FDG-PET assessment of the locus coeruleus in Alzheimer’s disease

Sensitive and reliable in vivo imaging of the locus coeruleus (LC) is important to develop and evaluate its potential as a biomarker in neurodegenerative diseases such as Alzheimer’s disease (AD). It is not known whether AD-related alterations in LC integrity can be detected using 18F-labelled fluoro-2-deoxyglucose (FDG) positron emission tomography (PET). Mean FDG-PET images from AD patients (N ​= ​193) and controls (N ​= ​256) from the ADNI database were co-registered to a study-wise anatomical template. Regional LC median standardized uptake value ratio (SUVR) values were obtained using four previously published LC masks and normalized to values from pons and cerebellar vermis reference regions. To support the validity of our methods, other regions previously reported to be most and least affected metabolically in AD were also compared to controls. The LC did not show between-group differences in FDG-PET signal, whereas the mammillary bodies did, despite these regions having comparable volumes and SUVR ranges. Brain regions previously reported to be most and least affected metabolically in AD compared to controls showed medium-to-large and small effect sizes for SUVR differences respectively. The results do not support the current application of LC FDG-PET signal as an in vivo biomarker for AD. Methodological and demographic factors potentially contributing to these findings are discussed. Future research may investigate age-related differences in LC FDG-PET signal and higher resolution images to fully explore its biomarker potential

A Mechanical Mass Sensor with Yoctogram Resolution

Nanoelectromechanical systems (NEMS) have generated considerable interest as inertial mass sensors. NEMS resonators have been used to weigh cells, biomolecules, and gas molecules, creating many new possibilities for biological and chemical analysis [1-4]. Recently, NEMS-based mass sensors have been employed as a new tool in surface science in order to study e.g. the phase transitions or the diffusion of adsorbed atoms on nanoscale objects [5-7]. A key point in all these experiments is the ability to resolve small masses. Here we report on mass sensing experiments with a resolution of 1.7 yg (1 yg = 10^-24 g), which corresponds to the mass of one proton, or one hydrogen atom. The resonator is made of a ~150 nm long carbon nanotube resonator vibrating at nearly 2 GHz. The unprecedented level of sensitivity allows us to detect adsorption events of naphthalene molecules (C10H8) and to measure the binding energy of a Xe atom on the nanotube surface (131 meV). These ultrasensitive nanotube resonators offer new opportunities for mass spectrometry, magnetometry, and adsorption experiments.Comment: submitted version of the manuscrip

The role of electrons? spin in DNA oxidative damage recognition

Formation of 8-oxo-7,8-dihydro-20-deoxyguanosine (OG) is one of the most common forms of DNA oxidative damage found in human cells. Although this damage is prevalent in many disease states, it only marginally influences the structure and stability of double -stranded DNA (dsDNA). Therefore, it is a challenge to establish the mechanism by which this damage is detected by repair enzymes. We investigated the position-dependent effect of the damage on the interactions between dsDNA and oligopeptides using atomic force microscopy. The results were confirmed by monitoring the spin and location-dependent polarizability of the damaged DNA, applying a Hall device. The observations suggest that the interac-tion of peptide with DNA depends on oxidative damage in the DNA and on its location relative to the point of contact between the peptide and the DNA. Hence, a remote search mechanism for damage in DNA is possible

Conditional Tek Promoter-Driven Deletion of Arginyltransferase in the Germ Line Causes Defects in Gametogenesis and Early Embryonic Lethality in Mice

Posttranslational protein arginylation mediated by Ate1 is essential for cardiovascular development, actin cytoskeleton functioning, and cell migration. Ate1 plays a role in the regulation of cytoskeleton and is essential for cardiovascular development and angiogenesis—capillary remodeling driven by in-tissue migration of endothelial cells. To address the role of Ate1 in cytoskeleton-dependent processes and endothelial cell function during development, we produced a conditional mouse knockout with Ate1 deletion driven by Tek endothelial receptor tyrosine kinase promoter expressed in the endothelium and in the germ line. Contrary to expectations, Tek-Ate1 mice were viable and had no visible angiogenesis-related phenotypes; however, these mice showed reproductive defects, with high rates of embryonic lethality in the second generation, at stages much earlier than the complete Ate1 knockout strain. While some of the early lethality originated from the subpopulation of embryos with homozygous Tek-Cre transgene—a problem that has not previously been reported for this commercial mouse strain—a distinct subpopulation of embryos had lethality at early post-implantation stages that could be explained only by a previously unknown defect in gametogenesis originating from Tek-driven Ate1 deletion in premeiotic germs cells. These results demonstrate a novel role of Ate1 in germ cell development

Fabrication of one-dimensional Ag/multiwalled carbon nanotube nano-composite

Composite made of multiwalled carbon nanotubes coated with silver was fabricated by an electroless deposition process. The thickness of silver layer is about 40 to 60 nm, characterized as nano-crystalline with (111) crystal orientation along the nanotube's axial direction. The characterization of silver/carbon nanotube [Ag/CNT] nanowire has shown the large current carrying capability, and the electric conductivity is similar to the pure silver nanowires that Ag/CNT would be promising as building blocks for integrated circuits

Characterization and System Identification of XY Flexural Mechanism Using Double Parallelogram Manipulator for High Precision Scanning

This article represents modeling of double parallelogram flexural manipulator derived from basic classical mechanics theory. Fourth order vibration wave equation is used for mathematical modeling and its performance is determined for step input and sinusoidal forced input. Static characterization of DFM is carried out to determine stiffness and force deflection characteristics over the entire motion range and dynamic characteristics is carried out using Transient response and Frequency response. Transient response is determined using step input to DFM which gives system properties such as damping, rise time and settling time. These parameters are then compared with theoretical model presented previously. Frequency response of DFM system gives characteristics of system with different frequency inputs which is used for experimental modeling of DFM device. Here, Voice Coil Motor is used as Actuator and optical encoder is used for positioning sensing of motion stage. It is noted that theoretical model is having 5% accuracy with experimental results. To achieve better position and accuracy, PID and LQR (Linear Quadratic Regulator) implementation was carried out on experimental model. PID gains are optimally tuned by using Ziegler Nichols approach. PID control is implemented experimentally using dSPACE DS1104 microcontroller and Control Desk software. Experimentally, it is observed that positioning accuracy is less than 5 μm. Further multiple DFM blocks are arranged for developing XY flexural mechanism and static characterization was carried out on it. The comparison of experimental and FEA results for X-direction and Y-direction is presented at end of paper

Crowd Verifiable Zero-Knowledge and End-to-end Verifiable Multiparty Computation

Auditing a secure multiparty computation (MPC) protocol entails the validation of the protocol transcript by a third party that is otherwise untrusted. In this work, we introduce the concept of end-to-end verifiable MPC (VMPC), that requires the validation to provide a correctness guarantee even in the setting that all servers, trusted setup primitives and all the client systems utilized by the input-providing users of the MPC protocol are subverted by an adversary. To instantiate VMPC, we introduce a new concept in the setting of zero-knowlegde protocols that we term crowd verifiable zero-knowledge (CVZK). A CVZK protocol enables a prover to convince a set of verifiers about a certain statement, even though each one individually contributes a small amount of entropy for verification and some of them are adversarially controlled. Given CVZK, we present a VMPC protocol that is based on discrete-logarithm related assumptions. At the high level of adversity that VMPC is meant to withstand, it is infeasible to ensure perfect correctness, thus we investigate the classes of functions and verifiability relations that are feasible in our framework, and present a number of possible applications the underlying functions of which can be implemented via VMPC

Klebsiella pneumoniae is able to trigger epithelial-mesenchymal transition process in cultured airway epithelial cells

The ability of some bacterial pathogens to activate Epithelial-Mesenchymal Transition normally is a consequence of the persistence of a local chronic inflammatory response or depends on a direct interaction of the pathogens with the host epithelial cells. In this study we monitored the abilities of the K. pneumoniae to activate the expression of genes related to EMT-like processes and the occurrence of phenotypic changes in airway epithelial cells during the early steps of cell infection. We describe changes in the production of intracellular reactive oxygen species and increased HIF-1α mRNA expression in cells exposed to K. pneumoniae infection. We also describe the upregulation of a set of transcription factors implicated in the EMT processes, such as Twist, Snail and ZEB, indicating that the morphological changes of epithelial cells already appreciable after few hours from the K. pneumoniae infection are tightly regulated by the activation of transcriptional pathways, driving epithelial cells to EMT. These effects appear to be effectively counteracted by resveratrol, an antioxidant that is able to exert a sustained scavenging of the intracellular ROS. This is the first report indicating that strains of K. pneumoniae may promote EMT-like programs through direct interaction with epithelial cells without the involvement of inflammatory cells