抗原变异可使得多种致病微生物易于逃避宿主免疫应答。表达在感染红细胞表面的恶性疟原虫红细胞表面蛋白1（PfPMP1）与感染红细胞、内皮细胞、树突状细胞以及胎盘的单个或多个受体作用，在黏附及免疫逃避中起关键的作用。每个单倍体基因组var基因家族编码约60种成员，通过启动转录不同的var基因变异体为抗原变异提供了分子基础。

疟原虫var基因转换速率变化导致抗原变异[英]／Paul H, Robert P, Christodoulou Z, et al//Proc Natl Acad Sci U S A

Infectious Diseases Society of America.

Memristive devices are electrical resistance switches that can retain a state of internal resistance based on the history of applied voltage and current. These devices can store and process information, and offer several key performance characteristics that exceed conventional integrated circuit technology. An important class of memristive devices are two-terminal resistance switches based on ionic motion, which are built from a simple conductor/insulator/conductor thin-film stack. These devices were originally conceived in the late 1960s and recent progress has led to fast, low-energy, high-endurance devices that can be scaled down to less than 10 nm and stacked in three dimensions. However, the underlying device mechanisms remain unclear, which is a significant barrier to their widespread application. Here, we review recent progress in the development and understanding of memristive devices. We also examine the performance requirements for computing with memristive devices and detail how the outstanding challenges could be met.

Memristive devices for computing

Transparent electronics is today one of the most advanced topics for a wide range of device applications. The key components are wide bandgap semiconductors, where oxides of different origins play an important role, not only as passive component but also as active component, similar to what is observed in conventional semiconductors like silicon. Transparent electronics has gained special attention during the last few years and is today established as one of the most promising technologies for leading the next generation of flat panel display due to its excellent electronic performance. In this paper the recent progress in n- and p-type oxide based thin-film transistors (TFT) is reviewed, with special emphasis on solution-processed and p-type, and the major milestones already achieved with this emerging and very promising technology are summarizeed. After a short introduction where the main advantages of these semiconductors are presented, as well as the industry expectations, the beautiful history of TFTs is revisited, including the main landmarks in the last 80 years, finishing by referring to some papers that have played an important role in shaping transparent electronics. Then, an overview is presented of state of the art n-type TFTs processed by physical vapour deposition methods, and finally one of the most exciting, promising, and low cost but powerful technologies is discussed: solution-processed oxide TFTs. Moreover, a more detailed focus analysis will be given concerning p-type oxide TFTs, mainly centred on two of the most promising semiconductor candidates: copper oxide and tin oxide. The most recent data related to the production of complementary metal oxide semiconductor (CMOS) devices based on n- and p-type oxide TFT is also be presented. The last topic of this review is devoted to some emerging applications, finalizing with the main conclusions. Related work that originated at CENIMAT|I3N during the last six years is included in more detail, which has led to the fabrication of high performance n- and p-type oxide transistors as well as the fabrication of CMOS devices with and on paper.

Oxide Semiconductor Thin‐Film Transistors: A Review of Recent Advances

Despite much progress in semiconductor integrated circuit technology, the extreme complexity of the human cerebral cortex, with its approximately 10(14) synapses, makes the hardware implementation of neuromorphic networks with a comparable number of devices exceptionally challenging. To provide comparable complexity while operating much faster and with manageable power dissipation, networks based on circuits combining complementary metal-oxide-semiconductors (CMOSs) and adjustable two-terminal resistive devices (memristors) have been developed. In such circuits, the usual CMOS stack is augmented with one or several crossbar layers, with memristors at each crosspoint. There have recently been notable improvements in the fabrication of such memristive crossbars and their integration with CMOS circuits, including first demonstrations of their vertical integration. Separately, discrete memristors have been used as artificial synapses in neuromorphic networks. Very recently, such experiments have been extended to crossbar arrays of phase-change memristive devices. The adjustment of such devices, however, requires an additional transistor at each crosspoint, and hence these devices are much harder to scale than metal-oxide memristors, whose nonlinear current-voltage curves enable transistor-free operation. Here we report the experimental implementation of transistor-free metal-oxide memristor crossbars, with device variability sufficiently low to allow operation of integrated neural networks, in a simple network: a single-layer perceptron (an algorithm for linear classification). The network can be taught in situ using a coarse-grain variety of the delta rule algorithm to perform the perfect classification of 3 × 3-pixel black/white images into three classes (representing letters). This demonstration is an important step towards much larger and more complex memristive neuromorphic networks.

Training and operation of an integrated neuromorphic network based on metal-oxide memristors

We have investigated the characteristics of read schemes using boosted channel potential of adjacent bit-line string in NAND flash memory. When all cells are programmed, the on-cell sting current of proposed read schemes is remarkable increased about ~3 times as compared with that of conventional read scheme because the channel resistance of pass cells is decreased by the electric field from the boosted adjacent bit-line strings. Proposed read schemes leads to suppress the read cell position dependency as compared with that of conventional read scheme. It was also shown that the proposed read schemes are more useful in the scaled device by measuring the threshold voltage shift with the channel potential of adjacent bit-line strings at each technology node.

The Characterization of Read Schemes Using Boosted Channel Potential of Adjacent Bit-Line Strings in NAND Flash Memory

The present invention relates to a three-dimensional stacked memory device having a vertical interconnection structure on a cell region The three-dimensional stacked memory device comprises: a cell region on which memory stacks are arranged over a substrate; and a vertical interconnection structure with vertical memory stacks on the cell region The vertical interconnection structure includes: a via hole formed in a vertical direction of the cell region; and a conductive pillar formed by filling the via hole with a conductive material The vertical interconnection structure is configured to interconnect an upper electrode of a vertical memory stack and a conductive region of the substrate in the vertical direction According to the present invention, the three-dimensional stacked memory device has a vertical interconnection structure consisting of a vertical wiring plug of a conductive material to facilitate manufacturing processes and allow vertical interconnection between upper electrodes and lower electrodes of stacked memory devices or a peripheral circuit of the substrate

3d stacked memory and vertical interconnect structures for 3d stacked memory

Disclosed is a method of manufacturing a solid oxide fuel cell using a calendering process. The method includes preparing a stack including an anode support layer (ASL) and an anode functional layer (AFL), calendering the stack to obtain an anode, stacking an electrolyte layer on the anode to obtain an assembly, calendering the assembly to obtain an electrolyte substrate, sintering the electrolyte substrate, and forming a cathode on the electrolyte layer of the electrolyte substrate.

A manufacturing method of solid oxide fuel cell via calendering process

Low-Thermal-Budget Fabrication of Transparent Ferroelectric Thin-Film Transistors on Glass Substrates


 Background and Preliminary Data: All the FDA-approved CD19 CAR-T cell therapies are based on an antigen-binding domain (scFv) based on the FMC63 antibody which binds to the membrane-distal region of CD19 to an epitope encoded by exons 3 and 4 (Klesmith JR, Biochemistry, 2019; Zhang Z, JITC, 2020). While these CART19 products are very effective in the clinic, the majority of patients still do not respond or eventually relapse due to several mechanisms of resistance, including T cell dysfunction and epitope CD19-negative escape. Novel strategies to enhance the activity of CART cells and reduce escape are critically needed. We recently demonstrated that modifications of the binding region of the CAR (scFv) (Singh N., Nat Med, 2021) can drastically change the interaction between the CAR T cell and the cancer cells, potentially improving the anti-tumor effect. To this goal, we developed a novel anti-CD19 antibody clone (1218) that binds to a membrane-proximal epitope of CD19 (exon 2 region K59-K63) thereby not competing with FMC63. We developed a novel CART19, called AT101, using a humanized 1218 scFv along with 4-1BB costimulatory and CD3zeta domain in a lentiviral backbone. In preclinical models, AT101 showed more potent in vitro cytotoxicity against CD19-positive B lymphoma cells in a long-term killing assay and in a B-ALL (NALM6) in vivo model as compared to the control of FMC63 based CAR-T cells. In addition, differently than FMC63-based CART, AT101 could target tumor cells expressing point mutations of CD19 that are associated with relapse post-CART19 (FMC63) (Zhang Z, JITC, 2020) and leukemic blasts aberrantly expressing FMC63 CAR19 on their surface (Ruella M, Nat Med, 2018). Based on the preclinical efficacy and safety, a phase 1 clinical trial testing autologous AT101 was started for patients with relapsed and refractory B-cell non-Hodgkin lymphoma.
 Trial Design and Methods: This open-label, multi-center, first-in-human Phase 1 study will assess the safety and feasibility of AT101 in patients with relapsed or refractory B cell non-Hodgkin lymphoma. Key eligibility criteria include patients aged ≥19 years of age with histologically confirmed relapsed or refractory aggressive B-cell non-Hodgkin lymphoma. In this phase 1 trial, patients (n=3 per dose level; up to n=18 in total) are treated with AT101 in 3 dose-escalation cohorts based on a standard 3 + 3 design. CART doses are 2.0 × 105, 1.0 × 106, or 5.0 × 106 CAR+T cells/kg. The primary objective is to determine the safety, the maximum tolerated dose (MTD), and the recommended phase 2 dose (RP2D) of AT101 in participants following lymphodepletion with cyclophosphamide and fludarabine (250 mg/m2 and 25 mg/m2). The secondary objective is to evaluate the preliminary efficacy assessments (overall response rate (ORR), duration of response (DOR), progression-free survival (PFS), overall survival (OS), event-free survival (EFS), and pharmacokinetics of AT101. Exploratory objectives include assessment of CD19 expression and cytokines in the blood. Patients will be followed for safety for at least 60 months post AT101 infusion. Clinical trial registry number: NCT05338931. As of January 11, 2023, AT101 has been infused to six patients in cohort 1 and three patients in cohort 2. Detailed results will be presented at the meeting.
 Citation Format: Yunlin Zhang, Ki Hyun Kim, Dok Hyun Yoon, Ruchi P. Patel, Jae-Cheol Jo, Hyungwoo Cho, Jong-Ho Lee, Hyun-Jong Lee, Lei-Guang Cui, In-Sik Hwang, Young Ha Lee, Jong-Hoon Kim, Yong Gu Lee, Puneeth Guruprasad, Jong-Seo Lee, Junho Chung, Marco Ruella. An open label, dose escalation, phase 1 study of AT101, a novel CD19-directed CAR-T cell therapy targeting a membrane-proximal epitope of CD19, in patients with relapsed or refractory B cell non-Hodgkin lymphoma [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 2 (Clinical Trials and Late-Breaking Research); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(8_Suppl):Abstract nr CT130.

Abstract CT130: An open label, dose escalation, phase 1 study of AT101, a novel CD19-directed CAR-T cell therapy targeting a membrane-proximal epitope of CD19, in patients with relapsed or refractory B cell non-Hodgkin lymphoma

Jong-Ho Lee

Papers

The Characterization of Read Schemes Using Boosted Channel Potential of Adjacent Bit-Line Strings in NAND Flash Memory

3d stacked memory and vertical interconnect structures for 3d stacked memory

A manufacturing method of solid oxide fuel cell via calendering process

Low-Thermal-Budget Fabrication of Transparent Ferroelectric Thin-Film Transistors on Glass Substrates

Abstract CT130: An open label, dose escalation, phase 1 study of AT101, a novel CD19-directed CAR-T cell therapy targeting a membrane-proximal epitope of CD19, in patients with relapsed or refractory B cell non-Hodgkin lymphoma