Regenerable Antibacterial Cotton Fabric by Plasma Treatment with Dimethylhydantoin: Antibacterial Activity against S. aureus

published_or_final_versio

Self-Correctable and Adaptable Inference for Generalizable Human Pose Estimation

A central challenge in human pose estimation, as well as in many other machine learning and prediction tasks, is the generalization problem. The learned network does not have the capability to characterize the prediction error, generate feedback information from the test sample, and correct the prediction error on the fly for each individual test sample, which results in degraded performance in generalization. In this work, we introduce a self-correctable and adaptable inference (SCAI) method to address the generalization challenge of network prediction and use human pose estimation as an example to demonstrate its effectiveness and performance. We learn a correction network to correct the prediction result conditioned by a fitness feedback error. This feedback error is generated by a learned fitness feedback network which maps the prediction result to the original input domain and compares it against the original input. Interestingly, we find that this self-referential feedback error is highly correlated with the actual prediction error. This strong correlation suggests that we can use this error as feedback to guide the correction process. It can be also used as a loss function to quickly adapt and optimize the correction network during the inference process. Our extensive experimental results on human pose estimation demonstrate that the proposed SCAI method is able to significantly improve the generalization capability and performance of human pose estimation.Comment: Accepted by CVPR 202

Effects of electrostatic screening on the conformation of single DNA molecules confined in a nanochannel

Single T4-DNA molecules were confined in rectangular-shaped channels with a depth of 300 nm and a width in the range 150-300 nm casted in a poly(dimethylsiloxane) nanofluidic chip. The extensions of the DNA molecules were measured with fluorescence microscopy as a function of the ionic strength and composition of the buffer as well as the DNA intercalation level by the YOYO-1 dye. The data were interpreted with scaling theory for a wormlike polymer in good solvent, including the effects of confinement, charge, and self-avoidance. It was found that the elongation of the DNA molecules with decreasing ionic strength can be interpreted in terms of an increase of the persistence length. Self-avoidance effects on the extension are moderate, due to the small correlation length imposed by the channel cross-sectional diameter. Intercalation of the dye results in an increase of the DNA contour length and a partial neutralization of the DNA charge, but besides effects of electrostatic origin it has no significant effect on the bare bending rigidity. In the presence of divalent cations, the DNA molecules were observed to contract, but they do not collapse into a condensed structure. It is proposed that this contraction results from a divalent counterion mediated attractive force between the segments of the DNA molecule.Comment: 38 pages, 10 figures, accepted for publication in The Journal of Chemical Physic

Effect of H-NS on the elongation and compaction of single DNA molecules in a nanospace

10.1039/c3sm51214bSoft Matter9409593-960

Design and implementation of an international, multi-arm, multi-stage platform master protocol for trials of novel SARS-CoV-2 antiviral agents: Therapeutics for Inpatients with COVID-19 (TICO/ACTIV-3)

BACKGROUND/AIMS: Safe and effective therapies for COVID-19 are urgently needed. In order to meet this need, the Accelerating COVID-19 Therapeutic Interventions and Vaccines public-private partnership initiated the Therapeutics for Inpatients with COVID-19. Therapeutics for Inpatients with COVID-19 is a multi-arm, multi-stage platform master protocol, which facilitates the rapid evaluation of the safety and efficacy of novel candidate antiviral therapeutic agents for adults hospitalized with COVID-19. Five agents have so far entered the protocol, with rapid answers already provided for three of these. Other agents are expected to enter the protocol throughout 2021. This protocol contains a number of key design and implementation features that, along with challenges faced by the protocol team, are presented and discussed. METHODS: Three clinical trial networks, encompassing a global network of clinical sites, participated in the protocol development and implementation. Therapeutics for Inpatients with COVID-19 utilizes a multi-arm, multi-stage design with an agile and robust approach to futility and safety evaluation at 300 patients enrolled, with subsequent expansion to full sample size and an expanded target population if the agent shows an acceptable safety profile and evidence of efficacy. Rapid recruitment to multiple agents is enabled through the sharing of placebo, the confining of agent-specific information to protocol appendices, and modular consent forms. In collaboration with the Food and Drug Administration, a thorough safety data collection and Data and Safety Monitoring Board schedule was developed for the study of potential therapeutic agents with limited in-human data in hospitalized patients with COVID-19. RESULTS: As of 8 August 2021, five agents have entered the Therapeutics for Inpatients with COVID-19 master protocol and a total of 1909 participants have been randomized to one of these agents or matching placebo. There were a number of challenges faced by the study team that needed to be overcome in order to successfully implement Therapeutics for Inpatients with COVID-19 across a global network of sites. These included ensuring drug supply and reliable recruitment allowing for changing infection rates across the global network of sites, the need to balance the collection of data and samples without overburdening clinical staff and obtaining regulatory approvals across a global network of sites. CONCLUSION: Through a robust multi-network partnership, the Therapeutics for Inpatients with COVID-19 protocol has been successfully used across a global network of sites for rapid generation of efficacy data on multiple novel antiviral agents. The protocol design and implementation features used in this protocol, and the approaches to address challenges, will have broader applicability. Mechanisms to facilitate improved communication and harmonization among country-specific regulatory bodies are required to achieve the full potential of this approach in dealing with a global outbreak

ETS1 Mediates MEK1/2-Dependent Overexpression of Cancerous Inhibitor of Protein Phosphatase 2A (CIP2A) in Human Cancer Cells

EGFR-MEK-ERK signaling pathway has an established role in promoting malignant growth and disease progression in human cancers. Therefore identification of transcriptional targets mediating the oncogenic effects of the EGFR-MEK-ERK pathway would be highly relevant. Cancerous inhibitor of protein phosphatase 2A (CIP2A) is a recently characterized human oncoprotein. CIP2A promotes malignant cell growth and is over expressed at high frequency (40–80%) in most of the human cancer types. However, the mechanisms inducing its expression in cancer still remain largely unexplored. Here we present systematic analysis of contribution of potential gene regulatory mechanisms for high CIP2A expression in cancer. Our data shows that evolutionary conserved CpG islands at the proximal CIP2A promoter are not methylated both in normal and cancer cells. Furthermore, sequencing of the active CIP2A promoter region from altogether seven normal and malignant cell types did not reveal any sequence alterations that would increase CIP2A expression specifically in cancer cells. However, treatment of cancer cells with various signaling pathway inhibitors revealed that CIP2A mRNA expression was sensitive to inhibition of EGFR activity as well as inhibition or activation of MEK-ERK pathway. Moreover, MEK1/2-specific siRNAs decreased CIP2A protein expression. Series of CIP2A promoter-luciferase constructs were created to identify proximal −27 to −107 promoter region responsible for MEK-dependent stimulation of CIP2A expression. Additional mutagenesis and chromatin immunoprecipitation experiments revealed ETS1 as the transcription factor mediating stimulation of CIP2A expression through EGFR-MEK pathway. Thus, ETS1 is probably mediating high CIP2A expression in human cancers with increased EGFR-MEK1/2-ERK pathway activity. These results also suggest that in addition to its established role in invasion and angiogenesis, ETS1 may support malignant cellular growth via regulation of CIP2A expression and protein phosphatase 2A inhibition

Supervised exercise training as an adjunctive therapy for venous leg ulcers: study protocol for a randomised controlled trial

Background: Venous leg ulcers are common, chronic wounds that are painful and reduce quality of life. Compression therapy is known to assist in the healing of venous leg ulceration. Supervised exercise training that targets an improvement in calf muscle pump function might be a useful adjunctive therapy for enhancing ulcer healing and other aspects of physical and mental health. However, the evidence of exercise for individuals with venous ulcers is sparse. Here, we describe the protocol for a study that aims to assess the feasibility of undertaking a randomised controlled trial of a supervised exercise programme in people who are receiving compression for venous ulceration. Methods/Design: This is a randomised, controlled, assessor-blinded, two-centre, feasibility trial with two parallel groups. Eighty adults who are receiving lower-limb compression for a venous leg ulcer will be randomly assigned to receive usual care (compression only) or usual care plus a 12-week supervised exercise programme. Participants in the exercise group will be invited to undertake three, 60-minute sessions of supervised exercise each week, and each session will involve a combination of treadmill walking, upright cycling and strength and flexibility exercises for the lower limbs. Participants will be assessed before randomisation and 3, 6 and 12 months after randomisation. Primary outcomes include rates of recruitment, retention and adherence. Secondary outcomes include time to ulcer healing, proportion of participants healed, percentage and absolute change in ulcer size, health-related quality of life (EQ-5D-5L and VEINES-QOL/Sym), lower-limb cutaneous microvascular function (laser Doppler flowmetry coupled with iontophoresis) and physical fitness (30-second sit-to-stand test, chair sit and reach test, 6-minute walk test and ankle range of motion). The costs associated with the exercise programme and health-care utilisation will be calculated. We will also complete interviews with a sub-sample of participants to explore their experiences of having a venous ulcer and the acceptability of the exercise intervention and study procedures. Discussion: Data from this study will be used to refine the supervised exercise programme, investigate the acceptability of the intervention and study design and determine the most appropriate outcome measures, thereby providing estimates of the factors needed to design an adequately powered trial across several centres