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Synthetic biology for pharmaceutical drug discovery
Synthetic biology (SB) is an emerging discipline, which is slowly reorienting the field of drug discovery. For thousands of years, living organisms such as plants were the major source of human medicines. The difficulty in resynthesizing natural products, however, often turned pharmaceutical industries away from this rich source for human medicine. More recently, progress on transformation through genetic manipulation of biosynthetic units in microorganisms has opened the possibility of in-depth exploration of the large chemical space of natural products derivatives. Success of SB in drug synthesis culminated with the bioproduction of artemisinin by microorganisms, a tour de force in protein and metabolic engineering. Today, synthetic cells are not only used as biofactories but also used as cell-based screening platforms for both target-based and phenotypic-based approaches. Engineered genetic circuits in synthetic cells are also used to decipher disease mechanisms or drug mechanism of actions and to study cell???cell communication within bacteria consortia. This review presents latest developments of SB in the field of drug discovery, including some challenging issues such as drug resistance and drug toxicity
An ex situ study of the adsorption of calcium phosphate from solution onto TiO2(110) and Al2O3(0001)
Ex situ atomic force microscopy and x-ray photoelectron spectroscopy are employed to characterise the adsorption of calcium phosphate from an aqueous solution of CaCl2.H2O and KH2PO4 onto rutile-TiO2(110) and α-Al2O3(0001). Prior to immersion, the substrates underwent wet chemical preparation to produce well-defined surfaces. Calcium phosphate adsorption is observed on both rutile-TiO2(110) and α-Al2O3(0001), with atomic force microscopy images indicating island-type growth. In contrast to other studies on less well-defined TiO2 and Al2O3 substrates, the induction period for calcium phosphate nucleation appears to be comparable on these two surfaces
2016: Book review of Indians on Display: Global Commodification of Native America in Performance, Art, and Museums by Norman K. Denzin
Representation of selected-reaction monitoring data in the mzQuantML data standard.
The mzQuantML data standard was designed to capture the output of quantitative software in proteomics, to support submissions to public repositories, development of visualization software and pipeline/modular approaches. The standard is designed around a common core that can be extended to support particular types of technique through the release of semantic rules that are checked by validation software. The first release of mzQuantML supported four quantitative proteomics techniques via four sets of semantic rules: (i) intensity-based (MS(1) ) label free, (ii) MS(1) label-based (such as SILAC or N(15) ), (iii) MS(2) tag-based (iTRAQ or tandem mass tags), and (iv) spectral counting. We present an update to mzQuantML for supporting SRM techniques. The update includes representing the quantitative measurements, and associated meta-data, for SRM transitions, the mechanism for inferring peptide-level or protein-level quantitative values, and support for both label-based or label-free SRM protocols, through the creation of semantic rules and controlled vocabulary terms. We have updated the specification document for mzQuantML (version 1.0.1) and the mzQuantML validator to ensure that consistent files are produced by different exporters. We also report the capabilities for production of mzQuantML files from popular SRM software packages, such as Skyline and Anubis
Routine versus As-Needed Bevacizumab with 12-Weekly Assessment Intervals for Neovascular Age-Related Macular Degeneration: 92-Week Results of the GMAN Trial.
PURPOSE: To evaluate the efficacy and safety of intravitreal bevacizumab (Avastin; Genentech, South San Francisco, CA) in patients with neovascular age-related macular degeneration (nAMD) using 2 different treatment regimens in which patients were assessed clinically at up to 12-week intervals. DESIGN: Randomized, controlled, noninferiority trial. PARTICIPANTS: A total of 331 patients with nAMD. METHODS: Patients were treated with 1.25 mg intravitreal bevacizumab and followed up to 92 weeks. They were randomized into 2 arms. All patients received 3 loading doses 4 weeks apart and thereafter were assessed every 12 weeks until the end of the study. One arm received a routine treatment at each 12-week assessment, and the other arm was treated at these assessments on an as-needed basis. After the loading doses, patients in either arm who showed signs of disease activity had an additional assessment after 6 weeks and at that visit had top-up treatments on an as-needed basis. MAIN OUTCOME MEASURES: Mean best-corrected visual acuity (BCVA) at 92 weeks. RESULTS: At 92 weeks, patients who had treatments every 12 weeks had superior BCVA to those treated on an as-needed basis every 12 weeks (P = 0.008), with the regular treatment arm gaining a mean BCVA of 5.5 letters and the as-needed treatment arm gaining 0.6 letters. The regular treatment arm of the study showed significantly improved outcomes with respect to 5-, 10-, and 15-letter changes in BCVA from baseline compared with the as-needed treatment arm, as well as superior reading speed. In patients who completed the study, up to but not including week 92, the mean number of treatments was 10.8 for the regular treatment arm and 9.1 for the as-needed treatment arm. CONCLUSIONS: A treatment regimen with regular bevacizumab injections every 12 weeks after loading doses supplemented with as-needed top-up treatments produced a stable improvement in BCVA from baseline. The improvement in BCVA was broadly similar to that obtained in other studies using anti-vascular endothelial growth factor drugs with more frequent assessments and treatments
Equivalence of generalized state-space averaging with DQ modelling methods in a balanced three-phase system
Why Machiavellianism Matters in Childhood: The Relationship Between Children's Machiavellian Traits and Their Peer Interactions in a Natural Setting
Common germline polymorphisms associated with breast cancer-specific survival.
INTRODUCTION: Previous studies have identified common germline variants nominally associated with breast cancer survival. These associations have not been widely replicated in further studies. The purpose of this study was to evaluate the association of previously reported SNPs with breast cancer-specific survival using data from a pooled analysis of eight breast cancer survival genome-wide association studies (GWAS) from the Breast Cancer Association Consortium. METHODS: A literature review was conducted of all previously published associations between common germline variants and three survival outcomes: breast cancer-specific survival, overall survival and disease-free survival. All associations that reached the nominal significance level of P valu