SMART - IWRM : Integrated Water Resources Management in the Lower Jordan Rift Valley; Project Report Phase I (KIT Scientific Reports ; 7597)

This book provides an overview of the large scale Integrated Water Resources Management (IWRM) research program SMART at the Lower Jordan River Basin which aims at local implementation, knowledge & capacity building. The focus of the first phase is placed on decentralised wastewater treatment and reuse, water quality including emerging pollutants, management and modelling of groundwater systems, artificial recharge, socio-economic frameworks, a transboundary database and decision support tools

A Computational Model of the Nucleus Accumbens: Network Properties and their Functional Implications

The Nucleus accumbens integrates convergent input from a number of limbic structures, and has been implicated in a variety of behavioral disorders including addiction and schizophrenia. The bistable membrane properties of the principal cell in the NAcb, the GABAergic medium spiny projection neuron (MSP), have been proposed to mediate afferent integration. To investigate how intrinsic properties may underlie this mechanism, we constructed a model of an MSP neuron in GENESIS, which preserves the main morphological features and relevant ionichynaptic currents. The model captures the major properties of in vivo neurons, including a non-linear response to the number of afferent inputs. In order to examine network properties of the NAcb and its response to varying patterns of afferent input, a 100- cell network with modifiable levels of gap junctions and GABAergic synaptic connectivity was constructed. Afferent inputs were modeled as Poisson-distributed spike trains. Addition of lateral inhibition in the network led to a decrease in spike output for cells receiving less synchronized input, suggesting that this may be a mechanism for increasing the signal to noise ratio. Dopaminergic modulation of the whole network led to a slight increase in overall synchronization, but did not further segregate cells that were already receiving synchronous input

The Role of NMDA Currents in State Transitions of the Nucleus Accumbens Medium Spiny Neuron

The nucleus accumbens (NAcb) integrates information from a wide range of glutamatergic afferent inputs, including the prefrontal cortex, hippocampus and amygdala. One of the glutamatergic receptors, the NMDA channel, has been implicated in the non-linearity of the current–voltage relationship in these cells under certain input conditions. In order to examine the relationship of the different glutamatergic receptors to the membrane response, we modeled the AMPA, GABAA and NMDA receptors in the medium spiny (MSP) cells and their afferent input. The model demonstrates that the NMDA current is capable of sustaining certain membrane states and contributes to the non-linearity of the membrane response to input

Computational Modeling of Medium Spiny Projection Neurons in Nucleus Accumbens: Toward the Cellular Mechanisms of Afferent Stream Integration

The nucleus accumbens (Nacc) regulates the major feedback pathways linking prefrontal cortex, hippocampus, and amygdala. We describe simulations of a biophysical level model of a single medium spiny projection (MSP) neuron, the principle cell of the Nacc. The model suggests that the unusual bistable membrane potential of MSP cells arises from the interplay between two potassium currents, KIR and KA. We find that the transition from the membrane potential down state (~-85mV) to the upstate (~-60mV)requires a significant barrage of synchronized inputs, and that ongoing afferent stimulation is required to maintain the cell in the up state. The Nacc receives the densest dopaminergic innervation in the brain, and the model demonstrates, in agreement with recent experimental evidence, that dopamine acts to increase the energy barrier to membrane potential state transitions. Through its action on KIR and L-type Ca2+ channels, dopamine selectively lowers cell gain in the down state and increases it in the up state, a mechanism for context-dependent gain control. These findings suggest a mechanism of afferent pattern integration in the accumbens arising from transient synchronization among ensembles of MSP neurons. We attempt to relate these findings to possible origins of abnormalities of sensory gating in schizophrenia

Afferent Stream Integration in a Model of the Nucleus Accumbens

The Nucleus Accumbens (Nacc) receives convergent input from a number of structures including prefrontal cortex, hippocampus, and amygdala, as well as substantial dopaminergic modulation. The principle cell in the Nacc, the medium spiny projection neuron (MSP), has bistable properties that have been proposed as a primary mediator of the integrative properties in the Nacc. In order to determine the minimum biophysical properties required to generate a nonlinear bistable membrane potential, we constructed a 29 compartment MSP cell in GENESIS. This included an inward rectifying K+ (KIR), an A-current K+, HVA Ca2+ and suitable fast Na+ and delayed rectifier K+ channels. Various amounts and distributions of afferent input were examined to determine the amount of coincident input required to move the membrane from the down state (-85 mV) to the up state (-60 mV) and to fire the cell. The number of synchronous afferents required was substantially higher than previously estimated. We modeled the effect of dopaminergic modulation by increasing the conductance of the KIR and Ca2+ channels, demonstrating that the response to input is dependent on state. In parallel studies, in vivo extracellular recordings were obtained from Nacc and neocortex in anesthetized mice. Simultaneous recordings revealed that cortex and Nacc oscillate in synchrony. Lesions that disrupt slow oscillations in the cortex alter rhythmicity in the Nacc, suggesting interdependency of the mechanisms generating bistability

Ripley Valley – an application of GIS based runoff modelling to strategic stormwater harvesting assessment

Stormwater management broadly has been well accepted as necessary for both flood avoidance and importantly also the prevention of aquatic ecosystem degradation within and around cities. Harvesting stormwater to provide diversification of water supplies offers a way of avoiding flooding and ecosystem degradation as well as acting to improve the climate resilience of cities. With Australia's population overwhelmingly urban in character, and the climate well known to oscillate between droughts and flooding rains, the opportunities represented by stormwater harvesting are significant, for both greenfield and brownfield developments

Heliospheric Magnetic Field 1835-2009

We use recently acquired geomagnetic archival data to extend our long-term reconstruction of the HMF strength. The 1835-2009 HMF series is based on an updated and substantiated IDV series from 1872-onwards and on Bartels' extension, by proxy, of his u-series from 1835-1871. The new IDV series, termed IDV09, has excellent agreement (R^2 = 0.98; RMS = 0.3 nT) with the earlier IDV05 series, and also with the negative component of Love's extended (to 1905) Dst series (R^2 = 0.91). Of greatest importance to the community, in an area of research that has been contentious, comparison of the extended HMF series with other recent reconstructions of solar wind B for the last ~100 years yields a strong consensus between series based on geomagnetic data. Differences exist from ~1900-1910 but they are far smaller than the previous disagreement for this key interval of low solar wind B values which closely resembles current solar activity. Equally encouraging, a discrepancy with an HMF reconstruction based on 10Be data for the first half of the 20th century has largely been removed by a revised 10Be-based reconstruction published after we submitted this paper, although a remaining discrepancy for the years ~1885-1905 will need to be resolved

Lessons for non-VA care delivery systems from the U.S. Department of Veterans Affairs Quality Enhancement Research Initiative: QUERI Series

The U.S. Veterans Health Administration (VHA) may have a very different structure and function from the organizations and practices that provide medical care to most Americans, but those organizations and practices could learn a lot from the VHA's Quality Enhancement Research Initiative (QUERI). There are at least six topics of increasing importance for implementation research where QUERI experience should be of value to other non-VHA organizations, both within and external to the United States: 1) Researcher-clinical leader partnerships for care improvement; 2) Attention to culture, capacity, leadership, and a supportive infrastructure; 3) Practical economic evaluation of quality implementation efforts; 4) Human subject protection problems; 5) Sustainability of improvements; and 6) Scale-up and spread of improvements

Single cell immune profiling by mass cytometry of newly diagnosed chronic phase chronic myeloid leukemia treated with nilotinib

Monitoring of single cell signal transduction in leukemic cellular subsets has been proposed to provide deeper understanding of disease biology and prognosis, but has so far not been tested in a clinical trial of targeted therapy. We developed a complete mass cytometry analysis pipeline for characterization of intracellular signal transduction patterns in the major leukocyte subsets of chronic phase chronic myeloid leukemia. Changes in phosphorylated Bcr-Abl1 and the signaling pathways involved were readily identifiable in peripheral blood single cells already within three hours of the patient receiving oral nilotinib. The signal transduction profiles of healthy donors were clearly distinct from those of the patients at diagnosis. Furthermore, using principal component analysis, we could show that phosphorylated transcription factors STAT3 (Y705) and CREB (S133) within seven days reflected BCR-ABL1(IS) at three and six months. Analyses of peripheral blood cells longitudinally collected from patients in the ENEST1st clinical trial showed that single cell mass cytometry appears to be highly suitable for future investigations addressing tyrosine kinase inhibitor dosing and effect. (clinicaltrials. gov identifier: 01061177)Peer reviewe