Behavior-level Analysis of a Successive Stochastic Approximation Analog-to-Digital Conversion System for Multi-channel Biomedical Data Acquisition

In the present paper, we propose a novel high-resolution analog-to-digital converter (ADC) for low-power biomedical analog frontends, which we call the successive stochastic approximation ADC. The proposed ADC uses a stochastic flash ADC (SF-ADC) to realize a digitally controlled variable-threshold comparator in a successive-approximationregister ADC (SAR-ADC), which can correct errors originating from the internal digital-to-analog converter in the SAR-ADC. For the residual error after SAR-ADC operation, which can be smaller than thermal noise, the SF-ADC uses the statistical characteristics of noise to achieve high resolution. The SF-ADC output for the residual signal is combined with the SAR-ADC output to obtain high-precision output data using the supervised machine learning method

Loss of GABARAP mediates resistance to immunogenic chemotherapy in multiple myeloma

: Immunogenic cell death (ICD) is a form of cell death by which cancer treatments can induce a clinically relevant anti-tumor immune response in a broad range of cancers. In multiple myeloma (MM), the proteasome inhibitor bortezomib is an ICD inducer and creates durable therapeutic responses in patients. However, eventual relapse and resistance to bortezomib appear inevitable. Here, by integrating patient transcriptomic data with an analysis of calreticulin (CRT) protein interactors, we found that GABARAP is a key player whose loss prevented tumor cell death from being perceived as immunogenic after bortezomib treatment. GABARAP is located on chromosome 17p, which is commonly deleted in high-risk MM patients. GABARAP deletion impaired the exposure of the eat-me signal CRT on the surface of dying MM cells in vitro and in vivo, thus reducing tumor cell phagocytosis by dendritic cells and the subsequent anti-tumor T cell response. Low GABARAP was independently associated with shorter MM patient survival and reduced tumor immune infiltration. Mechanistically, we found that GABARAP deletion blocked ICD signaling by decreasing autophagy and altering Golgi apparatus morphology, with consequent defects in the downstream vesicular transport of CRT. Conversely, upregulating autophagy using rapamycin restored Golgi morphology, CRT exposure and ICD signaling in GABARAPKO cells undergoing bortezomib treatment. Therefore, coupling an ICD inducer, like bortezomib, with an autophagy inducer, like rapamycin, may improve patient outcomes in MM, where low GABARAP in the form of del(17p) is common and leads to worse outcomes

Three‐dimensionally visualized ossification and mineralization process of the otic capsule in a postnatal developmental mouse

Abstract Objective We aimed to elucidate the ossification process of the otic capsule in postnatal C57BL/6 mice and depict the three‐dimensional (3D) process of otoconial mineralization in vivo. Methods The otic capsules of C57BL/6 mice were stained with alizarin red and imaged/compared using micro‐computed tomography on postnatal day (P) between P0 and P8, P10, P15, and P30 and 3–4 months old (P3–4Mo). We reconstructed 3D images of the otic capsule and otoconia and measured the bone mineral density using x‐ray absorptiometry on each age. Results The 3D reconstructed otic capsule images revealed two ossification centers of the otic capsule at P0. One was observed around the ampulla of the superior semicircular canal and utricle, and the other was observed around the ampulla of the posterior semicircular canal. The cross‐sectional views demonstrated that modiolar ossification developed from the base to the apex from P4 to P8. The inter‐scalar septum ossified bidirectionally from the modiolus and bony otic capsule from P8 to P15. The mineralized otoconia were first detected in the utricle at P3 and saccular otoconia at P6. The density of the utricle and saccular otoconia showed different growth trends. Conclusion To the best of our knowledge, this is the first study to demonstrate the 3D appearance of the otic capsule and otoconia in different developmental stages of mice. We also revealed that modiolar and inter‐scalar septal calcification is the final event in the cochlea and that it can be susceptible to pathological conditions (cochlear congenital malformations and hereditary vestibular diseases). The unique features of the ossification process and duration may explain these pathological conditions observed in humans. Level of Evidence