IL-17C Mitigates Murine Acute Graft-vs.-Host Disease by Promoting Intestinal Barrier Functions and Treg Differentiation

Acute graft-vs.-host disease (aGVHD) is one of the major complications and results in high mortality after allogeneic hematopoietic stem cell transplantation (allo-HSCT). IL-17C is involved in many inflammatory immune disorders. However, the role of IL-17C in aGVHD remains unknown. Here we demonstrated that IL-17C deficiency in the graft significantly promoted alloreactive T cell responses and induced aggravated aGVHD compared with wildtype donors in a fully MHC-mismatched allo-HSCT model. In contrast, IL-17C overexpression ameliorated aGVHD. IL-17C deficiency increased intestinal epithelial permeability and elevated inflammatory cytokine production, leading to an enhanced aGVHD progression. Tregs was reduced in recipients of IL-17C−/− graft, whilst restored after IL-17C overexpression. Decreased Treg differentiation was abrogated after neutralizing IFN-γ, but not IL-6. Moreover, depletion of Tregs diminished the protective effect of IL-17C. Of note, patients with low IL-17C expression displayed higher aGVHD incidence together with poor overall survival, thereby IL-17C could be an independent risk factor for aGVHD development. Our results are the first demonstrating the protective role of IL-17C in aGVHD by promoting intestinal barrier functions and Treg differentiation in a MHC fully mismatched murine aGVHD model. IL-17C may serve as a novel biomarker and potential therapeutic target for aGVHD

Golgi reassembly and stacking protein 65 downregulation is required for the anti-cancer effect of dihydromyricetin on human ovarian cancer cells.

Golgi reassembly and stacking protein 65 (GRASP65), which has been involved in cancer progression, is associated with tumor growth and cell apoptosis. Dihydromyricetin (DHM) has demonstrated antitumor activity in different types of human cancers. However, the pharmacological effects of DHM on ovarian cancer (OC) and the molecular mechanisms that underlie these effects are largely unknown. The present study showed that DHM reduced cell migration and invasion in a concentration- and time-dependent manner and induced cell apoptosis primarily through upregulation of Cleaved-caspase-3 and the Bax/Bcl-2 ratio in OCs. To further clarify the cancer therapeutic target, we assessed the effect of DHM on the expression of GRASP65, which is overexpressed in human ovarian cancer tissues. DHM activated caspase-3 and decreased GRASP65 expression to promote cell apoptosis, implying that downregulation of GRASP65 was related to DHM-induced cell apoptosis. Additionally, the knockdown of GRASP65 by siRNA resulted in increased apoptosis after DHM treatment, while western blot and flow cytometry analysis demonstrated that overexpression of GRASP65 attenuated DHM-mediated apoptosis. In addition, the JNK/ERK pathway may be involved in DHM-mediated caspase-3 activation and GRASP65 downregulation. Taken together, these findings provide novel evidence of the anti-cancer properties of DHM in OCs, indicating that DHM is a potential therapeutic agent for ovarian cancer through the inhibition of GRASP65 expression and the regulation of JNK/ERK pathway

Speedup Critical Stage of Machine Learning with Batch Scheduling in GPU

Part 6: Poster SessionsInternational audienceAs a superior data analysis method, Machine Learning suffers the bottleneck from limited computing capability for many years. With the advent of numerous parallel computing hardwares, modern GPU is becoming a promising carrier for the tasks of Machine Learning. In this paper, we propose an efficient GPU execution framework to speedup the forward propagation process of convolution neural network. By extending the convolution unrolling method to fit this batch mode, we get a significant increase of throughput but very little overhead

Balancing the Lifetime and Storage Overhead on Error Correction for Phase Change Memory.

As DRAM is facing the scaling difficulty in terms of energy cost and reliability, some nonvolatile storage materials were proposed to be the substitute or supplement of main memory. Phase Change Memory (PCM) is one of the most promising nonvolatile memory that could be put into use in the near future. However, before becoming a qualified main memory technology, PCM should be designed reliably so that it can ensure the computer system's stable running even when errors occur. The typical wear-out errors in PCM have been well studied, but the transient errors, that caused by high-energy particles striking on the complementary metal-oxide semiconductor (CMOS) circuit of PCM chips or by resistance drifting in multi-level cell PCM, have attracted little focus. In this paper, we propose an innovative mechanism, Local-ECC-Global-ECPs (LEGE), which addresses both soft errors and hard errors (wear-out errors) in PCM memory systems. Our idea is to deploy a local error correction code (ECC) section to every data line, which can detect and correct one-bit errors immediately, and a global error correction pointers (ECPs) buffer for the whole memory chip, which can be reloaded to correct more hard error bits. The local ECC is used to detect and correct the unknown one-bit errors, and the global ECPs buffer is used to store the corrected value of hard errors. In comparison to ECP-6, our method provides almost identical lifetimes, but reduces approximately 50% storage overhead. Moreover, our structure reduces approximately 3.55% access latency overhead by increasing 1.61% storage overhead compared to PAYG, a hard error only solution

rrdd: receiver-oriented robust data delivery in mobile sensor networks

Data forwarding in the wireless networks typically employs a sender-oriented approach in which the next hop node is pre-selected based on neighbor or network information. This method incurs large overhead when accurate information is neededfor making the optimal fonvarding decision. In this paper, a receiver-oriented robust data delivery scheme (RRDD) is proposed for mobile sensor networks. In RRDD, the sender does not appoint a specific fonvarder proactively, but allows its neighboring candidates to dynamically contendfor the data fonvarding task based on local state information. In this way, the best-suited node is elected at each hop to provide robust and efficient delivery service to data packets. Comprehensive simulations show that RRDD exhibits superior transmission performance over all of the compared schemes

Root-Securing and Brain-Fortifying Liquid Upregulates Caveolin-1 in Cell Model with Alzheimer’s Disease through Inhibiting Tau Phosphorylation

In order to explore the effect of root-securing and brain-fortifying Liquid- (RSBFL-) mediated caveolin-1 (CAV-1) on phosphorylation of Tau protein and to uncover underlying mechanisms of RSBFL for the prevention and treatment of Alzheimer’s disease (AD), hippocampal neurons isolated from neonatal SD rats and cultured in DMEM-F12 medium were induced by exogenous Aβ1–42 to establish a cell model with AD. Meanwhile, pEGFP-C1-CAV1 and CAV1-shRNA plasmids were transfected into hippocampal neurons for CAV-1 overexpression and silence, respectively. The serum containing RSBFL was prepared for the intervention of AD model cells. The expression of CAV-1, GSK-3β, and p-Tau in normal hippocampal neurons and AD model cells in the presence of serum containing RSBFL was evaluated. The model hippocampal neurons with AD induced by Aβ1–42 revealed an obvious CAV-1 inhibition, enhanced GSK-3β activity, and abnormal Tau phosphorylation. In contrast, the treatment with serum containing RSBFL could upregulate CAV-1 in AD hippocampal neurons (P<0.05) with improved p-GSK-3βSer9 and reduced p-GSK-3βTyr216 (P<0.01), as well as suppressed abnormal phosphorylation of Tau protein. Therefore, RSBFL has an excellent protective effect on hippocampal neurons through increasing CAV-1 expression, inhibiting GSK-3β activity, and reducing excessive abnormal phosphorylation of Tau protein

The structure of global ECPs buffer.

<p>When valid bit displayed ‘1’, it means these six G entries have already been occupied. we must use the address in pointer area to map to a collision pool line.</p

The proportion of one additional memory access among all accesses.

<p>This figure indicated that the proportion of LEGE and PAYG fetch data from global buffer among all accesses.</p

The structure of a global mapping line.

<p>Each global mapping line used a valid bit to indicate whether these six entries were all occupied. One G entry can be allocated to one memory line which had more than one error.</p

The structure of a detection and correction matrix line.

<p>Each detection and correction matrix had an 11-bit ECC, an 11-bit ECP-1 and a 2-bit valid bits.</p