Stratigraphy, geochemistry and palaeomagnetism of late quaternary bedrock and paleosols, Karisoke Area, Virunga Mountains, Northwestern Rwanda

Ein rezenter Boden und zwei begrabene Paläoböden, Einheiten II-III-IV (oberer) und IV (unterer)-V, liefern wichtige Informationen über Paläoklima und Abflußverhältnisse in den Virunga-Bergen von trockeneren zu feuchteren paläoklimatischen Phasen des Spätglazials bis zu mittleren postglazialen Zeiten. Zusammenfassend betrachtet, weist die stratigraphische Abfolge zunächst auf eine Verwitterungsperiode des Festgesteins hin, der eine Phase folgt, in der tuffige Schichten abgelagert wurden. Die Zeit war von einer Verwitterung unter trockeneren und vielleicht kälteren Bedingungen begleitet. Später, während des letzten Glazials, kam es bei verstärkter Aktivität der Flüsse zur Sedimentation von Schwemmlandablagerungen, die von einer dünnen Tuff-Schicht überdeckt wurden. Diese Sedimente sind intensiver verwittert als die liegenden Schichten. Der rezente Boden zeigt eine vergleichsweise geringe Verwitterung mobiler Elemente, was darauf hindeutet, daß die Klimaverhältnisse im späten Mittel-Holozän und Spät-Holozän etwas trockener und vielleicht kühler waren als im Früh-Holozän. Die Geochemie der drei Böden zeigt eine bedeutende Abnahme von Na, Ca und K im mittleren Paläoböden im Vergleich zum älteren Paläoböden und zu den rezenten Böden. Eisen als ein wichtiger Indikator für das Paläoklima deutet daraufhin, daß die mittleren Einheiten II und III des oberen Paläobodens unter feuchteren Klimabedingungen als heute entstanden sind. Die Radiokarbon-Datierungen des mittleren Paläobodens zeigen, daß dieser Boden einer sub-aerischen Verwitterung vom Kalambo-Interstadial (» 25000 Jahre vor heute) bis zum Mittel-Holozän ausgesetzt war. Die gesamte Verwitterung im mittleren Abschnitt ist zu weit fortgeschritten und während des Holozäns entstanden. Die relativ hohe Konzentration von Th in den anstehenden Festgesteinen, Tuffen, Schwemmlandsedimenten und Hangrutschmassen zeigt, daß Th die Quelle der Radioaktivität ist, von der andere Autoren aus den Virunga-Bergen berichten.researc

The National Lung Matrix Trial: translating the biology of stratification in advanced non-small-cell lung cancer

© The Author 2015.Background: The management of NSCLC has been transformed by stratified medicine. The National Lung Matrix Trial (NLMT) is a UK-wide study exploring the activity of rationally selected biomarker/targeted therapy combinations. Patients and methods: The Cancer Research UK (CRUK) Stratified Medicine Programme 2 is undertaking the large volume national molecular pre-screening which integrates with the NLMT. At study initiation, there are eight drugs being used to target 18 molecular cohorts. The aim is to determine whether there is sufficient signal of activity in any drug-biomarker combination to warrant further investigation. A Bayesian adaptive design that gives a more realistic approach to decision making and flexibility to make conclusions without fixing the sample size was chosen. The screening platform is an adaptable 28-gene Nextera next-generation sequencing platform designed by Illumina, covering the range of molecular abnormalities being targeted. The adaptive design allows new biomarker-drug combination cohorts to be incorporated by substantial amendment. The pre-clinical justification for each biomarker-drug combination has been rigorously assessed creating molecular exclusion rules and a trumping strategy in patients harbouring concomitant actionable genetic abnormalities. Discrete routes of pathway activation or inactivation determined by cancer genome aberrations are treated as separate cohorts. Key translational analyses include the deep genomic analysis of pre- and post-treatment biopsies, the establishment of patient-derived xenograft models and longitudinal ctDNA collection, in order to define predictive biomarkers, mechanisms of resistance and early markers of response and relapse. Conclusion: The SMP2 platform will provide large scale genetic screening to inform entry into the NLMT, a trial explicitly aimed at discovering novel actionable cohorts in NSCLC

Protection against P. aeruginosa with an adenovirus vector containing an OprF epitope in the capsid

Pseudomonas aeruginosa is an important opportunistic pathogen that can cause chronic and often life-threatening infections of the respiratory tract, particularly in individuals with cystic fibrosis (CF). Because infections with P. aeruginosa remain the major cause of the high morbidity and mortality of CF, a vaccine against P. aeruginosa would be very useful for preventing this disorder. The outer membrane protein F (OprF) of P. aeruginosa is a promising vaccine candidate and various B cell epitopes within OprF have been identified. Given that adenovirus (Ad) vectors have strong immunogenic potential and can function as adjuvants for genetic vaccines, the present study evaluates the immunogenic and protective properties of a novel replication-deficient Ad vector in which the Ad hexon protein was modified to include a 14–amino acid epitope of P. aeruginosa OprF (Epi8) in loop 1 of the hypervariable region 5 of the hexon (AdZ.Epi8). Immunization of C57BL/6 mice with AdZ.Epi8 resulted in detectable serum anti–P. aeruginosa and anti-OprF humoral responses. These responses were haplotype dependent, with higher serum anti-OprF titers in CBA mice than in BALB/c or C57BL/6 mice. AdZ.Epi8 induced Epi8-specific IFN-γ–positive CD4 and CD8 T cell responses and resulted in protection against a lethal pulmonary challenge with agar-encapsulated P. aeruginosa. Importantly, repeated administration of AdZ.Epi8 resulted in boosting of the anti-OprF humoral and anti-Epi8 cellular response, whereas no boosting effect was present in the response against the transgene β-galactosidase. These observations suggest that Ad vectors expressing pathogen epitopes in their capsid will protect against an extracellular pathogen and will allow boosting of the epitope-specific humoral response with repeated administration, a strategy that should prove useful in developing Ad vectors as vaccines where humoral immunity will be protective

Time-Resolved in Situ Neutron Diffraction under Supercritical Hydrothermal Conditions: A Study of the Synthesis of KTiOPO4

In the first in situ neutron powder diffraction study of a supercritical hydrothermal synthesis, the crystallization of KTiOPO(4) (KTP) at 450 °C and 380 bar has been investigated. The time-resolved diffraction data suggest that the crystallization of KTP occurs by the reaction between dissolved K(+)(aq), PO(4)(3-)(aq), and [Ti(OH)(x)]((4-x)+)(aq) species