bluuebunny/crossref_metadata_2025 huggingface dataset:
Optimization of Manipulability in the Design of a Surgery Trainer Based on Virtual Reality
Authors: San Martin Jose , Trivino Gracian
Published: September 2012

In the field of minimally invasive surgery (MIS), trainers based on virtual reality provide a very useful, nondegradable, realistic training environment. The project of building this new type of trainers requires the development of new tools. In this paper, we describe a set of new measures that allow calculating the optimal position and orientation of haptic devices versus the virtual workspace of the application. We illustrate the use of these new tools applying them to a practical application.
A nonlinear lag correction algorithm for a‐Si flat‐panel x‐ray detectors
Authors: Starman Jared , Star‐Lack Josh , Virshup Gary , Shapiro Edward , Fahrig Rebecca
Published: September 2012

Purpose:

Detector lag, or residual signal, in a‐Si flat‐panel (FP) detectors can cause significant shading artifacts in cone‐beam computed tomography reconstructions. To date, most correction models have assumed a linear, time‐invariant (LTI) model and correct lag by deconvolution with an impulse response function (IRF). However, the lag correction is sensitive to both the exposure intensity and the technique used for determining the IRF. Even when the LTI correction that produces the minimum error is found, residual artifact remains. A new non‐LTI method was developed to take into account the IRF measurement technique and exposure dependencies.

Methods:

First, a multiexponential (N = 4) LTI model was implemented for lag correction. Next, a non‐LTI lag correction, known as the nonlinear consistent stored charge (NLCSC) method, was developed based on the LTI multiexponential method. It differs from other nonlinear lag correction algorithms in that it maintains a consistent estimate of the amount of charge stored in the FP and it does not require intimate knowledge of the semiconductor parameters specific to the FP. For the NLCSC method, all coefficients of the IRF are functions of exposure intensity. Another nonlinear lag correction method that only used an intensity weighting of the IRF was also compared. The correction algorithms were applied to step‐response projection data and CT acquisitions of a large pelvic phantom and an acrylic head phantom. The authors collected rising and falling edge step‐response data on a Varian 4030CB a‐Si FP detector operating in dynamic gain mode at 15 fps at nine incident exposures (2.0%–92% of the detector saturation exposure). For projection data, 1st and 50th frame lag were measured before and after correction. For the CT reconstructions, five pairs of ROIs were defined and the maximum and mean signal differences within a pair were calculated for the different exposures and step‐response edge techniques.

Results:

The LTI corrections left residual 1st and 50th frame lag up to 1.4% and 0.48%, while the NLCSC lag correction reduced 1st and 50th frame residual lags to less than 0.29% and 0.0052%. For CT reconstructions, the NLCSC lag correction gave an average error of 11 HU for the pelvic phantom and 3 HU for the head phantom, compared to 14–19 HU and 2–11 HU for the LTI corrections and 15 HU and 9 HU for the intensity weighted non‐LTI algorithm. The maximum ROI error was always smallest for the NLCSC correction. The NLCSC correction was also superior to the intensity weighting algorithm.

Conclusions:

The NLCSC lag algorithm corrected for the exposure dependence of lag, provided superior image improvement for the pelvic phantom reconstruction, and gave similar results to the best case LTI results for the head phantom. The blurred ring artifact that is left over in the LTI corrections was better removed by the NLCSC correction in all cases.
Unifying the inertia and Riemann curvature tensors through geometric algebra
Authors: Berrondo M. , Greenwald J. , Verhaaren C.
Published: September 2012

We follow a common thread to express linear transformations of vectors and bivectors from different fields of physics in a unified way. The tensorial representations are coordinate independent and assume a compact form using Clifford products. As specific examples, we present (a) the inertia tensor as a vector-to-vector as well as a bivector-to-bivector linear transformation; (b) the Newtonian tidal acceleration; and (c) the Riemann tensor corresponding to a Schwarzschild black hole as a bivector-to-bivector tensorial transformation. The resulting expressions have a remarkable similarity when expressed in terms of geometric products.
Hipk Antagonizes Hippo
Authors: VanHook Annalisa M.
Published: September 2012

A kinase opposes Hippo signaling by promoting activity of the transcriptional coactivator Yorkie.
β Cells Lose Their Identity
Authors: Foley John F.
Published: September 2012

The dedifferentiation of pancreatic β cells into progenitor cells may underlie the development of type 2 diabetes.
Novel Antibiofilm Chemotherapy Targets Exopolysaccharide Synthesis and Stress Tolerance in Streptococcus mutans To Modulate Virulence Expression
In Vivo
Authors: Falsetta Megan L. , Klein Marlise I. , Lemos José A. , Silva Bruno B. , Agidi Senyo , Scott-Anne Kathy K. , Koo Hyun
Published: September 2012

Fluoride is the mainstay of dental caries prevention, and yet current applications offer incomplete protection and may not effectively address the infectious character of the disease. Therefore, we evaluated the effectiveness of a novel combination therapy (CT; 2 mM myricetin, 4 mM
tt
-farnesol, 250 ppm of fluoride) that supplements fluoride with naturally occurring, food-derived, antibiofilm compounds. Treatment regimens simulating those experienced clinically (twice daily for ≤60 s) were used both
in vitro
over a saliva-coated hydroxyapatite biofilm model and
in vivo
with a rodent model of dental caries. The effectiveness of CT was evaluated based on the incidence and severity of carious lesions (compared to fluoride or vehicle control). We found that CT was superior to fluoride (positive control,
P
< 0.05); topical applications dramatically reduced caries development in Sprague-Dawley rats, all without altering the
Streptococcus mutans
or total populations within the plaque. We subsequently identified the underlying mechanisms through which applications of CT modulate biofilm virulence. CT targets expression of key
Streptococcus mutans
genes during biofilm formation
in vitro
and
in vivo
. These are associated with exopolysaccharide matrix synthesis (
gtfB
) and the ability to tolerate exogenous stress (e.g.,
sloA
), which are essential for cariogenic biofilm assembly. We also identified a unique gene (
SMU.940
) that was severely repressed and may represent a potentially novel target; its inactivation disrupted exopolysaccharide accumulation and matrix development. Altogether, CT may be clinically more effective than current anticaries modalities, targeting expression of bacterial virulence associated with pathogenesis of the disease. These observations may have relevance for development of enhanced therapies against other biofilm-dependent infections.
Evaluation of Single and Combination Therapies with Tenofovir Disoproxil Fumarate and Emtricitabine
In Vitro
and in a Robust Mouse Model Supporting High Levels of Hepatitis B Virus Replication
Authors: Schinazi Raymond F. , Bassit Leda , Clayton Marcia M. , Sun Bill , Kohler James J. , Obikhod Aleksandr , Arzumanyan Alla , Feitelson Mark A.
Published: September 2012

Next-generation therapies for chronic hepatitis B virus (HBV) infection will involve combinations of established and/or experimental drugs. The current study investigated the
in vitro
and
in vivo
efficacy of tenofovir disoproxil fumarate (TDF) and/or emtricitabine [(−)-FTC] alone and in combination therapy for HBV infection utilizing the HepAD38 system (human hepatoblastoma cells transfected with HBV). Cellular pharmacology studies demonstrated increased levels of (−)-FTC triphosphate with coincubation of increasing concentrations of TDF, while (−)-FTC had no effect on intracellular tenofovir (TFV) diphosphate levels. Quantification of extracellular HBV by real-time PCR from hepatocytes demonstrated the anti-HBV activity with TDF, (−)-FTC, and their combination. Combination of (−)-FTC with TDF or TFV (ratio, 1:1) had a weighted average combination index of 0.7 for both combination sets, indicating synergistic antiviral effects. No cytotoxic effects were observed with any regimens. Using an
in vivo
murine model which develops robust HBV viremia in nude mice subcutaneously injected with HepAD38 cells, TDF (33 to 300 mg/kg of body weight/day) suppressed virus replication for up to 10 days posttreatment. At 300 mg/kg/day, (−)-FTC strongly suppressed virus titers to up to 14 days posttreatment. Combination therapy (33 mg/kg/day each drug) sustained suppression of virus titer/ml serum (<1 log
10
unit from pretreatment levels) at 14 days posttreatment, while single-drug treatments yielded virus titers 1.5 to 2 log units above the initial virus titers. There was no difference in mean alanine aminotransferase values or mean wet tumor weights for any of the groups, suggesting a lack of drug toxicity. TDF–(−)-FTC combination therapy provides more effective HBV suppression than therapy with each drug alone.
ASPECTS OF THE RIEMANNIAN GEOMETRY OF QUANTUM COMPUTATION
Authors: BRANDT HOWARD E.
Published: September 2012

A review is given of some aspects of the Riemannian geometry of quantum computation in which the quantum evolution is represented in the tangent space manifold of the special unitary unimodular group SU(2n) for n qubits. The Riemannian right-invariant metric, connection, curvature, geodesic equation for minimal complexity quantum circuits, Jacobi equation and the lifted Jacobi equation for varying penalty parameter are reviewed. Sharpened tools for calculating the geodesic derivative are presented. The geodesic derivative may facilitate the numerical investigation of conjugate points and the global characteristics of geodesic paths in the group manifold, the determination of optimal quantum circuits for carrying out a quantum computation, and the determination of the complexity of particular quantum algorithms.
QUANTUM MECHANICS AND THE ROLE OF TIME: ARE QUANTUM SYSTEMS MARKOVIAN?
Authors: DURT THOMAS
Published: September 2012

The predictions of the Quantum Theory have been verified so far with astonishingly high accuracy. Despite of its impressive successes, the theory still presents mysterious features such as the border line between the classical and quantum world, or the deep nature of quantum nonlocality. These open questions motivated in the past several proposals of alternative and/or generalized approaches. We shall discuss in the present paper alternative theories that can be infered from a reconsideration of the status of time in quantum mechanics. Roughly speaking, quantum mechanics is usually formulated as a memory free (Markovian) theory at a fundamental level, but alternative, nonMarkovian, formulations are possible, and some of them can be tested in the laboratory. In our paper we shall give a survey of these alternative proposals, describe related experiments that were realized in the past and also formulate new experimental proposals.
THE NUMBER OF CONJUGACY CLASSES CONTAINED IN NORMAL SUBGROUPS OF SOLVABLE GROUPS
Authors: SAEIDI AMIN , ZANDI SEIRAN
Published: September 2012

Let G be a finite group and let N be a normal subgroup of G. Assume that N is the union of ξ(N) distinct conjugacy classes of G. In this paper, we classify solvable groups G in which the set [Formula: see text] has at most three elements. We also compute the set [Formula: see text] in most cases.
Aggregate licenses validation for digital rights violation detection
Authors: Sachan Amit , Emmanuel Sabu , Kankanhalli Mohan S.
Published: September 2012

Digital Rights Management (DRM) is the term associated with the set of technologies to prevent illegal multimedia content distribution and consumption. DRM systems generally involve multiple parties such as owner, distributors, and consumers. The owner issues redistribution licenses to its distributors. The distributors in turn using their received redistribution licenses can generate and issue new redistribution licenses to other distributors and new usage licenses to consumers. As a part of rights violation detection, these newly generated licenses must be validated by a validation authority against the redistribution license used to generate them. The validation of these newly generated licenses becomes quite complex when there exist multiple redistribution licenses for a media with the distributors. In such cases, the validation process requires validation using an exponential number (to the number of redistribution licenses) of validation inequalities and each validation inequality may contain up to an exponential number of summation terms. This makes the validation process computationally intensive and necessitates to do the validation efficiently. To overcome this, we propose
validation tree
, a prefix-tree-based validation method to do the validation efficiently. Theoretical analysis and experimental results show that our proposed technique reduces the validation time significantly.
Army eEducation: The distance learning approach
Authors: Judy Jack
Published: September 2012

The United States Army Command and General Staff College's Department of Distance Education delivers the Advance Operations Course curriculum in a distance-learning format. This article discusses how instructors facilitate learning through different delivery methods (synchronous and asynchronous) to a student body geographically dispersed worldwide. Using a combination of delivery methods and available technology facilitators achieve a robust learning environment comparable to resident studies.
The Fetal Origins of the Metabolic Syndrome: Can We Intervene?
Authors: Ma Noelle , Hardy Daniel B.
Published: September 2012

Epidemiological studies have suggested that metabolic programming begins during fetal life and adverse eventsin uteroare a critical factor in the etiology of chronic diseases and overall health. While the underlying molecular mechanisms linking impaired fetal development to these adult diseases are being elucidated, little is known about how we can intervene early in life to diminish the incidence and severity of these long-term diseases. This paper highlights the latest clinical and pharmaceutical studies addressing how dietary intervention in fetal and neonatal life may be able to prevent aspects of the metabolic syndrome associated with IUGR pregnancies.
Exposure to Mebendazole and Pyrvinium during Pregnancy: A Danish Nationwide Cohort Study
Authors: Torp-Pedersen A. , Jimenez-Solem E. , Andersen J. T. , Broedbaek K. , Torp-Pedersen C. , Poulsen H. E.
Published: September 2012

Purpose. Families with children are frequently exposed to pinworm infection and treatment involves the whole family. Information on consequences of exposure during, pregnancy is limited. The aim of this study was to investigate the exposure to pyrvinium and mebendazole before, during, and after pregnancy in a Danish nationwide cohort.Methods. From nationwide administrative registers, we identified 718, 900 births in Denmark between January 1997 and December 2007 as well as maternal prescription data of anthelmintics and maternal characteristics. Redemption of a prescription for pyrvinium or mebendazole was used to identify exposure.Results. 4715 women redeemed a prescription for pyrvinium or mebendazole during pregnancy; 1606 for pyrvinium, 2575 for mebendazole, and 534 for both drugs. Having >2 children compared to having no previous children was associated with exposure to pyrvinium (OR: 7.1, 95% CI: 5.8–8.7) and mebendazole (OR: 20.8, 95% CI: 17.3–24.9).Conclusion. 4715 pregnant women redeemed a prescription for either mebendazole or pyrvinium. We believe the exposure to be even higher since pyrvinium is also sold over-the-counter. Limited information on birth outcomes is available at present time, and considering the number of exposed pregnancies, we recommend that studies are to be undertaken to assess the safety of pyrvinium and mebendazole during pregnancy.
How Normal Is the Liver in Which the Inflammatory Type Hepatocellular Adenoma Develops?
Authors: Han Jing , van den Heuvel Marius C. , Kusano Hironori , de Jong Koert P. , Gouw Annette S. H.
Published: September 2012

The inflammatory type hepatocellular adenoma (IHCA) is a subtype of HCA which is a benign liver tumor, predominantly occurring in young women in an otherwise normal liver. IHCA contains either a mutation of gp130 or STAT3. Both mutations lead to a similar morphologic phenotype and to increased expression of C-reactive protein (CRP) and/or serum amyloid-A (SAA). IHCA comprised about 40% of all HCAs and is associated with obesity. We investigated the histomorphological and immunophenotypical changes of the nontumorous liver of 32 resected IHCA specimens. Similar types of changes are present in samples taken adjacent to tumor and distant ones. The lobular architecture is well preserved. Mild/moderate steatosis is found in a high frequency which is in accordance with the median BMI of 32 in our cases. Of note are the regular findings of sinusoidal dilatation, single arteries, and minute CRP foci which are all features of HCA. These distinct CRP foci are mostly found in cases of multiple IHCA which indicates that the remnant liver may also contain IHCA foci. These findings show that the nonlesional liver in IHCA does contain abnormalities, and this may have consequences for the followup, especially since it is known that obesity may stimulate malignant growth.
Anterior and Posterior Meniscofemoral Ligaments: MRI Evaluation
Authors: Bintoudi A. , Natsis K. , Tsitouridis I.
Published: September 2012

Although meniscofemoral ligaments are distinct anatomic units, their anatomy and function are controversial from an anatomic and radiologic point of view. Five hundred knee MR examinations were retrospectively studied in an effort to demonstrate the incidence and variations regarding sex and age distribution, as well as the anatomy of the meniscofemoral ligament at magnetic resonance imaging. Patients were mostly men, three hundred and twelve, in contrast with women who were fewer, one hundred eighty-eight patients. The mean age of the patients who were included in this study was 46 years. More than half of them were between 20 and 40 years old; one hundred thirty-three patients among 20 to 30 years old and one hundred and one patients among 31 and 40 years old, in total two hundred thirty-four patients.
Morbidity and Mortality Patterns of Hospitalised Adult HIV/AIDS Patients in the Era of Highly Active Antiretroviral Therapy: A 4-year Retrospective Review from Zaria, Northern Nigeria
Authors: Ogoina Dimie , Obiako Reginald O. , Muktar Haruna M. , Adeiza Mukhtar , Babadoko Aliyu , Hassan Abdulaziz , Bansi Isa , Iheonye Henry , Iyanda Matthew , Tabi-Ajayi Eric
Published: September 2012

Background. This study, undertaken in major tertiary hospital in northern Nigeria, examined the morbidity and mortality patterns of hospitalised adult HIV/AIDS patients in the HAART era.Methods. Between January 2006 and December 2009, admission records and causes of deaths of hospitalised medical HIV-infected patients were retrieved and analysed according to antiretroviral (ART) status.Results. Of the 207 HIV/AIDS patients reviewed, majority were newly diagnosed (73.4%), and most were hospitalised and died from various AIDS-defining illnesses, mainly disseminated tuberculosis and sepsis. Immune-inflammatory-reconstitution-syndrome, ART-toxicity and ART-failure, contributed to morbidity and mortality in patients receiving ART. Sixty six (31.9%) patients died, with higher mortality in males and in those with lower CD4-cell count, lower PCV, and shorter hospital stay. However, hospital stay ≤3 days and severe anaemia (PCV < 24%) were independent predictors of mortality.Conclusion. In the current HAART era, late presentation and tuberculosis continue to fuel the HIV/AIDS pandemic in Africa, with emerging challenges due to ART-related complications.
Diphenyl (4′‐(Aryldiazenyl)biphenyl‐4‐ylamino)(pyridin‐3‐yl)methylphosphonates as Azo Disperse Dyes for Dyeing Polyester Fabrics
Authors: Abdel-Megeed Mohamed F. , Azaam Mohamed M. , El-Hiti Gamal A.
Published: September 2012

Diphenyl (4′‐aminobiphenyl‐4‐ylamino)(pyridin‐3‐yl)methylphosphonate (1) was synthesized in 88% yield from reaction of pyridine‐3‐carboxaldehyde with benzidine and triphenylphosphite in the presence of titanium tetrachloride as a catalyst. Diazotization of 1 gave the corresponding diazonium salt 2 which was coupled with several hydroxyl or amino compounds to give the corresponding azo dyes 3–8 in 82–88% yields after crystallization. The dyes produced were applied to polyesters as disperse dyes and their fastness properties were elevated.
Highly Porous Carbon Materials from Biomass by Chemical and Carbonization Method: A Comparison Study
Authors: Isahak Wan Nor Roslam Wan , Hisham Mohamed Wahab Mahamed , Yarmo Mohd Ambar
Published: September 2012

Porous carbon obtained by dehydrating agent, concentrated sulfuric acid (H2SO4), from biomass containing high cellulose (filter paper (FP), bamboo waste, and empty fruit bunches (EFB)) shows very high surface area and better thermal behavior. At room temperature (without heating), treatment of H2SO4 removed all the water molecules in the biomass and left the porous carbon without emitting any gaseous byproducts. Brunauer‐Emmett‐Teller (BET) surface analysis has shown that bamboo‐based carbon has good properties with higher surface area (507.8 m2/g), micropore area (393.3 m2/g), and better thermal behavior (compared to FP and EFB) without any activation or treatment process. By acid treatment of biomass, it was shown that higher carbon composition obtained from FP (85.30%), bamboo (77.72%), and EFB (76.55%) is compared to carbon from carbonization process. Under optimal sulfuric acid (20 wt.%) uses, high carbon yield has been achieved for FP (47.85 wt.%), bamboo (62.4 wt.%), and EFB (55.4 wt.%).
Synthesis and Antidepressant Activity of Some New 5‐(1H‐Indol‐3‐yl)‐3‐(substituted aryl)‐4,5‐dihydroisoxazoline Derivatives
Authors: Patil Pravin O. , Bari Sanjay B.
Published: September 2012

The present study refers to the synthesis of new antidepressant candidates using the indole scaffold. In an attempt to identify potential lead antidepressant agents, a number of indole molecules, incorporating isoxazoline, were synthesized by microwave‐assisted synthesis. The antidepressant activity of the synthesized compounds (3a–3n) was evaluated by forced swim test in mice and their locomotor activity was assessed using actophotometry. The present paper showed significant antidepressant activity for all compounds of the series and no significant change in locomotor activity of mice. Compounds 3d and 3j were found to be potent molecules of this series, when compared with the reference drugs imipramine and fluoxetine. It clearly demonstrated that replacement of aromatic core by appropriate heterocycles such as pyridine and pyrrole on the 5‐(1H‐Indol‐3‐yl)‐3‐(Phenyl)‐4,5‐dihydroisoxazoline (3a) would generate more potent derivatives. Thus, these compounds can serve as potential leads for further antidepressant studies.
Decoding Pure Rotational Molecular Spectra for Asymmetric Molecules
Authors: Cooke S. A. , Ohring P.
Published: September 2012

Rotational spectroscopy can provide insights of unparalleled precision with respect to the wavefunctions of molecular systems that have relevance in fields as diverse as astronomy and biology. In this paper, we demonstrate how asymmetric molecular pure rotational spectra may be analyzed “pictorially” and with simple formulae. It is shown that the interpretation of such spectra relies heavily upon pattern recognition. The presentation of some common spectral line positions in near-prolate asymmetric rotational spectra provides a means by which spectral assignment, and approximate rotational constant determination, may be usefully explored. To aid in this endeavor we have created a supporting, free, web page and mobile web page.
CD22 Antigen Is Broadly Expressed on Lung Cancer Cells and Is a Target for Antibody-Based Therapy
Authors: Tuscano Joseph M. , Kato Jason , Pearson David , Xiong Chengyi , Newell Laura , Ma Yunpeng , Gandara David R. , O'Donnell Robert T.
Published: September 2012

Most patients with lung cancer still die from their disease, necessitating additional options to improve treatment. Here, we provide evidence for targeting CD22, a cell adhesion protein known to influence B-cell survival that we found is also widely expressed in lung cancer cells. In characterizing the antitumor activity of an established anti-CD22 monoclonal antibody (mAb), HB22.7, we showed CD22 expression by multiple approaches in various lung cancer subtypes, including 7 of 8 cell lines and a panel of primary patient specimens. HB22.7 displayed in vitro and in vivo cytotoxicity against CD22-positive human lung cancer cells and tumor xenografts. In a model of metastatic lung cancer, HB22.7 inhibited the development of pulmonary metastasis and extended overall survival. The finding that CD22 is expressed on lung cancer cells is significant in revealing a heretofore unknown mechanism of tumorigenesis and metastasis. Our work suggests that anti-CD22 mAbs may be useful for targeted therapy of lung cancer, a malignancy that has few tumor-specific targets. Cancer Res; 72(21); 5556–65. ©2012 AACR.
OTX2 Represses Myogenic and Neuronal Differentiation in Medulloblastoma Cells
Authors: Bai Ren-Yuan , Staedtke Verena , Lidov Hart G. , Eberhart Charles G. , Riggins Gregory J.
Published: September 2012

The brain development transcription factor OTX2 is overexpressed and/or genomically amplified in most medulloblastomas, but the mechanistic basis for its contributions in this setting are not understood. In this study, we identified OTX2 as a transcriptional repressor and a gatekeeper of myogenic and neuronal differentiation in medulloblastoma cells. OTX2 binds to the MyoD1 core enhancer through its homeobox domain, and the remarkable repressor activity exhibited by the homeobox domain renders OTX2 transcriptionally repressive. RNA interference–mediated attenuation of OTX2 expression triggered myogenic and neuronal differentiation in vitro and prolonged the survival in an orthotopic medulloblastoma mouse model. Conversely, inducing myogenic conversion of medulloblastoma cells led to the loss of OTX2 expression. In medullomyoblastoma, a medulloblastoma subtype containing muscle elements, myogenic cells share cytogenetic signatures with the primitive tumor cells and OTX2 expression was lost in the differentiated myogenic cells. Thus, OTX2 functions via its homeobox domain as a suppressor of differentiation, and the loss of OTX2 expression is linked to the myogenesis in medullomyoblastoma. Together, our findings illustrate the origin of muscle cells in medullomyoblastomas and the oncogenic mechanism of OTX2 as a repressor of diverse differentiating potential. Cancer Res; 72(22); 5988–6001. ©2012 AACR.
SIRT1 Pathway Dysregulation in the Smoke-Exposed Airway Epithelium and Lung Tumor Tissue
Authors: Beane Jennifer , Cheng Luis , Soldi Raffaella , Zhang Xiaohui , Liu Gang , Anderlind Christina , Lenburg Marc E. , Spira Avrum , Bild Andrea H.
Published: September 2012

Cigarette smoke produces a molecular field of injury in epithelial cells lining the respiratory tract. However, the specific signaling pathways that are altered in the airway of smokers and the signaling processes responsible for the transition from smoking-induced airway damage to lung cancer remain unknown. In this study, we use a genomic approach to study the signaling processes associated with tobacco smoke exposure and lung cancer. First, we developed and validated pathway-specific gene expression signatures in bronchial airway epithelium that reflect activation of signaling pathways relevant to tobacco exposure, including ATM, BCL2, GPX1, NOS2, IKBKB, and SIRT1. Using these profiles and four independent gene expression datasets, we found that SIRT1 activity is significantly upregulated in cytologically normal bronchial airway epithelial cells from active smokers compared with nonsmokers. In contrast, this activity is strikingly downregulated in non–small cell lung cancer. This pattern of signaling modulation was unique to SIRT1, and downregulation of SIRT1 activity is confined to tumors from smokers. Decreased activity of SIRT1 was validated using genomic analyses of mouse models of lung cancer and biochemical testing of SIRT1 activity in patient lung tumors. Together, our findings indicate a role of SIRT1 in response to smoke and a potential role in repressing lung cancer. Furthermore, our findings suggest that the airway gene expression signatures derived in this study can provide novel insights into signaling pathways altered in the “field of injury” induced by tobacco smoke and thus may impact strategies for prevention of tobacco-related lung cancer. Cancer Res; 72(22); 5702–11. ©2012 AACR.
O(6)-Methylguanine-DNA Methyltransferase Is a Novel Negative Effector of Invasion in Glioblastoma Multiforme
Authors: Chahal Manik , Abdulkarim Bassam , Xu Yaoxian , Guiot Marie-Christine , Easaw Jacob C. , Stifani Nicolas , Sabri Siham
Published: September 2012

The dismal prognosis of glioblastoma multiforme (GBM) is mostly due to the high propensity of GBM tumor cells to invade. We reported an inverse relationship between GBM angiogenicity and expression of the DNA repair protein O6-methylguanine-DNA methyltransferase (MGMT), which has been extensively characterized for its role in resistance to alkylating agents used in GBM treatment. In the present study, given the major role of angiogenesis and invasion in GBM aggressiveness, we aimed to investigate the relationship between MGMT expression and GBM invasion. Stable overexpression of MGMT in the U87MG cell line significantly decreased invasion, altered expression of invasion-related genes, decreased expression of α5β1 integrin and focal adhesion kinase, and reduced their spindle-shaped morphology and migration compared with the empty vector control. Conversely, short hairpin RNA-mediated stable knockdown of MGMT or its pharmacologic depletion in the MGMT-positive T98G cell line were required for increased invasion. The inverse relationship between MGMT and invasion was further validated in primary GBM patient-derived cell lines. Using paraffin-embedded tumors from patients with newly diagnosed GBM (n = 59), tumor MGMT promoter hypermethylation (MGMT gene silencing) was significantly associated with increased immunohistochemical expression of the proinvasive matricellular protein secreted protein acidic and rich in cysteine (SPARC; P = 0.039, χ2 test). Taken together, our findings highlight for the first time the role of MGMT as a negative effector of GBM invasion. Future studies are warranted to elucidate the role of SPARC in the molecular mechanisms underlying the inverse relationship between MGMT and GBM invasion and the potential use of MGMT and SPARC as biomarkers of GBM invasion. Mol Cancer Ther; 11(11); 2440–50. ©2012 AACR.
Erythropoietin Ameliorates Oxidative Stress and Tissue Injury following Renal Ischemia/Reperfusion in Rat Kidney and Lung
Authors: Ardalan Mohammad Reza , Estakhri Rasoul , Hajipour Babak , Ansarin Khalil , Asl Naser Ahmadi , Nasirizade Mohammad Reza , Azar Alireza Nour , Ghorbanihaghjou Amir , Vatankhah Amir Mansour , Esmaili Heydar Ali
Published: September 2012

Objective: To study the effect of erythropoietin (EPO) treatment on renal and lung injury following renal ischemia/reperfusion (I/R). Materials and Methods: Thirty male Wistar rats were assigned to three groups of 10 rats each. The first group was sham-operated, the second was subjected to renal I/R (30 min of ischemia followed by 24 h of reperfusion). The third group was subjected to renal I/R and treated with EPO in two doses: the first dose 1 h prior to ischemia (1,000 U/kg) and the second dose 6 h after ischemia (1,000 U/kg). Results: The renal and lung tissue injury index, tissue serum blood urea nitrogen and creatinine (Cr) were higher in the renal I/R group compared to the renal I/R + EPO group; the difference was statistically significant (p < 0.05). Kidney and lung tissue glutathione peroxidase and superoxide dismutase levels were higher in the renal I/R + EPO group than the renal I/R group; the difference was also statistically significant (p < 0.05). Conclusion: The data showed that EPO pretreatment could be effective in reducing renal and lung injury following renal I/R and could improve the cellular antioxidant defense system. Hence EPO pretreatment may be effective for attenuating renal and lung injury after renal I/R-induced injury during surgical procedures, hypotension, renal transplantation and other conditions inducing renal I/R.
Effects of Extreme Temperatures on Years of Life Lost for Cardiovascular Deaths: A Time Series Study in Brisbane, Australia
Authors: Huang Cunrui , Barnett Adrian G. , Wang Xiaoming , Tong Shilu
Published: September 2012

Background—

Extreme temperatures are associated with cardiovascular disease (CVD) deaths. Previous studies have investigated the relative CVD mortality risk of temperature, but this risk is heavily influenced by deaths in frail elderly people. To better estimate the burden of extreme temperatures, we estimated their effects on years of life lost due to CVD.

Methods and Results—

The data were daily observations on weather and CVD mortality for Brisbane, Australia, between 1996 and 2004. We estimated the association between daily mean temperature and years of life lost due to CVD, after adjusting for trend, season, day of the week, and humidity. To examine the nonlinear and delayed effects of temperature, a distributed lag nonlinear model was used. The model’s residuals were examined to investigate whether there were any added effects due to cold spells and heat waves. The exposure–response curve between temperature and years of life lost was U-shaped, with the lowest years of life lost at 24°C. The curve had a sharper rise at extremes of heat than of cold. The effect of cold peaked 2 days after exposure, whereas the greatest effect of heat occurred on the day of exposure. There were significantly added effects of heat waves on years of life lost.

Conclusions—

Increased years of life lost due to CVD are associated with both cold and hot temperatures. Research on specific interventions is needed to reduce temperature-related years of life lost from CVD deaths.
MicroRNAs Are Involved in End-Organ Damage During Hypertension
Authors: Heggermont Ward A. , Heymans Stephane
Published: September 2012

Even in the new millennium, arterial hypertension remains a serious condition, with considerable morbidity and mortality worldwide. Crucial in managing the disease is not only lowering arterial blood pressure but also preventing or treating the typical end-organ damage caused by long-lasting and inadequately treated hypertension. In the past decade, it has been shown that microRNAs (miRs) are involved in several hypertension-related pathologies, such as cardiac hypertrophy and fibrosis, hypertensive heart failure, renal fibrosis, kidney failure, and, to a lesser extent, eye disease and hemorrhagic stroke. Whereas others extensively reviewed the role of miRs in atherosclerosis and vascular disease, this review focuses on their role in target organ damage during arterial hypertension. We emphasize the involvement of miRs in pathological end-organ remodeling processes and try to demonstrate some common miR signatures in distinct end organs. Hence, we aimed to provide proof of arterial hypertension being a systemic disease, similar to diabetes mellitus or metabolic syndrome. Furthermore, miRs that act on one particular process in different end organs are interesting therapeutic targets. Some future perspectives in miR research are highlighted with respect to novel therapeutic strategies in the cardiovascular field.
Negotiating Adaptation: Norm Selection and Hybridization in International Climate Negotiations
Authors: Moore Frances C.
Published: September 2012

Adaptation to the adverse impacts of climate change is a rapidly developing area of policy and the subject of active negotiation at the international level under the UN Framework Convention on Climate Change (UNFCCC). This article applies theories of norm evolution to the adaptation negotiations. It proposes that the history of these negotiations can best be understood as a contest between two proposed framings that can be roughly characterized as “adaptation as development” and “adaptation as restitution.” These two framings have some similar and some contradictory implications for policy. The article shows that the major areas of consensus and controversy around adaptation in the UNFCCC negotiations map closely to these areas of similarity and contradiction, respectively. Though the “adaptation as restitution” norm is relatively disadvantaged on many measures of norm-fitness suggested by previous authors, it nevertheless appears to help explain the development of adaptation institutions both within and outside the UNFCCC. A hybridized norm that can be described roughly as “like development but different” is coming to characterize international adaptation institutions.
ANDRO: An Argo-Based Deep Displacement Dataset
Authors: Ollitrault Michel , Rannou Jean-Philippe
Published: September 2012

During the first decade of the twenty-first century, more than 6000 Argo floats have been launched over the World Ocean, gathering temperature and salinity data from the upper 2000 m, at a 10-day or so sampling period. Meanwhile their deep displacements can be used to map the ocean circulation at their drifting depth (mostly around 1000 m). A comprehensive processing of the whole Argo dataset collected prior to 1 January 2010 has been performed to produce a world-wide dataset of deep displacements. This numerical atlas, named ANDRO, after a traditional dance of Brittany meaning a swirl, comprises some 600 000 deep displacements. These displacements, based on Argo or GPS surface locations only, have been fully checked and corrected for possible errors found in the public Argo data files (due to incorrect decoding or instrumental failure). Park pressures measured by the floats while drifting at depth are preserved in ANDRO (less than 2% of the park pressures are unknown): 63% of the float displacements are in the layer (900, 1100) dbar with a good (more or less uniform) degree of coverage of all the oceans, except around Antarctica (south of 60°S). Two deeper layers—(1400, 1600) and (1900, 2100) dbar—are also sampled (11% and 8% of the float displacements, respectively) but with poorer geographical coverage. Grounded cycles (i.e., if the float hits the sea bottom) are excluded. ANDRO is available online as an ASCII file.
What Percentage of Western North Pacific Tropical Cyclones Form within the Monsoon Trough?
Authors: Molinari John , Vollaro David
Published: September 2012

It is frequently stated that 70%–80% of western North Pacific tropical cyclones form “within the monsoon trough,” but without an objective definition of the term. Several definitions are tested here. When the monsoon trough (MT) is defined as the contiguous region where long-term (1988–2010) mean July–November 850-hPa relative vorticity is positive, 73% of all July–November tropical cyclones form within the MT. This percentage varies interannually, however, from as low as 50% to nearly 100%. The percentage correlates with the Niño-3.4 index, with more storms forming within the MT during warm periods. When the MT is defined instead using long-term monthly mean ζ850, more than 80% of tropical cyclones form within the MT in all months except July and August, when more than 30% of storms form poleward of the MT. It is hypothesized that the known peak in the frequency of upper-tropospheric midlatitude wave breaking in July and August is responsible. It is argued that any long-term mean provides a suitable definition of the MT. Defining it on less than seasonal time scales, however, creates a lack of conceptual separation between the MT and other tropical disturbances such as the MJO, equatorial waves, and easterly waves. The term monsoon trough should represent a climatological feature that provides an asymmetric background state within which other disturbances evolve.
Votes and Votive Candles
Authors: Ignazi Piero , Wellhofer E. Spencer
Published: September 2012

The authors examine the effects of modernization and secularization on the vote for the religious party in the Italian First Republic (1948–1992). In addition to modernization and secularization, they also introduce two new factors to the analysis: the importance of institutionalized Church and effects of the Church’s Vatican II reforms. Italy is of particular relevance because of the centrality of the Catholic religion in the Italian society and politics, and the domination of the religious party—the Christian Democracy (Democrazia Cristiana; DC) in the country’s party system until 1992. The authors analyze the impact on the DC vote of a series of indicators of modernization and secularization and of Church organization and reform. The uniqueness of the analysis rests on the exceptional detailed and historical data for the Italian commune ( N = 6,140) across this time period and the use of advanced quantitative techniques. The analysis confirms the traditional interpretation of secularization but also stresses effects of the failure of the Church’s reforms of Vatican II. These reforms, which deemphasized the institutionalized Church in favor of a more individualized, spiritual view, were intended as a response to modernization. Instead, the reforms hastened the decline affiliated organizations and the religious party.
Control Task Substitution in Semiautomated Driving
Authors: Carsten Oliver , Lai Frank C. H. , Barnard Yvonne , Jamson A. Hamish , Merat Natasha
Published: September 2012

Objective:

The study was designed to show how driver attention to the road scene and engagement of a choice of secondary tasks are affected by the level of automation provided to assist or take over the basic task of vehicle control. It was also designed to investigate the difference between support in longitudinal control and support in lateral control.

Background:

There is comparatively little literature on the implications of automation for drivers’ engagement in the driving task and for their willingness to engage in non-driving-related activities.

Method:

A study was carried out on a high-level driving simulator in which drivers experienced three levels of automation: manual driving, semiautomated driving with either longitudinal or lateral control provided, and highly automated driving with both longitudinal and lateral control provided. Drivers were free to pay attention to the roadway and traffic or to engage in a range of entertainment and grooming tasks.

Results:

Engagement in the nondriving tasks increased from manual to semiautomated driving and increased further with highly automated driving. There were substantial differences in attention to the road and traffic between the two types of semiautomated driving.

Conclusion:

The literature on automation and the various task analyses of driving do not currently help to explain the effects that were found. Lateral support and longitudinal support may be the same in terms of levels of automation but appear to be regarded rather differently by drivers.
Human Oral Mucosa and Gingiva
Authors: Zhang Q.Z. , Nguyen A.L. , Yu W.H. , Le A.D.
Published: September 2012

Mesenchymal stem cells (MSCs) represent a heterogeneous population of progenitor cells with self-renewal and multipotent differentiation potential. Aside from their regenerative role, extensive in vitro and in vivo studies have demonstrated that MSCs are capable of potent immunomodulatory effects on a variety of innate and adaptive immune cells. In this article, we will review recent experimental studies on the characterization of a unique population of MSCs derived from human oral mucosa and gingiva, especially their immunomodulatory and anti-inflammatory functions and their application in the treatment of several in vivo models of inflammatory diseases. The ease of isolation, accessible tissue source, and rapid ex vivo expansion, with maintenance of stable stem-cell-like phenotypes, render oral mucosa- and gingiva-derived MSCs a promising alternative cell source for MSC-based therapies.
An Exploration of Potential Factors Affecting Student Withdrawal From an Undergraduate Music Education Program
Authors: Gavin Russell B.
Published: September 2012

The purpose of this study was to examine the degree withdrawal patterns of undergraduate music education majors, with a specific focus on the individual experiences of students withdrawing from the major. Data from recently withdrawn students ( N = 14) were assembled using a qualitative methodology that included semistructured interviews, questionnaires, researcher journals, and meetings with experienced researchers. The data were analyzed and coded, generating a number of categories for discussion and analysis. Students’ experiences during college were diverse, with concerns focused on the applied music component of the degree surfacing as important to many students. The reasons given for withdrawal from the music education program also were diverse, including dismissal from the applied music studio, erosion of personal confidence as a musician, realizations about their feelings toward music versus their feelings about teaching in general as it related to their personal career goals, and personal life issues. Following withdrawal from the music education curriculum, all interviewed students reported that they remained actively involved in music in some way. Implications of these results are discussed in relation to individual experiences and the function of those experiences within the context of current models of student persistence.
Initial Open Trial of a Computerized Behavioral Activation Treatment for Depression
Authors: Spates C. Richard , Kalata Alyssa H. , Ozeki Satoshi , Stanton Cory E. , Peters Sofia
Published: September 2012

This article presents preliminary findings from use of a novel computer program that implements an evidence-based psychological intervention to treat depression based on behavioral activation (BA) therapy. The program is titled “Building a Meaningful Life Through Behavioral Activation”. The findings derive from an open trial with moderate to severely depressed individuals ( N = 15) in an Intention to Treat sample. Hierarchical linear modeling (HLM) analyses revealed significant change over time on Beck Depression Inventory–Second Edition (BDI-II) scores, Revised Hamilton Depression Rating Scale scores, and significant contribution to BDI-II score variance by participant age over time, change over time in negative automatic thoughts, and change over time in BA scores. Piecewise HLM analyses revealed that significant change over time was associated uniquely with active treatment and not during 3 weeks of baseline measurement. In addition to treatment-associated significant change on all dependent measures over time, effect sizes were in the moderate to large range. Limitations are small sample size, nonrandomized control, research-recruited patients instead of purely treatment-seeking patients, possible rating bias by independent assessors who had knowledge that participants had received active treatment in this open trial, and the influence of additional services received in the post acute-treatment phase by some participants could have contributed to maintenance of gains reported for that period.