Memory Cells Research Articles

Assessing the causal relationship between circulating immune cells and abdominal aortic aneurysm by bi-directional Mendelian randomization analysis

Although there is an association between abdominal aortic aneurysm (AAA) and circulating immune cell phenotypes, the exact causal relationship remains unclear. This study aimed to explore the causal relationships between immune cell phenotypes and AAA risk using a bidirectional two-sample Mendelian randomization approach. Data from genome-wide association studies pertaining to 731 immune cell traits and AAA were systematically analyzed. Using strict selection criteria, we identified 339 immune traits that are associated with at least 3 single nucleotide polymorphisms. A comprehensive MR analysis was conducted using several methods including Inverse Variance Weighted, Weighted Median Estimator, MR-Egger regression, Weighted Mode, and Simple Median methods. CD24 on switched memory cells (OR = 0.922, 95% CI 0.914–0.929, P = 2.62e−79) at the median fluorescence intensities level, and SSC-A on HLA-DR + natural killer cells (OR = 0.873, 95% CI 0.861–0.885, P = 8.96e−81) at the morphological parameter level, exhibited the strongest causal associations with AAA. In the reverse analysis, no significant causal effects of AAA on immune traits were found. The study elucidates the causal involvement of multiple circulating immune cell phenotypes in AAA development, signifying their potential as diagnostic markers or therapeutic targets. These identified immune traits may be crucial in modulating AAA-related inflammatory pathways.

FAM189A2 plays a tumour suppressor role in lung adenocarcinoma by influencing cell apoptosis, CXCR4 expression and tight junction proteins

Transmembrane proteins play key roles in the development of lung cancer. The family with sequence similarity 189 member A2 (FAM189A2) gene encodes a transmembrane structural protein, yet its involvement in lung adenocarcinoma remains largely unexplored. This study elucidated its role in lung adenocarcinoma and its possible molecular mechanism. Our findings revealed diminished expression levels of FAM189A2 in LUAD tissues. Additionally, the activity of LUAD cells was significantly inhibited by overexpression of FAM189A2. Following FAM189A2 overexpression, the expression of OCLN and TJP2 was upregulated in LUAD cells, while CXCR4 expression experiences a notable decrease. Moreover, the coimmunoprecipitation experiment confirmed the direct interaction between FAM189A2 and CXCR4. The infiltration levels of T cells (CD4+ memory resting, CD8+, regulatory), NK cells, B memory cells, endothelial cells and cancer-associated fibroblasts were significantly correlated with FAM189A2 expression. These results indicate FAM189A2 may act as a tumour suppressor in LUAD through tight junction protein (TJP) and CXCR4 regulation. Moreover, FAM189A2 is significantly correlated with the immune microenvironment of LUAD, which may be involved in prognosis and immunotherapeutic efficacy.

Effects of combined radiotherapy with immune checkpoint blockade on immunological memory in luminal-like subtype murine bladder cancer model

ABSTRACT MIBC is a highly lethal disease, and the patient survival rate has not improved significantly over the last decades. UPPL is a cell line that can be used to recapitulate the luminal-like molecular subtype of bladder cancer and to discover effective treatments to be translated in patients. Here, we investigate the effects of combinational treatments of radiotherapy and immunotherapy in this recently characterized UPPL tumor-bearing mice. We first characterized the baseline tumor microenvironment and the effect of radiation, anti-PD-L1, and combinatorial treatments. Then, the mice were re-challenged with a second tumor (rechallenged tumor) in the contralateral flank of the first tumor to assess the immunological memory. Radiation slowed down the tumor growth. All treatments also decreased the neutrophil population and increased the T cell population. Anti-PD-L1 therapy was not able to synergize with radiation to further delay tumor growth. Furthermore, none of the treatments were able to generate immune memory. The treatments were not sufficient to induce a significant and lasting pool of memory cells. We show here that anti-PD-L1 treatment added to radiotherapy was not enough to achieve T cell-mediated memory in UPPL tumors. Stronger T cell activation signals may be required to enhance radiation efficacy in luminal-like bladder cancer.

Pre-treatment peripheral blood immunophenotyping and response to neoadjuvant chemotherapy in operable breast cancer

BackgroundTumor immune infiltration and peripheral blood immune signatures have prognostic and predictive value in breast cancer. Whether distinct peripheral blood immune phenotypes are associated with response to neoadjuvant chemotherapy (NAC) remains understudied.MethodsPeripheral blood mononuclear cells from 126 breast cancer patients enrolled in a prospective clinical trial (NCT02022202) were analyzed using Cytometry by time-of-flight with a panel of 29 immune cell surface protein markers. Kruskal–Wallis tests or Wilcoxon rank-sum tests were used to evaluate differences in immune cell subpopulations according to breast cancer subtype and response to NAC.ResultsThere were 122 evaluable samples: 47 (38.5%) from patients with hormone receptor-positive, 39 (32%) triple-negative (TNBC), and 36 (29.5%) HER2-positive breast cancer. The relative abundances of pre-treatment peripheral blood T, B, myeloid, NK, and unclassified cells did not differ according to breast cancer subtype. In TNBC, higher pre-treatment myeloid cells were associated with lower pathologic complete response (pCR) rates. In hormone receptor-positive breast cancer, lower pre-treatment CD8 + naïve and CD4 + effector memory cells re-expressing CD45RA (TEMRA) T cells were associated with more extensive residual disease after NAC. In HER2 + breast cancer, the peripheral blood immune phenotype did not differ according to NAC response.ConclusionsPre-treatment peripheral blood immune cell populations (myeloid in TNBC; CD8 + naïve T cells and CD4 + TEMRA cells in luminal breast cancer) were associated with response to NAC in early-stage TNBC and hormone receptor-positive breast cancers, but not in HER2 + breast cancer.Trial registrationNCT02022202. Registered 20 December 2013.

Verification of neuromorphic processing accuracy against non‐ideal errors in synapse‐based neural network systems

AbstractThe synapse‐based neuromorphic systems for deep neural network (DNN) require neuron read/update circuit blocks which specifications depend on the synapse components. In this study, we implemented and verified the dedicated circuit system to operate the three‐terminal analog synaptic memory cells, electrochemical random access memory (ECRAM), for multi‐bit analog neuromorphic computing. In addition, we analyzed the impact of the noise/offset generated by the neuron circuit systems and synapse cell arrays, which can affect the neuromorphic processing accuracy, by using the Modified National Institute of Standards and Technology database (MNIST) dataset. The experiments with MNIST datasets were conducted in two ways: by performing ideal inference simulations with MATLAB and experiments with the neuromorphic system board. The results of the ideal inference simulation and experiment were 97.4% and 96.92%, respectively. The accuracy of 97.31% was measured when the weight of the hidden layer was set with the fixed resistance values to confirm the effectiveness of the synapse cells. According to the results, the effects of synapse cells and neuron circuits to the processing accuracy were 0.09% and 0.39%, respectively. Also, this MNIST experiments verified that about 10% or smaller variations of weight values in the synapse cells lead to negligible effects on processing accuracy through the training and inference.

Expansion of effector memory Vδ2neg γδ T cells associates with cytomegalovirus reactivation in allogeneic stem cell transplant recipients.

Cytomegalovirus (CMV) reactivation is a significant concern following allogeneic stem cell transplantation. While previous research has highlighted the anti-CMV reactivation effect of γδ T cells in immunocompromised transplant patients, their characterization in recipients at high risk of CMV reactivation remains limited. This study focused on D+/R+ recipients (where both donor and recipient are CMV seropositive) at high risk of CMV reactivation. We analyzed 28 patients who experienced CMV recurrence within 100 days post-allogeneic hematopoietic stem cell transplantation, along with 36 matched recipients who did not experience CMV recurrence. Clinical data from both groups were compared, and risk factors for CMV reactivation were identified. Additionally, CMV viral load was measured, and flow cytometric analysis was conducted to assess changes in peripheral blood γδ T cell proportions, subpopulation distribution, and differentiation status. We also analyzed the CDR3 repertoire of the TCR δ chain in different γδ T cell subsets. Functional analysis was performed by measuring the lysis of CMV-infected cells upon stimulation. CMV reactivation post-transplantation was associated with acute graft-versus-host disease (aGvHD) and reactivation of non-CMV herpesviruses. Notably, CMV reactivation led to sustained expansion of γδ T cells, primarily within the Vδ2neg γδ T cell subpopulation, with a trend toward differentiation from Naive to effector memory cells. Analysis of the δ chain CDR3 repertoire revealed a delay in the reconstitution of clonal diversity in Vδ2neg γδ T cells following CMV reactivation, while Vδ2pos T cells remained unaffected. Upon stimulation with CMV-infected MRC5 cells, the Vδ2neg γδ T cell subpopulation emerged as the primary effector cell group producing IFN-γ and capable of lysing CMV-infected cells. Moreover, our findings suggest that NKG2D is not necessary involved in Vδ2neg γδ T cell-mediated anti-CMV cytotoxicity. This study provides novel insights into the role of γδ T cells in the immune response to CMV reactivation in transplantation recipients at high risk of CMV infection. Specifically, the Vδ2neg γδ T cell subpopulation appears to be closely associated with CMV reactivation, underscoring their potential role in controlling infection and reflecting CMV reactivation in HSCT patients.

Nano-Pulse Treatment Overcomes the Immunosuppressive Tumor Microenvironment to Elicit In Situ Vaccination Protection against Breast Cancer.

We previously reported that nano-pulse treatment (NPT), a pulsed power technology, resulted in 4T1-luc mammary tumor elimination and a strong in situ vaccination, thereby completely protecting tumor-free animals against a second live tumor challenge. The mechanism whereby NPT mounts effective antitumor immune responses in the 4T1 breast cancer predominantly immunosuppressive tumor microenvironment (TME) remains unanswered. In this study, orthotopic 4T1 mouse breast tumors were treated with NPT (100 ns, 50 kV/cm, 1000 pulses, 3 Hz). Blood, spleen, draining lymph nodes, and tumors were harvested at 4-h, 8-h, 1-day, 3-day, 7-day, and 3-month post-treatment intervals for the analysis of frequencies, death, and functional markers of various immune cells in addition to the suppressor function of regulatory T cells (Tregs). NPT was verified to elicit strong in situ vaccination (ISV) against breast cancer and promote both acute and long-term T cell memory. NPT abolished immunosuppressive dominance systemically and in the TME by substantially reducing Tregs, myeloid-derived suppressor cells (MDSCs), and tumor-associated macrophages (TAMs). NPT induced apoptosis in Tregs and TAMs. It also functionally diminished the Treg suppression capacity, explained by the downregulation of activation markers, particularly 4-1BB and TGFβ, and a phenotypic shift from predominantly activated (CD44+CD62L-) to naïve (CD44-CD62L+) Tregs. Importantly, NPT selectively induced apoptosis in activated Tregs and spared effector CD4+ and CD8+ T cells. These changes were followed by a concomitant rise in CD8+CD103+ tissue-resident memory T cells and TAM M1 polarization. These findings indicate that NPT effectively switches the TME and secondary lymphatic systems from an immunosuppressive to an immunostimulatory state, allowing cytotoxic T cell function and immune memory formation to eliminate cancer cells and account for the NPT in situ vaccination.

Enhancing image data security with chain and non-chain Galois ring structures

The local ring-based cryptosystem is built upon the core mathematical operations of the algebraic structure of local rings, which provides a significant advantage in ensuring security against advanced cryptanalysis. However, using the entire set of units within this structure would be computationally impractical in practical applications. Thus, we present a novel approach for designing 16×16 and 32×32 substitution boxes over chain and non-chain Galois ring respectively, by utilizing subgroups of local rings in a computationally feasible manner. Our proposed scheme significantly reduces memory usage by integrating both chain and non-chain rings. Specifically, the 16×16 and 32×32 S-boxes require only 16×28and 32×28 memory cells, respectively, whereas S-boxes of these dimensions over fields have been shown to be highly inefficient due to their extensive memory requirements (16×216and 32×232,respectively). The proposed method offers a more efficient solution for constructing S-boxes over large Galois fields and integrates chain and non-chain local Galois rings, as well as finite fields, for efficient transmission designs in smart devices. The algebraic structures used in this approach are used to establish the most vital aspect of a block cipher, the substitution box. We use each of these algebraic structures, each with a different bit size, to construct three distinct S-boxes. We discuss the performance and sensitivity of the proposed S-boxes to demonstrate their effectiveness in data protection. In this technique, the substitution boxes established by the non-chain ring, maximal cyclic subgroup of the Galois ring, and Galois field are applied for the processes of substitution, exclusive-or function, and diffusion in image encryption, respectively. Furthermore, we have performed numerous standard analyses on the encrypted image, including statistical analysis, differential analysis, and NIST tests. The results of these tests demonstrate the effectiveness of the proposed approach for various cryptographic purposes. Overall, this work provides a valuable contribution to the field of cryptography, particularly in constructing efficient S-boxes over large Galois fields.

Quantitative Inversion of Multiantenna Ground-Penetrating Radar Data with Modeling Error Correction Based on Long Short-Term Memory Cells

Quantitative Inversion of Multiantenna Ground-Penetrating Radar Data with Modeling Error Correction Based on Long Short-Term Memory Cells

Unlocking large memory windows and 16-level data per cell memory operations in hafnia-based ferroelectric transistors

Ferroelectric transistors based on hafnia-based ferroelectrics exhibit tremendous potential as next-generation memories owing to their high-speed operation and low power consumption. Nevertheless, these transistors face limitations in terms of memory window, which directly affects their ability to support multilevel characteristics in memory devices. Furthermore, the absence of an efficient operational technique capable of achieving multilevel characteristics has hindered their development. To address these challenges, we present a gate stack engineering method and an efficient operational approach for ferroelectric transistors to achieve 16-level data per cell operation. By using the suggested engineering method, we demonstrate the attainment of a substantial memory window of 10 V without increasing the device area. Additionally, we propose a displacement current control method, facilitating one-shot programming to the desired state. Remarkably, we suggest the compatibility of these proposed methods with three-dimensional (3D) structures. This study underscores the potential of ferroelectric transistors for next-generation 3D memory applications.

Identification of potential immune-related mechanisms related to the development of multiple myeloma.

Although significant advances have been made in the treatment of multiple myeloma (MM), leading to unprecedented response and survival rates among patients, the majority eventually relapse, and a cure remains elusive. This situation is closely related to an incomplete understanding of the immune microenvironment, especially monocytes/macrophages in patients with treatment-naïve MM. The aim of this study was to provide insight into the immune microenvironment, especially monocytes/macrophages, in patients with treatment-naïve MM. This study used the single-cell RNA sequencing (scRNA-seq) data of both patients with MM and heathy donors to identify immune cells, including natural killer (NK) cells, T cells, dendritic cells (DCs), and monocytes/macrophages. Transcriptomic data and flow cytometry analysis of monocytes/macrophages were used to further examine the effect of monocytes/macrophages in treatment-naïve MM patients. A significant difference was observed between the bone marrow (BM) immune cells of the healthy controls and treatment-naïve MM patients through scRNA-seq. It is noteworthy that, through an scRNA-seq data analysis, this study found that interferon (IFN)-induced NK/T cells, terminally differentiated effector memory (TEMRA) cells, T-helper cells characterized by expression of IFN-stimulated genes (ISG + Th cells), IFN-responding exhausted T cells, mannose receptor C-type 1 (MRC1) + DCs, IFN-responding DCs, MHCII + DCs, and immunosuppressive monocytes/macrophages were enriched in patients with treatment-naïve MM. Significantly, transcriptomic data of monocytes/macrophages demonstrated that "don't eat me"-related genes and IFN-induced genes increase in treatment-naïve MM patients. Furthermore, scRNA-seq, transcriptomic data, and flow cytometry also showed an increased proportion of CD16 + monocytes/macrophages and expression level of CD16. Cell-cell communication analysis indicated that monocytes/macrophages, whose related important signaling pathways include migration inhibitory factor (MIF) and interleukin 16 (IL-16) signaling pathway, are key players in treatment-naïve MM patients. Our findings provide a comprehensive and in-depth molecular characterization of BM immune cell census in MM patients, especially for monocytes/macrophages. Targeting macrophages may be a novel treatment strategy for patients with MM.

Longitudinal dynamic single-cell mass cytometry analysis of peripheral blood mononuclear cells in COVID-19 patients within 6 months after viral RNA clearance

This study investigates the longitudinal dynamic changes in immune cells in COVID-19 patients over an extended period after recovery, as well as the interplay between immune cells and antibodies. Leveraging single-cell mass spectrometry, we selected six COVID-19 patients and four healthy controls, dissecting the evolving landscape within six months post-viral RNA clearance, alongside the levels of anti-spike protein antibodies. The T cell immunophenotype ascertained via single-cell mass spectrometry underwent validation through flow cytometry in 37 samples. Our findings illuminate that CD8 + T cells, gamma-delta (gd) T cells, and NK cells witnessed an increase, in contrast to the reduction observed in monocytes, B cells, and double-negative T (DNT) cells over time. The proportion of monocytes remained significantly elevated in COVID-19 patients compared to controls even after six-month. Subpopulation-wise, an upsurge manifested within various T effector memory subsets, CD45RA + T effector memory, gdT, and NK cells, whereas declines marked the populations of DNT, naive and memory B cells, and classical as well as non-classical monocytes. Noteworthy associations surfaced between DNT, gdT, CD4 + T, NK cells, and the anti-S antibody titer. This study reveals the changes in peripheral blood mononuclear cells of COVID-19 patients within 6 months after viral RNA clearance and sheds light on the interactions between immune cells and antibodies. The findings from this research contribute to a better understanding of immune transformations during the recovery from COVID-19 and offer guidance for protective measures against reinfection in the context of viral variants.

Superconducting spintronic heat engine

Heat engines are key devices that convert thermal energy into usable energy. Strong thermoelectricity, at the basis of electrical heat engines, is present in superconducting spin tunnel barriers at cryogenic temperatures where conventional semiconducting or metallic technologies cease to work. Here we realize a superconducting spintronic heat engine consisting of a ferromagnetic insulator/superconductor/insulator/ferromagnet tunnel junction (EuS/Al/AlOx/Co). The efficiency of the engine is quantified for bath temperatures ranging from 25 mK up to 800 mK, and at different load resistances. Moreover, we show that the sign of the generated thermoelectric voltage can be inverted according to the parallel or anti-parallel orientation of the two ferromagnetic layers, EuS and Co. This realizes a thermoelectric spin valve controlling the sign and strength of the Seebeck coefficient, thereby implementing a thermoelectric memory cell. We propose a theoretical model that allows describing the experimental data and predicts the engine efficiency for different device parameters.

Non-Glycosylated SARS-CoV-2 Omicron BA.5 Receptor Binding Domain (RBD) with a Native-like Conformation Induces a Robust Immune Response with Potent Neutralization in a Mouse Model.

The Omicron BA.5 variant of SARS-CoV-2 is known for its high transmissibility and its capacity to evade immunity provided by vaccine protection against the (original) Wuhan strain. In our prior research, we successfully produced the receptor-binding domain (RBD) of the SARS-CoV-2 spike protein in an E. coli expression system. Extensive biophysical characterization indicated that, even without glycosylation, the RBD maintained native-like conformational and biophysical properties. The current study explores the immunogenicity and neutralization capacity of the E. coli-expressed Omicron BA.5 RBD using a mouse model. Administration of three doses of the RBD without any adjuvant elicited high titer antisera of up to 7.3 × 105 and up to 1.6 × 106 after a booster shot. Immunization with RBD notably enhanced the population of CD44+CD62L+ T cells, indicating the generation of T cell memory. The in vitro assays demonstrated the antisera's protective efficacy through significant inhibition of the interaction between SARS-CoV-2 and its human receptor, ACE2, and through potent neutralization of a pseudovirus. These findings underscore the potential of our E. coli-expressed RBD as a viable vaccine candidate against the Omicron variant of SARS-CoV-2.

Innate acting memory Th1 cells modulate heterologous diseases

Through immune memory, infections have a lasting effect on the host. While memory cells enable accelerated and enhanced responses upon rechallenge with the same pathogen, their impact on susceptibility to unrelated diseases is unclear. We identify a subset of memory T helper 1 (Th1) cells termed innate acting memory T (TIA) cells that originate from a viral infection and produce IFN-γ with innate kinetics upon heterologous challenge in vivo. Activation of memory TIA cells is induced in response to IL-12 in combination with IL-18 or IL-33 but is TCR independent. Rapid IFN-γ production by memory TIA cells is protective in subsequent heterologous challenge with the bacterial pathogen Legionella pneumophila. In contrast, antigen-independent reactivation of CD4+ memory TIA cells accelerates disease onset in an autoimmune model of multiple sclerosis. Our findings demonstrate that memory Th1 cells can acquire additional TCR-independent functionality to mount rapid, innate-like responses that modulate susceptibility to heterologous challenges.

Sequential immunotherapy: towards cures for autoimmunity.

Despite major progress in the treatment of autoimmune diseases in the past two decades, most therapies do not cure disease and can be associated with increased risk of infection through broad suppression of the immune system. However, advances in understanding the causes of autoimmune disease and clinical data from novel therapeutic modalities such as chimeric antigen receptor T cell therapies provide evidence that it may be possible to re-establish immune homeostasis and, potentially, prolong remission or even cure autoimmune diseases. Here, we propose a 'sequential immunotherapy' framework for immune system modulation to help achieve this ambitious goal. This framework encompasses three steps: controlling inflammation; resetting the immune system through elimination of pathogenic immune memory cells; and promoting and maintaining immune homeostasis via immune regulatory agents and tissue repair. We discuss existing drugs and those in development for each of the three steps. We also highlight the importance of causal human biology in identifying and prioritizing novel immunotherapeutic strategies as well as informing their application in specific patient subsets, enabling precision medicine approaches that have the potential to transform clinical care.

Research on Improved Crystallization Properties and Underlying Mechanism of the Sb2Te3 Phase-Change Thin Film by Inserting Sn15Sb85 Layers.

As a non-volatile semiconductor memory technology, phase-change memory has a wide range of application prospects as a result of the excellent comprehensive performance. In this paper, multilayer thin films based on Sb2Te3 material were designed and prepared by inserting the Sn15Sb85 layer. The thermal and electrical properties of superlattice-like Sb2Te3/Sn15Sb85 phase-change films can be adjusted by controlling the thickness ratio of Sb2Te3/Sn15Sb85. In comparison to the monolayer Sb2Te3 film, the multilayer layer Sb2Te3/Sn15Sb85 materials have a higher crystallization temperature, larger crystallization activation energy, and longer data lifetime, indicating the great improvement of thermal stability. The changes in the phase structure and vibrational modes of multilayer Sb2Te3/Sn15Sb85 films were characterized by X-ray diffraction and Raman spectroscopy, respectively. The presence of Sn15Sb85 layers restrains grain growth and refines the grain size. The multilayer Sb2Te3/Sn15Sb85 films exhibit better surface flatness, smaller surface potential undulation, and lower thickness variations than single-layer Sb2Te3. Phase-change memory cells based on the [Sb2Te3 (1 nm)/Sn15Sb85 (9 nm)]5 thin film has a lower threshold voltage (1.9 V) and threshold current (3.1 μA) compared to the Ge2Sb2Te5 film. Meanwhile, the electrical heating model of a phase-change memory cell based on a [Sb2Te3 (1 nm)/Sn15Sb85 (9 nm)]5 multilayer structure was established by multiphysics coupling analysis, proving the great improvement in heat transfer performance and efficiency. The experimental and theoretical studies confirm that the insertion of the Sn15Sb85 layer can significantly improve the crystallization properties of Sb2Te3 films, paving the way for optimizing the phase-change materials by regulating the microstructural parameters.

A culture method with berbamine, a plant alkaloid, enhances CAR-T cell efficacy through modulating cellular metabolism

Memory T cells demonstrate superior in vivo persistence and antitumor efficacy. However, methods for manufacturing less differentiated T cells are not yet well-established. Here, we show that producing chimeric antigen receptor (CAR)-T cells using berbamine (BBM), a natural compound found in the Chinese herbal medicine Berberis amurensis, enhances the antitumor efficacy of CAR-T cells. BBM is identified through cell-based screening of chemical compounds using induced pluripotent stem cell-derived T cells, leading to improved viability with a memory T cell phenotype. Transcriptomics and metabolomics using stem cell memory T cells reveal that BBM broadly enhances lipid metabolism. Furthermore, the addition of BBM downregulates the phosphorylation of p38 mitogen-activated protein kinase and enhanced mitochondrial respiration. CD19-CAR-T cells cultured with BBM also extend the survival of leukaemia mouse models due to their superior in vivo persistence. This technology offers a straightforward approach to enhancing the antitumor efficacy of CAR-T cells.

Estimation of bandwidth, voltage swing and DC coefficients for VLSI interconnects: current mode technique

ABSTRACT Necessity of bandwidth requires the effective use of it for high speed data transmission and faster read/write operation in memory cells. In this paper the transfer function expressions for RC interconnect line is presented for resistive load. The line delay, bandwidth and step response for current and voltage mode signalling is formulated. The current mode and voltage mode signalling provides the 3-dB bandwidth of 6.8 GHz and 3.1 GHz, respectively. An interconnect line modelled as either RLC or RC line depending upon input signal rise time, damping, and range of interconnect length with significant inductance effect is investigated for global interconnect lines. Low swing for column bit line in memory architectures is very important and estimated in terms of dc coefficients. For RC global interconnect of 10 mm, a swing of 0.382 V is obtained for current mode signalling, when a power supply of 1.8 V is applied to the network. DC coefficient and steady state value has been obtained which is significant for power computation on column bit line. It is also analytically validated by SPICE and MATLAB simulations.

A guide to adaptive immune memory.

Immune memory - comprising T cells, B cells and plasma cells and their secreted antibodies - is crucial for human survival. It enables the rapid and effective clearance of a pathogen after re-exposure, to minimize damage to the host. When antigen-experienced, memory T cells become activated, they proliferate and produce effector molecules at faster rates and in greater magnitudes than antigen-inexperienced, naive cells. Similarly, memory B cells become activated and differentiate into antibody-secreting cells more rapidly than naive B cells, and they undergo processes that increase their affinity for antigen. The ability of T cells and B cells to form memory cells after antigen exposure is the rationale behind vaccination. Understanding immune memory not only is crucial for the design of more-efficacious vaccines but also has important implications for immunotherapies in infectious disease and cancer. This 'guide to' article provides an overview of the current understanding of the phenotype, function, location, and pathways for the generation, maintenance and protective capacity of memory T cells and memory B cells.