bluuebunny/crossref_metadata_2025 huggingface dataset:
The P2Y6 Receptor Stimulates Bone Resorption by Osteoclasts
Authors: Orriss Isabel R. , Wang Ning , Burnstock Geoffrey , Arnett Timothy R. , Gartland Alison , Robaye Bernard , Boeynaems Jean-Marie
Published: August 2011

Accumulating evidence indicates that extracellular nucleotides, signaling through P2 receptors, play a significant role in bone remodeling. Osteoclasts (the bone-resorbing cell) and osteoblasts (the bone-forming cell) display expression of the G protein-coupled P2Y6 receptor, but the role of this receptor in modulating cell function is unclear. Here, we demonstrate that extracellular UDP, acting via P2Y6 receptors, stimulates the formation of osteoclasts from precursor cells, while also enhancing the resorptive activity of mature osteoclasts. Furthermore, osteoclasts derived from P2Y6 receptor-deficient (P2Y6R−/−) animals displayed defective function in vitro. Using dual energy x-ray absorptiometry scanning and microcomputed tomographic analysis we showed that P2Y6R−/− mice have increased bone mineral content, cortical bone volume, and cortical thickness in the long bones and spine, whereas trabecular bone parameters were unaffected. Histomorphometric analysis showed the perimeter of the bone occupied by osteoclasts on the endocortical and trabecular surfaces was decreased in P2Y6R−/− mice. Taken together these results show the P2Y6 receptor may play an important role in the regulation of bone cell function in vivo.
Classical conditioning through auditory stimuli in Drosophila: methods and models
Authors: Menda Gil , Bar Haim Y. , Arthur Ben J. , Rivlin Patricia K. , Wyttenbach Robert A. , Strawderman Robert L. , Hoy Ronald R.
Published: August 2011

The role of sound in Drosophila melanogaster courtship, along with its perception via the antennae, is well established, as is the ability of this fly to learn in classical conditioning protocols. Here, we demonstrate that a neutral acoustic stimulus paired with a sucrose reward can be used to condition the proboscis-extension reflex, part of normal feeding behavior. This appetitive conditioning produces results comparable to those obtained with chemical stimuli in aversive conditioning protocols. We applied a logistic model with general estimating equations to predict the dynamics of learning, which successfully predicts the outcome of training and provides a quantitative estimate of the rate of learning. Use of acoustic stimuli with appetitive conditioning provides both an alternative to models most commonly used in studies of learning and memory in Drosophila and a means of testing hearing in both sexes, independently of courtship responsiveness.
Daily torpor reduces mass and changes stress and power output of soleus and EDL muscles in the Djungarian hamster, Phodopus sungorus
Authors: James Rob S. , Tallis Jason A. , Seebacher Frank , Storey Ken
Published: August 2011

Djungarian hamsters (Phodopus sungorus) undergo bouts of daily torpor in response to reduced photoperiod. Metabolic rate, body temperature and energy cost are reduced during torpor. The present study exposed Djungarian hamsters to two different photoperiod regimes at a room temperature of 19–21°C: long photoperiod (control, 16 h:8 h light:dark, N=8) and short photoperiod (torpor, 8 h:16 h light:dark, N=8). After 14 weeks, muscle mechanics were analyzed in each group, examining both extensor digitorum longus (EDL) muscle and soleus muscle from each individual. Control hamsters had significantly greater body mass (43%), EDL mass (24%), EDL length (9%) and soleus mass (48%) than the torpor hamsters. However, there were no significant differences between control and torpor groups in forearm length or soleus muscle length. There were no significant differences in either muscle between control and torpor hamsters in maximum twitch stress (force per unit area), tetanus force generation or relaxation times. Maximum soleus tetanic stress was 43% greater (P=0.039) and soleus work loop power output (P<0.001) was higher in torpor than in control hamsters. Maximum EDL tetanic stress was 26% greater in control than in torpor hamsters (P=0.046), but there was no significant effect on EDL power output (P=0.38). Rate of fatigue was not affected by torpor in either soleus or EDL muscles (P>0.43). Overall, extended use of daily torpor had no effect on the rate at which stress or work was produced in soleus and EDL muscles in Djungarian hamsters; however, torpor did increase the stress and power produced by the soleus.
Antioxidant capacity develops with maturation in the deep-diving hooded seal
Authors: Vázquez-Medina José Pablo , Soñanez-Organis José Guadalupe , Burns Jennifer M. , Zenteno-Savín Tania , Ortiz Rudy M.
Published: August 2011

Maturation in hooded seals is characterized by the rapid development of their physiological diving capacity and is accompanied by increases in oxidant production but not oxidative damage. To test the hypothesis that the antioxidant system of hooded seals develops as they transition from a terrestrial to an aquatic environment, we obtained the complete cDNA sequence that encodes the NF-E2-related factor 2 (Nrf2), a central regulator of the antioxidant response, and compared Nrf2 mRNA and protein expression levels in muscle samples from neonate, weaned pups and adult hooded seals, along with glutathione (GSH) levels and the activity/protein content of the antioxidant enzymes catalase, glutathione peroxidase (GPx), peroxyredoxin VI (PrxVI), thioredoxin 1 (Trx1), thioredoxin reductase (TrxR), glutaredoxin 1 (Glrx1), glutathione disulphide reductase, glutathione S-transferase and glutamate-cysteine ligase. The Nrf2 of the hooded seal is 1822 bp long and encodes a protein of 606 amino acids with a leucine zipper domain and Keap1-mediated proteosomal degradation residues, which are key for Nrf2 function and regulation. Although neither Nrf2 mRNA nor Nrf2 nuclear protein content are higher in adults than in pups, GSH levels along with GPx, PrxVI, Trx1, TrxR and Glrx1 activity/protein content increase with maturation, suggesting that the potential for peroxide removal increases with development in hooded seals, and that these enzymes contribute to the regulation of the intracellular redox state and the prevention of oxidative damage in these deep-diving mammals.
Boceprevir: A Protease Inhibitor for the Treatment of Chronic Hepatitis C
Authors: Foote Bryce S , Spooner Linda M , Belliveau Paul P
Published: August 2011

Objective:

To review the pharmacology, pharmacokinetics, safety, and efficacy of boceprevir, a novel oral hepatitis C virus (HCV) nonstructural 3 (NS3) protease inhibitor for the treatment of chronic HCV infection, specifically, genotype 1.

Data Sources:

A literature search was conducted through MEDLINE and EMBASE (1966-May 2011) using the terms boceprevir and SCH 503034. Data from the package insert, abstracts obtained from conferences, and unpublished Phase 2-3 clinical trials, obtained through clinicaltrials.gov, were also reviewed.

Study Selection And Data Extraction:

All English-language articles identified from the data sources were evaluated. References from selected articles were used to identify other pertinent citations. Article selection focused on pharmacology, clinical trials, safety analyses, and resistance. Preference was given to human data.

Data Synthesis:

Boceprevir is an oral protease inhibitor that binds to the NS3 protein of HCV, ultimately inhibiting viral intracellular replication. Boceprevir displays linear pharmacokinetics and is rapidly absorbed upon oral administration. In clinical studies of treatment-naïve and treatment-experienced patients, boceprevir, in combination with standard of care (pegylated interferon [Peg-IFN]-α-2b with or without ribavirin) achieved greater sustained viral response (SVR) rates compared to standard of care. Safety analyses showed an increased incidence of adverse effects when boceprevir was used with Peg-IFN-α-2b and ribavirin. The most common adverse events reported include fatigue, headache, nausea, dysguesia, and anemia; the incidence of the latter 2 adverse effects may be increased it boceprevir is added to standard therapy. Additional Phase 2 and 3 studies are currently enrolling participants.

Conclusions:

Boceprevir should be used in combination with Peg-IFN-α-2b and ribavirin in the treatment of chronic HCV genotype 1 infection. The improved response rates achieved with that combination will make boceprevir a viable option compared with other developing and approved NS3 protease inhibitors for treatment-naïve and treatment-experienced nonresponders/relapsers. Additional data are needed to clarify the potential for resistance and drug interactions.
A New Kinetic Framework for Synaptic Vesicle Trafficking Tested in Synapsin Knock-Outs
Authors: Gabriel Thomas , García-Pérez Elizabeth , Mahfooz Kashif , Goñi Joaquín , Martínez-Turrillas Rebeca , Pérez-Otaño Isabel , Lo Donald C. , Wesseling John F.
Published: August 2011

At least two rate-limiting mechanisms in vesicle trafficking operate at mouse Schaffer collateral synapses, but their molecular/physical identities are unknown. The first mechanism determines the baseline rate at which reserve vesicles are supplied to a readily releasable pool. The second causes the supply rate to depress threefold when synaptic transmission is driven hard for extended periods. Previous models invoked depletion of a reserve vesicle pool to explain the reductions in the supply rate, but the mass-action assumption at their core is not compatible with kinetic measurements of neurotransmission under maximal-use conditions. Here we develop a new theoretical model of rate-limiting steps in vesicle trafficking that is compatible with previous and new measurements. A physical interpretation is proposed where local reserve pools consisting of four vesicles are tethered to individual release sites and are replenished stochastically in an all-or-none fashion. We then show that the supply rate depresses more rapidly in synapsin knock-outs and that the phenotype can be fully explained by changing the value of the single parameter in the model that would specify the size of the local reserve pools. Vesicle-trafficking rates between pools were not affected. Finally, optical imaging experiments argue against alternative interpretations of the theoretical model where vesicle trafficking is inhibited without reserve pool depletion. This new conceptual framework will be useful for distinguishing which of the multiple molecular and cell biological mechanisms involved in vesicle trafficking are rate limiting at different levels of synaptic throughput and are thus candidates for physiological and pharmacological modulation.
TMS Perturbs Saccade Trajectories and Unmasks an Internal Feedback Controller for Saccades
Authors: Xu-Wilson Minnan , Tian Jing , Shadmehr Reza , Zee David S.
Published: August 2011

When we applied a single pulse of transcranial magnetic stimulation (TMS) to any part of the human head during a saccadic eye movement, the ongoing eye velocity was reduced as early as 45 ms after the TMS, and lasted ∼32 ms. The perturbation to the saccade trajectory was not due to a mechanical effect of the lid on the eye (e.g., from blinks). When the saccade involved coordinated movements of both the eyes and the lids, e.g., in vertical saccades, TMS produced a synchronized inhibition of the motor commands to both eye and lid muscles. The TMS-induced perturbation of the eye trajectory did not show habituation with repetition, and was present in both pro-saccades and anti-saccades. Despite the perturbation, the eye trajectory was corrected within the same saccade with compensatory motor commands that guided the eyes to the target. This within-saccade correction did not rely on visual input, suggesting that the brain monitored the oculomotor commands as the saccade unfolded, maintained a real-time estimate of the position of the eyes, and corrected for the perturbation. TMS disrupted saccades regardless of the location of the coil on the head, suggesting that the coil discharge engages a nonhabituating startle-like reflex system. This system affects ongoing motor commands upstream of the oculomotor neurons, possibly at the level of the superior colliculus or omnipause neurons. Therefore, a TMS pulse centrally perturbs saccadic motor commands, which are monitored possibly via efference copy and are corrected via internal feedback.
TRPM1 Forms Complexes with NyctalopinIn Vivoand Accumulates in Postsynaptic Compartment of ON-Bipolar Neurons in mGluR6-Dependent Manner
Authors: Cao Yan , Posokhova Ekaterina , Martemyanov Kirill A.
Published: August 2011

Synaptic transmission between light-sensory photoreceptor cells and downstream ON-bipolar neurons plays an important role for vertebrate vision. This process is mediated by the G-protein-coupled receptor pathway involving glutamate receptor mGluR6 and effector channel TRPM1. The signal transmission occurs on a rapid timescale; however, the molecular organization that ensures timely signaling in this cascade is unknown. Genetic studies in human patients and animal models reveal that ON-bipolar cell signaling depends on the synaptic protein nyctalopin. We have conducted a proteomic search for proteins associated with nyctalopin in the mouse retina and identified TRPM1 as the binding partner. We further demonstrate that nyctalopin additionally interacts with mGluR6 receptor. Disruption of mGluR6 prevented targeting of TRPM1 to the postsynaptic compartment of ON-bipolar neurons. These results reveal a unique macromolecular organization of the mGluR6 cascade, where principal signaling components are scaffolded by nyctalopin, creating an organization essential for the correct localization of the signaling ensemble and ultimately intact transmission of the signal at the first visual synapse.
Multiple Parietal–Frontal Pathways Mediate Grasping in Macaque Monkeys
Authors: Gharbawie Omar A. , Stepniewska Iwona , Qi Huixin , Kaas Jon H.
Published: August 2011

The nodes of a parietal–frontal pathway that mediates grasping in primates are in anterior intraparietal area (AIP) and ventral premotor cortex (PMv). Nevertheless, multiple somatosensory and motor representations of the hand, in parietal and frontal cortex, respectively, suggest that additional pathways remain unrealized. We explored this possibility in macaque monkeys by injecting retrograde tracers into grasp zones identified in primary motor cortex (M1), PMv, and area 2 with long train electrical stimulation. The M1 grasp zone was densely connected with other frontal cortex motor regions. The remainder of the connections originated from somatosensory areas 3a and second somatosensory cortex/parietal ventral area (S2/PV), and from the medial bank and fundus of the intraparietal sulcus (IPS). The PMv grasp zone was also densely connected with frontal cortex motor regions, albeit to a lesser extent than the M1 grasp zone. The remainder of the connections originated from areas S2/PV and aspects of the inferior parietal lobe such as PF, PFG, AIP, and the tip of the IPS. The area 2 grasp zone was densely connected with the hand representations of somatosensory areas 3b, 1, and S2/PV. The remainder of the connections was with areas 3a and 5 and the medial bank and fundus of the IPS. Connections with frontal cortex were relatively weak and concentrated in caudal M1. Thus, the three grasp zones may be nodes of parallel parietal–frontal pathways. Differential points of origin and termination of each pathway suggest varying functional specializations. Direct and indirect connections between those parietal–frontal pathways likely coordinate their respective functions into an accurate grasp.
The Same Core Rhythm Generator Underlies Different Rhythmic Motor Patterns
Authors: White Rachel S. , Nusbaum Michael P.
Published: August 2011

Rhythmically active motor circuits can generate different activity patterns in response to different inputs. In most systems, however, it is not known whether the same neurons generate the underlying rhythm for each different pattern. Thus far, information regarding the degree of conservation of rhythm generator neurons is limited to a few pacemaker-driven circuits, in most of which the core rhythm generator is unchanged across different output patterns. We are addressing this issue in the network-driven, gastric mill (chewing) circuit in the crab stomatogastric nervous system. We first establish that distinct gastric mill motor patterns are triggered by separate stimulation of two extrinsic input pathways, the ventral cardiac neurons (VCNs) and postoesophageal commissure (POC) neurons. A prominent feature that distinguishes these gastric mill motor patterns is the LG (lateral gastric) protractor motor neuron activity pattern, which is tonic during the VCN rhythm and exhibits fast rhythmic bursting during the POC rhythm. These two motor patterns also differed in their cycle period and some motor neuron phase relationships, duty cycles, and burst durations. Despite the POC and VCN motor patterns being distinct, rhythm generation during each motor pattern required the activity of the same two, reciprocally inhibitory gastric mill neurons [LG, Int1 (interneuron 1)]. Specifically, reversibly hyperpolarizing LG or Int1, but no other gastric mill neuron, delayed the start of the next gastric mill cycle until after the imposed hyperpolarization. Thus, the same circuit neurons can comprise the core rhythm generator during different versions of a network-driven rhythmic motor pattern.
Little Exercise, Big Effects: Reversing Aging and Infection-Induced Memory Deficits, and Underlying Processes
Authors: Barrientos Ruth M. , Frank Matthew G. , Crysdale Nicole Y. , Chapman Timothy R. , Ahrendsen Jared T. , Day Heidi E.W. , Campeau Serge , Watkins Linda R. , Patterson Susan L. , Maier Steven F.
Published: August 2011

We have previously found that healthy aged rats are more likely to suffer profound memory impairments following a severe bacterial infection than are younger adult rats. Such a peripheral challenge is capable of producing a neuroinflammatory response, and in the aged brain this response is exaggerated and prolonged. Normal aging primes, or sensitizes, microglia, and this appears to be the source of this amplified inflammatory response. Among the outcomes of this exaggerated neuroinflammatory response are impairments in synaptic plasticity and reductions of brain-derived neurotrophic factor (BDNF), both of which have been associated with cognitive impairments. Since it has been shown that physical exercise increases BDNF mRNA in the hippocampus, the present study examined voluntary exercise in 24-month-old F344×BN rats as a neuroprotective therapeutic in our bacterial infection model. Although aged rats ran only an average of 0.7 km per week, this small amount of exercise was sufficient to completely reverse infection-induced impairments in hippocampus-dependent long-term memory compared with sedentary animals. Strikingly, exercise prevented the infection-induced exaggerated neuroinflammatory response and the blunted BDNF mRNA induction seen in the hippocampus of sedentary rats. Moreover, voluntary exercise abrogated age-related microglial sensitization, suggesting a possible mechanism for exercise-induced neuroprotection in aging.
Prenatal Stress Inhibits Neuronal Maturation through Downregulation of Mineralocorticoid Receptors
Authors: Tamura Makoto , Sajo Mari , Kakita Akiyoshi , Matsuki Norio , Koyama Ryuta
Published: August 2011

Prenatal stress (PS) increases the risk of depressive disorders in adult offspring. The pathophysiology of depressive disorders has been linked to hippocampal dysfunction; however, whether and how PS attenuates the development and function of hippocampal networks remains unknown. Using a rat model of PS, in which pregnant mothers receive daily restraint stress during late gestation and their offspring exhibit depressive-like behavior later in life, we show that PS impairs the morphological and functional maturation of hippocampal granule cells in adult offspring via the downregulated expression of mineralocorticoid receptors. PS reduced the dendritic complexity and spine density of neonatal-generated granule cells, which persists into adulthood. These granule cells exhibited depressed synaptic responses to stimulation of the medial perforant path. We further revealed that the expression of mineralocorticoid receptors, which we found is necessary for proper dendritic maturation in this study, was significantly downregulated in granule cells after PS. These results suggest that PS-induced downregulation of mineralocorticoid receptors attenuates neuronal maturation, which results in dysfunction of neuronal network in adulthood.
Quasi-periodic Fluctuations in Default Mode Network Electrophysiology
Authors: Ko Andrew L. , Darvas Felix , Poliakov Andrew , Ojemann Jeffrey , Sorensen Larry B.
Published: August 2011

The study of human brain electrophysiology has extended beyond traditional frequency ranges identified by the classical EEG rhythms, encompassing both higher and lower frequencies. Changes in high-gamma-band (>70 Hz) power have been identified as markers of local cortical activity. Fluctuations at infra-slow (<0.1 Hz) frequencies have been associated with functionally significant cortical networks elucidated using fMRI studies. In this study, we examined infra-slow changes in band-limited power across a range of frequencies (1–120 Hz) in the default mode network (DMN). Measuring the coherence in band-limited power fluctuations between spatially separated electrodes makes it possible to detect small, spatially extended, and temporally coherent fluctuating components in the presence of much larger incoherent fluctuations. We show that the default network is characterized by significant high-gamma-band (65–110 Hz) coherence at infra-slow (<0.1 Hz) frequencies. This coherence occurs over a narrow frequency range, centered at 0.015 Hz, commensurate with the frequency of BOLD signal fluctuations seen by fMRI, suggesting that quasi-periodic, infra-slow changes in local cortical activity form the neurophysiological basis for this network.
Determination of trace impurities of chlorine in zirconium-alloy matrices using neutron activation technique
Authors: Naik H. , Sant V. L. , Suryanarayana S. V. , Prajapati P. M. , Newton Nathaniel T.
Published: August 2011

Trace impurities of chlorine in the zircaloy-2 and Zr-2.5% Nb alloy matrix have been determined using neutron activation analysis (NAA) and off-line γ-ray spectrometric technique. The results have been compared with the values obtained from pyrohydrolysis-IC and spark source mass spectrometric method. The limit of internal precision error from the neutron activation technique is 6.7% for zircolloy-2 and 9% for Zr-2.5% Nb alloy, which are lower than that of pyrohydrolysis-IC and spark source mass spectrometric measurements respectively. For both alloys the results from present work based on NAA technique are slightly higher than the results based on the other two methods but are comparable within the uncertainty.
Seasonal ratcheting and softening in clay slopes, leading to first-time failure
Authors: TAKE W.A. , BOLTON M.D.
Published: August 2011

Centrifuge tests have been carried out on kaolin clay slopes subject to variations in surface rainfall and humidity corresponding, at model scale, to successive wet and dry seasons in the field. These model slopes have been instrumented with miniature high-capacity tensiometers, and the deformations of their cross-sections have been observed by digital photography and analysed by particle image velocimetry. Sequences of swelling and shrinkage have been seen to be potentially irreversible, leading to creep in the form of down-slope ratcheting, accompanied by progressive regional softening within the zone affected by the seasonal moisture movements. Ultimately, this regional softening has been seen to lead to slope failures, in which segments of soil have separated from the mass through the opening of tension cracks and the formation of a localised shear rupture. An analysis of the phase of episodic regional softening is presented here, based on a Spencer limit-equilibrium approach. These back-analyses illustrate that clay slopes which temporarily mobilise an average stress ratio in excess of the critical state stress ratio during any portion of a typical year may eventually be brought to a long-term failure under the action of seasonal variations of pore pressure. Conversely, it is hypothesised that clay slopes which can maintain their overall equilibrium without exceeding the critical state stress ratio may not experience progressive seasonal softening.
Carbonation resistance of concrete with crystalline material coating
Authors: Yodmalai Dujthep , Sahamitmongkol Raktipong , Tangtermsirikul Somnuk , Lawtrakul Luckhana
Published: August 2011

The carbonation resistance of concrete coated with crystalline coating material (CCM) was experimentally investigated. Specimens with different water to binder ratios (0·4, 0·5, 0·6) and fly ash contents (0, 30%) with and without CCM coating were tested under an accelerated environment. It was found that carbonation resistance of concrete could be improved by coating with CCM. Carbonation depths of coated specimens were found to be lower than those of the uncoated specimens of the same mix proportion. The improved carbonation resistance was a result of both protection from the CCM coating layer and a reduction in the carbonation coefficient of the base concrete. When a CCM coating was applied to carbonated concrete, alkalisation (increase of pH) of the base concrete was observed. A mathematical approach to predict the carbonation depth of concrete with CCM coatings in different natural environments based on accelerated test results is also proposed.
Effect of w/c ratio on air-void system of foamed concrete and their influence on mechanical properties
Authors: Wee Tiong-Huan , Daneti Saradhi Babu , Tamilselvan Thangayah
Published: August 2011

A study was undertaken to investigate the effect of water to cementitious material (w/c) ratio (ranging from 0·22 to 0·60) on the air-void system (air content ranging from about 10 to 70%) of foamed concrete, and their effects on the mechanical properties of foamed concrete without sand. The cementitious material used in this study was blended cement with 50% ordinary Portland cement (OPC) and 50% ground granulated blastfurnace slag (ggbs) by weight. The linear traverse method was used to characterise the air-void system, referring to air content, average air-void size, air-void frequency and spacing factor. The results show that although the same quality of foam was introduced, the air-void size and frequency, and hence spacing factor, of the foamed concrete varied with different w/c ratios and air contents, which in turn affected the mechanical properties of the concrete. For the different w/c ratios and air contents adopted, it was found that an air-void system with a spacing factor of about 0·05 mm, air-void size of 0·15 mm and air content of 40% was optimal in terms of achieving a high strength to weight ratio. The compressive strength of foamed concrete seems to be influenced by the spacing factor, w/c ratio and air content in relation to density. The results also indicated that the inclusion of air-voids in foamed concrete had a greater effect on compressive strength than the modulus of elasticity and it increases with increase of w/c ratio. The results of a numerical analysis concurred with the experimental observations.
Properties of concrete containing copper slag waste
Authors: Najimi Meysam , Pourkhorshidi Ali Reza
Published: August 2011

In this paper, the effects of using copper slag wastes as a supplementary cementitious material on mechanical properties and durability aspects of concrete are studied. To this aim, mixtures are made by employing 5, 10 and 15% copper slag as cement replacement and the strength properties, water penetration, chloride ion permeability, sulfate expansions and alkali–silica reaction are investigated. The results indicate that using copper slag waste decreases mechanical stresses and in turn expansion during exposure in sulfate solution. Additionally, copper slag reduces expansion induced by alkali–silica reactions. These durability improvements are accompanied by an appropriate effect on penetration, with only a minor decrease in mechanical properties.
Preservation of reverse osmosis membranes with non oxidizing biocides – comparison with SMBS
Authors: Majamaa K. , Bertheas U. , Finlayson F. , Levy R. B.
Published: August 2011

Sodium metabisulphite (SMBS) is the current standard preservation chemical used in RO plants during shut down. It is a cheap and efficient preservative, but its tendency to oxidize easily has several drawbacks. The use of a non-oxidizing biocide instead could solve some of the issues currently seen with the SMBS, but little has been reported about membrane compatibility and preservation efficiency in the long-term mode. Long-term membrane preservation trials have been executed with three different non-oxidizing biocides: DBNPA (2,2-dibromo-3-nitrilopropionamide), CMIT/MIT (5-chloro-2-methyl-4-isothiazolin-3-one (CMIT) and 2-methyl-4-isothiazolin-3-one (MIT), OIT (2-octyl-2H-isothiazol-3-one) as well as SMBS as the reference chemical. The suitability of these chemicals in this application was confirmed using both new Brackish Water Reverse Osmosis (BWRO) and used membranes with various membrane chemistries (Nanofiltration (NF), BWRO, Sea Water Reverse Osmosis (SWRO)). The preservation trial with new membranes confirmed the long-term stability of the product when stored in the biocide solution while the trial with used elements is closer to realistic plant conditions and validated the efficiency of the biocide against biofouling in the long-term. These results show that the biocides can be equivalent preservatives to SMBS and that the application is economically feasible. The used active concentrations for biocides are storage time and temperature dependent and this should be taken into account when first applying them in the field.
Environmental and health concerns regarding the quality of water in a poor suburb of Kinshasa in the Democratic Republic of Congo
Authors: Vala R. M. K. , Tichagwa L. , Musibono D. E. , Lukanda V. M.
Published: August 2011

In many developing countries, the scarcity of potable water is an ongoing challenge. Even when water is plentiful, its quality may be unsuitable for household use such as in the city of Kinshasa in the Democratic Republic of Congo (DRC) which is the study area for this investigation. Shortage of potable water has forced inhabitants in the city to rely on water wells dug without adherence to regulations or specifications within perimeters of their homesteads. The water from such wells is often polluted with household waste being generally disposed by burning and burying in shallow pits, thrown in pit toilets or into rivers. Such practices have led to contamination of ground water. This study examines the water quality of drinking water drawn from wells in Fer-bois, which falls under the Kimbanseke municipality in the South East of Kinshasa. The dynamics of well design/location, sources of possible contamination with respect to water treatment and water quality as well as its possible impact on health are examined. The area was shown to have poor groundwater quality with significant amounts of pollutants such as NO3, Pb and Cd leading to environmental and health concerns.
Supporting the Water Safety Plan (WSP) approach with the Failure Experience Improvement System (FEIS)
Authors: Lukas A. , Mayr E. , Richard L. , Perfler R.
Published: August 2011

The Water Safety Plan (WSP) aims to ensure safe drinking water through risk assessment and preventive risk management which cover all steps of the water supply from catchment to the consumer. This approach requires a comprehensive hazard assessment including the identification and prioritisation of potential hazardous events. The Failure Experience Improvement System (FEIS) supports this key step in developing a WSP. The FEIS can assist water utilities in identifying the causes and effects of hazardous events, determining priorities for risk management and locating vulnerable points in their water supply system. This is achieved through the systematic collection of failure causes and their effects in a database and an analysis of the resulting failure network using Social Network Analysis (SNA). The FEIS provides both graphical visualisation of failure propagation and analytical indicators to evaluate hazardous events. This paper demonstrates the use of the FEIS to support the WSP approach.
Reuse of alum sludge in clay brick manufacturing
Authors: Elangovan C. , Subramanian K.
Published: August 2011

When alum is used as a coagulant in a water treatment plant (WTP), a large volume of sludge is generated. The characteristics of the sludge depend strongly on the water source and the quality and quantity of the chemicals used for processing. For a plant with total suspended solids (TSS)/turbidity unit (TU) factor of 1.7, the weight of the alum sludge produced at an average alum dose of 28.2 mg/L is approximately 25 kg/MLD. Disposal of sludge in a way that is economically and environmentally sustainable is a major challenge faced by WTPs around the globe. In this study, the alum sludge generated during water treatment was used as a partial substitute for clay in a clay brick manufacturing process. Alum sludge and commercial local clay were blended in various proportions and sintered at different temperatures to produce clay-sludge bricks. In this paper, the physical and mechanical properties of clay-sludge bricks, such as loss on ignition (LOI), water absorption, and compressive strength, are investigated. The results from this study indicate that alum sludge could be used as a partial substitute in commercial clay bricks to a maximum of 20% without compromising the strength of the bricks.
Personality Disorder Comorbidity and Outcome: Comparison of Three Age Groups
Authors: Stevenson Janine , Brodaty Henry , Boyce Philip , Byth Karen
Published: August 2011

Background: Personality disorder comorbidity has been extensively studied in young adult populations, to a lesser extent in elderly populations, and not at all in an Australian population. This study examines PD comorbidity over the life span 18-100.

Aim: The object of this study was to examine the interactions of comorbid personality disorder and age on outcome of Axis I disorders.

Method: A total of 238 consecutive consenting eligible psychiatric inpatients were assessed on admission, prior to discharge, and after 6 and 12 months as regards symptoms, function, well-being, relapse and readmission rates and social supports. Outcomes were compared for young (18–40 years old), middle-aged (41–64) and old (65+) patients.

Results: Patients improved over time symptomatically and functionally. Across all age groups patients with comorbid personality disorder had worse outcomes than those without, but improved though never to the same extent. Personality disorder was associated with increased rates of relapse and readmission in the whole sample and in the older group, but not increased length of stay. Severity of personality disorder was associated with poorer outcome.

Conclusion: Personality disorder adversely affects outcomes, particularly for younger (and older) patients with psychiatric disorders independently of diagnosis and other factors.
Der Wald – Schranke gegen die Zersiedelung (Essay)
Authors: Frey René L.
Published: August 2011

Urban sprawl, although not desirable, cannot effectively be opposed by existing land use planning: the forest is one of the few barriers which can keep it in check. That is why it would be inappropriate at the present time to relax the ban on clearances and to change forest areas into building zones. The protagonists of a less restrictive forest policy argue that it is necessary to optimize the use of land which is becoming more and more scarce. However, this would only be justifiable if landscape development could be correctly controlled through market forces. This is not the case. External costs in the dimension of ten billions of francs a year in transport and building development have in fact the effect of a kind of subsidy on land use and thus encourage uncontrolled development.
Der Wald: Hemmschuh oder Retter der Schweizer Raumordnungspolitik? (Essay)
Authors: Abt Thomas
Published: August 2011

The forest characterizes the landscape of the Swiss plateau and of other development areas by its surface area, its aspect and its distribution as a relatively stable element, whereas arable land is constantly diminishing in area on account of the uncontrolled development of building zones. Simultaneously, in the mountainous areas, the forest is spreading onto agricultural land not cultivated anymore. Ways to restrict these developments must be found in the current revision of the Land-Use legislation. A relaxation of the clearing prohibition will not solve the problem.
La forêt sous la pression du développement territorial: quelles réponses politiques? (Essai)
Authors: Martinson Catherine
Published: August 2011

The Swiss forests have been successfully preserved over the last 130 years thanks to a powerful legislation allowing its strict protection. The increasing rate of urbanisation of the Swiss territory is raising many questions about the exceptional status of the Swiss forest, which is not included in the land planning legislation. Political pressure to loosen the protection of forests is building up, particularly from the side of the agriculture lobbies who are trying to obtain surfaces to compensate the loss of farmland.
Stadtwald: Herausforderung für die Politik (Essay)
Authors: Attiger Stephan
Published: August 2011

Over the past hundred years, the population in the town of Baden has tripled, while the built-up area has increased almost tenfold. Thanks to the protection afforded by the statutory regulations, the forest surface area has remained practically unchanged, and its boundaries have not been displaced. Occupying a proportion of 56% of the town territory in Baden, the forest has a close interchange with civilisation and with the modifications in the landscape brought about by human activity. In the light of this situation, the author poses the question whether it would not be sensible to sometimes displace forest boundaries, or to re-allocate an area of forest land, in order to increase the settlement density in a meaningful fashion. Besides this, he appeals for landscape and forest planning to be placed in a wider context by increasingly coordinating them beyond the limits of a given commune, or indeed of a region.
Effects of Ramadan Fasting on Health
Authors: Muazzam MG
Published: August 2011

DOI: http://dx.doi.org/10.3329/bjms.v4i3.8231BJMS 1997; 4(3): 12-25
Islam and Human Rights - Tension and Possible Cooperation: The Case of Indonesia
Authors: Hikam Muhammad AS
Published: August 2011

DOI: http://dx.doi.org/10.3329/bjms.v4i3.8233BJMS 1997; 4(3): 31-37
Clinical Efficacy of Carvedilol In Treatment of Patients With Ischemic Heart Disease and Chronic Heart Failure
Authors: Jahan A , Ureevna SM , Vladimirovich SE
Published: August 2011

Background: In the pathogenesis of CHF neurohormonal changes, in particular, changes of activity of sympathetic nervous system (SNS) occupies an important position. For this reason, researchers concentrated on the use β-blockers in therapy of patients with CHF. They reduce heart rate, improve diastolic function of the myocardium, reduce secretion of renin and restore the sensitivity of β- adrenoreceptors to its regulatory influences. We studied the influence of the 3rdgeneration betaadrenoblocker – Carvedilol in patients with CHF- including clinical efficacy and reduction of oxidative stress. Methods: The study was conducted in Saint-Petersburg State Medical University, from January 2000 to June 2000. 37 patients (33 male and 4 female) with CHF class III or IV despite receiving standard therapy of heart failure were enrolled in the study for the treatment with Carvedilol. All of the patients received Carvedilol for 6 months at a dose of 12.5-50mg/day with standard therapy of Heart Failure, which was not changed during next 6 months. Results: The average age of the patients was 56.8±2.3 years. The cause of CHF was IHD. 34 patients had chronic stable angina (CCS class II-IV). The majority of the patients had a history of myocardial infarction (91.8%); of these 73.5% of the patients had a history of repeated MI. Hypertension stage 2 and 3 was associated in 32.4% patients.Long-term therapy with Carvedilol led to improvement of the clinical status of the patients. After 6 months therapy with Carvedilol frequency of hospitalization was significantly reduced (1.36±0.23 vs. 0.33±0.1; p<0,01). The patients were symptomatically improved after 6 months therapy with Carvedilol. There was a tendency of reduction of LV mass by 12.1% (214.0±11.1 gm/m2 vs. 188.1±10.8 gm/m2, p<0.05). After treatment with Carvedilol there was significant increase in LVEF by 10% (30.0±1.5% to 33.0±0.1%; p<0.01) and increase in fractional shortening of LV by 22.2% (from 17.25±1.14 vs. 21.09±1.25; p<0.01). There was a significant reduction in plasma MDA, indicator of oxidative stress, in comparison with the baseline data. Conclusion: Carvedilol therapy in patients with Chronic heart failure improves clinical symptoms of patients with improvement in systolic & diastolic function of LV. Carvedilol also reduces oxidative stress in patients with heart failure. Keywords: Carvedilol, Heart failure, Ischaemic heart disease DOI: http://dx.doi.org/10.3329/cardio.v1i2.8240 Cardiovasc. j. 2009; 1(2): 207-215
Chimeric DNA Vaccines against ErbB2+ Carcinomas: From Mice to Humans
Authors: Quaglino Elena , Riccardo Federica , Macagno Marco , Bandini Silvio , Cojoca Rodica , Ercole Elisabetta , Amici Augusto , Cavallo Federica
Published: August 2011

DNA vaccination exploits a relatively simple and flexible technique to generate an immune response against microbial and tumor-associated antigens (TAAs). Its effectiveness is enhanced by the application of an electrical shock in the area of plasmid injection (electroporation). In our studies we exploited a sophisticated electroporation device approved for clinical use (Cliniporator, IGEA, Carpi, Italy). As the target antigen is an additional factor that dramatically modulates the efficacy of a vaccine, we selected ErbB2 receptor as a target since it is an ideal oncoantigen. It is overexpressed on the cell membrane by several carcinomas for which it plays an essential role in driving their progression. Most oncoantigens are self-tolerated molecules. To circumvent immune tolerance we generated two plasmids (RHuT and HuRT) coding for chimeric rat/human ErbB2 proteins. Their immunogenicity was compared in wild type mice naturally tolerant for mouse ErbB2, and in transgenic mice that are also tolerant for rat or human ErbB2. In several of these mice, RHuT and HuRT elicited a stronger anti-tumor response than plasmids coding for fully human or fully rat ErbB2. The ability of heterologous moiety to blunt immune tolerance could be exploited to elicit a significant immune response in patients. A clinical trial to delay the recurrence of ErbB2+ carcinomas of the oral cavity, oropharynx and hypopharynx is awaiting the approval of the Italian authorities.
Identification and Role of Regulatory Non-Coding RNAs in Listeria monocytogenes
Authors: Izar Benjamin , Mraheil Mobarak Abu , Hain Torsten
Published: August 2011

Bacterial regulatory non-coding RNAs control numerous mRNA targets that direct a plethora of biological processes, such as the adaption to environmental changes, growth and virulence. Recently developed high-throughput techniques, such as genomic tiling arrays and RNA-Seq have allowed investigating prokaryotic cis- and trans-acting regulatory RNAs, including sRNAs, asRNAs, untranslated regions (UTR) and riboswitches. As a result, we obtained a more comprehensive view on the complexity and plasticity of the prokaryotic genome biology. Listeria monocytogenes was utilized as a model system for intracellular pathogenic bacteria in several studies, which revealed the presence of about 180 regulatory RNAs in the listerial genome. A regulatory role of non-coding RNAs in survival, virulence and adaptation mechanisms of L. monocytogenes was confirmed in subsequent experiments, thus, providing insight into a multifaceted modulatory function of RNA/mRNA interference. In this review, we discuss the identification of regulatory RNAs by high-throughput techniques and in their functional role in L. monocytogenes.
Fucoidan from Marine Brown Algae Inhibits Lipid Accumulation
Authors: Park Min-Kyoung , Jung Uhee , Roh Changhyun
Published: August 2011

In this study, we elucidated the inhibitory effect of fucoidan from marine brown algae on the lipid accumulation in differentiated 3T3-L1 adipocytes and its mechanism. The treatment of fucoidan in a dose-dependent manner was examined on lipid inhibition in 3T3-L1 cells by using Oil Red O staining. Fucoidan showed high lipid inhibition activity at 200 µg/mL concentration (P < 0.001). Lipolytic activity in adipocytes is highly dependent on hormone sensitive lipase (HSL), which is one of the most important targets of lipolytic regulation. Here, we examined the biological response of fucoidan on the protein level of lipolysis pathway. The expressed protein levels of total hormone sensitive lipase (HSL) and its activated form, phosphorylated-HSL were significantly increased at concentration of 200 µg/mL fucoidan. Furthermore, insulin-induced 2-deoxy-D-[3H] glucose uptake was decreased up to 51% in fucoidan-treated cells as compared to control. Since increase of HSL and p-HSL expression and decrease of glucose uptake into adipocytes are known to lead to stimulation of lipolysis, our results suggest that fucoidan reduces lipid accumulation by stimulating lipolysis. Therefore, these results suggest that fucoidan can be useful for the prevention or treatment of obesity due to its stimulatory lipolysis.
Monitoring Protein Fouling on Polymeric Membranes Using Ultrasonic Frequency-Domain Reflectometry
Authors: Kujundzic Elmira , Greenberg Alan R. , Fong Robin , Hernandez Mark
Published: August 2011

Novel signal-processing protocols were used to extend the in situ sensitivity of ultrasonic frequency-domain reflectometry (UFDR) for real-time monitoring of microfiltration (MF) membrane fouling during protein purification. Different commercial membrane materials, with a nominal pore size of 0.2 µm, were challenged using bovine serum albumin (BSA) and amylase as model proteins. Fouling induced by these proteins was observed in flat-sheet membrane filtration cells operating in a laminar cross-flow regime. The detection of membrane-associated proteins using UFDR was determined by applying rigorous statistical methodology to reflection spectra of ultrasonic signals obtained during membrane fouling. Data suggest that the total power reflected from membrane surfaces changes in response to protein fouling at concentrations as low as 14 μg/cm2, and results indicate that ultrasonic spectra can be leveraged to detect and monitor protein fouling on commercial MF membranes.
Molecular Analysis of the Interaction of the Snake Venom Rhodocytin with the Platelet Receptor CLEC-2
Authors: Watson Aleksandra A. , O’Callaghan Christopher A.
Published: August 2011

The Malayan pit viper, Calloselasma rhodostoma, produces a potent venom toxin, rhodocytin (aggretin) which causes platelet aggregation. Rhodocytin is a ligand for the receptor CLEC-2 on the surface of platelets. The interaction of these two molecules initiates a signaling pathway which results in platelet activation and aggregation. We have previously solved the crystal structures of CLEC-2 and of rhodocytin, and have proposed models by which tetrameric rhodocytin may interact with either two monomers of CLEC-2, or with one or two copies of dimeric CLEC-2. In the current study we use a range of approaches to analyze the molecular interfaces and dynamics involved in the models of the interaction of rhodocytin with either one or two copies of dimeric CLEC-2, and their implications for clustering of CLEC-2 on the platelet surface.