ATRA mechanically reprograms pancreatic stellate cells to suppress matrix remodelling and inhibit cancer cell invasion

Pancreatic ductal adenocarcinoma (PDAC) is a highly aggressive malignancy with a dismal survival rate. Persistent activation of pancreatic stellate cells (PSCs) can perturb the biomechanical homoeostasis of the tumour microenvironment to favour cancer cell invasion. Here we report that ATRA, an active metabolite of vitamin A, restores mechanical quiescence in PSCs via a mechanism involving a retinoic acid receptor beta (RAR-β)-dependent downregulation of actomyosin (MLC-2) contractility. We show that ATRA reduces the ability of PSCs to generate high traction forces and adapt to extracellular mechanical cues (mechanosensing), as well as suppresses force-mediated extracellular matrix remodelling to inhibit local cancer cell invasion in 3D organotypic models. Our findings implicate a RAR-β/MLC-2 pathway in peritumoural stromal remodelling and mechanosensory-driven activation of PSCs, and further suggest that mechanical reprogramming of PSCs with retinoic acid derivatives might be a viable alternative to stromal ablation strategies for the treatment of PDAC

Design Principles for Sparse Matrix Multiplication on the GPU

We implement two novel algorithms for sparse-matrix dense-matrix multiplication (SpMM) on the GPU. Our algorithms expect the sparse input in the popular compressed-sparse-row (CSR) format and thus do not require expensive format conversion. While previous SpMM work concentrates on thread-level parallelism, we additionally focus on latency hiding with instruction-level parallelism and load-balancing. We show, both theoretically and experimentally, that the proposed SpMM is a better fit for the GPU than previous approaches. We identify a key memory access pattern that allows efficient access into both input and output matrices that is crucial to getting excellent performance on SpMM. By combining these two ingredients---(i) merge-based load-balancing and (ii) row-major coalesced memory access---we demonstrate a 4.1x peak speedup and a 31.7% geomean speedup over state-of-the-art SpMM implementations on real-world datasets.Comment: 16 pages, 7 figures, International European Conference on Parallel and Distributed Computing (Euro-Par) 201

Evaluation of the sciatic nerve location regarding its relationship to the piriformis muscle

Background: The localisation of sciatic nerve (SN) is essential for the achievement of several procedures performed in the gluteal region. This study proposed to investigate the location of SN regarding its relationship to the piriformis (PM) by the line joining the posterior superior iliac spine (PSIS), ischial tuberosity (IT) and greater trochanter (GT).Materials and methods: SN-PM relationship was examined in 204 specimens from 102 embalmed cadavers (55 males, 47 females). Distances between PSIS, IT and GT were measured. Midpoints of SN at the lower edge of PM (S1) and IT-GT line (S2) were marked. Perpendicular line from S1 to PSIS-GT (S1-R) and to PSIS-IT (S1-Q), were created and measured. Distances of PSIS-R, PSIS-Q (S1) and IT-S2 were measured and calculated into percentage of PSIS-GT, PSIS-IT and IT-GT lengths, respectively.Results: Regarding the classification of Beaton and Anson, three types of SN-PM relationship (a, b and c) were obtained. The percentage of type a, b and c was 74.02, 22.55 and 3.43, respectively. Symmetrical SN-PM relationship was found in 75.49%. The mean length of PSIS-IT, PSIS-GT and IT-GT in all types was 129.63 ± 11.89 mm, 151.34 ± 14.78 mm and 73.02 ± 10.20 mm, respectively. A statistically significant difference was found between types a and b (p = 0.013) in PSIS-IT length, whereas mean length of IT-GT and PSIS-GT showed no statistically significant difference between SN-PM types. PSIS-IT line passed SN at the lower edge of PM (S1) in 112 specimens (54.90%). In these cases, S1 and Q were the same point. A statistically significant difference was also found between types a and b (p = 0.023) in PSIS-Q (S1) length. The mean lengths of PSIS-Q (S1), PSIS-R and IT-S2 in term of percentage of PSIS-IT, PSIS-GT and IT-GT line in all types were 60.06 ± 5.90%, 54.19 ± 6.10%, and 37.87 ± 8.27%, respectively. The mean lengths of S1-R and S1-Q were 30.07 ± 8.30 mm and 6.54 ± 7.99 mm. Therefore, SN at S1 could be located at the point of 54.19 ± 6.10% of PSIS-GT length (R) with a distance of 30.07 ± 8.30 mm perpendicular to PSIS-GT line (S1-R). Since the PSIS-IT line did not pass SN at S1 in every case, it might not be suitable for localizing SN at S1. SN at S2 could be located at the point of 37.87 ± 8.27% of IT-GT line. No significant difference was found between types.Conclusions: Sciatic nerve can be localised by PSIS-GT and IT-GT lines without statistically significant difference between types (a, b, and c) of SN-PM relationship

Clinical measurement of dart throwing motion of the wrist: variability, accuracy and correction

Despite being functionally important, dart throwing motion is difficult to assess accurately through goniometry. The objectives of this study were to describe a method for reliably quantifying the dart throwing motion using goniometric measurements within a healthy population. Wrist kinematics of 24 healthy participants were assessed using goniometry and optical motion tracking. Three wrist angles were measured at the starting and ending points of the motion: flexion-extension, radial-ulnar deviation and dart throwing motion angle. The orientation of the dart throwing motionplane relative to the flexion-extension axis ranged between 28° and 57° among the tested population. Plane orientations derived from optical motion capture differed from those calculated through goniometry by 25°. An equation to correct the estimation of the plane from goniometry measurements was derived. This was applied and differences in the orientation of the plane were reduced to non-significant levels, enabling dart throwing motion to be measured using goniometry alone

Comparison of 20nm silver nanoparticles synthesized with and without a gold core: Structure, dissolution in cell culture media, and biological impact on macrophages

Widespread use of silver nanoparticles raises questions of environmental and biological impact. Many synthesis approaches are used to produce pure silver and silver-shell gold-core particles optimized for specific applications. Since both nanoparticles and silver dissolved from the particles may impact the biological response, it is important to understand the physicochemical characteristics along with the biological impact of nanoparticles produced by different processes. The authors have examined the structure, dissolution, and impact of particle exposure to macrophage cells of two 20 nm silver particles synthesized in different ways, which have different internal structures. The structures were examined by electron microscopy and dissolution measured in Rosewell Park Memorial Institute media with 10% fetal bovine serum. Cytotoxicity and oxidative stress were used to measure biological impact on RAW 264.7 macrophage cells. The particles were polycrystalline, but 20 nm particles grown on gold seed particles had smaller crystallite size with many high-energy grain boundaries and defects, and an apparent higher solubility than 20 nm pure silver particles. Greater oxidative stress and cytotoxicity were observed for 20 nm particles containing the Au core than for 20 nm pure silver particles. A simple dissolution model described the time variation of particle size and dissolved silver for particle loadings larger than 9 μg/ml for the 24-h period characteristic of many in-vitro studies

Changing patterns of the prevalence of Helicobacter pylori among patients at a corporate hospital in Ghana

Introduction: Helicobacter pylori (H. pylori) discovered in 1982, has strongly been associated with multiple clinical disorders of the gastrointestinal tract. This study described the prevalence of H. pylori among large numbers of patients over two different time periods in Accra, Ghana.Methods: It was a retrospective records review on patients attending a quasi-government hospital in Accra, Ghana, during two time periods, 1999 and 2012. A total of 2401 records were reviewed, 1128 in first period and 1273 in second period. Biopsy was taken from the gastric antrum for Rapid Urease Test (RUT) in identifying H. Pylori. Data on patient characteristics, clinical diagnosis and findings upon endoscopy were analyzed by simple descriptive statistics. Associations between categorical outcome variables were determined by Chi square test at 95% significance level.Results: H. pylori infection was high in patients with upper gastrointestinal symptoms 69.7% (1999) and 45.2% (2012), and was even higher in patients with gastritis and duodenal ulcer. H. pylori infection however, decreased among patients over the period, 69.7% in 1999 to 45.2% in 2012. Sex differences in H. pylori infection was identified (higher among males) and young adults (21-40 years). Commonest symptom in all patients was non-ulcer dyspepsia, 86.9% in 1999 and 84.2% in 2012, while gastritis and duodenal ulcer were the commonest endoscopic finding in the two periods.Conclusion: Appropriate management guidelines in West Africa considering the high background H. pylori infection and other co-infections requiring particular antibiotic combination therapy is required.Key words: Helicobacter pylori; endoscopy; prevalence; sex differences; Ghan

Surface localisation of master knot of Henry, in situ and ex vivo length of flexor hallucis longus tendon: pertinent data for tendon harvesting and transfer

Background: Length of flexor hallucis longus (FHL), localisation of master knot of Henry (MKH) and relationship between MKH and neurovascular bundle are essential for the achievement of FHL tendon transfer. The purpose of this study is to define the localisation of MKH in reference to bony landmarks of the foot, its relationship to plantar neurovascular bundle and to investigate in situ and ex vivo length of FHL tendon in single incision, double incision and minimally invasive techniques. Materials and methods: Foot length was examined in 62 feet of 31 soft cadavers (9 males, 22 females). Various parameters including the relationship between MKH and neurovascular bundle, the distances from MKH to medial malleolus (MM), navicular tuberosity (NT) and the first interphalangeal joint of great toe (IP) were measured. Surface localisation of MKH in relation to a line joining the medial end of plantar flexion crease at the base of great toes (MC) to NT (MC-NT line) was determined. Lengths of FHL tendon graft from three surgical techniques were examined. In situ length was measured in the plantar surface of foot and ex vivo length was measured after tendon was cut from its insertion. Results: The mean length of foot was 230.98 ± 15.35 mm with a statistically significant difference between genders in both sides (p < 0.05). No distance was found between medial plantar neurovascular bundle (MPNVB) and MKH. Mean distance of 17.13 ± 3.55 mm was found between lateral plantar neurovascular bundle (LPNVB) and MKH. MKH was located at a mean distance of 117.11 ± 1.00 mm proximal to IP, 26.28 ± 4.75 mm under NT and 59.58 ± 7.51 mm distal to MM with a statistically significant difference of MKH-IP distance between genders in both sides and MKH-NT in right side. MKH was located anterior to NT (66.1%), at NT (27.4%) and posterior to NT (6.5%) on the MC-NT line. Surface localisation of MKH was 94.75 ± 8.43% of MC-NT line from MC with a perpendicular distance of 25.11 ± 5.37 mm below MC-NT line. The in situ and ex vivo tendon lengths from MTJ to ST, to MKH and to IP were 39.05 ± 10.88 mm and 34.43 ± 10.23 mm, 73.45 ± 9.91 mm and 68.63 ± 9.43 mm, 197.98 ± 13.89 and 191.79 ± 14.00 mm, respectively. A statistically significant difference between genders was found in MTJ-IP of in situ and ex vivo length of both sides (p < 0.05). The mean length of tendon between in situ and ex vivo was significantly different in all techniques (p < 0.05). A moderate positive correlation between foot length and tendon length was found in MTJ-IP of both in situ and ex vivo tendon length. Conclusions: A statistically significant difference between in situ and ex vivo tendon length was shown in all harvesting techniques. Surface location of MKH was approximately at 95% of MC-NT line from MC with a perpendicular distance of 25 mm from MC-NT line

Topological descriptors for 3D surface analysis

We investigate topological descriptors for 3D surface analysis, i.e. the classification of surfaces according to their geometric fine structure. On a dataset of high-resolution 3D surface reconstructions we compute persistence diagrams for a 2D cubical filtration. In the next step we investigate different topological descriptors and measure their ability to discriminate structurally different 3D surface patches. We evaluate their sensitivity to different parameters and compare the performance of the resulting topological descriptors to alternative (non-topological) descriptors. We present a comprehensive evaluation that shows that topological descriptors are (i) robust, (ii) yield state-of-the-art performance for the task of 3D surface analysis and (iii) improve classification performance when combined with non-topological descriptors.Comment: 12 pages, 3 figures, CTIC 201

The role of positive emotion and contributions of positive psychology in depression treatment: systematic review

The present study aims to conduct a systematic review of the literature by checking the impact of positive emotion in the treatment of depression and on the use of strategies of positive psychology which involves positive emotion to treat and reduce symptoms of depression. For this purpose, we conducted searches in databases ISI Web of Knowledge, PsycINFO and PubMed and found a total of 3400 studies. After inclusion application and exclusion criteria, 28 articles remained, presented and discussed in this study. The studies have important relations between humor and positive emotion as well as a significant improvement in signs and symptoms of depression using differents strategies of positive psychology. Another relevant aspect is the preventative character of the proposed interventions by positive psychology by the fact that increase well-being and produce elements such as resilience and coping resources that reduce the recurrent relapses in the treatment of depression. The strategies of positive psychology, such as increasing positive emotions, develop personal strengths: seeking direction, meaning and engagement for the day-to-day life of the patients, appear as potentially tools for the prophylaxis and treatment of depression, helping to reduce signs and symptoms as well as for prevention of relapses

Stability analysis and quasinormal modes of Reissner Nordstr{\o}m Space-time via Lyapunov exponent

We explicitly derive the proper time $(\tau)$ principal Lyapunov exponent ($\lambda_{p}$) and coordinate time ($t$) principal Lyapunov exponent ($\lambda_{c}$) for Reissner Nordstr{\o}m (RN) black hole (BH) . We also compute their ratio. For RN space-time, it is shown that the ratio is $\frac{\lambda_{p}}{\lambda_{c}}=\frac{r_{0}}{\sqrt{r_{0}^2-3Mr_{0}+2Q^2}}$ for time-like circular geodesics and for Schwarzschild BH it is $\frac{\lambda_{p}}{\lambda_{c}}=\frac{\sqrt{r_{0}}}{\sqrt{r_{0}-3M}}$. We further show that their ratio $\frac{\lambda_{p}}{\lambda_{c}}$ may vary from orbit to orbit. For instance, Schwarzschild BH at innermost stable circular orbit(ISCO), the ratio is $\frac{\lambda_{p}}{\lambda_{c}}\mid_{r_{ISCO}=6M}=\sqrt{2}$ and at marginally bound circular orbit (MBCO) the ratio is calculated to be $\frac{\lambda_{p}}{\lambda_{c}}\mid_{r_{mb}=4M}=2$. Similarly, for extremal RN BH the ratio at ISCO is $\frac{\lambda_{p}}{\lambda_{c}}\mid_{r_{ISCO}=4M}=\frac{2\sqrt{2}}{\sqrt{3}}$. We also further analyse the geodesic stability via this exponent. By evaluating the Lyapunov exponent, it is shown that in the eikonal limit , the real and imaginary parts of the quasi-normal modes of RN BH is given by the frequency and instability time scale of the unstable null circular geodesics.Comment: Accepted in Pramana, 07/09/201