bluuebunny/crossref_metadata_2025 huggingface dataset:
Model validation based on
in situ
radionuclide migration tests in Boom Clay: status of a large-scale migration experiment, 24 years after injection
Authors: Weetjens E. , Maes N. , Van Ravestyn L.
Published: May 2014

Demonstration of the long-term safety of a nuclear waste repository relies on earth science models, integrated in a performance assessment model chain. These models are subject to quality assurance procedures and principles of which model validation, qualification and verification are essential elements. However, in the context of performance assessment, model validation is often limited owing to extreme timescales and the use of natural barriers that can never be entirely characterized. Nevertheless, it is often possible to demonstrate that the models are valid or qualified to describe the processes at hand. In case of geological disposal in Boom Clay, the host formation is the dominant barrier for radionuclide migration and releases to the biosphere. Therefore, it has to be demonstrated that migration of solutes through Boom Clay at relevant scale is adequately understood. Large-scale and long-term
in situ
migration experiments, such as the CP1 experiment, form a cornerstone in this confidence-building process. In this experiment, accurate predictions of the tracer's breakthrough curves up to 3 m from the source have been obtained using the conventional advection–dispersion–reaction equation to describe solute transport and parameters obtained from (small-scale) migration experiments in the laboratory.
Biological functional annotation of retinoic acid alpha and beta in mouse liver based on genome-wide binding
Authors: He Yuqi , Tsuei Jessica , Wan Yu-Jui Yvonne
Published: May 2014

Retinoic acid (RA) has diverse biological effects. The liver stores vitamin A, generates RA, and expresses receptors for RA. The current study examines the hepatic binding profile of two RA receptor isoforms, RARA (RARα) and RARB (RARβ), in response to RA treatment in mouse livers. Our data uncovered 35,521, and 14,968 genomic bindings for RARA and RARB, respectively. Each expressed unique and common bindings, implying their redundant and specific roles. RARB has higher RA responsiveness than RARB. RA treatment generated 18,821 novel RARB bindings but only 14,798 of RARA bindings, compared with the control group. RAR frequently bound the consensus hormone response element [HRE; (A/G)G(G/T)TCA], which often contained the motifs assigned to SP1, GABPA, and FOXA2, suggesting potential interactions between those transcriptional factors. Functional annotation coupled with principle component analysis revealed that the function of RAR target genes were motif dependent. Taken together, the cistrome of RARA and RARB revealed their extensive biological roles in the mouse liver. RAR target genes are enriched in various biological processes. The hepatic RAR genome-wide binding data can help us understand the global molecular mechanisms underlying RAR and RA-mediated gene and pathway regulation.
Timed-daily ingestion of whey protein and exercise training reduces visceral adipose tissue mass and improves insulin resistance: the PRISE study
Authors: Arciero Paul J. , Baur Daniel , Connelly Scott , Ormsbee Michael J.
Published: May 2014

The present study examined the effects of timed ingestion of supplemental protein (20-g servings of whey protein, 3×/day), added to the habitual diet of free-living overweight/obese adults and subsequently randomized to either whey protein only (P; n = 24), whey protein and resistance exercise (P + RT; n = 27), or a whey protein and multimode exercise training program [protein and resistance exercise, intervals, stretching/yoga/Pilates, endurance exercise (PRISE); n = 28]. Total and regional body composition and visceral adipose tissue (VAT) mass (dual-energy X-ray absorptiometry), insulin sensitivity [homeostasis model assessment-estimated insulin resistance (HOMA-IR)], plasma lipids and adipokines, and feelings of hunger and satiety (visual analog scales) were measured before and after the 16-wk intervention. All groups lost body weight, fat mass (FM), and abdominal fat; however, PRISE lost significantly ( P < 0.01) more body weight (3.3 ± 0.7 vs. 1.1 ± 0.7 kg, P + RT) and FM (2.8 ± 0.7 vs. 0.9 ± 0.5 kg, P + RT) and gained ( P < 0.05) a greater percentage of lean body mass (2 ± 0.5 vs. 0.9 ± 0.3 and 0.6 ± 0.4%, P + RT and P, respectively). Only P + RT (0.1 ± 0.04 kg) and PRISE (0.21 ± 0.07 kg) lost VAT mass ( P < 0.05). Fasting glucose decreased only in P + RT (5.1 ± 2.5 mg/dl) and PRISE (15.3 ± 2.1 mg/dl), with the greatest decline occurring in PRISE ( P < 0.05). Similarly, HOMA-IR improved (0.6 ± 0.3, 0.6 ± 0.4 units), and leptin decreased (4.7 ± 2.2, 4.7 ± 3.1 ng/dl), and adiponectin increased (3.8 ± 1.1, 2.4 ± 1.1 μg/ml) only in P + RT and PRISE, respectively, with no change in P. In conclusion, we find evidence to support exercise training and timed ingestion of whey protein added to the habitual diet of free-living overweight/obese adults, independent of caloric restriction on total and regional body fat distribution, insulin resistance, and adipokines.
BACE1 Is Necessary for Experience-Dependent Homeostatic Synaptic Plasticity in Visual Cortex
Authors: Petrus Emily , Lee Hey-Kyoung
Published: May 2014

Alzheimer’s disease (AD) is the most common form of age-related dementia, which is thought to result from overproduction and/or reduced clearance of amyloid-beta (Aβ) peptides. Studies over the past few decades suggest that Aβis produced in an activity-dependent manner and has physiological relevance to normal brain functions. Similarly, physiological functions forβ- andγ-secretases, the two key enzymes that produce Aβby sequentially processing the amyloid precursor protein (APP), have been discovered over recent years. In particular, activity-dependent production of Aβhas been suggested to play a role in homeostatic regulation of excitatory synaptic function. There is accumulating evidence that activity-dependent immediate early gene Arc is an activity “sensor,” which acts upstream of Aβproduction and triggers AMPA receptor endocytosis to homeostatically downregulate the strength of excitatory synaptic transmission. We previously reported that Arc is critical for sensory experience-dependent homeostatic reduction of excitatory synaptic transmission in the superficial layers of visual cortex. Here we demonstrate that mice lacking the major neuronalβ-secretase, BACE1, exhibit a similar phenotype: stronger basal excitatory synaptic transmission and failure to adapt to changes in visual experience. Our results indicate that BACE1 plays an essential role in sensory experience-dependent homeostatic synaptic plasticity in the neocortex.
Dynamic Pull-In Investigation of a Clamped-Clamped Nanoelectromechanical Beam under Ramp-Input Voltage and the Casimir Force
Authors: Askari Amir R. , Tahani Masoud
Published: May 2014

The influence of the Casimir excitation on dynamic pull-in instability of a nanoelectromechanical beam under ramp-input voltage is studied. The ramp-input actuation has applications in frequency sweeping of RF-N/MEMS. The presented model is nonlinear due to the inherent nonlinearity of electrostatics and the Casimir excitations as well as the geometric nonlinearity of midplane stretching. A Galerkin based reduced order modeling is utilized. It is found that the calculated dynamic pull-in ramp input voltage leads to dynamic pull-in step input voltage by increasing the slope of voltage-time diagram. This fact is utilized to verify the results of present study.
An Improved Cockroach Swarm Optimization
Authors: Obagbuwa I. C. , Adewumi A. O.
Published: May 2014

Hunger component is introduced to the existing cockroach swarm optimization (CSO) algorithm to improve its searching ability and population diversity. The original CSO was modelled with three components: chase-swarming, dispersion, and ruthless; additional hunger component which is modelled using partial differential equation (PDE) method is included in this paper. An improved cockroach swarm optimization (ICSO) is proposed in this paper. The performance of the proposed algorithm is tested on well known benchmarks and compared with the existing CSO, modified cockroach swarm optimization (MCSO), roach infestation optimization RIO, and hungry roach infestation optimization (HRIO). The comparison results show clearly that the proposed algorithm outperforms the existing algorithms.
Neuron-Adaptive PID Based Speed Control of SCSG Wind Turbine System
Authors: Zuo Shan , Song Yongduan , Wang Lei , Zhou Zheng
Published: May 2014

In searching for methods to increase the power capacity of wind power generation system, superconducting synchronous generator (SCSG) has appeared to be an attractive candidate to develop large-scale wind turbine due to its high energy density and unprecedented advantages in weight and size. In this paper, a high-temperature superconducting technology based large-scale wind turbine is considered and its physical structure and characteristics are analyzed. A simple yet effective single neuron-adaptive PID control scheme with Delta learning mechanism is proposed for the speed control of SCSG based wind power system, in which the RBF neural network (NN) is employed to estimate the uncertain but continuous functions. Compared with the conventional PID control method, the simulation results of the proposed approach show a better performance in tracking the wind speed and maintaining a stable tip-speed ratio, therefore, achieving the maximum wind energy utilization.
Compatible Deductive Systems of Pulexes
Authors: Ghorbani Shokoofeh
Published: May 2014

The notion of (compatible) deductive system of a pulex is defined and some properties of deductive systems are investigated. We also define a congruence relation on a pulex and show that there is a bijective correspondence between the compatible deductive systems and the congruence relations. We define the quotient algebra induced by a compatible deductive system and study its properties.
Identification of Potential Herbal Inhibitor of Acetylcholinesterase Associated Alzheimer’s Disorders Using Molecular Docking and Molecular Dynamics Simulation
Authors: Seniya Chandrabhan , Khan Ghulam Jilani , Uchadia Kuldeep
Published: May 2014

Cholinesterase inhibitors (ChE-Is) are the standard for the therapy of AD associated disorders and are the only class of approved drugs by the Food and Drug Administration (FDA). Additionally, acetylcholinesterase (AChE) is the target for many Alzheimer’s dementia drugs which block the function of AChE but have some side effects. Therefore, in this paper, an attempt was made to elucidate cholinesterase inhibition potential of secondary metabolite fromCannabisplant which has negligible or no side effect. Molecular docking of 500 herbal compounds, against AChE, was performed using Autodock 4.2 as per the standard protocols. Molecular dynamics simulations have also been carried out to check stability of binding complex in water for 1000 ps. Our molecular docking and simulation have predicted high binding affinity of secondary metabolite (C28H34N2O6) to AChE. Further, molecular dynamics simulations for 1000 ps suggest that ligand interaction with the residues Asp72, Tyr70-121-334, and Phe288 of AChE, all of which fall under active site/subsite or binding pocket, might be critical for the inhibitory activity of AChE. This approach might be helpful to understand the selectivity of the given drug molecule in the treatment of Alzheimer's disease. The study provides evidence for consideration ofC28H34N2O6as a valuable small ligand molecule in treatment and prevention of AD associated disorders and furtherin vitroandin vivoinvestigations may prove its therapeutic potential.
Paleogenetic Studies in Guajajara Skeletal Remains, Maranhão State, Brazil
Authors: Leite Daniela , Leitão Alysson , Schaan Ana Paula , Marinho Anderson N. R. , Souza Sheila , Rodrigues-Carvalho Claudia , Cardoso Francisca , Ribeiro-dos-Santos Ândrea
Published: May 2014

In the early 17th century, French and Portuguese colonizers and Jesuit priests settled in the state of Maranhão and made contact with the Guajajara, an ethnic group that lived along the margins of the Pindaré River. The Guajajara maintained contact with Brazilian national society over the centuries, including with Brazilian admixed populations, and with African slaves that flocked towards the region from the 18th century onwards. The present study investigates the origins of this admixture using mitochondrial genetic variability. The bones of 12 individuals investigated, which are currently part of the collection of theNational Museum, were tested for genetic diversity. aDNA was extracted by the phenol-chloroform method and by DNA IQ (Promega, Madison, WI, USA). Amplification of the HVS I region was performed by PCR, followed by direct sequencing using the Big Dye kit (Life Technologies, Foster City, CA, USA). This region was found to represent haplogroups of Amerindians (A, C, and D) and Africans (L, L1b, L1c, and L3). The presence of African haplogroups in Guajajara bones from as early as the 18th century is consistent with historical and anthropological data, suggesting the admixture with Africans and/or Afrodescendants. Therefore, this study demonstrates that women with African haplogroups were introduced into the Guajajara population.
On the Oscillation of Even-Order Half-Linear Functional Difference Equations with Damping Term
Authors: Bolat Yaşar , Alzabut Jehad
Published: May 2014

We investigate the oscillatory behavior of solutions of themth order half-linear functional difference equations with damping term of the formΔ[pnQ(Δm-1yn)]+qnQ(Δm-1yn)+rnQ(yτn)=0,n≥n0, wheremis even andQ(s)=sα-2s,α>1is a fixed real number. Our main results are obtained via employing the generalized Riccati transformation. We provide two examples to illustrate the effectiveness of the proposed results.
Synchronization of Complex Networks with Random Coupling Strengths and Mixed Probabilistic Time-Varying Coupling Delays Using Sampled Data
Authors: Wang Jian-An
Published: May 2014

The sampled-data synchronization problem for complex networks with random coupling strengths, probabilistic time-varying coupling delay, and distributed delay (mixed delays) is investigated. The sampling period is assumed to be time varying and bounded. By using the properties of random variables and input delay approach, new synchronization error dynamics are constructed. Based on the delay decomposition method and reciprocally convex approach, a delay-dependent mean square synchronization condition is established in terms of linear matrix inequalities (LMIs). According to the proposed condition, an explicit expression for a set of desired sampled-data controllers can be achieved by solving LMIs. Numerical examples are given to demonstrate the effectiveness of the theoretical results.
Pulmonary Phaeohyphomycosis Caused byPhaeoacremoniumin a Kidney Transplant Recipient: Successful Treatment with Posaconazole
Authors: Monaganti Saivaralaxmi , Santos Carlos A. Q. , Markwardt Andrea , Pence Morgan A. , Brennan Daniel C.
Published: May 2014

We report a rare case of pulmonary phaeohyphomycosis in a 49-year-old woman 6 years after kidney transplantation. She presented with dyspnea, cough, and fatigue. Her chest CT scan revealed nodular opacities in the right upper lung. A fine needle aspirate biopsy culture yieldedPhaeoacremoniumand surgical pathology of the biopsy showed chronic inflammation. We successfully treated her with posaconazole and managed drug interactions between posaconazole and tacrolimus. This is the second reported case of biopsy-proven pulmonary infection byPhaeoacremoniumin a kidney transplant recipient and successfully treated with posaconazole.
The Constants in A Posteriori Error Indicator for State-Constrained Optimal Control Problems with Spectral Methods
Authors: Zhou Jianwei
Published: May 2014

We employ Legendre-Galerkin spectral methods to solve state-constrained optimal control problems. The constraint on the state variable is an integration form. We choose one-dimensional case to illustrate the techniques. Meanwhile, we investigate the explicit formulae of constants within a posteriori error indicator.
Comparative Pharmacokinetics of Cefquinome (Cobactan 2.5%) following Repeated Intramuscular Administrations in Sheep and Goats
Authors: El-Hewaity Mohamed , Abd El Latif Amera , Soliman Ahmed , Aboubakr Mohamed
Published: May 2014

The comparative pharmacokinetic profile of cefquinome was studied in sheep and goats following repeated intramuscular (IM) administrations of 2 mg/kg body weight. Cefquinome concentrations in serum were determined by microbiological assay technique using Micrococcus luteus (ATCC 9341) as test organism. Following intramuscular injection of cefquinome in sheep and goats, the disposition curves were best described by two-compartment open model in both sheep and goats. The pharmacokinetics of cefquinome did not differ significantly between sheep and goats; similar intramuscular dose rate of cefquinome should therefore be applicable to both species. On comparing the data of serum levels of repeated intramuscular injections with first intramuscular injection, it was revealed that repeated intramuscular injections of cefquinome have cumulative effect in both species sheep and goats. The in vitro serum protein-binding tendency was 15.65% in sheep and 14.42% in goats. The serum concentrations of cefquinome along 24 h after injection in this study were exceeding the MICs of different susceptible microorganisms responsible for serious disease problems. These findings indicate successful use of cefquinome in sheep and goats.
Prospective Evaluation of Whole Genome MicroRNA Expression Profiling in Childhood Acute Lymphoblastic Leukemia
Authors: Duyu Muhterem , Durmaz Burak , Gunduz Cumhur , Vergin Canan , Yilmaz Karapinar Deniz , Aksoylar Serap , Kavakli Kaan , Cetingul Nazan , Irken Gulersu , Yaman Yontem , Ozkinay Ferda , Cogulu Ozgur
Published: May 2014

Dysregulation of microRNA (miRNA) expression contributes to the pathogenesis of several clinical conditions. The aim of this study is to evaluate the associations between miRNAs and childhood acute lymphoblastic leukemia (ALL) to discover their role in the course of the disease. Forty-three children with ALL and 14 age-matched healthy controls were included in the study. MicroRNA microarray expression profiling was used for peripheral blood and bone marrow samples. Aberrant miRNA expressions associated with the diagnosis and outcome were prospectively evaluated. Confirmation analysis was performed by real time RT-PCR. miR-128, miR-146a, miR-155, miR-181a, and miR-195 were significantly dysregulated in ALL patients at day 0. Following a six-month treatment period, the change in miRNA levels was determined by real time RT-PCR and expression of miR-146a, miR-155, miR-181a, and miR-195 significantly decreased. To conclude, these miRNAs not only may be used as biomarkers in diagnosis of ALL and monitoring the disease but also provide new insights into the potential roles of them in leukemogenesis.
Dual Key Speech Encryption Algorithm Based Underdetermined BSS
Authors: Zhao Huan , He Shaofang , Chen Zuo , Zhang Xixiang
Published: May 2014

When the number of the mixed signals is less than that of the source signals, the underdetermined blind source separation (BSS) is a significant difficult problem. Due to the fact that the great amount data of speech communications and real-time communication has been required, we utilize the intractability of the underdetermined BSS problem to present a dual key speech encryption method. The original speech is mixed with dual key signals which consist of random key signals (one-time pad) generated by secret seed and chaotic signals generated from chaotic system. In the decryption process, approximate calculation is used to recover the original speech signals. The proposed algorithm for speech signals encryption can resist traditional attacks against the encryption system, and owing to approximate calculation, decryption becomes faster and more accurate. It is demonstrated that the proposed method has high level of security and can recover the original signals quickly and efficiently yet maintaining excellent audio quality.
Conservative Difference Scheme for Generalized Rosenau-KdV Equation
Authors: Luo Yan , Xu Youcai , Feng Minfu
Published: May 2014

A conservative Crank-Nicolson finite difference scheme for the initial-boundary value problem of generalized Rosenau-KdV equation is proposed. The difference scheme shows a discrete analogue of the main conservation law associated to the equation. On the other hand the scheme is implicit and stable with second order convergence. Numerical experiments verify the theoretical results.
Cyclin D1 Integrates Estrogen-Mediated DNA Damage Repair Signaling
Authors: Li Zhiping , Chen Ke , Jiao Xuanmao , Wang Chenguang , Willmarth Nicole E. , Casimiro Mathew C. , Li Weihua , Ju Xiaoming , Kim Sung Hoon , Lisanti Michael P. , Katzenellenbogen John A. , Pestell Richard G.
Published: May 2014

The cyclin D1 gene encodes the regulatory subunit of a holoenyzme that phosphorylates the retinoblastoma protein (pRb) and nuclear respiratory factor (NRF1) proteins. The abundance of cyclin D1 determines estrogen-dependent gene expression in the mammary gland of mice. Using estradiol (E2) and an E2–dendrimer conjugate that is excluded from the nucleus, we demonstrate that E2 delays the DNA damage response (DDR) via an extranuclear mechanism. The E2-induced DDR required extranuclear cyclin D1, which bound ERα at the cytoplasmic membrane and augmented AKT phosphorylation (Ser473) and γH2AX foci formation. In the nucleus, E2 inhibited, whereas cyclin D1 enhanced homology-directed DNA repair. Cyclin D1 was recruited to γH2AX foci by E2 and induced Rad51 expression. Cyclin D1 governs an essential role in the E2-dependent DNA damage response via a novel extranuclear function. The dissociable cytoplasmic function to delay the E2-mediated DDR together with the nuclear enhancement of DNA repair uncovers a novel extranuclear function of cyclin D1 that may contribute to the role of E2 in breast tumorigenesis. Cancer Res; 74(14); 3959–70. ©2014 AACR.
Flotillin-1 Regulates Oncogenic Signaling in Neuroblastoma Cells by Regulating ALK Membrane Association
Authors: Tomiyama Arata , Uekita Takamasa , Kamata Reiko , Sasaki Kazuki , Takita Junko , Ohira Miki , Nakagawara Akira , Kitanaka Chifumi , Mori Kentaro , Yamaguchi Hideki , Sakai Ryuichi
Published: May 2014

Neuroblastomas harbor mutations in the nonreceptor anaplastic lymphoma kinase (ALK) in 8% to 9% of cases where they serve as oncogenic drivers. Strategies to reduce ALK activity offer clinical interest based on initial findings with ALK kinase inhibitors. In this study, we characterized phosphotyrosine-containing proteins associated with ALK to gain mechanistic insights in this setting. Flotillin-1 (FLOT1), a plasma membrane protein involved in endocytosis, was identified as a binding partner of ALK. RNAi-mediated attenuation of FLOT1 expression in neuroblastoma cells caused ALK dissociation from endosomes along with membrane accumulation of ALK, thereby triggering activation of ALK and downstream effector signals. These features enhanced the malignant properties of neuroblastoma cells in vitro and in vivo. Conversely, oncogenic ALK mutants showed less binding affinity to FLOT1 than wild-type ALK. Clinically, lower expression levels of FLOT1 were documented in highly malignant subgroups of human neuroblastoma specimens. Taken together, our findings suggest that attenuation of FLOT1-ALK binding drives malignant phenotypes of neuroblastoma by activating ALK signaling. Cancer Res; 74(14); 3790–801. ©2014 AACR.
Activating and Propagating Polyclonal Gamma Delta T Cells with Broad Specificity for Malignancies
Authors: Deniger Drew C. , Maiti Sourindra N. , Mi Tiejuan , Switzer Kirsten C. , Ramachandran Vijaya , Hurton Lenka V. , Ang Sonny , Olivares Simon , Rabinovich Brian A. , Huls M. Helen , Lee Dean A. , Bast Robert C. , Champlin Richard E. , Cooper Laurence J.N.
Published: May 2014

Purpose: To activate and propagate populations of γδ T cells expressing polyclonal repertoire of γ and δ T-cell receptor (TCR) chains for adoptive immunotherapy of cancer, which has yet to be achieved.

Experimental Design: Clinical-grade artificial antigen-presenting cells (aAPC) derived from K562 tumor cells were used as irradiated feeders to activate and expand human γδ T cells to clinical scale. These cells were tested for proliferation, TCR expression, memory phenotype, cytokine secretion, and tumor killing.

Results: γδ T-cell proliferation was dependent upon CD137L expression on aAPC and addition of exogenous IL2 and IL21. Propagated γδ T cells were polyclonal as they expressed TRDV1, TRDV2-2, TRDV3, TRDV5, TRDV7, and TRDV8 with TRGV2, TRGV3F, TRGV7, TRGV8, TRGV9*A1, TRGV10*A1, and TRGV11 TCR chains. IFNγ production by Vδ1, Vδ2, and Vδ1negVδ2neg subsets was inhibited by pan-TCRγδ antibody when added to cocultures of polyclonal γδ T cells and tumor cell lines. Polyclonal γδ T cells killed acute and chronic leukemia, colon, pancreatic, and ovarian cancer cell lines, but not healthy autologous or allogeneic normal B cells. Blocking antibodies demonstrated that polyclonal γδ T cells mediated tumor cell lysis through combination of DNAM1, NKG2D, and TCRγδ. The adoptive transfer of activated and propagated γδ T cells expressing polyclonal versus defined Vδ TCR chains imparted a hierarchy (polyclonal>Vδ1>Vδ1negVδ2neg>Vδ2) of survival of mice with ovarian cancer xenografts.

Conclusions: Polyclonal γδ T cells can be activated and propagated with clinical-grade aAPCs and demonstrate broad antitumor activities, which will facilitate the implementation of γδ T-cell cancer immunotherapies in humans. Clin Cancer Res; 20(22); 5708–19. ©2014 AACR.
Drug-Eluting Stent, but Not Bare Metal Stent, Accentuates the Systematic Inflammatory Response in Patients
Authors: Liu Junhui , Zhuo Xiao-Zhen , Liu Weimin , Wan Zhaofei , Wang Xinhong , Zhang Weiping , Gao Shanshan , Yuan Zuyi , Wu Yue
Published: May 2014

Objective: The systematic pro-inflammatory responses after percutaneous coronary intervention with drug-eluting stents (DES) remain poorly defined. Therefore, we compared the systematic pro-inflammatory state of circulating mononuclear cells (MNCs) between DES and bare metal stent (BMS) implantation. Methods: Patients with indications for treatment with stents were randomized in a 1:1 ratio to placement of DES or BMS. The primary endpoint was a change of pro-inflammatory state at 12 weeks post-procedure. Results: Thirty-six consecutive patients received DES or BMS. At 12 weeks after stent implantation, the lipid profile and high-sensitivity C-reactive protein (hs-CRP) improved significantly in both groups. The mRNA levels and plasma concentrations of interleukin-6, tumor necrosis factor-a and matrix metalloproteinase-9 were significantly elevated in the DES group, which was not observed in the BMS group. An increase in NF-γB binding activity and a decrease in PPAR-γ expression in MNCs were observed in the DES group, along with increases in IγB phosphorylation and p50 expression. However, similar changes were not observed in the BMS group. Conclusions: Systematic inflammatory responses were accentuated after the patients were treated percutaneously with DES, despite their improved lipid profile and hs-CRP. These data may provide fundamental information for optimizing therapeutic strategy in the era of DES.
Stem Cells and Regeneration in Plants
Authors: Sena Giovanni
Published: May 2014

Background: Plants are characterized by indeterminate post-embryonic development that is evident, for example, in the continuous branching of shoots and roots. High competence to regenerate tissues is another consequence of such intrinsic developmental plasticity in plants. It has been suggested that specialized groups of cells within plant meristems should be compared to stem cells in animals, but the utility of this label in the context of post-embryonic plant development and regeneration is often debated. Summary: This paper is organized into 3 short sections, where (a) key observations and experimental results on tissue regeneration in plants - mainly in the model system Arabidopsis thaliana, (b) stem cell activity and (c) their role in regeneration are described. The main focus is maintained on the critical aspects of defining stem cell-ness in plants, particularly in the context of tissue regeneration. A number of recent excellent reviews are cited throughout the text to give the reader the appropriate tools to dig deeper into the various stimulating topics introduced here. Key Messages: Despite the remarkable somatic developmental plasticity characterizing post-embryonic development in plants, use of the classic concept of stem cells has been imported from the animal literature with the goal of facilitating our understanding and description of plant developmental processes. It is not clear if this is the case, especially in light of the recent experimental results on root regeneration in Arabidopsis mutants.
Cell Therapy for Kidney Injury: Different Options and Mechanisms - Mesenchymal and Amniotic Fluid Stem Cells
Authors: Morigi Marina , De Coppi Paolo
Published: May 2014

Background: Acute kidney injury (AKI) is emerging as a public health problem in developing and developed countries. It affects up to 7% of hospitalized patients, with a higher prevalence in critical care units. Despite major advances in preventive strategies and support measures, the mortality rate among patients remains higher than 50%. Several pharmacological approaches to improve renal function and survival after an AKI episode have been largely unsuccessful in clinical practice. Summary: Stem cell-based therapy has provided new hopes of innovative interventions to enhance the limited capability of kidney regeneration in AKI. An important target for cell therapy is represented by tubular epithelial cells which after acute ischemic or toxic insults undergo dysfunction and detachment. Among adult stem cells, mesenchymal stromal/stem cells (MSC) are an attractive therapeutic tool by virtue of their unique biological properties, tropism for damaged tissues, and proregenerative capacity. In the present review, we discuss the mechanisms underlying the renoprotective effects of therapies with stem cells of different origins in preclinical models of AKI by evaluating new modalities by which MSC interact with damaged cells via the release of soluble factors and exosomes/microvesicles. Several biological effects, including antiapoptotic, promitogenic, immunomodulatory, and anti-inflammatory activities, have been analyzed in renal tissue of AKI animals receiving stem cell treatments. The mechanisms of stem cell homing and engraftment to sites of tissue damage have also been discussed. Key Messages: The translation of preclinical data on stem cells into effective and safe new modalities of care is still limited, and further studies are needed before their application in patients with AKI.
Tubular Regeneration: When Can the Kidney Regenerate from Injury and What Turns Failure into Success
Authors: Johansson Martin E.
Published: May 2014

Background: The most common intrarenal cause for acute kidney injury/renal failure is tubular damage. The kidney tubules are arranged as compartments of cellular mosaics to perform their functions, and at rest almost a fifth of the human ATP consumption is allotted to the reabsorption of substances from the filtrate, rendering especially the proximal tubules highly sensitive to oxygen and/or nutrient deprivation. Normally mitotically quiescent, the tubular epithelium shows a brisk regenerative response following injury if supportive care is offered, allowing functional restoration. Despite this, the cellular machinery behind the regenerative capacity is still not unequivocally defined. This is at odds with other epithelia such as those of the skin and intestine, where stem cells maintain a continuous flow of new cells from designated niches. Summary: This review discusses the classical concept of renal regeneration, i.e. stochastically surviving cells undergoing dedifferentiation (or epithelial-mesenchymal transition) followed by replenishment of the tubular epithelium. Furthermore however, this view has recently been challenged by the concept of organ-confined stem/progenitor cells, bone marrow-derived stem cells, or mesenchymal stem cells taking part in the regenerative events. Whereas results from animal models support the classical view, morphologically distinct cells have been demonstrated in human kidneys, requiring interpretation. This review presents some of the previous work and techniques and highlights issues that need to be reconciled. Key Messages: In adult humans, the kidney tubules contain scattered cells with a distinct set of markers and properties, such as increased robustness during tubular damage. These cells may be induced by injury or represent a resident progenitor cell pool. To date, animal studies using lineage-tracing methods argue for an inductive scenario. In humans, the situation is less clear and one might speculate that the cellular heterogeneity might reflect elements of cellular reprogramming to a progenitor-like state, perhaps by induction. Due to intense investigational efforts, however, a scientific consensus may soon be reached, which will benefit further research.
Plasma Omentin Levels in Drug-Free Patients with Schizophrenia
Authors: Yildirim Osman , Canan Fatih , Tosun Mehmet , Kayka Nefise , Tuman Taha Can , Alhan Cafer , Alcelik Aytekin
Published: May 2014

Aims: We aimed to investigate plasma omentin concentrations in non-obese, drug-free patients with schizophrenia in comparison with healthy volunteers. Method: Thirty-two patients with schizophrenia and 33 control subjects were recruited. Plasma omentin levels were determined by enzyme-linked immunosorbent assay. Results: Plasma levels of omentin (ng/ml) were found to be markedly lower in patients with schizophrenia (median = 7.7, 25th percentile = 6.3, 75th percentile = 604.9) than in controls (median = 486, 25th percentile = 326, 75th percentile = 794.2, p < 0.01). No significant difference was found between drug-free (n = 23) and drug-naive (n = 9) patients with respect to plasma omentin levels. Omentin concentrations correlated negatively with severity of illness, suggesting that patients with more severe pathology had lower fasting levels of omentin (n = 32; r = -0.387; p = 0.029). Conclusion: The present results suggest that plasma omentin levels are decreased in physically healthy, non-obese, antipsychotic-free patients with schizophrenia when compared with physically and mentally healthy individuals. To our knowledge, this is the first study that demonstrated the association between omentin and schizophrenia.
Inhibitor of Differentiation 3, a Transcription Factor, Regulates Hyperlipidemia-Associated Kidney Disease
Authors: Nackiewicz Dominika , Dey Paromita , Szczerba Barbara , Mohammad Saleh , Kaplan Jennifer L. , McNamara Coleen A. , Deshmukh Umesh S. , Bagavant Harini
Published: May 2014

Background: Lipoprotein abnormalities are associated with a rapid decline in renal function in patients of chronic kidney disease. In addition, hyperlipidemia is associated with an increased risk of developing renal insufficiency. The underlying molecular mechanisms for these clinical findings are unclear. We have previously reported a role for inhibitor of differentiation 3 (ID3), a transcription factor, in regulating kidney disease in hyperlipidemia. Introducing a genetic deficiency of Id3 in spontaneously hyperlipidemic apolipoprotein E knockout (Apoe-/-) mice led to accelerated mesangioproliferative glomerulonephritis. The present study was carried out to further investigate the contribution of ID3 in hyperlipidemia-associated kidney disease. Methods: Female C57BL/6 mice that were ID3-sufficient wild-type (WT) or ID3-deficient (Id3-/-) were fed a Western diet and evaluated for proteinuria, glomerular pathology, and immune infiltrating cells. Primary mesangial cell lines were generated from both mouse strains and stimulated with oxidized phospholipids. Cytokines and chemokines produced were measured by multiplex assays, ELISA, and QPCR. Glomerular isolates were studied for CXCL1 expression by QPCR. Results:Id3-/- mice on a Western diet developed accelerated proteinuria and mesangioproliferative glomerulonephritis compared to WT controls. In vitro, Id3-/- glomerular mesangial cell lines produced higher levels of the monocyte chemoattractant CXCL1 in response to oxidized phospholipids. This was consistent with the rapid increase in glomerular CXCL1 expression followed by macrophage infiltration in Id3-/- mice fed a Western diet. Conclusions: A functional ID3 influences susceptibility to kidney disease and prevents glomerular injury by regulating local chemokine production and inflammatory cell recruitment.
Synergistic Effects of Leflunomide and Benazepril in Streptozotocin-Induced Diabetic Nephropathy
Authors: Jin Hua , Piao Shang Guo , Jin Ji Zhe , Jin Ying Shun , Cui Zhen Hua , Jin Hai Feng , Zheng Hai Lan , Li Jin Ji , Jiang Yu Ji , Yang Chul Woo , Li Can
Published: May 2014

Background: Leflunomide (LEF) and benazepril have renoprotective effects on diabetic nephropathy (DN) through their anti-inflammatory and anti-fibrotic activities. This study investigated whether combined treatment using LEF and benazepril affords superior protection compared with the respective monotherapies. Methods: Diabetes was induced with streptozotocin (STZ, 65 mg/kg) by intraperitoneal injection in male Wistar rats. Two weeks after STZ injection, diabetic rats were treated daily for 12 weeks with LEF (10 mg/kg), benazepril (10 mg/kg), or a combination of both. Basic parameters (body weight, fasting blood glucose level, and 24 h urinary protein excretion), histopathology, inflammatory [inflammatory cell infiltration (ED-1), monocyte chemoattractant protein-1 (MCP-1), and Toll-like receptor-2 (TLR-2)] and glomerulosclerotic factors [transforming growth factor-β1 (TGF-β1) and connective tissue growth factor (CTGF)], and oxidative stress (8-hydroxy-2'-deoxyguanosine, 8-OHdG) were studied. Results: Benazepril or LEF treatment significantly prevented body weight loss and 24 h urinary protein excretion induced by diabetes; combined treatment with LEF and benazepril further improved these parameters compared with giving each drug alone (all p < 0.01). Increased expression of inflammatory (MCP-1 and TLR-2) and glomerulosclerotic (TGF-β1 and CTGF) factors in diabetic rat kidney was reduced by treatment with either LEF or benazepril and was further reduced by the combined administration of the two drugs (p < 0.01). These effects were accompanied by suppression of urinary 8-OHdG excretion. There was no significant between-group difference in blood glucose level. Conclusions: LEF treatment lessens DN, and combined treatment with LEF and benazepril provides synergistic effects in preventing DN.
Cardiac-Specific YAP Activation Improves Cardiac Function and Survival in an Experimental Murine MI Model
Authors: Lin Zhiqiang , von Gise Alexander , Zhou Pingzhu , Gu Fei , Ma Qing , Jiang Jianming , Yau Allan L. , Buck Jessica N. , Gouin Katryna A. , van Gorp Pim R.R. , Zhou Bin , Chen Jinghai , Seidman Jonathan G. , Wang Da-Zhi , Pu William T.
Published: May 2014

Rationale
:

Yes-associated protein (YAP), the terminal effector of the Hippo signaling pathway, is crucial for regulating embryonic cardiomyocyte proliferation.

Objective
:

We hypothesized that YAP activation after myocardial infarction (MI) would preserve cardiac function and improve survival.

Methods and Results
:

We used a cardiac-specific, inducible expression system to activate YAP in adult mouse heart. Activation of YAP in adult heart promoted cardiomyocyte proliferation and did not deleteriously affect heart function. Furthermore, YAP activation after MI preserved heart function and reduced infarct size. Using adeno-associated virus subtype 9 (AAV9) as a delivery vector, we expressed human YAP (hYAP) in the adult murine myocardium immediately after MI. We found that AAV9:hYAP significantly improved cardiac function and mouse survival. AAV9:hYAP did not exert its salutary effects by reducing cardiomyocyte apoptosis. Rather, AAV9:hYAP stimulated adult cardiomyocyte proliferation. Gene expression profiling indicated that AAV9:hYAP stimulated expression of cell cycle genes and promoted a less mature cardiac gene expression signature.

Conclusions
:

Cardiac-specific YAP activation after MI mitigated myocardial injury, improved cardiac function, and enhanced survival. These findings suggest that therapeutic activation of YAP or its downstream targets, potentially through AAV-mediated gene therapy, may be a strategy to improve outcome after MI.
Towards an Asian Multitextual Theology
Authors: Adiprasetya Joas
Published: May 2014

Abstract

The article criticizes some shortcomings of Asian contextual and liberation theologies that methodologically employ ‘hermeneutical circle’. The method focuses on experience as the starting point of doing theology. Despite its powerful insights that enable theologians to engage with concrete human and social problems, the method can easily preserve a theologian’s blind spot that hinders her/him from perspectives other than his or her own. I also criticize such an experience-based method as being too linear which can easily result in a methodological imperialism. In response to the weakness, I propose a multitextual theology, which on the one hand acknowledges the importance of perspectivism in any theology but also, on the other hand, celebrates theological freedom in viewing reality from ‘manywheres’. Since reality provides plurality of texts, a multitextual theology can begin simultaneously from any text, without being trapped into a procedural rigidity as clearly demonstrated in contextual and liberation theologies.
Tell Us Our Story
Authors: van Liere Lucien
Published: May 2014

Abstract

This article raises the question about how definitions of religion and violence can be understood as links to the context in which they are formulated. The focus is on the context of academic learning. Understanding a definition as a micro-narrative that reflects the cultural ‘archive’, the author uses two academic contexts (i.e. Utrecht, The Netherlands and Jakarta, Indonesia) to show how religion and violence are differently understood. These differences are taken as significant information for understanding how the topic of ‘religion and violence’ is related to cultural understandings of the place of religion in society. The question is raised how ‘narrative learning’ can help as a strategy to raise awareness about the preconditioning of (academic) definitions of ‘religion and violence’.
Reading the Bible in Africa
Authors: Ngong David T.
Published: May 2014

Abstract

This paper describes inculturation biblical reading in a narrow way to include mainly that reading of the Bible that takes for granted what is believed to be a peculiarly African spiritualistic cosmology. A central element of this method includes pitting a supposedly African spiritualized cosmology against a supposedly Western rationalistic and disenchanted cosmology. Proponents of this method claim that a relevant biblical interpretation in the African context should enable Africans to deal with issues arising from their belief in an enchanted world. This essay problematizes the focus on this enchanted cosmology and argues that the African condition can be effectively addressed through interpreting the Bible in ways that encourage the development of the scientific imagination, which could lead to the development of science and technology and an improved standard of living for the people.
Mothers for a Christian Nation
Authors: van Geuns Suzanne
Published: May 2014

Abstract

Believers of the American Quiverfull movement reject all forms of contraception. They promote having as many children as God is willing to give and raising these children to be righteous Christians, with the explicit purpose of creating a Christian nation. The movement has no central institutions: believers communicate online, through blogs and forums.

This article investigates where the Quiverfull movement can be situated within the realm of American Christianity as well as its relation to modernity. By using Moojan Momen’s fundamentalism-liberalism spectrum to locate the movement on the map of Christianity, the article argues that the Quiverfull position can be best understood by relating its standpoints on gender and family politics to those of American evangelical fundamentalist churches.

Yet Quiverfull stances do not entirely fit the fundamentalist frame. The Quiverfull focus on a biblical future, rather than a biblical past, sets this movement apart from evangelical fundamentalism. Though the Quiverfull movement is small now, its tactics and strategies might provide Christian fundamentalists with new perspectives on growth and the preservation of Christian morals. Rearticulating their biblical convictions online in modern ways, Quiverfull women are working towards a modernity that is transformed to be wholly Christian, one baby at a time.
Hygiene in Nineteenth-Century Ottoman Bulgaria
Authors: Ianeva Svetla
Published: May 2014

The article examines the most important elements of personal, home and everyday life hygiene and several aspects of public hygiene such as the availability and public use of water, the state of cleanliness of the streets and other public places (bazaars, caravanserais, hospitals), the location and state of the graveyards, some public measures for the prevention of the spread of diseases (isolation and quarantine) in nineteenth-century Ottoman Bulgaria. The differences in the hygienic notions, habits and practices of the local population based on religion, culture and tradition as well as the existence or absence of mutual influences in this respect are considered. The article addresses also the question of the beginning of some transformations in the traditional patterns of hygiene in the region, mainly during the second half of the nineteenth century, under European influence and under the influence of modern education.
The Relacyja of Sefer Muratowicz: 1601–1602 Private Royal Envoy of Sigismund III Vasa to Shah ‘Abbas I
Authors: Połczyński Michael
Published: May 2014

Armenian merchant and Ottoman subject Sefer Muratowicz emigrated to the Polish-Lithuanian Commonwealth in the late sixteenth century. Soon after, he appeared before Safavid Shah ‘Abbas I as the personal envoy of King Sigismund III Vasa on a royal diplomatic mission unsanctioned by the Commonwealth's parliament. Though the trajectory of Sefer Muratowicz's life is not without precedence in the heterogeneous social milieu of Poland-Lithuania, his documented involvement in the private royal embassy of 1601–1602 to Safavid Persia presents an exceptional view into the critical role of the diasporic Armenian population in the diplomatic and economic relations between Europe's largest republic and the Islamic world in the early modern period.
slm is Dead, Long Live Sri Lanka Malay
Authors: Ansaldo Umberto
Published: May 2014

This paper discusses the results of scholarship on Sri Lanka Malay based on the studies presented in Nordhoff 2013 in terms of theory, method, and social impact. It touches on a variety of topics including the significance of recent genetic evidence for old theories of language genesis, as well as the efforts for revitalization sparked by the scientific interest in the speech community. In evaluating this collection of variable significance, the author reflects on the transition of ownership of Sri Lanka Malay: from object of scientific curiosity to ancestral language of communal value.