bluuebunny/crossref_metadata_2025 huggingface dataset:
ARITHMETIC QUANTUM GRAVITY
Authors: KLEINSCHMIDT AXEL , NICOLAI HERMANN
Published: January 2011

The arithmetic chaos of classical (super)gravity near a spacelike singularity is elevated to the quantum level via the construction of a cosmological quantum billiard system. Its precise formulation, together with its underlying algebraic structure, allows for a general analysis of the wavefunction of the universe near the singularity. We argue that the extension of these results beyond the billiard approximation may provide a concrete mechanism for emergent space as well as new perspectives on several long-standing issues in canonical quantum gravity. The exponentially growing complexity of the underlying symmetry structure could introduce an element of non-computability that effectively "screens" the cosmological singularity from a complete resolution.
LET'S TALK ABOUT VARYING G
Authors: MOSS ADAM , NARIMANI ALI , SCOTT DOUGLAS
Published: January 2011

It is possible that fundamental constants may not be constants at all. There is a generally accepted view that one can only talk about variations of dimensionless quantities, such as the fine structure constant α e ≡ e2/4πϵ0ℏc. However, constraints on the strength of gravity tend to focus on G itself, which is problematic. We stress that G needs to be multiplied by the square of a mass, and hence, for example, one should be constraining [Formula: see text], where m p is the proton mass. Failure to focus on such dimensionless quantities makes it difficult to interpret the physical dependence of constraints on the variation of G in many published studies. A thought-experiment involving talking to observers in another universe about the values of physical constants may be useful for distinguishing what is genuinely measurable from what is merely part of our particular system of units.
MEMBRANE PARADIGM REALIZED?
Authors: MATHUR SAMIR D.
Published: January 2011

Are there any degrees of freedom on the black hole horizon? Using the "membrane paradigm" we can reproduce coarse-grained physics outside the hole by assuming a fictitious membrane just outside the horizon. But to solve the information puzzle we need "real" degrees of freedom at the horizon, which can modify Hawking's evolution of quantum modes. We argue that recent results on gravitational microstates imply a set of real degrees of freedom just outside the horizon; the state of the hole is a linear combination of rapidly oscillating gravitational solutions with support concentrated just outside the horizon radius. The collective behavior of these microstate solutions may give a realization of the membrane paradigm, with the fictitious membrane now replaced by real, explicit degrees of freedom.
THE NECESSITY OF TORSION IN GRAVITY
Authors: HAMMOND RICHARD T.
Published: January 2011

It is shown that torsion is required for a complete theory of graviation, and that without it, the equations of gravitation violate fundamental laws. In the first case, we are reminded that, in the absence of external forces, the correct conservation law of total angular momentum arises only if torsion, whose origin is intrinsic spin, is included into gravitation. The second case considers the "mass reversal" transformation. It has been known that under a global chiral transformation and "mass to negative mass" transformation, the Dirac equation is invariant. But global transformations violate special relativity, so this transformation must be made local. It is shown that the torsion is the gauge field for this local invariance.
THREE VIEWS OF TWO DEGREES
Authors: JAEGER CARLO , JAEGER JULIA
Published: January 2011

Limiting global warming to 2°Celsius above pre-industrial global mean temperature has become a widely endorsed goal for climate policy. It has also been severely criticized. We show how the limit emerged out of a marginal remark in an early paper about climate policy and distinguish three possible views of it. The catastrophe view sees it as the threshold separating a domain of safety from a domain of catastrophe. The cost-benefit view sees it as a strategy to optimize the relation between the costs and benefits of climate policy. The focal point view sees it as a solution to a complex coordination problem. We argue that the focal point view is the most appropriate. It leads to an emphasis on implementing effective steps towards a near-zero emissions economy, without panicking in the face of a possible temporary overshooting. After several decades of practical experiences, the focal point may or may not be redefined on the basis of knowledge gathered thanks to these experiences.
DEVELOPMENT AND THE IMPACT OF CLIMATE CHANGE ON ENERGY DEMAND: EVIDENCE FROM BRAZIL
Authors: DEPAULA GUILHERME , MENDELSOHN ROBERT
Published: January 2011

This paper investigates the effects of climate on residential electricity use for households from different income classes in Brazil. Using cross-sectional data, the study finds that the temperature elasticity of electricity consumption varies significantly across income classes. The temperature elasticity of low income households is not significantly different from zero but middle and high income families have a long run temperature elasticity of 0.8 and 1.6 respectively. As emerging low latitude countries develop and incomes rise, the welfare damages of warming in the energy sector will become substantial.
COMBINING MULTIPLE CLIMATE POLICY INSTRUMENTS: HOW NOT TO DO IT
Authors: FANKHAUSER SAMUEL , HEPBURN CAMERON , PARK JISUNG
Published: January 2011

Putting a price on carbon is critical for climate change policy. Increasingly, policymakers combine multiple policy tools to achieve this, for example by complementing cap-and-trade schemes with a carbon tax, or with a feed-in tariff. Often, the motivation for doing so is to limit undesirable fluctuations in the carbon price, either from rising too high or falling too low. This paper reviews the implications for the carbon price of combining cap-and-trade with other policy instruments. We find that price intervention may not always have the desired effect. Simply adding a carbon tax to an existing cap-and-trade system reduces the carbon price in the market to such an extent that the overall price signal (tax plus carbon price) may remain unchanged. Generous feed-in tariffs or renewable energy obligations within a capped area have the same effect: they undermine the carbon price in the rest of the trading regime, likely increasing costs without reducing emissions. Policymakers wishing to support carbon prices should turn to hybrid instruments — that is, trading schemes with price-like features, such as an auction reserve price — to make sure their objectives are met.
Inhibition of xanthine oxidase reduces hyperglycemia-induced oxidative stress and improves mitochondrial alterations in skeletal muscle of diabetic mice
Authors: Bravard Amélie , Bonnard Charlotte , Durand Annie , Chauvin Marie-Agnès , Favier Roland , Vidal Hubert , Rieusset Jennifer
Published: January 2011

Reactive oxygen species (ROS) have been widely implicated in the pathogenesis of diabetes and more recently in mitochondrial alterations in skeletal muscle of diabetic mice. However, so far the exact sources of ROS in skeletal muscle have remained elusive. Aiming at better understanding the causes of mitochondrial alterations in diabetic muscle, we designed this study to characterize the sites of ROS production in skeletal muscle of streptozotocin (STZ)-induced diabetic mice. Hyperglycemic STZ mice showed increased markers of systemic and muscular oxidative stress, as evidenced by increased circulating H2O2 and muscle carbonylated protein levels. Interestingly, insulin treatment reduced hyperglycemia and improved systemic and muscular oxidative stress in STZ mice. We demonstrated that increased oxidative stress in muscle of STZ mice is associated with an increase of xanthine oxidase (XO) expression and activity and is mediated by an induction of H2O2 production by both mitochondria and XO. Finally, treatment of STZ mice, as well as high-fat and high-sucrose diet-fed mice, with oxypurinol reduced markers of systemic and muscular oxidative stress and prevented structural and functional mitochondrial alterations, confirming the in vivo relevance of XO in ROS production in diabetic mice. These data indicate that mitochondria and XO are the major sources of hyperglycemia-induced ROS production in skeletal muscle and that the inhibition of XO reduces oxidative stress and improves mitochondrial alterations in diabetic muscle.
Universal Verma Modules and the Misra‐Miwa Fock Space
Authors: Ram Arun , Tingley Peter
Published: January 2011

The Misra‐Miwa v‐deformed Fock space is a representation of the quantized affine algebra . It has a standard basis indexed by partitions, and the nonzero matrix
entries of the action of the Chevalley generators with respect to this basis are powers of v. Partitions also index the polynomial Weyl modules for Uq(𝔤𝔩N) as N tends to infinity. We explain how the powers of v which appear in the Misra‐Miwa Fock space also appear naturally
in the context of Weyl modules. The main tool we use is the Shapovalov determinant for a
universal Verma module.
Generalized Order and Best Approximation of Entire Function in Lp‐Norm
Authors: Harfaoui Mohammed
Published: January 2011

The aim of this paper is the characterization of the generalized growth of entire functions of several complex variables by means of the best polynomial approximation and interpolation on a compact K with respect to the set Ωr = {z ∈ Cn;   exp VK(z) ≤ r}, where is the Siciak extremal function of a L‐regular compact K.
Contributions of Cytogenetics and Molecular Cytogenetics to the Diagnosis of Adipocytic Tumors
Authors: Nishio Jun
Published: January 2011

Over the last 20 years, a number of tumor‐specific chromosomal translocations and associated fusion genes have been identified for mesenchymal neoplasms including adipocytic tumors. The addition of molecular cytogenetic techniques, especially fluorescence in situ hybridization (FISH), has further enhanced the sensitivity and accuracy of detecting nonrandom chromosomal translocations and/or other rearrangements in adipocytic tumors. Indeed, most resent molecular cytogenetic analysis has demonstrated a translocation t(11;16)(q13;p13) that produces a C11orf95‐MKL2 fusion gene in chondroid lipoma. Additionally, it is well recognized that supernumerary ring and/or giant rod chromosomes are characteristic for atypical lipomatous tumor/well‐differentiated liposarcoma and dedifferentiated liposarcoma, and amplification of 12q13–15 involving the MDM2, CDK4, and CPM genes is shown by FISH in these tumors. Moreover, myxoid/round cell liposarcoma is characterized by a translocation t(12;16)(q13;p11) that fuses the DDIT3 and FUS genes. This paper provides an overview of the role of conventional cytogenetics and molecular cytogenetics in the diagnosis of adipocytic tumors.
Genomic and Clinical Analysis of Amplification of the 13q31 Chromosomal Region in Alveolar Rhabdomyosarcoma: A Report from the Children's Oncology Group
Authors: Reichek Jennifer L. , Duan Fenghai , Smith Lynette M. , Gustafson Donna M. , O'Connor Roddy S. , Zhang Chune , Dunlevy Mandy J. , Gastier-Foster Julie M. , Barr Frederic G.
Published: January 2011

Purpose: This study determined the molecular characteristics and clinical significance of amplification of the 13q31 chromosomal region in alveolar rhabdomyosarcoma (ARMS), an aggressive pediatric cancer with frequent PAX3-FOXO1 and PAX7-FOXO1 gene fusions.

Experimental Design: The 13q31 amplicon was localized in an initial panel of ARMS cases using oligonucleotide arrays. A fluorescence in situ hybridization assay for this localized region was designed, and applied to more ARMS cases to determine the frequency and distribution of amplification. Quantitative reverse transcription-PCR assays were applied to measure gene expression. The clinical significance of copy number and expression was determined with Kaplan–Meier and Cox proportional hazard models.

Results: We localized the 13q31 amplicon to a 0.15 Mb region containing the MIR17HG gene encoding the polycistronic microRNA cluster, miR-17–92. This amplicon is present in 23% of ARMS cases with a marked preference for PAX7-FOXO1-positive cases. In tumors with 13q31 amplification, there is significantly increased expression of 5 of 6 microRNA's within the miR-17–92 cluster (miR-17, miR-19a, miR-19b, miR-20a, and miR-92a). In addition, a subset of nonamplified tumors with copy number-independent overexpression of all 6 microRNA's was identified. In clinical analyses, there was a significantly worse outcome associated with increased expression of the 5 microRNA's described above in 13q31-amplified cases when compared to nonamplified cases. There was also an improved outcome in 13q31-amplified cases with lower expression of these microRNA's.

Conclusions: 13q31 amplification and expression of the miR-17–92 cluster provide novel markers for identifying good and poor prognostic subsets of PAX7-FOXO1-positive ARMS. Clin Cancer Res; 17(6); 1463–73. ©2011 AACR.
MicroRNA-125a-5p Is an Independent Prognostic Factor in Gastric Cancer and Inhibits the Proliferation of Human Gastric Cancer Cells in Combination with Trastuzumab
Authors: Nishida Naohiro , Mimori Koshi , Fabbri Muller , Yokobori Takehiko , Sudo Tomoya , Tanaka Fumiaki , Shibata Kohei , Ishii Hideshi , Doki Yuichiro , Mori Masaki
Published: January 2011

Purpose: MicroRNA 125a-5p (miR-125a-5p) has been reported to be a tumor suppressor in malignancies of the breast, ovary, lung, and central nervous system. However, the clinical significance of miR-125a-5p in human gastrointestinal cancer has not been explored. We investigated a tumor inhibitory effect of miR-125a-5p in gastric cancer, focusing in particular on the miR-125a-ERBB2 (HER2, HER-2/neu) pathway.

Experimental Design: Quantitative RT-PCR was used to evaluate miR-125a-5p expression in 87 gastric cancer cases to determine the clinicopathologic significance of miR-125a-5p expression. The regulation of ERBB2 by miR-125a-5p was examined with precursor miR-125a–transfected cells. Furthermore, we investigated whether miR-125a-5p suppresses proliferation of gastric cancer cells in combination with trastuzumab, a monoclonal antibody against ERBB2.

Results: Low expression levels of miR-125a-5p were associated with enhanced malignant potential such as tumor size (P = 0.0068), tumor invasion (P = 0.031), liver metastasis (P = 0.029), and poor prognosis (P = 0.0069). Multivariate analysis indicated that low miR-125a-5p expression was an independent prognostic factor for survival. In vitro assays showed that ERBB2 is a direct target of miR-125a-5p, which potently suppressed the proliferation of gastric cancer cells, and, interestingly, the growth inhibitory effect was enhanced in combination with trastuzumab.

Conclusions: miR-125a-5p is a meaningful prognostic marker. Furthermore, miR-125a-5p mimic alone or in combination with trastuzumab could be a novel therapeutic approach against gastric cancer. Clin Cancer Res; 17(9); 2725–33. ©2011 AACR.
Monoclonal Antibody to CD31 (PECAM-1) Inhibits Tubular Regeneration after Ischemia Reperfusion Injury in the Rat
Authors: Valentini Xavier , Gossiaux Annabel , Caron Nathalie , Nonclercq Denis , Legrand Alexandre , Toubeau Gérard
Published: January 2011

Aims: We used a rat model of renal ischemia (35 min) to test the potential involvement of platelet/endothelial cell adhesion molecule 1 (PECAM-1/CD31) in the process of S3 tubule regeneration. Methods: A monoclonal antibody specific for murine PECAM-1 was injected i.p. immediately after kidney reperfusion or 48 h post-ischemia. One day before ischemia, each animal received an i.p. injection of 80 mg/kg 5-bromo-2′-deoxyuridine (BrdU). Experimental animals were sacrificed 1, 2, 3, 7 and 14 days post-ischemia. Renal sections were processed to characterize the histopathological alterations and the distribution of BrdU-immunopositive cells. Results: Our observations showed that anti-PECAM-1 administration was associated with an inhibition of S3 tubule regeneration along with a progressive cystic dilatation of renal tubules that was particularly prominent 2 weeks post-ischemia. Interestingly, injection of anti-PECAM-1 48 h post-ischemia failed to block renal regeneration and was followed by a normal re-epithelialization of S3 tubules. Conclusion: Our data showed that the blockade of PECAM-1 immediately after kidney reperfusion inhibits tubular regeneration. These observations suggest that transendothelial migration of extrarenal cells could be a precocious and pivotal step in kidney reparation, but also suggest that these extrarenal cells could be essential to the process of tubular regeneration.
Treatment of Advanced Emphysema with Emphysematous Lung Sealant (AeriSeal®)
Authors: Herth F.J.F. , Gompelmann D. , Stanzel F. , Bonnet R. , Behr J. , Schmidt B. , Magnussen H. , Ernst A. , Eberhardt R.
Published: January 2011

Background: This report summarizes initial tests of an emphysematous lung synthetic polymer sealant (ELS) designed to reduce lung volume in patients with advanced emphysema. Objectives: The primary study objective was to define a therapeutic strategy to optimize treatment safety and effectiveness. Methods: ELS therapy was administered bronchoscopically to 25 patients with heterogeneous emphysema in an open-label, noncontrolled study at 6 centers in Germany. Treatment was performed initially at 2–4 subsegments. After 12 weeks, patients were eligible for repeat therapy to a total of 6 sites. Safety and efficacy were assessed after 6 months. Responses were evaluated in terms of changes from baseline in lung physiology, functional capacity, and health-related quality of life. Follow-up is available for 21 of 25 patients. Results: Treatment was well tolerated. There were no treatment-related deaths (i.e. within 90 days of treatment), and an acceptable short- and long-term safety profile. Physiological and clinical benefits were observed at 24 weeks. Efficacy responses were better among Global Initiative for Chronic Obstructive Lung Disease (GOLD) stage III patients [n = 14; change in residual volume/total lung capacity (ΔRV/TLC) = –7.4 ± 10.3%; Δ forced expiratory volume in 1 s (ΔFEV1) = +15.9 ± 22.6%; change in forced vital capacity (ΔFVC) = +24.1 ± 22.7%; change in carbon monoxide lung diffusion capacity (ΔDLCO) = +19.3 ± 34.8%; change in 6-min walk test (Δ6MWD) = +28.7 ± 59.6 m; change in Medical Research Council Dyspnea (ΔMRCD) score = –1.0 ± 1.04 units; change in St. George’s Respiratory Questionnaire (ΔSGRQ) score = –9.9 ± 15.3 units] than for GOLD stage IV patients (n = 7; ΔRV/TLC = –0.5 ± 6.4%; ΔFEV1 = +2.3 ± 12.3%; ΔFVC = +2.6 ± 21.1%; ΔDLCO = –2.8 ± 17.2%; Δ6MWD = +28.3 ± 58.4 m; ΔMRCD = 0.3 ± 0.81 units; ΔSGRQ = –6.7 ± 7.0 units). Conclusions: ELS therapy shows promise for treating patients with advanced heterogeneous emphysema. Additional studies to assess responses in a larger cohort with a longer follow-up are warranted.
Effects of Clarithromycin and Dexamethasone on Mucus Production in Isografted Rat Trachea
Authors: Kitano Masako , Ishinaga Hajime , Shimizu Takeshi , Takeuchi Kazuhiko , Majima Yuichi
Published: January 2011

Objectives: The purpose of this study was to develop an animal model for the study of mucus overproduction and to assess the effect of a 14-membered macrolide antibiotic and a glucocorticoid on lipopolysaccharide (LPS)-induced mucus production. Methods: Tracheas from donor rats were homografted to recipient rats for 4 weeks, and the usefulness of this tracheal homograft model in the study of mucus production was examined. Results: Oral administration of clarithromycin (CAM) to recipient rats for 4 weeks significantly reduced LPS-induced mucus production in the homografted trachea. Dexamethasone administered for 4 weeks also significantly reduced the mucus volume in LPS-treated homografted trachea compared with that in the control rats. The implanted trachea containing control medium was not histologically different from normal trachea. When the medium instilled into the implanted trachea contained 1 µg/ml LPS, the volume and spinability of mucus produced in the tracheal lumen were significantly increased compared to those in the trachea instilled with control medium. Goblet cell metaplasia was also observed in the implanted trachea containing LPS. Conclusions: The present study shows that LPS-administered homografted trachea is a good animal model of chronic hypersecretory diseases of the upper and lower airways. CAM and dexamethasone could be treatment choices in such hypersecretory diseases.
Determinants of Blood Pressure in Preschool Children
Authors: Simonetti Giacomo D. , Schwertz Rainer , Klett Martin , Hoffmann Georg F. , Schaefer Franz , Wühl Elke
Published: January 2011

Background—

Hypertension is the leading risk factor for cardiovascular disease. Although accumulating evidence suggests tracking of blood pressure from childhood into adult life, there is little information regarding the relative contributions of genetic, prenatal, biological, behavioral, environmental, and social determinants to childhood blood pressure.

Methods and Results—

Blood pressure and an array of potential anthropometric, prenatal, environmental, and familial risk factors for high blood pressure, including parental smoking habits, were determined as part of a screening project in 4236 preschool children (age 5.7±0.4 years). Smoking was reported by 28.5% of fathers and 20.7% of mothers, and by both parents 11.9%. In addition to classic risk factors such as body mass index, prematurity, low birth weight, and parental hypertension, both systolic (+1.0 [95% confidence interval, +0.5 to +1.5] mm Hg;
P
=0.0001) and diastolic blood pressure (+0.5 [+0.03 to +0.9] mm Hg;
P
=0.03) were higher in children of smoking parents. Parental smoking independently affected systolic blood pressure (
P
=0.001) even after correction for other risk factors, such as body mass index, parental hypertension, or birth weight, increasing the likelihood of having a systolic blood pressure in the top 15% of the population by 21% (2% to 44%;
P
=0.02).

Conclusions—

In healthy preschool children, parental smoking is an independent risk factor for higher blood pressure, adding to other familial and environmental risk factors. Implementing smoke-free environments at home and in public places may provide a long-term cardiovascular benefit even to young children.
Association of Maternal Diabetes Mellitus in Pregnancy With Offspring Adiposity Into Early Adulthood
Authors: Lawlor Debbie A. , Lichtenstein Paul , Långström Niklas
Published: January 2011

Background—

Maternal diabetes mellitus in pregnancy results in greater offspring adiposity at birth. It is unclear whether it is associated with greater adiposity into adulthood, and if so, whether this is via intrauterine mechanisms or shared familial characteristics.

Methods and Results—

A record-linkage prospective cohort study of 280 866 singleton-born Swedish men from 248 293 families was used to explore the intrauterine effect of maternal diabetes mellitus on offspring body mass index (BMI) in early adulthood. Maternal diabetes mellitus during pregnancy was associated with greater mean BMI at age 18 in their sons. The difference in BMI was similar within brothers and between nonsiblings. BMI of men whose mothers had diabetes mellitus during their pregnancy was on average 0.94 kg/m
2
greater (95% confidence interval [CI], 0.35 to 1.52) than in their brothers born before their mother was diagnosed with diabetes, after adjustment for birth year, maternal age, parity and education, birth weight, gestational age, and age at assessment of BMI. Early-pregnancy BMI was positively associated with son's BMI between nonsiblings, but there was no association within brothers. Adjustment of the maternal diabetes–offspring BMI association for maternal BMI did not alter the association either within brothers or between nonsiblings. Results were also robust to sensitivity analyses restricting the within-sibling analyses to siblings born within 3 years of each other.

Conclusion—

Maternal diabetes mellitus has long-term consequences for greater BMI in offspring; this association is likely to be via intrauterine mechanisms, and is independent of maternal BMI in early pregnancy.
Nanoparticle-Mediated Delivery of Pitavastatin Into Lungs Ameliorates the Development and Induces Regression of Monocrotaline-Induced Pulmonary Artery Hypertension
Authors: Chen Ling , Nakano Kaku , Kimura Satoshi , Matoba Tetsuya , Iwata Eiko , Miyagawa Miho , Tsujimoto Hiroyuki , Nagaoka Kazuhiro , Kishimoto Junji , Sunagawa Kenji , Egashira Kensuke
Published: January 2011

Pulmonary artery hypertension (PAH) is an intractable disease of the small PAs in which multiple pathogenic factors are involved. Statins are known to mitigate endothelial injury and inhibit vascular remodeling and inflammation, all of which play crucial roles in the pathogenesis of PAH. We tested the hypothesis that nanoparticle (NP)-mediated delivery of pitavastatin into the lungs can be a novel therapeutic approach for the treatment of PAH. Among the marketed statins, pitavastatin was found to have the most potent effects on proliferation of PA smooth muscle cells in vitro. We formulated pitavastatin-NP and found that pitavastatin-NP was more effective than pitavastatin alone in inhibiting cellular proliferation and inflammation in vitro. In a rat model of monocrotaline-induced PAH, a single intratracheal instillation of NP resulted in the delivery of NP into alveolar macrophages and small PAs for up to 14 days after instillation. Intratracheal treatment with pitavastatin-NP, but not with pitavastatin, attenuated the development of PAH and was associated with a reduction of inflammation and PA remodeling. NP-mediated pitavastatin delivery was more effective than systemic administration of pitavastatin in attenuating the development of PAH. Importantly, treatment with pitavastatin-NP 3 weeks after monocrotaline injection induced regression of PAH and improved survival rate. This mode of NP-mediated pitavastatin delivery into the lungs is effective in attenuating the development of PAH and inducing regression of established PAH, suggesting potential clinical significance for developing a new treatment for PAH.
Nuclear Factor Kappa B and Matrix Metalloproteinase Induced Receptor Cleavage in the Spontaneously Hypertensive Rat
Authors: Wu Kwan-I Sharon , Schmid-Schönbein Geert W.
Published: January 2011

Recent evidence suggests that inflammation in the spontaneously hypertensive rat (SHR) is associated with an uncontrolled matrix metalloproteinase (MMP) activity. We hypothesize that the transcription factor nuclear factor kappa B (NFκB) is overexpressed in the SHR, enhancing its MMP activity and enzymatic cleavage of the β2 adrenergic receptor (β
2
AR), thereby diminishing catecholamine-mediated arteriolar vasodilation. NFκB expression level and translocation were compared between Wistar Kyoto rat and SHR kidney, heart, and brain. The animals were treated with NFκB inhibitor, pyrrolidine dithiocarbamate, for 10 weeks and correlations between NFκB and MMP activity were determined. Immunohistochemistry showed that NFκB expression is increased in untreated SHR kidney (≈14%) and brain hypothalamus (≈22%) compared to that in Wistar Kyoto rats (
P
<0.05), but not in myocardium and cerebral cortex. After pyrrolidine dithiocarbamate treatment, the SHR systolic blood pressure was reduced to close to Wistar Kyoto rat levels. NFκB expression level in treated SHR was also decreased in kidney and hypothalamus compared to nontreated animals (
P
<0.05). Furthermore, MMP-2 and MMP-9 activities in SHR plasma were significantly reduced (≈41%) by pyrrolidine dithiocarbamate treatment. Additionally, zymographic analyses and in situ zymography showed decreased MMP-2 activity in kidney homogenates and decreased MMP-1 and MMP-9 activities in brain. The level of the β
2
AR extracellular, but not intracellular, domain density was found to be reduced in kidney, showing a receptor cleavage process that can be blocked by pyrrolidine dithiocarbamate treatment. These results suggest NFκB is an important transcription factor in the SHR and may be involved in the enhanced MMP activity and, consequently, receptor cleavage.
Air Pollution, Blood Pressure, and the Risk of Hypertensive Complications During Pregnancy
Authors: van den Hooven Edith H. , de Kluizenaar Yvonne , Pierik Frank H. , Hofman Albert , van Ratingen Sjoerd W. , Zandveld Peter Y.J. , Mackenbach Johan P. , Steegers Eric A.P. , Miedema Henk M.E. , Jaddoe Vincent W.V.
Published: January 2011

Exposure to air pollution is associated with elevated blood pressure and cardiovascular disease. We assessed the associations of exposure to particulate matter (PM
10
) and nitrogen dioxide (NO
2
) levels with blood pressure measured in each trimester of pregnancy and the risks of pregnancy-induced hypertension and preeclampsia in 7006 women participating in a prospective cohort study in the Netherlands. Information on gestational hypertensive disorders was obtained from medical records. PM
10
exposure was not associated with first trimester systolic and diastolic blood pressure, but a 10-μg/m
3
increase in PM
10
levels was associated with a 1.11-mm Hg (95% confidence interval [CI] 0.43 to 1.79) and 2.11-mm Hg (95% CI 1.34 to 2.89) increase in systolic blood pressure in the second and third trimester, respectively. Longitudinal analyses showed that elevated PM
10
exposure levels were associated with a steeper increase in systolic blood pressure throughout pregnancy (
P
<0.01), but not with diastolic blood pressure patterns. Elevated NO
2
exposure was associated with higher systolic blood pressure levels in the first, second, and third trimester (
P
<0.05), and with a more gradual increase when analyzed longitudinally (
P
<0.01). PM
10
exposure, but not NO
2
exposure, was associated with an increased risk of pregnancy-induced hypertension (odds ratio 1.72 [95% CI 1.12 to 2.63] per 10-μg/m
3
increase). In conclusion, our results suggest that air pollution may affect maternal cardiovascular health during pregnancy. The effects might be small but relevant on a population level.
Urinary Albumin Excretion Is Associated With Nocturnal Systolic Blood Pressure in Resistant Hypertensives
Authors: Oliveras Anna , Armario Pedro , Martell-Clarós Nieves , Ruilope Luis M. , de la Sierra Alejandro
Published: January 2011

Microalbuminuria is a known marker of subclinical organ damage. Its prevalence is higher in patients with resistant hypertension than in subjects with blood pressure at goal. On the other hand, some patients with apparently well-controlled hypertension still have microalbuminuria. The current study aimed to determine the relationship between microalbuminuria and both office and 24-hour ambulatory blood pressure. A cohort of 356 patients (mean age 64±11 years; 40.2% females) with resistant hypertension (blood pressure ≥140 and/or 90 mm Hg despite treatment with ≥3 drugs, diuretic included) were selected from Spanish hypertension units. Patients with estimated glomerular filtration rate <30 mL/min/1.73 m
2
were excluded. All patients underwent clinical and demographic evaluation, complete laboratory analyses, and good technical-quality 24-hour ambulatory blood pressure monitoring. Urinary albumin/creatinine ratio was averaged from 3 first-morning void urine samples. Microalbuminuria (urinary albumin/creatinine ratio ≥2.5 mg/mmol in males or ≥3.5 mg/mmol in females) was detected in 46.6%, and impaired renal function (estimated glomerular filtration rate <60 mL/min/1.73 m
2
) was detected in 26.8%. Bivariate analyses showed significant associations of microalbuminuria with older age, reduced estimated glomerular filtration rate, increased nighttime systolic blood pressure, and elevated daytime, nighttime, and 24-hour diastolic blood pressure. In a logistic regression analysis, after age and sex adjustment, elevated nighttime systolic blood pressure (multivariate odds ratio, 1.014 [95% CI, 1.001 to 1.026];
P
=0.029) and reduced estimated glomerular filtration rate (multivariate odds ratio, 2.79 [95% CI, 1.57 to 4.96];
P
=0.0005) were independently associated with the presence of microalbuminuria. We conclude that microalbuminuria is better associated with increased nighttime systolic blood pressure than with any other office and 24-hour ambulatory blood pressure monitoring parameters.
Integration of Reinforcement Learning and Optimal Decision-Making Theories of the Basal Ganglia
Authors: Bogacz Rafal , Larsen Tobias
Published: January 2011

This article seeks to integrate two sets of theories describing action selection in the basal ganglia: reinforcement learning theories describing learning which actions to select to maximize reward and decision-making theories proposing that the basal ganglia selects actions on the basis of sensory evidence accumulated in the cortex. In particular, we present a model that integrates the actor-critic model of reinforcement learning and a model assuming that the cortico-basal-ganglia circuit implements a statistically optimal decision-making procedure. The values of corico-striatal weights required for optimal decision making in our model differ from those provided by standard reinforcement learning models. Nevertheless, we show that an actor-critic model converges to the weights required for optimal decision making when biologically realistic limits on synaptic weights are introduced. We also describe the model's predictions concerning reaction times and neural responses during learning, and we discuss directions required for further integration of reinforcement learning and optimal decision-making theories.
Targeted Inhibition of CD133+ Cells in Oral Cancer Cell Lines
Authors: Damek-Poprawa M. , Volgina A. , Korostoff J. , Sollecito T.P. , Brose M.S. , O’Malley B.W. , Akintoye S.O. , DiRienzo J.M.
Published: January 2011

Resistance to treatment and the appearance of secondary tumors in head and neck squamous cell carcinomas (HNSCC) have been attributed to the presence of cells with stem-cell-like properties in the basal layer of the epithelium at the site of the lesion. In this study, we tested the hypothesis that these putative cancer stem cells (CSC) in HNSCC could be specifically targeted and inhibited. We found that 9 of 10 head and neck tumor biopsies contained a subpopulation of cells that expressed CD133, an unusual surface-exposed membrane-spanning glycoprotein associated with CSC. A genetically modified cytolethal distending toxin (Cdt), from the periodontal pathogen Aggregatibacter actinomycetemcomitans, was conjugated to an anti-human CD133 monoclonal antibody (MAb). The Cdt-MAb complex preferentially inhibited the proliferation of CD133+ cells in cultures of established cell lines derived from HNSCC. Inhibition of the CD133+ cells was rate- and dose-dependent. Saturation kinetics indicated that the response to the Cdt-MAb complex was specific. Healthy primary gingival epithelial cells that are native targets of the wild-type Cdt were not affected. Analysis of these data provides a foundation for the future development of new therapies to target CSC in the early treatment of HNSCC. Abbreviations: Cdt, cytolethal distending toxin; CSC, cancer stem cells; HNSCC, head and neck squamous cell carcinoma; MAb, monoclonal antibody.
Sensitivity to Visual Prosodic Cues in Signers and Nonsigners
Authors: Brentari Diane , González Carolina , Seidl Amanda , Wilbur Ronnie
Published: January 2011

Three studies are presented in this paper that address how nonsigners perceive the visual prosodic cues in a sign language. In Study 1, adult American nonsigners and users of American Sign Language (ASL) were compared on their sensitivity to the visual cues in ASL Intonational Phrases. In Study 2, hearing, nonsigning American infants were tested using the same stimuli used in Study 1 to see whether maturity, exposure to gesture, or exposure to sign language is necessary to demonstrate this type of sensitivity. Study 3 addresses nonsigners’ and signers’ strategies for segmenting Prosodic Words in a sign language. Adult participants from six language groups (3 spoken languages and 3 sign languages) were tested. The results of these three studies indicate that nonsigners have a high degree of sensitivity to sign language prosodic cues at the Intonational Phrase level and the Prosodic Word level; these are attributed to modality or ‘channel’ effects of the visual signal.There are also some differences between signers’ and nonsigners’ sensitivity; these differences are attributed to language experience or language-particular constraints. This work is useful in understanding the gestural competence of nonsigners and the ways in which this type of competence may contribute to the grammaticalization of these properties in a sign language.
Impact of the ω‐3 to ω‐6 Polyunsaturated Fatty Acid Ratio on Cytokine Release in Human Alveolar Cells
Authors: Cotogni Paolo , Muzio Giuliana , Trombetta Antonella , Ranieri V. Marco , Canuto Rosa Angela
Published: January 2011

Background: ω‐3 polyunsaturated fatty acids (PUFAs) and ω‐6 PUFAs have opposing influences on inflammation. The objective was to determine whether lipopolysaccharide (LPS)–induced cytokine release by human alveolar cells was affected by changes in the ω‐3/ω‐6 ratio of cell membranes induced by different supplies of PUFAs. Methods: After LPS challenge, PUFAs were added to alveolar cells as docosahexaenoic acid (DHA, ω‐3) and arachidonic acid (AA, ω‐6) in 4 different DHA/AA ratios (1:1, 1:2, 1:4, and 1:7), and the effects on cytokine release were measured. Results: The supply of 1:1 and 1:2 DHA/AA ratios reversed the baseline predominance of ω‐6 over ω‐3 in the ω‐3/ω‐6 PUFA ratio of cell membranes. The release of proinflammatory cytokines (tumor necrosis factor α, interleukin‐6, and interleukin‐8) was reduced by 1:1 and 1:2 DHA/AA ratios (P < .01 to P < .001) but increased by 1:4 and 1:7 DHA/AA ratios (P < .01 to P < .001) vs control. The 1:1 and 1:2 ratios increased the release of anti‐inflammatory interleukin‐10 (P < .001). The balance between proinflammatory and anti‐inflammatory cytokines showed an anti‐inflammatory response with 1:1 and 1:2 ratios and a proinflammatory response with 1:4 and 1:7 ratios (P < .001). Conclusions: This study showed that proinflammatory cytokine release was dependent on the proportion of ω‐3 in the ω‐3/ω‐6 ratio of alveolar cell membranes, being reduced with the supply of a high proportion of DHA and increased with a high proportion of AA, respectively. These results support the biochemical basis for current recommendations to shift the PUFA supply from ω‐6 to ω‐3 in nutrition support of patients with acute lung injury.
Crocetin Reduces Activation of Hepatic Apoptotic Pathways and Improves Survival in Experimental Hemorrhagic Shock
Authors: Yang Rongjie , Vernon Kathy , Thomas Ann , Morrison David , Qureshi Nilofer , Van Way Charles W
Published: January 2011

Background:Hemorrhagic shock results in cellular damage and cell death. A primary mechanism is cellular apoptosis from mitochondrial damage. This study demonstrated that administration of crocetin to experimental animals during resuscitation from shock significantly improved postshock survival and reduced apoptosis. Crocetin is a component of saffron and has long been used in traditional medicine in Asia.Methods:Male Sprague‐Dawley rats (350 ± 30g) were randomly assigned to 1 of 4 groups of 8 animals. Hemorrhagic shock was induced by withdrawing blood until the mean arterial pressure was 35–40 mm Hg, and blood pressure was maintained at that level for 60 minutes with further withdrawals as needed. Resuscitation was carried out by administration of 21 mL/kg lactated Ringer's solution and return of shed blood, with or without concurrent administration of crocetin (2 mg/kg). Control animals were sham‐treated with surgical preparation, without shock or resuscitation, and with and without crocetin. Rats were sacrificed 24 hours after completion of resuscitation. The extent of activation of hepatic apoptosis was established by measuring levels of hepatic cytosolic cytochrome c, caspase‐3, and bcl‐2. A separate group of 53 animals treated identically was used to assess survival.Results:Crocetin administration during resuscitation resulted in less extensive activation of hepatic apoptosis and significantly increased survival relative to controls.Conclusions:Crocetin administration to experimental animals during resuscitation post hemorrhage increased survival, at least in part by protecting the liver from activation of apoptotic cell death. This agent continues to show promise as a potential treatment strategy for hemorrhagic shock.
Early Jejunal Feeding Initiation and Clinical Outcomes in Patients with Severe Acute Pancreatitis
Authors: Hegazi Refaat , Raina Amit , Graham Toby , Rolniak Susan , Centa Patty , Kandil Hossam , O'Keefe Stephen J.
Published: January 2011

Background: Compared with parenteral nutrition, enteral nutrition reduces infectious complications and mortality in patients with severe acute pancreatitis (SAP). This study used clinical outcomes to investigate the association between time to initiation of distal jejunal feeding (DJF) and time to achievement of goal enteral feeding with clinical outcomes. Methods: A retrospective chart review was performed on all patients with SAP admitted to the medical intensive care unit (ICU) during a 1‐year period. Collected data included demographic information, body mass index (BMI; kg/m2), Acute Physiology and Chronic Health Evaluation (APACHE) II scores at admission, time of onset of DJF, time to goal feeding, ICU length of stay, and mortality. Results: Time to starting DJF was longer in nonsurvivors (n = 4) than in survivors (n = 12) (17 vs 7 days, P < .05). All nonsurvivors had BMI >30 kg/m2 (50% had BMI > 50 kg/m2). ICU length of stay was significantly associated with achievement of goal feeding. Three patients never reached goal feeding and spent 45.3 ± 19.6 days in the ICU; 7 patients reached goal feeding within 3 days of initiating DJF and spent 18 ± 1.7 days in the ICU; and 4 patients reached goal feeding within 3 days and spent 10.5 ± 3.5 days in the ICU. APACHE II scores were not significantly different among the 3 groups (16.7 ± 1.5, 12 ± 0.7, and 16.2 ± 1.2, respectively, P > .05). Conclusions: Early initiation of DJF in the ICU was associated with reduced mortality in this cohort of patients with SAP. Early achievement of jejunal feeding goal early was associated with a shorter ICU length of stay, irrespective of the severity of SAP.
Nutrition Modulation of Gastrointestinal Toxicity Related to Cancer Chemotherapy
Authors: Xue Hongyu , Sawyer Michael B. , Wischmeyer Paul E. , Baracos Vickie E.
Published: January 2011

Chemotherapy‐induced gut toxicity is a major dose‐limiting toxicity for many anticancer drugs. Gastrointestinal (GI) complications compromise the efficacy of chemotherapy, promote overall malnutrition, aggravate cancer cachexia, and may contribute to worsened prognosis. The GI tract is an attractive target for nutrition modulation, owing to its direct exposure to the diet, participation in uptake and metabolism of nutrients, high rate of cell turnover, and plasticity to nutrition stimuli. Glutamine, ω‐3 polyunsaturated fatty acids, and probiotics/prebiotics are therapeutic factors that potentially modulate GI toxicity related to cancer treatments. Preclinical and clinical evidence are reviewed to critically define plausible benefits of these factors and their potential development into adjuncts to cancer chemotherapy. Mechanisms underlying the action of these nutrients are being unraveled in the laboratory. Optimal strategies to translate these findings into clinical care still remain to be elucidated. Key questions that remain to be answered include the following: which nutrient or combination of nutrients is selected for which patient and chemotherapy regimen? What mechanisms are responsible for modulation, and how are nutrient(s) administered in a clinically optimal manner? Research exploring interactions between different nutrients in GI protection is ongoing and demands further understanding. How nutrition preparations given to chemotherapy‐treated patients are formulated in terms of component selection and dose optimization should be carefully studied and justified.
Nirschl Surgical Technique for Concomitant Lateral and Medial Elbow Tendinosis
Authors: Schipper Oliver N. , Dunn Jonathan H. , Ochiai Derek H. , Donovan J. Skye , Nirschl Robert P.
Published: January 2011

Background: Combined lateral elbow tendinosis (tennis elbow) and medial elbow tendinosis (golfer’s elbow) can be a disabling condition that, if unresponsive to nonoperative treatments, may be effectively treated surgically. The authors are not aware of any study that reports the outcome of a combined operation for lateral and medial elbow tendinosis (country club elbow) performed in the same operative setting.

Hypothesis: Combined surgical treatment of country club elbow in the same operative setting has similar outcomes to those seen in the literature for single operative procedures.

Study Design: Case series; Level of evidence 4.

Methods: Outcome measurements included the Numeric Pain Intensity Scale, the Nirschl tennis elbow scoring system, and the American Shoulder and Elbow Surgeons elbow form. Forty-eight patients (53 clinical elbows) were available by telephone, with a minimum time to follow-up of 5 years (range, 5-19 years; mean, 11.7 years).

Results: The average Nirschl tennis elbow score improved from 16.7 preoperatively to 70.8 postoperatively ( P < .01). The average American Shoulder and Elbow Surgeons elbow score improved from 45.2 to 90.4 ( P < .01). The Numeric Pain Intensity Scale score improved from 8.8 to 1.7 ( P < .01). By the criteria of the Nirschl tennis elbow score, results were rated excellent in 38 elbows, good in 7 elbows, fair in 5 elbows, and poor in 3 elbows, with 85% (45 of 53) good to excellent results. Patient satisfaction with the surgery averaged 8.7 out of 10. Of the 46 patients who played sports, 44 (96%) reported returning to their sports.

Conclusion: When nonoperative treatment of lateral and medial elbow tendinosis fails, combined surgical intervention via the Nirschl operative techniques for country club elbow is highly effective, with results similar to those of single-sided intervention.
Living Donor Liver Transplantation
Authors: Gali Bhargavi , Rosen Charles B. , Plevak David J.
Published: January 2011

A perception that living donor liver transplantation can be accomplished with an acceptable donor complication rate and recipient survival rate has led to the acceptance of living donor liver transplantation as a viable alternative to decreased deceased donor transplantation. Careful candidate evaluation and selection has been crucial to the success of this procedure. Advancements in the understanding of the lobar nature of the liver and of liver regeneration have advanced the surgical technique. Initial attempts at adult-to-adult donation utilized the left hepatic lobe, but now have evolved into use of the right hepatic lobe. Size matching is very important to successful graft function in the recipient. There is great concern regarding morbidity and mortality in donors. Biliary complications and infections continue to be among the most highly reported complications, although rates vary among centers and countries. Reports of single center complications have ranged from 9% to 67%. A survey of centers in the United States in 2003 reported complications of 10%. A series from our institution reported complications arising in 13 (33%) of 39 patients. A review focused on documenting donor deaths found 33 living liver donor deaths worldwide. The much publicized immediate postoperative mishap of 2002 that resulted in a donor’s death resulted in a drop in the utilization of living donor liver transplantation in the United States, from which this procedure has never fully recovered. The future development and expansion of living donor liver transplantation depends on open communication regarding donor complications and deaths. Close immediate postoperative monitoring and meticulous management will remain an essential aspect in limiting donor complications and deaths.