Spatial Resolution of Local Field Potential Signals in Macaque V4

A main challenge for the development of cortical visual prostheses is to spatially localize individual spots of light, called phosphenes, by assigning appropriate stimulating parameters to implanted electrodes. Imitating the natural responses to phosphene-like stimuli at different positions can help in designing a systematic procedure to determine these parameters. The key characteristic of such a system is the ability to discriminate between responses to different positions in the visual field. While most previous prosthetic devices have targeted the primary visual cortex, the extrastriate cortex has the advantage of covering a large part of the visual field with a smaller amount of cortical tissue, providing the possibility of a more compact implant. Here, we studied how well ensembles of Multiunit activity (MUA) and Local Field Potentials (LFPs) responses from extrastriate cortical visual area V4 of a behaving macaque monkey can discriminate between two-dimensional spatial positions. We found that despite the large receptive field sizes in V4, the combined responses from multiple sites, whether MUA or LFP, has the capability for fine and coarse discrimination of positions. We identified a selection procedure that could significantly increase the discrimination performance while reducing the required number of electrodes. Analysis of noise correlation in MUA and LFP responses showed that noise correlations in LFP responses carry more information about the spatial positions. Overall, these findings suggest that spatial positions could be localized with patterned stimulation in extrastriate area V4

Bidirectional Parallel Capacitive Data Links: Modeling and Experimental Results

We present, in this paper, a bidirectional capacitive data link. Enhancement of the spatial pulse position modulation used on the downlink is introduced, and a load-shift keying modulation is implemented for the uplink. Different grounds on the transmitter and the receiver are discussed, and a compatible solution is proposed. A human skin electrical model is extracted using the agilent impedance analyzer 4294A while doing in vivo measurements on cheek skin and then applying curve fitting to the data between 2 and 20 MHz. Multiple geometries for the link are analyzed, and a 5-mm × 5-mm plate size is used for the design of the transceiver. The signal-to-noise ratio along with the capacity of the channel is analyzed theoretically while computing the limits for the downlink and the valid operating frequency to highlight the core parameters that affect the crosstalk interference between channels. The tradeoff in using the uplink on the same channel as the downlink is also discussed and analyzed. The operating frequency is 10 MHz, a bit-rate of 20 Mb/s is demonstrated on the uplink, and 10 Mb/s is demonstrated on the downlink. An in vivo human skin model for a 5-mm × 5-mm plate size with 21.2-mm separation is extracted, and the capacity's equation of the channel is computed using the equations for the analysis of the system.This work was supported by the Natural Sciences and Engineering Research Council of Canada, Canada. The authors would like to acknowledge the financial support from the Canada Research Chair in Smart Medical Devices and the design tools from CMC Microsystems.Scopu

Integrated multi‑omics analysis of ovarian cancer using variational autoencoders

Cancer is a complex disease that deregulates cellular functions at various molecular levels (e.g., DNA, RNA, and proteins). Integrated multi‑omics analysis of data from these levels is necessary to understand the aberrant cellular functions accountable for cancer and its development. In recent years, Deep Learning (DL) approaches have become a useful tool in integrated multi‑omics analysis of cancer data. However, high dimensional multi‑omics data are generally imbalanced with too many molecular features and relatively few patient samples. This imbalance makes a DL based integrated multi‑omics analysis difficult. DL‑based dimensionality reduction technique, including variational autoencoder (VAE), is a potential solution to balance high dimensional multi‑omics data. However, there are few VAE‑based integrated multi‑omics analyses, and they are limited to pancancer. In this work, we did an integrated multi‑omics analysis of ovarian cancer using the compressed features learned through VAE and an improved version of VAE, namely Maximum Mean Discrepancy VAE (MMD‑VAE). First, we designed and developed a DL architecture for VAE and MMD‑VAE. Then we used the architecture for mono‑omics, integrated di‑omics and tri‑omics data analysis of ovarian cancer through cancer samples identification, molecular subtypes clustering and classification, and survival analysis. The results show that MMD‑VAE and VAE‑based compressed features can respectively classify the transcriptional subtypes of the TCGA datasets with an accuracy in the range of 93.2‑95.5% and 87.1‑95.7%. Also, survival analysis results show that VAE and MMD‑VAE based compressed representation of omics data can be used in cancer prognosis. Based on the results, we can conclude that (i) VAE and MMD‑VAE outperform existing dimensionality reduction techniques, (ii) integrated multi‑omics analyses perform better or similar compared to their mono‑omics counterparts, and (iii) MMD‑VAE performs better than VAE in most omics dataset

Immediate vaginal reconstruction following pelvic exenteration using the pedicled vertical Deep Inferior Epigastric Perforator (DIEP) flap: A technical note

La reconstruction vaginale immédiate est généralement réalisée à la suite d'une exentération pelvienne pour cancer du col de l'utérus, en cas de récidive (après radiothérapie) ou de fistules radiques sévères. Le prélèvement des lambeaux sur des vaisseaux perforants, tels que le lambeau perforant basé sur le pédicule épigastrique inférieur (DIEP), permet d'obtenir des tissus viables pour la reconstruction vaginale et est associé à une réduction de la morbidité du site donneur. Ce rapport décrit la technique chirurgicale, qui est l'une des procédures de choix pour la reconstruction vaginale. Il s'agit d'une technique fiable et avantageuse, en particulier chez les femmes pour qui il ne restait plus que l'option de l'exentération en cas d’échec de l'irradiation

Earnings management and audit quality:stakeholders’ perceptions

This paper examines the perceptions of Libyan Commercial Banks’ (LCBs) stakeholders regarding the role of the external auditor in relation to earnings management (EM). A total of 28 semi-structured interviews were carried out with a range of LCB stakeholders comprising preparers of financial statements, users, regulators and academics. A questionnaire survey of stakeholders which yielded 102 Responses (response rate 53%) was also carried out. A variety of views were held which varied to some extent according to stakeholder group. A widely held perception amongst interviewees was that the auditor has the ability to detect EM practices but may not be able to prevent it. However questionnaire respondents were, in aggregate, more confident of the auditor’s ability to deter EM due to the influence of the audit report. The paper provides insights into stakeholders’ perceptions of the quality of bank audits. The findings are of particular relevance to regulators, and specifically, the Central Bank of Libya. Perceptions of audit quality raise questions about its guidance and regulations especially in connection with audit firm rotation. Perceptions of audit quality, and therefore, of the credibility of financial statements should be of interest to all stakeholders. The importance of the banking sector for society has been amply demonstrated in recent years. A well-functioning audit function is a key component of its regulation. To the best of our knowledge, this paper is the first to examine issues related to banks’ audit quality and audit firm rotation in Libya

Aberrant Epigenetic Silencing Is Triggered by a Transient Reduction in Gene Expression

Aberrant epigenetic silencing plays a major role in cancer formation by inactivating tumor suppressor genes. While the endpoints of aberrant silencing are known, i.e., promoter region DNA methylation and altered histone modifications, the triggers of silencing are not known. We used the tet-off system to test the hypothesis that a transient reduction in gene expression will sensitize a promoter to undergo epigenetic silencing.The tet responsive promoter (P(TRE)) was used to drive expression of the selectable human HPRT cDNA in independent transfectants of an Hprt deficient mouse cell line. In this system, high basal HPRT expression is greatly reduced when doxycycline (Dox) is added to the culture medium. Exposure of the P(TRE)-HPRT transfectants to Dox induced HPRT deficient clones in a time dependent manner. A molecular analysis demonstrated promoter region DNA methylation, loss of histone modifications associated with expression (i.e., H3 lysine 9 and 14 acetylation and lysine 4 methylation), and acquisition of the repressive histone modification H3 lysine 9 methylation. These changes, which are consistent with aberrant epigenetic silencing, were not present in the Dox-treated cultures, with the exception of reduced H3 lysine 14 acetylation. Silenced alleles readily reactivated spontaneously or after treatment of cells with inhibitors of histone deacetylation and/or DNA methylation, but re-silencing of reactivated alleles did not require a new round of Dox exposure. Inhibition of histone deacetylation inhibited both the induction of silencing and re-silencing, whereas inhibition of DNA methylation had no such effect.This study demonstrates that a transient reduction in gene expression triggers a pathway for aberrant silencing in mammalian cells and identifies histone deacetylation as a critical early step in this process. DNA methylation, in contrast, is a secondary step in the silencing pathway under study. A model to explain these observations is offered

FENDL: A library for fusion research and applications

The Fusion Evaluated Nuclear Data Library (FENDL) is a comprehensive and validated collection of nuclear cross section data coordinated by the International Atomic Energy Agency (IAEA) Nuclear Data Section (NDS). FENDL assembles the best nuclear data for fusion applications selected from available nuclear data libraries and has been under development for decades. FENDL contains sub-libraries for incident neutron, proton, and deuteron cross sections including general purpose and activation files used for particle transport and nuclide inventory calculations. We describe the history, selection of evaluations for the various sub-libraries (neutron, proton, deuteron) with the focus on transport and reactor dosimetry applications, the processing of the nuclear data for application codes, and the development of the TENDL-2017 library which is the currently recommended activation library for FENDL. We briefly describe the IAEA IRDFF library as the recommended library for dosimetry fusion applications. We also present work on validation of the neutron sub-library using a variety of fusion relevant computational and experimental benchmarks. A variety of cross section libraries are used for the validation work including FENDL-2.1, FENDL-3.1d, FENDL-3.2, ENDF/B-VIII.0, and JEFF-3.2 with the emphasis on the FENDL libraries. The results of the experimental validation showed that the performance of FENDL-3.2b is at least as good and in most cases better than FENDL-2.1. Future work will consider improved evaluations developed by the International Nuclear Data Evaluation Network (INDEN). Additional work will be needed to investigate differences in gas production in structural materials. Covariance matrices need to be updated to support the development of fusion technology. Additional validation work for high-energy neutrons, protons and deuterons, and the activation library will be needed.Comment: 81 pages, 114 figure

Heterochromatin Protein 1β (HP1β) has distinct functions and distinct nuclear distribution in pluripotent versus differentiated cells

Background: Pluripotent embryonic stem cells (ESCs) have the unique ability to differentiate into every cell type and to self-renew. These characteristics correlate with a distinct nuclear architecture, epigenetic signatures enriched for active chromatin marks and hyperdynamic binding of structural chromatin proteins. Recently, several chromatin-related proteins have been shown to regulate ESC pluripotency and/or differentiation, yet the role of the major heterochromatin proteins in pluripotency is unknown. Results: Here we identify Heterochromatin Protein 1β (HP1β) as an essential protein for proper differentiation, and, unexpectedly, for the maintenance of pluripotency in ESCs. In pluripotent and differentiated cells HP1β is differentially localized and differentially associated with chromatin. Deletion of HP1β, but not HP1aα, in ESCs provokes a loss of the morphological and proliferative characteristics of embryonic pluripotent cells, reduces expression of pluripotency factors and causes aberrant differentiation. However, in differentiated cells, loss of HP1β has the opposite effect, perturbing maintenance of the differentiation state and facilitating reprogramming to an induced pluripotent state. Microscopy, biochemical fractionation and chromatin immunoprecipitation reveal a diffuse nucleoplasmic distribution, weak association with chromatin and high expression levels for HP1β in ESCs. The minor fraction of HP1β that is chromatin-bound in ESCs is enriched within exons, unlike the situation in differentiated cells, where it binds heterochromatic satellite repeats and chromocenters. Conclusions: We demonstrate an unexpected duality in the role of HP1β: it is essential in ESCs for maintaining pluripotency, while it is required for proper differentiation in differentiated cells. Thus, HP1β function both depends on, and regulates, the pluripotent state