Autoimmune Neutropenia and Immune-Dysregulation in a Patient Carrying a TINF2 Variant

In recent years, the knowledge about the immune-mediated impairment of bone marrow precursors in immune-dysregulation and autoimmune disorders has increased. In addition, immune-dysregulation, secondary to marrow failure, has been reported as being, in some cases, the most evident and early sign of the disease and making the diagnosis of both groups of disorders challenging. Dyskeratosis congenita is a disorder characterized by premature telomere erosion, typically showing marrow failure, nail dystrophy and leukoplakia, although incomplete genetic penetrance and phenotypes with immune-dysregulation features have been described. We report on a previously healthy 17-year-old girl, with a cousin successfully treated for acute lymphoblastic leukemia, who presented with leukopenia and neutropenia. The diagnostic work-up showed positive anti-neutrophil antibodies, leading to the diagnosis of autoimmune neutropenia, a slightly low NK count and high TCR-αβ+-double-negative T-cells. A next-generation sequencing (NGS) analysis showed the 734C>A variant on exon 6 of the TINF2 gene, leading to the p.Ser245Tyr. The telomere length was short on the lymphocytes and granulocytes, suggesting the diagnosis of an atypical telomeropathy showing with immune-dysregulation. This case underlines the importance of an accurate diagnostic work-up of patients with immune-dysregulation, who should undergo NGS or whole exome sequencing to identify specific disorders that deserve targeted follow-up and treatment.     

Report on inaugural workshop RSA ReHi-Network ‘Interdisciplinary connections between history & regional studies’*

The RSA Research Network on Regional Economic and Policy History (ReHi) aims to investigate the role of the historic perspective on regional studies through a series of events. During the inaugural two-day workshop, held in London in April 2017, the participants highlighted historical methodologies and approaches that establish a common thread in the various regional disciplines. They defined interdisciplinary connections that need to be addressed to overcome the discontinuous dialogue among researchers of regional studies and history. The research papers that were presented at the conference focused on improving methodologies, analysing economic strategies, developing techniques, and understanding policy development. The workshop aimed at establishing the foundation for a common research framework to improve the scientific debate and provide impact on regional policy regulations.     

Computing the Types of the Relationships Between Autonomous Systems

We investigate the problem of computing the types of the relationships between Internet Autonomous Systems. We refer to the model introduced by Gao [IEEE/ACM Transactions on Networking, 9(6):733-645, 2001] and Subramanian (IEEE Infocom, 2002) that bases the discovery of such relationships on the analysis of the AS paths extracted from the BGP routing tables. We characterize the time complexity of the above problem, showing both NP-completeness results and efficient algorithms for solving specific cases. Motivated by the hardness of the general problem, we propose approximation algorithms and heuristics based on a novel paradigm and show their effectiveness against publicly available data sets. The experiments provide evidence that our algorithms perform significantly better than state-of-the-art heuristics     

Thermoelastic finite element model updating with application to monumental buildings

A reliable and predictive model of an existing structure entails the use of model updating techniques, which are usually performed on the basis of operational modal analysis campaigns. In this paper, a new model calibration strategy is proposed that adopts a multiphysics approach to exploit data collected by both static and dynamic monitoring systems. More specifically, mechanical and temperature data are assimilated into the model through a thermoelastic updating. The proposed scheme is validated with numerical simulations and applied on the Sanctuary of Vicoforte, a complex historical building that is subjected to both static and dynamic monitoring.     

A computational study of the flammability of methanol and gasoline fuel spills on hot engine manifolds

The fire hazards associated with gasoline and methanol are different because of the different physical and chemical properties of the fuels. In particular, the composition of the vapors they emit determines the comparative risk of a fire or explosion in cases of accidents or fuel leaks. This study compares the behavior of methanol and gasoline (n-octane) using mathematical models, so as to assist in determining whether there is an increased risk associated with the use of methanol fuels. The flammable zones surrounding a representative unconfined exhaust manifold were determined for methanol and n-octane at two manifold surface temperatures (700 and 1000 K) using computational fluid dynamics (CFD) techniques. Some of the CID computations were also confirmed experimentally. It was found that for a manifold surface temperature of 700 K, neither fuel would ignite, although the surface temperature is above the autoignition temperature for both fuels. At a surface temperature of 1000 K, it was found that each fuel could ignite and that this temperature would be near the minimum required for either fuel to be ignited by a hot surface. The predictions also confirm the experimentally observed phenomenon that real hot surface ignition temperatures are, generally, well above autoignition temperatures. It was concluded that the risk of spontaneous ignition is similar for both fuels for the type of leak scenario investigated (i.e. the risk with methanol is not significantly different than that of gasoline). The use of two-dimensional (2-D) steady-state CFD simulations can provide significant insight into the behavior of different fuels in what is generally a three-dimensional (3-D) transient phenomenon.     

Design of statistical databases: A methodology for the conceptual step

The aim of the conceptual step in database design is to describe data involving in the application in a formal and abstract way, without any concern to the specific model and language chosen for the implementation. In statistical applications, data are described at different levels of aggregation, from elementary facts of the reality to complex aggregations such as classifications, time series, indexes. The paper describes a methodology for conceptual design of statistical databases that provides the designer suitable strategies for defining such different levels of aggregation starting from user requirements, and checking the completeness, coherence and minimality of the conceptual schema at the different levels. The methodology makes use of two data models for the representation of data: for elementary data the Entity-Relationship model, widely used in database applications, and for summary data a new model is proposed, designed to be an effective trade-off between expressive power and simplicity of use.     

Visual discovery of the correlation between BGP routing and round-trip delay active measurements

Inter-domain routing data and Internet active probing measurements are two types of information commonly available in huge datasets and subject to extensive, focused analysis. However, the study of the correlation between these two complementary types of information still remains one of the most challenging problems in today’s research in networking. In this paper we describe a metaphor for the visualization of the interplay between the routing information exchanged via BGP and the round-trip delay measurements collected by several geolocated probes. We implemented a prototype based on the above metaphor. Our prototype highlights both the Autonomous System topology and the latency associated with each AS-path over time. Further, it shows how probes are partitioned into clusters associated with each border gateway, based on observed traffic patterns. The resulting visualization allows the user to explore the dynamics of the correlation between the two types of information.     

Nonlinear PI control of fed-batch processes for growth rate regulation

This paper deals with the regulation of the biomass specific growth rate, which is an important goal in many fed-batch fermentation processes. The proposed control system is based on the minimal model paradigm, requiring only biomass and volume measurement along with some bounds on the reaction rate. The controller has the structure of a partial state feed-back with adjustable gain. An integral-proportional control algorithm is designed to adjust this gain. It is inspired in concepts of invariant control and system immersion. First, a nonlinear integral action that makes invariant a goal manifold defined by a reference model dynamics is developed. Then, a proportional output error feed-back is incorporated to the control law with the aim of fastening convergence. Stability is investigated in detail using Lyapunov functions. To implement the control law, an estimation of the growth rate is required like any other PI-like controller. Because of its strong convergence properties, a sliding observer that requires the same process information as the controller is used for this task, although conventional continuous observers can alternatively be used provided they are fast enough to preserve stability. Simulation results showing the transient response and robustness features of the controller under nominal and perturbed scenarios are presented.     

Colloidal macromolecular phenomena. Part II. Novel microcrystals of polymers

Colloidal microcrystalline cellulose, introduced in 1961, now is a successful commercial product with growing world-wide markets. This paper describes some major findings of our continuing research to convert fibrous or fiber-forming polymer systems into new colloidal microcrystalline physical states without going through a homogeneous molecular solution phase. Several novel microcrystalline colloidal products from the following natural and/or synthetic polymeric raw materials are described and compared for the first time: cellulose, amylose, collagen, nylon, and chrysotile mineral silicates. Many previously unpublished electron micrographs are presented. These products demonstrate a new and growing field of colloidal microcrystalline polymer science. They open up increasing opportunities for new polymer products based on the original concept, namely, the unhinging of polymer microcrystals from their natural or synthetic network and then by appropriate mechanical energy, releasing them as discrete, submicron colloidal polymer microcrystals dispersed in various liquid media to form unique gel systems, or reaggregated in the dry state to form porous colloidal particles.