bluuebunny/crossref_metadata_2025 huggingface dataset:
Probing the basement of southern Tibet: evidence from crustal xenoliths entrained in a Miocene ultrapotassic dyke
Authors: Chan G.H.-N. , Waters D.J. , Searle M.P. , Aitchison J.C. , Horstwood M.S.A. , Crowley Q. , Lo C.-H. , Chan J.S.-L.
Published: February 2009

A variety of felsic and mafic granulites and ultramafic rocks occur as xenoliths within a 12.7 Ma ultrapotassic dyke intruding Xigaze flysch immediately to the north of the Yarlung–Tsangpo suture zone in southern Tibet. Garnet–clinopyroxene–plagioclase–quartz thermobarometry on mafic granulite xenoliths gives temperatures of 1130–1330 °C and pressures between 22 and 26 kbar indicating equilibration in the high-pressure and ultrahigh-temperature granulite field and defining a geotherm of
c
. 16 °C km
−1
. Ultramafic xenoliths consist mainly of hornblende and biotite, probably of restitic crustal rather than mantle origin, and attained peak metamorphic conditions of 920–1130 °C and 17–24 kbar, whereas felsic granulites equilibrated at 870–900 °C at an inferred pressure of 17 kbar.
In situ
U–(Th)–Pb laser ablation inductively coupled plasma mass spectrometry dating of zircons shows that protoliths may include Proterozoic basement rocks, Late Cretaceous calc-alkaline tonalites of the Gangdese batholith root and/or remnants of a Neo-Tethyan oceanic arc. Certain zircons from a felsic granulite and an ultramafic xenolith have mean
206
Pb/
238
U ages of 16.8 ± 0.9 Ma and 15.6 ± 0.6 Ma, respectively, and monazites from a micaceous xenolith yielded a mean
208
Pb/
232
Th age of 14.4 ± 0.4 Ma. These results show that the southern Tibet basement reached a thickness of
c
. 80 km by 17–14 Ma at the latest and has remained unchanged until the present day.

Supplementary material:

Mineral analyses used for pressure–temperature estimations and results of
40
Ar/
30
Ar laser single-grain fusion experiments are available at
http://www.geolsoc.org.uk/SUP18325
.
Constraints on
87
Sr/
86
Sr of Late Ediacaran seawater: insight from Siberian high-Sr limestones
Authors: Melezhik V.A. , Pokrovsky B.G. , Fallick A.E. , Kuznetsov A.B. , Bujakaite M.I.
Published: February 2009

In SE Siberia, carbonate formations with δ
13
C
carb
values ranging between −12‰ and −7‰ (V-PDB) and Sr concentrations of up to 2.5% occupy an area of 40 000 km
2
. Several successions exceed 1000 m in thickness and represent the world's largest known exposures of sedimentary carbonates exhibiting extreme depletion in
13
C. The carbonates were deposited on a carbonate platform evolving from a mixed carbonate–siliciclastic ramp to a carbonate ramp, and then from a peritidal rimmed shelf to a deep-water open shelf. All sequences reveal a facies-independent, upward rise in marine δ
13
C
carb
from −12‰ to −7‰. The trend and magnitude of the values mimic those that are characteristic of the 600–550 Ma Shuram–Wonoka isotope event. A coincident stratigraphic rise in
87
Sr/
86
Sr from 0.70802 to 0.70862 in several sections of limestones, containing 4400 μg g
−1
Sr on average, is considered to be by far the best available constraint on a temporal variation of seawater isotopic composition through the Late Ediacaran. If the greatest temporal rate of change in seawater
87
Sr/
86
Sr observed in the Cenozoic is applied to the Siberian sections, the calculated minimum duration for the Suram–Wonoka event is 10 Ma.

Supplementary material:

XRF and ICP-AES analysis, C, O and Sr isotopic data are available at
http://www.geolsoc.org.uk/SUP18324
.
Kinematics of the Greater Himalayan sequence, Dhaulagiri Himal: implications for the structural framework of central Nepal
Authors: Larson Kyle P. , Godin Laurent
Published: February 2009

In the Dhaulagiri region of central Nepal quartz-rich specimens sampled from the Greater Himalayan sequence yield well-defined quartz
c
-axis fabrics with a dominant top-to-the-SW sense of shear. These fabrics reflect pervasive crystal-plastic deformation extending more than 8 km structurally below previously mapped locations of the Main Central thrust fault. Quartz
c
-axis fabric opening angles suggest deformation temperatures of
c
. 500 ± 50 °C within the lower portion of the Greater Himalayan sequence and up to
c
. 670 ± 50 °C within the migmatitic upper portion. These temperatures generally plot within error of garnet–biotite temperature estimates for metamorphic assemblages and are interpreted to reflect Tertiary deformation during extrusion of the mid-crust. The quartz
c
-axis data, and a new, detailed tectonostratigraphic map, constrain the position of the Ramgarh thrust in the Dhaulagiri region to be coincident with the Main Central thrust at the base of the pervasively deformed exhumed mid-crustal core. Mean kinematic vorticity numbers (
W
m
) measured in specimens sampled from the lower portion of the Greater Himalayan sequence range between 0.49 and 0.80 (
c
. 66–41% pure shear) with an average value of 0.67 (
c
. 53% pure shear). These data indicate that extrusion of the mid-crust was facilitated by a significant component of pure shear strain.
The significance of the contemporaneous Logoisk impact structure (Belarus) and Afro-Arabian flood volcanism
Authors: Sherlock Sarah C. , Kelley Simon P. , Glazovskaya Liudmila , Peate Ingrid Ukstins
Published: February 2009

The relationships between meteorite impact craters, flood basalt volcanism and sudden environmental perturbation on Earth have been debated extensively. We present only the second example of contemporaneous meteorite impact and flood basalt volcanism: the 17 km diameter Logoisk impact structure (Belarus) and Afro-Arabian flood volcanism. The new precise
40
Ar/
39
Ar age of 29.71 ± 0.48 Ma for Logoisk is coincident with the acme of flood volcanism. We argue that at least one crater the size of Logoisk is likely to form during the emplacement of a flood volcanic province, and that contemporaneity of impacts and flood volcanism was the norm. The absence of a biotic effect from the combined Logoisk–Afro-Arabian volcanism we attribute to the magnitude of these combined events, which are both significantly smaller than the other known example of the Chicxulub impact event and the Deccan Traps flood volcanism.

Supplementary material:

40
Ar/
39
Ar data are available at
http://www.geolsoc.org.uk/SUP18329
.
Ichnotaxonomy of microbial trace fossils in volcanic glass
Authors: McLoughlin N. , Furnes H. , Banerjee N.R. , Muehlenbachs K. , Staudigel H.
Published: February 2009

Ancient microbial activity in volcanic glass creates micron-sized cavities that can be regarded as trace fossils. These are common in glassy rims of oceanic pillow lavas and volcanic breccias. Morphologically comparable mineralized traces are also found in (meta)-volcanic glasses from ophiolites and Precambrian greenstone belts. Multiple lines of evidence indicate microbial formation of these borings, although the affinity of the trace maker(s) is poorly constrained. Two broad morphological types have been previously recognized and termed ’granular' and ’tubular' bioalteration textures. Here optical microscopy and SEM observations are used to erect two new ichnogenera:
Granulohyalichnus
igen. nov. and
Tubulohyalichnus
igen. nov. Five ichnospecies are also defined:
Granulohyalichnus vulgaris
isp. nov., a granular species;
Tubulohyalichnus simplus
isp. nov., an unornamented tubular species;
Tubulohyalichnus annularis
isp. nov., an annulated tubular species;
Tubulohyalichnus spiralis
isp. nov., a helicoidal tubular species;
Tubulohyalichnus stipes
isp. nov., a branched tubular species. This systematic taxonomy is advanced to allow reliable comparisons to be made between new and existing reports of these microbial borings. Moreover, the adoption of a taxonomic framework will aid the development of these ichnofossils as palaeoenvironmental indicators and tracers of microbial evolution.
Blunting of AICAR-induced human skeletal muscle glucose uptake in type 2 diabetes is dependent on age rather than diabetic status
Authors: Babraj John Andree , Mustard Kristy , Sutherland Calum , Towler Mhari C. , Chen Shaui , Smith Kenneth , Green Kevin , Leese Graham , Hardie David Grahame , Rennie Michael J. , Cuthbertson Daniel James
Published: February 2009

We demonstrated previously that, in healthy young men, 5-aminoimidazole-4-carboxamide 1-β-d-ribofuranoside (AICAR) stimulates human muscle 2-deoxyglucose (2DG) uptake without detectable activation of muscle AMP-activated protein kinase (AMPK) but with extracellular-regulated kinase 1/2 (ERK1/2) activation. We tested whether AICAR stimulates muscle 2DG uptake in healthy older patients with or without type 2 diabetes (T2D). Six healthy young subjects (23 ± 3 yr, BMI 25 ± 2 kg/m−2; means ± SE), eight older subjects (59 ± 4 yr, BMI 28 ± 2 kg/m−2), and eight subjects with T2D (62 ± 4 yr, BMI 27 ± 2 kg/m−2) received a 6-h 2DG infusion (prime 10 mg/kg, 6 mg·kg−1·h−1) and AICAR (10 or 20 mg·kg−1·h−1) from 3 to 6 h. Quadriceps biopsies were taken at 0, 3, and 6 h. We determined 1) 2DG uptake, 2) total AMPKα activity, AMPK, acetyl-CoA carboxylase (ACC), and AS160 phosphorylation, and 3) ERK1/2 phosphorylation. Ten milligrams per kilogram per hour AICAR increased 2DG uptake by 2.9 ± 0.7-fold in young men ( P < 0.001), 1.8 ± 0.2-fold in older men ( P < 0.01), and 1.6 ± 0.1-fold in men with T2D; 20 mg·kg−1·h−1 AICAR increases were 2.5 ± 0.1-fold (older men, P < 0.001) and 2.2 ± 0.2-fold (men with T2D, P < 0.001). At 3-h AMPK activity and AMPK, ACC and AS160 phosphorylation were unchanged, but ERK1/2 phosphorylation increased at both AICAR doses. The fold changes of ERK1/2 phosphorylation and 2DG uptake closely correlated ( R2 = 0.55, P = 0.003). AICAR stimulates muscle 2DG uptake in T2D to the same extent as in healthy age-matched controls, but there is an age-related reduction.
Diurnal expression of functional and clock-related genes throughout the rat HPA axis: system-wide shifts in response to a restricted feeding schedule
Authors: Girotti Milena , Weinberg Marc S. , Spencer Robert L.
Published: February 2009

The diurnal rhythm of glucocorticoid secretion depends on the suprachiasmatic (SCN) and dorsomedial (putative food-entrainable oscillator; FEO) nuclei of the hypothalamus, two brain regions critical for coordination of physiological responses to photoperiod and feeding cues, respectively. In both cases, time keeping relies upon diurnal oscillations in clock gene ( per1, per2, and bmal) expression. Glucocorticoids may play a key role in synchronization of the rest of the body to photoperiod and food availability. Thus glucocorticoid secretion may be both a target and an important effector of SCN and FEO output. Remarkably little, however, is known about the functional diurnal rhythms of the individual components of the hypothalamic-pituitary-adrenal (HPA) axis. We examined the 24-h pattern of hormonal secretion (ACTH and corticosterone), functional gene expression (c- fos, crh, pomc, star), and clock gene expression ( per1, per2 and bmal) in each compartment of the HPA axis under a 12:12-h light-dark cycle and compared with relevant SCN gene expression. We found that each anatomic component of the HPA axis has a unique circadian signature of functional and clock gene expression. We then tested the susceptibility of these measures to nonphotic entrainment cues by restricting food availability to only a portion of the light phase of a 12:12-h light-dark cycle. Restricted feeding is a strong zeitgeber that can dramatically alter functional and clock gene expression at all levels of the HPA axis, despite ongoing photoperiod cues and only minor changes in SCN clock gene expression. Thus the HPA axis may be an important mediator of the body entrainment to the FEO.
Cross‐Correlation Properties of Costas Arrays and Their Images under Horizontal and Vertical Flips
Authors: Drakakis Konstantinos , Gow Rod , Healy John , Rickard Scott
Published: February 2009

We consider the cross‐correlation of a Costas array with
its image under a horizontal and/or a vertical flip. We propose and prove several bounds on the maximal
cross‐correlation and on its value at the origin, for both general
Costas arrays and for algebraically constructed ones.
Optical Intensity Modulation in an LiNbO3 Slab‐Coupled Waveguide
Authors: Lu Yalin , Reinhardt Kitt
Published: February 2009

Optical intensity modulation has been demonstrated through switching the optical beam between the main core waveguide and a closely attached leaky slab waveguide by applying a low‐voltage electrical field. Theory for simulating such an LiNbO3 slab‐coupled waveguide structure was suggested, and the result indicates the possibility of making the spatial guiding mode large, circular and symmetric, which further allows the potential to significantly reduce the coupling losses with adjacent lasers and optical networks. Optical intensity modulation using electro‐optic effect was experimentally demonstrated in a 5 cm long waveguide fabricated by using a procedure of soft proton exchange and then an overgrowth of thin LN film on top of a c‐cut LiNbO3 wafer.
Coordination Behavior of 3‐Ethoxycarbonyltetronic Acid towards Cu(II) and Co(II) Metal Ions
Authors: Athanasellis Giorgos , Zahariou Georgia , Kikionis Stefanos , Igglessi-Markopoulou Olga , Markopoulos John
Published: February 2009

Tetronic acids, 4‐hydroxy‐5H‐furan‐2‐ones, constitute a class of heterocyclic compounds with potent biological and pharmacological activity. The
β, β′‐tricarbonyl moiety plays an integral role in biological systems and forms a variety of metal complexes. In this report, we present the complexation reactions of 3‐ethoxycarbonyl tetronic acids with acetates and chlorides of Cu(II) and Co(II). These complexes have been studied by means of EPR spectroscopy and magnetic susceptibility measurements. From the obtained results, a preliminary complexation mode of the ligand is proposed.
A Modified Levenberg‐Marquardt Method for Nonsmooth Equations with Finitely Many Maximum Functions
Authors: Du Shou-qiang , Gao Yan
Published: February 2009

For solving nonsmooth systems of equations, the Levenberg‐Marquardt method
and its variants are of particular importance because of their locally fast convergent rates.
Finitely many maximum functions systems are very useful in the study of nonlinear complementarity
problems, variational inequality problems, Karush‐Kuhn‐Tucker systems of
nonlinear programming problems, and many problems in mechanics and engineering. In this
paper, we present a modified Levenberg‐Marquardt method for nonsmooth equations with
finitely many maximum functions. Under mild assumptions, the present method is shown
to be convergent Q‐linearly. Some numerical results comparing the proposed method with
classical reformulations indicate that the modified Levenberg‐Marquardt algorithm works
quite well in practice.
Ultrahydrophobicity of Polydimethylsiloxanes-Based Multilayered Thin Films
Authors: Gao Hongyan , Xu Karen Xiaohe , Chen Bin , Wu Li-Zhu , Tung Chen-Ho , Ji Hai-Feng
Published: February 2009

The formation of polydimethylsiloxanes (PDMSs)-based layer-by-layer multilayer ultrathin films on charged surfaces prepared from water and phosphate buffer solutions has been investigated. The multilayer films prepared under these conditions showed different surface roughness. Nanoscale islands and network structures were observed homogeneously on the multilayer film prepared from pure water solutions, which is attributing to the ultrahydrobic property of the multilayer film. The formation of nanoscale islands and network structures was due to the aggregation of PDMS-based polyelectrolytes in water. This work provides a facile approach for generating ultrahydrophobic thin films on any charged surfaces by PDMS polyelectrolytes.
Macro‐ and Microsimulations for a Sublimation Growth of SiC Single Crystals
Authors: Geiser Jürgen , Irle Stephan
Published: February 2009

The numerous technical applications in electronic and optoelectronic devices, such as lasers, diodes, and sensors, demand high‐quality silicon carbide (SiC) bulk single crystal for industrial applications. We consider an SiC crystal growth process by physical vapor transport (PVT), called modified Lely method. We deal with a model for the micro‐ and macroscales of the sublimation processes within the growth apparatus. The macroscopic model is based on the heat equation with heat sources due to induction heating and nonlocal interface conditions, representing the heat transfer by radiation. The microscopic model is based on the quantum interatomic potential and is computed with molecular dynamics. We study the temperature evolution in the apparatus and reflect the growth behavior of the microscopic model. We present results of some numerical simulations of
the micro‐ and macromodels of our growth apparatus.
Ionizing Radiation Up-regulates Telomerase Activity in Cancer Cell Lines by Post-translational Mechanism via Ras/Phosphatidylinositol 3-Kinase/Akt Pathway
Authors: Ram Ron , Uziel Orit , Eldan Orit , Fenig Eyal , Beery Einat , Lichtenberg Shelly , Nordenberg Yardena , Lahav Meir
Published: February 2009

Purpose: Telomerase is considered currently as a hallmark of cancer, and its inhibition is expected to become an important anticancer modality. In contrast to abundant data concerning the effect of cytotoxic drugs on telomerase activity (TA), there is scant information on the effect of radiation on telomerase. The mechanism of telomerase regulation by irradiation has never been evaluated in detail. In the present study, we investigated the effect of radiation on TA and its regulation in cancer cells.

Experimental Design: The effect of various radiation doses on TA in several malignant and nonmalignant cell lines was evaluated. All malignant cells exhibited similar telomerase response to radiation and its regulation was assessed at transcriptional and post-translational levels in K562 cells. Next step was the evaluation of the upstream signaling pathways leading to changes in TA using kinetics and specific inhibitors.

Results: Radiation up-regulated TA in dose-dependent manner only in cancer cells. Telomerase was activated by phosphorylation by Akt and by cytoplasmic-nuclear shift. Transcriptional processes were not involved in TA. This telomerase regulation is mediated by Ras/phosphatidylinositol 3-kinase/Akt pathway. The canonical membrane effectors of irradiation (epidermal growth factor receptor, insulin-like growth factor-I receptor, and Ca2+ influx) were not involved in this process.

Conclusions: Radiation up-regulates telomerase activity specifically in cancer cells. This study adds to accumulating evidence pointing to post-translational level as important mode of telomerase regulation. Telomerase activation due to radiation may be detrimental in treatment of cancer. Data described in this study may add to future interventions aiming at inhibition of telomerase activation during irradiation.
A Phase I Study of Samarium Lexidronam/Bortezomib Combination Therapy for the Treatment of Relapsed or Refractory Multiple Myeloma
Authors: Berenson James R. , Yellin Ori , Patel Ravi , Duvivier Herb , Nassir Youram , Mapes Russell , Abaya Christina DiLauro , Swift Regina A.
Published: February 2009

Purpose: This open-label, phase I dose-escalation study assessed the safety, tolerability, and initial efficacy of Samariam 153 (153Sm)-lexidronam/bortezomib combination therapy for patients with relapsed/refractory multiple myeloma.

Experimental Design: Patients were enrolled in six cohorts and given bortezomib (1.0 or 1.3 mg/m2) on days 1, 4, 8, and 11 and 153Sm-lexidronam (0.25, 0.5, or 1.0 mCi/kg) on day 3 of a 56-day cycle (maximum of four cycles). The primary endpoints were safety and tolerability of the 153Sm-lexidronam/bortezomib regimen.

Results: Twenty-four patients were enrolled. Median values for age, time since diagnosis, and number of prior treatments were 63 years, 29 months, and three regimens, respectively. The most common toxicities were hematologic; during the first cycle, median neutrophil and platelet nadirs were 1,000/mm3 and 98,500/mm3, respectively, and observed generally 3 to 4 weeks post-treatment. The incidences of grade 4 neutropenia and thrombocytopenia were 12.5% and 8.3%, respectively, during treatment cycle 1. Dose-limiting toxicity, reached in cohort 6 as a result of hematologic toxicity, defined the maximum tolerated dose as 0.5 mCi/kg 153Sm-lexidronam in combination with 1.3 mg/m2 bortezomib. The maximum tolerated dose for 153Sm-lexidronam in combination with the 1.0 mg/m2 bortezomib was not reached. No nonhematologic dose-limiting toxicities were observed; both the incidence and the severity of peripheral neuropathy were low. Responses occurred in 5 (21%) patients, including 3 (12.5%) complete and 2 (8.3%) minimal responses.

Conclusions: Bortezomib combined with 153Sm-lexidronam appears to be a well-tolerated regimen, which showed clinical activity in this phase I trial for patients with relapsed or refractory multiple myeloma.
Smoking Cessation Early in Pregnancy and Birth Weight, Length, Head Circumference, and Endothelial Nitric Oxide Synthase Activity in Umbilical and Chorionic Vessels
Authors: Andersen Malene R. , Simonsen Ulf , Uldbjerg Niels , Aalkjær Christian , Stender Steen
Published: February 2009

Background—

Reduced production of the vasodilator nitric oxide (NO) in fetal vessels in pregnant smokers may lower the blood flow to the fetus and result in lower birth weight, length, and head circumference. The present study measured endothelial NO synthase (eNOS) activity in fetal umbilical and chorionic vessels from nonsmokers, smokers, and ex-smokers and related the findings to the fetal outcome.

Methods and Results—

Of 266 healthy, singleton pregnancies, 182 women were nonsmokers, 43 were smokers, and 41 stopped smoking early in pregnancy. eNOS activity and concentration were quantified in endothelial cells of the fetal vessels. Cotinine, lipid profiles, estradiol,
l
-arginine, and dimethylarginines that may affect NO production were determined in maternal and fetal blood. Serum cotinine verified self-reported smoking. Newborns of smokers had a lower weight (
P
≤0.001) and a smaller head circumference (
P
≤0.041) and were shorter (
P
≤0.001) than newborns of nonsmokers and ex-smokers. eNOS activity in umbilical veins of smokers was 36% lower (
P
<0.001), eNOS concentration was 47% lower (
P
<0.001), and the fetal plasma level of high-density lipoprotein was 18% lower (
P
<0.001) than those of nonsmokers, whereas the same levels were found in umbilical veins from ex-smokers and nonsmokers. The same patterns in eNOS activity and concentration were found in umbilical arteries and chorionic vessels. Fetal plasma levels of estradiol,
l
-arginine, dimethylarginines, total cholesterol, and triglycerides were similar for nonsmokers, smokers, and ex-smokers.

Conclusions—

The findings suggest that maternal smoking reduces eNOS activity in the fetal vascular bed, contributing to retarded fetal growth caused by the reduction of vasodilatory capacity, and suggest that smoking cessation early in pregnancy prevents these effects in newborns.
Mechanism of Purinergic Activation of Endothelial Nitric Oxide Synthase in Endothelial Cells
Authors: da Silva Cleide Gonçalves , Specht Anke , Wegiel Barbara , Ferran Christiane , Kaczmarek Elzbieta
Published: February 2009

Background—Decreased endothelial nitric oxide (NO) synthase (eNOS) activity and NO production are critical contributors to the endothelial dysfunction and vascular complications observed in many diseases, including diabetes mellitus. Extracellular nucleotides activate eNOS and increase NO generation; however, the mechanism of this observation is not fully clarified.

Methods and Results—To elucidate the signaling pathway(s) leading to nucleotide-mediated eNOS phosphorylation at Ser-1177, human umbilical vein endothelial cells were treated with several nucleotides, including ATP, UTP, and ADP, in the presence or absence of selective inhibitors. These experiments identified P2Y1, P2Y2, and possibly P2Y4 as the purinergic receptors involved in eNOS phosphorylation and demonstrated that this process was adenosine independent. Nucleotide-induced eNOS phosphorylation and activity were inhibited by BAPTA-AM (an intracellular free calcium chelator), rottlerin (a protein kinase Cδ inhibitor), and protein kinase Cδ siRNA. In contrast, blockade of AMP-activated protein kinase, calcium/calmodulin-dependent kinase II, calcium/calmodulin-dependent kinase kinase, serine/threonine protein kinase B, protein kinase A, extracellular signal-regulated kinase 1/2, and p38 mitogen-activated protein kinase did not affect nucleotide-mediated eNOS phosphorylation.

Conclusions—The present study indicates that extracellular nucleotide–mediated eNOS phosphorylation is calcium and protein kinase Cδ dependent. This newly identified signaling pathway opens new therapeutic avenues for the treatment of endothelial dysfunction.
Diabetes Mellitus, Preexisting Coronary Heart Disease, and the Risk of Subsequent Coronary Heart Disease Events in Patients Infected With Human Immunodeficiency Virus
Authors: Worm Signe W. , De Wit Stephane , Weber Rainer , Sabin Caroline A. , Reiss Peter , El-Sadr Wafaa , Monforte Antonella D'Arminio , Kirk Ole , Fontas Eric , Dabis Francois , Law Matthew G. , Lundgren Jens D. , Friis-Møller Nina
Published: February 2009

Background—

Although guidelines in individuals not infected with the human immunodeficiency virus (HIV) consider diabetes mellitus (DM) to be a coronary heart disease (CHD) equivalent, there is little information on its association with CHD in those infected with HIV. We investigated the impact of DM and preexisting CHD on the development of a new CHD episode among 33 347 HIV-infected individuals in the Data Collection on Adverse Events of Anti-HIV Drugs (D:A:D Study).

Methods and Results—

Over 159 971 person-years, 698 CHD events occurred. After adjustment for gender, age, cohort, HIV transmission, ethnicity, family history of CHD, smoking, and calendar year, the rate of a CHD episode was 7.52 times higher (Poisson regression, 95% CI 6.02 to 9.39,
P
=0.0001) in those with preexisting CHD than in those without preexisting CHD, but it was only 2.41 times higher (95% CI 1.91 to 3.05,
P
=0.0001) in those with preexisting DM compared with those without DM. No statistical interactions were apparent between either diagnosis and sex; although older people with DM had an increased CHD rate compared with younger people, older people with preexisting CHD had a lower event rate. A statistically significant interaction between preexisting DM and CHD (
P
=0.003) suggested that the CHD rate in those with preexisting CHD and DM is lower than expected on the basis of the main effects alone.

Conclusions—

DM and preexisting CHD are both important risk factors for CHD events in HIV-infected individuals. There is a need for targeted interventions to reduce the risk of CHD in both high-risk groups of HIV-infected individuals.
Characteristics of Children Hospitalized With Infective Endocarditis
Authors: Day Michael D. , Gauvreau Kimberlee , Shulman Stanford , Newburger Jane W.
Published: February 2009

Background—

Infective endocarditis in children is rare, and most reports describe the experience in referral centers. The purpose of our study was to assess the characteristics of children with infective endocarditis in a large national sample.

Methods and Results—

We analyzed hospital discharge records with
International Classification of Diseases
, ninth revision, codes indicating infective endocarditis among admissions of patients <21 years of age in the Kids’ Inpatient Databases 2000 and 2003; analyses for the 2 years were combined. In 1588 hospitalizations, the age distribution was bimodal, with peaks in infancy and late adolescence. The organism was coded in 632 admissions;
Staphylococcus aureus
was most common (57%), followed by the viridans group of streptococci (20%). Preexisting heart disease was present in 662 patients admitted (42%), among whom 81% had congenital heart disease, 8% had prosthetic valve endocarditis, and 5% had rheumatic heart disease. In-hospital mortality occurred in 84 patients (5%), 38 with preexisting heart disease. Death occurred in 12 of 25 patients (48%) with tetralogy of Fallot and pulmonary atresia, and 4 of 54 (8%) with prosthetic valve endocarditis. Among 46 deaths without preexisting heart disease,
S aureus
was the causative organism in 13 of 14 patients (93%) beyond infancy; among 32 infants who died, 10 (31%) were premature.

Conclusions—

In 2000 and 2003, we found a continuing shift in the epidemiology of pediatric infective endocarditis toward a higher proportion of children without preexisting heart disease. Risk factors for mortality included some forms of congenital heart disease and, among patients without preexisting heart disease, premature/neonatal age and
S aureus
as an etiologic agent.
Comparison of Early Surgery Versus Conventional Treatment in Asymptomatic Severe Mitral Regurgitation
Authors: Kang Duk-Hyun , Kim Jeong Hoon , Rim Ji Hye , Kim Mi-Jeong , Yun Sung-Cheol , Song Jong-Min , Song Hyun , Choi Kee-Joon , Song Jae-Kwan , Lee Jae-Won
Published: February 2009

Background—

The optimal timing of surgical intervention in asymptomatic patients with severe mitral regurgitation is unclear. We therefore compared the long-term results of early surgery with a conventional treatment strategy.

Methods and Results—

From 1996 to 2005, 447 consecutive asymptomatic patients (253 men, age 50±15 years) with severe degenerative mitral regurgitation and preserved left ventricular function were evaluated prospectively. The end point was defined as the composite of operative mortality, cardiac death, repeat mitral valve surgery, and urgent admission due to congestive heart failure during follow-up. Early surgery was performed on 161 patients (operated group), and the conventional treatment strategy was used for 286 patients (conventional treatment group). There were no significant differences between the 2 groups in terms of age, gender, euroSCORE (European System for Cardiac Operative Risk Evaluation), or ejection fraction. During a median follow-up of 1988 days, there were 2 repeat surgeries and no cardiac deaths or operative mortality in the operated group compared with 12 cardiac deaths, 1 repeat surgery, and 22 admissions for congestive heart failure in the conventional treatment group. The estimated actuarial 7-year cardiac mortality rate was 0% in the operated group and 5±2% in the conventional treatment group (
P
=0.008), and for 127 propensity score-matched pairs, the estimated actuarial 7-year event-free survival rate was significantly higher in the operated than in the conventional treatment group (99±1% versus 85±4%,
P
=0.007). In the conventional treatment group, baseline grade of pulmonary hypertension (hazard ratio 1.87, 95% CI 1.22 to 2.87,
P
=0.003), age (hazard ratio 1.02, 95% CI 1.01 to 1.04,
P
=0.005), and effective regurgitant orifice area (hazard ratio 2.06, 95% CI 1.11 to 3.82,
P
=0.02) were independent variables that predicted late development of surgical indications or congestive heart failure on Cox multivariate analysis.

Conclusions—

Compared with conservative management, the strategy of early surgery was associated with an improved long-term event rate by decreasing cardiac mortality and congestive heart failure hospitalization more effectively in patients with severe degenerative mitral regurgitation. Early surgery may therefore further improve clinical outcomes in asymptomatic severe mitral regurgitation with preserved left ventricular systolic function and a high likelihood of mitral valve repair.
Cardiac Remote Ischemic Preconditioning in Coronary Stenting (CRISP Stent) Study
Authors: Hoole Stephen P. , Heck Patrick M. , Sharples Linda , Khan Sadia N. , Duehmke Rudolf , Densem Cameron G. , Clarke Sarah C. , Shapiro Leonard M. , Schofield Peter M. , O'Sullivan Michael , Dutka David P.
Published: February 2009

Background—

Myocyte necrosis as a result of elective percutaneous coronary intervention (PCI) occurs in approximately one third of cases and is associated with subsequent cardiovascular events. This study assessed the ability of remote ischemic preconditioning (IPC) to attenuate cardiac troponin I (cTnI) release after elective PCI.

Methods and Results—

Two hundred forty-two consecutive patients undergoing elective PCI with undetectable preprocedural cTnI were recruited. Subjects were randomized to receive remote IPC (induced by three 5-minute inflations of a blood pressure cuff to 200 mm Hg around the upper arm, followed by 5-minute intervals of reperfusion) or control (an uninflated cuff around the arm) before arrival in the catheter laboratory. The primary outcome was cTnI at 24 hours after PCI. Secondary outcomes included renal dysfunction and major adverse cardiac and cerebral event rate at 6 months. The median cTnI at 24 hours after PCI was lower in the remote IPC compared with the control group (0.06 versus 0.16 ng/mL;
P
=0.040). After remote IPC, cTnI was <0.04 ng/mL in 44 patients (42%) compared with 24 in the control group (24%;
P
=0.01). Subjects who received remote IPC experienced less chest discomfort (
P
=0.0006) and ECG ST-segment deviation (
P
=0.005) than control subjects. At 6 months, the major adverse cardiac and cerebral event rate was lower in the remote IPC group (4 versus 13 events;
P
=0.018).

Conclusion—

Remote IPC reduces ischemic chest discomfort during PCI, attenuates procedure-related cTnI release, and appears to reduce subsequent cardiovascular events.
Vascular Endothelial Growth Factor-B Induces Myocardium-Specific Angiogenesis and Arteriogenesis via Vascular Endothelial Growth Factor Receptor-1– and Neuropilin Receptor-1–Dependent Mechanisms
Authors: Lähteenvuo Johanna E. , Lähteenvuo Markku T. , Kivelä Antti , Rosenlew Carolina , Falkevall Annelie , Klar Joakim , Heikura Tommi , Rissanen Tuomas T. , Vähäkangas Elisa , Korpisalo Petra , Enholm Berndt , Carmeliet Peter , Alitalo Kari , Eriksson Ulf , Ylä-Herttuala Seppo
Published: February 2009

Background—

New revascularization therapies are urgently needed for patients with severe coronary heart disease who lack conventional treatment options.

Methods and Results—

We describe a new proangiogenic approach for these no-option patients using adenoviral (Ad) intramyocardial vascular endothelial growth factor (VEGF)-B
186
gene transfer, which induces myocardium-specific angiogenesis and arteriogenesis in pigs and rabbits. After acute infarction, AdVEGF-B
186
increased blood vessel area, perfusion, ejection fraction, and collateral artery formation and induced changes toward an ischemia-resistant myocardial phenotype. Soluble VEGF receptor-1 and soluble neuropilin receptor-1 reduced the effects of AdVEGF-B
186
, whereas neither soluble VEGF receptor-2 nor inhibition of nitric oxide production had this result. The effects of AdVEGF-B
186
involved activation of neuropilin receptor-1, which is highly expressed in the myocardium, via recruitment of G-protein-α interacting protein, terminus C (GIPC) and upregulation of G-protein-α interacting protein. AdVEGF-B
186
also induced an antiapoptotic gene expression profile in cardiomyocytes and had metabolic effects by inducing expression of fatty acid transport protein-4 and lipid and glycogen accumulation in the myocardium.

Conclusions—

VEGF-B
186
displayed strikingly distinct effects compared with other VEGFs. These effects may be mediated at least in part via a G-protein signaling pathway. Tissue-specificity, high efficiency in ischemic myocardium, and induction of arteriogenesis and antiapoptotic and metabolic effects make AdVEGF-B
186
a promising candidate for the treatment of myocardial ischemia.
Isolated Systolic Hypertension and Incident Heart Failure in Older Adults
Authors: Ekundayo O. James , Allman Richard M. , Sanders Paul W. , Aban Inmaculada , Love Thomas E. , Arnett Donna , Ahmed Ali
Published: February 2009

The association between isolated systolic hypertension (ISH) and incident heart failure (HF) has not been prospectively studied in a propensity-matched population of ambulatory older adults. Of the 5795 participants in the public-use copy of the Cardiovascular Health Study data set, 5248 had diastolic blood pressure <90 mm Hg and were free of HF at baseline. Of these, 2000 (38%) had ISH, defined as average seated systolic blood pressure ≥140 mm Hg. Propensity scores for baseline ISH were calculated for each participant (based on 64 baseline covariates) and were used to match 1260 pairs of participants with and without ISH. Matched Cox regression models were used to estimate the association of ISH with incident HF during a mean follow-up of 8.7 years. Matched participants (n=2520) had a mean (±SD) age of 74 (±6) years, 60% were women, 16% were nonwhites, 18% developed new-onset HF, and 35% died. Incident HF developed in 20% (rate: 242/10 000 person-years) and 16% (rate: 194/10 000 person-years) of participants with and without ISH, respectively (matched hazard ratio when ISH was compared with no ISH: 1.26; 95% CI: 1.04 to 1.51;
P
=0.016). Prematch unadjusted, multivariable-adjusted, and propensity-adjusted hazard ratios (95% CIs) for ISH-associated incident HF were, respectively, 1.72 (1.51 to 1.97;
P
<0.0001), 1.35 (1.18 to 1.56;
P
<0.0001), and 1.22 (1.04 to 1.44;
P
=0.016). ISH had no association with all-cause mortality (matched hazard ratio: 1.03; 95% CI: 0.88 to 1.19;
P
=0.732). In conclusion, in a propensity-matched cohort of community-dwelling older adults who were well balanced in 64 baseline covariates, ISH was associated with increased risk of incident HF but had no association with all-cause mortality.
Transient Receptor Potential Vanilloid Type 4–Deficient Mice Exhibit Impaired Endothelium-Dependent Relaxation Induced by Acetylcholine In Vitro and In Vivo
Authors: Zhang David X. , Mendoza Suelhem A. , Bubolz Aaron H. , Mizuno Atsuko , Ge Zhi-Dong , Li Rongshan , Warltier David C. , Suzuki Makoto , Gutterman David D.
Published: February 2009

Agonist-induced Ca
2+
entry is important for the synthesis and release of vasoactive factors in endothelial cells. The transient receptor potential vanilloid type 4 (TRPV4) channel, a Ca
2+
-permeant cation channel, is expressed in endothelial cells and involved in the regulation of vascular tone. Here we investigated the role of TRPV4 channels in acetylcholine-induced vasodilation in vitro and in vivo using the TRPV4 knockout mouse model. The expression of TRPV4 mRNA and protein was detected in both conduit and resistance arteries from wild-type mice. In small mesenteric arteries from wild-type mice, the TRPV4 activator 4α-phorbol-12,13-didecanoate increased endothelial [Ca
2+
]
i
in situ, which was reversed by the TRPV4 blocker ruthenium red. In wild-type animals, acetylcholine dilated small mesenteric arteries that involved both NO and endothelium-derived hyperpolarizing factors. In TRPV4-deficient mice, the NO component of the relaxation was attenuated and the endothelium-derived hyperpolarizing factor component was largely eliminated. Compared with their wild-type littermates, TRPV4-deficient mice demonstrated a blunted endothelial Ca
2+
response to acetylcholine in mesenteric arteries and reduced NO release in carotid arteries. Acetylcholine (5 mg/kg, IV) decreased blood pressure by 37.0±6.2 mm Hg in wild-type animals but only 16.6±2.7 mm Hg in knockout mice. We conclude that acetylcholine-induced endothelium-dependent vasodilation is reduced both in vitro and in vivo in TRPV4 knockout mice. These findings may provide novel insight into mechanisms of Ca
2+
entry evoked by chemical agonists in endothelial cells.
Adaptive Synchronization of Activities in a Recurrent Network
Authors: Voegtlin Thomas
Published: February 2009

Predictive learning rules, where synaptic changes are driven by the difference between a random input and its reconstruction derived from internal variables, have proven to be very stable and efficient. However, it is not clear how such learning rules could take place in biological synapses. Here we propose an implementation that exploits the synchronization of neural activities within a recurrent network. In this framework, the asymmetric shape of spike-timing-dependent plasticity (STDP) can be interpreted as a self-stabilizing mechanism. Our results suggest a novel hypothesis concerning the computational role of neural synchrony and oscillations.
Dynamical Analysis of Bayesian Inference Models for the Eriksen Task
Authors: Liu Yuan Sophie , Yu Angela , Holmes Philip
Published: February 2009

The Eriksen task is a classical paradigm that explores the effects of competing sensory inputs on response tendencies and the nature of selective attention in controlling these processes. In this task, conflicting flanker stimuli interfere with the processing of a central target, especially on short reaction time trials. This task has been modeled by neural networks and more recently by a normative Bayesian account. Here, we analyze the dynamics of the Bayesian models, which are nonlinear, coupled discrete time dynamical systems, by considering simplified, approximate systems that are linear and decoupled. Analytical solutions of these allow us to describe how posterior probabilities and psychometric functions depend on model parameters. We compare our results with numerical simulations of the original models and derive fits to experimental data, showing that agreements are rather good. We also investigate continuum limits of these simplified dynamical systems and demonstrate that Bayesian updating is closely related to a drift-diffusion process, whose implementation in neural network models has been extensively studied. This provides insight into how neural substrates can implement Bayesian computations.
Estimation of Positive Semidefinite Correlation Matrices by Using Convex Quadratic Semidefinite Programming
Authors: Fushiki Tadayoshi
Published: February 2009

The correlation matrix is a fundamental statistic that used in many fields. For example, GroupLens, a collaborative filtering system, uses the correlation between users for predictive purposes. Since the correlation is a natural similarity measure between users, the correlation matrix may be used as the Gram matrix in kernel methods. However, the estimated correlation matrix sometimes has a serious defect: although the correlation matrix is originally positive semidefinite, the estimated one may not be positive semidefinite when not all ratings are observed. To obtain a positive semidefinite correlation matrix, the nearest correlation matrix problem has recently been studied in the fields of numerical analysis and optimization. However, statistical properties are not explicitly used in such studies. To obtain a positive semidefinite correlation matrix, we assume an approximate model. By using the model, an estimate is obtained as the optimal point of an optimization problem formulated with information on the variances of the estimated correlation coefficients. The problem is solved by a convex quadratic semidefinite program. A penalized likelihood approach is also examined. The MovieLens data set is used to test our approach.
GABA Transporter Preserving Ongoing Spontaneous Neuronal Activity at Firing Subthreshold
Authors: Hoshino Osamu
Published: February 2009

There has been compelling evidence that the GABA transporter is crucial not only for removing gamma-aminobutyric acid (GABA) from but also releasing it into extracellular space, thereby clamping ambient GABA (GABA in extracellular space) at a certain level. The ambient GABA is known to activate extrasynaptic GABA receptors and provide tonic inhibitory current into neurons. We investigated how the transporter regulates the level of ambient GABA, mediates tonic neuronal inhibition, and influences ongoing spontaneous neuronal activity. A cortical neural network model is proposed in which GABA transporters on lateral (L) and feedback (F) inhibitory (GABAergic) interneurons are functionally made. Principal (P) cell assemblies participate in expressing information about elemental sensory features. At membrane potentials below the reversal potential, there is net influx of GABA, whereas at membrane potentials above the reversal potential, there is net efflux of GABA. Through this transport mechanism, ambient GABA concentration is kept within a submicromolar range during an ongoing spontaneous neuronal activity time period. Here we show that the GABA transporter on L cells regulates the overall level of ambient GABA across cell assemblies, and that on F cells it does so within individual cell assemblies. This combinatorial regulation of ambient GABA allows P cells to oscillate near firing threshold during the ongoing time period, thereby reducing their reaction time to externally applied stimuli. We suggest that the GABA transporter, with its forward and reverse transport mechanism, could regulate the ambient GABA. This transporter-mediated ambient GABA regulation may contribute to establishing an ongoing subthreshold neuronal state by which the network can respond rapidly to subsequent sensory input.
A Binary Variable Model for Affinity Propagation
Authors: Givoni Inmar E. , Frey Brendan J.
Published: February 2009

Affinity propagation (AP) was recently introduced as an unsupervised learning algorithm for exemplar-based clustering. We present a derivation of AP that is much simpler than the original one and is based on a quite different graphical model. The new model allows easy derivations of message updates for extensions and modifications of the standard AP algorithm. We demonstrate this by adjusting the new AP model to represent the capacitated clustering problem. For those wishing to investigate or extend the graphical model of the AP algorithm, we suggest using this new formulation since it allows a simpler and more intuitive model manipulation.
A New Hypothesis for Sleep: Tuning for Criticality
Authors: Pearlmutter Barak A. , Houghton Conor J.
Published: February 2009

We propose that the critical function of sleep is to prevent uncontrolled neuronal feedback while allowing rapid responses and prolonged retention of short-term memories. Through learning, the brain is tuned to react optimally to environmental challenges. Optimal behavior often requires rapid responses and the prolonged retention of short-term memories. At a neuronal level, these correspond to recurrent activity in local networks. Unfortunately, when a network exhibits recurrent activity, small changes in the parameters or conditions can lead to runaway oscillations. Thus, the very changes that improve the processing performance of the network can put it at risk of runaway oscillation. To prevent this, stimulus-dependent network changes should be permitted only when there is a margin of safety around the current network parameters. We propose that the essential role of sleep is to establish this margin by exposing the network to a variety of inputs, monitoring for erratic behavior, and adjusting the parameters. When sleep is not possible, an emergency mechanism must come into play, preventing runaway behavior at the expense of processing efficiency. This is tiredness.
Capacity of a Single Spiking Neuron Channel
Authors: Ikeda Shiro , Manton Jonathan H.
Published: February 2009

Information transfer through a single neuron is a fundamental component of information processing in the brain, and computing the information channel capacity is important to understand this information processing. The problem is difficult since the capacity depends on coding, characteristics of the communication channel, and optimization over input distributions, among other issues. In this letter, we consider two models. The temporal coding model of a neuron as a communication channel assumes the output is τ where τ is a gamma-distributed random variable corresponding to the interspike interval, that is, the time it takes for the neuron to fire once. The rate coding model is similar; the output is the actual rate of firing over a fixed period of time. Theoretical studies prove that the distribution of inputs, which achieves channel capacity, is a discrete distribution with finite mass points for temporal and rate coding under a reasonable assumption. This allows us to compute numerically the capacity of a neuron. Numerical results are in a plausible range based on biological evidence to date.