The effect of temperature on the excess charge carrier generation and collection, injected using two photon absorption at a wavelength of 1550 nm, is investigated in a 285 μm thick, p-type silicon ...planar detector, with a bulk resistivity of 3.7 kΩ cm. Charge collection measurements are performed for temperatures between −20 °C to 20 °C. The collected charge decreases by about 8% when the temperature is lowered from 20 °C to −20 °C, which is linked to a decreasing excess charge carrier generation. Further, a decreasing time over threshold is observed for decreasing temperatures, which is associated to an increasing charge carrier mobility.
The Low Gain Avalanche Detector (LGAD) technology is very promising for silicon timing detectors and currently heavily researched. Recent studies show that the gain of LGADs highly depends on the ...charge carrier density inside the gain layer. To study the charge carrier density related gain reduction, the Two Photon Absorption-Transient Current Technique (TPA-TCT) was employed to obtain information on the drift velocity and electric field of a LGAD for different charge carrier densities. The TPA-TCT uses fs-pulse infrared lasers to provide a three-dimensional resolution to study bulk effects. A compact TPA-TCT setup was developed at CERN and is used to measure current transients against the device depth of a 285μm thick PIN and LGAD, fabricated by IMB-CNM. Methods to extract information about the electric field are employed to verify the charge carrier density related gain reduction. The gain layer of the LGAD is spatially resolved for the first time.
Abstract Background Human mesenchymal stem cells (MSC) have been utilized for cardiac regeneration after myocardial damage. Their clinical effects are marginal and only a minority of administered ...cells could make their way into the myocardium. The chemokine receptor CXCR4 has been identified as crucial for migration and homing of stem cells. In this study we overexpressed CXCR4 on human MSC to improve cell trafficking and tissue repair. Methods Human MSC were isolated from the spongiosa of tibia and femur as well as from pelvic bone marrow. MSC were characterized by differentiation assays and FACS analysis. CXCR4 was overexpressed by mRNA-nucleofection. Intracellular signaling was analyzed to demonstrate functionality of CXCR4. The modified Boyden chamber, wounding assays and time lapse microscopy were utilized to investigate MSC migration. Results MSC did not express relevant amounts of CXCR4 spontaneously. CXCR4 could be overexpressed in 93% of MSC with a cell viability of 62%. Functionality of the overexpressed CXCR4 was demonstrated by a significant cytosolic Ca2+ increase and activation of different MAP kinases followed by SDF-1α stimulation. In contrast no improvement of cell migration could be observed. There was a strong basal MSC chemokinesis independent from CXCR4 expression. Conclusions CXCR4 could be effectively overexpressed in human MSC by mRNA-nucleofection. Despite functionality of CXCR4 MSC were characterized by a strong basal chemokinesis that could not be further enhanced by CXCR4 overexpression. As isolation, culture and nucleofection of pelvic bone marrow-derived MSC basically fulfill the GMP-requirements our approach seems suited for an in vivo application in patients.
Abstract
A tabletop Two Photon Absorption-Transient Current Technique (TPA-TCT) set-up built at CERN was used to investigate a non-irradiated PIN diode, an irradiated PIN diode, and a non-irradiated ...5 × 5-multipad HPK LGAD. The intrinsic three dimensional spatial resolution of this method is demonstrated under normal incidence of the laser probe. A charge collection versus depth profile of the non-irradiated PIN diode is presented, where reflection on the rear silicon-air interface was observed. It is found that the time-over-threshold versus depth profile is particularly suitable to determine the boundaries of the DUT’s active volume. A depth scan of the irradiated PIN diode is discussed and a method to omit the single photon absorption background is presented. Finally, a charge collection measurement in the inter-pad region of the 5 × 5-multipad HPK LGAD is presented and it is demonstrated that TPA-TCT can be used to image the implantation and the electric field of segmented silicon devices in a three dimensional manner.
Deep diffused Avalanche photodiodes for charged particles timing Centis Vignali, M.; Dias De Almeida, P.; Franconi, L. ...
Nuclear instruments & methods in physics research. Section A, Accelerators, spectrometers, detectors and associated equipment,
04/2020, Letnik:
958, Številka:
C
Journal Article
Recenzirano
Odprti dostop
The upgrades of ATLAS and CMS for the High Luminosity LHC (HL-LHC) highlighted physics objects timing as a tool to resolve primary interactions within a bunch crossing. Since the expected pile-up is ...around 200, with an r.m.s. time spread of 180ps, a time resolution of about 30ps is needed. The timing detectors will experience a 1-MeV neutron equivalent fluence of about Φeq=1014 and 1015cm−2 for the barrel and end-cap regions, respectively. In this contribution, deep diffused Avalanche Photo Diodes (APDs) produced by Radiation Monitoring Devices are examined as candidate timing detectors for HL-LHC applications. To improve the detector’s timing performance, the APDs are used to directly detect the traversing particles, without a radiator medium where light is produced. Devices with an active area of 8 × 8mm2 were characterized in beam tests. The timing performance and signal properties were measured as a function of position on the detector using a beam telescope and a microchannel plate photomultiplier (MCP-PMT). Devices with an active area of 2 × 2mm2 were used to determine the effects of radiation damage and characterized using a ps pulsed laser. These detectors were irradiated with neutrons up to Φeq=1015cm−2.
Background
Overexpression of interleukin‐10 (IL‐10) in murine CD11b+ monocytes/macrophages via GMP‐adapted mRNA‐nucleofection was expected to improve clinical outcome and reduce adverse side effects ...in autoimmune myocarditis. This study represents the proof of principle for a novel anti‐inflammatory therapy using overexpression of IL‐10 in murine monocytes/macrophages by mRNA‐nucleofection for the treatment of autoimmune myocarditis.
Methods and Results
Autoimmune myocarditis was induced in A/J mice by subcutaneous immunization with troponin I. CD11b+ monocytes/macrophages were isolated from the peritoneum and IL‐10 was overexpressed by mRNA‐nucleofection. These cells were injected intravenously. Myocardial inflammation was assessed via histological and immunohistochemical examinations. Myocardial fibrosis was analyzed with Masson's trichrome staining. Antitroponin I antibodies were determined within the serum. Physical performance was evaluated using a running wheel and echocardiography. In vitro overexpression of IL‐10 in CD11b+ monocytes/macrophages resulted in a 7‐fold increased production of IL‐10 (n=3). In vivo higher levels of IL‐10 and less inflammation were detected within the myocardium of treated compared with control mice (n=4). IL‐10–treated mice showed lower antitroponin I antibodies (n=10) and a better physical performance (n=10).
Conclusions
Application of IL‐10–overexpressing CD11b+ monocytes/macrophages reduced inflammation and improved physical performance in a murine model of autoimmune myocarditis. Thus, the use of genetically modified monocytes/macrophages facilitated a targeted therapy of local inflammation and may reduce systemic side effects. Because the nucleofection technique is GMP adapted, an in vivo use in humans seems basically feasible and the transfer to other inflammatory diseases seems likely.
The objective of this study was to examine the relation between hypertension and depression. In a cross-sectional study of the urban region of a State capital with more than 1.5 million inhabitants, ...1174 men and women aged 18-80 years, selected at random from the population, were studied. Blood pressure, hypertension (blood pressure readings >or=140/90 mm Hg or use of blood pressure-lowering agents), risk factors for hypertension and depression according to the Diagnostic and Statistical Manual of Mental Disorders (fourth edition) were investigated in home interviews. The prevalence of major depression and hypertension were 12.4% (95% confidence interval (CI): 10.5-14.3) and 34.7% (95% CI: 32.2-37.4), respectively. Systolic and diastolic blood pressures of individuals with and without a lifetime episode of depression were not different after adjustment for age and gender. Lifetime episodic major depression was not associated with hypertension in bivariate analysis (risk ratios (RR): 0.96, 95% CI: 0.76-1.23) and after adjustment for confounding (RR: 1.15; 95% CI:0.75-1.76). Hypertension and depression were not associated in this free-living population of adults, suggesting that their concomitant occurrence in clinical practice may be ascribed to chance.
Gene transfer into human CD34+ haematopoietic progenitor cells (HPC) and multi‐potent mesenchymal stromal cells (MSC) is an essential tool for numerous in vitro and in vivo applications including ...therapeutic strategies, such as tissue engineering and gene therapy. Virus based methods may be efficient, but bear risks like tumorigenesis and activation of immune responses. A safer alternative is non‐viral gene transfer, which is considered to be less efficient and accomplished with high cell toxicity. The truncated low affinity nerve growth factor receptor (ÄLNGFR) is a marker gene approved for human in vivo application. Human CD34+ HPC and human MSC were transfected with in vitro‐transcribed mRNA for ΔLNGFR using the method of nucleofection. Transfection efficiency and cell viability were compared to plasmid‐based nucleofection. Protein expression was assessed using flow cytometry over a time period of 10 days. Nucleofection of CD34+ HPC and MSC with mRNA resulted in significantly higher transfection efficiencies compared to plasmid transfection. Cell differentiation assays were performed after selecting ΔLNGFR positive cells using a fluorescent activating cell sorter. Neither cell differentiation of MSC into chondrocytes, adipocytes and osteoblasts, nor differentiation of HPC into burst forming unit erythroid (BFU‐E) colony forming unit‐granulocyte, erythrocyte, macrophage and megakaryocyte (CFU‐GEMM), and CFU‐granulocyte‐macrophage (GM) was reduced. mRNA based nucleofection is a powerful, highly efficient and non‐toxic approach for transient labelling of human progenitor cells or, via transfection of selective proteins, for transient manipulation of stem cell function. It may be useful to transiently manipulate stem cell characteristics and thus combine principles of gene therapy and tissue engineering.
IntroductionHealth-related quality of life (QoL) is largely affected by cardiovascular disease, but it not known the effect of accumulated risk factors.ObjectiveTo evaluate the association between ...cardiovascular risk factors and health-related QoL in a population-based sampling from southern Brazil.MethodsThis population-based cross-sectional study included 1858 adults, aged 18–90 years. Standardised interviews and measurements detected obesity (BMI ≥30 kg/m2); alcoholic beverage consumption (grams of ethanol/day); smoking, and physical inactivity (<150 min/day). Hypertension was identified by blood pressure ≥140/90 mm Hg or lowering drugs. QoL was detected by Short-Form Health Survey (SF-12) for Physical Component Summary (PCS) and Mental Component Summary (MCS). General Linear Model, of the SPSS-Complex Samples module, was used for multivariate analysis, controlling for design effect and confounding factors.ResultsParticipants had 48.9±19.1 years-old, 9.4±4.7 years at school, and 58% were women. Low PCS scores were determined for low education level, females, age ≥65 year, but only the last two risk factors were associated with low MCS score. Lower PCS were detected for obesity (46.9 vs 49.5; p<0.001), hypertension (47.6 vs 49.9; p<0.001), diabetes (45.6 vs 49.2; p<0.001), and physically inactive (46.7 vs 49.7; p<0.001), independently of confounding factors, as well as for MCS for non-smoking participants (49.4) (vs 51.9 ex-smokers and 51.2 smokers; p=0.003), physically inactive (49.9 vs 51.4; p=0.008), hypertensive (49.9 vs 51.9; p=0.007), and diabetics (48.6 vs 51.2; p=0.008). There was a curve-response between the number of risk factors and PCS (p<0.001) and MCS scores (p<0.001).ConclusionIndividuals who accumulated risk factors have poorer health-related QoL.
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