The KATRIN Pre-Spectrometer at reduced Filter Energy

The KArlsruhe TRItium Neutrino experiment, KATRIN, will determine the mass of the electron neutrino with a sensitivity of 0.2 eV (90% C.L.) via a measurement of the beta-spectrum of gaseous tritium near its endpoint of E_0 =18.57 keV. An ultra-low background of about b = 10 mHz is among the requirements to reach this sensitivity. In the KATRIN main beam-line two spectrometers of MAC-E filter type are used in a tandem configuration. This setup, however, produces a Penning trap which could lead to increased background. We have performed test measurements showing that the filter energy of the pre-spectrometer can be reduced by several keV in order to diminish this trap. These measurements were analyzed with the help of a complex computer simulation, modeling multiple electron reflections both from the detector and the photoelectric electron source used in our test setup.Comment: 22 pages, 12 figure

Commissioning of the vacuum system of the KATRIN Main Spectrometer

The KATRIN experiment will probe the neutrino mass by measuring the beta-electron energy spectrum near the endpoint of tritium beta-decay. An integral energy analysis will be performed by an electro-static spectrometer (Main Spectrometer), an ultra-high vacuum vessel with a length of 23.2 m, a volume of 1240 m^3, and a complex inner electrode system with about 120000 individual parts. The strong magnetic field that guides the beta-electrons is provided by super-conducting solenoids at both ends of the spectrometer. Its influence on turbo-molecular pumps and vacuum gauges had to be considered. A system consisting of 6 turbo-molecular pumps and 3 km of non-evaporable getter strips has been deployed and was tested during the commissioning of the spectrometer. In this paper the configuration, the commissioning with bake-out at 300{\deg}C, and the performance of this system are presented in detail. The vacuum system has to maintain a pressure in the 10^{-11} mbar range. It is demonstrated that the performance of the system is already close to these stringent functional requirements for the KATRIN experiment, which will start at the end of 2016.Comment: submitted for publication in JINST, 39 pages, 15 figure

Single-Cell Expression Profiling Reveals a Dynamic State of Cardiac Precursor Cells in the Early Mouse Embryo

In the early vertebrate embryo, cardiac progenitor/precursor cells (CPs) give rise to cardiac structures. Better understanding their biological character is critical to understand the heart development and to apply CPs for the clinical arena. However, our knowledge remains incomplete. With the use of single-cell expression profiling, we have now revealed rapid and dynamic changes in gene expression profiles of the embryonic CPs during the early phase after their segregation from the cardiac mesoderm. Progressively, the nascent mesodermal gene Mesp1 terminated, and Nkx2-5+/Tbx5+ population rapidly replaced the Tbx5low+ population as the expression of the cardiac genes Tbx5 and Nkx2-5 increased. At the Early Headfold stage, Tbx5-expressing CPs gradually showed a unique molecular signature with signs of cardiomyocyte differentiation. Lineage-tracing revealed a developmentally distinct characteristic of this population. They underwent progressive differentiation only towards the cardiomyocyte lineage corresponding to the first heart field rather than being maintained as a progenitor pool. More importantly, Tbx5 likely plays an important role in a transcriptional network to regulate the distinct character of the FHF via a positive feedback loop to activate the robust expression of Tbx5 in CPs. These data expands our knowledge on the behavior of CPs during the early phase of cardiac development, subsequently providing a platform for further study

Cyclin D1 and mammary carcinoma: new insights from transgenic mouse models

Cyclin D1 is one of the most commonly overexpressed oncogenes in breast cancer, with 45–50% of primary ductal carcinomas overexpressing this oncoprotein. Targeted deletion of the gene encoding cyclin D1 demonstrates an essential role in normal mammary gland development while transgenic studies provide evidence that cyclin D1 is a weak oncogene in mammary epithelium. In a recent exciting development, Yu et al. demonstrate that cyclin D1-deficient mice are resistant to mammary carcinomas induced by c-neu and v-Ha-ras, but not those induced by c-myc or Wnt-1. These findings define a pivotal role for cyclin D1 in a subset of mammary cancers in mice and imply a functional role for cyclin D1 overexpression in human breast cancer

Short-term resource allocation during extensive athletic competition

© 2017 The Authors. American Journal of Human Biology Published by Wiley Periodicals, Inc. Objectives: Following predictions from life history theory, we sought to identify acute trade-offs between reproductive effort (as measured by psychological arousal) and somatic maintenance (via functional measures of innate immunity) during conditions of severe energetic imbalance. Methods: Sixty-six male ultramarathon runners (ages 20 to 37 years) were sampled before and after a lengthy race. Saliva and sera were collected for testosterone and immunological analyses (hemolytic complement activity and bacterial killing ability). Lean body mass was assessed by bioelectrical impedance, and libido was measured using a slideshow of arousing and neutral images. Results: Following predictions, there was a significant decrease in salivary testosterone levels (109.59 pg/mL versus 97.61 pg/mL, P <.001) and arousal scores in response to provocative images (5.40 versus 4.89, P =.001) between prerace and postrace time points. Additionally, participant bacterial killing ability (P =.035) and hemolytic complement activity (P =.021) increased between prerace and postrace. Conclusions: Decreased libido and testosterone with concomitant heightened innate immune responses suggest a shift in energetic priorities away from reproduction and toward maintenance/defense during a period of energetic stress

Assessment of epidermal growth factor receptor (EGFR) expression in primary colorectal carcinomas and their related metastases on tissue sections and tissue microarray

Metastatic colorectal carcinomas (CRC) resistant to chemotherapy may benefit from targeting monoclonal therapy cetuximab when they express the epidermal growth factor receptor (EGFR). Because of its clinical implications, we studied EGFR expression by immunohistochemistry on tissue sections of primary CRC (n=32) and their related metastases (n=53). A tissue microarray (TMA) was generated from the same paraffin blocks to determine whether this technique could be used for EGFR screening in CRC. On tissue sections, 84% of the primary CRC and 94% of the metastases were EGFR-positive. When matched, they showed a concordant EGFR-positive status in 78% of the cases. Moreover, staining intensity and extent of EGFR-positive cells in the primary CRC correlated with those observed in the synchronous metastases. On TMA, 65% of the primary CRC, 66% of the metastases, and 43% of the matched primary CRC metastases were EGFR-positive. There was no concordant EGFR status between the primary and the metastatic sites. A strong discrepancy of EGFR status was noted between TMA and tissue sections. In conclusion, EGFR expression measured in tissue sections from primary CRC and their related metastases was found to be similar and frequent, but it was significantly underestimated by the TMA technique

Stochastic Heating by ECR as a Novel Means of Background Reduction in the KATRIN Spectrometers

The primary objective of the KATRIN experiment is to probe the absolute neutrino mass scale with a sensitivity of 200 meV (90% C.L.) by precision spectroscopy of tritium beta-decay. To achieve this, a low background of the order of 10^(-2) cps in the region of the tritium beta-decay endpoint is required. Measurements with an electrostatic retarding spectrometer have revealed that electrons, arising from nuclear decays in the volume of the spectrometer, are stored over long time periods and thereby act as a major source of background exceeding this limit. In this paper we present a novel active background reduction method based on stochastic heating of stored electrons by the well-known process of electron cyclotron resonance (ECR). A successful proof-of-principle of the ECR technique was demonstrated in test measurements at the KATRIN pre-spectrometer, yielding a large reduction of the background rate. In addition, we have carried out extensive Monte Carlo simulations to reveal the potential of the ECR technique to remove all trapped electrons within negligible loss of measurement time in the main spectrometer. This would allow the KATRIN experiment attaining its full physics potential

The influence of invasive growth pattern and microvessel density on prognosis in colorectal cancer and colorectal liver metastases

The nature of the invasive growth pattern and microvessel density (MVD) have been suggested to be predictors of prognosis in primary colorectal cancer (CRC) and colorectal liver metastases. The purpose of the present study was to determine whether these two histological features were interrelated and to assess their relative influence on disease recurrence and survival following surgical resection. Archival tissue was retrieved from 55 patients who had undergone surgical resection for primary CRC and matching liver metastases. The nature of the invasive margin was determined by haematoxylin and eosin (H&E) histochemistry. Microvessel density was visualised using immunohistochemical detection of CD31 antigen and quantified using image capture computer software. Clinical details and outcome data were retrieved by case note review and collated with invasive margin and MVD data in a statistical database. Primary CRCs with a pushing margin tended to form capsulated liver metastases (P<0.001) and had a significantly better disease-free survival than the infiltrative margin tumours (log rank P=0.01). Primary cancers with a high MVD tended to form high MVD liver metastases (P=0.007). Microvessel density was a significant predictor of disease recurrence in primary CRCs (P=0.006), but not liver metastases. These results suggest that primary CRCs and their liver metastases show common histological features. This may reflect common mechanisms underlying the tumour–host interaction