Denoising techniques reveal neural correlates of modulation masking release in auditory cortex

Hearing aids allow hearing impaired (HI) individuals to regain auditory perception in quiet settings. However, despite advances in hearing aid technology, HI individuals do not perform as well in situations with background sound as normally hearing (NH) listeners. An extensive literature demonstrates that when comparing tone detection performance in background noise, NH listeners have better thresholds when that noise is temporally modulated as compared to temporally unmodulated. However, this perceptual benefit, called Modulation Masking Release (MMR), is much reduced in HI listeners, and this is thought to be a reason for why HI listeners struggle in the presence of background sound. This study explores neural correlates of MMR in NH and HI gerbils. Trained, awake gerbils (Meriones unguiculatus) listen passively to a target tone (1 kHz) embedded in modulated or unmodulated noise while a 16-channel microelectrode array records multi-unit neural spike activity in core auditory cortex. In addition, microelectrodes also record nuisance signals due to animal movements and interference in the wireless recording setup. The current study examines the potency of three different denoising algorithms using signal detection theory. The first, amplitude rejection (AR) classifies events based on amplitude. The second, virtual referencing (VR) applies subtraction of a virtual common ground signal. The third, inter-electrode correlation (IEC) compares events across electrodes to decide whether to classify an event as noise or as spike. Using Receiver-Operator-Characteristics (ROC), these classifiers were ranked. Results suggest that combining IEC and VR leads to best denoising performance. Denoised spike train reveals a robust correlation of spike rate with behavioral performance. Results hint that neural correlates of MMR are not primarily based on spike rate coding, at least in the core auditory cortex

Analyzing The Regulation, Stability And Functional Differences Between Sin3 Isoforms In Drosophila

SIN3 is a master transcriptional regulator, conserved from yeast to mammals, that acts as a scaffold protein for a histone modifying complex. In Drosophila, a single Sin3A gene is alternatively spliced to produce distinct SIN3 isoforms; SIN3 220, SIN3 190 and SIN3 187, that differ only at their C-terminus. These isoforms are differentially expressed during development. We have shown that there is an interplay between the predominant isoforms of SIN3, SIN3 220 and SIN3 187, that possibly regulates the overall level of SIN3 in the cell. Exogenous expression of SIN3 187 reduces the level of transcript and accelerates the proteasomal degradation of endogenous SIN3 220. This feedback can possibly ensure that the appropriate isoform is present during the correct developmental stage during embryogenesis. Differential expression of the SIN3 isoforms during embryo development suggests that they perform unique and specialized functions. The SIN3 proteins form distinct isoform specific complexes. SIN3 187 interacts with a single catalytic enzyme, the HDAC RPD3, while SIN3 220 interacts with two enzymes, RPD3 and the HDM dKDM5/LID. This differential interaction of SIN3 isoforms with distinct histone modifying activities may play a role in the non-redundant functions performed by SIN3. Using previously published transcriptome data, we have identified common and unique gene targets of SIN3 and LID. In Drosophila S2 cells, knockdown of LID results in an increase in the level of H3K9ac, H3K14ac and H3K27ac at genes commonly regulated by SIN3 and LID. Since LID preferentially interacts with the SIN3 220 complex, we have investigated the histone modification patterns established by the SIN3 isoform specific complexes. We have established Drosophila cultured cells which express either the SIN3 187 or the SIN3 220 complex. The SIN3 187 and SIN3 220 complexes establish distinct histone modification patterns at target genes and differentially regulate the expression of these genes. It is possible, that the differential histone modification patterns and the consequent alteration of expression of target genes contributes to the functional differences between the SIN3 isoforms. This work enhances our understanding of SIN3 isoform function and provides further insight into the molecular mechanisms of epigenetic control of gene expression by histone modifying complexes

New Constructions with Quadratic Separation between Sensitivity and Block Sensitivity

Nisan and Szegedy [Nisan and Szegedy, 1994] conjectured that block sensitivity is at most polynomial in sensitivity for any Boolean function. There is a huge gap between the best known upper bound on block sensitivity in terms of sensitivity - which is exponential, and the best known separating examples - which give only a quadratic separation between block sensitivity and sensitivity. In this paper we give various new constructions of families of Boolean functions that exhibit quadratic separation between sensitivity and block sensitivity. Our constructions have several novel aspects. For example, we give the first direct constructions of families of Boolean functions that have both 0-block sensitivity and 1-block sensitivity quadratically larger than sensitivity

Software Architecture for Scalable Applications.

Software has traditionally been built based on a mix of the common architectures. Although several architectural styles have been documented, software developers repetitively solve the problems of scalability and extensibility and deal with the issues of incremental development and interoperability. Component Object Model (COM) is an advanced technology for object-based software development that facilitates interoperability and promotes extensibility. The extensible Markup Language (XML) is the universal format for structured documents and data on the World-Wide-Web (WWW). It describes a class of data objects called XML documents, and partially describes the behavior of the computer programs which process them. This thesis describes how the COM and the XML can be integrated to implement and extend common software architecture styles to address the problems of incremental development and scalability, and shows how the various architecture styles can be modified and how the implementation of certain COM interfaces make the solution scalable and extensible. Issues related to scalability of Web applications have been discussed and architectural solutions used to scale the software have been discussed. Guidelines to building scalable and extensible applications are given and samples to adapt common architectures using COM and XML have been introduced

Diameter Versus Certificate Complexity of Boolean Functions

In this paper, we introduce a measure of Boolean functions we call diameter, that captures the relationship between certificate complexity and several other measures of Boolean functions. Our measure can be viewed as a variation on alternating number, but while alternating number can be exponentially larger than certificate complexity, we show that diameter is always upper bounded by certificate complexity. We argue that estimating diameter may help to get improved bounds on certificate complexity in terms of sensitivity, and other measures. Previous results due to Lin and Zhang [Krishnamoorthy Dinesh and Jayalal Sarma, 2018] imply that s(f) ? ?(n^{1/3}) for transitive functions with constant alternating number. We improve and extend this bound and prove that s(f) ? ?n for transitive functions with constant alternating number, as well as for transitive functions with constant diameter. {We also show that bs(f) ? ?(n^{3/7}) for transitive functions under the weaker condition that the "minimum" diameter is constant.} Furthermore, we prove that the log-rank conjecture holds for functions of the form f(x ? y) for functions f with diameter bounded above by a polynomial of the logarithm of the Fourier sparsity of the function f

Bounds on Neutrino Mass in Viscous Cosmology

Effective field theory of dark matter fluid on large scales predicts the presence of viscosity of the order of $10^{-6} H_0 M_P^2$. It has been shown that this magnitude of viscosities can resolve the discordance between large scale structure observations and Planck CMB data in the $\sigma_8$-$\Omega_m^0$ and $H_0$-$\Omega_m^0$ parameters space. Massive neutrinos suppresses the matter power spectrum on the small length scales similar to the viscosities. We show that by including the effective viscosity, which arises from summing over non linear perturbations at small length scales, severely constrains the cosmological bound on neutrino masses. Under a joint analysis of Planck CMB and different large scale observation data, we find that upper bound on the sum of the neutrino masses at 2-$\sigma$ level, decreases from $\sum m_\nu \le 0.396\,$eV (normal hierarchy) and $\sum m_\nu \le 0.378 \,$eV (inverted hierarchy) to $\sum m_\nu \le 0.267\,$eV (normal hierarchy) and $\sum m_\nu \le 0.146\,$eV (inverted hierarchy) when the effective viscosities are included.Comment: 19 pages, 13 figure

Clinical relevance of circulating tumour cells in the bone marrow of patients with SCCHN

Background: Clinical outcome of patients with head and neck squamous cell carcinoma (SCCHN) depends on several risk factors like the presence of locoregional lymph node or distant metastases, stage, localisation and histologic differentiation of the tumour. Circulating tumour cells in the bone marrow indicate a poor prognosis for patients with various kinds of malignoma. The present study examines the clinical relevance of occult tumour cells in patients suffering from SCCHN. Patients and Methods: Bone marrow aspirates of 176 patients suffering from SCCHN were obtained prior to surgery and stained for the presence of disseminated tumour cells. Antibodies for cytokeratin 19 were used for immunohistochemical detection with APAAP on cytospin slides. Within a clinical follow-up protocol over a period of 60 months, the prognostic relevance of several clinicopathological parameters and occult tumour cells was evaluated. Results: Single CK19-expressing tumour cells could be detected in the bone marrow of 30.7% of the patients. There is a significant correlation between occult tumour cells in the bone marrow and relapse. Uni- and multivariate analysis of all clinical data showed the metastases in the locoregional lymph system and detection of disseminated tumour cells in the bone marrow to be statistically highly significant for clinical prognosis. Conclusion: The detection of minimal residual disease underlines the understanding of SCCHN as a systemic disease. Further examination of such cells will lead to a better understanding of the tumour biology, as well as to improvement of diagnostic and therapeutic strategies