Dendritic cells (DCs) are uniquely able to initiate and control the immune response to fungi. DCs function at three levels in the manipulation of the immune response to these pathogens. First, they ...mount an immediate or innate response to them, for example, by producing inflammatory mediators upon capture and phagocytosis; second, through these preceding innate functions, they decode the fungus-associated information and translate it in qualitatively different Th responses, and third, they are key in containing and dampening inflammatory responses by tolerization through the induction of regulatory T cells (Treg). DCs sense fungi in a morphotype-specific manner, through the engagement of distinct recognition receptors ultimately affecting cytokine production and costimulation. Both myeloid and plasmacytoid murine and human DCs phagocytose fungi and undergo functional maturation in response to them. However, their activation program for cytokine production was different, being IL-12 mainly produced by myeloid DCs and IL-12, IL-10 and IFN-α mainly produced by plasmacytoid DCs. This resulted in a distinct ability for T cell priming, being Th1, Th2, and Treg differently activated by the different DC subsets. The ability of fungus-pulsed DCs to prime for Th1 and Th2 cell activation upon adoptive transfer in vivo correlated with the occurrence of resistance and susceptibility to the infections, respectively. Antifungal protective immunity was also induced upon adoptive transfer of DCs transfected with fungal RNA. The efficacy was restricted to DCs transfected with RNA from yeasts or conidia but not with RNA from fungal hyphae. The effect was fungus-specific, as no cross-protection was observed upon adoptive transfer of DCs pulsed with either fungal species. The infusion of fungus-pulsed or RNA-transfected DCs accelerated the recovery of functional antifungal Th1 responses in mice with allogeneic hematopoietic stem cell transplantation (HSCT) and affected the outcome of the infections. As the ability of phagocytose fungi was defective in peripheral DCs from patients with HSCT, soon after the transplant, our findings suggest that the adoptive transfer of DCs may restore immunocompetence in HSCT by contributing to the educational program of T cells. Thus, the remarkable functional plasticity of DCs in response to fungi can be exploited for the deliberate targeting of cells and pathways of cell-mediated immunity in response to fungal vaccines.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UL, UM, UPCLJ, UPUK
Several fMRI studies have been performed to detect the neural correlates of stable bimanual coordination patterns in humans. Only few of those studies were accompanied by the on-line recording of the ...relative phase of fingers or hands, but none with high space and time resolutions. Conversely, the high-resolution recording of fingers' kinematics during fMRI would permit the quantification of the instantaneous fingers' positions, from which the instant at which transitions between different bimanual coordination patterns occur might be detected. This information could then be used to analyze fMRI data and detect the neural correlates of pattern transitions. We describe an a-magnetic optic-mechanical device (AMOMeD) able to monitor the fingers' positions during fMRI studies on bimanual coordination with 2 mm space resolution and 1 ms time resolution. From the instantaneous fingers' positions (recorded with an optical fiber system and a dedicated acquisition system), the oscillation amplitude, frequency, velocity and relative phase of fingers' are calculated. The signal from the fMRI trigger can be acquired simultaneously to synchronize the behavioral outcomes with the fMRI analysis. The results of our study show that this device does not affect fMRI signals, and that fMRI data can be processed using the simultaneous behavioral information to detect the brain areas activated during the transitions between different bimanual coordination patterns.
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EMUNI, FIS, FZAB, GEOZS, GIS, IJS, IMTLJ, KILJ, KISLJ, MFDPS, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, SBMB, SBNM, UKNU, UL, UM, UPUK, VKSCE, ZAGLJ
Transplantation of peripheral blood hematopoietic cells from HLA haplotype-mismatched family members is a therapeutic strategy for patients with high-risk acute leukemia who need transplantation and ...do not have matched donors. As T cell alloreactions cause lethal GvHD in mismatched transplants, only T cell-depleted hematopoietic grafts can be used. In adults, because of declining thymic function, immune-recovery originates from expansion of the mature T cells infused with the graft. In T cell depleted mismatched transplant immune recovery is hindered by the paucity of the starting T-cell population. Slow recovery of functional T cell immunity to pathogens is responsible for 35% infection-related mortality which remains the most pressing clinical issue. In murine MHC-haploidentical bone marrow transplant models we demonstrated donor-versus-recipient alloreactive NK cells ablate recipient-type lympho-hematopietic cells such as leukemic cells, the T cells that cause rejection and the antigen-presenting cells which trigger GvHD.
Consequently mismatched T cell-replete transplants can be performed without GvHD (Ruggeri et al., Science 2002). Unexpectedly, in recent experiments, we observed alloreactive NK cells hastened immune-reconstitution. Pre-transplant infusion of alloreactive NK cells promoted brisk recovery of donor B and T cell precursors which matured correctly and of donor DCs. Rapidly reconstistuting DCs were crcuicial in protecting mice from infectious challenges. We next demonstrated:interaction between alloreactive NK cells and NK-susceptible recipient DCs alone was responsible for immune-rebuilding,NK conditioned mice remain receptive to accelerated immune rebuilding even when transplanted a week after NK conditioning, therefore the NK-DC interaction appears to release an as yet unknown immune-rebuilding factor which acts upon bone marrow and thymus microenvironements stably over time,quantitative PCR on bone marrow and thimus of NK conditioned mice shows several-fold increased expression of cytokines implicated in B, T and myeloid cell maturation, such as IL-7 and c-Kit ligand;the accelerated immune rebuilding effect can be reproduced by conditioning mice with the infusion of NK:DC co-culture supernatants.
These observation prompted an analysis of infectious mortality in 178 acute leukemia patients who received haploidentical transplant at our Center. Transplantation from KIR ligand-mismatched (i.e., NK alloreactive) donors, in addition to controlling AML relapse, offers statistically significant protection from infectious mortality in AML and ALL patients. Studies are in progress to identify “immune rebuilding factor(s)”, produced in consequence of the interaction between donor alloreactive NK and recipient DCs, in the hope they might be exploited to boost immune-recovery and help reduce infection mortality after haploidentical hematopoietic transplantation.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
At the Department of Physics of the University of Bologna a new intensified linear array detector is under development. The core of the system is a digital intensified CCD camera, the electron ...bombarded charge coupled device (EBCCD). The main innovation is a coherent rectangular-to-linear fiber optics adapter coupling the 1 in. diameter photocathode of the camera with a linear 129 mm
×
1.45 mm strip of Gd
2O
2S:Tb. In this way a high spatial resolution over an extended length is obtained. The detector works as an X-ray scanner by means of a high-precision translation mechanical device to inspect a 13 cm
×
18 cm area. A complete characterisation of the system has been made in terms of linearity, dynamic range, modulation transfer function (MTF), noise power spectrum (NPS) and detective quantum efficiency (DQE). At last, radiographic tests on a set of samples have been made and will be presented.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UL, UM, UPCLJ, UPUK
Dendritic cells (DCs) are uniquely able to initiate and control the immune response to fungi. DCs function at three levels in the manipulation of the immune response to these pathogens: 1) they mount ...an immediate or innate response to them, for example by producing inflammatory mediators upon capture and phagocytosis; 2) through these preceding innate functions, they decode the fungus-associated information and translate it in qualitatively different Th responses; 3) and they are key in containing and dampening inflammatory responses by tolerization through the induction of regulatory T cells (Treg). We demonstrated that both murine and human DCs sense fungi in a morphotype-specific manner, through the engagement of distinct recognition receptors ultimately affecting cytokine production and costimulation (Romani et al. Int Immunol. 2003). In this study we analyzed both myeloid and plasmacytoid murine and human DCs and we observed that they phagocytose fungi and undergo functional maturation in response to them. However, their activation program for cytokine production was different, being IL-12 mainly produced by myeloid DCs and IL-12, IL-10 and IFN-gamma mainly produced by plasmacytoid DCs. This resulted in a distinct ability for T-cell priming, being Th1, Th2 and Treg differently activated by the different DC subsets. The ability of fungus-pulsed DCs to prime for Th1, and Th2 cell activation upon adoptive transfer in vivo correlated with the occurrence of resistance and susceptibility to the infections, respectively. Antifungal protective immunity was also induced upon adoptive transfer of DCs transfected with fungal RNA (Bacci et al. J Immunol. 2002; Bozza et al. Blood. 2003). The efficacy was restricted to DCs transfected with RNA from yeasts or conidia but not with RNA from fungal hyphae. The effect was fungus-specific, as no cross-protection was observed upon adoptive transfer of DCs pulsed with either fungal species. The infusion of fungus-pulsed or RNA-transfected DCs accelerated the recovery of functional antifungal Th1 responses in mice with allogeneic hematopoietic stem cell transplantation (HSCT) without triggering graft-versus-host disease (GvHD) and affected the outcome of the infections. As the ability to respond to fungi was defective in peripheral DCs from patients with HSCT in terms of phagocytosis, cytokine production, and donor T-cell priming, our findings suggest that the adoptive transfer of DCs may restore immunocompetence in HSCT by contributing to the educational program of T-cells. Thus, the remarkable functional plasticity of DCs in response to fungi can be exploited for the deliberate targeting of cells and pathways of cell-mediated immunity in response to fungal vaccines.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
Digital imaging has proven to be a valid technique to determine the spatial distribution of radioisotopes in nuclear applications. In the present work, an intensified EBCCD camera with 80 mm ...photocathode and a fiber optics plate covered by a thin Gadolinium oxysulfide layer was used as a detector to obtain a digital map of the activity distribution for a variety of beta sources. The distribution map was elaborated and displayed in a 1024
×
1024 pixel format by using digital imaging techniques. The decay constant of various radioisotopes was calculated in different regions of interest of the image, with a deviation of 5–9% (depending on the signal intensity) from theoretical values, even in single pixel areas. The EBCCD camera has shown strong detection capabilities even for single beta particle interaction and the response of the system has found to be very fast, allowing us to achieve a real time distribution map of radioisotopes. In fact, it is possible to load in RAM and display on a monitor a single distribution image map in about 1 s. Better distribution uniformity was obtained by integrating a sequence of 16, 32 or 64 images. By analysing a single beta interaction (i.e. a point spread function (PSF) on the image) the modulation transfer function (MTF) of the system has been calculated leading to a global resolution of about 80 m at 10% MTF.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UL, UM, UPCLJ, UPUK
In this paper we introduce a complete system architecture of a textile-based rectenna loaded by a novel power management platform able to be autonomously activated by ambient RF energy harvesters. An ...integral design approach of the system blocks is carried out to provide the actual nonlinear behavior of the rectenna output, which is a function of the operating frequencies and power levels, as the DC-DC converter input. The RF properties of the textile rectenna are computed by nonlinear techniques with textile materials and antenna layout numerically characterized by means of EM simulations. A novel integrated power converter is adopted. It is equipped with a start-up circuit and an energy storage unit and it is designed by microelectronic technology. Energy autonomy of the entire system, including a battery-less activation is expected for RF available power levels as low as -15 dBm. The system operation is computed with the wearable rectenna recovering RF energy upon user request from GSM 900, GSM 1800 and WiFi sources.
We designed a phase I/II clinical study to determine safety and efficacy of thymosin alpha1 (Talpha1) administration in recipients of one HLA haplotype (haploidentical) stem cell transplants for ...hematologic malignancies. Talpha1 administration did not cause acute or chronic graft versus host disease and was associated with significant improvement in polymorphonuclear (phagocytosis) and dendritic cell (phagocytosis, expression of costimulatory molecules, and cytokine production) functions. It was also associated with increased T-cell counts and earlier appearance of functional pathogen-specific T cell responses (by a sensitive limiting dilution assay that detects frequency of T cells specific for Aspergillus, Candida, CMV, ADV, VZV, HSV, Toxoplasma). Five of six haploidentical transplant recipients who received Talpha1 are alive and disease free at a median follow-up of 10 months after transplantation (range: 5-20). They experienced only a single nonlethal infectious episode and one patient developed fatal immune hemolytic anemia. At this very early stage of the clinical trial, we conclude Talpha1 administration is safe and may impact favorably on immune function. Larger numbers of patients and longer follow-up are, of course, needed to assess its impact on survival.
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BFBNIB, FZAB, GIS, IJS, IZUM, KILJ, NLZOH, NUK, OILJ, PILJ, PNG, SAZU, SBCE, SBMB, UL, UM, UPUK
