PAR2 receptors on colonic nociceptive neurons causes sustained hyperexcitability that is related, at least in part, to suppression of delayed rectifier IK currents. Both PKC and ERK1/2 mediate the PAR2‐induced hyperexcitability. These studies describe a novel mechanism of sensitization of colonic nociceptive neurons that may be implicated in conditions of visceral hyperalgesia such as irritable bowel syndrome.
Conjugate Heat Transfer Study of a Two-Dimensional Laminar Incompressible Wall Jet Over a Backward-Facing Step
Authors: Kanna P. Rajesh , Das Manab Kumar
Published: February 2007

Steady-state conjugate heat transfer study of a slab and a fluid is carried out for a two-dimensional laminar incompressible wall jet over a backward-facing step. Unsteady stream function-vorticity formulation is used to solve the governing equation in the fluid region. An explicit expression has been derived for the conjugate interface boundary. The energy equation in the fluid, interface boundary and the conduction equation in the solid are solved simultaneously. The conjugate heat transfer characteristics, Nusselt number are studied with flow property (Re), fluid property (Pr), and solid to fluid conductivity ratio (k). Average Nusselt number is compared with that of the nonconjugate case. As k is increased, average Nusselt number is increased, asymptotically approaching the non-conjugate value.
Nonlinear Time Dependent Corrosion Wastage of Deck Plates of Ballast and Cargo Tanks of Tankers
Authors: Garbatov Y. , Guedes Soares C. , Wang G.
Published: February 2007

The corrosion wastage of deck plates of ballast and cargo tanks is analyzed based on a nonlinear corrosion model. This model is able to describe an initial period without corrosion due to the presence of a corrosion protection system, a transition period with a nonlinear increase of wastage up to a steady state of long-term corrosion wastage. This model is applied to corrosion wastage data of deck plates collected by the American Bureau of Shipping. The objective of this work is to fit this corrosion wastage model to the service measured data, determining the values of the model parameters that represent the best fit to the data so as to describe how corrosion wastage varies in time as a result of generalized corrosion.
Stochastic Control of Sensitive Nonlinear Motions of an Ocean Mooring System
Authors: King Paul E. , Yim Solomon C.
Published: February 2007

Complex sensitive motions have been observed in ocean mooring systems consisting of nonlinear mooring geometries. These physical systems can be modeled as a system of first-order nonlinear ordinary differential equations, taking into account geometric nonlinearities in the restoring force, quadratic viscous drag, and harmonic excitation. This study examines the controllability of these systems utilizing an embedded approach to noise filtering and online controllers. The system is controlled using small perturbations about a selected unstable cycle and control is instigated for periodic cycles of varying periodicities. The controller, when applied to the system with additive random noise in the excitation, has marginal success. However, the addition of an iterated Kalman filter applied to the system increases the regime under which the controller behaves under the influence of noise. Because the Kalman filter is applied about locally linear trajectories, the feedback of the nonlinearities through the filter has little effect on the overall filtering system.
Rapid Changes in Ice Discharge from Greenland Outlet Glaciers
Authors: Howat Ian M. , Joughin Ian , Scambos Ted A.
Published: February 2007

Using satellite-derived surface elevation and velocity data, we found major short-term variations in recent ice discharge and mass loss at two of Greenland's largest outlet glaciers. Their combined rate of mass loss doubled in less than a year in 2004 and then decreased in 2006 to near the previous rates, likely as a result of fast re-equilibration of calving-front geometry after retreat. Total mass loss is a fraction of concurrent gravity-derived estimates, pointing to an alternative source of loss and the need for high-resolution observations of outlet dynamics and glacier geometry for sea-level rise predictions.
Assembly Dynamics of the Bacterial MinCDE System and Spatial Regulation of the Z Ring
Authors: Lutkenhaus Joe
Published: February 2007

The positioning of a cytoskeletal element that dictates the division plane is a fundamental problem in biology. The assembly and positioning of this cytoskeletal element has to be coordinated with DNA segregation and cell growth to ensure that equal-sized progeny cells are produced, each with a copy of the chromosome. In most prokaryotes, cytokinesis involves positioning a Z ring assembled from FtsZ, the ancestral homologue of tubulin. The position of the Z ring is determined by a gradient of negative regulators of Z-ring assembly. In Escherichia coli, the Min system consists of three proteins that cooperate to position the Z ring through a fascinating oscillation, which inhibits the formation of the Z ring away from midcell. Additional gradients of negative regulators of FtsZ assembly are used by E. coli and other bacteria to achieve spatial control of Z-ring assembly.
Structure and Mechanism of the 6-Deoxyerythronolide B Synthase
Authors: Khosla Chaitan , Tang Yinyan , Chen Alice Y. , Schnarr Nathan A. , Cane David E.
Published: February 2007

6-Deoxyerythronolide B, the macrocyclic aglycone of the antibiotic erythromycin, is synthesized by a polyketide synthase (PKS) that has emerged as the prototypical modular megasynthase. A variety of molecular biological, protein chemical, and biosynthetic experiments over the past two decades have yielded insights into its mechanistic features. More recently, high-resolution structural images of portions of the 6-deoxyerythronolide B synthase have provided a platform for interpreting this wealth of biochemical data, while at the same time presenting a fundamentally new basis for the design of more detailed investigations into this remarkable enzyme. For example, the critical roles of domain-domain interactions and nonconserved linkers, as well as large interdomain movements in the structure and function of modular PKSs, have been highlighted. In turn, these insights point the way forward for more sophisticated and efficient biosynthetic engineering of complex polyketide natural products.
The Role of Mass Spectrometry in Structure Elucidation of Dynamic Protein Complexes
Authors: Sharon Michal , Robinson Carol V.
Published: February 2007

The fact that ions of macromolecular complexes produced by electrospray ionization can be maintained intact in a mass spectrometer has stimulated exciting new lines of research. In this review we chart the progress of this research from the observation of simple homo-oligomers to complex heterogeneous macromolecular assemblies of mega-Dalton proportions. The applications described herein not only confirm the status of mass spectrometry (MS) as a structural biology approach to complement X-ray analysis or electron microscopy, but also highlight unique attributes of the methodology. This is exemplified in studies of the biogenesis of macromolecular complexes and in the exchange of subunits between macromolecular complexes. Moreover, recent successes in revealing the overall subunit architecture of complexes are set to promote MS from a complementary approach to a structural biology tool in its own right.
Molecular Mechanisms of Antibody Somatic Hypermutation
Authors: Di Noia Javier M. , Neuberger Michael S.
Published: February 2007

Functional antibody genes are assembled by V-D-J joining and then diversified by somatic hypermutation. This hypermutation results from stepwise incorporation of single nucleotide substitutions into the V gene, underpinning much of antibody diversity and affinity maturation. Hypermutation is triggered by activation-induced deaminase (AID), an enzyme which catalyzes targeted deamination of deoxycytidine residues in DNA. The pathways used for processing the AID-generated U:G lesions determine the variety of base substitutions observed during somatic hypermutation. Thus, DNA replication across the uracil yields transition mutations at C:G pairs, whereas uracil excision by UNG uracil-DNA glycosylase creates abasic sites that can also yield transversions. Recognition of the U:G mismatch by MSH2/MSH6 triggers a mutagenic patch repair in which polymerase eta plays a major role and leads to mutations at A:T pairs. AID-triggered DNA deamination also underpins immunoglobulin variable (IgV) gene conversion, isotype class switching, and some oncogenic translocations in B cell tumors.
Studying Individual Events in Biology
Authors: Wennmalm Stefan , Simon Sanford M.
Published: February 2007

Studying the properties of individual events and molecules offers a host of advantages over taking only macroscopic measurements of populations. Here we review such advantages, as well as some pitfalls, focusing on examples from biological imaging. Examples include single proteins, their interactions in cells, organelles, and their interactions both with each other and with parts of the cell. Additionally, we discuss constraints that limit the study of single events, along with the criteria that must be fulfilled to determine whether single molecules or events are being detected.
Antagonistic effects of two novel GIP analogs, (Hyp3)GIP and (Hyp3)GIPLys16PAL, on the biological actions of GIP and longer-term effects in diabeticob/obmice
Authors: O'Harte Finbarr P. M. , Hunter Kerry , Gault Victor A. , Irwin Nigel , Green Brian D. , Greer Brett , Harriott Patrick , Bailey Clifford J. , Flatt Peter R.
Published: February 2007

This study examines the actions of the novel enzyme-resistant, NH2-terminally modified GIP analog (Hyp3)GIP and its fatty acid-derivatized analog (Hyp3)GIPLys16PAL. Acute effects are compared with the established GIP receptor antagonist (Pro3)GIP. All three peptides exhibited DPP IV resistance, and significantly inhibited GIP stimulated cAMP formation and insulin secretion in GIP receptor-transfected fibroblasts and in clonal pancreatic BRIN-BD11 cells, respectively. Likewise, in obese diabetic ob/ob mice, intraperitoneal administration of GIP analogs significantly inhibited the acute antihyperglycemic and insulin-releasing effects of native GIP. Administration of once daily injections of (Hyp3)GIP or (Hyp3)GIPLys16PAL for 14 days resulted in significantly lower plasma glucose levels ( P < 0.05) after (Hyp3)GIP on days 12 and 14 and enhanced glucose tolerance ( P < 0.05) and insulin sensitivity ( P < 0.05 to P < 0.001) in both groups by day 14. Both (Hyp3)GIP and (Hyp3)GIPLys16PAL treatment also reduced pancreatic insulin ( P < 0.05 to P < 0.01) without affecting islet number. These data indicate that (Hyp3)GIP and (Hyp3)GIPLys16PAL function as GIP receptor antagonists with potential for ameliorating obesity-related diabetes. Acylation of (Hyp3)GIP to extend bioactivity does not appear to be of any additional benefit.
Hypoglycemic effect of isoleucine involves increased muscle glucose uptake and whole body glucose oxidation and decreased hepatic gluconeogenesis
Authors: Doi Masako , Yamaoka Ippei , Nakayama Mitsuo , Sugahara Kunio , Yoshizawa Fumiaki
Published: February 2007

Isoleucine, a branched chain amino acid, plays an important role in the improvement of glucose metabolism as evidenced by the increase of insulin-independent glucose uptake in vitro. This study evaluated the effect of isoleucine on glucose uptake and oxidation in fasted rats and on gluconeogenesis in vivo and in vitro. Oral administration of isoleucine decreased the plasma glucose level by 20% and significantly increased muscle glucose uptake by 71% without significant elevation of the plasma insulin level compared with controls at 60 min after administration. Furthermore, expiratory excretion of14CO2from [U-14C]glucose in isoleucine-administered rats was increased by 19% compared with controls. Meanwhile, isoleucine decreased AMP levels in the liver but did not affect hepatic glycogen synthesis. Under insulin-free conditions, isoleucine significantly inhibited glucose production when alanine was used as a glucogenic substrate in isolated hepatocytes. This inhibition by isoleucine was also associated with a decline in mRNA levels for phosphoenolpyruvate carboxykinase and glucose-6-phosphatase (G6Pase) and a decreased activity of G6Pase in isolated hepatocytes. These findings suggest that a reduction of gluconeogenesis in liver, along with an increase of glucose uptake in the muscle, is also involved in the hypoglycemic effect of isoleucine. In conclusion, isoleucine administration stimulates both glucose uptake in the muscle and whole body glucose oxidation, in addition to depressing gluconeogenesis in the liver, thereby leading to the hypoglycemic effect in rats.
Congenital Absence of the Right Pulmonary Artery with Coronary Collaterals Supplying the Affected Lung: Effect on Coronary Perfusion
Authors: Kadi Hasan , Kurtoglu Nuri , Karadag Bilgehan
Published: February 2007

We describe a unique case of congenital absence of a right pulmonary artery presenting in a patient of advanced age and initially misdiagnosed as coronary artery disease. Perfusion of the affected lung was accomplished via anomalous collaterals from right and left circumflex coronary arteries which induced myocardial ischemia, as demonstrated by myocardial perfusion scan. To our knowledge there are only three reports in the international literature, describing unilateral pulmonary artery agenesis with the coronary artery supplying the abnormal lung. All these reports described that the existence of such vessels does not affect the myocardial perfusion. However, here we describe, to our knowledge, for the first time that in a patient with unilateral pulmonary artery agenesis, the existence of collaterals from the coronary arteries to the affected lung can actually have a negative effect in myocardial perfusion and can induce myocardial ischemia. In conclusion, clinicians should be aware of the possibility of undiagnosed cases of unilateral pulmonary artery agenesis presenting with chest pain in advanced age.
VEGFR-1 and -2 Regulate Inflammation, Myocardial Angiogenesis, and Arteriosclerosis in Chronically Rejecting Cardiac Allografts
Authors: Raisky Olivier , Nykänen Antti I. , Krebs Rainer , Hollmén Maria , Keränen Mikko A.I. , Tikkanen Jussi M. , Sihvola Roope , Alhonen Leena , Salven Petri , Wu Yan , Hicklin Daniel J. , Alitalo Kari , Koskinen Petri K. , Lemström Karl B.
Published: February 2007

Objective—

Interplay between inflammation and angiogenesis is important in pathological reparative processes such as arteriosclerosis. We investigated how the two vascular endothelial growth factor receptors VEGFR-1 and -2 regulate these events in chronically rejecting cardiac allografts.

Methods and Results—

Chronic rejection in mouse cardiac allografts induced primitive myocardial, adventitial, and intimal angiogenesis with endothelial expression of CD31, stem cell marker c-kit, and VEGFR-2. Experiments using marker gene mice or rats as cardiac allograft recipients revealed that replacement of cardiac allograft endothelial cells with recipient bone marrow– or non–bone marrow–derived cells was rare and restricted only to sites with severe injury. Targeting VEGFR-1 with neutralizing antibodies in mice reduced allograft CD11b
+
myelomonocyte infiltration and allograft arteriosclerosis. VEGFR-2 inhibition prevented myocardial c-kit
+
and CD31
+
angiogenesis in the allograft, and decreased allograft inflammation and arteriosclerosis.

Conclusions—

These results suggest interplay of inflammation, primitive donor-derived myocardial angiogenesis, and arteriosclerosis in transplanted hearts, and that targeting VEGFR-1 and -2 differentially regulate these pathological reparative processes.
The Factor V Leiden, Prothrombin Gene 20210GA, Methylenetetrahydrofolate Reductase 677CT and Platelet Glycoprotein IIIa 1565TC Mutations in Patients With Acute Ischemic Stroke and Atrial Fibrillation
Authors: Berge Eivind , Haug Kari Bente Foss , Charlotte Sandset Else , Kristine Haugbro Kaia , Turkovic Meliha , Sandset Per Morten
Published: February 2007

Background and Purpose—

We wanted to investigate whether common prothrombotic mutations are more prevalent in patients with atrial fibrillation who have had a stroke than in healthy controls. We also wanted to assess whether early recurrent ischemic cerebrovascular events were more frequent among carriers of the factor V Leiden or the prothrombin gene mutations than among others.

Methods—

We used a case-control design with 367 patients with acute ischemic stroke and atrial fibrillation (cases) and 482 healthy blood donors (controls). All mutations were detected with conventional polymerase-chain reaction protocols.

Results—

The odds ratios for carriers of the factor V Leiden, prothrombin gene 20210GA, methylenetetrahydrofolate reductase 677CT, or platelet glycoprotein IIIa 1565TC (Pl
A2
) mutation were 0.91, (95% CI, 0.51 to 1.59), 2.25 (95% CI, 0.61 to 8.90), 0.83 (0.61 to 1.13), and 0.79 (0.57 to 1.10), respectively. Early recurrent ischemic stroke and total recurrent ischemic cerebrovascular events were slightly more frequent among carriers of the factor V Leiden mutation than among noncarriers: odds ratio 1.45 (95% CI, 0.41 to 5.1), and 1.59 (0.61 to 4.1), respectively. None of the patients with recurrent ischemic cerebrovascular events had the prothrombin gene mutation.

Conclusion—

These mutations are not important risk factors for thromboembolic stroke associated with atrial fibrillation. Carriers of the factor V Leiden mutation had a small, nonsignificantly higher risk of early recurrent ischemic cerebrovascular events.
A Multimodel Update on the Detection and Attribution of Global Surface Warming
Authors: Stone DáithíA. , Allen Myles R. , Stott Peter A.
Published: February 2007

This paper presents an update on the detection and attribution of global annual mean surface air temperature changes, using recently developed climate models. In particular, it applies a new methodology that permits the inclusion of many more general circulation models (GCMs) into the analysis, and it also includes more recent observations. This methodology involves fitting a series of energy balance models (EBMs) to the GCM output in order to estimate the temporal response patterns to the various forcings.

Despite considerable spread in estimated EBM parameters, characteristics of model performance, such as the transient climate response, appear to be more constrained for each of the forcings. The resulting estimated response patterns are provided as input to the standard fingerprinting method used in previous studies. The estimated GCM responses to changes in greenhouse gases are detected in the observed record for all of the GCMs, and are generally found to be consistent with the observed changes; the same is generally true for the responses to changes in stratospheric aerosols from volcanic eruptions. GCM responses to changes in tropospheric sulfate aerosols and solar irradiance also appear consistent with the observed record, although the uncertainty is larger. Greenhouse gas and solar irradiance changes are found to have contributed to a best guess of ∼0.8 and ∼0.3 K warming over the 1901–2005 period, respectively, while sulfate aerosols have contributed a ∼0.4 K cooling. This analysis provides an observationally constrained estimate of future warming, which is found to be fairly robust across GCMs. By 2100, a warming of between about 1.5 and 4.5 K can be expected according to the Intergovernmental Panel on Climate Change (IPCC) Special Report on Emissions Scenarios (SRES) A1B emissions scenario.

These results indicate an emerging constraint for global mean surface temperature responses to external forcings across GCMs, which is corroborated in the observed record. This implies that observationally constrained estimates of past warming and predictions of future warming are indeed becoming robust.
The Detection and Attribution of Climate Change Using an Ensemble of Opportunity
Authors: Stone DáithíA. , Allen Myles R. , Selten Frank , Kliphuis Michael , Stott Peter A.
Published: February 2007

The detection and attribution of climate change in the observed record play a central role in synthesizing knowledge of the climate system. Unfortunately, the traditional method for detecting and attributing changes due to multiple forcings requires large numbers of general circulation model (GCM) simulations incorporating different initial conditions and forcing scenarios, and these have only been performed with a small number of GCMs. This paper presents an extension to the fingerprinting technique that permits the inclusion of GCMs in the multisignal analysis of surface temperature even when the required families of ensembles have not been generated. This is achieved by fitting a series of energy balance models (EBMs) to the GCM output in order to estimate the temporal response patterns to the various forcings.

This methodology is applied to the very large Challenge ensemble of 62 simulations of historical climate conducted with the NCAR Community Climate System Model version 1.4 (CCSM1.4) GCM, as well as some simulations from other GCMs. Considerable uncertainty exists in the estimates of the parameters in fitted EBMs. Nevertheless, temporal response patterns from these EBMs are more reliable and the combined EBM time series closely mimics the GCM in the context of transient forcing. In particular, detection and attribution results from this technique appear self-consistent and consistent with results from other methods provided that all major forcings are included in the analysis.

Using this technique on the Challenge ensemble, the estimated responses to changes in greenhouse gases, tropospheric sulfate aerosols, and stratospheric volcanic aerosols are all detected in the observed record, and the responses to the greenhouse gases and tropospheric sulfate aerosols are both consistent with the observed record without a scaling of the amplitude being required. The result is that the temperature difference of the 1996–2005 decade relative to the 1940–49 decade can be attributed to greenhouse gas emissions, with a partially offsetting cooling from sulfate emissions and little contribution from natural sources.

The results support the viability of the new methodology as an extension to current analysis tools for the detection and attribution of climate change, which will allow the inclusion of many more GCMs. Shortcomings remain, however, and so it should not be considered a replacement to traditional techniques.
A Survey of Changes in Cloud Cover and Cloud Types over Land from Surface Observations, 1971–96
Authors: Warren Stephen G. , Eastman Ryan M. , Hahn Carole J.
Published: February 2007

From a dataset of weather observations from land stations worldwide, about 5400 stations were selected as having long periods of record with cloud-type information; they cover all continents and many islands. About 185 million synoptic reports were analyzed for total cloud cover and the amounts of nine different cloud types, for the 26-yr period 1971–96. Monthly and seasonal averages were formed for day and night separately.

Time series of total-cloud-cover anomalies for individual continents show a large decrease for South America, small decreases for Eurasia and Africa, and no trend for North America. The largest interannual variations (2.7%) are found for Australia, which is strongly influenced by ENSO. The zonal average trends of total cloud cover are positive in the Arctic winter and spring, 60°–80°N, but negative in all seasons at most other latitudes. The global average trend of total cloud cover over land is small, −0.7% decade−1, offsetting the small positive trend that had been found for the ocean, and resulting in no significant trend for the land–ocean average.

Significant regional trends are found for many cloud types. The night trends agree with day trends for total cloud cover and for all cloud types except cumulus. Cirrus trends are generally negative over all continents. A previously reported decline in total cloud cover over China and its neighbors appears to be largely attributable to high and middle clouds. Global trends of the cloud types exhibit trade-offs, with convective cloud types increasing at the expense of stratiform clouds, in both the low and middle levels.

Interannual variations over Europe, particularly of nimbostratus, are well correlated with the North Atlantic Oscillation; significant correlations are also found across northern Asia. Interannual variations in many parts of the Tropics are well correlated with an ENSO index. Little correlation was found with an index of smoke aerosol, in seven regions of seasonal biomass burning.

In the middle latitudes of both hemispheres, seasonal anomalies of cloud cover are positively correlated with surface temperature in winter and negatively correlated in summer, as expected if the direction of causality is from clouds to temperature.
Can Wavelets Improve the Representation of Forecast Error Covariances in Variational Data Assimilation?
Authors: Bannister Ross N.
Published: February 2007

Two wavelet-based control variable transform schemes are described and are used to model some important features of forecast error statistics for use in variational data assimilation. The first is a conventional wavelet scheme and the other is an approximation of it. Their ability to capture the position and scale-dependent aspects of covariance structures is tested in a two-dimensional latitude–height context. This is done by comparing the covariance structures implied by the wavelet schemes with those found from the explicit forecast error covariance matrix, and with a non-wavelet-based covariance scheme used currently in an operational assimilation scheme. Qualitatively, the wavelet-based schemes show potential at modeling forecast error statistics well without giving preference to either position or scale-dependent aspects. The degree of spectral representation can be controlled by changing the number of spectral bands in the schemes, and the least number of bands that achieves adequate results is found for the model domain used. Evidence is found of a trade-off between the localization of features in positional and spectral spaces when the number of bands is changed. By examining implied covariance diagnostics, the wavelet-based schemes are found, on the whole, to give results that are closer to diagnostics found from the explicit matrix than from the nonwavelet scheme. Even though the nature of the covariances has the right qualities in spectral space, variances are found to be too low at some wavenumbers and vertical correlation length scales are found to be too long at most scales. The wavelet schemes are found to be good at resolving variations in position and scale-dependent horizontal length scales, although the length scales reproduced are usually too short. The second of the wavelet-based schemes is often found to be better than the first in some important respects, but, unlike the first, it has no exact inverse transform.
The Characteristics of Key Analysis Errors. Part II: The Importance of the PV Corrections and the Impact of Balance
Authors: Caron Jean-François , Yau M. K. , Laroche Stéphane , Zwack Peter
Published: February 2007

This study examines a few approaches to isolate the balanced component of the initial corrections from the Canadian Meteorological Centre energy-norm-based key analysis error algorithm, in an attempt to capture the part of the key analysis errors responsible for short-range forecast errors. The best results were obtained with the nonlinear balance potential vorticity (PV) inversion technique. It was shown that the PV component of the initial corrections contains the essential information for reducing short-range forecast errors. The remaining imbalance part of the initial corrections does not grow in time and does not contribute to the improvement of the forecast. The removal of the imbalance part of the initial corrections makes the corrected analysis slightly closer to the observations, but remains systematically farther away as compared with the original analysis. Thus the balanced part of the key analysis errors cannot justifiably be associated to analysis errors. A methodology to balance the divergent part of the initial corrections, which reduces significantly the spinup in the vertical motion corrections, is also presented. Finally, in light of the results presented in this paper, some recommendations to improve the key analysis error algorithm are proposed.
A Synoptic–Dynamic Model of Subseasonal Atmospheric Variability
Authors: Weickmann Klaus , Berry Edward
Published: February 2007

A global synoptic–dynamic model (GSDM) of subseasonal variability is proposed to provide a framework for real-time weather–climate monitoring and to assist with the preparation of medium-range (e.g., week 1–3) predictions. The GSDM is used with a regional focus over North America during northern winter. A case study introduces the time scales of the GSDM and illustrates two circulation transitions related to eastward-moving wave energy signals and their connection to remote tropical forcing. Global and zonal atmospheric angular momentum (AAM) is used to help define the synoptic evolution of the GSDM components and to link regional synoptic variations with physical processes like the global mountain and frictional torque. The core of the GSDM consists of four stages based on the Madden–Julian oscillation (MJO) recurrence time. Additionally, extratropical behaviors including teleconnection patterns, baroclinic life cycles, and ∼monthly oscillations provide intermediate and fast time scales that are combined with the quasi-oscillatory (30–70 day) MJO to define multiple time-/space-scale linear relationships. A unique feature of the GSDM is its focus on global and regional circulation transitions and the related extreme weather events during periods of large global AAM tendency.
Assimilation of Screen-Level Variables in ECMWF’s Integrated Forecast System: A Study on the Impact on the Forecast Quality and Analyzed Soil Moisture
Authors: Drusch Matthias , Viterbo Pedro
Published: February 2007

In many operational numerical weather prediction applications, the soil moisture analysis is based on the modeled first-guess and screen-level variables; that is, 2-m temperature and 2-m relative humidity. A set of two global 61-day analysis/forecast experiments based on the Integrated Forecast System at the European Centre for Medium-Range Weather Forecasts (ECMWF) has been performed for June and July 2002. Analyses and forecasts based on the operational Optimal Interpolation (OI) scheme are compared against results obtained from an open loop system, in which soil moisture evolves freely. It is found that soil moisture assimilation or analysis has a significant impact on the model atmosphere. Temperature forecasts for the Northern Hemisphere up to a level of 700 hPa and up to nine days were significantly improved when the operational analysis was used. A comparison of volumetric soil moisture against in situ observations from the Oklahoma Mesonet reveals, however, that the operational OI system fails to improve both the analysis and the subsequent forecast of soil moisture itself. In addition, the system is not able to correct soil moisture for errors introduced through wrong precipitation in the background forecasts. Biweekly observations from the Illinois Climate Network support these findings. This study confirms the long assumed (but rarely proven) characteristics of analysis schemes using screen-level variables: The observations are efficient in improving the turbulent surface fluxes and consequently the weather forecast on large geographical domains. The quality of the resulting soil moisture profile is often not sufficient for hydrological or agricultural applications.
Impact of Ocean Observation Systems on Ocean Analysis and Seasonal Forecasts
Authors: Vidard A. , Anderson D. L. T. , Balmaseda M.
Published: February 2007

The relative merits of the Tropical Atmosphere–Ocean (TAO)/Triangle Trans-Ocean Buoy Network (TAO/TRITON) and Pilot Research Moored Array in the Tropical Atlantic mooring networks, the Voluntary Observing Ship (VOS) expendable bathythermograph (XBT) network, and the Argo float network are evaluated through their impact on ocean analyses and seasonal forecast skill. An ocean analysis is performed in which all available data are assimilated. In two additional experiments the moorings and the VOS datasets are withheld from the assimilation. To estimate the impact on seasonal forecast skill, the set of ocean analyses is then used to initialize a corresponding set of coupled ocean–atmosphere model forecasts. A further set of experiments is conducted to assess the impact of the more recent Argo array. A key parameter for seasonal forecast initialization is the depth of the thermocline in the tropical Pacific. This depth is quite similar in all of the experiments that involve data assimilation, but withdrawing the TAO data has a bigger effect than withdrawing XBT data, especially in the eastern half of the basin. The forecasts mainly indicate that the TAO/TRITON in situ temperature observations are essential to obtain optimum forecast skill. They are best combined with XBT, however, because this results in better predictions for the west Pacific. Furthermore, the XBTs play an important role in the North Atlantic. The ocean data assimilation performs less well in the tropical Atlantic. This may be partly a result of not having adequate observations of salinity.
Involvement of mast cells in IL-12/23 p40 production is essential for survival from polymicrobial infections
Authors: Nakano Nobuhiro , Nishiyama Chiharu , Kanada Shunsuke , Niwa Yusuke , Shimokawa Naomi , Ushio Hiroko , Nishiyama Makoto , Okumura Ko , Ogawa Hideoki
Published: February 2007

Interleukin-12 (IL-12), a heterodimeric cytokine (p35/p40) produced mainly from macrophages and dendritic cells, is an important regulator of T-helper 1 cell responses and for host defense. We found that interferon (IFN) consensus sequence binding protein (ICSBP), which is a transcription factor essential for the expression of p40, was expressed in mouse bone marrow–derived mast cells (BMMCs). The transcription levels of p35 and p40 were increased by stimulation of BMMCs with IFN-γ/lipopolysaccharide (LPS). IL-12 was secreted from BMMCs in response to LPS but not by FcϵRI cross-linking. The p40 levels in the peritoneal cavity of mast cell–deficient W/Wv and W/Wv reconstituted with p40−/− BMMCs were significantly lower than those of WBB6F1+/+ and wild-type (WT) BMMC-reconstituted W/Wv in the acute septic peritonitis model. The survival rate of W/Wv reconstituted with p40−/− BMMCs was significantly decreased compared to those of WBB6F1+/+ and WT-BMMC–reconstituted W/Wv, which was due to reduced production of IFN-γ and subsequent impaired activation of neutrophils in the peritoneal cavity. Survival rate of p40−/− mice was also restored by adoptive transfer of WT-BMMCs. These results demonstrate that mast cells play a significant role in the production of IL-12 required for host defense. This is the first report to demonstrate that mast cells are a crucial source of functional IL-12.
Prognostic impact of immunohistochemically defined germinal center phenotype in diffuse large B-cell lymphoma patients treated with immunochemotherapy
Authors: Nyman Heidi , Adde Magdalena , Karjalainen-Lindsberg Marja-Liisa , Taskinen Minna , Berglund Mattias , Amini Rose-Marie , Blomqvist Carl , Enblad Gunilla , Leppä Sirpa
Published: February 2007

Germinal center (GC) and non-GC phenotypes are predictors of outcome in diffuse large B-cell lymphoma (DLBCL) and can be used to stratify chemotherapy-treated patients into low- and high-risk groups. To determine how combination of rituximab with chemotherapy influences GC-associated clinical outcome, GC and non-GC phenotypes were identified immunohistochemically from samples of 90 de novo DLBCL patients treated with rituximab in combination with CHOP (cyclophosphamide, doxorubicin, vincristine, and prednisone)–like regimen (immunochemotherapy). One hundred and four patients previously treated with chemotherapy served as a control group. Consistent with previous studies, chemotherapy-treated patients with immunohistochemically defined GC phenotype displayed a significantly better overall (OS) and failure-free survival (FFS) than the non-GC group (OS, 70% vs 47%, P = .012; FFS, 59% vs 30%, P = .001). In contrast, immunohistochemically defined GC phenotype did not predict outcome in immunochemotherapy-treated patients (OS, 77% vs 76%, P = ns; FFS, 68% vs 63%, P = ns). In comparison, International Prognostic Index (IPI) could separate the high-risk patients from low- and intermediate-risk groups (OS, 84% vs 63%, P = .030; FFS, 79% vs 52%, P = .028). We conclude that rituximab in combination with chemotherapy seems to eliminate the prognostic value of immunohistochemically defined GC- and non-GC phenotypes in DLBCL.
Reporter Expression, Induced by a Growth Hormone Promoter-Driven Cre Recombinase (rGHp-Cre) Transgene, Questions the Developmental Relationship between Somatotropes and Lactotropes in the Adult Mouse Pituitary Gland
Authors: Luque Raul M. , Amargo Geraldine , Ishii Shinya , Lobe Corrinne , Franks Roberta , Kiyokawa Hiro , Kineman Rhonda D.
Published: February 2007

This report describes the development and validation of the rGHp-Cre transgenic mouse that allows for selective Cre-mediated recombination of loxP-modified alleles in the GH-producing cells of the anterior pituitary. Initial screening of the rGHp-Cre parental line showed Cre mRNA was specifically expressed in the anterior pituitary gland of adult Cre+/− mice and cephalic extracts of e17 Cre+/− fetuses. Heterozygote rGHp-Cre transgenic mice were crossbred with Z/AP reporter mice to generate Cre+/−,Z/AP+/− offspring. In this model system, the GH promoter-driven, Cre-mediated recombination of the Z/AP reporter leads to human placental alkaline phosphatase (hPLAP) expression that serves to mark cells that currently produce GH, in addition to cells that would have differentiated from GH cells but currently do not express the GH gene. Double immunocytochemistry of adult male and female Cre+/−,Z/AP+/− pituitary cells revealed the majority (∼99%) of GH-producing cells of the anterior pituitary also expressed hPLAP, whereas ACTH-, TSH-, and LH-producing cells were negative for hPLAP, confirming previous reports that corticotropes, thyrotropes, and gonadotropes develop independently of the somatotrope lineage. A small subset (∼10%) of the prolactin-producing cells was positive for hPLAP, consistent with previous reports showing lactotropes can arise from somatotropes during pituitary development. However, the fact that 90% of prolactin-producing cells were negative for hPLAP suggests that the majority of lactotropes in the adult mouse pituitary gland develop independently of the somatotrope lineage. In addition to developmental studies, the rGHp-Cre transgenic mouse will provide a versatile tool to study the role of a variety of genes in somatotrope function and neoplastic transformation.
Preanalytical mRNA Stabilization of Whole Bone Marrow Samples
Authors: Langebrake Claudia , Günther Kalle , Lauber Jürgen , Reinhardt Dirk
Published: February 2007

Background: Gene expression profiling is a useful tool for cancer diagnosis and basic research. A major limitation is that, even during short-term storage of native specimens of peripheral blood or bone marrow (BM) and/or RNA isolation, significant changes of gene expression pattern can occur because of gene induction, repression, and RNA degradation.

Methods: We investigated the effectiveness of a newly developed RNA stabilization and preparation system for BM specimens (PAXgene™ Bone Marrow RNA System) over time. We analyzed 256 RNA samples, processed from 64 BM specimens.

Results: Although the overall RNA yield (normalized to 1 × 107 leukocytes) was not different, the RNA preparation using unstabilized reference samples had an ∼3 times higher failure rate. With the PAXgene system, we observed significantly higher RNA integrity compared with the reference RNA preparation system (P <0.01). In the stabilized samples, we found very high pairwise correlation in gene expression (ΔΔCT 0.16–0.53) for the analyzed genes (GATA1, RUNX1, NCAM1, and SPI1) after 48-h storage compared with immediate preparation of RNA (2 h after BM collection). However, we found major differences in half of the analyzed genes using the reference RNA isolation procedure (ΔΔCT 1.07 and 1.32).

Conclusions: The PAXgene system is able to stabilize RNA from clinical BM samples and is suitable to isolate high-quality and -quantity RNA.
A Simple Connectivity Scheme for Sparse Coding in an Olfactory System
Authors: Jortner Ron A. , Farivar S. Sarah , Laurent Gilles
Published: February 2007

Recent studies, using unbiased sampling of neuronal activityin vivo, indicate the existence of sparse codes in the brain. These codes are characterized by highly specific, associative (i.e., dependent on combinations of features) and often invariant neuronal responses. Sparse representations present many advantages for memory storage and are, thus, of wide interest in sensory physiology. Here, we study the statistics of connectivity in an olfactory network that contributes to the generation of such codes: Kenyon cells (KCs), the intrinsic neurons of the mushroom body (a structure involved in learning and memory in insects) receive inputs from a small population of broadly tuned principal neurons; from these inputs, KCs generate exquisitely selective responses and, thus, sparse representations. We find, surprisingly, that KCs are on average each connected to about 50% of their input population. Simple analysis indicates that such connectivity indeed maximizes the difference between input vectors to KCs and helps to explain their high specificity.
Neuartiger, auf Dehnungsmessstreifen basierender Dehnungsaufnehmer für die Bauwerksüberwachung (A New Type of Strain-Gauge-based Strain-Sensor for the Monitoring of Buildings)
Authors: Tegtmeier Falk
Published: February 2007

Die Überwachung von Bauwerken erfordert eine präzise und dauerhafte Messung der mechanischen Lastzustände. Zu diesem Zweck wurde ein gekapselter Sensor entwickelt, der die empfindliche DMS-Technik in seinem Inneren schützt und der einfach in einer kleinen Messbohrung im Bauwerk montiert wird. Für die mechanische Adaption wurde eine Ausführung in Form zweier konischer, ineinander verspannter und im Querschnitt achteckiger Körper entwickelt. Die neuartige Sensorform erforderte sowohl einen speziellen Mehrfachgitter-DMS als auch ein spezielles Kalibrierverfahren. Zur Kapselung des DMS wurde eine ebenfalls neuartige Kunststoffkapselung erforscht, die in zeitlich stark beschleunigten Alterungstests bezüglich einer geforderten jahrzehntelangen Lebensdauer verifiziert wurde.
Poisoning the Planet: The Struggle for Environmental Justice
Authors: Pellow David Naguib , Brulle Robert J.
Published: February 2007

Like good things, bad things are unequally distributed in America. Poor minorities get more than their share of environmental hazards-but they are fighting back.
Effects of genetic immunization of Swiss outbred mice with human thyroid stimulating hormone receptor cDNA plasmids harboring gain-of-function mutations
Authors: Ho Su-Chin , Goh Sui-Sin , Kee Irene H C , Chow Pierce K H , Yeo Chin-Pin , Khoo Daphne H C
Published: February 2007

Animal models of Graves’ disease have been generated in recent years with various vaccination protocols using wild-type TSH receptor. In this study, we report the findings of genetic immunization of Swiss outbred mice with three different mutated human TSH receptor plasmids, each containing one constitutive activating mutation located at the ectodomain (S281N), exoloop (I486F), and transmembrane segment (D633H) respectively. Although the overall rate of thyrotoxicosis in the mice was < 10%, anti-TSH receptor antibodies could be detected in many animals by flow cytometry, radioreceptor assay, and functional bioassays using recombinant human TSH receptor. Mice injected with plasmids harboring activated mutants (S281N and D633H) showed production of predominantly stimulating antibodies, whilst those treated with wild-type receptor plasmids generated mainly blocking sera. Most of these antibodies displaced radiolabeled bovine TSH, and their epitopes, independent of functional characteristics, were mapped to the first 271 amino acids of the TSH receptor. This supports recent findings that binding of stimulatory or blocking antibodies lie in close proximity within the leucine-rich repeat region.