Co-universal algebras associated to product systems, and gauge-invariant uniqueness theorems

Let X be a product system over a quasi-lattice ordered group. Under mild hypotheses, we associate to X a C*-algebra which is co-universal for injective Nica covariant Toeplitz representations of X which preserve the gauge coaction. Under appropriate amenability criteria, this co-universal C*-algebra coincides with the Cuntz-Nica-Pimsner algebra introduced by Sims and Yeend. We prove two key uniqueness theorems, and indicate how to use our theorems to realise a number of reduced crossed products as instances of our co-universal algebras. In each case, it is an easy corollary that the Cuntz-Nica-Pimsner algebra is isomorphic to the corresponding full crossed product.Comment: 40 pages, 2 figures; v2: minor changes to the introduction, references added and update

Non-classical ProIL-1beta activation during mammary gland infection is pathogen-dependent but caspase-1 independent

Infection of the mammary gland with live bacteria elicits a pathogen-specific host inflammatory response. To study these host-pathogen interactions wild type mice, NF-kappaB reporter mice as well as caspase-1 and IL-1beta knockout mice were intramammarily challenged with Escherichia coli (E. coli) and Staphylococcus aureus (S. aureus). The murine mastitis model allowed to compare the kinetics of the induced cytokine protein profiles and their underlying pathways. In vivo and ex vivo imaging showed that E. coli rapidly induced NF-kappaB inflammatory signaling concomitant with high mammary levels of TNF-alpha, IL-1 alpha and MCP-1 as determined by multiplex analysis. In contrast, an equal number of S. aureus bacteria induced a low NF-kappaB activity concomitant with high mammary levels of the classical IL-1beta fragment. These quantitative and qualitative differences in local inflammatory mediators resulted in an earlier neutrophil influx and in a more extensive alveolar damage post-infection with E. coli compared to S. aureus. Western blot analysis revealed that the inactive proIL-1beta precursor was processed into pathogen-specific IL-1beta fragmentation patterns as confirmed with IL-1beta knockout animals. Additionally, caspase-1 knockout animals allowed to investigate whether IL-1beta maturation depended on the conventional inflammasome pathway. The lack of caspase-1 did not prevent extensive proIL-1beta fragmentation by either of S. aureus or E. coli. These non-classical IL-1beta patterns were likely caused by different proteases and suggest a sentinel function of IL-1beta during mammary gland infection. Thus, a key signaling nodule can be defined in the differential host innate immune defense upon E. coli versus S. aureus mammary gland infection, which is independent of caspase-1

Analysis of Functional Differences between Hepatitis C Virus NS5A of Genotypes 1–7 in Infectious Cell Culture Systems

Hepatitis C virus (HCV) is an important cause of chronic liver disease. Several highly diverse HCV genotypes exist with potential key functional differences. The HCV NS5A protein was associated with response to interferon (IFN)-α based therapy, and is a primary target of currently developed directly-acting antiviral compounds. NS5A is important for replication and virus production, but has not been studied for most HCV genotypes. We studied the function of NS5A using infectious NS5A genotype 1–7 cell culture systems, and through reverse genetics demonstrated a universal importance of the amphipathic alpha-helix, domain I and II and the low-complexity sequence (LCS) I for HCV replication; the replicon-enhancing LCSI mutation S225P attenuated all genotypes. Mutation of conserved prolines in LCSII led to minor reductions in virus production for the JFH1(genotype 2a) NS5A recombinant, but had greater effects on other isolates; replication was highly attenuated for ED43(4a) and QC69(7a) recombinants. Deletion of the conserved residues 414-428 in domain III reduced virus production for most recombinants but not JFH1(2a). Reduced virus production was linked to attenuated replication in all cases, but ED43(4a) and SA13(5a) also displayed impaired particle assembly. Compared to the original H77C(1a) NS5A recombinant, the changes in LCSII and domain III reduced the amounts of NS5A present. For H77C(1a) and TN(1a) NS5A recombinants, we observed a genetic linkage between NS5A and p7, since introduced changes in NS5A led to changes in p7 and vice versa. Finally, NS5A function depended on genotype-specific residues in domain I, as changing genotype 2a-specific residues to genotype 1a sequence and vice versa led to highly attenuated mutants. In conclusion, this study identified NS5A genetic elements essential for all major HCV genotypes in infectious cell culture systems. Genotype- or isolate- specific NS5A functional differences were identified, which will be important for understanding of HCV NS5A function and therapeutic targeting

Penn State University NSF GK-12 Project: Using Web-Based Education and Interaction with K-12 and College Freshman to Promote Science and Engineering

Penn State University has hosted an NSF-sponsored GK-12 Outreach project for the past five years, and has just begun the second phase of the project. The Penn State project utilizes the talents of many science and engineering graduate students as teachers, mentors and role models for the K-12 classrooms. The project focuses on developing skills of students in the areas of science, technology, engineering and mathematics through the use of Advanced Transportation Technologies. A new project component was devised and implemented-the interaction of K-12 students with college freshman via a website project. The college freshmen were asked to create a website describing a component of Clean Energy , which was to include an assessment tool to provide feedback on their website. When possible, the college freshmen were encouraged to use active learning and inquiry-based learning concepts. This was encouraged so that the college freshman had an opportunity to practice developing scientific inquiry as a skill through a presentation, and provided the K-12 classroom students a unique opportunity to learn through inquiry. The K-12 students were invited to participate in the research by reviewing and critiquing these websites through feedback via the website to the college freshman. The feedback could take many forms, including specific comments and critique along with a creative assessment tool that the college freshman decided to present with their subject materials. This paper will review the educational outcomes garnered by the students, and provide feedback and analysis from the K-12 and college freshman participants

Project MOSI: rationale and pilot-study results of an initiative to help protect zoo animals from mosquito-transmitted pathogens and contribute data on mosquito spatio–temporal distribution change

Mosquito-borne pathogens pose major threats to both wildlife and human health and, largely as a result of unintentional human-aided dispersal of their vector species, their cumulative threat is on the rise. Anthropogenic climate change is expected to be an increasingly significant driver of mosquito dispersal and associated disease spread. The potential health implications of changes in the spatio-temporal distribution of mosquitoes highlight the importance of ongoing surveillance and, where necessary, vector control and other health-management measures. The World Association of Zoos and Aquariums initiative, Project MOSI, was established to help protect vulnerable wildlife species in zoological facilities from mosquito-transmitted pathogens by establishing a zoo-based network of fixed mosquito monitoring sites to assist wildlife health management and contribute data on mosquito spatio-temporal distribution changes. A pilot study for Project MOSI is described here, including project rationale and results that confirm the feasibility of conducting basic standardized year-round mosquito trapping and monitoring in a zoo environment