Muscle signaling in exercise intolerance: Insights from the McArdle mouse model

We recently generated a knock-in mouse model (PYGM p.R50X/p.R50X) of McArdle disease (myophosphorylase deficiency). One mechanistic approach to unveil the molecular alterations caused by myophosphorylase deficiency, which is arguably the paradigm of 'exercise intolerance', is to compare the skeletal-muscle tissue of McArdle, heterozygous, and healthy (wild type (wt)) mice. We analyzed in quadriceps muscle of p.R50X/p.R50X (n=4), p.R50X/wt (n=6) and wt/wt mice (n=5) (all male, 8 wk-old) molecular markers of energy-sensing pathways, oxidative phosphorylation (OXPHOS) and autophagy/proteasome systems, oxidative damage and sarcoplamic reticulum (SR) Ca handling. We found a significant group effect for total AMPK (tAMPK) and ratio of phosphorylated (pAMPK)/tAMPK (P=0.012 and 0.033), with higher mean values in p.R50X/p.R50X mice vs. the other two groups. The absence of massive accumulation of ubiquitinated proteins, autophagosomes or lysosomes in p.R50X/p.R50X mice suggested no major alterations in autophagy/proteasome systems. Citrate synthase activity was lower in p.R50X/p.R50X mice vs. the other two groups (P=0.036) but no statistical effect existed for respiratory chain complexes. We found higher levels of 4-hydroxy-2-nonenal-modified proteins in p.R50X/p.R50X and p.R50X/wt mice compared with the wt/wt group (P=0.011). Sarco(endo)plasmic reticulum ATPase 1 (SERCA1) levels detected at 110kDa tended to be higher in p.R50X/p.R50X and p.R50X/wt mice compared with wt/wt animals (P=0.076), but their enzyme activity was normal. We also found an accumulation of phosphorylated SERCA1 in p.R50X/p.R50X animals. Myophosphorylase deficiency causes alterations in sensory energetic pathways together with some evidence of oxidative damage and alterations in Ca handling but with no major alterations in OXPHOS capacity or autophagy/ubiquitination pathways, which suggests that the muscle tissue of patients is likely to adapt overall favorably to exercise training interventions.

A trait specific model of competition in a spatially structured plant community

John Warren and Chris Topping (2004). A trait specific model of competition in a spatially structured plant community. Ecological Modelling, 180 pp.477-485 RAE2008

Síndrome de Burnout em farmacêuticos

Projeto de Pós-Graduação/Dissertação apresentado à Universidade Fernando Pessoa como parte dos requisitos para obtenção do grau de Mestre em Ciências Farmacêuticas

Cuaderno de diseño regional occidente departamento de Cauca.

190 hojas.

Periodic Motion Detection and Estimation via Space-Time Sampling

A novel technique to detect and localize periodic movements in video is presented. The distinctive feature of the technique is that it requires neither feature tracking nor object segmentation. Intensity patterns along linear sample paths in space-time are used in estimation of period of object motion in a given sequence of frames. Sample paths are obtained by connecting (in space-time) sample points from regions of high motion magnitude in the first and last frames. Oscillations in intensity values are induced at time instants when an object intersects the sample path. The locations of peaks in intensity are determined by parameters of both cyclic object motion and orientation of the sample path with respect to object motion. The information about peaks is used in a least squares framework to obtain an initial estimate of these parameters. The estimate is further refined using the full intensity profile. The best estimate for the period of cyclic object motion is obtained by looking for consensus among estimates from many sample paths. The proposed technique is evaluated with synthetic videos where ground-truth is known, and with American Sign Language videos where the goal is to detect periodic hand motions.

Efficient Support for Common Relations in Lightweight Formal Reasoning Systems

In work that involves mathematical rigor, there are numerous benefits to adopting a representation of models and arguments that can be supplied to a formal reasoning or verification system: reusability, automatic evaluation of examples, and verification of consistency and correctness. However, accessibility has not been a priority in the design of formal verification tools that can provide these benefits. In earlier work [Lap09a], we attempt to address this broad problem by proposing several specific design criteria organized around the notion of a natural context: the sphere of awareness a working human user maintains of the relevant constructs, arguments, experiences, and background materials necessary to accomplish the task at hand. This work expands one aspect of the earlier work by considering more extensively an essential capability for any formal reasoning system whose design is oriented around simulating the natural context: native support for a collection of mathematical relations that deal with common constructs in arithmetic and set theory. We provide a formal definition for a context of relations that can be used to both validate and assist formal reasoning activities. We provide a proof that any algorithm that implements this formal structure faithfully will necessary converge. Finally, we consider the efficiency of an implementation of this formal structure that leverages modular implementations of well-known data structures: balanced search trees and transitive closures of hypergraphs.

Safe Compositional Specification of Networking Systems: A Compositional Analysis Approach

We present a type inference algorithm, in the style of compositional analysis, for the language TRAFFIC—a specification language for flow composition applications proposed in [2]—and prove that this algorithm is correct: the typings it infers are principal typings, and the typings agree with syntax-directed type checking on closed flow specifications. This algorithm is capable of verifying partial flow specifications, which is a significant improvement over syntax-directed type checking algorithm presented in [3]. We also show that this algorithm runs efficiently, i.e., in low-degree polynomial time.

Type Systems for a Network Specification Language With Multiple-Choice Let

When analysing the behavior of complex networked systems, it is often the case that some components within that network are only known to the extent that they belong to one of a set of possible "implementations" – e.g., versions of a specific protocol, class of schedulers, etc. In this report we augment the specification language considered in BUCSTR-2004-021, BUCS-TR-2005-014, BUCS-TR-2005-015, and BUCS-TR-2005-033, to include a non-deterministic multiple-choice let-binding, which allows us to consider compositions of networking subsystems that allow for looser component specifications.

Traffic Characteristics and Communication Patterns in Blogosphere

We present a thorough characterization of the access patterns in blogspace -- a fast-growing constituent of the content available through the Internet -- which comprises a rich interconnected web of blog postings and comments by an increasingly prominent user community that collectively define what has become known as the blogosphere. Our characterization of over 35 million read, write, and administrative requests spanning a 28-day period is done from three different blogosphere perspectives. The server view characterizes the aggregate access patterns of all users to all blogs; the user view characterizes how individual users interact with blogosphere objects (blogs); the object view characterizes how individual blogs are accessed. Our findings support two important conclusions. First, we show that the nature of interactions between users and objects is fundamentally different in blogspace than that observed in traditional web content. Access to objects in blogspace could be conceived as part of an interaction between an author and its readership. As we show in our work, such interactions range from one-to-many "broadcast-type" and many-to-one "registration-type" communication between an author and its readers, to multi-way, iterative "parlor-type" dialogues among members of an interest group. This more-interactive nature of the blogosphere leads to interesting traffic and communication patterns, which are different from those observed in traditional web content. Second, we identify and characterize novel features of the blogosphere workload, and we investigate the similarities and differences between typical web server workloads and blogosphere server workloads. Given the increasing share of blogspace traffic, understanding such differences is important for capacity planning and traffic engineering purposes, for example.

Sequential Memory with ART: A Self-Organizing Network Capable of Learning Sequences of Patterns

A model which extends the adaptive resonance theory model to sequential memory is presented. This new model learns sequences of events and recalls a sequence when presented with parts of the sequence. A sequence can have repeated events and different sequences can share events. The ART model is modified by creating interconnected sublayers within ART's F2 layer. Nodes within F2 learn temporal patterns by forming recency gradients within LTM. Versions of the ART model like ART I, ART 2, and fuzzy ART can be used.

Current methods and advances in forecasting of wind power generation

Wind power generation differs from conventional thermal generation due to the stochastic nature of wind. Thus wind power forecasting plays a key role in dealing with the challenges of balancing supply and demand in any electricity system, given the uncertainty associated with the wind farm power output. Accurate wind power forecasting reduces the need for additional balancing energy and reserve power to integrate wind power. Wind power forecasting tools enable better dispatch, scheduling and unit commitment of thermal generators, hydro plant and energy storage plant and more competitive market trading as wind power ramps up and down on the grid. This paper presents an in-depth review of the current methods and advances in wind power forecasting and prediction. Firstly, numerical wind prediction methods from global to local scales, ensemble forecasting, upscaling and downscaling processes are discussed. Next the statistical and machine learning approach methods are detailed. Then the techniques used for benchmarking and uncertainty analysis of forecasts are overviewed, and the performance of various approaches over different forecast time horizons is examined. Finally, current research activities, challenges and potential future developments are appraised.

Analyses on Gold and US Dollar in Vietnam's Transitional Economy

This paper looks into economic insights offerred by considerations of two important financial markets in Vietnam, gold and USD. In general, the paper focuses on time series properties, mainly returns at different frequencies, and test the weak-form efficient market hypothesis. All the test rejects the efficiency of both gold and foreign exchange markets. All time series exhibit strong serial correlations. ARMA-GARCH specifications appear to have performed well with different time series. In all cases the changing volatility phenomenon is strongly supported through empirical data. An additional test is performed on the daily USD return to try to capture the impacts of Asian financial crisis and daily price limits applicable. No substantial impacts of the Asian crisis and the central bank-devised limits are found to influence the risk level of daily USD return.

Chondrogenesis and mineralization during in vitro culture of human mesenchymal stem cells on three-dimensional woven scaffolds.

Human mesenchymal stem cells (hMSCs) and three-dimensional (3D) woven poly(ɛ-caprolactone) (PCL) scaffolds are promising tools for skeletal tissue engineering. We hypothesized that in vitro culture duration and medium additives can individually and interactively influence the structure, composition, mechanical, and molecular properties of engineered tissues based on hMSCs and 3D poly(ɛ-caprolactone). Bone marrow hMSCs were suspended in collagen gel, seeded on scaffolds, and cultured for 1, 21, or 45 days under chondrogenic and/or osteogenic conditions. Structure, composition, biomechanics, and gene expression were analyzed. In chondrogenic medium, cartilaginous tissue formed by day 21, and hypertrophic mineralization was observed in the newly formed extracellular matrix at the interface with underlying scaffold by day 45. Glycosaminoglycan, hydroxyproline, and calcium contents, and alkaline phosphatase activity depended on culture duration and medium additives, with significant interactive effects (all p < 0.0001). The 45-day constructs exhibited mechanical properties on the order of magnitude of native articular cartilage (aggregate, Young's, and shear moduli of 0.15, 0.12, and 0.033 MPa, respectively). Gene expression was characteristic of chondrogenesis and endochondral bone formation, with sequential regulation of Sox-9, collagen type II, aggrecan, core binding factor alpha 1 (Cbfα1)/Runx2, bone sialoprotein, bone morphogenetic protein-2, and osteocalcin. In contrast, osteogenic medium produced limited osteogenesis. Long-term culture of hMSC on 3D scaffolds resulted in chondrogenesis and regional mineralization at the interface between soft, newly formed engineered cartilage, and stiffer underlying scaffold. These findings merit consideration when developing grafts for osteochondral defect repair.

The evolutionary origins of human patience: temporal preferences in chimpanzees, bonobos, and human adults.

To make adaptive choices, individuals must sometimes exhibit patience, forgoing immediate benefits to acquire more valuable future rewards [1-3]. Although humans account for future consequences when making temporal decisions [4], many animal species wait only a few seconds for delayed benefits [5-10]. Current research thus suggests a phylogenetic gap between patient humans and impulsive, present-oriented animals [9, 11], a distinction with implications for our understanding of economic decision making [12] and the origins of human cooperation [13]. On the basis of a series of experimental results, we reject this conclusion. First, bonobos (Pan paniscus) and chimpanzees (Pan troglodytes) exhibit a degree of patience not seen in other animals tested thus far. Second, humans are less willing to wait for food rewards than are chimpanzees. Third, humans are more willing to wait for monetary rewards than for food, and show the highest degree of patience only in response to decisions about money involving low opportunity costs. These findings suggest that core components of the capacity for future-oriented decisions evolved before the human lineage diverged from apes. Moreover, the different levels of patience that humans exhibit might be driven by fundamental differences in the mechanisms representing biological versus abstract rewards.

Mechanosensitive neurons on the internal reproductive tract contribute to egg-laying-induced acetic acid attraction in Drosophila.

Selecting a suitable site to deposit their eggs is an important reproductive need of Drosophila females. Although their choosiness toward egg-laying sites is well documented, the specific neural mechanism that activates females' search for attractive egg-laying sites is not known. Here, we show that distention and contraction of females' internal reproductive tract triggered by egg delivery through the tract plays a critical role in activating such search. We found that females start to exhibit acetic acid (AA) attraction prior to depositing each egg but no attraction when they are not laying eggs. Artificially distending the reproductive tract triggers AA attraction in non-egg-laying females, whereas silencing the mechanosensitive neurons we identified that can sense the contractile status of the tract eliminates such attraction. Our work uncovers the circuit basis of an important reproductive need of Drosophila females and provides a simple model for dissecting the neural mechanism that underlies a reproductive need-induced behavioral modification.