Electrode pooling: How to boost the yield of switchable silicon probes for neuronal recordings

State-of-the-art silicon probes for electrical recording from neurons have thousands of recording sites, but only a fraction of them can be used simultaneously due to the forbiddingly large volume of the associated wires. To overcome this fundamental constraint, we propose a novel method called "electrode pooling" that uses a single wire to serve multiple recording sites. Multiple electrodes are connected to a single wire through a set of controllable switches. Here we present the framework behind this method and an experimental strategy to support it. We show that under suitable conditions electrode pooling can save wires without compromising the content of the recordings. We make recommendations for the design of future devices to take advantage of this strategy

Complete response to FOLFOX4 therapy in a patient with advanced urothelial cancer: a case report

No standard has been established for salvage therapy in gemcitabine refractory advanced urothelial cancer. We report the complete response to FOLFOX4 therapy of a metastatic urothelial cancer patient, for whom adjuvant gemcitabine plus cisplatin combination chemotherapy had failed. A 54-year-old male patient with urothelial cancer (transitional cell carcinoma) in the right kidney underwent three rounds of adjuvant gemcitabine-cisplatin chemotherapy after extensive radical nephrectomy. However, he had new liver, lung metastases and synchronous two separate primary colon cancer. The lung metastasis lesion was confirmed as a metastatic urothelial cancer via percutaneous transthoracic needle biopsy (PTNB). Liver and lung metastasis lesions disappeared after the 4th cycle of FOLFOX4 chemotherapy. In addition, colon cancer also disappeared after the 8th cycle of FOLFOX4 chemotherapy. The patient was still showing a complete response after 4 months. Clinical trials using the FOLFOX regimen as salvage therapy for gemcitabine-refractory advanced urothelial cancer are warranted

Electrode pooling: boosting the yield of extracellular recordings with switchable silicon probes

State-of-the-art silicon probes for electrical recording from neurons have thousands of recording sites. However, due to volume limitations there are typically many fewer wires carrying signals off the probe, which restricts the number of channels that can be recorded simultaneously. To overcome this fundamental constraint, we propose a novel method called electrode pooling that uses a single wire to serve many recording sites through a set of controllable switches. Here we present the framework behind this method and an experimental strategy to support it. We then demonstrate its feasibility by implementing electrode pooling on the Neuropixels 1.0 electrode array and characterizing its effect on signal and noise. Finally we use simulations to explore the conditions under which electrode pooling saves wires without compromising the content of the recordings. We make recommendations on the design of future devices to take advantage of this strategy

Quantitative Understanding of Probabilistic Behavior of Living Cells Operated by Vibrant Intracellular Networks

For quantitative understanding of probabilistic behaviors of living cells, it is essential to construct a correct mathematical description of intracellular networks interacting with complex cell environments, which has been a formidable task. Here, we present a novel model and stochastic kinetics for an intracellular network interacting with hidden cell environments, employing a complete description of cell state dynamics and its coupling to the system network. Our analysis reveals that various environmental effects on the product number fluctuation of intracellular reaction networks can be collectively characterized by Laplace transform of the time-correlation function of the product creation rate fluctuation with the Laplace variable being the product decay rate. On the basis of the latter result, we propose an efficient method for quantitative analysis of the chemical fluctuation produced by intracellular networks coupled to hidden cell environments. By applying the present approach to the gene expression network, we obtain simple analytic results for the gene expression variability and the environment-induced correlations between the expression levels of mutually noninteracting genes. The theoretical results compose a unified framework for quantitative understanding of various gene expression statistics observed across a number of different systems with a small number of adjustable parameters with clear physical meanings.National Research Foundation of Korea (Grant 2011-0016412)National Research Foundation of Korea (Priority Research Center Program 2009-0093817

An Emerging Diabetes Mellitus Diagnosis Modality: HbA1c

Classically, the diagnosis of diabetes has been made using the fasting plasma glucose, random plasma glucose, or a 2-hr 75-g oral glucose tolerance test. There are many problems with the definition of diabetes based on blood glucose levels, such as the high intra-individual biological variability, variability in the collection and storage methods, and difficulty in ensuring a fasting state before measuring the blood glucose [1]. Recently, the hemoglobin A1c (HbA1c) assay has also been recommended for the diagnosis of diabetes. The HbA1c concentration is a good indicator of glycemic control over the previous 8-12 weeks; the time period is dictated by the 120-day lifespan of erythrocytes. HbA1c is used as the standard biomarker for the adequacy of glycemic management since it correlates well with both microvascular and, to a lesser extent, macrovascular complications based on

Parkin Promotes Mitophagic Cell Death in Adult Hippocampal Neural Stem Cells Following Insulin Withdrawal

Regulated cell death (RCD) plays a fundamental role in human health and disease. Apoptosis is the best-studied mode of RCD, but the importance of other modes has recently been gaining attention. We have previously demonstrated that adult rat hippocampal neural stem (HCN) cells undergo autophagy-dependent cell death (ADCD) following insulin withdrawal. Here, we show that Parkin mediates mitophagy and ADCD in insulin-deprived HCN cells. Insulin withdrawal increased the amount of depolarized mitochondria and their colocalization with autophagosomes. Insulin withdrawal also upregulated both mRNA and protein levels of Parkin, gene knockout of which prevented mitophagy and ADCD. c-Jun is a transcriptional repressor of Parkin and is degraded by the proteasome following insulin withdrawal. In insulin-deprived HCN cells, Parkin is required for Ca2+ accumulation and depolarization of mitochondria at the early stages of mitophagy as well as for recognition and removal of depolarized mitochondria at later stages. In contrast to the pro-death role of Parkin during mitophagy, Parkin deletion rendered HCN cells susceptible to apoptosis, revealing distinct roles of Parkin depending on different modes of RCD. Taken together, these results indicate that Parkin is required for the induction of ADCD accompanying mitochondrial dysfunction in HCN cells following insulin withdrawal. Since impaired insulin signaling is implicated in hippocampal deficits in various neurodegenerative diseases and psychological disorders, these findings may help to understand the mechanisms underlying death of neural stem cells and develop novel therapeutic strategies aiming to improve neurogenesis and survival of neural stem cells