Imaging of focal seizures with Electrical Impedance Tomography and depth electrodes in real time

Intracranial EEG is the current gold standard technique for localising seizures for surgery, but it can be insensitive to tangential dipole or distant sources. Electrical Impedance Tomography (EIT) offers a novel method to improve coverage and seizure onset localisation. The feasibility of EIT has been previously assessed in a computer simulation, which revealed an improved accuracy of seizure detection with EIT compared to intracranial EEG. In this study, slow impedance changes, evoked by cell swelling occurring over seconds, were reconstructed in real time by frequency division multiplexing EIT using depth and subdural electrodes in a swine model of epilepsy. EIT allowed to generate repetitive images of ictal events at similar time course to fMRI but without its significant limitations. EIT was recorded with a system consisting of 32 parallel current sources and 64 voltage recorders. Seizures triggered with intracranial injection of benzylpenicillin (BPN) in five pigs caused a repetitive peak impedance increase of 3.4±1.5 mV and 9.5±3% (N=205 seizures); the impedance signal change was seen already after a single, first seizure. EIT enabled reconstruction of the seizure onset 9±1.5 mm from the BPN cannula and 7.5±1.1 mm from the closest SEEG contact (p<0.05, n=37 focal seizures in three pigs) and it could address problems with sampling error in intracranial EEG. The amplitude of the impedance change correlated with the spread of the seizure on the SEEG (p <0.001, n=37). The results presented here suggest that combining a parallel EIT system with intracranial EEG monitoring has a potential to improve the diagnostic yield in epileptic patients and become a vital tool in improving our understanding of epilepsy

Imaging Circuit Activity in the Rat Brain with Fast Neural EIT and Depth Arrays

Few techniques are specialized for neuroscience at the 'mesoscopic' level of neural circuits. Fast neural electrical impedance tomography (fnEIT) is a novel imaging technique that offers affordability, portability, and high spatial (∼100 μm) and temporal (1 ms) resolution. fnEIT with depth arrays offers the opportunity to study the dynamics of circuits in the brains of animal models. However, current depth array geometries are not optimized for this imaging modality. They feature small, closely packed electrodes with high impedance that do not provide sufficient SNR for high resolution EIT image reconstruction. They also have a highly limited range. It is necessary to develop depth arrays suitable for fnEIT and evaluate their performance in a representative setting for circuit neuroscience. In this study, we optimized the geometry of depth arrays for fnEIT, and then investigated the prospects of imaging thalamocortical circuit activity in the rat brain. Optimization was consistent with the hypothesis that small, closely spaced electrodes were not suitable for fnEIT. In vivo experiments with the optimized geometry then showed that fnEIT can image thalamocortical circuit activity at a high enough resolution to see the activity propagating from specific thalamic nuclei to specific regions of the somatosensory cortex. This bodes well for fnEIT's potential as a technique for circuit neuroscience

Pulse Wave Velocity Measurement in the Carotid Artery Using an LED-LED Array Pulse Oximeter

Pulse wave velocity (PWV) is frequently used as an early indicator of risk of cardiovascular disease. Conventional methods of PWV measurement are invasive and measure the regional PWV, introducing errors from unknown measurement distance to masking local changes in compliance. This paper describes the development and testing of a non-invasive PWV sensor using photoplethysmograph signals. The sensor measures the pulse in the carotid artery with three sensor arrays spaced at 20 mm, 30 mm and 50 mm spacing. Each array of 20 LED-LED sensors are placed at 5 mm to get the largest amplitude pulse across the neck, and to allow for inaccurate sensor placement. LEDs are used as light emitters and the inherent capacitance of reverse biased LEDs measure the reflected light. The foot-foot and phase difference methods were used to calculate the PWV at each measurement distance. The foot-foot method was more reliable than the phase difference at all distances with a PWV of 5.26 m s−1 in a single-subject trial. The sample rate of 570 Hz was deemed too slow as one sample difference resulted in a PWV change of 1.5ms−1. The developed sensor measured the local PWV within the expected physiological range around 6 m s−1. All future measurements will be measured at 1 kHz and an increased LED output intensity

The genomes of two key bumblebee species with primitive eusocial organization

Background: The shift from solitary to social behavior is one of the major evolutionary transitions. Primitively eusocial bumblebees are uniquely placed to illuminate the evolution of highly eusocial insect societies. Bumblebees are also invaluable natural and agricultural pollinators, and there is widespread concern over recent population declines in some species. High-quality genomic data will inform key aspects of bumblebee biology, including susceptibility to implicated population viability threats. Results: We report the high quality draft genome sequences of Bombus terrestris and Bombus impatiens, two ecologically dominant bumblebees and widely utilized study species. Comparing these new genomes to those of the highly eusocial honeybee Apis mellifera and other Hymenoptera, we identify deeply conserved similarities, as well as novelties key to the biology of these organisms. Some honeybee genome features thought to underpin advanced eusociality are also present in bumblebees, indicating an earlier evolution in the bee lineage. Xenobiotic detoxification and immune genes are similarly depauperate in bumblebees and honeybees, and multiple categories of genes linked to social organization, including development and behavior, show high conservation. Key differences identified include a bias in bumblebee chemoreception towards gustation from olfaction, and striking differences in microRNAs, potentially responsible for gene regulation underlying social and other traits. Conclusions: These two bumblebee genomes provide a foundation for post-genomic research on these key pollinators and insect societies. Overall, gene repertoires suggest that the route to advanced eusociality in bees was mediated by many small changes in many genes and processes, and not by notable expansion or depauperation

Protection Induced by Plasmodium falciparum MSP142 Is Strain-Specific, Antigen and Adjuvant Dependent, and Correlates with Antibody Responses

Vaccination with Plasmodium falciparum MSP142/complete Freund's adjuvant (FA) followed by MSP142/incomplete FA is the only known regimen that protects Aotus nancymaae monkeys against infection by erythrocytic stage malaria parasites. The role of adjuvant is not defined; however complete FA cannot be used in humans. In rodent models, immunity is strain-specific. We vaccinated Aotus monkeys with the FVO or 3D7 alleles of MSP142 expressed in Escherichia coli or with the FVO allele expressed in baculovirus (bv) combined with complete and incomplete FA, Montanide ISA-720 (ISA-720) or AS02A. Challenge with FVO strain P. falciparum showed that suppression of cumulative day 11 parasitemia was strain-specific and could be induced by E. coli expressed MSP142 in combination with FA or ISA-720 but not with AS02A. The coli42-FVO antigen induced a stronger protective effect than the bv42-FVO antigen, and FA induced a stronger protective effect than ISA-720. ELISA antibody (Ab) responses at day of challenge (DOC) were strain-specific and correlated inversely with c-day 11 parasitemia (r = −0.843). ELISA Ab levels at DOC meeting a titer of at least 115,000 ELISA Ab units identified the vaccinees not requiring treatment (noTx) with a true positive rate of 83.3% and false positive rate of 14.3 %. Correlation between functional growth inhibitory Ab levels (GIA) and cumulative day 11 parasitemia was weaker (r = −0.511), and was not as predictive for a response of noTx. The lowest false positive rate for GIA was 30% when requiring a true positive rate of 83.3%. These inhibition results along with those showing that antigen/FA combinations induced a stronger protective immunity than antigen/ISA-720 or antigen/AS02 combinations are consistent with protection as ascribed to MSP1-specific cytophilic antibodies. Development of an effective MSP142 vaccine against erythrocytic stage P. falciparum infection will depend not only on antigen quality, but also upon the selection of an optimal adjuvant component

Strong interface-induced spin-orbit coupling in graphene on WS2

Interfacial interactions allow the electronic properties of graphene to be modified, as recently demonstrated by the appearance of satellite Dirac cones in the band structure of graphene on hexagonal boron nitride (hBN) substrates. Ongoing research strives to explore interfacial interactions in a broader class of materials in order to engineer targeted electronic properties. Here we show that at an interface with a tungsten disulfide (WS2) substrate, the strength of the spin-orbit interaction (SOI) in graphene is very strongly enhanced. The induced SOI leads to a pronounced low-temperature weak anti-localization (WAL) effect, from which we determine the spin-relaxation time. We find that spin-relaxation time in graphene is two-to-three orders of magnitude smaller on WS2 than on SiO2 or hBN, and that it is comparable to the intervalley scattering time. To interpret our findings we have performed first-principle electronic structure calculations, which both confirm that carriers in graphene-on-WS2 experience a strong SOI and allow us to extract a spin-dependent low-energy effective Hamiltonian. Our analysis further shows that the use of WS2 substrates opens a possible new route to access topological states of matter in graphene-based systems.Comment: Originally submitted version in compliance with editorial guidelines. Final version with expanded discussion of the relation between theory and experiments to be published in Nature Communication

Changes in Parasite Virulence Induced by the Disruption of a Single Member of the 235 kDa Rhoptry Protein Multigene Family of Plasmodium yoelii

Invasion of the erythrocyte by the merozoites of the malaria parasite is a complex process involving a range of receptor-ligand interactions. Two protein families termed Erythrocyte Binding Like (EBL) proteins and Reticulocyte Binding Protein Homologues (RH) play an important role in host cell recognition by the merozoite. In the rodent malaria parasite, Plasmodium yoelii, the 235 kDa rhoptry proteins (Py235) are coded for by a multigene family and are members of the RH. In P. yoelii Py235 as well as a single member of EBL have been shown to be key mediators of virulence enabling the parasite to invade a wider range of host erythrocytes. One member of Py235, PY01365 is most abundantly transcribed in parasite populations and the protein specifically binds to erythrocytes and is recognized by the protective monoclonal antibody 25.77, suggesting a key role of this particular member in virulence. Recent studies have indicated that overall levels of Py235 expression are essential for parasite virulence. Here we show that disruption of PY01365 in the virulent YM line directly impacts parasite virulence. Furthermore the disruption of PY01365 leads to a reduction in the number of schizonts that express members of Py235 that react specifically with the mcAb 25.77. Erythrocyte binding assays show reduced binding of Py235 to red blood cells in the PY01365 knockout parasite as compared to YM. While our results identify PY01365 as a mediator of parasite virulence, they also confirm that other members of Py235 are able to substitute for PY01365

Three-dimensional culture of human meniscal cells: Extracellular matrix and proteoglycan production

<p>Abstract</p> <p>Background</p> <p>The meniscus is a complex tissue whose cell biology has only recently begun to be explored. Published models rely upon initial culture in the presence of added growth factors. The aim of this study was to test a three-dimensional (3D) collagen sponge microenvironment (without added growth factors) for its ability to provide a microenvironment supportive for meniscal cell extracellular matrix (ECM) production, and to test the responsiveness of cells cultured in this manner to transforming growth factor-β (TGF-β).</p> <p>Methods</p> <p>Experimental studies were approved prospectively by the authors' Human Subjects Institutional Review Board. Human meniscal cells were isolated from surgical specimens, established in monolayer culture, seeded into a 3D scaffold, and cell morphology and extracellular matrix components (ECM) evaluated either under control condition or with addition of TGF-β. Outcome variables were evaluation of cultured cell morphology, quantitative measurement of total sulfated proteoglycan production, and immunohistochemical study of the ECM components chondroitin sulfate, keratan sulfate, and types I and II collagen.</p> <p>Result and Conclusion</p> <p>Meniscal cells attached well within the 3D microenvironment and expanded with culture time. The 3D microenvironment was permissive for production of chondroitin sulfate, types I and II collagen, and to a lesser degree keratan sulfate. This microenvironment was also permissive for growth factor responsiveness, as indicated by a significant increase in proteoglycan production when cells were exposed to TGF-β (2.48 μg/ml ± 1.00, mean ± S.D., vs control levels of 1.58 ± 0.79, p < 0.0001). Knowledge of how culture microenvironments influence meniscal cell ECM production is important; the collagen sponge culture methodology provides a useful in vitro tool for study of meniscal cell biology.</p

Study of the reaction e^{+}e^{-} -->J/psi\pi^{+}\pi^{-} via initial-state radiation at BaBar

We study the process $e^+e^-\to J/\psi\pi^{+}\pi^{-}$ with initial-state-radiation events produced at the PEP-II asymmetric-energy collider. The data were recorded with the BaBar detector at center-of-mass energies 10.58 and 10.54 GeV, and correspond to an integrated luminosity of 454 $\mathrm{fb^{-1}}$. We investigate the $J/\psi \pi^{+}\pi^{-}$ mass distribution in the region from 3.5 to 5.5 $\mathrm{GeV/c^{2}}$. Below 3.7 $\mathrm{GeV/c^{2}}$ the $\psi(2S)$ signal dominates, and above 4 $\mathrm{GeV/c^{2}}$ there is a significant peak due to the Y(4260). A fit to the data in the range 3.74 -- 5.50 $\mathrm{GeV/c^{2}}$ yields a mass value $4244 \pm 5$ (stat) $\pm 4$ (syst)$\mathrm{MeV/c^{2}}$ and a width value $114 ^{+16}_{-15}$ (stat)$\pm 7$(syst)$\mathrm{MeV}$ for this state. We do not confirm the report from the Belle collaboration of a broad structure at 4.01 $\mathrm{GeV/c^{2}}$. In addition, we investigate the $\pi^{+}\pi^{-}$ system which results from Y(4260) decay

Jet energy measurement with the ATLAS detector in proton-proton collisions at root s=7 TeV

The jet energy scale and its systematic uncertainty are determined for jets measured with the ATLAS detector at the LHC in proton-proton collision data at a centre-of-mass energy of √s = 7TeV corresponding to an integrated luminosity of 38 pb-1. Jets are reconstructed with the anti-kt algorithm with distance parameters R=0. 4 or R=0. 6. Jet energy and angle corrections are determined from Monte Carlo simulations to calibrate jets with transverse momenta pT≥20 GeV and pseudorapidities {pipe}η{pipe}<4. 5. The jet energy systematic uncertainty is estimated using the single isolated hadron response measured in situ and in test-beams, exploiting the transverse momentum balance between central and forward jets in events with dijet topologies and studying systematic variations in Monte Carlo simulations. The jet energy uncertainty is less than 2. 5 % in the central calorimeter region ({pipe}η{pipe}<0. 8) for jets with 60≤pT<800 GeV, and is maximally 14 % for pT<30 GeV in the most forward region 3. 2≤{pipe}η{pipe}<4. 5. The jet energy is validated for jet transverse momenta up to 1 TeV to the level of a few percent using several in situ techniques by comparing a well-known reference such as the recoiling photon pT, the sum of the transverse momenta of tracks associated to the jet, or a system of low-pT jets recoiling against a high-pT jet. More sophisticated jet calibration schemes are presented based on calorimeter cell energy density weighting or hadronic properties of jets, aiming for an improved jet energy resolution and a reduced flavour dependence of the jet response. The systematic uncertainty of the jet energy determined from a combination of in situ techniques is consistent with the one derived from single hadron response measurements over a wide kinematic range. The nominal corrections and uncertainties are derived for isolated jets in an inclusive sample of high-pT jets. Special cases such as event topologies with close-by jets, or selections of samples with an enhanced content of jets originating from light quarks, heavy quarks or gluons are also discussed and the corresponding uncertainties are determined. © 2013 CERN for the benefit of the ATLAS collaboration