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•HGNs were modified with anti-nucleolin aptamer to obtain PTT-active nanoconjugates.•AS1411@HGNs exhibit good biostability and high efficiency of photothermal conversion.•AS1411@HGNs ...were used as agents in PTT on skin tumor cells.
This article describes the work on synthesis, surface functionalization and characterization of hollow gold nanoshells (HGNs), and their application in a photothermal tumor therapy. The studied gold nanoshells were synthesized using a method based on a reduction of HAuCl4 onto silver nanoparticle templates. A selected aptamer - AS1411 – selective towards nucleolin, with a terminal thiol group was conjugated to HGNs. Surface functionalization of synthesized nanoparticles was necessary to gain the affinity to tumor cells, thus allowing the selective delivery of the modified nanoparticles to target cells. As expected, an increased selectivity of nanoconjugates towards tumor cells (A375) in a comparison to normal ones (HaCaT) was observed (2.67 times). In the framework of our studies the biological activity of the obtained nanoconjugates was evaluated using MTT assay. For this aim, both normal and tumor cell cultures respresenting skin tissue were exposed to gold nanoparticles solutions. It was found, that HGN-AS1411 conjugates cause less than 10% loss in a cell viability in the case of both cell lines at the highest tested concentration. The potential of the developed nanoconjugates as agents in PTT of skin cancer was investigated in a subsequent stage of our research. It was found, that A375 cell viability amounted to less than 40% for 75μM of nanoconjugates (expressed as a concentration of Au atoms) as a result of the laser irradiation of this cell culture after desired accumulation of the tested nanoconjugates inside A375 cells.
The paper deals with a quasi-static behaviour of cohesion-less granular material in active earth pressure state. Photo-elastic model tests on a rigid wall, translating out of the granular material, ...are analyzed. Grain crushing tests are used to estimate the range of contact forces during the model tests. Substitute granular material (low optical sensitivity glass granules) is employed. The focus is on the evolution of contact force network with deformation of granular material. The model tests are simulated using the discrete element method (DEM) to compare physical and numerical full-field force network structure and the maximum/minimum stress level. The same model geometry, loading scheme and grain size distribution, as in the model tests, are accepted in DEM simulations, although only a single layer of grains is modelled. DEM model correctly predicts the overall structure of the force network and its characteristic features, including localization. It also gives the stress level close to the experimental one and properly identifies the areas of phase transitions.
Graphical Abstract
Nanodosimetry is a branch of dosimetry for investigation and modeling of the interaction pattern of ionizing radiation in nanometre site-sizes (at unit density), which dates back to the 1970's ...(Pszona S. A track ion counter. Proceedings of Fifth Symposium on Microdosimetry EUR 5452 d-e-f, Published by the Commission of the European Communities, Luxemburg, pp. 1107-1122 (1976)). To date, the different experimental approaches have lead to developing of three fully functional nanodosimeters: the Jet Counter operated at NCBJ, the Ion Counter operated at PTB and Startrack Counter operated at INFN-LNL. Descriptions of each nanodosimeter as well as of the techniques used to investigate the track structure of ionizing particles are presented.
The biological action of ionizing charged particles is initiated at the DNA level, and the effectiveness with which the initial physical effect changes into measurable biological damage is likely ...ruled by the stochastics of ionizations produced by the incident ions in subcellular nanometric volumes. Based on this hypothesis, experimental nanodosimetry aims at establishing a new concept of radiation quality that builds on measurable characteristics of the particle track structure at the nanometer scale. Three different nanodosimetric detection systems have been developed to date that allow measurements of the number of ionizations produced by the passage of a primary particle in a nanometer-size gas volume (in unit density scale). Within the Italian project MITRA (MIcrodosimetry and TRAck structure), funded by the Italian Istituto Nazionale di Fisica Nucleare (INFN) and the EMRP Joint Research Project 'BioQuaRT' (Biologically Weighted Quantities in Radiotherapy), experiments have been carried out, in which the frequency distribution of ionizations produced by proton and carbon ion beams of given energy was measured with the three nanodosimetric detectors. Descriptors of the track structure can be derived from these distributions. In particular, the first moment M1, representing the mean number of ionizations produced in the target volume, and the cumulative probability Fk of measuring a number ν ≥ k of ionizations. The correlation between measured nanodosimetric quantities and experimental radiobiological data available in the literature is here presented and discussed.
Clinical immunity to P. falciparum malaria is non‐sterilizing, with adults often experiencing asymptomatic infection. Historically, asymptomatic malaria has been viewed as beneficial and required to ...help maintain clinical immunity. Emerging views suggest that these infections are detrimental and constitute a parasite reservoir that perpetuates transmission. To define the impact of asymptomatic malaria, we pursued a systems approach integrating antibody responses, mass cytometry, and transcriptional profiling of individuals experiencing symptomatic and asymptomatic P. falciparum infection. Defined populations of classical and atypical memory B cells and a TH2 cell bias were associated with reduced risk of clinical malaria. Despite these protective responses, asymptomatic malaria featured an immunosuppressive transcriptional signature with upregulation of pathways involved in the inhibition of T‐cell function, and CTLA‐4 as a predicted regulator in these processes. As proof of concept, we demonstrated a role for CTLA‐4 in the development of asymptomatic parasitemia in infection models. The results suggest that asymptomatic malaria is not innocuous and might not support the induction of immune processes to fully control parasitemia or efficiently respond to malaria vaccines.
Synopsis
Asymptomatic Plasmodium falciparum malaria infection supports protective humoral responses, but it also features an immunosuppressive transcriptional signature with upregulation of pathways involved in the inhibition of T‐cell function.
Asymptomatic malaria is thought to be beneficial for maintaining clinical immunity and remains untreated.
Despite supporting protective humoral immune responses, asymptomatic malaria infections feature an immunosuppressive blood transcriptional signature with upregulation of pathways involved in the control of T‐cell function.
These results suggest that asymptomatic malaria is not innocuous and might not support immune processes to fully control parasitemia or efficiently respond to malaria vaccines.
Asymptomatic Plasmodium falciparum malaria infection supports protective humoral responses, but it also features an immunosuppressive transcriptional signature with upregulation of pathways involved in the inhibition of T‐cell function.
Symptomatic uncomplicated diverticular disease (SUDD) is the most common manifestation of diverticulosis. Data concerning the optimal treatment after SUDD exacerbation are inconsistent.
To assess the ...effectiveness and necessity of cyclic rifaximin treatment for recurrent SUDD symptoms and for preventing exacerbations in patients who responded to the initial treatment.
A retrospective observational study was performed in 2017. Physicians responded to a survey on patients with recurrent SUDD during the observation period, who were cyclically treated with rifaximin 400 mg
for 7 days per month. The patients' SUDD history, diagnostic methods, treatment, and results were evaluated.
In total 294 patients were included in this study (67% women, median age: 65 years (26-87)). The mean duration of diverticular disease (DD) was 4.5 years (1-20), and 88% had at least one repeated episode of SUDD exacerbation before rifaximin. A total of 267 patients were treated with rifaximin. Changes in the severity of pain, abdominal tenderness, diarrhoea, constipation, and bloating were assessed every 2 months. After 6 months of rifaximin treatment there was a statistically significant reduction in the total severity score (median from 1.8 (max. 3 points) to 0.2;
< 0.0001; sum from 9.37 (max. 18 points) to 1.35;
< 0.0001) and an improvement in individual symptom score.
Cyclical rifaximin is effective in treating exacerbation of SUDD. This regimen leads to a gradual cessation of symptoms over a 6-month period. In patients who responded to the initial treatment, cyclic rifaximin therapy is needed to maintain remission.
The endometrial cancer (EC)‐specific Quality of Life module of the European Organization for Research and Treatment of Cancer (EORTC QLQ‐EN24), was developed and validated in one study. We ...independently validated and assessed the psychometric properties of the instrument. Two hundred and eight women with EC before surgery, during adjuvant treatment and follow‐up; in three different cancer centres completed the EORTC QLQ‐C30 and the EN24. The questionnaire's completion rate was 100%, except sexuality items, that were answered by 35% of patients. All item‐scale correlations for the multi‐item scales exceeded the .4 criterion and correlated well with their own scale, while correlations with the other scales were low. The internal consistency of all multi‐item scales were satisfactory (Cronbach's alpha coefficients ranging from .77 to .97). Discriminance for single‐item scales was low. The QLQ‐EN24 module discriminated well between clinically different patients, and there were no differences in quality of life questionnaire scales between patients with body mass index ≤30 when compared to those with >30. This validation study supports the reliability, as well as convergent and divergent validity of the EORTC QLQ‐EN24. The module is a useful instrument for the assessment of QOL in patients with EC. However, data concerning sexuality should be interpreted with caution.
IFN-γ-driven responses to malaria have been shown to modulate the development and function of T follicular helper (TFH) cells and memory B cells (MBCs), with conflicting evidence of their involvement ...in the induction of antibody responses required to achieve clinical immunity and their association with disease outcomes. Using high-dimensional single-cell mass cytometry, we identified distinct populations of TH1-polarized CD4+ T cells and MBCs expressing the TH1-defining transcription factor T-bet, associated with either increased or reduced risk of Plasmodium vivax (P. vivax) malaria, demonstrating that inflammatory responses to malaria are not universally detrimental for infection. Furthermore, we found that, whereas class-switched but not IgM+ MBCs were associated with a reduced risk of symptomatic malaria, populations of TH1 cells with a stem central memory phenotype, TH17 cells, and T regulatory cells were associated with protection from asymptomatic infection, suggesting that activation of cell-mediated immunity might also be required to control persistent P. vivax infection with low parasite burden.
This paper presents a modification of the surface of CdS/ZnS and CdSe
x
S
1−
x
/ZnS quantum dots (QDs) with 3-mercaptopropionic and 6-mercaptohexanoic acid. The obtained QDs were characterized using ...TEM, DLS, UV–Vis, and fluorescence spectroscopy. Flow cytometry was applied to evaluate the cytotoxicity of QDs and examine the type of death caused by the tested nanoparticles. In addition, the generation of reactive oxygen species after incubation of the tested cells with CdSe
x
S
1−
x
/ZnS–MPA and CdSe
x
S
1−
x
/ZnS–MHA QDs was evaluated. The study was conducted on three cell lines: adherent (A549 and MRC-5) and suspension ones (K562). The conducted research demonstrated that the tested nanoparticles exhibit concentration-dependent toxicity. It was observed that the surface modification influences the toxicity level of the examined QDs, and modification of their surface with the use of the ligand of longer carbon chain (MHA) reduces the toxicity in comparison with QDs–MPA. It was also found that all tested QDs caused the death of cells in the course of necrosis. Based on obtained results, it was concluded that the cytotoxicity of QDs is to a large extent related to reactive oxygen species (ROS) generation.
MCORD - MPD Cosmic Ray Detector a new features Bielewicz, M.; Milewicz-Zalewska, M.; Grodzicka-Kobylka, M. ...
EPJ Web of Conferences,
2019, Letnik:
204
Journal Article, Conference Proceeding
Recenzirano
Odprti dostop
The main detector system at the Nuclotron-based Ion Collider fAcility (NICA) located in Dubna, Russia is the Multi-Purpose Detector (MPD). For better calibration reason, the MPD needs an additional ...trigger system for an off-beam calibration of MPD sub-detectors and for rejection (veto) of cosmic muons. The system should also be useful for practical astrophysics observations of cosmic showers. The consortium NICA-PL group defines goals and basic assumptions for the MPD Cosmic Ray Detector (MCORD). This article describes the conceptual design and simulation plans of the MCORD detector based on plastic scintillators with SiPM photodetectors and electronic digital system based on the MicroTCA crate.
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