TimewarpVAE: Simultaneous Time-Warping and Representation Learning of Trajectories

Human demonstrations of trajectories are an important source of training data for many machine learning problems. However, the difficulty of collecting human demonstration data for complex tasks makes learning efficient representations of those trajectories challenging. For many problems, such as for handwriting or for quasistatic dexterous manipulation, the exact timings of the trajectories should be factored from their spatial path characteristics. In this work, we propose TimewarpVAE, a fully differentiable manifold-learning algorithm that incorporates Dynamic Time Warping (DTW) to simultaneously learn both timing variations and latent factors of spatial variation. We show how the TimewarpVAE algorithm learns appropriate time alignments and meaningful representations of spatial variations in small handwriting and fork manipulation datasets. Our results have lower spatial reconstruction test error than baseline approaches and the learned low-dimensional representations can be used to efficiently generate semantically meaningful novel trajectories.Comment: 17 pages, 12 figure

Transcripts for transforming growth factors in human breast cancer: clinical correlates.

The levels of mRNA for transforming growth factors (TGF alpha and beta) and the epidermal growth factor receptor (EGFR) were determined in 69 human breast carcinomas and 20 biopsies of non-neoplastic breast tissue by dot blot hybridisation analysis. TGF alpha mRNA was detected in 42% of cancers and 44% of non-neoplastic breast tissue at low levels. TGF beta mRNA was found in all breast cancers and non-neoplastic breast tissues, but the levels of TGF beta mRNA were found to be higher in breast cancers (P = 0.01). EGFR mRNA was detected in 55% of breast cancers and in all non-neoplastic breast tissue tested. The presence of EGFR mRNA was inversely related to oestrogen receptor (ER) status (P = 0.0001). Coexpression of TGF alpha and EGFR was observed in 28% of the carcinomas, and significantly more commonly in ER negative tumours (P = 0.01). No significant relationship was found between histological grade, tumour cellularity or tumour desmoplasia and expression of either the TGFs or of EGFR mRNA. High levels of TGF beta were, however, associated with the absence of lymph node metastases at presentation (P = 0.05). Levels of TGF alpha and beta and EGFR mRNA were analysed in relationship to the relapse-free and overall survival of patients with breast cancer, but none was found to predict significantly the outcome in these patients. Longer clinical follow-up and larger numbers of patients are required to determine whether TGFs will prove a useful marker for prognosis in breast cancer patients

Scale-free networks with tunable degree distribution exponents

We propose and study a model of scale-free growing networks that gives a degree distribution dominated by a power-law behavior with a model-dependent, hence tunable, exponent. The model represents a hybrid of the growing networks based on popularity-driven and fitness-driven preferential attachments. As the network grows, a newly added node establishes $m$ new links to existing nodes with a probability $p$ based on popularity of the existing nodes and a probability $1-p$ based on fitness of the existing nodes. An explicit form of the degree distribution $P(p,k)$ is derived within a mean field approach. For reasonably large $k$, $P(p,k) \sim k^{-\gamma(p)}{\cal F}(k,p)$, where the function ${\cal F}$ is dominated by the behavior of $1/\ln(k/m)$ for small values of $p$ and becomes $k$-independent as $p \to 1$, and $\gamma(p)$ is a model-dependent exponent. The degree distribution and the exponent $\gamma(p)$ are found to be in good agreement with results obtained by extensive numerical simulations.Comment: 12 pages, 2 figures, submitted to PR

The prognostic significance of transforming growth factors in human breast cancer.

Transforming growth factor alpha (TGF alpha) and Transforming growth factor beta-1 (TGF-beta 1) are growth regulatory for breast cancer cell lines in vitro and several studies have suggested that levels of the receptor for TGF alpha, the epidermal growth factor (EGFR) in tumour biopsies predict relapse and survival. We have examined the prognostic significance of TGF alpha, TGF-beta 1 and EGFR mRNA expression in a series of patients with primary breast cancer with a median follow up period of 60 months. In 167 patients the expression of TGF-beta 1 was inversely correlated with node status (P = 0.065) but not ER status, tumour size or menopausal status. Patients with high levels of TGF-beta 1 had a longer disease free interval with a significantly longer probability of survival at 80 months although the overall relapse free survival was not increased. EGFR mRNA expression was measured in 106 patients and was inversely correlated with ER status (P = 0.018). EGFR levels did not predict for early relapse or survival. TGF alpha mRNA levels were measured in 104 patients, no correlation was seen tumour size, node status, Er status, or clinical outcome

Increased Th2 activity and diminished skin barrier function cooperate in allergic skin inflammation

Atopic dermatitis (AD) is a chronic inflammatory skin disease induced by a complex interaction between susceptibility genes encoding skin barrier components and environmental allergen exposure that results in type 2 cytokine production. Although genetic lesions in either component can be risk factors for disease in patients, whether these pathways interact in the development of AD is not clear. To test this, we mated mice with T-cell specific expression of constitutively active Stat6 (Stat6VT) that spontaneously develop allergic skin inflammation with Flaky tail (Ft) mice that have mutations in Flg and Tmem79 genes that each affect skin barrier function. Our results demonstrate that over 90% of the Stat6VT transgenic mice carrying the Ft alleles (Stat6VTxFt−/−) develop severe atopic dermatitis lesions by 3-5 months of age, compared with only 40% of Stat6VT mice that develop disease by 6-7 months of age. Further, histopathological analysis of skin tissues from Stat6VTxFt−/− mice revealed extensive thickening of the dermis with increased inflammatory infiltrates as compared with Stat6VT mice. Our study suggests that skin barrier defects and altered Th2 responses independently cooperate in the pathogenesis of allergic skin inflammation, similar to effects observed in patients with AD

Extracellular vesicles derived from Staphylococcus aureus induce atopic dermatitis-like skin inflammation

P>Background: Recently, we found that Staphylococcus aureus produces extracellular vesicles (EV) that contain pathogenic proteins. Although S. aureus infection has been linked with atopic dermatitis (AD), the identities of the causative agents from S. aureus are controversial. We evaluated whether S. aureus-derived EV are causally related to the pathogenesis of AD. Methods: Extracellular vesicles were isolated by the ultracentrifugation of S. aureus culture media. The EV were applied three times per week to tape-stripped mouse skin. Inflammation and immune dysfunction were evaluated 48 h after the final application in hairless mice. Extracellular vesicles-specific IgE levels were measured by ELISA in AD patients and healthy subjects. Results: The in vitro application of S. aureus EV increased the production of pro-inflammatory mediators (IL-6, thymic stromal lymphopoietin, macrophage inflammatory protein-1 alpha, and eotaxin) by dermal fibroblasts. The in vivo application of S. aureus EV after tape stripping caused epidermal thickening with infiltration of the dermis by mast cells and eosinophils in mice. These changes were associated with the enhanced cutaneous production of IL-4, IL-5, IFN-gamma, and IL-17. Interestingly, the serum levels of S. aureus EV-specific IgE were significantly increased in AD patients relative to healthy subjects. Conclusion: These results indicate that S. aureus EV induce AD-like inflammation in the skin and that S. aureus-derived EV are a novel diagnostic and therapeutic target for the control of AD.X116764sciescopu

'Improving subnational disaster management in Sierra Leone': Evaluating Local Disaster Management in Sierra Leone (EVALDIS) Final Report 2023 No. 1

The EVALDIS Final Report No. 1 represents a comprehensive assessment of the challenges confronting provincial, district and local disaster management across the country and is designed to contribute valuable research based and evidenced recommendations that can help to shape the NDMA’s thinking and direction towards developing stronger regional capacities across the country in 2023. Research was conducted by a team from the internationally acclaimed Bournemouth University Disaster Management Centre (BUDMC), led by Professor Lee Miles, during 2022. EVALDIS constitutes one of the most extensive, contemporary studies undertaken in recent years. The Report draws on data collected from stakeholder interviews and Focus Groups as well as peer/participant observations in disaster management meetings at the national, provincial, district and local levels. At all stages, the research has involved cooperation with Sierra Leone’s disaster management institutions, the participation of local communities and incorporates peer- review feedback on the findings presented in the EVALDIS Final Report. Through the application of innovative Bournemouth University led research techniques, focusing primarily on identifying ‘resolvable single points of failure’ (SPOF), refined in conjunction with the NDMA, this Final Report highlights that: • There is an overwhelming consensus that the development of the NDMA’s provincial and district capacities, including the appointment of NDMA Provincial and District Officers, and the creation of NDMA Provincial and District Offices is a welcome development. • However, there remain 12 notable areas where SPOF exist that are likely to lead to the breakdown of part or all of this evolving subnational component of Sierra Leone’s disaster management system. This includes aspects of disaster risk reduction, response and recovery. • These 12 SPOF areas are clearly and commonly identifiable by all three participating constituencies of national stakeholders, representatives of local communities and provincial disaster management officers, and verified through participating interactions. Thus, there is a firm basis for concerted future subnational action and initiatives. There is a remarkably high level of consistency and consensus shared by all three participating constituencies that the top SPOF areas are resolvable and fixable over the short to medium terms (within 5 years), provided appropriate recommendations and immediate action points are implemented to address them. • There is resoundingly strong agreement that key initiatives such as the development of Facilitators Guides to increase the knowledge, skills and competencies of the NDMA Provincial and District Officers (and offices) represent important initiatives for the future. The EVALDIS Final Report calls for the NDMA to further develop an integrated NDMA regional strategy/document that can further underpin the development of the NDMA's provincial and district capacities during 2023-24. The Strategy would be wise to recognise and consider the 51 notable, resolvable SPOF identified in the EVALDIS Final Report, and implement most(if not all) of the 62 specific evidenced-based recommendations and immediate action points that are aimed at improving subnational disaster management in Sierra Leone now and in the future

c-Fos Expression in the Nucleus of the Solitary Tract in Response to Salt Stimulation in Rats

Salt signals in tongue are relayed to the nucleus of the solitary tract (NST). This signaling is very important to determine whether to swallow salt-related nutrition or not and suggests some implications in discrimination of salt concentration. Salt concentration-dependent electrical responses in the chorda tympani and the NST were well reported. But salt concentration-dependency and spatial distribution of c-Fos in the NST were not well established. In the present study, NaCl signaling in the NST was studied in urethane-anesthetized rats. The c-Fos immunoreactivity in the six different NST areas along the rostral-caudal axis and six subregions in each of bilateral NST were compared between applications of distilled water and different concentrations of NaCl to the tongue of experimental animals. From this study, salt stimulation with high concentration (1.0 M NaCl) induced significantly higher c-Fos expression in intermediate NST and dorsal-medial and dorsal-middle subregions of the NST compared to distilled water stimulation. The result represents the specific spatial distribution of salt taste perception in the NST

Putting the brakes on the unfolded protein response

The unfolded protein response is an ancient cellular pathway for rapidly responding to endoplasmic reticulum stress. Two studies in this issue (Rubio et al. 2011. J. Cell. Biol. doi:10.1083/jcb.201007077 and Chawla et al. 2011. J. Cell. Biol. doi:10.1083/jcb.201008071) provide insight into how the unfolded protein response is tamped down to restore normal endoplasmic reticulum function. Although both papers implicate the Ire1 kinase domain as the key effector of the off-switch mechanism, alternate models for how this is achieved are proposed