bluuebunny/crossref_metadata_2025 huggingface dataset:
Experimental investigations on combustion, performance, and emissions characteristics of a neat biodiesel-fuelled, turbocharged, direct injection diesel engine
Authors: Anand K , Sharma R P , Mehta P S
Published: February 2010

The concerns about clean environment, high oil prices, and stringent emission norms are the driving forces for the research on alternative fuels. Extensive investigations have been carried out in recent years on replacing diesel fuel by vegetable-oil-derived biodiesel fuel in compression ignition engines, mainly owing to its renewable source, reduced emissions, and direct usage without any engine modifications. The experimental work reported here has been carried out on a turbocharged, direct injection, multi-cylinder truck diesel engine using diesel fuel and neat karanja-oil-derived biodiesel under varying speed and load conditions.

The results of the experimental investigation indicate that a maximum of 2.3Â°CA (crank angle) advance in dynamic fuel injection timing is observed with biodiesel compared with the diesel fuel. The ignition delay is lower for biodiesel compared with diesel fuel at all engine speeds. The peak cylinder pressure is higher at most of the operating conditions and the maximum rate of pressure rise is lower at low speeds and higher at high speeds for biodiesel compared with diesel fuel. In general an earlier start of combustion and lower combustion duration are observed for biodiesel relative to diesel fuel. The maximum thermal efficiency occurring at the maximum torque speed of 1400r/min is observed to be 40.7 per cent and 40.5 per cent for diesel and neat biodiesel respectively. A significant reduction in unburnt hydrocarbon and smoke emissions, comparable carbon monoxide emissions, and higher nitric oxide emissions are observed with biodiesel compared with diesel fuel operation. In general, an improvement in combustion characteristics and exhaust emissions, except nitric oxide, are observed for biodiesel compared with diesel fuel, with a slight penalty in brake thermal efficiency.
Optimization of space radiators with step fins
Authors: Arslanturk C
Published: February 2010

The optimal design of the fin geometry of a heat pipe/fin radiator having fins with a step change in thickness, namely step fin (SF), has been performed in the present article. The optimization algorithm determines the thickness parameter describing the variation of fin thickness, intermediate fin length where the step change in thickness occurs, and the root thickness of the fins in order to provide the maximum heat radiated per element mass given the linear density of the heat pipe, the thermal conductivity and density of the fin material, the emissivity of the surface, and the operating temperature. The objective function is evaluated as the solution to a radiation thermal analysis problem performed using the Adomian decomposition method, which provides an analytical solution in the form of an infinite power series. The results of the new optimal design have been compared to heat pipe/fin radiators with flat fins (FFs). The results demonstrated that the maximum heat transfer rate per unit mass for a radiator with SF is always higher than that of a radiator with FF for the identical design condition.
Parametric experimental and numerical study on mixing characteristics in a supersonic combustor with gaseous fuel injection upstream of cavity flameholders
Authors: Sun M B , Zhang S P , Han X , Liu W D , Liang J H , Wang Z G
Published: February 2010

Non-reacting experiments and numerical simulations were performed to investigate the mixing characteristics of gaseous fuel injection upstream of a flameholding cavity in supersonic vitiated air flow. The investigation considered the effects of various flow or geometry parameters, including injection stagnation pressure, cavity length to depth ratio, and distance between the injection orifice and the cavity front wall. The nanoparticle-based laser scattering technique was used. Mix the injection nitrogen gas with nanoparticles; the fuel distribution and instantaneous displacement demonstrated by the nanoparticles were imaged with laser sheet scattering measurement. The flowfields with various mixing schemes were calculated by large eddy simulation. Experimental and numerical results showed that most of the fuel flows away upon the open cavity and only a small portion of the fuel is convected into the cavity shear layer. Fuel distribution and convection around cavity flameholders are determined by the interaction of the lifting counter-rotating vortex structures induced by the jet with the cavity shear layer. With the reduction of cavity length to depth ratio, the increase in distance between the cavity front wall and the injection exit or the increase in injection pressure, the coupling interaction between the injection, and the cavity shear layer would be changed, and the intensity of fuel mass transport from the jet to cavity would decrease.
Aerodynamics of aerofoil sections measured on a free-flying bird
Authors: Carruthers A C , Walker S M , Thomas A L R , Taylor G K
Published: February 2010

Birds are adapted to a wide range of flight conditions, from steady fixed-wing glides to high angle of attack manoeuvres involving unsteady separated flows. They naturally control and exploit the transitional Reynolds number regime of Re≈ 105 that is currently of interest in unmanned air vehicle technologies. This article presents a reconstruction of the inner portion of a wing of an eagle in free flight, during a rapid pitch-up manoeuvre at the end of a shallow glide to an elevated perch. Photogrammetric techniques were used to map the identified points on the wing and these were used to fit a mathematical model of the upper and lower surface topography using polynomial regression techniques. The surface model accounts for spanwise twist, spanwise bending, and varying chord distribution, as well as for the shape of the aerofoil. The aerodynamics of the two-dimensional aerofoil sections were analysed using XFOIL and were compared against two technical aerofoils, namely the Selig S1223 and Clark Y aerofoils, at 1×105≤ Re≤2×105. The bird aerofoil maintains a robust, near-constant drag coefficient over a wide lift coefficient range.
Complementarities and the Demand for Home Broadband Internet Services
Authors: Liu Hongju , Chintagunta Pradeep K. , Zhu Ting
Published: February 2010

Before the deregulation of digital subscriber line (DSL) services by the Federal Communications Commission (FCC) in 2005, phone companies were required to share their DSL bandwidth with independent DSL providers. Despite the large number of independent providers that entered the market, phone companies accounted for 95.3% of all DSL subscribers in 2005. A common explanation for this is based on supply-side factors such as the costs faced by these providers to lease phone lines from phone companies, as well as the price discounts offered by phone companies. In this paper, we look for a demand-side explanation for this market outcome. Analyzing consumer choices in the broadband category alone would lead us to the conclusion that consumers have a much higher preference for their local phone providers—a finding at odds with service awards received by independent DSL providers. Thus we look for a demand-side explanation that is based on the demand not just for broadband services but also for related services such as cable TV and local phone. We find evidence of strong complementarities between the consumption of broadband and of those related categories. The main source of such complementarities, in our data, is the benefits to consumers from having a single provider for multiple services. We then carry out counterfactual experiments assuming that there are no changes in the regular prices of the various services. Our results indicate that the share of phone companies in the broadband market would have been 43% smaller without complementarities stemming from such a single-provider effect, whereas shutting off the state dependence effects would have reduced their share by 30%, and shutting off the effects of price discounts on the DSL+local phone bundle would have resulted in their share declining by 21%.
Alliance Formation Among Perfectly Complementary Suppliers in a Price-Sensitive Assembly System
Authors: Yin Shuya
Published: February 2010

Independent parties that produce perfectly complementary components may form alliances (or coalitions or groups) to better coordinate their pricing decisions when they sell their products to downstream buyers. This paper studies how market demand conditions (i.e., the form of the demand function, demand uncertainty, and price-sensitive demand) drive coalition formation among complementary suppliers. In a deterministic demand model, we show that for an exponential or isoelastic demand function, suppliers always prefer selling in groups; for a linear-power demand function, suppliers may all choose to sell independently in equilibrium. These results are interpreted through the pass-through rate associated with the demand function. In an uncertain demand model, we show that, in general, the introduction of a multiplicative stochastic element in demand has an insignificant impact on stable coalitions and that an endogenous retail price (i.e., demand is price sensitive) increases suppliers' incentives to form alliances relative to the case with a fixed retail price. We also consider the impact of various other factors on stable outcomes in equilibrium, e.g., sequential decision making by coalitions of different sizes, the cost effect due to alliance formation (either cost savings or additional costs), and a system without an assembler.
Leadtime-Variety Tradeoff in Product Differentiation
Authors: Alptekinoğlu Aydın , Corbett Charles J.
Published: February 2010

The literature on mass customization generally focuses on the tradeoff between higher revenues from better matching customer preferences with product specifications, and higher costs of offering a broader—possibly fully customized—product line. Less well understood is the tradeoff between the increased ability to precisely meet customer preferences and the increased leadtime from order placement to delivery often associated with customized products. In this paper, we use a locational customer choice model to formulate a firm's integrated product line design problem that involves variety, leadtime (or inventory), and pricing decisions. We propose a dynamic programming based solution procedure that amounts to solving a shortest path problem on an acyclic network, and derive some structural results on the optimal product line design. We find that unimodal preferences generally result in hybrid product lines, with standard products clustering around the mode and custom products covering the tails, in contrast with the all-custom or all-standard product lines that are optimal under uniform preferences. We also numerically examine how the firm should adjust its leadtime and variety in response to changes in parameters such as customer dispersion and operational scale. We find that the tradeoff between leadtime and variety is sometimes nonintuitive and complex.
Drug Dosage Adjustment Using Renal Estimation Equations: A Review of the Literature
Authors: Greenberg Eric , Saad Nasser , Abraham Teena , Balmir Eric
Published: February 2010

Purpose

To examine the factors affecting drug clearance and the available evidence for drug dosing based on the Cockcroft-Gault (CG) equation and the abbreviated Modification of Diet in Renal Disease (abbrMDRD) equation. Factors that would distort the accuracy of these formulas and the affect of this distortion on the use of either formula in drug dosage adjustment were reviewed.

Methods

An updated review of the literature was performed that pertained to the accuracy of the CG and abbrMDRD equations and their use in drug dosage adjustment. MEDLINE was searched using the OVIDSP database, from the inception of the database (1950) through June 2008.

Discussion

To cover the major issues concerning the use of renal estimation equations in drug dosing adjustment, various areas were examined. Topics included the accuracy of the CG and abbrMDRD formulas, variability in these equations because of patient and laboratory factors, the isotope dilution-mass spectrometry standardization initiative, and the applicability of each formula to modifying medication doses.

Conclusion

Although the abbrMDRD equation has many advantages as compared with the CG equation, too little research has been completed at this time to recommend the clinical use of the abbrMDRD equation in pharmacy practice.
New Drugs Approved by the FDA; New Dosage Forms and Indications Approved by the FDA; Agents Pending FDA Approval; New Drug/Biologics License Applications Filed by Manufacturer; Supplemental Applications Filed by Manufacturer; Significant Labeling Changes or “Dear Health Care Professional” Letters Related to Safety
Authors: Baker Danial E.
Published: February 2010

This monthly feature will help readers keep current on new drugs, new indications, dosage forms, and safety-related changes in labeling or use. Efforts have been made to ensure the accuracy of this information; however, if there are any questions, please let us know at hospitalpharmacy@drugfacts.com .
The Constitutive Activity of Epidermal Growth Factor Receptor vIII Leads to Activation and Differential Trafficking of Wild-type Epidermal Growth Factor Receptor and erbB2
Authors: Zeineldin Reema , Ning Yan , Hudson Laurie G.
Published: February 2010

A constitutively active epidermal growth factor receptor (EGFR) mutant, EGFR variant III (EGFRvIII), has been detected at high frequencies in certain human cancers. This study evaluated transactivation and trafficking of erbB family members as a result of constitutive EGFR activity in a cancer cell line. Expression of EGFRvIII modulated erbB family members through different mechanisms; the erbB3 mRNA level was reduced, whereas wild-type EGFR (wtEGFR) and erbB2 protein levels were diminished, with no change in their mRNA levels, and there was no change in the erbB4 expression level. Both EGFR and erbB2 were internalized as a result of EGFRvIII's activity and redistributed to the cell surface upon addition of AG1478, an inhibitor of wtEGFR/EGFRvIII catalytic activity. Acute activation of EGFRvIII by removing AG1478 from cells increased phosphorylation of both wtEGFR and erbB2 and caused differential trafficking of EGFRvIII's activation partners; wtEGFR was directed primarily to lysosomal compartments and partially to recycling compartments, whereas erbB2 was directed primarily to recycling compartments and partially to lysosomal compartments. Our data demonstrate that the constitutive activity of EGFRvIII is sufficient to trigger endocytosis and trafficking of wtEGFR and erbB2, which may play a role in activating signaling pathways that are triggered during receptor endocytosis.
A new statistical method for evaluating long-term analytical performance of laboratories applied to an external quality assessment scheme for flow cytometry
Authors: Coucke Wim , Van Blerk Marjan , Libeer Jean-Claude , Van Campenhout Christel , Albert Adelin
Published: February 2010

Background: The Belgian External Quality Assessment Scheme for Flow Cytometry evaluates the long-term analytical performance of participating laboratories by calculating a regression line between the target and reported values of each parameter for each laboratory during the past 3 years. This study aims to develop a method to find laboratories with aberrant variability or bias using robust techniques and to obtain robust estimates of the variability.

Methods: A method is proposed to find outliers with respect to the individual regression line, followed by a step to find regression lines with excessive variability and finally a step to find regression lines with high bias.

Results: The model was applied to the results obtained by 52 laboratories for CD4%. From the 1340 data points, 35 were determined to be regression outliers. The second step revealed one regression line with excessive variability; the third step detected three regression lines with exceeding bias.

Conclusions: The methodology allows assessment of the long-term performance of laboratories, taking into account samples with different target values. Outliers in the first step indicate accidental mistakes, outliers in the second and third step point to high analytical variability or bias.

Clin Chem Lab Med 2010;48:645–50.
Cardiovascular risk factors and γ-glutamyltransferase fractions in healthy individuals
Authors: Franzini Maria , Paolicchi Aldo , Fornaciari Irene , Ottaviano Virginia , Fierabracci Vanna , Maltinti Maristella , Ripoli Andrea , Zyw Luc , Scatena Fabrizio , Passino Claudio , Pompella Alfonso , Emdin Michele
Published: February 2010

Background: Serum γ-glutamyltransferase activity (GGT), even when within its normal reference range, catalyzes low density lipoprotein oxidation in vitro and predicts cardiovascular events. Of the four GGT fractions (b-GGT, m-GGT, s-GGT, and f-GGT) recently identified in blood, only b-GGT is found within atherosclerotic plaques. Our goal was to identify the determinants of the GGT fractions (b-, m-, s-, and f-GGT) and their association with established cardiovascular risk factors in healthy subjects.

Methods: Multiple linear regression analysis was applied to estimate the association of fractional GGT with gender, age, body mass index, arterial pressure (AP), plasma glucose, alanine aminotransferase (ALT), high and low density lipoproteins (LDL-C) cholesterol (HDL-C), triglycerides (TG) and C-reactive protein (CRP) in 200 healthy subjects.

Results: All GGT fractions were associated with ALT; b-GGT with AP, TG, and CRP; m-GGT with LDL-C, TG and CRP; s-GGT with TG and CRP, and f-GGT only with LDL-C, whereas gender was associated with s-GGT and f-GGT only.

Conclusions: In healthy individuals, cardiovascular risk factors are associated with high molecular weight GGT fractions, namely with b-GGT, the only form present within the plaque. This finding adds to the present knowledge concerning the relevance of GGT, within its reference range, for atherosclerosis-related events.

Clin Chem Lab Med 2010;48:713–7.
Mixed mode fracture testing of adhesively bonded wood specimens using a dual actuator load frame
Authors: Singh Hitendra K. , Chakraborty Abhijit , Frazier Charles E. , Dillard David A.
Published: February 2010

An experimental evaluation of mixed mode fracture tests conducted on adhesively bonded wood specimens using a dual actuator load frame is presented. This unit allows the fracture mode mixity to be easily varied during testing of a given specimen, providing improved consistency, accuracy, and ease of testing over a range of loading modes. Double cantilever beam (DCB) type specimens made of southern yellow pine (Pinusspp.) wood substrates bonded with a commercially available one part polyurethane adhesive were tested over a wide range of mode mixities from pure mode I to pure mode II. The critical strain energy release rate (SERR) values were calculated from the measured load, displacement, and crack length data, in combination with material properties and specimen geometric parameters, and compared on aversusfracture envelope plot. Mean quasi-static fracture energy values were calculated to be 390 J m-2and 420 J m-2for mode I and mode II fracture, respectively. For various mixed mode phase angles, the critical SERR values were partitioned into mode I and mode II components. In mixed mode loading conditions the cracks were typically driven along the interface, which resulted in lower total fracture energy values when compared with those measured under pure mode I loading conditions. A drop in measured fracture energy of approximately 45% was observed with mode mixity phase angles as small as 16°, implying that engineering designs based on results from the popular mode I DCB test could be nonconservative in some situations. Fracture surfaces obtained at different mode mixities are also discussed. An improved understanding of fracture behavior of adhesively bonded wood joints under mixed mode loading through generation of fracture envelopes could lead to improved designs of bonded wood structures.
Application of non-symmetrical drying tests for assessment of drying behaviour of ntholo (Pseudolachnostylis maprounaefolia PAX)
Authors: Junior Ernesto Uetimane , Allegretti Ottaviano , Terziev Nasko , Söderström Ove
Published: February 2010

Experiments concerning drying behaviour of ntholo (Pseudolachnostylis maprounaefolia PAX) were conducted to find a suitable drying schedule. Two non-symmetrical drying (NSD) tests were carried out to determine the drying behaviour of ntholo in terms of drying rate and stress behaviour. A tentative drying schedule was selected for comparison of the test results with those of similar tests with other known species. The schedule was tested in a laboratory kiln on 28-mm thick boards. According to both NSD tests and laboratory tests, ntholo dries easily but slowly. The laboratory drying lasted 266 h and achieved standard drying quality characterised by 8.9% moisture content, a moisture gradient of 1.2% and a case-hardening (gap) of 1.2 mm. Twist was the largest deformation with 3.4 mm per 1000 mm on average. The assigned schedule provided standard drying quality and it could be tested further in industrial kilns.
Hippocampal Gamma Oscillations Increase with Memory Load
Authors: van Vugt Marieke K. , Schulze-Bonhage Andreas , Litt Brian , Brandt Armin , Kahana Michael J.
Published: February 2010

Although the hippocampus plays a crucial role in encoding and retrieval of contextually mediated episodic memories, considerable controversy surrounds the role of the hippocampus in short-term or working memory. To examine both hippocampal and neocortical contributions to working memory function, we recorded electrocorticographic activity from widespread cortical and subcortical sites as 20 neurosurgical patients performed working memory tasks. These recordings revealed significant increases in 48–90 Hz gamma oscillatory power with memory load for two classes of stimuli: letters and faces. Sites exhibiting gamma increases with memory load appeared primarily in the hippocampus and medial temporal lobe. These findings implicate gamma oscillatory activity in the maintenance of both letters and faces in working memory and provide the first direct evidence for modulation of hippocampal gamma oscillations as humans perform a working memory task.
Stochastic Transitions between Neural States in Taste Processing and Decision-Making
Authors: Miller Paul , Katz Donald B.
Published: February 2010

Noise, which is ubiquitous in the nervous system, causes trial-to-trial variability in the neural responses to stimuli. This neural variability is in turn a likely source of behavioral variability. Using Hidden Markov modeling, a method of analysis that can make use of such trial-to-trial response variability, we have uncovered sequences of discrete states of neural activity in gustatory cortex during taste processing. Here, we advance our understanding of these patterns in two ways. First, we reproduce the experimental findings in a formal model, describing a network that evinces sharp transitions between discrete states that are deterministically stable given sufficient noise in the network; as in the empirical data, the transitions occur at variable times across trials, but the stimulus-specific sequence is itself reliable. Second, we demonstrate that such noise-induced transitions between discrete states can be computationally advantageous in a reduced, decision-making network. The reduced network produces binary outputs, which represent classification of ingested substances as palatable or nonpalatable, and the corresponding behavioral responses of “spit” or “swallow”. We evaluate the performance of the network by measuring how reliably its outputs follow small biases in the strengths of its inputs. We compare two modes of operation: deterministic integration (“ramping”) versus stochastic decision-making (“jumping”), the latter of which relies on state-to-state transitions. We find that the stochastic mode of operation can be optimal under typical levels of internal noise and that, within this mode, addition of random noise to each input can improve optimal performance when decisions must be made in limited time.
A G-Protein-Coupled Neuropeptide Y-Like Receptor Suppresses Behavioral and Sensory Response to Multiple Stressful Stimuli in Drosophila
Authors: Xu Jie , Li Mo , Shen Ping
Published: February 2010

Recent studies suggest that human neuropeptide Y (NPY) plays a prominent role in management of stress response and emotion, and higher NPY levels observed in combat-exposed veterans may help coping with posttraumatic stress. Neuropeptide F (NPF), the counterpart of NPY inDrosophila melanogaster, also displays parallel activities, including promotion of resilience to diverse stressors and prevention of uncontrolled aggressive behavior. However, it remains unclear how NPY family peptides modulate physical and emotional responses to various stressors. Here we show that NPFR1, a G-protein-coupled NPF receptor, exerts an inhibitory effect on larval aversion to diverse stressful stimuli mediated by different subtypes of fly and mammalian transient receptor potential (TRP) family channels. Imaging analysis in larval sensory neurons and cultured human cells showed that NPFR1 attenuates Ca2+influx mediated by fly TRPA and rat TRPV1 channels. Our findings suggest that suppression of TRP channel-mediated neural excitation by the conserved NPF/NPFR1 system may be a major mechanism for attaining its broad anti-stress function.
Phase Response Curve Analysis of a Full Morphological Globus Pallidus Neuron Model Reveals Distinct Perisomatic and Dendritic Modes of Synaptic Integration
Authors: Schultheiss Nathan W. , Edgerton Jeremy R. , Jaeger Dieter
Published: February 2010

Synchronization of globus pallidus (GP) neurons and cortically entrained oscillations between GP and other basal ganglia nuclei are key features of the pathophysiology of Parkinson's disease. Phase response curves (PRCs), which tabulate the effects of phasic inputs within a neuron's spike cycle on output spike timing, are efficient tools for predicting the emergence of synchronization in neuronal networks and entrainment to periodic input. In this study we apply physiologically realistic synaptic conductance inputs to a full morphological GP neuron model to determine the phase response properties of the soma and different regions of the dendritic tree. We find that perisomatic excitatory inputs delivered throughout the interspike interval advance the phase of the spontaneous spike cycle yielding a type I PRC. In contrast, we demonstrate that distal dendritic excitatory inputs can either delay or advance the next spike depending on whether they occur early or late in the spike cycle. We find this latter pattern of responses, summarized by a biphasic (type II) PRC, was a consequence of dendritic activation of the small conductance calcium-activated potassium current, SK. We also evaluate the spike-frequency dependence of somatic and dendritic PRC shapes, and we demonstrate the robustness of our results to variations of conductance densities, distributions, and kinetic parameters. We conclude that the distal dendrite of GP neurons embodies a distinct dynamical subsystem that could promote synchronization of pallidal networks to excitatory inputs. These results highlight the need to consider different effects of perisomatic and dendritic inputs in the control of network behavior.
Distinct Roles of NR2A and NR2B Cytoplasmic Tails in Long-Term Potentiation
Authors: Foster Kelly A. , McLaughlin Nathan , Edbauer Dieter , Phillips Marnie , Bolton Andrew , Constantine-Paton Martha , Sheng Morgan
Published: February 2010

NMDA receptors (NMDARs) are critical mediators of activity-dependent synaptic plasticity, but the differential roles of NR2A- versus NR2B-containing NMDARs have been controversial. Here, we investigate the roles of NR2A and NR2B in long-term potentiation (LTP) in organotypic hippocampal slice cultures using RNA interference (RNAi) and overexpression, to complement pharmacological approaches. In young slices, when NR2B is the predominant subunit expressed, LTP is blocked by the NR2B-selective antagonist Ro25-6981 [R-(R,S)-α-(4-hydroxyphenyl)-β-methyl-4-(phenylmethyl)-1-piperidine propranol]. As slices mature and NR2A expression rises, activation of NR2B receptors became no longer necessary for LTP induction. LTP was blocked, however, by RNAi knockdown of NR2B, and this was rescued by coexpression of an RNAi-resistant NR2B (NR2B*) cDNA. Interestingly, a chimeric NR2B subunit in which the C-terminal cytoplasmic tail was replaced by that of NR2A failed to rescue LTP, whereas the reverse chimera, NR2A channel with NR2B tail, was able to restore LTP. Thus, expression of NR2B with its intact cytoplasmic tail is required for LTP induction, at an age when channel activity of NR2B–NMDARs is not required for LTP. Overexpression of wild-type NR2A failed to rescue LTP in neurons transfected with the NR2B–RNAi construct, despite restoring NMDA–EPSC amplitude to a similar level as NR2B*. Surprisingly, an NR2A construct lacking its entire C-terminal cytoplasmic tail regained its ability to restore LTP. Together, these data suggest that the NR2B subunit plays a critical role for LTP, presumably by recruiting relevant molecules important for LTP via its cytoplasmic tail. In contrast, NR2A is not essential for LTP, and its cytoplasmic tail seems to carry inhibitory factors for LTP.
AcuteIn VivoGenetic Rescue Demonstrates That Phosphorylation of RIM1α Serine 413 Is Not Required for Mossy Fiber Long-Term Potentiation
Authors: Yang Ying , Calakos Nicole
Published: February 2010

While presynaptic, protein kinase A (PKA)-dependent, long-term plasticity has been described in numerous brain regions, the target(s) of PKA and the molecular mechanisms leading to sustained changes in neurotransmitter release remain elusive. Here, we acutely reconstitute mossy fiber long-term potentiation (mfLTP)de novoin the mature brains of mutant mice that normally lack this form of plasticity. These results demonstrate that RIM1α, a presynaptic scaffold protein and a potential PKA target, can support mfLTP independent of a role in brain development. Using this approach, we study two mutations of RIM1α (S413A and V415P) and conclude that PKA-phosphorylation-dependent signaling by RIM1α serine 413 is not required for mfLTP, consistent with conclusions reached from the study of RIM1α S413A knockin mice. Together, these results provide insights into the mechanism of mossy fiber LTP and demonstrate a useful acute approach to genetically manipulate mossy fiber synapses in the mature brain.
Amyloid β Induces the Morphological Neurodegenerative Triad of Spine Loss, Dendritic Simplification, and Neuritic Dystrophies through Calcineurin Activation
Authors: Wu Hai-Yan , Hudry Eloise , Hashimoto Tadafumi , Kuchibhotla Kishore , Rozkalne Anete , Fan Zhanyun , Spires-Jones Tara , Xie Hong , Arbel-Ornath Michal , Grosskreutz Cynthia L. , Bacskai Brian J. , Hyman Bradley T.
Published: February 2010

Amyloid β (Aβ)-containing plaques are surrounded by dystrophic neurites in the Alzheimer's disease (AD) brain, but whether and how plaques induce these neuritic abnormalities remain unknown. We tested the hypothesis that soluble oligomeric assemblies of Aβ, which surround plaques, induce calcium-mediated secondary cascades that lead to dystrophic changes in local neurites. We show that soluble Aβ oligomers lead to activation of the calcium-dependent phosphatase calcineurin (CaN) (PP2B), which in turn activates the transcriptional factor nuclear factor of activated T cells (NFAT). Activation of these signaling pathways, even in the absence of Aβ, is sufficient to produce a virtual phenocopy of Aβ-induced dystrophic neurites, dendritic simplification, and dendritic spine loss in both neurons in culture and in the adult mouse brain. Importantly, the morphological deficits in the vicinity of Aβ deposits in a mouse model of AD are ameliorated by CaN inhibition, supporting the hypothesis that CaN–NFAT are aberrantly activated by Aβ and that CaN–NFAT activation is responsible for disruption of neuronal structure near plaques. In accord with this, we also detect increased levels of an active form of CaN and NFATc4 in the nuclear fraction from the cortex of patients with AD. Thus, Aβ appears to mediate the neurodegeneration of AD, at least in part, by activation of CaN and subsequent NFAT-mediated downstream cascades.
Distinct Functional Contributions of Primary Sensory and Association Areas to Audiovisual Integration in Object Categorization
Authors: Werner Sebastian , Noppeney Uta
Published: February 2010

Multisensory interactions have been demonstrated in a distributed neural system encompassing primary sensory and higher-order association areas. However, their distinct functional roles in multisensory integration remain unclear. This functional magnetic resonance imaging study dissociated the functional contributions of three cortical levels to multisensory integration in object categorization. Subjects actively categorized or passively perceived noisy auditory and visual signals emanating from everyday actions with objects. The experiment included two 2 × 2 factorial designs that manipulated either (1) the presence/absence or (2) the informativeness of the sensory inputs. These experimental manipulations revealed three patterns of audiovisual interactions. (1) In primary auditory cortices (PACs), a concurrent visual input increased the stimulus salience by amplifying the auditory response regardless of task-context. Effective connectivity analyses demonstrated that this automatic response amplification is mediated via both direct and indirect [via superior temporal sulcus (STS)] connectivity to visual cortices. (2) In STS and intraparietal sulcus (IPS), audiovisual interactions sustained the integration of higher-order object features and predicted subjects' audiovisual benefits in object categorization. (3) In the left ventrolateral prefrontal cortex (vlPFC), explicit semantic categorization resulted in suppressive audiovisual interactions as an index for multisensory facilitation of semantic retrieval and response selection. In conclusion, multisensory integration emerges at multiple processing stages within the cortical hierarchy. The distinct profiles of audiovisual interactions dissociate audiovisual salience effects in PACs, formation of object representations in STS/IPS and audiovisual facilitation of semantic categorization in vlPFC. Furthermore, in STS/IPS, the profiles of audiovisual interactions were behaviorally relevant and predicted subjects' multisensory benefits in performance accuracy.
Contribution of the Global Subunit Structure and Stargazin on the Maturation of AMPA Receptors
Authors: Shanks Natalie F. , Maruo Tomohiko , Farina Anthony N. , Ellisman Mark H. , Nakagawa Terunaga
Published: February 2010

Subunit assembly governs regulation of AMPA receptor (AMPA-R) synaptic delivery and determines biophysical parameters of the ion channel. However, little is known about the molecular pathways of this process. Here, we present single-particle EM three-dimensional structures of dimeric biosynthetic intermediates of the GluA2 subunit of AMPA-Rs. Consistent with the structures of intact tetramers, the N-terminal domains of the biosynthetic intermediates form dimers. Transmembrane domains also dimerize despite the two ligand-binding domains (LBDs) being separated. A significant difference was detected between the dimeric structures of the wild type and the L504Y mutant, a point mutation that blocks receptor trafficking and desensitization. In contrast to the wild type, whose LBD is separated, the LBD of the L504Y mutant was detected as a single density. Our results provide direct structural evidence that separation of the LBD within the intact dimeric subunits is critical for efficient tetramerization in the endoplasmic reticulum and further trafficking of AMPA-Rs. The contribution of stargazin on the subunit assembly of AMPA-R was examined. Our data suggest that stargazin affects AMPA-R trafficking at a later stage of receptor maturation.
Hormonal Modulation of Sensorimotor Integration
Authors: DeLong Nicholas D. , Nusbaum Michael P.
Published: February 2010

Neuronal circuits commonly receive simultaneous inputs from descending, ascending, and hormonal systems. Thus far, however, most such inputs have been studied individually to determine their influence on a given circuit. Here, we examine the integrated action of the hormone crustacean cardioactive peptide (CCAP) and the gastropyloric receptor (GPR) proprioceptor neuron on the biphasic gastric mill (chewing) rhythm driven by the projection neuron modulatory commissural neuron 1 (MCN1) in the isolated crab stomatogastric ganglion. In control saline, GPR stimulation selectively prolongs the gastric mill retractor phase, via presynaptic inhibition of MCN1. In the absence of GPR stimulation, CCAP does not alter retraction duration and modestly prolongs protraction. Here, we show, using computational modeling and dynamic-clamp manipulations, that the presence of CCAP weakens or eliminates the GPR effect on the gastric mill rhythm. This CCAP action results from its ability to activate the same modulator-activated conductance (GMI) as MCN1 in the gastric mill circuit neuron lateral gastric (LG). Because GPR prolongs retraction by weakening MCN1 activation ofGMIin LG, the parallelGMIactivation by CCAP reduces the impact of GPR regulation of this conductance. The CCAP-activatedGMIthus counteracts the GPR-mediated decrease in the MCN1-activatedGMIin LG and reduces the GPR ability to regulate the gastric mill rhythm. Consequently, although CCAP neither changes retraction duration nor alters GPR inhibition of MCN1, its activation of a modulator-activated conductance in a pivotal downstream circuit neuron enables CCAP to weaken or eliminate sensory regulation of motor circuit output.
Neural Correlates of Variations in Event Processing during Learning in Basolateral Amygdala
Authors: Roesch Matthew R. , Calu Donna J. , Esber Guillem R. , Schoenbaum Geoffrey
Published: February 2010

The discovery that dopamine neurons signal errors in reward prediction has demonstrated that concepts empirically derived from the study of animal behavior can be used to understand the neural implementation of reward learning. Yet the learning theory models linked to phasic dopamine activity treat attention to events such as cues and rewards as static quantities; other models, such as Pearce–Hall, propose that learning might be influenced by variations in processing of these events. A key feature of these accounts is that event processing is modulated by unsigned rather than signed reward prediction errors. Here we tested whether neural activity in rat basolateral amygdala conforms to this pattern by recording single units in a behavioral task in which rewards were unexpectedly delivered or omitted. We report that neural activity at the time of reward is providing an unsigned error signal with characteristics consistent with those postulated by these models. This neural signal increased immediately after a change in reward, and stronger firing was evident whether the value of the reward increased or decreased. Further, as predicted by these models, the change in firing developed over several trials as expectations for reward were repeatedly violated. This neural signal was correlated with faster orienting to predictive cues after changes in reward, and abolition of the signal by inactivation of basolateral amygdala disrupted this change in orienting and retarded learning in response to changes in reward. These results suggest that basolateral amygdala serves a critical function in attention for learning.
Overexpression of Serum Response Factor Restores Ocular Dominance Plasticity in a Model of Fetal Alcohol Spectrum Disorders
Authors: Paul Arco P. , Pohl-Guimaraes Fernanda , Krahe Thomas E. , Filgueiras Claudio C. , Lantz Crystal L. , Colello Raymond J. , Wang Weili , Medina Alexandre E.
Published: February 2010

Neuronal plasticity deficits underlie many of the neurobehavioral problems seen in fetal alcohol spectrum disorders (FASD). Recently, we showed that third trimester alcohol exposure leads to a persistent disruption in ocular dominance (OD) plasticity. For instance, a few days of monocular deprivation results in a robust reduction of cortical regions responsive to the deprived eye in normal animals, but not in ferrets exposed early to alcohol. This plasticity deficit can be reversed if alcohol-exposed animals are treated with a phosphodiesterase type 1 (PDE1) inhibitor during the period of monocular deprivation. PDE1 inhibition can increase cAMP and cGMP levels, activating transcription factors such as the cAMP response element binding protein (CREB) and the serum response factor (SRF). SRF is important for many plasticity processes such as LTP, LTD, spine motility, and axonal pathfinding. Here we attempt to rescue OD plasticity in alcohol-treated ferrets using a Sindbis viral vector to express a constitutively active form of SRF during the period of monocular deprivation. Using optical imaging of intrinsic signals and single-unit recordings, we observed that overexpression of a constitutively active form of SRF, but neither its dominant-negative nor GFP, restored OD plasticity in alcohol-treated animals. Surprisingly, this restoration was observed throughout the extent of the primary visual cortex and most cells infected by the virus were positive for GFAP rather than NeuN. This finding suggests that overexpression of SRF in astrocytes may reduce the deficits in neuronal plasticity seen in models of FASD.
Synthesis, structural and spectroscopic studies of BNSalanH2 and BPSalanH2
Authors: Ferreira Pimentel Luiz Claudio , Fernandez Tatiana Lopez , de Souza Andréa Luzia Ferreira , Wardell James L. , Antunes Octavio Augusto Ceva , Visentin Lorenzo do Canto
Published: February 2010

The synthesis and characterization of gauche-N,N′-bis-[(2-cyanoethyl)-(2-hydroxyphenylmethyl)]ethane diamine, BNSalanH2 and anti-N,N′-bis-[(methylpropanoate)-(2-hydroxyphenylmethyl)]ethane diamine, BPSalanH2 are reported. These BNSalanH2, O2N4, and BPSalanH2, O4N2, molecules have both acidic and basic groups. The BNSalanH2 and BPSalanH2 molecules adopt a gauche and anti conformation, respectively, and Z stereochemistries. The conformations are governed by intramolecular interactions of both classical and non classical hydrogen bond types. In addition, a 3D self-arrangement in BNSalanH2 is created by C-HNnitrile hydrogen bonds linking molecules along [100] and [010]. The X-ray data for BNSalanH2 are: tetragonal, P41212, a = 7.7030(11) Å, b = 7.7030(11) Å, c = 34.907(7) Å, V = 2071.2(6) Å3, Z = 4, R1 = 0.0483; for BPSalanH2 are: monoclinic, P21/c, a = 12.2572(5) Å, b = 7.9993(4), c = 13.4437(5) Å, β = 108.202(2)° V = 1252.18(9) Å3, Z = 2, R1 = 0.0614.
New quaternary complex borides, Ti9M2Ru18B8 (Cr, Mn, Co, Ni, Cu, Zn): synthesis, crystal structure and bonding analysis
Authors: Fokwa Boniface P. T. , Goerens Christian , Gilleßen Michael
Published: February 2010

Powder samples and single crystals of the Ti9M2Ru18B8 (Cr, Mn, Co, Ni, Cu, Zn) phases were synthesized from the elements and characterized by powder and single-crystal X-ray diffraction as well as energy-dispersive X-ray analysis. The new phases are all isotypic and crystallize in the tetragonal system as substitutional variants of the Zn11Rh18B8-type structure (space group P4/mbm, no. 127). M2 dumbbells are observed and interconnect to each other along the [001] direction to build “ladders”. The M–M dumbbell distances vary from 2.48 to 2.50 Å and the distances between two dumbbells (M2 · · · M2) are all close to 2.97 Å, whereas the chains are well separated from each other by distances of at least 11.20 Å. A strong variation of the unit cell volume with increasing valence electron count is observed in the series. According to the results of tight-binding electronic structure calculations, Ru–B and Ti–Ru contacts are responsible for the structural stability of these phases. The strength of the M–M and M–Ru interactions decreases with increasing valence electron count in the series. Non vanishing density of states at the Fermi level indicates metallic character for all phases.
First Turkish Experiences of Assisted Beating-Heart Coronary Artery Bypass Graft with the Impella Microaxial Ventricular Assist Device�
Authors: Yildiz Cenk Eray , Sayin Murat , Yerebakan Halit , Kucukaksu Suha
Published: February 2010

The importance of minimally invasive cardiac operations, performed off-pump, without the support of cardiopulmonary bypass (CPB), is continuously increasing. Complete revascularization of obstructed coronary arteries is needed to obtain a better long-term outcome. Insertion into the left ventricle of an efficient microaxial pump can be useful when targeting an important coronary artery located at posterior wall of the heart in a patient with hemodynamic deficiency. The use of such a device can enable surgeons to avoid conversion from a preplanned off-pump strategy to traditional on-pump coronary bypass surgery. The Impella Microaxial Ventricular Assist Device (VAD) (Abiomed, Aachen, Germany) is a miniature pump with a 7-mm catheter and a flow rate of approximately 2.5-5 L/min. This device can enable cardiovascular surgery to be performed without damaging the left ventricle and causing serious aortic deficiency. Therefore, in patients with serious comorbidity, complete revascularization may be performed off pump, with the heart beating, because of the hemodynamic stability provided with the support of the microaxial intracardiac pump. If required, this pump can also support the heart during the early postoperative period. We report the first assisted beating-heart coronary artery bypass graft surgery performed with the Impella Microaxial VAD in our country. The surgery was performed on 2 patients considered high risk on the basis of EUROSCORE testing.
Case Report: Nonarrhythmogenic Right Ventricular Dysplasia Presenting with Severe Right Ventricular Failure in an Adolescent
Authors: Pac Mustafa , Pac Aysenur , Polat Tugcin Bora , Balli Sevket , Turhan Nesrin , Aras Dursun , Oflaz Mehmet Burhan , K�c�ker Seref
Published: February 2010

Right ventricular dysplasia is usually discovered by the presence of ventricular arrhythmia. As arrhythmia is an epiphenomenon, the first presentation of some cases can be primarily heart failure. We describe an adolescent girl who presented with progressive right heart failure and whose hallmark was fibrofatty replacement of ventricular muscle, especially of the right side, without ventricular arrhythmia. The patient was successfully treated by orthotopic heart transplantation.
Off-Pump Coronary Artery Bypass in a Patient with Congenital Absence of the Left Pericardium and an Extremely Left-Rotated Heart
Authors: Beiras-Fernandez Andres , Sadoni Sebastian , Michel Sebastian , Kur Felix , Vogt Ferdinand , Mau Henning , Reichart Bruno , Vicol Calin
Published: February 2010

Congenital anomalies of the pericardium are extremely rare and often difficult to diagnose. We describe a 66-year-old woman presenting with multivessel coronary artery disease and right heart insufficiency complicated by an extremely leftrotated heart due to a congenital absence of left pericardium. A multidetector row computerized tomographic study was performed to evaluate the torsion of the heart as well as the physical relationship between the left internal thoracic artery and the left coronary system. Off-pump coronary surgery was scheduled. Both the operative and postoperative courses were uneventful and the patient was discharged after 11 days.