The Subversion of the Immune System by Francisella Tularensis

Francisella tularensis is a highly virulent bacterial pathogen and the causative agent of tularemia. Perhaps the most impressive feature of this bacterium is its ability to cause lethal disease following inoculation of as few as 15 organisms. This remarkable virulence is, in part, attributed to the ability of this microorganism to evade, disrupt, and modulate host immune responses. The objective of this review is to discuss the mechanisms utilized by F. tularensis to evade and inhibit innate and adaptive immune responses. The capability of F. tularensis to interfere with developing immunity in the host was appreciated decades ago. Early studies in humans were the first to demonstrate the ability of F. tularensis to suppress innate immunity. This work noted that humans suffering from tularemia failed to respond to a secondary challenge of endotoxin isolated from unrelated bacteria. Further, anecdotal observations of individuals becoming repeatedly infected with virulent strains of F. tularensis suggests that this bacterium also interferes with the generation of adequate adaptive immunity. Recent advances utilizing the mouse model for in vivo studies and human cells for in vitro work have identified specific bacterial and host compounds that play a role in mediating ubiquitous suppression of the host immune response. Compilation of this work will undoubtedly aid in enhancing our understanding of the myriad of mechanisms utilized by virulent F. tularensis for successful infection, colonization, and pathogenesis in the mammalian host

"Excess Ar" by laboratory alteration of biotite

Many biotite phenocrysts from marine tephra layers have substoichiometric potassium concentrations and alkali occupation << 2.0 atoms per formula unit. Diagenetic alteration is an expected effect of exposure of fresh magmatic minerals to interstitial water and brine intrusions after the deposition and burial of sediments. To test the effect of diagenetic alteration on potassium-argon ages, we irradiated and step heated untreated Fish Canyon biotite (t = 28.2 Ma) and several aliquots leached to various extents in strong and weak acids. Laboratory alteration caused loss of K, age spectrum discordance, high step ages and total gas ages, Ar release at lower furnace temperature, higher Cl/K and Ca/K, and a slight decrease in 36Ar concentration. Potassium loss was always higher than 40Ar* loss. Electron microprobe element maps document that acids preferentially penetrate in phyllosilicate interlayers, removing K (and Na). Because Ar* is removed to a lesser extent than K, we propose that natural 40K decay partly implants radiogenic Ar* into the tetrahedral-octahedral-tetrahedral (T-O-T) phyllosilicate layer, where Ar is shielded from interlayer leaching. The recoiled 39Ar, which was produced by irradiation after the leaching, also partitioned between T-O-T and the interlayer; age spectrum discordance was probably enhanced by the heterogeneous partition of 39Ar and 40Ar* in leached samples

Low Cost NBTI Degradation Detection and Masking Approaches

Performance degradation of integrated circuits due to aging effects, such as Negative Bias Temperature Instability (NBTI), is becoming a great concern for current and future CMOS technology. In this paper, we propose two monitoring and masking approaches that detect late transitions due to NBTI degradation in the combinational part of critical data paths and guarantee the correctness of the provided output data by adapting the clock frequency. Compared to recently proposed alternative solutions, one of our approaches (denoted as Low Area and Power (LAP) approach) requires lower area overhead and lower, or comparable, power consumption, while exhibiting the same impact on system performance, while the other proposed approach (denoted as High Performance (HP) approach) allows us to reduce the impact on system performance, at the cost of some increase in area and power consumption

Lateral cephalometric analysis of asymptomatic volunteers and symptomatic patients with and without bilateral temporomandibular joint disk displacement

Few studies of dentofacial and orthodontic structural relationships relative to temporomandibular joint (TMJ) dysfunction have been reported. We undertook this investigation to determine any correlation of orthodontic and dentofacial characteristics with TMJ bilateral disc displacement. The population of patients was selected from a TMJ clinic where a control group of asymptomatic volunteers had been previously established and standardized. Differences in skeletal structural features were determined among three study groups: (1) asymptomatic volunteers with no TMJ disk displacement, (2) symptomatic patients with no TMJ disc displacement, and (3) symptomatic patients with bilateral TMJ disk displacement. Thirty-two asymptomatic volunteers without disk displacement (25 female, 7 male) were compared with the same number each of symptomatic patients without TMJ disk displacement and symptomatic patients with bilateral TMJ disk displacement. All subjects had undergone a standardized clinical examination, bilateral TMJ magnetic resonance imaging, and lateral cephalometric radiographic analysis. The groups were matched according to sex, TMJ status, age, and Angle classification of malocclusion. Seventeen lateral cephalometric radiographic cranial base, maxillomandibular, and vertical dimension variables were evaluated and compared among the study groups. The mean angle of SNB, or the intersection of the sella-nasion plane and the nasion–point B line (indicating mandibular retrognathism relative to cranial base), of the symptomatic patients-with-displacement group was significantly smaller than that in the asymptomatic volunteers and symptomatic patients without bilateral disk displacement (p \u3c 0.05). Female subjects showed smaller linear measurements of mandibular length, lower facial height, and total anterior facial height than male subjects in all three groups (p \u3c 0.05). The mean angle of ANB, or the intersection of the nasion–point A and nasion–point B planes (indicating retrognathism of mandible relative to maxilla), was significantly greater in female than in male subjects, in all groups (p \u3c 0.05). Symptomatic patients with bilateral disk displacement had a retropositioned mandible, indicated by a smaller mean SNB angle compared with that in asymptomatic volunteers and symptomatic patients with no disk displacement on either side. Lateral cephalometric radiographic assessment may improve predictability of TMJ disk displacement in orthodontic patients but is not diagnostic; nor does the assessment explain any cause-and-effect relationship. (Am J Orthod Dentofacial Orthop 1998;114:248-55.

A Genetic-algorithm-based Approach to the Design of DCT Hardware Accelerators

As modern applications demand an unprecedented level of computational resources, traditional computing system design paradigms are no longer adequate to guarantee significant performance enhancement at an affordable cost. Approximate Computing (AxC) has been introduced as a potential candidate to achieve better computational performances by relaxing non-critical functional system specifications. In this article, we propose a systematic and high-abstraction-level approach allowing the automatic generation of near Pareto-optimal approximate configurations for a Discrete Cosine Transform (DCT) hardware accelerator. We obtain the approximate variants by using approximate operations, having configurable approximation degree, rather than full-precise ones. We use a genetic searching algorithm to find the appropriate tuning of the approximation degree, leading to optimal tradeoffs between accuracy and gains. Finally, to evaluate the actual HW gains, we synthesize non-dominated approximate DCT variants for two different target technologies, namely, Field Programmable Gate Arrays (FPGAs) and Application Specific Integrated Circuits (ASICs). Experimental results show that the proposed approach allows performing a meaningful exploration of the design space to find the best tradeoffs in a reasonable time. Indeed, compared to the state-of-the-art work on approximate DCT, the proposed approach allows an 18% average energy improvement while providing at the same time image quality improvement

Computational drug discovery under RNA times

RNA molecules play many functional and regulatory roles in cells, and hence, have gained considerable traction in recent times as therapeutic interventions. Within drug discovery, structure-based approaches have successfully identified potent and selective small-molecule modulators of pharmaceutically relevant protein targets. Here, we embrace the perspective of computational chemists who use these traditional approaches, and we discuss the challenges of extending these methods to target RNA molecules. In particular, we focus on recognition between RNA and small-molecule binders, on selectivity, and on the expected properties of RNA ligands

Efficient Neural Network Approximation via Bayesian Reasoning

Approximate Computing (AxC) trades off between the accuracy required by the user and the precision provided by the computing system to achieve several optimizations such as performance improvement, energy, and area reduction. Several AxC techniques have been proposed so far in the literature. They work at different abstraction levels and propose both hardware and software implementations. The standard issue of all existing approaches is the lack of a methodology to estimate the impact of a given AxC technique on the application-level accuracy. This paper proposes a probabilistic approach based on Bayesian networks to quickly estimate the impact of a given approximation technique on application-level accuracy. Moreover, we have also shown how Bayesian networks allow a backtrack analysis that automatically identifies the most sensitive components. That influence analysis dramatically reduces the space exploration for approximation techniques. Preliminary results on a simple artificial neural network shown the efficiency of the proposed approach

Surface Induced Order in Liquid Metals and Binary Alloys

Measurements of the surface x-ray scattering from several pure liquid metals (Hg, Ga, and In) and from three alloys (Ga-Bi, Bi-In, and K-Na) with different heteroatomic chemical interactions in the bulk phase are reviewed. Surface-induced layering is found for each elemental liquid metal. The surface structure of the K-Na alloy resembles that of an elemental liquid metal. Bi-In displays pair formation at the surface. Surface segregation and a wetting film are found for Ga-Bi.Comment: 10 pages, 3 fig, published in Journal of Physics: Condensed Matte

Interactive Educational Tool for Memory Testing

Memories are one of the most important components in digital systems like SoCs. The high density of their cell array makes memories extremely vulnerable to physical defects. Hence, memory testing and Design-for-Test became one of the crucial tasks in the design of complex and heterogeneous SoCs. Politecnico di Torino and the Institute of Informatics have a wide experience in the field of RAM testing (i.e., automatic march test generation, fault simulators, memory BIST generators etc.). This work is a tentative to put the joint experience of our research groups in developing an interactive educational tool for the students that should introduce standard and well-known methods of memory testing based on BIST. The MemBIST Java Applet and the March Test Generator were two individual tools designed and implemented at the two mentioned institutions. They were merged into one tool in order to facilitate its usage also by the professional