Secure state estimation against sensor attacks in the presence of noise

We consider the problem of estimating the state of a noisy linear dynamical system when an unknown subset of sensors is arbitrarily corrupted by an adversary. We propose a secure state estimation algorithm, and derive (optimal) bounds on the achievable state estimation error given an upper bound on the number of attacked sensors. The proposed state estimator involves Kalman filters operating over subsets of sensors to search for a sensor subset which is reliable for state estimation. To further improve the subset search time, we propose Satisfiability Modulo Theory-based techniques to exploit the combinatorial nature of searching over sensor subsets. Finally, as a result of independent interest, we give a coding theoretic view of attack detection and state estimation against sensor attacks in a noiseless dynamical system

Artificial neural network in classification of severity levels in crashes with guardrail

This research focuses on using artificial neural networks to classify the severity levels of crashes involving guardrails, and to subsequently identify the most significant variables explaining severity in such crashes. Most of the existing research in analyzing guardrail crashes employs statistical analysis to measure severity of crashes and, unfortunately, does not incorporate much information about the factors that affect the severity concerning guardrail crashes. In the mean time, artificial neural networks have been utilized in different areas of transportation to solve engineering problems because of their ability to model non-linearity, and flexibility with large complex data sets. Data for this research were obtained from the Highway Safety Information System and were divided into two groups, the first group included roadway characteristics including guardrail/environment as input, and severity was output. The results showed that light condition, road surface condition, end and type of the guardrail significantly affect severity levels. The second group included vehicle factors and human factors as input and crash severity was output. The resulting classification was significantly affected by the driver age and vehicle impact. Merging all factors in one model resulted in the best classification of different levels of severity (above 93% in testing classification for different class of severity) and MSE = 0.027089 in cross validation. The results have demonstrated that the Neural Networks are an effective tool to classify severity levels in crashes with guardrail if appropriate input data is available

Role of the type 3 cytokines IL-17 and IL-22 in modulating metabolic dysfunction-associated steatotic liver disease

Metabolic dysfunction-associated steatotic liver disease (MASLD) comprises a spectrum of liver diseases that span simple steatosis, metabolic dysfunction-associated steatohepatitis (MASH) and fibrosis and may progress to cirrhosis and cancer. The pathogenesis of MASLD is multifactorial and is driven by environmental, genetic, metabolic and immune factors. This review will focus on the role of the type 3 cytokines IL-17 and IL-22 in MASLD pathogenesis and progression. IL-17 and IL-22 are produced by similar adaptive and innate immune cells such as Th17 and innate lymphoid cells, respectively. IL-17-related signaling is upregulated during MASLD resulting in increased chemokines and proinflammatory cytokines in the liver microenvironment, enhanced recruitment of myeloid cells and T cells leading to exacerbation of inflammation and liver disease progression. IL-17 may also act directly by activating hepatic stellate cells resulting in increased fibrosis. In contrast, IL-22 is a pleiotropic cytokine with a dominantly protective signature in MASLD and is currently being tested as a therapeutic strategy. IL-22 also exhibits beneficial metabolic effects and abrogates MASH-related inflammation and fibrosis development via inducing the production of anti-oxidants and anti-apoptotic factors. A sex-dependent effect has been attributed to both cytokines, most importantly to IL-22 in MASLD or related conditions. Altogether, IL-17 and IL-22 are key effectors in MASLD pathogenesis and progression. We will review the role of these two cytokines and cells that produce them in the development of MASLD, their interaction with host factors driving MASLD including sexual dimorphism, and their potential therapeutic benefits

Impact of distinct poxvirus infections on the specificities and functionalities of CD4+ T cell responses.

UNLABELLED: The factors that determine CD4+ T cell (TCD4+) specificities, functional capacity, and memory persistence in response to complex pathogens remain unclear. We explored these parameters in the C57BL/6 mouse through comparison of two highly related (\u3e92% homology) poxviruses: ectromelia virus (ECTV), a natural mouse pathogen, and vaccinia virus (VACV), a heterologous virus that nevertheless elicits potent immune responses. In addition to elucidating several previously unidentified major histocompatibility complex class II (MHC-II)-restricted epitopes, we observed many qualitative and quantitative differences between the TCD4+ repertoires, including responses not elicited by VACV despite complete sequence conservation. In addition, we observed functional heterogeneity between ECTV- and VACV-specific TCD4+ at both a global and individual epitope level, particularly greater expression of the cytolytic marker CD107a from TCD4+ following ECTV infection. Most striking were differences during the late memory phase where, in contrast to ECTV, VACV infection failed to elicit measurable epitope-specific TCD4+ as determined by intracellular cytokine staining. These findings illustrate the strong influence of epitope-extrinsic factors on TCD4+ responses and memory. IMPORTANCE: Much of our understanding concerning host-pathogen relationships in the context of poxvirus infections stems from studies of VACV in mice. However, VACV is not a natural mouse pathogen, and therefore, the relevance of results obtained using this model may be limited. Here, we explored the MHC class II-restricted TCD4+ repertoire induced by mousepox (ECTV) infection and the functional profile of the responding epitope-specific TCD4+, comparing these results to those induced by VACV infection under matched conditions. Despite a high degree of homology between the two viruses, we observed distinct specificity and functional profiles of TCD4+ responses at both acute and memory time points, with VACV-specific TCD4+ memory being notably compromised. These data offer insight into the impact of epitope-extrinsic factors on the resulting TCD4+ responses

Innovative Structural and Joining Concepts for Lightweight Design of Heavy Vehicle Systems

Recent advances in the area of Metal Matrix Composites (MMC's) have brought these materials to a maturity stage where the technology is ready for transition to large-volume production and commercialization. The new materials seem to allow the fabrication of higher quality parts at less than 50 percent of the weight as compared to steel, especially when they are selectively reinforced with carbon, silicon carbide, or aluminum oxide fibers. Most of the developments in the MMC materials have been spurred, mainly by applications that require high structural performance at elevated temperatures, the heavy vehicle industry could also benefit from this emerging technology. Increasing requirements of weight savings and extended durability are the main drivers for potential insertion of MMC technology into the heavy vehicle market. Critical elements of a typical tractor-trailer combination, such as highly loaded sections of the structure, engine components, brakes, suspensions, joints and bearings could be improved through judicious use of MMC materials. Such an outcome would promote the DOE's programmatic objectives of increasing the fuel efficiency of heavy vehicles and reducing their life cycle costs and pollution levels. However, significant technical and economical barriers are likely to hinder or even prevent broad applications of MMC materials in heavy vehicles. The tradeoffs between such expected benefits (lower weights and longer durability) and penalties (higher costs, brittle behavior, and difficult to machine) must be thoroughly investigated both from the performance and cost viewpoints, before the transfer of MMC technology to heavy vehicle systems can be properly assessed and implemented. MMC materials are considered to form one element of the comprehensive, multi-faceted strategy pursued by the High Strength/Weight Reduction (HS/WR) Materials program of the U.S. Department of Energy (DOE) for structural weight savings and quality enhancements in heavy vehicles. The research work planed for the first year of this project (June 1, 2003 through May 30, 2004) focused on a theoretical investigation of weight benefits and structural performance tradeoffs associated with the design, fabrication, and joining of MMC components for heavy-duty vehicles. This early research work conducted at West Virginia University yielded the development of integrated material-structural models that predicted marginal benefits and significant barriers to MMC applications in heavy trailers. The results also indicated that potential applications of MMC materials in heavy vehicles are limited to components identified as critical for either loadings or weight savings. Therefore, the scope of the project was expanded in the following year (June 1, 2004 through May 30, 2005) focused on expanding the lightweight material-structural design concepts for heavy vehicles from the component to the system level. Thus, the following objectives were set: (1) Devise and evaluate lightweight structural configurations for heavy vehicles. (2) Study the feasibility of using Metal Matrix Composites (MMC) for critical structural components and joints in heavy vehicles. (3) Develop analysis tools, methods, and validated test data for comparative assessments of innovative design and joining concepts. (4) Develop analytical models and software for durability predictions of typical heavy vehicle components made of particulate MMC or fiber-reinforced composites. This report summarizes the results of the research work conducted during the past two years in this projects

HCV genome-wide genetic analyses in context of disease progression and hepatocellular carcinoma

<div><p>Hepatitis C virus (HCV) is a major cause of hepatitis and hepatocellular carcinoma (HCC) world-wide. Most HCV patients have relatively stable disease, but approximately 25% have progressive disease that often terminates in liver failure or HCC. HCV is highly variable genetically, with seven genotypes and multiple subtypes per genotype. This variation affects HCV’s sensitivity to antiviral therapy and has been implicated to contribute to differences in disease. We sequenced the complete viral coding capacity for 107 HCV genotype 1 isolates to determine whether genetic variation between independent HCV isolates is associated with the rate of disease progression or development of HCC. Consensus sequences were determined by sequencing RT-PCR products from serum or plasma. Positions of amino acid conservation, amino acid diversity patterns, selection pressures, and genome-wide patterns of amino acid covariance were assessed in context of the clinical phenotypes. A few positions were found where the amino acid distributions or degree of positive selection differed between in the HCC and cirrhotic sequences. All other assessments of viral genetic variation and HCC failed to yield significant associations. Sequences from patients with slow disease progression were under a greater degree of positive selection than sequences from rapid progressors, but all other analyses comparing HCV from rapid and slow disease progressors were statistically insignificant. The failure to observe distinct sequence differences associated with disease progression or HCC employing methods that previously revealed strong associations with the outcome of interferon α-based therapy implies that variable ability of HCV to modulate interferon responses is not a dominant cause for differential pathology among HCV patients. This lack of significant associations also implies that host and/or environmental factors are the major causes of differential disease presentation in HCV patients.</p></div

Innovative Structural and Joining Concepts for Lightweight Design of Heavy Vehicle Systems

The extensive research and development effort was initiated by the U.S. Department of Energy (DOE) in 2002 at West Virginia University (WVU) in order to investigate practical ways of reducing the structural weight and increasing the durability of heavy vehicles through the judicious use of lightweight composite materials. While this project was initially focused on specific Metal Matrix Composite (MMC) material, namely Aluminum/Silicon Carbide (Al/SiC) commercially referenced as ''LANXIDE'', the current research effort was expanded from the component level to the system level and from MMC to other composite material systems. Broadening the scope of this research is warranted not only by the structural and economical deficiencies of the ''LANXIDE'' MMC material, but also by the strong coupling that exists between the material and the geometric characteristics of the structure. Such coupling requires a truly integrated design approach, focused on the heaviest sections of a van trailer. Obviously, the lightweight design methods developed in this study will not be implemented by the commercial industry unless the weight savings are indeed impressive and proven to be economically beneficial in the context of Life Cycle Costs (LCC). ''Bulk Haul'' carriers run their vehicles at maximum certified weight, so that each pound saved in structural weight would translate into additional pound of cargo, and fewer vehicles necessary to transport a given amount of freight. It is reasonable to ascertain that a typical operator would be ready to pay a premium of about $3-4 for every additional pound of cargo, or every pound saved in structural weight. The overall scope of this project is to devise innovative, lightweight design and joining concepts for heavy vehicle structures, including cost effective applications of components made of metal matrix composite (MMC) and other composite materials in selected sections of such systems. The major findings generated by this research effort in its first two years have been summarized in the 2003 and 2004 Annual Progress Reports of DOE's Freedom Car and Vehicle Technologies Program. Consistent interactions with producers of heavy trailers, such as Great Dane and Wabash, as well as with their users, such as Old Dominion Freight Lines, have continued during this period to ensure that the research conducted at WVU will yield practical results that will benefit the industry in the near future. Furthermore, Dr. Gergis William and Mr. Thomas Evans participated in the 2005 Technology and Maintenance Council (TMC) annual meeting held in Tampa, Florida, in February 2005. This event offered the WVU researchers an effective opportunity to explore various technical needs and concerns of the industry, both from the performance and maintenance viewpoints, as well as to assess realistically potential benefits and barriers associated with practical implementation of lightweight materials and design technologies in heavy vehicle structures

Natural CD4+ T-Cell Responses against Indoleamine 2,3-Dioxygenase

The enzyme indoleamine 2,3-dioxygenase (IDO) contributes to immune tolerance in a variety of settings. In cancer IDO is expressed within the tumor itself as well as in antigen-presenting cells in tumor-draining lymph nodes, where it endorses the establishment of peripheral immune tolerance to tumor antigens. Recently, we described cytotoxic CD8(+) T-cell reactivity towards IDO-derived peptides.In the present study, we show that CD4(+) helper T cells additionally spontaneously recognize IDO. Hence, we scrutinized the vicinity of the previously described HLA-A*0201-restricted IDO-epitope for CD4(+) T-cell epitopes. We demonstrated the presence of naturally occurring IDO-specific CD4(+) T cells in cancer patients and to a lesser extent in healthy donors by cytokine release ELISPOT. IDO-reactive CD4(+) T cells released IFN-γ, TNF-α, as well as IL-17. We confirm HLA class II-restriction by the addition of HLA class II specific blocking antibodies. In addition, we detected a trend between class I- and class II-restricted IDO responses and detected an association between IDO-specific CD4(+) T cells and CD8(+) CMV-responses. Finally, we could detect IL-10 releasing IDO-reactive CD4(+) T cells.IDO is spontaneously recognized by HLA class II-restricted, CD4(+) T cells in cancer patients and in healthy individuals. IDO-specific T cells may participate in immune-regulatory networks where the activation of pro-inflammatory IDO-specific CD4(+) responses may well overcome or delay the immune suppressive actions of the IDO-protein, which are otherwise a consequence of the early expression of IDO in maturing antigen presenting cells. In contrast, IDO-specific regulatory T cells may enhance IDO-mediated immune suppression