A Library Approach to the Development of BenzaPhos, Highly Efficient Chiral Supramolecular Ligands for Asymmetric Hydrogenation

A library of chiral supramolecular ligands named BenzaPhos, of straightforward preparation (two steps from commercial or readily available starting materials) and modular structure, was designed and synthesized. The ligands were screened in the search of new rhodium catalysts for the enantioselective hydrogenation of several benchmark and industrially relevant substrates. Once a series of hits were identified, structural modifications were introduced on three of the best ligands and a small second-generation library was created. Members of the latter showed outstanding levels of activity and enantioselectivity in the hydrogenation of challenging olefins such as enamide S4 and beta-dehydroamino ester S5 (> 99% ee: best value ever reported in both cases). A series of control experiments were undertaken in order to clarify the role of hydrogen bonding in determining the catalytic properties of the new ligands. The results of these experiments, together with those of computational studies carried out on four dihydride complexes involved in the catalytic hydrogenation of substrate S4, strongly suggest that a substrate orientation takes place in the catalytic cycle by formation of a hydrogen bond between the ligand amide oxygen and the substrate amide NH

Clearance Operation of Teulada Site (Italy): A Novel Approach for Short Term MCM Missions in Seafloor Hard Conditions

In May 2007, following a request by Italian Navy (ITN), NURC agreed to provide the technology, developed during the port protection studies and 2006 MCM ops. in Baltic sea for Estonian Navy, to survey part of the Capo Teulada firing range (Sardinia Island, Italy), used by NATO Armed Forces. The goal of the service, fully funded by ITN, was to survey part of the firing range with acoustic, magnetic and optical instruments in order to detect and classify the ordnance laying on the seafloor. The team operated from CRV Leonardo to produce a detailed acoustic and magnetic map of the area. The positions of the targets of interest have been provided to Italian Navy for further identification and disposal. The activities have demonstrated that the NURC Autonomous Underwater Vehicles (AUVs) Remus type equipped with high frequency side scan sonar can detect and classify targets of the dimensions of unexploded ordnance laying proud on the sea floor. A multiple sonar images technique has also been used to improve the classification performances. However, in some areas, targets that were completely buried or concealed in Posidonia fields wouldn’t have been detectable with AUV sonar. To overcome this limitation, INGV supported the NURC team by using a new high definition magnetometer technique to detect and classify buried metal targets. A proton Overhauser sensor was towed from Leonardo vessel and a magnetometer reference station was set ashore in an appropriate site. A subset of interesting contacts (acoustic and magnetic) have been identified optically by means of the video camera installed on the ROV (Pluto Plus type by Gaymarine) operated from Leonardo. The positioning accuracy achieved was fully compatible with the reacquisition by ROV and then by divers or mine hunters for future disposal ops. The survey has also produced an accurate map of the Posidonia fields and a detailed bathymetry of the area. More than 300 contacts have been acquired and more than 200 were classified in less than 15 days. The success of Teulada operation has convinced ITN to ask NURC for a common development programme with the aim to validate at sea a fully integrated multi-sensor approach (sonar, magnetic and optical) in MCM short term ops. using USV/AUV platforms

Ectopic ACTH syndrome: Molecular bases and clinical heterogeneity

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Experimental Analysis and Modeling of Single-Sided vs Dual-Sided Filtering in Flex-Grid Switched Optical Networks

Flex-grid WSS filters embedded in Reconfigurable Add-Drop Multiplexers (ROADM) can selectively filter portions of the spectrum down to the GHz granularity enabling flexibility in optical channel add-drop operations. In this scenario, the signal's quality of transmission (QoT) can be severely impaired due to filters cascade by both single-sided (SS) and dualsided (DS) passband narrowing, due to filters' deviation from nominal frequency or multi-carrier transceivers switching. We experimentally observe lower penalties in the SS filtering case and their interplay w.r.t. ASE noise placement. We also propose an experimental calibration method able to directly estimate the overall signal QoT degradation suitable to integration in digital twins' lightpath computation engines and network planners

Experimental Validation of QoT Computation in Mixed 10G/100G Networks

We validate experimentally a quality-of-transmission estimator of the non-linear impairment on coherent 100G channels propagating with 10G channels on dispersion-managed links for network planning and path computation. Presented estimations are conservative, spectrally and spatially disaggregated

Spatially Disaggregated Modelling of Self-Channel NLI in Mixed Fibers Optical Transmission

We simulate and observe the buildup of coherency in self-channel interference. We propose a spatially disaggregated model for non-uniform links with uncompensated and compensated spans. We show that the correlation coefficient can be described by a unique curve

Harnessing the gatekeepers of glucocorticoids for chemoprevention of non-melanoma skin cancer

Despite effective surgical methods for non-melanoma skin cancer (NMSC), patients suffer from tissue damage, scarring, or even disfigurement; thus, there is a need for chemopreventive approaches. Because of the complex interplay between glucocorticoids (GCs), inflammation, and cancer, we sought to determine the role of 11β-hydroxysteroid dehydrogenase 1 and 2 (11βHSD1 and 2) in regulating GCs during skin cancer development and progression. 11βHSDs modulate the activation of GCs in a tissue-specific manner and have been reported to play a role in development and progression of other types of cancer, but their role has not yet been reported in NMSC. Here, we found a significant upregulation of 11βHSD2 protein in skin cancer cells when compared to normal skin cells, suggesting a role for this enzyme in the multifactorial process of skin cancer development. In addition, inhibition of 11βHSD2 with siRNA resulted in significant reduction in colony formation in vitro. Finally, our in vivo study elucidated that inhibition of 11βHSD2 with pharmacological inhibitor, Glycyrrhetinic acid (GA) could significantly diminish tumorigenesis in a well-studied in vivo mouse model of NMSC. Overall, these studies highlight for the first time a potential novel role for 11βHSD2 in NMSC development and may allow for new GC treatment approaches capable of avoiding deactivation by the enzyme. If 11βHSD2 can be inhibited as we have done here, or circumvented using modified GCs, this may lead to more efficacious outcomes for NMSC patients by preventing deactivation of the GC and minimizing resistance

Nano-indentation of a room-temperature ionic liquid film on silica: a computational experiment

We investigate the structure of the [bmim][Tf2N]/silica interface by simulating the indentation of a thin (4 nm) [bmim][Tf2N] film by a hard nanometric tip. The ionic liquid/silica interface is represented in atomistic detail, while the tip is modelled by a spherical mesoscopic particle interacting via an effective short-range potential. Plots of the normal force (Fz) on the tip as a function of its distance from the silica surface highlight the effect of weak layering in the ionic liquid structure, as well as the progressive loss of fluidity in approaching the silica surface. The simulation results for Fz are in near-quantitative agreement with new AFM data measured on the same [bmim][Tf2N]/silica interface at comparable thermodynamic conditions.Comment: 24 pages, including 8 fig