bluuebunny/crossref_metadata_2025 huggingface dataset:
Assessing wood quality by spatial variation of elastic properties within the stem: Case study of Pinus pinaster in the transverse plane
Authors: Pereira J. , Xavier J. , Morais J. , Lousada J.
Published: October 2013

The wood quality of maritime pine (Pinus pinaster Ait.) is discussed in view of spatial variability of density, annual growth ring characteristics, and transverse elastic properties within and among five basal logs. X-ray microdensitometry measurements are carried out to assess both average (Dmean) and local (DEW, DLW) densities of annual growth rings, as well as the respective dimensions (EWW, LWW) and fractions of earlywood (EW) and latewood (LW) layers. Mechanical tensile tests on a set of specimens with different ring orientation are proposed. Transverse elastic properties are determined by coupling an inverse identification strategy with full-field deformation measurements provided by digital image correlation. For a suitable range of off-axis angles, this method allows the simultaneous characterisation of the four orthotropic elastic properties in the RT plane: ER, ET, νRT, and GRT. These results are found in agreement with reference values. From the sampled specimens among logs, ER and GRT are robustly identified in all cases and therefore are selected for further analysis of structure-properties relationships. Correlations between Dmean and ER and GRT are positive and statistically significant. Furthermore, other parameters also show significant correlations with the elastic constants, especially Dmin, LWW, and DEW.
MATTERS ON A MOVING BRANE
Authors: KOIVISTO TOMI SEBASTIAN , WILLS DANIELLE ELIZABETH
Published: October 2013

A novel generalization of the Dirac–Born–Infeld string scenario is described. It is shown that matter residing on the moving brane is dark and has the so-called disformal coupling to gravity. This gives rise to cosmologies where dark matter stems from the oscillations of the open strings along the brane and the transverse oscillations result in dark energy. Furthermore, due to a new screening mechanism that conceals the fifth force from local experiments, one may even entertain the possibility that the visible sector is also moving along the extra dimensions.
ENHANCING THE SYSTEM DYNAMICS MODELING PROCESS WITH A DOMAIN MODELING METHOD
Authors: TULINAYO FIONA P. , VAN BOMMEL PATRICK , (ERIK) PROPER H. A.
Published: October 2013

Defining complex system dynamics (SD) models in complex organizational settings is hard. This is so because the numbers of variables to consider are many and the question of causation is complicated to untangle. Second, SD models are ambiguous and hard to conceptualize. In this paper, we explore the use of a domain modeling method object-role modeling (ORM) in the process of developing SD models. We do so, because domain modeling methods help to identify relationships among entities within the scope of the problem domain and provide a structural view of the domain. The addition of a domain modeling method to the process of developing SD models is to improve SD model conceptualization, enable transformation and reuse of information plus underpin SD with a domain modeling method that allows creation of database. To realize this, we come up with a procedure in our overall research which we refer to as grounded system dynamics (GSD) a combination of ORM and SD. To reason about the combination of SD with a domain modeling method (ORM), we identify and evaluate relationships between their constructs. Basing on the identified relations, ORM to stock and flow diagram (SFD) steps are defined and applied to a real-life case study national medical stores (NMS) situated in Uganda. On completion, we draw conclusions.
PARALLEL IMPLEMENTATION OF A NAVIER–STOKES SOLVER: TURBULENT EKMAN LAYER DIRECT SIMULATION
Authors: WAGGY SCOTT B. , KUCALA ALEC , BIRINGEN SEDAT
Published: October 2013

A massively parallel direct numerical solution procedure for the turbulent Ekman layer is presented. The simulations study the dynamics of turbulence in this flow by solving the incompressible Navier–Stokes equations with Coriolis and buoyancy terms. The governing equations are integrated via a semi-implicit time advancement algorithm which is massively parallelized using the Portable, Extensible Toolkit for Scientific Computation (PETSc) libraries. Accuracy of the numerical scheme was validated by comparisons of simulation results with the hydrodynamic linear stability theory for Poiseuille flow. Two cases are presented to demonstrate the capabilities of the code: (a) a neutrally stable case of Reynolds number, Re = 400 and (b) an unstably stratified case at Re = 1,000 requiring very high resolution in all coordinate directions. Results indicate that the scalability is not limited by the overall size of the problem, but rather by the number of mesh points per processor. Strong scaling is demonstrated for both cases with as few as 10,000 unknowns per processor.
GENERIC APPROXIMATE SPARSE INVERSE MATRIX TECHNIQUES
Authors: FILELIS-PAPADOPOULOS CHRISTOS K. , GRAVVANIS GEORGE A.
Published: October 2013

During the last decades explicit preconditioning methods have gained interest among the scientific community, due to their efficiency for solving large sparse linear systems in conjunction with Krylov subspace iterative methods. The effectiveness of explicit preconditioning schemes relies on the fact that they are close approximants to the inverse of the coefficient matrix. Herewith, we propose a Generic Approximate Sparse Inverse (GenASPI) matrix algorithm based on ILU(0) factorization. The proposed scheme applies to matrices of any structure or sparsity pattern unlike the previous dedicated implementations. The new scheme is based on the Generic Approximate Banded Inverse (GenAbI), which is a banded approximate inverse used in conjunction with Conjugate Gradient type methods for the solution of large sparse linear systems. The proposed GenASPI matrix algorithm, is based on Approximate Inverse Sparsity patterns, derived from powers of sparsified matrices and is computed with a modified procedure based on the GenAbI algorithm. Finally, applicability and implementation issues are discussed and numerical results along with comparative results are presented.
MODIFIED CHOLESKY DECOMPOSITION FOR SOLVING THE MOMENT MATRIX IN THE RADIAL POINT INTERPOLATION METHOD
Authors: STADLER DOMEN , ČELIČ DAMJAN , LIPEJ ANDREJ , KOSEL FRANC
Published: October 2013

The radial point interpolation method is frequently employed in numerical computations. It can be used to interpolate scattered data, as shape functions in meshless methods and mesh deformation scheme, etc. The main problem in calculating the radial point interpolation is solving the moment matrix of the interpolation scheme, which is usually done with LU decomposition. A new decomposition technique based on the Cholesky decomposition is introduced in this paper. A comparison of the error, the consumed time and the results between the new decomposition technique and the LU method is presented for two different numerical methods.
Skin Tumorigenesis Stimulated by Raf Inhibitors Relies Upon Raf Functions That Are Dependent and Independent of ERK
Authors: Doma Eszter , Rupp Christian , Varga Andrea , Kern Florian , Riegler Bettina , Baccarini Manuela
Published: October 2013

RAF inhibitors achieve unprecedented but mainly transient clinical responses in patients with melanoma whose tumors harbor an activating BRAF mutation. One notable side-effect of RAF inhibitors is the stimulation of cutaneous skin tumors, arising in about 30% of patients receiving these drugs, which are thought to develop as a result of inhibitor-induced activation of wild-type Raf in occult precursor skin lesions. This effect raises the possibility that less manageable tumors might also arise in other epithelial tissues. Here we provide preclinical evidence supporting this disquieting hypothesis by showing that the RAF inhibitors PLX-4032 (vemurafenib) and GDC-0879 precipitate the development of cell-autonomous, Ras-driven tumors in skin and gastric epithelia. The magnitude of the effects correlated with the inhibitors' relative abilities to induce ERK activation. Epidermis-restricted ablation of either B-Raf or C-Raf prevented PLX-4032–induced ERK activation and tumorigenesis. In contrast, GDC-0879 induced ERK activation and tumorigenesis in B-Raf–deficient epidermis, whereas C-Raf ablation blocked GDC-0879–induced tumorigenesis (despite strong ERK activation) by preventing Rokα–mediated keratinocyte dedifferentiation. Thus, inhibitor-induced ERK activation did not require a specific Raf kinase. ERK activation was necessary, but not sufficient for Ras + Raf inhibitor-induced tumorigenesis, whereas C-Raf downregulation of Rokα was essential even in the face of sustained ERK signaling to prevent differentiation and promote tumorigenesis. Taken together, our findings suggest that combination therapies targeting ERK-dependent and -independent functions of Raf may be more efficient but also safer for cancer treatment. Cancer Res; 73(23); 6926–37. ©2013 AACR.
Epigenetic Inactivation of microRNA-34b/c Predicts Poor Disease-Free Survival in Early-Stage Lung Adenocarcinoma
Authors: Nadal Ernest , Chen Guoan , Gallegos Marc , Lin Lin , Ferrer-Torres Daysha , Truini Anna , Wang Zhuwen , Lin Jules , Reddy Rishindra M. , Llatjos Roger , Escobar Ignacio , Moya Juan , Chang Andrew C. , Cardenal Felipe , Capellà Gabriel , Beer David G.
Published: October 2013

Purpose: The microRNA-34b/c (miR-34b/c) is considered a tumor suppressor in different tumor types and a transcriptional target of TP53. The main objectives of this study were to investigate the clinical implications of miR-34b/c methylation in patients with early-stage lung adenocarcinoma and to determine the functional role of miR-34b/c re-expression in lung adenocarcinoma cell lines.

Experimental Design: Aberrant methylation and expression of miR-34b/c were assessed in 15 lung adenocarcinoma cell lines and a cohort of 140 early-stage lung adenocarcinoma. Lung adenocarcinoma cell lines were transfected with miR-34b/c and the effects upon cell proliferation, migration, invasion, and apoptosis were investigated.

Results: Aberrant methylation of miR-34b/c was detected in 6 (40%) of 15 lung adenocarcinoma cell lines and 64 of 140 (46%) primary lung adenocarcinoma. Expression of miR-34b/c was significantly reduced in all methylated cell lines and primary tumors, especially with TP53 mutations. Patients with increased miR-34b/c methylation had significantly shorter disease-free and overall survival as compared to patients with unmethylated or low level of miR-34b/c methylation. Ectopic expression of miR-34b/c in lung adenocarcinoma cell lines decreased cell proliferation, migration, and invasion.

Conclusions: Epigenetic inactivation of miR-34b/c by DNA methylation has independent prognostic value in patients with early-stage lung adenocarcinoma. Reexpression of miR-34b/c leads to a less aggressive phenotype in lung adenocarcinoma cell lines. Clin Cancer Res; 19(24); 6842–52. ©2013 AACR.
A Comparative Analysis of Prognostic Factor Models for Follicular Lymphoma Based on a Phase III Trial of CHOP–Rituximab versus CHOP + 131Iodine—Tositumomab
Authors: Press Oliver W. , Unger Joseph M. , Rimsza Lisa M. , Friedberg Jonathan W. , LeBlanc Michael , Czuczman Myron S. , Kaminski Mark , Braziel Rita M. , Spier Catherine , Gopal Ajay K. , Maloney David G. , Cheson Bruce D. , Dakhil Shaker R. , Miller Thomas P. , Fisher Richard I.
Published: October 2013

Purpose: There is currently no consensus on optimal frontline therapy for patients with follicular lymphoma. We analyzed a phase III randomized intergroup trial comparing six cycles of CHOP-R (cyclophosphamide–Adriamycin–vincristine–prednisone (Oncovin)–rituximab) with six cycles of CHOP followed by iodine-131 tositumomab radioimmunotherapy (RIT) to assess whether any subsets benefited more from one treatment or the other, and to compare three prognostic models.

Experimental Design: We conducted univariate and multivariate Cox regression analyses of 532 patients enrolled on this trial and compared the prognostic value of the FLIPI (follicular lymphoma international prognostic index), FLIPI2, and LDH + β2M (lactate dehydrogenase + β2-microglobulin) models.

Results: Outcomes were excellent, but not statistically different between the two study arms [5-year progression-free survival (PFS) of 60% with CHOP-R and 66% with CHOP-RIT (P = 0.11); 5-year overall survival (OS) of 92% with CHOP-R and 86% with CHOP-RIT (P = 0.08); overall response rate of 84% for both arms]. The only factor found to potentially predict the impact of treatment was serum β2M; among patients with normal β2M, CHOP-RIT patients had better PFS compared with CHOP-R patients, whereas among patients with high serum β2M, PFS by arm was similar (interaction P value = 0.02).

Conclusions: All three prognostic models (FLIPI, FLIPI2, and LDH + β2M) predicted both PFS and OS well, though the LDH + β2M model is easiest to apply and identified an especially poor risk subset. In an exploratory analysis using the latter model, there was a statistically significant trend suggesting that low-risk patients had superior observed PFS if treated with CHOP-RIT, whereas high-risk patients had a better PFS with CHOP-R. Clin Cancer Res; 19(23); 6624–32. ©2013 AACR.
Small-Molecule Inhibitors of USP1 Target ID1 Degradation in Leukemic Cells
Authors: Mistry Helena , Hsieh Grace , Buhrlage Sara J. , Huang Min , Park Eunmi , Cuny Gregory D. , Galinsky Ilene , Stone Richard M. , Gray Nathanael S. , D'Andrea Alan D. , Parmar Kalindi
Published: October 2013

Inhibitor of DNA binding 1 (ID1) transcription factor is essential for the proliferation and progression of many cancer types, including leukemia. However, the ID1 protein has not yet been therapeutically targeted in leukemia. ID1 is normally polyubiquitinated and degraded by the proteasome. Recently, it has been shown that USP1, a ubiquitin-specific protease, deubiquitinates ID1 and rescues it from proteasome degradation. Inhibition of USP1 therefore offers a new avenue to target ID1 in cancer. Here, using a ubiquitin-rhodamine–based high-throughput screening, we identified small-molecule inhibitors of USP1 and investigated their therapeutic potential for leukemia. These inhibitors blocked the deubiquitinating enzyme activity of USP1 in vitro in a dose-dependent manner with an IC50 in the high nanomolar range. USP1 inhibitors promoted the degradation of ID1 and, concurrently, inhibited the growth of leukemic cell lines in a dose-dependent manner. A known USP1 inhibitor, pimozide, also promoted ID1 degradation and inhibited growth of leukemic cells. In addition, the growth of primary acute myelogenous leukemia (AML) patient-derived leukemic cells was inhibited by a USP1 inhibitor. Collectively, these results indicate that the novel small-molecule inhibitors of USP1 promote ID1 degradation and are cytotoxic to leukemic cells. The identification of USP1 inhibitors therefore opens up a new approach for leukemia therapy. Mol Cancer Ther; 12(12); 2651–62. ©2013 AACR.
Tunicamycin Potentiates Cisplatin Anticancer Efficacy through the DPAGT1/Akt/ABCG2 Pathway in Mouse Xenograft Models of Human Hepatocellular Carcinoma
Authors: Hou Helei , Sun Hefen , Lu Ping , Ge Chao , Zhang Lixing , Li Hong , Zhao Fangyu , Tian Hua , Zhang Lin , Chen Taoyang , Yao Ming , Li Jinjun
Published: October 2013

Hepatocellular carcinoma is highly chemoresistant, and ATP-binding cassette subfamily G member 2 (ABCG2) is thought to play a critical role in this drug resistance. The present study aims to develop effective therapeutic strategies to decrease ABCG2 expression level and to surmount drug resistance in hepatocellular carcinoma chemotherapy. First, we verified a positive correlation between the ABCG2 protein level and the drug resistance of hepatocellular carcinoma cell lines. ABCG2 was preferentially expressed in highly chemoresistant hepatocellular carcinoma cancer stem cells (CSC) enriched with CD133. In addition, ABCG2 was N-linked glycosylated in hepatocellular carcinoma cells, and this modification was involved in sustaining its protein stability. The N-linked glycosylation (NLG) inhibitor tunicamycin dramatically reduced ABCG2 expression, altered its subcellular localization, and reversed its drug efflux effect in multiple hepatocellular carcinoma cell lines. Furthermore, tunicamycin reduced the expression levels of several CSC markers and suppressed the tumorigenicity of CD133+ CSCs. Tunicamycin combined with cisplatin (CDDP) inhibited proliferating cell nuclear antigen (PCNA) expression and increased the cleavage of PARP; this effect was partially rescued by the overexpression of ABCG2 or Akt-myr. The combination therapy more effectively suppressed tumor growth in xenograft mice than did single-agent therapy with either drug. Finally, the CDDP treatment combined with UDP-GlcNAc-dolichol-phosphate N-acetylglucosamine-1 phosphate transferase (DPAGT1) knockdown recapitulated the effect observed when CDDP was used in combination with tunicamycin. In summary, our results suggest that tunicamycin may reverse the drug resistance and improve the efficacy of combination treatments for hepatocellular carcinomas by targeting the DPAGT1/Akt/ABCG2 pathway. Mol Cancer Ther; 12(12); 2874–84. ©2013 AACR.
Dual HER/VEGF Receptor Targeting Inhibits In Vivo Ovarian Cancer Tumor Growth
Authors: Becker Marc A. , Farzan Thahir , Harrington Sean C. , Krempski James W. , Weroha S. John , Hou Xiaonan , Kalli Kimberly R. , Wong Tai W. , Haluska Paul
Published: October 2013

Ovarian cancer mortality ranks highest among all gynecologic cancers with growth factor pathways playing an integral role in tumorigenesis, metastatic dissemination, and therapeutic resistance. The HER and VEGF receptor (VEGFR) are both overexpressed and/or aberrantly activated in subsets of ovarian tumors. While agents targeting either the HER or VEGF pathways alone have been investigated, the impact of these agents have not led to overall survival benefit in ovarian cancer. We tested the hypothesis that cotargeting HER and VEGFR would maximize antitumor efficacy at tolerable doses. To this end, ovarian cancer xenografts grown intraperitoneally in athymic nude mice were tested in response to AC480 (pan-HER inhibitor, “HERi”), cediranib (pan-VEGFR inhibitor “VEGFRi”), or BMS-690514 (combined HER/VEGFR inhibitor “EVRi”). EVRi was superior to both HERi and VEGFRi in terms of tumor growth, final tumor weight, and progression-free survival. Correlative tumor studies employing phosphoproteomic antibody arrays revealed distinct agent-specific alterations, with EVRi inducing the greatest overall effect on growth factor signaling. These data suggest that simultaneous inhibition of HER and VEGFR may benefit select subsets of ovarian cancer tumors. To this end, we derived a novel HER/VEGF signature that correlated with poor overall survival in high-grade, late stage, serous ovarian cancer patient tumors. Mol Cancer Ther; 12(12); 2909–16. ©2013 AACR.
Invisible Bleeding from Clean-Shave Haircuts: Detection with Blood Specific RNA Markers
Authors: Khumalo N.P. , Mkentane K. , Muthukarapan C. , Hardie D. , Korsman S. , Hu N. , Mthebe T. , Davids L.M. , Rousseau J.
Published: October 2013

Background: ‘Haircut-associated bleeding' is a newly recognized entity that affects at least a quarter of African men who wear shiny clean-shave (‘chiskop') haircuts. Aim: This pilot study aimed to elucidate whether invisible haircut-associated bleeding was detectable using blood specific RNA markers (16 participants, 5 with unknown HIV status) and whether surface virus could be detected using PCR from scalp swabs (of 11 known HIV-positive participants). Methods: Haircuts were performed professionally and scalps examined by a dermatologist to exclude injury. Serum samples for viral loads were also collected at the same time. Results: In all, 6/16 (37%) samples tested positive (>100 relative fluorescent units) for hemoglobin beta and albumin, confirming evidence of blood; of these, only 1/11 was HIV-positive but had an undetectable serum viral load. No surface HIV was detected from any scalp samples. Conclusions: This study confirms the entity of haircut-associated bleeding but goes further to show for the first time that invisible bleeding from clean-shave haircuts is also common. Both a high serum viral load and evidence of bleeding should ideally be present prior to surface HIV detection. Future investigations for potential HIV (and hepatitis B) transmission through clean-shave haircuts are warranted but should not delay public education for disease prevention.
Prevalence and Predictors of Nonadherence to Hemodialysis
Authors: Dantas L.G. , Cruz C. , Rocha M. , Moura Jr. J.A. , Paschoalin E. , Paschoalin S. , Marcilio de Souza C.
Published: October 2013

Background: The prevalence of nonadherence to dialysis (NAD) presents a wide variation, depending on the parameters used and demographic regions studied. This study aimed to assess the prevalence and predictors of NAD of patients with chronic kidney disease undergoing hemodialysis (HD). Materials and Methods: This was a cross-sectional study with 255 adult patients receiving HD for >3 months. Skipping a session per month, shortening a session for at least 10 min, phosphorus >7.5 mg/dl, potassium >6.0 mmol/l and interdialytic weight gain (IDWG) >5.7% of body weight were indicative of NAD. The association of sociodemographic and clinical variables with NAD was assessed using logistic regression. Results: Mean age was 50 ± 13.1 years, 62.7% were male, 85.5% were of African descent and 62% were married. The prevalence rates of NAD were: 49% of shortening sessions, 18% of hyperkalemia, 12% of hyperphosphatemia, 9% of IDWG >5.7% of dry weight and 8% of skipping HD. Independent predictors of NAD were: age ≤50 years, not being married, living alone, living in Salvador, attending dialysis without a companion, ethnic African descent, Kt/V <1.3 and residual diuresis <100 ml/day. Conclusion: NAD is frequent and distinct sociodemographic and clinical variables predict different parameters.
Cardiovascular Effects of 1 Year of Alagebrium and Endurance Exercise Training in Healthy Older Individuals
Authors: Fujimoto Naoki , Hastings Jeffrey L. , Carrick-Ranson Graeme , Shafer Keri M. , Shibata Shigeki , Bhella Paul S. , Abdullah Shuaib M. , Barkley Kyler W. , Adams-Huet Beverley , Boyd Kara N. , Livingston Sheryl A. , Palmer Dean , Levine Benjamin D.
Published: October 2013

Background—

Lifelong exercise training maintains a youthful compliance of the left ventricle (LV), whereas a year of exercise training started later in life fails to reverse LV stiffening, possibly because of accumulation of irreversible advanced glycation end products. Alagebrium breaks advanced glycation end product crosslinks and improves LV stiffness in aged animals. However, it is unclear whether a strategy of exercise combined with alagebrium would improve LV stiffness in sedentary older humans.

Methods and Results—

Sixty-two healthy subjects were randomized into 4 groups: sedentary+placebo; sedentary+alagebrium (200 mg/d); exercise+placebo; and exercise+alagebrium. Subjects underwent right heart catheterization to define LV pressure–volume curves; secondary functional outcomes included cardiopulmonary exercise testing and arterial compliance. A total of 57 of 62 subjects (67±6 years; 37 f/20 m) completed 1 year of intervention followed by repeat measurements. Pulmonary capillary wedge pressure and LV end-diastolic volume were measured at baseline, during decreased and increased cardiac filling. LV stiffness was assessed by the slope of LV pressure–volume curve. After intervention, LV mass and end-diastolic volume increased and exercise capacity improved (by ≈8%) only in the exercise groups. Neither LV mass nor exercise capacity was affected by alagebrium. Exercise training had little impact on LV stiffness (training×time effect,
P
=0.46), whereas alagebrium showed a modest improvement in LV stiffness compared with placebo (medication×time effect,
P
=0.04).

Conclusions—

Alagebrium had no effect on hemodynamics, LV geometry, or exercise capacity in healthy, previously sedentary seniors. However, it did show a modestly favorable effect on age-associated LV stiffening.

Clinical Trial Registration—

URL:
http://www.clinicaltrials.gov
. Unique identifier: NCT01014572.
Cognitive Trajectory After Transcatheter Aortic Valve Implantation
Authors: Ghanem Alexander , Kocurek Justine , Sinning Jan-Malte , Wagner Michael , Becker Benjamin V. , Vogel Marieke , Schröder Thomas , Wolfsgruber Steffen , Vasa-Nicotera Mariuca , Hammerstingl Christoph , Schwab Jörg O. , Thomas Daniel , Werner Nikos , Grube Eberhard , Nickenig Georg , Müller Andreas
Published: October 2013

Background—

Transcatheter aortic valve implantation (TAVI) is known to be associated with silent cerebral injury, which could contribute to cognitive impairment. Considering its increasing use, thorough longitudinal investigation of cognitive trajectory after TAVI is pivotal.

Methods and Results—

Repeatable battery for the assessment of neuropsychological status was performed before (E1), 3 days (E2), 3 months (E3), 1 (E4) year, and 2 years (E5) after TAVI. Baseline characteristics, procedural data, imaging parameters of brain injury (diffusion-weighted MRI), and the use of conceivable neuroprotective approaches were investigated for their effect on cognitive function. Cognitive performance was investigated in 111 patients (mean log EuroSCORE, 30±13%). Global cognitive function (repeatable battery for the assessment of neuropsychological status total score) increased transiently at E2 (
P
=0.02) and was comparable with baseline levels at E3, E4, and E5. Six patients (5.4%) demonstrated early cognitive decline. Persistence and late onset were seen infrequently (n=3, 2.7% and n=4, 3.6%, respectively). Hence, early cognitive decline was ruled out in 105 patients (94.6%), and a majority of patients (91%) demonstrated sustained cognitive performance throughout all investigated time points. Interestingly, only patient age (
P
=0.012), but not prior cerebrovascular events, cognitive status, direct TAVI, cerebral embolism in diffusion-weighted MRI, or the use of a cerebral embolic protection device was found to be independently associated with cognitive decline, linking higher age to cognitive impairment along the first 2 years after TAVI.

Conclusions—

Long-term cognitive performance was preserved in the great majority (91%) of patients throughout the first 2 years after TAVI, despite the high intrinsic risk for cognitive deterioration.

Clinical Trial Registration—

URL:
http://www.clinicaltrials.gov
. Unique identifier: NCT00883285.
Natural History of Left Ventricular Ejection Fraction in Patients With Heart Failure
Authors: Clarke Christina L. , Grunwald Gary K. , Allen Larry A. , Barón Anna E. , Peterson Pamela N. , Brand David W. , Magid David J. , Masoudi Frederick A.
Published: October 2013

Background—

Patients with heart failure (HF) are typically designated as having reduced or preserved ejection fraction (HFREF, HFPEF) because of the importance of left ventricular ejection fraction (LVEF) on therapeutic decisions and prognosis. Such designations are not necessarily static, yet few data exist to describe the natural history of LVEF over time.

Methods and Results—

We identified 2413 patients from Kaiser Permanente Colorado with a primary discharge diagnosis of HF between January 1, 2001, and December 31, 2008, who had ≥2 LVEF measurements separated by ≥30 days. We used multi-state Markov modeling to examine transitions among HFREF, HFPEF, and death. We observed a total of 8183 transitions. Women were more likely than men to transition from HFREF to HFPEF (hazard ratio, 1.85; 95% confidence interval, 1.38–2.47). Patients who were adherent to β-blockers were more likely to transition from HFREF to HFPEF (hazard ratio, 1.53; 95% confidence interval, 1.10–2.13) compared with patients who were nonadherent to β-blockers, whereas angiotensin-converting enzyme or angiotensin II receptor blocker adherence was not associated with LVEF transitions. Patients who had a previous myocardial infarction were more likely to transition from HFPEF to HFREF (hazard ratio, 1.75; 95% confidence interval, 1.26–2.42).

Conclusions—

In this cohort of patients with HF, LVEF is a dynamic factor related to sex, coexisting conditions, and drug therapy. These findings have implications for left ventricular systolic function ascertainment in patients with HF and support evidence-based therapy use, especially β-blockers.
Vasculogenesis in Experimental Stroke After Human Cerebral Endothelial Cell Transplantation
Authors: Ishikawa Hiroto , Tajiri Naoki , Shinozuka Kazutaka , Vasconcellos Julie , Kaneko Yuji , Lee Hong J. , Mimura Osamu , Dezawa Mari , Kim Seung U. , Borlongan Cesar V.
Published: October 2013

Background and Purpose—

Despite the reported functional recovery in transplanted stroke models and patients, the mechanism of action underlying stem cell therapy remains not well understood. Here, we examined the role of stem cell–mediated vascular repair in stroke.

Methods—

Adult rats were exposed to transient occlusion of the middle cerebral artery and 3 hours later randomly stereotaxically transplantated with 100K, 200K, or 400K human cerebral endothelial cell 6 viable cells or vehicle. Animals underwent neurological examination and motor test up to day 7 after transplantation then euthanized for immunostaining against neuronal, vascular, and specific human antigens. A parallel in vitro study cocultured rat primary neuronal cells with human cerebral endothelial cell 6 under oxygen-glucose deprivation and treated with vascular endothelial growth factor (VEGF) and anti-VEGF.

Results—

Stroke animals that received vehicle infusion displayed typical occlusion of the middle cerebral artery–induced behavioral impairments that were dose-dependently reduced in transplanted stroke animals at days 3 and 7 after transplantation and accompanied by increased expression of host neuronal and vascular markers adjacent to the transplanted cells. Some transplanted cells showed a microvascular phenotype and juxtaposed to the host vasculature. Infarct volume in transplanted stroke animals was significantly smaller than vehicle-infused stroke animals. Moreover, rat neurons cocultured with human cerebral endothelial cell 6 or treated with VEGF exhibited significantly less oxygen-glucose deprivation–induced cell death that was blocked by anti-VEGF treatment.

Conclusions—

We found attenuation of behavioral and histological deficits coupled with robust vasculogenesis and neurogenesis in endothelial cell–transplanted stroke animals, suggesting that targeting vascular repair sets in motion a regenerative process in experimental stroke possibly via the VEGF pathway.
Sex Is Associated With the Presence of Atherosclerotic Plaque Hemorrhage and Modifies the Relation Between Plaque Hemorrhage and Cardiovascular Outcome
Authors: Vrijenhoek Joyce E.P. , Den Ruijter Hester M. , De Borst Gert Jan , de Kleijn Dominique P.V. , De Vries Jean-Paul P.M. , Bots Michiel L. , Van de Weg Sander M. , Vink Aryan , Moll Frans L. , Pasterkamp Gerard
Published: October 2013

Background and Purpose—

Plaque hemorrhage (PH) may lead to accelerated progression of atherosclerotic disease. The presence of local PH in the carotid plaque predicts future cardiovascular events in any vascular territory. We investigated the prevalence of local PH and the predictive value of PH for the occurrence of cardiovascular events in men and women separately.

Methods—

Atherosclerotic plaques from 1422 patients (969 men, 453 women) who underwent carotid endarterectomy were analyzed histologically for the presence of PH. Patients were monitored for 3 years for cardiovascular events (nonfatal stroke, nonfatal myocardial infarction, vascular death, and vascular intervention).

Results—

Plaques from men showed a significantly higher prevalence of PH compared with women (67% versus 54%;
P
<0.001). In 1353 patients with available follow-up data, with a median duration of 2.9 years, 270 events had occurred in men (29%) and 94 in women (22%). Stratified by presence of PH, the event rate was 32% in men with PH versus 23% in men without PH, and 23% in women with PH versus 21% in women without PH. A multivariable Cox proportional hazards model found a significant interaction between sex and PH. PH was significantly associated with events in men (adjusted hazard ratio, 1.9; 95% CI, 1.2–2.8) but not in women (adjusted hazard ratio, 1.0; 95% CI, 0.6–1.7).

Conclusions—

Atherosclerotic carotid plaques obtained from men reveal a higher prevalence of PH compared with women. Local PH is strongly related to secondary manifestations of cardiovascular disease in men but not in women.
Theological Formation in the Church of ‘the Last Men and Women’
Authors: Lawson James
Published: October 2013

Every worldview has attendant disciplines. Late capitalism, as much to any Christian community, has its habits shaped by distinctive patterns of desire. Down the centuries, Christians have sought ways to live that line up with the vitality of their faith. We chart a course here through Kierkegaard, Bonhoeffer and Hauerwas. The route is distinctively shaped by pre-Reformation concerns as well as by Protestant ones, and in this it is deeply ecumenical. What, we ask, represents the excellence of the monastery as a community of formation in the present day? The answer will not necessarily be any literal monasticism but it will bear a strongly analogous relationship to it. We see this, not least for the Church of England, in the monastic roots of much of its approach to communal theological education and the question of our present willingness, or not, to live by its lessons.
Crenicichla taikyra (Teleostei: Cichlidae), a new species of pike cichlid from the middle río Paraná, Argentina
Authors: CASCIOTTA JORGE , ALMIRÓN ADRIANA , AICHINO DANILO , GÓMEZ SERGIO , PIÁLEK LUBOMÍR , ŘÍČAN OLDŘICH
Published: October 2013

Crenicichla taikyra, new species, is described from the middle río Paraná, Argentina. Crenicichla taikyra is distinguished from the other species of the genus by the following combination of characters: lower pharyngeal tooth plate stout, bearing molariform teeth, ascending arm of premaxilla longer than the dentigerous arm, posterior edge of preoperculum serrated, a well developed suborbital stripe, and absence of scattered dark dots on flanks. Molariform teeth on pharyngeal jaws is a derived character among Crenicichla species, however this character state has appeared several times in unrelated species.
A new species of Dexoris (Coleoptera: Lycidae) and parallel evolution of brachyptery in the soft-bodied elateroid beetles
Authors: BOCAK LADISLAV , GREBENNIKOV VASILY V. , MASEK MICHAL
Published: October 2013

Dexoris chome sp. nov. is described from South Pare mountains, Tanzania, based on a male specimen. This is the only Dexoris with shortened elytra, rudimentary hind wings and large, larviform abdomen. Unlike males of other species in the genus, D. chome sp. nov. has a modified number of palpomeres and remarkably short, robust legs and antennae. Such modifications are similar to those in the neotenic female of Omalisus fontisbellaquei Fourcroy, 1785 (Omalisidae), suggesting analogous morphological changes in unrelated lineages supposedly caused by similar modifications of their metamorphosis. The distribution of all 11 known species of African Dexoris closely overlap with the location of the hypothesized centres for evolution of new species in the Afrotropical region.
Kuroshio Extension Bimodality and the North Pacific Oscillation: A Case of Intrinsic Variability Paced by External Forcing
Authors: Pierini Stefano
Published: October 2013

A previous North Pacific Ocean circulation model forced by climatological winds is extended here to include a time-dependent North Pacific Oscillation (NPO) forcing. The Kuroshio Extension (KE) decadal bimodal cycle (which is a self-sustained intrinsic relaxation oscillation in the climatologically forced case) is now excited by the NPO forcing. Both the timing of the cycles and the Rossby wave teleconnection mechanism that is found to govern the synchronization from 1993 to 2012 are in good agreement with altimeter observations. Sensitivity numerical experiments are carried out by varying the zonal location and amplitude of the NPO forcing, and the lateral eddy viscosity. The emergence of the KE bimodality with a correct timing is found to be extremely sensitive to changes in the dissipative parameterization; the implications of such sensitivity for deficiencies found in more realistic North Pacific Ocean general circulation models are discussed. The dynamical mechanism that emerges from this study is explained as a case of intrinsic variability in an excitable dynamical system triggered, and therefore paced, by an external forcing.
A Trial to Improve Surface Heat Exchange Simulation through Sensitivity Experiments over a Desert Steppe Site
Authors: Zhang Guo , Zhou Guangsheng , Chen Fei , Barlage Michael , Xue Lulin
Published: October 2013

It is still a daunting challenge for land surface models (LSMs) to correctly represent surface heat exchange for water-limited desert steppe ecosystems. This study aims to improve the ability of the Noah LSM to simulate surface heat fluxes through addressing uncertainties in precipitation forcing conditions, rapidly evolving vegetation properties, soil hydraulic properties (SHPs), and key parameterization schemes. Three years (2008–10) of observed surface heat fluxes and soil temperature over a desert steppe site in Inner Mongolia, China, are used to verify model simulations. The proper seasonal distribution of precipitation, along with more realistic vegetation parameters, can improve the simulation of sensible heat flux (SH) and the seasonal variability of latent heat flux. Correctly representing the low-surface exchange coefficient is crucial for improving SH for short vegetation like this desert steppe site. Relating Czil, the coefficient in the Noah surface exchange coefficient calculation, with canopy height h improves the simulated SH and the diurnal range of soil temperature over the simulation compared with using the default constant Czil. The exponential water stress formulation proposed here for the Jarvis scheme improves the partitioning between soil evaporation and transpiration. It is found that the surface energy fluxes are very sensitive to SHPs. This study highlights the important role of the proper parameter values and appropriate parameterizations for the surface exchange coefficient and water stress function in canopy resistance in capturing the observed surface energy fluxes and soil temperature variations for this desert steppe site.
Bottom-Enhanced Diapycnal Mixing Driven by Mesoscale Eddies: Sensitivity to Wind Energy Supply
Authors: Stanley Geoff J. , Saenko Oleg A.
Published: October 2013

It has been estimated that much of the wind energy input to the ocean general circulation is removed by mesoscale eddies via baroclinic instability. While the fate of this energy remains a subject of research, arguments have been presented suggesting that a fraction of it may get transferred to lee waves that, upon breaking, result in bottom-enhanced diapycnal mixing. Here the authors propose several parameterizations of this process and explore their impact in a low-resolution ocean–climate model, focusing on their impact on the abyssal meridional overturning circulation (MOC) of Antarctic Bottom Water. This study shows that, when the eddy energy is allowed to maintain diapycnal mixing, the abyssal MOC generally intensifies with increasing wind energy input to the ocean. In such a case, the whole system is driven by the wind: wind steepens isopycnals and generates eddies, and the (parameterized) eddies generate small-scale mixing, driving the MOC. It is also demonstrated that if the model diapycnal diffusivity, eddy transfer coefficient, and surface climate are decoupled from the winds, then stronger wind stress in the Southern Ocean may lead to a weaker MOC in the abyss—in line with previous results. A simple scaling theory, describing the response of the abyssal MOC strength to wind energy input, is developed, providing a better insight on the numerical results.
A study on mechanical, thermal, and electrical properties of glass fiber-reinforced epoxy hybrid composites filled with plasma-synthesized AlN
Authors: Panda Pravuram , Mishra Gopa , Mantry Sisir , Singh Saroj Kumar , Sinha Swami Prasad
Published: October 2013

Glass fiber-reinforced epoxy resin (GFRE) composites filled with aluminum nitride (AlN) powder were fabricated, and their thermal and electrical properties were investigated. It is observed that with the increasing percentage of AlN particles, there is a significant enhancement in thermal conductivity and micro-hardness, but there is a decline in tensile strength. Experimental results demonstrate that the GFRE composites with 10 wt% of AlN loading show maximum dielectric breakdown strength of 30.26 kV/mm with minimum volume resistivity of 7.5 × 1014 Ω cm and thermal conductivity value of 0.300 W/mK. Scanning electron microscopy studies were conducted to observe the voids and distribution of filler in composites.
A unifying framework for specifying DEVS parallel and distributed simulation architectures
Authors: Adegoke Adedoyin , Togo Hamidou , Traoré Mamadou K
Published: October 2013

DEVS (Discrete Event System Specification) is an approach in the area of modeling and simulation that provides a means of specifying dynamic systems. A variety of DEVS tools have been implemented without a standard developmental guideline across the board, consequently revealing a lack of central frameworks for integrating heterogeneous DEVS simulators. When implementing a DEVS Simulator there are salient concepts that are intuitively defined, such as how events should be processed, what simulation architecture to use, what existing procedures (set of rules/algorithm) can be used, what should be the organizational architecture and so on. The aim of this paper is to propose a theoretical guide in building a DEVS distributed simulation as well as a formalization of underlying concepts to allow symbolic reasoning and automated code synthesis. From a review of existing implementation approaches, we propose a taxonomy of the identified concepts, including some formal definitions as they constitute the essential building blocks of performing Parallel Discrete-Event Simulation by utilizing DEVS. The contribution of this taxonomy and its impact as a unifying framework is that it provides a more systematic understanding of the process of constructing a DEVS simulator. Also, it offers an abstract way for integrating different and heterogeneous DEVS implementation strategies and thus can serve as a contribution to the on-going DEVS standardization efforts.
Comparative Hypothesis Testing Via Process Tracing
Authors: Rohlfing Ingo
Published: October 2013

Causal inference via process tracing has received increasing attention during recent years. A 2 × 2 typology of hypothesis tests takes a central place in this debate. A discussion of the typology demonstrates that its role for causal inference can be improved further in three respects. First, the aim of this article is to formulate case selection principles for each of the four tests. Second, in focusing on the dimension of uniqueness of the 2 × 2 typology, I show that it is important to distinguish between theoretical and empirical uniqueness when choosing cases and generating inferences via process tracing. Third, I demonstrate that the standard reading of the so-called doubly decisive test is misleading. It conflates unique implications of a hypothesis with contradictory implications between one hypothesis and another. In order to remedy the current ambiguity of the dimension of uniqueness, I propose an expanded typology of hypothesis tests that is constituted by three dimensions.
Implementation of the Power to Prevent Diabetes Prevention Educational Curriculum Into Rural African American Communities
Authors: Cené Crystal W. , Haymore Laura Beth , Ellis Danny , Whitaker Shaketa , Henderson Stacey , Lin Feng-Chang , Corbie-Smith Giselle
Published: October 2013

Purpose

The purpose of this study was to describe the feasibility of using a community-based participatory research (CBPR) approach to implement the Power to Prevent (P2P) diabetes prevention education curriculum in rural African American (AA) settings.

Methods

Trained community health workers facilitated the 12-session P2P curriculum across 3 community settings. Quantitative (based on the pre- and post-curriculum questionnaires and changes in blood glucose, blood pressure [BP], and weight at baseline and 6 months) and qualitative data (based on semi-structured interviews with facilitators) were collected. Indicators of feasibility included: demand, acceptability, implementation fidelity, and limited efficacy testing.

Results

Across 3 counties, 104 AA participants were recruited; 43% completed ≥ 75% of the sessions. There was great demand for the program. Fifteen community health ambassadors (CHAs) were trained, and 4 served as curriculum facilitators. Content and structure of the intervention was acceptable to facilitators but there were challenges to implementing the program as designed. Improvements were seen in diabetes knowledge and the impact of healthy eating and physical activity on diabetes prevention, but there were no significant changes in blood glucose, BP, or weight.

Conclusion

While it is feasible to use a CBPR approach to recruit participants and implement the P2P curriculum in AA community settings, there are significant challenges that must be overcome.
The Development of Myelin in the Brain of the Juvenile Rat
Authors: Downes Noel , Mullins Pamela
Published: October 2013

The development process of myelination varies between region and species. Fully myelinated fibers are required if mammalian neural circuits are to function normally. Histology samples at staggered time points throughout the study were examined at days 4, 5, 7, 8, 10, 14, 17, 24, 37, and 44. We suggest that the development of myelin in the juvenile rodent brain can be conveniently separated into 3 phases. Evaluation of myelin basic protein–stained sections of the areas of brain that contain the elements of the developing limbic system over the sensitive period from postnatal day (PND) 14 to 34 may provide an insight into possible toxicity that may lead to cognition and learning issues in adults. We will hope to develop this notion further in the future. The precise chronology of the development of the blood–brain barrier in rats has yet to be established; thus, there is potential for significant exposure of the juvenile brain to chemicals that do not cross the blood–brain barrier in the adult. Thus, it is suggested that evaluation of myelin development should probably be extended to all new chemical entities intended for pediatric use, and not just those that are intended for central nervous system use.