1,721,100 research outputs found
Fabrication of an electro-optical Bragg modulator based on plasma dispersion effect in silicon
No full textIn this paper we present a design as well as the fabrication procedure of a new type of electro-optical modulator based on plasma dispersion effect. The device consists from a regular single mode silicon waveguide and periodically patterned electrodes made out an indium thin oxide (ITO) located along both sides of the optical core through which the photonic signal is propagating. By applying voltage on the electrodes a periodic change in the free electrons is occurred along the optical core. This change affects both the imaginary and real part of the refractive index resulting in the generation of periodic change in the refractive index that creates an effective Bragg reflector. Different fabrication strategies are reported
Cross talk between cancer and immune cells: exploring complex dynamics in a microfluidic environment
No full textThe reconstitution of a complex microenvironment on microfluidic chips is one of the cornerstones to demonstrate the improved flexibility of these devices with respect to macroscale in vitro approaches. In this work, we realised an on-chip model to investigate the interactions between cancer and immune system. To this end, we exploited mice deficient (Knock Out, KO) for interferon regulatory factor 8 (IRF-8), a transcription factor essential for the induction of competent immune responses, to investigate how IRF-8 gene expression contributes to regulate immune and melanoma cells crosstalk. In vivo, IRF-8 KO mice are highly permissive to B16 melanoma growth due to failure of immune cells to properly exert immunosurveillance. B16 cells and immune cells isolated from the spleen of wild type (WT) and IRF-8 KO mice were co-cultured for one week in a PDMS platform and monitored by fluorescence microscopy and time-lapse recordings. We observed that WT spleen cells migrated through microchannels connecting the culturing chambers towards B16 cells and tightly interacted with tumor cells, forming clusters of activation. In contrast, IRF-8 KO immune cells poorly interacted with melanoma cells. In parallel, B16 cells were more attracted towards microchannels, acquiring a more invasive behaviour in the presence of IRF-8 KO spleen cells, with respect to WT cells. Our results strongly confirm the in vivo observations and highlight the value of on-chip co-culture systems as a useful in vitro tool to elucidate the reciprocal interactions between cancer cells and host immune system, with relevant impact in the development of more effective anti-tumor therapeutic strategies
Structural analysis of intrinsically disordered proteins: computer atomistic simulation
Full text linkIntrinsically disordered proteins (IDPs) are biomolecules that do not have a definite 3D structure; their role in the biochemical network of a cell relates to their ability to switch rapidly among different secondary and tertiary structures. For this reason, applying a simulation computer program to their structural study turns out to be problematic, as their dynamical simulation cannot start from a known list of atomistic positions, as is the case for globular proteins that do crystallize and that one can analyse by X-ray spectroscopy to determine their structure. We have established a method to perform a computer simulation of these proteins, apt to gather statistically significant data on their transient structures. The only required input to start the procedure is the primary sequence of the disordered domains of the protein, and the 3D structure of the ordered domains, if any. For a fully disordered protein the method is as follows: (a) The first step is the creation of a multi-rod-like configuration of the molecule, derived from its primary sequence. This structure evolves dynamically in vacuo or in an implicit model of solvent, until its gyration radius - or any other measure of the overall configuration of the molecule - reaches the experimental average value; at this point, one may follow two different paths. (b1) If the study focuses on transient secondary structures of the molecule, one puts the structure obtained at the end of the first step in a box containing solvent molecules in explicit implementation, and a standard molecular dynamics simulation follows. (b2) If the study focuses on the tertiary structure of the molecule, a larger sampling of the phase space is required, with the molecule moving in very large and diverse regions of the phase space. To this end, the structure of the IDP is let evolve dynamically in an implicit solvent using metadynamics, an algorithm that keeps track of the regions of the phase space already sampled, and forces the system to wander in further regions of the phase space. (c) One can increase the accuracy of the statistical information gathered in both cases by fitting, where available, experimental data of the protein. In this step one extracts an ensemble of ’best’ conformers from the pool of all configurations produced in the simulated dynamics. One derives this ensemble by means of an ensemble optimization method, implementing a genetic algorithm. We have applied this procedure to the simulation of tau, one of the largest fully disordered proteins, which is involved in the development of Alzheimer’s disease and of other neurodegenerative diseases. We have combined the results of our simulation with small-angle X-ray scattering experimental data to extract from the dynamics an optimized ensemble of most probable conformers of tau. The method can be easily adapted to IDPs entailing ordered domains
The Microstrain-Doping Phase Diagram of the Iron Pnictides: Heterostructures at Atomic Limit
No full textThe 3D phase diagram of iron pnictides where the critical temperature depends on charge density and microstrain in the active FeAs layers is proposed. The iron pnictides superconductors are shown to be a practical realization of a heterostructure at the atomic limit made of a superlattice of FeAs layers intercalated by spacer layers. We have focussed our interest on the A(1-x) B (x) Fe(2)As(2) (122) families and we show that FeAs layers have a tensile microstrain due to the misfit strain between the active layers and the spacers. We have identified the critical range of doping and microstrain where the critical temperature gets amplified to its maximum value
Wet sample confinement by superhydrophobic patterned surfaces for combined X-ray fluorescence and X-ray phase contrast imaging
No full textIn this work we propose a wet sample handling technique which enables the simultaneous collection of X-ray fluorescence (XRF) spectra and X-ray phase contrast imaging (XPCI) using a few microliters drop confined on a superhydrophobic surface. To this purpose, we fabricated and tested a superhydrophobic patterned surface entailing an hydrophilic region which leads to pinning of the drop, enabling X-ray beam effortless alignment and measuring in liquid phase. Our technique allows to acquire capillary-free XRF spectra, resulting in a significant fluorescence detection gain, which is particularly interesting for light elements. Simultaneous XPCI provides sample geometry assuring a fine control of the experimental conditions and allowing real time monitoring of the drop during measurements. As an additional advantage – after solvent evaporation – the solute is deposited on a precise spot, greatly increasing its concentration allowing further measurements, such as X-ray microanalysis and X-ray diffraction.
These results could have potential applications in the study of blood proteins, such as ferritin and low density lipoprotein, which are usually available in very limited quantity
Possible relationship between Al/ferritin complex and Alzheimer's disease
No full textObjectives
Ferritin is the main iron-storage protein capable of containing thousands of iron atoms. However, ferritin can bind in vitro other atoms such as aluminum and it has been shown that also in vivo atoms other than iron, as aluminum and zinc, are present in large amounts in ferritin.
Since aluminum appears to be involved in the development of Alzheimer's disease, in the present study the specific content of aluminum in ferritin of Alzheimer's patients was analyzed and compared with other control groups.
Design and methods
The content of Fe, Al and Zn of blood ferritin was measured by mass spectrometry in patients with Alzheimer's disease and compared with other clinical and control groups.
Results
The results obtained confirm the hypothesis of a functional role of ferritin as a regulatory protein of toxic metals and clearly indicate that ferritin from Alzheimer's patients has a content of aluminum higher than that of controls.
Conclusions
The specific aluminum content of ferritin seems to be related to different disease stages of Alzheimer's disease. This result confirms the hypothesis of aluminum as a possible factor inducing the Alzheimer's disease and opens the ways to possible new diagnostic tests
Transient tertiary structures in tau, an intrinsically disordered protein
No full textAn intrinsically disordered protein (IDP) does not have a definite 3D structure, and because of its highly flexible nature it evolves dynamically in very large and diverse regions of the phase space. A standard molecular dynamics run can sample only a limited region of the latter; even though this kind of simulation may be effective in sampling local temporary secondary structures, it is not sufficient to highlight properties that require a larger sampling of the phase space to be detected, like transient tertiary structures. But if the structure of an IDP is dynamically evolved using metadynamics (an algorithm that keeps track of the regions of the phase space already sampled), the system can be forced to wander in a much larger region of the phase space. We have applied this procedure to the simulation of tau, one of the largest totally disordered proteins. Combining the results of the simulation with small-angle X-ray scattering yields a significant improvement in the sampling of the phase space in comparison with standard molecular dynamics, and provides evidence of extended hairpin- and paperclip-like transient tertiary structures of the molecule. The more persistent tertiary pattern is a hairpin folding encompassing part of the N-terminal, the proline-rich domain, the former repeat and a functionally relevant part of the second repeat
Thermal compaction of the intrinsically disordered protein tau: entropic, structural, and hydrophobic factors
No full textGlobular denatured proteins have structural properties similar to those of random coils. Experiments on denatured proteins have shown that when the temperature is increased thermal compaction may take place, resulting in a reduction of their radius of gyration Rg to range between 5% and 35% of its initial value. This phenomenon has been attributed to various causes, namely entropic, hydrophobic, and structural factors. The intrinsically disordered protein tau, which helps in nucleating and stabilizing microtubules in the axons of the neurons, also undergoes a relevant compaction process: when its temperature is increased from 293 K to 333 K its gyration radius decreases by 18%. We have performed an atomistic simulation of this molecule, at the lowest and highest temperatures of the mentioned interval, using both standard molecular dynamics and metadynamics, in parallel with small-angle X-ray scattering experiments. Using the fit of the experimental data and a genetic algorithm to select the most probable configurations among those produced in both atomistic simulations (standard MD and metadynamics), we were able to compute relevant changes, related to the temperature increase, in the average angles between residues, in the transient secondary structures, in the solvent accessible surface area, and in the number of intramolecular H-bonds. The analysis of the data showed how to decompose the compaction phenomenon into three contributions. An estimate of the entropic contribution to the compaction was obtained using the changes in the mean values of the angles between contiguous residues. The computation of the solvent accessible surface at the two temperatures allowed an estimation of the second factor contributing to the compaction, namely the increase in the hydrophobic interaction. We also measured the change in the average number of residues temporarily being in α-helices, 3-helices, PP II helices, β-sheets and β-turns. Those changes in the secondary structure population produce a reduction in the contour length of the protein, yielding a structural contribution to the reduction of Rg. This analysis shows that in tau the entropic factor accounts for about 60% of the compaction, the hydrophobic factor for about 25%, and the change in the secondary structure for about 15%
Clinical Correlates of In-Hospital Mortality in Patients Undergoing Inferior Vena Cava Filter Placement for Acute Deep Vein Thrombosis
Full text linkBackground: It is reasonable to place an Inferior Vena Cava Filter (IVCF) when an acute deep vein thrombosis (DVT) of the lower limbs occurs in a patient with absolute contraindication to therapeutic anticoagulation. An additional potential reason for placing an IVCF is the need to stop therapeutic anticoagulation in a patient with acute DVT who must undergo urgent non-deferrable surgery. However, IVCFs are often used outside of such established indications and many authors argue about their actual utility, especially in terms of survival. In this retrospective study, we looked for clinical correlates of in-hospital mortality among patients who underwent IVCF placement, limiting our analysis to the cases for which a correct indication to IVCF placement existed. Methods: We retrospectively analyzed the electronic database of our University Hospital, searching for consecutive hospitalized patients who had acute DVT and underwent IVCF placement because of an established contraindication to therapeutic anticoagulation and/or because it was necessary to stop anticoagulation due to urgent surgery. The search covered the period between 1 January 2010 and 31 December 2020. Results: The search resulted in the identification of 168 individuals. An established contraindication to therapeutic anticoagulation was present in 116 patients (69.0%), while urgent non-deferrable surgery was the reason for IVCF placement in 52 patients (31.0%). A total of 24 patients (14.3%) died during the same hospital stay in which the IVCF was placed. Mortality rate was significantly higher in patients with a contraindication to anticoagulation than in patients who underwent IVCF placement because of urgent surgery (19.0% vs. 3.8%, OD 5.85 vs. 0.17). In-hospital mortality was also significantly higher among patients with chronic kidney disease and those who needed blood cell transfusion during hospitalization. Conclusions: This study provides novel information on clinical correlates of in-hospital mortality among patients with acute DVT who undergo IVCF. Prospective observational studies are needed to substantiate these findings
Exploring the post-mortem interval through blood biochemistry: a preliminary case series study and review of the literature
No full textPost-mortem biochemistry can be included among the methods reported in the literature to investigate the time since death. To address this issue, we collected blood samples from hospitalized patients who died in the presence of health personnel. Samples were collected 20 min after death and every 6 h until 24 h post-mortem, with the last Ante Mortem (A.M.) sample also included in the analyses. Each sample was immediately centrifuged and analyzed. Our preliminary results indicate a significant and consistent increase in phosphokinase (CPK) and lactodehydrogenase (LDH) blood levels, with low interindividual variation among subjects. Interestingly, the measured time trend follows an exponential function, characterized by a time-dependent growth rate. While a larger sample size is needed to confirm our preliminary findings, our results suggest that CPK and LDH blood levels could be valuable parameters for determining the post-mortem interval. Furthermore, our data were systematically compared to those reported in the literature, which was carefully reviewed
- …
