On the role of residue phosphorylation in 14-3-3 partners: AANAT as a case study

Twenty years ago, a novel concept in protein structural biology was discovered: the intrinsically disordered regions (IDRs). These regions remain largely unstructured under native conditions and the more are studied, more properties are attributed to them. Possibly, one of the most important is their ability to conform a new type of protein-protein interaction. Besides the classical domain-to-domain interactions, IDRs follow a ´fly-casting´ model including ´induced folding´. Unfortunately, it is only possible to experimentally explore initial and final states. However, the complete movie of conformational changes of protein regions and their characterization can be addressed by in silico experiments. Here, we simulate the binding of two proteins to describe how the phosphorylation of a single residue modulates the entire process. 14-3-3 protein family is considered a master regulator of phosphorylated proteins and from a modern point-of-view, protein phosphorylation is a three component system, with writers (kinases), erasers (phosphatases) and readers. This later biological role is attributed to the 14-3-3 protein family. Our molecular dynamics results show that phosphorylation of the key residue Thr31 in a partner of 14-3-3, the aralkylamine N-acetyltransferase, releases the fly-casting mechanism during binding. On the other hand, the non-phosphorylation of the same residue traps the proteins, systematically and repeatedly driving the simulations into wrong protein-protein conformations.Fil: Masone, Diego Fernando. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Mendoza. Instituto de Histología y Embriología de Mendoza Dr. Mario H. Burgos. Universidad Nacional de Cuyo. Facultad de Cienicas Médicas. Instituto de Histología y Embriología de Mendoza Dr. Mario H. Burgos; Argentina. Universidad Nacional de Cuyo. Facultad de Ingeniería; ArgentinaFil: Uhart, Marina. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Mendoza. Instituto de Histología y Embriología de Mendoza Dr. Mario H. Burgos. Universidad Nacional de Cuyo. Facultad de Cienicas Médicas. Instituto de Histología y Embriología de Mendoza Dr. Mario H. Burgos; ArgentinaFil: Bustos, Diego Martin. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Mendoza. Instituto de Histología y Embriología de Mendoza Dr. Mario H. Burgos. Universidad Nacional de Cuyo. Facultad de Cienicas Médicas. Instituto de Histología y Embriología de Mendoza Dr. Mario H. Burgos; Argentina. Universidad Nacional de Cuyo. Facultad de Ciencias Exactas y Naturales; Argentin

Resignifying Standard English: Marlene NourbeSe Philip’s She tries her tongue her silence softly breaks

There is no other field such as that of postcolonial literature in which creative writing acts as a fundamental device to dismantle the central Imperialnorm. Among the huge post-colonial production, Caribbean literature can be considered an outstanding example of how language contact can result in highly imaginative changes in language structure. The new english resulting from such a contact, widely shifting from the acrolect to the basilect, unfolds the starring role of linguistic transformation – by means of neologisms, innovations, semantic distortions etc. – in the constant process of re-affirming identity, a process that shows ‘the ironic inability of the English language to ward off [the linguistic]invasion by those whom they invaded (Ashcroft, 2009:9)’. English is my father tongue. A father tongue is a foreign language, therefore English is a foreign language not a mother tongue. What is my mother tongue my mummy tongue my mammy tongue my momsy tongue my modder tongue my ma tongue? (Philip, 1988:30) The extract is taken from Discourse on the Logic of Language, an emblematic chapter of the book chosen for analysis, which perfectly suits the purpose of this work, that is to show how the linguistic changes in the writer’s Mother tongue, Tobagonian Creole English, code-switched with and embedded in the Father tongue, the colonizer’s standard English, are used to shape the search for identity, rebellion, the deafening silence of black people forced to slavery, the inhuman treatments and the sexual violence to which black women were subjected

Role Definition Language (RDL): A Language to Describe Context-Aware Roles

As wireless networks become more prevalent, a widening array of computational resources becomes available to the mobile user. Since not all users should have unrestricted access to these resources, a method of access control must be devised. In a context-aware environment, context information can be used to supplement more conventional password-based access control systems. We believe the best way to achieve this is through the use of Context-Aware Role-Based Access Control, a model in which permissions are assigned to entities called roles, each principal is a member of one or more roles, and a role\u27s membership is determined using context information. We designed and implemented RDL (Role-Definition Language), a simple, expressive and somewhat extensible programming language to facilitate the description of roles in terms of context information

Attribute-Based, Usefully Secure Email

A secure system that cannot be used by real users to secure real-world processes is not really secure at all. While many believe that usability and security are diametrically opposed, a growing body of research from the field of Human-Computer Interaction and Security (HCISEC) refutes this assumption. All researchers in this field agree that focusing on aligning usability and security goals can enable the design of systems that will be more secure under actual usage. We bring to bear tools from the social sciences (economics, sociology, psychology, etc.) not only to help us better understand why deployed systems fail, but also to enable us to accurately characterize the problems that we must solve in order to build systems that will be secure in the real world. Trust, a critically important facet of any socio-technical secure system, is ripe for analysis using the tools provided for us by the social sciences. There are a variety of scopes in which issues of trust in secure systems can be stud- ied. We have chosen to focus on how humans decide to trust new correspondents. Current secure email systems such as S/MIME and PGP/MIME are not expressive enough to capture the real ways that trust flows in these sorts of scenarios. To solve this problem, we begin by applying concepts from social science research to a variety of such cases from interesting application domains; primarily, crisis management in the North American power grid. We have examined transcripts of telephone calls made between grid manage- ment personnel during the August 2003 North American blackout and extracted several different classes of trust flows from these real-world scenarios. Combining this knowl- edge with some design patterns from HCISEC, we develop criteria for a system that will enable humans apply these same methods of trust-building in the digital world. We then present Attribute-Based, Usefully Secure Email (ABUSE) and not only show that it meets our criteria, but also provide empirical evidence that real users are helped by the system

Enhanced sampling for lipid-protein interactions during membrane dynamics

The inflexible concept of membrane curvature as an independent property of lipid structures is today obsolete. Lipid bilayers behave as many-body entities with emergent properties that depend on their interactions with the environment. In particular, proteins exert crucial actions on lipid molecules that ultimately condition the collective properties of the membranes. In this review, the potential of enhanced molecular dynamics to address cell-biology problems is discussed. The cases of membrane deformation, membrane fusion, and the fusion pore are analyzed from the perspective of the dimensionality reduction by collective variables. Coupled lipid-protein interactions as fundamental determinants of large membrane remodeling events are also commented. Finally, novel strategies merging cell biology and physics are considered as future lines of research.Fil: Masone, Diego Fernando. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Mendoza. Instituto de Histología y Embriología de Mendoza Dr. Mario H. Burgos. Universidad Nacional de Cuyo. Facultad de Ciencias Médicas. Instituto de Histología y Embriología de Mendoza Dr. Mario H. Burgos; Argentina. Universidad de Buenos Aires. Facultad de Ingeniería; Argentin

Shared control of an aerial cooperative transportation system with a cable-suspended payload

This paper presents a novel bilateral shared framework for a cooperative aerial transportation and manipulation system composed by a team of micro aerial vehicles with a cable-suspended payload. The human operator is in charge of steering the payload and he/she can also change online the desired shape of the formation of robots. At the same time, an obstacle avoidance algorithm is in charge of avoiding collisions with the static environment. The signals from the user and from the obstacle avoidance are blended together in the trajectory generation module, by means of a tracking controller and a filter called dynamic input boundary (DIB). The DIB filters out the directions of motions that would bring the system too close to singularities, according to a suitable metric. The loop with the user is finally closed with a force feedback that is informative of the mismatch between the operator’s commands and the trajectory of the payload. This feedback intuitively increases the user’s awareness of obstacles or configurations of the system that are close to singularities. The proposed framework is validated by means of realistic hardware-in-the-loop simulations with a person operating the system via a force-feedback haptic interface

Newest Kid on the Block: Characterization of the Novel Multidrugresistant Pathogen, Candida auris

Candida auris is a novel and emerging fungal pathogen capable of causinginvasive, and often fatal, bloodstream and wound infections in immunocompromised patients. Several outbreaks have been reported in hospitals across the world, including the United States, and predominantly in New York. C.auris exhibits extensive multidrug resistance that has never been seen in any Candida species, and is often misdiagnosed for other Candida species, thus limiting treatment options for patients. Our laboratory obtained 10 C. auris isolates in order to perform in vitro antifungal susceptibility testing and determine the Minimum Inhibitory Concentration (MIC) under Clinical and Laboratory Standards Institute guidelines. An alarming percentage (70%) of C. auris isolates exhibited a strong resistance to the commonly prescribed drug, fluconazole (MICs of 128 ug/mL or above). Many of these strains are projected to have an elevated resistance to other classes of drugs, such as polyenes and echinochandins as well. An in vivo model using the waxworm, Galleria mellonella was used to further study the highly-resistant C. auris strains, which demonstrated significantly different virulence in this host. Outbreaks of C. auris continue to increase on a worldwide scale, posing an immediate global health risk. In vitro and in vivo studies to characterize C. auris pathogenesis are imperative and fundamental to the proper diagnosis and treatment of this emerging threat

Communication-Efficient Heterogeneous Federated Learning with Generalized Heavy-Ball Momentum

Federated Learning (FL) is the state-of-the-art approach for learning from decentralized data in privacy-constrained scenarios. As the current literature reports, the main problems associated with FL refer to system and statistical challenges: the former ones demand for efficient learning from edge devices, including lowering communication bandwidth and frequency, while the latter require algorithms robust to non-iidness. State-of-art approaches either guarantee convergence at increased communication cost or are not sufficiently robust to handle extreme heterogeneous local distributions. In this work we propose a novel generalization of the heavy-ball momentum, and present FedHBM to effectively address statistical heterogeneity in FL without introducing any communication overhead. We conduct extensive experimentation on common FL vision and NLP datasets, showing that our FedHBM algorithm empirically yields better model quality and higher convergence speed w.r.t. the state-of-art, especially in pathological non-iid scenarios. While being designed for cross-silo settings, we show how FedHBM is applicable in moderate-to-high cross-device scenarios, and how good model initializations (e.g. pre-training) can be exploited for prompt acceleration. Extended experimentation on large-scale real-world federated datasets further corroborates the effectiveness of our approach for real-world FL applications

Reimagine BiSeNet for Real-Time Domain Adaptation in Semantic Segmentation

Semantic segmentation models have reached remarkable performance across various tasks. However, this performance is achieved with extremely large models, using powerful computational resources and without considering training and inference time. Real-world applications, on the other hand, necessitate models with minimal memory demands, efficient inference speed, and executable with low-resources embedded devices, such as self-driving vehicles. In this paper, we look at the challenge of real-time semantic segmentation across domains, and we train a model to act appropriately on real-world data even though it was trained on a synthetic realm. We employ a new lightweight and shallow discriminator that was specifically created for this purpose. To the best of our knowledge, we are the first to present a real-time adversarial approach for assessing the domain adaption problem in semantic segmentation. We tested our framework in the two standard protocol: GTA5 to Cityscapes and SYNTHIA to Cityscapes. Code is available at: https://github.com/taveraantonio/RTDA.Comment: Accepted at I-RIM 3D 202