Spectral networks and Fenchel-Nielsen coordinates

We explain that spectral networks are a unifying framework that incorporates both shear (Fock-Goncharov) and length-twist (Fenchel-Nielsen) coordinate systems on moduli spaces of flat SL(2,C) connections, in the following sense. Given a spectral network W on a punctured Riemann surface C, we explain the process of "abelianization" which relates flat SL(2)-connections (with an additional structure called "W-framing") to flat C*-connections on a covering. For any W, abelianization gives a construction of a local Darboux coordinate system on the moduli space of W-framed flat connections. There are two special types of spectral network, combinatorially dual to ideal triangulations and pants decompositions; these two types of network lead to Fock-Goncharov and Fenchel-Nielsen coordinates respectively.Comment: 63 pages; v2: expository improvements, journal versio

Visual cue training to improve walking and turning after stroke:a study protocol for a multi-centre, single blind randomised pilot trial

Visual information comprises one of the most salient sources of information used to control walking and the dependence on vision to maintain dynamic stability increases following a stroke. We hypothesize, therefore, that rehabilitation efforts incorporating visual cues may be effective in triggering recovery and adaptability of gait following stroke. This feasibility trial aims to estimate probable recruitment rate, effect size, treatment adherence and response to gait training with visual cues in contrast to conventional overground walking practice following stroke.Methods/design: A 3-arm, parallel group, multi-centre, single blind, randomised control feasibility trial will compare overground visual cue training (O-VCT), treadmill visual cue training (T-VCT), and usual care (UC). Participants (n = 60) will be randomly assigned to one of three treatments by a central randomisation centre using computer generated tables to allocate treatment groups. The research assessor will remain blind to allocation. Treatment, delivered by physiotherapists, will be twice weekly for 8 weeks at participating outpatient hospital sites for the O-VCT or UC and in a University setting for T-VCT participants.Individuals with gait impairment due to stroke, with restricted community ambulation (gait spee

Study of the IgG endoglycosidase EndoS in group A streptococcal phagocyte resistance and virulence

<p>Abstract</p> <p>Background</p> <p>The secreted enzyme EndoS, an endoglycosidase from <it>Streptococcus pyogenes</it>, hydrolyzes the <it>N</it>-linked glycan of the constant region of immunoglobulin G (IgG) heavy chain and renders the antibody unable to interact with Fc receptors and elicit effector functions. In this study we couple targeted allelic replacement mutagenesis and heterologous expression to elucidate the contribution of EndoS to group A <it>Streptococcus </it>(GAS) phagocyte resistance and pathogenicity <it>in vitro </it>and <it>in vivo</it>.</p> <p>Results</p> <p>Knocking out the EndoS gene in GAS M1T1 background revealed no significant differences in bacterial survival in immune cell killing assays or in a systemic mouse model of infection. However, exogenous addition and heterologous expression of EndoS was found to increase GAS resistance to killing by neutrophils and monocytes <it>in vitro</it>. Additionally, heterologous expression of EndoS in M49 GAS increased mouse virulence <it>in vivo</it>.</p> <p>Conclusions</p> <p>We conclude that in a highly virulent M1T1 background, EndoS has no significant impact on GAS phagocyte resistance and pathogenicity. However, local accumulation or high levels of expression of EndoS in certain GAS strains may contribute to virulence.</p

8.9 hr rotation in the partly burnt runaway stellar remnant LP 40-365 (GD 492)

We report the detection of 8.914 hr variability in both optical and ultraviolet light curves of LP 40-365 (also known as GD 492), the prototype for a class of partly burnt runaway stars that have been ejected from a binary due to a thermonuclear supernova event. We first detected this 1.0% amplitude variation in optical photometry collected by the Transiting Exoplanet Survey Satellite (TESS). Reanalysis of observations from the Hubble Space Telescope at the TESS period and ephemeris reveal a 5.8% variation in the ultraviolet of this 9800 K stellar remnant. We propose that this 8.914 hr photometric variation reveals the current surface rotation rate of LP 40-365, and is caused by some kind of surface inhomogeneity rotating in and out of view, though a lack of observed Zeeman splitting puts an upper limit on the magnetic field of <20 kG. We explore ways in which the present rotation period can constrain progenitor scenarios if angular momentum was mostly conserved, which suggests that the survivor LP 40-365 was not the donor star but was most likely the bound remnant of a mostly disrupted white dwarf that underwent advanced burning from an underluminous (Type Iax) supernova.Peer ReviewedPostprint (published version

A key role for the urokinase plasminogen activator (uPA) in invasive Group A streptococcal infection

Recruitment of the serine protease plasmin is central to the pathogenesis of many bacterial species, including Group A streptococcus (GAS), a leading cause of morbidity and mortality globally. A key process in invasive GAS disease is the ability to accumulate plasmin at the cell surface, however the role of host activators of plasminogen in this process is poorly understood. Here, we demonstrate for the first time that the urokinase-type plasminogen activator (uPA) contributes to plasmin recruitment and subsequent invasive disease initiation in vivo. In the absence of a source of host plasminogen activators, streptokinase (Ska) was required to facilitate cell surface plasmin acquisition by GAS. However, in the absence of Ska, host activators were sufficient to promote cell surface plasmin acquisition by GAS strain 5448 during incubation with plasminogen or human plasma. Furthermore, GAS were able mediate a significant increase in the activation of zymogen pro-uPA in human plasma. In order to assess the contribution of uPA to invasive GAS disease, a previously undescribed transgenic mouse model of infection was employed. Both C57/black 6J, and AlbPLG1 mice expressing the human plasminogen transgene, were significantly more susceptible to invasive GAS disease than uPA−/− mice. The observed decrease in virulence in uPA−/−mice was found to correlate directly with a decrease in bacterial dissemination and reduced cell surface plasmin accumulation by GAS. These findings have significant implications for our understanding of GAS pathogenesis, and research aimed at therapeutic targeting of plasminogen activation in invasive bacterial infections

Azithromycin Synergizes with Cationic Antimicrobial Peptides to Exert Bactericidal and Therapeutic Activity Against Highly Multidrug-Resistant Gram-Negative Bacterial Pathogens

AbstractAntibiotic resistance poses an increasingly grave threat to the public health. Of pressing concern, rapid spread of carbapenem-resistance among multidrug-resistant (MDR) Gram-negative rods (GNR) is associated with few treatment options and high mortality rates. Current antibiotic susceptibility testing guiding patient management is performed in a standardized manner, identifying minimum inhibitory concentrations (MIC) in bacteriologic media, but ignoring host immune factors. Lacking activity in standard MIC testing, azithromycin (AZM), the most commonly prescribed antibiotic in the U.S., is never recommended for MDR GNR infection. Here we report a potent bactericidal action of AZM against MDR carbapenem-resistant isolates of Pseudomonas aeruginosa, Klebsiella pneumoniae, and Acinetobacter baumannii. This pharmaceutical activity is associated with enhanced AZM cell penetration in eukaryotic tissue culture media and striking multi-log-fold synergies with host cathelicidin antimicrobial peptide LL-37 or the last line antibiotic colistin. Finally, AZM monotherapy exerts clear therapeutic effects in murine models of MDR GNR infection. Our results suggest that AZM, currently ignored as a treatment option, could benefit patients with MDR GNR infections, especially in combination with colistin

Using a stair horizontal-vertical illusion to increase foot clearance over an inconsistently taller stair-riser

Introduction: Stair falls can be caused by inconsistent stair dimensions. During ascent, inconsistently taller stair risers lead to reduced foot clearances as the inconsistency goes unnoticed. A stair horizontal-vertical illusion increases perceived riser heights and foot clearance and could offset reduced foot clearances over inconsistently taller risers, though this might impact other stair safety measures. Method: Twelve participants (age: 22 (3) years) ascended a seven-step staircase under three conditions: i) all steps consistent in riser height (consistent), ii) a 1cm increase in step 5 riser height (inconsistent) and iii) a 1cm increase in step 5 riser height, superimposed with a stair horizontal-vertical illusion (illusion). Vertical foot clearance, foot overhang, and margins of stability were assessed over step 4, 5 and 6. Perceived riser height due to the illusion was determined through a computer perception test. A One-Way Repeated Measures ANOVA compared biomechanical variables between conditions. A One Sample t test compared perceived riser height to the true height. Results: Over the inconsistent step 5, foot clearance reduced by 0.8cm compared to consistent. Illusion increased foot clearance by 1.1cm and decreased foot overhang by 4% compared to inconsistent. On step 4 the illusion led to more anterior instability compared to inconsistent. Illusion and inconsistent led to more mediolateral stability compared to consistent. The illusion increased perceived riser height by 12%. Discussion: Foot clearance reductions over inconsistently taller risers can be offset by a stair horizontal-vertical illusion. Additional benefits included a safer foot overhang and unaffected stability over the inconsistent riser. Changes to step 4 stability might have resulted from leaning forward to look at the step 5 illusion. The stair horizontal-vertical illusion could be a practical solution for inconsistently taller stair risers, where a rebuild is usually the only solution

Reduced sensitivity for visual textures affects judgments of shape-from-shading and step climbing behaviour in older adults

Falls on stairs are a major hazard for older adults. Visual decline in normal aging can affect step climbing ability, altering gait and reducing toe clearance. Here we show that a loss of fine-grained visual information associated with age can affect the perception of surface undulations in patterned surfaces. We go on to show that such cues affect the limb trajectories of young adults, but due to their lack of sensitivity, not that of older adults. Interestingly neither the perceived height of a step nor conscious awareness are altered by our visual manipulation but stepping behaviour is: suggesting that the influence of shape perception on stepping behaviour is via the unconscious, action-centred, dorsal visual pathway