Stability and stabilizability of linear time-invariant interval systems.

In this paper, some new approaches for stability and stabilizability determination as well as state feedback stabilization controllers of linear time-invariant (LTI) interval systems are proposed. The presented stability conditions are less conservative than those of Kharitonov's theorem, and Gerschgorin's disc theorem methods. Moreover, some of the proposed stability, stabilizability, and feedback stabilization control methods for LTI interval systems are proved to be sufficient and necessary conditions. Compared with some traditional stability analysis and feedback stabilization design methods for LTI interval systems, these new approaches have lower computational complexity because of a special form of parameter vertex matrices developed in this work. Some numerical and practical examples are given to demonstrate the effectiveness and advantages of the proposed methods.

PEI-PLGA nanoparticles significantly enhanced the immunogenicity of IsdB137-361 proteins from Staphylococcus aureus.

INTRODUCTION: Staphylococcus aureus seriously threatens human and animal health. IsdB137-361 of the iron surface determinant B protein (IsdB) from S. aureus exhibits the strong immunogenicity, but its immunoprotective effect is still to be further promoted. Because PEI-PLGA nanoparticles are generated by PEI conjugate with PLGA to develop great potential as a novel immune adjuvant, the immunogenicity of IsdB137-361 is likely be strengthened by PEI-PLGA. METHODS: Here, PEI-PLGA nanoparticles containing IsdB137-361 proteins were prepared by optimizing the entrapment efficiency. Mice were immunized with IsdB137-361 -PEI-PLGA nanoparticles to assess their anti-S. aureus effects. The level of IFN-γ, IL-4, IL-17, and IL-10 cytokines from spleen lymphocytes in mice and generation of the antibodies against IsdB137-361 in serum was assessed by ELISA, the protective immune response was appraised by S. aureus challenge. RESULTS: IsdB137-361 proteins loaded by PEI-PLGA were able to stimulate effectively the proliferation of spleen lymphocytes and increase the secretion of IFN-γ, IL-4, IL-17, and IL-10 cytokine from spleen lymphocytes, and significantly enhance generation of the antibodies against IsdB137-361 in serum, reduce the level of bacterial load in liver, spleen and kidney, and greatly improve the survival rate of mice after challenge. CONCLUSION: These data showed that PEI-PLGA nanoparticles can significantly enhance the immunogenicity of IsdB137-361 proteins, and provide an important reference for the development of novel immune adjuvant.

Perfect control for nonminimum-phase unstable systems defined in the multivariable continuous-time state-space framework - An inverse-based approach.

In this paper, a new perfect control law dedicated to nonminimum-phase unstable LTI MIMO systems governed in the continuous-time state-space domain is proposed. Two algorithms are investigated, one of which has turned out to be definitely accurate. Henceforth, the inverse model control-based formula can be applied to any right-invertible plants having more input than output variables. Last, not least, through the application of some generalized inverses, the perfect control procedure guarantees the structural stability behavior even for unstable systems. Thus, the notion of the nonminimum-phase property should be understood in terms of a possible achieveability covering the entire class of LTI MIMO continuous-time plants. Theoretical and practical simulation examples performed in the Matlab/Simulink environment confirm the feasibility of the newly introduced approach.

Lymphoid tissue inducer cells in cancer: a potential therapeutic target.

Tumor cells are dynamic in nature; these cells first acquire immune surveillance and then escape from the immune system. Hence, progressed cancer cells distribute and metastasize to other organs via blood vessels as well as from the lymphatic system. Prognosis and treatment of metastatic cancer patients remain a major challenge nowadays. Till now, lots of target -based and immune checkpoint blocker therapies are used to treat disease patients. But these therapies fail to control the dissemination and metastasis of cancer. Before designing a treatment regimen for metastatic patients, understanding the mechanism of tumor cells spreading within lymph vessels remain undetermined. Construction of lymphoid structures since embryonic to adult stage are depend upon LTi. Foundation of lymph node, payer patches and TLO is initiated and regulated through these cells in any part of the body. During tumor growth, newly developed lymph node contained MDSCs and Treg cells which inhibit the immune response and promote tumor invasion and metastasis. LTi reconstituted lymph node can be used for both early and high risk detection of cancers. High and low risk of tumor growth and invasion depend upon the location and composition of immune cells within lymph nodes. However, LTi are not reported as predictive marker in cancer till date. Recent reports in cancer indicate that LTi cells are engaged in the spreading of tumor cells into a lymphatic vessel. Through this review we are trying to brief the development and role of the LTi in immune system during homeostasis and cancer.

An Easily Used Phenomenological Magnetization Model and Its Empirical Expressions Based on Jiles-Atherton Parameters.

In this paper, a simple magnetization model convenient for engineering applications is presented based on the expressions of the first-order LTI system model. Considering the trade-off between the nonlinearity of anhysteretic magnetization and the hysteresis width, the proposed model employs two different equations with different magnetic field amplitudes. Furthermore, the proposed model utilizes the first-order LTI system model with a low magnetic field amplitude and a simple nonlinear function, based on the amplitude-frequency function, with a high magnetic field amplitude. Two important characteristic parameters for engineering applications, namely, amplitude and the equivalent phase lag, were exacted and analyzed to validate the computation precision of the proposed model. Then, the model was verified through comparisons to the validated Jiles-Atherton model. For easy use, similar to a physics-based model instead of a fitting method, empirical expressions for the model parameters were given, and applicable ranges of these equations were determined using the parameters of the Jiles-Atherton model. Finally, an example of the magnetization model applied to an on/off type device was computed to further verify the effectiveness of the proposed model with quite a simple expression.

Tracking axon initial segment plasticity using high-density microelectrode arrays: A computational study.

Despite being composed of highly plastic neurons with extensive positive feedback, the nervous system maintains stable overall function. To keep activity within bounds, it relies on a set of negative feedback mechanisms that can induce stabilizing adjustments and that are collectively termed "homeostatic plasticity." Recently, a highly excitable microdomain, located at the proximal end of the axon-the axon initial segment (AIS)-was found to exhibit structural modifications in response to activity perturbations. Though AIS plasticity appears to serve a homeostatic purpose, many aspects governing its expression and its functional role in regulating neuronal excitability remain elusive. A central challenge in studying the phenomenon is the rich heterogeneity of its expression (distal/proximal relocation, shortening, lengthening) and the variability of its functional role. A potential solution is to track AISs of a large number of neurons over time and attempt to induce structural plasticity in them. To this end, a promising approach is to use extracellular electrophysiological readouts to track a large number of neurons at high spatiotemporal resolution by means of high-density microelectrode arrays (HD-MEAs). However, an analysis framework that reliably identifies specific activity signatures that uniquely map on to underlying microstructural changes is missing. In this study, we assessed the feasibility of such a task and used the distal relocation of the AIS as an exemplary problem. We used sophisticated computational models to systematically explore the relationship between incremental changes in AIS positions and the specific consequences observed in simulated extracellular field potentials. An ensemble of feature changes in the extracellular fields that reliably characterize AIS plasticity was identified. We trained models that could detect these signatures with remarkable accuracy. Based on these findings, we propose a hybrid analysis framework that could potentially enable high-throughput experimental studies of activity-dependent AIS plasticity using HD-MEAs.

Event-triggered controller design for LTI systems: A distributed interval observer-based approach.

This paper investigates the distributed event-triggered control design problem for networked linear time-invariant (LTI) systems with partially measurable states, in the presence of bounded external disturbances. A distributed interval observer-based event-triggered control scheme has been proposed, the main features of this scheme lie in a) designing a novel distributed interval observer to deal with the unknown states and bound disturbances problem; b) proposing a distributed feedback control method using interval estimation information, the partially measurable limitation has been solved; c) introducing a decreased time-varying function with dead-zone modification to avoid the Zeno behavior. Moreover, sufficient conditions for the stability of closed-loop systems are given in the Lyapunov sense by using matrix inequalities and transmission strategy. Finally, the uniformly ultimately bounded stability and Zeno behavior avoidance of the proposed approach have been numerically demonstrated.

Interval estimation for nabla fractional order linear time-invariant systems.

In this paper, we provide a framework to achieve interval estimation for nabla Caputo fractional order linear time-invariant (LTI) systems in the presence of bounded model uncertainties. Interval observers based on fractional order positive systems theory are designed by possessing desired stable and positive error dynamics. Specifically, the basic concepts and conditions for guaranteeing stability and positivity of the considered systems are derived systematically by finding the system responses. Using the developed criteria and the structure of Luenberger-type observers, a classic interval observer is designed directly which further extends the system classes of interval estimation. Besides, due to the possible absence of a gain matrix which ensures positivity requirement, a more general interval observer design scheme is given by exploiting the coordinate transformation technique. Finally, some simulated cases including fault detection and fractional order circuits related scenarios are developed to validate the usefulness and practicality of the framework.

Immunogenicity correlation in cynomolgus monkeys between Luminex-based total IgG immunoassay and pseudovirion-based neutralization assay for a 14-valent recombinant human papillomavirus vaccine.

A new virus-like particle based vaccine covering 14 types of high-risk and disease-inducing human papillomavirus (HPV) can offer better coverage against HPV-induced diseases, particularly cervical cancers. However, the assessment of immunogenicity of the vaccine is an important task, representing not only its significant clinical characteristics, but also a major challenge, in terms of both the suitability of methods and the clinical sample testing throughput supporting clinical development. This work covers the development and evaluation of a method based on Luminex technology (a coded-bead and flow-cytometric approach) to assess the HPV-type specific total immunoglobulin G (IgG). This method can evaluate the antibodies in sera post immunization against multiple types of HPV simultaneously (i.e., with multiplexing capability), save time and cost, and improve test throughput with higher sensitivity and precision than the classical, plate-based enzyme-linked immunoassay and competitive Luminex-based immunoassays. Using cynomolgus monkeys as model, we demonstrated the good correlation between the results from the pseudovirion-based neutralization assay (PBNA), and the Luminex-based total IgG assay, supporting that the latter method can be considered as a viable, dependable replacement method for the PBNA supporting immunogenicity evaluation of HPV vaccine in preclinical development and clinical investigation.

Thermal variation in gradient response: measurement and modeling.

PURPOSE: Many aspects and imperfections of gradient dynamics in MRI have been successfully captured by linear time-invariant (LTI) models. Changes in gradient behavior due to heating, however, violate time invariance. The goal of this work is to study such changes at the level of transfer functions and model them by thermal extension of the LTI framework. METHODS: To study the impact of gradient heating on transfer functions, a clinical MR system was heated using a range of high-amplitude DC and AC waveforms, each followed by measuring transfer functions in rapid succession while the system cooled down. Simultaneously, gradient temperature was monitored with an array of temperature sensors positioned according to initial infrared recordings of the gradient tube. The relation between temperatures and transfer functions is cast into local and global linear models. The models are analysed in terms of self-consistency, conditioning, and prediction performance. RESULTS: Pronounced thermal effects are observed in the time resolved transfer functions, largely attributable to in-coil eddy currents and mechanical resonances. Thermal modeling is found to capture these effects well. The keys to good model performance are well-placed temperature sensors and suitable training data. CONCLUSION: Heating changes gradient response, violating time invariance. The utility of LTI modeling can nevertheless be recovered by a linear thermal extension, relying on temperature sensing and adequate one-time training.

Variance of filtered signals: Characterization for linear reaction networks and application to neurotransmission dynamics.

Neurotransmission at chemical synapses relies on the calcium-induced fusion of synaptic vesicles with the presynaptic membrane. The distance of the synaptic vesicle to the calcium channels determines the release probability and consequently the postsynaptic signal. Suitable models of the process need to capture both the mean and the variance observed in electrophysiological measurements of the postsynaptic current. In this work, we propose a method to directly compute the exact first- and second-order moments for signals generated by a linear reaction network under convolution with an impulse response function, rendering computationally expensive numerical simulations of the underlying stochastic counting process obsolete. We show that the autocorrelation of the process is central for the calculation of the filtered signal's second-order moments, and derive a system of PDEs for the cross-correlation functions (including the autocorrelations) of linear reaction networks with time-dependent rates. Finally, we employ our method to efficiently compare different spatial coarse graining approaches for a specific model of synaptic vesicle fusion. Beyond the application to neurotransmission processes, the developed theory can be applied to any linear reaction system that produces a filtered stochastic signal.

Association of markers of patellofemoral maltracking to cartilage damage and bone marrow lesions on MRI: Data from the 2016 Olympic Games of Rio De Janeiro.

BACKGROUND: Patellofemoral joint (PFJ) disease is a common ailment in elite athletes. Our aim is to report the frequency of superolateral Hoffa's fat pad (SHFP) edema, and PFJ cartilage damage and bone marrow lesions (BML), among Olympian athletes, and to study the association between measurements of trochlear morphology and vertical patellar position and a) PFJ cartilage damage or BML, and b) SHFP edema. METHODS: All knee MRI, performed in the Olympic Village and polyclinics, of participating athletes in the 2016 Olympic Games of Rio de Janeiro were included. MRI were scored for PFJ cartilage damage and BML, and SHFP edema. Trochlear morphology measurements included sulcus angle, trochlear angle, lateral trochlear inclination, and medial trochlear inclination. Insall-Salvati ratio was also assessed. RESULTS: One hundred twenty-one knee MRIs were included (62 female, 51.2 %). The highest frequencies of PFJ cartilage damage, combination of PFJ cartilage damage and BML, and SHFP edema were found among Beach Volleyball and Volleyball athletes. SHFP edema was more common among female compared to male Olympian athletes. We found no statistically significant associations between different measurements of trochlear morphology/vertical patellar position, and 1. SHFP edema, and 2. PFJ cartilage damage/BML. CONCLUSION: SHFP edema and the combination of PFJ cartilage damage and BML are highly frequent among Olympic athletes especially those competing in Beach volleyball and Volleyball. SHFP edema is more common among female athletes. Further studies are needed to determine whether PFJ cartilage damage has a stronger association to sports disciplines rather than trochlear morphology.

Dynamic Expectation Maximization Algorithm for Estimation of Linear Systems with Colored Noise.

The free energy principle from neuroscience has recently gained traction as one of the most prominent brain theories that can emulate the brain's perception and action in a bio-inspired manner. This renders the theory with the potential to hold the key for general artificial intelligence. Leveraging this potential, this paper aims to bridge the gap between neuroscience and robotics by reformulating an FEP-based inference scheme-Dynamic Expectation Maximization-into an algorithm that can perform simultaneous state, input, parameter, and noise hyperparameter estimation of any stable linear state space system subjected to colored noises. The resulting estimator was proved to be of the form of an augmented coupled linear estimator. Using this mathematical formulation, we proved that the estimation steps have theoretical guarantees of convergence. The algorithm was rigorously tested in simulation on a wide variety of linear systems with colored noises. The paper concludes by demonstrating the superior performance of DEM for parameter estimation under colored noise in simulation, when compared to the state-of-the-art estimators like Sub Space method, Prediction Error Minimization (PEM), and Expectation Maximization (EM) algorithm. These results contribute to the applicability of DEM as a robust learning algorithm for safe robotic applications.

Unbounded-Time Safety Verification of Guarded LTI Models with Inputs by Abstract Acceleration.

Reachability analysis of dynamical models is a relevant problem that has seen much progress in the last decades, however with clear limitations pertaining to the nature of the dynamics and the soundness of the results. This article focuses on sound safety verification of unbounded-time (infinite-horizon) linear time-invariant (LTI) models with inputs using reachability analysis. We achieve this using counterexample-guided Abstract Acceleration: this approach over-approximates the reachability tube of the LTI model over an unbounded time horizon by using abstraction, possibly finding concrete counterexamples for refinement based on the given safety specification. The technique is applied to a number of LTI models and the results show robust performance when compared to state-of-the-art tools.

Evaluation of actions of the official veterinary service to mitigate outbreaks of infectious laryngotracheitis and improve biosecurity on laying hen farms

ABSTRACT: Infectious laryngotracheitis (ILT), caused by an Alphaherpesvirus (Gallid herpesvirus-1; GaHV-1), has been noticed in the region of the Terras Altas da Mantiqueira, Minas Gerais. From 2010 to 2018, the Serviço Veterinário Oficial (SVO) of the Instituto Mineiro Agropecuário (IMA), implemented measures to prevent spread of the virus to other regions and control the disease in the area. Due to the close proximity and consequent epidemiological link among farms, the region was considered a unique epidemiological unit. To check the efficiency of the ILT control measures, we carried out: (1) a seroepidemiological survey, (2) questionnaires for evaluating biosecurity measures; and (3) an evaluation of the influence of farm population density on the occurrence of ILT. In 2016, 2017, and 2018, ILT was investigated using epidemiological and clinicopathological methods, along with GaHV-1 molecular detection. Serological survey was carried out on 24 farms in the quarantined region and on 13 farms from other regions of the state. In 2010 and 2018, questionnaires were applied to collect data and determine indicators of biosecurity practices in all farms of the quarantined area. The differences were then assessed (Wilcoxons p 0.05). The results indicated positive serology throughout the region, although only on four farms (16.6%) the chickens have clinical signs, macroscopic and histological lesions of ILT. The prevalence of viral infection increased from 2016 (27%) to 2017 (50%) and was higher in farms with a high stock density (p=0.033). No disease, virus or antibodies were detected in the farms outside of the quarantined area. Although the biosecurity indicators had improved on all farms in the quarantined area (p 0.05), the virus was active and circulating in the region. The contingency measures have contained the outbreak, but biosecurity practices are paramount in the control of new outbreaks. Official control will be maintained in the region, including surveillance of new cases and biosecurity procedures to mitigate the risk of the virus reaching other regions.

RESUMO: Laringotraqueíte infecciosa (LTI), causada por um alfaherpesvírus (herpesvírus Gallid-1; GaHV-1), foi observada na região das Terras Altas da Mantiqueira, Minas Gerais. De 2010 a 2018, o Serviço Veterinário Oficial (SVO) do Instituto Mineiro Agropecuário (IMA) implementou medidas para impedir a disseminação do vírus para outras regiões do estado e controlar a doença na região interditada. Devido à proximidade e consequente vínculo epidemiológico entre as granjas, a região foi considerada uma unidade epidemiológica única. Para verificar a eficiência das medidas de controle de LTI, foram realizados: (1) pesquisa soroepidemiológica, (2) questionários para avaliar medidas de biosseguridade; e (3) avaliação da influência da densidade populacional da granja na ocorrência de LTI. Em 2016, 2017 e 2018, a LTI foi investigada usando métodos epidemiológicos e clínico-patológicos, com a detecção molecular de GaHV-1. O levantamento sorológico foi realizado em 24 granjas da região interditada e em 13 granjas de outras regiões do estado. Em 2010 e 2018, foram aplicados questionários para coletar dados e determinar indicadores de medidas de biosseguridade em todas as granjas da área interditada. As diferenças foram avaliadas (p 0,05 de Wilcoxon). Os resultados indicaram sorologia positiva em toda a região, embora apenas em quatro granjas (16,6%) as galinhas apresentaram sinais clínicos, lesões macroscópicas e histológicas da LTI. A prevalência de infecção viral aumentou de 2016 (27%) para 2017 (50%) e foi maior em fazendas com alta densidade de alojamento (p=0,033). Presença da doença, vírus ou anticorpos foram detectados nas granjas fora da área interditada. Embora os indicadores de biosseguridade tenham melhorado em todas as fazendas da área interditada (p 0,05), o vírus está ativo e circulava na região. As medidas de contingência contiveram o surto, mas as práticas de biosseguridade são fundamentais para o controle de novos surtos. O controle oficial será mantido na região, incluindo a vigilância de novos casos e procedimentos de biosseguridade para mitigar o risco de transmissão do vírus para outras regiões.

Evaluation of actions of the official veterinary service to mitigate outbreaks of infectious laryngotracheitis and improve biosecurity on laying hen farms / Avaliação de ações do serviço veterinário oficial para bloqueio de foco de laringotraqueite infecciosa e melhoria da biosseguridade em granjas de postura

Infectious laryngotracheitis (ILT), caused by an Alphaherpesvirus (Gallid herpesvirus-1; GaHV-1), has been noticed in the region of the Terras Altas da Mantiqueira, Minas Gerais. From 2010 to 2018, the "Serviço Veterinário Oficial" (SVO) of the "Instituto Mineiro Agropecuário" (IMA), implemented measures to prevent spread of the virus to other regions and control the disease in the area. Due to the close proximity and consequent epidemiological link among farms, the region was considered a unique epidemiological unit. To check the efficiency of the ILT control measures, we carried out: (1) a seroepidemiological survey, (2) questionnaires for evaluating biosecurity measures; and (3) an evaluation of the influence of farm population density on the occurrence of ILT. In 2016, 2017, and 2018, ILT was investigated using epidemiological and clinicopathological methods, along with GaHV-1 molecular detection. Serological survey was carried out on 24 farms in the quarantined region and on 13 farms from other regions of the state. In 2010 and 2018, questionnaires were applied to collect data and determine indicators of biosecurity practices in all farms of the quarantined area. The differences were then assessed (Wilcoxon's p<0.05). The results indicated positive serology throughout the region, although only on four farms (16.6%) the chickens have clinical signs, macroscopic and histological lesions of ILT. The prevalence of viral infection increased from 2016 (27%) to 2017 (50%) and was higher in farms with a high stock density (p=0.033). No disease, virus or antibodies were detected in the farms outside of the quarantined area. Although the biosecurity indicators had improved on all farms in the quarantined area (p<0.05), the virus was active and circulating in the region. The contingency measures have contained the outbreak, but biosecurity practices are paramount in the control of new outbreaks. Official control will be maintained in the region, including surveillance of new cases and biosecurity procedures to mitigate the risk of the virus reaching other regions.(AU)

Laringotraqueíte infecciosa (LTI), causada por um alfaherpesvírus (herpesvírus Gallid-1; GaHV-1), foi observada na região das Terras Altas da Mantiqueira, Minas Gerais. De 2010 a 2018, o Serviço Veterinário Oficial (SVO) do Instituto Mineiro Agropecuário (IMA) implementou medidas para impedir a disseminação do vírus para outras regiões do estado e controlar a doença na região interditada. Devido à proximidade e consequente vínculo epidemiológico entre as granjas, a região foi considerada uma unidade epidemiológica única. Para verificar a eficiência das medidas de controle de LTI, foram realizados: (1) pesquisa soroepidemiológica, (2) questionários para avaliar medidas de biosseguridade; e (3) avaliação da influência da densidade populacional da granja na ocorrência de LTI. Em 2016, 2017 e 2018, a LTI foi investigada usando métodos epidemiológicos e clínico-patológicos, com a detecção molecular de GaHV-1. O levantamento sorológico foi realizado em 24 granjas da região interditada e em 13 granjas de outras regiões do estado. Em 2010 e 2018, foram aplicados questionários para coletar dados e determinar indicadores de medidas de biosseguridade em todas as granjas da área interditada. As diferenças foram avaliadas (p<0,05 de Wilcoxon). Os resultados indicaram sorologia positiva em toda a região, embora apenas em quatro granjas (16,6%) as galinhas apresentaram sinais clínicos, lesões macroscópicas e histológicas da LTI. A prevalência de infecção viral aumentou de 2016 (27%) para 2017 (50%) e foi maior em fazendas com alta densidade de alojamento (p=0,033). Presença da doença, vírus ou anticorpos foram detectados nas granjas fora da área interditada. Embora os indicadores de biosseguridade tenham melhorado em todas as fazendas da área interditada (p<0,05), o vírus está ativo e circulava na região. As medidas de contingência contiveram o surto, mas as práticas de biosseguridade são fundamentais para o controle de novos surtos. O controle oficial será mantido na região, incluindo a vigilância de novos casos e procedimentos de biosseguridade para mitigar o risco de transmissão do vírus para outras regiões.(AU)

Distinct Waves from the Hemogenic Endothelium Give Rise to Layered Lymphoid Tissue Inducer Cell Ontogeny.

During embryogenesis, lymphoid tissue inducer (LTi) cells are essential for lymph node organogenesis. These cells are part of the innate lymphoid cell (ILC) family. Although their earliest embryonic hematopoietic origin is unclear, other innate immune cells have been shown to be derived from early hemogenic endothelium in the yolk sac as well as the aorta-gonad-mesonephros. A proper model to discriminate between these locations was unavailable. In this study, using a Cxcr4-CreERT2 lineage tracing model, we identify a major contribution from embryonic hemogenic endothelium, but not the yolk sac, toward LTi progenitors. Conversely, embryonic LTi cells are replaced by hematopoietic stem cell-derived cells in adults. We further show that, in the fetal liver, common lymphoid progenitors differentiate into highly dynamic alpha-lymphoid precursor cells that, at this embryonic stage, preferentially mature into LTi precursors and establish their functional LTi cell identity only after reaching the periphery.

The Interaction between Lymphoid Tissue Inducer-Like Cells and T Cells in the Mesenteric Lymph Node Restrains Intestinal Humoral Immunity.

Lymphoid tissue inducer (LTi)/LTi-like cells are critical for lymphoid organogenesis and regulation of adaptive immunity in various tissues. However, the maintenance and regulation mechanisms of LTi-like cells among different tissues are not clear yet. Here, we find that LTi-like cells from different tissues display heterogeneity. The maintenance of LTi-like cells in the mesenteric lymph node (mLN), but not the gut, requires RANKL signaling from CD4+ T cells. LTi-like cells from the mLN, but not the gut, could in turn inhibit the development of T follicular helper cells and subsequent humoral responses during intestinal immunization in an ID2- and PD-L1-dependent manner. Together, our findings implicate that the interaction between LTi-like cells and T cells in the mLN could precisely control the intestinal mucosal adaptive immune response.

Analysis of 25% duty-cycle up-conversion passive mixer for UWB transmitter.

The performance of differential up-conversion passive mixer operating in the 3-5 GHz band for UWB transmitter driven by 25% duty-cycle clocks is studied and analyzed. A reasonably accurate LTI equivalent circuit accounting for harmonics is derived. We have demonstrated that the conversion gain, input and output impedances of the proposed LTI equivalent circuit matches those of the LTV up-conversion passive mixer. The LTI model can be used to define the reachable design space. The mixer input and output impedance can be tuned by varying resistor at the mixer output allowing for impedance match to connected circuits. We have shown how each design parameters impacts critical performance of the up-conversion passive mixer. Simulations of the proposed up-conversion passive mixer show -3.68 dB of conversion gain, 15.9 dBm of OIP3, 116.7dBm of OIP2 and a NF as low as 5.2 dB while consuming 1.5 pW. Furthermore linearity and ports isolation performances due to voltage threshold mismatch variation of ±60 mV shows an OIP3 greater than 15.85dBm and an LO_RF isolation smaller than -51.9 dB.

STING Gain-of-Function Disrupts Lymph Node Organogenesis and Innate Lymphoid Cell Development in Mice.

STING gain-of-function causes autoimmunity and immunodeficiency in mice and STING-associated vasculopathy with onset in infancy (SAVI) in humans. Here, we report that STING gain-of-function in mice prevents development of lymph nodes and Peyer's patches. We show that the absence of secondary lymphoid organs is associated with diminished numbers of innate lymphoid cells (ILCs), including lymphoid tissue inducer (LTi) cells. Although wild-type (WT) α4ß7+ progenitors differentiate efficiently into LTi cells, STING gain-of-function progenitors do not. Furthermore, STING gain-of-function impairs development of all types of ILCs. Patients with STING gain-of-function mutations have fewer ILCs, although they still have lymph nodes. In mice, expression of the STING mutant in RORγT-positive lineages prevents development of lymph nodes and reduces numbers of LTi cells. RORγT lineage-specific expression of STING gain-of-function also causes lung disease. Since RORγT is expressed exclusively in LTi cells during fetal development, our findings suggest that STING gain-of-function prevents lymph node organogenesis by reducing LTi cell numbers in mice.