bluuebunny/crossref_metadata_2025 huggingface dataset:
Characterization of multilayer structures in fiber reinforced polymer employing synchrotron and laboratory X-ray CT
Authors: Wirjadi Oliver , Godehardt Michael , Schladitz Katja , Wagner Björn , Rack Alexander , Gurka Martin , Nissle Sebastian , Noll Andreas
Published: May 2014

Specimens of carbon or glass fiber reinforced polymer can be imaged using both conventional laboratory X-ray micro-computed tomography equipment and synchrotron light sources. The image quality when using intense (partially) coherent synchrotron light is still superior, especially when applying phase-retrieval algorithms. In the resulting volume images, the fiber direction distribution and other mechanically relevant parameters such as volume fractions or layer thickness can be determined. In this contribution, we will demonstrate how fiber direction results can be used to detect regions with locally different fiber orientations in carbon or glass fiber reinforced polymer which arise in the molding process of such samples. To this end, we evaluate the three-dimensional fiber orientation tensor locally across the thickness of different specimens. For each resulting individual layer, we can automatically detect the layer thickness and the preferred fiber direction. These methods have been successfully applied to various commercial specimens. We will demonstrate results on volume images of samples from both synchrotron and laboratory micro-computed tomography and discuss the specific advantages and disadvantages in this application.
Tribological and micro/nano-structural characterization of some Fe-based sintered composites
Authors: Merie Violeta , Pustan Marius , Bîrleanu Corina , Cândea Viorel , Popa Cătălin
Published: May 2014

New iron-based composites were investigated for applications within the friction materials domain. This study presents the elaboration and the structural and tribological characterization of iron-based friction composites containing iron, copper, graphite and/or nickel, introduced in a powder state. The technology employed for obtaining these materials is via a classical powder metallurgy route. The porosity of the studied materials, the tribological characterization, the roughness of researched composites and their structure are marked out. Results showed that the samples elaborated from the material with 10 wt.% Cu, 7 wt.% graphite, 12 wt.% Ni and the rest iron, compacted at 600 MPa, presented the best tribological behavior. The presence of pearlite, ferrite, nickel-based and copper-based solid solutions and free graphite in composite structures is highlighted.
Impact toughness of welds deposited on H13 hot work tool steel
Authors: Mulc Matjaž , Skumavc Andrej , Taljat Boštjan , Tušek Janez
Published: May 2014

This paper presents the experimental results of the impact toughness and hardness of welds deposited on H13 hot work tool steel. To obtain the optimum combination of high hardness and high toughness, multipass gas tungsten arc welding was used to melt four different commercially available filler materials suitable for repair welding of HWTS. Special geometry of the welding sample is presented in this work. The focus is also on the technique of the preparation of the V-shaped notch in order to precisely evaluate the impact toughness. Two different preheating temperatures and two different post weld heat treatments were applied to the samples in order to obtain the effect of heat treatment on the impact toughness and hardness. Data show that weld deposited with filler material C on the base of the hot work tool steel and alloyed with vanadium exhibits high impact toughness in combination with high hardness in the as-welded condition and also after tempering.
Industrialised nanocrystalline bainitic steels. Design approach
Authors: Garcia-Mateo Carlos , Caballero Francisca G. , Sourmail Thomas , Smanio Veronique , de Andres Carlos Garcia
Published: May 2014

Nanostructured microstructures consisting of a mixture of very thin plates of bainitic ferrite separated by C-enriched austenite are the main characteristics of the so called NANOBAIN steel family. This paper shows the theoretical approach followed in the design of a new, industrially viable, generation of NANOBAIN steels, a process in which industrial demands such as simpler chemical compositions, faster transformation kinetics and sufficient hardenability have also been considered. The microstructural and mechanical characterization of the bainitic microstructures obtained by isothermal transformation at different temperatures, come to confirm and to validate the theoretical approach used.
Metallurgical Failure Investigation of Minor Leakage in a Fuel Oil Return Line of a Combined Cycle Gas Turbine Engine
Authors: Fischer B. , Cagliyan E. , Neidel A.
Published: May 2014

A small fuel oil return line of a stationary gas turbine engine failed by high cycle fatigue cracking. In the metallurgical root cause investigation, performed by the original equipment manufacturer's laboratory, it was determined that insufficient support of the fuel line and the ensuing vibration led to dynamic alternating bending stresses, that had their maximum immediately adjacent to the connector weld of the flange. The piping system was made of metastable austenitic stainless steels. Constraint in the system at the flange, geometric notches in the weld caused by root reinforcement and excess weld metal at the weld toe, were all determined to have been contributing factors. What is more, the unavoidable metallurgical notch represented by the heat affected zone (HAZ) of the weld joint with its coarse-grained microstructure, may also have contributed to the cracking. The root cause of the failure was a design problem, because sufficient pipe support was not specified. The primary cause of failure was assembly, where the missing supports were not realised to be a potential problem. The organisational cause of failure was insufficient training of design and assembly personnel. Finally, the metallurgical or physical cause of failure was fatigue. It was recommended to provide for additional support brackets in the affected pipe length, in order to prevent the fuel oil return line from vibrating excessively.
External Calibration in PA12 Tube Extrusion
Authors: Carin A. , Haudin J.-M. , Vincent M. , Monasse B. , Bellet G. , Amouroux N.
Published: May 2014

In polyamide 12 (PA12) tube extrusion, calibration is crucial for the major final properties such as elongation at break or burst pressure. In external calibration, the extruded tube is pulled through a cylindrical calibrator located in a water tank under vacuum. A water flow rate is applied at the calibrator inner side, creating a lubricating water layer at the polymer outer surface. A combination of a quenching and a mechanical drawing was highlighted during calibration by on-line measurements. A subsequent high molecular orientation in the outer tube layers was also featured by X-Ray diffraction and birefringence evaluation in light microscopy. Besides, influence of lubrication level in the sizing-sleeve was investigated by an estimate of the lubricating water layer and a characterization of the tube final surface state in different calibration conditions. Firstly, we quantitatively showed that rising the water layer thickness leads to a diminution of the draw ratio in the calibration tank, DrCAL (ratio between line velocity and velocity at the calibrator entrance). Excellent correlation has been found between tube superficial orientation and DrCAL: a reduced elongation of the polymer in the calibrator leads to a lower level of superficial orientation. Secondly, two kinds of surface defects were detected on the tubes by light microscopy and microtopography. At last, several correlations were featured with mechanical properties. Elongation at break was found to strongly depend on the molecular orientation resulting from calibration. Moreover, origin of rupture was investigated during tensile testing in light microscopy. We emphasized that surface defects alignments perpendicular to the extrusion initiate the rupture by creating a significant crack via coalescence of initial defects. Thus, microstructure, surface state and tensile properties can be controlled by fitting the calibration parameters to improve lubrication and reduce the draw ratio in calibrator.
Heat Transfer through Metal Walls of Finite Thickness
Authors: Janeschitz-Kriegl M. , Janeschitz-Kriegl H. , Eder G. , Forstner R.
Published: May 2014

A quenching technique is scrutinized, where the surface of a polymer melt is brought into contact with a metal wall of a well defined lower temperature at time zero. Usually, this wall temperature has approximately been kept constant with the aid of a streaming heat transfer fluid. It turns out, however, that an exactly invariable wall temperature or a finite Biot number (finite heat transfer coefficient to the cooling fluid) are inadequate assumptions. However, an exact interface temperature is to berealized, if the crystallization kinetics of the polymer is to be investigated painstakingly at this interface. The reason for this requirement lies in the fact that the said kinetics is extremely sensitive to small temperature changes. The present contribution shows that a water cooled metal wall of small thickness is inadequate for the purpose. A rather thick metal wall, which is preheated to the required temperature and thermally insulated at the outside, is clearly preferable. Copper is better than steel.
Quantitative Analysis for Polymer Degradation in the Extrusion Process
Authors: Kometani H. , Matsumura T. , Suga T. , Kanai T.
Published: May 2014

Polymer degradation in the extrusion process decreases quality and productivity. For this reason, it is necessary to prevent polymer degradation. In the extrusion process, polymer degradation is caused by oxidation. It depends on the processing temperature and the amount of dissolved oxygen in the molten polymer. Therefore, a quantitative analysis of these factors is required.

As for the degradation characteristics of the material used in this study, temperature and oxygen concentration dependency of the oxidation rate could be quantitatively characterized with an apparatus to evaluate polymer degradation which utilized chemiluminescence generated by an oxidation reaction.

Moreover, an online measuring apparatus to analyze dissolved gas in the extruded molten polymer was developed. With this apparatus, the volume ratio of dissolved gases (N2, O2 etc.) to the extruded molten polymer could be quantitatively analyzed and the quality of the extruded molten polymer evaluated.

With this apparatus, dissolved nitrogen (an index of entrained air) was analyzed with a full-flight screw and a barrier screw. Furthermore, observation of cross sectional views in the screw channel obtained from the cooling experiment under the operating conditions was carried out for the full-flight screw and the barrier screw. With the full-flight screw, break up phenomenon (collapse of solid polymer) occurred in the screw channel and the amount of nitrogen increased. With the barrier screw, the amount of nitrogen decreased because of prevention of the break up phenomenon in the screw channel.

Consequently, it is shown that the use of the barrier screw is suitable for oxygen reduction in the molten polymer, which is a factor in causing polymer degradation.
Volumetric response to radiosurgery for brain metastasis varies by cell of origin
Authors: Iyer Aditya , Harrison Gillian , Kano Hideyuki , Weiner Gregory M. , Luther Neal , Niranjan Ajay , Flickinger John C. , Lunsford L. Dade , Kondziolka Douglas
Published: May 2014

Object

The aim of this study was to evaluate the imaging response of brain metastases after radiosurgery and to correlate the response with tumor type and patient survival.

Methods

The authors conducted a retrospective review of patients who had undergone Gamma Knife radiosurgery for brain metastases from non–small cell lung cancer (NSCLC), breast cancer, or melanoma. The imaging volumetric response by tumor type was plotted at 3-month intervals and classified as a sustained decrease in tumor volume (Type A), a transient decrease followed by a delayed increase in tumor volume (Type B), or a sustained increase in tumor volume (Type C). These imaging responses were then compared with patient survival and tumor type.

Results

Two hundred thirty-three patients with metastases from NSCLC (96 patients), breast cancer (98 patients), and melanoma (39 patients) were eligible for inclusion in this study. The patients with NSCLC were most likely to exhibit a Type A response; those with breast cancer, a Type B response; and those with melanoma, a Type C response. Among patients with NSCLC, the median overall survival was 11.2 months for those with a Type A response (76 patients), 8.6 months for those with a Type B response (6 patients), and 10.5 months for those with a Type C response (14 patients). Among patients with breast cancer, the median overall survival was 16.6 months in those with a Type A response (65 patients), 18.1 months in those with a Type B response (20 patients), and 7.5 months in those with a Type C response (13 patients). For patients with melanoma, the median overall survival was 5.2 months in those with a Type A response (26 patients) and 6.7 months in those with a Type C response (13 patients). None of the patients with melanoma had a Type B response. The imaging response was significantly associated with survival only in patients with breast cancer.

Conclusions

The various types of imaging responses of metastatic brain tumors after stereotactic radiosurgery depend in part on tumor type. However, the type of response only correlates with survival in patients with breast cancer.
Early sensory protection in reverse end-to-side neurorrhaphy to improve the functional recovery of chronically denervated muscle in rat: a pilot study
Authors: Li Qingtian , Zhang Peixun , Yin Xiaofeng , Han Na , Kou Yuhui , Jiang Baoguo
Published: May 2014

Object

Early innervation by sensory nerves has been proposed to prevent atrophy of chronically denervated muscle, but conventional end-to-end (ETE) neurorrhaphy has been demonstrated to have adverse effects on muscle contractile function. The aim of the present study was to investigate the potential for modified sensory nerve protection in reverse end-to-side (ETS) neurorrhaphy as a way of improving the functional recovery of denervated muscle.

Methods

Four groups of rats underwent surgical denervation of the tibial nerve projecting to the right hindlimbs (Group 1, unprotected controls; Group 2, positive control [immediate repair without delayed denervation]; Group 3, ETS protected; and Group 4, ETE protected). The proximal and distal stumps of the tibial nerve were ligated in all animals except for those in the immediate-repair group. Other animals underwent denervation without sural nerve protection, or with ETE or ETS neurorrhaphy. The ETE- and ETS-protected and unprotected groups underwent an additional surgery in which the trimmed proximal and distal tibial nerve stumps were sutured together. After 3 months of recovery, the tibial function index was determined, and electrophysiological, histological, and morphometric parameters were assessed.

Results

Significant muscle atrophy was observed in the unprotected group, while a well-preserved ultrastructure was observed for the gastrocnemius muscle in the ETE- and ETS-protected groups. Enhanced recovery in the ETS-protected group was indicated by the tibial function index, motor nerve conduction velocity, muscle contractile force tests, and the histological results. In contrast, early sensory nerve protection in ETE neurorrhaphy impaired the recovery of the regenerated axons and diminished the contractile force of the denervated muscle.

Conclusions

Early sensory protection in reverse ETS neurorrhaphy is an effective method for improving the functional recovery of chronically denervated muscle following peripheral nerve injury in rats.
Magnetic resonance neurography evaluation of chronic extraspinal sciatica after remote proximal hamstring injury: a preliminary retrospective analysis
Authors: Bucknor Matthew D. , Steinbach Lynne S. , Saloner David , Chin Cynthia T.
Published: May 2014

Object

Extraspinal sciatica can present unique challenges in clinical diagnosis and management. In this study, the authors evaluated qualitative and quantitative patterns of sciatica-related pathology at the ischial tuberosity on MR neurography (MRN) studies performed for chronic extraspinal sciatica.

Methods

Lumbosacral MRN studies obtained in 14 patients at the University of California, San Francisco between 2007 and 2011 were retrospectively reviewed. The patients had been referred by neurosurgeons or neurologists for chronic unilateral sciatica (≥ 3 months), and the MRN reports described asymmetrical increased T2 signal within the sciatic nerve at the level of the ischial tuberosity. MRN studies were also performed prospectively in 6 healthy volunteers. Sciatic nerve T2 signal intensity (SI) and cross-sectional area at the ischial tuberosity were calculated and compared between the 2 sides in all 20 subjects. The same measurements were also performed at the sciatic notch as an internal reference. Adjacent musculoskeletal pathology was compared between the 2 sides in all subjects.

Results

Seven of the 9 patients for whom detailed histories were available had a specific history of injury or trauma near the proximal hamstring preceding the onset of sciatica. Eight of the 14 patients also demonstrated soft-tissue abnormalities adjacent to the proximal hamstring origin. The remaining 6 had normal muscles, tendons, and marrow in the region of the ischial tuberosity. There was a significant difference in sciatic nerve SI and size between the symptomatic and asymptomatic sides at the level of the ischial tuberosity, with a mean adjusted SI of 1.38 compared with 1.00 (p < 0.001) and a mean cross-sectional nerve area of 0.66 versus 0.54 cm2 (p = 0.002). The control group demonstrated symmetrical adjusted SI and sciatic nerve size.

Conclusions

This study suggests that chronic sciatic neuropathy can be seen at the ischial tuberosity in the setting of prior proximal hamstring tendon injury or adjacent soft-tissue abnormalities. Because hamstring tendon injury as a cause of chronic sciatica remains a diagnosis of exclusion, this distinct category of patients has not been described in the radiographic literature and merits special attention from clinicians and radiologists in the management of extraspinal sciatica. Magnetic resonance neurography is useful for evaluating chronic sciatic neuropathy both qualitatively and quantitatively, particularly in patients for whom electromyography and traditional MRI studies are unrevealing.
Minimizing transfusion requirements for children undergoing craniosynostosis repair: the CHoR protocol
Authors: Vega Rafael A. , Lyon Camila , Kierce Jeannette F. , Tye Gary W. , Ritter Ann M. , Rhodes Jennifer L.
Published: May 2014

Object

Children with craniosynostosis may require cranial vault remodeling to prevent or relieve elevated intracranial pressure and to correct the underlying craniofacial abnormalities. The procedure is typically associated with significant blood loss and high transfusion rates. The risks associated with transfusions are well documented and include transmission of infectious agents, bacterial contamination, acute hemolytic reactions, transfusion-related lung injury, and transfusion-related immune modulation. This study presents the Children's Hospital of Richmond (CHoR) protocol, which was developed to reduce the rate of blood transfusion in infants undergoing primary craniosynostosis repair.

Methods

A retrospective chart review of pediatric patients treated between January 2003 and Febuary 2012 was performed. The CHoR protocol was instituted in November 2008, with the following 3 components; 1) the use of preoperative erythropoietin and iron therapy, 2) the use of an intraoperative blood recycling device, and 3) acceptance of a lower level of hemoglobin as a trigger for transfusion (< 7 g/dl). Patients who underwent surgery prior to the protocol implementation served as controls.

Results

A total of 60 children were included in the study, 32 of whom were treated with the CHoR protocol. The control (C) and protocol (P) groups were comparable with respect to patient age (7 vs 8.4 months, p = 0.145). Recombinant erythropoietin effectively raised the mean preoperative hemoglobin level in the P group (12 vs 9.7 g/dl, p < 0.001). Although adoption of more aggressive surgical vault remodeling in 2008 resulted in a higher estimated blood loss (212 vs 114.5 ml, p = 0.004) and length of surgery (4 vs 2.8 hours, p < 0.001), transfusion was performed in significantly fewer cases in the P group (56% vs 96%, p < 0.001). The mean length of stay in the hospital was shorter for the P group (2.6 vs 3.4 days, p < 0.001).

Conclusions

A protocol that includes preoperative administration of recombinant erythropoietin, intraoperative autologous blood recycling, and accepting a lower transfusion trigger significantly decreased transfusion utilization (p < 0.001). A decreased length of stay (p < 0.001) was seen, although the authors did not investigate whether composite transfusion complication reductions led to better outcomes.
Outcomes after decompressive laminectomy for lumbar spinal stenosis: comparison between minimally invasive unilateral laminectomy for bilateral decompression and open laminectomy
Authors: Mobbs Ralph Jasper , Li Jane , Sivabalan Praveenan , Raley Darryl , Rao Prashanth J.
Published: May 2014

Object

The development of minimally invasive surgical techniques is driven by the quest for better patient outcomes. There is some evidence for the use of minimally invasive surgery for degenerative lumbar spine stenosis (LSS), but there are currently no studies comparing outcomes with matched controls. The object of this study was to compare outcomes following minimally invasive unilateral laminectomy for bilateral decompression (ULBD) to a standard “open” laminectomy for LSS.

Methods

The authors conducted a prospective, 1:1 randomized trial comparing ULBD to open laminectomy for degenerative LSS. The study enrolled 79 patients between 2007 and 2009, and adequate data for analysis were available in 54 patients (27 in each arm of the study). Patient demographic characteristics and clinical characteristics were recorded and clinical outcomes were obtained using pre- and postoperative Oswestry Disability Index (ODI) scores, visual analog scale (VAS) scores for leg pain, patient satisfaction index scores, and postoperative 12-Item Short Form Health Survey (SF-12) scores.

Results

Significant improvements were observed in ODI and VAS scores for both open and ULBD interventions (p < 0.001 for both groups using either score). In addition, the ULBD-treated patients had a significantly better mean improvement in the VAS scores (p = 0.013) but not the ODI scores (p = 0.055) compared with patients in the open-surgery group. ULBD-treated patients had a significantly shorter length of postoperative hospital stay (55.1 vs 100.8 hours, p = 0.0041) and time to mobilization (15.6 vs 33.3 hours, p < 0.001) and were more likely to not use opioids for postoperative pain (51.9% vs 15.4%, p = 0.046).

Conclusions

Based on short-term follow-up, microscopic ULBD is as effective as open decompression in improving function (ODI score), with the additional benefits of a significantly greater decrease in pain (VAS score), postoperative recovery time, time to mobilization, and opioid use.
Electrical Properties of Graphene for Interconnect Applications
Authors: Maffucci Antonio , Miano Giovanni
Published: May 2014

A semi-classical electrodynamical model is derived to describe the electrical transport along graphene, based on the modified Boltzmann transport equation. The model is derived in the typical operating conditions predicted for future integrated circuits nano-interconnects, i.e., a low bias condition and an operating frequency up to 1 THz. A generalized non-local dispersive Ohm’s law is derived, which can be regarded as the constitutive equation for the material. The behavior of the electrical conductivity is studied with reference to a 2D case (the infinite graphene layer) and a 1D case (the graphene nanoribbons). The modulation effects of the nanoribbons’ size and chirality are highlighted, as well as the spatial dispersion introduced in the 2D case by the dyadic nature of the conductivity.
What Causes Environmental Inequalities and Related Health Effects? An Analysis of Evolving Concepts
Authors: Kruize Hanneke , Droomers Mariël , Van Kamp Irene , Ruijsbroek Annemarie
Published: May 2014

Early environmental justice studies were exposure-oriented, lacked an integrated approach, and did not address the health impact of environmental inequalities. A coherent conceptual framework, needed to understand and tackle environmental inequalities and the related health effects, was lacking. We analyzed the more recent environmental justice literature to find out how conceptual insights have evolved. The conceptual framework of the WHO Commission on Social Determinants of Health (CSDH) was analyzed for additional explanations for environmental inequalities and the related health effects. This paper points out that recent environmental justice studies have broadened their scope by incorporating a broader set of physical and social environmental indicators, and by focusing on different geographic levels and on health impacts of environmental inequalities. The CSDH framework provided additional elements such as the role of structural determinants, the role of health-related behavior in relation to the physical and social environment, access to health care, as well as the life course perspective. Incorporating elements of the CSDH framework into existing environmental justice concepts, and performing more empirical research on the interactions between the different determinants at different geographical levels would further improve our understanding of environmental inequalities and their health effects and offer new opportunities for policy action.
Differential Proteomic Analysis of the Pancreas of Diabetic db/db Mice Reveals the Proteins Involved in the Development of Complications of Diabetes Mellitus
Authors: Pérez-Vázquez Victoriano , Guzmán-Flores Juan , Mares-Álvarez Daniela , Hernández-Ortiz Magdalena , Macías-Cervantes Maciste , Ramírez-Emiliano Joel , Encarnación-Guevara Sergio
Published: May 2014

Type 2 diabetes mellitus is characterized by hyperglycemia and insulin-resistance. Diabetes results from pancreatic inability to secrete the insulin needed to overcome this resistance. We analyzed the protein profile from the pancreas of ten-week old diabetic db/db and wild type mice through proteomics. Pancreatic proteins were separated in two-dimensional polyacrylamide gel electrophoresis (2D-PAGE) and significant changes in db/db mice respect to wild type mice were observed in 27 proteins. Twenty five proteins were identified by matrix-assisted laser desorption/ionization (MALDI) time-of-flight (TOF) and their interactions were analyzed using search tool for the retrieval of interacting genes/proteins (STRING) and database for annotation, visualization and integrated discovery (DAVID). Some of these proteins were Pancreatic α-amylase, Cytochrome b5, Lithostathine-1, Lithostathine-2, Chymotrypsinogen B, Peroxiredoxin-4, Aspartyl aminopeptidase, Endoplasmin, and others, which are involved in the metabolism of carbohydrates and proteins, as well as in oxidative stress, and inflammation. Remarkably, these are mostly endoplasmic reticulum proteins related to peptidase activity, i.e., they are involved in proteolysis, glucose catabolism and in the tumor necrosis factor-mediated signaling pathway. These results suggest mechanisms for insulin resistance, and the chronic inflammatory state observed in diabetes.
NOD-Like Receptors in Intestinal Homeostasis and Epithelial Tissue Repair
Authors: Parlato Marianna , Yeretssian Garabet
Published: May 2014

The intestinal epithelium constitutes a dynamic physical barrier segregating the luminal content from the underlying mucosal tissue. Following injury, the epithelial integrity is restored by rapid migration of intestinal epithelial cells (IECs) across the denuded area in a process known as wound healing. Hence, through a sequence of events involving restitution, proliferation and differentiation of IECs the gap is resealed and homeostasis reestablished. Relapsing damage followed by healing of the inflamed mucosa is a hallmark of several intestinal disorders including inflammatory bowel diseases (IBD). While several regulatory peptides, growth factors and cytokines stimulate restitution of the epithelial layer after injury, recent evidence in the field underscores the contribution of innate immunity in controlling this process. In particular, nucleotide-binding and oligomerization domain-like receptors (NLRs) play critical roles in sensing the commensal microbiota, maintaining homeostasis, and regulating intestinal inflammation. Here, we review the process of intestinal epithelial tissue repair and we specifically focus on the impact of NLR-mediated signaling mechanisms involved in governing epithelial wound healing during disease.
Computational and Experimental Approaches to Reveal the Effects of Single Nucleotide Polymorphisms with Respect to Disease Diagnostics
Authors: Kucukkal Tugba , Yang Ye , Chapman Susan , Cao Weiguo , Alexov Emil
Published: May 2014

DNA mutations are the cause of many human diseases and they are the reason for natural differences among individuals by affecting the structure, function, interactions, and other properties of DNA and expressed proteins. The ability to predict whether a given mutation is disease-causing or harmless is of great importance for the early detection of patients with a high risk of developing a particular disease and would pave the way for personalized medicine and diagnostics. Here we review existing methods and techniques to study and predict the effects of DNA mutations from three different perspectives: in silico, in vitro and in vivo. It is emphasized that the problem is complicated and successful detection of a pathogenic mutation frequently requires a combination of several methods and a knowledge of the biological phenomena associated with the corresponding macromolecules.
Molecular Imaging of Bacterial Infections in vivo: The Discrimination between Infection and Inflammation
Authors: Eggleston Heather , Panizzi Peter
Published: May 2014

Molecular imaging by definition is the visualization of molecular and cellular processes within a given system. The modalities and reagents described here represent a diverse array spanning both pre-clinical and clinical applications. Innovations in probe design and technologies would greatly benefit therapeutic outcomes by enhancing diagnostic accuracy and assessment of acute therapy. Opportunistic pathogens continue to pose a worldwide threat, despite advancements in treatment strategies, which highlights the continued need for improved diagnostics. In this review, we present a summary of the current clinical protocol for the imaging of a suspected infection, methods currently in development to optimize this imaging process, and finally, insight into endocarditis as a model of infectious disease in immediate need of improved diagnostic methods.
Experimental Analysis of the Influence of Drill Point Angle and Wear on the Drilling of Woven CFRPs
Authors: Feito Norberto , Díaz-Álvarez José , Díaz-Álvarez Antonio , Cantero José , Miguélez María
Published: May 2014

This paper focuses on the effect of the drill geometry on the drilling of woven Carbon Fiber Reinforced Polymer composite (CFRPs). Although different geometrical effects can be considered in drilling CFRPs, the present work focuses on the influence of point angle and wear because they are the important factors influencing hole quality and machining forces. Surface quality was evaluated in terms of delamination and superficial defects. Three different point angles were tested representative of the geometries commonly used in the industry. Two wear modes were considered, being representative of the wear patterns commonly observed when drilling CFRPs: flank wear and honed cutting edge. It was found that the crossed influence of the point angle and wear were significant to the thrust force. Delamination at the hole entry and exit showed opposite trends with the change of geometry. Also, cutting parameters were checked showing the feed’s dominant influence on surface damage.
Nanoporous Anodic Alumina: A Versatile Platform for Optical Biosensors
Authors: Santos Abel , Kumeria Tushar , Losic Dusan
Published: May 2014

Nanoporous anodic alumina (NAA) has become one of the most promising nanomaterials in optical biosensing as a result of its unique physical and chemical properties. Many studies have demonstrated the outstanding capabilities of NAA for developing optical biosensors in combination with different optical techniques. These results reveal that NAA is a promising alternative to other widely explored nanoporous platforms, such as porous silicon. This review is aimed at reporting on the recent advances and current stage of development of NAA-based optical biosensing devices. The different optical detection techniques, principles and concepts are described in detail along with relevant examples of optical biosensing devices using NAA sensing platforms. Furthermore, we summarise the performance of these devices and provide a future perspective on this promising research field.
Quorum Quenching Agents: Resources for Antivirulence Therapy
Authors: Tang Kaihao , Zhang Xiao-Hua
Published: May 2014

The continuing emergence of antibiotic-resistant pathogens is a concern to human health and highlights the urgent need for the development of alternative therapeutic strategies. Quorum sensing (QS) regulates virulence in many bacterial pathogens, and thus, is a promising target for antivirulence therapy which may inhibit virulence instead of cell growth and division. This means that there is little selective pressure for the evolution of resistance. Many natural quorum quenching (QQ) agents have been identified. Moreover, it has been shown that many microorganisms are capable of producing small molecular QS inhibitors and/or macromolecular QQ enzymes, which could be regarded as a strategy for bacteria to gain benefits in competitive environments. More than 30 species of marine QQ bacteria have been identified thus far, but only a few of them have been intensively studied. Recent studies indicate that an enormous number of QQ microorganisms are undiscovered in the highly diverse marine environments, and these marine microorganism-derived QQ agents may be valuable resources for antivirulence therapy.
The Protective Effect of Fucoidan in Rats with Streptozotocin-Induced Diabetic Nephropathy
Authors: Wang Jing , Liu Huaide , Li Ning , Zhang Quanbin , Zhang Hong
Published: May 2014

Diabetic nephropathy (DN) has long been recognized as the leading cause of end-stage renal disease, but the efficacy of available strategies for the prevention of DN remains poor. The aim of this study was to investigate the possible beneficial effects of fucoidan (FPS) in streptozotocin (STZ)-induced diabetes in rats. Wistar rats were made diabetic by injection of STZ after removal of the right kidney. FPS was administered to these diabetic rats for 10 weeks. Body weight, physical activity, renal function, and renal morphometry were measured after 10 weeks of treatment. In the FPS-treated group, the levels of blood glucose, BUN, Ccr and Ucr decreased significantly, and microalbumin, serum insulin and the β2-MG content increased significantly. Moreover, the FPS-treated group showed improvements in renal morphometry. In summary, FPS can ameliorate the metabolic abnormalities of diabetic rats and delay the progression of diabetic renal complications.
Identification of Marine Neuroactive Molecules in Behaviour-Based Screens in the Larval Zebrafish
Authors: Long Si-Mei , Liang Feng-Yin , Wu Qi , Lu Xi-Lin , Yao Xiao-Li , Li Shi-Chang , Li Jing , Su Huanxing , Pang Ji-Yan , Pei Zhong
Published: May 2014

High-throughput behavior-based screen in zebrafish is a powerful approach for the discovery of novel neuroactive small molecules for treatment of nervous system diseases such as epilepsy. To identify neuroactive small molecules, we first screened 36 compounds (1–36) derived from marine natural products xyloketals and marine isoprenyl phenyl ether obtained from the mangrove fungus. Compound 1 demonstrated the most potent inhibition on the locomotor activity in larval zebrafish. Compounds 37–42 were further synthesized and their potential anti-epilepsy action was then examined in a PTZ-induced epilepsy model in zebrafish. Compound 1 and compounds 39, 40 and 41 could significantly attenuate PTZ-induced locomotor hyperactivity and elevation of c-fos mRNA in larval zebrafish. Compound 40 showed the most potent inhibitory action against PTZ-induced hyperactivity. The structure-activity analysis showed that the OH group at 12-position played a critical role and the substituents at the 13-position were well tolerated in the inhibitory activity of xyloketal derivatives. Thus, these derivatives may provide some novel drug candidates for the treatment of epilepsy.
Mesoporous Silicas with Tunable Morphology for the Immobilization of Laccase
Authors: Gascón Victoria , Díaz Isabel , Márquez-Álvarez Carlos , Blanco Rosa
Published: May 2014

Siliceous ordered mesoporous materials (OMM) are gaining interest as supports for enzyme immobilization due to their uniform pore size, large surface area, tunable pore network and the introduction of organic components to mesoporous structure. We used SBA-15 type silica materials, which exhibit a regular 2D hexagonal packing of cylindrical mesopores of uniform size, for non-covalent immobilization of laccase. Synthesis conditions were adjusted in order to obtain supports with different particle shape, where those with shorter channels had higher loading capacity. Despite the similar isoelectric points of silica and laccase and the close match between the size of laccase and the pore dimensions of these SBA-15 materials, immobilization was achieved with very low leaching. Surface modification of macro-/mesoporous amorphous silica by grafting of amine moieties was proved to significantly increase the isoelectric point of this support and improve the immobilization yield.
Synthesis and Biological Evaluation of Novel 2-Arylalkylthio-5-iodine-6-substituted-benzyl-pyrimidine-4(3H)-ones as Potent HIV-1 Non-Nucleoside Reverse Transcriptase Inhibitors
Authors: Zhang Liang , Tang Xiaowan , Cao Yuanyuan , Wu Shaotong , Zhang Yu , Zhao Jianxiong , Guo Ying , Tian Chao , Zhang Zhili , Liu Junyi , Wang Xiaowei
Published: May 2014

A novel series of 2-arylalkylthio-5-iodine-6-substitutedbenzyl-pyrimidine-4(3H)-ones (S-DABOs) 8a–x had been synthesized via an efficient method. Their biological activity against HIV virus and RT assay were evaluated. Some compounds, especially 8h, 8l and 8n, displayed promising activity against HIV-1 RT with IC50 values in a range of 0.41 μM to 0.71 μM, which were much better than that of nevirapine. Molecular modeling studies revealed that the binding mode would be affected via forming an additional hydrogen bond by incorporating an oxygen atom on the C-2 side chain. The biological activity was in accordance with the docking results.
miR-221/222 Promotes S-Phase Entry and Cellular Migration in Control of Basal-Like Breast Cancer
Authors: Li Yuan , Liang Chunli , Ma Haizhong , Zhao Qian , Lu Ying , Xiang Zhendong , Li Li , Qin Jie , Chen Yihan , Cho William , Pestell Richard , Liang Li , Yu Zuoren
Published: May 2014

The miR-221/222 cluster has been demonstrated to function as oncomiR in human cancers. miR-221/222 promotes epithelial-to-mesenchymal transition (EMT) and confers tamoxifen resistance in breast cancer. However, the effects and mechanisms by which miR-221/222 regulates breast cancer aggressiveness remain unclear. Here we detected a much higher expression of miR-221/222 in highly invasive basal-like breast cancer (BLBC) cells than that in non-invasive luminal cells. A microRNA dataset from breast cancer patients indicated an elevated expression of miR-221/222 in BLBC subtype. S-phase entry of the cell cycle was associated with the induction of miR-221/222 expression. miRNA inhibitors specially targeting miR-221 or miR-222 both significantly suppressed cellular migration, invasion and G1/S transition of the cell cycle in BLBC cell types. Proteomic analysis demonstrated the down-regulation of two tumor suppressor genes, suppressor of cytokine signaling 1 (SOCS1) and cyclin-dependent kinase inhibit 1B (CDKN1B), by miR-221/222. This is the first report to reveal miR-221/222 regulation of G1/S transition of the cell cycle. These findings demonstrate that miR-221/222 contribute to the aggressiveness in control of BLBC.
Acute and 4-Week Repeated-Dose Oral Toxicity Studies of Cirsium setidens in Rats
Authors: Lee Jong , Kim Young-Hyun , Kim Dan-Bi , Bang Woo-Suk , Lee Ok-Hwan
Published: May 2014

Cirsium setidens is a wild perennial plant species found in Korea that may have anti-oxidative, anti-adipogenic, and hepatoprotective activities. However, details of the toxicology of C. setidens remain unknown. This study was performed to evaluate the toxicological effects of an acute administration and 4-week repeated dosing of a C. setidens extract in Sprague-Dawley rats to ensure the safe use of this extract. C. setidens (1250, 2500, and 5000 mg/kg body weight/day) did not induce significant toxicological changes in groups matched by gender with respect to mortality, clinical signs, body weight, urinalysis, ophthalmoscopy, necropsy findings, hematology, and histopathology. Therefore, this study demonstrates that acute administration and 4-week repeated dosing of C. setidens extract orally using this administration protocol is safe.
Effects of the Total Saponins from Rosa laevigata Michx Fruit against Acetaminophen-Induced Liver Damage in Mice via Induction of Autophagy and Suppression of Inflammation and Apoptosis
Authors: Dong Deshi , Xu Lina , Han Xu , Qi Yan , Xu Youwei , Yin Lianhong , Liu Kexin , Peng Jinyong
Published: May 2014

The effect of the total saponins from Rosa laevigata Michx fruit (RLTS) against acetaminophen (APAP)-induced liver damage in mice was evaluated in the present paper. The results showed that RLTS markedly improved the levels of liver SOD, CAT, GSH, GSH-Px, MDA, NO and iNOS, and the activities of serum ALT and AST caused by APAP. Further research confirmed that RLTS prevented fragmentation of DNA and mitochondrial ultrastructural alterations based on TdT-mediated dUTP nick end labeling (TUNEL) and transmission electron microscopy (TEM) assays. In addition, RLTS decreased the gene or protein expressions of cytochrome P450 (CYP2E1), pro-inflammatory mediators (IL-1β, IL-4, IL-6, TNF-α, iNOS, Bax, HMGB-1 and COX-2), pro-inflammatory transcription factors (NF-κB and AP-1), pro-apoptotic proteins (cytochrome C, p53, caspase-3, caspase-9, p-JNK, p-p38 and p-ERK), and increased the protein expressions of Bcl-2 and Bcl-xL. Moreover, the gene expression of IL-10, and the proteins including LC3, Beclin-1 and Atg5 induced by APAP were even more augmented by the extract. These results demonstrate that RLTS has hepatoprotective effects through antioxidative action, induction of autophagy, and suppression of inflammation and apoptosis, and could be developed as a potential candidate to treat APAP-induced liver damage in the future.
Is Omega-3 Fatty Acids Enriched Nutrition Support Safe for Critical Ill Patients? A Systematic Review and Meta-Analysis
Authors: Chen Wei , Jiang Hua , Zhou Zhi-Yuan , Tao Ye-Xuan , Cai Bin , Liu Jie , Yang Hao , Lu Charles , Zeng Jun
Published: May 2014

Objective: To systematically review the effects of omega-3 poly unsaturated fatty acids (FA) enriched nutrition support on the mortality of critically illness patients. Methods: Databases of Medline, ISI, Cochrane Library, and Chinese Biomedicine Database were searched and randomized controlled trials (RCTs) were identified. We enrolled RCTs that compared fish oil enriched nutrition support and standard nutrition support. Major outcome is mortality. Methodological quality assessment was conducted based on Modified Jadad’s score scale. For control heterogeneity, we developed a method that integrated I2 test, nutritional support route subgroup analysis and clinical condition of severity. RevMan 5.0 software (The Nordic Cochrane Centre, Copenhagen, Denmark) was used for meta-analysis. Results: Twelve trials involving 1208 patients that met all the inclusion criteria. Heterogeneity existed between the trials. A random model was used, there was no significant effect on mortality RR, 0.82, 95% confidence interval (CI) (0.62, 1.09), p = 0.18. Knowing that the route of fish oil administration may affect heterogeneity, we categorized the trials into two sub-groups: parenteral administration (PN) of omega-3 and enteral administration (EN) of omega-3. Six trials administered omega-3 FA through PN. Pooled results indicated that omega-3 FA had no significant effect on mortality, RR 0.76, 95% CI (0.52, 1.10), p = 0.15. Six trials used omega-3 fatty acids enriched EN. After excluded one trial that was identified as source of heterogeneity, pooled data indicated omega-3 FA enriched EN significant reduce mortality, RR=0.69, 95% CI [0.53, 0.91] (p = 0.007). Conclusion: Omega-3 FA enriched nutrition support is safe. Due to the limited sample size of the included trials, further large-scale RCTs are needed.
A Coarse-Grained DNA Model Parameterized from Atomistic Simulations by Inverse Monte Carlo
Authors: Korolev Nikolay , Luo Di , Lyubartsev Alexander , Nordenskiöld Lars
Published: May 2014

Computer modeling of very large biomolecular systems, such as long DNA polyelectrolytes or protein-DNA complex-like chromatin cannot reach all-atom resolution in a foreseeable future and this necessitates the development of coarse-grained (CG) approximations. DNA is both highly charged and mechanically rigid semi-flexible polymer and adequate DNA modeling requires a correct description of both its structural stiffness and salt-dependent electrostatic forces. Here, we present a novel CG model of DNA that approximates the DNA polymer as a chain of 5-bead units. Each unit represents two DNA base pairs with one central bead for bases and pentose moieties and four others for phosphate groups. Charges, intra- and inter-molecular force field potentials for the CG DNA model were calculated using the inverse Monte Carlo method from all atom molecular dynamic (MD) simulations of 22 bp DNA oligonucleotides. The CG model was tested by performing dielectric continuum Langevin MD simulations of a 200 bp double helix DNA in solutions of monovalent salt with explicit ions. Excellent agreement with experimental data was obtained for the dependence of the DNA persistent length on salt concentration in the range 0.1–100 mM. The new CG DNA model is suitable for modeling various biomolecular systems with adequate description of electrostatic and mechanical properties.