Control of cell surface expression of GABA receptors by a conserved region at the end of the N-terminal extracellular domain of receptor subunits.

Type A γ-aminobutyric acid receptors (GABARs) represent a family of pentameric GABA-gated Cl/HCO ion channels which mediate inhibitory transmission in the central nervous system. Cell surface expression of GABARs, a prerequisite for their function, is dependent on the appropriate assembly of the receptor subunits and their transient interactions with molecular chaperones within the endoplasmic reticulum (ER) and Golgi apparatus. Here, we describe a highly conserved amino acid sequence within the extracellular N-terminal domain of the receptor subunits adjoining the first transmembrane domain as a region important for GABAR processing within the ER.

The Perils of Being Unhinged: On the Accuracy of Classifiers Minimizing a Noise-Robust Convex Loss.

van Rooyen, Menon, and Williamson (2015) introduced a notion of convex loss functions being robust to random classification noise and established that the "unhinged" loss function is robust in this sense. In this letter, we study the accuracy of binary classifiers obtained by minimizing the unhinged loss and observe that even for simple linearly separable data distributions, minimizing the unhinged loss may only yield a binary classifier with accuracy no better than random guessing.

Motion Polytopes in Virtual Reality for Shared Control in Remote Manipulation Applications.

In remote applications that mandate human supervision, shared control can prove vital by establishing a harmonious balance between the high-level cognition of a user and the low-level autonomy of a robot. Though in practice, achieving this balance is a challenging endeavor that largely depends on whether the operator effectively interprets the underlying shared control. Inspired by recent works on using immersive technologies to expose the internal shared control, we develop a virtual reality system to visually guide human-in-the-loop manipulation.

A Holistic Approach to Human-Supervised Humanoid Robot Operations in Extreme Environments.

Nuclear energy will play a critical role in meeting clean energy targets worldwide. However, nuclear environments are dangerous for humans to operate in due to the presence of highly radioactive materials. Robots can help address this issue by allowing remote access to nuclear and other highly hazardous facilities under human supervision to perform inspection and maintenance tasks during normal operations, help with clean-up missions, and aid in decommissioning.

Benign overfitting in linear regression.

The phenomenon of benign overfitting is one of the key mysteries uncovered by deep learning methodology: deep neural networks seem to predict well, even with a perfect fit to noisy training data. Motivated by this phenomenon, we consider when a perfect fit to training data in linear regression is compatible with accurate prediction. We give a characterization of linear regression problems for which the minimum norm interpolating prediction rule has near-optimal prediction accuracy.

On the Effect of the Activation Function on the Distribution of Hidden Nodes in a Deep Network.

We analyze the joint probability distribution on the lengths of the vectors of hidden variables in different layers of a fully connected deep network, when the weights and biases are chosen randomly according to gaussian distributions. We show that if the activation function satisfies a minimal set of assumptions, satisfied by all activation functions that we know that are used in practice, then, as the width of the network gets large, the "length process" converges in probability to a length map that is determined as a simple function of the variances of the random weights and biases and the activation function . We also show that this convergence may fail for that violate our assumptions.

Mutation p.R356Q in the Collybistin Phosphoinositide Binding Site Is Associated With Mild Intellectual Disability.

The recruitment of inhibitory GABA receptors to neuronal synapses requires a complex interplay between receptors, neuroligins, the scaffolding protein gephyrin and the GDP-GTP exchange factor collybistin (CB). Collybistin is regulated by protein-protein interactions at the N-terminal SH3 domain, which can bind neuroligins 2/4 and the GABAR α2 subunit. Collybistin also harbors a RhoGEF domain which mediates interactions with gephyrin and catalyzes GDP-GTP exchange on Cdc42.

Gradient Descent with Identity Initialization Efficiently Learns Positive-Definite Linear Transformations by Deep Residual Networks.

We analyze algorithms for approximating a function mapping to using deep linear neural networks, that is, that learn a function parameterized by matrices and defined by . We focus on algorithms that learn through gradient descent on the population quadratic loss in the case that the distribution over the inputs is isotropic. We provide polynomial bounds on the number of iterations for gradient descent to approximate the least-squares matrix , in the case where the initial hypothesis has excess loss bounded by a small enough constant.

Machiavellian Ways to Academic Cheating: A Mediational and Interactional Model.

Academic cheating has become a pervasive practice from primary schools to university. This study aims at investigating this phenomenon through a nomological network which integrates different theoretical frameworks and models, such as trait and social-cognitive theories and models regarding the approaches to learning and contextual/normative environment. Results on a sample of more than 200 Italian university students show that the Amoral Manipulation facet of Machiavellianism, Academic Moral Disengagement, Deep Approach to Learning, and Normative Academic Cheating are significantly associated with Individual Academic Cheating.

Field Application of U/U Measurements To Detect Reoxidation and Mobilization of U(IV).

Biostimulation to induce reduction of soluble U(VI) to relatively immobile U(IV) is an effective strategy for decreasing aqueous U(VI) concentrations in contaminated groundwater systems. If oxidation of U(IV) occurs following the biostimulation phase, U(VI) concentrations increase, challenging the long-term effectiveness of this technique. However, detecting U(IV) oxidation through dissolved U concentrations alone can prove difficult in locations with few groundwater wells to track the addition of U to a mass of groundwater.

Nonproliferative and Proliferative Lesions of the Rat and Mouse Skeletal Tissues (Bones, Joints, and Teeth).

The INHAND (International Harmonization of Nomenclature and Diagnostic Criteria for Lesions in Rats and Mice) Project (www.toxpath.org/inhand.

Microbial Metagenomics Reveals Climate-Relevant Subsurface Biogeochemical Processes.

Microorganisms play key roles in terrestrial system processes, including the turnover of natural organic carbon, such as leaf litter and woody debris that accumulate in soils and subsurface sediments. What has emerged from a series of recent DNA sequencing-based studies is recognition of the enormous variety of little known and previously unknown microorganisms that mediate recycling of these vast stores of buried carbon in subsoil compartments of the terrestrial system. More importantly, the genome resolution achieved in these studies has enabled association of specific members of these microbial communities with carbon compound transformations and other linked biogeochemical processes-such as the nitrogen cycle-that can impact the quality of groundwater, surface water, and atmospheric trace gas concentrations.

Missense Mutation R338W in ARHGEF9 in a Family with X-linked Intellectual Disability with Variable Macrocephaly and Macro-Orchidism.

Non-syndromal X-linked intellectual disability (NS-XLID) represents a broad group of clinical disorders in which ID is the only clinically consistent manifestation. Although in many cases either chromosomal linkage data or knowledge of the >100 existing XLID genes has assisted mutation discovery, the underlying cause of disease remains unresolved in many families. We report the resolution of a large family (K8010) with NS-XLID, with variable macrocephaly and macro-orchidism.

Novel Missense Mutation A789V in IQSEC2 Underlies X-Linked Intellectual Disability in the MRX78 Family.

Disease gene discovery in neurodevelopmental disorders, including X-linked intellectual disability (XLID) has recently been accelerated by next-generation DNA sequencing approaches. To date, more than 100 human X chromosome genes involved in neuronal signaling pathways and networks implicated in cognitive function have been identified. Despite these advances, the mutations underlying disease in a large number of XLID families remained unresolved.

Physico-Chemical Heterogeneity of Organic-Rich Sediments in the Rifle Aquifer, CO: Impact on Uranium Biogeochemistry.

The Rifle alluvial aquifer along the Colorado River in west central Colorado contains fine-grained, diffusion-limited sediment lenses that are substantially enriched in organic carbon and sulfides, as well as uranium, from previous milling operations. These naturally reduced zones (NRZs) coincide spatially with a persistent uranium groundwater plume. There is concern that uranium release from NRZs is contributing to plume persistence or will do so in the future.

Identification of Bacteria Synthesizing Ribosomal RNA in Response to Uranium Addition During Biostimulation at the Rifle, CO Integrated Field Research Site.

Understanding which organisms are capable of reducing uranium at historically contaminated sites provides crucial information needed to evaluate treatment options and outcomes. One approach is determination of the bacteria which directly respond to uranium addition. In this study, uranium amendments were made to groundwater samples from a site of ongoing biostimulation with acetate.

Long-term in situ oxidation of biogenic uraninite in an alluvial aquifer: impact of dissolved oxygen and calcium.

Oxidative dissolution controls uranium release to (sub)oxic pore waters from biogenic uraninite produced by natural or engineered processes, such as bioremediation. Laboratory studies show that uraninite dissolution is profoundly influenced by dissolved oxygen (DO), carbonate, and solutes such as Ca(2+). In complex and heterogeneous subsurface environments, the concentrations of these solutes vary in time and space.

Spatial distribution of an uranium-respiring betaproteobacterium at the Rifle, CO field research site.

The Department of Energy's Integrated Field-Scale Subsurface Research Challenge Site (IFRC) at Rifle, Colorado was created to address the gaps in knowledge on the mechanisms and rates of U(VI) bioreduction in alluvial sediments. Previous studies at the Rifle IFRC have linked microbial processes to uranium immobilization during acetate amendment. Several key bacteria believed to be involved in radionuclide containment have been described; however, most of the evidence implicating uranium reduction with specific microbiota has been indirect.

Uranium bioreduction rates across scales: biogeochemical hot moments and hot spots during a biostimulation experiment at Rifle, Colorado.

We aim to understand the scale-dependent evolution of uranium bioreduction during a field experiment at a former uranium mill site near Rifle, Colorado. Acetate was injected to stimulate Fe-reducing bacteria (FeRB) and to immobilize aqueous U(VI) to insoluble U(IV). Bicarbonate was coinjected in half of the domain to mobilize sorbed U(VI).

Disturbed subsurface microbial communities follow equivalent trajectories despite different structural starting points.

Microbial community structure, and niche and neutral processes can all influence response to disturbance. Here, we provide experimental evidence for niche versus neutral and founding community effects during a bioremediation-related organic carbon disturbance. Subsurface sediment, partitioned into 22 flow-through columns, was stimulated in situ by the addition of acetate as a carbon and electron donor source.

Metabolic interdependencies between phylogenetically novel fermenters and respiratory organisms in an unconfined aquifer.

Fermentation-based metabolism is an important ecosystem function often associated with environments rich in organic carbon, such as wetlands, sewage sludge and the mammalian gut. The diversity of microorganisms and pathways involved in carbon and hydrogen cycling in sediments and aquifers and the impacts of these processes on other biogeochemical cycles remain poorly understood. Here we used metagenomics and proteomics to characterize microbial communities sampled from an aquifer adjacent to the Colorado River at Rifle, CO, USA, and document interlinked microbial roles in geochemical cycling.

Field evidence of selenium bioreduction in a uranium-contaminated aquifer.

Removal of selenium from groundwater was documented during injection of acetate into a uranium-contaminated aquifer near Rifle, Colorado (USA). Bioreduction of aqueous selenium to its elemental form (Se0) concentrated it within mineralized biofilms affixed to tubing used to circulate acetate-amended groundwater. Scanning and transmission electron microscopy revealed close association between Se0 precipitates and cell surfaces, with Se0 aggregates having a diameter of 50-60 nm.

Expression of integrin and CD44 receptors recognising osteopontin in the normal and LPS-lesioned rat substantia nigra.

The multifunctional protein osteopontin (OPN) is expressed in the substantia nigra (SN) and protects nigral dopaminergic neurones against toxic insult in animal models of Parkinson's disease, although the mechanisms involved are uncertain. In the periphery, OPN regulates inflammatory processes by interacting with integrin and CD44 receptors but the presence and distribution of these sites in SN is unknown. We investigated the expression of integrin receptor subunits and CD44 receptors in the normal SN and after induction of inflammation by lipopolysaccharide (LPS), and their interaction with OPN.