Axessibility: a LaTeX Package for Mathematical Formulae Accessibility in PDF Documents

Accessing mathematical formulae within digital documents is challenging for blind people. In particular, document formats designed for printing, such as PDF, structure math content for visual access only. While accessibility features exist to present PDF content non-visually, formulae support is limited to providing replacement text that can be read by a screen reader or displayed on a braille bar. However, the operation of inserting replacement text is left to document authors, who rarely provide such content. Furthermore, at best, description of the formulae are provided. Thus, conveying detailed understanding of complex formulae is nearly impossible. In this contribution we report our ongoing research on Axessibility, a LATEX package framework that automates the process of making mathematical formulae accessible by providing the formulae LATEX code as PDF replacement text. Axessibility is coupled with external scripts to automate its integration in existing documents, expand user shorthand macros to standard LATEX representation, and custom screen reader dictionaries that improve formulae reading on screen readers

STRATIGRAPHY, PALEOGEOGRAPHY AND GENETIC MODEL OF LATE CARNIAN CARBONATE BRECCIAS (CASTRO FORMATION, LOMBARDY, ITALY)

The stratigraphic and paleogeographic analysis of the Carnian-Norian boundary succession in central Lombardy allows the recognition of a new unit, the Castro Formation. This unit, 100-250 m thick, is represented by carbonatic intraformational breccias and associated limestones. Two lithozones have been recognized in the Castro Fm.: the lower one, heteropic with the S.Giovanni Bianco Fm., with dark dolomitic limestones and breccias intercalations, and the upper lithozone, massive, with amalgamated calcareous breccias. Microfacies, recrystallized and often tectonized, consist of mudstones, wackestones and fine packstones, locally rich in ostracods. Geochemical analyses show differences between the Castro Fm. and the overlying and underlying units, possibly because of early diagenetic meteoric imprint. The Castro Fm. depositional setting is represented by coastal ephemeral lakes with periodic emersions and erosional, tectonically controlled phenomena in a monsoonal regime

Dynein Function and Protein Clearance Changes in Tumor Cells Induced by a Kunitz-Type Molecule, Amblyomin-X

Amblyomin-X is a Kunitz-type recombinant protein identified from the transcriptome of the salivary glands of the tick Amblyomma cajennense and has anti-coagulant and antitumoral activity. the supposed primary target of this molecule is the proteasome system. Herein, we elucidated intracellular events that are triggered by Amblyomin-X treatment in an attempt to provide new insight into how this serine protease inhibitor, acting on the proteasome, could be comparable with known proteasome inhibitors. the collective results showed aggresome formation after proteasome inhibition that appeared to occur via the non-exclusive ubiquitin pathway. Additionally, Amblyomin-X increased the expression of various chains of the molecular motor dynein in tumor cells, modulated specific ubiquitin linkage signaling and inhibited autophagy activation by modulating mTOR, LC3 and AMBRA1 with probable dynein involvement. Interestingly, one possible role for dynein in the mechanism of action of Amblyomin-X was in the apoptotic response and its crosstalk with autophagy, which involved the factor Bim; however, we observed no changes in the apoptotic response related to dynein in the experiments performed. the characteristics shared among Amblyomin-X and known proteasome inhibitors included NF-kappa B blockage and nascent polypeptide-dependent aggresome formation. Therefore, our study describes a Kunitz-type protein that acts on the proteasome to trigger distinct intracellular events compared to classic known proteasome inhibitors that are small-cell-permeable molecules. in investigating the experiments and literature on Amblyomin-X and the known proteasome inhibitors, we also found differences in the structures of the molecules, intracellular events, dynein involvement and tumor cell type effects. These findings also reveal a possible new target for Amblyomin-X, i.e., dynein, and may serve as a tool for investigating tumor cell death associated with proteasome inhibition.Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)Butantan Inst, Biochem & Biophys Lab, São Paulo, BrazilUniversidade Federal de São Paulo, Dept Biochem, São Paulo, BrazilUniversidade Federal de São Paulo, Dept Biochem, São Paulo, BrazilFAPESP: 2011/05969-4FAPESP: CAT/CEPID 1998/14307-9FAPESP: CETICs 2013/07467-1Web of Scienc

Bayesian spatio-temporal models for mapping TB mortality risk and its relationship with social inequities in a region from Brazilian Legal Amazon

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Intermittent C1-Inhibitor Deficiency Associated with Recessive Inheritance: Functional and Structural Insight

C1-inhibitor is a serine protease inhibitor (serpin) controlling complement and contact system activation. Gene mutations result in reduced C1-inhibitor functional plasma level causing hereditary angioedema, a life-threatening disorder. Despite a stable defect, the clinical expression of hereditary angioedema is unpredictable, and the molecular mechanism underlying this variability remains undisclosed. Here we report functional and structural studies on the Arg378Cys C1-inhibitor mutant found in a patient presenting reduced C1-inhibitor levels, episodically undergoing normalization. Expression studies resulted in a drop in mutant C1-innhibitor secretion compared to wild-type. Notwithstanding, the purified proteins had similar features. Thermal denaturation experiments showed a comparable denaturation profile, but the mutant thermal stability decays when tested in conditions reproducing intracellular crowding.Our findings suggest that once correctly folded, the Arg378Cys C1-inhibitor is secreted as an active, although quite unstable, monomer. However, it could bear a folding defect, occasionally promoting protein oligomerization and interfering with the secretion process, thus accounting for its plasma level variability. This defect is exacerbated by the nature of the mutation since the acquired cysteine leads to the formation of non-functional homodimers through inter-molecular disulphide bonding. All the proposed phenomena could be modulated by specific environmental conditions, rendering this mutant exceptionally vulnerable to mild stress

Association of Accelerometry-Measured Physical Activity and Cardiovascular Events in Mobility-Limited Older Adults: The LIFE (Lifestyle Interventions and Independence for Elders) Study.

BACKGROUND:Data are sparse regarding the value of physical activity (PA) surveillance among older adults-particularly among those with mobility limitations. The objective of this study was to examine longitudinal associations between objectively measured daily PA and the incidence of cardiovascular events among older adults in the LIFE (Lifestyle Interventions and Independence for Elders) study. METHODS AND RESULTS:Cardiovascular events were adjudicated based on medical records review, and cardiovascular risk factors were controlled for in the analysis. Home-based activity data were collected by hip-worn accelerometers at baseline and at 6, 12, and 24 months postrandomization to either a physical activity or health education intervention. LIFE study participants (n=1590; age 78.9±5.2 [SD] years; 67.2% women) at baseline had an 11% lower incidence of experiencing a subsequent cardiovascular event per 500 steps taken per day based on activity data (hazard ratio, 0.89; 95% confidence interval, 0.84-0.96; P=0.001). At baseline, every 30 minutes spent performing activities ≥500 counts per minute (hazard ratio, 0.75; confidence interval, 0.65-0.89 [P=0.001]) were also associated with a lower incidence of cardiovascular events. Throughout follow-up (6, 12, and 24 months), both the number of steps per day (per 500 steps; hazard ratio, 0.90, confidence interval, 0.85-0.96 [P=0.001]) and duration of activity ≥500 counts per minute (per 30 minutes; hazard ratio, 0.76; confidence interval, 0.63-0.90 [P=0.002]) were significantly associated with lower cardiovascular event rates. CONCLUSIONS:Objective measurements of physical activity via accelerometry were associated with cardiovascular events among older adults with limited mobility (summary score >10 on the Short Physical Performance Battery) both using baseline and longitudinal data. CLINICAL TRIAL REGISTRATION:URL: http://www.clinicaltrials.gov. Unique identifier: NCT01072500