Catalytic hydrogenation of nitriles to amines

The adiponitrile hydrogenation reaction, relevant for the production of aminocapronittile and hexamemyldiamine precursors for Nylon 6 and Nylon 6, 6 respectively, has been investigated. Three different reactor systems were used trickle-bed reactor, fixed-bed gas-phase reactor and the stirred-tank autoclave reactor. This meant comparisons between flow system and batch process could be made. Supported metal catalysts were investigated as alternatives for the currendy industrially used Raney catalyst. Precious metals, specifically rhodium, were compared with the base metals nickel and cobalt on the basis of activity and selectivity. Mixed metal alloy catalysts were also prepared and comparisons drawn. Finally a range of supports were also tested. Both flow systems were found to be of limited use with problems attributed to the practical applications of the reactor systems. Using Autoclave activity data as a standard it was possible to define differences in activity between each of the catalysts prepared.EThOS - Electronic Theses Online ServiceGBUnited Kingdo

Catalytic hydrogenation of nitriles to amines

The adiponitrile hydrogenation reaction, relevant for the production of aminocapronittile and hexamemyldiamine precursors for Nylon 6 and Nylon 6, 6 respectively, has been investigated. Three different reactor systems were used trickle-bed reactor, fixed-bed gas-phase reactor and the stirred-tank autoclave reactor. This meant comparisons between flow system and batch process could be made. Supported metal catalysts were investigated as alternatives for the currendy industrially used Raney catalyst. Precious metals, specifically rhodium, were compared with the base metals nickel and cobalt on the basis of activity and selectivity. Mixed metal alloy catalysts were also prepared and comparisons drawn. Finally a range of supports were also tested. Both flow systems were found to be of limited use with problems attributed to the practical applications of the reactor systems. Using Autoclave activity data as a standard it was possible to define differences in activity between each of the catalysts prepared.

Buried shallow fault slip from the South Napa earthquake revealed by near-field geodesy.

Earthquake-related fault slip in the upper hundreds of meters of Earths surface has remained largely unstudied because of challenges measuring deformation in the near field of a fault rupture. We analyze centimeter-scale accuracy mobile laser scanning (MLS) data of deformed vine rows within ±300 m of the principal surface expression of the M (magnitude) 6.0 2014 South Napa earthquake. Rather than assuming surface displacement equivalence to fault slip, we invert the near-field data with a model that allows for, but does not require, the fault to be buried below the surface. The inversion maps the position on a preexisting fault plane of a slip front that terminates ~3 to 25 m below the surface coseismically and within a few hours postseismically. The lack of surface-breaching fault slip is verified by two trenches. We estimate near-surface slip ranging from ~0.5 to 1.25 m. Surface displacement can underestimate fault slip by as much as 30%. This implies that similar biases could be present in short-term geologic slip rates used in seismic hazard analyses. Along strike and downdip, we find deficits in slip: The along-strike deficit is erased after ~1 month by afterslip. We find no evidence of off-fault deformation and conclude that the downdip shallow slip deficit for this event is likely an artifact. As near-field geodetic data rapidly proliferate and will become commonplace, we suggest that analyses of near-surface fault rupture should also use more sophisticated mechanical models and subsurface geomechanical tests

Impaired CD4 T Cell Memory Response to Streptococcus pneumoniae Precedes CD4 T Cell Depletion in HIV-Infected Malawian Adults

Objective: Invasive pneumococcal disease (IPD) is a leading cause of morbidity and mortality in HIV-infected African Adults. CD4 T cell depletion may partially explain this high disease burden but those with relatively preserved T cell numbers are still at increased risk of IPD. This study evaluated the extent of pneumococcal-specific T cell memory dysfunction in asymptomatic HIV infection early on in the evolution of the disease. Methods: Peripheral blood mononuclear cells were isolated from asymptomatic HIV-infected and HIV-uninfected Malawian adults and stained to characterize the underlying degree of CD4 T cell immune activation, senescence and regulation. Pneumococcal-specific T cell proliferation, IFN-c, IL-17 production and CD154 expression was assessed using flow cytometry and ELISpot. Results: We find that in asymptomatic HIV-infected Malawian adults, there is considerable immune disruption with an increase in activated and senescent CD4+CD38+PD-1+ and CD4+CD25highFoxp3+ Treg cells. In the context of high pneumococcal exposure and therefore immune stimulation, show a failure in pneumococcal-specific memory T cell proliferation, skewing of T cell cytokine production with preservation of interleukin-17 but decreased interferon-gamma responses, and failure of activated T cells to express the co-stimulatory molecule CD154. Conclusion: Asymptomatic HIV-infected Malawian adults show early signs of pneumococcal- specific immune dysregulation with a shift in the balance of CD4 memory, T helper 17 cells and Treg. Together these data offer a mechanistic understanding of how antigen-specific T cell dysfunction occurs prior to T cell depletion and may explain the early susceptibility to IPD in those with relatively preserved CD4 T cell numbers

Incomplete Recovery of Pneumococcal CD4 T Cell Immunity after Initiation of Antiretroviral Therapy in HIV-Infected Malawian Adults

HIV-infected African adults are at a considerably increased risk of life-threatening invasive pneumococcal disease (IPD) which persists despite antiretroviral therapy (ART). Defects in naturally acquired pneumococcal-specific T-cell immunity have been identified in HIV-infected adults. We have therefore determined the extent and nature of pneumococcal antigen-specific immune recovery following ART. HIV-infected adults were followed up at 3, 6 and 12 months after initiating ART. Nasopharyngeal swabs were cultured to determine carriage rates. Pneumococcal-specific CD4 T-cell immunity was assessed by IFN-γ ELISpot, proliferation assay, CD154 expression and intracellular cytokine assay. S. pneumoniae colonization was detected in 27% (13/48) of HIV-infected patients prior to ART. The rates remained elevated after 12 months ART, 41% (16/39) (p = 0.17) and significantly higher than in HIV-uninfected individuals (HIVneg 14%(4/29); p = 0.0147). CD4+ T-cell proliferative responses to pneumococcal antigens increased significantly to levels comparable with HIV-negative individuals at 12 months ART (p = 0.0799). However, recovery of the pneumococcal-specific CD154 expression was incomplete (p = 0.0015) as were IFN-γ ELISpot responses (p = 0.0040) and polyfunctional CD4+ T-cell responses (TNF-α, IL-2 and IFN-γ expression) (p = 0.0040) to a pneumolysin-deficient mutant strain. Impaired control of pneumococcal colonisation and incomplete restoration of pneumococcal-specific immunity may explain the persistently higher risk of IPD amongst HIV-infected adults on ART. Whether vaccination and prolonged ART can overcome this immunological defect and reduce the high levels of pneumococcal colonisation requires further evaluation

Crowdsourced earthquake early warning

Earthquake early warning (EEW) can reduce harm to people and infrastructure from earthquakes and tsunamis, but it has not been implemented in most high earthquake-risk regions because of prohibitive cost. Common consumer devices such as smartphones contain low-cost versions of the sensors used in EEW. Although less accurate than scientific-grade instruments, these sensors are globally ubiquitous. Through controlled tests of consumer devices, simulation of an M_w (moment magnitude) 7 earthquake on California’s Hayward fault, and real data from the M_w 9 Tohoku-oki earthquake, we demonstrate that EEW could be achieved via crowdsourcing

Naturally-Acquired Influenza-Specific CD4+ T-Cell Proliferative Responses Are Impaired in HIV-Infected African Adults

BACKGROUND Seasonal influenza has been associated with greater morbidity and mortality in AIDS patients. Highly-active antiretroviral therapy (HAART) has led to some reduction in influenza-related complications but the nature of naturally-acquired T-cell immunity to influenza virus in an African setting, and how this changes with immune reconstitution following HAART is unknown. We measured influenza-specific CD4(+) T-cell immunity in unimmunized HIV-infected Malawian adults and then investigated immune reconstitution following HAART. METHODS Peripheral blood mononuclear cells were isolated from HIV-infected and HIV-uninfected Malawian adults. CFSE proliferation and CD154 expression flow cytometry-based assays were used to measure influenza-specific CD4(+) T-cell immunity. RESULTS We found lower naturally-acquired proliferative influenza-specific CD4(+) T-cell responses in AIDS patients that was also present in asymptomatic HIV-infected adults with relatively high CD4 counts (>350 cells/µl). Influenza-specific CD4(+) T-cell immune reconstitution in HIV-infected patients on HAART for 12 months was poor despite a marked reduction in viral load and an increase in CD4 count. This poor immune reconstitution was characterised by a low influenza-specific proliferative CD4(+) T-cell response and reduced proportions of CD154-expressing influenza-specific CD4(+) T-cells in peripheral blood. CONCLUSION Our data suggest that asymptomatic HIV-infected adults may also be at risk of influenza-related complications and that HAART alone may not circumvent this risk in AIDS patients. This study highlights the need to identify possible interventions early in HIV infection to reduce the risk of influenza and to intensify influenza surveillance in these susceptible African populations

Evaluation of high-throughput genomic assays for the Fc gamma receptor locus

Cancer immunotherapy has been revolutionised by the use of monoclonal antibodies (mAb) that function through their interaction with Fc gamma receptors (FcγRs). The low-affinity FcγR genes are highly homologous, map to a complex locus at 1p23 and harbour single nucleotide polymorphisms (SNPs) and copy number variation (CNV) that can impact on receptor function and response to therapeutic mAbs. This complexity can hinder accurate characterisation of the locus. We therefore evaluated and optimised a suite of assays for the genomic analysis of the FcγR locus amenable to peripheral blood mononuclear cells and formalin-fixed paraffin-embedded (FFPE) material that can be employed in a high-throughput manner. Assessment of TaqMan genotyping for FCGR2A-131H/R, FCGR3A-158F/V and FCGR2B-232I/T SNPs demonstrated the need for additional methods to discriminate genotypes for the FCGR3A-158F/V and FCGR2B-232I/T SNPs due to sequence homology and CNV in the region. A multiplex ligation-dependent probe amplification assay provided high quality SNP and CNV data in PBMC cases, but there was greater data variability in FFPE material in a manner that was predicted by the BIOMED-2 multiplex PCR protocol. In conclusion, we have evaluated a suite of assays for the genomic analysis of the FcγR locus that are scalable for application in large clinical trials of mAb therapy. These assays will ultimately help establish the importance of FcγR genetics in predicting response to antibody therapeutics