Reduced lipoapoptosis, hedgehog pathway activation and fibrosis in caspase-2 deficient mice with non-alcoholic steatohepatitis

International audience

Rail passenger crowding, stress, health and safety in Britain

There has long been a question as to whether crowding in rail passenger transport poses a threat to passenger health related to the experience of stress. A review of the scientific literature was conducted. Little rail-specific empirical research was identified. The more general research that does exist suggests that high-density environments are not necessarily perceived as crowded and that stress-related physiological, psychological and behavioural reactions do not necessarily follow from exposure to such environments. Several factors are identified that may moderate the impact of a high-density environment on perceptions of crowding and the subsequent experience and effects of stress. These include, inter alia, perceptions of control and predictability of events. However, if caused, the experience and effects of stress may be made worse by inadequate coach design that gives rise to discomfort. The model that emerges from these findings offers a suitable framework for the development of research questions that should help translate emerging knowledge into practical interventions, for the reduction of any adverse health outcomes associated with crowding.

Preferential location of prilocaine and etidocaine in phospholipid bilayers: A molecular dynamics study

In this work, we report a 20-ns constant pressure molecular dynamics simulation of the uncharged form of two amino-amide local anesthetics (LA). etidocaine and prilocaine, present at 1:3 LA:lipid, molar ratio inside the membrane, in the hydrated liquid crystal bilayer phase of 1-palmitoyl-2-oleoyl-sn-glycero-3-phosphatidylcholine (POPC). Both LAs induced lateral expansion and a concomitant contraction in the bilayer thickness. A decrease in the acyl chain segment order parameter, -S(CD), compared to neat bilayers, was also observed. Besides, both LA molecules got preferentially located in the hydrophobic acyl chains region, with a maximum probability at similar to 12 and similar to 10 angstrom from the center of the bilayer for prilocaine and etidocaine, respectively. (C) 2009 Elsevier B.V. All rights reserved.

Preferential location of lidocaine and etidocaine in lecithin bilayers as determined by EPR, fluorescence and H-2 NMR

We have examined the effect of the uncharged species of lidocaine (LDC) and etidocaine (EDC) on the acyl chain moiety of egg phosphatidylcholine liposomes. Changes in membrane organization caused by both anesthetics were detected through the use of EPR spin labels (5, 7 and 12 doxyl stearic acid methyl ester) or fluorescence probes (4, 6, 10, 16 pyrene-fatty acids). The disturbance caused by the LA was greater when the probes were inserted in more external positions of the acyl chain and decreased towards the hydrophobic core of the membrane. The results indicate a preferential insertion of LDC at the polar interface of the bilayer and in the first half of the acyl chain, for EDC. Additionally, 2 H NMR spectra of multilamellar liposomes composed by acyl chain-perdeutero DMPC and EPC (1:4 mol%) allowed the determination of the segmental order (S-mol) and dynamics (T-1) of the acyl chain region. In accordance to the fluorescence and EPR results, changes in molecular orientation and dynamics are more prominent if the LA preferential location is more superficial, as for LDC while EDC seems to organize the acyl chain region between carbons 2-8, which is indicative of its positioning. We propose that the preferential location of LDC and EDC inside the bilayers creates a "transient site", which is related to the anesthetic potency since it could modulate the access of these molecules to their binding site(s) in the voltage-gated sodium channel. (C) 2007 Elsevier B.V. All rights reserved.

PUBLIC-PRIVATE PARTNERSHIP FOR RESPONSIVE EXTENSION EDUCATION: THE CASE OF SAFE AND UCC IN GHANA

Developing nations in Africa are not shielded from the pressures of a globalized competitive agricultural marketplace. With an appreciable bulk of her people deriving livelihoods from diverse agricultural enterprises, these nations must respond to important contemporary issues shaping global agriculture. Farmers from such nations, including Ghana, will be able to improve their participation in the competitive local, regional and global agricultural marketplace if the appropriate agricultural technologies and extension information support are available. To achieve this, a new breed of agricultural extension graduates who can respond to current and emerging challenges in agriculture and interface effectively with farmers must be produced through responsive extension education and training. While extension education can produce effective extensionists to hasten agricultural development, budgetary constraints make it difficult for most African governments to successfully and sustainably implement such educational programs. However, public-private partnership (PPP) initiatives offer a way out of this financial dilemma. Beginning in 1993, the Sasakawa Africa Fund for Extension Education (SAFE) worked with the University of Cape Coast (UCC) in Ghana to develop an innovative extension education program through a public private partnership. The program, comprising a BSc. and Diploma components, was designed to respond to the myriad of challenges facing higher agricultural extension education in Ghana. A key practical feature of the curricula is the “Supervised Enterprise Projects” (SEPS), which enable students to work with relevant stakeholders to identify and tackle agricultural problems in farming communities through experiential extension approaches and action research. The SAFE-UCC initiative fulfils important education goals such as: expanding and improving access; ensuring quality and relevance; ensuring funding and mobilizing resources for sustainability; building partnerships and linkages; and promoting international co-operation. The paper discusses the underlying conditions for a successful public private partnership in agricultural and extension education and sheds light on the impacts, lessons learned and challenges.

Clostridium difficile ribotypes in humans and animals in Brazil

Clostridium difficile is an emerging enteropathogen responsible for pseudomembranous colitis in humans and diarrhoea in several domestic and wild animal species. Despite its known importance, there are few studies about C. difficile polymerase chain reaction (PCR) ribotypes in Brazil and the actual knowledge is restricted to studies on human isolates. The aim of the study was therefore to compare C. difficile ribotypes isolated from humans and animals in Brazil. Seventysix C. difficile strains isolated from humans (n = 25), dogs (n = 23), piglets (n = 12), foals (n = 7), calves (n = 7), one cat, and one manned wolf were distributed into 24 different PCR ribotypes. Among toxigenic strains, PCR ribotypes 014/020 and 106 were the most common, accounting for 14 (18.4%) and eight (10.5%) samples, respectively. Fourteen different PCR ribotypes were detected among human isolates, nine of them have also been identified in at least one animal species. PCR ribotype 027 was not detected, whereas 078 were found only in foals. This data suggests a high diversity of PCR ribotypes in humans and animals in Brazil and support the discussion of C. difficile as a zoonotic pathogen.

Synthetic Circuits for Feedback and Detection in Bacteria

Synthetic biology, by co-opting molecular machinery from existing organisms, can be used as a tool for building new genetic systems from scratch, for understanding natural networks through perturbation, or for hybrid circuits that piggy-back on existing cellular infrastructure. Although the toolbox for genetic circuits has greatly expanded in recent years, it is still difficult to separate the circuit function from its specific molecular implementation. In this thesis, we discuss the function-driven design of two synthetic circuit modules, and use mathematical models to understand the fundamental limits of circuit topology versus operating regimes as determined by the specific molecular implementation. First, we describe a protein concentration tracker circuit that sets the concentration of an output protein relative to the concentration of a reference protein. The functionality of this circuit relies on a single negative feedback loop that is implemented via small programmable protein scaffold domains. We build a mass-action model to understand the relevant timescales of the tracking behavior and how the input/output ratios and circuit gain might be tuned with circuit components. Second, we design an event detector circuit with permanent genetic memory that can record order and timing between two chemical events. This circuit was implemented using bacteriophage integrases that recombine specific segments of DNA in response to chemical inputs. We simulate expected population-level outcomes using a stochastic Markov-chain model, and investigate how inferences on past events can be made from differences between single-cell and population-level responses. Additionally, we present some preliminary investigations on spatial patterning using the event detector circuit as well as the design of stationary phase promoters for growth-phase dependent activation. These results advance our understanding of synthetic gene circuits, and contribute towards the use of circuit modules as building blocks for larger and more complex synthetic networks.

Optimal resource allocation and budgeting in libraries

Libraries since their inception 4000 years ago have been in a process of constant change. Although, changes were in slow motion for centuries, in the last decades, academic libraries have been continuously striving to adapt their services to the ever-changing user needs of students and academic staff. In addition, e-content revolution, technological advances, and ever-shrinking budgets have obliged libraries to efficiently allocate their limited resources among collection and services. Unfortunately, this resource allocation is a complex process due to the diversity of data sources and formats required to be analyzed prior to decision-making, as well as the lack of efficient integration methods. The main purpose of this study is to develop an integrated model that supports libraries in making optimal budgeting and resource allocation decisions among their services and collection by means of a holistic analysis. To this end, a combination of several methodologies and structured approaches is conducted. Firstly, a holistic structure and the required toolset to holistically assess academic libraries are proposed to collect and organize the data from an economic point of view. A four-pronged theoretical framework is used in which the library system and collection are analyzed from the perspective of users and internal stakeholders. The first quadrant corresponds to the internal perspective of the library system that is to analyze the library performance, and costs incurred and resources consumed by library services. The second quadrant evaluates the external perspective of the library system; user’s perception about services quality is judged in this quadrant. The third quadrant analyses the external perspective of the library collection that is to evaluate the impact of the current library collection on its users. Eventually, the fourth quadrant evaluates the internal perspective of the library collection; the usage patterns followed to manipulate the library collection are analyzed. With a complete framework for data collection, these data coming from multiple sources and therefore with different formats, need to be integrated and stored in an adequate scheme for decision support. A data warehousing approach is secondly designed and implemented to integrate, process, and store the holistic-based collected data. Ultimately, strategic data stored in the data warehouse are analyzed and implemented for different purposes including the following: 1) Data visualization and reporting is proposed to allow library managers to publish library indicators in a simple and quick manner by using online reporting tools. 2) Sophisticated data analysis is recommended through the use of data mining tools; three data mining techniques are examined in this research study: regression, clustering and classification. These data mining techniques have been applied to the case study in the following manner: predicting the future investment in library development; finding clusters of users that share common interests and similar profiles, but belong to different faculties; and predicting library factors that affect student academic performance by analyzing possible correlations of library usage and academic performance. 3) Input for optimization models, early experiences of developing an optimal resource allocation model to distribute resources among the different processes of a library system are documented in this study. Specifically, the problem of allocating funds for digital collection among divisions of an academic library is addressed. An optimization model for the problem is defined with the objective of maximizing the usage of the digital collection over-all library divisions subject to a single collection budget. By proposing this holistic approach, the research study contributes to knowledge by providing an integrated solution to assist library managers to make economic decisions based on an “as realistic as possible” perspective of the library situation.

SECURITY, PRIVACY AND APPLICATIONS IN VEHICULAR AD HOC NETWORKS

With wireless vehicular communications, Vehicular Ad Hoc Networks (VANETs) enable numerous applications to enhance traffic safety, traffic efficiency, and driving experience. However, VANETs also impose severe security and privacy challenges which need to be thoroughly investigated. In this dissertation, we enhance the security, privacy, and applications of VANETs, by 1) designing application-driven security and privacy solutions for VANETs, and 2) designing appealing VANET applications with proper security and privacy assurance. First, the security and privacy challenges of VANETs with most application significance are identified and thoroughly investigated. With both theoretical novelty and realistic considerations, these security and privacy schemes are especially appealing to VANETs. Specifically, multi-hop communications in VANETs suffer from packet dropping, packet tampering, and communication failures which have not been satisfyingly tackled in literature. Thus, a lightweight reliable and faithful data packet relaying framework (LEAPER) is proposed to ensure reliable and trustworthy multi-hop communications by enhancing the cooperation of neighboring nodes. Message verification, including both content and signature verification, generally is computation-extensive and incurs severe scalability issues to each node. The resource-aware message verification (RAMV) scheme is proposed to ensure resource-aware, secure, and application-friendly message verification in VANETs. On the other hand, to make VANETs acceptable to the privacy-sensitive users, the identity and location privacy of each node should be properly protected. To this end, a joint privacy and reputation assurance (JPRA) scheme is proposed to synergistically support privacy protection and reputation management by reconciling their inherent conflicting requirements. Besides, the privacy implications of short-time certificates are thoroughly investigated in a short-time certificates-based privacy protection (STCP2) scheme, to make privacy protection in VANETs feasible with short-time certificates. Secondly, three novel solutions, namely VANET-based ambient ad dissemination (VAAD), general-purpose automatic survey (GPAS), and VehicleView, are proposed to support the appealing value-added applications based on VANETs. These solutions all follow practical application models, and an incentive-centered architecture is proposed for each solution to balance the conflicting requirements of the involved entities. Besides, the critical security and privacy challenges of these applications are investigated and addressed with novel solutions. Thus, with proper security and privacy assurance, these solutions show great application significance and economic potentials to VANETs. Thus, by enhancing the security, privacy, and applications of VANETs, this dissertation fills the gap between the existing theoretic research and the realistic implementation of VANETs, facilitating the realistic deployment of VANETs.

Irrigation with Treated Wastewater: Potential Impacts on Microbial Function and Diversity in Agricultural Soils

The reuse of treated wastewater could be a promising measure to attenuate the water scarcity burden. In agriculture, irrigation with wastewater may contribute to improve production yields, reduce the ecological footprint and promote socioeconomic benefits. However, it cannot be considered exempt of adverse consequences in environmental and human health. Apart from the introduction of some biological and chemical hazardous agents, the disturbance of the indigenous soil microbial communities and, thus, of vital soil functions impacting soil fertility may occur. The consequences of these disturbances are still poorly understood. This chapter summarises the physicochemical and microbiological alterations in soil resultant from irrigation with treated wastewater that are described in scientific literature. These alterations, which involve a high complexity of variables (soil, wastewater, climate, vegetal cover), may have impacts on soil quality and productivity. In addition, possible health risks may arise, in particular through the direct or indirect contamination of the food chain with micropollutants, pathogens or antibiotic resistance determinants. The current state of the art suggests that irrigation with treated wastewater may have a multitude of long-term implications on soil productivity and public health. Although further research is needed, it seems evident that the analysis of risks associated with irrigation with treated wastewater must take into account not only the quality of water, but other aspects as diverse as soil microbiota, soil type or the cultivated plant species.

Learning curves: analysing pace and challenge in four successful puzzle games

The pace at which challenges are introduced in a game has long been identified as a key determinant of both the enjoyment and difficulty experienced by game players, and their ability to learn from game play. In order to understand how to best pace challenges in games, there is great value in analysing games already demonstrated as highly engaging. Play-through videos of four puzzle games (Portal, Portal 2 Co-operative mode, Braid and Lemmings), were observed and analysed using metrics derived from a behavioural psychology understanding of how people solve problems. Findings suggest that; 1) the main skills learned in each game are introduced separately, 2) through simple puzzles that require only basic performance of that skill, 3) the player has the opportunity to practice and integrate that skill with previously learned skills, and 4) puzzles increase in complexity until the next new skill is introduced. These data provide practical guidance for designers, support contemporary thinking on the design of learning structures in games, and suggest future directions for empirical research.

The Students’ Perspective of Geometry Teaching and Learning in High School

The purpose of this article is to present the results obtained from a questionnaire applied to Costa Rican high school students, in order to know their perspectives about geometry teaching and learning. The results show that geometry classes in high school education have been based on a traditional system of teaching, where the teacher presents the theory; he presents examples and exercises that should be solved by students, which emphasize in the application and memorization of formulas. As a consequence, visualization processes, argumentation and justification don’t have a preponderant role. Geometry is presented to students like a group of definitions, formulas, and theorems completely far from their reality and, where the examples and exercises don’t possess any relationship with their context. As a result, it is considered not important, because it is not applicable to real life situations. Also, the students consider that, to be successful in geometry, it is necessary to know how to use the calculator, to carry out calculations, to have capacity to memorize definitions, formulas and theorems, to possess capacity to understand the geometric drawings and to carry out clever exercises to develop a practical ability.

Plant density and mineral nitrogen fertilization influencing yield, yield components and concentration of oil and protein in soybean grains.

There are few studies on the interaction between soybean plant density and nitrogen fertilization. This research aimed to assess the effect of mineral nitrogen associated to different plant densities on yield, yield components and oil and protein concentrations of soybean grains. Two experiments were conducted in the 2013/2014 and 2014/2015 growing seasons, with randomized complete block design, in a split plots scheme, with six replications. Four sowing densities (150, 300, 440 and 560 thousand viable seeds; ha-1) were allocated in the plots, and two nitrogen levels (0 and 45 kg N; ha-1, applied at V2, using ammonium sulfate) were allocated in the subplots. There was no interaction between soybean plant density and the application of mineral nitrogen on yield, yield components and oil and protein concentrations in soybean grains. Higher plant population reduced the number of pods per plant and the contribution of branch sinks to the grain yield, but the effects on yield differed among the growing seasons. The mineral nitrogen fertilization did not increase yield and protein and oil concentrations in the grains, thus it was unnecessary.

Novel hydroxystearoyl-, heterocyclic and carbocyclic derivatives: synthesis and applications in biological field

This PhD project has been mainly focused on the synthesis of novel organic compounds containing heterocyclic and/or carbocyclic scaffold and on the study of stearic acid derivatives and their applications in biological field. The synthesis of novel derivatives of 9-hydroxystearic acid (9-HSA) evidenced how the presence of substituents on C9, able to make hydrogen bonds is of crucial importance for the biological activity. Also the position of the hydroxy group along the chain of hydroxystearic acids was investigated: regioisomers with the hydroxy group bound to odd carbons resulted more active than those bearing the hydroxy group on even carbons. Further, the insertion of (R)-9-HSA in magnetic nanoparticles gave a novel material which characterization remarked its suitability for drug delivery. Structural hybrids between amino aza-heterocycles and azelaic acid have been synthesized and some of them showed a selective activity towards osteosarcoma cell line U2OS. Several Apcin analogues bearing indole, benzothiazole, benzofurazan moieties connected to tryptaminyl-, amino pyridinyl-, pyrimidinyl- and pyrazinyl ring through a 1,1,1-trichloroethyl group were synthesized. Biological tests showed the importance of both the tryptaminyl and the pyrimidinyl moieties, confirming the effectiveness against acute leukemia models. The SNAr between 2-aminothiazole derivatives and 7-chlorodinitrobenzofuroxan revealed different behaviour depending from amino substituent of the thiazole. The reaction with 2-N-piperidinyl-, 2-N-morpholinyl-, or 2-N-pyrrolidinyl thiazole gave two isomeric species derived from the attack on C-5 of thiazole ring. Thiazoles substituted with primary- or not-cyclic secondary amines reacted with the exocyclic amino nitrogen atom giving a series of compounds whose biological activity have highlighted as they might be promising candidates for further development of antitumor agents. A series of 9-fluorenylidene derivatives, of interest in medical and optoelectronic field as organic scintillators, was synthesized through Wittig or Suzuky reaction and will be analyzed to test their potential scintillatory properties.

Digital Forensics AI: on Practicality, Optimality, and Interpretability of Digital Evidence Mining Techniques

Digital forensics as a field has progressed alongside technological advancements over the years, just as digital devices have gotten more robust and sophisticated. However, criminals and attackers have devised means for exploiting the vulnerabilities or sophistication of these devices to carry out malicious activities in unprecedented ways. Their belief is that electronic crimes can be committed without identities being revealed or trails being established. Several applications of artificial intelligence (AI) have demonstrated interesting and promising solutions to seemingly intractable societal challenges. This thesis aims to advance the concept of applying AI techniques in digital forensic investigation. Our approach involves experimenting with a complex case scenario in which suspects corresponded by e-mail and deleted, suspiciously, certain communications, presumably to conceal evidence. The purpose is to demonstrate the efficacy of Artificial Neural Networks (ANN) in learning and detecting communication patterns over time, and then predicting the possibility of missing communication(s) along with potential topics of discussion. To do this, we developed a novel approach and included other existing models. The accuracy of our results is evaluated, and their performance on previously unseen data is measured. Second, we proposed conceptualizing the term “Digital Forensics AI” (DFAI) to formalize the application of AI in digital forensics. The objective is to highlight the instruments that facilitate the best evidential outcomes and presentation mechanisms that are adaptable to the probabilistic output of AI models. Finally, we enhanced our notion in support of the application of AI in digital forensics by recommending methodologies and approaches for bridging trust gaps through the development of interpretable models that facilitate the admissibility of digital evidence in legal proceedings.