Effects of Motion Sickness on Encoding and Retrieval Performance and on Psychophysiological Responses

Background: Motion sickness has previously been found to deteriorate performance. In complex working environments, sustained ability to perform despite motion sickness is crucial. This study focuses on effects of motion sickness on encoding and retrieval of words. In addition, the temporal development of psychophysiological responses and their relationship with perceived motion sickness were investigated. Methods: Forty healthy participants (20 male and 20 female, age 19-51) performed an encoding and retrieval task during exposure to an optokinetic drum and were compared with 20 controls (8 male and 12 female, age 21-47) not exposed to motion sickness. Measurements of heart rate, heart rate variability, skin conductance, blood volume pulse, respiration rate, and skin temperature were made throughout optokinetic drum exposure. Results: Moderate levels of motion sickness did not affect the ability to encode or retrieve words. Perceived motion sickness was positively related to heart rate, blood volume pulse and skin temperature and negatively related to respiration rate. Conclusions: The psychophysiological measurements did not show consistent patterns of sympathetic activation and parasympathetic withdrawal, as could be expected. Subjective reports of progressing symptoms are still likely to be the most reliable way of assessing motion sickness

Alkane-modified short polyethyleneimine for siRNA delivery

RNA interference (RNAi) is a highly specific gene-silencing mechanism triggered by small interfering RNA (siRNA). Effective intracellular delivery requires the development of potent siRNA carriers. Here, we describe the synthesis and screening of a series of siRNA delivery materials. Short polyethyleneimine (PEI, Mw 600) was selected as a cationic backbone to which lipid tails were conjugated at various levels of saturation. In solution these polymer–lipid hybrids self-assemble to form nanoparticles capable of complexing siRNA. The complexes silence genes specifically and with low cytotoxicity. The efficiency of gene knockdown increased as the number of lipid tails conjugated to the PEI backbone increased. This is explained by reducing the binding affinity between the siRNA strands to the complex, thereby enabling siRNA release after cellular internalization. These results highlight the importance of complexation strength when designing siRNA delivery materials.Misrock FoundationAmerican Society for Engineering Education. National Defense Science and Engineering Graduate FellowshipNational Institutes of Health (U.S) (Grant EB000244)National Cancer Institute (U.S.) (MIT-Harvard Center of Cancer Nanotechnology Excellence. Grant CA151884)National Science Foundation (U.S.)Massachusetts Institute of Technology (Presidential Fellowships

Interaction between integrin α5 and PDE4D regulates endothelial inflammatory signalling

Atherosclerosis is primarily a disease of lipid metabolism and inflammation; however, it is also closely associated with endothelial extracellular matrix (ECM) remodelling, with fibronectin accumulating in the laminin–collagen basement membrane. To investigate how fibronectin modulates inflammation in arteries, we replaced the cytoplasmic tail of the fibronectin receptor integrin α5 with that of the collagen/laminin receptor integrin α2. This chimaera suppressed inflammatory signalling in endothelial cells on fibronectin and in knock-in mice. Fibronectin promoted inflammation by suppressing anti-inflammatory cAMP. cAMP was activated through endothelial prostacyclin secretion; however, this was ECM-independent. Instead, cells on fibronectin suppressed cAMP via enhanced phosphodiesterase (PDE) activity, through direct binding of integrin α5 to phosphodiesterase-4D5 (PDE4D5), which induced PP2A-dependent dephosphorylation of PDE4D5 on the inhibitory site Ser651. In vivo knockdown of PDE4D5 inhibited inflammation at athero-prone sites. These data elucidate a molecular mechanism linking ECM remodelling and inflammation, thereby identifying a new class of therapeutic targets.United States. National Institutes of Health (5R01HL75092)National Science Foundation (U.S.). Materials Research Science and Engineering Centers (Program) (MR/J007412/1

Adipose tissue pathways involved in weight loss of cancer cachexia

White adipose tissue (WAT) constitutes our most expandable tissue and largest endocrine organ secreting hundreds of polypeptides collectively termed adipokines. Changes in WAT mass induce alterations in adipocyte secretion and function, which are linked to disturbed whole-body metabolism. Although the mechanisms controlling this are not clear they are dependent on changes in gene expression, a complex process which is regulated at several levels. Results in recent years have highlighted the role of small non-coding RNA molecules termed microRNAs (miRNAs), which regulate gene expression via post-transcriptional mechanisms. The aim of this thesis was to characterize global gene expression levels and describe novel miRNAs and adipokines controlling the function of human WAT in conditions with pathological increases or decreases in WAT mass. Obesity and cancer cachexia were selected as two models since they are both clinically relevant and characterized by involuntary changes in WAT mass. In Study I, expressional analyses were performed in subcutaneous WAT from cancer patients with or without cachexia and obese versus non-obese subjects. In total, 425 transcripts were found to be regulated in cancer cachexia. Pathway analyses based on this set of genes revealed that processes involving extracellular matrix, actin cytoskeleton and focal adhesion were significantly downregulated, whereas fatty acid metabolism was upregulated comparing cachectic with weight-stable cancer subjects. Furthermore, by overlapping these results with microarray data from an obesity study, many transcripts were found to be reciprocally regulated comparing the two conditions. This suggests that WAT gene expression in cancer cachexia and obesity are regulated by similar, albeit opposing, mechanisms. In Study II, the focus was on the family of fibroblast growth factors (FGFs), members of which have recently been implicated in the development of obesity and insulin resistance. A retrospective analysis of global gene expression data identified several FGFs (FGF1/2/7/9/13/18) to be expressed in WAT. However, only one, FGF1, was actively secreted from WAT and predominantly so from the adipocyte fraction. Moreover, FGF1 release was increased in obese compared to non-obese subjects, but was not normalized by weight loss. Although the clinical significance of these findings is not yet clear, it can be hypothesized that FGF1 may play a role in WAT growth, possibly by promoting fat cell proliferation and/or differentiation. In Study III, we identified adipose miRNAs regulated in obesity. Out of eleven miRNAs regulated by changes in body fat mass, ten controlled the production of the pro-inflammatory chemoattractant chemokine (C-C motif) ligand 2 (CCL2) when overexpressed in fat cells and for two, miR-126 and -193b, signaling circuits were defined. In Study IV, a novel adipokine, semaphorin 3C (SEMA3C), was identified by combining transcriptome and secretome data. Detailed studies focusing on SEMA3C revealed that this factor was secreted from adipocytes and induced the expression of extracellular matrix and matricellular genes in preadipocytes. Furthermore, SEMA3C mRNA levels correlated with interstitial fibrosis and insulin resistance in WAT derived from subjects with a wide range in BMI. In summary, the results presented in this thesis have delineated transcriptional alterations in WAT in two clinically relevant conditions, obesity and cancer cachexia. This has allowed the identification of novel adipokines and microRNAs with potential pathophysiological importance. These findings form the basis for further studies aiming at understanding the central role of WAT in disorders associated with metabolic complications

Performance Analysis of Data Traffic in Small Cells Networks with User Mobility

We analyze the impact of inter-cell mobility on data traffic performance in dense networks with small cells. To this end, a multi-class queuing system with impatience is proposed as a generic model that captures mobility through the sojourn time of users in the cell. We provide mathematical proofs for the stability and the regularity of this multi-class queuing system. We then show how the performance of a homogeneous network is amenable to the application of the generic model to a single representative cell. This model is applied to derive the throughput of both mobile and static users, along with the handover probability. Numerical evaluation and simulation results are provided to assess the accuracy of the approach; we show, in particular, that both classes of users benefit from a throughput gain induced by the opportunistic displacement of mobile users among cells

The role of ICT in modulating the effect of education and lifelong learning on income inequality and economic growth in Africa

This study assesses the role of ICT in modulating the impact of education and lifelong learning on income inequality and economic growth. It focuses on a sample of 48 African countries from 2004 to 2014. The empirical evidence is based on the generalised method of moments (GMM). The following findings are established. First, mobile phone and internet each interact with primary school education to decrease income inequality. Second, all ICT indicators interact with secondary school education to exert a negative impact on the Gini index. Third, fixed broadband distinctly interacts with primary school education and lifelong learning to have a positive effect on economic growth. Fourth, ICT indicators do not significantly influence inequality and economic growth through tertiary school education and lifelong learning. These main findings are further substantiated. Policy implications are discussed