Assessing the Impact of Sample Heterogeneity on Transcriptome Analysis of Human Diseases Using MDP Webtool

Transcriptome analyses have increased our understanding of the molecular mechanisms underlying human diseases. Most approaches aim to identify significant genes by comparing their expression values between healthy subjects and a group of patients with a certain disease. Given that studies normally contain few samples, the heterogeneity among individuals caused by environmental factors or undetected illnesses can impact gene expression analyses. We present a systematic analysis of sample heterogeneity in a variety of gene expression studies relating to inflammatory and infectious diseases and show that novel immunological insights may arise once heterogeneity is addressed. The perturbation score of samples is quantified using nonperturbed subjects (i.e., healthy subjects) as a reference group. Such a score allows us to detect outlying samples and subgroups of diseased patients and even assess the molecular perturbation of single cells infected with viruses. We also show how removal of outlying samples can improve the “signal” of the disease and impact detection of differentially expressed genes. The method is made available via the mdp Bioconductor R package and as a user-friendly webtool, webMDP, available at http://mdp.sysbio.tools

Transcatheter Arterial Embolization of Nonvariceal Upper Gastrointestinal Bleeding with N-Butyl Cyanoacrylate

OBJECTIVE: To evaluate the clinical efficacy and safety of transcatheter arterial embolization (TAE) with N-Butyl Cyanoacrylate (NBCA) for nonvariceal upper gastrointestinal bleeding. MATERIALS AND METHODS: Between March 1999 and December 2002, TAE for nonvariceal upper gastrointestinal bleeding was performed in 93 patients. The endoscopic approach had failed or was discarded as an approach for control of bleeding in all study patients. Among the 93 patients NBCA was used as the primary embolic material for TAE in 32 patients (28 men, four women; mean age, 59.1 years). The indications for choosing NBCA as the embolic material were: inability to advance the microcatheter to the bleeding site and effective wedging of the microcatheter into the bleeding artery. TAE was performed using 1:1-1:3 mixtures of NBCA and iodized oil. The angiographic and clinical success rate, recurrent bleeding rate, procedure related complications and clinical outcomes were evaluated. RESULTS: The angiographic and clinical success rates were 100% and 91% (29/32), respectively. There were no serious ischemic complications. Recurrent bleeding occurred in three patients (9%) and they were managed with emergency surgery (n = 1) and with a successful second TAE (n = 2). Eighteen patients (56%) had a coagulopathy at the time of TAE and the clinical success rate in this group of patients was 83% (15/18). CONCLUSION: TAE with NBCA is a highly effective and safe treatment modality for nonvariceal upper gastrointestinal bleeding, especially when it is not possible to advance the microcatheter to the bleeding site and when the patient has a coagulopathy

Strain-induced Evolution of Electronic Band Structures in a Twisted Graphene Bilayer

Here we study the evolution of local electronic properties of a twisted graphene bilayer induced by a strain and a high curvature. The strain and curvature strongly affect the local band structures of the twisted graphene bilayer; the energy difference of the two low-energy van Hove singularities decreases with increasing the lattice deformations and the states condensed into well-defined pseudo-Landau levels, which mimic the quantization of massive Dirac fermions in a magnetic field of about 100 T, along a graphene wrinkle. The joint effect of strain and out-of-plane distortion in the graphene wrinkle also results in a valley polarization with a significant gap, i.e., the eight-fold degenerate Landau level at the charge neutrality point is splitted into two four-fold degenerate quartets polarized on each layer. These results suggest that strained graphene bilayer could be an ideal platform to realize the high-temperature zero-field quantum valley Hall effect.Comment: 4 figure

Performance evaluation of bluetooth low energy for high data rate body area networks

Bluetooth Low Energy (BLE) is a promising wireless network technology, in the context of body area network (BAN) applications, to provide the required quality of service (QoS) support concerning the communication between sensor nodes placed on a user’s body and a personal device, such as a smartphone. Most previous BLE performance studies in the literature have focused primarily in networks with a single slave (point-to-point link) or traffic scenarios with relatively low data rate. However, many BAN sensors generate high data rate traffic, and several sensor nodes (slaves) may be actively sending data in the same BAN. Therefore, this work focuses on the evaluation of the suitability of BLE mainly under these conditions. Results show that, for the same traffic, the BLE protocol presents lower energy consumption and supports more sensor nodes than an alternative IEEE 802.15.4-based protocol. This study also identifies and characterizes some implementation constraints on the tested platforms that impose limits on the achievable performance.This work has been supported by FCT (Fundação para a Ciência e Tecnologia) in the scope of the projects UID/EEA/04436/2013 and UID/CTM/50025/2013, and by FEDER funds through the COMPETE 2020 Programme

Towards critical physics in 2+1d with U(2N )-invariant fermions

Interacting theories of N relativistic fermion flavors in reducible spinor rep- resentations in 2+1 spacetime dimensions are formulated on a lattice using domain wall fermions (DWF), for which a U(2N) global symmetry is recovered in the limit that the wall separation Ls is made large. The Gross-Neveu (GN) model is studied in the large-N limit and an exponential acceleration of convergence to the large-Ls limit is demonstrated if the usual parity-invariant mass mψ ̄ψ is replaced by the U(2N)-equivalent im3ψ ̄γ3ψ. The GN model and two lattice variants of the Thirring model are simulated for N = 2 using a hybrid Monte Carlo algorithm, and studies made of the symmetry-breaking bilinear con- densate and its associated susceptibility, the axial Ward identity, and the mass spectrum of both fermion and meson excitations. Comparisons are made with existing results ob- tained using staggered fermions. For the GN model a symmetry-breaking phase transition is observed, the Ward identity is recovered, and the spectrum found to be consistent with large-N expectations. There appears to be no obstruction to the study of critical UV fixed-point physics using DWF. For the Thirring model the Ward identity is not recovered, the spectroscopy measurements are inconclusive, and no symmetry breaking is observed all the way up to the effective strong coupling limit. This is consistent with a critical Thirring flavor number Nc < 2, contradicting earlier staggered fermion results

Artificial graphene as a tunable Dirac material

Artificial honeycomb lattices offer a tunable platform to study massless Dirac quasiparticles and their topological and correlated phases. Here we review recent progress in the design and fabrication of such synthetic structures focusing on nanopatterning of two-dimensional electron gases in semiconductors, molecule-by-molecule assembly by scanning probe methods, and optical trapping of ultracold atoms in crystals of light. We also discuss photonic crystals with Dirac cone dispersion and topologically protected edge states. We emphasize how the interplay between single-particle band structure engineering and cooperative effects leads to spectacular manifestations in tunneling and optical spectroscopies.Comment: Review article, 14 pages, 5 figures, 112 Reference

'Mitochondrial energy imbalance and lipid peroxidation cause cell death in Friedreich's ataxia'

Friedreich's ataxia (FRDA) is an inherited neurodegenerative disease. The mutation consists of a GAA repeat expansion within the FXN gene, which downregulates frataxin, leading to abnormal mitochondrial iron accumulation, which may in turn cause changes in mitochondrial function. Although, many studies of FRDA patients and mouse models have been conducted in the past two decades, the role of frataxin in mitochondrial pathophysiology remains elusive. Are the mitochondrial abnormalities only a side effect of the increased accumulation of reactive iron, generating oxidative stress? Or does the progressive lack of iron-sulphur clusters (ISCs), induced by reduced frataxin, cause an inhibition of the electron transport chain complexes (CI, II and III) leading to reactive oxygen species escaping from oxidative phosphorylation reactions? To answer these crucial questions, we have characterised the mitochondrial pathophysiology of a group of disease-relevant and readily accessible neurons, cerebellar granule cells, from a validated FRDA mouse model. By using live cell imaging and biochemical techniques we were able to demonstrate that mitochondria are deregulated in neurons from the YG8R FRDA mouse model, causing a decrease in mitochondrial membrane potential (▵Ψm) due to an inhibition of Complex I, which is partially compensated by an overactivation of Complex II. This complex activity imbalance leads to ROS generation in both mitochondrial matrix and cytosol, which results in glutathione depletion and increased lipid peroxidation. Preventing this increase in lipid peroxidation, in neurons, protects against in cell death. This work describes the pathophysiological properties of the mitochondria in neurons from a FRDA mouse model and shows that lipid peroxidation could be an important target for novel therapeutic strategies in FRDA, which still lacks a cure

Estimation of lung vital capacity before and after coronary artery bypass grafting surgery: a comparison of incentive spirometer and ventilometry

<p>Abstract</p> <p>Background</p> <p>Measurement of vital capacity (VC) by spirometry is the most widely used technique for lung function evaluation, however, this form of assessment is costly and further investigation of other reliable methods at lower cost is necessary. Objective: To analyze the correlation between direct vital capacity measured with ventilometer and with incentive inspirometer in patients in pre and post cardiac surgery.</p> <p>Methodology</p> <p>Cross-sectional comparative study with patients undergoing cardiac surgery. Respiratory parameters were evaluated through the measurement of VC performed by ventilometer and inspirometer. To analyze data normality the Kolmogorov-Smirnov test was applied, for correlation the Pearson correlation coefficient was used and for comparison of variables in pre and post operative period Student's t test was adopted. We established a level of ignificance of 5%. Data was presented as an average, standard deviation and relative frequency when needed. The significance level was set at 5%.</p> <p>Results</p> <p>We studied 52 patients undergoing cardiac surgery, 20 patients in preoperative with VC-ventilometer: 32.95 ± 11.4 ml/kg and VC-inspirometer: 28.9 ± 11 ml/Kg, r = 0.7 p < 0.001. In the post operatory, 32 patients were evaluated with VC-ventilometer: 28.27 ± 12.48 ml/kg and VC-inspirometer: 26.98 ± 11 ml/Kg, r = 0.95 p < 0.001. Presenting a very high correlation between the evaluation forms studied.</p> <p>Conclusion</p> <p>There was a high correlation between DVC measures with ventilometer and incentive spirometer in pre and post CABG surgery. Despite this, arises the necessity of further studies to evaluate the repercussion of this method in lowering costs at hospitals.</p