bluuebunny/crossref_metadata_2025 huggingface dataset:
Modelling of residual stresses during laser cutting of small-diameter holes
Authors: Yilbas B S , Arif A F M
Published: November 2008

Laser hole cutting in a sheet metal is modelled, and temperature as well as the stress fields developed around the hole circumference are examined. The finite element method is used to predict the temperature and stress fields during and after completion of the cutting process. An experiment resembling the simulation conditions is carried out and the residual stress developed in the cutting region is measured using the X-ray diffraction (XRD) technique. It is found that the principal stresses are tensile in the region close to the hole surface, and the stress components become compressive as the distance from the hole surface to the solid bulk increases. The residual stress predicted agrees with the measured data.
A combined TOPSIS-AHP-method-based approach for non-traditional machining processes selection
Authors: Chakladar N D , Chakraborty S
Published: November 2008

With the introduction and increased use of newer and harder materials such as titanium, stainless steel, high-strength temperature-resistant (HSTR) alloys, fibre-reinforced composites, and ceramics in the aerospace, nuclear, missile, turbine, automobile, tool, and die-making industries, a different class of machining processes has emerged. Instead of employing the conventional cutting tools, these non-traditional machining (NTM) processes use energy in its direct form to remove materials from the workpiece. Selection of the most suitable NTM process for machining a shape feature on a given work material requires consideration of several factors. A combined method using the ‘technique for order preference by similarity to ideal solution’ (TOPSIS) and an analytical hierarchy process (AHP) is proposed to select the most appropriate NTM process for a specific work material and shape feature combination, while taking into account different attributes affecting the NTM process selection decision. This paper also includes the design and development of a TOPSIS-AHP-method-based expert system that can automate the decision-making process with the help of a graphical user interface and visual aids. The expert system not only segregates the acceptable NTM processes from the list of the available processes, but also ranks them in decreasing order of preference. It also helps the user as a responsible guide to select the best NTM process by incorporating all the possible error-trapping mechanisms.
Strategy for a loading force induced overlay position shift in step imprint lithography
Authors: Shao J Y , Ding Y C , Liu H Z , Wang L , Yin L , Shi Y S , Jiang W T
Published: November 2008

Imprint lithography has the potential to be a cost-effective successor to optical lithography, but there are a number of problems that need to be solved for this to happen. Imprint lithography is a mechanical process, and the overlay for imprint lithography depends not only on the alignment measurement accuracy but also on the loading force used for pattern transferring. A large force seriously deteriorates the overlay accuracy. How to eliminate the influence of loading force on the overlay accuracy is a practical challenge. This paper proposes a step imprint lithography tool for multilayer microstructure fabrication and emphasizes the importance of reporting the overlay process development. The loading process is investigated first. Relative movement and interaction force between the mould and the wafer are two main causes for an overlay position shift in the loading process. Though it can be compensated by the readjustment process, the deformation recoveries of the mechanical system in the demoulding process still bring about serious deterioration in pattern fidelity and overlay accuracy. An optimized overlay process is proposed to solve these problems. Some crucial issues in the optimized overlay process, like loading force optimization, the load pre-release process, and the demoulding process, are investigated by experiments to determine the best performing approaches using the developed step imprint lithography (SIL) tool. It was found that the proposed overlay process can eliminate the influence of loading force effectively.
Effect of crystalline orientation of a diamond tool on the machined surface in ductile mode cutting of silicon
Authors: Li X P , Cai M B , Neo W C L , Seah K H W
Published: November 2008

In nanoscale ductile mode cutting of monocrystalline silicon with single-crystal diamond tools, it was observed that under certain crystalline orientations of the diamond tool, such as with {110} or {100} for the tool rake face, good integrity of the machined surface could be generated. However, when the tool had the {111} orientation for the rake face, the machined surface was fractured. In the present study, the crystalline behaviour of the monocrystalline diamond tool in nanoscale cutting of monocrystalline silicon and its effect on the machined surface were experimentally investigated using the {100}, {110}, and {111} orientations for the rake faces of single-crystal diamond tools. The results showed that when the rake face orientation of the diamond cutter was changed from {100} or {110} to {111}, the chip formation mode changed from ductile to brittle. The cause of such behaviour of single-crystal diamond tools was found to be the different values of the Young's modulus of single-crystal diamond in the {100}, {110}, and {111} orientations.
Business re-engineering through integration of methods and tools for process innovation
Authors: Cascini G , Rissone P , Rotini F
Published: November 2008

A business process may be considered a technical system that generates value by turning available resources into products or services to be sold. When the process is not able to exploit all available resources in terms of market demand, raw materials, etc., the value generated by the system decreases owing to a lack of functionality or performance. The current paper presents an original road-map, based on the integration of different methods and tools (namely IDEF, TRIZ, TOC), able to support the analysis of an industrial production process in order to identify business opportunities that are not exploited to their maximum extent. The proposed approach goes from the As-Is process to the definition of a To-Be model by moving from the actual reality to the economic domain and then back to the desired or expected future reality. The link between these two domains is constituted by the functional domain, and the identification of the functional needs is the step to define innovation challenges aimed at removing business limits.

An application of the road-map to improve the production process of solid biofuels is also presented as a case study in order to clarify and validate the proposed approach.
Designing for ‘use phase’ energy losses of domestic products
Authors: Elias E W A , Dekoninck E A , Culley S J
Published: November 2008

The energy efficiency of products can be established by calculating the energy losses of the product. This paper shows that there are two kinds of losses: intrinsic losses, determined by the technology and materials used to construct the product, and user-related losses, which are caused by varying and inefficient use of that product by the user. User-related losses are a significant proportion of energy use of products and are likely to increase in proportion as engineers use good design and technology to drive the intrinsic losses closer and closer to what the authors call the theoretical minimum. The paper goes on to set out a theoretical framework for understanding and calculating the intrinsic and user-related losses of products and concludes by suggesting an outline of appropriate design strategies for tackling them.
Development of a six-axis wire electrical discharge machine for the fabrication of micro end mills
Authors: Cheng X , Wang Z G , Kobayashi S , Nakamoto K , Yamazaki K
Published: November 2008

Micro/nano milling applications are needed due to the miniaturization tendency of components used in medical devices and aerospace equipments. Accordingly, micro end mills are needed. However, there are no special purpose machine tools designed for the fabrication of such tools made of ultra hard materials and with complicated three-dimensional geometries. In this paper, a six-axis wire electrical discharge machine (WEDM) designed for the fabrication of micro end mills is developed. Direct drive linear motors and rotary motors are used for linear and rotary axes respectively to realize direct drive instead of ball screws or gearboxes. A special cooling system for all motors makes the thermal effect minimum on the mechanical structures. After the introduction of the developed WEDM, its kinematics model is built. The error analysis for the key axis directly supporting the wire is introduced and the corresponding results are used to guide the mechanical design of the six-axis WEDM and to compensate for position errors during machining. Based on these techniques, high machining accuracy is achieved. Finally, the fabrications of a cutter with complicated geometry and a cutter made of ultra hard material are successfully demonstrated on the developed machine tool.
Tip injection as a means for rotating stall control in an axial flow fan
Authors: Salunkhe P B , Reddy V S R K , Pradeep A M
Published: November 2008

The present experimental investigation is aimed at studying the effect of tip injection on the performance and flow characteristics in the tip region of an axial flow fan under uniform and distorted inflow conditions. A detailed parametric study was carried out by varying injection parameters such as pitch and skew angles, jet-to-free-stream velocity ratio, number of injectors, and the axial location of the injectors. The configuration with six injectors, jet-to-free-stream velocity ratio of 3.5, 0° pitch angle, and injector skew angle of-15° (in an orientation opposing the direction of rotor rotation) resulted in the highest stall margin improvement of ∼9.4 per cent. This study was further extended to determine the effects of circumferential and combined circumferential and radial inflow distortion on fan performance and the effectiveness of tip injection under these conditions. A preliminary study of the effect of pulsed injection was also carried out at different pulsing frequencies in order to optimize injection flowrates. Interestingly, pulsed injection resulted in less stall margin improvement when compared with continuous injection. These results have been supported by flow behaviour studies carried out in the tip region using a seven-hole probe. A qualitative study was carried out using unsteady pressure transducers, and it revealed that the trailing edge of the distortion screen acts as a source of disturbances.
Energy and exergy analyses of compressor inlet air-cooled gas turbines using the Joule—Brayton refrigeration cycle
Authors: Khaliq A , Choudhary K , Dincer I
Published: November 2008

In this article, a novel method of inlet air cooling is proposed to enhance the performance of a gas turbine operating in hot climates. The intake air at the compressor bell-mouth is cooled by an air Brayton refrigerator driven by the gas turbine, and the refrigerator uses air as the working fluid. Introducing the air refrigeration cycle provides the advantage of quite low temperatures close to 0 °C and even lower. This is not possible with other methods of intake air cooling, namely evaporative cooling or use of waste heat-driven absorption machines. A thermodynamic analysis through energy and exergy is employed, and a comprehensive parametric study is performed to investigate the effects of extraction pressure ratio, extracted mass rate, turbine inlet temperature (TIT), and ambient relative humidity (RH) on increase in net work output, first law efficiency, and second law efficiency of a compressor inlet air-cooled gas turbine cycle using a Joule—Brayton refrigerator. The analysis of the results indicates that the maximum exergy destroyed in the combustion chamber, which represents>80 per cent of the total exergy destruction in the overall system, is significantly affected by the extraction pressure ratio and TIT and is slightly affected by ambient RH. The increase in the net work output, the first law efficiency, and the second law efficiency of the cycle significantly varies with a change in the extraction pressure ratio, extraction mass rate, TIT, and ambient RH. Results clearly show that performance evaluation based on first law analysis alone is not adequate, and hence more meaningful evaluation must include second law analysis. Decision-makers should find the methodology presented in this article useful in comparison and selection of various methods for inlet air cooling in gas turbines.
Comparative evaluation of gas turbine power plant performance for different blade cooling means
Authors: Sanjay  , Singh O , Prasad B N
Published: November 2008

The thermodynamic performance of a gas turbine power plant has been compared for different means of blade cooling in this work. Seven schemes involving air and steam as coolants under open- and closed-loop cooling means have been studied. The closed-loop cooling includes only the internal convection cooling (ICC) technique, while the open-loop cooling schemes include the internal convection, film, and transpiration cooling means. Comparative evaluation shows that among all the cooling schemes considered, the open-loop steam ICC offers highest specific work and thus highest values of plant efficiency of about 50 per cent, whereas open-loop film steam cooling, transpiration air cooling, film air cooling, and internal convection air cooling have been found to yield lower values of plant efficiency in decreasing order. The specific work is higher for all open-loop steam cooling means due to steam injection into the hot gas stream of the turbine.
Obesity and arthritis
Authors: Magliano Malgorzata
Published: November 2008

Obesity affects over 20% of the UK's adult population and its prevalence is rising. Obesity can lead to a variety of musculoskeletal problems and is independently associated with locomotor disability and joint pain. Obesity increases the risk of radiographic knee osteoarthritis (OA), but has a lesser effect on disease progression. The association with hip and hand OA is weaker, but implies that excess adipose tissue produces humoral factors, altering articular cartilage metabolism. It has been postulated that the leptin system could be a link between metabolic abnormalities in obesity and increased risk of OA. Although obesity was initially thought to increase the risk of rheumatoid arthritis (RA), further studies showed, that heavier patients with RA have less radiological disease progression and possibly better survival. On the other hand, obesity is strongly associated with hypeuricaemia and gouty arthritis. High body weight correlates independently with metabolic syndrome and may contribute to increased cardiovascular morbidity in patients with gout. Weight reduction should be an important part of treatment for OA and gout. Because obesity at a young age correlates with the development of OA and gout in later life, preventive public health strategies aimed at lowering the incidence of obesity are of most importance.
HIV and the menopause
Authors: Fan Maria D , Maslow Bat-Sheva , Santoro Nanette , Schoenbaum Ellie
Published: November 2008

Dramatic improvement in the survival of the HIV population has occurred with the ascendance of highly active antiretroviral therapy (HAART). In the foreseeable future, HIV-infected women who acquired disease during the peak years of the epidemic are expected to survive to experience menopause and even years beyond. The HIV epidemic may be viewed as ‘mature’, as its earlier victims become part of the geriatric population. Research about the process of menopause in HIV-infected women and, conversely, about HIV infection in women undergoing menopause is currently limited. Existing research suggests that the process of menopause is affected by HIV infection, inasmuch as infected women appear to experience menopause at an earlier age, with greater symptomatology, and with different reproductive hormone profiles compared with HIV-uninfected women. HIV infection also appears to affect bone mineral density, cardiovascular disease and cognition, with some age-related interactions. Lifestyle and demographic factors have pervasive importance for both HIV infection and the menopause in women. This article reviews the current state of knowledge about the menopausal process in HIV-infected women, and the common conditions in postmenopausal women that are likely to be affected by HIV infection. Clinicians should appreciate the potential role of HIV infection in caring for menopause-aged women.
The incidence of reoperation for surgically treated pelvic organ prolapse: an 11-year experience
Authors: Price Natalia , Slack Alex , Jwarah Eman , Jackson Simon
Published: November 2008

Objective

The purpose of this study was to measure the rate of reoperation for surgically treated pelvic organ prolapse.

Study design

An 11-year retrospective audit was conducted of women who had undergone surgery for pelvic organ prolapse between 1995 and 2005 in a large teaching hospital in the UK.

Main outcome measure

Variables examined included the type of primary procedure for pelvic organ prolapse overall and per year, the type of the repeat procedure and the interval between primary and repeat procedures. Analysis included calculation of the number and proportion of primary operations, the rate of reoperation, the type of repeat prolapse operation and the cumulative risk of reoperation each year for 11 years.

Results

During the study period, 2099 women underwent surgery for pelvic organ prolapse. Of these women, 142 underwent a second operation for prolapse and 13 a third. The overall cumulative rate of reoperation following surgery for pelvic organ prolapse was 10.8% at 11 years following the initial procedure. The majority (61.5%) of repeat procedures did not involve the same compartment as the initial operation and recurrences tended to occur in the first few years after the first operation.

Conclusion

Women who undergo surgery for pelvic organ prolapse are at 10.8% risk of requiring a reoperation within the next 11 years, usually at a different site.
Visualizing protein–RNA interactions inside cells by fluorescence resonance energy transfer
Authors: Lorenz Mike
Published: November 2008

Approaches for studying protein–protein interactions in living cells have been broadly developed, but the temporal and spatial association of proteins with nucleic acids has been less explored. Here, we report a novel approach to study and visualize the association of an RNA-binding protein with its native RNA target in situ by fluorescence resonance energy transfer (FRET). The RNA-binding protein is tagged with a yellow variant of GFP and the RNA stained with SytoxOrange. RNA binding results in a decrease of the fluorescence lifetime of YFP due to FRET, which can be measured by fluorescence lifetime imaging microscopy (FLIM). With this method we analyzed the RNA binding of the alternative splicing repressors PTB and Raver1 and could show an RNA-specific FRET signal. Interestingly, PTB and Raver1 were bound to RNAs all over the nucleus, as expected, but additionally interacted with RNAs in the perinucleolar compartment (PNC), where only noncoding Pol III transcripts are present.
The Next Generation: Technology Adoption and Integration Through Internal Competition in New Product Development
Authors: Taylor Alva
Published: November 2008

This paper examines the impact of internal competition that occurs when new technology challenges the technology in a firm's existing products. New-technology development projects are traditionally judged by market success—and most fail. If we examine their impact on existing-technology product development, a different interpretation arises. Drawing on the literature on the influence of social factors on interfirm search and adoption of new technologies, this study argues that similar processes occur intrafirm. Evidence from a field study on new-technology product development in high-technology firms shows that internal competition influences existing-technology product development groups to integrate the new technology into the next generation of their own products. The reason is twofold. First, these groups shift their search toward the new technology and allocate resources to gain a deeper understanding of it. Second, access to internal information and the mobility of workers across project boundaries benefit the existing-technology groups. The findings provide a model of innovation that illustrates an endogenous process of internal competition. This often political and contentious process can have a strong influence on technology adoption and integration.
Multidrug-Resistant Pseudomonas aeruginosa Ventilator-Associated Pneumonia: The Role of Endotracheal Aspirate Surveillance Cultures
Authors: Yang Katherine , Zhuo Hanjing , Guglielmo B Joseph , Wiener-Kronish Jeanine
Published: November 2008

BACKGROUND

Inappropriate antibacterial treatment of ventilator-associated pneumonia (VAP) due to multidrug-resistant (MDR) pathogens is associated with increased mortality. Endotracheal aspirate (ETA) surveillance cultures potentially identify MDR pathogens, particularly MDR Pseudomonas aeruginosa, resulting in improved selection of therapy in patients who subsequently develop VAP.

OBJECTIVE

To investigate the role of ETA surveillance cultures in the identification of MDR P. aeruginosa in newly intubated adults who subsequently develop VAP.

METHODS

Daily ETA surveillance cultures for P. aeruginosa were collected in all adults newly intubated for 48 hours or more. Patients with preexisting lung disease or colonization or infection with P. aeruginosa were excluded. Risk factors and outcomes of patients newly colonized with MDR P. aeruginosa were assessed.

RESULTS

Seventy-five patients newly colonized with P aeruginosa were identified. Twenty (27%) of these patients were colonized with a P. aeruginosa isolate that was MDR (resistant to >3 classes of antibiotics). Six patients were colonized by an isolate resistant to all tested classes of antibiotics. Forty-five percent of patients colonized with MDR P. aeruginosa subsequently developed VAP. Prior receipt of fluoroquinolones was an independent predictor of colonization with MDR P. aeruginosa (OR 11.82; 95% CI 2.10 to 66.46; p = 0.005).

CONCLUSIONS

Performance of routine surveillance cultures may aid in the early detection of MDR P. aeruginosa, improving the initiation of early and appropriate antibiotic therapy for patients who subsequently develop VAP.
Clinically Significant Drug–Drug Interactions Between Oral Anticancer Agents and Nonanticancer Agents: Profiling and Comparison of Two Drug Compendia
Authors: Wong Chen-May , Ko Yu , Chan Alexandre
Published: November 2008

Background:

Use of oral anticancer agents is gaining wide acceptance in the treatment of cancer. However, patients receiving oral therapy are at high risk for drug–drug interactions (DDIs).

Objective:

To create a drug profile for each clinically significant DDI involving selected oral anticancer agents and evaluate the agreement between 2 commonly used DDI compendia: Drug Interaction Facts (DIF) 2008 and Micromedex DRUGDEX.

Methods:

DDI profiles were developed based on primary and tertiary literature reviews. DIF 2008 and Micromedex DRUGDEX were compared to assess the consistency of listings, severity, and scientific evidence ratings of DDIs involving the oral anticancer agents that were selected. The Spearman correlation test was used to assess the correlation of the severity ratings between the 2 compendia.

Results:

A total of 184 DDIs were identified. A DDI profile was created for 40 of these that met the predetermined criteria for clinically significant interactions. The comparative assessment showed inconsistency in DDI listings (15.2% of those identified were listed in DIF only and 46.7% were listed in Micromedex only), severity ratings (Spearman correlation coefficient 0.49), and scientific evidence ratings (disagreement 25.8%).

Conclusions:

The discrepancies in DDI listing and rating systems between the compendia evaluated here reflect the need for more studies to standardize the definitions and classifications of DDIs.
Antagonistic Effects of Doublecortin and MARK2/Par-1 in the Developing Cerebral Cortex
Authors: Sapir Tamar , Shmueli Anat , Levy Talia , Timm Thomas , Elbaum Michael , Mandelkow Eva-Maria , Reiner Orly
Published: November 2008

Abnormal neuronal migration is manifested in brain malformations such as lissencephaly. The impairment in coordinated cell motility likely reflects a faulty mechanism of cell polarization or coupling between polarization and movement. Here we report on the relationship between the polarity kinase MARK2/Par-1 and its substrate, the well-known lissencephaly-associated gene doublecortin (DCX), during cortical radial migration. We have previously shown usingin uteroelectroporation that reduced MARK2 levels resulted in multipolar neurons stalled at the intermediate zone border, similar to the phenotype observed in the case of DCX silencing. However, whereas reduced MARK2 stabilized microtubules, we show here that knock-down of DCX increased microtubule dynamics. This led to the hypothesis that simultaneous reduction may alleviate the phenotype. Coreduction of MARK2 and DCX resulted in a partial restoration of the normal neuronal migration phenotypein vivo. The kinetic behavior of the centrosomes reflected the different molecular mechanisms activated when either protein was reduced. In the case of reducing MARK2 processive motility of the centrosome was hindered, whereas when DCX was reduced, centrosomes moved quickly but bidirectionally. Our results stress the necessity for successful coupling between the polarity pathway and cytoplasmic dynein-dependent activities for proper neuronal migration.
Corticotropin-Releasing Factor Increases GABA Synaptic Activity and Induces Inward Current in 5-Hydroxytryptamine Dorsal Raphe Neurons
Authors: Kirby Lynn G. , Freeman-Daniels Emily , Lemos Julia C. , Nunan John D. , Lamy Christophe , Akanwa Adaure , Beck Sheryl G.
Published: November 2008

Stress-related psychiatric disorders such as anxiety and depression involve dysfunction of the serotonin [5-hydroxytryptamine (5-HT)] system. Previous studies have found that the stress neurohormone corticotropin-releasing factor (CRF) inhibits 5-HT neurons in the dorsal raphe nucleus (DRN)in vivo. The goals of the present study were to characterize the CRF receptor subtypes (CRF-R1 and -R2) and cellular mechanisms underlying CRF–5-HT interactions. Visualized whole-cell patch-clamp recording techniques in brain slices were used to measure spontaneous or evoked GABA synaptic activity in DRN neurons of rats and CRF effects on these measures. CRF-R1 and -R2-selective agonists were bath applied alone or in combination with receptor-selective antagonists. CRF increased presynaptic GABA release selectively onto 5-HT neurons, an effect mediated by the CRF-R1 receptor. CRF increased postsynaptic GABA receptor sensitivity selectively in 5-HT neurons, an effect to which both receptor subtypes contributed. CRF also had direct effects on DRN neurons, eliciting an inward current in 5-HT neurons mediated by the CRF-R2 receptor and in non-5-HT neurons mediated by the CRF-R1 receptor. These results indicate that CRF has direct membrane effects on 5-HT DRN neurons as well as indirect effects on GABAergic synaptic transmission that are mediated by distinct receptor subtypes. The inhibition of 5-HT DRN neurons by CRFin vivomay therefore be primarily an indirect effect via stimulation of inhibitory GABA synaptic transmission. These results regarding the cellular mechanisms underlying the complex interaction between CRF, 5-HT, and GABA systems could contribute to the development of novel treatments for stress-related psychiatric disorders.
Spatial and Temporal Scales of Neuronal Correlation in Primary Visual Cortex
Authors: Smith Matthew A. , Kohn Adam
Published: November 2008

The spiking activity of cortical neurons is correlated. For instance, trial-to-trial fluctuations in response strength are shared between neurons, and spikes often occur synchronously. Understanding the properties and mechanisms that generate these forms of correlation is critical for determining their role in cortical processing. We therefore investigated the spatial extent and functional specificity of correlated spontaneous and evoked activity. Because feedforward, recurrent, and feedback pathways have distinct extents and specificity, we reasoned that these measurements could elucidate the contribution of each type of input. We recorded single unit activity with microelectrode arrays which allowed us to measure correlation in many hundreds of pairings, across a large range of spatial scales. Our data show that correlated evoked activity is generated by two mechanisms that link neurons with similar orientation preferences on different spatial scales: one with high temporal precision and a limited spatial extent (∼3 mm), and a second that gives rise to correlation on a slow time scale and extends as far as we were able to measure (10 mm). The former is consistent with common input provided by horizontal connections; the latter likely involves feedback from extrastriate cortex. Spontaneous activity was correlated over a similar spatial extent, but approximately twice as strongly as evoked activity. Visual stimuli thus caused a substantial decrease in correlation, particularly at response onset. These properties and the circuit mechanism they imply provide new constraints on the functional role that correlation may play in visual processing.
Human Immunodeficiency Virus Protein Tat Induces Synapse Loss via a Reversible Process That Is Distinct from Cell Death
Authors: Kim Hee Jung , Martemyanov Kirill A. , Thayer Stanley A.
Published: November 2008

Human immunodeficiency virus (HIV)-1 infection of the CNS produces changes in dendritic morphology that correlate with cognitive decline in patients with HIV-1 associated dementia (HAD). Here, we investigated the effects of HIV-1 transactivator of transcription (Tat), a protein released by virus-infected cells, on synapses between hippocampal neurons using an imaging-based assay that quantified clusters of the scaffolding protein postsynaptic density 95 fused to green fluorescent protein (PSD95–GFP). Tat (24 h) decreased the number of PSD95–GFP puncta by 50 ± 7%. The decrease was concentration-dependent (EC50= 6 ± 2 ng/ml) and preceded cell death. Tat acted via the low-density lipoprotein receptor-related protein (LRP) because the specific LRP blocker, receptor associated protein (RAP), prevented the Tat-induced decrease in the number of PSD95–GFP puncta. Ca2+influx through the NMDA receptor was necessary for Tat-induced synapse loss. Expression of an ubiquitin ligase inhibitor protected synapses, implicating the ubiquitin–proteasome pathway. In contrast to synapse loss, Tat induced cell death (48 h) required activation of nitric oxide synthase. The ubiquitin ligase-inhibitor nutlin-3 prevented synapse loss but not cell death induced by Tat. Thus, the pathways diverged, consistent with the hypothesis that synapse loss is a mechanism to reduce excess excitatory input rather than a symptom of the neuron's demise. Furthermore, application of RAP to cultures treated with Tat for 16 h reversed synapse loss. These results suggest that the impaired network function and decreased neuronal survival produced by Tat involve distinct mechanisms and that pharmacologic targets, such as LRP, might prove useful in restoring function in HAD patients.
Shared versus Specialized Glycinergic Spinal Interneurons in Axial Motor Circuits of Larval Zebrafish
Authors: Liao James C. , Fetcho Joseph R.
Published: November 2008

The neuronal networks in spinal cord can produce a diverse array of motor behaviors. In aquatic vertebrates such as fishes and tadpoles, these include escape behaviors, swimming across a range of speeds, and struggling. We addressed the question of whether these behaviors are accomplished by a shared set of spinal interneurons activated in different patterns or, instead, involve specialized spinal interneurons that may shape the motor output to produce particular behaviors. We used larval zebrafish because they are capable of several distinct axial motor behaviors using a common periphery and a relatively small set of spinal neurons, easing the task of exploring the extent to which cell types are specialized for particular motor patterns. We performed targetedin vivowhole-cell patch recordings in 3 d post fertilization larvae to reveal the activity pattern of four commissural glycinergic interneuron types during escape, swimming and struggling behaviors. While some neuronal classes were shared among different motor patterns, we found others that were active only during a single one. These specialized neurons had morphological and functional properties consistent with a role in shaping key features of the motor behavior in which they were active. Our results, in combination with other evidence from excitatory interneurons, support the idea that patterns of activity in a core network of shared spinal neurons may be shaped by more specialized interneurons to produce an assortment of motor behaviors.
Activated Protein C Promotes Neovascularization and Neurogenesis in Postischemic Brain via Protease-Activated Receptor 1
Authors: Thiyagarajan Meenakshisundaram , Fernández José A. , Lane Steven M. , Griffin John H. , Zlokovic Berislav V.
Published: November 2008

Activated protein C (APC) is a serine protease with anticoagulant and direct cytoprotective activities. Early postischemic APC application activates the cellular protein C pathway in brain endothelium and neurons, which is neuroprotective. Whether late APC administration after a transient ischemic attack is neuroprotective and whether APC influences brain repair is not known. Here, we determined safety and efficacy of late APC and tissue-plasminogen activator (tPA) administrations in a mouse model of transient brain ischemia. tPA given at 6 h after onset of ischemia killed all mice within 2 d, whereas APC given at 6 or 24 h after ischemia onset improved significantly functional outcome and reduced spread of the ischemic lesion. At 7 d postischemia, APC multiple dosing (0.8 mg/kg, i.p.) at 6–72 or 72–144 h enhanced comparably cerebral perfusion in the ischemic border by ∼40% as shown byin vivolectin-FITC angiography, blocked blood–brain barrier leakage of serum proteins, and increased the number of endothelial replicating cells by 4.5- to 4.7-fold. APC multidosing at 6–72 h or 72–144 h increased proliferation of neuronal progenitor cells in the subventricular zone (SVZ) by 40–50% and migration of newly formed neuroblasts from the SVZ toward the ischemic border by approximately twofold. The effects of APC on neovascularization and neurogenesis were mediated by protease-activated receptor 1 and were independent of the reduction by APC of infarction volume. Our data show that delayed APC administration is neuroprotective and mediates brain repair (i.e., neovascularization and neurogenesis), suggesting a significant extension of the therapeutic window for APC intervention in postischemic brain.
Interleukin-18-Mediated Microglia/Astrocyte Interaction in the Spinal Cord Enhances Neuropathic Pain Processing after Nerve Injury
Authors: Miyoshi Kan , Obata Koichi , Kondo Takashi , Okamura Haruki , Noguchi Koichi
Published: November 2008

Interleukin (IL)-18 is an important regulator of innate and acquired immune responses. Here we show that both the IL-18 and IL-18 receptor (IL-18R), which are induced in spinal dorsal horn, are crucial for tactile allodynia after nerve injury. Nerve injury induced a striking increase in IL-18 and IL-18R expression in the dorsal horn, and IL-18 and IL-18R were upregulated in hyperactive microglia and astrocytes, respectively. The functional inhibition of IL-18 signaling pathways suppressed injury-induced tactile allodynia and decreased the phosphorylation of nuclear factor κB in spinal astrocytes and the induction of astroglial markers. Conversely, intrathecal injection of IL-18 induced behavioral, morphological, and biochemical changes similar to those observed after nerve injury. Our results indicate that IL-18-mediated microglia/astrocyte interactions in the spinal cord have a substantial role in the generation of tactile allodynia. Thus, blocking IL-18 signaling in glial cells might provide a fruitful strategy for treating neuropathic pain.
Sequential Generation of Two Distinct Synapse-Driven Network Patterns in Developing Neocortex
Authors: Allène Camille , Cattani Adriano , Ackman James B. , Bonifazi Paolo , Aniksztejn Laurent , Ben-Ari Yehezkel , Cossart Rosa
Published: November 2008

Developing cortical networks generate a variety of coherent activity patterns that participate in circuit refinement. Early network oscillations (ENOs) are the dominant network pattern in the rodent neocortex for a short period after birth. These large-scale calcium waves were shown to be largely driven by glutamatergic synapses albeit GABA is a major excitatory neurotransmitter in the cortex at such early stages, mediating synapse-driven giant depolarizing potentials (GDPs) in the hippocampus. Using functional multineuron calcium imaging together with single-cell and field potential recordings to clarify distinct network dynamics in rat cortical slices, we now report that the developing somatosensory cortex generates first ENOs then GDPs, both patterns coexisting for a restricted time period. These patterns markedly differ by their developmental profile, dynamics, and mechanisms: ENOs are generated before cortical GDPs (cGDPs) by the activation of glutamatergic synapses mostly through NMDARs; cENOs are low-frequency oscillations (∼0.01 Hz) displaying slow kinetics and gradually involving the entire network. At the end of the first postnatal week, GABA-driven cortical GDPs can be reliably monitored; cGDPs are recurrent oscillations (∼0.1 Hz) that repetitively synchronize localized neuronal assemblies. Contrary to cGDPs, cENOs were unexpectedly facilitated by short anoxic conditions suggesting a contribution of glutamate accumulation to their generation. In keeping with this, alterations of extracellular glutamate levels significantly affected cENOs, which are blocked by an enzymatic glutamate scavenger. Moreover, we show that a tonic glutamate current contributes to the neuronal membrane excitability when cENOs dominate network patterns. Therefore, cENOs and cGDPs are two separate aspects of neocortical network maturation that may be differentially engaged in physiological and pathological processes.
Polarized Targeting of Neurexins to Synapses Is Regulated by their C-Terminal Sequences
Authors: Fairless Richard , Masius Henriette , Rohlmann Astrid , Heupel Katharina , Ahmad Mohiuddin , Reissner Carsten , Dresbach Thomas , Missler Markus
Published: November 2008

Two families of cell-adhesion molecules, predominantly presynaptic neurexins and postsynaptic neuroligins, are important for the formation and functioning of synapses in the brain, and mutations in several genes encoding these transmembrane proteins have been found in autism patients. However, very little is known about how neurexins are targeted to synapses and which mechanisms regulate this process. Using various epitope-tagged neurexins in primary hippocampal neurons of wild-type and knock-out micein vitroand in transgenic animalsin vivo, we show that neurexins are trafficked throughout neurons via transport vesicles and the plasma membrane insertion of neurexins occurs preferentially in the axonal/synaptic compartment. We also observed that exit of neurexins from the ER/Golgi and correct targeting require their PDZ-binding motif at the C terminus, whereas two presumptive ER retention signals are inactive. The ubiquitous presence of neurexin-positive transport vesicles and absence of bassoon colabeling demonstrate that these carriers are not active zone precursor vesicles, but colocalization with CASK, RIM1α, and calcium channels suggests that they may carry additional components of the exocytotic machinery. Our data indicate that neurexins are delivered to synapses by a polarized and regulated targeting process that involves PDZ-domain mediated interactions, suggesting a novel pathway for the distribution of neurexins and other synaptic proteins.
Continuity in Composing the American Cross-Cultural: Eichheim, Cowell, and Japan
Authors: Sheppard W. Anthony
Published: November 2008

Japanese music has repeatedly served as an exotic model for those American composers seeking “ultra-modern” status. Henry Eichheim's and Henry Cowell's engagements with Japan offer rich case studies for reconsidering our common critical approaches to cross-cultural works, prompting us to question the temporal, geographic, generic, and high/low boundaries typically employed in modernist taxonomy. I find that attempts to employ categorically such terms as “appropriation” and “influence” and “modernist” and “post-modernist” in evaluating cross-cultural compositions limits our experience of such works and that specific examples tend to demonstrate the full contradictory and multifaceted nature of musical exoticism.

I turn first to the impact of literary japonisme and travel on Eichheim and consider his aesthetic and didactic motivations. The writings of Lafcadio Hearn provided Eichheim with ready-made impressions of Japan and directly shaped his compositional responses. I note the influence of gagaku and shōō pitch clusters and briefly compare Eichheim's work with that of Hidemaro Konoye (Konoe). I then chronicle Cowell's lifelong encounters with Japanese music, focusing on his study of the shakuhachi with Kitaro Tamada, his experiences at the 1961 Tokyo East-West Music Encounter Conference, and his collaboration with the koto performer Kimio Eto, which reveal the limits of Cowell's embrace of musical hybridity. I argue that Cowell's mature Japanese-inspired works should be considered within the context of American Cold War cultural diplomacy and contemporaneous works of popular, jazz, and film music.
Biomimetics: Learning from diamonds
Authors: Sommer Andrei P. , Zhu Dan , Franke Ralf-Peter , Fecht Hans-Joerg
Published: November 2008

There is increasing observational evidence for an implication of the order of interfacial water layers in biology, for instance in processes of cellular recognition and during first contact events, where cells decide to survive or enter apoptosis. Experimental methods that allow access to the order of interfacial water layers are thus crucial in biomedical engineering. In this study, we show that interfacial water structures can be nondestructively analyzed on the nanocrystalline diamond. Results open the gate to a new chapter in the design of biomaterials inspired by biomimetic principles.
Effect of pulse current on structure and adhesion of apatite electrochemically deposited onto titanium substrates
Authors: Hayakawa Tomoyasu , Kawashita Masakazu , Takaoka Gikan H. , Miyazaki Toshiki
Published: November 2008

Apatite films were deposited onto titanium (Ti) metal substrates by an electrodeposition method under a pulse current. Metastable calcium phosphate solution was used as the electrolyte. The ion concentration of the solution was 1.5 times that of human body fluid, but the solution did not contain magnesium ions at 36.5 °C. We used an average current density of 0.01 A/cm2and current-on time (TON) equal to current-off time (TOFF) of 10 ms, 100 ms, 1 s, and 15 s. The adhesive strength between apatite and Ti substrates were relatively high atTON=TOFF= 10 ms. It is considered that small calcium phosphate (C–P) crystals with low crystallinity were deposited on the Ti surface without reacting with other C–P crystals, H2O, and HCO3−in the surrounding environment. This resulted in relaxation of the lattice mismatch and enhancement of the adhesive strength between the apatite crystals and Ti substrates.
Bioinspired synthesis of self-assembled calcium phosphate nanocomposites using block copolymer-peptide conjugates
Authors: Yusufoglu Yusuf , Hu Yanyan , Kanapathipillai Mathumai , Kramer Matthew , Kalay Yunus E. , Thiyagarajan P. , Akinc Mufit , Schmidt-Rohr Klaus , Mallapragada Surya
Published: November 2008

Thermoreversibly gelling block copolymers conjugated to hydroxyapatite-nucleating peptides were used to template the growth of inorganic calcium phosphate in aqueous solutions. Nuclear magnetic resonance (NMR), Fourier transform infrared (FTIR), transmission electron microscopy, x-ray diffraction, and small-angle scattering were used to characterize these samples and confirm that the peptides promoted the growth of hydroxyapatite as the inorganic phase. Three different polymer templates were used with varying charges on the polymer chains (nonionic, anionic, and zwitterionic), to investigate the role of charge on mineralization. All of the polymer-inorganic solutions exhibited thermoreversible gelation above room temperature. Nanocomposite formation was confirmed by solid-state NMR, and several methods identified the inorganic component as hydroxyapatite. Small angle x-ray scattering and electron microscopy showed thin, elongated crystallites. Thermogravimetric analysis showed an inorganic content of 30–45 wt% (based on the mass of the dried gel at ∼200 °C) in the various samples. Our work offers routes for bioinspired bottom-up approaches for the development of novel, self-assembling, injectable nanocomposite biomaterials for potential orthopedic applications.
Transmission electron microscopy observation of nanoscale deformation structures in nacre
Authors: Sumitomo Taro , Kakisawa Hideki , Owaki Yusuke , Kagawa Yutaka
Published: November 2008

The mechanical performance of nacre in seashells is generally described in terms of mesoscale mechanisms between mineral plates within the organic polymer matrix. However, recent work has reported nanostructures and organic material within individual plates and associated deformation mechanisms. In this work, we further investigated the nanoscale structure and mechanical behavior within individual plates of nacre by using two methods to induce fracture of plates: microindentation with focused ion beam preparation and ultramicrotomy. Using transmission electron microscopy, we observed deformation nanostructures and organic matrix within plates and identified nanoscale mechanisms, such as separation, shear, and matrix crack bridging.
Fabrication, chemical etching, and compressive strength of porous biomimetic SiC for medical implants
Authors: Torres-Raya Carmen , Hernandez-Maldonado David , Ramirez-Rico Joaquin , Garcia-Gañan Carmen , de Arellano-Lopez Antonio R. , Martinez-Fernandez Julian
Published: November 2008

BioSiC is a biomimetic SiC-based ceramic material fabricated by Si melt infiltration of carbon preforms obtained from wood. The microstructure of bioSiC mimics that of the wood precursor, which can be chosen for tailored properties. When the remaining, unreacted Si is removed, a SiC material with interconnected porosity is obtained. This porous bioSiC is under study for its use as a medical implant material. We have successfully fabricated bioSiC from Sipo wood and studied the kinetics of Si removal by wet etching. The results suggest that the reaction is diffusion-limited, and the etch rate follows at−0.5law. The etching rate is found to be anisotropic, which can be explained attending to the anisotropy of the pore distribution. The compressive strength was studied as a function of etching time, and the results show a quadratic dependence with density. In the attainable range of densities, the strength is similar or better than that of human bone.