bluuebunny/crossref_metadata_2025 huggingface dataset:
Role of Matrix Metalloproteinase Activity in the Neurovascular Protective Effects of Angiotensin Antagonism
Authors: Ishrat Tauheed , Kozak Anna , Alhusban Ahmed , Pillai Bindu , Johnson Maribeth H. , El-Remessy Azza B. , Ergul Adviye , Fagan Susan C.
Published: July 2014

Background and Purpose. Oxidative stress and matrix metalloproteinase (MMP) activity have been identified as key mediators of early vascular damage after ischemic stroke. Somewhat surprisingly, the angiotensin II type 1 receptor (AT1) blocker, candesartan, has been shown to acutely increase MMP activity while providing neurovascular protection. We aimed to determine the contribution of MMP and nitrative stress to the effects of angiotensin blockade in experimental stroke.Methods. Wistar rats (n = 9–14/group; a total of 99) were treated in a factorial design with candesartan 1 mg/kg IV, alone or in combination with either a peroxynitrite decomposition catalyst, FeTPPs, 30 mg/kg IP or GM6001 50 mg/kg IP (MMP inhibitor). Neurological deficit, infarct, size and hemorrhagic transformation (HT) were measured after 3 h of middle cerebral artery occlusion (MCAO) and 21 h of reperfusion. MMP activity and nitrotyrosine expression were also measured.Results. Candesartan reduced infarct size and HT when administered alone (P=0.0011) and in combination with FeTPPs (P=0.0016). GM6001 did not significantly affect HT when administered alone, but the combination with candesartan caused increased HT (P<0.0001) and worsened neurologic score (P=0.028).Conclusions. Acute administration of candesartan reduces injury after stroke despite increasing MMP activity, likely by an antioxidant mechanism.
The Parameters of Transcutaneous Electrical Nerve Stimulation Are Critical to Its Regenerative Effects When Applied Just after a Sciatic Crush Lesion in Mice
Authors: Cavalcante Miranda de Assis Diana , Martins Lima Êmyle , Teixeira Goes Bruno , Zugaib Cavalcanti João , Barbosa Paixão Alaí , Vannier-Santos Marcos André , Martinez Ana Maria Blanco , Baptista Abrahão Fontes
Published: July 2014

We investigated the effect of two frequencies of transcutaneous electrical nerve stimulation (TENS) applied immediately after lesion on peripheral nerve regeneration after a mouse sciatic crush injury. The animals were anesthetized and subjected to crushing of the right sciatic nerve and then separated into three groups: nontreated, Low-TENS (4 Hz), and High-TENS (100 Hz). The animals of Low- and High-TENS groups were stimulated for 2 h immediately after the surgical procedure, while the nontreated group was only positioned for the same period. After five weeks the animals were euthanized, and the nerves dissected bilaterally for histological and histomorphometric analysis. Histological assessment by light and electron microscopy showed that High-TENS and nontreated nerves had a similar profile, with extensive signs of degeneration. Conversely, Low-TENS led to increased regeneration, displaying histological aspects similar to control nerves. High-TENS also led to decreased density of fibers in the range of 6–12 μm diameter and decreased fiber diameter and myelin area in the range of 0–2 μm diameter. These findings suggest that High-TENS applied just after a peripheral nerve crush may be deleterious for regeneration, whereas Low-TENS may increase nerve regeneration capacity.
Palmitoleic Acid (N-7) Attenuates the Immunometabolic Disturbances Caused by a High-Fat Diet Independently of PPARα
Authors: Souza Camila O. , Teixeira Alexandre A. S. , Lima Edson A. , Batatinha Helena A. P. , Gomes Lara M. , Carvalho-Silva Milena , Mota Isabella T. , Streck Emilio L. , Hirabara Sandro M. , Neto José C. Rosa
Published: July 2014

Palmitoleic acid (PMA) has anti-inflammatory and antidiabetic activities. Here we tested whether these effects of PMA on glucose homeostasis and liver inflammation, in mice fed with high-fat diet (HFD), are PPAR-αdependent. C57BL6 wild-type (WT) and PPAR-α-knockout (KO) mice fed with a standard diet (SD) or HFD for 12 weeks were treated after the 10th week with oleic acid (OLA, 300 mg/kg of b.w.) or PMA 300 mg/kg of b.w. Steatosis induced by HFD was associated with liver inflammation only in the KO mice, as shown by the increased hepatic levels of IL1-beta, IL-12, and TNF-α; however, the HFD increased the expression of TLR4 and decreased the expression of IL1-Ra in both genotypes. Treatment with palmitoleate markedly attenuated the insulin resistance induced by the HFD, increased glucose uptake and incorporation into muscle in vitro, reduced the serum levels of AST in WT mice, decreased the hepatic levels of IL1-beta and IL-12 in KO mice, reduced the expression of TLR-4 and increased the expression of IL-1Ra in WT mice, and reduced the phosphorylation of NF𝜅B (p65) in the livers of KO mice. We conclude that palmitoleate attenuates diet-induced insulin resistance, liver inflammation, and damage through mechanisms that do not depend on PPAR-α.
Immunomodulation by Gut Microbiota: Role of Toll-Like Receptor Expressed by T Cells
Authors: Valentini Mariagrazia , Piermattei Alessia , Di Sante Gabriele , Migliara Giuseppe , Delogu Giovanni , Ria Francesco
Published: July 2014

A close relationship exists between gut microbiota and immune responses. An imbalance of this relationship can determine local and systemic immune diseases. In fact the immune system plays an essential role in maintaining the homeostasis with the microbiota that normally resides in the gut, while, at the same time, the gut microbiota influences the immune system, modulating number and function of effector and regulatory T cells. To achieve this aim, mutual regulation between immune system and microbiota is achieved through several mechanisms, including the engagement of toll-like receptors (TLRs), pathogen-specific receptors expressed on numerous cell types. TLRs are able to recognize ligands from commensal or pathogen microbiota to maintain the tolerance or trigger the immune response. In this review, we summarize the latest evidences about the role of TLRs expressed in adaptive T cells, to understand how the immune system promotes intestinal homeostasis, fights invasion by pathogens, and is modulated by the intestinal microbiota.
Critically Reflexive Theory: A Proposal for Nursing Education
Authors: Josephsen Jayne
Published: July 2014

Nursing is a discipline in transition. As the complexity and acuity of patients increase, nurses are taking on a more comprehensive role in health care leadership and patient outcomes. As the discipline has evolved so has the curricular framework of nursing educational programs, moving from being based on a specific nursing theory, to a general metaparadigm, to the current focus on meeting curricular content standards developed by national accrediting agencies. When considering the skills needed to fully engage in critical thinking and patient advocacy there may be room for an additional curricular focus: that of metacognitive development based on critical theory and constructivism. The empowerment of students via metacognitive and self-evaluative practices also supports the critical theory pedagogy. If graduating nurses are presented with a cohesive and comprehensive curriculum that meets the need for competent and critically reflexive nurses the discipline of nursing can continue to expand in function and voice. The use of metacognition, constructivism, competency, and critical pedagogies in a unified and broad curricular framework allows for the development of these essential skills in contemporary nursing practice. This paper presents this innovative curricular framework that embodies these various teaching and learning perspectives.
Medicinal Plants and Other Living Organisms with Antitumor Potential against Lung Cancer
Authors: Monteiro Luara de Sousa , Bastos Katherine Xavier , Barbosa-Filho José Maria , de Athayde-Filho Petrônio Filgueiras , Diniz Margareth de Fátima Formiga Melo , Sobral Marianna Vieira
Published: July 2014

Lung cancer is a disease with high morbidity and mortality rates. As a result, it is often associated with a significant amount of suffering and a general decrease in the quality of life. Herbal medicines are recognized as an attractive approach to lung cancer therapy with little side effects and are a major source of new drugs. The aim of this work was to review the medicinal plants and other living organisms with antitumor potential against lung cancer. The assays were conducted with animals and humans, and Lewis lung carcinoma was the most used experimental model. China, Japan, South Korea, and Ethiopia were the countries that most published studies of species with antitumor activity. Of the 38 plants evaluated, 27 demonstrated antitumor activity. In addition, six other living organisms were cited for antitumor activity against lung cancer. Mechanisms of action, combination with chemotherapeutic drugs, and new technologies to increase activity and reduce the toxicity of the treatment are discussed. This review was based on the NAPRALERT databank, Web of Science, and Chemical Abstracts. This work shows that natural products from plants continue to be a rich source of herbal medicines or biologically active compounds against cancer.
Mechanical Models of the Dynamics of Vitreous Substitutes
Authors: Isakova Krystyna , Pralits Jan O. , Repetto Rodolfo , Romano Mario R.
Published: July 2014

We discuss some aspects of the fluid dynamics of vitreous substitutes in the vitreous chamber, focussing on the flow induced by rotations of the eye bulb. We use simple, yet not trivial, theoretical models to highlight mechanical concepts that are relevant to understand the dynamics of vitreous substitutes and also to identify ideal properties for vitreous replacement fluids. We first recall results by previous authors, showing that the maximum shear stress on the retina grows with increasing viscosity of the fluid up to a saturation value. We then investigate how the wall shear stress changes if a thin layer of aqueous humour is present in the vitreous chamber, separating the retina from the vitreous replacement fluid. The theoretical predictions show that the existence of a thin layer of aqueous is sufficient to substantially decrease the shear stress on the retina. We finally discuss a theoretical model that predicts the stability conditions of the interface between the aqueous and a vitreous substitute. We discuss the implications of this model to understand the mechanisms leading to the formation of emulsion in the vitreous chamber, showing that instability of the interface is possible in a range of parameters relevant for the human eye.
A Shocking Complication of a Pneumothorax: Chest Tube-Induced Arrhythmias and Review of the Literature
Authors: Cardozo Shaun , Belgrave Kevin
Published: July 2014

We describe a patient with a recent chest tube insertion leading to atrial fibrillation with rapid ventricular rate that led to multiple inappropriate internal cardiac defibrillator (ICD) shocks. This is the first reported case of this occurring in a patient with an ICD leading to inappropriate shocks. Our elderly patient with emphysema presented with a spontaneous pneumothorax and developed rapid atrial fibrillation following emergency tube thoracostomy. The patient had a single lead ICD and received multiple inappropriate shocks for the rapid ventricular rate in the therapy zone. Although medical treatment helped stabilize the patient, resolution of the atrial fibrillation occurred only after the chest tube was removed. In a patient with a chest tube or other intrathoracic catheters, maintaining a high index of suspicion that chest tube insertions can cause secondary life threatening cardiovascular complications needs to be considered. In such patients, removal of the device proves to be the most prudent treatment action.
The Adverse Effect of Spasticity on 3-Month Poststroke Outcome Using a Population-Based Model
Authors: Belagaje S. R. , Lindsell C. , Moomaw C. J. , Alwell K. , Flaherty M. L. , Woo D. , Dunning K. , Khatri P. , Adeoye O. , Kleindorfer D. , Broderick J. , Kissela B.
Published: July 2014

Several devices and medications have been used to address poststroke spasticity. Yet, spasticity’s impact on outcomes remains controversial. Using data from a cohort of 460 ischemic stroke patients, we previously published a validated multivariable regression model for predicting 3-month modified Rankin Score (mRS) as an indicator of functional outcome. Here, we tested whether including spasticity improved model fit and estimated the effect spasticity had on the outcome. Spasticity was defined by a positive response to the question “Did you have spasticity following your stroke?” on direct interview at 3 months from stroke onset. Patients who had expired by 90 days(n=30)or did not have spasticity data available(n=102)were excluded. Spasticity affected the 3-month functional status (β=0.420,95 CI=0.194to 0.645) after accounting for age, diabetes, leukoaraiosis, and retrospective NIHSS. Using spasticity as a covariable, the model’sR2changed from 0.599 to 0.622. In our model, the presence of spasticity in the cohort was associated with a worsened 3-month mRS by an average of 0.4 after adjusting for known covariables. This significant adverse effect on functional outcomes adds predictive value beyond previously established factors.
Cationic Polyene Phospholipids as DNA Carriers for Ocular Gene Therapy
Authors: Machado Susana , Calado Sofia , Bitoque Diogo , Oliveira Ana Vanessa , Øpstad Christer L. , Zeeshan Muhammad , Sliwka Hans-Richard , Partali Vassilia , Pungente Michael D. , Silva Gabriela A.
Published: July 2014

Recent success in the treatment of congenital blindness demonstrates the potential of ocular gene therapy as a therapeutic approach. The eye is a good target due to its small size, minimal diffusion of therapeutic agent to the systemic circulation, and low immune and inflammatory responses. Currently, most approaches are based on viral vectors, but efforts continue towards the synthesis and evaluation of new nonviral carriers to improve nucleic acid delivery. Our objective is to evaluate the efficiency of novel cationic retinoic and carotenoic glycol phospholipids, designated C20-18, C20-20, and C30-20, to deliver DNA to human retinal pigmented epithelium (RPE) cells. Liposomes were produced by solvent evaporation of ethanolic mixtures of the polyene compounds and coformulated with 1,2-dioleoyl-sn-glycero-3-phosphoethanolamine (DOPE) or cholesterol (Chol). Addition of DNA to the liposomes formed lipoplexes, which were characterized for binding, size, biocompatibility, and transgene efficiency. Lipoplex formulations of suitable size and biocompatibility were assayed for DNA delivery, both qualitatively and quantitatively, using RPE cells and a GFP-encoding plasmid. The retinoic lipoplex formulation with DOPE revealed a transfection efficiency comparable to the known lipid references 3β-[N-(N′,N′-dimethylaminoethane)-carbamoyl]-cholesterol (DC-Chol) and 1,2-dioleoyl-sn-glycero-3-ethylphosphocholine (EPC) and GeneJuice. The results demonstrate that cationic polyene phospholipids have potential as DNA carriers for ocular gene therapy.
New Neumann System Associated with a 3 × 3 Matrix Spectral Problem
Authors: Li Fang , Lu Liping
Published: July 2014

The nonlinearization approach of Lax pair is applied to the case of the Neumann constraint associated with a 3 × 3 matrix spectral problem, from which a new Neumann system is deduced and proved to be completely integrable in the Liouville sense. As an application, solutions of the first nontrivial equation related to the 3 × 3 matrix spectral problem are decomposed into solving two compatible Hamiltonian systems of ordinary differential equations.
Flexural Toughness Properties of Reinforced Steel Fibre Incorporated Alkali Activated Slag Concrete
Authors: Karunanithi Srinivasan , Anandan Sivakumar
Published: July 2014

The influence of steel fibre addition on the flexural properties of geopolymer based cementitious matrix was investigated in the present study. Slag based geopolymer mixtures were prepared with different binder and aggregate combinations. Strength gain and hardened properties of different geopolymer concrete mixtures were evaluated using accelerated curing techniques subjected to hot air oven and steam curing. Further, the steel fibre additions on the mechanical strength properties of a high strength geopolymer mixture were studied. A comprehensive evaluation on the post-crack toughness properties was assessed using four-point bend test. Test results exhibited that a geopolymer concrete of maximum compressive strength of 56.6 MPa can be achieved with steam curing. Experimental observations also demonstrated that the steel fibre inclusions in geopolymer concrete provided adequate improvement on post-crack toughness properties and showed higher composite performance with increased volume fraction of steel fibres.
PSO-RBF Neural Network PID Control Algorithm of Electric Gas Pressure Regulator
Authors: Zhong Yuanchang , Huang Xu , Meng Pu , Li Fachuan
Published: July 2014

The current electric gas pressure regulator often adopts the conventional PID control algorithm to take drive control of the core part (micromotor) of electric gas pressure regulator. In order to further improve tracking performance and to shorten response time, this paper presents an improved PID intelligent control algorithm which applies to the electric gas pressure regulator. The algorithm uses the improved RBF neural network based on PSO algorithm to make online adjustment on PID parameters. Theoretical analysis and simulation result show that the algorithm shortens the step response time and improves tracking performance.
Pulmonary Hypertension and Right Heart Dysfunction in Chronic Lung Disease
Authors: Zangiabadi Amirmasoud , De Pasquale Carmine G. , Sajkov Dimitar
Published: July 2014

Group 3 pulmonary hypertension (PH) is a common complication of chronic lung disease (CLD), including chronic obstructive pulmonary disease (COPD), interstitial lung disease, and sleep-disordered breathing. Development of PH is associated with poor prognosis and may progress to right heart failure, however, in the majority of the patients with CLD, PH is mild to moderate and only a small number of patients develop severe PH. The pathophysiology of PH in CLD is multifactorial and includes hypoxic pulmonary vasoconstriction, pulmonary vascular remodeling, small vessel destruction, and fibrosis. The effects of PH on the right ventricle (RV) range between early RV remodeling, hypertrophy, dilatation, and eventual failure with associated increased mortality. The golden standard for diagnosis of PH is right heart catheterization, however, evidence of PH can be appreciated on clinical examination, serology, radiological imaging, and Doppler echocardiography. Treatment of PH in CLD focuses on management of the underlying lung disorder and hypoxia. There is, however, limited evidence to suggest that PH-specific vasodilators such as phosphodiesterase-type 5 inhibitors, endothelin receptor antagonists, and prostanoids may have a role in the treatment of patients with CLD and moderate-to-severe PH.
The Effects of Amphiregulin Induced MMP-13 Production in Human Osteoarthritis Synovial Fibroblast
Authors: Chen Yi-Te , Hou Chun-Han , Hou Sheng-Mou , Liu Ju-Fang
Published: July 2014

Osteoarthritis (OA) belongs to a group of degenerative diseases. Synovial inflammation, cartilage abrasion, and subchondral sclerosis are characteristics of OA. Researchers do not fully understand the exact etiology of OA. However, matrix metalloproteinases (MMPs), which are responsible for cartilage matrix degradation, play a pivotal role in the progression of OA. Amphiregulin (AREG) binds to the EGF receptor (EGFR) and activates downstream proteins. AREG is involved in a variety of pathological processes, such as the development of tumors, inflammatory diseases, and rheumatoid arthritis. However, the relationship between AREG and MMP-13 in OA synovial fibroblasts (SFs) remains unclear. We investigated the signaling pathway involved in AREG-induced MMP-13 production in SFs. AREG caused MMP-13 production in a concentration- and time-dependent manner. The results of using pharmacological inhibitors and EGFR siRNA to block EGFR revealed that the EGFR receptor was involved in the AREG-mediated upregulation of MMP-13. AREG-mediated MMP-13 production was attenuated by PI3K and Akt inhibitors. The stimulation of cells by using AREG activated p65 phosphorylation and p65 translocation from the cytosol to the nucleus. Our results provide evidence that AREG acts through the EGFR and activates PI3K, Akt, and finally NF-kappaB on the MMP-13 promoter, thus contributing to cartilage destruction during osteoarthritis.
Tailored PVA/ECM Scaffolds for Cartilage Regeneration
Authors: Stocco Elena , Barbon Silvia , Dalzoppo Daniele , Lora Silvano , Sartore Leonardo , Folin Marcella , Parnigotto Pier Paolo , Grandi Claudio
Published: July 2014

Articular cartilage lesions are a particular challenge for regenerative medicine due to cartilage low self-ability repair in case of damage. Hence, a significant goal of musculoskeletal tissue engineering is the development of suitable structures in virtue of their matrix composition and biomechanical properties. The objective of our study was to designin vitroa supporting structure for autologous chondrocyte growth. We realized a biohybrid composite scaffold combining a novel and nonspecific extracellular matrix (ECM), which is decellularized Wharton’s jelly ECM, with the biomechanical properties of the synthetic hydrogel polyvinyl alcohol (PVA). Wharton’s jelly ECM was tested for its ability in promoting scaffold colonization by chondrocytes and compared with polyvinyl alcohol itself and the more specific decellularized cartilage matrix. Our preliminary evidences highlighted the chance of using Wharton’s jelly ECM in combination with PVA hydrogels as an innovative and easily available scaffold for cartilage restoration.
Expert System for Competences Evaluation 360° Feedback Using Fuzzy Logic
Authors: Aguilar Lasserre Alberto Alfonso , Lafarja Solabac Marina Violeta , Hernandez-Torres Roberto , Posada-Gomez Rubén , Juárez-Martínez Ulises , Fernández Lambert Gregorio
Published: July 2014

Performance evaluation (PE) is a process that estimates the employee overall performance during a given period, and it is a common function carried out inside modern companies. PE is important because it is an instrument that encourages employees, organizational areas, and the whole company to have an appropriate behavior and continuous improvement. In addition, PE is useful in decision making about personnel allocation, productivity bonuses, incentives, promotions, disciplinary measures, and dismissals. There are many performance evaluation methods; however, none is universal and common to all companies. This paper proposes an expert performance evaluation system based on a fuzzy logic model, with competences 360° feedback oriented to human behavior. This model uses linguistic labels and adjustable numerical values to represent ambiguous concepts, such as imprecision and subjectivity. The model was validated in the administrative department of a real Mexican manufacturing company, where final results and conclusions show the fuzzy logic method advantages in comparison with traditional 360° performance evaluation methodologies.
The Role of Haptoglobin Genotypes in Chagas Disease
Authors: Mundaray Fernández Ninomar , Fernández-Mestre Mercedes
Published: July 2014

Although the number of people infected withT. cruziis on the rise, host genetic and immune components that are crucial in the development of the Chagas disease have been discovered. We investigated the frequency of polymorphisms in the gene encoding haptoglobin of patients with chronic Chagas disease. The results suggest that while theHP1-1genotype may confer protection against infection and the development of chronic Chagas disease due to the rapid metabolism of the Hp1-1-Hb complex and its anti-inflammatory activity, the presence ofHP2-2genotype may increase susceptibility towards a chronic condition of the disease due to a slow metabolism of the Hp2-2-Hb complex, lower antioxidant activity, and increased inflammatory reactivity, which lead to cell damage and a deterioration of the cardiac function. Finally, correlations betweenHPgenotypes in different age groups and cardiac manifestations suggest thatHPpolymorphism could influence the prognosis of this infectious disease. This study shows some of the relevant aspects of the haptoglobin gene polymorphism and its implications in theT. cruziinfection.
Splenic Metastasis of Squamous Cell Carcinoma of the Uterine Cervix: A Case Report and Review of the Literature
Authors: Taga Shigeki , Sawada Mari , Nagai Aya , Yamamoto Dan , Hayase Ryoji
Published: July 2014

Metastasis from various neoplasms to the spleen is very rare and most of the cases are found at autopsy. We report a patient presenting with uterine cervical cancer with splenic metastases. A 49-year-old woman presenting with genital bleeding was referred to our hospital and diagnosed with stage IIB cervical cancer. She underwent concomitant chemoradiotherapy (CCRT) consisting of 50 Gy whole pelvis irradiation, high-dose-rate intracavitary brachytherapy 24 Gy/4 fractions and six weeks of paclitaxel and carboplatin administration. Ten months after the initial therapy, CT revealed recurrence at spleen. Although she received 5 courses of nedaplatin, enlargement of the tumor was noticed. She underwent a splenectomy and the result of histology was compatible with metastasis of cervical cancer.
Inhibition of MMP-2 Expression with siRNA Increases Baseline Cardiomyocyte Contractility and Protects against Simulated Ischemic Reperfusion Injury
Authors: Lin Han-Bin , Cadete Virgilio J. J. , Sra Bikramjit , Sawicka Jolanta , Chen Zhicheng , Bekar Lane K. , Cayabyab Francisco , Sawicki Grzegorz
Published: July 2014

Matrix metalloproteinases (MMPs) significantly contribute to ischemia reperfusion (I/R) injury, namely, by the degradation of contractile proteins. However, due to the experimental models adopted and lack of isoform specificity of MMP inhibitors, the cellular source and identity of the MMP(s) involved in I/R injury remain to be elucidated. Using isolated adult rat cardiomyocytes, subjected to chemically induced I/R-like injury, we show that specific inhibition of MMP-2 expression and activity using MMP-2 siRNA significantly protected cardiomyocyte contractility from I/R-like injury. This was also associated with increased expression of myosin light chains 1 and 2 (MLC1/2) in comparison to scramble siRNA transfection. Moreover, the positive effect of MMP-2 siRNA transfection on cardiomyocyte contractility and MLC1/2 expression levels was also observed under control conditions, suggesting an important additional role for MMP-2 in physiological sarcomeric protein turnover. This study clearly demonstrates that intracellular expression of MMP-2 plays a significant role in sarcomeric protein turnover, such as MLC1 and MLC2, under aerobic (physiological) conditions. In addition, this study identifies intracellular/autocrine, cardiomyocyte-produced MMP-2, rather than paracrine/extracellular, as responsible for the degradation of MLC1/2 and consequent contractile dysfunction in cardiomyocytes subjected to I/R injury.
Accumulation of Extracellular Hyaluronan by Hyaluronan Synthase 3 Promotes Tumor Growth and Modulates the Pancreatic Cancer Microenvironment
Authors: Kultti Anne , Zhao Chunmei , Singha Netai C. , Zimmerman Susan , Osgood Ryan J. , Symons Rebecca , Jiang Ping , Li Xiaoming , Thompson Curtis B. , Infante Jeffrey R. , Jacobetz Michael A. , Tuveson David A. , Frost Gregory I. , Shepard H. Michael , Huang Zhongdong
Published: July 2014

Extensive accumulation of the glycosaminoglycan hyaluronan is found in pancreatic cancer. The role of hyaluronan synthases 2 and 3 (HAS2, 3) was investigated in pancreatic cancer growth and the tumor microenvironment. Overexpression of HAS3 increased hyaluronan synthesis in BxPC-3 pancreatic cancer cells. In vivo, overexpression of HAS3 led to faster growing xenograft tumors with abundant extracellular hyaluronan accumulation. Treatment with pegylated human recombinant hyaluronidase (PEGPH20) removed extracellular hyaluronan and dramatically decreased the growth rate of BxPC-3 HAS3 tumors compared to parental tumors. PEGPH20 had a weaker effect on HAS2-overexpressing tumors which grew more slowly and contained both extracellular and intracellular hyaluronan. Accumulation of hyaluronan was associated with loss of plasma membrane E-cadherin and accumulation of cytoplasmicβ-catenin, suggesting disruption of adherens junctions. PEGPH20 decreased the amount of nuclear hypoxia-related proteins and induced translocation of E-cadherin andβ-catenin to the plasma membrane. Translocation of E-cadherin was also seen in tumors from a transgenic mouse model of pancreatic cancer and in a human non-small cell lung cancer sample from a patient treated with PEGPH20. In conclusion, hyaluronan accumulation by HAS3 favors pancreatic cancer growth, at least in part by decreasing epithelial cell adhesion, and PEGPH20 inhibits these changes and suppresses tumor growth.
Progress in the Identification of Dengue Virus Entry/Fusion Inhibitors
Authors: De La Guardia Carolina , Lleonart Ricardo
Published: July 2014

Dengue fever, a reemerging disease, is putting nearly 2.5 billion people at risk worldwide. The number of infections and the geographic extension of dengue fever infection have increased in the past decade. The disease is caused by the dengue virus, a flavivirus that uses mosquitosAedessp. as vectors. The disease has several clinical manifestations, from the mild cold-like illness to the more serious hemorrhagic dengue fever and dengue shock syndrome. Currently, there is no approved drug for the treatment of dengue disease or an effective vaccine to fight the virus. Therefore, the search for antivirals against dengue virus is an active field of research. As new possible receptors and biological pathways of the virus biology are discovered, new strategies are being undertaken to identify possible antiviral molecules. Several groups of researchers have targeted the initial step in the infection as a potential approach to interfere with the virus. The viral entry process is mediated by viral proteins and cellular receptor molecules that end up in the endocytosis of the virion, the fusion of both membranes, and the release of viral RNA in the cytoplasm. This review provides an overview of the targets and progress that has been made in the quest for dengue virus entry inhibitors.
Chitosan Oligosaccharides Attenuate Ocular Inflammation in Rats with Experimental Autoimmune Anterior Uveitis
Authors: Fang I-Mo , Yang Chang-Hao , Yang Chung-May
Published: July 2014

We investigated the protective effects and mechanisms of chitosan oligosaccharides (COS) on experimental autoimmune anterior uveitis (EAAU) in rats. EAAU was induced in Lewis rats by footpad and intraperitoneal injections of melanin-associated antigen. The rats received intraperitoneal injections of low-dose (5 mg/kg) or high-dose (10 mg/kg) COS or PBS daily after the immunization. The effects of COS were evaluated by determining the clinical scores and the morphology of the iris/ciliary body (ICB). The expression of inflammatory mediators was evaluated using western blot, immunofluorescence, and ELISA. Treatment with COS significantly attenuated the clinical scores and the leukocyte infiltration in the ICB in a dose-dependent manner. COS effectively reduced the expression of inflammatory mediators (TNF-α, iNOS, MCP-1, RANTES, fractalkine, and ICAM-1). Moreover, COS decreased the IκB degradation and p65 presence in the ICB, which resulted in the inhibition of NF-κB/DNA binding activity. In an in vitro study, sensitized spleen-derived lymphocytes of the COS-treated group showed less chemotaxis toward their aqueous humor and decreased secretion of the above inflammatory mediators in the culture media. COS treated EAAU by inhibiting the activation of NF-κB and reducing the expression of inflammatory mediators. COS might be a potential treatment for acute anterior uveitis.
The Fence Methods
Authors: Jiang Jiming
Published: July 2014

This paper provides an overview of a recently developed class of strategies for model selection, known as the fence methods. It also offers directions of future research as well as challenging problems.
A Partition-Based Active Contour Model Incorporating Local Information for Image Segmentation
Authors: Shi Jiao , Wu Jiaji , Paul Anand , Jiao Licheng , Gong Maoguo
Published: July 2014

Active contour models are always designed on the assumption that images are approximated by regions with piecewise-constant intensities. This assumption, however, cannot be satisfied when describing intensity inhomogeneous images which frequently occur in real world images and induced considerable difficulties in image segmentation. A milder assumption that the image is statistically homogeneous within different local regions may better suit real world images. By taking local image information into consideration, an enhanced active contour model is proposed to overcome difficulties caused by intensity inhomogeneity. In addition, according to curve evolution theory, only the region near contour boundaries is supposed to be evolved in each iteration. We try to detect the regions near contour boundaries adaptively for satisfying the requirement of curve evolution theory. In the proposed method, pixels within a selected region near contour boundaries have the opportunity to be updated in each iteration, which enables the contour to be evolved gradually. Experimental results on synthetic and real world images demonstrate the advantages of the proposed model when dealing with intensity inhomogeneity images.
Some New Lacunary Strong Convergent Vector-Valued Sequence Spaces
Authors: Mursaleen M. , Alotaibi A. , Sharma Sunil K.
Published: July 2014

We introduce some vector-valued sequence spaces defined by a Musielak-Orlicz function and the concepts of lacunary convergence and strong (A)-convergence, whereA=(aik)is an infinite matrix of complex numbers. We also make an effort to study some topological properties and some inclusion relations between these spaces.
Behavioral and Histopathological Study of Changes in Spinal Cord Injured Rats Supplemented with Spirulina platensis
Authors: Aziz Izzuddin , Che Ramli Muhammad Danial , Mohd Zain Nurul Suraya , Sanusi Junedah
Published: July 2014

Spinal cord injury (SCI) is a devastating disease that leads to permanent disability and causes great suffering. The resulting neurological dysfunction and paralysis is proportional to the severity of the trauma itself. Spirulina is widely used as a nutritional supplement due to its high protein and antioxidant content. In the present study, the protective effect of the Spirulina treatment on locomotor function and morphological damage after SCI was investigated. Seventy Sprague‐Dawley (SD) rats were divided into three groups: Sham (laminectomy alone), Control (laminectomy with SCI), and Experimental (laminectomy with SCI +180 mg/kg per day Spirulina platensis). A laminectomy was performed at T12 and an Inox No.2 modified forceps was used to perform a partial crush injury on the spinal cord. The rats were then perfused at 3, 7, 14, 21, and 28 days after injury for morphological investigations. The injured rat spinal cord indicated a presence of hemorrhage, cavity, and necrosis. Pretreatment with Spirulina significantly improved the locomotor function and showed a significant reduction on the histological changes. The experimental results observed in this study suggest that treatment with Spirulina platensis possesses potential benefits in improving hind limb locomotor function and reducing morphological damage to the spinal cord.
Multiobjective Decision Making Policies and Coordination Mechanisms in Hierarchical Organizations: Results of an Agent-Based Simulation
Authors: Leitner Stephan , Wall Friederike
Published: July 2014

This paper analyses how different coordination modes and different multiobjective decision making approaches interfere with each other in hierarchical organizations. The investigation is based on an agent-based simulation. We apply a modified NK-model in which we map multiobjective decision making as adaptive walk on multiple performance landscapes, whereby each landscape represents one objective. We find that the impact of the coordination mode on the performance and the speed of performance improvement is critically affected by the selected multiobjective decision making approach. In certain setups, the performances achieved with the more complex multiobjective decision making approaches turn out to be less sensitive to the coordination mode than the performances achieved with the less complex multiobjective decision making approaches. Furthermore, we present results on the impact of the nature of interactions among decisions on the achieved performance in multiobjective setups. Our results give guidance on how to control the performance contribution of objectives to overall performance and answer the question how effective certain multiobjective decision making approaches perform under certain circumstances (coordination mode and interdependencies among decisions).
Childhood Renal Tumor: A Report from a Chinese Children’s Cancer Group
Authors: Cai Jiaoyang , Pan Ci , Lu Qin , Yan Jie , Ju Xiuli , Ma Futian , Zhu Yiping , Liu Qiuling , Sun Lirong , Jiang Lian , Cao Lizhi , Li Fu , Liu Zhigang , Qiao Lijing , Huang Dongsheng , Tian Xin , Tang Jingyan
Published: July 2014

Here we investigated the establishment of multicenter cooperative treatment groups in China, as well as radiotherapy compliance and effectiveness among children with renal tumors. Medical records were reviewed for 316 children with renal tumors diagnosed by a multicenter cooperative group from 14 hospitals in China from 1998 to 2012. Median patient age was 29.5 months (range, 2–173 months old), and male-to-female ratio was 1.4 : 1. After a median follow-up of 22 months (range, 1–177 months), five-year event-free survival rates were 72% overall; 76.1% for favorable histology (251 cases); 59% for unfavorable histology (27 cases); and 91%, 75%, 71%, 53%, and 48.5%, respectively for Stages I, II, III, IV, and V. Following standardized criteria, radiation therapy was indicated for 153 patients, among whom five-year event-free survival was 72.8% for the 95 who received radiation and 24% for the 58 patients who did not. Our results are reasonable but can be further improved and show the feasibility of a multicenter cooperative group model for childhood renal tumor treatment in China. Radiation therapy is important for stage III and IV patients but remains difficult to implement in some parts of China. Government management departments and medical professionals must pay attention to this situation. This clinical trial is registered with ChiCTR-PRCH-14004372.
Mechanical Ventilation Weaning in Inclusion Body Myositis: Feasibility of Isokinetic Inspiratory Muscle Training as an Adjunct Therapy
Authors: Cordeiro de Souza Leonardo , Campos Josué Felipe , Daher Leandro Possidente , Furtado da Silva Priscila , Ventura Alex , do Prado Pollyana Zamborlini , Brasil Daniele , Mendonça Debora , Lugon Jocemir Ronaldo
Published: July 2014

Inclusion body myositis is a rare myopathy associated with a high rate of respiratory complications. This condition usually requires prolonged mechanical ventilation and prolonged intensive care stay. The unsuccessful weaning is mainly related to respiratory muscle weakness that does not promptly respond to immunosuppressive therapy. We are reporting a case of a patient in whom the use of an inspiratory muscle-training program which started after a two-week period of mechanical ventilation was associated with a successful weaning in one week and hospital discharge after 2 subsequent weeks.
The TIR Domain Containing Locus ofEnterococcus faecalisIs Predominant among Urinary Tract Infection Isolates and Downregulates Host Inflammatory Response
Authors: Kraemer Thomas Daniel , Quintanar Haro Orlando Daniel , Domann Eugen , Chakraborty Trinad , Tchatalbachev Svetlin
Published: July 2014

Based on Toll/interleukin-1 receptor (TIR) domain structure homology, we detected a previously uncharacterized gene encoding for a TIR domain containing protein (Tcp) in the genome ofEnterococcus faecalis. We assigned this gene the nametcpF(as in Tcp ofE. faecalis). Screening ofE. faecalissamples revealed thattcpFis more common in isolates from urinary tract infections (UTIs) than in human faecal flora.tcpFalleles showed moderate single nucleotide polymorphism (SNP) among UTI isolates. Infection of mouse RAW264.7 macrophages with atcpFknock-out mutant led to elevated cytokine response compared to the isogenic wild typeE. faecalisstrain.In silicoanalysis predicted significant tertiary structure homology to the TIR domain of human TLR1 (TLR1-TIR). When transiently expressed in cultured eukaryotic cells, TcpF caused suppression of TLR2-dependent NF-κB activation suggesting for TcpF a role as a factor inE. faecalisthat benefits colonization by modulating the host’s immune responses.
Studying the Complex Expression Dependences between Sets of Coexpressed Genes
Authors: Huerta Mario , Casanova Oriol , Barchino Roberto , Flores Jose , Querol Enrique , Cedano Juan
Published: July 2014

Organisms simplify the orchestration of gene expression by coregulating genes whose products function together in the cell. The use of clustering methods to obtain sets of coexpressed genes from expression arrays is very common; nevertheless there are no appropriate tools to study the expression networks among these sets of coexpressed genes. The aim of the developed tools is to allow studying the complex expression dependences that exist between sets of coexpressed genes. For this purpose, we start detecting the nonlinear expression relationships between pairs of genes, plus the coexpressed genes. Next, we form networks among sets of coexpressed genes that maintain nonlinear expression dependences between all of them. The expression relationship between the sets of coexpressed genes is defined by the expression relationship between theskeletonsof these sets, where thisskeletonrepresents the coexpressed genes with a well-defined nonlinear expression relationship with theskeletonof the other sets. As a result, we can study the nonlinear expression relationships between a target gene and other sets of coexpressed genes, or start the study from theskeletonof the sets, to study the complex relationships of activation and deactivation between the sets of coexpressed genes that carry out the different cellular processes present in the expression experiments.
Synthesis and Characterization of Imide Containing Hybrid Epoxy Resin with Improved Mechanical and Thermal Properties
Authors: Rane U. G. , Sabnis A. A. , Shertukde V. V.
Published: July 2014

Phosphorous containing amine, tripropyldiamine phosphine oxide (TPDAP), and hybrid monomer 4-(N-phthalimidophenyl) glycidylether (PPGE) were synthesized and characterized by Fourier transform infrared (FTIR) spectroscopy, nuclear magnetic resonance (NMR) spectroscopy, and elemental analysis (EDX). PPGE was incorporated in bisphenol A epoxy resin (BPA) in various concentrations (5% to 20%), based on a weight percentage of BPA resin. Curing was carried out with the stoichiometric amount of TPDAP and 1,3-propanediamine (PDA) to result in cross-link network. Various mechanical, chemical, thermal, and flame retardant properties of modified and unmodified epoxy resin were studied. The coatings obtained with the addition of PPGE were found to have improved properties as compared with those of the unmodified resin. Coatings with 15% loading of PPGE showed improved flame retardant and mechanical properties with stable thermal behaviour.
Edgeworth Expansion Based Model for the Convolutional Noise pdf
Authors: Rivlin Yonatan , Pinchas Monika
Published: July 2014

Recently, the Edgeworth expansion up to order 4 was used to represent the convolutional noise probability density function (pdf) in the conditional expectation calculations where the source pdf was modeled with the maximum entropy density approximation technique. However, the applied Lagrange multipliers were not the appropriate ones for the chosen model for the convolutional noise pdf. In this paper we use the Edgeworth expansion up to order 4 and up to order 6 to model the convolutional noise pdf. We derive the appropriate Lagrange multipliers, thus obtaining new closed‐form approximated expressions for the conditional expectation and mean square error (MSE) as a byproduct. Simulation results indicate hardly any equalization improvement with Edgeworth expansion up to order 4 when using optimal Lagrange multipliers over a nonoptimal set. In addition, there is no justification for using the Edgeworth expansion up to order 6 over the Edgeworth expansion up to order 4 for the 16QAM and easy channel case. However, Edgeworth expansion up to order 6 leads to improved equalization performance compared to the Edgeworth expansion up to order 4 for the 16QAM and hard channel case as well as for the case where the 64QAM is sent via an easy channel.
Biodemographic Analyses of Longitudinal Data on Aging, Health, and Longevity: Recent Advances and Future Perspectives
Authors: Arbeev Konstantin G. , Akushevich Igor , Kulminski Alexander M. , Ukraintseva Svetlana V. , Yashin Anatoliy I.
Published: July 2014

Biodemography became one of the most innovative and fastest growing areas in demography. This progress is fueled by the growing variability and amount of relevant data available for analyses as well as by methodological developments allowing for addressing new research questions using new approaches that can better utilize the potential of these data. In this review paper, we summarize recent methodological advances in biodemography and their diverse practical applications. Three major topics are covered: (1) computational approaches to reconstruction of age patterns of incidence of geriatric diseases and other characteristics such as recovery rates at the population level using Medicare claims data; (2) methodological advances in genetic and genomic biodemography and applications to research on genetic determinants of longevity and health; and (3) biodemographic models for joint analyses of time-to-event data and longitudinal measurements of biomarkers collected in longitudinal studies on aging. We discuss how such data and methodology can be used in a comprehensive prediction model for joint analyses of incomplete datasets that take into account the wide spectrum of factors affecting health and mortality transitions including genetic factors and hidden mechanisms of aging-related changes in physiological variables in their dynamic connection with health and survival.