IMU-based Deep Neural Networks for Locomotor Intention Prediction

This paper focuses on the design and comparison of different deep neural networks for the real-time prediction of locomotor intentions by using data from inertial measurement units. The deep neural network architectures are convolutional neural networks, recurrent neural networks, and convolutional recurrent neural networks. The input to the architectures are features in the time domain, which have been derived either from one inertial measurement unit placed on the upper right leg of ten healthy subjects, or two inertial measurement units placed on both the upper and lower right leg of ten healthy subjects. The study shows that a WaveNet, i.e., a full convolutional neural network, achieves a peak F1-score of 87.17% in the case of one IMU, and a peak of 97.88% in the case of two IMUs, with a 5-fold cross-validation

Gene Expression Signature of Cigarette Smoking and Its Role in Lung Adenocarcinoma Development and Survival

Tobacco smoking is responsible for over 90% of lung cancer cases, and yet the precise molecular alterations induced by smoking in lung that develop into cancer and impact survival have remained obscure.We performed gene expression analysis using HG-U133A Affymetrix chips on 135 fresh frozen tissue samples of adenocarcinoma and paired noninvolved lung tissue from current, former and never smokers, with biochemically validated smoking information. ANOVA analysis adjusted for potential confounders, multiple testing procedure, Gene Set Enrichment Analysis, and GO-functional classification were conducted for gene selection. Results were confirmed in independent adenocarcinoma and non-tumor tissues from two studies. We identified a gene expression signature characteristic of smoking that includes cell cycle genes, particularly those involved in the mitotic spindle formation (e.g., NEK2, TTK, PRC1). Expression of these genes strongly differentiated both smokers from non-smokers in lung tumors and early stage tumor tissue from non-tumor tissue (p<0.001 and fold-change >1.5, for each comparison), consistent with an important role for this pathway in lung carcinogenesis induced by smoking. These changes persisted many years after smoking cessation. NEK2 (p<0.001) and TTK (p = 0.002) expression in the noninvolved lung tissue was also associated with a 3-fold increased risk of mortality from lung adenocarcinoma in smokers.Our work provides insight into the smoking-related mechanisms of lung neoplasia, and shows that the very mitotic genes known to be involved in cancer development are induced by smoking and affect survival. These genes are candidate targets for chemoprevention and treatment of lung cancer in smokers

Nuclear pore protein NUP210 depletion suppresses metastasis through heterochromatin-mediated disruption of tumor cell mechanical response.

Mechanical signals from the extracellular microenvironment have been implicated in tumor and metastatic progression. Here, we identify nucleoporin NUP210 as a metastasis susceptibility gene for human estrogen receptor positive (ER+) breast cancer and a cellular mechanosensor. Nup210 depletion suppresses lung metastasis in mouse models of breast cancer. Mechanistically, NUP210 interacts with LINC complex protein SUN2 which connects the nucleus to the cytoskeleton. In addition, the NUP210/SUN2 complex interacts with chromatin via the short isoform of BRD4 and histone H3.1/H3.2 at the nuclear periphery. In Nup210 knockout cells, mechanosensitive genes accumulate H3K27me3 heterochromatin modification, mediated by the polycomb repressive complex 2 and differentially reposition within the nucleus. Transcriptional repression in Nup210 knockout cells results in defective mechanotransduction and focal adhesion necessary for their metastatic capacity. Our study provides an important role of nuclear pore protein in cellular mechanosensation and metastasis

Diabetes-associated breast cancer has a distinct transcriptome and metabolome and shows DNA repair deficiency

Diabetes commonly affects cancer patients. As a comorbidity, it may modify tumor biology and therapy response. Yet, we still lack an understanding of the diabetes-induced molecular changes in human breast tumors and their implication for therapy. The goal of this study was aimed to identify diabetes induced phenotypes and molecular signatures in breast cancer. Here, we investigated the effect of diabetes on breast cancer biology using a three-pronged approach that included analysis of orthotopic human tumor xenografts, patient tumors, and breast cancer cells exposed to diabetes and hyperglycemia. Diabetes and hyperglycemia induced a mesenchymal and stem cell-like phenotypes. Further Diabetes and hyperglycemia also associated with oxidative stress and both gene expression and mutational signatures of DNA repair deficiency. Breast cancer cells cultured under hyperglycemia acquired increased DNA damage and sensitivity to DNA damage response inhibitors. Based on these observations, diabetes-associated breast tumors may show an increased drug response to DNA repair pathway inhibitors that are cancer therapeutics

Urinary PGE-M in Men with Prostate Cancer and Urinary Thromboxane B2 and Lethal Prostate Cancer in African American Men

Elevated levels of urinary prostaglandin E metabolite (PGE-M), a marker of inflammation, have previously been associated with cancer incidence and metastasis. Studies investigating PGE-M in prostate cancer are lacking even though chronic inflammation is a candidate risk factor for the disease. We investigated the association of PGE-M with lethal prostate cancer. We measured PGE-M in the urine of men with prostate cancer and in men without prostate cancer (population controls). Our participants included African American and European American men. Because African American men die more frequently from prostate cancer than European American men, we investigated whether high PGE-M may contribute to the increased mortality among African American prostate cancer patients. We did not observe a relationship between PGE-M and prostate cancer aggressiveness or prostate cancer-specific mortality in our study population, neither in the combined cohort nor in the race/ethnicity stratified analysis. Interestingly, however, we observed a significant relationship between high PGE-M and all-cause mortality in African American men with prostate cancer. Yet, there was no association between high PGE-M and all-cause mortality when these men were regular aspirin users. Thromboxane A2 (TXA2) is a platelet- and cyclooxygenase-derived eicosanoid that has been linked to metasta- sis. We investigated the role of TXA2 in the development of lethal prostate cancer in African American (AA) and European American (EA) men. Methods: We measured urinary 11-dehydrothromboxane B2 (TXB2), a stable metabolite of TXA2, with mass spectrometry. Samples were obtained from 977 cases and 1022 controls at time of recruitment. We applied multivariable logistic and Cox regression modeling to examine associations of TXB2 with prostate cancer and patient survival. The median survival follow-up was 8.4 years, with 246 deaths among cases. Aspirin use was assessed with a ques- tionnaire. Race was self-reported. Results: Urinary TXB2 was inversely associated with aspirin use. High (&gt;median) TXB2 was associated with prostate cancer in AA (adjusted odds ratio [OR] 1⁄4 1.50, 95% confidence interval [CI] 1⁄4 1.13 to 2.00) but not EA men (OR 1⁄4 1.07, 95% CI 1⁄4 0.82 to 1.40), suggesting upregulated TXA2 synthesis in AA men with prostate cancer. High TXB2 was positively associated with metastatic prostate cancer (OR 1⁄4 2.60, 95% CI 1⁄4 1.08 to 6.28) compared with low (?median) TXB2. Furthermore, high TXB2 was also associated with all-cause (adjusted hazard ratio 1⁄4 1.59, 95% CI 1⁄4 1.06 to 2.40) and prostate cancer-specific mortality (hazard ratio 1⁄4 4.74, 95% CI 1⁄4 1.62 to 13.88) in AA men only. Conclusions: We report a distinct association of TXB2 with prostate cancer outcomes in AA men. In this high-risk group of men, upregulation of TXA2 synthesis may promote metastasis and lethal disease. Our observation identifies a potential benefit of aspirin in preventing lethal prostate cancer through inhibition of TXA2 synthesis

Power flow control scheme for multiport power electronics transformers

Development of power electronics transformers (PETs) has made dc distribution and hybrid ac/dc systems a competitive solution for future network expansion. This study focuses on the functions of a multiport PET interfacing medium-voltage and low-voltage networks. A comprehensive power flow control scheme based on a globalised multiport transmission model of the PET and droop control is derived. This allows for a coordinated energy exchange between the ports of the PET, which enables autonomous operation. Simulations of the proposed approach in a hybrid ac/dc distribution network with different levels of distributed generation and loads verify the effectiveness of the method

Specifically Targeting the CD22 Receptor of Human B-cell Lymphomas with RNA Damaging Agents

Targeting CD22 on human B-cells with a monoclonal antibody conjugated to a cytotoxic RNAse causes potent and specific killing of the lymphoma cells in vitro. This translates to anti-tumor effects in human lymphoma models in SCID mice. RNA damage caused by RNAses could be an important alternative to standard DNA damaging chemotherapeutics. Moreover, targeted RNAses may overcome problems of toxicity and immunogenicity associated with plant or bacterial toxin containing immunotoxins