bluuebunny/crossref_metadata_2025 huggingface dataset:
T-bet is induced by interferon-γ to mediate chemokine secretion and migration in human airway smooth muscle cells
Authors: Singer Cherie A.
Published: January 2011

An inappropriate balance between T-helper (Th)1 and Th2 cytokine production underlies inflammatory changes that result in airway disease. Expression of the T-box transcription factor T-bet regulates differentiation of Th cells and production of Th1 cytokines, particularly IFNγ. T-bet-deficient mice develop airway hyperreactivity, undergo airway remodeling, and exhibit defects in IFNγ production while overproducing Th2 cytokines. T-bet is also reduced in the airways of asthmatic patients, suggesting loss of T-bet expression or activity promotes development of inflammatory airway disease. We present novel data demonstrating T-bet expression is induced in human airway smooth muscle cells (ASMC) by IFNγ. This IFNγ-stimulated expression of T-bet is dependent on signaling through JAK2 and signal transducers and activators of transcription 1 (STAT1) and activates T-bet-dependent DNA binding activity. Expression of T-bet stimulates IFNγ-stimulated IFNγ expression, secretion, and promoter activity, while inhibiting IFNγ-stimulated release of chemokines including monocyte chemoattractant protein (MCP)-1/CCL2, regulated on activation normal T-expressed and secreted (RANTES)/CCL5, and eotaxin/CCL11. This is accompanied by changes in expression of the chemokine receptors CCR3 and IL12Rβ2 and TNFα. T-bet expression also reduces chemotactic migration of ASMC in response to serum and PDGF, which contributes to airway hyperplasia. These results are the first to identify T-bet expression and activity in a structural cell of the lung and may provide new insights into therapeutic targets for inflammatory airway disease.
Long-term failure of alveologenesis after an early short-term exposure to a PDGF-receptor antagonist
Authors: Lau Mandy , Masood Azhar , Yi Man , Belcastro Rosetta , Li Jun , Tanswell A. Keith
Published: January 2011

Survivors of moderate-to-severe bronchopulmonary dysplasia have impaired alveologenesis lasting at least into early adult life. The mechanisms underlying this long-term effect are unknown. We hypothesized that short-term inhibition of growth factor-mediated early alveolar formation would result in a long-term impairment of subsequent alveologenesis. Neonatal rats were injected daily with the platelet-derived growth factor (PDGF) receptor antagonist, imatinib mesylate, from day 1– 7 of life, to inhibit the early alveolar formation occurring by in-growth of secondary crests into precursor saccules. The pups were then allowed to recover for 7, 14, 21, or 58 days. In imatinib-treated pups, DNA synthesis in total lung cells, and specifically in cells of secondary crests, was reduced at day 8 of life, had rebounded on day 14 of life but was then again reduced by day 28 of life. At day 8 of life, imatinib-treated pups had impaired alveologenesis as reflected by a decrease in secondary crests, an increase in alveolar size, and an overall decrease in both estimated alveolar number and generations compared with age-matched controls. No meaningful recovery was observed, even after a 21- or 58-day recovery period. The lungs of imatinib-treated pups had increased fibulin-5 content and an abnormal deposition of elastin. We conclude that reduced signaling through the PDGF pathways, at an early stage of alveologenesis, can result in long-lasting changes in lung architecture. A likely mechanism is through impaired formation of the elastin scaffold required for alveolarization.
Quantifying mitochondrial and plasma membrane potentials in intact pulmonary arterial endothelial cells based on extracellular disposition of rhodamine dyes
Authors: Gan Zhuohui , Audi Said H. , Bongard Robert D. , Gauthier Kathryn M. , Merker Marilyn P.
Published: January 2011

Our goal was to quantify mitochondrial and plasma potential (Δψmand Δψp) based on the disposition of rhodamine 123 (R123) or tetramethylrhodamine ethyl ester (TMRE) in the medium surrounding pulmonary endothelial cells. Dyes were added to the medium, and their concentrations in extracellular medium ([Re]) were measured over time. R123 [Re] fell from 10 nM to 6.6 ± 0.1 (SE) nM over 120 min. TMRE [Re] fell from 20 nM to a steady state of 4.9 ± 0.4 nM after ∼30 min. Protonophore or high K+concentration ([K+]), used to manipulate contributions of membrane potentials, attenuated decreases in [Re], and P-glycoprotein (Pgp) inhibition had the opposite effect, demonstrating the qualitative impact of these processes on [Re]. A kinetic model incorporating a modified Goldman-Hodgkin-Katz model was fit to [Re] vs. time data for R123 and TMRE, respectively, under various conditions to obtain (means ± 95% confidence intervals) Δψm(−130 ± 7 and −133 ± 4 mV), Δψp(−36 ± 4 and −49 ± 4 mV), and a Pgp activity parameter ( KPgp, 25 ± 5 and 51 ± 11 μl/min). The higher membrane permeability of TMRE also allowed application of steady-state analysis to obtain Δψm(−124 ± 6 mV). The consistency of kinetic parameter values obtained from R123 and TMRE data demonstrates the utility of this experimental and theoretical approach for quantifying intact cell Δψmand Δψp.Finally, steady-state analysis revealed that although room air- and hyperoxia-exposed (95% O2for 48 h) cells have equivalent resting Δψm, hyperoxic cell Δψmwas more sensitive to depolarization with protonophore, consistent with previous observations of pulmonary endothelial hyperoxia-induced mitochondrial dysfunction.
Recent Advances in the Pathobiology of Hodgkin's Lymphoma: Potential Impact on Diagnostic, Predictive, and Therapeutic Strategies
Authors: Banerjee Diponkar
Published: January 2011

From its first description by Thomas Hodgkin in 1832, Hodgkin's disease, now called Hodgkin's lymphoma, has continued to be a fascinating neoplasm even to this day. In this review, historical aspects, epidemiology, diagnosis, tumor biology, new observations related to host-microenvironment interactions, gene copy number variation, and gene expression profiling in this complex neoplasm are described, with an exploration of chemoresistance mechanisms and potential novel therapies for refractory disease.
Variational-Like Inclusions and Resolvent Equations Involving Infinite Family of Set-Valued Mappings
Authors: Ahmad Rais , Dilshad Mohd
Published: January 2011

We study variational-like inclusions involving infinite family of set-valued mappings and their equivalence with resolvent equations. It is established that variational-like inclusions in real Banach spaces are equivalent to fixed point problems. This equivalence is used to suggest an iterative algorithm for solving resolvent equations. Some examples are constructed.
6-Thioguanine Reactivates Epigenetically Silenced Genes in Acute Lymphoblastic Leukemia Cells by Facilitating Proteasome-mediated Degradation of DNMT1
Authors: Yuan Bifeng , Zhang Jing , Wang Hongxia , Xiong Lei , Cai Qian , Wang Tina , Jacobsen Steven , Pradhan Sriharsa , Wang Yinsheng
Published: January 2011

Thiopurines including 6-thioguanine (SG), 6-mercaptopurine, and azathioprine are effective anticancer agents with remarkable success in clinical practice, especially in effective treatment of acute lymphoblastic leukemia (ALL). SG is understood to act as a DNA hypomethylating agent in ALL cells, however, the underlying mechanism leading to global cytosine demethylation remains unclear. Here we report that SG treatment results in reactivation of epigenetically silenced genes in T leukemia cells. Bisulfite genomic sequencing revealed that SG treatment universally elicited demethylation in the promoters and/or first exons of the genes that were reactivated. SG treatment also attenuated the expression of histone lysine-specific demethylase 1 (LSD1), thereby stimulating lysine methylation of the DNA methylase DNMT1 and triggering its degradation via the ubiquitin-proteasomal pathway. Taken together, our findings reveal a previously uncharacterized but vital mechanistic link between SG treatment and DNA hypomethylation. Cancer Res; 71(5); 1904–11. ©2011 AACR.
KRASMutation Is Associated with Lung Metastasis in Patients with Curatively Resected Colorectal Cancer
Authors: Tie Jeanne , Lipton Lara , Desai Jayesh , Gibbs Peter , Jorissen Robert N. , Christie Michael , Drummond Katharine J. , Thomson Benjamin N.J. , Usatoff Valery , Evans Peter M. , Pick Adrian W. , Knight Simon , Carne Peter W.G. , Berry Roger , Polglase Adrian , McMurrick Paul , Zhao Qi , Busam Dana , Strausberg Robert L. , Domingo Enric , Tomlinson Ian P.M. , Midgley Rachel , Kerr David , Sieber Oliver M.
Published: January 2011

Purpose: Oncogene mutations contribute to colorectal cancer development. We searched for differences in oncogene mutation profiles between colorectal cancer metastases from different sites and evaluated these as markers for site of relapse.

Experimental Design: One hundred colorectal cancer metastases were screened for mutations in 19 oncogenes, and further 61 metastases and 87 matched primary cancers were analyzed for genes with identified mutations. Mutation prevalence was compared between (a) metastases from liver (n = 65), lung (n = 50), and brain (n = 46), (b) metastases and matched primary cancers, and (c) metastases and an independent cohort of primary cancers (n = 604). Mutations differing between metastasis sites were evaluated as markers for site of relapse in 859 patients from the VICTOR trial.

Results: In colorectal cancer metastases, mutations were detected in 4 of 19 oncogenes: BRAF (3.1%), KRAS (48.4%), NRAS (6.2%), and PIK3CA (16.1%). KRAS mutation prevalence was significantly higher in lung (62.0%) and brain (56.5%) than in liver metastases (32.3%; P = 0.003). Mutation status was highly concordant between primary cancer and metastasis from the same individual. Compared with independent primary cancers, KRAS mutations were more common in lung and brain metastases (P < 0.005), but similar in liver metastases. Correspondingly, KRAS mutation was associated with lung relapse (HR = 2.1; 95% CI, 1.2 to 3.5, P = 0.007) but not liver relapse in patients from the VICTOR trial.

Conclusions: KRAS mutation seems to be associated with metastasis in specific sites, lung and brain, in colorectal cancer patients. Our data highlight the potential of somatic mutations for informing surveillance strategies. Clin Cancer Res; 17(5); 1122–30. ©2011 AACR.
Novel Chemosensitive Single-Nucleotide Polymorphism Markers to Targeted Regimens in Metastatic Colorectal Cancer
Authors: Kim Jin C. , Kim Seon Y. , Cho Dong H. , Ha Ye J. , Choi Eun Y. , Kim Chan W. , Roh Seon A. , Kim Tae W. , Ju Hyoungseok , Kim Yong S.
Published: January 2011

Purpose: Methods for predicting individual responsiveness to targeted chemotherapy are urgently needed, considering the frequent resistance and extremely high cost.

Experimental Design: A chemosensitive single-nucleotide polymorphism (SNP) discovery schema is presented that utilizes (i) genome-wide SNP screening with a human SNP array and an in vitro chemosensitivity assay in 118 colorectal cancers, (ii) clinical association analysis in the other 98 patients who had received chemotherapy for metastatic cancer, and (iii) biological utility assessment using cell viability assays of transfected colorectal cancer (CRC) cells.

Results: Nine SNPs related to bevacizumab and cetuximab regimen sensitivity were chosen during screening. Overall responses for bevacizumab regimens revealed that patients carrying the TT genotype at ANXA11 rs1049550 or at least one G allele at LINS1 rs11247226 seemed greater chemosensitive than those carrying at least one C allele or the AA genotype, respectively (P < 0.05). For cetuximab regimens, patients carrying the GG genotype at DFNB31 rs2274159 or LIFR rs3729740 seemed greater chemosensitive than those carrying at least one A allele (P = 0.025 and P = 0.07). Cytotoxicity analyses showed that all RKO and HCT116 CRC clones transfected with the G allele at LIFR rs3729740 and the C allele at ISX rs361863 were more sensitive to cetuximab regimens than those with the A and T allele, respectively (P ≤ 0.001–0.024).

Conclusions: Chemosensitive SNP markers were identified using a novel three-step process. The candidate marker LIFR rs3729740 and possibly ISX rs361863 will hopefully predict responsive patients to cetuximab regimens, although further validation is needed in large cohorts. Clin Cancer Res; 17(5); 1200–9. ©2011 AACR.
Quantification of Ventricular Resynchronization Reserve by Radionuclide Phase Analysis in Heart Failure Patients
Authors: Dauphin Raphael , Nonin Emilie , Bontemps Laurence , Vincent Madeleine , Pinel Alain , Bonijoly Serge , Barborier Denis , Ribier Arnaud , Mestre Fernandes Christine , Bert-Marcaz Patrick , Itti Roland , Chevalier Philippe
Published: January 2011

Background—

Phase analysis, developed to assess dyssynchrony from ECG-gated radionuclide ventriculography, has shown promising results. We hypothesized that quantifying the cardiac resynchronization reserve, that is, the extent of response to cardiac resynchronization therapy (CRT), by radionuclide imaging could potentially identify patients who are best suited for CRT.

Methods and Results—

Seventy-four patients ages 64.8±10.1 years were prospectively studied from July 2004 to July 2006, of whom 62.2% and 37.8%, respectively, were in New York Heart Association class 3 and 4. Mean QRS width was 173±25 ms. ECG-gated radionuclide ventriculography to quantify interventricular and intraventricular dyssynchrony was performed at baseline with and without CRT and at the 3-month follow-up visit. Amino-terminal-pro-brain natriuretic peptide (NT-pro-BNP) levels were also determined at baseline and at 3 months. During a mean follow-up of 10.1±7.6 months, there were 37 (50%) clinical events that defined the nonresponder group, including cardiac death or readmission for worsening heart failure. In multivariate Cox model analysis, higher NT-pro-BNP blood levels were associated with a significant increase in the risk for event (hazard ratio=1.085 for a 100 pg/L increase in NT-pro-BNP; 95% confidence interval, 1.014 to 1.161). Each 10° elevation in intraventricular dyssynchrony was associated with a decrease in the risk of events (hazard ratio=0.456, 95% confidence interval, 0.304 to 0.683). Receiver operating characteristic curve analysis demonstrated that an interventricular dyssynchrony cutoff value of 25.5° for intraventricular synchrony yielded 91.4% sensitivity and 84.4% specificity for predicting a good response to CRT.

Conclusions—

The quantification of interventricular dyssynchrony with radionuclide phase analysis suggests that early postimplantation interventricular dyssynchrony may provide identification of CRT responders.
Creation and Characterization of a Renin Knockout Rat
Authors: Moreno Carol , Hoffman Mathew , Stodola Timothy J. , Didier Daniela N. , Lazar Jozef , Geurts Aron M. , North Paula E. , Jacob Howard J. , Greene Andrew S.
Published: January 2011

The renin-angiotensin system plays an important role in the control of blood pressure (BP) and renal function. To illuminate the importance of renin in the context of a disease background in vivo, we used zinc-finger nucleases (ZFNs) designed to target the renin gene and create a renin knockout in the SS/JrHsdMcwi (SS) rat. ZFN against renin caused a 10-bp deletion in exon 5, resulting in a frameshift mutation. Plasma renin activity was undetectable in the
Ren
−/− rat, and renin protein was absent from the juxtaglomerular cells in the kidney. Body weight was lower in the
Ren
−/− rats (than in the
Ren
+/− or wild-type littermates), and conscious BP on low-salt diet (0.4% NaCl) was 58±2 mm Hg in the
Ren
−/− male rats versus 117 mm Hg in the
Ren
+/− littermates, a reduction of almost 50 mm Hg. Blood urea nitrogen (BUN) and plasma creatinine levels were elevated in the
Ren
−/− strain (BUN 112±7 versus 23±2 mg/dL and creatinine 0.53±0.02 versus 0.26±0.02 mg/dL), and kidney morphology was abnormal with a rudimentary inner renal medulla, cortical interstitial fibrosis, thickening of arterial walls, and abnormally shaped glomeruli. The development of the first rat knockout in the renin-angiotensin system demonstrates the efficacy of the ZFN technology for creating knockout rats for cardiovascular disease on any genetic background and emphasizes the role of renin in BP regulation and kidney function even in the low-renin SS rat.
The estimation of cell density in isotropic microcellular polymeric foams using the critical bubble lattice
Authors: Buahom Piyapong , Areerat Surat
Published: January 2011

In this study, models for estimating the cell density of isotropic polymeric foams using the surface cell density were developed. The basic morphological unit cell for these models is a gas-filled pentagonal dodecahedral cell cavity. The critical bubble lattice model was introduced to associate the packing structure of the pentagonal dodecahedral cells with a face-centered cubic (FCC) packing structure, and the cell density was estimated. This model was then used to investigate the effect of nonperfect cell cross-sections as found in the micrographs of cell densities of foams. Two cases were examined: first, the ideal case of a perfect cross-section, and second, the actual case of a nonperfect cross-section. The plots of cell density versus surface cell density from recently published data show the effect of a nonperfect cross-section on the estimation of cell density within an FCC lattice with perfect and nonperfect cell cross-sections. The percentage average absolute deviation (AAD) showed that the nonperfect cell cross-sectional model reliably predicts the cell density of isotropic low-density foam with an AAD of 39.2%. The perfect cell cross-sectional model reliably predicts the cell density of isotropic high-density foam with an AAD of 57.2%. These new models are more reliable than the conventional model, which give AADs 59.4% for low-density foams and 62.4% for high-density foams. Furthermore, the isotropic foam index was introduced as a parameter to indicate the isotropic foam behavior.
Preparation and characterization of HDPE/PA6 foam blends
Authors: Reyes-Lozano Cinthia Astrid , Gudiño Pedro Ortega , González-Núñez Rubén , Rodrigue Denis
Published: January 2011

In this work, preparation and characterization of HDPE/PA6 foam blends is presented. Using a chemical blowing agent based on azodicarbonamide, foams were produced via extrusion using different concentrations of the dispersed phase PA6. Due to very different thermal and rheological properties of the polymers, good cellular structures could only be obtained by a careful selection of the temperature profile and feeding strategy of the materials. Furthermore, the use of a coupling agent was also found necessary to stabilize the blend before foaming. The final foam morphology was controlled by post-extrusion conditions and the results are discussed in terms of deformation and dimensions of foam cells and dispersed phase particles. The tensile and impact properties of the resulting foams are also reported.
Mechanical properties of polypropylene structural foams with fiber-reinforced skins
Authors: Mechraoui A. , Riedl B. , Rodrigue Denis
Published: January 2011

This article reports on the effect of skin thickness, core density, and skin composition on the mechanical properties of sandwich structural foams. In this study, the skin layers are polypropylene reinforced by different amounts of hemp fibers while the core is the same polypropylene foamed using different amounts of chemical blowing agent. The sandwich structures are characterized mechanically in terms of tensile and flexural properties. The results show that fiber introduction in the skins not only improved the mechanical properties, but also produced finer cell structures in the core. Finally, a mechanical model including fiber concentration, skin thickness, and density profile in the core is proposed to predict with high accuracy the elastic modulus of the sandwich foams.
Political Philosophy in Political Science: Sixty Years on
Authors: Leca Jean
Published: January 2011

Political philosophy is that area of philosophy dealing with politics and government, that unstable mix of war and foedus, conflictual division and authoritative union. As ‘philosophy’ it is part of the vita contemplativa, which is pure thinking; as ‘political’ it has always something to do with vita activa, that is action and praxis in a world that exists with its own rules and language games before any philosophical attempt to make that world the embodiment of a theory as Plato did (Arendt, 1953, 1959). Philosophy, like science, is about truth whereas politics is about power or, more accu¬rately, ‘the constrained use of social power’ (Goodin and Klingemann, 1996). This formulation reintroduces truth into the possible constraints alongside rhetoric, persuasion, compromise and negotiation.
Care or custody? An evaluation of palliative care in prisons in North West England
Authors: Turner Mary , Payne Sheila , Barbarachild Zephyrine
Published: January 2011

This study aimed to evaluate health professionals’ views about palliative care provision in prisons in the counties of Cumbria and Lancashire in the North West of England. Seventeen prison healthcare staff and nine specialist palliative care staff participated in semi-structured interviews and 16 prison healthcare staff completed a questionnaire designed to measure knowledge, skills and confidence in relation to palliative care. The findings highlighted tensions between the philosophies of care and custody, and the many challenges in providing palliative care in a custodial setting. This paper presents two illustrative case study examples, and suggests ways in which some of these challenges can be overcome in practice.
The relationship between affect, uses of music, and music preferences in a sample of South African adolescents
Authors: Getz Laura M. , Chamorro-Premuzic Tomas , Roy Michael M. , Devroop Karendra
Published: January 2011

The current study examined the relationship between individual differences in uses of music (i.e. motives for listening to music), music preferences (for different genres), and positive affect (PA) and negative affect (NA), thus linking two areas of past research into a more comprehensive model. A sample of 193 South African adolescents (ages 12–17) completed measures of the above constructs and data were analyzed via correlations and structural equation modeling (SEM). Significant correlations between affect and uses of music were tested using SEM; a model whereby PA influenced background and cognitive uses of music, NA influenced emotional use of music, and higher uses of music led to increased preferences for music styles was supported. Future research for uses of music and music preferences are discussed.
‘Rock music for myself and justice to the world!’: Musical identity, values, and music preferences
Authors: Gardikiotis Antonis , Baltzis Alexandros
Published: January 2011

The present study examined the relationship between music preferences, values, and musical identities in a sample of 606 Greek college students. Students indicated the importance of music in defining and evaluating themselves and their values on an abbreviated version of the Schwartz Value Survey ( Schwartz, 1992 ). A typology of music preferences was revealed, with five factors: sophisticated and complex (e.g., jazz); native-Greek traditional (e.g., ‘rebetika’); sentimental and sensational (e.g., pop); established rebellious (e.g., rock); and non-mainstream dissonant (e.g., punk). Hierarchical regression analyses showed that values and perceived importance of music to self-definition (i.e., musical identities) contribute differentially in predicting the music preference structures, for example self-transcendence predicted established rebellious and conservation predicted sentimental and sensational; also musical identity was positively related to established rebellious and negatively to sentimental and sensational. These findings are discussed and interpreted within a psychological, as well as an interdisciplinary, theoretical framework.
Biomechanical Comparison of Anatomic Double-Bundle, Anatomic Single-Bundle, and Nonanatomic Single-Bundle Anterior Cruciate Ligament Reconstructions
Authors: Kondo Eiji , Merican Azhar M. , Yasuda Kazunori , Amis Andrew A.
Published: January 2011

Background: Although both anatomic double-bundle and single-bundle anterior cruciate ligament reconstruction procedures are in use, it remains controversial whether the anatomic double-bundle procedure is biomechanically superior.

Hypothesis: The anatomic double-bundle procedure would be better than both laterally placed anatomic and nonanatomic transtibial single-bundle procedures at restoring to normal the tibial anterior translation, internal rotation, and pivot-shift instability. It was also hypothesized that tibial internal rotation would be closer to normal after laterally placed anatomic single-bundle reconstruction than after the nonanatomic reconstruction.

Study Design: Controlled laboratory study.

Methods: Eight cadaveric knees were mounted in a 6 degrees of freedom rig and tested using the following loading conditions: 90-N anterior and posterior tibial forces, 5-N·m internal and external tibial rotation torques, and a simulated pivot-shift test. Tibiofemoral kinematics during the flexion-extension cycle were recorded with an optical tracking system for (1) intact, (2) anterior cruciate ligament–deficient knee, (3) anatomic double-bundle reconstruction, (4) nonanatomic single-bundle reconstruction, and (5) laterally placed single-bundle reconstruction.

Results: Rotational laxity with internal tibial torque and anterior laxity in the simulated pivot shift were significantly less in the double-bundle reconstruction and laterally placed single-bundle reconstruction compared with the nonanatomic single-bundle reconstruction. There were no significant differences between the 3 procedures when anterior and posterior tibial translation forces and external rotation torques were applied. In addition, there were no significant differences between the double-bundle reconstruction and laterally placed single-bundle reconstruction.

Conclusion: The postoperative rotational and pivot-shift laxity after anatomic double-bundle anterior cruciate ligament reconstruction was significantly better than that after nonanatomic single-bundle reconstruction. However, there were no significant differences between the double-bundle reconstruction and laterally placed single-bundle reconstruction.

Clinical Relevance: This work suggests that a single-bundle reconstruction may be better able to control both knee laxity and pivot-shift instability if the femoral tunnel is moved to a more lateral position and that then the double-bundle reconstruction may not offer significant further advantages.
A Refined Sinus Finite Element Model for the Analysis of Piezoelectric-Laminated Beams
Authors: Beheshti-Aval S.B. , Lezgy-Nazargah M. , Vidal P. , Polit O.
Published: January 2011

A three-nodded beam finite element is developed for the analysis of composite-laminated beams with distributed piezoelectric sensor/actuator layers. The mechanical part of the proposed element is based on the refined sinus model. This element does not require shear correction factor and ensures continuity conditions for displacements, transverse shear stresses as well as boundary conditions on the upper and lower surfaces of the beam. This conforming finite element is totally free of shear locking, and the number of mechanical unknowns is independent of the number of layers. For each piezoelectric layer, a high-order electrical potential field is considered. The virtual work principle leads to a derivation that could include dynamic analysis. However, in this study, only static problems have been considered. Comparison of numerical results obtained from this formulation with previous works shows that the present finite element is suitable for predicting fully coupled behaviors of both thick and thin smart-laminated beams under mechanical and electrical loadings.
Dendritic Spine Plasticity: New Regulatory Roles of Dynamic Microtubules
Authors: Hoogenraad Casper C. , Akhmanova Anna
Published: January 2011

Dendritic spines are small actin-rich protrusions that form the postsynaptic part of most excitatory synapses. They play critical roles in synaptic function and exhibit a striking degree of structural plasticity, which is closely linked to changes in strength of synaptic connections. Here the authors summarize recent work that has revealed an important relationship between the microtubule and actin cytoskeleton in controlling spine morphology and plasticity. Dynamic microtubules and the proteins that specifically associate with the growing microtubule plus-ends recently emerged as temporal and spatial regulators of actin organization, which controls dynamic changes in structure and function of dendritic spines.
Transient responses of Timoshenko beams subject to a moving mass
Authors: Jiang Ji-Qing
Published: January 2011

The dynamic behavior of beam structures subject to a moving mass is a topic of practical importance in many research fields. In this study, the method of reverberation-ray matrix is presented to investigate the dynamic responses of an undamped Timoshenko beam subject to a moving mass. Based on Inglis’s assumption, the moving mass is simplified into a moving force and a concentrated mass fixed at the mid-span of the beam. Two dual local coordinates are introduced. Based on the theory of elastodynamics, the general wave solutions with two sets of unknown amplitude coefficients are derived in the transformed domain by the dual integral transform. From continuity conditions of forces and displacements at each joint and the compatibility conditions with respect to the dual coordinates, the unknown amplitude coefficients can be determined exactly. The transient dynamic motions for a Timoshenko beam under a moving mass are then determined numerically by inverse integral transform in which the Neumann series expansion is employed to avoid the integral singularities. Two simple numerical examples are presented and the results so obtained are compared with both the experimental and theoretical ones. It is shown that the present method can be a simple alternative for determining dynamic responses of bridges subject to a moving vehicle.
Impact of clinical pharmacy services on patients in an outpatient chemotherapy academic clinic
Authors: McKee Megan , Frei Bradi L , Garcia Anita , Fike David , Soefje Scott A
Published: January 2011

Background. Assessing the role of the pharmacist in an outpatient oncology clinic requires quantification of parameters that are important to the patient and the healthcare system. Patient evaluations not only serve as benchmarks for a process; but may also predict behavior such as utilization of care, continuity with the provider, and compliance.

Purpose. To identify the role of the patient–pharmacist relationship and enhance patient satisfaction with care, a survey tool was developed and utilized.

Methods. A 20-item, 2-page survey tool was developed and administered to oncology patients actively receiving treatment at the Cancer Therapy & Research Center (CTRC) in San Antonio, Texas. Following approval from the Investigational Review Board, survey distribution began on December 1, 2009 and continued through February 2010. Basic social and demographic data were collected. Satisfaction with pharmacy service was assessed with questions on a Likert ranking scale detailing time spent with pharmacists, knowledge of medication therapy, willingness to pay for clinical pharmacy services, etc. The primary outcome was the impact of the pharmacist–patient relationship assessed by examining the interaction between time spent with pharmacist, understanding of medications, and desire for future pharmacy counseling services.

Results. A total of 77 surveys were administered and collected. Of the patients surveyed, 86% stated that it is important for patients to discuss their treatment with a pharmacist and 76% requested pharmacy follow-up at future visits.

Conclusion. This cross-sectional survey reveals that patients are interested in visiting with a pharmacist regularly during chemotherapy treatment and patients may be willing to pay for pharmacy counseling services.
Distributed changes in default-mode resting-state connectivity in multiple sclerosis
Authors: Bonavita Simona , Gallo Antonio , Sacco Rosaria , Corte Marida Della , Bisecco Alvino , Docimo Renato , Lavorgna Luigi , Corbo Daniele , Costanzo Alfonso Di , Tortora Fabio , Cirillo Mario , Esposito Fabrizio , Tedeschi Gioacchino
Published: January 2011

Background: The default-mode network (DMN) has been increasingly recognized as relevant to cognitive status.

Objectives: To explore DMN changes in patients with relapsing–remitting (RR) multiple sclerosis (MS) and to relate these to the cognitive status.

Methods: Eighteen cognitively impaired (CI) and eighteen cognitively preserved (CP) RRMS patients and eighteen healthy controls (HCs), matched for age, sex and education, underwent neuropsychological evaluation and anatomical and resting-state functional MRI (rs-fMRI). DMN functional connectivity was evaluated from rs-fMRI data via independent component analysis. T2 lesion load (LL) was computed by a semi-automatic method and global and local atrophy was estimated by SIENAX and SPM8 voxel-based morphometry analyses from 3D-T1 images.

Results: When the whole group of RRMS patients was compared with HCs, DMN connectivity was significantly weaker in the anterior cingulate cortex, whereas it was significantly weaker in the core but stronger at the periphery of the posterior cingulate cortex. These findings were more evident in CP than CI patients. Observed DMN changes did not correlate with global atrophy or T2-LL, but were locally associated with regional grey matter loss.

Conclusion: Relapsing–remitting multiple sclerosis patients show a consistent dysfunction of DMN at the level of the anterior node. DMN distribution changes in the posterior node may reflect a possible compensatory effect on cognitive performance.
High-risk syndrome for neuromyelitis optica: a descriptive and comparative study
Authors: Collongues N , Marignier R , Zéphir H , Blanc F , Vukusic S , Outteryck O , Fleury M , Ruet A , Borgel F , Thouvenot E , Moreau T , Defer G , Derache N , Pelletier J , Audoin B , Debouverie M , Labauge P , Gout O , Camu W , Brassat D , Brochet B , Vermersch P , Confavreux C , Seze J de
Published: January 2011

Background: Neuromyelitis optica (NMO) frequently begins with a monofocal episode of optic neuritis or myelitis. A concept named high-risk syndrome (HRS) for NMO has been proposed for patients with monofocal episodes and NMO-IgG antibodies.

Objective: To describe HRS patients and compare them with NMO patients.

Methods: We identified 30 patients with HRS: 18 with extensive myelitis (HRM) and 12 with optic neuritis (HRON), in a database pooling patients from 25 centres in France. Clinical, laboratory/magnetic resonance imaging (MRI) data and outcome were analysed and compared with a national cohort of 125 NMO patients extracted from the same database.

Results: Mean follow-up was 4.8 years. Mean age at onset was 42.8 years (range: 12.4–70) with a female:male ratio of 0.9. Asymptomatic lesions were report on visual evoked potentials in 4/8 tested HRM patients and on spinal cord MRI in 2/7 HRON patients. Three patients died, two owing to a cervical lesion. HRS and NMO patients had similar clinical/paraclinical data, except for a predominance of men in the HRS group and a later mean age at onset in the HRM subgroup.

Conclusion: The description of HRS patients is compatible with a monofocal form of NMO. Asymptomatic lesions could be included in a new set of NMO diagnostic criteria.
Incentivizing deceased organ donation: A Swedish priority-setting perspective
Authors: Omar Faisal , Tinghög Gustav , Welin Stellan
Published: January 2011

Aims: The established deceased organ donation models in many countries, relying chiefly on altruism, have failed to motivate a sufficient number of donors. As a consequence organs that could save lives are routinely missed leading to a growing gap between demand and supply. The aim of this paper is twofold; firstly to develop a proposal for compensated deceased organ donation that could potentially address the organ shortage; secondly to examine the compatibility of the proposal with the ethical values of the Swedish healthcare system. Methods: The proposal for compensating deceased donation is grounded in behavioural agency theory and combines extrinsic, intrinsic and signalling incentives in order to increase prosocial behaviour. Furthermore the compatibility of our proposal with the values of the Swedish healthcare system is evaluated in reference to the principles of human dignity, needs and solidarity, and cost effectiveness. Results: Extrinsic incentives in the form of a 5,000 compensation towards funeral expenses paid to the estate of the deceased or family is proposed. Intrinsic and signalling incentives are incorporated by allowing all or part of the compensation to be diverted as a donation to a reputable charity. The decision for organ donation must not be against the explicit will of the donor. Conclusions: We find that our proposal for compensated deceased donation is compatible with the values of the Swedish healthcare system, and therefore merits serious consideration. It is however important to acknowledge issues relating to coercion, commodification and loss of public trust and the ethical challenges that they might pose.
Industrial differences in female fertility treatment rates - A new approach to assess differences related to occupation?
Authors: Feveile Helene , Schmidt Lone , Hannerz Harald , Hougaard Karin Sørig
Published: January 2011

Aims: Infertility is highly prevalent and 16—26% of women trying to achieve a pregnancy experience infertility in one or more periods. Several exposures in the work environment have been hypothesized to affect female reproduction. This study aimed to estimate relative rates (RR) of female fertility treatment in the 57 industrial groups in Denmark. Methods: The closed cohort of all 20—39 year old economically active women in Denmark by January 2001 (n = 567,816) were followed-up for hospital contacts due to infertility from 2001 to 2005 as registered in the Danish Occupational Hospital Register. Age-standardized relative rates for being diagnosed as infertile were estimated by industry. Further standardization with respect to socioeconomic status was also performed. Results: In total, 12,575 women were diagnosed with infertility during the follow-up period. Three industries presented with statistically significant elevations in age-standardized RRs: hospitals (RR = 1.27, 95% confidence interval (CI): 1.20—1.35), general and dental practice (RR = 1.17, 95% CI: 1.02—1.35) and other health care (RR = 1.24, 95% CI: 1.09—1.41). Standardization for socioeconomic status rendered two industries that were statistically significantly elevated: manufacture of wood and wood products (RR = 1.20, 95% CI: 1.02—1.42) and hospitals (RR = 1.17, 95% CI: 1.10—1.24). Conclusions: Interpretation of the results is complex, since the relative contributions to the observed inequalities of the work environment and, for example, differences in inclination to start a family or in proneness to seek treatment are difficult to resolve. Withstanding shortcomings and limitations, register data of fertility treatment offers a possibility to suggest industries for further investigation of reproductive health.
The diagnosis of acute lower limb compartment syndrome: Applications of near infrared spectroscopy
Authors: Barker Tom , Midwinter Mark , Porter Keith
Published: January 2011

Acute compartment syndrome of the lower limb is a significant problem in surgical practice, the successful management of which depends upon swift diagnosis and intervention.

Conventionally, diagnosis has been based upon clinical assessment; however, this can be unreliable and the potential for missed compartment syndrome remains. The supplementary use of compartment pressure monitoring has addressed some of these issues, but it remains an invasive technique, the exact role of which is still debated in the literature.

Near infrared spectroscopy (NIRS) is an emerging technique in medical practice which provides a non-invasive, continuous and real time measure of local tissue oxygenation. Early experimental work and subsequent clinical studies have demonstrated that NIRS provides an accurate means of detecting compartment syndrome, and that its sensitivity in some circumstances may exceed that of monitoring compartment pressures. Despite this promise, limitations of the technique, such as difficultly monitoring the deep posterior compartment of leg using current systems, and the relative expense of the equipment, have hindered broader adoption.
Maintenance and Generalization Effects of Semantic and Phonological Treatments of Anomia
Authors: Macoir Joël , Routhier Sonia , Simard Anne , Picard Josée
Published: January 2011

Anomia is one of the most frequent manifestations in aphasia. Model-based treatments for anomia usually focus on semantic and/or phonological levels of processing. This study reports treatment of anomia in an individual with chronic aphasia. After baseline testing, she received a training program in which semantic and phonological treatments were contrasted. The semantic treatment resulted in generalization to closely semantically related untreated items. Moreover, this beneficial effect was highly durable and maintained at the immediate posttreatment level for at least 3 months. However, the positive response to the phonological treatment was limited to treated stimuli only. This case study demonstrates that improvement in word-finding abilities may be possible in chronic anomic aphasia, even after a relatively short period of therapy. It also underlines the importance of relying on theoretical models of language processing to adapt treatments to each specific deficit.
Partial Differential Equations versus Cellular Automata for Modeling Combat
Authors: Keane Therese
Published: January 2011

We reproduce apparently complex cellular automaton behaviour with partial differential equations as developed in the author’s previous work. Our partial differential equation (PDE) model easily explains behaviour observed in selected scenarios of the cellular automaton wargame ISAAC without resorting to anthropomorphization of autonomous ‘agents’. The insinuation that agents have a reasoning and planning ability is replaced with a deterministic numerical approximation which encapsulates basic motivational factors and demonstrates a variety of spatial behaviours approximating the mean behaviour of the ISAAC scenarios. All scenarios presented here highlight the dangers associated with attributing intelligent reasoning to behaviour shown, when this can be explained quite simply through the effects of the terms in our equations. A continuum of forces is able to behave in a manner similar to a collection of individual autonomous agents, and shows decentralized self-organization and adaptation of tactics to suit a variety of combat situations.
Down-regulation of NF-κB signalling by polyphenolic compounds prevents endotoxin-induced liver injury in a rat model
Authors: Bharrhan Sushma , Chopra Kanwaljit , Arora Sunil K , Toor Jaideep S , Rishi Praveen
Published: January 2011

Activation of NF-κB has been reported to play a key role in causing endotoxin-induced hepatic damage through enhanced production of reactive oxygen species and pro-inflammatory mediators. In this context, the potential of polyphenolic phytochemicals in preventing endotoxin-induced liver damage remains unclear. Here, we demonstrate that catechin and quercetin have the potential to down-regulate the initial signalling molecule NF-κB which may further inhibit the downstream cascade including TNF-α and NO. These results were confirmed using N-nitro-L-arginine methyl ester (L-NAME), the inhibitor of inducible nitric oxide synthase (iNOS) along with the biochemical and histological alterations occurring in the presence and absence of supplementation with both the polyphenols. However, catechin was found to be more effective than quercetin against endotoxin-induced liver injury. These findings suggest that these polyphenols may form a pharmacological basis for designing a therapeutic agent against endotoxin-mediated oxidative damage.
Adipocyte-macrophage interaction may mediate LPS-induced low-grade inflammation: Potential link with metabolic complications
Authors: Nakarai Hideo , Yamashita Akiko , Nagayasu Shintaro , Iwashita Misaki , Kumamoto Sonoko , Ohyama Hideki , Hata Masaki , Soga Yoshihiko , Kushiyama Akifumi , Asano Tomoichiro , Abiko Yoshimitsu , Nishimura Fusanori
Published: January 2011

Chronic low-grade infection has been suggested to be associated with metabolic disorder such as diabetes. However, the molecular mechanism underlying this important association is largely unknown. The only clue established so far is that many subjects exhibit elevated levels of C-reactive protein as measured by highly sensitive assay. Here, we hypothesized that adipocyte–macrophage interaction plays a key role in amplifying such low grade infection to the level of influencing metabolic disorders. The presence of macrophages in abdominal adipose tissues was investigated by immunohistochemistry. To see whether molecules associated with acute phase protein, LPS signaling, and persistent recruitment of monocytes, are produced at higher amounts in adipocytes co-cultured with macrophages stimulated with low concentration of LPS (1 ng/ml), we measured serum amyloid A (SAA), LPS binding protein (LBP), soluble CD14 (sCD14), and RANTES levels in culture supernatant of co-cultures. Lastly, we investigated in vivo effect of low-grade LPS infusion on the production of these molecules using obese model mice. The macrophages were certainly identified in abdominal adipose tissues. Investigated molecules, especially LBP, SAA, and RANTES were produced at higher amounts in co-cultures stimulated with LPS compared with the cells without LPS. The ob/ob, and high-fat diet-induced obesity mice produced higher amounts of LBP, SAA, and RANTES one day after LPS infusion (1 ng/ml/g body weight) compared with ob/– and normal-fat fed control mice. Thus, adipocytes and infiltrated macrophages, and their interaction with low endotoxin stimulation appear to play an important role in amplifying and maintaining LPS-induced low-grade inflammation.
The role of DNA sensing and innate immune receptor TLR9 in otitis media
Authors: Leichtle Anke , Hernandez Michelle , Lee Jasmine , Pak Kwang , Webster Nicholas J , Wollenberg Barbara , Wasserman Stephen I , Ryan Allen F
Published: January 2011

Otitis media (OM), a common infectious disease in children, is associated with bacterial middle ear (ME) infection. Toll-like receptors (TLRs) are important mediators of innate immune responses, and TLR9 specifically recognizes the unmethylated cytidine-phosphate-guanosine (CpG) motifs in bacterial DNA. Additional sensors of foreign DNA have recently been identified. The role of DNA sensing and TLR9 was investigated in a murine model of OM induced by non-typeable Haemophilus influenzae (NTHi). Expression of genes related to DNA-sensing pathways involved in innate immunity was assessed via DNA microarray, qPCR and immunohistochemistry. Middle ear responses to NTHi were examined in wild-type and TLR9−/− mice by histopathology and bacterial culture. Expression of TLR9 signaling genes was modestly up-regulated during OM, as was TLR9 protein in both ME mucosal cells and infiltrating leukocytes. However, genes known to be regulated by CpG DNA were dramatically up-regulated, as were genes involved in DNA sensing by DIA, Pol-III and AIM2. Toll-like receptor 9 deletion significantly prolonged the inflammatory response induced by NTHi in the ME and delayed bacterial clearance. The results suggest that DNA sensing via TLR9 plays a role in OM pathogenesis and recovery. Alternative forms of DNA sensing may also contribute to OM.