Nitric oxide as a putative retinal axon pathfinding and target recognition cue in Xenopus laevis

Nitric oxide (NO) is an atypical neurotransmitter synthesized by the enzyme nitric oxide synthase (NOS) during many stages of the Xenopus laevis life cycle. This research investigates whether the gas NO is involved in axon guidance, the neurodevelopmental process in which axons travel through the brain to their appropriate target locations to form functional neural circuitry. Through immunocytochemistry and direct labeling of the NO gas with a fluorescent dye, we have found that NOS expression corresponds spatiotemporally with the beginning of retinal axon innervation of the optic tectum in X. laevis. Our function-blocking studies in which NO is chemically inhibited suggest that NO may be necessary for correct pathfinding and targeting, evidenced by qualitative widening of the optic tract and aberrant target innervation

Initial Usability Testing of a Hand-Held Electronic Logbook Prototype for the Human Research Facility

The Apple(R) Newton(TM) MessagePad 110 was flown aboard the KC-135 reduced gravity aircraft for microgravity usability testing. The Newton served as the initial hand-held electronic logbook prototype for the International Space Station (ISS) Human Research Facility (HRF). Subjects performed three different tasks with the Newton: (1) using the stylus to tap on different sections of the screen in order to launch an application and to select options within it; (2) using the stylus to write, and; (3) correcting handwriting recognition errors in a handwriting-intensive application. Subjects rated handwriting in microgravity 'Borderline' and had great difficulties finding a way in which to adequately restrain themselves at the lower body in order to have their hands free for the Newton. Handwriting recognition was rated 'Unacceptable,' but this issue is hardware-related and not unique to the microgravity environment. It is suggested that the restraint and handwriting issues are related and require further joint research with the current Handheld Electronic Logbook prototype: the Norand Pen*key Model #6300

The practice of avant-garde in the theatre of the postavant-garde

La vanguardia histórica en su versión teatral ha dejado vigentes ciertas prácticas que materializaron en el lenguaje, en la construcción de los cuerpos y en las interrogaciones sobre el hecho de hacer teatro. En este artículo analizaremos dos puestas contemporáneas: Máquina Hamlet de El Periférico de Objetos y Proyecto Filoctetes: Lemnos en Buenos Aires, de Emilio García Wehbi, en las que focalizaremoslos procedimientoscon los quelas vanguardias históricas han funcionado en tanto condición de producción

Independent Verification and Validation of Complex User Interfaces: A Human Factors Approach

The Usability Testing and Analysis Facility (UTAF) at the NASA Johnson Space Center has identified and evaluated a potential automated software interface inspection tool capable of assessing the degree to which space-related critical and high-risk software system user interfaces meet objective human factors standards across each NASA program and project. Testing consisted of two distinct phases. Phase 1 compared analysis times and similarity of results for the automated tool and for human-computer interface (HCI) experts. In Phase 2, HCI experts critiqued the prototype tool's user interface. Based on this evaluation, it appears that a more fully developed version of the tool will be a promising complement to a human factors-oriented independent verification and validation (IV&V) process

MultiGrain: a unified image embedding for classes and instances

MultiGrain is a network architecture producing compact vector representations that are suited both for image classification and particular object retrieval. It builds on a standard classification trunk. The top of the network produces an embedding containing coarse and fine-grained information, so that images can be recognized based on the object class, particular object, or if they are distorted copies. Our joint training is simple: we minimize a cross-entropy loss for classification and a ranking loss that determines if two images are identical up to data augmentation, with no need for additional labels. A key component of MultiGrain is a pooling layer that takes advantage of high-resolution images with a network trained at a lower resolution. When fed to a linear classifier, the learned embeddings provide state-of-the-art classification accuracy. For instance, we obtain 79.4% top-1 accuracy with a ResNet-50 learned on Imagenet, which is a +1.8% absolute improvement over the AutoAugment method. When compared with the cosine similarity, the same embeddings perform on par with the state-of-the-art for image retrieval at moderate resolutions

The LARP1 La-Module recognizes both ends of TOP mRNAs

La-Related Protein 1 (LARP1) is an RNA-binding protein that regulates the stability and translation of mRNAs encoding the translation machinery, including ribosomal proteins and translation factors. These mRNAs are characterized by a 5ʹ-terminal oligopyrimidine (TOP) motif that coordinates their temporal and stoichiometric expression. While LARP1 represses TOP mRNA translation via the C-terminal DM15 region, the role of the N-terminal La-Module in the recognition and translational regulation of TOP mRNAs remains elusive. Herein we show that the LARP1 La-Module also binds TOP motifs, although in a cap-independent manner. We also demonstrate that it recognizes poly(A) RNA. Further, our data reveal that the LARP1 La-Module can simultaneously engage TOP motifs and poly(A) RNA. These results evoke an intriguing molecular mechanism whereby LARP1 could regulate translation and stabilization of TOP transcripts

ANODE: anomalous and heavy-atom density calculation

The program ANODE determines anomalous (or heavy-atom) densities by reversing the usual procedure for experimental phase determination. Instead of adding a phase shift to the heavy-atom phases to obtain a starting value for the native protein phase, this phase shift is subtracted from the native phase to obtain the heavy-atom substructure phase

The La-related protein 1-specific domain repurposes HEAT-like repeats to directly bind a 5′TOP sequence

La-related protein 1 (LARP1) regulates the stability of many mRNAs. These include 5′TOPs, mTOR-kinase responsive mRNAs with pyrimidine-rich 5′ UTRs, which encode ribosomal proteins and translation factors. We determined that the highly conserved LARP1-specific C-terminal DM15 region of human LARP1 directly binds a 5′TOP sequence. The crystal structure of this DM15 region refined to 1.86 Å resolution has three structurally related and evolutionarily conserved helix-turn-helix modules within each monomer. These motifs resemble HEAT repeats, ubiquitous helical protein-binding structures, but their sequences are inconsistent with consensus sequences of known HEAT modules, suggesting this structure has been repurposed for RNA interactions. A putative mTORC1-recognition sequence sits within a flexible loop C-terminal to these repeats. We also present modelling of pyrimidine-rich single-stranded RNA onto the highly conserved surface of the DM15 region. These studies lay the foundation necessary for proceeding toward a structural mechanism by which LARP1 links mTOR signaling to ribosome biogenesis

Defining Tobacco Regulatory Science Competencies

In 2013, the National Institutes of Health and the Food and Drug Administration funded a network of 14 Tobacco Centers of Regulatory Science (TCORS) with a mission that included research and training. A cross-TCORS Panel was established to define tobacco regulatory science (TRS) competencies to help harmonize and guide their emerging educational programs. The purpose of this paper is to describe the Panel’s work to develop core TRS domains and competencies