Evaluating multi-loop Feynman diagrams with infrared and threshold singularities numerically

We present a method to evaluate numerically Feynman diagrams directly from their Feynman parameters representation. We first disentangle overlapping singularities using sector decomposition. Threshold singularities are treated with an appropriate contour deformation. We have validated our technique comparing with recent analytic results for the gg->h two-loop amplitudes with heavy quarks and scalar quarks.Comment: 8 pages, 3 figures; references added, version to appear in JHE

Wandering behaviour prevents inter and intra oceanic speciation in a coastal pelagic fish

Small pelagic fishes have the ability to disperse over long distances and may present complex evolutionary histories. Here, Old World Anchovies (OWA) were used as a model system to understand genetic patterns and connectivity of fish between the Atlantic and Pacific basins. We surveyed 16 locations worldwide using mtDNA and 8 microsatellite loci for genetic parameters, and mtDNA (cyt b; 16S) and nuclear (RAG1; RAG2) regions for dating major lineage-splitting events within Engraulidae family. The OWA genetic divergences (0-0.4%) are compatible with intra-specific divergence, showing evidence of both ancient and contemporary admixture between the Pacific and Atlantic populations, enhanced by high asymmetrical migration from the Pacific to the Atlantic. The estimated divergence between Atlantic and Pacific anchovies (0.67 [0.53-0.80] Ma) matches a severe drop of sea temperature during the Gunz glacial stage of the Pleistocene. Our results support an alternative evolutionary scenario for the OWA, suggesting a coastal migration along south Asia, Middle East and eastern Africa continental platforms, followed by the colonization of the Atlantic via the Cape of the Good Hope.Portuguese Foundation for Science & Technology (FCT) [SFRH/BD/36600/2007]; FCT [UID/MAR/04292/2013, SFRH/BPD/65830/2009]; FCT strategic plan [UID/Multi/04326/2013]info:eu-repo/semantics/publishedVersio

Population history, gene flow, and bottlenecks in island populations of a secondary seed disperser, the southern grey shrike (Lanius meridionalis koenigi)

Studying the population history and demography of organisms with important ecological roles can aid understanding of evolutionary processes at the community level and inform conservation. We screened genetic variation (mtDNA and microsatellite) across the populations of the southern grey shrike (Lanius meridionalis koenigi) in the Canary Islands, where it is an endemic subspecies and an important secondary seed disperser. We show that the Canarian subspecies is polyphyletic with L. meridionalis elegans from North Africa and that shrikes have colonized the Canary Islands from North Africa multiple times. Substantial differences in genetic diversity exist across islands, which are most likely the product of a combination of historical colonization events and recent bottlenecks. The Eastern Canary Islands had the highest overall levels of genetic diversity and have probably been most recently and/or frequently colonized from Africa. Recent or ongoing bottlenecks were detected in three of the islands and are consistent with anecdotal evidence of population declines due to human disturbance. These findings are troubling given the shrike's key ecological role in the Canary Islands, and further research is needed to understand the community-level consequences of declines in shrike populations. Finally, we found moderate genetic differentiation among populations, which largely reflected the shrike's bottleneck history; however, a significant pattern of isolation-by-distance indicated that some gene flow occurs between islands. This study is a useful first step toward understanding how secondary seed dispersal operates over broad spatial scales

Essential function for ErbB3 in breast cancer proliferation

The overexpression of the ErbB family of tyrosine kinase receptors is thought to be important in the development of many breast tumours. To date, most attention has focused on the ErbB2 receptor. Now, in a recent report, it has been shown that ErbB3 is a critical partner for the transforming activity of ErbB2 in breast cancer cells. Importantly, the proliferative signals from this transforming complex appear to act via the PI-3 kinase pathway

Novel Antibody Drug Conjugates Targeting Tumor-Associated Receptor Tyrosine Kinase ROR2 by Functional Screening of Fully Human Antibody Libraries Using Transpo-mAb Display on Progenitor B Cells

Receptor tyrosine kinase-like orphan receptor 2 (ROR2) has been identified as a highly relevant tumor-associated antigen in a variety of cancer indications of high unmet medical need, including renal cell carcinoma and osteosarcoma, making it an attractive target for targeted cancer therapy. Here, we describe the de novo discovery of fully human ROR2-specific antibodies and potent antibody drug conjugates (ADCs) derived thereof by combining antibody discovery from immune libraries of human immunoglobulin transgenic animals using the Transpo-mAb mammalian cell-based IgG display platform with functional screening for internalizing antibodies using a secondary ADC assay. The discovery strategy entailed immunization of transgenic mice with the cancer antigen ROR2, harboring transgenic IgH and IgL chain gene loci with limited number of fully human V, D, and J gene segments. This was followed by recovering antibody repertoires from the immunized animals, expressing and screening them as full-length human IgG libraries by transposon-mediated display in progenitor B lymphocytes (“Transpo-mAb Display”) for ROR2 binding. Individual cellular “Transpo-mAb” clones isolated by single cell sorting and capable of expressing membrane-bound as well as secreted human IgG were directly screened during antibody discovery, not only for high affinity binding to human ROR2, but also functionally as ADCs using a cytotoxicity assay with a secondary anti-human IgG-toxin-conjugate. Using this strategy, we identified and validated 12 fully human, monoclonal anti-human ROR2 antibodies with nanomolar affinities that are highly potent as ADCs and could be promising candidates for the therapy of human cancer. The screening for functional and internalizing antibodies during the early phase of antibody discovery demonstrates the utility of the mammalian cell-based Transpo-mAb Display platform to select for functional binders and as a powerful tool to improve the efficiency for the development of therapeutically relevant ADCs

Exploring rationales for branding a university: Should we be seeking to measure branding in UK universities?

Although branding is now widespread among UK universities, the application of branding principles in the higher education sector is comparatively recent and may be controversial for internal audiences who question its suitability and efficiency. This paper seeks to investigate how and whether the effectiveness of branding activity in the higher education sector should be evaluated and measured, through exploratory interviews with those who often drive it; UK University marketing professionals. Conclusions suggest that university branding is inherently complex and therefore application of commercial approaches may be over simplistic. Whilst marketing professionals discuss challenges they do not necessarily have a consistent view of the objectives of branding activity although all were able to clearly articulate branding objectives for their university, including both qualitative and, to some extent, quantitative metrics. Some measures of the real value of branding activity are therefore suggested but a key debate is perhaps whether the objectives and role of branding in higher education needs to be clarified, and a more consistent view of appropriate metrics reached? Various challenges in implementing branding approaches are also highlighted

Inertial picobalance reveals fast mass fluctuations in mammalian cells

The regulation of size, volume and mass in living cells is physiologically important, and dysregulation of these parameters gives rise to many diseases. Cell mass is largely determined by the amount of water, proteins, lipids, carbohydrates and nucleic acids present in a cell, and is tightly linked to metabolism, proliferation and gene expression. Technologies have emerged in recent years that make it possible to track the masses of single suspended cells and adherent cells. However, it has not been possible to track individual adherent cells in physiological conditions at the mass and time resolutions required to observe fast cellular dynamics. Here we introduce a cell balance (a 'picobalance'), based on an optically excited microresonator, that measures the total mass of single or multiple adherent cells in culture conditions over days with millisecond time resolution and picogram mass sensitivity. Using our technique, we observe that the mass of living mammalian cells fluctuates intrinsically by around one to four per cent over timescales of seconds throughout the cell cycle. Perturbation experiments link these mass fluctuations to the basic cellular processes of ATP synthesis and water transport. Furthermore, we show that growth and cell cycle progression are arrested in cells infected with vaccinia virus, but mass fluctuations continue until cell death. Our measurements suggest that all living cells show fast and subtle mass fluctuations throughout the cell cycle. As our cell balance is easy to handle and compatible with fluorescence microscopy, we anticipate that our approach will contribute to the understanding of cell mass regulation in various cell states and across timescales, which is important in areas including physiology, cancer research, stem-cell differentiation and drug discovery

Targeted plasmid integration into the human genome by an engineered zinc-finger recombinase

The development of new methods for gene addition to mammalian genomes is necessary to overcome the limitations of conventional genetic engineering strategies. Although a variety of DNA-modifying enzymes have been used to directly catalyze the integration of plasmid DNA into mammalian genomes, there is still an unmet need for enzymes that target a single specific chromosomal site. We recently engineered zinc-finger recombinase (ZFR) fusion proteins that integrate plasmid DNA into a synthetic target site in the human genome with exceptional specificity. In this study, we present a two-step method for utilizing these enzymes in any cell type at randomly-distributed target site locations. The piggyBac transposase was used to insert recombinase target sites throughout the genomes of human and mouse cell lines. The ZFR efficiently and specifically integrated a transfected plasmid into these genomic target sites and into multiple transposons within a single cell. Plasmid integration was dependent on recombinase activity and the presence of recombinase target sites. This work demonstrates the potential for broad applicability of the ZFR technology in genome engineering, synthetic biology and gene therapy