Modelling personal thermal sensations using C-Support Vector Classification (C-SVC) algorithm

The personalised conditioning system (PCS) is widely studied. Potentially, it is able to reduce energy consumption while securing occupants’ thermal comfort requirements. It has been suggested that automatic optimised operation schemes for PCS should be introduced to avoid energy wastage and discomfort caused by inappropriate operation. In certain automatic operation schemes, personalised thermal sensation models are applied as key components to help in setting targets for PCS operation. In this research, a novel personal thermal sensation modelling method based on the C-Support Vector Classification (C-SVC) algorithm has been developed for PCS control. The personal thermal sensation modelling has been regarded as a classification problem. During the modelling process, the method ‘learns’ an occupant’s thermal preferences from his/her feedback, environmental parameters and personal physiological and behavioural factors. The modelling method has been verified by comparing the actual thermal sensation vote (TSV) with the modelled one based on 20 individual cases. Furthermore, the accuracy of each individual thermal sensation model has been compared with the outcomes of the PMV model. The results indicate that the modelling method presented in this paper is an effective tool to model personal thermal sensations and could be integrated within the PCS for optimised system operation and control

Over-expression of lysophosphatidic acid receptor-2 in human invasive ductal carcinoma

INTRODUCTION: Lysophosphatidic acid (LPA) is a bioactive phospholipid with diverse effects on various cells. It interacts with at least three G-protein-coupled transmembrane receptors, namely LPA1, LPA2 and LPA3, whose expression in various tumours has not been fully characterized. In the present study we characterized the expression profile of LPA receptors in human breast cancer tissue and assessed the possible roles of each receptor. METHODS: The relative expression levels of each receptor's mRNA against β-actin mRNA was examined in surgically resected invasive ductal carcinomas and normal gland tissue using real-time RT-PCR. LPA2 expression was also examined immunohistochemically using a rat anti-LPA2 monoclonal antibody. RESULTS: In 25 cases normal and cancer tissue contained LPA1 mRNA at similar levels, whereas the expression level of LPA2 mRNA was significantly increased in cancer tissue as compared with its normal counterpart (3479.0 ± 426.6 versus 1287.3 ± 466.8; P < 0.05). LPA3 was weakly expressed in both cancer and normal gland tissue. In 48 (57%) out of 84 cases, enhanced expression of LPA2 protein was confirmed in carcinoma cells as compared with normal mammary epithelium by immunohistochemistry. Over-expression of LPA2 was detected in 17 (45%) out of 38 premenopausal women, as compared with 31 (67%) out of 46 postmenopausal women, and the difference was statistically significant (P < 0.05). CONCLUSION: These findings suggest that upregulation of LPA2 may play a role in carcinogenesis, particularly in postmenopausal breast cancer

Discerning Tumor Status from Unstructured MRI Reports—Completeness of Information in Existing Reports and Utility of Automated Natural Language Processing

Information in electronic medical records is often in an unstructured free-text format. This format presents challenges for expedient data retrieval and may fail to convey important findings. Natural language processing (NLP) is an emerging technique for rapid and efficient clinical data retrieval. While proven in disease detection, the utility of NLP in discerning disease progression from free-text reports is untested. We aimed to (1) assess whether unstructured radiology reports contained sufficient information for tumor status classification; (2) develop an NLP-based data extraction tool to determine tumor status from unstructured reports; and (3) compare NLP and human tumor status classification outcomes. Consecutive follow-up brain tumor magnetic resonance imaging reports (2000–­2007) from a tertiary center were manually annotated using consensus guidelines on tumor status. Reports were randomized to NLP training (70%) or testing (30%) groups. The NLP tool utilized a support vector machines model with statistical and rule-based outcomes. Most reports had sufficient information for tumor status classification, although 0.8% did not describe status despite reference to prior examinations. Tumor size was unreported in 68.7% of documents, while 50.3% lacked data on change magnitude when there was detectable progression or regression. Using retrospective human classification as the gold standard, NLP achieved 80.6% sensitivity and 91.6% specificity for tumor status determination (mean positive predictive value, 82.4%; negative predictive value, 92.0%). In conclusion, most reports contained sufficient information for tumor status determination, though variable features were used to describe status. NLP demonstrated good accuracy for tumor status classification and may have novel application for automated disease status classification from electronic databases

Midgut Barrier Imparts Selective Resistance to Filarial Worm Infection in Culex pipiens pipiens

Mosquitoes in the Culex pipiens complex thrive in temperate and tropical regions worldwide, and serve as efficient vectors of Bancroftian lymphatic filariasis (LF) caused by Wuchereria bancrofti in Asia, Africa, the West Indies, South America, and Micronesia. However, members of this mosquito complex do not act as natural vectors for Brugian LF caused by Brugia malayi, or for the cat parasite B. pahangi, despite their presence in South Asia where these parasites are endemic. Previous work with the Iowa strain of Culex pipiens pipiens demonstrates that it is equally susceptible to W. bancrofti as is the natural Cx. p. pipiens vector in the Nile Delta, however it is refractory to infection with Brugia spp. Here we report that the infectivity barrier for Brugia spp. in Cx. p. pipiens is the mosquito midgut, which inflicts internal and lethal damage to ingested microfilariae. Following per os Brugia exposures, the prevalence of infection is significantly lower in Cx. p. pipiens compared to susceptible mosquito controls, and differs between parasite species with <50% and <5% of Cx. p. pipiens becoming infected with B. pahangi and B. malayi, respectively. When Brugia spp. mf were inoculated intrathoracically to bypass the midgut, larvae developed equally well as in controls, indicating that, beyond the midgut, Cx. p. pipiens is physiologically compatible with Brugia spp. Mf isolated from Cx. p. pipiens midguts exhibited compromised motility, and unlike mf derived from blood or isolated from the midguts of Ae. aegypti, failed to develop when inoculated intrathoracically into susceptible mosquitoes. Together these data strongly support the role of the midgut as the primary infection barrier for Brugia spp. in Cx. p. pipiens. Examination of parasites recovered from the Cx. p. pipiens midgut by vital staining, and those exsheathed with papain, suggest that the damage inflicted by the midgut is subcuticular and disrupts internal tissues. Microscopic studies of these worms reveal compromised motility and sharp bends in the body; and ultrastructurally the presence of many fluid or carbohydrate-filled vacuoles in the hypodermis, body wall, and nuclear column. Incubation of Brugia mf with Cx. p. pipiens midgut extracts produces similar internal damage phenotypes; indicating that the Cx. p. pipiens midgut factor(s) that damage mf in vivo are soluble and stable in physiological buffer, and inflict damage on mf in vitro

New highlights on stroma–epithelial interactions in breast cancer

Although the stroma in which carcinomas arise has been previously regarded as a bystander to the clonal expansion and acquisition of malignant characteristics of tumor cells, it is now generally acknowledged that stromal changes are required for the establishment of cancer. In the present article, we discuss three recent publications that highlight the complex role the stroma has during the development of cancer and the potential for targeting the stroma by therapeutic approaches

How to do an evaluation: pitfalls and traps

The recent literature is replete with papers evaluating computational tools (often those operating on 3D structures) for their performance in a certain set of tasks. Most commonly these papers compare a number of docking tools for their performance in cognate re-docking (pose prediction) and/or virtual screening. Related papers have been published on ligand-based tools: pose prediction by conformer generators and virtual screening using a variety of ligand-based approaches. The reliability of these comparisons is critically affected by a number of factors usually ignored by the authors, including bias in the datasets used in virtual screening, the metrics used to assess performance in virtual screening and pose prediction and errors in crystal structures used

How to do an evaluation: pitfalls and traps

The recent literature is replete with papers evaluating computational tools (often those operating on 3D structures) for their performance in a certain set of tasks. Most commonly these papers compare a number of docking tools for their performance in cognate re-docking (pose prediction) and/or virtual screening. Related papers have been published on ligand-based tools: pose prediction by conformer generators and virtual screening using a variety of ligand-based approaches. The reliability of these comparisons is critically affected by a number of factors usually ignored by the authors, including bias in the datasets used in virtual screening, the metrics used to assess performance in virtual screening and pose prediction and errors in crystal structures used

Genetic Evidence for Inhibition of Bacterial Division Protein FtsZ by Berberine

Background: Berberine is a plant alkaloid that is widely used as an anti-infective in traditional medicine. Escherichia coli exposed to berberine form filaments, suggesting an antibacterial mechanism that involves inhibition of cell division. Berberine is a DNA ligand and may induce filamentation through induction of the SOS response. Also, there is biochemical evidence for berberine inhibition of the cell division protein FtsZ. Here we aimed to assess possible berberine mechanism(s) of action in growing bacteria using genetics tools. Methodology/Principal Findings: First, we tested whether berberine inhibits bacterial growth through DNA damage and induction of the SOS response. The SOS response induced by berberine was much lower compared to that induced by mitomycin C in an SOS response reporter strain. Also, cell filamentation was observed in an SOS-negative E. coli strain. To test whether berberine inhibits FtsZ, we assessed its effects on formation of the cell division Z-rings, and observed a dramatic reduction in Z-rings in the presence of berberine. We next used two different strategies for RNA silencing of ftsZ and both resulted in sensitisation of bacteria to berberine, visible as a drop in the Minimum Inhibitory Concentration (MIC). Furthermore, Fractional Inhibitory Concentration Indices (FICIs) showed a high level of synergy between ftsZ silencing and berberine treatment (FICI values of 0.23 and 0.25 for peptide nucleic acid- and expressed antisense RNA-based silencing of ftsZ, respectively). Finally, over-expression of ftsZ led to a mild rescue effect in berberine-treated cells

Therapeutically relevant structural and functional mechanisms triggered by physical and cognitive exercise

Corrected by: Erratum: Molecular Psychiatry (2016) 21, 1645–1645; doi:10.1038/mp.2016.57; published online 19 April 2016. Following publication of the above article, the authors noticed that the second author’s name was presented incorrectly. The author’s name should have appeared as M Fiatarone Singh. The publisher regrets the error.Physical and cognitive exercise may prevent or delay dementia in later life but the neural mechanisms underlying these therapeutic benefits are largely unknown. We examined structural and functional magnetic resonance imaging (MRI) brain changes after 6 months of progressive resistance training (PRT), computerized cognitive training (CCT) or combined intervention. A total of 100 older individuals (68 females, average age=70.1, s.d.±6.7, 55-87 years) with dementia prodrome mild cognitive impairment were recruited in the SMART (Study of Mental Activity and Resistance Training) Trial. Participants were randomly assigned into four intervention groups: PRT+CCT, PRT+SHAM CCT, CCT+SHAM PRT and double SHAM. Multimodal MRI was conducted at baseline and at 6 months of follow-up (immediately after training) to measure structural and spontaneous functional changes in the brain, with a focus on the hippocampus and posterior cingulate regions. Participants' cognitive changes were also assessed before and after training. We found that PRT but not CCT significantly improved global cognition (F(90)=4.1, P<0.05) as well as expanded gray matter in the posterior cingulate (Pcorrected <0.05), and these changes were related to each other (r=0.25, P=0.03). PRT also reversed progression of white matter hyperintensities, a biomarker of cerebrovascular disease, in several brain areas. In contrast, CCT but not PRT attenuated decline in overall memory performance (F(90)=5.7, P<0.02), mediated by enhanced functional connectivity between the hippocampus and superior frontal cortex. Our findings indicate that physical and cognitive training depend on discrete neuronal mechanisms for their therapeutic efficacy, information that may help develop targeted lifestyle-based preventative strategies.Molecular Psychiatry advance online publication, 22 March 2016; doi:10.1038/mp.2016.19.C Suo, M Fiatarone Singh, N Gates, W Wen, P Sachdev, H Brodaty, N Saigal, GC Wilson, J Meiklejohn, N Singh, BT Baune, M Baker, N Foroughi, Y Wang, Y Mavros, A Lampit, I Leung, and MJ Valenzuel