Apoptosis, a genetically controlled process of cell death, plays a central role in metazoan development and homeostasis (61,74). The apoptotic program is highly conserved during evolution, and striking similarities have been observed in the cell death programs of rodents, mammalian cells, Drosophila melanogaster, and Caenorhabditis elegans (28,81,85,91). In normally proliferating cells, the apoptotic program is actively suppressed or inactivated; however, withdrawal or inhibition of the apoptosis suppressor mechanisms triggers apoptotic pathways (16,37,86). One mechanism by which apoptotic gene products may be prevented from executing their effect may involve direct interaction with specific proteins that act to attenuate the function of the apoptotic activators or effectors. The interaction between antiapoptotic protein Bcl-2 and proapoptotic protein Bax illustrates this point: whether a cell undergoes apoptosis or not is dependent upon the relative levels of these two proteins; an excess of Bax will trigger apoptosis, whereas an excess of Bcl-2 will prevent apoptosis (38,66,68,89,90). Identification of other such antiapoptotic and proapoptotic protein pairs that dictate the survival of cells should enhance our understanding of the apoptosis process.Apoptosis is characterized by cell membrane blebbing, chromatin condensation, changes in nuclear architecture, and oligonucleosome-length DNA fragmentation (87, 88). The process of apoptotic cell death is triggered by diverse stimuli such as cytokines, withdrawal of growth factors, DNA damage, expression of oncogenes or immediate-early genes, and fluctuations in the levels of Bcl-2 family members (3,13,16,37,47,48,54,71,78,86,89). Certain apoptotic stimuli can sequentially activate the basal cell death machinery composed of initiator, amplifier, and effector proteases belonging to the interleukin-1-converting enzyme (ICE) subfamily or an ICE-related family (9,17,21,41,46,91). Downstream targets of these proteases include the ICE subfamily proteases themselves; nuclear enzymes poly(ADP-ribose) polymerase and DNA-dependent protein kinase, which are involved in DNA repair; the nuclear protein U1 ribonucleoprotein and nuclear lamins; and cytoplasmic components such as protein kinase C␦ and cytoskeleton components such as actin (cited in reference 21). However, it is unclear whether any of these cellular components are directly linked to the morphological changes associated with apoptosis.Prostate tissue, which is composed of androgen-dependent and -independent cells (8, 58), provides an excellent model system for studying apoptosis. Androgen ablation in animals leads to an elevation of intracellular calcium that subsequently results in apoptosis of the androgen-dependent but not of the androgen-independent prostatic cells (11,(42)(43)(44). However, apoptosis can be induced in androgen-independent cell cultures by artificially upregulating intracellular calcium with calcium ionophores (53, 69) or with thapsigargin (TG) (22), an

Resistive RAM crossbar arrays offer an attractive solution to minimize off-chip data transfer and parallelize on-chip computations for neural networks. Here, we report a hardware/software co-design approach based on low energy subquantum conductive bridging RAM (CBRAM®) devices and a network pruning technique to reduce network level energy consumption. First, we demonstrate low energy subquantum CBRAM devices exhibiting gradual switching characteristics important for implementing weight updates in hardware during unsupervised learning. Then we develop a network pruning algorithm that can be employed during training, different from previous network pruning approaches applied for inference only. Using a 512 kbit subquantum CBRAM array, we experimentally demonstrate high recognition accuracy on the MNIST dataset for digital implementation of unsupervised learning. Our hardware/software co-design approach can pave the way towards resistive memory based neuro-inspired systems that can autonomously learn and process information in power-limited settings.

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Electrophysiology is a decades-old technique widely used for monitoring activity of individual neurons and local field potentials. Optogenetics has revolutionized neuroscience studies by offering selective and fast control of targeted neurons and neuron populations. The combination of these two techniques is crucial for causal investigation of neural circuits and understanding their functional connectivity. However, electrical artifacts generated by light stimulation interfere with neural recordings and hinder the development of compact closed-loop systems for precise control of neural activity. Here, we demonstrate that transparent graphene micro-electrodes fabricated on a clear polyethylene terephthalate film eliminate the light-induced artifact problem and allow development of a compact battery-powered closed-loop optogenetics system. We extensively investigate light-induced artifacts for graphene electrodes in comparison to metal control electrodes. We then design optical stimulation module using micro-LED chips coupled to optical fibers to deliver light to intended depth for optogenetic stimulation. For artifact-free integration of graphene micro-electrode recordings with optogenetic stimulation, we design and develop a compact closed-loop system and validate it for different frequencies of interest for neural recordings. This compact closed-loop optogenetics system can be used for various applications involving optogenetic stimulation and electrophysiological recordings.

Toosendanin, a triterpenoid derivative isolated from the barks of Melia toosendan Sieb et Zucc, has been used as an anthelmintic vermifuge against ascaris for more than fifty years in China. In the present study, we investigated the growth inhibition and apoptosis-induced effect of toosendanin on human cancer cells. The result showed that toosendanin significantly suppressed the proliferation of tested human cancer cell lines. The IC(50) values were less than 1.7 x 10(-7) M and U937 was the most sensitive cell line with a IC(50) of 5.4 x 10(-9) M. Flow cytometric analysis revealed that treatment of U937 cells with toosendanin resulted in a dose- and time-dependent accumulation of cells in the S phase with a concomitant decrease in cells processing to G(0)/G(1) phase. The growth inhibition of U937 cells after exposure to toosendanin was subsequently associated with the induction of apoptosis, as evidence by the typical condensed and fragmented nuclei, DNA fragmentation, and exposure of phosphatidylserine on the outer leaflet of plasma membrane. All these results indicated that toosendanin could serve as a potential candidate for anticancer drug.