Contingent negative variation in epilepsy

The contingent negative variation (CNV) is a long-latency event-related potential elicited by paired or associated stimuli. We recorded contingent negative variation in 50 patients with complex partial and secondarily generalized seizures and in 20 neurologically and psychiatrically normal unmedicated controls.CNV was recorded from Fz, Cz, and Pz. A 2000 Hz tone was followed after 1.5 s by 1000 microsecond light flash, at which a button press was to be executed. Filter band pass was 0.1–20 Hz, analysis time was 10s and 10 responses were replicated.Patients with complex partial seizures with and without secondary generalization had lower measurements of area under the CNV curve (AUC) than did controls, and CNV amplitude was significantly reduced. Patients with interictal behavioural symptoms had significantly smaller AUC and lower amplitude. No significant difference was found between depressed and non-depressed seizure patients with respect to AUC, but amplitude was significantly lower in depressed patients. Seizure patients with psychosis had significantly lower AUC but did not differ from non-psychotic patients in CNV amplitude. No differences were found between seizure patients with and without personality disorder with respect to CNV AUC or amplitude. Post-imperative negative variation was significantly more common in seizure patients than in controls and among patients with epilepsy, was significantly increased in those with inter-ictal behaviour disturbance generally and psychosis particularly. No specific effect of anticonvulsant monotherapy on AUC or amplitude was identified.These findings suggest that CNV may differ between partial epilepsy patients and controls, and that inter-ictal behaviour disturbance may particularly affect CNV measures. They also agree with previous evidence for a frontal lobe generator for the CNV, and a possible role for central dopaminergic pathways in the production of PINV

Investigating the eddy diffusivity concept in the coastal ocean

Author Posting. © American Meteorological Society, 2016. This article is posted here by permission of American Meteorological Society for personal use, not for redistribution. The definitive version was published in Journal of Physical Oceanography 46 (2016): 2201-2218, doi:10.1175/JPO-D-16-0020.1.This paper aims to test the validity, utility, and limitations of the lateral eddy diffusivity concept in a coastal environment through analyzing data from coupled drifter and dye releases within the footprint of a high-resolution (800 m) high-frequency radar south of Martha’s Vineyard, Massachusetts. Specifically, this study investigates how well a combination of radar-based velocities and drifter-derived diffusivities can reproduce observed dye spreading over an 8-h time interval. A drifter-based estimate of an anisotropic diffusivity tensor is used to parameterize small-scale motions that are unresolved and underresolved by the radar system. This leads to a significant improvement in the ability of the radar to reproduce the observed dye spreading.IR, AK, and SL were supported by the NSF OCE Grant 1332646. IR was also supported by NASA Grant NNX14AH29G.2016-12-2

Deep learning optimized single-pixel LiDAR

Interest in autonomous transport has led to a demand for 3D imaging technologies capable of resolving fine details at long range. Light detection and ranging (LiDAR) systems have become a key technology in this area, with depth information typically gained through time-of-flight photon-counting measurements of a scanned laser spot. Single-pixel imaging methods offer an alternative approach to spot-scanning, which allows a choice of sampling basis. In this work, we present a prototype LiDAR system, which compressively samples the scene using a deep learning optimized sampling basis and reconstruction algorithms. We demonstrate that this approach improves scene reconstruction quality compared to an orthogonal sampling method, with reflectivity and depth accuracy improvements of 57% and 16%, respectively, for one frame per second acquisition rates. This method may pave the way for improved scan-free LiDAR systems for driverless cars and for fully optimized sampling to decision-making pipelines

Multivariate analysis using high definition flow cytometry reveals distinct T cell repertoires between the fetal–maternal interface and the peripheral blood

The human T cell compartment is a complex system and while some information is known on repertoire composition and dynamics in the peripheral blood, little is known about repertoire composition at different anatomical sites. Here, we determine the T cell receptor beta variable (TRBV) repertoire at the decidua and compare it with the peripheral blood during normal pregnancy and pre-eclampsia. We found total T cell subset disparity of up to 58% between sites, including large signature TRBV expansions unique to the fetal–maternal interface. Defining the functional nature and specificity of compartment-specific T cells will be necessary if we are to understand localized immunity, tolerance, and pathogenesis

Metabolic gatekeeper function of B-lymphoid transcription factors.

B-lymphoid transcription factors, such as PAX5 and IKZF1, are critical for early B-cell development, yet lesions of the genes encoding these transcription factors occur in over 80% of cases of pre-B-cell acute lymphoblastic leukaemia (ALL). The importance of these lesions in ALL has, until now, remained unclear. Here, by combining studies using chromatin immunoprecipitation with sequencing and RNA sequencing, we identify a novel B-lymphoid program for transcriptional repression of glucose and energy supply. Our metabolic analyses revealed that PAX5 and IKZF1 enforce a state of chronic energy deprivation, resulting in constitutive activation of the energy-stress sensor AMPK. Dominant-negative mutants of PAX5 and IKZF1, however, relieved this glucose and energy restriction. In a transgenic pre-B ALL mouse model, the heterozygous deletion of Pax5 increased glucose uptake and ATP levels by more than 25-fold. Reconstitution of PAX5 and IKZF1 in samples from patients with pre-B ALL restored a non-permissive state and induced energy crisis and cell death. A CRISPR/Cas9-based screen of PAX5 and IKZF1 transcriptional targets identified the products of NR3C1 (encoding the glucocorticoid receptor), TXNIP (encoding a glucose-feedback sensor) and CNR2 (encoding a cannabinoid receptor) as central effectors of B-lymphoid restriction of glucose and energy supply. Notably, transport-independent lipophilic methyl-conjugates of pyruvate and tricarboxylic acid cycle metabolites bypassed the gatekeeper function of PAX5 and IKZF1 and readily enabled leukaemic transformation. Conversely, pharmacological TXNIP and CNR2 agonists and a small-molecule AMPK inhibitor strongly synergized with glucocorticoids, identifying TXNIP, CNR2 and AMPK as potential therapeutic targets. Furthermore, our results provide a mechanistic explanation for the empirical finding that glucocorticoids are effective in the treatment of B-lymphoid but not myeloid malignancies. Thus, B-lymphoid transcription factors function as metabolic gatekeepers by limiting the amount of cellular ATP to levels that are insufficient for malignant transformation

SecureMEMS: Selective Deposition of Energetic Materials

There exists a pressing operational need to secure and control access to high-valued electromechanical systems, and in some cases render them inoperable. Developing a reliable method for depositing energetic materials will allow for the near-seamless integration of electromechanical systems and energetic material, and, in turn, provide the pathway for security and selective destruction that is needed. In this work, piezoelectric inkjet printing was used to selectively deposit energetic materials. Nanothermites, comprising of nanoscale aluminum and nanoscale copper oxide suspended in dimethyl-formamide (DMF), were printed onto silicon wafers, which enabled both thermal and thrust measurements of the decomposing energetic material. Various solids loadings were studied in order to optimize printing characteristics. Going forward, further studies will focus on the plausibility of inkjet printing other energetic materials for the purposes of the degradation of electromechanical systems

Controlling the self-assembly and material properties of β-sheet peptide hydrogels by modulating intermolecular interactions

Self-assembling peptides are a promising biomaterial with potential applications in medical devices and drug delivery. In the right combination of conditions, self-assembling peptides can form self-supporting hydrogels. Here, we describe how balancing attractive and repulsive intermolecular forces is critical for successful hydrogel formation. Electrostatic repulsion is tuned by altering the peptide’s net charge, and intermolecular attractions are controlled through the degree of hydrogen bonding between specific amino acid residues. We find that an overall net peptide charge of +/−2 is optimal to facilitate the assembly of self-supporting hydrogels. If the net peptide charge is too low then dense aggregates form, while a high molecular charge inhibits the formation of larger structures. At a constant charge, altering the terminal amino acids from glutamine to serine decreases the degree of hydrogen bonding within the assembling network. This tunes the viscoelastic properties of the gel, reducing the elastic modulus by two to three orders of magnitude. Finally, hydrogels could be formed from glutamine-rich, highly charged peptides by mixing the peptides in combinations with a resultant net charge of +/−2. These results illustrate how understanding and controlling self-assembly mechanisms through modulating intermolecular interactions can be exploited to derive a range of structures with tuneable properties

microRNA-seq of cartilage reveals an over-abundance of miR-140-3p which contains functional isomiRs

miR-140 is selectively expressed in cartilage. Deletion of the entire Mir140 locus in mice results in growth retardation and early-onset osteoarthritis-like pathology; however, the relative contribution of miR-140-5p or miR-140-3p to the phenotype remains to be determined. An unbiased small RNA sequencing approach identified miR-140-3p as significantly more abundant (>10-fold) than miR-140-5p in human cartilage. Analysis of these data identified multiple miR-140-3p isomiRs differing from the miRBase annotation at both the 5' and 3' end, with >99% having one of two seed sequences (5' bases 2-8). Canonical (miR-140-3p.2) and shifted (miR-140-3p.1) seed isomiRs were overexpressed in chondrocytes and transcriptomics performed to identify targets. miR-140-3p.1 and miR-140-3p.2 significantly down-regulated 694 and 238 genes, respectively, of which only 162 genes were commonly down-regulated. IsomiR targets were validated using 3'UTR luciferase assays. miR-140-3p.1 targets were enriched within up-regulated genes in rib chondrocytes of Mir140- null mice and within down-regulated genes during human chondrogenesis. Finally, through imputing the expression of miR-140 from the expression of the host gene WWP2 in 124 previously published data sets, an inverse correlation with miR-140-3p.1 predicted targets was identified. Together these data suggest the novel seed containing isomiR miR-140- 3p.1 is more functional than original consensus miR-140-3p seed containing isomiR