DEVELOPING INTEGRATED MACHINE LEARNING MODELS FOR AUTOMATIC COMPUTER-AIDED DIAGNOSIS IN ISCHEMIC ACUTE STROKE MRI

Fast detection and quantification of lesion cores in diffusion weighted images (DWIs) has been highly anticipated in clinical and research communities for planning treatment of acute stroke. The recent emergence of successful machine learning (ML) methods, especially Deep Learning (DL), enables automatic Computer Aided Diagnosis (CAD) of stroke in DWIs. However, the lack of publicly available large-scale data and ML models in clinical acute stroke DWI application are still the bottlenecks. In this work, we established the first large annotated open-source database of 2,888 clinical acute stroke MRIs (Chapter 2) to train and develop ML models for automatic stroke lesion detection and segmentation in clinical acute stroke MRI (Chapter 3). For automatic measurement of infarcted arterial territories, the first digital 3D deformable brain arterial territory atlas was created (Chapter 4). In addition, a fully automatic ML system is created to generate automatic radiological reports (Chapter 5 and 6) for calculation of ASPECTS, prediction and quantification of infarcted arterial and anatomical regions, and estimation of hydrocephalus presented in acute stroke MRI. The complete ML system in this work runs locally in real time with minimal computational requirements. It is publicly available and readily useful for non-expert users

Paper-based enzymatic microfluidic fuel cell: From a two-stream flow device to a single-stream lateral flow strip

This work presents a first approach towards the development of a cost-effective enzymatic paper-based glucose/O2 microfluidic fuel cell in which fluid transport is based on capillary action. A first fuel cell configuration consists of a Y-shaped paper device with the fuel and the oxidant flowing in parallel over carbon paper electrodes modified with bioelectrocatalytic enzymes. The anode consists of a ferrocenium-based polyethyleneimine polymer linked to glucose oxidase (GOx/Fc-C6-LPEI), while the cathode contains a mixture of laccase, anthracene-modified multiwall carbon nanotubes, and tetrabutylammonium bromide-modified Nafion (MWCNTs/laccase/TBAB-Nafion). Subsequently, the Y-shaped configuration is improved to use a single solution containing both, the anolyte and the catholyte. Thus, the electrolytes pHs of the fuel and the oxidant solutions are adapted to an intermediate pH of 5.5. Finally, the fuel cell is run with this single solution obtaining a maximum open circuit of 0.55 ± 0.04 V and a maximum current and power density of 225 ± 17 μA cm−2 and 24 ± 5 μW cm−2, respectively. Hence, a power source closer to a commercial application (similar to conventional lateral flow test strips) is developed and successfully operated. This system can be used to supply the energy required to power microelectronics demanding low power consumption.F. Javier del Campo acknowledges funding from the Spanish Ministry of Economy through the DADDi2 project (TEC2013-48506-C3). Juan Pablo Esquivel would like to thank the support from Marie Curie International Outgoing Fellowship (APPOCS-328144) within the 7th European Community Framework Programme. Shelley D. Minteer and Fabien Giroud would like to thank the National Science Foundation (CHE-1057597) for funding. Neus Sabaté acknowledges funding from the European H2020 Framework Programme (Grant Agreement 648518 - SUPERCELL - ERC 2014 CoG).Peer reviewe

Regulation of High-Temperature Stress Response by Small RNAs

Temperature extremes constitute one of the most common environmental stresses that adversely affect the growth and development of plants. Transcriptional regulation of temperature stress responses, particularly involving protein-coding gene networks, has been intensively studied in recent years. High-throughput sequencing technologies enabled the detection of a great number of small RNAs that have been found to change during and following temperature stress. The precise molecular action of some of these has been elucidated in detail. In the present chapter, we summarize the current understanding of small RNA-mediated modulation of high- temperature stress-regulatory pathways including basal stress responses, acclimation, and thermo-memory. We gather evidence that suggests that small RNA network changes, involving multiple upregulated and downregulated small RNAs, balance the trade-off between growth/development and stress responses, in order to ensure successful adaptation. We highlight specific characteristics of small RNA-based tem- perature stress regulation in crop plants. Finally, we explore the perspectives of the use of small RNAs in breeding to improve stress tolerance, which may be relevant for agriculture in the near future

Risk Factors for HIV-1 seroconversion among Taiwanese men visiting gay saunas who have sex with men

<p>Abstract</p> <p>Background</p> <p>Men having sex with men (MSM) accounts for 33.6% of all reported cases of HIV-1 infection in Taiwan. The aim of this study was to investigate the epidemiology of HIV-1 infection among MSM in gay saunas in Taiwan.</p> <p>Methods</p> <p>Patrons of 5 gay saunas were recruited for a weekly volunteer counseling and testing program from 2001 to 2005. Questionnaires were collected for a risk factor analysis. HIV-1 subtypes were determined using DNA sequencing and phylogenetic analyses.</p> <p>Results</p> <p>HIV-1 prevalence rates among MSM in gay saunas in 2001 through 2005 were 3.4%, 5.1%, 8.9%, 8.5%, and 8.3%, respectively. In total, 81 of 1, 093 (7.4%) MSM had HIV-1 infection. Fifty-two HIV-1 strains were genotyped, and all of them were subtype B. HIV-seropositive men were significantly younger than the seronegatives. Only 37.1% used condoms every time during sexual intercourse. A multivariate logistic regression analysis showed that the risk factors for HIV-1 were being uncircumcised (odds ratio (OR) = 2.19; 95% confidence interval (CI), 1.08~4.45); having sexual intercourse with at least 2 partners during each sauna visit (≥ 2 vs. ≤ 1, OR = 1.71; 95% CI, 1.02~2.89); and the role played during anal intercourse (versatile vs. an exclusively insertive role, OR = 2.76; 95% CI, 1.42~5.36).</p> <p>Conclusions</p> <p>Overall, 7.4% Taiwanese MSM participating in this study had HIV-1 subtype B infection. Uncircumcised, being versatile role during anal intercourse, and having sex with more than one person during each sauna visit were main risk factors for HIV-1 infection.</p

Foxp2 controls synaptic wiring of corticostriatal circuits and vocal communication by opposing Mef2c

Cortico-basal ganglia circuits are critical for speech and language and are implicated in autism spectrum disorder, in which language function can be severely affected. We demonstrate that in the mouse striatum, the gene Foxp2 negatively interacts with the synapse suppressor gene Mef2c. We present causal evidence that Mef2c inhibition by Foxp2 in neonatal mouse striatum controls synaptogenesis of corticostriatal inputs and vocalization in neonates. Mef2c suppresses corticostriatal synapse formation and striatal spinogenesis, but can itself be repressed by Foxp2 through direct DNA binding. Foxp2 deletion de-represses Mef2c, and both intrastriatal and global decrease of Mef2c rescue vocalization and striatal spinogenesis defects of Foxp2-deletion mutants. These findings suggest that Foxp2-Mef2C signaling is critical to corticostriatal circuit formation. If found in humans, such signaling defects could contribute to a range of neurologic and neuropsychiatric disorders.National Institutes of Health (U.S.) (Grant R37 HD028341)Eunice Kennedy Shriver National Institute of Child Health and Human Development (U.S.) (Award R37 HD028341

Rosiglitazone Inhibits Transforming Growth Factor-β1 Mediated Fibrogenesis in ADPKD Cyst-Lining Epithelial Cells

BACKGROUND: Interstitial fibrosis plays an important role in progressive renal dysfunction in autosomal dominant polycystic kidney disease (ADPKD). In our previous studies, we confirmed that PPAR-γ agonist, rosiglitazone could protect renal function and prolong the survival of a slowly progressive ADPKD animal model by reducing renal fibrosis. However, the mechanism remains unknown. METHODS: Primary culture epithelial cells pretreated with TGF-β1 were incubated with rosiglitazone. Extracellular matrix proteins were detected using real-time PCR and Western blotting. MAPK and Smad2 phosphorylation were measured with western blot. ERK1/2 pathway and P38 pathway were inhibited with the specific inhibitors PD98059 and SB203580. The Smad2 pathway was blocked with the siRNA. To address whether PPAR-γ agonist-mediated inhibition of TGF-β1-induced collagen type I expression was mediated through a PPAR-γ dependent mechanism, genetic and pharmaceutical approaches were used to block the activity of endogenous PPARγ. RESULTS: TGF-β1-stimulated collagen type I and fibronectin expression of ADPKD cyst-lining epithelia were inhibited by rosiglitazone in a dosage-dependent manner. Smad2, ERK1/2 and P38 pathways were activated in response to TGF-β1; however, TGF-β1 had little effect on JNK pathway. Rosiglitazone suppressed TGF-β1 induced Smad2 activation, while ERK1/2 and P38MAPK signals remained unaffected. Rosiglitazone could also attenuate TGF-β1-stimulated collagen type I and fibronectin expression in primary renal tubular epithelial cells, but had no effect on TGF-β1-induced activation of Smad2, ERK1/2 and P38 pathways. There was no crosstalk between the Smad2 and MAPK pathways in ADPKD cyst-lining epithelial cells. These inhibitory effects of rosiglitazone were reversed by the PPARγ specific antagonist GW9662 and PPARγ siRNA. CONCLUSION: ADPKD cyst-lining epithelial cells participate in TGF-β1 mediated fibrogenesis. Rosiglitazone could suppress TGF-β1-induced collagen type I and fibronectin expression in ADPKD cyst-lining epithelia through modulation of the Smad2 pathway. Our study may provide therapeutic basis for clinical applications of rosiglitazone in retarding the progression of ADPKD

Plasmodium knowlesi: Reservoir Hosts and Tracking the Emergence in Humans and Macaques

Plasmodium knowlesi, a malaria parasite originally thought to be restricted to macaques in Southeast Asia, has recently been recognized as a significant cause of human malaria. Unlike the benign and morphologically similar P. malariae, these parasites can lead to fatal infections. Malaria parasites, including P. knowlesi, have not yet been detected in macaques of the Kapit Division of Malaysian Borneo, where the majority of human knowlesi malaria cases have been reported. In order to extend our understanding of the epidemiology and evolutionary history of P. knowlesi, we examined 108 wild macaques for malaria parasites and sequenced the circumsporozoite protein (csp) gene and mitochondrial (mt) DNA of P. knowlesi isolates derived from macaques and humans. We detected five species of Plasmodium (P. knowlesi, P. inui, P. cynomolgi, P. fieldi and P. coatneyi) in the long-tailed and pig-tailed macaques, and an extremely high prevalence of P. inui and P. knowlesi. Macaques had a higher number of P. knowlesi genotypes per infection than humans, and some diverse alleles of the P. knowlesi csp gene and certain mtDNA haplotypes were shared between both hosts. Analyses of DNA sequence data indicate that there are no mtDNA lineages associated exclusively with either host. Furthermore, our analyses of the mtDNA data reveal that P. knowlesi is derived from an ancestral parasite population that existed prior to human settlement in Southeast Asia, and underwent significant population expansion approximately 30,000–40,000 years ago. Our results indicate that human infections with P. knowlesi are not newly emergent in Southeast Asia and that knowlesi malaria is primarily a zoonosis with wild macaques as the reservoir hosts. However, ongoing ecological changes resulting from deforestation, with an associated increase in the human population, could enable this pathogenic species of Plasmodium to switch to humans as the preferred host

Expression of a Novel Antimicrobial Peptide Penaeidin4-1 in Creeping Bentgrass (Agrostis stolonifera L.) Enhances Plant Fungal Disease Resistance

BACKGROUND: Turfgrass species are agriculturally and economically important perennial crops. Turfgrass species are highly susceptible to a wide range of fungal pathogens. Dollar spot and brown patch, two important diseases caused by fungal pathogens Sclerotinia homoecarpa and Rhizoctonia solani, respectively, are among the most severe turfgrass diseases. Currently, turf fungal disease control mainly relies on fungicide treatments, which raises many concerns for human health and the environment. Antimicrobial peptides found in various organisms play an important role in innate immune response. METHODOLOGY/PRINCIPAL FINDINGS: The antimicrobial peptide - Penaeidin4-1 (Pen4-1) from the shrimp, Litopenaeus setiferus has been reported to possess in vitro antifungal and antibacterial activities against various economically important fungal and bacterial pathogens. In this study, we have studied the feasibility of using this novel peptide for engineering enhanced disease resistance into creeping bentgrass plants (Agrostis stolonifera L., cv. Penn A-4). Two DNA constructs were prepared containing either the coding sequence of a single peptide, Pen4-1 or the DNA sequence coding for the transit signal peptide of the secreted tobacco AP24 protein translationally fused to the Pen4-1 coding sequence. A maize ubiquitin promoter was used in both constructs to drive gene expression. Transgenic turfgrass plants containing different DNA constructs were generated by Agrobacterium-mediated transformation and analyzed for transgene insertion and expression. In replicated in vitro and in vivo experiments under controlled environments, transgenic plants exhibited significantly enhanced resistance to dollar spot and brown patch, the two major fungal diseases in turfgrass. The targeting of Pen4-1 to endoplasmic reticulum by the transit peptide of AP24 protein did not significantly impact disease resistance in transgenic plants. CONCLUSION/SIGNIFICANCE: Our results demonstrate the effectiveness of Pen4-1 in a perennial species against fungal pathogens and suggest a potential strategy for engineering broad-spectrum fungal disease resistance in crop species