Cop1 constitutively regulates c-Jun protein stability and functions as a tumor suppressor in mice

Biochemical studies have suggested conflicting roles for the E3 ubiquitin ligase constitutive photomorphogenesis protein 1 (Cop 1; also known as Rfwd2) in tumorigenesis, providing evidence for both the oncoprotein c-Jun and the tumor suppressor p53 as its targets. Here we present what we believe to be the first in vivo investigation of the role of Cop1 in cancer etiology. Using an innovative genetic approach to generate an allelic series of Cop1, we found that Cop1 hypomorphic mice spontaneously developed malignancy at a high frequency in the first year of life and were highly susceptible to radiation-induced lymphomagenesis. Further analysis revealed that c-Jun was a key physiological target for Cop1 and that Cop1 constitutively kept c-Jun at low levels in vivo and thereby modulated c-Jun/AP-1 transcriptional activity. Importantly, Cop1 deficiency stimulated cell proliferation in a c-Jun-dependent manner. Focal deletions of COP1 were observed at significant frequency across several cancer types, and COP1 loss was determined to be one of the mechanisms leading to c-Jun upregulation in human cancer. We therefore conclude that Cop1 is a tumor suppressor that functions, at least in part, by antagonizing c-Jun oncogenic activity. In the absence of evidence for a genetic interaction between Cop1 and p53, our data strongly argue against the use of Cop1-inhibitory drugs for cancer therapy

First responders occupancy, activity and vital signs monitoring - SAFESENS

This paper describes the development and implementation of the SAFESENS (Sensor Technologies for Enhanced Safety and Security of Buildings and its Occupants) location tracking and first responder monitoring demonstrator. An international research collaboration has developed a stateof-the-art wireless indoor location tracking system for first responders, focused initially on fire fighter monitoring. Integrating multiple gas sensors and presence detection technologies with building safety sensors and personal monitors has resulted in more accurate and reliable fire and occupancy detection information. This is invaluable to firefighters in carrying out their duties in hostile environments. This demonstration system is capable of tracking occupancy levels in an indoor environment as well as the specific location of fire fighters within those buildings, using a multi-sensor hybrid tracking system. This ultra-wideband indoor tracking system is one of the first of itsâ kind to provide indoor localization capability to sub meter accuracies with combined Bluetooth low energy capability for low power communications and additional inertial, temperature and pressure sensors. This facilitates increased precision in accuracy detection through data fusion, as well as the capability to communicate directly with smartphones and the cloud, without the need for additional gateway support. Glove based, wearable technology has been developed to monitor the vital signs of the first responder and provide this data in real time. The helmet mounted, wearable technology will also incorporate novel electrochemical sensors which have been developed to be able to monitor the presence of dangerous gases in the vicinity of the firefighter and again to provide this information in real time to the fire fighter controller. A SAFESENS demonstrator is currently deployed in Tyndall and is providing real time occupancy levels of the different areas in the building, as well as the capability to track the location of the first responders, their health and the presence of explosive gases in their vicinity. This paper describes the system building blocks and results obtained from the first responder tracking system demonstrator depicted

Terrestrial Very-Long-Baseline Atom Interferometry:Workshop Summary

This document presents a summary of the 2023 Terrestrial Very-Long-Baseline Atom Interferometry Workshop hosted by CERN. The workshop brought together experts from around the world to discuss the exciting developments in large-scale atom interferometer (AI) prototypes and their potential for detecting ultralight dark matter and gravitational waves. The primary objective of the workshop was to lay the groundwork for an international TVLBAI proto-collaboration. This collaboration aims to unite researchers from different institutions to strategize and secure funding for terrestrial large-scale AI projects. The ultimate goal is to create a roadmap detailing the design and technology choices for one or more km-scale detectors, which will be operational in the mid-2030s. The key sections of this report present the physics case and technical challenges, together with a comprehensive overview of the discussions at the workshop together with the main conclusions

Spektroskopische Untersuchungen hochgeladener Krypton-Ionen im Röntgen-Bereich

Diese Dissertation widmet sich der spektroskopischen Untersuchung verschiedener Aspekte der Strahlungsemis\-sion hochgeladener Krypton-Ionen mit Relevanz für die Fusionsforschung. Die Experimente hierzu erfolgten an der Berliner Elektronenstrahl-Ionenfalle (EBIT). Der erste Teil der Arbeit hat die Messung kanalspezifischer Wirkungsquerschnitte für die dielektronische Rekombination (DR) der KL$n$-Resonanzserie ($n$=2, \ldots, 5) von Helium- bis Kohlenstoff-ähnlichen Kr-Ionen (\mbox{Kr}^{(34\, \ldots\,30)+}) zum Inhalt, die relativ zum Wirkungsquerschnitt der nichtresonanten strahlenden Rekombination (RR) bestimmt wurden. Die Anpassung der Anregungskurven durch eine Modellfunktion aus berechneten Resonanzst ärken ermöglichte den Vergleich mit theoretischen DR-Wirkungsquerschnitten. Es zeigt sich, dass Vorhersagen des HULLAC-Atomstrukturcodes für die Resonanz\-st"ar\-ken der Kr-Ionen durch das Experiment innerhalb der Me"sunsicherheiten best"a\-tigt werden. Darüber hinaus wurde auch die Relaxation der einfach angeregten Ionen nach erfolgtem DR-Stabilisierungsübergang analysiert. Die zur Auswertung der DR-Anre\-gungs\-kurven angewandte Technik eröffnet gleichzeitig eine spektroskopische Methode für die Bestimmung der relativen Konzentration hochgeladener Ionen in EBIT. Die Messung der Strahlungskühlungsrate von Krypton, die den zweiten inhaltlichen Schwerpunkt der Dissertation darstellt, wäre ohne diese in situ Diagnostik der Ladungbilanz nicht möglich gewesen. Hier wurde die Ionenfalle so eingestellt, dass sich eine Ladungsverteilung herausbildet, die dem Ionisationsgleichgewicht eines Plasmas bei einer Temperatur von etwa 5\;\mbox{keV} entspricht. Die Bestimmung der Strahlungsk"uhlungsrate profitierte von dem Potential einer EBIT, die gefangenen Ionen mit Elektronenenergien aus einem weiten Bereich abzutasten und einzelne Strahlunsprozesse selektiv anzuregen. Die Röntgenemission verschiedener Strahlungskanäle, wie Bremsstrahlung, strahlende Rekombination, dielektronische Rekombination und Linienstrahlung nach direkter Anregung wurde separat erfaßt. Hieraus konnten erstmals kanalspezifische Strahlungskühlungsraten bestimmt werden. Es stellte sich heraus, dass der dominante Beitrag zur Strahlungskühlungsrate durch die direkt angeregte Linienstr ahlung des L-Schalen-Spektrums zustande kommt, die etwa 75\% der gesamten Verlustleistung ausmacht. Beim Vergleich der totalen Strahlungsverlustleistung mit Vorhersagen der Theorie sind Abweichungen festzustellen. Die berechneten Werte sind je nach Modell um einen Faktor 1.5 - 2.0 kleiner als das Ergebnis der Messung. Dieser Unterschied liegt außerhalb der experimentellen Unsicherheit von maximal 30\%.This thesis deals with the spectroscopic investigation of various aspects of the x-ray emission of highly charged krypton ions with relevance for fusion research. The experiments have been performed at the Berlin electron beam ion trap (EBIT). One part of the work was devoted to the measurement of channel-specific cross sections for dielectronic recombination (DR) via the KL$n$ ($n$=2, \ldots, 5) resonance series of He- to C-like krypton ions (\mbox{Kr}^{(34\, \ldots\,30)+}). The DR cross sections were determined relative to the cross section for non-resonant radiative recombination (RR). A fit procedure was used to compare the measured data with theoretical calculations. Predictions of the HULLAC atomic structure code are confirmed within the experimental uncertainties. Additionally, the radiative relaxation mechanism following the stabilizing transition in the DR process was analyzed. The approach used to obtain the DR excitation function opens up a spectroscopic method to determine the relative abundance of the highly charged ions in the trap. This in situ diagnostic of the charge state balance allowed for the measurement of the radiative cooling rates of krypton being the second focus of the thesis. For this purpose EBIT was tuned to a charge state distribution approaching the ionization balance of a plasma at a temperature of about 5\;\mbox{keV}. EBIT's capability to sample a wide range of electron-beam energies and distinguish between different radiation channels was utilized to determine the cooling rate. The x-ray emission from the various plasma radiation channels, like bremsstrahlung, radiative recombination, dielectronic recombination, and line radiation following electron-impact excitation was analyzed. For the first time, channel-specific cooling rates could be obtained from these data. It was found, that the dominant contribution to the cooling rate is made up by the directly excited x-rays of the L-shell spectra of krypton, producing more than 75\% of the total radiation loss. A difference with theoretical calculations is noted for the total cooling rate. The predicted values are lower by a factor of 1.5 - 2.0, depending on the theoretical model. This discrepancy is clearly beyond the experimental uncertainty of 30\% at maximum

Direct wafer bonding for encapsulation of fused silica optical gratings

We report on encapsulation of fusedsilica transmission gratings for diffractive optical applications in the visible or near infra-red spectral range. High quality binary gratings with periods ranging from 500 nm to 2000 nm and lateral dimensions of up to 60 mm × 20 mm were generated in 6 inch fusedsilica glass wafers by standard lithography techniques and low pressure reactive ion etching. The structured glass wafers were joined to unstructured wafers of identical material by directwaferbonding. Extended wet cleaning and low pressure plasma activation processes were applied to achieve highly hydrophilic surfaces for bonding. Subsequently, both types of wafers were joined and bonded in a vacuum environment at low temperatures under compressive pressure. High quality, virtually "defect free" bonding was achieved across the whole wafer area. Bonding strength and transmission efficiency in Littrow configuration were determined to about 0.6 J/m2 and 98.8%, respectively

An extreme ultraviolet Michelson interferometer for experiments at free-electron lasers

We present a Michelson interferometer for 13.5 nm soft x-ray radiation. It is characterized in a proof of-principle experiment using synchrotron radiation, where the temporal coherence is measured to be 13 fs. The curvature of the thin-film beam splitter membrane is derived from the observed fringe pattern. The applicability of this Michelson interferometer at intense free-electron lasers is investigated,particularly with respect to radiation damage. This study highlights the potential role of such Michelson interferometers in solid density plasma investigations using, for instance, extreme soft x-ray free electron lasers. A setup using the Michelson interferometer for pseudo-Nomarski-interferometry is proposed

Compact integrated magnetometer based on nitrogen-vacancy centres in diamond

We demonstrate an integrated and miniaturised magnetic field sensor based on the negatively charged nitrogen-vacancy centres (NV−) in diamond. The compact device includes all optical components, both for the optical excitation path and for the detection of the emitted fluorescence signal. We experimentally verify that it enables optically detected magnetic resonance (ODMR) measurements and we specify noise and sensitivity of the magnetometer. The minimal detectable magnetic field of the device is ≈ 1 μT for a given integration time of 1 ms, which is approximately one order of magnitude larger than its photon shot-noise limit. It has the significant advantage over traditional setups using NV− centres (including a laser and a complex optical system) that the specific construction volume is about 2.9 cm3 with a total power consumption of ≈ 1.5 W, which enables the device for a wide range of industrial sensing applications

Fiberized Diamond-Based Vector Magnetometers

We present two fiberized vector magnetic-field sensors, based on nitrogen-vacancy (NV) centers in diamond. The sensors feature sub-nT/$\sqrt{\textrm{Hz}}$ magnetic sensitivity. We use commercially available components to construct sensors with a small sensor size, high photon collection, and minimal sensor-sample distance. Both sensors are located at the end of optical fibres with the sensor-head freely accessible and robust under movement. These features make them ideal for mapping magnetic fields with high sensitivity and spatial resolution ($\leq$\,mm). As a demonstration we use one of the sensors to map the vector magnetic field inside the bore of a $\geq$ 100\,mT Halbach array. The vector field sensing protocol translates microwave spectroscopy data addressing all diamonds axes and including double quantum transitions to a 3D magnetic field vector

Integrated and Portable Magnetometer Based on Nitrogen‐Vacancy Ensembles in Diamond

Magnetic field sensors that exploit quantum effects have shown that they can outperform classical sensors in terms of sensitivity enabling a range of novel applications in future, such as a brain machine interface. Negatively charged nitrogen‐vacancy (NV) centers in diamond have emerged as a promising high sensitivity platform for measuring magnetic fields at room temperature. Transferring this technology from laboratory setups into products and applications, the total size of the sensor, the overall power consumption, and the costs need to be reduced and optimized. Here, a fiber‐based NV magnetometer featuring a complete integration of all functional components is demonstrated without using any bulky laboratory equipment. This integrated prototype allows portable measurement of magnetic fields with a sensitivity of 344 pT Hz−1/2