bluuebunny/crossref_metadata_2025 huggingface dataset:
Molecular Docking and Quantum Mechanical Studies on Pelargonidin-3-Glucoside as Renoprotective ACE Inhibitor
Authors: Usha Talambedu , Tripathi Pranav , Pande Veena , Middha Sushil Kumar
Published: March 2013

Background and Aim. Despite tangible progress in recent years, substantial therapeutic challenges remain unexplored in nephropathy, particularly in diabetic patient. Addressing these challenges requires identification of novel drugs and development of noninvasive and cost-effective methods to select the most appropriate therapeutic option for the disease. Angiopathic nephropathy is one of the complications of diabetes mellitus and is becoming the single most important reason for end-stage renal disease in the western world. This study has investigated the inhibitory effect of a library naturally occurring nonprotein compounds that inhibit angiotensin converting enzyme (ACE). Materials and Methods. Docking studies of ACE protein with natural compounds and synthetic commercial drug perindopril were done using AutoDock, FlexX, and Hex. Toxicity predictions were carried out using OpenTox. Quantum mechanical properties were studied using GAMESS. Results. Pelargonidin-3-glucoside could be used as a potent renoprotective drug candidate, which inhibits ACEII. It has low toxicity and its quantum mechanical properties are comparable to those of commercial drugs.
Review and Progress towards the Capacity Boost of Overhead and Underground Medium-Voltage and Low-Voltage Broadband over Power Lines Networks: Cooperative Communications through Two- and Three-Hop Repeater Systems
Authors: Lazaropoulos Athanasios G.
Published: March 2013

This paper reviews and analyzes the broadband capacity and the coexistence potential of overhead and underground medium-voltage/broadband over power lines (MV/BPL) and low-voltage/broadband over power lines (LV/BPL) topologies when one and two repeaters are additively deployed between their existing transmitting and receiving ends (overhead and underground MV/BPL and LV/BPL topologies with two- and three-hop repeater system, respectively). The contribution of this paper is four fold. First, the factors that influence the broadband capacity performance of overhead and underground MV/BPL and LV/BPL topologies with multihop repeater systems are identified, namely the number of repeaters, the distribution power grid type—either overhead or underground, either MV or LV, the initial distribution BPL topology, the multiconductor transmission line configuration, and coupling scheme applied. Second, the well-validated applicability of two-hop repeater systems is now extended in overhead and underground LV/BPL and MV/BPL networks. The significant mitigating role of two-hop repeater systems against capacity losses due to aggravated topologies or different coupling schemes is verified. Third, the deployment upgrade of two- to three-hop repeater systems in distribution BPL topologies is first examined in terms of broadband capacity performance. To study the occurred capacity improvement, suitable capacity contour plots are first proposed. Fourth, multi-hop repeater systems are identified as valuable technology solution so that the required intraoperability between overhead and underground MV/BPL and LV/BPL networks, which is a prerequisite condition before BPL systems symbiosis with other broadband technologies (interoperability), is promoted.
An Algorithm of Auto-Update Threshold for Singularity Analysis of Pipeline Pressure
Authors: Liu Jinhai , Feng Jian , Tan Liang , Ma Dazhong
Published: March 2013

A precise auto-update threshold algorithm (AUTA) which imitates the short-term memory of human brain is proposed to search singularities in pipeline pressure signal. According to the characteristics of the pressure signal, the pressure can be divided into two states known as nonsteady state and steady state. The AUTA can distinguish these two states and then choose corresponding method to calculate the dynamic thresholds of pressure variation in real time. Then, the parameters of AUTA are analyzed to determine their values or ranges. Finally, in the simulations to the actual pressure signal from oil pipelines, we verified the effectiveness of AUTA in estimating the dynamic threshold value of pressure.
Assessment of Hepatic and Pancreatic Iron Overload in Pediatric Beta-Thalassemic Major Patients by Weighted Gradient Echo Magnetic Resonance Imaging
Authors: Youssef Doaa Mohammed , Fawzy Mohammad Faten , Ahmed Fathy Ayman , Aly Abdelbasset Maha
Published: March 2013

Background. MRI has emerged for the noninvasive assessment of iron overload in various tissues. The aim of this paper is to evaluate hepatic and pancreatic iron overload by weighted gradient echo MRI in young beta-thalassemia major patients and to correlate it with glucose disturbance and postsplenectomy status.Subjects and Methods. 50 thalassemic patients, in addition to 15 healthy controls. All patients underwent clinical assessment and laboratory investigations. Out of 50 thalassemic patients, 37 patients were splenectomized. MRI was performed for all subjects.Results. All patients showed significant reduction in the signal intensity of the liver and the pancreas on GRD compared to controls, thalassemic patients who had abnormal glucose tolerance; diabetic and impaired glucose tolerance patients displayed a higher degree of pancreatic and hepatic siderosis and more drop in their signal intensity than those with normal blood sugar level. Splenectomized thalassemic patients had significantly lower signal intensity of the liver and pancreas compared to nonsplenectomized patients.Conclusion. gradient echo MRI is noninvasive highly sensitive method in assessing hepatic and pancreatic iron overload in thalassemic patients, more evident in patients with abnormal glucose tolerance, and is accelerated in thalassemic splenectomized patients.
A Third-Orderp-Laplacian Boundary Value Problem Solved by an SL(3,ℝ)Lie-Group Shooting Method
Authors: Liu Chein-Shan
Published: March 2013

The boundary layer problem for power-law fluid can be recast to a third-orderp-Laplacian boundary value problem (BVP). In this paper, we transform the third-orderp-Laplacian into a new system which exhibits a Lie-symmetry SL(3,ℝ). Then, the closure property of the Lie-group is used to derive a linear transformation between the boundary values at two ends of a spatial interval. Hence, we can iteratively solve the missing left boundary conditions, which are determined by matching the right boundary conditions through a finer tuning ofr∈[0,1]. The present SL(3,ℝ)Lie-group shooting method is easily implemented and is efficient to tackle the multiple solutions of the third-orderp-Laplacian. When the missing left boundary values can be determined accurately, we can apply the fourth-order Runge-Kutta (RK4) method to obtain a quite accurate numerical solution of thep-Laplacian.
Characterisation of Used PP-Based Car Bumpers and Their Recycling Properties
Authors: Luda M. P. , Brunella V. , Guaratto D.
Published: March 2013

Three used PP-based car bumpers are characterized by many techniques (fractionation, IR, TGA, DSC, DMTA, and SEM). They show different impact and static and dynamic mechanical properties depending on their composition and morphology. It appears that block copolymer compatibilizers constituted by polyethylene-polypropylene sequences allow a better compatibility between the rubber domains and the PP matrix leading to relatively high impact resistance. Indeed if the ethylene sequences of the copolymer are large enough to crystallize, the decreased mobility of the whole system impairs the impact resistance. In addition, a higher amount of rubber in domains regular in shape and of greater dimension (1–3 μm) promotes a more homogeneous dispersion of external force inside the material, decreasing the risk of fracture. The amount of mineral fillers regulates the elastic modulus (the higher the load, the higher the modulus); however, a fairly good interfacial adhesion is required for satisfactory impact strength. All PP-based bumpers have been mechanically recycled in an internal mixer to redistribute oxidized species and to reestablish phase compatibilization. Recycling improves mechanical properties in slow speed test but fails to increase impact strength particularly in filled bumper, in which the quality of the matrix/filler interphase is hard to improve by simple remixing.
Some Similarity Measures for Triangular Fuzzy Number and Their Applications in Multiple Criteria Group Decision-Making
Authors: Zhang Liyuan , Xu Xuanhua , Tao Li
Published: March 2013

We propose some similarity measures between two triangular fuzzy numbers (TFNs) based on the vector similarity measures in vector space, which can be used to aggregate the decision information with TFNs. A methodology for multiple criteria group decision-making (MCGDM) problems with triangular fuzzy information is proposed; the criteria values take the form of linguistic values, which can be converts to TFNs. According to the weighted similarity measures between each alternative and ideal alternative, it is easy to rank alternatives and select the most desirable alternative. Finally, we apply the proposed methods to an illustrative example of MCGDM; the numerical results show that our method is effective and practical. For comparison, we also apply our similarity measures method to solve the fuzzy decision-making problem in Wei (2011); our method has simpler computation and gets the same results more rapidly than the FLOWHM method.
Obstructing Hamartomatous Polyp in Peutz-Jeghers Syndrome
Authors: Bentley Brian S. , Hal Hassan M.
Published: March 2013

A 53-year-old male presented with complaints of abdominal pain and weight loss. On physical exam he was noted to have mucocutaneous pigmentation around his lips and oral mucosa. Radiologic and endoscopic investigations demonstrated an obstructing mass in the second portion of the duodenum along with additional smaller soft tissue masses throughout the bowel. Histology of biopsied specimens revealed architectural disorganization without dysplasia, suggestive of Peutz-Jeghers hamartomatous polyps.
Sudden Pressurization of a Spherical Cavity in a Poroelastic Medium
Authors: Ozyazicioglu Mehmet
Published: March 2013

Governing equations of poroelastodynamics in time and frequency domain are derived. The continuity equation complements the momentum balance equations. After reduction for spherical symmetry (geometry and loading), the governing equations in frequency domain are solved by introducing wave potentials. The wave propagation velocities are obtained as the real parts of the characteristic equation of the coupled ODE system. Time domain solution for Dirac type boundary pressure is obtained through numerical inversion of transformed solutions. The results are compared to the solution in classical elasticity theory found in the literature.
Noncovalent Functionalization of Graphene in Suspension
Authors: Yang Wenzhi , Akhtar Sultan , Leifer Klaus , Grennberg Helena
Published: March 2013

Suspensions of graphene, prepared from graphite foil by sonochemical exfoliation, have been treated with new nonpolar pyrenebutyric amides. The assemblies, in suspension and after deposition on solid supports, were characterized by NMR, absorption, and fluorescence spectroscopy and by transmission electron microscopy, where the well-defined shape and size of an appended [60]fulleropyrrolidine unit facilitates TEM detection of the nonstationary molecules. The accumulated evidence, also including direct comparisons of carbon nanotubes treated with pyrene amides under the same conditions, proves the successful noncovalent functionalization of graphene suspended in non-polar solvent with non-polar pyrene derivatives.
On the Fine Spectrum of the Operator Defined by the Lambda Matrix over the Spaces of Null and Convergent Sequences
Authors: Yeşilkayagil Medine , Başar Feyzi
Published: March 2013

The main purpose of this paper is to determine the fine spectrum with respect to Goldberg's classification of the operator defined by the lambda matrix over the sequence spaces andc. As a new development, we give the approximate point spectrum, defect spectrum, and compression spectrum of the matrix operator on the sequence spaces andc. Finally, we present a Mercerian theorem. Since the matrix is reduced to a regular matrix depending on the choice of the sequence having certain properties and its spectrum is firstly investigated, our work is new and the results are comprehensive.
Development of Image Segmentation Methods for Intracranial Aneurysms
Authors: Sen Yuka , Qian Yi , Avolio Alberto , Morgan Michael
Published: March 2013

Though providing vital means for the visualization, diagnosis, and quantification of decision-making processes for the treatment of vascular pathologies, vascular segmentation remains a process that continues to be marred by numerous challenges. In this study, we validate eight aneurysms via the use of two existing segmentation methods; the Region Growing Threshold and Chan-Vese model. These methods were evaluated by comparison of the results obtained with a manual segmentation performed. Based upon this validation study, we propose a new Threshold-Based Level Set (TLS) method in order to overcome the existing problems. With divergent methods of segmentation, we discovered that the volumes of the aneurysm models reached a maximum difference of 24%. The local artery anatomical shapes of the aneurysms were likewise found to significantly influence the results of these simulations. In contrast, however, the volume differences calculated via use of the TLS method remained at a relatively low figure, at only around 5%, thereby revealing the existence of inherent limitations in the application of cerebrovascular segmentation. The proposed TLS method holds the potential for utilisation in automatic aneurysm segmentation without the setting of a seed point or intensity threshold. This technique will further enable the segmentation of anatomically complex cerebrovascular shapes, thereby allowing for more accurate and efficient simulations of medical imagery.
Artificially Positive Crossmatches Not Leading to the Refusal of Kidney Donations due to the Usage of Adequate Diagnostic Tools
Authors: Schlaf G. , Pollok-Kopp B. , Schabel E. , Altermann W.
Published: March 2013

Allografting patients with human leukocyte antigens (HLA) which are recognized by preformed antibodies constitutes the main cause for hyper-acute or acute rejections. In order to select recipients without these donor-specific antibodies, the complement-dependent cytotoxicity crossmatch (CDC-CM) assay was developed as a standard procedure about forty years ago. The negative outcome of pretransplant crossmatching represents the most important requirement for a successful kidney graft survival. The artificially positive outcomes of CDC-based crossmatches due to the underlying disease Systemic Lupus Erythematosus (SLE), however, may lead to the unjustified refusal of adequate kidney grafts. Two prospective female recipients destined for a living as well as for a cadaver kidney donation, respectively, exhibited positive CDC-based crossmatch outcomes although for both patients no historical immunizing events were known. Furthermore, solid phase-based screening or antibody differentiation analyses never led to positive results. Immediate reruns of the CDC-based crossmatch assays using the alternative antibody monitoring system (AMS-)crossmatch ELISA resulted in unequivocally negative outcomes. Consequently both transplantations were performed without any immunological complications for the hitherto follow-up time of 25 and 28 months, respectively. We here show two case reports demonstrating an alternative methodical approach to circumvent CDC-based artefacts and point to the urgent need to substitute the CDC-based crossmatch procedure at least for special groups of patients.
Ischaemic Heart Disease: Accuracy of the Prehospital Diagnosis—A Retrospective Study
Authors: Hansen Louise Houlberg , Mikkelsen Søren
Published: March 2013

Purpose. Correct prehospital diagnosis of ischaemic heart disease (IHD) may accelerate and improve the treatment. We sought to evaluate the accuracy of prehospital diagnoses of ischemic heart diseases assigned by physicians.Methods. The Mobile Emergency Care Unit (MECU) in Odense, Denmark, services a population of 260.000. All admissions in 2009 concerning patients diagnosed in the IHD category were assessed. Outcome and diagnosis of each patient were manually validated in accordance to the final diagnosis established following admission to hospital, using the discharge summary from the relevant department as reference.Results. 428 MECU runs with a prehospital diagnosis of IHD were registered. 422 of these were included in the study and 354 of those patients were suitable for this analysis. 73,4% of the patients hospitalized with a prehospital diagnosis of IHD were initially admitted to the relevant ward. Of these patients, 40,0% had their preliminary diagnosis of IHD confirmed. 14,1% of all patients admitted to the hospital were diagnosed with nonheart conditions. Preliminary diagnoses of STEMI had an accuracy of 87,5%.Conclusions. The preliminary IHD diagnoses assigned by the MECU physicians were acceptable. In case of STEMI patients the diagnostic accuracy was excellent. In this study there was an apparent overtriage.
Common Fixed Point for Three Pairs of Self-Maps Satisfying Common (E.A) Property in Generalized Metric Spaces
Authors: Gu Feng , Yin Yun
Published: March 2013

Using the concept of common (E.A) property, we prove a common fixed point theorem for three pairs of weakly compatible self-maps satisfying a new contractive condition in the framework of a generalized metric space. Our results do not rely on any commuting or continuity condition of mappings. An example is provided to support our result. The results obtained in this paper differ from the recent relative results in the literature.
Differences in the Characteristics of Barrett’s Esophagus and Barrett’s Adenocarcinoma between the United States and Japan
Authors: Oryu Makoto , Mori Hirohito , Kobara Hideki , Nishiyama Noriko , Fujihara Shintaro , Kobayashi Mitsuyoshi , Yasuda Mitsugu , Masaki Tsutomu
Published: March 2013

In Europe and the United States, the incidence of esophageal adenocarcinoma has increased 6-fold in the last 25 years and currently accounts for more than 50% of all esophageal cancers. Barrett’s esophagus is the source of Barrett’s adenocarcinoma and is characterized by the replacement of squamous epithelium with columnar epithelium in the lower esophagus due to chronic gastroesophageal reflux disease (GERD). Even though the prevalence of GERD has recently been increasing in Japan as well as in Europe and the United States, the clinical situation of Barrett’s esophagus and Barrett’s adenocarcinoma differs from that in Western countries. In this paper, we focus on specific differences in the background factors and pathophysiology of these lesions.
Exact Solutions of a Generalized Weighted Scale Free Network
Authors: Tan Li , Lei Dingyou
Published: March 2013

We investigate a class of generalized weighted scale-free networks, where the new vertex connects tompairs of vertices selected preferentially. The key contribution of this paper is that, from the standpoint of random processes, we provide rigorous analytic solutions for the steady state distributions, including the vertex degree distribution, the vertex strength distribution and the edge weight distribution. Numerical simulations indicate that this network model yields three power law distributions for the vertex degrees, vertex strengths and edge weights, respectively.
A Nonlinear Optimization Technique of Tunnel Construction Based on DE and LSSVM
Authors: Jun Xing , Annan Jiang , Zhiwu Wen , Jingping Qiu
Published: March 2013

Tunnel construction is a dynamic controlling system with observability and controllability; the feedback analysis requires identifying geophysics parameters and adjusting supporting parameters, and both of them are optimisation problems. The paper proposed a nonlinear optimization technique based on difference evolution arithmetic (DEA), least square support vector machine (LSSVM), and three dimensional numerical simulation. This method employs support vector machine with optimal architecture trained by the difference evolution arithmetic, instead of the time-consuming finite element analysis. Firstly, the three dimensional numerical simulation is used to create training and testing samples for LSSVM model construction. Then the nonlinear relationship between rock or anchoring parameters and displacement is constructed by support vector machine. Finally, the geophysics and supporting parameters are obtained by DE optimization arithmetic. The technique overcomes the conventional optimization method shortages of expending too much computing time and easily being limited in local optimal solution. This technique was verified by applying it to the feedback analysis of Dalian Metro in China, and the influence of the parameters of LSSVM and DE on the simulation ability of the algorithm was investigated.
Multidisciplinary Management of a Giant Plexiform Neurofibroma by Double Sequential Preoperative Embolization and Surgical Resection
Authors: Vélez Roberto , Barrera-Ochoa Sergi , Barastegui David , Pérez-Lafuente Mercedes , Romagosa Cleofe , Pérez Manuel
Published: March 2013

Plexiform neurofibromas are benign tumors originating from subcutaneous or visceral peripheral nerves, which are usually associated with neurofibromatosis type 1. Giant neurofibromas are very difficult to manage surgically as they are extensively infiltrative and highly vascularized. These types of lesions require complex preoperative and postoperative management strategies. This case report describes a 22-year-old female with a giant plexiform neurofibroma of the lower back and buttock who underwent pre-operative embolization and intraoperative use of a linear cutting stapler system to assist with haemostasis during the surgical resection. Minimal blood transfusion was required and the patient made a good recovery. This case describes how a multidisciplinary management of these large and challenging lesions is technically feasible and appears to be beneficial in reducing perioperative blood loss and morbidity. Giant neurofibroma is a poorly defined term used to describe a neurofibroma that has grown to a significant but undefined size. Through a literature review, we propose that the term “giant neurofibroma” be used for referring to those neurofibromas weighing 20% or more of the patient's total corporal weight.
Bazedoxifene Exhibits Antiestrogenic Activity in Animal Models of Tamoxifen-Resistant Breast Cancer: Implications for Treatment of Advanced Disease
Authors: Wardell Suzanne E. , Nelson Erik R. , Chao Christina A. , McDonnell Donald P.
Published: March 2013

Purpose: There is compelling evidence to suggest that drugs that function as pure estrogen receptor (ER-α) antagonists, or that downregulate the expression of ER-α, would have clinical use in the treatment of advanced tamoxifen- and aromatase-resistant breast cancer. Although such compounds are currently in development, we reasoned, based on our understanding of ER-α pharmacology, that there may already exist among the most recently developed selective estrogen receptor modulators (SERM) compounds that would have usage as breast cancer therapeutics. Thus, our objective was to identify among available SERMs those with unique pharmacologic activities and to evaluate their potential clinical use with predictive models of advanced breast cancer.

Experimental Design: A validated molecular profiling technology was used to classify clinically relevant SERMs based on their impact on ER-α conformation. The functional consequences of these observed mechanistic differences on (i) gene expression, (ii) receptor stability, and (iii) activity in cellular and animal models of advanced endocrine-resistant breast cancer were assessed.

Results: The high-affinity SERM bazedoxifene was shown to function as a pure ER-α antagonist in cellular models of breast cancer and effectively inhibited the growth of both tamoxifen-sensitive and -resistant breast tumor xenografts. Interestingly, bazedoxifene induced a unique conformational change in ER-α that resulted in its proteasomal degradation, although the latter activity was dispensable for its antagonist efficacy.

Conclusion: Bazedoxifene was recently approved for use in the European Union for the treatment of osteoporosis and thus may represent a near-term therapeutic option for patients with advanced breast cancer. Clin Cancer Res; 19(9); 2420–31. ©2013 AACR.
Endothelial Cells Enhance Prostate Cancer Metastasis via IL-6→Androgen Receptor→TGF-β→MMP-9 Signals
Authors: Wang Xiaohai , Lee Soo Ok , Xia Shujie , Jiang Qi , Luo Jie , Li Lei , Yeh Shuyuan , Chang Chawnshang
Published: March 2013

Although the potential roles of endothelial cells in the microvascules of prostate cancer during angiogenesis have been documented, their direct impacts on the prostate cancer metastasis remain unclear. We found that the CD31-positive and CD34-positive endothelial cells are increased in prostate cancer compared with the normal tissues and that these endothelial cells were decreased upon castration, gradually recovered with time, and increased after prostate cancer progressed into the castration-resistant stage, suggesting a potential linkage of these endothelial cells with androgen deprivation therapy. The in vitro invasion assays showed that the coculture of endothelial cells with prostate cancer cells significantly enhanced the invasion ability of the prostate cancer cells. Mechanism dissection found that coculture of prostate cancer cells with endothelial cells led to increased interleukin (IL)-6 secretion from endothelial cells, which may result in downregulation of androgen receptor (AR) signaling in prostate cancer cells and then the activation of TGF-β/matrix metalloproteinase-9 (MMP-9) signaling. The consequences of the IL-6→AR→TGFβ→MMP-9 signaling pathway might then trigger the increased invasion of prostate cancer cells. Blocking the IL-6→AR→TGFβ→MMP-9 signaling pathway either by IL-6 antibody, AR-siRNA, or TGF-β1 inhibitor all interrupted the ability of endothelial cells to influence prostate cancer invasion. These results, for the first time, revealed the important roles of endothelial cells within the prostate cancer microenvironment to promote the prostate cancer metastasis and provide new potential targets of IL-6→AR→TGFβ→MMP-9 signals to battle the prostate cancer metastasis. Mol Cancer Ther; 12(6); 1026–37. ©2013 AACR.
Old genes and new genes: The evolution of the kallikrein locus
Authors: Lundwall Åke
Published: March 2013

The human kallikrein locus consists of KLK1, the gene of major tissue kallikrein, and 14 genes of kallikrein-related peptidases (KLKs) located in tandem on chromosome 19q13.3-13.4. In this review, based on information retrieved from the literature or extracted from genome databases, it is hypothesised that the kallikrein locus is unique to mammals. The majority of genes are highly conserved, as demonstrated by the identification of 11 KLK genes in the opossum, a metatherian species. In contrast, a sublocus, encompassing KLK1-4, has gone through major transformations that have generated new genes, which in most cases are closely related to KLK1. In the primate lineage, this process created KLK3, the gene of the prostate cancer marker, prostate-specific antigen (PSA), whereas in the murine lineage it gave rise to 13 genes unique to the mouse and nine unique to the rat. The KLK proteases are effector molecules that emerged early in mammalian evolution and their importance in skin homeostasis and male reproductive function is undisputed and there are also accumulating evidence for a role of KLK proteases in the development of the brain. It is speculated that the KLK gene family arose as part of the process that generated distinguishing mammalian features, like skin with hair and sweat glands, and specialised anatomical attributes of the brain and the reproductive tract.
Cardiac-Selective Expression of Extracellular Superoxide Dismutase After Systemic Injection of Adeno-Associated Virus 9 Protects the Heart Against Post–Myocardial Infarction Left Ventricular Remodeling
Authors: Konkalmatt Prasad R. , Beyers Ronald J. , O’Connor Daniel M. , Xu Yaqin , Seaman Marc E. , French Brent A.
Published: March 2013

Background—

Cardiac magnetic resonance imaging has not been used previously to document the attenuation of left ventricular (LV) remodeling after systemic gene delivery. We hypothesized that targeted expression of extracellular superoxide dismutase (EcSOD) via the cardiac troponin-T promoter would protect the mouse heart against both myocardial infarction (MI) and subsequent LV remodeling.

Methods and Results—

Using reporter genes, we first compared the specificity, time course, magnitude, and distribution of gene expression from adeno-associated virus (AAV) 1, 2, 6, 8, and 9 after intravenous injection. The troponin-T promoter restricted gene expression largely to the heart for all AAV serotypes tested. AAV1, 6, 8, and 9 provided early-onset gene expression that approached steady-state levels within 2 weeks. Gene expression was highest with AAV9, which required only 3.15×10
11
viral genomes per mouse to achieve an 84% transduction rate. AAV9-mediated, cardiac-selective gene expression elevated EcSOD enzyme activity in heart by 5.6-fold (
P
=0.015), which helped protect the heart against both acute MI and subsequent LV remodeling. In acute MI, infarct size in EcSOD-treated mice was reduced by 40% compared with controls (
P
=0.035). In addition, we found that cardiac-selective expression of EcSOD increased myocardial capillary fractional area and decreased neutrophil infiltration after MI. In a separate study of LV remodeling, after a 60-minute coronary occlusion, cardiac magnetic resonance imaging revealed that LV volumes at days 7 and 28 post-MI were significantly lower in the EcSOD group compared with controls.

Conclusions—

Cardiac-selective expression of EcSOD from the cardiac troponin-T promoter after systemic administration of AAV9 provides significant protection against both acute MI and LV remodeling.
MicroRNA in Cardiovascular Calcification
Authors: Goettsch Claudia , Hutcheson Joshua D. , Aikawa Elena
Published: March 2013

Cardiovascular calcification is a prominent feature of chronic inflammatory disorders—such as chronic kidney disease, type 2 diabetes mellitus, and atherosclerosis—that associate with significant morbidity and mortality. The concept that similar pathways control both bone remodeling and vascular calcification is widely accepted, but the precise mechanisms of calcification remain largely unknown. The central role of microRNAs (miRNA) as fine-tune regulators in the cardiovascular system and bone biology has gained acceptance and has raised the possibility for novel therapeutic targets. Additionally, circulating miRNAs have been proposed as biomarkers for a wide range of cardiovascular diseases, but knowledge of miRNA biology in cardiovascular calcification is very limited. This review focuses on the role of miRNAs in cardiovascular disease, with emphasis on osteogenic processes. Herein, we discuss the current understanding of miRNAs in cardiovascular calcification. Furthermore, we identify a set of miRNAs common to diseases associated with cardiovascular calcification (chronic kidney disease, type 2 diabetes mellitus, and atherosclerosis), and we hypothesize that these miRNAs may provide a molecular signature for calcification. Finally, we discuss this novel hypothesis with emphasis on known biological and pathological osteogenic processes (eg, osteogenic differentiation, release of calcifying matrix vesicles). The aim of this review is to provide an organized discussion of the known links between miRNA and calcification that provide emerging concepts for future studies on miRNA biology in cardiovascular calcification, which will be critical for developing new therapeutic strategies.
Weighted elliptic curve-fitting method with sub-pixel level in the light-probe vision measuring system
Authors: Chen Yuming , Zhang Guangming , Yuan Yuhao , Zhao Yinkai
Published: March 2013

In a light-probe vision measuring system, we first extract a rough contour of the marking points based on adaptive canny edge detection, in order to improve the extracting accuracy of the image co-ordinate of the marking points’ centre. This paper shows that the edge of rough contour may be sub-pixel extracted with the method of the grey moment. This method can be extrapolated to any position in the image plane. Finally, the image co-ordinates of marking points’ centre can be obtained with the weighted least-squares curve-fitting. In this paper, we extend the existing technique and provide a comprehensive evaluation of the proposed method. The results show that this method has higher stability precision than the exiting one. The extraction accuracy of this technique can achieve as low as 0.01 pixels. We have incorporated these ideas into the actual vision measurement of the Canny Elevator Co., Ltd.
Building leadership capacity in the involving network state
Authors: Pedersen Dorthe , Tangkjær Christian
Published: March 2013

New partnerships, cross-organisational collaborations and co-creation, digitalisation, involvement of citizens, public design and innovation stand out as new and emerging solutions in welfare delivery. However, New Public Management (NPM) seems to represent a historical repertoire of perspectives and tools that falls short of dealing with public sector challenges and the complex problems of producing welfare and public value in times of austerity. In the article, we outline a diagnosis of the emerging governance regime of the Involving Network State, and we discuss how to build involving learning communities in order to conduct the needed leadership capabilities and incorporate the impact of leadership education in a multi-contextual public sector. We argue that critical reflexivity needs to be a pivotal point in leadership programmes.
The role of serotonin in cognitive function: evidence from recent studies and implications for understanding depression
Authors: Cowen Philip , Sherwood Ann C
Published: March 2013

Background:

Symptoms of cognitive impairment such as poor concentration, memory loss and difficulty with decision making are prevalent in patients with depression, but currently are not specific targets for treatment. However, patients can continue to demonstrate cognitive impairments even when apparently clinically recovered. Drugs that potentiate serotonin (5-HT) function, such as selective serotonin reuptake inhibitors (SSRIs), are the mainstay of treatment for depression. Nevertheless, our understanding of the effects of SSRIs and other conventional antidepressant therapy on cognitive function in healthy humans and depressed patients remains limited.

Objective:

The purpose of this article is to provide a concise overview for clinicians on the impact of pharmacological manipulation of 5-HT on cognitive function in healthy humans with additional reference to animal models where human data are lacking, particularly regarding specific 5-HT receptor subtype modulation.

Findings:

The most consistent observation following manipulation of serotonin levels in humans is that low extracellular 5-HT levels are associated with impaired memory consolidation. Preclinical data show that agonism and antagonism at specific 5-HT receptors can exert effects in animal models of cognition.

Conclusions:

Larger, consistently designed studies are needed to understand the roles of 5-HT in cognition in healthy and depressed individuals. Efforts to target specific 5-HT receptors to improve cognitive outcomes are warranted.
The Medicine of the Manuka
Authors: Old Natasha
Published: March 2013

As nursing moves into the next paradigm of health care, there is an increasing shift toward integrative health care that is founded on the integration of traditional or complementary medicines alongside biomedicine. As part of the shift nurses are increasingly observing clients accessing traditional forms of medicine. One such product that has been used for hundreds of years and is more recently being incorporated into nursing care is the honey produced by bees pollinating Leptospermum scoparium, traditionally known as Manuka. Manuka honey is currently used widely in wound care and as a topical antibacterial, antifungal, and anti-inflammatory. Review of the literature supports a very effective and low-risk botanical intervention that is both cost-effective and easily accessible. There is future scope for the use of L. scoparium oil products in nursing and potential for further research to continue to discover its effectiveness.
From ClinicalTrials.gov trial registry to an analysis-ready database of clinical trial results
Authors: Cepeda M Soledad , Lobanov Victor , Berlin Jesse A
Published: March 2013

Background

The ClinicalTrials.gov web site provides a convenient interface to look up study results, but it does not allow downloading data in a format that can be readily used for quantitative analyses.

Purpose

To develop a system that automatically downloads study results from ClinicalTrials.gov and provides an interface to retrieve study results in a spreadsheet format ready for analysis.

Methods

Sherlock® identifies studies by intervention, population, or outcome of interest and in seconds creates an analytic database of study results ready for analyses. The outcome classification algorithms used in Sherlock were validated against a classification by an expert.

Conclusions

Having a database ready for analysis that can be updated automatically, dramatically extends the utility of the ClinicalTrials.gov trial registry. It increases the speed of comparative research, reduces the need for manual extraction of data, and permits answering a vast array of questions.
Bivariate distribution models using copulas for reliability analysis
Authors: Tang Xiao-Song , Li Dian-Qing , Zhou Chuang-Bing , Zhang Li-Min
Published: March 2013

The modeling of joint probability distributions of correlated variables and the evaluation of reliability under incomplete probability information remain a challenge that has not been studied extensively. This article aims to investigate the effect of copulas for modeling dependence structures between variables on reliability under incomplete probability information. First, a copula-based method is proposed to model the joint probability distributions of multiple correlated variables with given marginal distributions and correlation coefficients. Second, a reliability problem is formulated and a direct integration method for calculating probability of failure is presented. Finally, the reliability is investigated to demonstrate the effect of copulas on reliability. The joint probability distribution of multiple variables, with given marginal distributions and correlation coefficients, can be constructed using copulas in a general and flexible way. The probabilities of failure produced by different copulas can differ considerably. Such a difference increases with decreasing probability of failure. The reliability index defined by the mean and standard deviation of a performance function cannot capture the difference in the probabilities of failure produced by different copulas. In addition, the Gaussian copula, often adopted out of expedience without proper validation, produces only one of the various possible solutions of the probability of failure and such a probability of failure may be biased towards the non-conservative side. The tail dependence of copulas has a significant influence on reliability.
Impact of isolated germline JAK2V617I mutation on human hematopoiesis
Authors: Mead Adam J. , Chowdhury Onima , Pecquet Christian , Dusa Alexandra , Woll Petter , Atkinson Deborah , Burns Adam , Score Joannah , Rugless Michelle , Clifford Ruth , Moule Simon , Bienz Nicola , Vyas Paresh , Cross Nick , Gale Rosemary E. , Henderson Shirley , Constantinescu Stefan N. , Schuh Anna , Jacobsen Sten Eirik W.
Published: March 2013

Key Points

Germline JAK2V617I mutation as a sole genetic event does not suppress hematopoietic stem cells. JAK2V617I induces weaker constitutive activation than JAK2V617F but considerable cytokine hyperresponsiveness.
Tat engagement of p38 MAP kinase and IRF7 pathways leads to activation of interferon-stimulated genes in antigen-presenting cells
Authors: Kim Nayoung , Kukkonen Sami , Martinez-Viedma Maria Del Pilar , Gupta Sumeet , Aldovini Anna
Published: March 2013

Key Points

Tat acts as an inflammatory cytokine and as an antiviral factor via interaction with MAP2K6, MAP2K3, and IRF7 promoters in APCs. These interactions are the molecular events that link HIV to p38 MAPK activation, which is a mediator of HIV-associated pathology and immune activation.
Construction of a plant-transformation-competent BIBAC library and genome sequence analysis of polyploid Upland cotton (Gossypium hirsutumL.)
Authors: Lee Mi-Kyung , Zhang Yang , Zhang Meiping , Goebel Mark , Kim Hee Jin , Triplett Barbara A , Stelly David M , Zhang Hong-Bin
Published: March 2013

Background

Cotton, one of the world’s leading crops, is important to the world’s textile and energy industries, and is a model species for studies of plant polyploidization, cellulose biosynthesis and cell wall biogenesis. Here, we report the construction of a plant-transformation-competent binary bacterial artificial chromosome (BIBAC) library and comparative genome sequence analysis of polyploid Upland cotton (Gossypium hirsutum L.) with one of its diploid putative progenitor species, G. raimondii Ulbr.

Results

We constructed the cotton BIBAC library in a vector competent for high-molecular-weight DNA transformation in different plant species through either Agrobacterium or particle bombardment. The library contains 76,800 clones with an average insert size of 135 kb, providing an approximate 99% probability of obtaining at least one positive clone from the library using a single-copy probe. The quality and utility of the library were verified by identifying BIBACs containing genes important for fiber development, fiber cellulose biosynthesis, seed fatty acid metabolism, cotton-nematode interaction, and bacterial blight resistance. In order to gain an insight into the Upland cotton genome and its relationship with G. raimondii, we sequenced nearly 10,000 BIBAC ends (BESs) randomly selected from the library, generating approximately one BES for every 250 kb along the Upland cotton genome. The retroelement Gypsy/DIRS1 family predominates in the Upland cotton genome, accounting for over 77% of all transposable elements. From the BESs, we identified 1,269 simple sequence repeats (SSRs), of which 1,006 were new, thus providing additional markers for cotton genome research. Surprisingly, comparative sequence analysis showed that Upland cotton is much more diverged from G. raimondii at the genomic sequence level than expected. There seems to be no significant difference between the relationships of the Upland cotton D- and A-subgenomes with the G. raimondii genome, even though G. raimondii contains a D genome (D5).

Conclusions

The library represents the first BIBAC library in cotton and related species, thus providing tools useful for integrative physical mapping, large-scale genome sequencing and large-scale functional analysis of the Upland cotton genome. Comparative sequence analysis provides insights into the Upland cotton genome, and a possible mechanism underlying the divergence and evolution of polyploid Upland cotton from its diploid putative progenitor species, G. raimondii.
Demonstration of protein-fragment complementation assay using purified firefly luciferase fragments
Authors: Ohmuro-Matsuyama Yuki , Chung Chan-I , Ueda Hiroshi
Published: March 2013

Background

Human interactome is predicted to contain 150,000 to 300,000 protein-protein interactions, (PPIs). Protein-fragment complementation assay (PCA) is one of the most widely used methods to detect PPI, as well as Förster resonance energy transfer (FRET). To date, successful applications of firefly luciferase (Fluc)-based PCA have been reported in vivo, in cultured cells and in cell-free lysate, owing to its high sensitivity, high signal-to-background (S/B) ratio, and reversible response. Here we show the assay also works with purified proteins with unexpectedly rapid kinetics.

Results

Split Fluc fragments both fused with a rapamycin-dependently interacting protein pair were made and expressed in E. coli system, and purified to homogeneity. When the proteins were used for PCA to detect rapamycin-dependent PPI, they enabled a rapid detection (~1 s) of PPI with high S/B ratio. When Fn7-8 domains (7 nm in length) that was shown to abrogate GFP mutant-based FRET was inserted between split Fluc and FKBP12 as a rigid linker, it still showed some response, suggesting less limitation in interacting partner’s size. Finally, the stability of the probe was investigated. Preincubation of the probes at 37 degreeC up to 1 h showed marked decrease of the luminescent signal to 1.5%, showing the limited stability of this system.

Conclusion

Fluc PCA using purified components will enable a rapid and handy detection of PPIs with high S/B ratio, avoiding the effects of concomitant components. Although the system might not be suitable for large-scale screening due to its limited stability, it can detect an interaction over larger distance than by FRET. This would be the first demonstration of Fluc PCA in vitro, which has a distinct advantage over other PPI assays. Our system enables detection of direct PPIs without risk of perturbation by PPI mediators in the complex cellular milieu.
Optimized gold nanoshell ensembles for biomedical applications
Authors: Sikdar Debabrata , Rukhlenko Ivan D , Cheng Wenlong , Premaratne Malin
Published: March 2013

We theoretically study the properties of the optimal size distribution in the ensemble of hollow gold nanoshells (HGNs) that exhibits the best performance at in vivo biomedical applications. For the first time, to the best of our knowledge, we analyze the dependence of the optimal geometric means of the nanoshells’ thicknesses and core radii on the excitation wavelength and the type of human tissue, while assuming lognormal fit to the size distribution in a real HGN ensemble. Regardless of the tissue type, short-wavelength, near-infrared lasers are found to be the most effective in both absorption- and scattering-based applications. We derive approximate analytical expressions enabling one to readily estimate the parameters of optimal distribution for which an HGN ensemble exhibits the maximum efficiency of absorption or scattering inside a human tissue irradiated by a near-infrared laser.
Design of a multi-walled carbon nanotube field emitter with micro vacuum gauge
Authors: Dong Ki-Young , Lee Yang Doo , Kang Byung Hyun , Choi Jinnil , Ju Byeong-Kwon
Published: March 2013

The variation of vacuum level inside a field emission device when electron is emitted from multi-walled carbon nanotubes (MWCNTs) by electric field was measured where MWCNT gauge packaged with a vacuum device was used to measure the degree of a vacuum until the end of the vacuum device life. It was found that the electrical properties of MWCNTs altered with the degree of a vacuum. We fabricated MWCNT gauge which were printed and pasted by the screen printer. In this paper, we report the successful detection of the ionization of gases in vacuum state.