The increasing interest in Support Vector Machines (SVMs) over the past 15 years is described. Methods are illustrated using simulated case studies, and 4 experimental case studies, namely mass ...spectrometry for studying pollution, near infrared analysis of food, thermal analysis of polymers and UV/visible spectroscopy of polyaromatic hydrocarbons. The basis of SVMs as two-class classifiers is shown with extensive visualisation, including learning machines, kernels and penalty functions. The influence of the penalty error and radial basis function radius on the model is illustrated. Multiclass implementations including one vs. all, one vs. one, fuzzy rules and Directed Acyclic Graph (DAG) trees are described. One-class Support Vector Domain Description (SVDD) is described and contrasted to conventional two- or multi-class classifiers. The use of Support Vector Regression (SVR) is illustrated including its application to multivariate calibration, and why it is useful when there are outliers and non-linearities.
Engages in a wide-ranging exploration of what we can learn from the study of ancient civilizations, which is relevant to fundamental problems, both intellectual and moral, that we continue to face ...today. How far is it possible to arrive at an understanding of alien systems of belief? Is it possible to talk meaningfully of 'science' and of its various constituent disciplines, 'astronomy', 'geography', 'anatomy', and so on, in the ancient world? Are logic and its laws universal? Is there one ontology—a single world—to which all attempts at understanding must be considered to be directed? When we encounter apparently very different views of reality, how far can that be put down to a difference in conceptions of what needs explaining, or of what counts as an explanation, or to different preferred modes of reasoning or styles of enquiry? Do the notions of truth and belief represent reliable cross-cultural universals? Are the discourses of human nature and of human rights universally applicable? What political institutions do we need to help secure equity and justice within nation states and between them? Lloyd provides compelling evidence that the science and culture of ancient Greece and China have much to offer contemporary debates in many fields of study.
This book challenges the common assumption that the predominant focus of the history of science should be the achievements of Western scientists since the so-called Scientific Revolution. The ...conceptual frameworks within which the members of earlier societies and of modern indigenous groups worked admittedly pose severe problems for our understanding. But rather than dismiss them on the grounds that they are incommensurable with our own and to that extent unintelligible, we should see them as offering opportunities for us to revise many of our own preconceptions. We should accept that the realities to be accounted for are multi-dimensional and that all such accounts are to some extent value-laden. In the process insights from current anthropology and the study of ancient Greece and China especially are brought to bear to suggest how the remit of the history of science can be expanded to achieve a cross-cultural perspective on the problems.
The blood feeding poultry red mite (PRM), Dermanyssus gallinae, causes substantial economic damage to the egg laying industry worldwide, and is a serious welfare concern for laying hens and poultry ...house workers. In this study we have investigated the temporal gene expression across the 6 stages/sexes (egg, larvae, protonymph and deutonymph, adult male and adult female) of this neglected parasite in order to understand the temporal expression associated with development, parasitic lifestyle, reproduction and allergen expression.
RNA-seq transcript data for the 6 stages were mapped to the PRM genome creating a publicly available gene expression atlas (on the OrcAE platform in conjunction with the PRM genome). Network analysis and clustering of stage-enriched gene expression in PRM resulted in 17 superclusters with stage-specific or multi-stage expression profiles. The 6 stage specific superclusters were clearly demarked from each other and the adult female supercluster contained the most stage specific transcripts (2725), whilst the protonymph supercluster the fewest (165). Fifteen pairwise comparisons performed between the different stages resulted in a total of 6025 Differentially Expressed Genes (DEGs) (P > 0.99). These data were evaluated alongside a Venn/Euler analysis of the top 100 most abundant genes in each stage. An expanded set of cuticle proteins and enzymes (chitinase and metallocarboxypeptidases) were identified in larvae and underpin cuticle formation and ecdysis to the protonymph stage. Two mucin/peritrophic-A salivary proteins (DEGAL6771g00070, DEGAL6824g00220) were highly expressed in the blood-feeding stages, indicating peritrophic membrane formation during feeding. Reproduction-associated vitellogenins were the most abundant transcripts in adult females whilst, in adult males, an expanded set of serine and cysteine proteinases and an epididymal protein (DEGAL6668g00010) were highly abundant. Assessment of the expression patterns of putative homologues of 32 allergen groups from house dust mites indicated a bias in their expression towards the non-feeding larval stage of PRM.
This study is the first evaluation of temporal gene expression across all stages of PRM and has provided insight into developmental, feeding, reproduction and survival strategies employed by this mite. The publicly available PRM resource on OrcAE offers a valuable tool for researchers investigating the biology and novel interventions of this parasite.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Mid-infrared (MIR) imaging has emerged as a valuable tool to investigate biological samples, such as tissue histological sections and cell cultures, by providing non-destructive chemical specificity ...without recourse to labels. While feasibility studies have shown the capabilities of MIR imaging approaches to address key biological and clinical questions, these techniques are still far from being deployable by non-expert users. In this review, we discuss the current state of the art of MIR technologies and give an overview on technical innovations and developments with the potential to make MIR imaging systems more readily available to a larger community. The most promising developments over the last few years are discussed here. They include improvements in MIR light sources with the availability of quantum cascade lasers and supercontinuum IR sources as well as the recently developed upconversion scheme to improve the detection of MIR radiation. These technical advances can substantially speed up data acquisition of multispectral or hyperspectral datasets thus providing the end user with vast amounts of data when imaging whole tissue areas of many mm2. Therefore, effective data analysis is of tremendous importance, and progress in method development is discussed with respect to the specific biomedical context.
The search for materials and systems, capable of operating long term under physiological conditions, has been a strategy for many research groups during the past years. Silicon carbide (SiC) is a ...material, which can meet the demands due to its high biocompatibility, high inertness to biological tissues and to aggressive environment, and the possibility to make all types of electronic devices.
While grouping/read-across is widely used to fill data gaps, chemical registration dossiers are often rejected due to weak category justifications based on structural similarity only. Metabolomics ...provides a route to robust chemical categories via evidence of shared molecular effects across source and target substances. To gain international acceptance, this approach must demonstrate high reliability, and best-practice guidance is required. The MetAbolomics ring Trial for CHemical groupING (MATCHING), comprising six industrial, government and academic ring-trial partners, evaluated inter-laboratory reproducibility and worked towards best-practice. An independent team selected eight substances (WY-14643, 4-chloro-3-nitroaniline, 17α-methyl-testosterone, trenbolone, aniline, dichlorprop-p, 2-chloroaniline, fenofibrate); ring-trial partners were blinded to their identities and modes-of-action. Plasma samples were derived from 28-day rat tests (two doses per substance), aliquoted, and distributed to partners. Each partner applied their preferred liquid chromatography–mass spectrometry (LC–MS) metabolomics workflows to acquire, process, quality assess, statistically analyze and report their grouping results to the European Chemicals Agency, to ensure the blinding conditions of the ring trial. Five of six partners, whose metabolomics datasets passed quality control, correctly identified the grouping of eight test substances into three categories, for both male and female rats. Strikingly, this was achieved even though a range of metabolomics approaches were used. Through assessing intrastudy quality-control samples, the sixth partner observed high technical variation and was unable to group the substances. By comparing workflows, we conclude that some heterogeneity in metabolomics methods is
not
detrimental to consistent grouping, and that assessing data quality prior to grouping is essential. We recommend development of international guidance for quality-control acceptance criteria. This study demonstrates the reliability of metabolomics for chemical grouping and works towards best-practice.
Genome duplication necessarily involves the replication of imperfect DNA templates and, if left to their own devices, replication complexes regularly run into problems. The details of how cells ...overcome these replicative 'hiccups' are beginning to emerge, revealing a complex interplay between DNA replication, recombination and repair that ensures faithful passage of the genetic material from one generation to the next.
Celotno besedilo
Dostopno za:
DOBA, IJS, IZUM, KILJ, NUK, PILJ, PNG, SAZU, UILJ, UKNU, UL, UM, UPUK
Summary
Background
The proinflammatory cytokine interleukin (IL)‐17A plays a pivotal role in psoriasis pathogenesis. Secukinumab, a fully human monoclonal antibody (mAb) that selectively targets ...IL‐17A, has been demonstrated to be highly efficacious for the treatment of moderate‐to‐severe psoriasis, starting at early time points, with a sustained effect and a favourable safety profile. mAb therapies may be associated with production of antidrug antibodies (ADAs) that can affect drug pharmacokinetics, diminish response or cause hypersensitivity reactions.
Objectives
To investigate the immunogenicity of secukinumab across six phase III clinical trials in which patients with plaque psoriasis were treated with secukinumab for up to 52 weeks and additionally followed up at week 60.
Methods
Immunogenicity in patients with plaque psoriasis exposed to secukinumab was evaluated at baseline and at weeks 12, 24, 52 and 60. Treatment‐emergent (TE)‐ADAs were defined as a positive ADA signal detected in post‐treatment samples from patients with a negative baseline signal. Confirmed positive samples were further analysed for their drug‐neutralizing potential.
Results
Among 2842 patients receiving secukinumab and evaluated for ADAs, 11 (0·4%) developed TE‐ADAs. Associations between TE‐ADAs and secukinumab dose, frequency or mode of administration were not observed. Neutralizing antibodies were detected in three of nine evaluable patients with TE‐ADAs.
Conclusions
Secukinumab immunogenicity was low, as shown by TE‐ADA detection in only 11 of 2842 (0·4%) patients with moderate‐to‐severe plaque psoriasis treated with secukinumab. All but one of the patients with TE‐ADAs were biologic naive. Neither TE‐ADAs nor neutralizing antibodies were associated with loss of secukinumab efficacy or issues of clinical concern.
What's already known about this topic?
The proinflammatory cytokine interleukin (IL)‐17A plays a pivotal role in psoriasis pathogenesis.
Secukinumab is a therapeutic fully human monoclonal antibody that selectively targets IL‐17A.
Secukinumab has demonstrated efficacy in phase III clinical trials of patients with moderate‐to‐severe psoriasis.
Biologics can be immunogenic, and the resulting antidrug antibodies can compromise efficacy.
What does this study add?
Secukinumab demonstrated low immunogenicity, and the antidrug antibodies that were detected were of no clinical concern.
Linked Comment: Makrygeorgou. Br J Dermatol 2017; 176:573–574.
Abstract
Emerging bacterial pathogens threaten global health and food security, and so it is important to ask whether these transitions to pathogenicity have any common features. We present a ...systematic study of the claim that pathogenicity is associated with genome reduction and gene loss. We compare broad-scale patterns across all bacteria, with detailed analyses of Streptococcus suis, an emerging zoonotic pathogen of pigs, which has undergone multiple transitions between disease and carriage forms. We find that pathogenicity is consistently associated with reduced genome size across three scales of divergence (between species within genera, and between and within genetic clusters of S. suis). Although genome reduction is also found in mutualist and commensal bacterial endosymbionts, genome reduction in pathogens cannot be solely attributed to the features of their ecology that they share with these species, that is, host restriction or intracellularity. Moreover, other typical correlates of genome reduction in endosymbionts (reduced metabolic capacity, reduced GC content, and the transient expansion of nonfunctional elements) are not consistently observed in pathogens. Together, our results indicate that genome reduction is a consistent correlate of pathogenicity in bacteria.
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