bluuebunny/crossref_metadata_2025 huggingface dataset:
Film Thickness Prediction in an Annular Two-Phase Flow around C-shaped Bend
Authors: Tkaczyk P.M. , Morvan H.P.
Published: April 2011

A finite volume method-based CFD model has been developed in the commercial code Star CD to simulate the annular gas-liquid flow through pipes and bends. The liquid film is solved explicitly by means of a modified Volume of Fluid (VOF) method. The droplets are traced using a Lagrangian technique. The film to droplets (entrainment) and droplets to film (stick, bounce, spread and splash) interactions are taken into account using sub-models to complement the VOF model. A good agreement is found between the computed film thickness value and those cited in the literature.
Understanding Contrasting Approaches to Nationwide Implementations of Electronic Health Record Systems: England, the USA and Australia
Authors: Morrison Zoe , Robertson Ann , Cresswell Kathrin , Crowe Sarah , Sheikh Aziz
Published: April 2011

As governments commit to national electronic health record (EHR) systems, there is increasing international interest in identifying effective implementation strategies. We draw on Coiera′s typology of national programmes ‐ ‘top‐down’, ‘bottom‐up’ and ‘middle‐out’ ‐ to review EHR implementation strategies in three exemplar countries: England, the USA and Australia. In comparing and contrasting three approaches, we show how different healthcare systems, national policy contexts and anticipated benefits have shaped initial strategies. We reflect on progress and likely developments in the face of continually changing circumstances. Our review shows that irrespective of the initial strategy, over time there is likely to be convergence on the negotiated, devolved middle‐out approach, which aims to balance the interests and responsibilities of local healthcare constituencies and national government to achieve national connectivity. We conclude that, accepting the current lack of empirical evidence, the flexibility offered by the middle‐out approach may make this the best initial national strategy.
A Two-Step Numerical Method for Efficient Analysis of Structural Response to Blast Load
Authors: Li J. , Hao H.
Published: April 2011

Even with modern computer power, detailed numerical modeling and simulation of structure response to blast loads are still extremely expensive and sometimes prohibitive because it is very time consuming and requires huge computer memory. Often compromise has to be made between simulation efficiency and simulation accuracy. A lot of research efforts have been spent on improving the computational efficiency. Most of these researches concentrate on simplifying the structures, such as simplifying a structure to an equivalent SDOF system, use smeared reinforcement steel and concrete model, use substructure approach to only model part of the structure in detail. Although these approaches under certain conditions yield reliable predictions, each of them has its associated limitations. Recently a two-step method was developed to improve the computation and modeling efficiency of structure response to blast loads. Instead of simplifying the structure, the proposed method calculates the structural responses in two steps. The first step calculates the structural responses in the loading phase and the second calculates the free vibration responses with the velocity profile of the structure at the end of the loading phase as initial conditions. Using a reinforced concrete beam as the example, it was found that the proposed method yields reliable predictions of the overall beam deflection and stress in longitudinal reinforcement bars with less than 10% computational time as compared to a detailed FE model simulation. However, the predicted stress in hoop reinforcements near the beam supports is not as good. In this paper, the method is improved by also including displacement response at the end of the forced-vibration phase as the initial conditions in the free vibration analysis. The same reinforced concrete beam is used. The results show that including the displacement initial conditions in the two-step method leads to an improved prediction of the beam responses. Parametric calculations are performed in this study by varying the blast loading amplitude and duration. Using the detailed FE model simulation results as benchmark, the prediction errors on various response quantities and savings on computational times of the proposed two-step method with respect to different blast loading scenarios are presented. The accuracy and efficiency of the proposed method in predicting structural responses and damage to blast loadings are demonstrated in this paper.
Multivitamin Supplement Use and Risk of Breast Cancer: A Meta-Analysis
Authors: Chan Agnes LF , Leung Henry WC , Wang Shiao-Fung
Published: April 2011

Background

The association between consumption of multivitamins and breast cancer is inconsistent in epidemiologic studies.

Objective:

To perform a meta-analysis of cohort and case-control studies to evaluate multivitamin intake and its relationship with breast cancer risk.

Methods:

The published literature was systematically searched and reviewed using MEDLINE (1950 through July 2010), EMBASE (1980 through July 2010). and the Cochrane Central Register of Controlled Trials (The Cochrane Library 2010 issue 1). Studies that included specific risk estimates were pooled using a random-effects model. The bias and quality of these studies were assessed with REVMAN statistical software (version 5.0) and the GRADE method of the Cochrane Collaboration.

Results:

Eight of 27 studies that included 355,080 subjects were available for analysis. The total duration of multivitamin use in these trials ranged from 3 to 10 years. The frequency of current use in these studies ranged from 2 to 6 times/week. In analyses by duration of use 10 years or longer or 3 years or longer and by frequency 7 or more times/week that were reported in these studies, multivitamin use was not significantly associated with the risk of breast cancer. Only 1 recent Swedish cohort study concluded that multivitamin use is associated with an increased risk of breast cancer. The results of a meta-analysis that pooled data from 5 cohort studies and 3 case-control studies indicated that the overall multivariable relative risk and odds ratio were 0.10 (95% CI 0.60 to 1.63; p = 0.98) and 1.00 (95% CI 0.51 to 1.00; p = 1.00), respectively. The association was not statistically significant.

Conclusions:

Multivitamin use is likely not associated with a significant increased or decreased risk of breast cancer, but these results highlight the need for more case-control studies or randomized controlled clinical trials to further examine this relationship.
Children use verb semantics to retreat from overgeneralization errors: A novel verb grammaticality judgment study
Authors: Ambridge Ben , Pine Julian M. , Rowland Caroline F.
Published: April 2011

Whilst certain verbs may appear in both the intransitive inchoative and the transitive causative constructions (The ball rolled/The man rolled the ball), others may appear in only the former (The man laughed/*The joke laughed the man). Some accounts argue that children acquire these restrictions using only (or mainly) statistical learning mechanisms such as entrenchment and pre-emption. Others have argued that verb semantics are also important. To test these competing accounts, adults (Experiment 1) and children aged 5–6 and 9–10 (Experiment 2) were taught novel verbs designed to be construed — on the basis of their semantics — as either intransitive-only or alternating. In support of the latter claim, participants' grammaticality judgments revealed that even the youngest group respected these semantic constraints. Frequency (entrenchment) effects were observed for familiar, but not novel, verbs (Experiment 1). We interpret these findings in the light of a new theoretical account designed to yield effects of both verb semantics and entrenchment/pre-emption.
German children use prosody to identify participant roles in transitive sentences
Authors: Grünloh Thomas , Lieven Elena , Tomasello Michael
Published: April 2011

Most studies examining children's understanding of transitive sentences focus on the morphosyntactic properties of the construction and ignore prosody. But adults use prosody in many different ways to interpret ambiguous sentences. In two studies we investigated whether 5-year-old German children use prosody to determine participant roles in object-first (OVS) sentences with novel verbs (i.e., whether they use prosodic marking to overrule word order as a cue). Results showed that children identify participant roles better in this atypically ordered construction when sentences are realized with the marked, OVS-typical intonational pattern, especially in combination with case marking (Study 1). In a second study, we embedded these sentences into an appropriate discourse context. The results show that, even in the absence of any case marking, children understand participant roles when they are realized with the appropriate intonational pattern. These findings demonstrate that young children can use intonation to help identify participant roles in transitive sentences, at least in marked constructions such as the German object-first (OVS) construction.
Toxicological Issues of Nanoparticles Employed in Photocatalysis
Authors: Wagner Stefanie , Bloh Jonathan , Kasper Cornelia , Bahnemann Detlef
Published: April 2011

A huge amount of different nanomaterials is nowadays on the market used for various specific applications. Some nanomaterials such as TiO

Hence these materials are used for many applications, e.g., for self-cleaning and antibacterial coatings on different surfaces and for the purification of wastewater where the cleaning can be induced by simple exposure to sunlight. Because of the frequent use of these nanoparticles it is important to investigate the life cycles of these nanostructured materials as well as their environmental impact and their toxicity to animals and humans.

This review first gives a short overview about nanotechnology and nanotechnological products as well as about photocatalysis and semiconductors used in this field. We then discuss the need for a new technology named nanotoxicology and the problems occurring when investigating the toxic potential of nanomaterials as well as the life cycle of nanomaterials. Furthermore, we focus on the environmental impact of TiO
The Exact Planning of the GMPLS-based Metro Core Network
Authors: Naas Nabil , Mouftah Hussein
Published: April 2011

The continuing rapid increase in the number of wavelengths per fiber will dramatically increase the size of OXCs/ROADMs in the WDM-based metro core networks. This calls for the use of the multi-granular switching concept introduced in Generalized Multiprotocol Label Switching (GMPLS) to avoid the cost explosion of these optical switches. This paper addresses the optimal planning problem of the GMPLS-based (or multi-granular) metro core network by (i) considering the whole traffic flow hierarchy defined in GMPLS, and (ii) maintaining the color-continuity constraint for all optical flows. We call such a planning problem the Routing and Multi-Granular Paths Assignment (RMGPA). The objective of the problem is to minimize the total weighted port count in the metro core network. The problem is formulated as a Mixed Integer Linear Programming (MILP) model. Due to the computational complexity of the problem, the MILP model is solved for small-sized problems.
A Method to Measure Optical Parameters of the Diffraction Grating Using the Ratio of ±1 Orders Diffraction Efficiencies
Authors: Zhang Lijuan , Li Jianlong
Published: April 2011

A method for obtaining optical parameters of the diffraction grating from the ratio of symmetric-order diffraction efficiency (±1 orders) is proposed in this paper. We have demonstrated that our method yields better results and the surface roughness of the diffractive grating has little impact on the ratio of ±1 orders diffraction efficiencies.
Performance Analysis of Free Space Optical Systems in the Presence of Channel Physical Limitations
Authors: Jh Jamal. H. , Chin Tan. S. , Abbou F. M.
Published: April 2011

The atmospheric attenuation in optical waves due to low atmospheric visibility conditions causes a performance degradation of free space optical (FSO) communication systems. A simulation was conducted to determine the relationship between visibility in fog and optical attenuation (dB/km) at an optical wavelength of 1550 nm. In this paper, we investigate the bit error rate (BER) performance for free space optical systems operating over atmospheric attenuation channels. Simulation results are demonstrated to confirm the analytical results. From the results, we conclude that BER increases as the adverse weather and greater distance. The BER performance of free space optical (FSO) communication systems employing on-off keying (OOK) modulation format is derived. Because the fog consists mainly of particles much larger than the laser wavelength, the application of the Kruse equation to attenuation in fog is not appropriate. Because fog is the only type of weather that is likely to disrupt short (< 1 km) free space optical links, short FSO links will be necessary to meet the high availability requirements of the telecommunications industry. The key finding is that the generally accepted Kruse equation relating visibility and optical attenuation may be too pessimistic at low visibilities. A new equation describing the atmospheric attenuation of optical power is proposed.
A New TH-CDMA Scheme for Dispersive Infrared Channel and Its Performance Evaluation
Authors: Hamdi Mazda , Nasiri-Kenari Masoumeh
Published: April 2011

Infrared indoor wireless communications using nondirected links are subject to severe multipath distortion which causes intersymbol interference (ISI). To lessen multipath distortion effect and thereby to improve the system performance, in this paper, we consider a new time-hopping based multiple access scheme for this channel, in which one pulse is transmitted in each bit interval. The position of the pulse is determined based on the output of a low rate error correcting code along with the user's dedicated PN code. We evaluate the multiple access performance of the system for correlation receiver considering background noise, dark current, and thermal noise. We compare the performance of our proposed multiple access scheme with those of the previously introduced code division multiple access schemes for infrared communications, like CDMA and Frame Time Hopping (FTH). Our results show that, for the same bandwidth and bit rate, the proposed system substantially excels the other methods in term of bit error rate, or equivalently the number of the users supported at a fixed bit error rate.
DNA Endoreplication in the Brain Neurons during Body Growth of an Adult Slug
Authors: Yamagishi Miki , Ito Etsuro , Matsuo Ryota
Published: April 2011

Endoreplication is DNA synthesis without cell division. Giant neurons observed in the brains of mollusks are thought to be generated as a result of DNA endoreplication. It has been hypothesized that neuronal size becomes larger in parallel with an increase in body size and that DNA endoreplication is involved in this process to meet the increasing demand for macromolecules in neurons. There is, however, no experimental evidence for this hypothesis to date. In the present study, we investigated the following quantitatively: (1) the size of the brain and each ganglion, (2) the size of identified neurons, (3) the total number of neurons undergoing DNA endoreplication, (4) the total number of the neurons containing a cardioexcitatory peptide, and (5) the gene expression level per neuron, using terrestrial slugs whose body growth was regulated through the amount of food supplied in the laboratory. The body growth was accompanied by increases in the sizes of both neurons and ganglia and triggered more frequent DNA endoreplication events in each ganglion of the growth-promoted slugs, without increasing the total number of neurons. Increase in the neuronal size also involved the increase in the amount of transcripts expressed in a single neuron. This is the first quantitative evidence showing that the DNA endoreplication, neuronal size, and gene expression are increased concomitantly with body growth in adult mollusks.
Calcium-Permeable AMPA Receptors Are Present in Nucleus Accumbens Synapses after Prolonged Withdrawal from Cocaine Self-Administration But Not Experimenter-Administered Cocaine
Authors: McCutcheon James E. , Wang Xiaoting , Tseng Kuei Y. , Wolf Marina E. , Marinelli Michela
Published: April 2011

Repeated noncontingent cocaine injections, which lead to behavioral sensitization, increase AMPA receptor (AMPAR) transmission in the rodent nucleus accumbens (NAc) in a withdrawal-dependent manner. On withdrawal days (WD) 10–21, this is attributable to upregulation of GluA1A2-containing AMPARs. However, synaptic incorporation of GluA2-lacking/Ca2+-permeable AMPARs (CP-AMPARs) was observed after longer withdrawal (WD35) from repeated noncontingent cocaine injections in young mice (Mameli et al., 2009). CP-AMPARs had previously been observed in NAc synapses only after prolonged (WD30–WD47) withdrawal from extended-access cocaine self-administration. Our goal was to determine whether rats receiving repeated noncontingent cocaine injections during adulthood similarly exhibit CP-AMPARs in the NAc after prolonged withdrawal. For comparison, we began by evaluating CP-AMPARs on WD35–WD49 after extended-access cocaine self-administration. Confirming our previous results, whole-cell recordings revealed inwardly rectifying AMPAR EPSCs, a hallmark of CP-AMPARs. This was observed in both core and shell. Next, we conducted the same analysis in adult rats treated with eight daily noncontingent cocaine injections and recorded on WD35–WD49. AMPAR EPSCs in core and shell did not show inward rectification and were insensitive to 1-naphthylacetylspermine (a selective antagonist of CP-AMPARs). Locomotor sensitization could still be demonstrated after this long withdrawal period, although the upregulation of GluA1A2-containing AMPARs observed at earlier withdrawal times was no longer detected. In conclusion, in adult rats, accumulation of synaptic CP-AMPARs in the NAc occurs after prolonged withdrawal from extended-access cocaine self-administration but not after prolonged withdrawal from noncontingent cocaine injections.
The Long-Term Memory Trace Formed in theDrosophilaα/β Mushroom Body Neurons Is Abolished in Long-Term Memory Mutants
Authors: Akalal David-Benjamin G. , Yu Dinghui , Davis Ronald L.
Published: April 2011

A prior screen identified dozens ofDrosophila melanogastermutants that possess defective long-term memory (LTM). Using spaced olfactory conditioning, we trained 26 of these mutant lines to associate an odor cue with electric shock and then examined the memory of this conditioning 24 h later. All of the mutants tested revealed a deficit in LTM compared to the robust LTM observed in control flies. We usedin vivofunctional optical imaging to measure the magnitude of a previously characterized LTM trace, which is manifested as increased calcium influx into the axons of α/β mushroom body neurons in response to the conditioned odor. This memory trace was defective in all 26 of the LTM mutants. These observations elevate the significance of this LTM trace given that 26 independent mutants all exhibit a defect in the trace, and further suggest that the calcium trace is a fundamental mechanism underlyingDrosophilaLTM.
Naturally Occurring Autoantibodies against β-Amyloid: Investigating Their Role in Transgenic Animal andIn VitroModels of Alzheimer's Disease
Authors: Dodel Richard , Balakrishnan Karthikeyan , Keyvani Kathy , Deuster Oliver , Neff Frauke , Andrei-Selmer Luminita-Cornelia , Röskam Stephan , Stüer Carsten , Al-Abed Yousef , Noelker Carmen , Balzer-Geldsetzer Monika , Oertel Wolfgang , Du Yansheng , Bacher Michael
Published: April 2011

Alzheimer's disease (AD) is a neurodegenerative disorder primarily affecting regions of the brain responsible for higher cognitive functions. Immunization against β-amyloid (Aβ) in animal models of AD has been shown to be effective on the molecular level but also on the behavioral level. Recently, we reported naturally occurring autoantibodies against Aβ (NAbs–Aβ) being reduced in Alzheimer's disease patients. Here, we further investigated their physiological role: in epitope mapping studies, NAbs–Aβ recognized the mid-/C-terminal end of Aβ and preferentially bound to oligomers but failed to bind to monomers/fibrils. NAbs–Aβ were able to interfere with Aβ peptide toxicity, but NAbs–Aβ did not readily clear senile plaques although early fleecy-like plaques were reduced. Administration of NAbs–Aβ in transgenic mice improved the object location memory significantly, almost reaching performance levels of wild-type control mice. These findings suggest a novel physiological mechanism involving NAbs–Aβ to dispose of proteins or peptides that are prone to forming toxic aggregates.
Somatic Depolarization Enhances GABA Release in Cerebellar Interneurons via a Calcium/Protein Kinase C Pathway
Authors: Bouhours Brice , Trigo Federico F. , Marty Alain
Published: April 2011

In cortical and hippocampal neurons, tonic somatic depolarization is partially transmitted to synaptic terminals, where it enhances transmitter release. It is not known to what extent such “analog signaling” applies to other mammalian neurons, and available evidence concerning underlying mechanisms is fragmentary and partially controversial. In this work, we investigate the presence of analog signaling in molecular layer interneurons of the rat cerebellum. GABA release was estimated by measuring autoreceptor currents in single recordings, or postsynaptic currents in paired recordings of synaptically connected neurons. We find with both assays that moderate subthreshold somatic depolarization results in enhanced GABA release. In addition, changes in the calcium concentration were investigated in the axon compartment using the calcium-sensitive dye OGB-1 (Oregon Green BAPTA-1). After a step somatic depolarization, the axonal calcium concentration and the GABA release probability rise with a common slow time course. However, the amount of calcium entry that is associated to one action potential is not affected. The slow increase in calcium concentration is inhibited by the P/Q calcium channel blocker ω-agatoxin-IVA. The protein kinase C inhibitor Ro 31-8220 (3-[3-[2,5-dihydro-4-(1-methyl-1H-indol-3-yl)-2,5-dioxo-1H-pyrrol-3-yl]-1H-indol-1-yl]propyl carbamimidothioic acid ester mesylate) did not affect the calcium concentration changes but it blocked the increase in GABA release. EGTA was a weak blocker of analog signaling, implicating a close association of protein kinase C to the site of calcium entry. We conclude that analog signaling is prominent in cerebellar interneurons and that it is triggered by a pathway involving activation of axonal P/Q channels, followed by calcium entry and local activation of protein kinase C.
Recovery from Short-Term Depression and Facilitation Is Ultrafast and Ca2+Dependent at Auditory Hair Cell Synapses
Authors: Cho Soyoun , Li Geng-Lin , von Gersdorff Henrique
Published: April 2011

Short-term facilitation and depression coexist at many CNS synapses. Facilitation, however, has not been fully characterized at hair cell synapses. Using paired recordings and membrane capacitance measurements we find that paired-pulse plasticity at an adult frog auditory hair cell synapse depends on pulse duration and interpulse intervals. For short 20 ms depolarizing pulses, and interpulse intervals between 15 and 50 ms, facilitation occurred when hair cells were held at −90 mV. However, hair cells held at −60 mV displayed only paired-pulse depression. Facilitation was dependent on residual free Ca2+levels because it was greatly reduced by the Ca2+buffers EGTA and BAPTA. Furthermore, low external Ca2+augmented facilitation, whereas depression was augmented by high external Ca2+, consistent with depletion of a small pool of fast releasing synaptic vesicles. Recovery from depression had a double-exponential time course with a fast component that may reflect the rapid replenishment of a depleted vesicle pool. We suggest that hair cells held at more depolarizedin vivo-like resting membrane potentials have a tonic influx of Ca2+; they are thus in a dynamic state of continuous vesicle release, pool depletion and replenishment. Further Ca2+influx during paired-pulse stimuli then leads to depression. However, at membrane potentials of −90 mV, ongoing release and pool depletion are minimized, so facilitation is revealed at time intervals when rapid vesicle pool replenishment occurs. Finally, we propose that vesicle pool replenishment kinetics is not rate limited by vesicle endocytosis, which is too slow to influence the rapid pool replenishment process.
Sympathetic Activity Controls Fat-Induced Oleoylethanolamide Signaling in Small Intestine
Authors: Fu Jin , DiPatrizio Nicholas V. , Guijarro Ana , Schwartz Gary J. , Li Xiaosong , Gaetani Silvana , Astarita Giuseppe , Piomelli Daniele
Published: April 2011

Ingestion of dietary fat stimulates production of the small-intestinal satiety factors oleoylethanolamide (OEA) andN-palmitoyl-phosphatidylethanolamine (NPPE), which reduce food intake through a combination of local (OEA) and systemic (NPPE) actions. Previous studies have shown that sympathetic innervation of the gut is necessary for duodenal infusions of fat to induce satiety, suggesting that sympathetic activity may engage small-intestinal satiety signals such as OEA and NPPE. In the present study, we show that surgical resection of the sympathetic celiac-superior mesenteric ganglion complex, which sends projections to the upper gut, abolishes feeding-induced OEA production in rat small-intestinal cells. These effects are accounted for by suppression of OEA biosynthesis, and are mimicked by administration of the selective β2-adrenergic receptor antagonist ICI-118,551. We further show that sympathetic ganglionectomy or pharmacological blockade of β2-adrenergic receptors prevents NPPE release into the circulation. In addition, sympathetic ganglionectomy increases meal frequency and lowers satiety ratio, and these effects are corrected by pharmacological administration of OEA. The results suggest that sympathetic activity controls fat-induced satiety by enabling the coordinated production of local (OEA) and systemic (NPPE) satiety signals in the small intestine.
CCL2 Released from Neuronal Synaptic Vesicles in the Spinal Cord Is a Major Mediator of Local Inflammation and Pain after Peripheral Nerve Injury
Authors: Van Steenwinckel Juliette , Reaux-Le Goazigo Annabelle , Pommier Blandine , Mauborgne Annie , Dansereau Marc-André , Kitabgi Patrick , Sarret Philippe , Pohl Michel , Mélik Parsadaniantz Stéphane
Published: April 2011

CCL2 chemokine and its receptor CCR2 may contribute to neuropathic pain development. We tested the hypothesis that injury to peripheral nerves triggers CCL2 release from afferents in the dorsal horn spinal cord (DHSC), leading to pronociceptive effects, involving the production of proinflammatory factors, in particular. Consistent with the release of CCL2 from primary afferents, electron microscopy showed the CCL2 immunoreactivity in glomerular boutons and secretory vesicles in the DHSC of naive rats. Through theex vivosuperfusion of DHSC slices, we demonstrated that the rate of CCL2 secretion was much lower in neonatal capsaicin-treated rats than in controls. Thus, much of the CCL2 released in the DHSC originates from nociceptive fibers bearing TRPV1 (transient receptor potential vanilloid 1). In contrast, high levels of CCL2 released from the DHSC were observed in neuropathic pain animal model induced by chronic constriction of the sciatic nerve (SN-CCI). The upregulated expression of proinflammatory markers and extracellular signal-regulated kinase (ERK) 1/2 pathway activation (ERK1/2 phosphorylation) in the DHSC of SN-CCI animals were reversed by intrathecal administration of the CCR2 antagonist INCB3344 (N-[2-[[(3S,4S)-1-E4-(1,3-benzodioxol-5-yl)-4-hydroxycyclohexyl]-4-ethoxy-3-pyrrolidinyl]amino]-2-oxoethyl]-3-(trifluoromethyl)benzamide). These pathological pain-associated changes in the DHSC were mimicked by the intrathecal injection of exogenous CCL2 in naive rats and were prevented by the administration of INCB3344 or ERK inhibitor (PD98059). Finally, mechanical allodynia, which was fully developed 2 weeks after SN-CCI in rats, was attenuated by the intrathecal injection of INCB3344. Our data demonstrate that CCL2 has the typical characteristics of a neuronal mediator involved in nociceptive signal processing and that antagonists of its receptor are promising agents from treating neuropathic pain.
Group I mGluR Agonist-Evoked Long-Term Potentiation in Hippocampal Oriens Interneurons
Authors: Le Duigou Caroline , Kullmann Dimitri M.
Published: April 2011

Several subtypes of interneurons in the feedback circuit in stratum oriens of the hippocampus exhibit NMDA receptor-independent long-term potentiation (LTP) at glutamatergic synapses made by local pyramidal neurons. LTP has been reported with both “Hebbian” and “anti-Hebbian” induction protocols, where high-frequency presynaptic stimulation is paired with either postsynaptic depolarization or hyperpolarization. Do these phenomena represent distinct forms of plasticity, dependent on group I metabotropic receptors (mGluRs) and rectifying Ca2+-permeable AMPA receptors, respectively? Blockade of either mGluR1 or mGluR5 prevented anti-Hebbian LTP induction in stratum oriens interneurons in rat hippocampal slices. Exogenous activation of group I mGluRs by the selective agonist (S)-3,5-dihydroxyphenylglycine (DHPG) was unable to induce LTP on its own, and instead depressed excitatory transmission. However, when paired with postsynaptic hyperpolarization, DHPG or the group I metabotropic receptor (mGluR5)-selective agonist (R,S)-2-chloro-5-hydroxyphenylglycine (CHPG) elicited a delayed long-lasting potentiation, which was accompanied by a decrease in paired-pulse facilitation. Anti-Hebbian LTP occluded the effect of DHPG paired with hyperpolarization, implying that the induction cascades triggered by both conjunctions of stimuli converge on common expression mechanisms.
Mixed Mode Oscillations in Mouse Spinal Motoneurons Arise from a Low Excitability State
Authors: Iglesias Caroline , Meunier Claude , Manuel Marin , Timofeeva Yulia , Delestrée Nicolas , Zytnicki Daniel
Published: April 2011

We explain the mechanism that elicits the mixed mode oscillations (MMOs) and the subprimary firing range that we recently discovered in mouse spinal motoneurons. In this firing regime, high-frequency subthreshold oscillations appear a few millivolts below the spike voltage threshold and precede the firing of a full blown spike. By combining intracellular recordingsin vivo(including dynamic clamp experiments) in mouse spinal motoneurons and modeling, we show that the subthreshold oscillations are due to the spike currents and that MMOs appear each time the membrane is in a low excitability state. Slow kinetic processes largely contribute to this low excitability. The clockwise hysteresis in theI–Frelationship, frequently observed in mouse motoneurons, is mainly due to a substantial slow inactivation of the sodium current. As a consequence, less sodium current is available for spiking. This explains why a large subprimary range with numerous oscillations is present in motoneurons displaying a clockwise hysteresis. In motoneurons whoseI–Fcurve exhibits a counterclockwise hysteresis, it is likely that the slow inactivation operates on a shorter time scale and is substantially reduced by the de-inactivating effect of the afterhyperpolarization (AHP) current, thus resulting in a more excitable state. This accounts for the short subprimary firing range with only a few MMOs seen in these motoneurons. Our study reveals a new role for the AHP current that sets the membrane excitability level by counteracting the slow inactivation of the sodium current and allows or precludes the appearance of MMOs.
Transport of the Major Myelin Proteolipid Protein Is Directed by VAMP3 and VAMP7
Authors: Feldmann Anke , Amphornrat Jesa , Schönherr Madeleine , Winterstein Christine , Möbius Wiebke , Ruhwedel Torben , Danglot Lydia , Nave Klaus-Armin , Galli Thierry , Bruns Dieter , Trotter Jacqueline , Krämer-Albers Eva-Maria
Published: April 2011

CNS myelination by oligodendrocytes requires directed transport of myelin membrane components and a timely and spatially controlled membrane expansion. In this study, we show the functional involvement of the R-solubleN-ethylmaleimide-sensitive factor attachment protein receptor (R-SNARE) proteins VAMP3/cellubrevin and VAMP7/TI-VAMP in myelin membrane trafficking. VAMP3 and VAMP7 colocalize with the major myelin proteolipid protein (PLP) in recycling endosomes and late endosomes/lysosomes, respectively. Interference with VAMP3 or VAMP7 function using small interfering RNA-mediated silencing and exogenous expression of dominant-negative proteins diminished transport of PLP to the oligodendroglial cell surface. In addition, the association of PLP with myelin-like membranes produced by oligodendrocytes cocultured with cortical neurons was reduced. We furthermore identified Syntaxin-4 and Syntaxin-3 as prime acceptor Q-SNAREs of VAMP3 and VAMP7, respectively. Analysis of VAMP3-deficient mice revealed no myelination defects. Interestingly, AP-3δ-deficientmochamice, which suffer from impaired secretion of lysosome-related organelles and missorting of VAMP7, exhibit a mild dysmyelination characterized by reduced levels of select myelin proteins, including PLP. We conclude that PLP reaches the cell surface via at least two trafficking pathways with distinct regulations: (1) VAMP3 mediates fusion of recycling endosome-derived vesicles with the oligodendroglial plasma membrane in the course of the secretory pathway; (2) VAMP7 controls exocytosis of PLP from late endosomal/lysosomal organelles as part of a transcytosis pathway. Ourin vivodata suggest that exocytosis of lysosome-related organelles controlled by VAMP7 contributes to myelin biogenesis by delivering cargo to the myelin membrane.
Extra Forces Evoked during Electrical Stimulation of the Muscle or Its Nerve Are Generated and Modulated by a Length-Dependent Intrinsic Property of Muscle in Humans and Cats
Authors: Frigon Alain , Thompson Christopher K. , Johnson Michael D. , Manuel Marin , Hornby T. George , Heckman C. J.
Published: April 2011

Extra forces or torques are defined as forces or torques that are larger than would be expected from the input or stimuli, which can be mediated by properties intrinsic to motoneurons and/or to the muscle. The purpose of this study was to determine whether extra forces/torques evoked during electrical stimulation of the muscle or its nerve with variable frequency stimulation are modulated by muscle length/joint angle. A secondary aim was to determine whether extra forces/torques are generated by an intrinsic neuronal or muscle property. Experiments were conducted in 14 able-bodied human subjects and in eight adult decerebrate cats. Torque and force were measured in human and cat experiments, respectively. Extra forces/torques were evoked by stimulating muscles with surface electrodes (human experiments) or by stimulating the nerve with cuff electrodes (cat experiments). In humans and cats, extra forces/torques were larger at short muscle lengths, indicating that a similar regulatory mechanism is involved. In decerebrate cats, extra forces and length-dependent modulation were unaffected by intrathecal methoxamine injections, despite evidence of increased spinal excitability, and by transecting the sciatic nerve proximal to the nerve stimulations. Anesthetic nerve block experiments in two human subjects also failed to abolish extra torques and the length-dependent modulation. Therefore, these data indicate that extra forces/torques evoked during electrical stimulation of the muscle or nerve are muscle length-dependent and primarily mediated by an intrinsic muscle property.
The Unusual Response of Serotonergic Neurons after CNS Injury: Lack of Axonal Dieback and Enhanced Sprouting within the Inhibitory Environment of the Glial Scar
Authors: Hawthorne Alicia L. , Hu Hongmei , Kundu Bornali , Steinmetz Michael P. , Wylie Christi J. , Deneris Evan S. , Silver Jerry
Published: April 2011

Serotonergic neurons possess an enhanced ability to regenerate or sprout after many types of injury. To understand the mechanisms that underlie their unusual properties, we used a combinatorial approach comparing the behavior of serotonergic and cortical axon tips over time in the same injury environmentin vivoand to growth-promoting or growth-inhibitory substratesin vitro. After a thermocoagulatory lesion in the rat frontoparietal cortex, callosal axons become dystrophic and die back. Serotonergic axons, however, persist within the lesion edge. At the third week post-injury, 5-HT+ axons sprout robustly. The lesion environment contains both growth-inhibitory chondroitin sulfate proteoglycans (CSPGs) and growth-promoting laminin. Transgenic mouse serotonergic neurons specifically labeled by enhanced yellow fluorescent protein under control of the Pet-1 promoter/enhancer or cortical neurons were cultured on low amounts of laminin with or without relatively high concentrations of the CSPG aggrecan. Serotonergic neurons extended considerably longer neurites than did cortical neurons on low laminin and exhibited a remarkably more active growth cone on low laminin plus aggrecan during time-lapse imaging than did cortical neurons. Chondroitinase ABC treatment of laminin/CSPG substrates resulted in significantly longer serotonergic but not cortical neurite lengths. This increased ability of serotonergic neurons to robustly grow on high amounts of CSPG may be partially due to significantly higher amounts of growth-associated protein-43 and/or β1 integrin than cortical neurons. Blocking β1 integrin decreased serotonergic and cortical outgrowth on laminin. Determining the mechanism by which serotonergic fibers persist and sprout after lesion could lead to therapeutic strategies for both stroke and spinal cord injury.
Cleft Lip and Palate in the Arts: A Critical Reflection
Authors: Saman Masoud , Gross Justin , Ovchinsky Alexander , Wood-Smith Donald
Published: April 2011

Background

The aesthetics of facial structure are used by humans to measure one's beauty, character, and overall “goodness.” Individuals born with cleft lip and/or palate are often stigmatized and face much psychosocial adversity. Social attitudes and beliefs have a direct impact upon the psychological development of these individuals. Such social norms are in large part shaped by the physical representations of “good” and “attractive” in various art media including films, advertisements, and paintings.

Objective

Individuals born with a cleft have been portrayed in the artworks of different eras. The light in which they are portrayed stems from the prevalent beliefs of each period and sheds light on the social attitudes of each epoch toward clefts. Here we discuss the social and psychological ramifications of these works. We then review several artworks representing cleft lip and/or palate and propose an active role for the artist in shaping social attitudes regarding facial deformities.

Methods

Numerous articles and works of arts were examined and inspected for signs of facial deformity, with particular attention to cleft lip and/or palate.

Conclusion

Social media have an important role in defining the norms of society. Much of the art of the past has depicted negatively individuals born with cleft lip and/or palate deformity, thus excluding them from the norm. In order to decrease the negative social stigmas of cleft lip and/or palate, it is now the responsibility of society to widen its range of norms to include individuals born with these deformities through “normal” representations in the various media.
Influence of a Machined Collar on Crestal Bone Changes Around Titanium Implants: A Histometric Study in the Canine Mandible
Authors: Hermann Joachim S. , Jones Archie A. , Bakaeen Lara G. , Buser Daniel , Schoolfield John D. , Cochran David L.
Published: April 2011

Background: It has been shown that peri‐implant crestal bone reactions are influenced by both a rough–smooth implant border in one‐piece, non‐submerged, as well as an interface (microgap [MG] between implant/abutment) in two‐piece butt‐joint, submerged and non‐submerged implants being placed at different levels in relation to the crest of the bone. According to standard surgical procedures, the rough–smooth implant border for implants with a smooth collar should be aligned with the crest of the bone exhibiting a smooth collar adjacent to peri‐implant soft tissues. No data, however, are available for implants exhibiting a sandblasted, large‐grit and acid‐etched (SLA) surface all the way to the top of a non‐submerged implant. Thus, the purpose of this study is to histometrically examine crestal bone changes around machined versus SLA‐surfaced implant collars in a side‐by‐side comparison.

Methods: A total of 60 titanium implants (30 machined collars and 30 SLA collars) were randomly placed in edentulous mandibular areas of five foxhounds forming six different subgroups (implant subgroups A to F). The implants in subgroups A to C had a machined collar (control), whereas the implants in subgroups D to F were SLA‐treated all the way to the top (MG level; test). Furthermore, the MGs of the implants were placed at different levels in relation to the crest of the bone: the implants in subgroups A and E were 2 mm above the crest, in subgroups C and D 1 mm above, in subgroup B 3 mm above, and in subgroup F at the bone crest level. For all implants, abutment healing screws were connected the day of surgery. These caps were loosened and immediately retightened monthly. At 6 months, animals were sacrificed and non‐decalcified histology was analyzed by evaluating peri‐implant crestal bone levels.

Results: For implants in subgroup A, the estimated mean crestal bone loss (± SD) was −0.52 ± 0.40 mm; in subgroup B, +0.16 ± 0.40 mm (bone gain); in subgroup C, −1.28 ± 0.21 mm; in subgroup D, −0.43 ± 0.43 mm; in subgroup E, −0.03 ± 0.48 mm; and in subgroup F, −1.11 ± 0.27 mm. Mean bone loss for subgroup A was significantly greater than for subgroup E (P = 0.034) and bone loss for subgroup C was significantly greater than for subgroup D (P <0.001).

Conclusions: Choosing a completely SLA‐surfaced non‐submerged implant can reduce the amount of peri‐implant crestal bone loss and reduce the distance from the MG to the first bone–implant contact around unloaded implants compared to implants with a machined collar. Furthermore, a slightly exposed SLA surface during implant placement does not seem to compromise the overall hard and soft tissue integration and, in some cases, results in coronal bone formation in this canine model.
Comparison of Fractured-Horizontal-Well Performance in Tight Sand and Shale Reservoirs
Authors: Ozkan E. , Brown M , Raghavan R. , Kazemi H.
Published: April 2011

This paper presents a discussion of fractured-horizontal-well performance in millidarcy permeability (conventional) and micro- to nanodarcy permeability (unconventional) reservoirs. It provides interpretations of the reasons to fracture horizontal wells in both types of formations. The objective of the paper is to highlight the special productivity features of unconventional shale reservoirs. By using a trilinear-flow model, it is shown that the drainage volume of a multiple-fractured horizontal well in a shale reservoir is limited to the inner reservoir between the fractures. Unlike conventional reservoirs, high reservoir permeability and high hydraulic-fracture conductivity may not warrant favorable productivity in shale reservoirs. An efficient way to improve the productivity of ultratight shale formations is to increase the density of natural fractures. High natural-fracture conductivities may not necessarily contribute to productivity either. Decreasing hydraulic-fracture spacing increases the productivity of the well, but the incremental production gain for each additional hydraulic fracture decreases. The trilinear-flow model presented in this work and the information derived from it should help the design and performance prediction of multiple-fractured horizontal wells in shale reservoirs.
Generating 3D Permeability Map of Fracture Networks Using Well, Outcrop, and Pressure-Transient Data
Authors: Jafari A.. , Babadagli T..
Published: April 2011

Well-log and core information, seismic surveys, outcrop studies, and pressure-transient tests are usually insufficient to generate representative 3D fracture-network maps individually. Any combination of these sources of data could potentially be used for accurate preparation of static models.

Our previous attempts showed that there exists a strong correlation between the statistical and fractal parameters of 2D fracture networks and their permeability (Jafari and Babadagli 2009). We extend this work to fracture-network permeability estimation using the statistical and fractal properties data conditioned to well-test information. For this purpose, 3D fracture models of 19 natural-fracture patterns with all known fracture-network parameters were generated initially. It is assumed that 2D fracture traces on the top of these models and 1D data from imaginary wells that penetrated the whole thickness of the cubic models were available, as well as pressure-transient tests of different kinds. The 1D and 2D data include statistical parameters and fractal characteristics of different features of the fracture system. Next, the permeability of each 3D fracture-network model was measured and then converted to a grid-based permeability map for drawdown well-test simulations using commercial software packages.

Finally, an extensive multivariable-regression analysis (MRA) using the statistical and fractal properties and well-test permeability as independent variables was performed to obtain a correlation for equivalent fracture-network permeability. The equations were derived using different natural-fracture-network patterns. The cases requiring well (logs and cores) and reservoir (pressure-transient tests) data were identified. It was found that an equation honoring all types of data [i.e., outcrop (2D), wellbore data (1D), and welltest analysis (3D)] can accurately predict the actual permeability of the fracture system. For certain fracture-network types, reliable correlations can be obtained without 2D data, which are relatively difficult to obtain. These types of patterns were identified.