Relating side chain organization of PNIPAm with its conformation in aqueous methanol

Combining nuclear magnetic resonance (NMR), dynamic light scattering (DLS), and μs long all-atom simulations with two million particles, we establish a delicate correlation between increased side chain organization of PNIPAm and its collapse in aqueous methanol mixtures. We find that the preferential binding of methanol with PNIPAm side chains, bridging distal monomers along the polymer backbone, results in increased organization. Furthermore, methanol–PNIPAm preferential binding is dominated by hydrogen bonding. Our findings reveal that the collapse of PNIPAm is dominated by enthalpic interactions and that the standard poor solvent (entropic) effects play no major role

Некоторые результаты применения метода геометрического анализа дизъюнктов для поисков смещенного крыла пласта в Прокопьевском районе Кузбасса

In this paper we present the development of a compact, thermo-optically stable and vibration and mechanical shock resistant mounting technique by soldering of optical components. Based on this technique, new generations of laser pump sources for aerospace applications are designed. In these laser systems the used soldering technique replaces the glued connection between the optical component and its join partner. The main challenges are the alignment accuracy in the arc second range and the realization of the long term stability of every single part in the laser system (e.g. resonator mirrors)

О необходимости прослеживания Балейско-Дарасунского разлома в пределах Борщевочного кряжа

In this paper we present the development of a compact, thermo-optically stable and vibration and mechanical shock resistant mounting technique by soldering of optical components. Based on this technique a new generation of laser sources for aerospace applications is designed. In these laser systems solder technique replaces the glued and bolted connections between optical component, mount and base plate. Alignment precision in the arc second range and realization of long term stability of every single part in the laser system is the main challenge. At the Fraunhofer Institute for Laser Technology ILT a soldering and mounting technique has been developed for high precision packaging. The specified environmental boundary conditions (e.g. a temperature range of -40 °C to +50 °C) and the required degrees of freedom for the alignment of the components have been taken into account for this technique. In general the advantage of soldering compared to gluing is that there is no outgassing. In addition no flux is needed in our special process. The joining process allows multiple alignments by remelting the solder. The alignment is done in the liquid phase of the solder by a 6 axis manipulator with a step width in the nm range and a tilt in the arc second range. In a next step the optical components have to pass the environmental tests. The total misalignment of the component to its adapter after the thermal cycle tests is less than 10 arc seconds. The mechanical stability tests regarding shear, vibration and shock behavior are well within the requirements

A pulsed, mono-energetic and angular-selective UV photo-electron source for the commissioning of the KATRIN experiment

The KATRIN experiment aims to determine the neutrino mass scale with a sensitivity of 200 meV/c^2 (90% C.L.) by a precision measurement of the shape of the tritium $\beta$-spectrum in the endpoint region. The energy analysis of the decay electrons is achieved by a MAC-E filter spectrometer. To determine the transmission properties of the KATRIN main spectrometer, a mono-energetic and angular-selective electron source has been developed. In preparation for the second commissioning phase of the main spectrometer, a measurement phase was carried out at the KATRIN monitor spectrometer where the device was operated in a MAC-E filter setup for testing. The results of these measurements are compared with simulations using the particle-tracking software "Kassiopeia", which was developed in the KATRIN collaboration over recent years.Comment: 19 pages, 16 figures, submitted to European Physical Journal

Моделирование уравнений проекционного осциллографирования на машине "ЭМУ-10"

The passive-alignment-packaging technique presented in this work provides a method for mounting tolerance-insensitive optical components e.g. non-linear crystals by means of mechanical stops. The requested tolerances for the angle deviation are ±100 µrad and for the position tolerance ±100 µm. Only the angle tolerances were investigated, because they are more critical. The measurements were carried out with an autocollimator. Fused silica components were used for test series. A solder investigation was carried out. Different types of solder were tested. Due to good solderability on air and low induced stress in optical components, Sn based solders were indicated as the most suitable solders. In addition several concepts of reflow soldering configuration were realized. In the first iteration a system with only the alignment of the yaw angle was implemented. The deviation for all materials after the thermal and mechanical cycling was within the tolerances. The solderability of BBO and LBO crystals was investigated and concepts for mounting were developed

Relating Side Chain Organization of PNIPAm with its Conformation in Aqueous Methanol

Combining nuclear magnetic resonance (NMR), dynamic light scattering (DLS), and μs long all-atom simulations with two million particles, we establish a delicate correlation between increased side chain organization of PNIPAm and its collapse in aqueous methanol mixtures. We find that the preferential binding of methanol with PNIPAm side chains, bridging distal monomers along the polymer backbone, results in increased organization. Furthermore, methanol–PNIPAm preferential binding is dominated by hydrogen bonding. Our findings reveal that the collapse of PNIPAm is dominated by enthalpic interactions and that the standard poor solvent (entropic) effects play no major role

A Probabilistic Approach to the Spatial Variability of Ground Properties in the Design of Urban Deep Excavation

Uncertainty in ground datasets often stems from spatial variability of soil parameters and changing groundwater regimes. In urban settings and where engineering ground interventions need to have minimum and well-anticipated ground movements, uncertainty in ground data leads to uncertain analysis, with substantial unwelcomed economical and safety implications. A probabilistic random set finite element modelling (RSFEM) approach is used to revisit the stability and serviceability of a 27 m deep submerged soil nailed excavation built into a cemented soil profile, using a variable water level and soil shear strength. Variation of a suite of index parameters, including mobilized working loads and moments in facing and soil inclusion elements, as well as stability and serviceability of facing and the integrated support system, are derived and contrasted with field monitoring data and deterministic FE modelling outputs. The validated model is then deployed to test the viability of using independent hydraulic actions as stochastic variables as an alternative to dependent hydraulic actions and soil shear strength. The achieved results suggest that utilizing cohesion as a stochastic variable alongside the water level predicts system uncertainty reasonably well for both actions and material response; substituting the hydraulic gradient produces a conservative probability range for the action response only

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

Two additive mechanisms impair the differentiation of 'substrate-selective' p38 inhibitors from classical p38 inhibitors in vitro

<p>Abstract</p> <p>Background</p> <p>The success of anti-TNF biologics for the treatment of rheumatoid arthritis has highlighted the importance of understanding the intracellular pathways that regulate TNF production in the quest for an orally-available small molecule inhibitor. p38 is known to strongly regulate TNF production via MK2. The failure of several p38 inhibitors in the clinic suggests the importance of other downstream pathways in normal cell function. Recent work has described a 'substrate-selective' p38 inhibitor that is able to preferentially block the activity of p38 against one substrate (MK2) versus another (ATF2). Using a combined experimental and computational approach, we have examined this mechanism in greater detail for two p38 substrates, MK2 and ATF2.</p> <p>Results</p> <p>We found that in a dual (MK2 and ATF2) substrate assay, MK2-p38 interaction reduced the activity of p38 against ATF2. We further constructed a detailed kinetic mechanistic model of p38 phosphorylation in the presence of multiple substrates and successfully predicted the performance of classical and so-called 'substrate-selective' p38 inhibitors in the dual substrate assay. Importantly, it was found that excess MK2 results in a stoichiometric effect in which the formation of p38-MK2-inhibitor complex prevents the phosphorylation of ATF2, despite the preference of the compound for the p38-MK2 complex over the p38-ATF2 complex. MK2 and p38 protein expression levels were quantified in U937, Thp-1 and PBMCs and found that [MK2] > [p38].</p> <p>Conclusion</p> <p>Our integrated mechanistic modeling and experimental validation provides an example of how systems biology approaches can be applied to drug discovery and provide a basis for decision-making with limited chemical matter. We find that, given our current understanding, it is unlikely that 'substrate-selective' inhibitors of p38 will work as originally intended when placed in the context of more complex cellular environments, largely due to a stoichiometric excess of MK2 relative to p38.</p

miR-27b Targets KSRP to Coordinate TLR4-Mediated Epithelial Defense against Cryptosporidium parvum Infection

Cryptosporidium is a protozoan parasite that infects the gastrointestinal epithelium and causes a diarrheal disease. Toll-like receptor (TLR)- and NF-κB-mediated immune responses from epithelial cells, such as production of antimicrobial peptides and generation of reactive nitrogen species, are important components of the host's defense against cryptosporidial infection. Here we report data demonstrating a role for miR-27b in the regulation of TLR4/NF-κB-mediated epithelial anti-Cryptosporidium parvum responses. We found that C. parvum infection induced nitric oxide (NO) production in host epithelial cells in a TLR4/NF-κB-dependent manner, with the involvement of the stabilization of inducible NO synthase (iNOS) mRNA. C. parvum infection of epithelial cells activated NF-κB signaling to increase transcription of the miR-27b gene. Meanwhile, downregulation of KH-type splicing regulatory protein (KSRP) was detected in epithelial cells following C. parvum infection. Importantly, miR-27b targeted the 3′-untranslated region of KSRP, resulting in translational suppression. C. parvum infection decreased KSRP expression through upregulating miR-27b. Functional manipulation of KSRP or miR-27b caused reciprocal alterations in iNOS mRNA stability in infected cells. Forced expression of KSRP and inhibition of miR-27b resulted in an increased burden of C. parvum infection. Downregulation of KSRP through upregulating miR-27b was also detected in epithelial cells following LPS stimulation. These data suggest that miR-27b targets KSRP and modulates iNOS mRNA stability following C. parvum infection, a process that may be relevant to the regulation of epithelial anti-microbial defense in general