Energy-Efficient Neural Network Architectures

Emerging systems for artificial intelligence (AI) are expected to rely on deep neural networks (DNNs) to achieve high accuracy for a broad variety of applications, including computer vision, robotics, and speech recognition. Due to the rapid growth of network size and depth, however, DNNs typically result in high computational costs and introduce considerable power and performance overheads. Dedicated chip architectures that implement DNNs with high energy efficiency are essential for adding intelligence to interactive edge devices, enabling them to complete increasingly sophisticated tasks by extending battery lie. They are also vital for improving performance in cloud servers that support demanding AI computations. This dissertation focuses on architectures and circuit technologies for designing energy-efficient neural network accelerators. First, a deep-learning processor is presented for achieving ultra-low power operation. Using a heterogeneous architecture that includes a low-power always-on front-end and a selectively-enabled high-performance back-end, the processor dynamically adjusts computational resources at runtime to support conditional execution in neural networks and meet performance targets with increased energy efficiency. Featuring a reconfigurable datapath and a memory architecture optimized for energy efficiency, the processor supports multilevel dynamic activation of neural network segments, performing object detection tasks with 5.3x lower energy consumption in comparison with a static execution baseline. Fabricated in 40nm CMOS, the processor test-chip dissipates 0.23mW at 5.3 fps. It demonstrates energy scalability up to 28.6 TOPS/W and can be configured to run a variety of workloads, including severely power-constrained ones such as always-on monitoring in mobile applications. To further improve the energy efficiency of the proposed heterogeneous architecture, a new charge-recovery logic family, called zero-short-circuit current (ZSCC) logic, is proposed to decrease the power consumption of the always-on front-end. By relying on dedicated circuit topologies and a four-phase clocking scheme, ZSCC operates with significantly reduced short-circuit currents, realizing order-of-magnitude power savings at relatively low clock frequencies (in the order of a few MHz). The efficiency and applicability of ZSCC is demonstrated through an ANSI S1.11 1/3 octave filter bank chip for binaural hearing aids with two microphones per ear. Fabricated in a 65nm CMOS process, this charge-recovery chip consumes 13.8µW with a 1.75MHz clock frequency, achieving 9.7x power reduction per input in comparison with a 40nm monophonic single-input chip that represents the published state of the art. The ability of ZSCC to further increase the energy efficiency of the heterogeneous neural network architecture is demonstrated through the design and evaluation of a ZSCC-based front-end. Simulation results show 17x power reduction compared with a conventional static CMOS implementation of the same architecture.PHDElectrical and Computer EngineeringUniversity of Michigan, Horace H. Rackham School of Graduate Studieshttps://deepblue.lib.umich.edu/bitstream/2027.42/147614/1/hsiwu_1.pd

Sox2, a stemness gene, regulates tumor-initiating and drug-resistant properties in CD133-positive glioblastoma stem cells

AbstractBackgroundGlioblastoma multiforme (GBM) is the most lethal type of adult brain cancer and performs outrageous growth and resistance regardless of adjuvant chemotherapies, eventually contributing to tumor recurrence and poor outcomes. Considering the common heterogeneity of cancer cells, the imbalanced regulatory mechanism could be switched on/off and contribute to drug resistance. Moreover, the subpopulation of GBM cells was recently discovered to share similar phenotypes with neural stem cells. These cancer stem cells (CSCs) promote the potency of tumor initiation. As a result, targeting of glioma stem cells has become the dominant way of improving the therapeutic outcome against GBM and extending the life span of patients. Among the biomarkers of CSCs, CD-133 (prominin-1) has been known to effectively isolate CSCs from cancer population, including GBM; however, the underlying mechanism of how stemness genes manipulate CSC-associated phenotypes, such as tumor initiation and relapse, is still unclear.MethodsTumorigenicity, drug resistance and embryonic stem cell markers were examined in primary CD133-positive (CD133+) GBM cells and CD133+ subpopulation. Stemness signature of CD133+ GBM cells was identified using microarray analysis. Stem cell potency, tumorigenicity and drug resistance were also tested in differential expression of SOX2 in GBM cells.ResultsIn this study, high tumorigenic and drug resistance was noticed in primary CD-133+ GBM cells; meanwhile, plenty of embryonic stem cell markers were also elevated in the CD-133+ subpopulation. Using microarray analysis, we identified SOX2 as the most enriched gene among the stemness signature in CD133+ GBM cells. Overexpression of SOX2 consistently enhanced the stem cell potency in the GBM cell lines, whereas knockdown of SOX2 dramatically withdrew CD133 expression in CD133+ GBM cells. Additionally, we silenced SOX2 expression using RNAi system, which abrogated the ability of tumor initiation as well as drug resistance of CD133+ GBM cells, suggesting that SOX2 plays a crucial role in regulating tumorigenicity in CD133+ GBM cells.ConclusionSOX2 plays a crucial role in regulating tumorigenicity in CD133+ GBM cells. Our results not only revealed the genetic plasticity contributing to drug resistance and stemness but also demonstrated the dominant role of SOX2 in maintenance of GBM CSCs, which may provide a novel therapeutic target to overcome the conundrum of poor survival of brain cancers

Suppression of Cell Growth, Migration and Drug Resistance by Ethanolic Extract of Antrodia cinnamomea in Human Lung Cancer A549 Cells and C57BL/6J Allograft Tumor Model

The purpose of this study was to investigate the inhibitory activities of ethanolic extracts from Antrodia cinnamomea (EEAC) on lung cancer. Cell proliferation and cell cycle distribution were analyzed using (3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide) (MTT) assay and flow cytometry, respectively. Wound-healing assay, Western blotting, and a murine tumor model were separately used to examine cell migration, protein expression, and tumor repression. Our results showed that EEAC induced cell cycle arrest at the G0/G1 phase resulting decreased cell viability in A549 cells. Moreover, EEAC up-regulated the growth-suppressing proteins, adenosine 5′-monophosphate-activated protein kinase (AMPK), p21 and p27, but down-regulated the growth-promoting proteins, protein kinase B (Akt), mammalian tarfet of rapamycin (mTOR), extracellular signal-regulating kinase 1/2 (ERK1/2), retinoblastoma protein (Rb), cyclin E, and cyclin D1. EEAC also inhibited A549 cell migration and reduced expression of gelatinases. In addition, our data showed that tumor growth was suppressed after treatment with EEAC in a murine allograft tumor model. Some bioactive compounds from EEAC, such as cordycepin and zhankuic acid A, were demonstrated to reduce the protein expressions of matrix metalloproteinase (MMP)-9 and cyclin D1 in A549 cells. Furthermore, EEAC enhanced chemosensitivity of A549 to paclitaxel by reducing the protein levels of caveolin-1. Our data suggests that EEAC has the potential to be an adjuvant medicine for the treatment of lung cancer

Neurologic and Non-neurologic Predictors of Mortality in Ischemic Stroke Patients Admitted to the Intensive Care Unit

Patients with severe strokes may have different associated medical comorbidities from those with mild strokes. This study evaluated the neurologic and non-neurologic medical predictors of mortality in patients with severe cerebral infarction in the acute stage. Methods: Patients admitted to a neurologic intensive care unit (ICU) due to cerebral infarction were included. Neurologic and non-neurologic predictors for in-unit mortality were determined by logistic regression analyses. Two models using (A) neurologic factors and (B) combined neurologic and non-neurologic factors as mortality predictors were developed. The performance of the models in predicting overall, neurologic and non-neurologic mortalities was compared by areas under the receiver-operating characteristic curves (AUC) of the derived regressive equations. Results: Of 231 patients with cerebral infarction admitted to the ICU, 34 (14.7%) died during ICU stay. Conscious state and acute physiologic abnormalities were significant predictors of mortality. The length of ICU stay in patients with non-neurologic mortality was longer than in those with neurologic mortality (p= 0.044). The AUC of Model B was larger than that of Model A in predicting overall (0.768 ± 0.045 vs. 0.863 ± 0.033, p=0.005) and non-neurologic mortalities (0.570 ± 0.073 vs. 0.707 ± 0.074, p=0.009), while there was no difference in predicting death from neurologic causes (0.858 ± 0.044 vs. 0.880 ± 0.032, p=0.217). Conclusion: Impaired consciousness and acute physiologic abnormalities are independent predictors of mortality for severe ischemic stroke during the acute stage. Neurologic factors predict early mortality from intrinsic cerebral dysfunction, while non-neurologic factors, especially the associated physiologic abnormalities, predict late mortality from medical complications

EGF up-regulates miR-31 through the C/EBPβ signal cascade in oral carcinoma.

Oral squamous cell carcinoma (OSCC) is one of the most prevalent carcinomas worldwide. MicroRNAs (miRNAs) are short, non-coding RNAs that regulate gene expression and modulate physiological or pathological processes including OSCC carcinogenesis. miR-31 has been found to be up-regulated in OSCC and to act as an oncogenic miRNA. However, the molecular mechanism underlying miR-31 up-regulation in OSCC is still obscure. The activation of epidermal growth factor receptor (EGFR) signaling axis plays key roles in driving oral carcinogenesis. Our screening identified that there is up-regulation of miR-31, miR-181b and miR-222 in OSCC cells following EGF treatment. Subsequent analysis showed that EGF treatment led to AKT activation, which then resulted in miR-31 up-regulation. Moreover, EGF treatment and the AKT activation induced by exogenous expression up-regulated C/EBPβ expression. The miR-31 up-regulation induced by EGF was abrogated by AKT inhibition or by the knockdown of C/EBPβ expression. In OSCC cell subclones stably overexpressing the functional isoform of C/EBPβ, miR-31 expression was up-regulated. Curcumin is a natural ingredient exhibiting anti-cancer potential. It was found that curcumin attenuated AKT activation and the up-regulation of C/EBPβ and miR-31 caused by EGF stimulation in OSCC cells. Lastly, concordance across the expression of EGFR, the expression of C/EBPβ and the expression of miR-31 in OSCC tissues was found. This study describes a novel scenario where the up-regulation of miR-31 expression in OSCC is, at least in part, a consequence of EGFR oncogenic activation. Although the AKT activation and C/EBPβ expression after EGF treatment might not be directly linked, both events are the crucial mediators underlying miR-31 up-regulation in the EGFR signaling axis

Lysophosphatidic acid alters the expression profiles of angiogenic factors, cytokines, and chemokines in mouse liver sinusoidal endothelial cells.

Lysophosphatidic acid (LPA) is a multi-function glycerophospholipid. LPA affects the proliferation of hepatocytes and stellate cells in vitro, and in a partial hepatectomy induced liver regeneration model, the circulating LPA levels and LPA receptor (LPAR) expression levels in liver tissue are significantly changed. Liver sinusoidal endothelial cells (Lsecs) play an important role during liver regeneration. However, the effects of LPA on Lsecs are not well known. Thus, we investigated the effects of LPA on the expression profiles of angiogenic factors, cytokines, and chemokines in Lsecs.Mouse Lsecs were isolated using CD31-coated magnetic beads. The mRNA expression levels of LPAR's and other target genes were determined by quantitative RT-PCR. The protein levels of angiogenesis factors, cytokines, and chemokines were determined using protein arrays and enzyme immunoassay (EIA). Critical LPAR related signal transduction was verified by using an appropriate chemical inhibitor.LPAR1 and LPAR3 mRNA's were expressed in mouse LPA-treated Lsecs. Treating Lsecs with a physiological level of LPA significantly enhanced the protein levels of angiogenesis related proteins (cyr61 and TIMP-1), cytokines (C5/C5a, M-CSF, and SDF-1), and chemokines (MCP-5, gp130, CCL28, and CXCL16). The LPAR1 and LPAR3 antagonist ki16425 significantly inhibited the LPA-enhanced expression of cyr61, TIMP-1, SDF-1, MCP-5, gp130, CCL28, and CXCL16, but not that of C5/C5a or M-CSF. LPA-induced C5/C5a and M-CSF expression may have been through an indirect regulation mechanism.LPA regulated the expression profiles of angiogenic factors, cytokines, and chemokines in Lsecs that was mediated via LPAR1 and LPAR3 signaling. Most of the factors that were enhanced by LPA have been found to play critical roles during liver regeneration. Thus, these results may prove useful for manipulating LPA effects on liver regeneration

Primary antibodies used in the present study.

<p>*IHC analysis;</p>+<p>IF analysis.</p><p>Primary antibodies used in the present study.</p

Curcumin down-regulates <i>miR-31</i> expression via EGF downstream signals in OSCC cells.

<p>(A) Western blot analysis. (B, C) qRT-PCR analysis. (A) SAS cells. (B, C) SAS cells (Upper) and HSC-3 cells (Lower). (A) The analysis shows the attenuation of EGF induced AKT activation and C/EBPβ up-regulation after treatment with 12 µM curcumin for 24 h. EGF induced ERK activation was not obviously attenuated by curcumin. Treatment with EGF or curcumin had little effect on the expression of β-catenin or Bcl2. (B) Curcumin treatment down-regulates endogenous <i>C/EBPβ</i> mRNA expression and EGF induced <i>C/EBPβ</i> mRNA expression in SAS cells and HSC-3 cells. (C) Curcumin attenuates endogenous <i>miR-31</i> expression and EGF induced <i>miR-31</i> expression in both types of cell. The numbers below the pictures are normalized values. #, quantification unavailable due to faint image signals. Data are the means ± SE from at least triplicate analysis. *, <i>p</i><0.05; **, <i>p</i><0.01; ***, <i>p</i><0.001; un-paired <i>t</i>-test.</p