Diffraction-limited ultrabroadband terahertz spectroscopy

Diffraction is the ultimate limit at which details of objects can be resolved in conventional optical spectroscopy and imaging systems. In the THz spectral range, spectroscopy systems increasingly rely on ultra-broadband radiation (extending over more 5 octaves) making a great challenge to reach resolution limited by diffraction. Here, we propose an original easy-to-implement wavefront manipulation concept to achieve ultrabroadband THz spectroscopy system with diffraction-limited resolution. Applying this concept to a large-area photoconductive emitter, we demonstrate diffraction-limited ultra-broadband spectroscopy system up to 14.5 THz with a dynamic range of 103. The strong focusing of ultrabroadband THz radiation provided by our approach is essential for investigating single micrometer-scale objects such as graphene flakes or living cells, and besides for achieving intense ultra-broadband THz electric fields

Modelling human visual navigation using multi-view scene reconstruction

It is often assumed that humans generate a 3D reconstruction of the environment, either in egocentric or world-based coordinates, but the steps involved are unknown. Here, we propose two reconstruction-based models, evaluated using data from two tasks in immersive virtual reality. We model the observer’s prediction of landmark location based on standard photogrammetric methods and then combine location predictions to compute likelihood maps of navigation behaviour. In one model, each scene point is treated independently in the reconstruction; in the other, the pertinent variable is the spatial relationship between pairs of points. Participants viewed a simple environment from one location, were transported (virtually) to another part of the scene and were asked to navigate back. Error distributions varied substantially with changes in scene layout; we compared these directly with the likelihood maps to quantify the success of the models. We also measured error distributions when participants manipulated the location of a landmark to match the preceding interval, providing a direct test of the landmark-location stage of the navigation models. Models such as this, which start with scenes and end with a probabilistic prediction of behaviour, are likely to be increasingly useful for understanding 3D vision

Conserved genes and pathways in primary human fibroblast strains undergoing replicative and radiation induced senescence

Additional file 3: Figure S3. Regulation of genes of Arrhythmogenic right ventricular cardiomyopathy pathway during senescence induction in HFF strains Genes of the “Arrhythmogenic right ventricular cardiomyopathy” pathway which are significantly up- (green) and down- (red) regulated (log2 fold change >1) during irradiation induced senescence (120 h after 20 Gy irradiation) in HFF strains. Orange color signifies genes which are commonly up-regulated during both, irradiation induced and replicative senescence

A Pooled Analysis of Infections, Malignancy, and Mortality in Infliximab- and Immunomodulator-Treated Adult Patients With Inflammatory Bowel Disease

The objective of this study was to analyze the safety of long-term infliximab treatment, with/without concomitant immunomodulators, across Crohn's disease (CD) and ulcerative colitis (UC) clinical trials.status: publishe

Evaluation of high-throughput genomic assays for the Fc gamma receptor locus

Cancer immunotherapy has been revolutionised by the use of monoclonal antibodies (mAb) that function through their interaction with Fc gamma receptors (FcγRs). The low-affinity FcγR genes are highly homologous, map to a complex locus at 1p23 and harbour single nucleotide polymorphisms (SNPs) and copy number variation (CNV) that can impact on receptor function and response to therapeutic mAbs. This complexity can hinder accurate characterisation of the locus. We therefore evaluated and optimised a suite of assays for the genomic analysis of the FcγR locus amenable to peripheral blood mononuclear cells and formalin-fixed paraffin-embedded (FFPE) material that can be employed in a high-throughput manner. Assessment of TaqMan genotyping for FCGR2A-131H/R, FCGR3A-158F/V and FCGR2B-232I/T SNPs demonstrated the need for additional methods to discriminate genotypes for the FCGR3A-158F/V and FCGR2B-232I/T SNPs due to sequence homology and CNV in the region. A multiplex ligation-dependent probe amplification assay provided high quality SNP and CNV data in PBMC cases, but there was greater data variability in FFPE material in a manner that was predicted by the BIOMED-2 multiplex PCR protocol. In conclusion, we have evaluated a suite of assays for the genomic analysis of the FcγR locus that are scalable for application in large clinical trials of mAb therapy. These assays will ultimately help establish the importance of FcγR genetics in predicting response to antibody therapeutics

Maslow in the Mud: Contrast between qualitative and quantitative assessment of thermal performance in historic buildings.

This paper argues that the notion of comfort is first and foremost re-lated to subjective choices and individual value systems. The article presents re-sults from research on the perception and measurements of the thermal qualities of heritage buildings in Lincolnshire, UK. The qualitative and quantitative re-sults identified a strong contrast between different methodologies. Inhabitants describe as comfortable houses which would not be considered comfortable if a standard positivist approach was used. The conflict presented will be dis-cussed in the context of sustainable strategies in architecture

Serum after Autologous Transplantation Stimulates Proliferation and Expansion of Human Hematopoietic Progenitor Cells

Regeneration after hematopoietic stem cell transplantation (HSCT) depends on enormous activation of the stem cell pool. So far, it is hardly understood how these cells are recruited into proliferation and self-renewal. In this study, we have addressed the question if systemically released factors are involved in activation of hematopoietic stem and progenitor cells (HPC) after autologous HSCT. Serum was taken from patients before chemotherapy, during neutropenia and after hematopoietic recovery. Subsequently, it was used as supplement for in vitro culture of CD34+ cord blood HPC. Serum taken under hematopoietic stress (4 to 11 days after HSCT) significantly enhanced proliferation, maintained primitive immunophenotype (CD34+, CD133+, CD45−) for more cell divisions and increased colony forming units (CFU) as well as the number of cobblestone area-forming cells (CAFC). The stimulatory effect decays to normal levels after hematopoietic recovery (more than 2 weeks after HSCT). Chemokine profiling revealed a decline of several growth-factors during neutropenia, including platelet-derived growth factors PDGF-AA, PDGF-AB and PDGF-BB, whereas expression of monocyte chemotactic protein-1 (MCP-1) increased. These results demonstrate that systemically released factors play an important role for stimulation of hematopoietic regeneration after autologous HSCT. This feedback mechanism opens new perspectives for in vivo stimulation of the stem cell pool

Decoupling Environment-Dependent and Independent Genetic Robustness across Bacterial Species

The evolutionary origins of genetic robustness are still under debate: it may arise as a consequence of requirements imposed by varying environmental conditions, due to intrinsic factors such as metabolic requirements, or directly due to an adaptive selection in favor of genes that allow a species to endure genetic perturbations. Stratifying the individual effects of each origin requires one to study the pertaining evolutionary forces across many species under diverse conditions. Here we conduct the first large-scale computational study charting the level of robustness of metabolic networks of hundreds of bacterial species across many simulated growth environments. We provide evidence that variations among species in their level of robustness reflect ecological adaptations. We decouple metabolic robustness into two components and quantify the extents of each: the first, environmental-dependent, is responsible for at least 20% of the non-essential reactions and its extent is associated with the species' lifestyle (specialized/generalist); the second, environmental-independent, is associated (correlation = ∼0.6) with the intrinsic metabolic capacities of a species—higher robustness is observed in fast growers or in organisms with an extensive production of secondary metabolites. Finally, we identify reactions that are uniquely susceptible to perturbations in human pathogens, potentially serving as novel drug-targets

FcγRIIb differentially regulates pre-immune and germinal center B cell tolerance in mouse and human.

Several tolerance “checkpoints” exist throughout B cell development to control autoreactive B cells and prevent the generation of pathogenic autoantibodies. FcγRIIb is an Fc receptor that inhibits B cell activation and, if defective, is associated with autoimmune disease. Its impact on specific B cell tolerance checkpoints is unknown. Here we show that reduced expression of FcγRIIb leads to increased deletion and anergy of autoreactive immature B cells, but despite this autoreactive B cells expand in the germinal center and serum autoantibodies are produced, even in response to exogenous non-self antigen. Thus, we show FcγRIIb has opposing effects on pre- and post-immune tolerance checkpoints, and suggest B cell tolerance requires the control of “bystander” germinal center B cells with low or no affinity for the immunization antigen

Adult zebrafish as a model organism for behavioural genetics

Recent research has demonstrated the suitability of adult zebrafish to model some aspects of complex behaviour. Studies of reward behaviour, learning and memory, aggression, anxiety and sleep strongly suggest that conserved regulatory processes underlie behaviour in zebrafish and mammals. The isolation and molecular analysis of zebrafish behavioural mutants is now starting, allowing the identification of novel behavioural control genes. As a result of this, studies of adult zebrafish are now helping to uncover the genetic pathways and neural circuits that control vertebrate behaviour