Dark Matter-Neutrino Interconversion at COHERENT, Direct Detection, and the Early Universe

We study a dark matter (DM) model in which the dominant coupling to the standard model occurs through a neutrino-DM-scalar coupling. The new singlet scalar will generically have couplings to nuclei/electrons arising from renormalizable Higgs portal interactions. As a result, the DM particle X can convert into a neutrino via scattering on a target nucleus N: X+N→ν+N, leading to striking signatures at direct detection experiments. Similarly, DM can be produced in neutrino scattering events at neutrino experiments: ν+N→X+N, predicting spectral distortions at experiments such as COHERENT. Furthermore, the model allows for late kinetic decoupling of dark matter with implications for small-scale structure. At low masses, we find that COHERENT and late kinetic decoupling produce the strongest constraints on the model, while at high masses the leading constraints come from DM down-scattering at XENON1T and Borexino. Future improvement will come from CEνNS data, ultralow threshold direct detection, and rare kaon decays

Emerging aspects of oesophageal and gastro-oesophageal junction cancer histopathology – an update for the surgical oncologist

Adenocarcinoma of the oesophagus and gastro-oesophageal junction are rapidly increasing in incidence and have a well described sequence of carcinogenesis: the Barrett's metaplasia-dysplasia-adenocarcinoma sequence. During recent years there have been changes in the knowledge surrounding disease progression, cancer management and histopathology specimen reporting. Tumours around the gastro-oesophageal junction (GOJ) pose several specific challenges. Numerous difficulties arise when the existing TNM staging systems for gastric and oesophageal cancers are applied to GOJ tumours. The issues facing the current TNM staging and GOJ tumour classification systems are reviewed in this article. Recent evidence regarding the importance of several histopathologically derived prognostic factors, such as circumferential resection margin status and lymph node metastases, have implications for specimen reporting. With the rising use of multimodal treatments for oesophageal cancer it is important that the response of the tumour to this therapy is carefully documented pathologically. In addition, several controversial and novel areas such as endoscopic mucosal resection, lymph node micrometastases and the sentinel node concept are being studied. We aim to review these aspects, with special relevance to oesophageal and gastro-oesophageal cancer specimen reporting, to update the surgical oncologist with an interest in upper gastrointestinal cancer

Deletion of genes encoding PU.1 and Spi-B in B cells impairs differentiation and induces pre-B cell acute lymphoblastic leukemia

The E26 transformation-specific (Ets) transcription factor PU.1 is required to generate lymphoid progenitor cells from hematopoietic stem cells, but it is not required to generate B cells from committed B-cell lineage progenitors.We hypothesized that PU.1 function in B-cell differentiation is complemented by the related Ets transcription factor Spi-B. To test this hypothesis, mice were generated lacking both PU.1 and Spi-B in the B-cell lineage. Unlike mice lacking PU.1 or Spi-B, mice deficient in both PU.1 and Spi-B in the B-cell lineage had reduced frequencies of B cells as well as impaired B-cell differentiation. Strikingly, all PU.1 and Spi-B-deficient mice developed pre-B cell acute lymphoblastic leukemia before 30 weeks of age. Pre-B cells accumulated in the thymus resulting in massive thymic enlargement and dyspnea. These findings demonstrate that PU.1 and Spi-B are essential transcriptional regulators of B-cell differentiation as well as novel tumor suppressors in the B-cell lineage. © 2011 by The American Society of Hematology

Deletion of Panx3 Prevents the Development of Surgically Induced Osteoarthritis

© 2015, Springer-Verlag Berlin Heidelberg. Abstract: Osteoarthritis (OA) is a highly prevalent, disabling joint disease with no existing therapies to slow or halt its progression. Cartilage degeneration hallmarks OA pathogenesis, and pannexin 3 (Panx3), a member of a novel family of channel proteins, is upregulated during this process. The function of Panx3 remains poorly understood, but we consistently observed a strong increase in Panx3 immunostaining in OA lesions in both mice and humans. Here, we developed and characterized the first global and conditional Panx3 knockout mice to investigate the role of Panx3 in OA. Interestingly, global Panx3 deletion produced no overt phenotype and had no obvious effect on early skeletal development. Mice lacking Panx3 specifically in the cartilage and global Panx3 knockout mice were markedly resistant to the development of OA following destabilization of medial meniscus surgery. These data indicate a specific catabolic role of Panx3 in articular cartilage and identify Panx3 as a potential therapeutic target for OA. Lastly, while Panx1 has been linked to over a dozen human pathologies, this is the first in vivo evidence for a role of Panx3 in disease. Key message: Panx3 is localized to cartilage lesions in mice and humans.Global Panx3 deletion does not result in any developmental abnormalities.Mice lacking Panx3 are resistant to the development of osteoarthritis.Panx3 is a novel therapeutic target for the treatment of osteoarthritis

Seminal fluid compromises visual perception in honeybee queens reducing their survival during additional mating flights

Queens of social insects make all mate-choice decisions on a single day, except in honeybees whose queens can conduct mating flights for several days even when already inseminated by a number of drones. Honeybees therefore appear to have a unique, evolutionarily derived form of sexual conflict: a queen's decision to pursue risky additional mating flights is driven by later-life fitness gains from genetically more diverse worker-offspring but reduces paternity shares of the drones she already mated with. We used artificial insemination, RNA-sequencing and electroretinography to show that seminal fluid induces a decline in queen vision by perturbing the phototransduction pathway within 24-48 hr. Follow up field trials revealed that queens receiving seminal fluid flew two days earlier than sister queens inseminated with saline, and failed more often to return. These findings are consistent with seminal fluid components manipulating queen eyesight to reduce queen promiscuity across mating flights

A timeband framework for modelling real-time systems

Complex real-time systems must integrate physical processes with digital control, human operation and organisational structures. New scientific foundations are required for specifying, designing and implementing these systems. One key challenge is to cope with the wide range of time scales and dynamics inherent in such systems. To exploit the unique properties of time, with the aim of producing more dependable computer-based systems, it is desirable to explicitly identify distinct time bands in which the system is situated. Such a framework enables the temporal properties and associated dynamic behaviour of existing systems to be described and the requirements for new or modified systems to be specified. A system model based on a finite set of distinct time bands is motivated and developed in this paper

A retinoblastoma allele that is mutated at its common E2F interaction site inhibits cell proliferation in gene-targeted mice

The retinoblastoma protein (pRB) is best known for regulating cell proliferation through E2F transcription factors. In this report, we investigate the properties of a targeted mutation that disrupts pRB interactions with the transactivation domain of E2Fs. Mice that carry this mutation endogenously (Rb1δG) are defective for pRB-dependent repression of E2F target genes. Except for an accelerated entry into S phase in response to serum stimulation, cell cycle regulation in Rb1δG/δG mouse embryonic fibroblasts (MEFs) strongly resembles that of the wild type. In a serum deprivation-induced cell cycle exit, Rb1δG/δG MEFs display a magnitude of E2F target gene derepression similar to that of Rb1-/- cells, even though Rb1δG/δG cells exit the cell cycle normally. Interestingly, cell cycle arrest in Rb1δG/δG MEFs is responsive to p16 expression and gamma irradiation, indicating that alternate mechanisms can be activated in G1 to arrest proliferation. Some Rb1δG/δG mice die neonatally with a muscle degeneration phenotype, while the others live a normal life span with no evidence of spontaneous tumor formation. Most tissues appear histologically normal while being accompanied by derepression of pRB-regulated E2F targets. This suggests that non- E2F-, pRB-dependent pathways may have a more relevant role in proliferative control than previously identified. © 2014, American Society for Microbiology

Engaging with History after Macpherson

The Race Relations Amendment Act (2000) identifies a key role for education, and more specifically history, in promoting ‘race equality’ in Britain. In this article Ian Grosvenor and Kevin Myers consider the extent of young people’s current engagement with the history of ‘diversity, change and immigration’ which underpins the commitment to ‘race equality’. Finding that in many of Britain’s schools and universities a singular and exclusionary version of history continues to dominate the curriculum, they go on to consider the reasons for the neglect of multiculturalism. The authors identify the development of an aggressive national identity that depends on the past for its legitimacy and argue that this sense of the past is an important obstacle to future progress

Structural-Thermal-Optical-Performance (STOP) Model Development and Analysis of a Field-widened Michelson Interferometer

An integrated Structural-Thermal-Optical-Performance (STOP) model was developed for a field-widened Michelson interferometer which is being built and tested for the High Spectral Resolution Lidar (HSRL) project at NASA Langley Research Center (LaRC). The performance of the interferometer is highly sensitive to thermal expansion, changes in refractive index with temperature, temperature gradients, and deformation due to mounting stresses. Hand calculations can only predict system performance for uniform temperature changes, under the assumption that coefficient of thermal expansion (CTE) mismatch effects are negligible. An integrated STOP model was developed to investigate the effects of design modifications on the performance of the interferometer in detail, including CTE mismatch, and other three- dimensional effects. The model will be used to improve the design for a future spaceflight version of the interferometer. The STOP model was developed using the Comet SimApp'TM' Authoring Workspace which performs automated integration between Pro-Engineer, Thermal Desktop, MSC Nastran'TM', SigFit'TM', Code V'TM', and MATLAB. This is the first flight project for which LaRC has utilized Comet, and it allows a larger trade space to be studied in a shorter time than would be possible in a traditional STOP analysis. This paper describes the development of the STOP model, presents a comparison of STOP results for simple cases with hand calculations, and presents results of the correlation effort to bench-top testing of the interferometer. A trade study conducted with the STOP model which demonstrates a few simple design changes that can improve the performance seen in the lab is also presented