In vitro mesenchymal stem cell responses on laser-welded NiTi alloy

The biocompatibility of NiTi after laser welding was studied by examining the in vitro (mesenchymal stem cell) MSC responses at different sets of time varying from early (4 to 12 h) to intermediate phases (1 and 4 days) of cell culture. The effects of physical (surface roughness and topography) and chemical (surface Ti/Ni ratio) changes as a consequence of laser welding in different regions (WZ, HAZ, and BM) on the cell morphology and cell coverage were studied. The results in this research indicated that the morphology of MSCs was affected primarily by the topographical factors in the WZ: the well-defined and directional dendritic pattern and the presence of deeper grooves. The morphology of MSCs was not significantly modulated by surface roughness. Despite the possible initial Ni release in the medium during the cell culture, no toxic effect seemed to cause to MSCs as evidenced by the success of adhesion and spreading of the cells onto different regions in the laser weldment. The good biocompatibility of the NiTi laser weldment has been firstly reported in this study.

Anthrax lethal toxin and the induction of CD4 T cell immunity

Bacillus anthracis secretes exotoxins which act through several mechanisms including those that can subvert adaptive immunity with respect both to antigen presenting cell and T cell function. The combination of Protective Antigen (PA) and Lethal Factor (LF) forming Lethal Toxin (LT), acts within host cells to down-regulate the mitogen activated protein kinase (MAPK) signaling cascade. Until recently the MAPK kinases were the only known substrate for LT; over the past few years it has become evident that LT also cleaves Nlrp1, leading to inflammasome activation and macrophage death. The predicted downstream consequences of subverting these important cellular pathways are impaired antigen presentation and adaptive immunity. In contrast to this, recent work has indicated that robust memory T cell responses to B. anthracis antigens can be identified following natural anthrax infection. We discuss how LT affects the adaptive immune response and specifically the identification of B. anthracis epitopes that are both immunogenic and protective with the potential for inclusion in protein sub-unit based vaccines.

Th1 not Th17 cells drive spontaneous MS-like disease despite a functional regulatory T cell response

Multiple sclerosis is considered a disease of complex autoimmune etiology, yet there remains a lack of consensus as to specific immune effector mechanisms. Recent analyses of experimental autoimmune encephalomyelitis, the common mouse model of multiple sclerosis, have investigated the relative contribution of Th1 and Th17 CD4 T cell subsets to initial autoimmune central nervous system (CNS) damage. However, inherent in these studies are biases influenced by the adjuvant and toxin needed to break self-tolerance. We investigated spontaneous CNS disease in a clinically relevant, humanized, T cell receptor transgenic mouse model. Mice develop spontaneous, ascending paralysis, allowing unbiased characterization of T cell immunity in an HLA-DR15-restricted T cell repertoire. Analysis of naturally progressing disease shows that IFN?(+) cells dominate disease initiation with IL-17(+) cells apparent in affected tissue only once disease is established. Tregs accumulate in the CNS but are ultimately ineffective at halting disease progression. However, ablation of Tregs causes profound acceleration of disease, with uncontrolled infiltration of lymphocytes into the CNS. This synchronous, severe disease allows characterization of the responses that are deregulated in exacerbated disease: the correlation is with increased CNS CD4 and CD8 IFN? responses. Recovery of the ablated Treg population halts ongoing disease progression and Tregs extracted from the central nervous system at peak disease are functionally competent to regulate myelin specific T cell responses. Thus, in a clinically relevant mouse model of MS, initial disease is IFN? driven and the enhanced central nervous system responses unleashed through Treg ablation comprise IFN? cytokine production by CD4 and CD8 cells, but not IL-17 responses.

HpMC: An Energy- Aware Management System for Multi-Level Memory Architectures

DRAM technology faces density and power challenges to increase capacity because of limitations of physical cell design. To overcome these limitations, system designers are exploring alternative solutions that combine DRAM and emerging NVRAM technologies. Previous work on heterogeneous memories focuses, mainly, on two system designs: PCache, a hierarchical, inclusive memory system, and HRank, a flat, non-inclusive memory system. We demonstrate that neither of these designs can universally achieve high performance and energy efficiency across a suite of HPC workloads. In this work, we investigate the impact of a number of multilevel memory designs on the performance, power, and energy consumption of applications. To achieve this goal and overcome the limited number of available tools to study heterogeneous memories, we created HMsim, an infrastructure that enables n-level, heterogeneous memory studies by leveraging existing memory simulators. We, then, propose HpMC, a new memory controller design that combines the best aspects of existing management policies to improve performance and energy. Our energy-aware memory management system dynamically switches between PCache and HRank based on the temporal locality of applications. Our results show that HpMC reduces energy consumption from 13% to 45% compared to PCache and HRank, while providing the same bandwidth and higher capacity than a conventional DRAM system.

Refresh-free dynamic standard-cell based memories: Application to a QC-LDPC decoder

The area and power consumption of low-density parity check (LDPC) decoders are typically dominated by embedded memories. To alleviate such high memory costs, this paper exploits the fact that all internal memories of a LDPC decoder are frequently updated with new data. These unique memory access statistics are taken advantage of by replacing all static standard-cell based memories (SCMs) of a prior-art LDPC decoder implementation by dynamic SCMs (D-SCMs), which are designed to retain data just long enough to guarantee reliable operation. The use of D-SCMs leads to a 44% reduction in silicon area of the LDPC decoder compared to the use of static SCMs. The low-power LDPC decoder architecture with refresh-free D-SCMs was implemented in a 90nm CMOS process, and silicon measurements show full functionality and an information bit throughput of up to 600 Mbps (as required by the IEEE 802.11n standard).

Corrosion Fatigue Behaviour of Laser-welded Shape Memory NiTi Wires in a Simulated Body Fluid

Corrosion fatigue is a fracture process as a consequence of synergistic interactions between the material structure, corrosive environment and cyclic loads/strains. It is difficult to be detected and can cause unexpected failure of engineering components in use. This study reveals a comparison of corrosion fatigue behaviour of laser-welded and bare NiTi wires using bending rotation fatigue (BRF) test coupled with a specifically-designed corrosion cell. The testing medium was Hanks’ solution (simulated body fluid) at 37.5 oC. Electrochemical impedance spectroscopic (EIS) measurement was carried out to monitor the change of corrosion resistance of sample during the BRF test at different periods of time. Experiments indicate that the laser-welded NiTi wire would be more susceptible to the corrosion fatigue attack than the bare NiTi wire. This study can serve as a benchmark for the product designers and engineers to understand the corrosion fatigue behaviour of the NiTi laser weld joint and determine the fatigue life safety factor for NiTi medical devices/implants involving laser welding in the fabrication process.