bluuebunny/crossref_metadata_2025 huggingface dataset:
Protection against tuberculosis by a single intranasal administration of DNA-hsp65 vaccine complexed with cationic liposomes
Authors: Rosada Rogério S , Torre Lucimara Gaziola de la , Frantz Fabiani G , Trombone Ana PF , Zárate-Bladés Carlos R , Fonseca Denise M , Souza Patrícia RM , Brandão Izaíra T , Masson Ana P , Soares Édson G , Ramos Simone G , Faccioli Lúcia H , Silva Célio L , Santana Maria HA , Coelho-Castelo Arlete AM
Published: July 2008

Background

The greatest challenges in vaccine development include optimization of DNA vaccines for use in humans, creation of effective single-dose vaccines, development of delivery systems that do not involve live viruses, and the identification of effective new adjuvants. Herein, we describe a novel, simple technique for efficiently vaccinating mice against tuberculosis (TB). Our technique consists of a single-dose, genetic vaccine formulation of DNA-hsp65 complexed with cationic liposomes and administered intranasally.

Results

We developed a novel and non-toxic formulation of cationic liposomes, in which the DNA-hsp65 vaccine was entrapped (ENTR-hsp65) or complexed (COMP-hsp65), and used to immunize mice by intramuscular or intranasal routes. Although both liposome formulations induced a typical Th1 pattern of immune response, the intramuscular route of delivery did not reduce the number of bacilli. However, a single intranasal immunization with COMP-hsp65, carrying as few as 25 μg of plasmid DNA, leads to a remarkable reduction of the amount of bacilli in lungs. These effects were accompanied by increasing levels of IFN-γ and lung parenchyma preservation, results similar to those found in mice vaccinated intramuscularly four times with naked DNA-hsp65 (total of 400 μg).

Conclusion

Our objective was to overcome the significant obstacles currently facing DNA vaccine development. Our results in the mouse TB model showed that a single intranasal dose of COMP-hsp65 elicited a cellular immune response that was as strong as that induced by four intramuscular doses of naked-DNA. This formulation allowed a 16-fold reduction in the amount of DNA administered. Moreover, we demonstrated that this vaccine is safe, biocompatible, stable, and easily manufactured at a low cost. We believe that this strategy can be applied to human vaccines to TB in a single dose or in prime-boost protocols, leading to a tremendous impact on the control of this infectious disease.
The function of Shp2 tyrosine phosphatase in the dispersal of acetylcholine receptor clusters
Authors: Qian Yueping K , Chan Ariel WS , Madhavan Raghavan , Peng H Benjamin
Published: July 2008

Background

A crucial event in the development of the vertebrate neuromuscular junction (NMJ) is the postsynaptic enrichment of muscle acetylcholine (ACh) receptors (AChRs). This process involves two distinct steps: the local clustering of AChRs at synapses, which depends on the activation of the muscle-specific receptor tyrosine kinase MuSK by neural agrin, and the global dispersal of aneural or "pre-patterned" AChR aggregates, which is triggered by ACh or by synaptogenic stimuli. We and others have previously shown that tyrosine phosphatases, such as the SH2 domain-containing phosphatase Shp2, regulate AChR cluster formation in muscle cells, and that tyrosine phosphatases also mediate the dispersal of pre-patterned AChR clusters by synaptogenic stimuli, although the specific phosphatases involved in this latter step remain unknown.

Results

Using an assay system that allows AChR cluster assembly and disassembly to be studied separately and quantitatively, we describe a previously unrecognized role of the tyrosine phosphatase Shp2 in AChR cluster disassembly. Shp2 was robustly expressed in embryonic Xenopus muscle in vivo and in cultured myotomal muscle cells, and treatment of the muscle cultures with an inhibitor of Shp2 (NSC-87877) blocked the dispersal of pre-patterned AChR clusters by synaptogenic stimuli. In contrast, over-expression in muscle cells of either wild-type or constitutively active Shp2 accelerated cluster dispersal. Significantly, forced expression in muscle of the Shp2-activator SIRPα1 (signal regulatory protein α1) also enhanced the disassembly of AChR clusters, whereas the expression of a truncated SIRPα1 mutant that suppresses Shp2 signaling inhibited cluster disassembly.

Conclusion

Our results suggest that Shp2 activation by synaptogenic stimuli, through signaling intermediates such as SIRPα1, promotes the dispersal of pre-patterned AChR clusters to facilitate the selective accumulation of AChRs at developing NMJs.
ENMD-1198, a novel tubulin-binding agent reduces HIF-1alpha and STAT3 activity in human hepatocellular carcinoma(HCC) cells, and inhibits growth and vascularization in vivo
Authors: Moser Christian , Lang Sven A , Mori Akira , Hellerbrand Claus , Schlitt Hans J , Geissler Edward K , Fogler William E , Stoeltzing Oliver
Published: July 2008

Background

Hepatocellular carcinoma (HCC) represents a highly vascularized tumor entity and the process of angiogenesis is essential for the growth of HCC. Importantly, the pro-angiogenic transcription factors HIF-1α and STAT3 have been implicated in HCC progression, thus representing interesting targets for molecular targeted therapy. We hypothesized that therapeutic inhibition of HIF-1α could be achieved by using a novel tubulin-binding agent (ENMD-1198). ENMD-1198 is an analog of 2-methoxyestradiol (2ME2) with antiproliferative and antiangiogenic activity.

Methods

The human HCC cell lines HUH-7 and HepG2 were used for experiments. Effects of ENMD-1198 on constitutive and inducible (hypoxia, growth factors) activation of signaling cascades, including HIF-1α and STAT3, were investigated by Western blotting. Changes in VEGF expression were determined by real-time PCR. Effects of ENMD-1198 on cancer cell migration and invasion were evaluated in in vitro-assays. The growth-inhibitory effects of ENMD-1198 (200 mg/kg/day) were determined in a subcutaneous tumor model (HUH-7).

Results

ENMD-1198 inhibited the phosphorylation of MAPK/Erk, PI-3K/Akt and FAK. Moreover, activation of HIF-1α and STAT3 was dramatically reduced by ENMD-1198, which resulted in lower VEGF mRNA expression (P < 0.05). In addition, tumor cell migratory and invasive properties were significantly inhibited (P < 0.05, for both). In vivo, treatment with ENMD-1198 led to a significant reduction in tumor growth, tumor vascularization, and numbers of proliferating tumor cells (P < 0.05 for all).

Conclusion

The novel microtubule destabilizing agent ENMD-1198 is suitable for inhibiting HIF-1α and STAT3 in human HCC cells and leads to reduced tumor growth and vascularization in vivo. Hence, inhibition of HIF-1α and STAT3 could prove valuable for therapy of hepatocellular carcinoma.
Stress load during childhood affects psychopathology in psychiatric patients
Authors: Weber Katja , Rockstroh Brigitte , Borgelt Jens , Awiszus Barbara , Popov Tzvetan , Hoffmann Klaus , Schonauer Klaus , Watzl Hans , Pröpster Karl
Published: July 2008

Background

Childhood stress and trauma have been related to adult psychopathology in different psychiatric disorders. The present study aimed at verifying this relationship for stressful experiences during developmental periods by screening stress load across life in adult psychiatric inpatients with different diagnoses compared to healthy subjects. In addition, a relationship between the amount of adverse experiences and the severity of pathology, which has been described as a 'building block' effect in posttraumatic stress disorder (PTSD), was explored for non-traumatic events in psychiatric disorders other than PTSD.

Methods

96 patients with diagnoses of Major Depressive Disorder (MDD), schizophrenia, drug addiction, or personality disorders (PD) and 31 subjects without psychiatric diagnosis were screened for adverse experiences in childhood (before the age of six years), before onset of puberty, and in adulthood using the Early Trauma Inventory and the Posttraumatic Stress Diagnostic Scale. Effects of stress load on psychopathology were examined for affective symptoms, PTSD, and severity of illness by regression analyses and comparison of subgroups with high and low stress load.

Results

High stress load in childhood and before puberty, but not in adulthood, was related to negative affect in all participants. In patients, high stress load was related to depressive and posttraumatic symptoms, severity of disorder, and the diagnoses of MDD and PD.

Conclusion

Results support the hypothesis of stress-sensitive periods during development, which may interact with genetic and other vulnerability factors in their influence on the progress of psychiatric disorders. A 'dose' effect of stress load on the severity of psychopathology is not restricted to the relationship between traumata and PTSD.
Risk factors for bone mineral density at the calcaneus in 40–59 year-old male workers: A cross-sectional study in Korea
Authors: Seo Hyun-Ju , Kim Soo-Geun , Kim Chong-Soon
Published: July 2008

Background

Few epidemiologic studies have attempted to investigate the prevalence and risk factors for osteopenia and osteoporosis in middle-aged Asian men. We performed this study to determine the prevalence and risk factors of osteopenia and osteoporosis in this population.

Methods

This cross-sectional study was conducted from March to July, 2004. The subjects were 2,073 males aged from 40 to 59 years in the KHNP (Korea Hydro & Nuclear Power) workplace-based cohort. Bone mineral density (BMD) was measured by peripheral, dual-energy, X-ray absorptiometry (DXA) at the calcaneus. Anthropometric and lifestyle factors were investigated using a standard, self-reported questionnaire.

Results

BMD was 0.60 ± 0.09 g/cm2 (mean ± standard deviation) and was negatively correlated with age (r = -0.18, P < 0.001), but positively correlated with waist-to-hip ratio (WHR; r = 0.15, P < 0.001), body fat (r = 0.10, P < 0.001), BMI (r = 0.35, P < 0.001), height (r = 0.26, P < 0.001), and weight (r = 0.43, P < 0.001).

In multiple linear regression analysis, the independent determinants associated with BMD were increasing age (coefficient = -0.002, P < 0.001), physical activity (≤ 2/week vs. ≥ 3/week; coefficient = 0.017, P < 0.001), WHR (coefficient = -0.796, P < 0.001), body mass index (BMI; coefficient = 0.023, P < 0.001) and smoking status (never vs. ever; coefficient = -0.018, P < 0.001).

Conclusion

We suggest that BMD of the calcaneus is correlated negatively with exposure to smoke and increased WHR, but positively with regular exercise and increased BMI.
Activation of Erk in the Anterior Cingulate Cortex During the Induction and Expression of Chronic Pain
Authors: Wei Feng , Zhuo Min
Published: July 2008

The extracellular signal-regulated kinase (Erk) activity contributes to synaptic plasticity, a key mechanism for learning, memory and chronic pain. Although the anterior cingulate cortex (ACC) has been reported as an important cortical region for neuronal mechanisms underlying the induction and expression of chronic pain, it has yet to be investigated whether or not Erk activity in the ACC may be affected by peripheral injury or in chronic pain state. In the present study, we use adult rat animal models of inflammatory and neuropathic pain and demonstrate that Erk signaling pathway in the ACC is potently activated after peripheral tissue or nerve injury. Furthermore, we demonstrate that mechanical allodynia significantly activated Erk activity at synaptic sites at two weeks after the injury. We propose a synaptic model for explaining the roles of Erk activity during different phases of chronic pain. Our findings suggest that cortical activation of Erk may contribute to both induction and expression of chronic pain.
Velocity, attenuation, and quality factor in anisotropic viscoelastic media: A perturbation approach
Authors: Vavryčuk Václav
Published: July 2008

Velocity, attenuation, and the quality [Formula: see text] factor of waves propagating in homogeneous media of arbitrary anisotropy and attenuation strength are calculated in high-frequency asymptotics using a stationary slowness vector, the vector evaluated at the stationary point of the slowness surface. This vector is generally complex-valued and inhomogeneous, meaning that the real and imaginary parts of the vector have different directions. The slowness vector can be determined by solving three coupled polynomial equations of the sixth order or by a nonlinear inversion. The procedure is simplified if perturbation theory is applied. The elastic medium is viewed as a background medium, and the attenuation effects are incorporated as perturbations. In the first-order approximation, the phase and ray velocities and their directions remain unchanged, being the same as those in the background elastic medium. The perturbation of the slowness vector is calculated by solving a system of three linear equations. The phase attenuation and phase [Formula: see text]-factor are linear functions of the perturbation of the slowness vector. Calculating the ray attenuation and ray [Formula: see text]-factor is even simpler than calculating the phase quantities because they are expressed in terms of perturbations of the medium without the need to evaluate the perturbation of the slowness vector. Numerical modeling indicates that the perturbations are highly accurate; the errors are less than 0.3% for a medium with a [Formula: see text]-factor of 20 or higher. The accuracy can be enhanced further by a simple modification of the first-order perturbation formulas.
Role of Corticotropin-Releasing Hormone Testing in Assessment of Hypothalamic-Pituitary-Adrenal Axis Function in Infants with Congenital Central Hypothyroidism
Authors: van Tijn David A. , de Vijlder Jan J. M. , Vulsma Thomas
Published: July 2008

Context: The Dutch neonatal congenital hypothyroidism (CH) screening program detects infants with CH of central origin (CH-C). These infants have a high likelihood of multiple pituitary hormone deficiencies. ACTH deficiency especially poses an additional risk for brain damage and may be fatal.

Objective: Our objective was to evaluate different tools for assessment of the integrity of the hypothalamus-pituitary-adrenocortex (HPA) axis in young infants, aiming for a strategy for reliable and timely diagnosis.

Design, Setting: This is a Dutch nationwide prospective study (enrollment 1994–1996). Patients were included if neonatal CH screening results were indicative of CH-C and HPA axis function could be tested within 6 months of birth.

Patients: Nine male and three female infants with CH-C and four infants with false-positive screening results or transient hypothyroidism were included in the study.

Main Outcome Measures: CRH test results, multiple cortisol plasma concentrations, and cortisol excretion in 24-h urine were measured.

Results: Six (50%) of the CH-C patients had abnormal CRH test results. Three of them had discordant test results: impaired increase of plasma cortisol in response to CRH, despite substantial increase of plasma ACTH. The other three infants, with concordant impaired responses of both ACTH and cortisol to CRH, had a very low urinary cortisol excretion in comparison with the subjects with normal CRH test results.

Conclusions: The CRH test proves to be a fast and reliable tool in the assessment of HPA axis (dys)function. It enables timely diagnosis in (asymptomatic) neonates at risk for serious morbidity and mortality. The discordant response type, which has not been described before, may be an early phase of HPA axis dysfunction. Alternatively, patients with this response type may constitute a separate pathogenetic subset of HPA axis-deficient patients.
Direct integration of carbon nanotubes on micromachined hotplates
Authors: Vincent M , Briand D , Schürmann G , de Rooij N F
Published: July 2008

This communication reports on the localized growth of carbon nanotubes (CNTs) on the surface of classical micro-hotplates with integrated heater and transducing electrodes. A catalytic thermal CVD process has been developed and adapted to grow CNTs by only using the heat provided by the integrated heater. Spatial control of the CNTs' growth was achieved thanks to this method; CNTs are localized only on the heating area of the micro-hotplate, and electrical contact with the integrated electrodes can be obtained. The influence of the catalyst, gas flow, and temperature cycles on the growth of CNT was investigated in order to optimize growth and avoid micro-hotplate degradation. Different strategies were investigated to get the electrical connection between the CNTs and the platinum electrodes. The electrically connected grown CNTs could be used directly as gas-sensitive resistors with superior performance in terms of sensitivity than metal—oxide gas sensors integrated on such platforms.
The highest affinity binding site of small protein B on transfer messenger RNA is outside the tRNA domain
Authors: Metzinger Laurent , Hallier Marc , Felden Brice
Published: July 2008

Eubacterial ribosomes stalled on defective mRNAs are released through a mechanism referred to as trans-translation, depending on the coordinated actions of small protein B (SmpB) and transfer messenger RNA (tmRNA). A series of tmRNA variants with deletions in each structural domain were produced. Their structures were monitored by enzymatic and chemical probes in vitro, in the presence and absence of SmpB. Dissociation constants between these RNAs and SmpB from Aquifex aeolicus were derived by surface plasmon resonance (SPR) combined with filter binding assays. Three independent experimental evidences, including filter binding assays, SPR, and concentration titrations of the RNA–protein reactivity changes toward structural probes, indicate that the binding site that has the highest affinity for the protein is located outside the tRNA domain, upstream of the internal tag. The minimal tmRNA fragment that contains this high affinity site for SmpB, and also contains another site of lower affinity, includes the tag reading frame and three downstream pseudoknots that form a ring structure in solution.
The bureaucracy�democracy tango: a dual-source empirical revalidation by structural equation modelling in the Israeli public sector
Authors: Vigoda-Gadot Eran , Miller-Mor Rotem , Mizrahi Shlomo , Tevet Eyal
Published: July 2008

The relationship between bureaucracy and democracy in modern nations has gained the attention of scholars and experts worldwide. This article uses the allegory of a tango dance to illuminate core pandemics of the bureaucracy–democracy interface. First, we propose a theoretical model that relates these arenas in the public realm. The model is then tested empirically based on four in-depth field studies of Israeli public sector organisations (in the fields of public energy, healthcare, policing and local governance). The studies were conducted simultaneously and were based on both qualitative and quantitative data collected in the intra-organisational and extra-organisational arenas. Respondents were 159 public sector personnel and 158 citizens who received services from the same organisations. Data were analysed with a structural equation modelling (SEM) technique. The findings reconfirmed a solid positive relationship between elements of an effective bureaucracy and segments of an active democracy. Moreover, strongest support was found for a mediating model where perceived performance mediated the bureaucratic–democratic relationship. Implications of the findings are discussed in both the intra- and extra-organisational context.
The generational contract in Sweden: age-specific attitudes to age-related policies
Authors: Svallfors Stefan
Published: July 2008

This article analyses age differences in attitudes towards public policies to support older people and to support families with children in Sweden. It is shown that support for older people becomes increasingly popular over time, so that it is more popular in all age groups than support for families with children, and that age and class differences in attitudes tend to rise and recede in tandem regarding support for older people, while class differences supplant age differences in the case of support for families with children.
The institutional embeddedness of social capital: a multi-level investigation across 24 European countries
Authors: Koster Ferry , Bruggeman Jeroen
Published: July 2008

This study contributes to earlier studies aimed at the question of whether the welfare state crowds out social capital or not by examining to what extent the welfare state affects the value of social capital. This article investigates the effects of three sources of social capital on occupational prestige and tests whether these effects are moderated by welfare state effort in terms of social spending. Multi-level analyses based on European Social Survey (ESS) 2002/03 and International Monetary Fund (IMF) data, including 39,299 people from 24 European countries, provides evidence that welfare state effort decreases the value of social capital.
Ramelteon: A Novel Approach in the Treatment of Insomnia
Authors: Reynoldson Jill N , Elliott Ellie SR , Nelson Leigh Anne
Published: July 2008

Objective:

To review the pharmacology, pharmacokinetics, efficacy, and safety of ramelteon in the treatment of primary insomnia in adults, including elderly adults.

Data Sources:

MEDLINE (1966–July 2008) and PsyclNFO (1985–July 2008) literature searches were conducted to idontify clinical data involving ramelteon. The manufacturer provided a summary of clinical data and abstracts of unpublished studies.

Study Selection And Data Extraction:

All primary literature, including abstracts, focusing on the pharmacology and pharmacokinetics of ramelteon and clinical trials evaluating its use was reviewed. Information deemed most relevant was incorporated. Our search revealed 5 controlled trials evaluating the short-term efficacy and safety of ramelteon in the treatment of primary insomnia: 3 in adults and 2 in geriatric patients. Additionally, 2 studies in abstract form that evaluated the long-term effects of ramelteon were included.

Data Synthesis:

Ramelteon is the first selective melatonin receptor agonist approved by the Food and Drug Administration. It has no affinity for the γ-aminobutyric acid receptor complex or for receptors that bind acetylcholine, cytokines, dopamine, norepinephrine, neuropeptides, opiates, and serotonin. In the only published Phase 3 trial in adults, investigators found that latency to persistent sleep decreased with ramelteon to 31.5 ± 2.91 minutes with 8 mg and 29.5 ± 2.96 minutes with 16 mg compared with 42.5 ± 2.97 minutes with placebo (p = 0.007 and p = 0.002, respectively). Total sleep time was not significantly different from that with placebo. Safety data from short-term studies showed advantages of ramelteon over other sleep agents including no potential for abuse, no rebound insomnia, and lack of effect on motor and cognitive function. The adverse effects seen most frequently in ramelteon clinical trials were headache, somnolence, fatigue, nausea, dizziness, and insomnia. The overall incidence was similar to that of placebo.

Conclusions:

Ramelteon offers a novel mechanism of action for the treatment of insomnia. Studies support its short- and long-term use in adults and elderly adults for the treatment of primary insomnia characterized by difficulty with sleep initiation. Efficacy studies comparing ramelteon with other sleep agents are needed to further solidify the role of ramelteon in the treatment of insomnia.
Book Reviews
Authors: Richmond Jill
Published: July 2008

Hardwired behaviour: What neuroscience reveals about morality

Laurence Tancredi Cambridge, MA: Cambridge University Press, 2005, p. 226. Hardback, ISBN‐13 9780521860017
Highly Selective Receptive Fields in Mouse Visual Cortex
Authors: Niell Cristopher M. , Stryker Michael P.
Published: July 2008

Genetic methods available in mice are likely to be powerful tools in dissecting cortical circuits. However, the visual cortex, in which sensory coding has been most thoroughly studied in other species, has essentially been neglected in mice perhaps because of their poor spatial acuity and the lack of columnar organization such as orientation maps. We have now applied quantitative methods to characterize visual receptive fields in mouse primary visual cortex V1 by making extracellular recordings with silicon electrode arrays in anesthetized mice. We used current source density analysis to determine laminar location and spike waveforms to discriminate putative excitatory and inhibitory units. We find that, although the spatial scale of mouse receptive fields is up to one or two orders of magnitude larger, neurons show selectivity for stimulus parameters such as orientation and spatial frequency that is near to that found in other species. Furthermore, typical response properties such as linear versus nonlinear spatial summation (i.e., simple and complex cells) and contrast-invariant tuning are also present in mouse V1 and correlate with laminar position and cell type. Interestingly, we find that putative inhibitory neurons generally have less selective, and nonlinear, responses. This quantitative description of receptive field properties should facilitate the use of mouse visual cortex as a system to address longstanding questions of visual neuroscience and cortical processing.
Amphetamine Exposure Enhances Accumbal Responses to Reward-Predictive Stimuli in a Pavlovian Conditioned Approach Task
Authors: Wan Xun , Peoples Laura L.
Published: July 2008

Acute and repeated exposure to psychostimulants such as amphetamine enhances the effects of pavlovian conditioned stimuli on conditioned behavior. It is hypothesized that amphetamine facilitates conditioned stimulus (CS) effects by selectively enhancing accumbal neuronal responses to stimuli. To test this hypothesis, rats were trained to discriminate between two pavlovian stimuli. One stimulus (i.e., CS+) was paired with sucrose delivery [i.e., unconditioned stimulus (US)], and the other stimulus (i.e., CS−) was paired with the absence of sucrose. Animals developed a conditioned approach response that occurred during the CS+ but not during the CS−. We tested the effect of different doses of amphetamine (0, 0.25, 0.5, or 1.0 mg/kg) on this conditioned approach behavior as well as on accumbal neuronal responses time locked to the CS+, the CS−, and the US. Acute amphetamine exposure increased conditioned approach behavior during the CS+, but not during the CS−. This change in behavior was associated with a selective increase in the magnitude of accumbal responses during the CS+. Repeated amphetamine administration followed by a drug-free period and reexposure did not affect the conditioned behavior, but increased accumbal responses to the CS+. These findings support the hypothesis that amphetamine exposure enhances behavioral responses to pavlovian conditioned stimuli by amplifying accumbal responses to those stimuli.
Channel Density Distributions Explain Spiking Variability in the Globus Pallidus: A Combined Physiology and Computer Simulation Database Approach
Authors: Günay Cengiz , Edgerton Jeremy R. , Jaeger Dieter
Published: July 2008

Globus pallidus (GP) neurons recorded in brain slices show significant variability in intrinsic electrophysiological properties. To investigate how this variability arises, we manipulated the biophysical properties of GP neurons using computer simulations. Specifically, we created a GP neuron model database with 100,602 models that had varying densities of nine membrane conductances centered on a hand-tuned model that replicated typical physiological data. To test the hypothesis that the experimentally observed variability can be attributed to variations in conductance densities, we compared our model database results to a physiology database of 146 slice recordings. The electrophysiological properties of generated models and recordings were assessed with identical current injection protocols and analyzed with a uniform set of measures, allowing a systematic analysis of the effects of varying voltage-gated and calcium-gated conductance densities on the measured properties and a detailed comparison between models and recordings. Our results indicated that most of the experimental variability could be matched by varying conductance densities, which we confirmed with additional partial block experiments. Further analysis resulted in two key observations: (1) each voltage-gated conductance had effects on multiple measures such as action potential waveform and spontaneous or stimulated spike rates; and (2) the effect of each conductance was highly dependent on the background context of other conductances present. In some cases, such interactions could reverse the effect of the density of one conductance on important excitability measures. This context dependence of conductance density effects is important to understand drug and neuromodulator effects that work by affecting ion channels.
Distinct Regulation of β2 and β3 Subunit-Containing Cerebellar Synaptic GABAAReceptors by Calcium/Calmodulin-Dependent Protein Kinase II
Authors: Houston Catriona M. , Hosie Alastair M. , Smart Trevor G.
Published: July 2008

Modulation of GABAAreceptor function and inhibitory synaptic transmission by phosphorylation has profound consequences for the control of synaptic plasticity and network excitability. We have established that activating α-calcium/calmodulin-dependent protein kinase II (α-CaMK-II) in cerebellar granule neurons differentially affects populations of IPSCs that correspond to GABAAreceptors containing different subtypes of β subunit. By using transgenic mice, we ascertained that α-CaMK-II increased IPSC amplitude but not the decay time by acting via β2 subunit-containing GABAAreceptors. In contrast, IPSC populations whose decay times were increased by α-CaMK-II were most likely mediated by β3 subunit-containing receptors. Expressing α-CaMK-II with mutations that affected kinase function revealed that Ca2+and calmodulin binding is crucial for α-CaMK-II modulation of GABAAreceptors, whereas kinase autophosphorylation is not. These findings have significant consequences for understanding the role of synaptic GABAAreceptor heterogeneity within neurons and the precise regulation of inhibitory transmission by CaMK-II phosphorylation.
Aging of rolled erosion control products for channel erosion control
Authors: Li M.-H. , Khanna S.
Published: July 2008

The purpose of this study was to investigate the aging effects of environmental factors on rolled erosion control products (RECPs). Seven RECPs made of natural, synthetic or composite materials were evaluated. Used (installed in channels of a field laboratory for 3 years) and unused (stored in a limited climate-controlled laboratory for 3 years) samples of each product were tested to determine 10 physical properties, including mass per unit area, thickness, tensile strength, stiffness, light penetration, resilience, water absorption, swell, specific gravity and smolder resistance. The results indicate that all materials exhibited a significant loss of tensile strength after 3 years of use. Used materials of the natural type showed a 68% strength loss whereas the composite and synthetic types had smaller strength losses in the range of 37–61%. Other property testing results showed less conclusive or inconsistent trends, which implies that tensile strength is a critical and reliable property for use to evaluate the aging effects on RECPs.
Analysis of sand slopes stabilized with facing of soil bags with extended reinforcement strips
Authors: Huang C.-C. , Matsushima K. , Mohri Y. , Tatsuoka F.
Published: July 2008

A limit-equilibrium-based stability analysis method was developed to simulate the stability of unreinforced sand slopes and geosynthetic-reinforced sand slopes that had been stabilized with soil bags stacked on the slope face. The stability of unreinforced and reinforced sand slopes when loaded with a rigid strip footing placed on the slope crest was evaluated by performing physical model tests. The stabilizing effects of an inclined stacked soil bag facing with extended reinforcement strips (tails) were confirmed. The results of limit-equilibrium analyses showed good agreement with the physical model test results. A parametric study performed using the proposed method also revealed that the effects of the soil bag inclination angle, αb, and internal friction angle of the backfill soil, ϕs, on the slope stability of the unreinforced and reinforced sand slopes are significant. The ultimate footing loads observed in five physical model tests on reinforced and unreinforced slopes can be simulated by the proposed analysis method when using a single ‘operational’ friction angle (ϕop) that is 82 to 86% of the peak internal friction angle obtained from conventional drained plane strain compression tests (namely, ϕp) under low pressure levels as in the unloaded model slope. This ratio of ϕop/ϕp is consistent with the value found in stability analyses of reinforced and unreinforced shallow sand slopes reported in the literature.
Reliability analysis of reinforced soil walls under static and seismic forces
Authors: Sayed S. , Dodagoudar G. R. , Rajagopal K.
Published: July 2008

The traditional factor of safety does not account for the variability and uncertainty of the different parameters considered in the analysis. On the other hand, the reliability approach considers the possible variations in the design parameters and gives more realistic estimates of the safety of the structure and the possible risk of failure. In the present investigation, reliability analysis was carried out to study the stability aspects of reinforced soil retaining walls under static and seismic conditions using three methods: first-order second-moment method (FOSM), point estimate method (PEM) and first-order reliability method (FORM). A parametric sensitivity analysis is presented to bring out the effect of uncertainties in the soil and reinforcement parameters on the value of the minimum reliability index for internal and external stability of reinforced soil walls under static and seismic loads. The reliability indices evaluated by the three methods of reliability analyses were compared for both the internal and external stability of the wall. Based on the results, it is concluded that the friction angle (ϕ) is the most sensitive random variable affecting the overall stability of the reinforced soil walls under static and seismic loads.
An Examination of Anxiety Sensitivity as a Moderator of the Relation Between Sleep Anticipatory Anxiety and Sleep Onset Latency
Authors: Babson Kimberly A. , Trainor Casey D. , Bunaciu Liviu , Feldner Matthew T.
Published: July 2008

Evidence suggests that advancing currently limited knowledge about self-reported sleep onset latency is important for better understanding insomnia. Relatively little research has been conducted to understand factors that affect sleep onset latency. The current study tested a hypothesized role of factors of the global anxiety sensitivity (AS) construct as moderators of the relation between sleep onset latency and physical and cognitive components of sleep anticipatory anxiety. As hypothesized, AS-Physical Concerns moderated the relation between the physical component of sleep anticipatory anxiety and sleep onset latency, even after controlling for age, gender, negative affect, and substance use variables. However, in contrast to prediction, AS-Mental Incapacitation Concerns did not appear to moderate the relation between sleep onset latency and the cognitive component of sleep anticipatory anxiety. These findings are discussed in terms of extant research on sleep onset latency, and future directions for research to advance this body of knowledge are considered.
Odour monitoring of small wastewater treatment plant located in sensitive environment
Authors: Zarra T. , Naddeo V. , Belgiorno V. , Reiser M. , Kranert M.
Published: July 2008

Small wastewater treatment plants are often localized nearby tourist areas. Odour emissions are a major environmental issue in these plants and are considered to be the main cause of disturbance noticed by the exposed population. Odour measurement is carried out using analytical or sensorial methods. Sensorial analysis, being assigned to the “human sensor”, is the cause of a considerable uncertainty.

In this study, a novel procedure based on highly innovative analytical tool was used to identify and characterise the odour sources and the volatile substances that cause annoyance in a SWWTP located in a sensitive area, with the aim to remove the subjective component in the measure of the odours and define the induced impact. At the same time key odour compounds are detected, and the relationship between their concentration and the performances of the plant are investigated.

The sources and the main chemical substances responsible for the olfactory annoyances were identified. Results highlight the applicability of the highly innovative tool in odour emission monitoring. Around 39 different substances were detected, with almost half being smell relevant components as well as responsible. Dimethyl disulphide was identified as key compound connected to the efficiency of the process.
A novel solution for hydroxylated PAHs removal by oxidative coupling reaction using Mn oxide
Authors: Kang Ki-Hoon , Lim Dong-Min , Shin Hyun-Sang
Published: July 2008

In this study, removals of 1-naphthol by oxidative-coupling reaction using birnessite, one of the natural Mn oxides present in soil, was investigated in various experimental conditions (reaction time, Mn oxide loadings, pH). The removal efficiency of 1-naphthol by birnessite was high in all the experimental conditions, and UV-visible and mass spectrometric analyses on the supernatant after reaction confirmed that the reaction products were oligomers formed by oxidative-coupling reaction. Pseudo-first order rate constants, k, for the oxidative transformation of 1-naphthol by birnessite was derived from the kinetic experiments under various amounts of birnessite loadings, and using the observed pseudo-first order rate constants with respect to birnessite loadings, the surface area normalised specific rate constant, ksurf, was also determined to be 9.3 × 10−4 (L/m2·min) for 1-naphthol. In addition, the oxidative transformation of 1-naphthol was found to be dependent on solution pH, and the pseudo-first order rate constants were increased from 0.129 at pH 10 to 0.187 at pH 4.
A membrane biofilm reactor achieves aerobic methane oxidation coupled to denitrification (AME-D) with high efficiency
Authors: Modin O. , Fukushi K. , Nakajima F. , Yamamoto K.
Published: July 2008

Methane would potentially be an inexpensive, widely available electron donor for denitrification of wastewaters poor in organics. Currently, no methanotrophic microbe is known to denitrify. However, aerobic methane oxidation coupled to denitrification (AME-D) has been observed in several laboratory studies. In the AME-D process, aerobic methanotrophs oxidise methane and release organic metabolites and lysis products, which are used by coexisting denitrifiers as electron donors for denitrification. Due to the presence of oxygen, the denitrification efficiency in terms of methane-to-nitrate consumption is usually low. To improve this efficiency the use of a membrane biofilm reactor was investigated. The denitrification efficiency of an AME-D culture in (1) a suspended growth reactor, and (2) a membrane biofilm reactor was studied. The methane-to-nitrate consumption ratio for the suspended culture was 8.7. For the membrane-attached culture the ratio was 2.2. The results clearly indicated that the membrane-attached biofilm was superior to the suspended culture in terms of denitrification efficiency. This study showed that for practical application of the AME-D process, focus should be placed on development of a biofilm reactor.
Experimental study on municipal and industrial reclaimed wastewater refinement for agricultural reuse
Authors: Gori R. , Caretti C.
Published: July 2008

The present study is aimed at verifying the possibility of reusing municipal and industrial reclaimed wastewaters for the irrigation of container-grown ornamental shrubs, paying attention to the refinery treatment. The research has been carried out in the district of Pistoia (Central Italy), which represents one of the main nursery areas in Europe. Two experimental sites, each consisting of a refinery treatment pilot plant (filtration and disinfection) and an agronomic area, were set-up. In this paper the attention is focused on the selection of the refinery treatment. The combined process of peracetic acid (PAA) and ultraviolet irradiation (UV) chosen for the disinfection treatment proved to be very effective for the inactivation of microorganisms for both municipal and industrial wastewaters. The high efficiency is recognised as being brought about by the formation of free radicals due to the photolysis of the PAA when in the presence of the UV rays. A preliminary cost analysis has been carried out in order to highlight the most economically advantageous solution which guarantees the compliance to the Italian limits for wastewater reuse in agriculture (Escherichia Coli 10 CFU/100 mL).
PHA-accumulating microorganisms in full-scale wastewater treatment plants
Authors: Oshiki Mamoru , Satoh Hiroyasu , Mino Takashi , Onuki Motoharu
Published: July 2008

A study was conducted to clarify phylogenetic affiliations of polyhydroxyalkanoate (PHA)-accumulating microorganisms in full-scale activated sludge processes. Activated sludge samples obtained from three full-scale activated sludge processes were aerobically incubated with excess acetate to increase their PHA content. The buoyant density separation method was applied to selectively collect PHA-accumulating cells, which were then analysed by the group-level FISH and the PCR-DGGE-sequencing methods, and possible PHA-accumulating microbial groups were screened. A set of oligonucleotide probes targeting the microbial groups suspected to accumulate PHA was introduced, and seven oligonucleotide probes were newly designed for this purpose. PHA accumulation of probe-positive cells was confirmed by the post-FISH PHA staining method, wherein PHA staining with Nile Blue A (NBA) was applied after FISH. As a result, the following seven bacterial groups were found to have PHA: Dechloromonas, Accumulibacter, Thauera, Zoogloea, Comamonas, Competibacter and a novel cluster in Beta-proteobacteria. Based on the results of the post-FISH PHA staining method, these seven bacterial groups were estimated to account for around four-tenths to two-thirds of total PHA-accumulating microorganisms.
Relevant approach to assess performances of wastewater biosolids composting in terms of micropollutants removal
Authors: Patureau D. , Hernandez-Raquet G. , Balaguer P. , Delgenes N. , Muller M. , Dagnino S. , Delgenes J. P.
Published: July 2008

The presence of organic pollutants in wastewater biosolids and their possible impact to the environment contribute to decrease interest for the agricultural spreading of biosolids. It is thus important to have a better overview of sewage sludge quality in terms of organic pollutant content and ecotoxicity assessment. It is also necessary to better understand the impact of biosolid composting processes on the pollutant and toxicity removal. Therefore, concentrations of oestrogens (E), nonyphenol ethoxylates (NPE), polycyclic aromatic hydrocarbons (PAH), polychlorinated biphenyls (PCB) and linear alkyl benzene sulphonates (LAS) and some of their associated toxic effects were determined at different stages of a composting process using, respectively, chemical analysis and in vitro bioassays (estrogen receptor α, dioxin receptor and pregnan X receptor reporter cell lines). Pollutants concentrations were higher in the final compost than in biosolid due to dry matter reduction through composting. Mass balance calculation shows a positive impact of the aerobic treatment on the removal of the most degradable pollutants. The three toxicological activities were measured in both biosolids and in the initial and final compost: oestrogenic activity increased whereas dioxin-like and pregnan X activities decreased. The difficulty in correlating chemical and toxicological results underlines the importance of combining both approaches in order to improve the assessment of the compost quality.
Pragmatic study of efficiency of controlled-release carbamazepine (TEGRETOL CR 400) in the treatment of patients with partial seizures
Authors: Vojvodic Nikola , Sokic Dragoslav , Jankovic Slavko , Levic Zvonimir
Published: July 2008

In patients with partial seizures controlled-release vs. conventional carbamazepine had better efficiency, based on an excellent tolerance favorable daily dosage and superior compliance.
Small bowel mesentery fibroma
Authors: Colovic Radoje , Micev Marjan , Zogovic Sergej , Grubor Nikica , Stojkovic Mirjana
Published: July 2008

Fibromas are rarely localized in the abdomen, but almost always in the mesentery or omentum. We present a 63-year old woman in whom the examination of the upper abdominal pain showed a well distinct abdominal mass at the level of the lower edge of the pancreas. During the operation a tumor 100 ? 87 x 70 mm in size, from the radix of small bowel mesentery, was excised, Seven months later the patient is symptom-free with normal ultrasonographic and CT findings.
Eticko-pravne dileme u tretmanu infertiliteta na pocetku novog milenijuma
Authors: Dragojevic-Dikic Svetlana , Markovic Atanasije
Published: July 2008

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Analysis of mutations in 17p 11.2 region in patients with Charcot-Marie-Tooth type 1 disease and patients with tomaculose neuropathy
Authors: Zamurovic Natasa , Milic Vedrana , Dackovic Jelena , Zamurovic Dragan , Culjkovic Biljana , Pavlovic Sanja , Apostolski Slobodan , Romac Stanka
Published: July 2008

Charcot-Marie-Tooth type 1? disease (CMT1A) and hereditary neuropathy with liability to pressure palsies (HNPP) are common inherited disorders of the peripheral nervous system associated with duplication and deletion respectively, of the 17p11.2 segment including the gene of peripheral myelin protein 22. We studied 48 subjects belonging to 29 families with clinical and electrophysiological signs of definite CMT1, 20 patients with suspected CMT phenotype, and 17 patients and healthy members of their families with HNPP. Blood sampling and DNA isolation, PCR, restriction analysis, southern blotting were performed using standard procedures. Of 48 patients with diagnosis of definite CMT1 in 25 (52%) we found a 1.5 Mb tandem duplication in chromosome 17p11.2. These duplications were not found in any of 20 sporadic cases with the clinical phenotype of CMT but without reliable electrophysiological data. Only 13 (44.8%)of 29 unrelated CMT1 patients from the first group had 17p11.2 duplications. Three of 4 sporadic cases (75%) with definite CMT1 had 17p11.2 duplications. Of 17 patients from 6 families with HNPP deletion of 17p11.2 segment was found in 15 (88.2%), as well as in 5 (83.3%) of six unrelated cases. Detection of CMT1A/HNPP recombination hotspot is a simple and reliable DNA diagnostic method, which is useful only for the patients with clinically already verified CMT1, and HNPP for further genetic counseling of patients and members of their families.