Aberrant protein expression in plasma and kidney tissue during experimental obstructive nephropathy

Kidney failure is a major health problem worldwide. Patients with end-stage renal disease require intensive medical support by dialysis or kidney transplantation. Current methods for diagnosis of kidney disease are either invasive or insensitive, and renal function may decline by as much as 50% before it can be detected using current techniques. The goal of this study was, therefore, to identify biomarkers of kidney disease (associated with renal fibrosis) that can be used for the development of a non-invasive clinical test for early disease detection. We utilized two protein-profiling technologies (SELDI-TOF MS and 2-D) to screen the plasma and kidney proteome for aberrantly expressed proteins in an experimental mouse model of unilateral uretric obstruction, which mimics the pathology of human renal disease. Several differentially regulated proteins were detected at the plasma level of day-3-obstructed animals, which included serum amyloid A1, fibrinogen α, haptoglobin precursor protein, haptoglobin and major urinary proteins 11 and 8. Differentially expressed proteins detected at the tissue level included ras-like activator protein 2, haptoglobin precursor protein, malate dehydrogenase, α enolase and murine urinary protein (all p<0.05 versus controls). Immunohistochemistry was used to confirm the up-regulation of fibrinogen. Interestingly, these proteins are largely separated into four major classes: (i) acute-phase reactants (ii) cell-signaling molecules (iii) molecules involved in cell growth and metabolism and (iv) urinary proteins. These results provide new insights into the pathology of obstructive nephropathy and may facilitate the development of specific assay(s) to detect and monitor renal fibrosis.     

Design and Development of Flexible PDMS Antenna for UWB-WBAN Applications

Wireless Personal Communications - This paper presents the design and development of a flexible Ultra Wide Band (UWB) antenna using polydimethylsiloxane as a substrate. Copper foil having a...     

Mammogram Learning System for Breast Cancer Diagnosis Using Deep Learning SVM

The most common form of cancer for women is breast cancer. Recent advances in medical imaging technologies increase the use of digital mammograms to diagnose breast cancer. Thus, an automated computerized system with high accuracy is needed. In this study, an efficient Deep Learning Architecture (DLA) with a Support Vector Machine (SVM) is designed for breast cancer diagnosis. It combines the ideas from DLA with SVM. The state-of-the-art Visual Geometric Group (VGG) architecture with 16 layers is employed in this study as it uses the small size of 3 × 3 convolution filters that reduces system complexity. The softmax layer in VGG assumes that the training samples belong to exactly only one class, which is not valid in a real situation, such as in medical image diagnosis. To overcome this situation, SVM is employed instead of the softmax layer in VGG. Data augmentation is also employed as DLA usually requires a large number of samples. VGG model with different SVM kernels is built to classify the mammograms. Results show that the VGG-SVM model has good potential for the classification of Mammographic Image Analysis Society (MIAS) database images with an accuracy of 98.67%, sensitivity of 99.32%, and specificity of 98.34%.     

Oxygen saturation-dependent effects on blood transverse relaxation at low fields

Objective

Blood oxygenation can be measured using magnetic resonance using the paramagnetic effect of deoxy-haemoglobin, which decreases the \(\textit{T}_{2}\) relaxation time of blood. This \(\textit{T}_{2}\) contrast has been well characterised at the \(\textit{B}_{{0}}\) fields used in MRI (1.5 T and above). However, few studies have characterised this effect at lower magnetic fields. Here, the feasibility of blood oximetry at low field based on \(\textit{T}_{2}\) changes that are within a physiological relevant range is explored. This study could be used for specifying requirements for construction of a monitoring device based on low field permanent magnet systems.

Methods

A continuous flow circuit was used to control parameters such as oxygen saturation and temperature in a sample of blood. It flowed through a variable field magnet, where CPMG experiments were performed to measure its \(\textit{T}_{2}\). In addition, the oxygen saturation was monitored by an optical sensor for comparison with the \(\textit{T}_{2}\) changes.

Results

These results show that at low \(\textit{B}_{{0}}\) fields, the change in blood \(\textit{T}_{2}\) due to oxygenation is small, but still detectable. The data measured at low fields are also in agreement with theoretical models for the oxy-deoxy \(\textit{T}_{2}\) effect.

Conclusion

\(\textit{T}_{2}\) changes in blood due to oxygenation were observed at fields as low as 0.1 T. These results suggest that low field NMR relaxometry devices around 0.3 T could be designed to detect changes in blood oxygenation.

     

Study of DNA Origami Dimerization and Dimer Dissociation Dynamics and of the Factors that Limit Dimerization

Organizing DNA origami building blocks into higher order structures is essential for fabrication of large structurally and functionally diverse devices and molecular machines. Unfortunately, the yields of origami building block attachment reactions are typically not sufficient to allow programed assembly of DNA devices made from more than a few origami building blocks. To investigate possible reasons for these low yields, a detailed single‐molecule fluorescence study of the dynamics of rectangular origami dimerization and origami dimer dissociation reactions is conducted. Reactions kinetics and yields are investigated at different origami and ion concentrations, for different ion types, for different lengths of bridging strands, and for the “sticky end” and “weaving welding” attachment techniques. Dimerization yields are never higher than 86%, which is typical for such systems. Analysis of the dynamic data shows that the low yield cannot be explained by thermodynamic instability or structural imperfections of the origami constructs. Atomic force microscopy and gel electrophoresis evidence reveal self‐dimerization of the origami monomers, likely via blunt‐end interactions made possible by the presence of bridging strands. It is suggested that this mechanism is the major factor that inhibits correct dimerization and means to overcome it are discussed.     

Spray-Coating of Superhydrophobic Coatings for Advanced Applications

Superhydrophobic coatings are widely applicable, e.g., as self-cleaning surfaces or water–oil separation membranes, yet their wider usage is impeded due to costs of fabrication, size, or substrate limitation. Spray-coating is a versatile coating procedures and might offer a good solution for the fabrication of these superhydrophobic coatings, due to the fact that coatings can be fabricated on various materials in a simple, fast, and inexpensive manner. Most procedures rely on hybrid coatings of hydrophobized nanoparticles and a polymeric matrix, which have several drawbacks including the easy loss of nanoparticles and difficult waste handling. Here, the fabrication of the superhydrophobic material, called Fluoropor, for the first time, by spray-coating on various substrates including metals, tissues, concrete, and glass is presented. It is fabricated by spray-coating a mixture of a highly fluorinated monomer blended with porogens followed by photopolymerization. The superhydrophobicity of the material relies on the porous structure on the micro-/nanoscale across the bulk material and does not require any nanoparticles. Excellent self-cleaning ability of these coatings, resistance against thermal and abrasive impact, and their application as oil–water separation membranes are shown. This versatile applicability is highly promising for real-world application as self-cleaning coatings or oil–water separating membranes.     

Measures for investigating the contextual modulation of information transmission

The aim of this paper is to show how information theoretic measures can be used to analyse and interpret the results of psychophysical experiments designed to search for conditions under which information from one source modulates the transmission of information from another source. We therefore use measures of mutual and conditional information to analyse systems with two inputs. The information transmitted by such a system can be split into three components depending on whether it is shared between the two inputs or is specific to each. We are concerned here with distinguishing systems that use one input to modulate transmission of information about the other from systems that simply add both inputs, and show how the three components provide evidence for distinguishing between additive and modulatory effects. We also report numerical simulations of the sampling biasses and variances of these measures as a function of the sample size and propose minimum sample sizes that should be used to overcome the bias.     

Adapting application execution in CMPs using helper threads

In parallel to the changes in both the architecture domain–the move toward chip multiprocessors (CMPs)–and the application domain–the move toward increasingly data-intensive workloads–issues such as performance, energy efficiency and CPU availability are becoming increasingly critical. The CPU availability can change dynamically due to several reasons such as thermal overload, increase in transient errors, or operating system scheduling. An important question in this context is how to adapt, in a CMP, the execution of a given application to CPU availability change at runtime. Our paper studies this problem, targeting the energy-delay product (EDP) as the main metric to optimize. We first discuss that, in adapting the application execution to the varying CPU availability, one needs to consider the number of CPUs to use, the number of application threads to accommodate and the voltage/frequency levels to employ (if the CMP has this capability). We then propose to use helper threads to adapt the application execution to CPU availability change in general with the goal of minimizing the EDP. The helper thread runs parallel to the application execution threads and tries to determine the ideal number of CPUs, threads and voltage/frequency levels to employ at any given point in execution. We illustrate this idea using four applications (Fast Fourier Transform, MultiGrid, LU decomposition and Conjugate Gradient) under different execution scenarios. The results collected through our experiments are very promising and indicate that significant EDP reductions are possible using helper threads. For example, we achieved up to 66.3%, 83.3%, 91.2%, and 94.2% savings in EDP when adjusting all the parameters properly in applications FFT, MG, LU, and CG, respectively. We also discuss how our approach can be extended to address multi-programmed workloads.     

Proteomic examination of Leishmania chagasi plasma membrane proteins: Contrast between avirulent and virulent (metacyclic) parasite forms

Purpose: About two million new cases of leishmaniasis with 50 000 associated deaths occur worldwide each year. Promastigotes of the causative Leishmania spp. develop from the procyclic stage to the highly virulent metacyclic stage within the sand fly vector. We hypothesized that proteins important for promastigote virulence might be uniquely represented in the plasma membrane of metacyclic, but not procyclic, promastigotes. Experimental design: Procyclic (logarithmic) promastigotes and purified metacyclic promastigotes from stationary phase cultures of Leishmania chagasi were used to prepare membrane preparations either by surface biotinylation‐streptavidin affinity separation or by octyl glucoside detergent extraction. Results: These membrane fractions were enriched over 130‐ and 250‐fold, respectively, as estimated by Western blotting for the plasma membrane's major surface protease. Hundreds or dozens of proteins were identified by LC‐MS/MS in the surface biotinylation or detergent extraction, respectively. Confocal microscopy suggested the difference between the lists was due to the fact that proteins localized both on the surface membrane and within the flagellar pocket were accessible to surface biotinylation, whereas only proteins on the membrane were obtained by detergent extraction. Using detergent extraction, we found different proteins were present in membranes of the procyclic stage compared to metacyclic stage promastigotes. Several dozen were stage specific. Conclusions and clinical relevance: These data provide a foundation for identifying virulence factors in the plasma membranes of Leishmania spp. promastigotes during metacyclogenesis.