Design of an experimental setup for delivering intracortical microstimulation in vivo via Spiking Neural Network

Electroceutical approaches for the treatment of neurological disorders, such as stroke, can take advantage of neuromorphic engineering, to develop devices able to achieve a seamless interaction with the neural system. This paper illustrates the development and test of a hardware-based Spiking Neural Network (SNN) to deliver neural-like stimulation patterns in an open-loop fashion. Neurons in the SNN have been designed by following the Hodgkin-Huxley formalism, with parameters taken from neuroscientific literature. We then built the set-up to deliver the SNN-driven stimulation in vivo. We used deeply anesthetized healthy rats to test the potential effect of the SNN-driven stimulation. We analyzed the neuronal firing activity pre- and post-stimulation in both the primary somatosensory and the rostral forelimb area. Our results showed that the SNN-based neurostimulation was able increase the spontaneous level of neuronal firing at both monitored locations, as found in the literature only for closed-loop stimulation. This study represents the first step towards translating the use of neuromorphic-based devices into clinical applications

Phenotypic expression and founder effect of PANK2 c.1583C > T (p.T528M) mutation in Serbian pantothenate kinase-associated neurodegeneration patients.

Pantothenate kinase-associated neurodegeneration (PKAN) is an autosomal recessive disorder characterized by dystonia, parkinsonism, cognitive and visual impairment, and iron accumulation in the brain. Many cases of PKAN result from mutations in the PANK2 gene that encodes pantothenate kinase 2, a key regulatory enzyme in the biosynthesis of coenzyme A. We previously detected six Serbian patients with clinically suggestive PKAN, all of whom had PANK2 c.1583C>T (p.T528M) mutation either in the homozygous or in the heterozygous state. In this study we explored the phenotypic expression and a possible founder effect of this substitution. We performed the analysis of linkage disequilibrium (LD) and organization in haplotypes of 23 single nucleotide polymorphisms (SNPs) adjacent to the PANK2 gene in all of the six patients and their parents, as well as in control healthy child-parents trios. The age of PANK2 c.1583C>T mutation was determined using the r(2) degeneration method. Clinical findings in our patients were markedly similar. Different LD structures between patients and controls is revealed, and PANK2 c.1583T allele was significantly associated with a particular haplotype. The age of PANK2 c.1583C>T mutation was estimated to be about 15 generations. Our results suggest that PANK2 c.1583C>T in Serbian PKAN patients represents a founder mutation descended from one common ancestor

Oxidation-Assisted Cracking at 650 °C in Superalloy 718 Manufactured by Laser Beam Melting: Effect of Temperature and Strain Rate

Additive manufacturing of complex parts in superalloy 718 by Laser Beam Melting (LBM, also referred to Selective Laser Melting, SLM) is currently under the evaluation by the aerospace industry, due to the opportunity to combine alloy 718 excellent properties and versatility of use, with the benefits and increasing maturity of LBM technology. In this work, the interactions between fracture modes and deformation modes for LBM-manufactured 718 were studied at 20, 450 and 650 °C. Vertical and horizontal tensile specimens were fabricated, then heat-treated with two sets of standard solution-aging treatments, before being tested in air over a range of strain rate from 8 × 10–5 to 3 × 10−2 s−1. Results of these tests showed evidence of a coupling effect between oxidation and mechanical loading, resulting in oxidation-assisted cracking of LBM 718 alloy for the same temperature and strain rate conditions than conventionally-manufactured alloy 718. Also, in spite of consisting of fundamentally different microstructures, relationships between fracture modes and deformation modes for laser beam melted 718 were found to be surprisingly consistent with the ones previously established for conventional 718. These results suggests that microstructure parameters such as grain size and morphology, or phase distribution are not involved at the first order in the mechanisms controlling these interactions. To further describe these phenomena, the interactions between solute elements, mobile dislocations and interfaces must be considered

High expression of HMGA2 independently predicts poor clinical outcomes in acute myeloid leukemia

In acute myeloid leukemia (AML), risk stratification based on cytogenetics and mutation profiling is essential but remains insufficient to select the optimal therapy. Accurate biomarkers are needed to improve prognostic assessment. We analyzed RNA sequencing and survival data of 430 AML patients and identified HMGA2 as a novel prognostic marker. We validated a quantitative PCR test to study the association of HMGA2 expression with clinical outcomes in 358 AML samples. In this training cohort, HMGA2 was highly expressed in 22.3% of AML, mostly in patients with intermediate or adverse cytogenetics. High expression levels of HMGA2 (H + ) were associated with a lower frequency of complete remission (58.8% vs 83.4%, P < 0.001), worse 3-year overall survival (OS, 13.2% vs 43.5%, P < 0.001) and relapse-free survival (RFS, 10.8% vs 44.2%, P < 0.001). A positive HMGA2 test also identified a subgroup of patients unresponsive to standard treatments. Multivariable analyses showed that H + was independently associated with significantly worse OS and RFS, including in the intermediate cytogenetic risk category. These associations were confirmed in a validation cohort of 260 patient samples from the UK NCRI AML17 trial. The HMGA2 test could be implemented in clinical trials developing novel therapeutic strategies for high-risk AML