Autopiquer - a robust and reliable peak detection algorithm for mass spectrometry

We present a simple algorithm for robust and unsupervised peak detection by determining a noise threshold in isotopically resolved mass spectrometry data. Solving this problem will greatly reduce the subjective and time consuming manual picking of mass spectral peaks and so will prove beneficial in many research applications. The Autopiquer approach uses autocorrelation to test for the presence of (isotopic) structure in overlapping windows across the spectrum. Within each window, a noise threshold is optimized to remove the most unstructured data whilst keeping as much of the (isotopic) structure as possible. This algorithm has been successfully demonstrated for both peak detection and spectral compression on data from many different classes of mass spectrometer and for different sample types and this approach should also be extendible to other types of data that contain regularly spaced discrete peaks

A Professional Learning Program for Novice Online Teachers Using Threshold Concepts

The professional development of online teachers is now commonplace in higher education. Alongside the relatively straightforward decision to provide professional learning support for novice and experienced online educators within universities, decisions about the nature and content of such support are not always as clear cut. The study aimed to gather evidence about the online teaching and learning experiences and views of current students and staff which, in turn, informed a set of pedagogical guidelines that could be used as the basis of professional learning programs for novice online teachers. Using a mixed methods research design, data were gathered using questionnaires, reflective journals, and focus groups to determine the threshold concepts about online teaching and perceptions of ideal online learning environments. As well as identifying threshold concepts about online teaching and perceptions of teachers’ and students’ ideal views of online learning contexts (reported elsewhere), the study produced curricular guidelines to inform the design of professional development outputs for online teachers in higher education. This article reports on an example of how these professional development guidelines, based on identified threshold concepts of online pedagogy, were implemented at one higher education institution to provide wide-scale implementation of a professional development program for academic staff engaged in online teaching

Re-identification of c. 15 700 cal yr BP tephra bed at Kaipo Bog, eastern North Island: implications for dispersal of Rotorua and Puketarata tephra beds.

A 10 mm thick, c. 15 700 calendar yr BP (c. 13 100 14C yr BP) rhyolitic tephra bed in the well-studied montane Kaipo Bog sequence of eastern North Island was previously correlated with Maroa-derived Puketarata Tephra. We revise this correlation to Okataina-derived Rotorua Tephra based on new compositional data from biotite phenocrysts and glass. The new correlation limits the known dispersal of Puketarata Tephra (sensu stricto, c. 16 800 cal yr BP) and eliminates requirements to either reassess its age or to invoke dual Puketarata eruptive events. Our data show that Rotorua Tephra comprises two glass-shard types: an early-erupted low-K2O type that was dispersed mostly to the northwest, and a high-K2O type dispersed mostly to the south and southeast, contemporary with late-stage lava extrusion. Late-stage Rotorua eruptives contain biotite that is enriched in FeO compared with biotite from Puketarata pyroclastics. The occurrence of Rotorua Tephra in Kaipo Bog (100 km from the source) substantially extends its known distribution to the southeast. Our analyses demonstrate that unrecognised syn-eruption compositional and dispersal changes can cause errors in fingerprinting tephra deposits. However, the compositional complexity, once recognised, provides additional fingerprinting criteria, and also documents magmatic and dispersal processes

Determination of protein thiol reduction potential by isotope labeling and intact mass measurement

Oxidation/reduction of thiol residues in proteins is an important type of post-translational modification that is implicated in regulating a range of biological processes. The nature of the modification makes it possible to define a quantifiable electrochemical potential, E⊕, for oxidation/reduction that allows cysteine-containing proteins to be ranked based on their propensity to be oxidized. Measuring oxidation of cysteine residues in proteins is difficult using standard electrochemical methods but recently top-down mass-spectrometry has been shown to enable the quantification of E⊕ for thiol oxidations. In this paper we demonstrate that mass spectrometry of intact proteins can be used in combination with an isotopic labeling strategy and an automated data analysis algorithm to measure E⊕ for the thiols in both E Coli Thioredoxin 1 and Human Thioredoxin 1. Our methodology relies on accurate mass measurement of proteins using LC-MS analyses and does not necessarily require top-down fragmentation. As well as analyzing homogeneous protein samples, we also demonstrate that our methodology can be used to determine thiol E⊕ measurements in samples which contain mixtures of proteins. Thus the combination of experiential methodology and data analysis regime have the potential to make such measurements in a high-throughput manner and in a manner more accessible to a broad community of protein scientists

A randomized, open-label study of the efficacy and safety of AZD4547 monotherapy versus paclitaxel for the treatment of advanced gastric adenocarcinoma with FGFR2 polysomy or gene amplification

Background:Approximately 5%-10% of gastric cancers have a fibroblast growth factor receptor-2 (FGFR2) gene amplification. AZD4547 is a selective FGFR-1, 2, 3 tyrosine kinase inhibitor with potent preclinical activity in FGFR2 amplified gastric adenocarcinoma SNU16 and SGC083 xenograft models. The randomized phase II SHINE study (NCT01457846) investigated whether AZD4547 improves clinical outcome versus paclitaxel as second-line treatment in patients with advanced gastric adenocarcinoma displaying FGFR2 polysomy or gene amplification detected by fluorescence in situ hybridization. Patients and methods:Patients were randomized 3:2 (FGFR2 gene amplification) or 1:1 (FGFR2 polysomy) to AZD4547 or paclitaxel. Patients received AZD4547 80 mg twice daily, orally, on a 2 weeks on/1 week off schedule of a 21-day cycle or intravenous paclitaxel 80 mg/m2 administered weekly on days 1, 8, and 15 of a 28-day cycle. The primary end point was progression-free survival (PFS). Safety outcomes were assessed and an exploratory biomarker analysis was undertaken. Results:Of 71 patients randomized (AZD4547 n = 41, paclitaxel n = 30), 67 received study treatment (AZD4547 n = 40, paclitaxel n = 27). Among all randomized patients, median PFS was 1.8 months with AZD4547 and 3.5 months with paclitaxel (one-sided P = 0.9581); median follow-up duration for PFS was 1.77 and 2.12 months, respectively. The incidence of adverse events was similar in both treatment arms. Exploratory biomarker analyses revealed marked intratumor heterogeneity of FGFR2 amplification and poor concordance between amplification/polysomy and FGFR2 mRNA expression. Conclusions:AZD4547 did not significantly improve PFS versus paclitaxel in gastric cancer FGFR2 amplification/polysomy patients. Considerable intratumor heterogeneity for FGFR2 gene amplification and poor concordance between FGFR2 amplification/polysomy and FGFR2 expression indicates the need for alternative predictive biomarker testing. AZD4547 was generally well tolerated