Detection of Delay Faults in Memory Address Decoders

In this paper we present an efficient test concept for detection of delay faults in memory address decoders based on the march test tactic. The proposed Transition Sequence Generator (TSG) generates an optimal transition sequence for sensitization of the delay faults in address decoders by Hayes's transformation on a reflected Gray code. It can be used for parallel Built-In Self-Testing (BIST) of high-density RAMs. We also present an efficient Design For Test (DFT) approach for immediate detection of the effects of the delay faults in the address decoders which does not change memory access time. It requires extra logic to be attached to the outputs of the address decoders. This DFT approach can be used to increase memory testability for both on-line and off-line testing of single- and multi-port RAMs.     

Alpha-Synuclein Autoimmune Decline in Prodromal Multiple System Atrophy and Parkinson’s Disease

Multiple-system trophy (MSA) and Parkinson’s Disease (PD) are both progressive, neurodegenerative diseases characterized by neuropathological deposition of aggregated alpha-synuclein (αSyn). The causes behind this aggregation are still unknown. We have reported aberrancies in MSA and PD patients in naturally occurring autoantibodies (nAbs) against αSyn (anti-αSyn-nAbs), which are important partakers in anti-aggregatory processes, immune-mediated clearance, and anti-inflammatory functions. To elaborate further on the timeline of autoimmune aberrancies towards αSyn, we investigated here the Immunoglobulin (Ig) affinity profile and subclass composition (IgG-total, IgG1-4 and IgM) of anti-αSyn-nAbs in serum samples from prodromal (p) phases of MSA and PD. Using an electrochemiluminescence competition immunoassay, we confirmed that the repertoire of high-affinity anti-αSyn-nAbs is significantly reduced in pMSA and pPD. Further, we demonstrated that pPD had increased anti-αSyn IgG-total levels compared to pMSA and controls, concordant with increased anti-αSyn IgG1 levels in pPD. Anti-αSyn IgG2 and IgG4 levels were reduced in pMSA and pPD compared with controls, whereas anti-αSyn IgG3 levels were reduced in pMSA compared to pPD and controls. The results indicate that the impaired reactivity towards αSyn occurs prior to disease onset. The apparent lack of high-affinity anti-αSyn nAbs may result in reduced clearance of αSyn, leading to aggregation of the protein. Thus, this study provides novel insights into possible causes behind the pathogenesis in synucleinopathies such as MSA and PD.     

HIV-2 Neutralization Sensitivity in Relation to Co-Receptor Entry Pathways and Env Motifs

HIV-2, compared to HIV-1, elicits potent and broadly neutralizing antibodies, and uses a broad range of co-receptors. However, both sensitivity to neutralization and breadth of co-receptor use varies between HIV-2 isolates, and the molecular background is still not fully understood. Thus, in the current study, we have deciphered relationships between HIV-2 neutralization sensitivity, co-receptor use and viral envelope glycoprotein (Env) molecular motifs. A panel of primary HIV-2 isolates, with predefined use of co-receptors, was assessed for neutralization sensitivity using a set of HIV-2 Env-directed monoclonal antibodies and co-receptor indicator cell lines. Neutralization sensitivity of the isolates was analysed in relation target cell co-receptor expression, in addition to amino acid motifs and predicted structures of Env regions. Results showed that HIV-2 isolates were more resistant to neutralizing antibodies when entering target cells via the alternative co-receptor GPR15, as compared to CCR5. A similar pattern was noted for isolates using the alternative co-receptor CXCR6. Sensitivity to neutralizing antibodies appeared also to be linked to specific Env motifs in V1/V2 and C3 regions. Our findings suggest that HIV-2 sensitivity to neutralization depends both on which co-receptor is used for cell entry and on specific Env motifs. This study highlights the multifactorial mechanisms behind HIV-2 neutralization sensitivity.     

Enhanced chain dynamics in loop-sorting-systems by means of layout optimization and a kinematic model of the polygon action

Poor dynamics owing to polygon action is a known concern in mechanical applications of closed articulated chains. In this paper a kinematic model of the polygon action in large chains of loop-sorting-systems is proposed. Through optimization techniques the chain dynamics is improved by minimizing the polygon action using a parametric model of the track layout as design variables. Three formulations of the kinematic polygon action are tested on an average sized planer tracks layout to find a superior model. Verification of the proposed optimization method is performed using a state-of-the-art multi-body simulation model of the chain dynamics.     

Facile Microwave Assisted Synthesis of Silver Nanostars for Ultrasensitive Detection of Biological Analytes by SERS

We report a very simple, rapid and reproducible method for the fabrication of anisotropic silver nanostars (AgNS) that can be successfully used as highly efficient SERS substrates for different bioanalytes, even in the case of a near-infra-red (NIR) excitation laser. The nanostars have been synthesized using the chemical reduction of Ag⁺ ions by trisodium citrate. This is the first research reporting the synthesis of AgNS using only trisodium citrate as a reducing and stabilizing agent. The key elements of this original synthesis procedure are rapid hydrothermal synthesis of silver nanostars followed by a cooling down procedure by immersion in a water bath. The synthesis was performed in a sealed bottom flask homogenously heated and brought to a boil in a microwave oven. After 60 s, the colloidal solution was cooled down to room temperature by immersion in a water bath at 35 °C. The as-synthesized AgNS were washed by centrifugation and used for SERS analysis of test molecules (methylene blue) as well as biological analytes: pharmaceutical compounds with various Raman cross sections (doxorubicin, atenolol & metoprolol), cell lysates and amino acids (methionine & cysteine). UV-Vis absorption spectroscopy, (Scanning) Transmission Electron Microscopy ((S)TEM) and Atomic Force Microscopy (AFM) have been employed for investigating nanostars’ physical properties.     

Induced Zinc Loss Produces Heterogenous Biological Responses in Melanoma Cells

Zinc levels in serum and/or tissue are reported to be altered in melanoma with unknown effects on melanoma development and biology. The purpose of this study was to examine the effects of acute chelation of free intracellular zinc pools in melanoma cell lines Bowes and A375, as well as selected melanoma tissue explants with high or low intracellular free zinc. Zinc chelating agent TPEN at the concentration of 25 µM was employed during 48 h, which significantly reduced intracellular free zinc while decreasing melanoma cell proliferation, inducing G1/S arrest and cell damage leading to mitochondrial, caspase-dependent apoptosis. Chelation of free zinc was also associated with increased generation of superoxide in cell lines but not marked lysosomal membrane damage. Conversely, melanoma explant cultures mostly displayed time-dependent loss of lysosomal membrane integrity in the presence of slowly growing superoxide levels. Loss of free zinc-dependent p53 activity was similarly disparate in individual melanoma models. Surviving melanoma cells were arrested in the cell cycle, and varying proportions of them exhibited features characteristic of premature senescence, which increased in time despite zinc reloading. The present results show that melanoma cells with varying free zinc levels respond to its acute loss in a number of individual ways, reflecting activated mechanisms including oxidative stress, lysosomal damage, and p53 activity leading to heterogenous outcomes including cell death, transient, and/or permanent cell cycle arrest and premature senescence.     

Experimental Study of Classical and Quantum Internal Friction in Solid 4He

We measured the dissipation resulting from internal friction in hcp solid ⁴He at temperatures between 0.8 K and 2.5 K. Solid ⁴He is contained inside an annular metal cell forming a part of a torsional oscillator. An oscillatory motion of the cell walls applies shear stress on the solid ⁴He. The resulting shear strain within the solid ⁴He generates dissipation because of the internal friction. The experimental sensitivity was high enough to detect dissipation caused by internal friction associated with elementary excitations of the solid. At temperatures below 1.6 K, internal friction is associated with diffusion of single point defects responsible for the climb of dislocations. At higher temperatures, the main mechanism of internal friction appears to be associated with phonon exchange between parts of the solid moving relative to each other under the applied shear stress. This particular dissipative mechanism was called “quantum phonon friction” [Popov in Phys. Rev. Lett. 83:1632–1635, 1999]. The physical mechanism associated with this type of friction involves an irreversible transfer of momentum from the phonons to the lattice via an Umklapp process. Our data are in a very good agreement with this model.

     

Pathways to controlled 3D deformation of graphene: Manipulating the motion of topological defects

Functional properties of 2D materials like graphene can be tailored by designing their 3D structure at the Angstrom to nanometer scale. While there are routes to tailoring 3D structure at larger scales, achieving controllable sub-micron 3D deformations has remained an elusive goal since the original discovery of graphene. In this contribution, we summarize the state-of-the-art in controllable 3D structures, and present our perspective on pathways to realizing atomic-scale control. We propose an approach based on strategic application of mechanical load to precisely relocate and position topological defects that give rise to curvature and corrugation to achieve a desired 3D structure. Realizing this approach requires establishing the detailed nature of defect migration and pathways in response to applied load. From a computational perspective, the key needed advances lie in the identification of defect migration mechanisms. These needed advances define new forward and inverse problems: when a fixed stress or strain field is applied, along which pathways will defects migrate?, and vice versa. We provide a formal statement of these forward and inverse problems, and review recent methods that may enable solving them. The forward problem is addressed by determining the potential energy surface of allowable topological configurations through Monte Carlo and Gaussian process models to determine defect migration paths through dynamic programming algorithms or Monte Carlo tree search. Two inverse models are suggested, one based on genetic algorithms and another on convolutional neural networks, to predict the applied loads that induce migration and position defects to achieve desired curvature and corrugation. The realization of controllable 3D structures enables a vast design space at multiple scales to enable new functionality in flexible electronics, soft robotics, biomimetics, optics, and other application areas.