Use of Everolimus in Liver Transplantation: Recommendations From a Working Group

Immunosuppression after liver transplantation (LT) is presently based on use of calcineurin inhibitors (CNI), although they are associated with an increased incidence of renal dysfunction, cardiovascular complications, and de novo and recurrent malignancies. Over the past decade, mTOR inhibitors have received considerable attention as immunosuppressants as they are associated with a more favorable renal profile vs. CNI, as well as anti-proliferative activity in clinical studies. Comprehensive guidelines on use of everolimus (EVR) in LT are still lacking. In Italy, a project "Everolimus: the road to long-term functioning" was initiated to collect the experience on EVR after LT with the aim of providing guidance for transplant clinicians. Herein, recommendations by this national consensus group, based on Delphi methodology, are presented. Consensus was reached on 20 of the 23 statements proposed, and their level of evidence, grade of recommendation, and percent of agreement are reported. Statements are grouped into 4 areas: A) renal function; B) time of EVR introduction, CNI reduction and elimination, and risk for graft rejection; C) anti-proliferative effects of EVR; and D) EVR adverse events. The high level of consensus shows that there is good agreement on the routine use of EVR in predefined clinical scenarios, especially in light of posttransplant nephrotoxicity and other adverse events associated with long-term administration of CNIs

MPC-based humanoid pursuit-evasion in the presence of obstacles

We consider a pursuit-evasion problem between humanoids in the presence of obstacles. In our scenario, the pursuer enters the safety area of the evader headed for collision, while the latter executes a fast evasive motion. Control schemes are designed for both the pursuer and the evader. They are structurally identical, although the objectives are different: the pursuer tries to align its direction of motion with the line- of-sight to the evader, whereas the evader tries to move in a direction orthogonal to the line-of-sight to the pursuer. At the core of the control architecture is a Model Predictive Control scheme for generating a stable gait. This allows for the inclusion of workspace obstacles, which we take into account at two levels: during the determination of the footsteps orientation and as an explicit MPC constraint. We illustrate the results with simulations on NAO humanoids

Electroweak bremsstrahlung for wino-like Dark Matter annihilations

If the Dark Matter is the neutral Majorana component of a multiplet which is charged under the electroweak interactions of the Standard Model, its main annihilation channel is into W+W-, while the annihilation into light fermions is helicity suppressed. As pointed out recently, the radiation of gauge bosons from the initial state of the annihilation lifts the suppression and opens up an s-wave contribution to the cross section. We perform the full tree-level calculation of Dark Matter annihilations, including electroweak bremsstrahlung, in the context of an explicit model corresponding to the supersymmetric wino. We find that the fermion channel can become as important as the di-boson one. This result has significant implications for the predictions of the fluxes of particles originating from Dark Matter annihilations.Comment: 13 pages, 3 figures. Minor corrections to match published versio

Female preference and predation risk models can explain the maintenance of a Fallow deer (<i>Dama dama</i>) lek and its ‘handy’ location

We tested the predictions of three models (female preference; hotspot; predator avoidance) on lek formation in the fallow deer population of San Rossore, Tuscany. We collected behavioural observations in two leks and radiotracking data on 67 deer over 7 years. Two deer sub-populations were present in the northern and southern sides of the area, respectively, the two sectors being delimited by a river and including one lek each. Predictions were tested for one lek (SG), located in the south-side where we set up our 7-year radiotracking program. Data from a second lek (FO, north-side) were used to test those predictions which imply the occurrence of multiple leks in the same population. We showed that the majority of females made one single visit to one lek, only during the rut. The lek was located outside areas of higher female traffic and home range overlap, and females increased home range sizes during the rut to reach it. Twilight routes of females never crossed the lek; instead, females walked atypical routes and at a faster pace to reach the lek and mate. The distance between the two leks was higher than the average diameter of female home ranges, and only one lek was present within female home ranges. Males reached the lek one month before the arrival of females, corroborating that lekking is a female-initiated process (females moving towards large clumped male aggregations) rather than a male-initiated process (males moving towards female hotspots). Our results supported the female preference model, and rejected the predictions of the hotspot model. Also, leks were located far from areas with higher predation risk, supporting the predator avoidance model. The position of lek SG resulted ‘handy’ at the sub-population level because of the optimal trade-off between travel costs for females to reach it and avoidance of human predators

Toward fractioning of isomers through binding-induced acceleration of azobenzene switching

The E/Z isomerization process of a uracil-azobenzene derivative in which the nucleobase is conjugated to a phenyldiazene tail is studied in view of its ability to form triply-H-bonded complexes with a suitably complementary 2,6-diacetylamino-4-pyridine ligand. UV-Vis and 1H-NMR investigations of the photochemical and thermal isomerization kinetics show that the thermal Z→E interconversion is four-fold accelerated upon formation of the H-bonded complex. DFT calculations show that the formation of triple H-bonds triggers a significant elongation of the N=N double bond, caused by an increase of its πg∗ antibonding character. This results in a reduction of the N=N torsional barrier and thus in accelerated thermal Z→E isomerization. Combined with light controlled E→Z isomerization this enables controllable fractional tuning of the two configurational isomers

Unveiling quantum-limited operation of interband cascade lasers

A comprehensive experimental analysis of the frequency fluctuations of a mid-infrared interband cascade laser, down to the quantum-limited operation, is reported. These lasers differ from any other class of semiconductor lasers in their structure and internal carrier generation and transport processes. Although already commercially available, a full evaluation of their potential has not been possible, until now, mainly because their internal dynamics are not yet understood well enough. The measured intrinsic linewidth, down to 10 kHz, ranks them in between quantum cascade and bipolar semiconductor lasers. Understanding the noise features is especially important for demanding applications and is a necessary step for a deeper knowledge of the physical behavior for this class of lasers, in view of the development of novel designs for improved performance.A comprehensive experimental analysis of the frequency fluctuations of a mid-infrared interband cascade laser, down to the quantum-limited operation, is reported. These lasers differ from any other class of semiconductor lasers in their structure and internal carrier generation and transport processes. Although already commercially available, a full evaluation of their potential has not been possible, until now, mainly because their internal dynamics are not yet understood well enough. The measured intrinsic linewidth, down to 10 kHz, ranks them in between quantum cascade and bipolar semiconductor lasers. Understanding the noise features is especially important for demanding applications and is a necessary step for a deeper knowledge of the physical behavior for this class of lasers, in view of the development of novel designs for improved performance