The folding of RNA and DNA strands plays crucial roles in biological systems and bionanotechnology. However, studying these processes with high-resolution numerical models is beyond current ...computational capabilities due to the timescales and system sizes involved. In this article, we present a new coarse-grained model for investigating the folding dynamics of nucleic acids. Our model represents three nucleotides with a patchy particle and is parameterized using well-established nearest-neighbor models. Thanks to the reduction of degrees of freedom and to a bond-swapping mechanism, our model allows for simulations at timescales and length scales that are currently inaccessible to more detailed models. To validate the performance of our model, we conducted extensive simulations of various systems: We examined the thermodynamics of DNA hairpins, capturing their stability and structural transitions, the folding of an MMTV pseudoknot, which is a complex RNA structure involved in viral replication, and also explored the folding of an RNA tile containing a k-type pseudoknot. Finally, we evaluated the performance of the new model in reproducing the melting temperatures of oligomers and the dependence on the toehold length of the displacement rate in toehold-mediated displacement processes, a key reaction used in molecular computing. All in all, the successful reproduction of experimental data and favorable comparisons with existing coarse-grained models validate the effectiveness of the new model.
We developed genetically-encoded fluorescent sensors based on Förster Resonance Energy Transfer to monitor phosphatidic acid (PA) fluctuations in the plasma membrane using Spo20 as PA-binding motif. ...Basal PA levels and phospholipase D activity varied in different cell types. In addition, stimuli that activate PA phosphatases, leading to lower PA levels, increased lamellipodia and filopodia formation. Lower PA levels were observed in the leading edge than in the trailing edge of migrating HeLa cells. In MSC80 and OLN93 cells, which are stable cell lines derived from Schwann cells and oligodendrocytes, respectively, a higher ratio of diacylglycerol to PA levels was demonstrated in the membrane processes involved in myelination, compared to the cell body. We propose that the PA sensors reported here are valuable tools to unveil the role of PA in a variety of intracellular signaling pathways.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
The present study discuss the effects systematic additions of boron (up to 1.197 wt%) on the microstructure, bulk hardness and abrasive wear of a 17Cr– 3C–1Ni–1Mo white cast iron. The alloys were ...melted in an open induction furnace and cast into 25.4 mm × 12.5 mm cross-section bars. Characterization was carried out by optical and electronic microscopy, energy dispersive spectroscopy, and X-ray diffraction in the as-cast conditions and after a destabilization heat treatment. Hardness was also measured in both conditions. The results show that, boron addition produced a considerable increase of the carbide volume fraction from 27.1 to 53.84% (percentage by volume) and promotes the transition from the Cr rich M7C3 eutectic carbides to the lower C and Cr content M23(C,B)6carbide. However, the hardness values of the experimental alloys were not affected by this transition, and thus, the hardness values increased with the boron content due to a higher carbide volume fraction and the strengthening of the iron matrix reaching a maximum value of 767 HV for the higher B content. Likewise, a secondary hardening effect was produced by the destabilization heat treatment, increasing the hardness values of the different alloys. However, as the boron content increased, this hardening effect becomes less significant. Abrasive wear test were consistent with the hardness values in the as-cast condition by decreasing the wear losses with the increase in B for high and low loads. Similarly, for the destabilized irons, which exhibited higher harness values, a decrease in the wear volume losses were observed for B contents up to 0.598 wt% and the wear losses increased with the increase in applied load.
In the case of the heat treated 1.197 wt% B added iron, the wear losses were significantly affected by the applied load during the wear tests. For this alloy, a volume lost of 0.639 mm3 was observed for the test with 54 N a load, which corresponds to the lower value obtained for any B content and experimental condition, while in the case of the test performed with 130 N a relatively high volume lost of 1.319 mm3 was measured which is considerably higher compared with the lower boron alloys in the same condition. This behavior was attributed to the massive carbide cracking observed after heat treatment promoting the carbide detachment during the test with 130 N of load.
From the author's review of the literature, the effect of such a high boron addition on the microstructure and wear behavior have never been performed or published for high chromium white cast irons. And the based in the experimental results of the present study, the addition up to 1.197%wt boron in the as cast condition represents an effective way to increase the hardness and wear resistance of these kind of alloys in the as-cast condition suppressing the destabilization heat treatment.
•Hardness values are increased with boron addition.•A secondary hardening effect is produced by destabilization heat treatment.•Boron addition in the as-cast condition considerably reduces the wear losses•Destabilized irons exhibit higher harness values and lower wear losses•High B alloying is suitable for low-impact applications and high wear resistance
Diabetic nephropathy and inflammation Montserrat B Duran-Salgado Alberto F Rubio-Guerra
World journal of diabetes,
06/2014, Letnik:
5, Številka:
3
Journal Article
Odprti dostop
Diabetic nephropathy(DN) is the leading cause of end-stage renal failure worldwide. Besides, diabetic nephropathy is associated with cardiovascular disease, and increases mortality of diabetic ...patients. Several factors are involved in the pathophysiology of DN, including metabolic and hemodynamic alterations, oxidative stress, and activation of the renin-angiotensin system. In recent years, new pathways involved in the development and progression of diabetic kidney disease have been elucidated; accumulated data have emphasized the critical role of inflammation in the pathogenesis of diabetic nephropathy. Expression of cell adhesion molecules, growth factors, chemokines and pro-inflammatory cytokines are increased in the renal tissues of diabetic patients, and serum and urinary levels of cytokines and cell adhesion molecules, correlated with albuminuria. In this paper we review the role of inflammation in the development of diabetic nephropathy, discussing some of the major inflammatory cytokines involved in the pathogenesis of diabetic nephropathy, including the role of adipokines, and take part in other mediators of inflammation, as adhesion molecules.
In the current context of emerging drug-resistant fungal pathogens such as Candida albicans and Candida parapsilosis, discovery of new antifungal agents is an urgent matter. This research aimed to ...evaluate the antifungal potential of 2-chloro-N-phenylacetamide against fluconazole-resistant clinical strains of C. albicans and C. parapsilosis. The antifungal activity of 2-chloro-N-phenylacetamide was evaluated in vitro by the determination of the minimum inhibitory concentration (MIC), minimum fungicidal concentration (MFC), inhibition of biofilm formation and its rupture, sorbitol and ergosterol assays, and association between this molecule and common antifungal drugs, amphotericin B and fluconazole. The test product inhibited all strains of C. albicans and C. parapsilosis, with a MIC ranging from 128 to 256 µg.mL-1, and a MFC of 512-1,024 µg.mL-1. It also inhibited up to 92% of biofilm formation and rupture of up to 87% of preformed biofilm. 2-chloro-N-phenylacetamide did not promote antifungal activity through binding to cellular membrane ergosterol nor it damages the fungal cell wall. Antagonism was observed when combining this substance with amphotericin B and fluconazole. The substance exhibited significant antifungal activity by inhibiting both planktonic cells and biofilm of fluconazole-resistant strains. Its combination with other antifungals should be avoided and its mechanism of action remains to be established.
To gain insight into the possible origin of the gold used in the production of tesserae containing gold leaf less than 0.5 µm thick placed between two layers of glass, we propose a non-destructive ...synchrotron radiation (SR) XRF protocol based on sequential analysis under optimised analytical conditions. Using this protocol, trace element analysis is achieved with detection limits of 1–6 mg/kg. As Pt and Au have adjacent fluorescence energies, we tested the most challenging situation, when Pt is present in very low concentrations in gold. Data obtained by double-dispersive XRF (D
2
XRF) and µXRF for fourth–ninth-century mosaics decorating nine Eastern and Western religious buildings show that the Eastern and Western tesserae are made from different alloys. However, these alloys are identical to those used to make gold leaf for gilding, because plastic deformation requires the use of gold alloys with high ductility and malleability. Although trace element composition of gold used in the concerned period is only available for coins, by comparing the amounts of Pt contained in the tesserae and in the coins we show that Roman tesserae are made from Roman gold, as described in the documentary sources. We observe for the Byzantine period the use of a Byzantine gold and of gold supposedly from different stages of recycling, and we suggest the use of Umayyad and Abbasid gold for the production of Islamic tesserae.
Graphical Abstract
Oral squamous cell carcinoma (OSCC) remains a challenge for head and neck surgeons, with low 5-year survival rates despite improvements in diagnostic techniques and therapies. This retrospective ...observational study was performed to evaluate the epidemiology and risk factors in a cohort of 666 patients with invasive OSCC over a 39-year period. Risk factors assessed were age, sex, toxic habits, premalignant lesions, tumour location and size, and neck involvement, and pathological factors such as surgical margins, tumour thickness, perineural invasion, and bone invasion. These factors were analysed over time, and their influence on recurrence and survival rates examined. Results were compared with those of current epidemiological studies in the literature. This series showed a tendency to diagnosis at older ages (P<0.001) and decreased differences in sex distribution (P<0.001) over time. Regarding risk factors, tobacco and alcohol drinking increased significantly in females, but remained stable in males. Forty percent of the patients developed recurrences during follow-up; the relapse rate did not improve over time (45.6% in the 1980s to 36.1% in 2010–2017). The 5-year survival rate also remained stable over time, ranging from 62.7% (1980s) to 71.7% (2010–2017). This epidemiological study analysed trends across four decades in a stable cohort, with results that may be extrapolated to the populations of European countries. The results confirmed that recurrence rates and survival rates have not improved over time, despite better surgical treatments and new therapies. Further studies are needed to improve knowledge about genetics and tumour behaviour in oral cancer.
Photovoltaic solar energy has been explored as an energy solution to the decline of energy production, as well as environmental concerns. However, generate electricity through the sun still ...considered uncompetitive freight to other sources, cause it presents low efficiency and high production cost. In attempt to make it more attractive from a financial point view, solar trackers has been used to increase the photovoltaic systems efficiency. Considering its facts, this paper aims to perform a comparative study between a static photovoltaic solar panel and a one-axis mobility panel, installed in the city of Mossoró/RN. The city in study is located in the Brazilian semiarid, under high solar radiation levels, in a dry climate and hot region, reaching high temperatures during the day. After assembly the proposed systems, were performed operating analysis and performance comparative study between the static and mobile systems, which allowed to conclude that the panel using the sun tracking showed a low average gain in power generated relative to the fixed panel to the region where the systems installed.
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