Role of Inhibition in Binaural Processing

The medial and lateral superior olives (MSO, LSO) are the lowest order cell groups in the mammalian auditory circuit to receive massive binaural input. The MSO functions in part to encode interaural time differences (ITD), the predominant cue for localization of low frequency sounds. Binaural inputs to the MSO consist of excitatory projections from the cochlear nuclei (CN) and inhibitory projections from both the medial nucleus of the trapezoid body (MNTB) and lateral nucleus of the trapezoid body (LNTB). The interaction of excitatory and inhibitory currents within an MSO cell\u27s soma and dendrites over the backdrop of its intrinsic ionic conductances imbues ITD sensitivity to these neurons. Lloyd Jeffress proposed a coincidence detection circuit in which arrays of neurons receive sub-threshold excitatory inputs via delay lines that represent sound location as a place code of activity patterns within the cell group (Jeffress, 1948). The Jeffress place code model later found a neural instantiation in the MSO. Recent in vivo (McAlpine et al., 2001; Brand et al., 2002) studies have shown that peak discharge rates do not fall within the ecological range as the Jeffress model predicts but instead ITD is coded by changes in discharge rate. The timing of inhibition relative to excitation modulates the discharge rates of MSO cells (Brand et al., 2002; Chirila et al., 2007); however, the details of this circuit, such as the onset time of inhibition, are not well known. Although the MNTB and LNTB have been investigated in vivo and in vitro , they have not been well characterized with respect to their function in ITD processing in larger mammals. Additionally, inhibition is modulated by anesthesia and confounds in vivo experiments that examine the careful interplay of excitatory and inhibitory effects in the MSO. For this reason, these physiological experiments were performed on decerebrate unanaesthetized animals. Further investigation of the anatomical organization of inhibitory inputs was carried out as the basis for a comprehensive model of the MSO that incorporates the effects of binaural inhibiting projections to MSO neurons.;Unbiased stereological counts of the MNTB, MSO and subdivisions of the LNTB showed that the MSO and MNTB contain approximately the same number of cells. The main (m)LNTB, posteroventral (pv)LNTB and the hilus (h)LNTB are estimated to contain 3800, 1400, and 200 neurons respectively. Tonotopic organization of the MNTB and MSO show that in the low frequency area, MSO cells outnumber MNTB cells 2 to 1, suggesting a divergent innervation of the MSO from the MNTB. Injection of the retrograde tracer, biotinylated dextrane amine, in the MSO, labeled cells in the MNTB, pvLNTB and mLNTB and defines the important role that these sub-nuclei, and in particular the pvLNTB, have in ITD coding. Computational modeling of a single MSO cell suggests that when two sources of inhibition temporally frame excitation the coincidence detection window is refined and less sensitive to temporal fluctuations that otherwise might degrade ITD sensitivity. Finally, physiological properties of MNTB cells reveal a heterogeneous population of responses and less precise temporal coding than are found in their inputs, globular bushy cells

Thermal Degradation Comparison of Amino Acid Salts, Alkanolamines and Diamines in CO2 Capture

In the selection of candidates for post-combustion CO2 absorption, solvent degradation has become a general concern due to the significant impact on operational cost and the intention to use thermal compression from high temperature stripping to minimize the overall process energy. In this research, structural analogs of amino acid salts, alkanolamines and diamines were thermally degraded in order to explore their thermal stability from a structural standpoint. Functional groups, amine orders and steric effect were investigated for their impact on amine thermal degradation. Primary amines with chain structures showed a thermal stability trend as diamine \u3e alkanolamine \u3e amino acid salt. For alknolamine and diamine structural isomers, the primary amines are more stable than the secondary amines. Steric hindrance around the amine group was shown to play a positive role in protecting amines against thermal degradation

Nine Strategies to Guide Efforts to Reduce Youth Gun Violence

Gun violence, including that perpetrated by young people, is a pernicious problem for many communities, particularly those facing historically high levels of concentrated disadvantage and disinvestment. To effectively address youth gun violence and establish and maintain peace, communities need stable safety infrastructures and effective interventions.We developed a research-based practice guide to help local governments, law enforcement agencies, and antiviolence organizations determine how to shape their approaches to reducing gun violence perpetrated by young people ages 10 to 25 in gangs or groups. Here, we summarize the guide's recommendations on how to develop effective interventions and build a broader safety infrastructure that supports the success of different partners working to protect young people and communities from gun violence

A Research-Based Practice Guide to Reduce Youth Gun and Gang/Group Violence

While extensive research exists, the field lacks a current and translational synthesis of what works to reduce youth group and gun violence. In response, the Urban Institute developed a research-based practice guide to inform local government, law enforcement, and community-violence-intervention stakeholders as they implement new antiviolence interventions and refine existing ones. To inform the development of the guide, Urban researchers conducted a comprehensive literature synthesis of research on violence reduction interventions and conducted a scan of interventions representing well-known antiviolence models and other innovative strategies. Drawing on the findings from the literature synthesis and scan of practice, the practice guide presents recommendations around nine practice areas related to building an infrastructure to support a multi-faceted antiviolence strategy and implementing effective violence reduction programs

Boolean analysis identifies CD38 as a biomarker of aggressive localized prostate cancer.

The introduction of serum Prostate Specific Antigen (PSA) testing nearly 30 years ago has been associated with a significant shift towards localized disease and decreased deaths due to prostate cancer. Recognition that PSA testing has caused over diagnosis and over treatment of prostate cancer has generated considerable controversy over its value, and has spurred efforts to identify prognostic biomarkers to distinguish patients who need treatment from those that can be observed. Recent studies show that cancer is heterogeneous and forms a hierarchy of tumor cell populations. We developed a method of identifying prostate cancer differentiation states related to androgen signaling using Boolean logic. Using gene expression data, we identified two markers, CD38 and ARG2, that group prostate cancer into three differentiation states. Cancers with CD38-, ARG2- expression patterns, corresponding to an undifferentiated state, had significantly lower 10-year recurrence-free survival compared to the most differentiated group (CD38+ARG2+). We carried out immunohistochemical (IHC) staining for these two markers in a single institution (Stanford; n = 234) and multi-institution (Canary; n = 1326) cohorts. IHC staining for CD38 and ARG2 in the Stanford cohort demonstrated that combined expression of CD38 and ARG2 was prognostic. In the Canary cohort, low CD38 protein expression by IHC was significantly associated with recurrence-free survival (RFS), seminal vesicle invasion (SVI), extra-capsular extension (ECE) in univariable analysis. In multivariable analysis, ARG2 and CD38 IHC staining results were not independently associated with RFS, overall survival, or disease-specific survival after adjusting for other factors including SVI, ECE, Gleason score, pre-operative PSA, and surgical margins

Towards local electromechanical probing of cellular and biomolecular systems in a liquid environment

Electromechanical coupling is ubiquitous in biological systems with examples ranging from simple piezoelectricity in calcified and connective tissues to voltage-gated ion channels, energy storage in mitochondria, and electromechanical activity in cardiac myocytes and outer hair cell stereocilia. Piezoresponse force microscopy (PFM) has originally emerged as a technique to study electromechanical phenomena in ferroelectric materials, and in recent years, has been employed to study a broad range of non-ferroelectric polar materials, including piezoelectric biomaterials. At the same time, the technique has been extended from ambient to liquid imaging on model ferroelectric systems. Here, we present results on local electromechanical probing of several model cellular and biomolecular systems, including insulin and lysozyme amyloid fibrils, breast adenocarcinoma cells, and bacteriorhodopsin in a liquid environment. The specific features of SPM operation in liquid are delineated and bottlenecks on the route towards nanometer-resolution electromechanical imaging of biological systems are identified.Comment: 37 pages (including refs), 8 figure

Thrombolytic removal of intraventricular haemorrhage in treatment of severe stroke: results of the randomised, multicentre, multiregion, placebo-controlled CLEAR III trial

Background: Intraventricular haemorrhage is a subtype of intracerebral haemorrhage, with 50% mortality and serious disability for survivors. We aimed to test whether attempting to remove intraventricular haemorrhage with alteplase versus saline irrigation improved functional outcome. Methods: In this randomised, double-blinded, placebo-controlled, multiregional trial (CLEAR III), participants with a routinely placed extraventricular drain, in the intensive care unit with stable, non-traumatic intracerebral haemorrhage volume less than 30 mL, intraventricular haemorrhage obstructing the 3rd or 4th ventricles, and no underlying pathology were adaptively randomly assigned (1:1), via a web-based system to receive up to 12 doses, 8 h apart of 1 mg of alteplase or 0·9% saline via the extraventricular drain. The treating physician, clinical research staff, and participants were masked to treatment assignment. CT scans were obtained every 24 h throughout dosing. The primary efficacy outcome was good functional outcome, defined as a modified Rankin Scale score (mRS) of 3 or less at 180 days per central adjudication by blinded evaluators. This study is registered with ClinicalTrials.gov, NCT00784134. Findings: Between Sept 18, 2009, and Jan 13, 2015, 500 patients were randomised: 249 to the alteplase group and 251 to the saline group. 180-day follow-up data were available for analysis from 246 of 249 participants in the alteplase group and 245 of 251 participants in the placebo group. The primary efficacy outcome was similar in each group (good outcome in alteplase group 48% vs saline 45%; risk ratio [RR] 1·06 [95% CI 0·88–1·28; p=0·554]). A difference of 3·5% (RR 1·08 [95% CI 0·90–1·29], p=0·420) was found after adjustment for intraventricular haemorrhage size and thalamic intracerebral haemorrhage. At 180 days, the treatment group had lower case fatality (46 [18%] vs saline 73 [29%], hazard ratio 0·60 [95% CI 0·41–0·86], p=0·006), but a greater proportion with mRS 5 (42 [17%] vs 21 [9%]; RR 1·99 [95% CI 1·22–3·26], p=0·007). Ventriculitis (17 [7%] alteplase vs 31 [12%] saline; RR 0·55 [95% CI 0·31–0·97], p=0·048) and serious adverse events (114 [46%] alteplase vs 151 [60%] saline; RR 0·76 [95% CI 0·64–0·90], p=0·002) were less frequent with alteplase treatment. Symptomatic bleeding (six [2%] in the alteplase group vs five [2%] in the saline group; RR 1·21 [95% CI 0·37–3·91], p=0·771) was similar. Interpretation: In patients with intraventricular haemorrhage and a routine extraventricular drain, irrigation with alteplase did not substantially improve functional outcomes at the mRS 3 cutoff compared with irrigation with saline. Protocol-based use of alteplase with extraventricular drain seems safe. Future investigation is needed to determine whether a greater frequency of complete intraventricular haemorrhage removal via alteplase produces gains in functional status

Identification and quantification of microplastics in wastewater using focal plane array-based reflectance micro-FT-IR imaging

Microplastics (<5 mm) have been documented in environmental samples on a global scale. While these pollutants may enter aquatic environments via wastewater treatment facilities, the abundance of microplastics in these matrices has not been investigated. Although efficient methods for the analysis of microplastics in sediment samples and marine organisms have been published, no methods have been developed for detecting these pollutants within organic-rich wastewater samples. In addition, there is no standardized method for analyzing microplastics isolated from environmental samples. In many cases, part of the identification protocol relies on visual selection before analysis, which is open to bias. In order to address this, a new method for the analysis of microplastics in wastewater was developed. A pretreatment step using 30% hydrogen peroxide (H2O2) was employed to remove biogenic material, and focal plane array (FPA)-based reflectance micro-Fourier-transform (FT-IR) imaging was shown to successfully image and identify different microplastic types (polyethylene, polypropylene, nylon-6, polyvinyl chloride, polystyrene). Microplastic-spiked wastewater samples were used to validate the methodology, resulting in a robust protocol which was nonselective and reproducible (the overall success identification rate was 98.33%). The use of FPA-based micro-FT-IR spectroscopy also provides a considerable reduction in analysis time compared with previous methods, since samples that could take several days to be mapped using a single-element detector can now be imaged in less than 9 h (circular filter with a diameter of 47 mm). This method for identifying and quantifying microplastics in wastewater is likely to provide an essential tool for further research into the pathways by which microplastics enter the environment.This work is funded by a NERC (Natural Environment Research Council) CASE studentship (NE/K007521/1) with contribution from industrial partner Fera Science Ltd., United Kingdom. The authors would like to thank Peter Vale, from Severn Trent Water Ltd, for providing access to and additionally Ashley Howkins (Brunel University London) for providing travel and assistance with the sampling of the Severn Trent wastewater treatment plant in Derbyshire, UK. We are grateful to Emma Bradley and Chris Sinclair for providing helpful suggestions for our research

Electronic structure in a transition metal dipnictide TaAs2

The family of transition metal dipnictides (TMDs) has been of theoretical and experimental interest because this family hosts topological states and extremely large magnetoresistance (MR). Recently, TaAs2, a member of this family, has been predicted to support a topological crystalline insulating state. Here, by using high resolution. Angle resolved photoemission spectroscopy (ARPES), we reveal both closed and open pockets in the metallic Fermi surface and linearly dispersive bands on the (201) surface, along with the presence of extreme MR observed from magneto-transport measurements. A comparison of the ARPES results with first-principles computations show that the linearly dispersive bands on the measured surface of TaAs2 are trivial bulk bands. The absence of symmetry-protected surface state on the (201) surface indicates its topologically dark nature. The presence of open Fermi surface features suggests that the open orbit fermiology could contribute to the extremely large MR of TaAs.Comment: 13 pages, 5 figure

Telomeric expression sites are highly conserved in trypanosoma brucei

Subtelomeric regions are often under-represented in genome sequences of eukaryotes. One of the best known examples of the use of telomere proximity for adaptive purposes are the bloodstream expression sites (BESs) of the African trypanosome Trypanosoma brucei. To enhance our understanding of BES structure and function in host adaptation and immune evasion, the BES repertoire from the Lister 427 strain of T. brucei were independently tagged and sequenced. BESs are polymorphic in size and structure but reveal a surprisingly conserved architecture in the context of extensive recombination. Very small BESs do exist and many functioning BESs do not contain the full complement of expression site associated genes (ESAGs). The consequences of duplicated or missing ESAGs, including ESAG9, a newly named ESAG12, and additional variant surface glycoprotein genes (VSGs) were evaluated by functional assays after BESs were tagged with a drug-resistance gene. Phylogenetic analysis of constituent ESAG families suggests that BESs are sequence mosaics and that extensive recombination has shaped the evolution of the BES repertoire. This work opens important perspectives in understanding the molecular mechanisms of antigenic variation, a widely used strategy for immune evasion in pathogens, and telomere biology