Effects of Noise on Galaxy Isophotes

The study of shapes of the images of objects is an important issue not only because it reveals its dynamical state but also it helps to understand the object's evolutionary history. We discuss a new technique in cosmological image analysis which is based on a set of non-parametric shape descriptors known as the Minkowski Functionals (MFs). These functionals are extremely versatile and under some conditions give a complete description of the geometrical properties of objects. We believe that MFs could be a useful tool to extract information about the shapes of galaxies, clusters of galaxies and superclusters. The information revealed by MFs can be utilized along with the knowledge obtained from currently popular methods and thus could improve our understanding of the true shapes of cosmological objects.Comment: 3 pages, 1 figure, to appear in "The IGM/Galaxy Connection - The Distribution of Baryons at z=0" Conference Proceeding

Rapid, Single-Step Protein Encapsulation via Flash NanoPrecipitation

Flash NanoPrecipitation (FNP) is a rapid method for encapsulating hydrophobic materials in polymer nanoparticles with high loading capacity. Encapsulating biologics such as proteins remains a challenge due to their low hydrophobicity (logP \u3c 6) and current methods require multiple processing steps. In this work, we report rapid, single-step protein encapsulation via FNP using bovine serum albumin (BSA) as a model protein. Nanoparticle formation involves complexation and precipitation of protein with tannic acid and stabilization with a cationic polyelectrolyte. Nanoparticle self-assembly is driven by hydrogen bonding and electrostatic interactions. Using this approach, high encapsulation efficiency (up to ~80%) of protein can be achieved. The resulting nanoparticles are stable at physiological pH and ionic strength. Overall, FNP is a rapid, efficient platform for encapsulating proteins for various applications

Verification and Control of Partially Observable Probabilistic Real-Time Systems

We propose automated techniques for the verification and control of probabilistic real-time systems that are only partially observable. To formally model such systems, we define an extension of probabilistic timed automata in which local states are partially visible to an observer or controller. We give a probabilistic temporal logic that can express a range of quantitative properties of these models, relating to the probability of an event's occurrence or the expected value of a reward measure. We then propose techniques to either verify that such a property holds or to synthesise a controller for the model which makes it true. Our approach is based on an integer discretisation of the model's dense-time behaviour and a grid-based abstraction of the uncountable belief space induced by partial observability. The latter is necessarily approximate since the underlying problem is undecidable, however we show how both lower and upper bounds on numerical results can be generated. We illustrate the effectiveness of the approach by implementing it in the PRISM model checker and applying it to several case studies, from the domains of computer security and task scheduling

A combined computational-experimental approach to define the structural origin of antibody recognition of sialyl-Tn, a tumor-associated carbohydrate antigen.

Anti-carbohydrate monoclonal antibodies (mAbs) hold great promise as cancer therapeutics and diagnostics. However, their specificity can be mixed, and detailed characterization is problematic, because antibody-glycan complexes are challenging to crystallize. Here, we developed a generalizable approach employing high-throughput techniques for characterizing the structure and specificity of such mAbs, and applied it to the mAb TKH2 developed against the tumor-associated carbohydrate antigen sialyl-Tn (STn). The mAb specificity was defined by apparent KD values determined by quantitative glycan microarray screening. Key residues in the antibody combining site were identified by site-directed mutagenesis, and the glycan-antigen contact surface was defined using saturation transfer difference NMR (STD-NMR). These features were then employed as metrics for selecting the optimal 3D-model of the antibody-glycan complex, out of thousands plausible options generated by automated docking and molecular dynamics simulation. STn-specificity was further validated by computationally screening of the selected antibody 3D-model against the human sialyl-Tn-glycome. This computational-experimental approach would allow rational design of potent antibodies targeting carbohydrates

Effects of External Vibration Stimulation on Internal Rotation Range of Motion and Hamstring Strength

Introduction Whole body and localized vibration therapy have gained increased use in the fitness community, clinical setting, and research Efficacy as a modality option is yet to be determined Objective Evaluate the effects of localized vibration treatment (LVT) to the sacral region on shoulder internal rotation (IR) range of motion (ROM) and isometric hamstring strength Participants 50 Concordia University DPT Students 28 females 22 males Age: 22-33 (Avg. 24) Methods Baseline dominant extremity shoulder IR ROM measured in supine with manual goniometry Baseline hamstring strength measurements in prone using MicroFETTM (hand held dynamometer), taken post 1 practice test Therapeutic intervention: application of LVT using the Hypervolt PlusR tool to 5 predetermined landmarks on sacral region for 40 seconds total Post-therapeutic intervention measurements Prone hamstring strength using MicroFETTM Supine shoulder IR ROM with manual goniometry Results Statistical significance (p \u3c 0.05) was demonstrated for increased shoulder IR (mean difference 3.5 degrees) Hamstring strength did not rise to statistical significance (p=0.09) Conclusion Vibration stimulation to neural dense area such as the sacral region can improve shoulder internal rotation range of motion. Clinical Relevance Potential acute gains in ROM and strength to allow for greater effectiveness in subsequent PT interventions In sport training, LVT could be used as a quick and effective tool for increased athletic performance Future Research Procedural modifications may improve outcomes Pelvis stabilization methods may demonstrate clinically significant improvements in hamstring strength Incremental testing post LVT delivery to assess duration of effect

Vitamin D deficiency in Malawian adults with pulmonary tuberculosis : risk factors and treatment outcomes

The study was supported by a Wellcome Trust (London, UK) Clinical PhD Fellowship awarded to DS (086757/Z/08/A) and the Malawi Liverpool Wellcome Trust (MLW) Core grant from the Wellcome Trust.SETTING: Vitamin D deficiency is common in African adults with tuberculosis (TB), and may be exacerbated by the metabolic effects of anti-tuberculosis drugs and antiretroviral therapy (ART). It is unclear whether vitamin D deficiency influences response to antituberculosis treatment. OBJECTIVES : To describe risk factors for baseline vitamin D deficiency in Malawian adults with pulmonary TB, assess the relationship between serum 25-hydroxy vitamin D (25[OH]D) concentration and treatment response, and evaluate whether the administration of anti-tuberculosis drugs and ART is deleterious to vitamin D status during treatment. DESIGN: A prospective longitudinal cohort study. RESULTS : The median baseline 25(OH)D concentration of the 169 patients (58% human immunodeficiency virus [HIV] infected) recruited was 57 nmol/l; 47 (28%) had vitamin D deficiency (<50 nmol/l). Baseline 25(OH)D concentrations were lower during the cold season (P < 0.001), with food insecurity (P = 0.034) or in patients who consumed alcohol (P = 0.019). No relationship between vitamin D status and anti-tuberculosis treatment response was found. 25(OH)D concentrations increased during anti-tuberculosis treatment, irrespective of HIV status or use of ART. CONCLUSIONS : Vitamin D deficiency is common among TB patients in Malawi, but this does not influence treatment response. Adverse metabolic effects of drug treatment may be compensated by the positive impact of clinical recovery preventing exacerbation of vitamin D deficiency during anti-tuberculosis treatment.Publisher PDFPeer reviewe

Kinetics of Mycobacterium tuberculosis-specific IFN-γ responses and sputum bacillary clearance in HIV-infected adults during treatment of pulmonary tuberculosis

This work was supported by funding from the Wellcome Trust (UK) through Fellowships 092773/Z/10/Z (to D.T.M), 086757/Z/08/Z (to D.J.S) and 088696/Z/09/Z (to H.C.M). Core funding from the Wellcome Trust supports the laboratory and office facilities at the Malawi-Liverpool-Wellcome Trust Clinical Research Programme.In HIV-uninfected adults with pulmonary tuberculosis (TB), anti-TB treatment is associated with changes in Mycobacterium tuberculosis (Mtb)-specific immune responses, which correlate with sputum bacillary load. It is unclear if this occurs in HIV-infected TB patients. We investigated changes in Mtb-specific immune responses and sputum bacillary clearance during anti-TB treatment in HIV-infected and HIV-uninfected adults with pulmonary TB. Sputum bacillary load was assessed by smear microscopy and culture. Mtb-specific IFN-γ secreting peripheral blood mononuclear cells were enumerated using an ELISPOT assay following stimulation with PPD, ESAT-6 and CFP-10. The baseline frequency of Mtb-specific IFN-γ secreting cells was lower in HIV-infected than HIV-uninfected patients (median PPD 32 vs. 104 Spot Forming Units (SFU), p = 0.05; CFP-10 19 vs. 74 SFU, p = 0.01). ESAT-6-specific IFN-γ secreting cells and sputum bacillary load declined progressively during treatment in both HIV-infected and HIV-uninfected patients. HIV infection did not influence the 2-month sputum culture conversion rate (Odds Ratio 0.89, p = 0.95). These findings suggest that changes in ESAT-6-specific immune responses during anti-TB treatment correspond with changes in sputum bacillary load irrespective of host HIV infection status. The utility of Mtb-specific IFN-γ responses as a proxy measure of treatment response in HIV-infected TB patients warrants further evaluation in other settings.Publisher PDFPeer reviewe

\u27Mutiny on the Bounty\u27: the genetic history of Norfolk Island reveals extreme gender-biased admixture

Background The Pacific Oceania region was one of the last regions of the world to be settled via human migration. Here we outline a settlement of this region that has given rise to a uniquely admixed population. The current Norfolk Island population has arisen from a small number of founders with mixed Caucasian and Polynesian ancestry, descendants of a famous historical event. The ‘Mutiny on the Bounty’ has been told in history books, songs and the big screen, but recently this story can be portrayed through comprehensive molecular genetics. Written history details betrayal and murder leading to the founding of Pitcairn Island by European mutineers and the Polynesian women who left Tahiti with them. Investigation of detailed genealogical records supports historical accounts. Findings Using genetics, we show distinct maternal Polynesian mitochondrial lineages in the present day population, as well as a European centric Y-chromosome phylogeny. These results comprehensively characterise the unique gender-biased admixture of this genetic isolate and further support the historical records relating to Norfolk Island. Conclusions Our results significantly refine previous population genetic studies investigating Polynesian versus Caucasian diversity in the Norfolk Island population and add information that is beneficial to future disease and gene mapping studies

Outcomes in patients with severe COVID-19 disease treated with tocilizumab: a case-controlled study

© The Author(s) 2020. Published by Oxford University Press on behalf of the Association of Physicians. All rights reserved. For permissions, please email: [email protected]. BACKGROUND: COVID-19 is an ongoing threat to society. Patients who develop the most severe forms of the disease have high mortality. The interleukin-6 inhibitor tocilizumab has the potential to improve outcomes in these patients by preventing the development of cytokine release storm. AIMS: To evaluate the outcomes of patients with severe COVID-19 disease treated with the interleukin-6 inhibitor tocilizumab. METHODS: We conducted a retrospective, case-control, single-center study in patients with severe to critical COVID-19 disease treated with tocilizumab. Disease severity was defined based on the amount of oxygen supplementation required. The primary endpoint was the overall mortality. Secondary endpoints were mortality in non-intubated patients and mortality in intubated patients. RESULTS: A total of 193 patients were included in the study. Ninety-six patients received tocilizumab, while 97 served as the control group. The mean age was 60 years. Patients over 65 years represented 43% of the population. More patients in the tocilizumab group reported fever, cough and shortness of breath (83%, 80% and 96% vs. 73%, 69% and 71%, respectively). There was a non-statistically significant lower mortality in the treatment group (52% vs. 62.1%, P = 0.09). When excluding intubated patients, there was statistically significant lower mortality in patients treated with tocilizumab (6% vs. 27%, P = 0.024). Bacteremia was more common in the control group (24% vs. 13%, P = 0.43), while fungemia was similar for both (3% vs. 4%, P = 0.72). CONCLUSION: Our study showed a non-statistically significant lower mortality in patients with severe to critical COVID-19 disease who received tocilizumab. When intubated patients were excluded, the use of tocilizumab was associated with lower mortality