Aims/hypothesis Interphotoreceptor retinoid-binding protein (IRBP) plays a major role in the visual cycle and is essential to the maintenance of photoreceptors. The aim of this study was to determine ...whether a decrease in IRBP production exists in the early stages of diabetic retinopathy. Methods Vitreous samples from diabetic patients with proliferative and non-proliferative diabetic retinopathy (PDR, NPDR), and from non-diabetic patients with macular hole (control group) were selected for IRBP quantitative assessment by proteomic analysis (fluorescence-based difference gel electrophoresis) and western blot. Human post mortem eyes (n = 16) from diabetic donors without clinically detectable retinopathy and from non-diabetic donors (n = 16) were used to determine IRBP (also known as RBP3) mRNA levels (RT-PCR) and protein content (western blot and confocal microscopy). Retinal neurodegeneration was assessed by measuring glial fibrillar acidic protein (GFAP) and the apoptotic rate. Y79 human retinoblastoma cells were used to test the effects of glucose, TNF-α and IL-1β on IRBP expression and IRBP levels. Results Intravitreous IRBP concentration was significantly lower in PDR < NPDR < control in proteomic and western blot analysis. IRBP mRNA levels and IRBP protein content were significantly lower in the retinas from diabetic donors than in those from non-diabetic donors. Increased GFAP and a higher degree of apoptosis were observed in diabetic retinas compared with non-diabetic retinas. A dose-dependent downregulation of IRBP mRNA expression and IRBP content was detected with glucose, TNF-α and IL-1β in cultures of Y79 human retinoblastoma cells. Conclusions/interpretation Underproduction of IRBP is an early event in the human diabetic retina and is associated with retinal neurodegeneration. The mechanisms leading to this deficit deserve further investigation.
We discuss here the quantification of magnetite and maghemite from x-ray absorption near edge spectroscopy at the Fe K-edge in fluorescence mode. We show that the modification of the spectral shape ...due to self-absorption effects can lead to erroneous results for certain thicknesses. However, for homogeneous samples containing just magnetite and maghemite without other phases, the quantification of magnetite and maghemite can be obtained from the spectra measured in fluorescence mode without correcting the spectra for the self-absorption effects. We describe the conditions to carry on this analysis that requires measuring the reference compounds exactly under the same conditions as the studied samples and using the appropriate thickness.
Nanostructure-based plasmonic biosensors have quickly positioned themselves as interesting candidates for the design of portable optical biosensor platforms considering the potential benefits they ...can offer in integration, miniaturization, multiplexing, and real-time label-free detection. We have developed a simple integrated nanoplasmonic sensor taking advantage of the periodic nanostructured array of commercial Blu-ray discs. Sensors with two gold film thicknesses (50 and 100nm) were fabricated and optically characterized by varying the oblique-angle of the incident light in optical reflectance measurements. Contrary to the use normal light incidence previously reported with other optical discs, we observed an enhancement in sensitivity and a narrowing of the resonant linewidths as the light incidence angle was increased, which could be related to the generation of Fano resonant modes. The new sensors achieve a figure of merit (FOM) up to 35 RIU−1 and a competitive bulk limit of detection (LOD) of 6.3×10−6 RIU. These values significantly improve previously reported results obtained with normal light incidence reflectance measurements using similar structures. The sensor has been combined with versatile, simple, ease to-fabricate microfluidics. The integrated chip is only 1cm2 (including a PDMS flow cell with a 50µm height microfluidic channel fabricated with double-sided adhesive tape) and all the optical components are mounted on a 10cm×10cm portable prototype, illustrating its facile miniaturization, integration and potential portability. Finally, to assess the label-free biosensing capability of the new sensor, we have evaluated the presence of specific antibodies against the GTF2b protein, a tumor-associate antigen (TAA) related to colorectal cancer. We have achieved a LOD in the pM order and have assessed the feasibility of directly measuring biological samples such as human serum.
•An integrated nanostructured plasmonic biosensor based on Blu-ray disc is proposed.•A performance enhancement at high angles of incidence light is observed.•A figure of merit (FOM) up to 35 RIU−1 and a LOD of 6.34×10−6 RIU is reached.•Detection of antibodies related to colorectal cancer is achieved at the pM level.
With the performance of central processing units (CPUs) having effectively reached a limit, parallel processing offers an alternative for applications with high computational demands. Modern graphics ...processing units (GPUs) are massively parallel processors that can execute simultaneously thousands of light-weight processes. In this study, we propose and implement a parallel GPU-based design of a popular method that is used for the analysis of brain magnetic resonance imaging (MRI). More specifically, we are concerned with a model-based approach for extracting tissue structural information from diffusion-weighted (DW) MRI data. DW-MRI offers, through tractography approaches, the only way to study brain structural connectivity, non-invasively and in-vivo. We parallelise the Bayesian inference framework for the ball & stick model, as it is implemented in the tractography toolbox of the popular FSL software package (University of Oxford). For our implementation, we utilise the Compute Unified Device Architecture (CUDA) programming model. We show that the parameter estimation, performed through Markov Chain Monte Carlo (MCMC), is accelerated by at least two orders of magnitude, when comparing a single GPU with the respective sequential single-core CPU version. We also illustrate similar speed-up factors (up to 120x) when comparing a multi-GPU with a multi-CPU implementation.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
We report clinical and biochemical finding from three unrelated patients presenting ONCE (Optic Neuropathy, Cardiomyopathy and Encephalopathy with lactic acidosis and combined oxidative ...phosphorylation deficiency) syndrome. Whole‐exome sequencing (WES) of the three patients and the healthy sister of one of them was used to identify the carry gene. Clinical and biochemical findings were used to filter variants, and molecular, in silico and genetic studies were performed to characterize the candidate variants. Mitochondrial DNA (mtDNA) defects involving mutations, deletions or depletion were discarded, whereas WES uncovered a double homozygous mutation in the MTO1 gene (NM_001123226:c.1510C>T, p.R504C, and c.1669G>A, p.V557M) in two of the patients and the homozygous mutation p.R504C in the other. Therefore, our data confirm p.R504C as pathogenic mutation responsible of ONCE syndrome, and p.V557M as a rare polymorphic variant.
The R504C mutation in MTO1 gene is the responsible of ONCE syndrome (Optic Neuropathy, Cardiomyopathy and Encephalopathy with lactic acidosis and combined OXPHOS deficiency) and V557M is a rare polymorphic variant.
The Cadiz Contourite Channel is the largest and most prominent contourite channel in the middle slope of the Gulf of Cadiz, and is known to channelise the southern branch of the Lower Core of ...Mediterranean Outflow Water (MOW) as it flows westwards from the Gibraltar Gateway. The channel lies in water depth between 650 and 1500m, is 150km long, 2–12km wide, up to 120m deep, and broadly s-shaped in plan view. It has several associated subparallel marginal channels and shorter spillover channel segments. Its geometry is controlled by the interaction of a strong bottom current with the seafloor morphology, affected by neotectonic deformation and diapiric intrusion. Bottom photographs and dredge hauls reveal a channel floor shaped by high-energy flow, in places with bare rock, boulders and gravel, and elsewhere covered with sandy contourites. The rocky substrate and derived clasts are formed of authigenic iron-rich carbonates, testifying the high degree of fluid escape from adjacent diapiric ridges and mud volcanoes. The sandy substrate shows a wide range of current-induced bedforms including small, straight-crested ripples, large sinuous sand waves and dunes (wavelength 3.5–5m, height 0.3–0.9m), weak surface lineation on sands, and aligned gravel stringers and deep erosive scours around large boulders. Bedform orientation indicates flows directed to the south/south-west (main channel) and west (spillover channel), which can be related to MOW bottom currents, and current velocities that vary between about 0.2 and 0.8ms−1, even in the same channel location. However, current vane orientation was clearly responding, at least in part, to tidal effects and periodicity in the Gulf of Cadiz at the time the photographs were taken. Maximum current velocities are achieved by a combination of barotropic and internal tides (probably generated at the continental slope) that reinforce the normal MOW flow. In addition, meteorologically-induced internal waves with periods shorter than tidal ones may exert an even greater influence on current intensity, especially when they occur at times of sudden changes of meteorological forcing. This effect further influences MOW variability. In all cases, the funnelling effect of the Cadiz Channel amplifies tidal or meteorologically-induced bottom currents.
•We studied a contourite channel shaped by bottom currents.•Mediterranean Outflow Water. Middle slope of the Gulf of Cadiz•This paper contributes to the better understanding of clean sandy contourites.•Internal tides (IT) and meteorologically-induced internal waves (IW) over the slopes•No previous direct observations of the effects of IT and IW in contourite channels
► API X52 steel corrosion in H
2SO
4 was evaluated with EIS. ► The corrosion inhibition efficiency of six thiadiazole compounds were evaluated. ► The alkyl chain length of these compounds was related ...to their corrosion IE. ► 2-Amino-5-undecyl-1,3,4-thiadiazole, IC-11, was the best inhibitor at 100
ppm. ► IC-11 corrosion inhibition lasted over 90% for at least 720
h.
The corrosion inhibition efficiency of 2 amino 5 alkyl 1,3,4 thiadiazole compounds with different alkyl chain lengths, namely: 2 ethyl, 3
n propyl, 5
n penthyl, 7 hepthyl, 11 undecyl and 13 tridecyl, was evaluated in the system steel/1
M H
2SO
4. These compounds were synthesized, characterized by FT-IR and NMR spectroscopy analysis and evaluated using electrochemical impedance spectroscopy and SEM analysis. The results showed that the inhibition mechanism involves blockage of the steel surface by the inhibitor molecules by a Langmuir-type adsorption process and that the alkyl chain length plays an important role in the inhibition efficiency of the synthesized inhibitors.
Here we put forward a mathematical model describing the response of low-grade (WHO grade II) oligodendrogliomas (LGO) to temozolomide (TMZ). The model describes the longitudinal volumetric dynamics ...of tumor response to TMZ of a cohort of 11 LGO patients treated with TMZ. After finding patient-specific parameters, different therapeutic strategies were tried computationally on the 'in-silico twins' of those patients. Chemotherapy schedules with larger-than-standard rest periods between consecutive cycles had either the same or better long-term efficacy than the standard 28-day cycles. The results were confirmed in a large trial of 2000 virtual patients. These long-cycle schemes would also have reduced toxicity and defer the appearance of resistances. On the basis of those results, a combination scheme consisting of five induction TMZ cycles given monthly plus 12 maintenance cycles given every three months was found to provide substantial survival benefits for the in-silico twins of the 11 LGO patients (median 5.69 years, range: 0.67 to 68.45 years) and in a large virtual trial including 2000 patients. We used 220 sets of experiments in-silico to show that a clinical trial incorporating 100 patients per arm (standard intensive treatment versus 5 + 12 scheme) could demonstrate the superiority of the novel scheme after a follow-up period of 10 years. Thus, the proposed treatment plan could be the basis for a standardized TMZ treatment for LGO patients with survival benefits.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Ni-Mo2C particles supported over hydroxyapatite were synthesized as potential catalysts to hydrogen production applications due their physiochemical properties observed in characterization results, ...this favorable for biomass gasification. Mo2C particles doped with Ni were synthesized by temperature programmed reaction method at 900 °C under hydrogen reducing atmosphere. Hydroxyapatite support was obtained from thermal extraction of bovine bones, in a temperature range from 700 to 900 °C. Ni-Mo2C impregnation over hydroxyapatite support was made by incipient humidity method. X-ray diffraction analysis determined crystallographic phases of β-Mo2C, NiC and hydroxyapatite. Though, bone organic matter degradation was observed by X-ray diffraction and confirmed by Infrared Spectroscopy with Fourier Transform (FTIR) the final structure of hydroxyapatite was maintained. Finally, textural properties analysis of support showed an increase in porosity structure with the increment of temperature. β-Mo2C and NiC were obtained with similar catalytic activity than noble metals, also nickel improves hydrocarbons bonds rupture. Hydroxyapatite showed high stability and porosity at elevated temperatures attributable to synthesis conditions.
•NiMo2C/hydroxyapatite catalysts were prepared for hydrogen production applications.•β-molybdenum carbide was obtained with different wt% Ni loading.•Porous and stable hydroxyapatite structure at high temperature was observed.•NiMo2C was successfully impregnated over hydroxyapatite support.
Background & Aims There is not a consensus on the best irrigation approach for super-high density (SHD) olive orchards. Our aim was to design and test a regulated deficit irrigation (RDI) strategy ...for a sustainable balance between water saving, tree vigour and oil production. Methods We tested our RDI strategy for 3 years in an 'Arbequina' orchard with 1,667 trees ha⁻¹. Two levels of irrigation reduction were applied, 60RDI and 30RDI, scaled to replacing 60 % and 30 %, respectively, of the of irrigation needs (IN). We also had a full irrigation (FI) treatment as control, with IN totalling 4,701 m³ ha⁻¹ Results The 30RDI treatment showed the best balance between water saving, tree vigour and oil production. With a yearly irrigation amount (IA) of 1,366 m³ ha⁻¹, which meant 72 % water saving as compared to FI, the reduction in oil yield was 26 % only. Conclusions Our results, together with recent knowledge on the effect of water stress on fruit development, allowed us to suggest a potentially improved RDI strategy for which a total IA of ca. 2,100 m³ ha⁻¹ was calculated. Both some management details and the benefits of this suggested RDI strategy are still to be tested.
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