An all-glass microfluidic network with integrated amorphous silicon photosensors for on-chip monitoring of enzymatic biochemical assay

A lab-on-chip system, integrating an all-glass microfluidics and on-chip optical detection, was developed and tested. The microfluidic network is etched in a glass substrate, which is then sealed with a glass cover by direct bonding. Thin film amorphous silicon photosensors have been fabricated on the sealed microfluidic substrate preventing the contamination of the micro-channels. The microfluidic network is then made accessible by opening inlets and outlets just prior to the use, ensuring the sterility of the device. The entire fabrication process relies on conventional photolithographic microfabrication techniques and is suitable for low-cost mass production of the device. The lab-on-chip system has been tested by implementing a chemiluminescent biochemical reaction. The inner channel walls of the microfluidic network are chemically functionalized with a layer of polymer brushes and horseradish peroxidase is immobilized into the coated channel. The results demonstrate the successful on-chip detection of hydrogen peroxide down to 18 mu M by using luminol and 4-iodophenol as enhancer agent

An algebraic proof of Bogomolov-Tian-Todorov theorem

We give a completely algebraic proof of the Bogomolov-Tian-Todorov theorem. More precisely, we shall prove that if X is a smooth projective variety with trivial canonical bundle defined over an algebraically closed field of characteristic 0, then the L-infinity algebra governing infinitesimal deformations of X is quasi-isomorphic to an abelian differential graded Lie algebra.Comment: 20 pages, amspro

Comment on Maravelis et al. “Accretionary prism-forearc interactions as reflected in the sedimentary fill of southern Thrace Basin (Lemnos Island, NE Greece)”

This contribution is intended to shed light on the content of the paper by Maravelis et al. (2015) about the evolution of the island of Limnos, a small portion of the Cenozoic Thrace Basin (Turkey, Greece and Bulgaria). Although we appreciate their approach to use sediment provenance for paleotectonic reconstructions, we have concerns how this subject has been dealt with and how it is presented to the scientific community. Most of our criticism is about the attempt of Maravelis et al. to provide a review of the evolution of the Thrace Basin using (1) an inadequate dataset, (2) an inadequate area (Limnos is <5 % of the Thrace Basin) and (3) the interpretation provided by different authors in previous papers without properly citing the source of the information

Synthesis, in vitro, and in vivo biological evaluation and molecular docking simulations of chiral alcohol and ether derivatives of the 1,5-diarylpyrrole scaffold as novel anti-inflammatory and analgesic agents.

Following our previous research on anti-inflammatory drugs (NSAIDs), we report here the synthesis of chiral 1,5-diarylpyrroles derivatives that were characterized for their in vitro inhibitory effects toward cyclooxygenase (COX) isozymes. Analysis of enzymatic affinity and COX-2 selectivity led us to the selection of one compound (+/-)-10b that was further tested in vitro in the human whole blood (HWB) and in vivo for its anti-inflammatory activity in mice. The affinity data have been rationalized through docking simulations

Continental rift architecture and patterns of magma migration: a dynamic analysis based on centrifuge models.

Small-scale centrifuge models were used to investigate the role of continental rift structure in controlling patterns of magma migration and emplacement. Experiments considered the reactivation of weakness zones in the lower crust and the presence of magma at Moho depths. Results suggest that surface deformation, which reflects the weakness zone geometry, exerts a major control on patterns of magma migration. In the case of a single rift segment, the experimental lower crust and magma were both transferred in an extension-parallel direction toward the rift flanks. This lateral migration reflected the dominance of far-field stresses over extension-induced buoyancy forces. Local pressure gradients favored the raise of experimental magma in correspondence of marginal grabens. The lateral migration gave rise to major accumulations below the footwall of major boundary faults, providing the magma source able to feed off-axis volcanoes in nature, as inferred for the Main Ethiopian Rift. In the case of two offset rift segments, a major transfer zone developed. This transfer zone was characterized by prominent experimental lower crust doming and strong magma accumulation. Dynamic analysis showed that the transfer zone development caused a strong pressure difference in a rift-parallel direction, which dominated over the farfield thinning. Owing to this pressure gradient, almost all the underplated experimental magma collected below the lower crust dome, suggesting a rift-parallel (extension-orthogonal) migration. This process has a direct relevance for the localization of magmatic activity at transfer zones in natural continental rifts, such as in the Western Branch of the East African Rift System. Copyright 2004 by the American Geophysical Union

Cyclooxygenase-2 inhibitors. 1,5-diarylpyrrol-3-acetic esters with enhanced inhibitory activity toward cyclooxygenase-2 and improved cyclooxygenase-2/cyclooxygenase-1 selectivity.

he important role of cyclooxygenase-2 (COX-2) in the pathogenesis of inflammation and side effect limitations of current COX-2 inhibitor drugs illustrates a need for the design of new compounds based on alternative structural templates. We previously reported a set of substituted 1,5-diarylpyrrole derivatives, along with their inhibitory activity toward COX enzymes. Several compounds proved to be highly selective COX-2 inhibitors and their affinity data were rationalized through docking simulations. In this paper, we describe the synthesis of new 1,5-diarylpyrrole derivatives that were assayed for their in vitro inhibitory effects toward COX isozymes. Among them, the ethyl-2-methyl-5-[4-(methylsulfonyl)phenyl]-1-[3-fluorophenyl]-1H-pyrrol-3- acetate (1d), which was the most potent and COX-2 selective compound, also showed a very interesting in vivo anti-inflammatory and analgesic activity, laying the foundations for developing new lead compounds that could be effective agents in the armamentarium for the management of inflammation and pain

Comparative health technology assessment of robotic-assisted, direct manual laparoscopic and open surgery:a prospective study

Background: Despite many publications reporting on the increased hospital cost of robotic-assisted surgery (RAS) compared to direct manual laparoscopic surgery (DMLS) and open surgery (OS), the reported health economic studies lack details on clinical outcome, precluding valid health technology assessment (HTA). Methods: The present prospective study reports total cost analysis on 699 patients undergoing general surgical, gynecological and thoracic operations between 2011 and 2014 in the Italian Public Health Service, during which period eight major teaching hospitals treated the patients. The study compared total healthcare costs of RAS, DMLS and OS based on prospectively collected data on patient outcome in addition to healthcare costs incurred by the three approaches. Results: The cost of RAS operations was significantly higher than that of OS and DMLS for both gynecological and thoracic operations (p < 0.001). The study showed no significant difference in total costs between OS and DMLS. Total costs of general surgery RAS were significantly higher than those of OS (p < 0.001), but not against DMLS general surgery. Indirect costs were significantly lower in RAS compared to both DMLS general surgery and OS gynecological surgery due to the shorter length of hospital stay of RAS approach (p < 0.001). Additionally, in all specialties compared to OS, patients treated by RAS experienced a quicker recovery and significantly less pain during the hospitalization and after discharge. Conclusions: The present HTA while confirming higher total healthcare costs for RAS operations identified significant clinical benefits which may justify the increased expenditure incurred by this approach

Novel ester and acid derivatives of the 1,5-diarylpyrrole scaffold as anti-inflammatory and analgesic agents. Synthesis and in vitro and in vivo biological evaluation.

A new generation of selective cyclooxygenase-2 (COX-2) inhibitors (coxibs) was developed to circumvent the major side effects of cyclooxygenase-1 (COX-1) and COX-2 inhibitors (stomach ulceration and nephrotoxicity). As a consequence, coxibs are extremely valuable in treating acute and chronic inflammatory conditions. However, the use of coxibs, such as rofecoxib (Vioxx), was discontinued because of the high risk of cardiovascular adverse events. More recent clinical findings highlighted how the cardiovascular toxicity of coxibs could be mitigated by an appropriate COX-1 versus COX-2 selectivity. We previously reported a set of substituted 1,5-diarylpyrrole derivatives, selective for COX-2. Here, we describe the synthesis of new1,5-diarylpyrroles along with their inhibitory effects in vitro, ex vivo, and in vivo toward COX isoenzymes and their analgesic activity. Isopropyl-2-methyl-5-[4- (methylsulfonyl)phenyl]-1-phenyl-1H-pyrrole-3-acetate (10a), a representative member of the series, was selected for pharmacokinetic and metabolic studies

Subclinical hyperthyroidism: The cardiovascular point of view

– OBJECTIVE: Subclinical hyperthyroidism (SHyper), defined as reduced thyrotropin with free hormones within the reference range, is a common medical finding, in particular in elderly people. In the last years has gained attention due to its health-related conditions, in particular at the cardiovascular level. MATERIALS AND METHODS: We searched electronic database (PubMed) and search engines (Google Scholar) of articles and reviews using the terms “subclinical hyperthyroidism”, “Atrial fibrillation”, Ischemic stroke”, “Hypertension”, Heart failure”, and “Mortality”. RESULTS: Subclinical hyperthyroidism was clearly associated with the onset of atrial fibrillation and, consequently, with ischemic stroke. However, the latter association is less clear. The effect on hypertension is doubtful and fair. Subclinical hyperthyroidism could increase the risk of acute heart failure, possibly by increasing heart rhythm. Data on mortality are scanty but seem to suggest a possible association, probably linked to the detrimental effect on the cardiovascular system. CONCLUSIONS: Current findings mainly described possible associations with rhythm alterations, heart failure, and stroke but the effective beneficial effects of the treatment of subclinical hyperthyroidism are still lacking

Recurrence quantification analysis as a tool for the characterization of molecular dynamics simulations

A molecular dynamics simulation of a Lennard-Jones fluid, and a trajectory of the B1 immunoglobulin G-binding domain of streptococcal protein G (B1-IgG) simulated in water are analyzed by recurrence quantification, which is noteworthy for its independence from stationarity constraints, as well as its ability to detect transients, and both linear and nonlinear state changes. The results demonstrate the sensitivity of the technique for the discrimination of phase sensitive dynamics. Physical interpretation of the recurrence measures is also discussed.Comment: 7 pages, 8 figures, revtex; revised for review for Phys. Rev. E (clarifications and expansion of discussion)-- addition of the 8 postscript figures previously omitted, but unchanged from version