The discovery of disease-specific biomarkers, such as microRNAs (miRNAs), holds the potential to transform the landscape of Amyotrophic Lateral Sclerosis (ALS) by facilitating timely diagnosis, ...monitoring treatment response, and accelerating drug discovery. Such advancement could ultimately improve the quality of life and survival rates for ALS patients. Despite more than a decade of research, no miRNA biomarker candidate has been translated into clinical practice. We conducted a systematic review and meta-analysis to quantitatively synthesize data from original studies that analyzed miRNA expression from liquid biopsies via PCR and compared them to healthy controls. Our analysis encompasses 807 miRNA observations from 31 studies, stratified according to their source tissue. We identified consistently dysregulated miRNAs in serum (hsa-miR-3665, -4530, -4745–5p, −206); blood (hsa-miR-338–3p, -183–5p); cerebrospinal fluid (hsa-miR-34a-3p); plasma (hsa-miR-206); and neural-enriched extracellular vesicles from plasma (hsa-miR-146a-5p, −151a-5p, −10b-5p, −29b-3p, and −4454). The meta-analyses provided further support for the upregulation of hsa-miR-206, hsa-miR-338–3p, hsa-miR-146a-5p and hsa-miR-151a-5p, and downregulation of hsa-miR-183–5p, hsa-miR-10b-5p, hsa-miR-29b-3p, and hsa-miR-4454 as consistent indicators of ALS across independent studies. Our findings provide valuable insights into the current understanding of miRNAs' dysregulated expression in ALS patients and on the researchers’ choices of methodology. This work contributes to the ongoing efforts towards discovering disease-specific biomarkers.
► Porous alumina substrates were fabricated from Al2O3-loaded preceramic papers. ► Post SiO2-slurry and polysiloxane infiltrations lead to improvement of the properties. ► Density of preceramic ...paper-derived porous alumina can be controlled by post infiltration.
Preceramic papers loaded with inorganic fillers may be used as preforms in a novel manufacturing technique to fabricate lightweight ceramic structures. In order to reduce the porosity caused by burning out cellulosic fibers and organics, porous preceramic paper-derived alumina substrates were post-treated via two different coating routes using silica suspension or methylphenylvinylhydrogen polysiloxane. Sintering of the alumina-filled preceramic papers in air at 1600°C for 2h resulted in a non-uniform distributed open porosity ranging from 23 to 26%. After coating and infiltration, all samples were additionally heat treated up to at 1500°C for 2h. Thermal analysis (DTA/TG) was applied to determine the pyrolysis temperature of polysiloxane. Microstructure and phase analysis were performed respectively by SEM and XRD. After sintering, water absorption, apparent density and open porosity of test pieces were determined, and mechanical properties of the substrates were evaluated before and after coating. For the samples coated with silica suspension, the mechanical strength remained in the same range of those for uncoated samples, while for the polysiloxane coated samples the mechanical strength steadily increases after repeated impregnation steps, reaching ∼350MPa.
A significant fraction of patients are affected by persistent fear and anxiety. Currently, there are several anxiolytic drug options, however their clinical outcomes do not fully manage the symptoms. ...Here, we evaluated the effects of a bromazepam‑palladium derivative 2-{(7-bromo-2-oxo-1,3-dihydro-2H-1,4-benzodiazepin-5-il)pyridinyl-κ2-N,N}chloropalladium(II), (BMZ)PdCl2, on fear/anxiety and memory-related behavior in mice. For this, female Swiss mice were treated intraperitoneally (i.p.) with saline (NaCl 0.9%) or (BMZ)PdCl2 (0.5, 5.0, or 50 μg/kg). After 30 min, different tests were performed to evaluate anxiety, locomotion, and memory. We also evaluated the acute toxicity of (BMZ)PdCl2 using a cell viability assay (neutral red uptake assay), and whether the drugs mechanism of action involves the γ-aminobutyric acid type A (GABAA) receptor complex by pre-treating animals with flumazenil (1.0 mg/kg, i.p., a competitive antagonist of GABAA-binding site). Our results demonstrate that (BMZ)PdCl2 induces an anxiolytic-like phenotype in the elevated plus-maze test and that this effect can be blocked by flumazenil. Furthermore, there were no behavioral alterations induced by (BMZ)PdCl2, as evaluated in the light-dark box, open field, and step-down passive avoidance tests. In the acute toxicity assay, (BMZ)PdCl2 presented IC50 and LD50 values of 218 ± 60 μg/mL and 780 ± 80 mg/kg, respectively, and GSH category 4. Taken together, our results show that the anxiolytic-like effect of acute treatment with (BMZ)PdCl2 occurs through the modulation of the benzodiazepine site in the GABAA receptor complex. Moreover, we show indications that (BMZ)PdCl2 does not promote sedation and amnesia and presents the same toxicity as the bromazepam prototype.
We evaluated the effects of a bromazepam-palladium complex on fear, anxiety and memory-related behaviors in mice. The results showed that the anxiolytic-like occurs through modulation of the benzodiazepine site in the GABAA receptor complex. There are indications that the complex does not promote sedation, amnesia and toxicity higher than bromazepam. Display omitted
•Palladium-bromazepam complex, (BMZ)PdCl2.•(BMZ)PdCl2 showed an anxiolytic-like effect.•(BMZ)PdCl2 did not affect locomotor activity and memory.•(BMZ)PdCl2 showed similar acute toxicity to bromazepam.
Detectors manufactured on p-type silicon material are known to have significant advantages in very harsh radiation environment over n-type detectors, traditionally used in High Energy Physics ...experiments for particle tracking. In p-type (n+ segmentation on p substrate) position-sensitive strip detectors, however, the fixed oxide charge in the silicon dioxide is positive and, thus, causes electron accumulation at the Si/SiO2 interface. As a result, unless appropriate interstrip isolation is applied, the n-type strips are short-circuited. Widely adopted methods to terminate surface electron accumulation are segmented p-stop or p-spray field implantations. A different approach to overcome the near-surface electron accumulation at the interface of silicon dioxide and p-type silicon is to deposit a thin film field insulator with negative oxide charge. We have processed silicon strip detectors on p-type Magnetic Czochralski silicon (MCz-Si) substrates with aluminum oxide (Al2O3) thin film insulator, grown with Atomic Layer Deposition (ALD) method. The electrical characterization by current–voltage and capacitance−voltage measurement shows reliable performance of the aluminum oxide. The final proof of concept was obtained at the test beam with 200GeV/c muons. For the non-irradiated detector the charge collection efficiency (CCE) was nearly 100% with a signal-to-noise ratio (S/N) of about 40, whereas for the 2×1015neq/cm2 proton irradiated detector the CCE was 35%, when the sensor was biased at 500V. These results are comparable with the results from p-type detectors with the p-spray and p-stop interstrip isolation techniques. In addition, interestingly, when the aluminum oxide was irradiated with Co-60 gamma-rays, an accumulation of negative fixed oxide charge in the oxide was observed.
The present work was aimed at producing waste-only ceramics with higher added value, while finding a viable end-use, other than landfilling, for wastes from extraction and beneficiation of mineral ...resources. Based on their fluxing character and plasticity, four non-hazardous industrial wastes were selected and characterized: one clay mining tail, the sludge from potable water treatment and two sludges from gneiss and varvite cutting processes. Using the phase diagram of the SiO2–Al2O3–K2O system, four mixtures located within the wastes-defined polygon were formulated, uniaxially pressed and fired for 40min at 900–1150°C. The results obtained for the properties of fired samples show that water absorption values below 10% (ceramic tiles) and 3% (porcelain tiles) were reached upon firing at 1100 and 1150°C, respectively, without firing warpage. Density values were also within the usual range but flexural strength, although adequate for common application, is lower than usual (at least 3MPa). In terms of industrial production, although process adjustments are still required (green processing, firing cycle) the obtained results demonstrate that porcelain-like ceramic tiles can be manufactured using only the selected wastes as raw materials, suggesting that, for the composition range investigated, firing temperatures should be ~1100°C and a fast-firing type processing might be feasible.
► A viable end use was found for wastes from the beneficiation of mineral resources. ► Such end use might lead to the production of waste-only porcelain-like ceramics. ► The choice of compositions and processing parameters was guided by phase diagrams. ► Results suggest the possibility of low temperature fast-firing ceramic processing. ► Initial results might easily be furthered towards a suitable commercial application.
On the timing performance of thin planar silicon sensors Akchurin, N.; Ciriolo, V.; Currás, E. ...
Nuclear instruments & methods in physics research. Section A, Accelerators, spectrometers, detectors and associated equipment,
07/2017, Letnik:
859, Številka:
C
Journal Article
Recenzirano
Odprti dostop
We report on the signal timing capabilities of thin silicon sensors when traversed by multiple simultaneous minimum ionizing particles (MIP). Three different planar sensors, with depletion ...thicknesses 133, 211, and 285µm, have been exposed to high energy muons and electrons at CERN. We describe signal shape and timing resolution measurements as well as the response of these devices as a function of the multiplicity of MIPs. We compare these measurements to simulations where possible. We achieve better than 20ps timing resolution for signals larger than a few tens of MIPs.
The majority of patients with myelodysplastic syndrome (MDS) present with anemia and will become dependent on regular transfusions of packed red blood cells (PRBC) with the risk of iron overload ...(IOL). Liver iron content best reflects the total body iron content, and measurement of liver iron concentration (LIC) by MRI is a validated tool for detection, but data in MDS is rather limited. Here we present the results of a multi-center trial evaluating the efficacy and safety of deferasirox (DFX) in low and intermediate-1 risk MDS patients with transfusion-dependent IOL. Three patients with transfusion frequency of > 4 units PRBC per month were initially treated with 30 mg/kg/day while in 46 patients with a lower transfusion burden deferasirox was initiated at 20 mg/kg/day, due to patient related reasons one patient received DFX in a dose of 6 mg/kg/day only. LIC was measured by MRI at baseline and end of study using the method by St. Pierre et al. The intention to treat population consisted of 50 MDS patients (28 male; 22 female) with a median age of 69 years who were treated with DFX for a median duration of 354 days. Mean daily dose of DFX was 19 mg/kg/day. Median serum ferritin level (SF) at baseline was 2,447 ng/mL and decreased to 1,685 ng/mL (reduction by 31 %) at end of study (
p
= 0.01). In 7 (13 %) patients the initially chosen dose had to be increased due to unsatisfactory efficacy of chelation therapy. For 21 patients, LIC measurement by liver MRI was performed at baseline and for 19 of these patients at the end of study: mean LIC decreased significantly from 16,8 mg/g dry tissue weight (± 8.3 mg/g dry tissue weight) at study entry to 10,8 mg/g dry tissue weight (± 10.4 mg/g dry tissue weight) at end of study (
p
= 0.01). Of all patients exposed to the study drug (
n
= 54), 28 (52 %) did not complete the 12 month study period most commonly due to AEs in 28 % (
n
= 15) and abnormal laboratory values in 7 % (
n
= 4), respectively. The most common adverse events (≥ 10 % of all patients) with suspected drug relationship were diarrhea (
n
= 25, 46 %), nausea (
n
= 13, 24 %), upper abdominal pain (
n
= 8, 15 %), serum creatinine increase (
n
= 16, 30 %) and rash (
n
= 5, 9 %). Adverse events making dose adjustments or interruption of study drug necessary occurred in 33 patients (61 %). Hematologic improvement according to IWG criteria (2006) was observed in 6 patients (11 %). Initiation of treatment of IOL with DFX depending on the transfusion burden yields sufficient reduction of excess iron indicated by serum ferritin levels and most importantly by liver MRI. The safety profile of DFX was comparable to previous observations.
The optimal formulation and processing conditions were investigated for the preparation of the phosphorescent ceramic pigment BaAl1.7B0.3O4 doped with Eu2+ and Dy3+ using the polymeric precursor ...method or Pechini method. The properties of the synthesized pigment were analyzed by X-ray diffraction, excitation by ultraviolet light, Raman spectroscopy, photoluminescence, and luminescence decay. The hexagonal barium aluminate phase BaAl2O4 could be identified in all doped compounds. The photoluminescence spectra analysis indicated that phosphorescence efficiency increased with higher Eu2+concentrations, and that the pigments emitted green light in the visible range of 430–500nm corresponding to the 4f6–5d →4f7 of Eu2+ transition with curves of luminescence decay between 160 and 790s. We conclude that these techniques and analyses are suitable to produce a high quality phosphorescent pigment suitable for use in the ceramic industry.
In this report we cover two special applications of Atomic Layer Deposition (ALD) thin films to solve these challenges of the very small size pixel detectors. First, we propose to passivate the ...p-type pixel detector with ALD grown Al2O3 field insulator with a negative oxide charge instead of using the commonly adopted p-stop or p-spray technologies with SiO2, and second, to use plasma-enhanced ALD grown titanium nitride (TiN) bias resistors instead of the punch through biasing structures. Surface passivation properties of Al2O3 field insulator was studied by Photoconductive Decay (PCD) method and our results indicate that after appropriate annealing Al2O3 provides equally low effective surface recombination velocity as thermally oxidized Si/SiO2 interface. Furthermore, with properly designed annealing steps, the TiN thin film resistors can be tuned to have up to several MΩ resistances with a few µm of physical size required in ultra-fine pitch pixel detectors.
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