Compatible Protocol Research Articles

Human CD8+ Tregs expressing a MHC-specific CAR display enhanced suppression of human skin rejection and GVHD in NSG mice

AbstractPolyclonal CD8+CD45RClow/− Tregs are potent regulatory cells able to control solid organ transplantation rejection and even induce tolerance. However, donor major histocompatibility complex (MHC)–specific Tregs are more potent than polyclonal Tregs in suppressing T-cell responses and preventing acute as well as chronic rejection in rodent models. The difficulty of identifying disease-relevant antigens able to stimulate Tregs has reduced the possibility of obtaining antigen-specific Tregs. To bypass this requirement and gain the advantage of antigen specificity, and thus improve the therapeutic potential of CD8+ Tregs, we stably introduced a chimeric antigen receptor (CAR) derived from a HLA-A*02 antigen-specific antibody (A2-CAR) in human CD8+ Tregs and developed a clinically compatible protocol of transduction and expansion. We demonstrated that A2-CAR CD8+ Tregs were not phenotypically altered by the process, were specifically activated, and did not exhibit cytotoxic activity toward HLA-A*02+ kidney endothelial cells (ECs). We showed that A2-CAR CD8+ Tregs were more potent suppressors of immune responses induced by HLA-A*02 mismatch than control-CAR CD8+ Tregs, both in vitro and in vivo, in models of human skin graft rejection and graft-versus-host disease (GVHD) in NOD.Cg-PrkdcscidIl2rgtm1Wjl/SzJ (NSG) mice. We showed that integrity of human skin graft was preserved with A2-CAR CD8+ Tregs at least 100 days in vivo after administration, and that interaction between the A2-CAR CD8+ Tregs and HLA-A*02+ kidney ECs resulted in a fine-tuned and protolerogenic activation of the ECs without cytotoxicity. Together, our results demonstrated the relevance of the CAR engineering approach to develop antigen-specific CAR-CD8+ Tregs for clinical trials in transplantation, and potentially in other diseases.

ДОСЛІДЖЕННЯ ДАТЧИКА ТЕМПЕРАТУРИ DS18B20 WI-FI МОДУЛЕМ NODEMCU V3 ESP8266

The past decade can be characterized by the accelerating Internet of Things (IoT) development. Currently, the European Research Cluster on the Internet of Things (IERC) defines IoT as a dynamic global network infrastructure with the possibility of self-tuning based on standard and compatible communication protocols. The Internet and microprocessor technology development caused the rise of IoT. Other factors influencing the rapid IoT development were cloud computing and wireless networks popularity growth. As a result, the widespread use of IoT required an increase in the reliability of the devices.In many areas of modern technological processes and physical researches, the temperature is a significant physical characteristic. The paper describes the hardware and software complex connecting the DS18B20 temperature meter (sensor). The complex is designed to study the fault-tolerance of temperature measurements in IoT. The Wi-Fi module NodeMCU V3 based on ESP8266 is applied as a control unit of the complex.The IoT appearance brought to a new level such an important segment of technical researches as the development of the fault-tolerant solutions. One of the important subsystems of such an application is the physical parameters detection of various devices in real-time. The temperature is a significant physical characteristic in many areas of modern technological processes and physical researches. The hardware and software complex for connecting a DS18B20 temperature measurer (sensor) is described in the paper. The complex is designed to examine the temperature measurement fault-tolerance in IoT. The Wi-Fi module NodeMCU V3 based on ESP8266 is applied as the complex controller.As far as the work of IoT depends mainly on the information provided by the sensors, the sensor performance monitoring is critically important. The autonomous system architecture of IoT includes such tasks as perception, localization, planning, management and control over systems exchanging information with each other. For this reason, the reliability of the sensors is of high concern. Therefore, one failure can lead to the IoT system dangerous behavior.The IoT fault-tolerance is an important direction of modern systems design. The research of the ensuring possibility of the IoT fault-tolerance functioning is an urgent task. For such studies, hardware and software complexes are developed.

Exploring the Treasure of Plant Molecules With Integrated Biorefineries.

Despite significant progress toward the commercialization of biobased products, today’s biorefineries are far from achieving their intended goal of total biomass valorization and effective product diversification. The problem is conceptual. Modern biorefineries were built around well-optimized, cost-effective chemical synthesis routes, like those used in petroleum refineries for the synthesis of fuels, plastics, and solvents. However, these were designed for the conversion of fossil resources and are far from optimal for the processing of biomass, which has unique chemical characteristics. Accordingly, existing biomass commodities were never intended for modern biorefineries as they were bred to meet the needs of conventional agriculture. In this perspective paper, we propose a new path toward the design of efficient biorefineries, which capitalizes on a cross-disciplinary synergy between plant, physical, and catalysis science. In our view, the best opportunity to advance profitable and sustainable biorefineries requires the parallel development of novel feedstocks, conversion protocols and synthesis routes specifically tailored for total biomass valorization. Above all, we believe that plant biologists and process technologists can jointly explore the natural diversity of plants to synchronously develop both, biobased crops with designer chemistries and compatible conversion protocols that enable maximal biomass valorization with minimum input utilization. By building biorefineries from the bottom-up (i.e., starting with the crop), the envisioned partnership promises to develop cost-effective, biomass-dedicated routes which can be effectively scaled-up to deliver profitable and resource-use efficient biorefineries.

Gram-scale economical synthesis of trans-coniferyl alcohol and its corresponding thiol

AbstractConiferyl alcohol is considered to be a potent antioxidant and a precursor of several bioactive products. In addition, it is a frequently used as a model compound in lignin chemistry. Coniferyl thiol is used analogously to study the sulfur chemistry in technical lignins. Coniferyl alcohol was synthesized in a large scale from commercially available ferulic acid by a mixed anhydride reduction method which affords high yields (84%) under very mild conditions and allows using sodium borohydride. The nucleophilic substitution of 4-O-acetylated coniferyl alcohol (3) with thioacetic acid in the presence of dimethylformamide (DMF) dineopentylacetal afforded 4-O-acetylated coniferyl thioacetate (5) in a 70% yield, which, in a 72% yield, was deprotected to the respective thiol (6). Both coniferyl alcohol and coniferyl thiol were comprehensively analytically characterized [one-dimensional (1D) and two-dimensional (2D) nuclear magnetic resonance (NMR) spectroscopy]. The presented approach renders the two model substances readily available on a gram scale and according to low-risk, environmentally compatible protocols.

Visible-Light-Driven C-H Oxidation of Cyclic Tertiary Amines: Access to Synthetic Strychnos Alkaloids with Antiviral Activity.

Air and visible light have been used in facile direct C-H oxidation of cyclic tertiary amines at ambient conditions, employing organic dyes as photocatalysts and LED. Tolerance of this new environmentally compatible protocol to various side-chain derivatizations of tryptoline and tetrahydroisoquinoline substrates was demonstrated. The developed method provides a straightforward and sustainable route towards δ-lactams, which feature strong antiviral properties (EC50 down to 4.6±1.8 μm) against human cytomegalovirus (HCMV). The clear advantages, which are easily available and inexpensive reagents, organic dyes, visible light, air/O2 and atom efficiency, make this system highly appealing for synthesis of versatile Strychnocarpine alkaloid derivatives with antiviral activity.

Capillary electrophoresis integrated immobilized enzyme reactor for kinetic and inhibition assays of β-secretase as the Alzheimer's disease drug target.

Capillary electrophoresis integrated immobilized enzyme reactors are becoming an increasingly popular alternative for enzyme kinetic and inhibition assays thanks to their unique set of features including cost effectiveness, repeated use of the enzyme, minuscule sample consumption, rapid analysis time and easy automation. In this work we present the development and application of a capillary electrophoresis integrated immobilized enzyme reactor based on magnetic particles for kinetic and inhibition studies of β-secretase, a key enzyme in the development of Alzheimer's disease and a promising drug target. We document the optimization of the immobilization procedure, characterization of immobilized β-secretase, optimization of a mutually compatible incubation protocol and separation method as well as the production of the capillary electrophoresis integrated immobilized enzyme reactor. The applicability of the capillary electrophoresis integrated immobilized enzyme reactor was demonstrated by kinetic assay with an unlabelled substrate and by inhibition assays using three structurally different reference inhibitors. The resulting kinetic and inhibition parameters clearly support the applicability of the herein presented method as well as document the fundamental phenomena which need to be taken in account when comparing the results to other methods.

Application of lateral branching to overcome the recalcitrance of in vitro regeneration of Agrobacterium-infected pigeonpea (Cajanus cajan L.)

Establishment of a compatible and suitable regeneration and gene transformation protocol is of immense significance to achieve the desired improvement in pigeonpea through biotechnological approach. However, no reproducible protocol for large-scale generation of independent primary transformants plant lines through organogenesis virtually exists. Therefore, an attempt was initiated to develop a simple and straightforward protocol for easy generation of transformed lines through the facilitation of the production of multiple shooting and their lateral branching followed by selection of generated axillary buds. The protocol involves infection of longitudinally dissected cotyledonary node and shoot-tips of germinated seedling with Agrobacterium harboring genetic cassette having both the bialaphos-resistant and green fluorescent protein (gfp) genes as a plant selection marker and reporter gene respectively. The infected explants were allowed to grow in medium with 0.25 mg/L BAP and 0.1 mg/L gibberellic acid (GA3) for development of multiple shoots followed by micropropagation of nodal segments and selection under 4 mg/L bialaphos. The selected plants were found to contain integrated genes and carried through successive generations as revealed by dot blot, Southern hybridization, and expression of the reporter gene. In spite of having the scope of the generation of siblings, the resulted transformation frequency was found to be 6.66% irrespective of genotypes used in the present study as revealed by dot blot analysis. Overall, the protocol ensured generation of pigeonpea transgenic plants with considerable easy within a short time irrespective of genotypes/cultivars of the crop.

Efficient Scale-up and Pre-Clinical Evaluation of NKG2C+ Adaptive NK Cell Expansion for Therapy Against High-Risk AML/MDS

Natural killer (NK) cells hold great promise as a source for allogeneic cell therapy against hematological malignancies, including acute myeloid leukemia (AML) and myelodysplastic syndrome (MDS). NK cell recognition of allogeneic tumors is strictly regulated by inhibitory killer cell immunoglobulin-like receptors (KIR) that bind to groups of HLA class I alleles. However, KIR expression on NK cells is highly diverse due to variation in gene content, polymorphism and copy number in combination with stochastic expression of the protein in individual cells. As a consequence, the number of efficacious allogeneic NK cells within a product isolated and expanded from random donors can vary a great deal and potentially be negligible. Our group has defined a repertoire of NK cells that is uniquely found in individuals with prior exposure to cytomegalovirus (CMV). Interestingly, these cells were shown to share many attributes usually reserved for adaptive immune cells including increased longevity, memory, and serial killing. We have previously described a 14-day protocol to enrich for adaptive NKG2C+CD57+ NK cells from CMV sero-positive donors with a homogenous expression of one single self-HLA specific KIR (self KIR). Here, we present new data on the GMP-transfer and clinical scale-up of this protocol, providing a route to off-the-shelf adaptive NK cell therapy for refractory high-risk AML/MDS. By screening >250 healthy donors, we first established the prerequisites for robust expansion of adaptive NK cells from peripheral blood of CMV+ donors and found that donors with >15% pre-existing adaptive NK cells showed efficient expansion of adaptive NK cells (Figure 1A-B). Apheresis products from a pool of pre-screened third-party donors are currently being collected for GMP freezing and use in an off-the-shelf setting intended for HLA mismatched patients to maximize alloreactivity by “missing” self. The GMP compatible protocol led to a robust expansion of clinical doses of self-KIR+ adaptive NK cells, with an average frequency of 60% self-specific KIR+ cells in the end product (Figure 1C-D). Based on the expression of self-KIR the expanded cells were educated, showing large dense-core granules and high levels of granzyme B. Further characterization in CyTOF using 36 phenotypic and functional markers revealed a highly activated state with high expression of DNAM-1 and CD2, which are critical for NK cell adhesion and function (Figure 1E). Notably, the expanded adaptive NK cells were negative for the HLA-E binding inhibitory receptor NKG2A, which is a major check point for T- and NK-cell based therapies. A microchip single-cell imaging platform revealed high serial killing capacity of the expanded adaptive NK cells. In flow cytometry-based killing assays and long-term killing assays this enhanced capacity for serial killing correlated with highly efficient targeting of mismatched PHA blasts (Figure 1F), tumor cell lines (Figure 1G), and MDS blasts. These pre-clinical data demonstrate the feasibility of off-the-shelf therapy with a non-engineered and yet highly specific NK cell population, representing the first route to clinical testing of missing self-recognition as it was originally defined over thirty years ago. [Display omitted] DisclosuresValamehr:Fate Therapeutics Inc.: Employment. Alici:Vycellix: Consultancy, Equity Ownership, Patents & Royalties, Research Funding; Intellia: Membership on an entity's Board of Directors or advisory committees. Ljunggren:Fate Therapeutics: Patents & Royalties; Vycellix: Equity Ownership, Membership on an entity's Board of Directors or advisory committees. Malmberg:Fate Therapeutics Inc.: Consultancy, Research Funding.

Consistently High MIMO Rates via Switched-Beam Antennas

The demand for wireless bandwidth is rising to unprecedented levels. The industry has responded with the inclusion of advanced PHY techniques, most notably multi-user (MU) MIMO, in the most recent Wi-Fi and LTE standards. However, despite the theoretical promise for large multiplexing gains, in practice the rate gains are modest due to a combination of large overhead to collect channel state information and not-so-well-conditioned channel matrices. In this paper, we propose to replace omni-directional antennas with inexpensive switched-beam antennas to produce well-conditioned channel matrices for MU-MIMO purposes with very low overhead. Remarkably, the experimental results with both software-defined radios and commercial Wi-Fi chipsets show that, when appropriate antenna modes are used, this leads to a $3.5\times-5\times $ average throughput improvement in indoor environments. What is more, our backward compatible protocol extension coupled with an efficient algorithm to select appropriate antenna modes, achieve the aforementioned gains with almost zero overhead.

Robust Revascularization in Models of Limb Ischemia Using a Clinically Translatable Human Stem Cell-Derived Endothelial Cell Product.

Pluripotent stem cell-derived differentiated endothelial cells offer high potential in regenerative medicine in the cardiovascular system. With the aim of translating the use of a human stem cell-derived endothelial cell product (hESC-ECP) for treatment of critical limb ischemia (CLI) in man, we report a good manufacturing practice (GMP)-compatible protocol and detailed cell tracking and efficacy data in multiple preclinical models. The clinical-grade cell line RC11 was used to generate hESC-ECP, which was identified as mostly endothelial (60% CD31+/CD144+), with the remainder of the subset expressing various pericyte/mesenchymal stem cell markers. Cell tracking using MRI, PET, and qPCR in a murine model of limb ischemia demonstrated that hESC-ECP was detectable up to day 7 following injection. Efficacy in several murine models of limb ischemia (immunocompromised/immunocompetent mice and mice with either type I/II diabetes mellitus) demonstrated significantly increased blood perfusion and capillary density. Overall, we demonstrate a GMP-compatible hESC-ECP that improved ischemic limb perfusion and increased local angiogenesis without engraftment, paving the way for translation of this therapy.

Traffic differentiation in dense collision-free WLANs using CSMA/ECA

The ability to perform traffic differentiation is a promising feature of the current Medium Access Control (MAC) in Wireless Local Area Networks (WLANs). The Enhanced Distributed Channel Access (EDCA) protocol for WLANs proposes up to four Access Categories (AC) that can be mapped to different traffic priorities. High priority ACs are allowed to transmit more often than low priority ACs, providing a way of prioritising delay sensitive traffic like voice calls or video streaming. Further, EDCA also considers the intricacies related to the management of multiple queues, virtual collisions and traffic differentiation. Nevertheless, EDCA falls short in efficiency when performing in dense WLAN scenarios. Its collision-prone contention mechanism degrades the overall throughput to the point of starving low priority ACs, and produce priority inversions at high number of contenders.Carrier Sense Multiple Access with Enhanced Collision Avoidance (CSMA/ECA) is a compatible MAC protocol for WLANs which is also capable of providing traffic differentiation. Contrary to EDCA, CSMA/ECA uses a contention mechanism with a deterministic backoff technique which is capable of constructing collision-free schedules for many nodes with multiple active ACs, extending the network capacity without starving low priority ACs, as experienced in EDCA. This work analyses traffic differentiation with CSMA/ECA by describing the mechanisms used to construct collision-free schedules with multiple queues. Additionally, evaluates the performance under different traffic conditions and a growing number of contenders. Furthermore, it introduces a way to eliminate Virtual Collisions (VC), which also contributes to the throughput degradation in EDCA WLANs. Simulation tests are performed using voice and video packet sources that emulate commonly used codecs. Results show CSMA/ECA outperforming EDCA in different commonly-found scenarios with high number of users, including when both MAC protocols coexist in the same WLAN.

Traffic differentiation in dense collision-free WLANs using CSMA/ECA

The ability to perform traffic differentiation is a promising feature of the current Medium Access Control (MAC) in Wireless Local Area Networks (WLANs). The Enhanced Distributed Channel Access (EDCA) protocol for WLANs proposes up to four Access Categories (AC) that can be mapped to different traffic priorities. High priority ACs are allowed to transmit more often than low priority ACs, providing a way of prioritising delay sensitive traffic like voice calls or video streaming. Further, EDCA also considers the intricacies related to the management of multiple queues, virtual collisions and traffic differentiation. Nevertheless, EDCA falls short in efficiency when performing in dense WLAN scenarios. Its collision-prone contention mechanism degrades the overall throughput to the point of starving low priority ACs, and produce priority inversions at high number of contenders. Carrier Sense Multiple Access with Enhanced Collision Avoidance (CSMA/ECA) is a compatible MAC protocol for WLANs which is also capable of providing traffic differentiation. Contrary to EDCA, CSMA/ECA uses a contention mechanism with a deterministic backoff technique which is capable of constructing collision-free schedules for many nodes with multiple active ACs, extending the network capacity without starving low priority ACs, as experienced in EDCA. This work analyses traffic differentiation with CSMA/ECA by describing the mechanisms used to construct collision-free schedules with multiple queues. Additionally, evaluates the performance under different traffic conditions and a growing number of contenders. (arXiv's abstract field is not large enough for the paper's abstract, please download the paper for the complete abstract.)

Asynchronously Coordinated Multi-Timescale Beamforming Architecture for Multi-Cell Networks

Modern wireless devices such as smartphones are pushing the demand for higher wireless data rates. The ensuing increase in wireless traffic demand can be met by a denser deployment of access points, coupled with a coordinated deployment of advanced physical layer techniques to reduce inter-cell interference. Unfortunately, advanced physical layer techniques, e.g., multi-user (MU) MIMO found in 802.11ac and LTE-advanced, are not designed to operate efficiently in a coordinated fashion across multiple densely deployed transmitters. In this paper, we introduce a new coordination architecture, which can achieve high performance gains without the high overhead and deployment cost that usually comes with coordination, thus making the vision of high capacity wireless access via densely deployed transmitters practical. The basic idea is to loosely coordinate nearby transmitters using slow varying channel statistics, while keeping all the functionality which depends on fast varying channel state information and has tight time deadlines locally. We achieve this via a smart combination of analog and digital beamforming using inexpensive front ends, a provably efficient algorithm to select compatible users and analog beams across all transmitters, and backward compatible protocol extensions. Our performance results, which include analysis, simulations, and experiments with software defined radios and directional antennas, show that our approach can achieve the $10\times $ gains of the theoretically optimal coordinated MU-MIMO approach, without the need to either tightly coordinate the clocks of the remote transmitters or meet tight delay constraints.

Daiktų interneto objektų identifikavimo metodų palyginimas

The Internet of Things is an integral part of the future Web part, which is defined as a global and dynamic network infrastructure, which is capable of self-configuring and is based on standardized and compatible communications protocols, where physical and virtual objects have identification characteristics, physical attributes, virtual personalities that use intelligent interfaces and are directly integrated into the unified information network. The resources of the Internet of Things and services are globally distributed within the information network, so it is necessary to have a mechanism which allows the identification of global smart devices, their services and resources. Typically, the identification consists of the assigning names for the resources and the mechanism of the addressing resources in order to discover and access the remote resources of the Internet of things. Modern networks use the Universal Resource Identifier (URI), which identifies a global resource, its type and a set of equivalent names. The URI uniquely allows to identify physical objects, which are located anywhere in the world, using the Electronic Product Code (EPC) technology. EPC allows URI to also be used with Radio-Frequency Identification (RFID). The RFID technology is used for marking and tracing items, which is based on the use of the frequency signal of the radio in the object tag for information recording and reading. This technology in literature is mentioned as one of the main identification and realization measures of the Internet of Things. The purpose of this article is to review and compare the identification methods of objects of the Internet of Things.

Electrical performance of lightweight CNT-Cu composite wires impacted by surface and internal Cu spatial distribution

We report ultralong conducting lightweight multiwall carbon nanotube (MWCNT)-Cu composite wires with MWCNTs uniformly distributed in a continuous Cu matrix throughout. With a high MWCNT vol% (40–45%), the MWCNT-Cu wire density was 2/3rd that of Cu. Our composite wires show manufacturing potential because we used industrially compatible Cu electrodeposition protocols on commercial CNT wires. Further, we systematically varied Cu spatial distribution on the composite wire surface and bulk and measured the associated electrical performance, including resistivity (ρ), temperature dependence of resistance, and stability to current (measured as current carrying capacity, CCC in vacuum). We find that a continuous Cu matrix with homogeneous MWCNT distribution, i.e., maximum internal Cu filling within MWCNT wires, is critical to high overall electrical performances. Wires with maximum internal Cu filling exhibit (i) low room temperature ρ, 1/100th of the starting MWCNT wires, (ii) suppressed resistance-rise with temperature-increase and temperature coefficient of resistance (TCR) ½ that of Cu, and (iii) vacuum-CCC 28% higher than Cu. Further, the wires showed real-world applicability and were easily soldered into practical circuits. Hence, our MWCNT-Cu wires are promising lightweight alternatives to Cu wiring for weight-reducing applications. The low TCR is specifically advantageous for stable high-temperature operation, e.g., in motor windings.

Clinical-Grade–Expanded Regulatory T Cells Prevent Graft-versus-Host Disease While Allowing a Powerful T Cell–Dependent Graft-versus-Leukemia Effect in Murine Models

We developed a good manufacturing practices–compatible expansion protocol to improve number and purity of regulatory T cells (Tregs) available for clinical trials. Six clinical-grade separation procedures were performed, followed by expansion with high-dose interleukin (IL)-2, anti-CD3/anti-CD28 TCR stimulation, and rapamycin for 19 days achieving a median of 8.5-fold (range, 6.25 to 13.7) expansion. FOXP3 expression was stably maintained over the culture period, while the percentage of CD127 was significantly reduced. The in vitro suppression assay showed a strong Mixed Lymphocytes Reaction inhibition. In vitro amplification did not induce any karyotypic modification. To evaluate the graft-versus-host disease (GVHD)/graft-versus-leukemia (GVL) bifunctional axis, expanded Tregs and conventional T cells (Tcons) were tested in NOD/SCID/IL2Rgnull mice injected with primary acute myeloid leukemia (AML) cells, AML cell line, acute lymphoid leukemia Philadelphia cell line, or Burkitt-like lymphoma cell line. All mice that received leukemia cells together with expanded Tregs and Tcons were rescued from leukemia and survived without GVHD, showing that Treg expansion procedure did not compromise GVHD control and the strong Tcon-mediated GVL activity. This report might represent the basis for treating high-risk leukemia and/or relapsed/refractory leukemia patients with high-dose Treg/Tcons.

Abstract 2684: Multiplex immunofluorescence profiling of tumor infiltrating immune subsets in HNSCC biopsies provides a powerful tool when combined with patient outcome data

Abstract Head and neck squamous cell carcinoma (HNSCC) is one of the growing number of tumors for which an anti-tumor immune response is implicated to play a role in the course of the disease. Profiling of the tumor microenvironment including specific infiltrating lymphocyte subsets, antigen presenting cells, expression of regulatory molecules on both tumor and immune cells and spatial relationships between cells could lead to predictive signatures for responsiveness to both conventional and immune modulatory therapies. While flow cytometry results in multi-parametric analysis of immune populations within the tumor, their context i.e. the spatial relationship of these cells to tumor and to other immune cells, is lost. In this current study we use Cell IDx’s novel UltraPlex technology, which is based on a simple two-step, autostainer compatible protocol using hapten labeled primary antibody cocktails followed by fluor labeled anti-hapten secondary cocktails to simultaneously detect 4 cellular markers on the same cell in tumor biopsies. Image registration of serial sections increases multiplexing to 12-16 markers. This technology, which allows generation of full immune subset profiling, quantitative marker expression and relative cellular localization, was applied to a HNSCC tumor microarray as a test system. Data are presented showing the potential of this technology for correlation of tumor “immune signature” with patient outcome. Citation Format: Matt Levin, Mark Lingen, David Schwartz, Helen Snyder. Multiplex immunofluorescence profiling of tumor infiltrating immune subsets in HNSCC biopsies provides a powerful tool when combined with patient outcome data [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2017; 2017 Apr 1-5; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2017;77(13 Suppl):Abstract nr 2684. doi:10.1158/1538-7445.AM2017-2684

From anticipation to integration: the role of integrated action-effects in building sensorimotor contingencies.

Ideomotor approaches to action control have provided evidence that the activation of an anticipatory image of previously learned action-effects plays a decisive role in action selection. This study sought for converging evidence by combining three previous experimental paradigms: the response-effect compatibility protocol introduced by Kunde (Journal of Experimental Psychology: Human Perception and Performance, 27(2), 387-394, 2001), the acquisition-test paradigm developed by Elsner and Hommel (Journal of Experimental Psychology: Human Perception and Performance, 27(1), 229, 2001), and the object-action compatibility manipulation of Tucker and Ellis (Visual Cognition, 8(6), 769-800, 2001). Three groups of participants first performed a response-effect compatibility task, in which they carried out power and precision grasps that produced either grasp-compatible or grasp-incompatible pictures, or no action effects. Performance was better in the compatible than in the incompatible group, which replicates previous observations and extends them to relationships between grasps and objects. Then, participants were to categorize object pictures by carrying out grasp responses. Apart from replicating previous findings of better performance in trials in which object size and grasp type was compatible, we found that this stimulus-response compatibility effect depended on previous response-effect learning. Taken together, these findings support the assumption that the experience of action-effect contingencies establishes durable event files that integrate representations of actions and their effects.

Scalable and Multimedia Compatible Dynamic Routing Protocol for MANET

Objectives: This paper concentrates on exchanging the multimedia content through MANET nodes in a reliable and scalable manner. Methods/Statistical Analysis: Recently Wireless Mobile Adhoc Networks become reliable, Internet Independent and low-cost solution for communication and data exchange in personal digital computers. As on MANETs are used only for vocal communication and text message sending purpose. Due to the wide usage of multimedia content like images, videos and audio files is a need to upgrade the MANETs for multimedia support. To achieve this, a hybrid routing protocol for multimedia data exchange is introduced, it is named as “Scalable and Multimedia compatible Dynamic Routing Protocol (SMDR) for MANETS”. Findings: After implementation of the proposed protocol the several things from results are obtained. It conducted the experiments with SMDR protocol and compared the results with popular ad-hoc protocols like AODV and OLSR. This protocol resolves the issues of multimedia content exchange over MANET nodes under various circumstances. In perspective of speed, scalability and efficiency SMDR protocol recorded the best results over AODV and OLSR. From the experimental analysis and result is noticed that, the protocol is very suitable for mobile ad-hoc networks to transfer multimedia content. Application/Improvements: In future, we are trying to extend this paper to elaborate this protocol to support multimedia content in a distinct way at each multimedia type level. This future work process increases the scalability in multimedia transfer content and also improves the accuracy in a reliable manner.

Generation of donor-specific Tr1 cells to be used after kidney transplantation and definition of the timing of their in vivo infusion in the presence of immunosuppression

BackgroundOperational tolerance is an alternative to lifelong immunosuppression after transplantation. One strategy to achieve tolerance is by T regulatory cells. Safety and feasibility of a T regulatory type 1 (Tr1)-cell—based therapy to prevent graft versus host disease in patients with hematological malignancies has been already proven. We are now planning to perform a Tr1-cell—based therapy after kidney transplantation.MethodsUpon tailoring the lab-grade protocol to patients on dialysis, aims of the current work were to develop a clinical-grade compatible protocol to generate a donor-specific Tr1-cell—enriched medicinal product (named T10 cells) and to test the Tr1-cell sensitivity to standard immunosuppression in vivo to define the best timing of cell infusion.ResultsWe developed a medicinal product that was enriched in Tr1 cells, anergic to donor-cell stimulation, able to suppress proliferation upon donor- but not third-party stimulation in vitro, and stable upon cryopreservation. The protocol was reproducible upon up scaling to leukapheresis from patients on dialysis and was effective in yielding the expected number of T10 cells necessary for the planned infusions. The tolerogenic gene signature of circulating Tr1 cells was minimally compromised in kidney transplant recipients under standard immunosuppression and it eventually started to recover 36 weeks post-transplantation, providing rationale for selecting the timings of the cell infusions.ConclusionsThese data provide solid ground for proceeding with the trial and establish robust rationale for defining the correct timing of cell infusion during concomitant immunosuppressive treatment.