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Background Dry-electrode-based transcranial direct current stimulation is a new type of non-invasive brain stimulation system which relieves chronic low back pain and improves related muscle movement, in a way that overcomes the drawback of conventional systems. Objective To investigate the effectiveness of dry-electrode-based transcranial direct current stimulation in relieving chronic low back pain and altering pain-related low back muscles movement, by using pain assessment tool and surface electromyographic topography. Methods We conducted a prospective, double-blind, randomized, sham-controlled study. 60 patients with non-specific chronic low back pain were randomly and evenly allocated into tDCS and sham groups. Each group accepted a single 20-minute stimulation at 2 mA on the primary motor cortex. Numeric rating scale for pain intensity assessment and root-mean-square difference parameter from surface electromyographic topography were measured before and after stimulation. The current direction in brain using finite element method was simulated to verify the current distribution under dry stimulation electrode. Results After stimulation, the pain intensity in the tDCS group significantly decreased, while it did not show evident change in the sham group. However, change of root-mean-square difference parameters between tDCS and sham groups showed no significant difference. Simulation results based on finite element method showed most of current focused on primary motor cortex while peak value of current density was 0.225 A/m2. Conclusions Dry-electrode-based transcranial direct current stimulation can lower pain perception in patients with chronic low back pain. The analgesic mechanism can affect the top-down modulation pathway of pain.

A memristor with a bilayer electrolyte structure (Pt/C/NbOx/TiN) is proposed as a self-rectification and quasi-linear electronic synapse. The device shows self-rectifying analogue memristive behavior with > 106 rectification ratio, which can solve the sneak current problem in crossbar array without additional hardware burden. Under identical pulses in potentiation process, the device conductance is quasi-linearly changed with 9.16% nonlinearity. In addition, the conductance change rate of device is effectively tuned by altering amplitudes and frequencies of spike pulses. Benefiting from the quasi-linear conductance change characteristics, excellent classification accuracy (95.7%) is achieved for the application of handwritten digit classification with a two-layer perceptron based on MINST stimulation.

Biological neural networks are connected in a highly recurrent manner, which displays complex activity patterns spontaneously upon an awareness stimulus. Here, we emulate such a network based on a recurrently connected memristor array. To generate a target function, a first-order and controlled error (FORCE) learning rule that only needs to modify a small fraction of connections is introduced. This rule tries to minimize the amount of modification and thus is especially suitable for memristor-based synapses. After learning, the network could spontaneously generate the desired function after a random stimulus, just as the biological systems do.

In this work, a multi-functional self-rectifying memristor (Pt/TiO x /Ti) is fabricated. The device shows convertible volatile and non-volatile resistive switching. More importantly, the device has a high rectifying ratio in both switching modes (~105 for volatile and 106 for non-volatile), which is favorable for high-density 3D vertical integration. The convertible multi-switching behaviors and high self-rectifying ratio in a single memristor provide the flexibility for multi-functional applications in a large-scale array.

Spiking neural network, inspired by the human brain, consisting of spiking neurons and plastic synapses, is a promising solution for highly efficient data processing in neuromorphic computing. Recently, memristor-based neurons and synapses are becoming intriguing candidates to build spiking neural networks in hardware, owing to the close resemblance between their device dynamics and the biological counterparts. However, the functionalities of memristor-based neurons are currently very limited, and a hardware demonstration of fully memristor-based spiking neural networks supporting in-situ learning is very challenging. Here, a hybrid spiking neuron combining a memristor with simple digital circuits is designed and implemented in hardware to enhance neuron functions. The hybrid neuron with memristive dynamics not only realizes the basic leaky integrate-and-fire neuron function but also enables the in-situ tuning of the connected synaptic weights. Finally, a fully hardware spiking neural network with the hybrid neurons and memristive synapses is experimentally demonstrated for the first time, and in-situ Hebbian learning is achieved with this network. This work opens up a way towards the implementation of spiking neurons, supporting in-situ learning for future neuromorphic computing systems.

In this work, by incorporating different electrodes (Ta/Ti) onto TaOx dielectric layer, we studied both the conductance reading and conductance updating (long term potentiation and depression) linearities in the two RRAM devices. Owing to the composition modulation (CM) mechanism, the Ta-electrode device shows better conductance reading and updating linearities. The RRAM device linearities directly influence the performance of the neural network when the devices are used as synapses. System evaluation of a two-layer neural network considering the conductance reading and updating linearity factors further confirm that both the training and inference accuracies of Ta electrode device are better than those of the Ti electrode one. We believe that this work could serve as a powerful reference for engineering synaptic devices with good linearity for neuromorphic computing applications.

In this paper, we put forward an asynchronous spiking neural network (SNN) accelerator with 1024 neurons and 1 million synapses, which is reconfigurable in terms of network connection and neuron parameters. Bundled data asynchronous circuits are adopted to design the neuromorphic computation core and mesh network. Multicast communication is used to transmit packet among and within each core for less packet transmission and better energy efficiency. A novel time step update mechanism, which updates neurons in an event-driven manner without considering the chip-wide activity of other unrelated neurons, is proposed to improve the performance of speed. The SNN accelerator is verified by classifying MNIST handwritten digit with Xilinx VC707 FPGA. The results show that the accelerator achieves 98% accuracy with MINST database, and more than 1 GIPS/W energy efficiency which is 32 times better than previous work.

At present, the neuromorphic hardware with analog neuron is widely studied by researchers. Address event representation (AER) is an event protocol, which usually used for inter-chip communication between neuromorphic chips. Fixed priority arbiter often results in unfair allocation of bus resource to only the high priority neuron, thus introducing fixed noise in the neural network. In this paper, we propose an asynchronous AER circuits with rotation priority tree arbiter to alleviate this issue. Moreover, to match the different delay between AER's handshake signal and neuron's handshake signal, a special handshake circuits is designed. Simulation results show that the 64 channels AER circuits can perform up to 143M event/s. The design is designed with SMIC180 process for fabricating RRAM based neuromorphic chip.

// Jinsong Wei 1 , Ming Li 2 , Feng Gao 3 , Rong Zeng 1 , Guiyou Liu 4 , Keshen Li 5, 6 1 Department of Orthopedic Surgery, Affiliated Hospital of Guangdong Medical University, Zhanjiang, China 2 Departmentof Endocrinology and Metabolism, The Fourth Affiliated Hospital of Harbin Medical University, Harbin, Heilongjiang, China 3 Department of Trauma and Emergency Surgeon, The Second Affiliated Hospital, Harbin Medical University, Harbin, China 4 Genome Analysis Laboratory, Tianjin Institute of Industrial Biotechnology, Chinese Academy of Sciences, China 5 Institute of Neurology, Affiliated Hospital of Guangdong Medical University, Zhanjiang, China 6 Stroke Center, Neurology & Neurosurgery Division, The Clinical Medicine Research Institute & The First Affiliated Hospital, Jinan University, Guangzhou, China Correspondence to: Guiyou Liu, e-mail: liuguiyou1981@163.com Keshen Li, e-mail: keshenli2012@163.com Keywords: osteoporosis, bone mineral density, pathway analysis, genome-wide association studies Received: November 12, 2015 Accepted: March 29, 2016 Published: April 23, 2016 ABSTRACT Osteoporosis is a common human complex disease. It is mainly characterized by low bone mineral density (BMD) and low-trauma osteoporotic fractures (OF). Until now, a large proportion of heritability has yet to be explained. The existing large-scale genome-wide association studies (GWAS) provide strong support for the investigation of osteoporosis mechanisms using pathway analysis. Recent findings showed that different risk pathways may be involved in BMD in different tissues. Here, we conducted multiple pathway analyses of a large-scale lumbar spine BMD GWAS dataset (2,468,080 SNPs and 31,800 samples) using two published gene-based analysis software including ProxyGeneLD and the PLINK. Using BMD genes from ProxyGeneLD, we identified 51 significant KEGG pathways with adjusted P

Objective To explore the effect of suppressive oligodeoxynucleotide-induced dendritic cells (S-DCs) in the osteoarthritis (OA) therapy. Methods S-DCs were prepared from splenic CD11c + cells by in vitro culture with suppressive oligodeoxynucleotide. The function and phenotypes of S-DCs were measured by ELISA and flow cytometry. The innate immune signaling pathways were detected by western blotting in the non-treated DCs and S-DCs upon stimulation. In vivo, we employed an iodoacetate-induced OA mice model. S-DCs were transferred by intravenous route. The weight bearing of mice was evaluated and pro-inflammatory factors in OA joint were measured by real-time PCR. Treg cell ratio and CD4 + IL10+ cells in spleen were detected by flow cytometry at day 5 post OA induction. Results The S-DCs showed less inflammatory phenotypes upon stimulation. The expression of pro-inflammatory cytokines and mature makers in the S-DCs were blunt, due to the impaired innate immune signal transduction. In an iodoacetate-induced OA model, transfer of S-DCs significantly controlled the process of OA. Restricted inflammatory responses were observed in the joint of S-DC recipients. Moreover, after S-DC transfer, Tregs and CD4 + IL10+ cells were mounted in the spleen. Conclusion Transfer of suppressive oligodeoxynucleotides-induced autologous DCs may represent a potential agent to control the aggravation of OA in patients.

We report a fully CMOS compatible bilayer, forming-free and non-filamentary memristive device with excellent bidirectional analog switching behavior as artificial synapse for neuromorphic computing applications. The bilayer stack structure, consisting of 8 nm TaO x formed via oxidation process on Ta bottom electrode and 7 nm Al 2 O 3 via atom layer deposition (ALD), is sandwiched between the Ta bottom electrode and Pd top electrode. The Pd/Al 2 O 3 /TaO x /Ta device shows bidirectional analog resistive switching behaviors, and multilevel conductance states (>60) with satisfying retention time can be obtained. Long term plasticity, consisting of long-term potentiation (LTP) and long-term depression (LTD), have been demonstrated based our device. And a nearly linear conductance change behavior is obtained by optimizing the training scheme: adopting non-identical training pulses.Atwo-layer perceptron neural networkwas performed to estimate the synapse characteristics of our devices. More than 94% recognition accuracy of MNIST handwritten digit dataset are achieved. Based on these results, the device is a promising emulator for biology synapse, and has a great potential to be used in neuromorphic systems.

BACKGROUND Transcranial direct current stimulation (tDCS) on primary motor cortex (M1) provides a new way to relieve postoperative pain. Previous studies only found postoperative analgesia dosage significantly reduced in tDCS group while the patient-controlled analgesia (PCA) was applied. However, there lacks the study about the effect of M1-tDCS on pain intensity and brain activity while the analgesia dosage is the same for both groups. OBJECTIVE To investigate whether M1-tDCS can (1) reduce pain intensity and (2) change spontaneous electroencephalography (EEG) oscillations in prefrontal cortex, in patients with postoperative pain, after taking the constant dosage of analgesics. METHODS A prospective, single-blind, randomized, sham-controlled study was conducted. 32 patients with postoperative pain after lumbar spine surgery were recruited. All patients received same dosage of dezocine before intervention. In the morning of the first day after surgery and before dezocine injection, a single 20-minute session of anodal M1-tDCS was applied to 'tDCS' group while sham stimulation to 'sham' group. Numeric rating scale (NRS) and resting-state EEG with eyes-closed were measured and analyzed. EEG spectral powers were analyzed using repeated measures analysis of variance (ANOVA). Correlation analysis was conducted between the change of NRS and the change of spectral power. RESULTS The NRS in "tDCS" group significantly decreased (p < 0.01) while not in "sham" group after intervention. Only spectral power within alpha2 band (10-13 Hz) in Fp1 and beta1 band (13-20 Hz) in Fp1 showed significant Time×Intervention interaction effect. These changes of the spectral power also showed significant correlation with the change of NRS. CONCLUSIONS The postoperative pain intensity in patients receiving surgery could reduce after a single session of anodal M1-tDCS compared to sham M1-tDCS. The effect to the top-down dimension of postoperative pain might account for the analgesic effect of M1-tDCS, which reflecting slow oscillations in left prefrontal EEG.

Adhesion of pattern structures is a very important issue in laser thermal lithography. In this paper, Si"3N"4 and ZnS-SiO"2 were investigated as interface layers to improve patterns' adhesion to substrate on pattern fabrication with Ge"2Sb"2Te"5 as laser thermal lithography film. Patterns were fabricated by laser direct irradiation with 650nm and 405nm laser writing systems (both NA=0.9) and wet etching with 25wt.% tetramethylammonium hydroxide solution. Experimental results showed that patterns were flaked off mostly and partly from the substrate in wet-etching process for samples without interface layer and with Si"3N"4 film as interface layer, respectively; but for samples with ZnS-SiO"2 film as interface layer, regular and clear patterns were fabricated successfully under different fabrication conditions, and sub-wavelength line structures with width approaching to 390nm were achieved by 405nm laser system. The mechanism analysis implied that the matches of materials' thermal parameters might play important roles in the adhesion effect of interface layers on pattern fabrication.

We evaluated the efficacy of platelet-rich plasma (PRP) in combination with allogeneic bone marrow mesenchymal stem cells (BMSCs) for the treatment of osteoporotic bone defects in an ovariectomized rat model. By day 42 after injury, in vivo microcomputed tomography (micro-CT) imaging revealed that bone defects of control rats and ovariectomized rats treated with PRP and BMSCs were completely repaired, whereas those of ovariectomized rats treated with PRP or BMSCs alone exhibited slower healing. Histological data were consistent with these results. We also assessed changes to bone trabeculae in the proximal tibial growth plate. In ovariectomized rats treated with PRP or with a combination of PRP and BMSCs, the trabecular connectivity densities (Conn.D), bone volume ratios (BV/TV), and numbers (Tb.N) in the defect areas increased significantly from day 7 to day 42. These results indicate that PRP treatment enhances bone microarchitecture in osteoporosis. Moreover, expression levels of osteogenesis-specific marker genes including RUNX2, OSX, and OPN were significantly upregulated in rats treated with PRP and BMSCs compared to those of other groups. Thus, we conclude that treatment with PRP combined with BMSCs significantly promotes healing of osteoporotic bone defects. This study provides an alternative strategy for the treatment of osteoporotic bone loss.

Antimony-based bismuth-doped thin film, a new kind of super-resolution mask layer, is prepared by magnetron sputtering. The structures and optical constants of the thin films before and after annealing are examined in detail. The as-deposited film is mainly in an amorphous state. After annealing at 170–370 oC, it is converted to the rhombohedral-type of structure. The extent of crystallization increased with the annealing temperature. When the thin film is annealed, its refractive index decreased in the most visible region, whereas the extinction coefficient and reflectivity are markedly increased. The results indicate that the optical parameters of the film strongly depend on its microstructure and the bonding of the atoms.

Objective: A randomized trial was performed to evaluate the contribution of gan lu fu zheng soup with chemotherapy plus radiotherapy (CT/RT) in the patients with histologically proven nasopharyngeal carcinoma with local metastasis to lymph nodes. Methods: Sixty-eight patients with nasopharyngeal carcinoma were treated either with gan lu fu zheng soup alongside with chemotherapy and radiotherapy (TCM/CT/RT group) or with chemotherapy and radiotherapy (CT/RT group) alone. All patients in the two groups were treated with a uniform definitive-intent radiation therapy and chemotherapy, while those patients in the TCM/CT/RT group were treated with extra gan lu fu zheng soup. Results: From 1999 to 2002, 68 patients (38 in TCM/CT/RT, 30 in CT/RT group) were enrolled and eligible. The rates of complete resolution of nasopharyngeal tumors in the treatment group and the control group were respectively, 94.7% and 90%; the rates of complete resolution of cervical lymph node metastases were respectively, 92.1% and 83%; the resolution rates of nasopharyngeal foci examined by CT were respectively, 73.6% and 63.3%; and the total survival rates of one year were respectively, 100.0% and 96.7% (P > 0.05). Changes in clinical symptoms: the total amelioration rates of the two groups were respectively, 97.4% and 76.7%; changes in life quality: the amelioration rates of the two groups were respectively, 89.5% and 66.7%; toxic and side reactions: in comparison with the control group, the treatment group were also distinctly relieved from leukopenia, nausea and vomiting, toxic and side reaction of oral mucosa. Through statistic analysis, the differences are of significances (P < 0.05). Conclusions: Treating nasopharyngeal carcinoma with gan lu fu zheng soup in combination with radiotherapy and chemotherapy is helpful to increase the rates of tumor resolution and complete resolution, to protect immunocompetence of organism, to promote the amelioration of clinical symptoms, to alleviate the toxic and side reaction of radiotherapy and chemotherapy, to increase life quality and prolong survival time, which provides an effective auxiliary means for the treatment of nasopharyngeal carcinoma.

The objective of the present study was to assess the effectiveness of combined salmon calcitonin (sCT) and aspirin [acetylsalicylic acid (ASA)] treatment in an ovariectomized (OVX) rat model of postmenopausal osteoporosis. Following 12 weeks of treatment, therapeutic efficacy was assessed by evaluating changes in the biochemical and biophysical properties of bone (n=8 rats per group). Serological markers of bone metabolism were measured by ELISA; bone mineral densities (BMD) by dual energy X-ray absorptiometry; bone biomechanics of the femur and lumbar vertebrae by three-point stress test; trabecular bone morphology of lumbar vertebrae by hematoxylin and eosin staining; messenger RNA expression levels of osteoprotegerin (OPG) and receptor activator of nuclear factor κB ligand (RANKL) in bone marrow cells by reverse transcription-quantitative polymerase chain reaction and OPG and RANKL protein expression levels in the proximal tibia were analyzed by immunohistochemistry. Compared with treatment by sCT or ASA alone, combined treatment (sCT+ASA) increased BMD, improved femur bone strength, normalized trabecular network architecture and morphology, and increased mRNA and protein expression of OPG, while reducing the expression of RANKL. Collectively, these results demonstrated that combined treatment (sCT+ASA) of osteoporotic symptoms in OVX rats was more effective than treatment with sCT or ASA alone. Furthermore, these two drugs appeared to alter the expression of two distinct factors in the OPG/RANKL/RANK system, suggesting that their effects may be synergistic. Since sCT and ASA are currently approved for use in humans, the results of the present study suggest that the safety and efficacy of sCT+ASA combined therapy for post-menopausal osteoporosis should be assessed in clinical trials.

There are more than 90 million smokers in the United States who are at elevated risk for lung adenocarcinoma (LUAD), the most common lung cancer subtype. LUADs in smokers frequently (greater than 25%) harbor activating mutations in the Kras oncogene. Kras mutant LUAD exhibits very poor prognosis warranting the need for new strategies to prevent and treat this fatal lung cancer subtype. Limiting these advances is a poor understanding of the earliest events that drive Kras mutant LUAD development in smokers and that would constitute targets for early treatment. The retinoic acid-inducible G-protein coupled receptor Gprc5a is preferentially expressed in normal lung and mice with knockout of the gene (Gprc5a-/-) develop late onset lung tumors spontaneously. In our data aimed at understanding smoking-associated lung cancer pathogenesis, we found that Gprc5a-/- mice, in contrast to wild type (WT) littermates, not only developed LUADs after tobacco carcinogen exposure but also that these lesions harbored somatic Kras mutations, the same variants thought to act as drivers of human LUAD in smokers. In the present study we construed that pinpointing early events preceding lung oncogenesis in Gprc5a-/- mice will help us comprehend how smoke-associated LUADs with Kras mutations evolve. Towards this, we performed RNA-sequencing, using the Ion Proton platform, of visually normal airway epithelia in Gprc5a-/- mice prior to tumor development compared to epithelia in WT mice. We noted distinctively marked up-regulation of the Lcn2 oncogene in normal airways of Gprc5a-/- mice. Functional pathways and gene set enrichment analyses revealed that Lcn2 up-regulation was associated with activation of mitogen activated protein kinase- and interleukin-associated pathways and with gene sets attributable to cigarette smoke. We then analyzed Lcn2 expression in murine cell lines we had derived and found that Lcn2 was significantly elevated in both Gprc5a-/- LUAD and airway cell lines compared to WT airway cells. Moreover, immunohistochemical expression of Lcn2 protein was elevated, compared to normal lung tissue, in early lesions (hyperplasias and adenomas) and in the LUADs of tobacco carcinogen exposed Gprc5a-/- mice. Of note, we also found that alternatively activated M2 macrophages surrounding all lesions were positive for Lcn2. We then analyzed human LCN2 expression in publicly available array datasets and found that the gene was significantly elevated in human KRAS mutant LUADs compared to wild type LUADs or normal lung (all P < 0.05). Our preliminary findings suggest that elevated Lcn2 expression, in lung (airway and tumor) epithelia and in the protumorigenic inflammatory environment, may be implicated in the early development of smoking-associated Kras mutant LUAD. Efforts are underway to further probe this supposition in mice with knockout of Lcn2. Citation Format: Joshua Ochieng, Sayuri Nunomura, Wenhua Lang, Jinsong Wei, Li Xu, Christina McDowell, Edwin Ostrin, Ralph Arlinghaus, Junya Fujimoto, Humam Kadara. Expression of the lipocalin 2 oncogene in the development of smoking-associated and Kras mutant lung adenocarcinoma. [abstract]. In: Proceedings of the 107th Annual Meeting of the American Association for Cancer Research; 2016 Apr 16-20; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2016;76(14 Suppl):Abstract nr 1124.