bluuebunny/crossref_metadata_2025 huggingface dataset:
ON QUARKS AND FLAVOR SYMMETRY
Authors: HØGAASEN H. , SORBA P.
Published: February 2008

Hadronic spectroscopy can be introduced to students and developed rather far without requiring SU(N) flavor symmetry. In such a "minimalist" presentation, we are naturally led to comment and clarify the concept of the "generalized" Pauli principle.
DYNAMIC ANALYSIS OF THE CAROTID–KUNDALINI MAP
Authors: WANG XINGYUAN , LIANG QINGYONG , MENG JUAN
Published: February 2008

The nature of the fixed points of the Carotid–Kundalini (C–K) map was studied and the boundary equation of the first bifurcation of the C–K map in the parameter plane is presented. Using the quantitative criterion and rule of chaotic system, the paper reveals the general features of the C–K Map transforming from regularity to chaos. The following conclusions are obtained: (i) chaotic patterns of the C–K map may emerge out of double-periodic bifurcation; (ii) the chaotic crisis phenomena are found. At the same time, the authors analyzed the orbit of critical point of the complex C–K Map and put forward the definition of Mandelbrot–Julia set of the complex C–K Map. The authors generalized the Welstead and Cromer's periodic scanning technique and using this technology constructed a series of the Mandelbrot–Julia sets of the complex C–K Map. Based on the experimental mathematics method of combining the theory of analytic function of one complex variable with computer aided drawing, we investigated the symmetry of the Mandelbrot–Julia set and studied the topological inflexibility of distribution of the periodic region in the Mandelbrot set, and found that the Mandelbrot set contains abundant information of the structure of Julia sets by finding the whole portray of Julia sets based on Mandelbrot set qualitatively.
CONTROLLING INSTABILITIES OF HYDROGENERATED a-Si:H TFT UNDER BIAS TEMPERATURE STRESSING
Authors: LEE YONG K.
Published: February 2008

The hydrogenerated amorphous silicon a-Si:H thin film transistors TFT with silicon nitride as a gate insulator have been stressed with independently varying gate (Vg), source (Vs), and gate-source (Vgs) bias voltage in order to elucidate the instability mechanism and suggest the new a-Si:H TFT structure. It was found that there was dependency of threshold voltage shift not only on Vgs, but also on Vg and Vs, which had not ever been reported. Its shift amount increased with increasing Vs and/or Vg. In this reports, we suggested the new TFT device structure to eliminate the dependency of Vth shift on Vg and Vs and found that with the new suggested TFT structure, the Vth shift controlling factor can only be Vgs.
BINARY NONLINEARIZATION OF THE SUPER AKNS SYSTEM
Authors: HE JINGSONG , YU JING , CHENG YI , ZHOU RUGUANG
Published: February 2008

We establish the binary nonlinearization approach of the spectral problem of the super AKNS system, and then use it to obtain the super finite-dimensional integrable Hamiltonian system in the supersymmetry manifold ℝ4N|2N. The super Hamiltonian forms and integrals of motion are given explicitly.
DESIGN AND OPTIMIZATION OF AN ATHERMAL ASYMMETRIC ALL-POLYMER ARRAYED WAVEGUIDE GRATING
Authors: LI DELU , MA CHUNSHENG , WANG YUHAI , ZHANG DAMING
Published: February 2008

This study demonstrates a novel athermal asymmetric arrayed waveguide grating (AWG), which is composed of polymer waveguides on a polymer substrate. The temperature-dependent wavelength shift of the AWG depends on the refractive indices of the polymer materials and the coefficient of thermal expansion (CTE) of the polymer substrate. The athermalization of the AWG can be realized by the selection of the polymer materials and the structural parameters of the waveguide and the substrate.
Alkaloid Biosynthesis: Metabolism and Trafficking
Authors: Ziegler Jörg , Facchini Peter J.
Published: February 2008

Alkaloids represent a highly diverse group of compounds that are related only by the occurrence of a nitrogen atom in a heterocyclic ring. Plants are estimated to produce approximately 12,000 different alkaloids, which can be organized into groups according to their carbon skeletal structures. Alkaloid biosynthesis in plants involves many catalytic steps, catalyzed by enzymes that belong to a wide range of protein families. The characterization of novel alkaloid biosynthetic enzymes in terms of structural biochemistry, molecular and cell biology, and biotechnological applications has been the focus of research over the past several years. The application of genomics to the alkaloid field has accelerated the discovery of cDNAs encoding previously elusive biosynthetic enzymes. Other technologies, such as large-scale gene expression analyses and metabolic engineering approaches with transgenic plants, have provided new insights into the regulatory architecture of alkaloid metabolism.
Ionomics and the Study of the Plant Ionome
Authors: Salt David E. , Baxter Ivan , Lahner Brett
Published: February 2008

The ionome is defined as the mineral nutrient and trace element composition of an organism and represents the inorganic component of cellular and organismal systems. Ionomics, the study of the ionome, involves the quantitative and simultaneous measurement of the elemental composition of living organisms and changes in this composition in response to physiological stimuli, developmental state, and genetic modifications. Ionomics requires the application of high-throughput elemental analysis technologies and their integration with both bioinformatic and genetic tools. Ionomics has the ability to capture information about the functional state of an organism under different conditions, driven by genetic and developmental differences and by biotic and abiotic factors. The relatively high throughput and low cost of ionomic analysis means that it has the potential to provide a powerful approach to not only the functional analysis of the genes and gene networks that directly control the ionome, but also to the more extended gene networks that control developmental and physiological processes that affect the ionome indirectly. In this review we describe the analytical and bioinformatics aspects of ionomics, as well as its application as a functional genomics tool.
Sealing Plant Surfaces: Cuticular Wax Formation by Epidermal Cells
Authors: Samuels Lacey , Kunst Ljerka , Jetter Reinhard
Published: February 2008

The vital importance of plant surface wax in protecting tissue from environmental stresses is reflected in the huge commitment of epidermal cells to cuticle formation. During cuticle deposition, a massive flux of lipids occurs from the sites of lipid synthesis in the plastid and the endoplasmic reticulum to the plant surface. Recent genetic studies in Arabidopsis have improved our understanding of fatty acid elongation and of the subsequent modification of the elongated products into primary alcohols, wax esters, secondary alcohols, and ketones, shedding light on the enzymes involved in these pathways. In contrast, the biosynthesis of alkanes is still poorly understood, as are the mechanisms of wax transport from the site of biosynthesis to the cuticle. Currently, nothing is known about wax trafficking from the endoplasmic reticulum to the plasma membrane, or about translocation through the cell wall to the cuticle. However, a first breakthrough toward an understanding of wax export recently came with the discovery of ATP binding cassette (ABC) transporters that are involved in releasing wax from the plasma membrane into the apoplast. An overview of our present knowledge of wax biosynthesis and transport and the regulation of these processes during cuticle assembly is presented, including the evidence for coordination of cutin polyester and wax production.
Quantitative gene expression profiling of mouse brain regions reveals differential transcripts conserved in human and affected in disease models
Authors: Brochier Camille , Gaillard Marie-Claude , Diguet Elsa , Caudy Nicolas , Dossat Carole , Ségurens Béatrice , Wincker Patrick , Roze Emmanuel , Caboche Jocelyne , Hantraye Philippe , Brouillet Emmanuel , Elalouf Jean-Marc , de Chaldée Michel
Published: February 2008

Using serial analysis of gene expression, we collected quantitative transcriptome data in 11 regions of the adult wild-type mouse brain: the orbital, prelimbic, cingulate, motor, somatosensory, and entorhinal cortices, the caudate-putamen, the nucleus accumbens, the thalamus, the substantia nigra, and the ventral tegmental area. With >1.2 million cDNA tags sequenced, this database is a powerful resource to explore brain functions and disorders. As an illustration, we performed interregional comparisons and found 315 differential transcripts. Most of them are poorly characterized and 20% lack functional annotation. For 78 differential transcripts, we provide independent expression level measurements in mouse brain regions by real-time quantitative RT-PCR. We also show examples where we used in situ hybridization to achieve infrastructural resolution. For 30 transcripts, we next demonstrated that regional enrichment is conserved in the human brain. We then quantified the expression levels of region-enriched transcripts in the R6/2 mouse model of Huntington disease and the 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) mouse model of Parkinson disease and observed significant alterations in the striatum, cerebral cortex, thalamus and substantia nigra of R6/2 mice and in the striatum of MPTP-treated mice. These results show that the gene expression data provided here for the mouse brain can be used to explore pathophysiological models and disclose transcripts differentially expressed in human brain regions.
A Functional Role for KLF6-SV1 in Lung Adenocarcinoma Prognosis and Chemotherapy Response
Authors: DiFeo Analisa , Feld Lauren , Rodriguez Estefania , Wang Christine , Beer David G. , Martignetti John A. , Narla Goutham
Published: February 2008

Kruppel-like factor 6 (KLF6) is a tumor suppressor gene that is functionally inactivated in human cancer by loss of heterozygosity, somatic mutation, decreased expression, and increased alternative splicing into an oncogenic splice variant, KLF6-SV1. Here we show that increased expression of KLF6-SV1 is associated with decreased survival in patients with lung adenocarcinoma. In addition, KLF6-SV1 is a novel antiapoptotic protein in lung cancer cell lines, and targeted reduction of KLF6-SV1 using siRNA induces apoptosis both alone and in combination with the chemotherapeutic drug cisplatin. Together, these findings highlight a critical role for KLF6-SV1 in lung cancer, and show a potential novel therapeutic strategy for the treatment of lung cancer. [Cancer Res 2008;68(4):965–70]
Use of Alternative Thresholds Defining Insulin Resistance to Predict Incident Type 2 Diabetes Mellitus and Cardiovascular Disease
Authors: Rutter Martin K. , Wilson Peter W.F. , Sullivan Lisa M. , Fox Caroline S. , D’Agostino Ralph B. , Meigs James B.
Published: February 2008

Background—

The performance characteristics of surrogate insulin resistance (IR) measures, commonly defined as the top 25% of the measure’s distribution, used to predict incident type 2 diabetes mellitus (DM) and cardiovascular disease (CVD) have not been critically assessed in community samples.

Methods and Results—

Baseline IR was assessed among 2720 Framingham Offspring Study subjects by use of fasting insulin, the homeostasis model assessment of IR (HOMA-IR), and the reciprocal of the Gutt insulin sensitivity index, with 7- to 11-year follow-up for incident DM (130 cases) or CVD (235). Area under the receiver operating characteristic curve, sensitivity, specificity, and positive likelihood ratio were estimated at 12 diagnostic thresholds (quantiles) of IR measures. Positive likelihood ratios for DM or CVD increased in relation to IR quantiles; risk gradients were greater for DM than for CVD, with no 9th to 10th quantile (76th centile) threshold effects. IR had better discrimination for incident DM than for CVD (HOMA-IR area under the receiver operating characteristic curve: DM 0.80 versus CVD 0.63). The HOMA-IR ≥76th centile threshold was associated with these test-performance values: sensitivity (DM 68%, CVD 40%), specificity (DM 77%, CVD 76%), and positive likelihood ratio (DM 3.0, CVD 1.7). The HOMA-IR threshold that yielded >90% sensitivity was the 6th quantile for DM prediction and the 3rd quantile for CVD. Compared with the ≥76th centile threshold, these alternative thresholds yielded lower specificity (DM 43%, CVD 17%) and positive likelihood ratios (DM 1.6, CVD 1.1).

Conclusions—

Surrogate IR measures have modest performance at the 76th centile, with no threshold effects. Different centile thresholds might be selected to optimize sensitivity versus specificity for DM versus CVD prediction if surrogate IR measures are used for risk prediction.
Two-Year Clinical Outcomes With Drug-Eluting Stents for Diabetic Patients With De Novo Coronary Lesions
Authors: Ortolani Paolo , Balducelli Marco , Marzaroli Paolo , Piovaccari Giancarlo , Menozzi Alberto , Guiducci Vincenzo , Sangiorgio Pietro , Tarantino Fabio , Geraci Giuseppe , Castriota Fausto , Tondi Stefano , Saia Francesco , Cooke Robin M.T. , Guastaroba Paolo , Grilli Roberto , Marzocchi Antonio , Maresta Aleardo
Published: February 2008

Background—

The long-term effectiveness of drug-eluting stents (DES) in unselected diabetics in routine practice is currently unclear.

Methods and Results—

To evaluate the long-term effectiveness of bare metal stents and DES in a real-world setting of diabetic patients, we analyzed 2-year follow-up data from all diabetic patients with de novo lesions enrolled in a prospective Web-based multicenter registry (Registro Regionale Angioplastiche dell’Emilia-Romagna; study period, 2002 to 2004) comprising all 13 hospitals performing percutaneous coronary interventions in the Emilia-Romagna region of Italy. Among the 1648 eligible patients treated with either bare metal stents alone (n=1089) or DES alone (n=559), 27% were insulin dependent and 83% had multivessel coronary disease. At 2 years, use of DES was associated with lower crude incidence of major adverse cardiac advents (all-cause mortality, nonfatal myocardial infarction, and target vessel revascularization) compared with bare metal stents (22.5% versus 28.1%;
P
=0.01). After propensity score adjustment, only target vessel revascularization appeared significantly lower in the DES group (11.6% versus 15.0%; hazard ratio, 0.66; 95% confidence interval, 0.46 to 0.96;
P
=0.041). Two-year angiographic stent thrombosis occurred in 1.5% DES patients and 0.7% of the bare-metal-stents patients (
P
=0.18). At Cox regression analysis, predictors of 2-year major adverse cardiac advents were left ventricular ejection fraction <35%, Charlson comorbidity index, insulin-dependent diabetes, and total lesion length.

Conclusions—

In this large, real-world, diabetic population, the use of DES was associated with a moderate reduction in the 2-year risk of target vessel revascularization, a benefit that was limited to non–insulin-dependent diabetic patients. Larger long-term studies are needed to clarify the long-term effectiveness and safety of such devices in diabetic patients.
Monitoring of the Biological Response to Murine Hindlimb Ischemia With
64
Cu-Labeled Vascular Endothelial Growth Factor-121 Positron Emission Tomography
Authors: Willmann Jürgen K. , Chen Kai , Wang Hui , Paulmurugan Ramasamy , Rollins Mark , Cai Weibo , Wang David S. , Chen Ian Y. , Gheysens Olivier , Rodriguez-Porcel Martin , Chen Xiaoyuan , Gambhir Sanjiv S.
Published: February 2008

Background—

Vascular endothelial growth factor-121 (VEGF
121
), an angiogenic protein secreted in response to hypoxic stress, binds to VEGF receptors (VEGFRs) overexpressed on vessels of ischemic tissue. The purpose of this study was to evaluate
64
Cu-VEGF
121
positron emission tomography for noninvasive spatial, temporal, and quantitative monitoring of VEGFR2 expression in a murine model of hindlimb ischemia with and without treadmill exercise training.

Methods and Results—

64
Cu-labeled VEGF
121
and a VEGF mutant were tested for VEGFR2 binding specificity in cell culture. Mice (n=58) underwent unilateral ligation of the femoral artery, and postoperative tissue ischemia was assessed with laser Doppler imaging. Longitudinal VEGFR2 expression in exercised and nonexercised mice was quantified with
64
Cu-VEGF
121
positron emission tomography at postoperative day 8, 15, 22, and 29 and correlated with postmortem γ-counting. Hindlimbs were excised for immunohistochemistry, Western blotting, and microvessel density measurements. Compared with the VEGF mutant, VEGF
121
showed specific binding to VEGFR2. Perfusion in ischemic hindlimbs fell to 9% of contralateral hindlimb on postoperative day 1 and recovered to 82% on day 29.
64
Cu-VEGF
121
uptake in ischemic hindlimbs increased significantly (
P
<0.001) from a control level of 0.61±0.17% ID/g (percentage of injected dose per gram) to 1.62±0.35% ID/g at postoperative day 8, gradually decreased over the following 3 weeks (0.59±0.14% ID/g at day 29), and correlated with γ-counting (
R
2
=0.99). Compared with nonexercised mice,
64
Cu-VEGF
121
uptake was increased significantly (
P
≤0.0001) in exercised mice (at day 15, 22, and 29) and correlated with VEGFR2 levels as obtained by Western blotting (
R
2
=0.76). Ischemic hindlimb tissue stained positively for VEGFR2. In exercised mice, microvessel density was increased significantly (
P
<0.001) compared with nonexercised mice.

Conclusions—

64
Cu-VEGF
121
positron emission tomography allows longitudinal spatial and quantitative monitoring of VEGFR2 expression in murine hindlimb ischemia and indirectly visualizes enhanced angiogenesis stimulated by treadmill exercise training.
Phosphorylation of LKB1 at Serine 428 by Protein Kinase C-ζ Is Required for Metformin-Enhanced Activation of the AMP-Activated Protein Kinase in Endothelial Cells
Authors: Xie Zhonglin , Dong Yunzhou , Scholz Roland , Neumann Dietbert , Zou Ming-Hui
Published: February 2008

Background—

Metformin, one of most commonly used antidiabetes drugs, is reported to exert its therapeutic effects by activating AMP-activated protein kinase (AMPK); however, the mechanism by which metformin activates AMPK is poorly defined. The objective of the present study was to determine how metformin activates AMPK in endothelial cells.

Methods and Results—

Exposure of human umbilical vein endothelial cells or bovine aortic endothelial cells to metformin significantly increased AMPK activity and the phosphorylation of both AMPK at Thr172 and LKB1 at Ser428, an AMPK kinase, which was paralleled by increased activation of protein kinase C (PKC)-ζ, as evidenced by increased activity, phosphorylation (Thr410/403), and nuclear translocation of PKC-ζ. Consistently, either pharmacological or genetic inhibition of PKC-ζ ablated metformin-enhanced phosphorylation of both AMPK-Thr172 and LKB1-Ser428, suggesting that PKC-ζ might act as an upstream kinase for LKB1. Furthermore, adenoviral overexpression of LKB1 kinase-dead mutants abolished but LKB1 wild-type overexpression enhanced the effects of metformin on AMPK in bovine aortic endothelial cells. In addition, metformin increased the phosphorylation and nuclear export of LKB1 into the cytosols as well as the association of AMPK with LKB1 in bovine aortic endothelial cells. Similarly, overexpression of LKB1 wild-type but not LKB1 S428A mutants (serine replaced by alanine) restored the effects of metformin on AMPK in LKB1-deficient HeLa-S3 cells, suggesting that Ser428 phosphorylation of LKB1 is required for metformin-enhanced AMPK activation. Moreover, LKB1 S428A, like kinase-dead LKB1 D194A, abolished metformin-enhanced LKB1 translocation as well as the association of LKB1 with AMPK in HeLa-S3 cells. Finally, inhibition of PKC-ζ abolished metformin-enhanced coimmunoprecipitation of LKB1 with both AMPKα1 and AMPKα2.

Conclusions—

We conclude that PKC-ζ phosphorylates LKB1 at Ser428, resulting in LKB1 nuclear export and hence AMPK activation.
Deficient Zebrafish
Ether-à-Go-Go
–Related Gene Channel Gating Causes Short-QT Syndrome in Zebrafish
Reggae
Mutants
Authors: Hassel David , Scholz Eberhard P. , Trano Nicole , Friedrich Oliver , Just Steffen , Meder Benjamin , Weiss Daniel L. , Zitron Edgar , Marquart Sabine , Vogel Britta , Karle Christoph A. , Seemann Gunnar , Fishman Mark C. , Katus Hugo A. , Rottbauer Wolfgang
Published: February 2008

Background—

Genetic predisposition is believed to be responsible for most clinically significant arrhythmias; however, suitable genetic animal models to study disease mechanisms and evaluate new treatment strategies are largely lacking.

Methods and Results—

In search of suitable arrhythmia models, we isolated the zebrafish mutation
reggae
(
reg
), which displays clinical features of the malignant human short-QT syndrome such as accelerated cardiac repolarization accompanied by cardiac fibrillation. By positional cloning, we identified the
reg
mutation that resides within the voltage sensor of the zebrafish
ether-à-go-go
–related gene (zERG) potassium channel. The mutation causes premature zERG channel activation and defective inactivation, which results in shortened action potential duration and accelerated cardiac repolarization. Genetic and pharmacological inhibition of zERG rescues recessive
reg
mutant embryos, which confirms the gain-of-function effect of the
reg
mutation on zERG channel function in vivo. Accordingly, QT intervals in ECGs from heterozygous and homozygous
reg
mutant adult zebrafish are considerably shorter than in wild-type zebrafish.

Conclusions—

With its molecular and pathophysiological concordance to the human arrhythmia syndrome, zebrafish
reg
represents the first animal model for human short-QT syndrome.
Intracoronary KAI-9803 as an Adjunct to Primary Percutaneous Coronary Intervention for Acute ST-Segment Elevation Myocardial Infarction
Authors:   Direct Inhibition of δ-Protein Kinase C Enzyme to Limit Total Infarct Size in Acute Myocardial Infarction (DELTA MI) Investigators
Published: February 2008

Background—

KAI-9803, a δ-protein kinase C inhibitor, has been shown to ameliorate injury associated with ischemia and reperfusion in animal models of acute myocardial infarction (MI).

Methods and Results—

Direct Inhibition of δ-Protein Kinase C Enzyme to Limit Total Infarct Size in Acute Myocardial Infarction (DELTA MI) was a “first-in-human,” dose-escalation study that evaluated the safety, tolerability, and activity of KAI-9803 for patients with acute anterior ST-segment elevation MI undergoing primary percutaneous coronary intervention. Patients who presented within 6 hours of symptom onset and had an occluded left anterior descending infarct artery on angiography were randomized in a 2:1 fashion to receive 1 of 4 doses of KAI-9803 (cohort 1, 0.05 mg; cohort 2, 0.5 mg; cohort 3, 1.25 mg; cohort 4, 5.0 mg) versus blinded concurrent placebo delivered in 2 divided doses via intracoronary injection before and after reestablishment of antegrade epicardial flow with percutaneous coronary intervention. Safety and biomarker end points were assessed. Overall, 154 patients were randomized and treated with study drug (37 in cohort 1, 38 in cohort 2, 38 in cohort 3, 41 in cohort 4). The incidence of serious adverse events was similar between patients treated with KAI-9803 versus placebo. Other safety end points, including changes in QT intervals and standard laboratory values after study drug administration, were similar between treatment groups. Although the study was not powered to demonstrate efficacy with the biomarker end points assessed, signs of drug activity with KAI-9803 were suggested by trends for consistent, nonsignificant reductions in creatine kinase–MB area under the curve and ST-recovery area under the curve values across all dosing cohorts with KAI-9803 compared with concurrent placebo, and similar trends were demonstrated for improvements in
99m
technetium sestamibi infarct size values with active study drug in cohorts 1, 2, and 3.

Conclusions—

KAI-9803 had an acceptable safety and tolerability profile when delivered via intracoronary injection during primary percutaneous coronary intervention for ST-segment elevation MI. Signs of potential drug activity were demonstrated with biomarker end points in this small exploratory study, indicating that further testing of KAI-9803 as an adjunctive therapy for ST-segment elevation MI is warranted.
α2-Adrenoceptors Enhance Angiotensin II–Induced Renal Vasoconstriction
Authors: Jackson Edwin K. , Gillespie Delbert G. , Zhu Chongxue , Ren Jin , Zacharia Lefteris C. , Mi Zaichuan
Published: February 2008

α2-Adrenoceptors potentiate renal vascular responses to angiotensin II via coincident signaling at phospholipase C. This leads to increased activation of the phospholipase C/protein kinase C/c-src pathway. Studies suggest that c-src activates the reduced nicotinamide-adenine dinucleotide phosphate (NADPH) oxidase/superoxide system, and reactive oxygen species stimulate the RhoA/Rho kinase pathway. Therefore, we hypothesized that NADPH oxidase/superoxide and RhoA/Rho kinase are downstream components of the signal transduction pathway that mediate the interaction between α2-adrenoceptors and angiotensin II on renal vascular resistance. In rat kidneys, both in vivo and in vitro, intrarenal infusions of angiotensin II increased renal vascular resistance, and UK14,304 (α2-adrenoceptor agonist) enhanced this response. Intrarenal Tempol (superoxide dismutase mimetic) or Y27632 (Rho kinase inhibitor) abolished the interaction between UK14,304 and angiotensin II both in vivo and in vitro. The interaction was also blocked by inhibitors of NADPH oxidase (in vivo using chronic gp91ds-tat administration and in vitro with diphenyleneiodonium). In cultured preglomerular vascular smooth muscle cells, UK14,304 enhanced angiotensin II–induced intracellular superoxide (2-hydroxyethidium production) and potentiated activation of RhoA (Western blot of activated RhoA bound to the binding domain of rhotekin). The interaction between angiotensin II and UK14,304 on superoxide generation and RhoA activation was blocked by inhibitors of phospholipase C (U73312), protein kinase C (GF109203X), c-src (PP1), NADPH oxidase (diphenyleneiodonium), or superoxide (Tempol). We conclude that NADPH oxidase/superoxide and RhoA/Rho kinase are involved in the interaction between α2-adrenoceptors and angiotensin II on renal vascular resistance by mediating signaling events downstream of the phospholipase C/protein kinase C/c-src pathway.
Cardiac Overexpression of Angiotensin Converting Enzyme 2 Protects the Heart From Ischemia-Induced Pathophysiology
Authors: Der Sarkissian Shant , Grobe Justin L. , Yuan Lihui , Narielwala Dhruv R. , Walter Glenn A. , Katovich Michael J. , Raizada Mohan K.
Published: February 2008

Angiotensin converting enzyme 2 (ACE2) has been linked to cardiac dysfunction and hypertension-induced cardiac pathophysiology. In this study, we used a gene overexpression approach to investigate the role of ACE2 in cardiac function and remodeling after myocardial infarction. Rats received an intracardiac injection of 4.5×10
8
lentivirus containing ACE2 cDNA, followed by permanent coronary artery ligation (CAL) of the left anterior descending artery. At 24 hours and 6 weeks after surgery, cardiac functions, viability, and pathophysiology were assessed by MRI) and by histological analysis. At 24 hours post-CAL, left ventricular (LV) anterior wall motion was stunted to the same extent in control CAL and lenti-ACE2–treated CAL rats. However lenti-ACE2–treated CAL rats showed a 60% reduction in delayed contrast-enhanced LV volume after gadodiamide injection, indicating early ischemic protection of myocardium by ACE2. At 6 weeks after CAL, lenti-ACE2 rats demonstrated a complete rescue of cardiac output, a 41% rescue of ejection fraction, a 44% rescue in contractility, a 37% rescue in motion, and a 53% rescue in LV anterior (infracted) wall thinning compared with control CAL rats. No changes were observed in the LV posterior (noninfarcted) wall other than an 81% rescue in motion produced by ACE2 in CAL rats. Finally, infarct size measured by 2,3,5-triphenyl-tetrazolium chloride staining was not significantly different between the ligated groups. These observations demonstrate that cardiac overexpression of ACE2 exerts protective influence on the heart during myocardial infarction by preserving cardiac functions, LV wall motion and contractility, and by attenuating LV wall thinning.
Effect of Telmisartan on Nitric Oxide–Asymmetrical Dimethylarginine System
Authors: Scalera Fortunato , Martens-Lobenhoffer Jens , Bukowska Alicja , Lendeckel Uwe , Täger Michael , Bode-Böger Stefanie M.
Published: February 2008

Telmisartan, in addition to blocking angiotensin (Ang) II type 1 receptor (AT
1
R), activates peroxisome proliferator activated receptor γ (PPARγ) signaling that interferes with nitric oxide (NO) system. Because aging of endothelial cells (ECs) is hallmarked by a reduction in NO synthesis, we hypothesized that telmisartan increases NO formation by regulated asymmetrical dimethylarginine (ADMA)-dimethylarginine dimethylaminohydrolase (DDAH)-system through blocking AT
1
R and activating PPARγ signaling. To test this hypothesis, ECs were cultured with telmisartan, eprosartan, Ang II, and GW9662 (PPARγ antagonist) until the twelfth passage. During the process of aging, PPARγ protein expression decreased significantly, whereas the expression of AT
1
R increased. Telmisartan reversed these effects and dose-dependently decreased reactive oxygen species and 8-iso-prostaglandin (PG) F
2α
formation. This effect was associated with an upregulated activity and protein expression of DDAH, accompanied by a decrease in ADMA concentration, an increase in NO metabolites, and delayed senescence. Blockade of PPARγ signaling by GW9662 or PPARγ small-interference RNA prevented the effect of telmisartan on ADMA-DDAH-NO system. Coincubation with Ang II did not affect the effect of telmisartan-delayed senescence, whereas Ang II itself accelerated endothelial aging. Moreover, AT
1
R blocker eprosartan that did not influence PPARγ protein expression had no effect on ADMA system and senescence. We have demonstrated that telmisartan mainly by activating PPARγ signaling can alter the catabolism and release of ADMA as an important cardiovascular risk factor. We therefore propose that telmisartan translationally and posttranslationally upregulated DDAH expression via activation of PPARγ signaling, causing ADMA to diminish and increase NO synthesis sufficient to delay senescence.
High-Normal Blood Pressure Is Associated With Poor Cognitive Performance
Authors: Knecht Stefan , Wersching Heike , Lohmann Hubertus , Bruchmann Maximilian , Duning Thomas , Dziewas Rainer , Berger Klaus , Ringelstein E. Bernd
Published: February 2008

While the relation between systolic blood pressure (SBP) and vascular events is linear down to the high-normal range, the relation between SBP and cognition is less clear. We cross-sectionally assessed the relation between SBP and cognition in a cohort extending from mid- to late-life. From a total of 2200 community-dwelling individuals we recruited 377 aged 44 to 82 years (median: 64 years, 171 male) in the SEARCH-Health study (Systematic evaluation and alteration of risk factors for cognitive health). Participants were studied with a comprehensive neuropsychological test battery that provided, based on principal component analysis, 5 composite scores for cognition (learning and memory, attention and executive function, spatial skills, working memory, and verbal skills). Global cognition was calculated from the sum of the composite scores. SBP (corrected
R
2
=0.007), education (corrected
R
2
=0.203), age (corrected
R
2
=0.102), and gender (corrected
R
2
=0.011) explained one third of variance in global cognitive performance (
P
<0.001) on multivariate analyses. Moreover, the relation between SBP (based on 10 mm Hg-categories from <120 mm Hg to >170 mm Hg) and global cognitive performance was linear in this range of SBP-values, ie, even in the normotensive range (β=−0.110,
P
<0.05). Subgroup analysis showed that the association of SBP and cognition was driven by results in midlife (<60 years) individuals (β=−0.291,
P
<0.005). Thus, even in the normotensive range increasing systolic blood pressure is inversely related to cognition.
Betting on Hitler—The Value of Political Connections in Nazi Germany*
Authors: Ferguson Thomas , Voth Hans-Joachim
Published: February 2008

This paper examines the value of connections between German industry and the Nazi movement in early 1933. Drawing on previously unused contemporary sources about management and supervisory board composition and stock returns, we find that one out of seven firms, and a large proportion of the biggest companies, had substantive links with the National Socialist German Workers' Party. Firms supporting the Nazi movement experienced unusually high returns, outperforming unconnected ones by 5% to 8% between January and March 1933. These results are not driven by sectoral composition and are robust to alternative estimators and definitions of affiliation.
Evaluating the Effects of Height-Variable Reflectivity and Antenna Sidelobes on the Radar Equation
Authors: Campos Edwin F. , Hocking Wayne , Fabry Frédéric
Published: February 2008

Using radar observations to quantify precipitation intensity requires the intervention of the radar equation, which converts the precipitation signal into reflectivity units. This equation generally assumes that the reflectivity is uniform within each sampling gate and that the sidelobes of the antenna pattern are negligible. The purpose here is to provide a more realistic approach that eliminates these assumptions when computing profiles of precipitation intensity (by using a height-variable reflectivity and antenna pattern of significant sidelobes to compute profiles of a radar reflectivity factor). To achieve this, simultaneous observations of collocated vertically pointing radars operating in the VHF and X bands were obtained. Raindrop measurements were used to correct for attenuation in the precipitation signal at the X band. Then the precipitation signal in the VHF radar was simulated by combining this X-band signal and the VHF antenna pattern into a general version of the radar equation. The simulated precipitation signal at VHF compares well with actual measurements of the rain signal (range gates centered at 2.5, 3.0, and 3.5 km) by the VHF radar, and this validates the analysis methods. In conclusion, the analysis indicates that VHF reflectivity at gates above the melting layer is artificially enhanced by the precipitation signal collected in the sidelobe direction. Similar enhancement will be expected wherever there is a strong vertical gradient of reflectivity (i.e., on the order of 10 dB km−1 or larger).
Detection of Fog and Low Cloud Boundaries with Ground-Based Remote Sensing Systems
Authors: Nowak Daniela , Ruffieux Dominique , Agnew Judith L. , Vuilleumier Laurent
Published: February 2008

The performance of the boundary determination of fog and low stratiform cloud layers with data from a frequency-modulated continuous-wave (FMCW) cloud radar and a Vaisala ceilometer is assessed. During wintertime stable episodes, fog and low stratiform cloud layers often occur in the Swiss Plateau, where the aerological station of Payerne, Switzerland, is located. During the international COST 720 Temperature, Humidity, and Cloud (TUC) profiling experiment in winter 2003/04, both a cloud radar and a ceilometer were operated in parallel, among other profiling instruments. Human eye observations (“synops”) and temperature and humidity profiles from radiosoundings were used as reference for the validation. In addition, two case studies were chosen to demonstrate the possibilities and limitations of such ground-based remote sensing systems in determining low clouds. In these case studies the cloud boundaries determined by ceilometer and cloud radar were furthermore compared with wind profiler signal-to-noise ratio time series. Under dry conditions, cloud-base and -top detection was possible in 59% and 69% of the cases for low stratus clouds and fog situations, respectively. When cases with any form of precipitation were included, performances were reduced with detection rates of 41% and 63%, respectively. The combination of ceilometer and cloud radar has the potential for providing the base and top of a cloud layer with optimal efficiency in the continuous operational mode. The cloud-top height determination by the cloud radar was compared with cloud-top heights detected using radiosounding humidity profiles. The average height difference between the radiosounding and cloud radar determination of the cloud upper boundary is 53 ± 32 m.
An Atmospheric Soliton Observed with Doppler Radar, Differential Absorption Lidar, and a Molecular Doppler Lidar
Authors: Koch Steven E. , Flamant Cyrille , Wilson James W. , Gentry Bruce M. , Jamison Brian D.
Published: February 2008

Airborne Leandre II differential absorption lidar (DIAL), S-band dual-polarization Doppler radar (S-Pol), and Goddard Lidar Observatory for Winds (GLOW) Doppler lidar data are used, in conjunction with surface mesonet and special sounding data, to derive the structure and dynamics of a bore and associated solitary wave train (soliton) that were generated in southwestern Kansas during the International H20 Project (IHOP_2002). Vertical cross sections of S-Pol reflectivity, S-Pol radial velocity, and DIAL water vapor mixing ratio show a stunning amplitude-ordered train of trapped solitary waves. DIAL data reveal that the leading wave in the soliton increasingly flattened with time as the soliton dissipated.

A method is developed for using the GLOW Doppler winds to obtain the complex two-dimensional vertical circulation accompanying the dissipating soliton. The results show multiple circulations identical in number to the oscillations seen in the S-Pol and DIAL data. The leading updraft occurred precisely at the time that the bore passed over the GLOW facility, as well as when the photon count values suddenly ramped up (suggesting lifting of the low-level inversion by the bore). Additional evidence in support of the validity of the results is provided by the fact that layer displacements computed using the derived vertical motions agree well with those implied by the changes in height of the DIAL mixing ratio surfaces.

The depth and speed of propagation of the bore seen in the DIAL and surface mesoanalyses were shown to be consistent with the predictions from bore hydraulic theory. Analysis of National Center for Atmospheric Research (NCAR) Integrated Sounding System (ISS) data shows that a highly pronounced curvature in the profile of bore-relative winds, related to the existence of a very strong low-level jet, effectively trapped the upward leakage of solitary wave energy below 3 km. This finding explains the trapped lee wave–type structures seen in the DIAL, GLOW, and S-Pol data.
In Situ Samplings and Remote Sensing Measurements to Characterize Aerosol Properties over Southeast Italy
Authors: Bellantone V. , Carofalo I. , De Tomasi F. , Perrone M. R. , Santese M. , Tafuro A. M. , Turnone A.
Published: February 2008

Ground-based particulate matter (PM) samplers, an XeF Raman lidar operating in the framework of the European Aerosol Research Lidar Network (EARLINET), and a sun/sky radiometer operating in the framework of the Aerosol Robotic Network (AERONET) have been used to characterize vertical profiles, optical and microphysical properties, and chemical composition of aerosols during the 29 June–1 July 2005 dust outbreak that occurred over the central-eastern Mediterranean. Aerosol backscatter coefficient, total depolarization, and lidar ratio vertical profiles revealed that a well-mixed dust layer extending from ∼0.5 to 6 km was present over southeastern Italy on 30 June. Sun/sky radiometer measurements revealed a bimodal lognormal size distribution during all measurement days. The particle volume distribution was found to be well correlated either to the PM mass distribution measured at ground by a seven-stage cascade impactor and to the fine to total suspended PM mass ratio measured by ground-based PM samplers. Scanning electron microscopy and ion chromatography analyses on PM samples revealed that coarse-mode aerosols were mainly made of carbonate, aluminum-silicate, and sea salt particles. Carbon, sulfate, and nitrate particles were the main components of fine-mode aerosols representing more than 50% of the total aerosol load; the significant role of fine-mode anthropogenic particles during a dust event is highlighted.

Finally, the potential capabilities of complementary measurements by passive and active remote sensing techniques and in situ observations to retrieve the vertical distribution of the particle number and mass concentration are analyzed and discussed.
Advances in Continuously Profiling the Thermodynamic State of the Boundary Layer: Integration of Measurements and Methods
Authors: Löhnert Ulrich , Crewell S. , Krasnov O. , O’Connor E. , Russchenberg H.
Published: February 2008

This paper describes advances in ground-based thermodynamic profiling of the lower troposphere through sensor synergy. The well-documented integrated profiling technique (IPT), which uses a microwave profiler, a cloud radar, and a ceilometer to simultaneously retrieve vertical profiles of temperature, humidity, and liquid water content (LWC) of nonprecipitating clouds, is further developed toward an enhanced performance in the boundary layer and lower troposphere. For a more accurate temperature profile, this is accomplished by including an elevation scanning measurement modus of the microwave profiler. Height-dependent RMS accuracies of temperature (humidity) ranging from ∼0.3 to 0.9 K (0.5–0.8 g m−3) in the boundary layer are derived from retrieval simulations and confirmed experimentally with measurements at distinct heights taken during the 2005 International Lindenberg Campaign for Assessment of Humidity and Cloud Profiling Systems and its Impact on High-Resolution Modeling (LAUNCH) of the German Weather Service. Temperature inversions, especially of the lower boundary layer, are captured in a very satisfactory way by using the elevation scanning mode. To improve the quality of liquid water content measurements in clouds the authors incorporate a sophisticated target classification scheme developed within the European cloud observing network CloudNet. It allows the detailed discrimination between different types of backscatterers detected by cloud radar and ceilometer. Finally, to allow IPT application also to drizzling cases, an LWC profiling method is integrated. This technique classifies the detected hydrometeors into three different size classes using certain thresholds determined by radar reflectivity and/or ceilometer extinction profiles. By inclusion into IPT, the retrieved profiles are made consistent with the measurements of the microwave profiler and an LWC a priori profile. Results of IPT application to 13 days of the LAUNCH campaign are analyzed, and the importance of integrated profiling for model evaluation is underlined.
Lidar Observations of the Vertical Aerosol Flux in the Planetary Boundary Layer
Authors: Engelmann Ronny , Wandinger Ulla , Ansmann Albert , Müller Detlef , Žeromskis Egidijus , Althausen Dietrich , Wehner Birgit
Published: February 2008

The vertical aerosol transport in the planetary boundary layer (PBL) is investigated with lidars. Profiles of the vertical wind velocity are measured with a 2-μm Doppler wind lidar. Aerosol parameters are derived from observations with an aerosol Raman lidar. Both instruments were operated next to each other at the Institute for Tropospheric Research (IfT) in Leipzig, Germany. The eddy correlation technique is applied to calculate turbulent particle mass fluxes on the basis of aerosol backscatter and vertical wind data obtained with a resolution of 75 m and 5 s throughout the PBL. A conversion of particle backscatter to particle mass is performed by applying the IfT inversion scheme to three-wavelength Raman lidar observations. The method, so far, is restricted to stationary and dry atmospheric conditions under which hygroscopic particle growth can be neglected. In a case study, particle mass fluxes of 0.5–2.5 μg m−2 s−1 were found in the upper part of a convective PBL on 12 September 2006.
Effects of Wind Field Inhomogeneities on Doppler Beam Swinging Revealed by an Imaging Radar
Authors: Cheong B. L. , Palmer R. D. , Yu T-Y. , Yang K-F. , Hoffman M. W. , Frasier S. J. , Lopez-Dekker F. J.
Published: February 2008

In this work, the accuracy of the Doppler beam-swinging (DBS) technique for wind measurements is studied using an imaging radar—the turbulent eddy profiler (TEP) developed by the University of Massachusetts, with data collected in summer 2003. With up to 64 independent receivers, and using coherent radar imaging (CRI), several hundred partially independent beams can be formed simultaneously within the volume defined by the transmit beam. By selecting a subset of these beams, an unprecedented number of DBS configurations with varying zenith angle, azimuth angle, and number of beams can be investigated. The angular distributions of echo power and radial velocity obtained by CRI provide a unique opportunity to validate the inherent assumption in the DBS method of homogeneity across the region defined by the beam directions. Through comparison with a reference wind field, calculated as the optimal uniform wind field derived from all CRI beams with sufficient signal-to-noise ratio (SNR), the accuracy of the wind estimates for various DBS configurations is statistically analyzed. It is shown that for a three-beam DBS configuration, although the validity of the homogeneity assumption is enhanced at smaller zenith angles, the root-mean-square (RMS) error increases because of the ill-conditioned matrix in the DBS algorithm. As expected, inhomogeneities in the wind field produce large bias for the three-beam DBS configuration for large zenith angles. An optimal zenith angle, in terms of RMS error, of approximately 9°–10° was estimated. It is further shown that RMS error can be significantly reduced by increasing the number of off-vertical beams used for the DBS processing.
Evaluation of an LES-Based Wind Profiler Simulator for Observations of a Daytime Atmospheric Convective Boundary Layer
Authors: Scipión Danny E. , Chilson Phillip B. , Fedorovich Evgeni , Palmer Robert D.
Published: February 2008

The daytime atmospheric convective boundary layer (CBL) is characterized by strong turbulence that is primarily caused by buoyancy forced from the heated underlying surface. The present study considers a combination of a virtual radar and large eddy simulation (LES) techniques to characterize the CBL. Data representative of a daytime CBL with wind shear were generated by LES and used in the virtual boundary layer radar (BLR) with both vertical and multiple off-vertical beams and frequencies. To evaluate the virtual radar, a multiple radar experiment (MRE) was conducted using five virtual radars with common resolution volumes at two different altitudes. Three-dimensional wind fields were retrieved from the virtual radar data and compared with the LES output. It is shown that data produced from the virtual BLR are representative of what one expects to retrieve using a real BLR and the measured wind fields match those of the LES. Additionally, results from a frequency domain interferometry (FDI) comparison are presented, with the ultimate goal of enhancing the resolution of conventional radar measurements. The virtual BLR produces measurements consistent with the LES data fields and provides a suitable platform for validating radar signal processing algorithms.