Letter from the Special Issue Editor

Editorial work for DEBULL on a special issue on data management on Storage Class Memory (SCM) technologies

The AMCIS 2003 Panels of IS Education-II: The Chicken and the Egg Debate: Positioning Database Content in the Information Systems Curriculum

This paper summarizes the results of a panel on how database content is covered in current university programs, with reference to the IS2002 model curriculum. Panelists included information systems (IS) faculty members who are actively involved in determining the coverage of database content at their institutions and in establishing academy-wide database content and technology resources. Topics included positioning database content in the overall curriculum, sequencing of content within the database course(s), and summary suggestions for tailoring database coverage at colleges and universities

Corporate influence and the academic computer science discipline.

Prosopography of a major academic center for computer science

Synthesis and properties of new macrocyclic derivates

2017 - 2018This PhD thesis is concerned with the design, synthesis and the characterization of new macrocyclic derivatives. Development of new macrocyclic compounds is a particularly interesting because they can involve like building block in Supramolecular chemistry and Nanochemistry. In the first place, I studied the supramolecular properties of different derivatives of the resorcin[6]arenes. Crystal of Resorcin[6]arene was obtained and it reveals that in the solid state the resorcin[6]arene assembles in a twin molecular capsule able to host toluene and ethyl acetate solvent molecules. Subsequently, I have reported the first example of resorcin[6]arene-based cavitand. Sulfate bridges play a double role, both, as structural element for the preorganization of the larger resorcin[6]arene macrocycle and as functional supramolecular interacting groups. Finally, I develop a new multivalent systems resorcin[n]arene based for inhibition of glycosidases and mannosidase that are involved in the malignant transformation of cells. These derivatives were synthetized starting to a pyrrolidine-based iminosugar and resorcinarenes compounds through CuAAS cycloaddition. Biological essays showed that all the resorcinarene derivatives have a good inhibitory activity towards mannosidase enzymes. In second instance, I synthetized new Cycloparaphenylenes (CPP) derivatives to molecular recognition and optoelectronic application. Particularly about molecular recognition field, I reported the synthesis of a [8]CPP derivative incorporating an electron-rich 1,4-dimethoxybenzene ring. This is the first example of substituted CPP derivative reported in literature able to recognize pyridinium guests. Owing to the presence of the 1,4-dimethoxybenzene ring a fine-tuning of the binding abilities toward pyridinium guests was obtained with respect to the native [8]CPP macrocycle. Hybrid Calixarene-CPP derivative that combine the supramolecular features of both the hosts was synthetized and studied in molecular recognition of Na+, Li+ and K+. This derivative shows a noncommon Li+ selectivity due to a more favorable interaction between the cation and the aromatic rings of the CPP bridge. Synthesis of incorporate the 9,10-diphenyl anthracene - [8]CPP derivative was performed and were studied optical and electronical features to obtain the first example of a CPP-based emitter in photon upconversion in the presence of the of octaethylporphyrin Pd(II) complex as a sensitizer, thus widening the application fields of this class of compounds. Finally, [8]CPP and [10]CPP was tested to produce Luminescent Solar Concentrators (LSCs). The high Stokes shift of the CPP macrocycles, enables the preparation of slabs in which a low reabsorption was observed. The results here obtained show clearly the photophysical performances of the CPPbased LSC closely matches with that of the lanthanide chelates based LSC, of interest for applications in colorless LSC. [edited by Author]XXXI cicl

Clostridium difficile: expression of virulence factors, resistance to disinfectants and interactions with human cells

Clostridium difficile is the most common cause of nosocomial diarrhoea today. Through the changing epidemiology of C. difficile infection, the emergence and decline of different strains of varying virulence and a broad spectrum of disease from asymptomatic carriage and mild infection to severe pseudomembranous colitis have been observed. The main aim of this three-part thesis was to identify bacterial factors that might explain these variations by comparing five C. difficile strains - strain 630, an historic strain, strain VPI 10463, a reference strain, the hypervirulent ribotype 027 and the current locally endemic ribotypes 001 and 106. The first study focussed on the growth-related phenotypic and genotypic expression of virulence factors in C. difficile. Growth was studied over twenty-four hours, with simultaneous assessment of toxin and spore production. Total toxin production was measured by a commercial ELISA, while a quantitative ELISA for toxin A and a quantitative cytotoxicity assay for toxin B were developed for individual toxin levels, and spores were enumerated by viable counts. Ribotype 027 produced large amounts of toxin A and toxin B and was the second highest spore producer after ribotype 106. Growth may not affect virulence, but the ability to produce more toxins and spores could. To study the transcription of the genes involved in these processes, a real-time RT-PCR was developed. The transcription of the pathogenicity locus (tcdA-E) that regulates toxin production in C. difficile, and of spo0A, the initiator of sporulation, was studied. There were three key observations: firstly, the transcription of tcdC, the negative regulator of toxin production, did not decrease over time, suggesting it has a modulatory rather than repressive effect on the process. Secondly, tcdE expression was highest in ribotype 027, which might explain its hypertoxicity by greater toxin release. Thirdly, there was almost steady state expression of spo0A during the exponential growth phase in ribotypes 106 and 027, the highest spore producers, suggesting prolonged activation of sporulation. Thus, distinct inter-strain differences exist between C. difficile strains in vitro, which could mirror their virulence in vivo, and several traits contribute synergistically to the hypervirulence of ribotype 027. The second study aimed to identify suitable laboratory disinfectants against C. difficile. The efficacy of four commonly-used disinfectants and one decontaminant was tested; one disinfectant was a chlorine-based agent commonly used in hospitals. In conventional susceptibility tests, all five agents were effective against vegetative cells and spores of C. difficile. However, only the chlorine-based disinfectant was effective against spores dried onto surfaces, but this too required more than two minutes of treatment. The presence of organic matter significantly impaired the efficacy of the non-chlorine agents. The spores of epidemic strains were destroyed less effectively and exposure to sub-MIC levels of disinfectant increased sporulation, especially in ribotype 001, a common outbreak strain. Environmental sampling of the laboratory and surrounding areas showed considerable dissemination of C. difficile, highlighting the need for effective decontamination in conjunction with basic hygiene methods like hand-washing. The third study examined the biological activity of C. difficile. Macrophages were challenged in vitro with S-layer proteins, flagella, heat-shock proteins and culture supernatants of the five strains and cytokine production was measured by specially developed ELISAs. No significant inter-strain differences were observed, although the epidemic strains generally elicited a slightly greater cytokine response. Using epithelial cell lines it was observed that epidemic strains showed greater adherence; from inhibition assays, flagella and S-layer proteins were found to contribute equally to this. Through these studies, inter-strain differences between epidemic and historic isolates were identified with respect to virulence factors, survival in the environment and possible behaviour within the host. A sum of these observations suggests increased virulence in contemporary versus historical C. difficile strains. Finally, a supplementary study characterising a collection of ribotype 027 strains isolated in Scotland and the Netherlands by typing schemes, gene sequencing, susceptibility testing and phenotypic studies was performed. In agreement with other studies, the clonality of these hypervirulent strains was observed

Annual report of the town officers of the town of Stratford, New Hampshire, including report of the school district, for the year ending December 31, 2002. Happy 230th, Stratford!

This is an annual report containing vital statistics for a town/city in the state of New Hampshire

The presence of Clostridium difficile on environmental surfaces in healthcare facilities pre- and post-decontamination of patient rooms

Healthcare-associated infections (HAIs) are infections related to receiving medical care. HAIs are responsible for an excess of morbidity and mortality among hospitalized patients. Though most HAIs rates are on the decline, Clostridium difficile infection rates are at an all-time high, primarily due to the persistence of C. difficile spores in the environment. In the United States, Clostridium difficile-related mortality rates per million have increased from 5.7 in 1999 to 23.7 in 2004, with an estimated 26,642 deaths due to Clostridium difficile infections (CDIs). Clostridium difficile is transmitted via the fecal-oral route or aerosolized endospores, but it can also be transmitted from high touch surfaces in healthcare facilities, such as door handles, bed rails, and bed pans contaminated with C. difficile spores. Various methods of detection have been established since the 1970s, but they have limitations, such as cost, time, and availability. The use of a molecular method of detection, such as polymerase chain reaction (PCR), could provide more rapid and sensitive results for the detection of Clostridium difficile. The objective of this study was to determine the presence of Clostridium difficile pre- and post-decontamination of patients’ rooms in a healthcare facility environment using culture and PCR analysis of surface samples. No culturable C. difficile were detected; however, the culture analysis results showed a significant difference between the number of facultative and anaerobic bacteria in pre-decontamination samples and post-decontamination samples (Z = -5.852, p = 0.000). Of the 128 samples tested using PCR analysis, five samples were positive for Clostridium difficile DNA (3.9%); three were from pre-decontamination samples and two were from post-decontamination samples. Reducing the rate of transmission of Clostridium difficile infections in hospitals is dependent on a number of factors (e.g., proper use of antibiotics, environmental decontamination, and proper hand-hygiene). The results of this study indicate decontamination methods used at these facilities were effective in preventing environmental contamination of hospital rooms with facultative and anaerobic bacteria such as, C. difficile

Mechanisms of Neutrophil Recruitment and Immunopathology During Acute Clostridium difficile Colitis.

C. difficile infection in mice is associated with acute colitis characterized by the induction of inflammatory cytokines, intestinal histopathology, and robust neutrophil recruitment. Our objective was to determine the roles of the inflammatory cytokines GM-CSF, TNFa, IL-23, IL-22, and IL-17a in promoting neutrophil recruitment and innate inflammation in response to C. difficile infection. Ablation of GM-CSF signaling in vivo using a depleting anti-GM-CSF mAb was associated with significant reduction in colonic expression of Il1b, Tnfa, and Inos. Furthermore, expression of the neutrophil chemotactic factors Cxcl1 and Cxcl2 was also reduced in the colonic mucosa of anti-GM-CSF treated mice. Notably, anti-GM-CSF treatment did not affect intestinal histopathology. Direct reduction in neutrophil recruitment through the use of a depleting anti-Gr-1 antibody was not associated with reduction in the host inflammatory response. Colonic expression of inflammatory cytokines, including Tnfa, Il6, and Il33, and the neutrophil chemotactic factors Cxcl1 and Cxcl2 was unchanged following anti-Gr-1 treatment. Furthermore, colonic histopathology was no attenuated in anti-Gr-1 treated mice. Ablation of TNFa signaling was associated with increased inflammatory cytokine expression. While anti-TNFa treatment did not reduced neutrophil recruitment or expression of Cxcl1 and Cxcl2, the expression of numerous inflammatory cytokines including Il1b and Il6 were increased in anti TNFa-treated mice. Additionally, anti-TNFa treatment was associated with the development of more severe colonic histopathology following C. difficile infection. IL-23 deficiency was associated with significantly decreased neutrophil recruitment. Concomitant with the reduced neutrophilic influx, the expression of the neutrophil-recruiting chemokines Cxcl1, Cxcl2, and Ccl3 was also significantly reduced. IL-17 and IL-22 expression were also significantly reduced in the absence of IL-23, as was expression of the antimicrobial peptide RegIIIg. Furthermore, the induction of inflammatory cytokines including Tnfa, Il33, and Il6 was significantly reduced in IL-23-/- mice. Inflammatory cytokine expression and neutrophilic inflammation were not reduced in IL-17a-deficient mice or in mice treated with anti-IL-22 depleting mAb. However, RegIIIg expression was significantly reduced in anti-IL-22 treated animals. Taken together these data suggest that IL-23 and GM-CSF, independent of IL-17a, IL-22, and TNFa, drive neutrophil recruitment and inflammatoryPHDMicrobiology and ImmunologyUniversity of Michigan, Horace H. Rackham School of Graduate Studieshttp://deepblue.lib.umich.edu/bitstream/2027.42/113375/1/mcderand_1.pdfhttp://deepblue.lib.umich.edu/bitstream/2027.42/113375/2/mcderand_3.pdfhttp://deepblue.lib.umich.edu/bitstream/2027.42/113375/3/mcderand_2.pd