SALSA: Sequential Approximate Leverage-Score Algorithm with Application in Analyzing Big Time Series Data

We develop a new efficient sequential approximate leverage score algorithm, SALSA, using methods from randomized numerical linear algebra (RandNLA) for large matrices. We demonstrate that, with high probability, the accuracy of SALSA's approximations is within $(1 + O({\varepsilon}))$ of the true leverage scores. In addition, we show that the theoretical computational complexity and numerical accuracy of SALSA surpass existing approximations. These theoretical results are subsequently utilized to develop an efficient algorithm, named LSARMA, for fitting an appropriate ARMA model to large-scale time series data. Our proposed algorithm is, with high probability, guaranteed to find the maximum likelihood estimates of the parameters for the true underlying ARMA model. Furthermore, it has a worst-case running time that significantly improves those of the state-of-the-art alternatives in big data regimes. Empirical results on large-scale data strongly support these theoretical results and underscore the efficacy of our new approach.Comment: 42 pages, 7 figure

FRUIT REMOVAL BY LARGE AVIAN FRUGIVORES VARIES IN RELATION TO HABITAT QUALITY IN CONTINUOUS NEOTROPICAL RAINFOREST

Abstract ∙ Animal-mediated seed dispersal shapes key ecological processes including seedling recruitment and demography. Anthropogenic activities have substantively impacted tropical habitats, yet the degree of sensitivity exhibited by different frugivores to changes in habitat quality and how this may impact seed dispersal outcomes remains poorly understood. This is particularly true in contexts of low to moderate habitat alteration. To address this knowledge gap, we characterized the diurnal disperser community for an ecologically important canopy palm, Oenocarpus bataua, in continuous forest with differing degrees of human modification in northwest Ecuador. Our specific goal was to assess the degree to which visitation and fruit removal rates vary in relation to fine-scale forest structure. Frugivory and seed dispersal (i.e., removal of fruits with intact seeds) was dominated by three large bird species; smaller birds and some mammals visited fruiting trees but did not substantively contribute to seed dispersal. One of the three effective dispersal agents, the Long-wattled Umbrellabird (Cephalopterus penduliger), an endangered species threatened by habitat loss and degradation, exhibited higher visitation and fruit consumption rates in areas characterized by denser canopies, suggesting preference for foraging in undisturbed habitat. In contrast, two relatively common toucan species, Chocó Toucan (Ramphastos brevis) and Chestnut-mandibled Toucan (R. swainsonii), exhibited no variation in foraging behavior in relation to the habitat metrics we assessed. These findings highlight the degree to which differences in sensitivity to habitat disturbance among frugivore species may impact foraging ecology and suggest that variation in forest structure within continuous forest can impact seed removal and seed dispersal processes.Resumen ∙ La remoción de frutas por aves frugívoras de gran tamaño varía con respecto a la calidad de hábitat en bosques continuos Neotropicales La dispersión de semillas mediada por animales moldea procesos ecológicos claves como la posterior supervivencia y demografía de plántulas. Las actividades antropogénicas han afectado substancialmente los hábitats tropicales, sin embargo, el nivel de sensibilidad que presentan los diferentes frugívoros a cambios en la calidad del hábitat y cómo esto afecta a la dispersión de semillas, sigue siendo poco conocido. Esto es particularmente cierto en un contexto de poca a moderada alteración de hábitat. Para lograr comprender este vacío de conocimiento caracterizamos la comunidad de dispersores diurnos de una palma de dosel de importancia ecológica, Oenocarpus bataua, en bosques continuos con niveles diferentes de afectación humana en el noroccidente del Ecuador. Nuestro objetivo principal era de conocer el nivel en el cual las visitas y las tasas de remoción de frutas varía en relación a la estructura del bosque a escala muy fina. La frugivoría y la dispersión de semillas (es decir remoción de frutos con semillas intactas) fue dominada por tres especies de aves de gran tamaño; las aves más pequeñas y ciertos mamíferos visitaron palmas en fruto pero no contribuyeron substancialmente a la dispersión de semillas. Uno de los tres agentes de dispersión efectiva – el Pájaro Toro (Cephalopterus penduliger), una especie amenazada debido a la pérdida y degradación de su hábitat – realizó un mayor número de visitas y tasa de consumo de frutos en áreas caracterizadas por doseles más densos, lo cual sugiere una preferencia de forrajeo en hábitats no alterados. Por el contrario, dos especies relativamente comunes de tucanes, Tucán del Chocó (Ramphastos brevis) y Tucán de Pico Castaño (R. swainsonii), no presentaron diferencias en el comportamiento de forrajeo con respecto a las métricas de hábitat que nosotros utilizamos. Estos hallazgos resaltan el nivel en el cual diferencias en la sensibilidad a la alteración del hábitat entre especies frugívoras pueden impactar la ecología de forrajeo. Sugiere también que la variación en la estructura del bosque dentro de bosques continuos puede impactar la remoción de semillas y el proceso de dispersión de las mismas

Motor Function and Dopamine Release Measurements in Transgenic Huntington’s Disease Model Rats

Huntington’s disease (HD) is a fatal, genetic, neurodegenerative disorder characterized by deficits in motor and cognitive function. Here, we have quantitatively characterized motor deficiencies and dopamine release dynamics in transgenic HD model rats. Behavioral analyses were conducted using a newly-developed force-sensing runway and a previously-developed force-plate actometer. Gait disturbances were readily observed in transgenic HD rats at 12 to 15 months of age. Additionally, dopamine system challenge by ip injection of amphetamine also revealed that these rats were resistant to the expression of focused stereotypy compared to wild-type controls. Moreover, dopamine release, evoked by the application of single and multiple electrical stimulus pulses applied at different frequencies, and measured using fast-scan cyclic voltammetry at carbon-fiber microelectrodes, was diminished in transgenic HD rats compared to age-matched wild-type control rats. Collectively, these results underscore the potential contribution of dopamine release alterations to the expression of motor impairments in transgenic HD rats

The Grizzly, October 22, 2009

Big Brothers, Big Sisters: UC\u27s New Chapter • WVOU is Ursinus\u27 Hidden Treasure • Freelance Journalist Offers Students Advice • Ursinus Focuses on Pedestrian Safety, Adds More Lights to Main Street • USGA Meeting Talks Senior Halloween and New Clubs • Technology and its Role in College Student Recruitment • Dollar Store Bizarre Foods • Sophomore Week Celebration 2009 • Opinions: HPV Vaccine: One Less Reason for Some to Think That Protection is Necessary? • Men\u27s Basketball Comes Together for Another Great Season • UC Intramurals Give More Athletic Optionshttps://digitalcommons.ursinus.edu/grizzlynews/1796/thumbnail.jp

Concurrent Oral 9 - Rheumatoid Arthritis: Aetiopathogenesis [OP59-OP64]: OP59. The Value of Interleukin-17 Serum Level in Rheumatoid Arthritis Immunopathogenesis

Background: Interleukin (IL)-17 is the main Th-1 cytokine, produced by activated T-lymphocytes. The potential IL-17 value in rheumatoid arthritis (RA) pathogenesis consists of its independent inflammatory response induction and mediated stimulation of proinflammatory factors synthesis resulting in joint destruction. The aim of study was to determine the role of IL-17 in immuno-inflammatory/autoimmune reactions development and to reveal IL-17 serum level associations with clinical and immunological characteristics of RA. Methods: 50 patients with early RA (disease duration >, Russia), anti-CCP antibodies (Axies-Shield Diagnostic, UK) were revealed using ELISA immunoassay. Results: On the base of IL-17 serum level patients were divided in two groups: group1 (n = 28) were patients with normal IL-17 serum level and group2 (n = 22) were those with high IL-17 serum level. In the group2, the rate of patients' pain assessment by visual analogue scale (67.3 ± 7.2 vs 32.8 ± 4.6; P < 0.001), tender (16.7 ± 2.0 vs 8.4 ± 1.1; P < 0.01) and swollen (12.3 ± 2.3 vs 3.9 ± 0.8; P < 0.01) joint count, DAS28 (5.0 ± 0.4 vs 2.8 ± 0.2 P < 0.01) were significantly higher compare to group1. It was found that in group2 the higher T-lymphocyte amount (CD3) was due to CD4 higher quantity, at the same time CD8 amount was significantly lower (22.2 ± 1.5% vs 28.4 ± 1.7%, P < 0.05) compare to group1. This caused the immunoregulative index increasing and indicated in the lost of autoimmune process regulation, including B-lymphocytes (CD19) activation. The CD154 expression was significantly lower in the group2 (3.4 ± 0.4% vs 10.8 ± 2.8%, P < 0.05) compare to group1. The difference in autoimmune reaction indices wasn't significant between groups except antibody-producing B-lymphocytes (13.7 ± 1.5% vs 8.5 ± 1.0%, P < 0.05) and IgM RF serum level (2.9 ± 0.3 U/ml vs 1.6 ± 0.5 U/ml, P < 0.05), which were significantly higher in group1. The IL-17 level had a positive correlative connections with DAS28 (r = 0.7; P < 0.05), circulative immune complex level (r = 0.38; P < 0.05), anti-CCP antibodies (r = 0.4; P < 0.05), IgM RF (r = 0.41; P < 0.05), CD4 (r = 0.38; P < 0.05) and negative correlative connection with CD8 (r = -0.39; P < 0.05). Conclusions: The importance of IL-17 value in immuno-inflammatory and autoimmune reactions development through T-lymphocytes activation in RA pathogenesis was confirmed. Thus the influence on T-depended immuno-inflammatory reaction products synthesis could be a new therapeutic target of RA patients' management. Disclosure statement: All authors have declared no conflicts of interes

Target cell-specific synaptic dynamics of excitatory to inhibitory neuron connections in supragranular layers of human neocortex.

Rodent studies have demonstrated that synaptic dynamics from excitatory to inhibitory neuron types are often dependent on the target cell type. However, these target cell-specific properties have not been well investigated in human cortex, where there are major technical challenges in reliably obtaining healthy tissue, conducting multiple patch-clamp recordings on inhibitory cell types, and identifying those cell types. Here, we take advantage of newly developed methods for human neurosurgical tissue analysis with multiple patch-clamp recordings, post-hoc fluorescent in situ hybridization (FISH), machine learning-based cell type classification and prospective GABAergic AAV-based labeling to investigate synaptic properties between pyramidal neurons and PVALB- vs. SST-positive interneurons. We find that there are robust molecular differences in synapse-associated genes between these neuron types, and that individual presynaptic pyramidal neurons evoke postsynaptic responses with heterogeneous synaptic dynamics in different postsynaptic cell types. Using molecular identification with FISH and classifiers based on transcriptomically identified PVALB neurons analyzed by Patch-seq, we find that PVALB neurons typically show depressing synaptic characteristics, whereas other interneuron types including SST-positive neurons show facilitating characteristics. Together, these data support the existence of target cell-specific synaptic properties in human cortex that are similar to rodent, thereby indicating evolutionary conservation of local circuit connectivity motifs from excitatory to inhibitory neurons and their synaptic dynamics

Functional enhancer elements drive subclass-selective expression from mouse to primate neocortex

Viral genetic tools to target specific brain cell types in humans and non-genetic model organisms will transform basic neuroscience and targeted gene therapy. Here we used comparative epigenetics to identify thousands of human neuronal subclass-specific putative enhancers to regulate viral tools, and 34% of these were conserved in mouse. We established an AAV platform to evaluate cellular specificity of functional enhancers by multiplexed fluorescent in situ hybridization (FISH) and single cell RNA sequencing. Initial testing in mouse neocortex yields a functional enhancer discovery success rate of over 30%. We identify enhancers with specificity for excitatory and inhibitory classes and subclasses including PVALB, LAMP5, and VIP/LAMP5 cells, some of which maintain specificity in vivo or ex vivo in monkey and human neocortex. Finally, functional enhancers can be proximal or distal to cellular marker genes, conserved or divergent across species, and could yield brain-wide specificity greater than the most selective marker genes

Robot Assisted Training for the Upper Limb after Stroke (RATULS): study protocol for a randomised controlled trial.

BACKGROUND: Loss of arm function is a common and distressing consequence of stroke. We describe the protocol for a pragmatic, multicentre randomised controlled trial to determine whether robot-assisted training improves upper limb function following stroke. METHODS/DESIGN: Study design: a pragmatic, three-arm, multicentre randomised controlled trial, economic analysis and process evaluation. SETTING: NHS stroke services. PARTICIPANTS: adults with acute or chronic first-ever stroke (1 week to 5 years post stroke) causing moderate to severe upper limb functional limitation. Randomisation groups: 1. Robot-assisted training using the InMotion robotic gym system for 45 min, three times/week for 12 weeks 2. Enhanced upper limb therapy for 45 min, three times/week for 12 weeks 3. Usual NHS care in accordance with local clinical practice Randomisation: individual participant randomisation stratified by centre, time since stroke, and severity of upper limb impairment. PRIMARY OUTCOME: upper limb function measured by the Action Research Arm Test (ARAT) at 3 months post randomisation. SECONDARY OUTCOMES: upper limb impairment (Fugl-Meyer Test), activities of daily living (Barthel ADL Index), quality of life (Stroke Impact Scale, EQ-5D-5L), resource use, cost per quality-adjusted life year and adverse events, at 3 and 6 months. Blinding: outcomes are undertaken by blinded assessors. Economic analysis: micro-costing and economic evaluation of interventions compared to usual NHS care. A within-trial analysis, with an economic model will be used to extrapolate longer-term costs and outcomes. Process evaluation: semi-structured interviews with participants and professionals to seek their views and experiences of the rehabilitation that they have received or provided, and factors affecting the implementation of the trial. SAMPLE SIZE: allowing for 10% attrition, 720 participants provide 80% power to detect a 15% difference in successful outcome between each of the treatment pairs. Successful outcome definition: baseline ARAT 0-7 must improve by 3 or more points; baseline ARAT 8-13 improve by 4 or more points; baseline ARAT 14-19 improve by 5 or more points; baseline ARAT 20-39 improve by 6 or more points. DISCUSSION: The results from this trial will determine whether robot-assisted training improves upper limb function post stroke. TRIAL REGISTRATION: ISRCTN, identifier: ISRCTN69371850 . Registered 4 October 2013

cGMP-Phosphodiesterase Inhibition Enhances Photic Responses and Synchronization of the Biological Circadian Clock in Rodents

The master circadian clock in mammals is located in the hypothalamic suprachiasmatic nuclei (SCN) and is synchronized by several environmental stimuli, mainly the light-dark (LD) cycle. Light pulses in the late subjective night induce phase advances in locomotor circadian rhythms and the expression of clock genes (such as Per1-2). The mechanism responsible for light-induced phase advances involves the activation of guanylyl cyclase (GC), cGMP and its related protein kinase (PKG). Pharmacological manipulation of cGMP by phosphodiesterase (PDE) inhibition (e.g., sildenafil) increases low-intensity light-induced circadian responses, which could reflect the ability of the cGMP-dependent pathway to directly affect the photic sensitivity of the master circadian clock within the SCN. Indeed, sildenafil is also able to increase the phase-shifting effect of saturating (1200 lux) light pulses leading to phase advances of about 9 hours, as well as in C57 a mouse strain that shows reduced phase advances. In addition, sildenafil was effective in both male and female hamsters, as well as after oral administration. Other PDE inhibitors (such as vardenafil and tadalafil) also increased light-induced phase advances of locomotor activity rhythms and accelerated reentrainment after a phase advance in the LD cycle. Pharmacological inhibition of the main downstream target of cGMP, PKG, blocked light-induced expression of Per1. Our results indicate that the cGMP-dependent pathway can directly modulate the light-induced expression of clock-genes within the SCN and the magnitude of light-induced phase advances of overt rhythms, and provide promising tools to design treatments for human circadian disruptions