Automotive three-microphone voice activity detector and noise-canceller

This paper addresses issues in improving hands-free speech recognition performance in car environments. A three-microphone array has been used to form a beamformer with leastmean squares (LMS) to improve Signal to Noise Ratio (SNR). A three-microphone array has been paralleled to a Voice Activity Detection (VAD). The VAD uses time-delay estimation together with magnitude-squared coherence (MSC)

Nanotechnology-Based Strategies for Berberine Delivery System in Cancer Treatment: Pulling Strings to Keep Berberine in Power

Cancer is a multifactorial disease characterized by complex molecular landscape and altered cell pathways that results in an abnormal cell growth. Natural compounds are target-specific and pose a limited cytotoxicity; therefore, can aid in the development of new therapeutic interventions for the treatment of this versatile disease. Berberine is a member of the protoberberine alkaloids family, mainly present in the root, stem, and bark of various trees, and has a reputed anticancer activity. Nonetheless, the limited bioavailability and low absorption rate are the two major hindrances following berberine administration as only 0.5% of ingested berberine absorbed in small intestine while this percentage is further decreased to 0.35%, when enter in systemic circulation. Nano-based formulation is believed to be an ideal candidate to increase absorption percentage as at nano scale level, compounds can absorb rapidly in gut. Nanotechnology-based therapeutic approaches have been implemented to overcome such problems, ultimately promoting a higher efficacy in the treatment of a plethora of diseases. This review present and critically discusses the anti-proliferative role of berberine and the nanotechnology-based therapeutic strategies used for the nano-scale delivery of berberine. Finally, the current approaches and promising perspectives of latest delivery of this alkaloid are also critically analyzed and discussed.NC-M acknowledges the Portuguese Foundation for Science and Technology under Horizon 2020 Program (PTDC/PSI-GER/28076/2017)

Differential neutrino condensation onto cosmic structure

Astrophysical techniques have pioneered the discovery of neutrino mass properties. Current cosmological observations give an upper bound on neutrino masses by attempting to disentangle the small neutrino contribution from the sum of all matter using precise theoretical models. We discover the differential neutrino condensation effect in our TianNu N-body simulation. Neutrino masses can be inferred using this effect by comparing galaxy properties in regions of the universe with different neutrino relative abundance (i.e. the local neutrino to cold dark matter density ratio). In “neutrino-rich” regions, more neutrinos can be captured by massive halos compared to “neutrino-poor” regions. This effect differentially skews the halo mass function and opens up the path to independent neutrino mass measurements in current or future galaxy surveys

Peptide exchange on MHC-I by TAPBPR is driven by a negative allostery release cycle.

Chaperones TAPBPR and tapasin associate with class I major histocompatibility complexes (MHC-I) to promote optimization (editing) of peptide cargo. Here, we use solution NMR to investigate the mechanism of peptide exchange. We identify TAPBPR-induced conformational changes on conserved MHC-I molecular surfaces, consistent with our independently determined X-ray structure of the complex. Dynamics present in the empty MHC-I are stabilized by TAPBPR and become progressively dampened with increasing peptide occupancy. Incoming peptides are recognized according to the global stability of the final pMHC-I product and anneal in a native-like conformation to be edited by TAPBPR. Our results demonstrate an inverse relationship between MHC-I peptide occupancy and TAPBPR binding affinity, wherein the lifetime and structural features of transiently bound peptides control the regulation of a conformational switch located near the TAPBPR binding site, which triggers TAPBPR release. These results suggest a similar mechanism for the function of tapasin in the peptide-loading complex

Measuring our universe from galaxy redshift surveys

Galaxy redshift surveys have achieved significant progress over the last couple of decades. Those surveys tell us in the most straightforward way what our local universe looks like. While the galaxy distribution traces the bright side of the universe, detailed quantitative analyses of the data have even revealed the dark side of the universe dominated by non-baryonic dark matter as well as more mysterious dark energy (or Einstein's cosmological constant). We describe several methodologies of using galaxy redshift surveys as cosmological probes, and then summarize the recent results from the existing surveys. Finally we present our views on the future of redshift surveys in the era of Precision Cosmology.Comment: 82 pages, 31 figures, invited review article published in Living Reviews in Relativity, http://www.livingreviews.org/lrr-2004-

Interplay of LFV and slepton mass splittings at the LHC as a probe of the SUSY seesaw

We study the impact of a type-I SUSY seesaw concerning lepton flavour violation (LFV) both at low-energies and at the LHC. The study of the di-lepton invariant mass distribution at the LHC allows to reconstruct some of the masses of the different sparticles involved in a decay chain. In particular, the combination with other observables renders feasible the reconstruction of the masses of the intermediate sleptons involved in $\chi_2^0\to \tilde \ell \,\ell \to \ell \,\ell\,\chi_1^0$ decays. Slepton mass splittings can be either interpreted as a signal of non-universality in the SUSY soft breaking-terms (signalling a deviation from constrained scenarios as the cMSSM) or as being due to the violation of lepton flavour. In the latter case, in addition to these high-energy processes, one expects further low-energy manifestations of LFV such as radiative and three-body lepton decays. Under the assumption of a type-I seesaw as the source of neutrino masses and mixings, all these LFV observables are related. Working in the framework of the cMSSM extended by three right-handed neutrino superfields, we conduct a systematic analysis addressing the simultaneous implications of the SUSY seesaw for both high- and low-energy lepton flavour violation. We discuss how the confrontation of slepton mass splittings as observed at the LHC and low-energy LFV observables may provide important information about the underlying mechanism of LFV.Comment: 50 pages, 42 eps Figures, typos correcte

A survey of free software for the design, analysis, modelling, and simulation of an unmanned aerial vehicle

The objective of this paper is to analyze free software for the design, analysis, modelling, and simulation of an unmanned aerial vehicle (UAV). Free software is the best choice when the reduction of production costs is necessary; nevertheless, the quality of free software may vary. This paper probably does not include all of the free software, but tries to describe or mention at least the most interesting programs. The first part of this paper summarizes the essential knowledge about UAVs, including the fundamentals of flight mechanics and aerodynamics, and the structure of a UAV system. The second section generally explains the modelling and simulation of a UAV. In the main section, more than 50 free programs for the design, analysis, modelling, and simulation of a UAV are described. Although the selection of the free software has been focused on small subsonic UAVs, the software can also be used for other categories of aircraft in some cases; e.g. for MAVs and large gliders. The applications with an historical importance are also included. Finally, the results of the analysis are evaluated and discussed—a block diagram of the free software is presented, possible connections between the programs are outlined, and future improvements of the free software are suggested. © 2015, CIMNE, Barcelona, Spain.Internal Grant Agency of Tomas Bata University in Zlin [IGA/FAI/2015/001, IGA/FAI/2014/006

A Human-Specific De Novo Protein-Coding Gene Associated with Human Brain Functions

To understand whether any human-specific new genes may be associated with human brain functions, we computationally screened the genetic vulnerable factors identified through Genome-Wide Association Studies and linkage analyses of nicotine addiction and found one human-specific de novo protein-coding gene, FLJ33706 (alternative gene symbol C20orf203). Cross-species analysis revealed interesting evolutionary paths of how this gene had originated from noncoding DNA sequences: insertion of repeat elements especially Alu contributed to the formation of the first coding exon and six standard splice junctions on the branch leading to humans and chimpanzees, and two subsequent substitutions in the human lineage escaped two stop codons and created an open reading frame of 194 amino acids. We experimentally verified FLJ33706's mRNA and protein expression in the brain. Real-Time PCR in multiple tissues demonstrated that FLJ33706 was most abundantly expressed in brain. Human polymorphism data suggested that FLJ33706 encodes a protein under purifying selection. A specifically designed antibody detected its protein expression across human cortex, cerebellum and midbrain. Immunohistochemistry study in normal human brain cortex revealed the localization of FLJ33706 protein in neurons. Elevated expressions of FLJ33706 were detected in Alzheimer's brain samples, suggesting the role of this novel gene in human-specific pathogenesis of Alzheimer's disease. FLJ33706 provided the strongest evidence so far that human-specific de novo genes can have protein-coding potential and differential protein expression, and be involved in human brain functions

Mapping alterations to the endogenous elemental distribution within the lateral ventricles and choroid plexus in brain disorders using X-ray fluorescence imaging

The choroid plexus and cerebral ventricles are critical structures for the production of cerebral spinal fluid (CSF) and play an important role in regulating ion and metal transport in the brain, however many aspects of its roles in normal physiology and disease states, such as psychiatric illness, remain unknown. The choroid plexus is difficult to examine in vivo, and in situ ex vivo, and as such has typically been examined indirectly with radiolabeled tracers or ex vivo stains, making measurements of the endogenous K+, Cl-, and Ca+ distributions unreliable. In the present study, we directly examined the distribution of endogenous ions and biologically relevant transition metals in the choroid plexus and regions surrounding the ventricles (ventricle wall, cortex, corpus callosum, striatum) using X-ray fluorescence imaging (XFI). We find that the choroid plexus was rich in Cl- and Fe while K+ levels increase further from the ventricle as Cl- levels decrease, consistent with the known role of ion transporters in the choroid plexus CSF production. A polyI:C offspring displayed enlarged ventricles, elevated Cl- surrounding the ventricles, and intraventricular calcifications. These observations fit with clinical findings in patients with schizophrenia and suggest maternal treatment with polyI:C may lead to dysfunctional ion regulation in offspring. This study demonstrates the power of XFI for examining the endogenous elemental distributions of the ventricular system in healthy brain tissue as well as disease models

Methods to Quantify Nanomaterial Association with, and Distribution across, the Blood-Brain Barrier in Vivo

The role and functional anatomy of the blood-brain barrier (BBB) is summarized to enable the investigator to appropriately address evaluation of nanomaterial interaction with, and distribution across, it into brain tissue (parenchyma). Transport mechanisms across the BBB are presented, in relation to nanomaterial physicochemical properties. Measures and test substances to assess BBB integrity/disruption/permeation are introduced, along with how they are used to interpret the results obtained with the presented methods. Experimental pitfalls and misinterpretation of results of studies of brain nanomaterial uptake are briefly summarized, that can be avoided with the methods presented in this chapter. Two methods are presented. The in situ brain perfusion technique is used to determine rate and extent of nanomaterial distribution into the brain. The capillary depletion method separates brain parenchymal tissue from the endothelial cells that contribute to the BBB. It is used to verify nanomaterial brain tissue entry. These methods are best used together, the latter refining the results obtained with the former. Details of the materials and equipment needed to conduct these methods, and description of the procedures and data interpretation, are provided