Evidence for Structural Variants of a- and b-Type Peptide Fragment Ions Using Combined Ion Mobility/Mass Spectrometry

Tandem mass spectrometry (MS/MS) of peptides plays a key role in the field of proteomics, and an understanding of the fragmentation mechanisms involved is vital for data interpretation. Not all the fragment ions observed by low-energy collision-induced dissociation of protonated peptides are readily explained by the generally accepted structures for a- and b-ions. The possibility of a macrocyclic structure for b-type ions has been recently proposed. In this study, we have undertaken investigations of linear protonated YAGFL-NH2, N-acetylated-YAGFL-NH2, and cyclo-(YAGFL) peptides and their fragments using a combination of ion mobility (IM) separation and mass spectrometry. The use of IM in this work both gives insight into relative structural forms of the ion species and crucial separation of isobaric species. Our study provides compelling evidence for the formation of a stable macrocyclic structure for the b5 ion generated by fragmentation of protonated linear YAGFL-NH2. Additionally we demonstrate that the a4 ion fragment of protonated YAGFL-NH2 has at least two structures; one of which is attributable to a macrocyclic structure on the basis of its subsequent fragmentation. More generally, this work emphasizes the value of combined IM-MS/MS in probing the detailed fragmentation mechanisms of peptide ions, and illustrates the use of combined ion mobility/collisional activation/mass spectrometry analysis in achieving an effective enhancement of the resolution of the mobility separator

Investigating the influence of the sulfur oxidation state on solid state conformation

Design, synthesis and structural characterization of a series of diphenylacetylene derivatives bearing organosulfur, amide and amine moieties has been achieved in which the molecular conformation is controlled through variation of the hydrogen bond properties on alteration of the oxidisation level of sulfur

The reality of managing asthma in sub-Saharan Africa – Priorities and strategies for improving care

Asthma is the most common non-communicable disease in children and remains one of the most common throughout the life course. The great majority of the burden of this disease is seen in low-income and middle-income countries (LMICs), which have disproportionately high asthma-related mortality relative to asthma prevalence. This is particularly true for many countries in sub-Saharan Africa. Although inhaled asthma treatments (particularly those containing inhaled corticosteroids) markedly reduce asthma morbidity and mortality, a substantial proportion of the children, adolescents, and adults with asthma in LMICs do not get to benefit from these, due to poor availability and affordability. In this review, we consider the reality faced by clinicians managing asthma in the primary and secondary care in sub-Saharan Africa and suggest how we might go about making diagnosis and treatment decisions in a range of resource-constrained scenarios. We also provide recommendations for research and policy, to help bridge the gap between current practice in sub-Saharan Africa and Global Initiative for Asthma (GINA) recommended diagnostic processes and treatment for children, adolescents, and adults with asthma

Youth Justice Reinvestment Custody Pathfinder - Findings and delivery lessons from the first year of implementation

The pilots began in October 2011 and will run until September 2013. This report presents findings from the first year of implementation in four sites in England and Wales: one local authority and three consortia of local authorities. Individual end of pilot targets were set, as measured by the number of custody bed nights. At the end of the first year of a two year pilot, Site 1 had already exceeded its targets, while the other three sites showed varying increases (4%, 14% and 23% respectively). The report identifies a number of factors which appeared to have facilitated or hindered implementation in the first year. The sites which made the most progress towards their targets conducted detailed data analysis to identify interventions that could be delivered with the potential to reduce custody bed nights during the first year

Evaluacion de Impacto: Informe final, resultado y recomendaciones

A efectos de avanzar en la formulación de la iniciativa “Agricultura baja en emisiones y resiliente a la variabilidad y cambio climático en Colombia (LECRA)” se desarrolló una evaluación de impacto de los resultados del convenio de cooperación del 2013 y de las estrategias previstas para la iniciativa a futuro. En este documento, se presentan los principales resultados de dicha evaluación de impacto. El estudio fue llevado a cabo por la unión temporal entre la firma consultora INSUCO y la Universidad del Rosario, con el apoyo de la Alianza Bioversity – CIAT

Higher harmonic anisotropic flow measurements of charged particles at 2.76 TeV with the ALICE detector

We report the measurements of elliptic flow $v_{2}$, as well as higher harmonics triangular flow $v_{3}$ and quadrangular flow $v_{4}$, in $\sqrt{s_{_{NN}}} =$ 2.76 TeV Pb--Pb collisions, measured with the ALICE detector. We show that the measured elliptic and triangular flow can be understood from the initial spatial anisotropy and its event--by--event fluctuations. The resulting fluctuations of $v_{2}$ and $v_{3}$ are also discussed.Comment: 6 pages, 4 figures, proceeding of Strangeness in Quark Matter 2011, Cracow, Polan

Development of a simple reliable radiographic scoring system to aid the diagnosis of pulmonary tuberculosis

Rationale: Chest radiography is sometimes the only method available for investigating patients with possible pulmonary tuberculosis (PTB) with negative sputum smears. However, interpretation of chest radiographs in this context lacks specificity for PTB, is subjective and is neither standardized nor reproducible. Efforts to improve the interpretation of chest radiography are warranted. Objectives To develop a scoring system to aid the diagnosis of PTB, using features recorded with the Chest Radiograph Reading and Recording System (CRRS). METHODS: Chest radiographs of outpatients with possible PTB, recruited over 3 years at clinics in South Africa were read by two independent readers using the CRRS method. Multivariate analysis was used to identify features significantly associated with culture-positive PTB. These were weighted and used to generate a score. RESULTS: 473 patients were included in the analysis. Large upper lobe opacities, cavities, unilateral pleural effusion and adenopathy were significantly associated with PTB, had high inter-reader reliability, and received 2, 2, 1 and 2 points, respectively in the final score. Using a cut-off of 2, scores below this threshold had a high negative predictive value (91.5%, 95%CI 87.1,94.7), but low positive predictive value (49.4%, 95%CI 42.9,55.9). Among the 382 TB suspects with negative sputum smears, 229 patients had scores <2; the score correctly ruled out active PTB in 214 of these patients (NPV 93.4%; 95%CI 89.4,96.3). The score had a suboptimal negative predictive value in HIV-infected patients (NPV 86.4, 95% CI 75,94). CONCLUSIONS: The proposed scoring system is simple, and reliably ruled out active PTB in smear-negative HIV-uninfected patients, thus potentially reducing the need for further tests in high burden settings. Validation studies are now required