Melatonin Induces Apoptosis and Modulates Cyclin Expression and MAPK Phosphorylation in Pancreatic Stellate Cells Subjected to Hypoxia

In certain diseases of the pancreas, pancreatic stellate cells form an important part of fibrosis and are critical for the development of cancer cells. A hypoxic condition develops within the tumor, to which pancreatic stellate cells adapt and are able to proliferate. The consequence is the growth of the tumor. Melatonin, the product of the pineal gland, is gaining attention as an agent with therapeutic potential against pancreatic cancers. Its actions on tumor cells lead, in general, to a reduction in cell viability and proliferation. However, its effects on pancreatic stellate cells subjected to hypoxia are less known. In this study, we evaluated the actions of pharmacological concentrations of melatonin (1 mM–1 µM) on pancreatic stellate cells subjected to hypoxia. The results show that melatonin induced a decrease in cell viability at the highest concentrations tested. Similarly, the incorporation of BrdU into DNA was diminished by melatonin. The expression of cyclins A and D also was decreased in the presence of melatonin. Upon treatment of cells with melatonin, increases in the expression of major markers of ER stress, namely BIP, phospho-eIF2α and ATF-4, were detected. Modulation of apoptosis was noticed as an increase in caspase-3 activation. In addition, changes in the phosphorylated state of p44/42, p38 and JNK MAPKs were detected in cells treated with melatonin. A slight decrease in the content of α-smooth muscle actin was detected in cells treated with melatonin. Finally, treatment of cells with melatonin decreased the expression of matrix metalloproteinases 2, 3, 9 and 13. Our observations suggest that melatonin, at pharmacological concentrations, diminishes the proliferation of pancreatic stellate cells subjected to hypoxia through modulation of cell cycle, apoptosis and the activation of crucial MAPKs. Cellular responses might involve certain ER stress regulator proteins. In view of the results, melatonin could be taken into consideration as a potential therapeutic agent for pancreatic fibrosis.     

Comparative study of layer-by-layer deposition techniques for poly(sodium phosphate) and poly(allylamine hydrochloride)

An inorganic short chain polymer, poly(sodium phosphate), PSP, together with poly(allylamine hydrochloride), PAH, is used to fabricate layer-by-layer (LbL) films. The thickness, roughness, contact angle, and optical transmittance of these films are studied depending on three parameters: the precursor solution concentrations (10^-3 and 10^-4 M), the number of bilayers deposited (20, 40, 60, 80, and 100 bilayers), and the specific technique used for the LbL fabrication (dipping or spraying). In most cases of this experimental study, the roughness of the nanofilms increases with the number of bilayers. This contradicts the basic observations made in standard LbL assemblies where the roughness decreases for thicker coatings. In fact, a wide range of thickness and roughness was achieved by means of adjusting the three parameters mentioned above. For instance, a roughness of 1.23 or 205 nm root mean square was measured for 100 bilayer coatings. Contact angles close to 0 were observed. Moreover, high optical transmittance is also reported, above 90%, for 80 bilayer films fabricated with the 10^-4 M solutions. Therefore, these multilayer structures can be used to obtain transparent superhydrophilic surfaces.     

Evolution of a Transition State: Role of Lys100 in the Active Site of Isocitrate Dehydrogenase

An active site lysine essential to catalysis in isocitrate dehydrogenase (IDH) is absent from related enzymes. As all family members catalyze the same oxidative β‐decarboxylation at the (2R)‐malate core common to their substrates, it seems odd that an amino acid essential to one is not found in all. Ordinarily, hydride transfer to a nicotinamide C4 neutralizes the positive charge at N1 directly. In IDH, the negatively charged C4‐carboxylate of isocitrate stabilizes the ground state positive charge on the adjacent nicotinamide N1, opposing hydride transfer. The critical lysine is poised to stabilize—and perhaps even protonate—an oxyanion formed on the nicotinamide 3‐carboxamide, thereby enabling the hydride to be transferred while the positive charge at N1 is maintained. IDH might catalyze the same overall reaction as other family members, but dehydrogenation proceeds through a distinct, though related, transition state. Partial activation of lysine mutants by K⁺ and NH₄⁺ represents a throwback to the primordial state of the first promiscuous substrate family member.     

Ring Opening of Decalin Over Zeolite-Supported Iridium Catalysts

Selective ring opening of decalin was investigated over various metal-modified zeolites in order to shed light on the key parameters affecting the selectivity to ring-opening products at low extent of cracking reactions. Ir-modified zeolites H-Y and H-Beta having different concentration and strength of acid sites were studied in a batch reactor at 250–310 °C and 20–60 bar H₂ and their performance was compared with that of Pt-modified zeolites. The concentration of Brønsted acid sites, reaction temperature and hydrogen pressure were shown to be the crucial reaction parameters. To obtain high selectivity to formation of ring-opening products from decalin, mildly acidic Ir-modified Beta was the best choice when the reaction was carried out at temperature of 270 °C or lower and at H₂ pressure of 60 bar. Under these conditions the selectivity and yield of ring-opening products exceeded 65 and 60%, respectively.     

Study of the selective catalytic reduction of NOx on an efficient Fe/HBEA zeolite catalyst for heavy duty diesel engines

The present paper addresses the removal of NO_x from the exhaust of heavy duty vehicles using the SCR technique. The studies were conducted with a highly active H-BEA zeolite exhibiting a molar Si/Al ratio of 12.5 and a Fe load of 1.0 wt.% (1Fe/HBEA). The pronounced efficiency of 1Fe/HBEA is reflected by the apparent turnover frequency being superior to traditional V₂O₅/WO₃/TiO₂. The nature of the Fe sites was investigated with high resolution transmission electron microscopy (HRTEM), ⁵⁷Fe Mössbauer spectroscopy and powder X-ray diffraction (PXRD). In connection with previous examinations it is deduced that the iron sites represent octahedrally coordinated high spin Fe³⁺ cations. Furthermore, highly dispersed species, which are the most active sites, are supposed to be paramagnetic, while oligomeric and particulate structures indicate superparamagnetic behaviour.The practical evaluation of the 1Fe/HBEA catalyst was systematically carried out including laboratory studies of granulated powder and honeycomb samples as well as engine bench tests. For the latter studies a coated honeycomb prototype was employed showing very similar efficiency as referred to a commercial V₂O₅/WO₃/TiO₂ pattern.Furthermore, 1Fe/HBEA exhibits pronounced hydrothermal stability after aging at 550 °C which represents an elevated exhaust temperature of heavy duty vehicles. The aging caused no change in fast SCR, i.e. when a c(NO₂)/c(NO_x) ratio of 0.5 was used, and only minor decline in standard SCR. The slight aging effect is mainly referred to little decrease in BET surface area and NH₃ uptake, respectively. PXRD indicated maintenance of the BEA structure, whereas ²⁷Al nuclear magnetic resonance spectroscopy showed removal of some Al from the zeolite framework. Contrary, UV–vis spectroscopy evidenced no effect of hydrothermal aging on the composition of the Fe sites. Finally, the catalyst also maintained its efficiency after SO₂ aging at 300 °C. Diffuse reflectance infrared Fourier transform spectroscopic studies showed adsorption of molecular SO₂ on the zeolite substrate releasing already at about 400 °C.     

Remote internet access to advanced analytical facilities: a new approach with web-based services

Over the past decade, the increasing availability of the World Wide Web has held out the possibility that the efficiency of scientific measurements could be enhanced in cases where experiments were being conducted at distant facilities. Examples of early successes have included X-ray diffraction (XRD) experimental measurements of protein crystal structures at synchrotrons and access to scanning electron microscopy (SEM) and NMR facilities by users from institutions that do not possess such advanced capabilities. Experimental control, visual contact, and receipt of results has used some form of X forwarding and/or VNC (virtual network computing) software that transfers the screen image of a server at the experimental site to that of the users' home site. A more recent development is a web services platform called Science Studio that provides teams of scientists with secure links to experiments at one or more advanced research facilities. The software provides a widely distributed team with a set of controls and screens to operate, observe, and record essential parts of the experiment. As well, Science Studio provides high speed network access to computing resources to process the large data sets that are often involved in complex experiments. The simple web browser and the rapid transfer of experimental data to a processing site allow efficient use of the facility and assist decision making during the acquisition of the experimental results. The software provides users with a comprehensive overview and record of all parts of the experimental process. A prototype network is described involving X-ray beamlines at two different synchrotrons and an SEM facility. An online parallel processing facility has been developed that analyzes the data in near-real time using stream processing. Science Studio and can be expanded to include many other analytical applications, providing teams of users with rapid access to processed results along with the means for detailed discussion of their significance.     

Nanodeposition of materials with complex refractive index in long-period fiber gratings

An overlay of higher refractive index than the cladding is deposited on a long-period fiber grating (LPFG). This causes large attenuation-band shifts in the transmission spectrum, which permits the improvement of the sensitivity of the device to ambient and overlay refractive-index changes. To obtain maximum sensitivity for specific overlay and ambient refractive indexes, an optimum overlay thickness (OOT) must be selected. For complex overlay refractive indexes, there is an additional phenomenon of vanishing of the attenuation bands. This occurs for specific overlay-thickness values. The problem is analyzed with a numerical method based on linearly polarized (LP)-mode approximation and coupled-mode theory. Experimental results are contrasted with theoretical ones.     

Algorithms for computing the maximum weight region decomposable into elementary shapes

Motivated by the image segmentation problem, we consider the following geometric optimization problem: Given a weighted n × n pixel grid, find the maximum weight region whose shape is decomposable into a set of disjoint elementary shapes. We give efficient algorithms for several interesting shapes. This is in strong contrast to finding the maximum weight region that is the union of elementary shapes for the corresponding cases—a problem that we prove to be NP-hard. We implemented one of the algorithms and demonstrate its applicability for image segmentation.     

Single-mode—multimode—single-mode and lossy mode resonance-based devices: a comparative study for sensing applications

In this work, a thin-film consisting of 15 bilayers (estimated thickness: 210 nm) of titanium (IV) oxide and poly(sodium 4-styrenesulfonate) is simultaneously deposited onto two optical fiber structures: a single-mode—multimode—single-mode (SMS) device and a lossy mode resonance (LMR)-based device. The performance of both structures, as refractometers and relative humidity sensors, is studied and compared. In both cases, the sensitivity of the LMR-based device (955 nm/RIU and 3.54 nm/RH %, respectively) highly improves the one of the SMS (142 nm/RIU and 0.3 nm/RH %). These facts can be taken into account when developing sensors based on either SMS or LMR technologies.