bluuebunny/crossref_metadata_2025 huggingface dataset:
Azacytidine causes complex DNA methylation responses in myeloid leukemia
Authors: Stresemann Carlo , Bokelmann Imke , Mahlknecht Ulrich , Lyko Frank
Published: September 2008

Aberrant DNA methylation patterns play an important role in the pathogenesis of hematologic malignancies. The DNA methyltransferase inhibitors azacytidine and decitabine have shown significant clinical benefits in the treatment of myelodysplastic syndrome (MDS), but their precise mode of action remains to be established. Both drugs have been shown the ability to deplete DNA methyltransferase enzymes and to induce DNA demethylation and epigenetic reprogramming in vitro. However, drug-induced methylation changes have remained poorly characterized in patients and therapy-related models. We have now analyzed azacytidine-induced demethylation responses in myeloid leukemia cell lines. These cells showed remarkable differences in the drug-induced depletion of DNA methyltransferases that coincided with their demethylation responses. In agreement with these data, DNA methylation analysis of blood and bone marrow samples from MDS patients undergoing azacytidine therapy also revealed substantial differences in the epigenetic responses of individual patients. Significant, transient demethylation could be observed in 3 of 6 patients and affected many hypermethylated loci in a complex pattern. Our results provide important proof-of-mechanism data for the demethylating activity of azacytidine in MDS patients and provide detailed insight into drug-induced demethylation responses. [Mol Cancer Ther 2008;7(9):2998–3005]
Atypical retinoids ST1926 and CD437 are S-phase-specific agents causing DNA double-strand breaks: significance for the cytotoxic and antiproliferative activity
Authors: Valli Claudia , Paroni Gabriela , Di Francesco Angela Maria , Riccardi Riccardo , Tavecchio Michele , Erba Eugenio , Boldetti Andrea , Gianni' Maurizio , Fratelli Maddalena , Pisano Claudio , Merlini Lucio , Antoccia Antonio , Cenciarelli Chiara , Terao Mineko , Garattini Enrico
Published: September 2008

Retinoid-related molecules (RRM) are novel agents with tumor-selective cytotoxic/antiproliferative activity, a different mechanism of action from classic retinoids and no cross-resistance with other chemotherapeutics. ST1926 and CD437 are prototypic RRMs, with the former currently undergoing phase I clinical trials. We show here that ST1926, CD437, and active congeners cause DNA damage. Cellular and subcellular COMET assays, H2AX phosphorylation (γ-H2AX), and scoring of chromosome aberrations indicate that active RRMs produce DNA double-strand breaks (DSB) and chromosomal lesions in NB4, an acute myeloid leukemia (AML) cell line characterized by high sensitivity to RRMs. There is a direct quantitative correlation between the levels of DSBs and the cytotoxic/antiproliferative effects induced by RRMs. NB4.437r blasts, which are selectively resistant to RRMs, do not show any sign of DNA damage after treatment with ST1926, CD437, and analogues. DNA damage is the major mechanism underlying the antileukemic activity of RRMs in NB4 and other AML cell lines. In accordance with the S-phase specificity of the cytotoxic and antiproliferative responses of AML cells to RRMs, increases in DSBs are maximal during the S phase of the cell cycle. Induction of DSBs precedes inhibition of DNA replication and is associated with rapid activation of ataxia telangectasia mutated, ataxia telangectasia RAD3-related, and DNA-dependent protein kinases with subsequent stimulation of the p38 mitogen-activated protein kinase. Inhibition of ataxia telangectasia mutated and DNA-dependent protein kinases reduces phosphorylation of H2AX. Cells defective for homologous recombination are particularly sensitive to ST1926, indicating that this process is important for the protection of cells from the RRM-dependent DNA damage and cytotoxicity. [Mol Cancer Ther 2008;7(9):2941–54]
Increased cyclin D1 expression can mediate BRAF inhibitor resistance in BRAF V600E–mutated melanomas
Authors: Smalley Keiran S.M. , Lioni Mercedes , Palma Maurizia Dalla , Xiao Min , Desai Brijal , Egyhazi Suzanne , Hansson Johan , Wu Hong , King Alastair J. , Van Belle Patricia , Elder David E. , Flaherty Keith T. , Herlyn Meenhard , Nathanson Katherine L.
Published: September 2008

Recent studies have shown that there is a considerable heterogeneity in the response of melanoma cell lines to MEK and BRAF inhibitors. In the current study, we address whether dysregulation of cyclin-dependent kinase 4 (CDK4) and/or cyclin D1 contribute to the BRAF inhibitor resistance of melanoma cells. Mutational screening identified a panel of melanoma cell lines that harbored both a BRAF V600E mutation and a CDK4 mutation: K22Q (1205Lu), R24C (WM39, WM46, and SK-Mel-28), and R24L (WM902B). Pharmacologic studies showed that the presence of a CDK4 mutation did not alter the sensitivity of these cell lines to the BRAF inhibitor. The only cell line with significant BRAF inhibitor resistance was found to harbor both a CDK4 mutation and a CCND1 amplification. Array comparative genomic hybridization analysis showed that CCND1 was amplified in 17% of BRAF V600E–mutated human metastatic melanoma samples, indicating the clinical relevance of this finding. As the levels of CCND1 amplification in cell lines are lower than those seen in clinical specimens, we overexpressed cyclin D1 alone and in the presence of CDK4 in a drug-sensitive melanoma line. Cyclin D1 overexpression alone increased resistance and this was enhanced when cyclin D1 and CDK4 were concurrently overexpressed. In conclusion, increased levels of cyclin D1, resulting from genomic amplification, may contribute to the BRAF inhibitor resistance of BRAF V600E–mutated melanomas, particularly when found in the context of a CDK4 mutation/overexpression. [Mol Cancer Ther 2008;7(9):2876–83]
Administration of PLK-1 small interfering RNA with atelocollagen prevents the growth of liver metastases of lung cancer
Authors: Kawata Eri , Ashihara Eishi , Kimura Shinya , Takenaka Kazumasa , Sato Kiyoshi , Tanaka Ruriko , Yokota Asumi , Kamitsuji Yuri , Takeuchi Miki , Kuroda Junya , Tanaka Fumihiro , Yoshikawa Toshikazu , Maekawa Taira
Published: September 2008

Liver metastasis is one of the most important prognostic factors in lung cancer patients. However, current therapies are not sufficient. RNA interference provides us a powerful and promising approach for treating human diseases including cancers. Herein, we investigated the in vitro effects of PLK-1 small interfering RNA (siRNA) on human lung cancer cell lines and the in vivo usage of PLK-1 siRNA with atelocollagen as a drug delivery system in a murine liver metastasis model of lung cancer. PLK-1 was overexpressed in cell lines and in cancerous tissues from lung cancer patients. PLK-1 siRNA treatment inhibited growth and induced apoptosis in a concentration-dependent manner. To verify in vivo efficacy, we confirmed that atelocollagen was a useful drug delivery system in our model of implanted luciferase-labeled A549LUC cells by detecting reduced bioluminescence after an i.v. injection of luciferase GL3 siRNA/atelocollagen. PLK-1 siRNA/atelocollagen was also successfully transfected into cells and inhibited the progression of metastases. This study shows the efficacy of i.v. administration of PLK-1 siRNA/atelocollagen for liver metastases of lung cancer. We believe siRNA therapy will be a powerful and promising strategy against advanced lung cancer. [Mol Cancer Ther 2008;7(9):2904–12]
An orally bioavailable small-molecule inhibitor of Hedgehog signaling inhibits tumor initiation and metastasis in pancreatic cancer
Authors: Feldmann Georg , Fendrich Volker , McGovern Karen , Bedja Djahida , Bisht Savita , Alvarez Hector , Koorstra Jan-Bart M. , Habbe Nils , Karikari Collins , Mullendore Michael , Gabrielson Kathleen L. , Sharma Rajni , Matsui William , Maitra Anirban
Published: September 2008

Recent evidence suggests that blockade of aberrant Hedgehog signaling can be exploited as a therapeutic strategy for pancreatic cancer. Our previous studies using the prototype Hedgehog small-molecule antagonist cyclopamine had shown the striking inhibition of systemic metastases on Hedgehog blockade in spontaneously metastatic orthotopic xenograft models. Cyclopamine is a natural compound with suboptimal pharmacokinetics, which impedes clinical translation. In the present study, a novel, orally bioavailable small-molecule Hedgehog inhibitor, IPI-269609, was tested using in vitro and in vivo model systems. In vitro treatment of pancreatic cancer cell lines with IPI-269609 resembled effects observed using cyclopamine (i.e., Gli-responsive reporter knockdown, down-regulation of the Hedgehog target genes Gli1 and Ptch, as well as abrogation of cell migration and colony formation in soft agar). Single-agent IPI-269609 profoundly inhibited systemic metastases in orthotopic xenografts established from human pancreatic cancer cell lines, although Hedgehog blockade had minimal effect on primary tumor volume. The only discernible phenotype observed within the treated primary tumor was a significant reduction in the population of aldehyde dehydrogenase–bright cells, which we have previously identified as a clonogenic tumor-initiating population in pancreatic cancer. Selective ex vivo depletion of aldehyde dehydrogenase–bright cells with IPI-269609 was accompanied by significant reduction in tumor engraftment rates in athymic mice. Pharmacologic blockade of aberrant Hedgehog signaling might prove to be an effective therapeutic strategy for inhibition of systemic metastases in pancreatic cancer, likely through targeting subsets of cancer cells with tumor-initiating (“cancer stem cell”) properties. [Mol Cancer Ther 2008;7(9):2725–35]
Cytoskeletal Protein 4.1R Affects Repolarization and Regulates Calcium Handling in the Heart
Authors: Stagg Mark A. , Carter Edward , Sohrabi Nadia , Siedlecka Urszula , Soppa Gopal K. , Mead Fiona , Mohandas Narla , Taylor-Harris Pamela , Baines Anthony , Bennett Pauline , Yacoub Magdi H. , Pinder Jennifer C. , Terracciano Cesare M.N.
Published: September 2008

The 4.1 proteins are a family of multifunctional adaptor proteins. They promote the mechanical stability of plasma membranes by interaction with the cytoskeletal proteins spectrin and actin and are required for the cell surface expression of a number of transmembrane proteins. Protein 4.1R is expressed in heart and upregulated in deteriorating human heart failure, but its functional role in myocardium is unknown. To investigate the role of protein 4.1R on myocardial contractility and electrophysiology, we studied 4.1R-deficient (knockout) mice (4.1R KO). ECG analysis revealed reduced heart rate with prolonged Q-T interval in 4.1R KO. No changes in ejection fraction and fractional shortening, assessed by echocardiography, were found. The action potential duration in isolated ventricular myocytes was prolonged in 4.1R KO. Ca
2+
transients were larger and slower to decay in 4.1R KO. The sarcoplasmic reticulum Ca
2+
content and Ca
2+
sparks frequency were increased. The Na
+
/Ca
2+
exchanger current density was reduced in 4.1R KO. The transient inward current inactivation was faster and the persistent Na
+
current density was increased in the 4.1R KO group, with possible effects on action potential duration. Although no major morphological changes were noted, 4.1R KO hearts showed reduced expression of NaV1.5α and increased expression of protein 4.1G. Our data indicate an unexpected and novel role for the cytoskeletal protein 4.1R in modulating the functional properties of several cardiac ion transporters with consequences on cardiac electrophysiology and with possible significant roles during normal cardiac function and disease.
BMPER Is an Endothelial Cell Regulator and Controls Bone Morphogenetic Protein-4–Dependent Angiogenesis
Authors: Heinke Jennifer , Wehofsits Leonie , Zhou Qian , Zoeller Christoph , Baar Kim-Miriam , Helbing Thomas , Laib Anna , Augustin Hellmut , Bode Christoph , Patterson Cam , Moser Martin
Published: September 2008

Bone morphogenetic proteins (BMPs) are involved in embryonic and adult blood vessel formation in health and disease. BMPER (BMP endothelial cell precursor–derived regulator) is a differentially expressed protein in embryonic endothelial precursor cells. In earlier work, we found that BMPER interacts with BMPs and when overexpressed antagonizes their function in embryonic axis formation. In contrast, in a BMPER-deficient zebrafish model, BMPER behaves as a BMP agonist. Furthermore, lack of BMPER induces a vascular phenotype in zebrafish that is driven by disarray of the intersomitic vasculature. Here, we investigate the impact of BMPER on endothelial cell function and signaling and elucidate its role in BMP-4 function in gain- and loss-of-function models. As shown by Western blotting and immunocytochemistry, BMPER is an extracellular matrix protein expressed by endothelial cells in skin, heart, and lung. We show that BMPER is a downstream target of FoxO3a and consistently exerts activating effects on endothelial cell sprouting and migration in vitro and in vivo. Accordingly, when BMPER is depleted from endothelial cells, sprouting is impaired. In terms of BMPER related intracellular signaling, we show that BMPER is permissive and necessary for Smad 1/5 phosphorylation and induces Erk1/2 activation. Most interestingly, BMPER is necessary for BMP-4 to exert its activating role in endothelial function and to induce Smad 1/5 activation. Vice versa, BMP-4 is necessary for BMPER activity. Taken together, BMPER is a dose-dependent endothelial cell activator that plays a unique and pivotal role in fine-tuning BMP activity in angiogenesis.
Moyamoya Disease in Europeans
Authors: Kraemer Markus , Heienbrok Wilhelm , Berlit Peter
Published: September 2008

Background and Purpose—

We describe the clinical, diagnostic, and outcome features of a cohort of white patients with idiopathic moyamoya disease treated in a German institution.

Methods—

Our cohort included 21 white patients with moyamoya disease. Clinical and diagnostic features were obtained by retrospective chart review; follow-up information and outcome were obtained prospectively. We used the Kaplan–Meier methods to estimate stroke risk by treatment status.

Results—

The mean age at onset of symptoms was 31 years. The female predominance was 4.25:1. In our cohort, the initial symptom was a cerebral ischemic event in all patients. There was no patient with a hemorrhage at onset; only one patient experienced subarachnoidal hemorrhage in the further course of disease. The Kaplan–Meier risk for recurrent stroke was very high after the first ischemic event and smaller after angiographic diagnosis. The 5-year-Kaplan–Meier risk of recurrent stroke was 80.95% after the first ischemic event for all patients. Most subsequent ischemic events appeared in the first 2 years after symptom onset. Eleven patients (52.3%) underwent neurosurgical revascularizing procedures. After surgery, the Kaplan–Meier risk of perioperative or subsequent stroke was 27.27% within the first month and was stable thereafter.

Conclusion—

Clinical features and course of moyamoya disease of whites analyzed in this German study are comparable to American results. Moyamoya disease in whites differs clearly from Asian moyamoya disease in timing of onset of vasculopathy and lower rate of hemorrhages.
The Prevalence of Joint Contractures, Pressure Sores, Painful Shoulder, Other Pain, Falls, and Depression in the Year After a Severely Disabling Stroke
Authors: Sackley Catherine , Brittle Nicola , Patel Smitaa , Ellins Julie , Scott Martin , Wright Cristine , Dewey Michael E.
Published: September 2008

Background and Purpose—

Complications after stroke have been shown to impede rehabilitation, lead to poor functional outcome, and increase cost of care. This inception cohort study sought to investigate the prevalence of immobility-related complications during the first year after severely disabling stroke in relation to functional independence and place of residence.

Methods—

Over a 7-month period, 600 stroke survivors were identified in the hospital through the Nottingham Stroke Register. Those who had a Barthel Index score ≤10 3 months poststroke and did not have a primary diagnosis of dementia were eligible to participate in the study. Assessments of complications were carried out at 3, 6, and 12 months poststroke.

Results—

Complications were recorded for 122 stroke survivors (mean age, 76 years; 57% male). Sixty-three (52%) had significant language impairment and of the remaining 59 who were able to complete an assessment of cognitive function, 10 (8%) were cognitively impaired. The numbers of reported complications over 12 months, in rank order, were falls, 89 (73%); contracture, 73 (60%); pain, 67 (55%); shoulder pain, 64 (52%); depression, 61 (50%); and pressure sores, 26 (22%). A negative correlation was found between Barthel Index score and the number of complications experienced (low scores on the Barthel Index correlate with a high number of complications). The highest relative percentages of complications were experienced by patients who were living in a nursing home at the time of their last completed assessment.

Conclusions—

Immobility-related complications are very common in the first year after a severely disabling stroke. Patients who are more functionally dependent in self-care are likely to experience a greater number of complications than those who are less dependent. Trials of techniques to limit and prevent complication are required.
Is Mobile Teleconsulting Equivalent to Hospital-Based Telestroke Services?
Authors: Audebert Heinrich J. , Boy Sandra , Jankovits Ralf , Pilz Philipp , Klucken Jochen , Fehm Nando P. , Schenkel Johannes
Published: September 2008

Background and Purpose—

Telemedicine is increasingly used to provide acute stroke expertise for hospitals without full-time neurological services. Teleconsulting through mobile laptop computers may offer more flexibility compared with hospital-based services, but concerns about quality and technical reliability remain.

Methods—

We conducted a controlled trial, allocating hospital-based or mobile teleconsulting in a shift-by-shift sequence and evaluating technical parameters, acceptability, and impact on immediate clinical decisions. Both types of telemedicine workstations were equipped with DICOM (Digital-Imaging-and-Communications-in-Medicine) viewer and videoconference software. The laptop connected by asymmetrical broadband UMTS (Universal-Mobile-Telecommunication-Systems) technology with a one-way spoke-to-hub video transmission, whereas the hospital-based device used landline symmetrical telecommunication, including a 2-way videoconference.

Results—

One hundred twenty-seven hospital-based and 96 mobile teleconsultations were conducted within 2 months without any technical breakdown. The rates per allocated time were similar with 3.8 and 4.0 per day. No significant differences were found for durations of videoconference (mean: 11±3 versus 10±3 minutes,
P
=0.07), DICOM download (3±3 versus 4±3 minutes,
P
=0.19), and total duration of teleconsultations (44±19 versus 45±21 minutes,
P
=0.98). Technical quality of mobile teleconsultations was rated worse on both sides, but this did not affect the ability to make remote clinical decisions like initiating thrombolysis (17% versus 13% of all,
P
=0.32).

Conclusions—

Teleconsultation using a laptop workstation and broadband mobile telecommunication was technically stable and allowed remote clinical decision-making. There remain disadvantages regarding videoconference quality on the hub side and lack of video transmission to the spoke side.
Male Predominance in Childhood Ischemic Stroke
Authors: Golomb Meredith R. , Fullerton Heather J. , Nowak-Gottl Ulrike , deVeber Gabrielle
Published: September 2008

Background and Purpose—

Previous studies suggested a male predominance in childhood ischemic stroke, mirroring gender differences in adults but were limited by small sample sizes or unconfirmed diagnoses. We sought to study gender within a large international series of confirmed cases of pediatric ischemic stroke.

Methods—

From January 2003 to July 2007, the International Pediatric Stroke Study enrolled children (0 up to 19 years) with arterial ischemic stroke or cerebral sinovenous thrombosis at 30 centers in 10 countries. Neonates were those <29 days of age. We calculated the “expected” gender ratio for our study as the weighted average of population-based childhood gender ratios in enrolling countries weighted by the number of subjects enrolled in each country. χ
2
tests were used to compare the observed gender ratios in our series with this expected ratio (51.7%).

Results—

Among 1187 children with confirmed ischemic stroke, 710 were boys (60%,
P
<0.0001). Male predominance persisted after stratification by age (61% for neonates,
P
=0.011; 59% for later childhood,
P
=0.002) and stroke subtype (58% for arterial ischemic stroke,
P
=0.004; 65% for cerebral sinovenous thrombosis,
P
=0.002). The greatest proportion of males occurred among children with arterial ischemic stroke and a history of trauma (75%,
P
=0.008), although boys were also overrepresented among those with arterial ischemic stroke and no trauma (57%;
P
=0.07). There were no gender differences in case fatality or deficits at discharge.

Conclusions—

Childhood ischemic stroke appears to be more common in boys regardless of age, stroke subtype, or history of trauma. Further exploration of this gender difference could shed light on stroke mechanisms in both children and adults.
Segment-Specific Genetic Effects on Carotid Intima-Media Thickness
Authors: Liao Yi-Chu , Lin Hsiu-Fen , Rundek Tatjana , Cheng Rong , Guo Yuh-Cherng , Sacco Ralph L. , Juo Suh-Hang Hank
Published: September 2008

Background and Purpose—

Carotid intima-media thickness (IMT) is a surrogate marker of subclinical atherosclerosis and a strong predictor of stroke and myocardial infarction. The object of this study was to determine the association between carotid IMT and 702 single nucleotide polymorphisms in 145 genes.

Methods—

B-mode carotid ultrasound was performed among 408 Hispanics from the Northern Manhattan Study. The common carotid artery IMT and bifurcation IMT were phenotypes of interest. Genetic effects were evaluated by the multivariate regression model adjusting for traditional vascular risk factors. For each individual, we calculated a gene risk score (GRS) defined as the total number of the significant single nucleotide polymorphisms in different genes. Subjects were then divided into 3 GRS categories using the 2 cutoff points: mean GRS ±1 SD.

Results—

We identified 6 significant single nucleotide polymorphisms in 6 genes for common carotid artery IMT and 7 single nucleotide polymorphisms in 7 genes for bifurcation IMT using the probability value of 0.005 as the significant level. There were no common significant genes for both phenotypes. The most significant genes were the tissue plasminogen activator (
P
=0.0005 for common carotid artery IMT) and matrix metallopeptidase-12 genes (
P
=0.0004 for bifurcation IMT). Haplotype analysis did not yield a more significant result. Subjects with GRS ≥9 had significantly increased IMT than those with GRS ≤5 (
P
<0.001). GRS was an independent predictor of both common carotid artery IMT (
P
=2.3×10
−9
) and bifurcation MT (
P
=7.2×10
−8
).

Conclusions—

Multiple genes contributed to the variation in carotid IMT. IMT in different carotid segments may be regulated by different sets of susceptibility genes.
Gustav Mie and the Evolving Discipline of Electromagnetic Scattering by Particles
Authors: Mishchenko Michael I. , Travis Larry D.
Published: September 2008

The year 2008 marks the centenary of the seminal paper by Gustav Mie on electromagnetic scattering by homogeneous spherical particles. Having been cited in almost 4,000 journal articles since 1955 (according to the Science Citation Index Expanded database), Mie s paper has been among the more influential scientific publications of the twentieth century. It has affected profoundly the development of a great variety of natural science disciplines including atmospheric radiation, meteorological optics, remote sensing, aerosol physics, astrophysics, and biomedical optics. Mies paper represented a fundamental advancement over the earlier publications by Ludvig Lorenz in that it was explicitly based on the Maxwell equations, gave the final solution in a convenient form suitable for practical computations, and imparted physical reality to the abstract concept of electromagnetic scattering. The Mie solution anticipated such general concepts as far-field scattering and the Sommerfeld-Silver-Müller boundary conditions at infinity as well as paved the way to such important extensions as the separation of variables method for spheroids and the T-matrix method. Key ingredients of the Mie theory are quite prominent in the superposition T-matrix method for clusters of particles and even in the recent microphysical derivation of the radiative transfer equation. Among the most illustrative uses of the Mie solution have been the explanation of the spectacular optical displays caused by cloud and rain droplets, the identification of sulfuric acid particles in the atmosphere of Venus from Earth-based polarimetry, and optical particle characterization based on measurements of morphology-dependent resonances. Yet it is clear that the full practical potential of the Mie theory is still to be revealed.
How Well Does Water Activity Determine Homogeneous Ice Nucleation Temperature in Aqueous Sulfuric Acid and Ammonium Sulfate Droplets?
Authors: Swanson Brian D.
Published: September 2008

Frozen fraction measurements made using a droplet free-fall freezing tube apparatus are presented and used, along with other recent laboratory measurements, to evaluate how well both the water activity idea and the translated melting-point curve idea of Koop et al. predict homogeneous freezing-point temperatures for aqueous ammonium sulfate and sulfuric acid solution droplets. The new freezing-point temperature datasets agree with the previous lowest-temperature results for both solutes. The lowest measured freezing-point temperatures for aqueous ammonium sulfate solutions agree with a curve shaped like the translated melting-point curve. However, those for aqueous sulfuric acid solutions are significantly lower than predicted by the translated melting-point curve idea, and a single water activity freezing-point temperature curve does not represent the lowest-temperature freezing-point temperature data for both solutes. A linear extrapolation of the new aqueous sulfuric acid solution freezing data to low temperatures predicts that high critical supersaturations in cloud-free regions of the upper troposphere will occur when homogeneous ice nucleation in an aqueous sulfuric acid aerosol is the primary ice formation mechanism.
Effects of Tropical Deforestation on Global Hydroclimate: A Multimodel Ensemble Analysis
Authors: Hasler Natalia , Werth David , Avissar Roni
Published: September 2008

Two multimodel ensembles (MME) were produced with the GISS Model II (GM II), the GISS Atmosphere Model (AM), and the NCAR Community Climate System Model (CCSM) to evaluate the effects of tropical deforestation on the global hydroclimate. Each MME used the same 48-yr period but the two were differentiated by their land-cover types. In the “control” case, current vegetation was used, and in the “deforested” case, all tropical rain forests were converted to a mixture of shrubs and grassland. Globally, the control simulations produced with the three GCMs compared well to observations, both in the time mean and in the temporal variability, although various biases exist in the different tropical rain forests.

The local precipitation response to deforestation is very strong. The remote effect in the tropics (away from the deforested tropical areas) is strong as well, but the effects at midlatitudes are weaker. In the MME, the impacts tend to be attenuated relative to the individual models.

The significance of the geopotential and precipitation responses was evaluated with a bootstrap method, and results varied during the year. Tropical deforestation also produced anomalous fluxes in potential energy that were a direct response to the deforestation. These different analyses confirmed the existence of a teleconnection mechanism due to deforestation.
Tropical Water Vapor and Cloud Feedbacks in Climate Models: A Further Assessment Using Coupled Simulations
Authors: Sun De-Zheng , Yu Yongqiang , Zhang Tao
Published: September 2008

By comparing the response of clouds and water vapor to ENSO forcing in nature with that in Atmospheric Model Intercomparison Project (AMIP) simulations by some leading climate models, an earlier evaluation of tropical cloud and water vapor feedbacks has revealed the following two common biases in the models: 1) an underestimate of the strength of the negative cloud albedo feedback and 2) an overestimate of the positive feedback from the greenhouse effect of water vapor. Extending the same analysis to the fully coupled simulations of these models as well as other Intergovernmental Panel on Climate Change (IPCC) coupled models, it is found that these two biases persist. Relative to the earlier estimates from AMIP simulations, the overestimate of the positive feedback from water vapor is alleviated somewhat for most of the coupled simulations. Improvements in the simulation of the cloud albedo feedback are only found in the models whose AMIP runs suggest either a positive or nearly positive cloud albedo feedback. The strength of the negative cloud albedo feedback in all other models is found to be substantially weaker than that estimated from the corresponding AMIP simulations. Consequently, although additional models are found to have a cloud albedo feedback in their AMIP simulations that is as strong as in the observations, all coupled simulations analyzed in this study have a weaker negative feedback from the cloud albedo and therefore a weaker negative feedback from the net surface heating than that indicated in observations. The weakening in the cloud albedo feedback is apparently linked to a reduced response of deep convection over the equatorial Pacific, which is in turn linked to the excessive cold tongue in the mean climate of these models. The results highlight that the feedbacks of water vapor and clouds—the cloud albedo feedback in particular—may depend on the mean intensity of the hydrological cycle. Whether the intermodel variations in the feedback from cloud albedo (water vapor) in the ENSO variability are correlated with the intermodel variations of the feedback from cloud albedo (water vapor) in global warming has also been examined. While a weak positive correlation between the intermodel variations in the feedback of water vapor during ENSO and the intermodel variations in the water vapor feedback during global warming was found, there is no significant correlation found between the intermodel variations in the cloud albedo feedback during ENSO and the intermodel variations in the cloud albedo feedback during global warming. The results suggest that the two common biases revealed in the simulated ENSO variability may not necessarily be carried over to the simulated global warming. These biases, however, highlight the continuing difficulty that models have in simulating accurately the feedbacks of water vapor and clouds on a time scale of the observations available.
Southern Hemisphere Westerly Wind Control over the Ocean's Thermohaline Circulation
Authors: Sijp Willem P. , England Matthew H.
Published: September 2008

The effect of the position of the Southern Hemisphere subpolar westerly winds (SWWs) on the thermohaline circulation (THC) of the World Ocean is examined. The latitudes of zero wind stress curl position exert a strong control on the distribution of overturning between basins in the Northern Hemisphere. A southward wind shift results in a stronger Atlantic THC and enhanced stratification in the North Pacific, whereas a northward wind shift leads to a significantly reduced Atlantic THC and the development of vigorous sinking (up to 1500-m depth) in the North Pacific. In other words, the Atlantic dominance of the meridional overturning circulation depends on the position of the zero wind stress curl over the Southern Ocean in the experiments. This position has a direct influence on the surface salinity contrast between the Pacific and the Atlantic, which is then further amplified by changes in the distribution of Northern Hemisphere sinking between these basins. The results show that the northward location of the SWW stress maximum inferred for the last glacial period may have contributed to significantly reduced North Atlantic Deep Water formation during this period, and perhaps an enhanced and deeper North Pacific THC. Also, a more poleward location of the SWW stress maximum in the current warming climate may entail stronger salinity stratification of the North Pacific.
Ability to Forecast Regional Soil Moisture with a Distributed Hydrological Model Using ECMWF Rainfall Forecasts
Authors: Schuurmans J. M. , Bierkens M. F. P.
Published: September 2008

This study mimics an online forecast system to provide nine day-ahead forecasts of regional soil moisture. It uses modified ensemble rainfall forecasts from the numerical weather prediction model of the European Centre for Medium-Range Weather Forecasts (ECMWF), which is provided by the Royal Netherlands Meteorological Office (KNMI). Both the individual ensembles as well as the mean of the ensembles are used as input for a hydrological model of a 70-km2 study area during March–November 2006. The outcomes are compared to the model run with high-resolution rainfall fields (based on 14 rain gauges within the study area and meteorological radar) as input. It is shown that the total spatial mean rainfall is forecasted very well for all lead times. The measured rainfall (spatial mean) shows a distribution with peaks at 0–1 and >10 mm day−1. These peaks are underestimated by the ensemble mean of the forecasts and this underestimation increases with lead time. This is not the case when ensemble members are used. Besides, the modeled uncertainty in rainfall by ECMWF underestimates the true uncertainty for all lead times and the number of rainfall events (thresholds 0.1, 0.5, and 1.0 mm) is overestimated. Absolute temporal mean bias values in root zone storage—that is, soil moisture—larger than 1 mm start to show for lead times longer than 3 days. The lower and upper bounds of bias for a lead time of 9 days are approximately −4 and 7 mm, respectively (negative values mean the forecasted soil moisture is underestimated). The bias in root zone storage shows a spatial pattern that represents the spatial pattern of total rainfall: areas with less rainfall than spatial average show a negative bias and vice versa. Local differences within this spatial pattern are due to land use and soil type. The results suggest that ensemble forecasts of soil moisture using ensemble rainfall forecasts from ECMWF are of practical use for water management, even at regional scales.
ASCAT Soil Moisture: An Assessment of the Data Quality and Consistency with the ERS Scatterometer Heritage
Authors: Naeimi Vahid , Bartalis Zoltan , Wagner Wolfgang
Published: September 2008

This article presents a first comparison between remotely sensed surface soil moisture retrieved with the European Remote Sensing Satellite-2 (ERS-2) scatterometer (SCAT) and the corresponding product provided by the Advanced Scatterometer (ASCAT) on board Meteorological Operation satellite (MetOp), the first of a series of three satellites providing, among other things, continuity of global soil moisture observations using active microwave techniques for the next 15 yr. Three months of collocated 2007 data were used from the SCAT and ASCAT, limited to two study regions with different land cover composition. The result of the assessment is satisfactory and ensures consistency of migrating soil moisture retrieval from the long-term SCAT dataset to ASCAT measurements. The influence of a shift of observation incidence angle ranges between the two instrument generations was not found to be significant for the soil moisture retrieval. The correlation coefficients (R) between two relative soil moisture (normalized water content) datasets compared in different incidence angle ranges are around 0.90 with root-mean-square error (RMSE) values in the order of 8.5. Results are expected to improve slightly further once the calibration of the ASCAT instrument is finalized.
Seasonal Variations of the Seychelles Dome Simulated in the CMIP3 Models
Authors: Yokoi Takaaki , Tozuka Tomoki , Yamagata Toshio
Published: September 2008

Using outputs from the “twentieth-century climate in coupled models” (20c3m) control run of the Coupled Model Intercomparison Project, phase 3 (CMIP3), coupled GCMs, the authors have examined how seasonal variations of the Seychelles Dome (SD) are simulated in the southwestern Indian Ocean. The observed SD shows a dominant semiannual signal due to the semiannual variation in the local Ekman upwelling resulting from a combination of two terms related to the wind stress curl and the zonal wind stress. However, all models fail to reproduce this important mechanism. In particular, the latter contribution—that determined by the seasonal variation of the zonal wind stress associated with the Indian monsoon—is not well simulated. Successful models need to reproduce the asymmetric nature of the monsoon: a shorter and stronger summer monsoon and a longer and weaker winter monsoon. Possible remedies for the model bias are also discussed.
Seasonal Kinetic Energy Variability of Near-Inertial Motions
Authors: Silverthorne Katherine E. , Toole John M.
Published: September 2008

Seasonal variability of near-inertial horizontal kinetic energy is examined using observations from a series of McLane Moored Profiler moorings located at 39°N, 69°W in the western North Atlantic Ocean in combination with a one-dimensional, depth-integrated kinetic energy model. The time-mean kinetic energy and shear vertical wavenumber spectra of the high-frequency motions at the mooring site are in reasonable agreement with the Garrett–Munk internal wave description. Time series of depth-dependent and depth-integrated near-inertial kinetic energy are calculated from available mooring data after filtering to isolate near-inertial-frequency motions. These data document a pronounced seasonal cycle featuring a wintertime maximum in the depth-integrated near-inertial kinetic energy deriving chiefly from the variability in the upper 500 m of the water column. The seasonal signal in the near-inertial kinetic energy is most prominent for motions with vertical wavelengths greater than 100 m but observable wintertime enhancement is seen down to wavelengths of the order of 10 m. Rotary vertical wavenumber spectra exhibit a dominance of clockwise-with-depth energy, indicative of downward energy propagation and implying a surface energy source. A simple depth-integrated near-inertial kinetic energy model consisting of a wind forcing term and a dissipation term captures the order of magnitude of the observed near-inertial kinetic energy as well as its seasonal cycle.
Baroclinicity Influences on Storm Divergence and Stratiform Rain: Subtropical Upper-Level Disturbances
Authors: Hopper Larry J. , Schumacher Courtney
Published: September 2008

Divergence structures associated with the spectrum of precipitating systems in the subtropics and midlatitudes are not well documented. A mesoscale model is used to quantify the relative importance different baroclinic environments have on divergence profiles for storms primarily caused by upper-level disturbances in southeastern Texas, a subtropical region. The divergence profiles simulated for a subset of the modeled storms are consistent with those calculated from an S-band Doppler radar. Realistic convective and stratiform divergence signals are also generated when applying a two-dimensional convective–stratiform separation algorithm to reflectivities derived from the mesoscale model, although the model appears to underestimate stratiform rain area. Divergence profiles from the modeled precipitating systems vary in magnitude and structure across the wide range of baroclinicities common in southeastern Texas. Barotropic storms more characteristic of the tropics generate the most elevated divergence (and thus diabatic heating) structures with the largest magnitudes. In addition, stratiform rain regions in barotropic storms contain thicker, more elevated midlevel convergence signatures than more baroclinic storms. As the degree of baroclinicity increases, stratiform area fractions generally increase while the levels of nondivergence (LNDs) decrease. However, some weakly baroclinic storms contain stratiform area fractions and/or divergence profiles with magnitudes and LNDs that are similar to barotropic storms, despite having lower tropopause heights and less deep convection. Additional convection forms after the passage of barotropic and weakly baroclinic storms that contain elevated divergence signatures, circumstantially suggesting that heating at upper levels may cause diabatic feedbacks that help to drive regions of persistent convection in the subtropics.
Generalized Linear Models for Site-Specific Density Forecasting of U.K. Daily Rainfall
Authors: Little Max A. , McSharry Patrick E. , Taylor James W.
Published: September 2008

Site-specific probability density rainfall forecasts are needed to price insurance premiums, contracts, and other financial products based on precipitation. The spatiotemporal correlations in U.K. daily rainfall amounts over the Thames Valley are investigated and statistical Markov chain generalized linear models (Markov GLM) of rainfall are constructed. The authors compare point and density forecasts of total rainfall amounts, and forecasts of probability of occurrence of rain from these models and from other proposed density models, including persistence, statistical climatology, Markov chain, unconditional gamma and exponential mixture models, and density forecasts from GLM regression postprocessed NCEP numerical ensembles, at up to 45-day forecast horizons. The Markov GLMs and GLM processed ensembles produced skillful 1-day-ahead and short-term point forecasts. Diagnostic checks show all models are well calibrated, but GLMs perform best under the continuous-ranked probability score. For lead times of greater than 1 day, no models were better than the GLM processed ensembles at forecasting occurrence probability. Of all models, the ensembles are best able to account for the serial correlations in rainfall amounts. In conclusion, GLMs for future site-specific density forecasting are recommended. Investigations explain this conclusion in terms of the interaction between the autocorrelation properties of the data and the structure of the models tested.
Objective Estimation of the 24-h Probability of Tropical Cyclone Formation
Authors: Schumacher Andrea B. , DeMaria Mark , Knaff John A.
Published: September 2008

A new product for estimating the 24-h probability of TC formation in individual 5° × 5° subregions of the North Atlantic, eastern North Pacific, and western North Pacific tropical basins is developed. This product uses environmental and convective parameters computed from best-track tropical cyclone (TC) positions, National Centers for Environmental Prediction (NCEP) Global Forecasting System (GFS) analysis fields, and water vapor (∼6.7 μm wavelength) imagery from multiple geostationary satellite platforms. The parameters are used in a two-step algorithm applied to the developmental dataset. First, a screening step removes all data points with environmental conditions highly unfavorable to TC formation. Then, a linear discriminant analysis (LDA) is applied to the screened dataset. A probabilistic prediction scheme for TC formation is developed from the results of the LDA.

Coefficients computed by the LDA show that the largest contributors to TC formation probability are climatology, 850-hPa circulation, and distance to an existing TC. The product was evaluated by its Brier and relative operating characteristic skill scores and reliability diagrams. These measures show that the algorithm-generated probabilistic forecasts are skillful with respect to climatology, and that there is relatively good agreement between forecast probabilities and observed frequencies. As such, this prediction scheme has been implemented as an operational product called the National Environmental Satellite, Data, and Information Services (NESDIS) Tropical Cyclone Formation Probability (TCFP) product. The TCFP product updates every 6 h and displays plots of TC formation probability and input parameter values on its Web site. At present, the TCFP provides real-time, objective TC formation guidance used by tropical cyclone forecast offices in the Atlantic, eastern Pacific, and western Pacific basins.
Integrating Practice Guidelines Into Professional Training
Authors: Miville Marie L. , Changming Duan  , Nutt Roberta L. , Waehler Charles A. , Suzuki Lisa , Pistole M. Carole , Arredondo Patricia , Duffy Michael , Mejia Brenda X. , Corpus Melissa
Published: September 2008

The authors present the findings of a special task group (STG) organized to explore effective training strategies for the practice guidelines focused on diverse populations. They provide a brief literature review and summarize survey data from academic training directors regarding current use of practice guidelines. The authors then describe the Integrative Training Model (ITM), developed by the STG, as a framework for students and professionals to incorporate the complex array of information contained in each set of guidelines. Unique challenges associated with incorporating the ITM are described, as well as pedagogical considerations for both students and current professionals. The authors believe the ITM may help students and professionals increase their diversity competence by developing a more holistic understanding of the various dimensions and social group experiences that affect their clients and themselves.
Sociology in the Canadian Military Academy Curriculum
Authors: Pinch Franklin C. , Ouellet Eric
Published: September 2008

Despite its content being perceived as highly relevant to Canadian Forces (CF) leader development and current and future role demands, sociology has not become permanently embedded in the Canadian military college (milcol) curriculum. We argue that among other factors, this has been the result of such influences as lack of interest and/or support from academic sociologists outside the military; hegemony of other disciplines within the military; reaction of the military system to sociological topics and results; the number and organization of uniformed and civilian sociologists internally; and the failure of military sociologists to adequately market themselves or to follow up on the gains they have made. Notwithstanding, the authors note that recent developments both outside and inside the military college environment offer some promise of improved prospects for sociology (and anthropology): preferably, within a more multidisciplinary instructional context.
The Enigmatic History of Sociology at the United States Naval Academy
Authors: Trainor Stephen C. , Horner Donald H. , Segal David R.
Published: September 2008

Since its inception in 1845, the United States Naval Academy in Annapolis, Maryland, has often faced the challenge of balancing technical and professional training demands of the naval service against the social and cultural conditions of an increasingly complex world. Despite the institution's attempts to address the multiple demands of the social and military contexts, the study of behavioral science in general, and sociology in particular, has been until recently largely absent. In response to challenges and deficiencies associated with its educational program, the Naval Academy has undertaken a path of reform to balance professional training with the need to educate graduates as competent and effective leaders. This article addresses some of the institutional, organizational, and curricular changes at the Naval Academy, with a focus on the inclusion and development of courses in human behavior and sociology as a means to study this process of leadership education.