Recent breakthroughs in tumor immunotherapy such as immune checkpoint blockade (ICB) antibodies, have demonstrated the capacity of the immune system to fight cancer in a number of malignancies such ...as melanoma and lung cancer. The numbers, localization and phenotypes of tumor-infiltrating lymphocytes (TIL) are not only predictive of response to immunotherapy but also key modulators of disease progression. In this review, we focus on TIL profiling in cutaneous melanoma using histopathological approaches and highlight the observed prognostic value of the primary TIL subsets. The quantification of TIL in formalin-fixed tumor samples ranges from visual scoring of lymphocytic infiltrates in H&E to multiplex immunohistochemistry and immunofluorescence followed by enumeration using image analysis software. Nevertheless, TIL enumeration in the current literature primarily relies upon single marker immunohistochemistry analyses of major lymphocyte subsets such as conventional T cells (CD3, CD4, CD8), regulatory T cells (FOXP3) and B cells (CD20). We review key studies in the literature on associations between TIL subsets and patient survival. We also cover recent findings with respect to the existence of ectopic lymphoid aggregates found in the TME which are termed tertiary lymphoid structures (TLS) and are generally a positive prognostic feature. In addition to their prognostic significance, the existence of various TIL sub-populations has also been reported to predict a patient's response to ICB. Thus, the literature on the predictive potential of TIL subsets in melanoma patients receiving ICB has also been discussed. Finally, we describe recently developed state-of-the-art profiling approaches for tumor infiltrating immune cells such as digital pathology scoring algorithms (e.g., Immunoscore) and multiplex proteomics-based immunophenotyping platforms (e.g., imaging mass cytometry). Translating these novel technologies have the potential to revolutionize tumor immunopathology leading to altering our current understanding of cancer immunology and dramatically improving outcomes for patients.
In this work, anthocyanin stability and color of encapsulated freeze-dried saffron petal's extract with various matrices consisting gum Arabic (AG) and maltodextrin (M7 and M20) were studied. Total ...anthocyanins of powders and color parameters (a*, b*, L*, C, H° and TCD) were measured immediately after production and during storage up to 10 weeks by pH differential method and computer vision, respectively. Different compounds of wall materials did not show any significant differences in terms of stabilizing anthocyanins (P<0.01) and no significant decrease in anthocyanin content of the powders was observed after storage. The efficiency order of wall materials considering total color differences (TCD) was AG>M20>M7. By evaluating 3D surface and Cox trace plots it was revealed that wall formulas which had the lowest amount of AG and highest amounts of M20 and M7 showed the lowest total color differences after storage (P<0.05). To conclude, microencapsulation by freeze drying could be recommended as a suitable method for stabilizing anthocyanins of saffron petal's extract.
IMPORTANCE: In spite of progress in understanding the mechanisms underlying hidradenitis suppurativa (HS) as an inflammatory skin disease, there is still a demand for an overview on ...immunopathogenesis of HS. OBJECTIVE: To demonstrate the importance of the type 1/type 17 immune response in lesional HS skin by drawing a semantic connectivity map. DESIGN, SETTING, AND PARTICIPANTS: Single-center case series of 24 patients with HS. Association of HS with T helper 1/T helper 17 (TH1/TH17) phenotype was assessed using semantic map analysis. MAIN OUTCOMES AND MEASURES: Association of HS with TH1/TH17 phenotype. RESULTS: The analysis was performed on 24 lesional HS biopsy samples from untreated patients with HS (16 67% female; median age, 36.5 years range, 21-51 years) with a mean (SD) Hurley stage of 2.29 (0.62) and 9 punch biopsy samples from healthy controls (6 67% female; median age, 43 years range, 23-66 years). The map shows a clustering of all TH1/TH17-associated cytokines (interleukin 17 IL-17, interferon γ, IL-12, IL-23, IL-32, IL-1β, tumor necrosis factor) around overall lesional inflammation. Tumor necrosis factor, IL-12, and IL-17 are even directly connected via interferon γ. In contrast, IL-13, a TH2-associated cytokine, was inversely correlated with the presence of TH1/TH17-associated cytokines, further highlighting the importance of the TH1/TH17 cytokines in HS pathogenesis. CONCLUSIONS AND RELEVANCE: These findings suggest that HS may be a TH1/TH17-driven inflammatory skin disease.
In this work, the chaotic motions of relativistic electrons in X-ray free-electron lasers are investigated using an optical undulator in the presence of a magnetized ion-channel background. To ...miniaturize X-ray light sources, the optical undulator is a promising concept. The optical undulator provides higher optical gain than conventional magnetostatic undulators due to its micrometer wavelength. In addition, it reduces the required electron beam energy from several GeV to the multi-MeV range to produce X-ray pulses. The interaction of an optical undulator with an intense relativistic electron beam is a highly non-linear phenomenon that can lead to chaotic dynamics. At synchrotron radiation sources, the possibility of chaos control for X-ray FELs can be critical for certain classes of experimental studies. The equations of motion for a relativistic electron propagating through the optical undulator in the presence of a magnetized ion-channel can be derived from the Hamiltonian of the interaction region. Simulation results revealed that the intensity of the perturbation route from orderly behavior to chaos depends on the beam density, axial magnetic field strength, ion-channel density parameter, and pump laser undulator. Specific values of parameters were obtained for the transition from regular to chaotic paths. Bifurcation diagrams of the system were plotted to demonstrate the origin of chaos at a critical point, and Poincaré maps were created to distinguish between chaotic and orderly motions of electrons. The proposed new scheme can help to improve X-ray FELs, which have potential usages in basic sciences, medicine, and industry.
We present a formulation for the nonlinear optical response in gapped graphene, where the low-energy single-particle spectrum is modeled by massive Dirac theory. As a representative example of the ...formulation presented here, we obtain a closed form formula for the third harmonic generation in gapped graphene. It turns out that the covariant form of the low-energy theory gives rise to peculiar logarithmic singularities in the nonlinear optical spectra. The universal functional dependence of the response function on dimensionless quantities indicates that the optical nonlinearity can be largely enhanced by tuning the gap to smaller values.
Recent studies suggest an important role of immunoglobulin E (IgE) as an alternative pathogenic pathway in the development of bullous pemphigoid (BP), as the most frequent subepidermal blistering ...disease of the skin Use of IgE targeted therapies, such as omalizumab, has been shown promising in recent studies. The aim of this study was to assess the effect of omalizumab on FcεRI and IgE expression on circulating basophils and on lesional intradermal cells in BP to generate insight into the immunological effects of omalizumab in BP. We report two cases of BP patients treated with omalizumab. Efficacy of treatment was assessed clinically 4 months after initiation of the therapy. Lesional and non-lesional skin biopsies where taken before and 4 weeks after initiation of omalizumab therapy. In addition, FcεRI expression on circulating cells and IgE levels in serum and in the skin samples, as well as anti-BP180 and anti-BP230 in serum and eosinophils and basophils counts in blood were assessed before and during treatment. Both patients showed a marked improvement after 4 months, with no adverse effects. Down-regulation of FcεRI, IgE in lesional skin and on circulating basophils were observed in parallel with clinical improvement. The current case study supports the role of omalizumab in the treatment of a subset of BP patients. Our observations suggest that omalizumab represents a valuable therapeutic option in the management of BP patients. Its efficacy might be related to reduction in FcεRI+ and IgE+ basophils and intradermal cells.
An advanced incremental scheme for generating tunable coherent radiation in a free-electron laser has been presented: the basic concept is the use of a relativistic electron beam propagating through ...a magnetized dusty plasma channel where dust helicon, dust Alfven and coupled dust cyclotron-Alfven waves can play a role as a low-frequency wiggler, triggering coherent emissions. The wiggler wavelength at the sub-mm level allows one to reach the wavelength range from a few nm down to a few Å with moderately relativistic electrons of kinetic energies of a few tens/hundreds of MeV. The laser gain and the effects of beam self-electric and self-magnetic fields on the gain have been estimated and compared with findings of the helical magnetic and electromagnetic wigglers in vacuum. To study the chaotic regions of the electron motion in the dusty plasma wave wiggler, a time independent Hamiltonian has been obtained. The Poincare surface of a section map has been used numerically to analyze the nonintegrable system where chaotic regions in phase-space emerge. This concept opens a path toward a new generation of synchrotron sources based on compact plasma structures.
Utilizing meta-heuristic global optimization algorithms in gas turbine aero-engines modelling and control problems is proposed over the past two decades as a methodological approach. The purpose of ...the review is to establish evident shortcomings of these approaches and to identify the remaining research challenges. These challenges need to be addressed to enable the novel, cost-effective techniques to be adopted by aero-engine designers. First, the benefits of global optimization algorithms are stated in terms of philosophy and the nature of different types of these methods. Then, a historical coverage is given for the applications of different optimization techniques applied in different aspects of gas turbine modelling, controller design, and tuning fields. The main challenges for the application of meta-heuristic global optimization algorithms in new advanced engine designs are presented. To deal with these challenges, two efficient optimization algorithms, Competent Genetic Algorithm in single objective feature and aggregative gradient-based algorithm in multi-objective feature are proposed and applied in a turbojet engine controller gain-tuning problem as a case study. A comparison with the publicly available results show that optimization time and convergence indices will be enhanced noticeably. Based on this comparison and analysis, the potential solutions for the remaining research challenges for application to aerospace engineering problems in the future include the implementation of enhanced and modified optimization algorithms and hybrid optimization algorithms in order to achieve optimal results for the advanced engine modelling and controller design procedure with affordable computational effort.
Finding new markers to assess prognosis of melanoma without the necessity to perform a surgical interventions is an important goal in melanoma research. The current study aimed to assess the ...correlation of clinical course and prognosis of primary and metastatic melanoma with expression of VEGF family and their receptors.
A ngTMA block was made from the randomly selected paraffin tissue blocks of the patients with melanocytic nevi, primary and metastatic melanoma. Then sections cut from ngTMA-block were immunohistochemically stained with proper antibodies. Expression of these proteins was investigated using automated image analysis and compared among the study groups.
We analyzed the tissue of 238 patients with following diagnoses: 101 (42.4%) with a diagnosis of nevus, 86 (36.1%) Malignant melanoma and 51 (21.4%) metastasis. Median follow-up time for the malignant lesions was 5.71 years. Among the tested antigen, VEGF-C (p = 0.016), VEGF-R2 (p<0.001) and VEGF-R3 (p = 0.002) were significantly higher expressed in the metastatic tissues. When these scores were assessed in multiple regression models, the only independent factor linked to patient's diagnosis was VEGF-R2 (p<0.001). In addition, groups of highly correlated variables (VEGF-C and VEGF-R3, VEGF-A and VEGF-R1) were found to form separate sub-clusters. On the other side, high values of VEGF-C were associated with both overall and disease-free survival with a statically significant HR of 2.76 (95% CI: 1.27, 5.98; p = 0.01) and 2.82 (95%CI: 1.62, 4.91; p<0.001), respectively.
This study shows that VEGF-C and VEGF-R2 might represent new prognostic marker in MM. However, further prospective studies are warranted to test their real efficacy as a prognostic marker.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Abstract
In the present study, the laser wakefield acceleration of electrons in a magnetically-controlled plasma is investigated. The results indicate that by employing a linearly-chirped laser pulse ...propagating through magnetized plasma with a reversed external magnetic field, higher energy electrons are obtained than with unmagnetized plasma and/or a nonchirped laser pulse. By considering an appropriate constant chirping magnitude and an axial external magnetic field, one can obtain remarkable GeV electron energies. It is also found that the effect of the external magnetic field direction on the electron energy is not sensed much in the mildly relativistic regime, while the reversed magnetic field increases the peak of electron energy gains compared with the forward magnetic field in the highly relativistic regime. For the mildly relativistic case, a peak energy of 412 MeV and a relative energy spread of 7% is obtained. In addition, for the highly relativistic case, a peak energy of 1.55 GeV is obtained.
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