Selective Deamidation and Enzymatic Methylation of Seminal Ribonuclease

Isoenzymatic forms alfa2, alfa-beta, and beta2 of bovine seminal ribonuclease are generated by the transformation of beta-type into alfa-type subunit through deamidation of a single amide group. The residue involved in this selective deamidation has been identified as Asn67 . Deamidation occurs by formation of a cyclic imide intermediate involving the Gly at position 68. Opening of the cyclic imide may occur on either side of the nitrogen, generating both the normal alfa-aspartyl and an isoaspartyl residue at position 67. The alfa-carboxyl of the isoaspartyl residue is effectively methylated by bovine brain protein carboxylmethyltransferase

Local manifold learning and its link to domain-based physics knowledge

In many reacting flow systems, the thermo-chemical state-space is known or assumed to evolve close to a low-dimensional manifold (LDM). Various approaches are available to obtain those manifolds and subsequently express the original high-dimensional space with fewer parameterizing variables. Principal component analysis (PCA) is one of the dimensionality reduction methods that can be used to obtain LDMs. PCA does not make prior assumptions about the parameterizing variables and retrieves them empirically from the training data. In this paper, we show that PCA applied in local clusters of data (local PCA) is capable of detecting the intrinsic parameterization of the thermo-chemical state-space. We first demonstrate that utilizing three common combustion models of varying complexity: the Burke-Schumann model, the chemical equilibrium model and the homogeneous reactor. Parameterization of these models is known a priori which allows for benchmarking with the local PCA approach. We further extend the application of local PCA to a more challenging case of a turbulent non-premixed $n$-heptane/air jet flame for which the parameterization is no longer obvious. Our results suggest that meaningful parameterization can be obtained also for more complex datasets. We show that local PCA finds variables that can be linked to local stoichiometry, reaction progress and soot formation processes

The accuracy of burn depth diagnosis: Clinical assessment before and after enzymatic debridement

Abstract Introduction The most common technique used to determine burn depth is clinical assessment by experienced burn surgeons, although this has been shown to be reliable in only 60–75% of the cases. Overestimation of burn depth may result in needles surgery, while burn depth underestimation can led to an increased length of stay in the hospital, risk of contracture and hypertrophic scar formation. The aim of this study was to assess the clinical evaluation of burn depth before and after enzymatic debridement with Nexobrid®. Methods The study model was retrospective. 69 patient records were collected at our burn units, from Jan 2018 to Jan 2019. Each target wound was directly assessed by a single expert physician before and after enzymatic debridement. It was investigated whether the expert, by single wound, would have indicated the need for skin grafts before treatment with Nexobrid® and after treatment. Results Prior to treatment with Nexobrid®, the expert physician assessed that a graft was necessary for 47/69 patients (68.1%). Following debridement, the same expert deemed that the patients needing a graft were 19/69 (27.5%); analysing K-agreement, a 40.6% discrepancy between the pre and post-treatment opinion with Nexobrid® was observed. Discussion The use of Nexobrid® enzymatic debridement can positively affect burn depth clinical assessment, increasing its specificity and sensitivity, without any need for delay. This can lead to a significant change in clinical practice, minimizing the use of surgery, therefore increasing quality and precision of the reconstructive phase

REM: Automatic for the People

We present the result of a year-long effort to think, design, build, realize, and manage the robotic, autonomous REM observatory, placed since June 2003 on the cerro La Silla, ESO Chile. The various aspects of the management and control are here surveyed, with the nice ideas and the wrong dead ends we encountered under way. Now REM is offered to the international astronomical community, a real, schedulable telescope, automatic for the People

the rem observing software

The Rapid Eye Mount (REM) is a 60 cm robotic telescope located at La Silla, Chile. Its Observing Software (REMOS) is constituted by a set of distributed intercommunicating processes organized around a central manager. Together they grant the system safety, automatically schedule and perform observations with two simultaneous cameras of user-defined targets, and drive fast reaction to satellite alerts. Subsequent data reduction is left to pipelines managed by each camera

Italian recommendations on enzymatic debridement in burn surgery.

Abstract Introduction Nexobrid®, a bromelain-based type of enzymatic debridement, has become more prevalent in recent years. We present the recommendations on enzymatic debridement (Nexobrid®)'s role based on the practice knowledge of expert Italian users. Methods The Italian recommendations, endorsed by SIUST (Italian Society of Burn Surgery), on using enzymatic debridement to remove eschars for burn treatment were defined. The definition followed a process to evaluate the level of agreement (a measure of consensus) among selected experts, representing Italian burn centers, concerning defined clinical aspects of enzymatic debridement. The consensus involved a multi-phase process based on the Delphi method. Results The consensus panel included experts from Italy with a combined experience of 1068 burn patients treated with enzymatic debridement. At the end of round 3 of the Delphi method, the panel reached 100% consensus on 26 out of 27 statements. The panel achieved full, strong consensus (all respondents strongly agreed on the statement) on 24 out of 27 statements. Discussion The statements provided by the Italian consensus panel represent a "ready to use" set of recommendations for enzymatic debridement in burn surgery that both draw from and complete the existing scientific literature on the topic. These recommendations are specific to the Italian experience and are neither static nor definitive. As such, they will be updated periodically as further quality evidence becomes available

Resolved images of self-gravitating circumstellar discs with ALMA

In this paper we present simulated observations of massive self-gravitating circumstellar discs using the Atacama Large Millimetre/sub-millimetre Array (ALMA). Using a smoothed particle hydrodynamics model of a $0.2M_{\odot}$ disc orbiting a $1M_{\odot}$ protostar, with a cooling model appropriate for discs at temperatures below $\sim 160$K and representative dust opacities, we have constructed maps of the expected emission at sub-mm wavelengths. We have then used the CASA ALMA simulator to generate simulated images and visibilities with various array configurations and observation frequencies, taking into account the expected thermal noise and atmospheric opacities. We find that at 345 GHz (870 $\mu$m) spiral structures at a resolution of a few AU should be readily detectable in approximately face-on discs out to distances of the Taurus-Auriga star-forming complex.Comment: 8 pages, 6 figures, accepted to MNRAS. Figure quality degraded. Full paper with higher quality figures available at http://www2.fisica.unimi.it/lodato/CossinsLodatoTesti1.pd

Decipher non-canonical SPAST splicing mutations with the help of functional assays in patients affected by spastic paraplegia 4 (SPG4)

Flowchart showing the molecular approach used to decipher the non-canonical splicing mutations

Mechanisms of Resistance to Immunotherapy in Hepatocellular Carcinoma

: Systemic treatment for advanced hepatocellular carcinoma (HCC) has been revolutionized over the last few years following the approval of immune checkpoint inhibitors (ICI). Despite the promising survival extension seen with ICI combination regimens, responses are not universally seen and the optimal partner for programmed cell death 1 pathway inhibitors remains to be identified. Even fewer encouraging results have been demonstrated with ICI used for monotherapy. Several mechanisms of resistance have been described so far, involving characteristics of cancer cells (intrinsic mechanisms) and of the surrounding tumor microenvironment (extrinsic mechanisms). Factors related to therapy may also contribute to the development of resistance. Increasing research efforts are being dedicated to the discovery of novel approaches and targets to overcome resistance, some of which may be introduced into clinic in the future. Herein we describe a selection of resistance mechanisms that have been involved in impairing response to ICI and propose potential therapeutic approaches to overcome resistance

A Path to the Stars: The Evolution of the Species

During the last years, a number of telescopes have been dedicated to the followup of the GRBs. But after the Swift launch, the average observed intensity of the GRBs showed to be lower than thought before. Our experience with the robotic 60 cm REM telescope confirmed this evidence, with a large number oflostGRBs. Then, we proposed to study the feasibility of a 4 m fast pointing class telescope, equipped with a multichannel imagers, from Visible to Near Infrared. In this paper, we present the main result of the feasibility study we performed so far