2T Cell Research Articles

PLEK2 and IFI6, representing mesenchymal and immune-suppressive microenvironment, predicts resistance to neoadjuvant immunotherapy in esophageal squamous cell carcinoma.

Immunotherapy has largely improved clinical outcome of patients with esophageal squamous cell carcinoma (ESCC). However, a proportion of patients still fail to benefit. Thus, biomarkers predicting therapeutic resistance and underlying mechanism needs to be investigated. Transcriptomic profiling was applied in FFPE tissues from 103 ESCC patients, including surgical samples from 66 treatment-naïve patients with long-term follow-up, and endoscopic biopsies from 37 local advanced ESCC cases receiving neoadjuvant immunotherapy plus chemotherapy. Unsupervised clustering indicated an aggressive phenotype with mesenchymal character in 66 treatment-naïve samples. Univariant logistic regression was applied to identify candidate biomarkers potentially predicted resistance to neoadjuvant immunotherapy within the range of mesenchymal phenotype enriched genes. These biomarkers were further validated by immunohistochemistry. Putative mechanisms mediating immunotherapy resistance, as indicated by microenvironment and immune cell infiltration, were evaluated by transcriptomic data, and validated by multiplex immunofluorescence. PLEK2 and IFI6, highly expressed in mesenchymal phenotype, were identified as novel biomarkers relating to non-MPR in neoadjuvant immunotherapy cohort [PLEK2high, OR (95% CI): 2.15 (1.07-4.33), P = 0.032; IFI6high, OR (95% CI): 2.21 (1.16-4.23), P = 0.016). PLEK2high and IFI6 high ESCC patients (versus low expressed patients) further exhibit higher chance of non-major pathological remissions (90%, P = 0.004) in neoadjuvant immunotherapy cohort and high mortality (78.9%, P = 0.05), poor prognosis in retrospective cohort. PLEK2high/IFI6high ESCC recapitulated mesenchymal phenotype, characterized by extracellular matrix composition and matrix remodeling. In addition, PLEK2high or IFI6high ESCC displayed an immune-unfavored microenvironment, represented by positive correlating with regulatory T cells, Helper 2T cell as well as less infiltration of B cells, effector T cells and mast cells. PLEK2 and IFI6 was discovered of first time to identify a distinct ESCC subpopulation cannot be benefited from neoadjuvant immunotherapy and present a poor survival, which putatively associated with mesenchymal and immune-suppressive microenvironment.

Area and Energy Efficient Joint 2T SOT-MRAM-Based on Diffusion Region Sharing With Adjacent Cells

In this brief, we present a novel low area joint 2T spin orbit torque magnetic random access memory (SOT-MRAM) cell architecture. The proposed joint 2T cell achieves up to 15 % of SOT-MRAM cell area reduction by sharing the diffusion regions of transistors between adjacent cells. In addition, the small bit-line capacitance of the proposed SOT-MRAM can lead to 27% read energy reduction in comparison to the conventional SOT-MRAM. When the proposed 1 MB SOT-MRAM is used as L2 cache of X86 processor, the gem5 simulation results show the average of 18% dynamic energy savings in various workloads of SPEC2006 benchmarks.

A Reconfigurable Two‐WSe2‐Transistor Synaptic Cell for Reinforcement Learning

Reward-modulated spike-timing-dependent plasticity (R-STDP) is a brain-inspired reinforcement learning (RL) rule, exhibiting potential for decision-making tasks and artificial general intelligence. However, the hardware implementation of the reward-modulation process in R-STDP usually requires complicated Si complementary metal-oxide-semiconductor (CMOS) circuit design that causes high power consumption and large footprint. Here, a design with two synaptic transistors (2T) connected in a parallel structure is experimentally demonstrated. The 2T unit based on WSe2 ferroelectric transistors exhibits reconfigurable polarity behavior, where one channel can be tuned as n-type and the other as p-type due to nonvolatile ferroelectric polarization. In this way, opposite synaptic weight update behaviors with multilevel (>6 bit) conductance states, ultralow nonlinearity (0.56/-1.23), and large Gmax /Gmin ratio of 30 are realized. By applying positive/negative reward to (anti-)STDP component of 2T cell, R-STDP learning rules are realized for training the spiking neural network and demonstrated to solve the classical cart-pole problem, exhibiting a way for realizing low-power (32 pJ per forward process) and highly area-efficient (100 µm2 ) hardware chip for reinforcement learning.

A Study on High Density Gate-Oxide Anti-Fuse PROM Memory Cell Program Features

The program consistency of high density gate-oxide anti-fuse PROM (programmable read only memory) memory cell is considered in this paper. To solve this problem, we do research on the mechanism and models of gate-oxide break down. A test chip based on 2T memory cell is also designed for the experiment. During the test, we have found that the program consistency of 2T cell is really pessimistic. What’s more, the program voltage has effect on the consistency. Through research and test, we have got the optimal program voltage-6.5V for 2T memory cell in 180nm technology. To further improve the consistency, we modify the 2T memory cell and propose a 3T memory cell. It consumes 18% more area, but the standard deviation of equivalent resistance decreases 15.3% in the worst situation. The deviation can decrease 80.3% at most. The program consistency is greatly improved.

A 2T Dual Port Capacitor-Less DRAM

A novel two-transistor (2T) dual port capacitor-less DRAM concept based on bulk floating body is demonstrated for the first time in this letter. The read operation can be performed without disturbance of refresh or write. A novel read method is proposed to improve device performance especially at high temperature. Experimental results show a refresh cycle time of 1.28 s, an initial memory window of 192.84 μA/μm, and an initial signal sensing margin of 112.75 μA/μm with ±5 sigma variations at 85°C. The 2T cell is very promising for high-speed, low-power, and low-cost embedded DRAM application.

A 2T1C Embedded DRAM Macro With No Boosted Supplies Featuring a 7T SRAM Based Repair and a Cell Storage Monitor

A truly logic-compatible gain cell eDRAM macro with no boosted supplies is presented. A 2T1C gain cell implemented only with regular thin oxide devices consists of an asymmetric 2T cell and a coupling PMOS capacitor. The PMOS capacitor ensures proper operation even without a boosted supply by utilizing a beneficial coupling for read and a preferential boosting for write. A repair scheme based on a single-ended 7T SRAM has features such as a local differential write and shared control with the main 2T1C array. A storage voltage monitor is proposed to track the retention characteristics of a gain cell eDRAM under PVT variations and to adjust its refresh rate adaptively. A 128 kb eDRAM test chip implemented in a 65 nm Low-Power (LP) process operates at a random access frequency of 714 MHz with a static power dissipation of 161.8 μW per Mb for a 500 μs refresh rate at 1.1 V and 85°C.

A Novel Two-Transistor Floating-Body/Gate Cell for Low-Power Nanoscale Embedded DRAM

A novel two-transistor (2T) floating-body cell (FBC) for embedded-DRAM applications is proposed and demonstrated via device/circuit simulations using a process/physics-based compact model, with numerical-simulation support. Significant advantages of the 2T cell, in which the charged/discharged body of one transistor (1T) drives the gate of the other, over the currently popular 1T-DRAM FBC are noted and explained. Furthermore, a modification of the basic 2T-FBC structure, which in essence results in a floating-body/gate cell (FBGC), is shown to yield dramatic reduction in power dissipation in addition to better signal margin, longer data retention, and higher memory density. Design and processing issues that need to be addressed for optimal performance and for sustained FBGC viability in nanoscale CMOS are discussed.

Effect of prolactin on CD 2T cell activation pathway

To evaluate the effect of irradiation on microvascular endothelial cells in miniature pig parotid glands.A single 25-Gy dose of irradiation (IR) was delivered to parotid glands of 6 miniature pigs. Three other animals served as non-IR controls. Local blood flow rate in glands was measured pre- and post-IR with an ultrasonic Doppler analyzer. Samples of parotid gland tissue were taken at 4 h, 24 h, 1 week, and 2 weeks after IR for microvascular density (MVD) analysis and sphingomyelinase (SMase) assay. Histopathology and immunohistochemical staining (anti-CD31 and anti-AQP1) were used to assess morphological changes. MVD was determined by calculating the number of CD31- or AQP1-stained cells per field. A terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) apoptosis assay was used to detect apoptotic cells. The activity of acid and neutral Mg2+-dependent SMase (ASMase and NSMase, respectively) was also assayed.Local parotid gland blood flow rate decreased rapidly at 4 h post-IR and remained below control levels throughout the 14-day observation period. Parotid MVD also declined from 4 to 24 hours and remained below control levels thereafter. The activity levels of ASMase and NSMase in parotid glands increased rapidly from 4 to 24 h post-IR and then declined gradually. The frequency of detecting apoptotic nuclei in the glands followed similar kinetics.Single-dose IR led to a significant reduction of MVD and local blood flow rate, indicating marked damage to microvascular endothelial cells in miniature pig parotid glands. The significant and rapid increases of ASMase and NSMase activity levels may be important in this IR-induced damage.

LYMPHOTOXIN-β AND TNF REGULATION IN T CELL SUBSETS: DIFFERENTIAL EFFECTS OF PGE 2

The effects of prostaglandin E 2(PGE 2) on lymphotoxin β (LT-β) and tumour necrosis factor alpha (TNF) were assessed in murine CD4 +Th 1and Th 2T cell clones. LT-β mRNA was constitutively expressed by both T cell subsets. However, PGE 2inhibited its accumulation only in Th 1, but not Th 2clones. PGE 2inhibited TNF mRNA accumulation and production and release of bioactive material by both Th 1and Th 2T cells. The effects of PGE 2were also evaluated on production of IL-3, another cytokine produced by both T cell subsets, and interleukin 4 (IL-4), which is produced only by Th 2cells. Though IL-3 was produced by both T cell subsets it was only inhibited in Th 1cells, a pattern similar to that observed for LT-β. Accumulation of IL-4 mRNA in Th 2cells was not inhibited by PGE 2. These results demonstrate that PGE 2does not affect LT-β, IL-4, or IL-3 in Th 2cells, but inhibits TNF mRNA accumulation and production in this T cell subset. Thus, TNF appears to be the only cytokine susceptible to inhibition by PGE 2in Th 2cells. The fact that PGE 2inhibits LT-β and IL-3 in Th 1but not Th 2cells points to a different mechanism of regulation of the same cytokine in different subsets. The mechanisms that contribute to TNF mRNA accumulation also may differ in the two CD4 +T cell subsets, because cycloheximide superinduced TNF mRNA in Th 2cells, but not in Th 1cells. The inhibitory effects of PGE 2on TNF mRNA accumulation by either T cell subset did not require de novoprotein synthesis since preincubation with the protein synthesis inhibitor, cycloheximide, did not alter the PGE 2-mediated effects. Cross-regulation of cytokine production and function has been demonstrated for both T cell subsets, and PGE 2may modulate the outcome of an immune response via differential regulation of cytokine production.

Classification of Eye Changes of Graves' Disease

Classification of Eye Changes of Graves' Disease