\u3csup\u3e1\u3c/sup\u3eH, \u3csup\u3e13\u3c/sup\u3eC, and \u3csup\u3e15\u3c/sup\u3eN NMR assignments for the \u3ci\u3eBacillus subtilis\u3c/i\u3e yndB START domain

The steroidogenic acute regulatory-related lipid transfer (START) domain is found in both eukaryotes and prokaryotes, with putative functions including signal transduction, transcriptional regulation, GTPase activation and thioester hydrolysis. Here we report the near complete 1H, 15N and 13C backbone and side chain NMR resonance assignments for the Bacillus subtilis START domain protein yndB

Structure and Function of Human DnaJ Homologue Subfamily A Member 1 (DNAJA1) and Its Relationship to Pancreatic Cancer

Pancreatic cancer has a dismal 5 year survival rate of 5.5% that has not been improved over the past 25 years despite an enormous amount of effort. Thus, there is an urgent need to identify truly novel yet druggable protein targets for drug discovery. The human protein DnaJ homologue subfamily A member 1 (DNAJA1) was previously shown to be downregulated 5- fold in pancreatic cancer cells and has been targeted as a biomarker for pancreatic cancer, but little is known about the specific biological function for DNAJA1 or the other members of the DnaJ family encoded in the human genome. Our results suggest the overexpression of DNAJA1 suppresses the stress response capabilities of the oncogenic transcription factor, c-Jun, and results in the diminution of cell survival. DNAJA1 likely activates a DnaK protein by forming a complex that suppresses the JNK pathway, the hyperphosphorylation of c-Jun, and the anti-apoptosis state found in pancreatic cancer cells. A high-quality nuclear magnetic resonance solution structure of the J-domain of DNAJA1 combined with a bioinformatics analysis and a ligand affinity screen identifies a potential DnaK binding site, which is also predicted to overlap with an inhibitory binding site, suggesting DNAJA1 activity is highly regulated

Characterization and calibration of the James Webb space telescope mirror actuators fine stage motion

The James Webb Space Telescope’s (Webb’s) deployable primary and secondary mirrors are actively controlled to achieve and maintain precise optical alignment on-orbit. Each of the 18 primary mirror segment assemblies (PMSAs) and the secondary mirror assembly (SMA) are controlled in six degrees of freedom by using six linear actuators in a hexapod arrangement. In addition, each PMSA contains a seventh actuator that adjusts radius of curvature (RoC). The actuators are of a novel stepper motor-based cryogenic two-stage design that is capable of sub-10 nm motion accuracy over a 20 mm range. The nm-level motion of the 132 actuators were carefully tested and characterized before integration into the mirror assemblies. Using these test results as an initial condition, knowledge of each actuator’s length (and therefore mirror position) has relied on software bookkeeping and configuration control to keep an accurate motor step count from which actuator position can be calculated. These operations have been carefully performed through years of Webb test operations using both ground support actuator control software as well as the flight Mirror Control Software (MCS). While the actuator’s coarse stage length is cross-checked using a linear variable differential transformer (LVDT), no on-board cross-check exists for the nm-level length changes of the actuators’ fine stage. To ensure that the software bookkeeping of motor step count is still accurate after years of testing and to test that the actuator position knowledge was properly handed off from the ground software to the flight MCS, a series of optical tests were devised and performed through the Center of Curvature (CoC) ambient optical test campaigns at the Goddard Space Flight Center (GSFC) and during the thermal-vacuum tests of the entire optical payload that were conducted in Chamber A at Johnson Space Center (JSC). In each test, the actuator Fine Step Count (FSC) value is compared to an external measurement provided by an optical metrology tool with the goal of either confirming the MCS database value, or providing a recommendation for an updated calibration if the measured FSC differs significantly from the MCS-based expectation. During ambient testing of the PMSA hexapods, the nm-level actuator length changes were measured with a custom laser deflectometer by measuring tilts of the PMSA. The PMSA RoC fine stage characterization was performed at JSC using multi-wave interferometric measurements with the CoC Optical Assembly (COCOA). Finally, the SMA hexapod fine stage characterization test was performed at JSC using the NIRCam instrument in the “pass-and-a-half” test configuration using a test source from the Aft-Optics System Source Plate Assembly (ASPA). In this paper, each of these three tests, subsequent data analyses, and uncertainty estimations will be presented. Additionally, a summary of the ensemble state of Webb’s actuator fine stages is provided, along with a comparison to a Wavefront Sensing and Control (WFSC)-based requirement for FSC errors as they relate to the optical alignment convergence of the telescope on-orbit

High Resolution Observations using Adaptive Optics: Achievements and Future Needs

Over the last few years, several interesting observations were obtained with the help of solar Adaptive Optics (AO). In this paper, few observations made using the solar AO are enlightened and briefly discussed. A list of disadvantages with the current AO system are presented. With telescopes larger than 1.5m are expected during the next decade, there is a need to develop the existing AO technologies for large aperture telescopes. Some aspects of this development are highlighted. Finally, the recent AO developments in India are also presented

Structure Determination and Biochemical Characterization of a Putative HNH Endonuclease from Geobacter metallireducens GS-15

The crystal structure of a putative HNH endonuclease, Gmet_0936 protein from Geobacter metallireducens GS-15, has been determined at 2.6 Å resolution using single-wavelength anomalous dispersion method. The structure contains a two-stranded anti-parallel β-sheet that are surrounded by two helices on each face, and reveals a Zn ion bound in each monomer, coordinated by residues Cys38, Cys41, Cys73, and Cys76, which likely plays an important structural role in stabilizing the overall conformation. Structural homologs of Gmet_0936 include Hpy99I endonuclease, phage T4 endonuclease VII, and other HNH endonucleases, with these enzymes sharing 15–20% amino acid sequence identity. An overlay of Gmet_0936 and Hpy99I structures shows that most of the secondary structure elements, catalytic residues as well as the zinc binding site (zinc ribbon) are conserved. However, Gmet_0936 lacks the N-terminal domain of Hpy99I, which mediates DNA binding as well as dimerization. Purified Gmet_0936 forms dimers in solution and a dimer of the protein is observed in the crystal, but with a different mode of dimerization as compared to Hpy99I. Gmet_0936 and its N77H variant show a weak DNA binding activity in a DNA mobility shift assay and a weak Mn2+-dependent nicking activity on supercoiled plasmids in low pH buffers. The preferred substrate appears to be acid and heat-treated DNA with AP sites, suggesting Gmet_0936 may be a DNA repair enzyme

Searching for Anomalous Weak Couplings of Heavy Flavors at the SLC and LEP

The existence of anomalous electric($\tilde \kappa$) and/or magnetic($\kappa$) dipole moment couplings between the heavy flavor fermions ($c,b,\tau$) and the $Z$ boson can cause significant shifts in the values of several electroweak observables currently being probed at both the SLC and LEP. Using the good agreement between existing data and the predictions of the Standard Model we obtain strict bounds on the possible strength of these new interactions for all of the heavy flavors. The decay $Z\rightarrow b\bar b$, however, provides some possible hint of new physics. The corresponding anomalous couplings of $\tau$'s to photons is briefly examined.Comment: 21 pages, 14 figs(available on request), LaTex, SLAC-PUB-667

Advancing climate services for the European renewable energy sector through capacity building and user engagement

The development of successful climate services faces a number of challenges, including the identification of the target audience and their needs and requirements, and the effective communication of complex climate information, through engagement with a range of stakeholders. This paper describes how these challenges were tackled during the European Climatic Energy Mixes (ECEM) project, part of the Copernicus Climate Change Service (C3S), in order to deliver a pre-operational, proof-of-concept climate service for the European renewable energy sector. The process of iterative user engagement adopted in ECEM is described, from the initial presentation of the team's first vision for such a service to support external stakeholders, through to evaluation of the final interactive tool for visualisation, data download and supporting documentation (the C3S ECEM Demonstrator). The outcomes of this evaluation are outlined, together with a retrospective reflection on the engagement and development process. The extent to which co-production and co-design were achieved in practice is assessed. The paper also highlights the distance travelled from the start to end of ECEM in terms of building capacity, developing a community of practice, and raising the Technology Readiness Level. The relevance of ECEM for the European climate services market is briefly considered, including the development of downstream commercial services which build upon the public C3S services.European Commission | Ref. 2015/C3S_441_Lot2_UE

The campaign for a National Strategy for Gypsy site provision and the role of Public Health activism in the 1960–1970s

We trace the post-war evolution of a national approach to providing caravan sites for Gypsies and Travellers—something essential to protect the health of that population in the United Kingdom (UK). Throughout the 1950s and 1960s, the late Norman Dodds MP championed in Parliament the plight of the UK’s Gypsies and other nomads. He was instrumental in galvanising support for the 1968 Caravan Sites Act. The vision of influential individuals working in public and environmental health surmounted practical considerations and local opposition to implement the national programme of site provision envisioned by the Act. We detail this hitherto neglected aspect of Gypsy politics and policy development. In doing so, we highlight the transformative potential of public health and argue for a return to the comprehensive vision motivating these pioneers in the 1960s and 1970s

Structure and Function of Human DnaJ Homologue Subfamily A Member 1 (DNAJA1) and Its Relationship to Pancreatic Cancer

Pancreatic cancer has a dismal 5 year survival rate of 5.5% that has not been improved over the past 25 years despite an enormous amount of effort. Thus, there is an urgent need to identify truly novel yet druggable protein targets for drug discovery. The human protein DnaJ homologue subfamily A member 1 (DNAJA1) was previously shown to be downregulated 5- fold in pancreatic cancer cells and has been targeted as a biomarker for pancreatic cancer, but little is known about the specific biological function for DNAJA1 or the other members of the DnaJ family encoded in the human genome. Our results suggest the overexpression of DNAJA1 suppresses the stress response capabilities of the oncogenic transcription factor, c-Jun, and results in the diminution of cell survival. DNAJA1 likely activates a DnaK protein by forming a complex that suppresses the JNK pathway, the hyperphosphorylation of c-Jun, and the anti-apoptosis state found in pancreatic cancer cells. A high-quality nuclear magnetic resonance solution structure of the J-domain of DNAJA1 combined with a bioinformatics analysis and a ligand affinity screen identifies a potential DnaK binding site, which is also predicted to overlap with an inhibitory binding site, suggesting DNAJA1 activity is highly regulated

Characterization and calibration of the James Webb space telescope mirror actuators fine stage motion

The James Webb Space Telescope’s (Webb’s) deployable primary and secondary mirrors are actively controlled to achieve and maintain precise optical alignment on-orbit. Each of the 18 primary mirror segment assemblies (PMSAs) and the secondary mirror assembly (SMA) are controlled in six degrees of freedom by using six linear actuators in a hexapod arrangement. In addition, each PMSA contains a seventh actuator that adjusts radius of curvature (RoC). The actuators are of a novel stepper motor-based cryogenic two-stage design that is capable of sub-10 nm motion accuracy over a 20 mm range. The nm-level motion of the 132 actuators were carefully tested and characterized before integration into the mirror assemblies. Using these test results as an initial condition, knowledge of each actuator’s length (and therefore mirror position) has relied on software bookkeeping and configuration control to keep an accurate motor step count from which actuator position can be calculated. These operations have been carefully performed through years of Webb test operations using both ground support actuator control software as well as the flight Mirror Control Software (MCS). While the actuator’s coarse stage length is cross-checked using a linear variable differential transformer (LVDT), no on-board cross-check exists for the nm-level length changes of the actuators’ fine stage. To ensure that the software bookkeeping of motor step count is still accurate after years of testing and to test that the actuator position knowledge was properly handed off from the ground software to the flight MCS, a series of optical tests were devised and performed through the Center of Curvature (CoC) ambient optical test campaigns at the Goddard Space Flight Center (GSFC) and during the thermal-vacuum tests of the entire optical payload that were conducted in Chamber A at Johnson Space Center (JSC). In each test, the actuator Fine Step Count (FSC) value is compared to an external measurement provided by an optical metrology tool with the goal of either confirming the MCS database value, or providing a recommendation for an updated calibration if the measured FSC differs significantly from the MCS-based expectation. During ambient testing of the PMSA hexapods, the nm-level actuator length changes were measured with a custom laser deflectometer by measuring tilts of the PMSA. The PMSA RoC fine stage characterization was performed at JSC using multi-wave interferometric measurements with the CoC Optical Assembly (COCOA). Finally, the SMA hexapod fine stage characterization test was performed at JSC using the NIRCam instrument in the “pass-and-a-half” test configuration using a test source from the Aft-Optics System Source Plate Assembly (ASPA). In this paper, each of these three tests, subsequent data analyses, and uncertainty estimations will be presented. Additionally, a summary of the ensemble state of Webb’s actuator fine stages is provided, along with a comparison to a Wavefront Sensing and Control (WFSC)-based requirement for FSC errors as they relate to the optical alignment convergence of the telescope on-orbit