bluuebunny/crossref_metadata_2025 huggingface dataset:
Adjuvant gemcitabine versus NEOadjuvant gemcitabine/oxaliplatin plus adjuvant gemcitabine in resectable pancreatic cancer: a randomized multicenter phase III study (NEOPAC study)
Authors: Heinrich Stefan , Pestalozzi Bernhard , Lesurtel Mickael , Berrevoet Frederik , Laurent Stéphanie , Delpero Jean-Robert , Raoul Jean-Luc , Bachellier Phillippe , Dufour Patrick , Moehler Markus , Weber Achim , Lang Hauke , Rogiers Xavier , Clavien Pierre-Alain
Published: August 2011

Background

Despite major improvements in the perioperative outcome of pancreas surgery, the prognosis of pancreatic cancer after curative resection remains poor. Adjuvant chemotherapy increases disease-free and overall survival, but this treatment cannot be offered to a significant proportion of patients due to the surgical morbidity. In contrast, almost all patients can receive (neo)adjuvant chemotherapy before surgery. This treatment is safe and effective, and has resulted in a median survival of 26.5 months in a recent phase II trial. Moreover, neoadjuvant chemotherapy improves the nutritional status of patients with pancreatic cancer. This multicenter phase III trial (NEOPAC) has been designed to explore the efficacy of neoadjuvant chemotherapy.

Methods/Design

This is a prospective randomized phase III trial. Patients with resectable cytologically proven adenocarcinoma of the pancreatic head are eligible for this study. All patients must be at least 18 years old and must provide written informed consent. An infiltration of the superior mesenteric vein > 180° or major visceral arteries are considered exclusion criteria. Eligible patients will be randomized to surgery followed by adjuvant gemcitabine (1000 mg/m2) for 6 months or neoadjuvant chemotherapy (gemcitabine 1000 mg/m2, oxaliplatin 100 mg/m2) followed by surgery and the same adjuvant treatment. Neoadjuvant chemotherapy is given four times every two weeks. The staging as well as the restaging protocol after neoadjuvant chemotherapy include computed tomography of chest and abdomen and diagnostic laparoscopy. The primary study endpoint is progression-free survival. According to the sample size calculation, 155 patients need to be randomized to each treatment arm. Disease recurrence will be documented by scheduled computed tomography scans 9, 12, 15, 21 and thereafter every 6 months until disease progression. For quality control, circumferential resection margins are marked intraoperatively, and representative histological sections will be centrally reviewed by a dedicated pathologist.

Discussion

The NEOPAC study will determine the efficacy of neoadjuvant chemotherapy in pancreatic cancer for the first time and offers a unique potential for translational research. Furthermore, this trial will provide the unbiased overall survival of all patients undergoing surgery for resectable cancer of the pancreatic head.

Trial registration

clinicalTrials.gov NCT01314027
A trigger model of apoptosis induced by tumor necrosis factor signaling
Authors: Gu Chang , Zhang Junjie , Chen Yingyu , Lei Jinzhi
Published: August 2011

Background

The ability of living cells to respond appropriately to apoptosis signals is crucial for the proper development and homeostasis of multicellular organisms. For example, viable cells must be stable enough to appropriately respond to apoptosis signaling so that an irreversible death program is only induced when apoptosis signaling reaches a certain threshold. Previous studies have introduced bistability models in which signaling by caspase-3 activity represents a key regulator of cell fate in response to apoptosis stimuli.

Results

In this study, apoptosis induced by tumor necrosis factor (TNF) signaling is investigated, and a mathematical model without the requirement for bistability is proposed. In this model, rapid degradation of the active forms of caspases -8 and -3 are included, and TNF-signaling is found to induce a pulse of caspase-3 activation and trigger an irreversible death program. This result agrees with experimental observations. The ability of a cell to respond to, or resist, apoptosis stimuli is also discussed. Furthermore, the activation efficiencies of caspases -8 and -3 that are essential to a cell’s response to extracellular apoptosis stimuli are defined. Based on the simulations performed, it is observed that activation efficiencies must be sufficiently sensitive to appropriately compromise a cell’s resistance and effectiveness in response to apoptosis stimuli.

Conclusions

Our results suggest that bistability may not be a necessary condition for the induction of apoptosis by TNF signaling. Rather, a sharp increase in caspase-3 activity might be sufficient to trigger the induction of an irreversible death program. Accordingly, regulation of caspase activity and degradation of active caspases is essential for a cell’s response to apoptosis stimuli.
Health financing in Africa: overview of a dialogue among high level policy makers
Authors: Sambo Luis Gomes , Kirigia Joses Muthuri , Ki-Zerbo Georges
Published: August 2011

Background

Even though Africa has the highest disease burden compared with other regions, it has the lowest per capita spending on health. In 2007, 27 (51%) out the 53 countries spent less than US$50 per person on health. Almost 30% of the total health expenditure came from governments, 50% from private sources (of which 71% was from out-of-pocket payments by households) and 20% from donors. The purpose of this article is to reflect on the proceedings of the African Union Side Event on Health Financing in the African continent.

Methods

Methods employed in the session included presentations, panel discussion and open public discussion with ministers of health and finance from the African continent.

Discussion

The current unsatisfactory state of health financing was attributed to lack of clear vision and plan for health financing; lack of national health accounts and other evidence to guide development and implementation of national health financing policies and strategies; low investments in sectors that address social determinants of health; predominance of out-of-pocket spending; underdeveloped prepaid health financing mechanisms; large informal sectors vis-à-vis small formal sectors; and unpredictability and non-alignment of majority of donor funds with national health priorities.

Countries need to develop and adopt a comprehensive national health policy and a costed strategic plan; a comprehensive evidence-based health financing strategy; allocate at least 15% of the national budget to health development; use GFATM and PEPFAR funds for health systems strengthening; strengthen intersectoral collaboration to address health determinants; advocate among donors to implement the Paris Declaration on Aid Effectiveness and its Accra Agenda for Action; ensure universal access to health services for pregnant women, lactating mothers and children aged under five years; strengthen financial management capacities; and develop prepaid health financing systems, especially health insurance to complement tax funding.

In addition, countries need to institutionalize national health accounts; undertake feasibility studies of various health financing mechanisms; and document and share best practices in health financing.

Conclusion

There was consensus that every country ought to have an evidence-based comprehensive health financing strategy with a road map for attaining universal health service coverage vision; and increase physical and financial access by pregnant women, lactating mothers and by children under five years to quality health services.
Activation of protease activated receptor 1 increases the excitability of the dentate granule neurons of hippocampus
Authors: Han Kyung-Seok , Mannaioni Guido , Hamill Cecily E , Lee Jaekwang , Junge Candice E , Lee C Justin , Traynelis Stephen F
Published: August 2011

Protease activated receptor-1 (PAR1) is expressed in multiple cell types in the CNS, with the most prominent expression in glial cells. PAR1 activation enhances excitatory synaptic transmission secondary to the release of glutamate from astrocytes following activation of astrocytically-expressed PAR1. In addition, PAR1 activation exacerbates neuronal damage in multiple in vivo models of brain injury in a manner that is dependent on NMDA receptors. In the hippocampal formation, PAR1 mRNA appears to be expressed by a subset of neurons, including granule cells in the dentate gyrus. In this study we investigate the role of PAR activation in controlling neuronal excitability of dentate granule cells. We confirm that PAR1 protein is expressed in neurons of the dentate cell body layer as well as in astrocytes throughout the dentate. Activation of PAR1 receptors by the selective peptide agonist TFLLR increased the intracellular Ca2+ concentration in a subset of acutely dissociated dentate neurons as well as non-neuronal cells. Bath application of TFLLR in acute hippocampal slices depolarized the dentate gyrus, including the hilar region in wild type but not in the PAR1-/- mice. PAR1 activation increased the frequency of action potential generation in a subset of dentate granule neurons; cells in which PAR1 activation triggered action potentials showed a significant depolarization. The activation of PAR1 by thrombin increased the amplitude of NMDA receptor-mediated component of EPSPs. These data suggest that activation of PAR1 during normal function or pathological conditions, such as during ischemia or hemorrhage, can increase the excitability of dentate granule cells.
Hypothyroidism and mood disorders: integrating novel insights from brain imaging techniques
Authors: Pilhatsch Maximilian , Marxen Michael , Winter Christine , Smolka Michael N , Bauer Michael
Published: August 2011

Thyroid hormones play a critical role in brain development but also in the adult human brain by modulating metabolic activity. Hypothyroid states are associated with both functional and structural brain alterations also seen in patients with major depression. Recent animal experimental and preclinical data indicate subtle changes in myelination, microvascular density, local neurogenesis, and functional networks. The translational validity of such studies is obviously limited. Clinical evidence for neurobiological correlates of different stages and severities of hypothyroidism and effects of pharmacological intervention is lacking but may be achieved using advanced imaging techniques, e.g. functional and quantitative MRI techniques applied to patients with hypothyroidism before and after hormone replacement therapy.
O2 delivery and CO2 production during cardiopulmonary bypass as determinants of acute kidney injury: time for a goal-directed perfusion management?
Authors: de Somer Filip , Mulholland John W , Bryan Megan R , Aloisio Tommaso , Van Nooten Guido J , Ranucci Marco
Published: August 2011

Introduction

Acute kidney injury (AKI) is common after cardiac operations. There are different risk factors or determinants of AKI, and some are related to cardiopulmonary bypass (CPB). In this study, we explored the association between metabolic parameters (oxygen delivery (DO2) and carbon dioxide production (VCO2)) during CPB with postoperative AKI.

Methods

We conducted a retrospective analysis of prospectively collected data at two different institutions. The study population included 359 adult patients. The DO2 and VCO2 levels of each patient were monitored during CPB. Outcome variables were related to kidney function (peak postoperative serum creatinine increase and AKI stage 1 or 2). The experimental hypothesis was that nadir DO2 values and nadir DO2/VCO2 ratios during CPB would be independent predictors of AKI. Multivariable logistic regression models were built to detect the independent predictors of AKI and any kind of kidney function damage.

Results

A nadir DO2 level < 262 mL/minute/m2 and a nadir DO2/VCO2 ratio < 5.3 were independently associated with AKI within a model including EuroSCORE and CPB duration. Patients with nadir DO2 levels and nadir DO2/VCO2 ratios below the identified cutoff values during CPB had a significantly higher rate of AKI stage 2 (odds ratios 3.1 and 2.9, respectively). The negative predictive power of both variables exceeded 90%. The most accurate predictor of AKI stage 2 postoperative status was the nadir DO2 level.

Conclusions

The nadir DO2 level during CPB is independently associated with postoperative AKI. The measurement of VCO2-related variables does not add accuracy to the AKI prediction. Since DO2 during CPB is a modifiable factor (through pump flow adjustments), this study generates the hypothesis that goal-directed perfusion management aimed at maintaining the DO2 level above the identified critical value might limit the incidence of postoperative AKI.
Typological Seismic Risk Maps for Italy
Authors: Rota Maria , Penna Andrea , Strobbia Claudio , Magenes Guido
Published: August 2011

This paper describes the methodology followed to derive typological seismic risk maps for Italy and then presents the results. In its classical definition, seismic risk is obtained from the convolution of hazard, vulnerability and exposure. Due to the absence of reliable data on exposure for the entire Italian territory, this study proposes typological seismic risk maps, obtained by simply convolving hazard and vulnerability for several building typologies characteristic of the Italian building stock. A specific hazard study in terms of PGA has been carried out. The results have then been convolved with empirical typological fragility curves, that were derived from data collected during post-earthquake surveys after the main Italian events of the last 30 years. Useful applications can be found for the typological seismic risk maps, both for risk mitigation strategies and for purely economical evaluations (e.g., insurance and reinsurance studies).
Risk-Based Seismic Design for Optimal Structural and Nonstructural System Performance
Authors: Rojas Hugo A. , Foley Christopher , Pezeshk Shahram
Published: August 2011

An automated performance-based design methodology to optimize structural and nonstructural system performance is outlined and it is shown that it can be used to enhance understanding of structural steel system design for minimum life-cycle costs. Performance is assessed using loss probability with direct economic loss expressed as a percentage of the building replacement cost. Time-based performance assessment is used to compute the expected annual loss of a given steel framing system assuming exposure to three seismic hazard levels. Damage to the structural system, nonstructural displacement-sensitive components, and nonstructural acceleration-sensitive components is characterized using fragility functions. A steel building with three-story, four-bay topology taken from the literature is used to demonstrate application of the algorithm with subsequent comparison of designs obtained using the proposed methodology and others found in the literature.
Elastic deformation and energy loss of flapping fly wings
Authors: Lehmann Fritz-Olaf , Gorb Stanislav , Nasir Nazri , Schützner Peter
Published: August 2011

During flight, the wings of many insects undergo considerable shape changes in spanwise and chordwise directions. We determined the origin of spanwise wing deformation by combining measurements on segmental wing stiffness of the blowfly Calliphora vicina in the ventral and dorsal directions with numerical modelling of instantaneous aerodynamic and inertial forces within the stroke cycle using a two-dimensional unsteady blade elementary approach. We completed this approach by an experimental study on the wing's rotational axis during stroke reversal. The wing's local flexural stiffness ranges from 30 to 40 nN m2 near the root, whereas the distal wing parts are highly compliant (0.6 to 2.2 nN m2). Local bending moments during wing flapping peak near the wing root at the beginning of each half stroke due to both aerodynamic and inertial forces, producing a maximum wing tip deflection of up to 46 deg. Blowfly wings store up to 2.30 μJ elastic potential energy that converts into a mean wing deformation power of 27.3 μW. This value equates to approximately 5.9 and 2.3% of the inertial and aerodynamic power requirements for flight in this animal, respectively. Wing elasticity measurements suggest that approximately 20% or 0.46 μJ of elastic potential energy cannot be recovered within each half stroke. Local strain energy increases from tip to root, matching the distribution of the wing's elastic protein resilin, whereas local strain energy density varies little in the spanwise direction. This study demonstrates a source of mechanical energy loss in fly flight owing to spanwise wing bending at the stroke reversals, even in cases in which aerodynamic power exceeds inertial power. Despite lower stiffness estimates, our findings are widely consistent with previous stiffness measurements on insect wings but highlight the relationship between local flexural stiffness, wing deformation power and energy expenditure in flapping insect wings.
Sink and swim: kinematic evidence for lifting-body mechanisms in negatively buoyant electric rays Narcine brasiliensis
Authors: Rosenblum Hannah G. , Long John H. , Porter Marianne E.
Published: August 2011

Unlike most batoid fishes, electric rays neither oscillate nor undulate their body disc to generate thrust. Instead they use body–caudal–fin (BCF) locomotion. In addition, these negatively buoyant rays perform unpowered glides as they sink in the water column. In combination, BCF swimming and unpowered gliding are opposite ends on a spectrum of swimming, and electric rays provide an appropriate study system for understanding how the performance of each mode is controlled hydrodynamically. We predicted that the dorso-ventrally flattened body disc generates lift during both BCF swimming and gliding. To test this prediction, we examined 10 neonate lesser electric rays, Narcine brasiliensis, as they swam and glided. From video, we tracked the motion of the body, disc, pelvic fins and tail. By correlating changes in the motions of those structures with swimming performance, we have kinematic evidence that supports the hypothesis that the body disc is generating lift. Most importantly, both the pitch of the body disc and the tail, along with undulatory frequency, interact to control horizontal swimming speed and Strouhal number during BCF swimming. During gliding, the pitch of the body disc and the tail also interact to control the speed on the glide path and the glide angle.
Vector-based and landmark-guided navigation in desert ants inhabiting landmark-free and landmark-rich environments
Authors: Bühlmann Cornelia , Cheng Ken , Wehner Rüdiger
Published: August 2011

Two species of desert ants – the North African Cataglyphis fortis and the central Australian Melophorus bagoti – differ markedly in the visual complexity of their natural habitats: featureless salt pans and cluttered, steppe-like terrain, respectively. Here we ask whether the two species differ in their navigational repertoires, in particular, whether in homing they place different emphasis on their vector-based and landmark-based routines. In trying to answer this question, we applied the same experimental paradigms to individual foragers of either species on either continent: training and/or testing with and/or without artificial landmark arrays. We found that the open-terrain species C. fortis runs off its (path integration) home vector much more readily even in unfamiliar landmark settings than the cluttered-terrain species M. bagoti. These data support the hypothesis that C. fortis has a higher propensity to rely on vector-mediated navigation, whereas in the same experimental situations M. bagoti more easily switches to landmark-guided behaviour. In the actual navigational performances, such species-specific propensities are most likely shaped by environment-dependent individual experiences.
Sheep rumen and omasum primary cultures and source epithelia: barrier function aligns with expression of tight junction proteins
Authors: Stumpff Friederike , Georgi Maria-Ifigenia , Mundhenk Lars , Rabbani Imtiaz , Fromm Michael , Martens Holger , Günzel Dorothee
Published: August 2011

The forestomachs of cows and sheep have historically served as important models for the study of epithelial transport. Thus, the ruminal epithelium was among the first tissues in which absorption of chloride against an electrochemical gradient was observed, requiring a tight paracellular barrier to prevent back-leakage. However, little is known about ruminal barrier function, despite the considerable implications for ruminant health. The tight junction proteins of the omasum have never been investigated, and no cell culture model exists. We present a new method for the isolation of cells from forestomach epithelia. Protein expression of cells and source tissues of sheep were studied using western blot, PCR and confocal laser scanning microscopy. Cultured cells were characterized by transepithelial resistance (TER) measurements and patch clamping. Cells developed TER values of 729±134 Ω cm2 (rumen) and 1522±126 Ω cm2 (omasum). Both primary cells and source epithelia of rumen and omasum expressed cytokeratin, occludin and claudins 1, 4 and 7 (but not claudins 2, 3, 5, 8 and 10), consistent with the observed paracellular sealing properties. Staining for claudin-1 reached the stratum basale. The full mRNA coding sequence of claudins 1, 4 and 7 (sheep) was obtained. Patch-clamp analyses of isolated cells proved expression of an anion conductance with a permeability sequence of gluconate<acetate<chloride. This is in accordance with a model that ruminal and omasal transport of anions such as chloride and acetate has to occur via a transcellular route and involves channel-mediated basolateral efflux, driven by Na+/K+-ATPase.
Implementing a hysterosalpingo-contrast-ultrasonography service at a district general hospital
Authors: Coppack Collette Maria , Gillespie Allison
Published: August 2011

Until recently, tubal patency at this centre was investigated via hysterosalpingography (HSG). However, in response to national recommendations, highlighted at a study day, we believed it was possible to improve the quality of the current service by replacing it with a contrast-enhanced ultrasound study, thus avoiding the radiation burden associated with HSG. This article describes the process involved in implementing the changeover.
Neural Development of Binaural Tuning through Hebbian Learning Predicts Frequency-Dependent Best Delays
Authors: Fontaine Bertrand , Brette Romain
Published: August 2011

Birds use microsecond differences in the arrival times of the sounds at the two ears to infer the location of a sound source in the horizontal plane. These interaural time differences (ITDs) are encoded by binaural neurons which fire more when the ITD matches their “best delay.” In the textbook model of sound localization, the best delays of binaural neurons reflect the differences in axonal delays of their monaural inputs, but recent observations have cast doubts on this classical view because best delays were found to depend on preferred frequency. Here, we show that these observations are in fact consistent with the notion that best delays are created by differences in axonal delays, provided ITD tuning is created during development through spike-timing-dependent plasticity: basilar membrane filtering results in correlations between inputs to binaural neurons, which impact the selection of synapses during development, leading to the observed distribution of best delays.
Convergence of Vestibular and Visual Self-Motion Signals in an Area of the Posterior Sylvian Fissure
Authors: Chen Aihua , DeAngelis Gregory C. , Angelaki Dora E.
Published: August 2011

Convergence of visual motion information (optic flow) and vestibular signals is important for self-motion perception, and such convergence has been observed in the dorsal medial superior temporal (MSTd) and ventral intraparietal areas. In contrast, the parieto-insular vestibular cortex (PIVC), a cortical vestibular area in the sylvian fissure, is not responsive to optic flow. Here, we explore optic flow and vestibular convergence in the visual posterior sylvian area (VPS) of macaque monkeys. This area is located at the posterior end of the sylvian fissure, is strongly interconnected with PIVC, and receives projections from MSTd. We found robust optic flow and vestibular tuning in more than one-third of VPS cells, with all motion directions being represented uniformly. However, visual and vestibular direction preferences for translation were mostly opposite, unlike in area MSTd where roughly equal proportions of neurons have visual/vestibular heading preferences that are congruent or opposite. Overall, optic flow responses in VPS were weaker than those in MSTd, whereas vestibular responses were stronger in VPS than in MSTd. When visual and vestibular stimuli were presented together, VPS responses were dominated by vestibular signals, in contrast to MSTd, where optic flow tuning typically dominates. These findings suggest that VPS is proximal to MSTd in terms of vestibular processing, but distal to MSTd in terms of optic flow processing. Given the preponderance of neurons with opposite visual/vestibular heading preferences in VPS, this area may not play a major role in multisensory heading perception.
Developmental Changes in Short-Term Plasticity at the Rat Calyx of Held Synapse
Authors: Crins Tom T. H. , Rusu Silviu I. , Rodríguez-Contreras Adrian , Borst J. Gerard G.
Published: August 2011

The calyx of Held synapse of the medial nucleus of the trapezoid body functions as a relay synapse in the auditory brainstem.In vivorecordings have shown that this synapse displays low release probability and that the average size of synaptic potentials does not depend on recent history. We used a ventral approach to makein vivoextracellular recordings from the calyx of Held synapse in rats aged postnatal day 4 (P4) to P29 to study the developmental changes that allow this synapse to function as a relay. Between P4 and P8, we observed evidence for the presence of large short-term depression, which was counteracted by short-term facilitation at short intervals. Major changes occurred in the last few days before the onset of hearing for air-borne sounds, which happened at P13. The bursting pattern changed into a primary-like pattern, the amount of depression and facilitation decreased strongly, and the decay of facilitation became much faster. Whereas short-term plasticity was the most important cause of variability in the size of the synaptic potentials in immature animals, its role became minor around hearing onset and afterward. Similar developmental changes were observed during stimulation experiments both in brain slices andin vivofollowing cochlear ablation. Our data suggest that the strong reduction in release probability and the speedup of the decay of synaptic facilitation that happen just before hearing onset are important events in the transformation of the calyx of Held synapse into an auditory relay synapse.
AGS-3 AltersCaenorhabditis elegansBehavior after Food Deprivation via RIC-8 Activation of the Neural G Protein Gαo
Authors: Hofler Catherine , Koelle Michael R.
Published: August 2011

Proteins containing the G protein regulator (GPR) domain bind the major neural G protein Gαoin vitro. However, the biological functions of GPR proteins in neurons remain undefined, and based on thein vitroactivities of GPR proteins it is unclear whether these proteins activate or inhibit G protein signalingin vivo. We found that the conserved GPR domain protein AGS-3 activates Gαosignalingin vivoto allowCaenorhabditis elegansto alter several behaviors after food deprivation, apparently so that the animals can more effectively seek food. AGS-3 undergoes a progressive change in its biochemical fractionation upon food deprivation, suggesting that effects of food deprivation are mediated by modifying this protein. We analyzed oneC. elegansfood-regulated behavior in depth; AGS-3 activates Gαoin the ASH chemosensory neurons to allow food-deprived animals to delay response to the aversive stimulus octanol. Genetic epistasis experiments show the following: (1) AGS-3 and the guanine nucleotide exchange factor RIC-8 act in ASH in a mutually dependent fashion to activate Gαo; (2) this activation requires interaction of the GPR domains of AGS-3 with Gαo; and (3) Gαo-GTP is ultimately the signaling molecule that acts in ASH to delay octanol response. These results identify a biological role for AGS-3 in response to food deprivation and indicate the mechanism for its activation of Gαosignalingin vivo.
NMDA Receptors in Retrosplenial Cortex Are Necessary for Retrieval of Recent and Remote Context Fear Memory
Authors: Corcoran Kevin A. , Donnan Michael D. , Tronson Natalie C. , Guzmán Yomayra F. , Gao Can , Jovasevic Vladimir , Guedea Anita L. , Radulovic Jelena
Published: August 2011

Over time, memory retrieval is thought to transfer from the hippocampus to a distributed network of neocortical sites. Of these sites, the retrosplenial cortex (RSC) is robustly activated during retrieval of remotely acquired, emotionally valenced memories. It is unclear, however, whether RSC is specifically involved in memory storage or retrieval, and which neurotransmitter receptor mechanisms serve its function. We addressed these questions by inhibiting NMDARs in RSC via infusions of APV before tests for context fear in mice. Anterior cingulate cortex (ACC) and dorsal hippocampus (DH), which have been implicated in the retrieval of remote and recent memory, respectively, served as neuroanatomical controls. Surprisingly, infusion of APV only into RSC, but not ACC or DH, abolished retrieval of remote memory, as revealed by lack of freezing to the conditioning context. APV infused into RSC also impaired retrieval of recent memory, but had no effect on conditioning or memory storage. Within-subject experiments confirmed that the role of RSC in memory retrieval is not time limited. RSC-dependent context fear memory retrieval was mediated by NR2A, but not NR2B, subunit-containing NMDARs. Collectively, these data are the first demonstration that NMDARs in RSC are necessary for the retrieval of remote and recent memories of fear-evoking contexts. Dysfunction of RSC may thereby contribute significantly to the reexperiencing of traumatic memories in patients with posttraumatic stress disorder.
Mapping Human Cortical AreasIn VivoBased on Myelin Content as Revealed by T1- and T2-Weighted MRI
Authors: Glasser Matthew F. , Van Essen David C.
Published: August 2011

Noninvasively mapping the layout of cortical areas in humans is a continuing challenge for neuroscience. We present a new method of mapping cortical areas based on myelin content as revealed by T1-weighted (T1w) and T2-weighted (T2w) MRI. The method is generalizable across different 3T scanners and pulse sequences. We use the ratio of T1w/T2w image intensities to eliminate the MR-related image intensity bias and enhance the contrast to noise ratio for myelin. Data from each subject were mapped to the cortical surface and aligned across individuals using surface-based registration. The spatial gradient of the group average myelin map provides an observer-independent measure of sharp transitions in myelin content across the surface—i.e., putative cortical areal borders. We found excellent agreement between the gradients of the myelin maps and the gradients of published probabilistic cytoarchitectonically defined cortical areas that were registered to the same surface-based atlas. For other cortical regions, we used published anatomical and functional information to make putative identifications of dozens of cortical areas or candidate areas. In general, primary and early unimodal association cortices are heavily myelinated and higher, multimodal, association cortices are more lightly myelinated, but there are notable exceptions in the literature that are confirmed by our results. The overall pattern in the myelin maps also has important correlations with the developmental onset of subcortical white matter myelination, evolutionary cortical areal expansion in humans compared with macaques, postnatal cortical expansion in humans, and maps of neuronal density in non-human primates.
Endocytosis of the Glutamate Receptor Subunit GluK3 Controls Polarized Trafficking
Authors: Huyghe Deborah , Veran Julien , Labrousse Virginie F. , Perrais David , Mulle Christophe , Coussen Françoise
Published: August 2011

Kainate receptors (KARs) are widely expressed in the brain and are present at both presynaptic and postsynaptic sites. GluK3-containing KARs are thought to compose presynaptic autoreceptors that facilitate hippocampal mossy fiber synaptic transmission. Here we identify molecular mechanisms that underlie the polarized trafficking of KARs composed of the GluK3b splice variant. Endocytosis followed by degradation is driven by a dileucine motif on the cytoplasmic C-terminal domain of GluK3b in heterologous cells, in cultured hippocampal neurons, and in dentate granule cells from organotypic slice cultures. The internalization of GluK3b is clathrin and dynamin2 dependent. GluK3b is differentially endocytosed in dendrites as compared to the axons. These data suggest that the polarized trafficking of KARs in neurons could be controlled by the regulation of receptor endocytosis.
Nestin Is Not Essential for Development of the CNS But Required for Dispersion of Acetylcholine Receptor Clusters at the Area of Neuromuscular Junctions
Authors: Mohseni Paria , Sung Hoon-Ki , Murphy Amanda J. , Laliberte Christine L. , Pallari Hanna-Mari , Henkelman Mark , Georgiou John , Xie Gang , Quaggin Susan E. , Thorner Paul S. , Eriksson John E. , Nagy Andras
Published: August 2011

Nestin is expressed in many different progenitors during development including those of the CNS, heart, skeletal muscle, and kidney. The adult expression is mainly restricted to the subependymal zone and dentate gyrus of the brain, the neuromuscular junction, and renal podocytes. In addition, this intermediate filament protein has served as a marker of neural stem/progenitor cells for close to 20 years. Therefore it is surprising that its function in development and adult physiology is still poorly understood. Here we report that nestin deficiency is compatible with normal development of the CNS. The mutant mice, however, show impaired motor coordination. Furthermore, we found that the number of acetylcholine receptor clusters, the nerve length, and the endplate bandwidth are significantly increased in neuromuscular junction area of nestin-deficient mice. This is similar to the phenotype described for deficiency of cyclin-dependent kinase 5 (Cdk5), a candidate downstream affecter of nestin. Moreover, we demonstrate that nestin deficiency can rescue maintenance of acetylcholine receptor clusters in the absence of agrin, similar to Cdk5/agrin double knock-outs, suggesting that the observed nestin deficiency phenotype is the consequence of aberrant Cdk5 activity.
EphB2 Tyrosine Kinase-Dependent Forward Signaling in Migration of Neuronal Progenitors That Populate and Form a Distinct Region of the Dentate Niche
Authors: Catchpole Timothy , Henkemeyer Mark
Published: August 2011

The dentate gyrus (DG) is one of two areas in the mature brain where stem cells reside to continuously produce new neurons throughout adulthood. While much research has focused on the DG for its roles in adult neurogenesis, little is known regarding how this key region of the brain initially develops to form its distinct architecture. We show here that the murine EphB2 receptor tyrosine kinase is critical for embryonic/postnatal development of a specific region of the DG known as the lateral suprapyramidal blade (LSB). Intracellular truncation and point mutants demonstrate that EphB2 catalytic activity is essential for LSB formation. This is consistent with expression of EphB2 in nestin-positive neural progenitor cells that migrate medially from the lateral ventricle dentate notch neuroepithelium to populate the tertiary matrix and form the DG near the midline of the brain. Animals lacking ephrin-B1 recapitulate loss of the receptor and show that this molecule acts as the ligand to stimulate EphB2 forward signaling and direct migration of the neural progenitors into the dorsal compartment of the tertiary matrix and form the LSB. Immunoreactivity against the extracellular matrix protein Reelin in a region directly above the developing LSB is dramatically reduced when EphB2 forward signaling is disrupted. Together, these results indicate ephrin-B1 interacting with EphB2 controls the migration of dentate progenitor cells into the dorsal half of the developing DG, perhaps in part by affecting Reelin expression in a key compartment directly above the LSB.
Aqueous curium(III) phosphate species characterized by time-resolved laser-induced fluorescence spectroscopy
Authors: Moll H. , Brendler V. , Bernhard Gert
Published: August 2011

The formation of aqueous Cm(III) phosphate complexes was studied at room temperature by time-resolved laser-induced fluorescence spectroscopy (TRLFS) in 0.1 M NaClO4solutions. The experiments were perfomed at a fixed total Cm(III) concentration of 3 × 107or 2 × 108 M by varying the phosphoric acid concentration (3 × 105–0.1 M) and the pH (1.4–6.0). The red shift of the excitation and emission spectra, as well as the increase of luminescence lifetimes clearly showed the influence of phosphate on the aqueous Cm(III) speciation. In acidic phosphate solutions ([H3PO4] ≤0.1 M, pH 1.4–2.6) an increase in luminescence intensity was detected due to complexation with H2PO4−. At [H3PO4] ≥4 × 104 M and between pH 4.0 and 6.0 in general a decrease in luminescence intensity affiliates the complexation with HPO42−. Two Cm(III)-phosphate complexes could be identified from the emission data, CmH2PO42+and CmHPO4+, having peak maxima at 599.6 and 600.8 nm, respectively. TRLFS in combination with ultra-filtration (1 kD) showed that the formation of CmHPO4+is accompanied by the generation of Cm(III)-phosphate colloids especially at [H3PO4] ≥0.002 M and pH ≥ 5. Cm(III)-phosphate colloids formed at pH 5 and 6 are characterized by an emission maximum at 603.1 nm. Based on the factor analysis of the emission data the stability constants of the two complexes were calculated to be logβ121= 20.23 ± 0.13 and logβ111= 16.54 ± 0.80 at an ionic strength of 0.1 M (NaClO4).
Macro- and micro-indicators of ASR in concrete pavement
Authors: Šachlová Šarka , Burdová Anna , Pertold Zdeněk , Přikryl Richard
Published: August 2011

Alkali–silica reaction produces deterioration of concrete, visible on the macro- and micro-scale. Macro-indicators of alkali–silica reaction are important in the field inspection of concrete. Micro-indicators help to verify the presence of alkali–silica reaction and make it easier to distinguish ASR from other degradation mechanisms. Three parameters were determined to evaluate the deterioration of concrete pavements: the specific length of cracks measured on the pavement surface; the specific length of cracks in the drill cores; and the volume of alkali–silica gels and microcracks in thin sections. According to these indicators, it was possible to distinguish two types of pavement degradation: degradation mainly associated by ASR and degradation connected with another mechanism. The macro- and micro-indicators linked the deterioration to alkali–silica reaction in six sites on the Czech highways. One site was attributed to another degradation mechanism. The rock types (and/or quartz recrystallisation of aggregates) affecting ASR were determined.
Concrete incorporating high-calcium fly ash and EAF slag aggregates
Authors: Papayianni Ioanna , Anastasiou Eleftherios
Published: August 2011

Concrete mixtures with high volumes of electric arc furnace slag as aggregates and high-calcium fly ash as part of the binding system were produced and tested for their properties. The properties tested included strength development, microstructure and abrasion resistance, and the results were compared to those of conventional concrete. Results showed that compressive strength levels equal to or higher than those of conventional concrete can be achieved by using more than 90% by mass industrial by-products in the concrete mixture. These concretes of greater unit weight have shown very good aggregate–matrix transition zone and abrasion resistance, which makes them particularly suitable for pavement applications. The possibility of heavy metals leaching was also tested using a tank-leaching test, which showed minimal risk from the incorporation of electric arc furnace slag and high-calcium fly ash in concrete.
An assessment on Spirulina platensis as a biosorbent for arsenic removal
Authors: Ranjith L. , Shukla S. P. , Vennila A. , Purushothaman C. S. , Lakshmi M. S. , Aruna S. , Padmanabhan A. K.
Published: August 2011

A column consisting of algal biosorbents like agar-agar, alginic acid, calcium alginate and Spirulina platensis biomass entrapped in polyurethane foam matrix was designed and tested for the removal of As(V) from the aqueous medium. The performance of the column was studied in terms of removal efficiency, metal sequestered in the column during a specified time and biosorption capacity. The observations recorded during the study showed that the removal efficiency of As(V) after 60 min of treatment varied from 0.7 to 45.0% for 25–100 μg/L initial concentrations. The best removal efficiency of As(V) was exhibited by agar-agar and S. platensis biomass combination (45%), whereas agar-agar alone showed only 18.0% removal efficiency at 25 μg/L initial concentration. The biosorption capacity of As(V) varied from 108 to 694 μg/g for 25–100 μg/L initial concentration and the highest value (694 μg/g) was recorded for agar-agar and S. platensis biomass combination. This value was 20% higher than agar-agar alone (556 μg/g) after 60 min of treatment time. The results of the present study suggest that physical entrapment of an appropriate combination of algal adsorbents in polyurethane matrix offers a cost-effective solution for the treatment of water contaminated with arsenic.
Nitrosamine formation from the oxidation of secondary amines
Authors: Bond Tom , Templeton Michael R.
Published: August 2011

The nitrosamines are potent carcinogens which can be formed as by-products during water treatment. Much recent research activity has been focussed upon the formation, occurrence and control of N-nitrosodimethylamine (NDMA) in particular. In this study, seven secondary amines were oxidised by chlorine, ozone, and UV-irradiation, with and without post-chloramination, to quantify the effect on the formation of seven nitrosamines, including NDMA. While the yields of nitrosamines ranged from 0.01% for N-nitroso-di-n-butylamine (NDBA) to 2.01% for N-nitrosopyrrolidine (NPYR) under conditions of excess monochloramine at pH 7, yields from other oxidants were zero. Pre-oxidation with chlorine reduced nitrosamine formation by up to 83% compared with chloramination alone. This illustrates that in situations where secondary amines are key precursors, chlorine addition before ammonia during chloramination can be expected to limit nitrosamine formation. UV irradiation at 40 mJ cm−2 had little observed impact. Ozonation enhanced NDMA and N-nitrosomethylethylamine (NMEA) formation by subsequent chloramination to 7.48% and 10.15%, respectively.
Submerged membrane coagulation hybrid system as pretreatment to organic matter removal from seawater
Authors: Jeong Sanghyun , Nguyen Tien Vinh , Vigneswaran Saravanamuthu
Published: August 2011

In this study, a commonly used ferric chloride was utilised as coagulant for removing organic compounds from seawater. More than 57% of dissolved organic carbon (DOC) was removed at optimum dosage of 3 mg Fe+3/L. The coagulation by FeCl3 at optimum dosage could remove a majority (95%) of hydrophobic compounds. The results from Liquid Chromatography – Organic Carbon Detector showed that only <0.02 mg/L of hydrophobic compounds was found after coagulation. In addition, the modified fouling index decreased considerably from 15,848 s/L2 with raw seawater to 3,025 s/L2 with seawater after coagulation. In-line coagulation coupled with submerged membrane system (ICSMS) was also trialled. It is observed that critical flux was increased from 20 L/m2·h in the conventional submerged membrane system to 55 L/m2 h in ICSMS. The ICSMS could remain the high DOC removal efficiency (more than 70%) at filtration rate of 20 L/m2 h when keeping the development of trans-membrane pressure was significant lower than that of conventional submerged membrane system.
Energy consumption and greenhouse gases emissions from the use of alternative water sources in South East Queensland
Authors: Poussade Y. , Vince F. , Robillot C.
Published: August 2011

Between 1999 and 2007, several successive years of severe drought put South East Queensland's water supply under immense pressure. The decision was taken in 2005 to build a seawater desalination plant and three water recycling advanced treatment plants as part of a large investment plan to secure the region's potable water supply. The infrastructure built and commissioned in the past 3 years has a combined capacity producing more than 350,000 m3 per day of very high quality water that can be used either directly (seawater desalination) or indirectly (recycled water) for supplying drinking water. All the plants primarily rely on reverse osmosis membranes for water purification which is an effective and reliable barrier to contaminants, but also requires high energy consumption and a high level of pre-treatment and chemicals. In this paper, the actual energy consumption of two of the plants (the seawater desalination plant and one water recycling plant) was investigated with the perspective of drinking water production over the July 2009–June 2010 period. Eolia™ Potable Water, a Life Cycle Analysis tool developed by Veolia Environnement Research & Innovation, was used to model the processes and estimate the greenhouse gases (GHG) emissions from both plants. As expected, the energy requirement of the desalination was higher (approximately 2.2 times) than the water recycling plant. The plants were found to be significantly more energy efficient when operated at higher flow. In both cases, the purchase of electrical energy represented by far the major contribution to GHG emissions. Indirect GHG emissions from chemical consumption could be reduced at the water recycling plant by optimising the dose of ferric chloride used at the plant and sourcing the chemical from a less distant supplier.
On two theorems regarding exponential stability
Authors: Hai Viet
Published: August 2011

There are two remarkable results in the theory of stability of dynamical
systems which were obtained by R. Datko in 1970 and E.A. Barbashin in 1967.
After the seminal researches of Datko and Barbashin, there have been a great
number of works devoted to this results. For the case of discrete-time
systems analogous results have been obtained. This paper will give the new
versions which unify the discrete-time versions of Barbashin's theorem and
Datko's theorem.