Levitating the noise performance of ultra-stable laser cavities assisted by a deep neural network: The non-intuitive role of the mirrors

The most precise measurand available to science is the frequency of ultra-stable lasers. With a relative deviation of 4 × 10−17 over a wide range of measuring times between one second and 100 seconds, the smallest effects in nature can thus be made measurable. To enable cutting-edge precision, the laser frequency is stabilized to an external optical cavity. This complex optical device must be manufactured to the highest standards and shielded from environmental influences. Given this assumption, the smallest internal sources of perturbation become dominant, namely the internal noise of the optical components. In this work, we present the optimization of all relevant noise sources from all components of the frequency-stabilized laser. We discuss the correlation between each individual noise source and the different parameters of the system and discover the significance of the mirrors. The optimized laser offers a design stability of 8 × 10−18 for an operation at room temperature for measuring times between one second and 100 seconds

Passive room conditioning using phase change materials—Demonstration of a long-term real size experiment

The thermal properties of lightweight buildings can be efficiently improved by using phase change materials (PCMs). The heat storage capacity of the building can be extended exactly at the desired temperature level, which leads to an enormous increase in residential comfort. This is shown in the present paper using the example of a prefabricated wooden house. The house was divided into two identical rooms. One of them was equipped with almost one ton of phase change material based on salt hydrates with a melting temperature of approx. 21°C. The material was encapsulated in 1-l Polyethylene containers and installed in two back-ventilated layers inside of the walls. The house was monitored for a period of 87 days in terms of temperatures, solar radiation and air velocity inside the PCM wall system. A considerable temperature buffering could be observed in the PCM room compared to the reference room. An overall reduction of the temperature fluctuations of 57% and a reduction of the day/night fluctuations of 62% compared to the reference room could be obtained. In addition, a prediction regarding the energy demand of such buildings is discussed on the basis of a simulation program. Thus, the annual cooling capacity can be reduced by 36.5% compared to the regular timber construction technique by introducing PCM. Furthermore, the good correlation of the simulation results with the experimental ones allows using the simulation as a tool to design a house with additional thermal storages

Globular domain of the prion protein needs to be unlocked by domain swapping to support prion protein conversion

Prion diseases are fatal transmissible neurodegenerative diseases affecting many mammalian species. The normal prion protein (PrP) converts into a pathological aggregated form, PrPSc, which is enriched in the β-sheet structure. While the high resolution structure of the normal PrP was determined, the structure of the converted form of PrP remains inaccessible to high resolution techniques. In order to map the PrP conversion process we introduced disulfide bridges into different positions within the globular domain of PrP, tethering selected secondary structure elements. The majority of tethered PrP mutants exhibited increased thermodynamic stability, nevertheless they converted efficiently. Only the disulfides which tether subdomain B1-H1-B2 to subdomain H2-H3 prevented PrP conversion in vitro and in prion infected cell cultures. Reduction of disulfides recovered the ability of these mutants to convert, demonstrating that the separation of subdomains is an essential step in conversion. Formation of disulfide-linked proteinase K-resistant dimers in fibrils composed of a pair of single cysteine mutants supports the model based on domain-swapped dimers as the building blocks of prion fibrils. In contrast to previously proposed structural models of PrPSc suggesting conversion of large secondary structure segments, we provide evidence for the conservation of secondary structure elements of the globular domain upon PrP conversion. Previous studies already showed that dimerization is the rate-limiting step in PrP conversion. We show that separation and swapping of subdomains of the globular domain is necessary for conversion. Therefore, we propose that domain-swapped dimer of PrP precedes amyloid formation and represents a potential target for therapeutic intervention

Characterization of changes in the proteome in different regions of 3D multicell tumor spheroids.

Three dimensional multicell tumor spheroids (MCTS) provide an experimental model where the influence of microenvironmental conditions on protein expression can be determined. Sequential trypsin digestion of HT29 colon carcinoma MCTS enabled segregation into four populations comprising proliferating cells from the surface (SL), an intermediate region (IR), nonproliferating hypoxic cells from the perinecrotic region (PN), and a necrotic core (NC). Total protein was extracted from each population and subjected to iTRAQ-based quantitative proteomics analysis. From a total of 887 proteins identified, 209 were observed to be up-regulated and 114 were down-regulated in the PN and NC regions relative to the SL. Among the up-regulated proteins, components of glycolysis, TCA cycle, lipid metabolism, and steroid biosynthesis increased progressively toward the PN and NC regions. Western blotting, immunohistochemistry, and enzyme assays confirmed that significant changes in the expression of proteins involved in cellular metabolism occur in the nonproliferating fraction of cells within the viable rim. The presence of full length, functional proteins within the NC was unexpected, and further analysis demonstrated that this region contains cells that are undergoing autophagy. This study has identified possible targets that may be suitable for therapeutic intervention, and further studies to validate these are required