The Oman exotics : a key to the understanding of the Neotethyan geodynamic evolution

The study of the exotic blocks of the Hawasina Nappes (Sultanate of Oman) leads to give apposit data that allow us to propose a new paleogeographic evolution of the Oman margin in time and space. A revised classification of exotic blocks into different paleogeographical units is presented. Two newly introduced stratigraphic groups, the Ramaq Group (Ordovician to Triassic) and the Al Buda'ah Group (upper Permian to Jurassic) are interpreted as tilted blocks related to the Oman continental margin. The Kawr Group (middle Triassic to Cretaceous) is redefined and interpreted as an atoll-type seamount. The paleogeography and paleoenvironments of these units are integrated into a new scheme of the Neotethyan rifting history. Brecciae and olisto¬liths of the Hawasina series are interpreted to have originated from tectonic movements affecting the Oman margin and the Neotethyan ocean floor. The breccias of late Permian age were generated by the extension processes affecting the margin, and by the creation of the Neotethyan oceanic floor. The breccias of mid-late Triassic age coincide in time with the collision of the Cimmerian continents with Eurasia. In constrast, the breccias of late Jurassic and Cretaceous age are interpreted as resulting to the creation of a new oceanic crust (Semail) off the Oman margin

Pre-Mesozoic Alpine basements - Their place in the European Paleozoic framework

Prior to their Alpine overprinting, most of the pre-Mesozoic basement areas in Alpine orogenic structures shared a complex evolution, starting with Neoproterozoic sediments that are thought to have received detrital input from both West and East Gondwanan cratonic sources. A subsequent Neoproterozoic-Cambrian active margin setting at the Gondwana margin was followed by a Cambrian-Ordovician rifting period, including an Ordovician cordillera-like active margin setting. During the Late Ordovician and Silurian periods, the future Alpine domains recorded crustal extension along the Gondwana margin, announcing the future opening of the Paleotethys oceanic domain. Most areas then underwent Variscan orogenic events, including continental subduction and collisions with Avalonian-type basement areas along Laurussia and the juxtaposition and the duplication of terrane assemblages during strike slip, accompanied by contemporaneous crustal shortening and the subduction of Paleotethys under Laurussia. Thereafter, the final Pangea assemblage underwent Triassic and Jurassic extension, followed by Tertiary shortening, and leading to the buildup of the Alpine mountain chain. Recent plate-tectonic reconstructions place the Alpine domains in their supposed initial Cambrian-Ordovician positions in the eastern part of the Gondwana margin, where a stronger interference with the Chinese blocks is proposed, at least from the Ordovician onward. For the Visean time of the Variscan continental collision, the distinction of the former tectonic lower-plate situation is traceable but becomes blurred through the subsequent oblique subduction of Paleotethys under Laurussia accompanied by large-scale strike slip. Since the Pennsylvanian, this global collisional scenario has been replaced by subsequent and ongoing shortening and strike slip under rising geothermal conditions, and all of this occurred before all these puzzle elements underwent the complex Alpine reorganization.

Comparison of the polynomial model against explicit measurements of noise components for different mammography systems.

Given the adverse impact of image noise on the perception of important clinical details in digital mammography, routine quality control measurements should include an evaluation of noise. The European Guidelines, for example, employ a second-order polynomial fit of pixel variance as a function of detector air kerma (DAK) to decompose noise into quantum, electronic and fixed pattern (FP) components and assess the DAK range where quantum noise dominates. This work examines the robustness of the polynomial method against an explicit noise decomposition method. The two methods were applied to variance and noise power spectrum (NPS) data from six digital mammography units. Twenty homogeneously exposed images were acquired with PMMA blocks for target DAKs ranging from 6.25 to 1600 µGy. Both methods were explored for the effects of data weighting and squared fit coefficients during the curve fitting, the influence of the additional filter material (2 mm Al versus 40 mm PMMA) and noise de-trending. Finally, spatial stationarity of noise was assessed.Data weighting improved noise model fitting over large DAK ranges, especially at low detector exposures. The polynomial and explicit decompositions generally agreed for quantum and electronic noise but FP noise fraction was consistently underestimated by the polynomial method. Noise decomposition as a function of position in the image showed limited noise stationarity, especially for FP noise; thus the position of the region of interest (ROI) used for noise decomposition may influence fractional noise composition. The ROI area and position used in the Guidelines offer an acceptable estimation of noise components. While there are limitations to the polynomial model, when used with care and with appropriate data weighting, the method offers a simple and robust means of examining the detector noise components as a function of detector exposure.

In vitro functionality of isolated embryonic hypothalamic vasopressinergic and oxytocinergic neurons: modulatory effects of brain-derived neurotrophic factor and angiotensin II.

There are only a few studies on the ontogeny and differentiation process of the hypothalamic supraoptic-paraventriculo-neurohypophysial neurosecretory system. In vitro neuron survival improves if cells are of embryonic origin; however, surviving hypothalamic neurons in culture were found to express small and minimal amounts of arginine-vasopressin (AVP) and oxytocin (OT), respectively. The aim of this study was to develop a primary neuronal culture design applicable to the study of magnocellular hypothalamic system functionality. For this purpose, a primary neuronal culture was set up after mechanical dissociation of sterile hypothalamic blocks from 17-day-old Sprague-Dawley rat embryos (E17) of both sexes. Isolated hypothalamic cells were cultured with supplemented (B27)-NeuroBasal medium containing an agent inhibiting non-neuron cell proliferation. The neurosecretory process was characterized by detecting AVP and OT secreted into the medium on different days of culture. Data indicate that spontaneous AVP and OT release occurred in a culture day-dependent fashion, being maximal on day 13 for AVP, and on day 10 for OT. Interestingly, brain-derived neurotrophic factor (BDNF) and Angiotensin II (A II) were able to positively modulate neuropeptide output. Furthermore, on day 17 of culture, non-specific (high-KCl) and specific (Angiotensin II) stimuli were able to significantly (P < 0.05) enhance the secretion of both neuropeptides over respective baselines. This study suggests that our experimental design is useful for the study of AVP- and OT-ergic neuron functionality and that BDNF and A II are positive modulators of embryonic hypothalamic cell development.

Modular support for developing mobile ad hoc applications

Abstract This PhD thesis addresses the issue of alleviating the burden of developing ad hoc applications. Such applications have the particularity of running on mobile devices, communicating in a peer-to-peer manner and implement some proximity-based semantics. A typical example of such application can be a radar application where users see their avatar as well as the avatars of their friends on a map on their mobile phone. Such application become increasingly popular with the advent of the latest generation of mobile smart phones with their impressive computational power, their peer-to-peer communication capabilities and their location detection technology. Unfortunately, the existing programming support for such applications is limited, hence the need to address this issue in order to alleviate their development burden. This thesis specifically tackles this problem by providing several tools for application development support. First, it provides the location-based publish/subscribe service (LPSS), a communication abstraction, which elegantly captures recurrent communication issues and thus allows to dramatically reduce the code complexity. LPSS is implemented in a modular manner in order to be able to target two different network architectures. One pragmatic implementation is aimed at mainstream infrastructure-based mobile networks, where mobile devices can communicate through fixed antennas. The other fully decentralized implementation targets emerging mobile ad hoc networks (MANETs), where no fixed infrastructure is available and communication can only occur in a peer-to-peer fashion. For each of these architectures, various implementation strategies tailored for different application scenarios that can be parametrized at deployment time. Second, this thesis provides two location-based message diffusion protocols, namely 6Shot broadcast and 6Shot multicast, specifically aimed at MANETs and fine tuned to be used as building blocks for LPSS. Finally this thesis proposes Phomo, a phone motion testing tool that allows to test proximity semantics of ad hoc applications without having to move around with mobile devices. These different developing support tools have been packaged in a coherent middleware framework called Pervaho.

An architecture for adaptive replication-based multimedia streaming in P2P networks

This PhD thesis addresses the issue of scalable media streaming in large-scale networking environments. Multimedia streaming is one of the largest sink of network resources and this trend is still growing as testified by the success of services like Skype, Netflix, Spotify and Popcorn Time (BitTorrent-based). In traditional client-server solutions, when the number of consumers increases, the server becomes the bottleneck. To overcome this problem, the Content-Delivery Network (CDN) model was invented. In CDN model, the server copies the media content to some CDN servers, which are located in different strategic locations on the network. However, they require heavy infrastructure investment around the world, which is too expensive. Peer-to-peer (P2P) solutions are another way to achieve the same result. These solutions are naturally scalable, since each peer can act as both a receiver and a forwarder. Most of the proposed streaming solutions in P2P networks focus on routing scenarios to achieve scalability. However, these solutions cannot work properly in video-on-demand (VoD) streaming, when resources of the media server are not sufficient. Replication is a solution that can be used in these situations. This thesis specifically provides a family of replication-based media streaming protocols, which are scalable, efficient and reliable in P2P networks. First, it provides SCALESTREAM, a replication-based streaming protocol that adaptively replicates media content in different peers to increase the number of consumers that can be served in parallel. The adaptiveness aspect of this solution relies on the fact that it takes into account different constraints like bandwidth capacity of peers to decide when to add or remove replicas. SCALESTREAM routes media blocks to consumers over a tree topology, assuming a reliable network composed of homogenous peers in terms of bandwidth. Second, this thesis proposes RESTREAM, an extended version of SCALESTREAM that addresses the issues raised by unreliable networks composed of heterogeneous peers. Third, this thesis proposes EAGLEMACAW, a multiple-tree replication streaming protocol in which two distinct trees, named EAGLETREE and MACAWTREE, are built in a decentralized manner on top of an underlying mesh network. These two trees collaborate to serve consumers in an efficient and reliable manner. The EAGLETREE is in charge of improving efficiency, while the MACAWTREE guarantees reliability. Finally, this thesis provides TURBOSTREAM, a hybrid replication-based streaming protocol in which a tree overlay is built on top of a mesh overlay network. Both these overlays cover all peers of the system and collaborate to improve efficiency and low-latency in streaming media to consumers. This protocol is implemented and tested in a real networking environment using PlanetLab Europe testbed composed of peers distributed in different places in Europe.

The synthetic Plasmodium falciparum circumsporozoite peptide PfCS102 as a malaria vaccine candidate: a randomized controlled phase I trial.

BACKGROUND: Fully efficient vaccines against malaria pre-erythrocytic stage are still lacking. The objective of this dose/adjuvant-finding study was to evaluate the safety, reactogenicity and immunogenicity of a vaccine candidate based on a peptide spanning the C-terminal region of Plasmodium falciparum circumsporozoite protein (PfCS102) in malaria naive adults. METHODOLOGY AND PRINCIPAL FINDINGS: Thirty-six healthy malaria-naive adults were randomly distributed into three dose blocks (10, 30 and 100 microg) and vaccinated with PfCS102 in combination with either Montanide ISA 720 or GSK proprietary Adjuvant System AS02A at days 0, 60, and 180. Primary end-point (safety and reactogenicity) was based on the frequency of adverse events (AE) and of abnormal biological safety tests; secondary-end point (immunogenicity) on P. falciparum specific cell-mediated immunity and antibody response before and after immunization. The two adjuvant formulations were well tolerated and their safety profile was good. Most AEs were local and, when systemic, involved mainly fatigue and headache. Half the volunteers in AS02A groups experienced severe AEs (mainly erythema). After the third injection, 34 of 35 volunteers developed anti-PfCS102 and anti-sporozoite antibodies, and 28 of 35 demonstrated T-cell proliferative responses and IFN-gamma production. Five of 22 HLA-A2 and HLA-A3 volunteers displayed PfCS102 specific IFN-gamma secreting CD8(+) T cell responses. Responses were only marginally boosted after the 3(rd) vaccination and remained stable for 6 months. For both adjuvants, the dose of 10 microg was less immunogenic in comparison to 30 and 100 microg that induced similar responses. AS02A formulations with 30 microg or 100 microg PfCS102 induced about 10-folds higher antibody and IFN-gamma responses than Montanide formulations. CONCLUSIONS/SIGNIFICANCE: PfCS102 peptide was safe and highly immunogenic, allowing the design of more advanced trials to test its potential for protection. Two or three immunizations with a dose of 30 microg formulated with AS02A appeared the most appropriate choice for such studies. TRIAL REGISTRATION: Swissmedic.ch 2002 DR 1227.

A Miocene mud volcano and its plumbing system: A chaotic complex revisited (Monferrato, NW Italy)

Chaotic deposits are frequently reported in the geological literature and are commonly interpreted as olistostromes or tectonic melanges. A chaotic complex in the Cenozoic succession of Monferrato (NW Italy) consists of interbedded mud breccia and burrowed silty clays that are pierced by sheared mud breccias and embed carbonate-cemented blocks. These may be represented by microcrystalline limestones or strongly cemented matrix-supported breccias locally containing remains of chemosymbiotic organisms (lucinid bivalves). Moreover, cylindrical concretions, up to 15 cm in diameter and 1 m long, occur in the chaotic complex and crosscut bedding planes at high angles. The cement of all these lithified portions is mainly dolomite characterized by low delta(13)C values (from -10.3 to -23parts per thousand PDB) and delta(18)O values up to + 7parts per thousand PDB. The delta(13)C values testify to precipitation of carbonates induced by microbial oxidation of methane, whereas the markedly positive delta(18)C signature, ubiquitous in the cylindrical concretions, is the evidence for the presence and destabilization of gas hydrates. The studied section provides a well-exposed example of the geological record of the birth, life, and death of a mud volcano. Unsheared, soft mud breccias represent mud flows along the flanks of the volcano, whereas sheared mud breccias are the result of the injection of unconsolidated overpressured fine-grained sediments, both taking place during ``eruptive'' phases. They were followed by more quiet stages of hemipelagic sedimentation, burrowing, and CH4 seeping. The cylindrical concretions represent the first described ancient example of the chimneys observed in present-day mud-volcano settings. They are the remnants of a cold-seep plumbing network that crosscut the mud volcano edifice. The chimneys were the pathway for the expulsion toward the sea floor of gas- and sediment-charged fluids likely originated from destabilization of methane gas hydrates. The association of mud breccias and methane-derived carbonates may not be due to mass gravity flows but can be primary and, therefore, is a diagnostic criterion for recognizing chaotic deposits due to mud volcano activity in the geological record.

International Olympic Committee consensus statement on thermoregulatory and altitude challenges for high-level athletes.

Challenging environmental conditions, including heat and humidity, cold, and altitude, pose particular risks to the health of Olympic and other high-level athletes. As a further commitment to athlete safety, the International Olympic Committee (IOC) Medical Commission convened a panel of experts to review the scientific evidence base, reach consensus, and underscore practical safety guidelines and new research priorities regarding the unique environmental challenges Olympic and other international-level athletes face. For non-aquatic events, external thermal load is dependent on ambient temperature, humidity, wind speed and solar radiation, while clothing and protective gear can measurably increase thermal strain and prompt premature fatigue. In swimmers, body heat loss is the direct result of convection at a rate that is proportional to the effective water velocity around the swimmer and the temperature difference between the skin and the water. Other cold exposure and conditions, such as during Alpine skiing, biathlon and other sliding sports, facilitate body heat transfer to the environment, potentially leading to hypothermia and/or frostbite; although metabolic heat production during these activities usually increases well above the rate of body heat loss, and protective clothing and limited exposure time in certain events reduces these clinical risks as well. Most athletic events are held at altitudes that pose little to no health risks; and training exposures are typically brief and well-tolerated. While these and other environment-related threats to performance and safety can be lessened or averted by implementing a variety of individual and event preventative measures, more research and evidence-based guidelines and recommendations are needed. In the mean time, the IOC Medical Commission and International Sport Federations have implemented new guidelines and taken additional steps to mitigate risk even further.

Shedding light on proteolytic cleavage of CD44: the responsible sheddase and functional significance of shedding.

CD44 is the major cell-surface receptor for hyaluronan, which is implicated in cell-cell and cell-matrix adhesion, cell migration, and signaling. Studies have shown that CD44-dependent migration requires CD44 to be shed from the cell surface and that matrix metalloproteinase-mediated cleavage may provide an underlying mechanism. However, the full spectrum of proteases that may participate in CD44 shedding has yet to be defined. In this issue, Anderegg et al. demonstrate that ADAM10, but not ADAM17 or MMP14, mediates constitutive shedding of CD44 in human melanoma cells and that knockdown of ADAM10 blocks the antiproliferative activity of the soluble proteolytic cleavage product of CD44.

Emplacement of Jurassic - Lower Cretaceous radiolarites of the Nicoya Complex (Costa Rica)

We present a new model to explain the origin, emplacement and stratigraphy of the Nicoya Complex in the NW part of the Nicoya Peninsula (Costa Rica) based on twenty-five years of field work, accompanied with the evolution of geochemical, vulcanological, petrological, sedimentological and paleontological paradigms. The igneous-sedimentary relation, together with radiolarian biochronology of the NW-Nicoya Peninsula is re-examined. We interpret the Nicoya Complex as a cross-section of a fragment of the Late Cretaceous Caribbean Plateau, in which the deepest levels are exposed in the NW-Nicoya Peninsula. Over 50% of the igneous rocks are intrusive (gabbros and in less proportion plagiogranites) which have a single mantle source; the remainder are basalts with a similar geochemical signature. Ar39/Ar40 radioisotopic whole rock and plagioclase ages range throughout the area from 84 to 83 Ma (Santonian) for the intrusives, and from 139 to 88 Ma (Berriasian-Turonian) for the basalts. In contrast, Mn-radiolarites that crop out in the area are older in age, Bajocian (Middle Jurassic) to Albian (middle Cretaceous). These Mn-radiolaritic blocks are set in a "matrix" of multiple gabbros and diabases intrusions. Chilled margins of magmatites, and hydrothermal baking and leaching of the radiolarites confirm the Ar39/Ar40 dating of igneous rocks being consistently younger than most of the radiolarian cherts. No Jurassic magmatic basement has been identified on the Nicoya Peninsula. We interpret the Jurassic-Cretaceous chert sediment pile to have been disrupted and detached from its original basement by multiple magmatic events that occurred during the formation of the Caribbean Plateau. Coniacian-Santonian (Late Cretaceous), Fe-rich radiolarites are largely synchronous and associated with late phases of the Plateau.

The central Sesia-Lanzo zone (Western Italian Alps) - New field observations and lithostratigraphic subdivisions

An extensive study of the central part of the Sesia Lanzo Zone has been undertaken to identify pre-Alpine protoliths and to reconstruct the lithologic and tectonic setting of this part of the Western Alps. Three main complexes have been defined: 1) the Polymetamorphic Basement Complex, corresponding to the lower unit of the Sesia Lanzo Zone after COMPAGNONI et al. (1977), is further subdivided into the three following units: a) an Internal Unit characterized by eo-Alpine high pressure (HP) assemblages (DAL PIAZ et al., 1972) (Eclogitic Micaschists); b) an Intermediate Unit where HP parageneses are partially re-equilibrated under greenschist conditions and c) an External Unit where the main foliation is defined by a greenschist paragenesis (Gneiss Minuti auct.). 2) the Monometamorphic Cover Complex, subdivided into the followings: a) the Bonze Unit, composed of sheared metagabbros, eclogitized metabasalts with MORB geochemical affinity and related metasediments (micaschists, quartzites and Mn-cherts) and b) the Scalaro Unit, containing predominantly metasediments of supposed Permo-Triassic age (yellow dolomitic marbles, calcschists and conglomeratic limestones, micaschists and quartzites with thin levels of basic rocks with within plate basalts [WPB] geochimical affinity). Multiple lithostratigraphic sequences for the Monometamorphic Cover Complex are proposed. The contact between the Bonze and Scalaro Units is defined by repetitions of dolomitic marbles and metabasalts; the ages of the metasediments have been assigned solely by analogy with other sediments of the Western Alps, due to the absence of fossils. The Monometamorphic Cover Complex can be considered as the autochthonous cover of the Sesia Lanzo Zone because of the primary contacts with the basement and because of the presence of preAlpine HT basement blocks in the cover sequences. 3) The pre-Alpine high temperature (HT) Basement Complex (or `'Seconda Zona Diorito-Kinzigitica''), comprises HT Hercynian rocks like kinzigites, amphibolites, granulites and calcite marbles; this Complex is always located between the Internal and the External Units and can be followed continuously for several kilometers south of the Gressoney Valley to the Orco Valley. A schematic evolution for the Sesia Lanzo Zone is proposed; based on available data together with new geochronological data, this study shows that the internal and external parts of the polymetamorphic basement of the Sesia Zone experienced different cooling histories .

The Variscan evolution in the External massifs of the Alps and place in their Variscan framework

In the general discussion on the Variscan evolution of central Europe the pre-Mesozoic basement of the Alps is, in many cases, only included with hesitation. Relatively well-preserved from Alpine metamorphism, the Alpine External massifs can serve as an excellent example of evolution of the Variscan basement, including the earliest Gondwana-derived microcontinents with Cadomian relics. Testifying to the evolution at the Gondwana margin, at least since the Cambrian, such pieces took part in the birth of the Rheic Ocean. After the separation of Avalonia, the remaining Gondwana border was continuously transformed through crustal extension with contemporaneous separation of continental blocks composing future Pangea, but the opening of Palaeotethys had only a reduced significance since the Devonian. The Variscan evolution in the External domain is characterised by an early HP-evolution with subsequent granulitic decompression melts. During Visean crustal shortening, the areas of future formation of migmatites and intrusion of monzodioritic magmas in a general strike-slip regime, were probably in a lower plate situation, whereas the so called monometamorphic areas may have been in an upper plate position of the nappe pile. During the Latest Carboniferous, the emplacement of the youngest granites was associated with the strike-slip faulting and crustal extension at lower crustal levels, whereas, at the surface, detrital sediments accumulated in intramontaneous transtensional basins on a strongly eroded surface. To cite this article: J.R von Raumer et al., C. R. Geoscience 341 (2009). (C) 2008 Academie des sciences. Published by Elsevier Masson SAS. All rights reserved.

Regulation of the Activity of the Dual-Function DnaA Protein in Caulobacter crescentus.

DnaA is a conserved essential bacterial protein that acts as the initiator of chromosomal replication as well as a master transcriptional regulator in Caulobacter crescentus. Thus, the intracellular levels of active DnaA need to be tightly regulated during the cell cycle. Our previous work suggested that DnaA may be regulated at the level of its activity by the replisome-associated protein HdaA. Here, we describe the construction of a mutant DnaA protein [DnaA(R357A)]. The R357 residue in the AAA+ domain of the C. crescentus DnaA protein is equivalent to the R334 residue of the E. coli DnaA protein, which is required for the Regulatory Inactivation of DnaA (RIDA). We found that the expression of the DnaA(R357A) mutant protein in C. crescentus, but not the expression of the wild-type DnaA protein at similar levels, causes a severe phenotype of over-initiation of chromosomal replication and that it blocks cell division. Thus, the mutant DnaA(R357A) protein is hyper-active to promote the initiation of DNA replication, compared to the wild-type DnaA protein. DnaA(R357A) could not replace DnaA in vivo, indicating that the switch in DnaA activity once chromosomal replication has started may be an essential process in C. crescentus. We propose that the inactivation of DnaA is the main mechanism ensuring that chromosomal replication starts only once per cell cycle. We further observed that the R357A substitution in DnaA does not promote the activity of DnaA as a direct transcriptional activator of four important genes, encoding HdaA, the GcrA master cell cycle regulator, the FtsZ cell division protein and the MipZ spatial regulator of cell division. Thus, the AAA+ domain of DnaA may play a role in temporally regulating the bifunctionality of DnaA by reallocating DnaA molecules from initiating DNA replication to transcribing genes within the unique DnaA regulon of C. crescentus.

An Adeno-Associated Virus-Based Intracellular Sensor of Pathological Nuclear Factor-κB Activation for Disease-Inducible Gene Transfer.

Stimulation of resident cells by NF-κB activating cytokines is a central element of inflammatory and degenerative disorders of the central nervous system (CNS). This disease-mediated NF-κB activation could be used to drive transgene expression selectively in affected cells, using adeno-associated virus (AAV)-mediated gene transfer. We have constructed a series of AAV vectors expressing GFP under the control of different promoters including NF-κB -responsive elements. As an initial screen, the vectors were tested in vitro in HEK-293T cells treated with TNF-α. The best profile of GFP induction was obtained with a promoter containing two blocks of four NF-κB -responsive sequences from the human JCV neurotropic polyoma virus promoter, fused to a new tight minimal CMV promoter, optimally distant from each other. A therapeutical gene, glial cell line-derived neurotrophic factor (GDNF) cDNA under the control of serotype 1-encapsidated NF-κB -responsive AAV vector (AAV-NF) was protective in senescent cultures of mouse cortical neurons. AAV-NF was then evaluated in vivo in the kainic acid (KA)-induced status epilepticus rat model for temporal lobe epilepsy, a major neurological disorder with a central pathophysiological role for NF-κB activation. We demonstrate that AAV-NF, injected in the hippocampus, responded to disease induction by mediating GFP expression, preferentially in CA1 and CA3 neurons and astrocytes, specifically in regions where inflammatory markers were also induced. Altogether, these data demonstrate the feasibility to use disease-activated transcription factor-responsive elements in order to drive transgene expression specifically in affected cells in inflammatory CNS disorders using AAV-mediated gene transfer.