RosettaBackrub--a web server for flexible backbone protein structure modeling and design.

The RosettaBackrub server (http://kortemmelab.ucsf.edu/backrub) implements the Backrub method, derived from observations of alternative conformations in high-resolution protein crystal structures, for flexible backbone protein modeling. Backrub modeling is applied to three related applications using the Rosetta program for structure prediction and design: (I) modeling of structures of point mutations, (II) generating protein conformational ensembles and designing sequences consistent with these conformations and (III) predicting tolerated sequences at protein-protein interfaces. The three protocols have been validated on experimental data. Starting from a user-provided single input protein structure in PDB format, the server generates near-native conformational ensembles. The predicted conformations and sequences can be used for different applications, such as to guide mutagenesis experiments, for ensemble-docking approaches or to generate sequence libraries for protein design

Security and Privacy Issues in Cloud Computing

Cloud computing transforming the way of information technology (IT) for consuming and managing, promising improving cost efficiencies, accelerate innovations, faster time-to-market and the ability to scale applications on demand (Leighton, 2009). According to Gartner, while the hype grew ex-ponentially during 2008 and continued since, it is clear that there is a major shift towards the cloud computing model and that the benefits may be substantial (Gartner Hype-Cycle, 2012). However, as the shape of the cloud computing is emerging and developing rapidly both conceptually and in reality, the legal/contractual, economic, service quality, interoperability, security and privacy issues still pose significant challenges. In this chapter, we describe various service and deployment models of cloud computing and identify major challenges. In particular, we discuss three critical challenges: regulatory, security and privacy issues in cloud computing. Some solutions to mitigate these challenges are also proposed along with a brief presentation on the future trends in cloud computing deployment

Fog Computing: A Taxonomy, Survey and Future Directions

In recent years, the number of Internet of Things (IoT) devices/sensors has increased to a great extent. To support the computational demand of real-time latency-sensitive applications of largely geo-distributed IoT devices/sensors, a new computing paradigm named "Fog computing" has been introduced. Generally, Fog computing resides closer to the IoT devices/sensors and extends the Cloud-based computing, storage and networking facilities. In this chapter, we comprehensively analyse the challenges in Fogs acting as an intermediate layer between IoT devices/ sensors and Cloud datacentres and review the current developments in this field. We present a taxonomy of Fog computing according to the identified challenges and its key features.We also map the existing works to the taxonomy in order to identify current research gaps in the area of Fog computing. Moreover, based on the observations, we propose future directions for research

Structural Prediction of Protein–Protein Interactions by Docking: Application to Biomedical Problems

A huge amount of genetic information is available thanks to the recent advances in sequencing technologies and the larger computational capabilities, but the interpretation of such genetic data at phenotypic level remains elusive. One of the reasons is that proteins are not acting alone, but are specifically interacting with other proteins and biomolecules, forming intricate interaction networks that are essential for the majority of cell processes and pathological conditions. Thus, characterizing such interaction networks is an important step in understanding how information flows from gene to phenotype. Indeed, structural characterization of protein–protein interactions at atomic resolution has many applications in biomedicine, from diagnosis and vaccine design, to drug discovery. However, despite the advances of experimental structural determination, the number of interactions for which there is available structural data is still very small. In this context, a complementary approach is computational modeling of protein interactions by docking, which is usually composed of two major phases: (i) sampling of the possible binding modes between the interacting molecules and (ii) scoring for the identification of the correct orientations. In addition, prediction of interface and hot-spot residues is very useful in order to guide and interpret mutagenesis experiments, as well as to understand functional and mechanistic aspects of the interaction. Computational docking is already being applied to specific biomedical problems within the context of personalized medicine, for instance, helping to interpret pathological mutations involved in protein–protein interactions, or providing modeled structural data for drug discovery targeting protein–protein interactions.Spanish Ministry of Economy grant number BIO2016-79960-R; D.B.B. is supported by a predoctoral fellowship from CONACyT; M.R. is supported by an FPI fellowship from the Severo Ochoa program. We are grateful to the Joint BSC-CRG-IRB Programme in Computational Biology.Peer ReviewedPostprint (author's final draft

The Dilemma of Security Smells and How to Escape It

A single mobile app can now be more complex than entire operating systems ten years ago, thus security becomes a major concern for mobile apps. Unfortunately, previous studies focused rather on particular aspects of mobile application security and did not provide a holistic overview of security issues. Therefore, they could not accurately understand the fundamental flaws to propose effective solutions to common security problems. In order to understand these fundamental flaws, we followed a hybrid strategy, i.e., we collected reported issues from existing work, and we actively identified security-related code patterns that violate best practices in software development. We further introduced the term ``security smell,'' i.e., a security issue that could potentially lead to a vulnerability. As a result, we were able to establish comprehensive security smell catalogues for Android apps and related components, i.e., inter-component communication, web communication, app servers, and HTTP clients. Furthermore, we could identify a dilemma of security smells, because most security smells require unique fixes that increase the code complexity, which in return increases the risk of introducing more security smells. With this knowledge, we investigate the interaction of our security smells with the 192 Mitre CAPEC attack mechanism categories of which the majority could be mitigated with just a few additional security measures. These measures, a String class with behavior and the more thorough use of secure default values and paradigms, would simplify the application logic and at the same time largely increase security if implemented appropriately. We conclude that application security has to focus on the String class, which has not largely changed over the last years, and secure default values and paradigms since they are the smallest common denominator for a strong foundation to build resilient applications. Moreover, we provide an initial implementation for a String class with behavior, however the further exploration remains future work. Finally, the term ``security smell'' is now widely used in academia and eases the communication among security researchers

PIKA: A Network Service for Multikernel Operating Systems

PIKA is a network stack designed for multikernel operating systems that target potential future architectures lacking cache-coherent shared memory but supporting message passing. PIKA splits the network stack into several servers that communicate using a low-overhead message passing layer. A key challenge faced by PIKA is the maintenance of shared state, such as a single accept queue and load balance information. PIKA addresses this challenge using a speculative 3-way handshake for connection acceptance, and a new distributed load balancing scheme for spreading connections. A PIKA prototype achieves competitive performance, excellent scalability, and low service times under load imbalance on commodity hardware. Finally, we demonstrate that splitting network stack processing by function across separate cores is a net loss on commodity hardware, and we describe conditions under which it may be advantageous

Methods for protein complex prediction and their contributions towards understanding the organization, function and dynamics of complexes

Complexes of physically interacting proteins constitute fundamental functional units responsible for driving biological processes within cells. A faithful reconstruction of the entire set of complexes is therefore essential to understand the functional organization of cells. In this review, we discuss the key contributions of computational methods developed till date (approximately between 2003 and 2015) for identifying complexes from the network of interacting proteins (PPI network). We evaluate in depth the performance of these methods on PPI datasets from yeast, and highlight challenges faced by these methods, in particular detection of sparse and small or sub- complexes and discerning of overlapping complexes. We describe methods for integrating diverse information including expression profiles and 3D structures of proteins with PPI networks to understand the dynamics of complex formation, for instance, of time-based assembly of complex subunits and formation of fuzzy complexes from intrinsically disordered proteins. Finally, we discuss methods for identifying dysfunctional complexes in human diseases, an application that is proving invaluable to understand disease mechanisms and to discover novel therapeutic targets. We hope this review aptly commemorates a decade of research on computational prediction of complexes and constitutes a valuable reference for further advancements in this exciting area.Comment: 1 Tabl