News Article | March 1, 2017
No statistical method was used to predetermine the sample size. The experiments were not randomized, and the investigators were not blinded to allocation during experiments and outcome assessment. Highly active PSII was isolated from Thermosynechococcus vulcanus and crystallized as described previously with slight modifications4, 27, 28. The final PSII core dimers were suspended in 20 mM Mes (pH 6.0), 10 mM NaCl, 3 mM CaCl , and the final crystallization buffer contained 20 mM Mes, 20 mM NaCl, 40 mM MgSO , 10 mM CaCl , 5–7% polyethylene glycol 1,450, 0.85% n-heptyl-β-d-thioglucopyranoside (Dojindo). No re-crystallization procedure was applied. We screened various sizes of PSII crystals and post-crystallization treatment conditions (see below) to prepare suitable samples for TR-SFX by XFEL, and found that too small crystals did not diffract to a high resolution, whereas larger crystals gave rise to a lower efficiency of the S -state transition induced by the laser excitations. The optimal crystal size was determined to have a maximum length of 100 μm, which diffracted up to a resolution of 2.1 Å by a SACLA–XFEL pulse (Extended Data Fig. 1) and a final population of 46% S state upon 2F illumination (see below). All of the procedures for the preparation, crystallization, pre-flash illumination and diffraction experiments were conducted in the dark or in very dim green light. To prepare a large amount of micro-sized crystals, crystallization was performed in 1.5-ml micro-centrifuge tubes with a sample volume of 50 μl at a concentration of 2.3 mg chlorophyll per ml at 20 °C. The crystals appeared in a few hours; when the crystal size reached a maximum length of 100 μm, 50 μl of the crystallization buffer in which the concentration of PEG1,450 was increased by 1–2% from the crystallization condition was added to stop further growth of the crystals (see Extended Data Fig. 1a for a picture of typical crystals). The crystals were washed several times with this buffer to remove PSII samples that were not crystallized, and stored overnight. Prior to the XFEL experiments, the crystals were transferred to fresh mother liquid containing 10 mM potassium ferricyanide as an electron acceptor for the pre-flashing samples, and 2 mM potassium ferricyanide for the samples without pre-flash (non-pre-flash). The concentration of ‘cryo-protectant’ was then increased to 22% glycerol, 9% PEG1,450 and 9% PEG5,000 MME by stepwise replacement of the mother solution over 1.5 h. Finally, the crystals were carefully mixed with a grease matrix, Super Lube nuclear grade grease (Synco Chemical Co.), and loaded into a high viscosity micro-extrusion injector as described previously13. Although SFX can be performed at room temperature and there is no need to freeze the crystals, we found that this post-crystallization procedure to increase the cryo-protectant concentration was important for obtaining good diffracting PSII crystals. When the post-crystallization procedure was not adequate, some crystals gave rise to larger unit cell dimensions of a = 129.1 Å, b = 228.8 Å and c = 305.4 Å (Extended Data Fig. 6a–c). Diffraction spots from the crystals with this larger unit cell were found to be lower than 3.0 Å resolution, probably owing to the loose crystal packing. Indeed, we found that the PSII dimer in this crystal packing harboured two PsbY subunits (one PsbY per monomer PSII; Extended Data Fig. 6e). On the other hand, only one PsbY was found in the PSII dimer (one monomer contained PsbY whereas the other monomer did not) in the structure with unit cell dimensions of a = 126.5 Å, b = 231.2 Å and c = 287.5 Å analysed in this study (Extended Data Fig. 6f). When the two structures were superimposed, one of the two PsbY subunits in the dimer structure with the larger crystal packing interfered with the adjacent monomer in the structure with the smaller crystal packing (Extended Data Fig. 6d–f). To decrease the possible contamination of the S state in the dark-adapted crystals, PSII micro-crystals were illuminated with one pre-flash before the post-crystallization treatment. An aliquot of 100 μl solution containing micro-crystals of PSII was transferred into a dialysis button, and the pre-flash was provided by a Nd:YAG laser (Minilite-I, Continuum) at 532 nm with a diameter of 7 mm (large enough to cover the entire sample area) at an energy of ~52 mJ cm−2 at the sample position. After the pre-flash illumination, the sample was stored for 1–3 h in the dark while being transferred into the cryo-protectant conditions. This dark-incubation time was long enough to allow the higher S -states (S and S ) to decay into the S state, and therefore to minimize the possible contamination of the S state in the dark-adapted crystals, if there are any. The population of the S state after 2 flashes in the PSII micro-crystals was estimated using light-induced FTIR difference spectroscopy combined with the attenuated total reflection (ATR) method. PSII crystals in the same buffer as the SACLA experiments (including 10 mM potassium ferricyanide) were loaded onto a three-reflection silicon prism and then sealed with a transparent plate and a silicone rubber spacer. For the measurement of standard spectra, the PSII core solution was loaded onto the silicon prism, and the sample temperature was maintained at 20 °C. FTIR spectra were recorded at 4 cm−1 resolution using a Bruker IFS-66/S spectrophotometer equipped with an MCT detector. Flash illumination was provided by a Q-switched Nd:YAG laser (Quanta-Ray INDI-40-10; 532 nm, ~7 ns FWHM, ~21 mJ cm−2). Saturation of the laser flash was confirmed by checking the power dependence of the FTIR signal. After two pre-flashes with subsequent dark adaptation for 30 min, two flashes with an interval of 10 s were applied to the sample and FTIR difference spectra were measured upon each flash. We confirmed that the higher S-states decayed very little during this 10-s interval. This measurement was repeated 10 times to increase the signal-to-noise ratio of the spectra, with each measurement separated by 30 min dark incubation. The FTIR difference spectra obtained upon the 1st (a) and 2nd (b) flashes of PSII complexes in solution (black lines) and crystals (red lines) are shown in Extended Data Fig. 2. The spectra were normalized to the intensity of the amide II band, which reflects the protein amount. The efficiencies of the S-state transitions in the PSII crystals were estimated following the method previously described29, 30. The 1st- and 2nd-flash spectra in the PSII crystal, f (ν) and f (ν), respectively, were fitted with linear combinations of the 1st- and 2nd-flash spectra in solution, F (ν) and F (ν), respectively, as standard spectra: f (ν) = c F (ν); f (ν) = c F (ν) + c F (ν), where c , c , and c are the coefficients of linear combination. The least-squares fitting was performed in the symmetric COO− region (Extended Data Fig. 2b). The coefficients were estimated to be c = 0.73 ± 0.02, c = 0.27 ± 0.01, and c = 0.64 ± 0.02. The efficiencies of the S →S and S →S transitions are expressed as α c and α (c /c ), respectively, and the population of the S state after the second flash is calculated as α 2c . Here, α is the average efficiency of S-state transitions in solution and it was determined to be 0.85 ± 0.01 from the oscillation pattern of the intensity at 1,400 cm−1 (refs 31, 32) obtained by 12 consecutive flashes. Based on this, the population of the S state in the PSII micro-crystals after two flashes is estimated to be 0.46 ± 0.03. Single-shot XFEL data collection was performed using femtosecond X-ray pulses from the SACLA at BL3. The pulse parameters of SACLA were as follows: pulse duration, 2–10 fs; X-ray energy, 7 keV; energy bandwidth, 0.5% (FWHM); pulse flux, ~7 × 1010 photons per pulse; beam size 3.0 μm (H) × 3.0 μm (W); repetition rate, 30 Hz. The PSII crystals mixed with grease were loaded into an injector with a nozzle diameter of 150 μm, and set in a diffraction chamber filled with helium gas in a setup called Diverse Application Platform for Hard X-ray Diffraction in SACLA (DAPHNIS)33. The flow rate was set to 5.6 μl min−1 (5.28 mm s−1) for the 2F data and 2.8 μl m−1 (2.64 mm s−1) for the dark data. The diffraction patterns were recorded using a multiport CCD detector34. Because the excitation laser pulses were provided at 10 Hz and the XFEL pulses had a repetition rate of 30 Hz, each ‘pump-on’ image was followed by two ‘pump-off’ images, which were recorded separately. The pump-on images were used to analyse the 2F-state structure, whereas the diffraction data for the dark-state was collected by a separate run. To advance the PSII samples to the S -state, two consecutive excitation laser flashes were provided from two separate Nd:YAG laser sources (Minilite-I, Continuum) to the sample at t = 0 ms and t = 10 ms (that is, the two flashes were separated by 10 ms) for the pre-flashed samples, and t = 0 ms and t = 5 ms (separated by 5 ms) for the non-pre-flashed samples. To ensure sufficient excitation, each of the pump lasers was split into two beams, and each beam from the same pump laser (pump 1 or pump 2) was focused on the same sample point with an angle of 160° with respect to each other (a nearly counter-propagating geometry). The two beams from pump 1 were used for the first flash illumination, whereas the other two beams from pump 2 were used for the second flash illumination. The pump focal diameter of all beams was set to 240 μm (top-hat) and its energy was 42 mJ cm−2 from each direction. The XFEL pulses were provided 93 μm downstream from the pump focal centre at a time of 10 ms for the pre-flashed samples and 15 ms for the non-pre-flashed samples following the second excitation laser (the total time following the first flash is therefore 20 ms in both cases) (Fig. 1d, e). At the flow rate of 5.6 μl min−1, each pump-illuminated crystal for the pump-on XFEL images was separated by 528 μm, which was long enough to avoid influence from the previous excitation lasers, as the illumination point by the last laser extends to only 120 μm from its centre of illumination. The background of the detector was estimated by averaging dark images and subtracted from diffraction patterns. Diffraction images were filtered by the program Cheetah35, 36 adapted to SACLA, and processed by the program CrystFEL37. The parameters ‘min-snr’, ‘thresholds’ and ‘min-gradient’ used for peak detection during spot finding were as follows: 6, 500 and 10,000, respectively, for the pre-flashed dark data and pre-flashed 2F data; 5, 500 and 10,000 for the non-pre-flashed dark data; and 5, 500 and 5,000 for the non-pre-flashed 2F data. Indexing was performed using DirAx38 and Mosflm39 with peak integration parameters int-radius = 3, 5, 7, where the unit cell information was provided to avoid integration of the diffraction images from crystals with a longer c axis. Before Monte-Carlo integration, the indexed images with either a diffraction_resolution_limit lower than 4.2 Å or a num_peaks less than 400 were discarded. The numbers of total images collected, the hit images filtered by Cheetah, the indexed images and the number of images used for refinement for pre-flashed samples were as follows: 408,071, 76,047, 64,985 and 27,497, respectively, for the dark data; and 273,550, 60,885, 51,482 and 21,680 for the 2F data. The corresponding numbers for the non-pre-flashed samples are 462,343, 70,083, 54,956 and 22,341 for the dark data; and 876,874, 165,463, 63,711 and 23,903 for the 2F data (Extended Data Table 1). The Lorentz factor for still snapshots was applied manually to the averaged intensities of the pre-flashed dark and 2F data sets40. The statistics for the data collection are given in Extended Data Tables 1, 2, which show that our data for both dark and 2F states had a resolution of 2.35 Å for the pre-flashed samples and 2.5 Å for the non-pre-flashed samples, based on the cut-off value of around 50% for CC . We should point out that the overall multiplicities of all our data are very high, and even at the highest resolution shell, the multiplicity exceeded 500. Together with the facts that: (i) the values of CC in the highest resolution shells are reasonably high; (ii) CC decreases gradually without any abnormal disrupt from the low resolution to higher resolution shells; and (iii) the value of CC in the highest resolution shell is reasonably consistent with the value of I/σ(I) (theoretically 0.5 of CC corresponds to 2.0 of I/σ(I), and any substantial deviations from these values are indicators of systematic bias and/or problems in the error model41), we consider that the quality of the data in the present study is sufficiently high to allow us to reveal the small structural changes induced by the flash illuminations. The initial phases up to 4 Å resolution were obtained by molecular replacement with the program Phaser in the CCP4 suite42 using the 1.95 Å resolution XFEL structure of PSII (PDB accession code 4UB6; ref. 5) as the search model, in which the OEC and its direct ligands, Q , waters and glycerol molecules were omitted. After a few cycles of rigid body refinement and subsequent real space density modification using solvent flattening, histogram matching and non-crystallographic symmetry averaging with the program DM in the CCP4 suite42, the electron density map obtained showed features clear enough to allow us to build the model with confidence. Structural refinement was performed with Phenix43 and the model was manually modified with COOT44. After a few cycles of restrained refinement, water molecules were placed in positions corresponding to the water molecules in the higher-resolution structure where positive peaks higher than 3.5σ in the mF − DF map were clearly identified. Then, based on the resulting mF − DF map, water molecules and glycerol molecules were additionally located when positive peaks higher than 3σ were found. Q , the OEC and its direct ligand residues were modelled in the final step. In our previous XFEL structural analysis at 1.95 Å resolution5, the exact positions of the oxo-bridges were identified in the mF − DF map by omitting the oxo-bridged oxygen atoms; however, when the restrained refinement was performed in the same way in this study, the temperature factors of the manganese and/or calcium atoms in OEC were not converged, and gave rise to very high values owing to the limited resolution of 2.35–2.5 Å. Thus, we built the OEC structure using the geometric restraints based on the Mn CaO cluster in the 1.95 Å resolution XFEL structure, and applied tight distance restraints of σ = 0.02 Å to the Mn–O bonds, Ca–O bonds and Mn–ligand residue distances during the refinement. No restraints were given to the Mn–Mn distances and Mn–Ca distances. The R and R values obtained were 0.133 and 0.171, respectively, for the pre-flashed dark state, 0.139 and 0.186 for the non-pre-flashed dark state, and 0.139 and 0.187 for the non-pre-flashed 2F state (Extended Data Table 1). Given the population of the S state estimated from the FTIR measurement, the diffraction data obtained from the 2F illuminated sample is expected to contain those partly from the S and S states of PSII, which means that the resulted electron density would be a mixture of these S-states, including the S state. Even with a high-resolution data set, the structural refinement of the mixed states (or mixed structures) would be challenging, especially when the mixed structures are very similar, as in the case of PSII. As we did not have the structure corresponding to the S state, we refined the pre-flashed 2F data set as a mixture of the S state structure and the 2F state structure45. The occupancies for the S structure and the 2F state structure were set to 0.2 and 0.8, respectively, on the basis of the distributions of the temperature factors. The region in which the structure was refined in multiple states was selected on the basis of the large peaks observed in the isomorphous difference Fourier map, and the rest was refined as a single conformation. As a result, thirty-five amino acid residues, five water molecules, one non-haem iron, one Q and one OEC per monomeric PSII were modelled as multiple states. During the restrained refinement, the coordinate for the S state structure was fixed. Relatively loose geometric restraints for distance, angle and plane with relatively high sigma values (3–10 times larger than the default values) were applied to the OEC and Q during the refinement. Large positive peaks of 10.3σ for monomer A and 9.5σ for monomer B, found at a position with distances of 1.5 Å and 2.3 Å from O5 and Mn1D, respectively, were modelled as a new oxo-oxygen O6 with an occupancy of 0.4, which gave rise to a temperature factor similar to its nearby atoms. This is also consistent with the population of the S -state estimated from the FTIR results. The R and R values thus obtained were 0.129 and 0.176, respectively. The structure factors and atomic coordinates have been deposited in the Protein Data Bank (PDB) with accession numbers 5WS5 and 5WS6 for the pre-flashed dark-stable S state and 2F states, and 5GTH and 5GTI for the non-pre-flashed dark-stable S state and 2F state, respectively. All other data associated with this manuscript are available from the authors on reasonable request.
News Article | February 15, 2017
PHILADELPHIA - Casting one of the largest genomic nets to date for the rare tumors of the autonomic nervous system known as pheochromocytoma and paraganglioma (PCC/PGL) captured several new mutations driving the disease that could serve as potential drug targets, researchers from Penn Medicine and other institutions reported this week in Cancer Cell. Analyzing genetic data of 173 patients from The Cancer Genome Atlas, researchers, including senior author Katherine Nathanson, MD, a professor in the division of Translational Medicine and Human Genetics at the Perelman School of Medicine at the University of Pennsylvania and associate director for Population Science at Penn's Abramson Cancer Center, identified CSDE1 and fusion genes in MAML3 as drivers of the disease, both a first for any cancer type. The researchers also classified PCC/PGL into four distinct subtypes, each driven by mutations in distinct biological pathways, two of which are novel. "What's interesting about these tumors is that while they are astonishingly diverse genetically, with both inherited and somatic drivers influencing tumorigenesis, each has a single driver mutation, not multiple mutations," Nathanson said. "This characteristic makes these tumors ideal candidates for targeted therapy." Other cancer types typically contain anywhere from two to eight of these driver mutations. The discovery of these single drivers in PCC/PGL provides more opportunities for molecular diagnosis and prognosis in these patients, particularly those with more aggressive cancers, the authors said. PGLs are rare tumors of nerve ganglia in the body, whereas PCCs form in the center of the adrenal gland, which is responsible for producing adrenaline. The tumor causes the glands to overproduce adrenaline, leading to elevated blood pressure, severe headaches, and heart palpitations. Both are found in about two out of every million people each year. An even smaller percentage of those tumors become malignant - and become very aggressive. For that group, the five-year survival rate is about 50 percent. Matthew D. Wilkerson, MD, the Bioinformatics Director at the Collaborative Health Initiative Research Program at the Uniformed Services University, is the paper's co-senior author. To identify and characterize the genetic missteps, researchers analyzed tumor specimens using whole-exome sequencing, mRNA and microRNA sequencing, DNA-methylation arrays, and reverse-phase protein arrays. The four molecularly defined subgroups included: a kinase-signaling subtype, a pseudohypoxia subtype, a cortical admixture subtype, and a Wnt-altered subtype. The last two have been newly classified. The results also provided clinically actionable information by confirming and identifying several molecular markers associated with an increased risk of aggressive and metastatic disease, including germline mutations in SDBH, somatic mutations in ATRX (previously established in a Penn Medicine study), and new gene fusions - a genetic hybrid, of sorts - in MAML3. Because the MAML3 fusion gene activates the Wnt-altered subtype, the authors said, existing targeted therapies that inhibit the beta-catenin and STAT3 pathways may also prove effective in certain PCC/PGL tumors. Other mutations identified in the analysis may also serve as potential targets for drugs currently being investigated in other cancers. For example, glutaminase inhibitors are being tested in SDH-mutant tumors, including breast and lung, and ATR inhibitors are being investigated in blood cancers. Today, there are several U.S. Food and Drug Administration-approved targeted therapies for mutations, such as BRAF and FGFR1, among others, also found in PCC/PGL. "The study gives us the most comprehensive understanding of this disease to date - which we believe will help researchers design better trials and target mutations that will ultimately help improve treatment for these patients," Nathanson said. "The next step is to focus more on aggressive cancers that metastasize and the drivers behind those tumors." Lauren Fishbein, MD, PhD, MTR, a former instructor in the division of Endocrinology, Diabetes and Metabolism at Penn who is now at the University of Colorado Hospital, served as the study's first author. The study was supported with grants by the National Institutes of Health (U54 HG003273, U54 HG003067, U54 HG003079, U24 CA143799, U24 CA143835, U24 CA143840, U24 CA143843, U24 CA143845, U24 CA143848, U24 CA143858, U24 CA143866, U24 CA143867, U24 CA143882, U24 CA143883, U24 CA144025, P30 CA016672). Penn Medicine is one of the world's leading academic medical centers, dedicated to the related missions of medical education, biomedical research, and excellence in patient care. Penn Medicine consists of the Raymond and Ruth Perelman School of Medicine at the University of Pennsylvania (founded in 1765 as the nation's first medical school) and the University of Pennsylvania Health System, which together form a $5.3 billion enterprise. The Perelman School of Medicine has been ranked among the top five medical schools in the United States for the past 18 years, according to U.S. News & World Report's survey of research-oriented medical schools. The School is consistently among the nation's top recipients of funding from the National Institutes of Health, with $373 million awarded in the 2015 fiscal year. The University of Pennsylvania Health System's patient care facilities include: The Hospital of the University of Pennsylvania and Penn Presbyterian Medical Center -- which are recognized as one of the nation's top "Honor Roll" hospitals by U.S. News & World Report -- Chester County Hospital; Lancaster General Health; Penn Wissahickon Hospice; and Pennsylvania Hospital -- the nation's first hospital, founded in 1751. Additional affiliated inpatient care facilities and services throughout the Philadelphia region include Chestnut Hill Hospital and Good Shepherd Penn Partners, a partnership between Good Shepherd Rehabilitation Network and Penn Medicine. Penn Medicine is committed to improving lives and health through a variety of community-based programs and activities. In fiscal year 2015, Penn Medicine provided $253.3 million to benefit our community.
News Article | March 2, 2017
DUBLIN--(BUSINESS WIRE)--Research and Markets has announced the addition of the "Global Market for Regional Aircrafts - 2017-2025 - Market Dynamics, Competitive Landscape, OEM Strategies & Plans, Trends & Growth Opportunities, Market Outlook through 2025" report to their offering. The global market for regional aircrafts is in a flux with stagnation of market demand for new aircrafts in 2016 after a marked demand boom phase and increasing competitive intensity with the entry of new players making a market foray with new, scratch up aircraft programs which is set to alter & transform market dynamics. The regional aircraft market continues to be dominated by Bombardier & Embraer respectively in the jets segment with new, underdevelopment aircraft programs from incumbents getting delayed & still far from entry into service while ATR continues to play second fiddle with its traditional turboprop offerings, the demand for which have been impacted as of-late with the softening of oil prices putting significant pressure on order intake in 2016. The demand for regional aircrafts, however, may have an impact going forward from the emerging aviation trend making a departure from the traditional hub and spoke model relying significantly on regional aircrafts with the opening of new point to point routes by airlines enabled by the introduction of new longer range narrow body and medium wide body aircrafts by the OEMs which has already spelled an uncertain future for large capacity wide body aircrafts operating from the hubs, especially, Airbus A380 & the Boeing 747. However, the opening of new regional routes over medium to long term is likely to be the key & most significant driver of regional aircraft segment by catalyzing fleet growth across carriers globally led by the Asia-Pacific region. The long term outlook for regional aircrafts, thus, is bullish with strong projected passenger traffic growth and focus on air connectivity as a priority for regional development. Section 4: Financial Performance Snapshot Charts & Analysis for each OEM Section 5: Strategic Positioning & SWOT Analysis For Each of the 3 Key Regional Aircraft Manufacturers Section 6: Key Strategies & Plans For Each of the Top 3 Regional Aircraft OEMs For more information about this report visit http://www.researchandmarkets.com/research/69fjgb/global_market_for
News Article | March 2, 2017
GLEN MILLS, Pa.--(BUSINESS WIRE)--Dr. Chen Ling, Senior Scientist at Axalta Coating Systems (NYSE: AXTA), a leading global supplier of liquid and powder coatings, will present new developments in the detection and characterization of chemical molecule migrations in multi-layer automotive coatings at the PITTCON Conference and Expo 2017. Dr. Ling’s presentation titled, Application of ATR-FTIR Microspectroscopy in Understanding Interlayer Migration of Automotive Coatings, is at 10 a.m. on March 8, on the Exposition Floor, Section 2030, Aisle 2500-2600, at McCormick Place in Chicago, Illinois. Dr. Ling’s presentation will explore the new method she and her team have developed to better understand the chemical migration in a wet-on-wet coating process. Automotive coatings typically consist of multiple layers, individually sprayed and dried before another layer is applied. However, in a wet-on-wet coating process, a second layer is applied before the first layer is dry, and multiple layers are dried with a single bake, which can result in reduced energy consumption and increased manufacturing productivity. “Our new method allows us to really zoom in to track and characterize the chemical migrations across the multiple coating layers produced in the wet-on-wet process. Specifically, we can characterize migrations of chemical molecules at a high resolution of about two micrometers, which is about one hundredth the width of a human hair,” said Dr. Ling. “Results from our tests can help us to better understand the relationship between the chemical migration and the overall coating appearance, which can lead to the development of improved coatings and coating processes for our customers.” “Axalta is committed to meeting customers’ needs through technical development and innovation,” said Dr. Brian Priore, Research Manager for Analytical and Weathering Technologies, Axalta Coating Systems. “Analytical technology is one of Axalta’s core strengths that enables us to explore new areas to improve products and services. The developments by Dr. Ling and her team are examples of Axalta’s commitment to meet customers’ needs by supporting the continued growth of highly productive and more environmentally sustainable processes with reduced energy consumption like wet-on-wet coating applications.” PITTCON attracts researchers and experts in laboratory sciences from industry, academic and government institutions around the globe and will take place March 5-9, 2017. For more information, visit www.pittcon.org. Axalta is a leading global company focused solely on coatings and providing customers with innovative, colorful, beautiful and sustainable solutions. From light OEM vehicles, commercial vehicles and refinish applications to electric motors, buildings and pipelines, our coatings are designed to prevent corrosion, increase productivity and enable the materials we coat to last longer. With more than 150 years of experience in the coatings industry, the approximately 12,800 people of Axalta continue to find ways to serve our more than 100,000 customers in 130 countries better every day with the finest coatings, application systems and technology. For more information visit axalta.com and follow us @Axalta on Twitter and on LinkedIn.
News Article | February 28, 2017
Advanced nuclear technology development is such a hot topic these days that the hashtag #AdvancingNuclear took over Twitter on Tuesday, Feb 22 while Third Way, several national labs and the Paul G. Allen Family Foundation sponsored the second annual Advanced Nuclear Summit. At least five entities in the United States or Canada (TerraPower, ARC, GE Prism, LeadCold and Westinghouse) are expending significant sums of corporate or venture capital to pursue an elusive technical achievement; commercially viable nuclear power systems that achieve substantially greater fuel economy than conventional reactors. Though nuclear fuel is "cheap," substantially better fuel use provides improved longevity and produces less waste material. Efforts to achieve fuel economy objectives has reopened a discussion whose roots extend back more than 50 years into the middle of the 1960s. Given that there are United States entities that believe there is a need for advanced nuclear technology with fuel consumption characteristics that surpass those available from conventional reactors, those entities need a facility that can provide conditions for the fuel and materials testing required to support design, development and licensing. Currently available facilities that can provide the necessary conditions are located in Russia and China. For obvious reasons, those choices are not optimal. Conventional commercial nuclear reactors operate with slow [thermal] neutrons. They use light materials like water or graphite to moderate [slow] the high speed, high energy [fast] neutrons that are liberated when uranium or plutonium atoms are broken apart. Thermal neutrons have a higher probability of being absorbed and causing fission, thus they can work with fuel that is only slightly purified [aka enriched] to have a little more fissile material than natural uranium. The disadvantage of thermal spectrum reactors is that commercially proven configurations fission only 3-5% of the uranium in the fuel elements. Though technical specialists can quibble with this statement, thermal reactors only obtain heat from the 0.7% of natural uranium that is fissile U-235. The U-238 atoms that make up 99.3% of natural uranium are treated as if they were useless waste materials. In commercial fuel elements, natural uranium has been purified so that 3-5% of the uranium is fissile U-235. As a result, conventional reactors consume 3-5% of the loaded fuel, leaving 95-97% of the potential energy behind as waste if not recycled. Many nuclear advocates or nuclear technology observers claim there is no immediate need to spend money to improve fuel cycle efficiency. Uranium is cheaper now in nominal dollars than it was in 1973 ($24/lb versus $40/lb). The market is oversupplied to the point where mines are being closed for economic reasons, not because they have exhausted the known deposits. Storing used fuel [which some people insist on calling "nuclear waste"] is technically simple and not a major cost item, even though it can lead to heated political controversies. Those objections do not prevent others from pursuing improvements because they seek other measures of effectiveness or have discovered ways to position their technology to compete in unique ways. LWR "waste" material is capable of being broken apart and releasing just as much energy for each fission as splitting U-235. Uranium-238 can fission either directly if impacted by a neutron moving fast enough to carry substantial momentum [about 1 MeV of energy] or it can fission after absorbing a neutron, undergoing two beta decays to become Pu-239 and then being split by a second neutron. In a reactor that has no or little moderation [either zero or a small portion of light materials like graphite or water in the core] neutrons retain high enough energy to either directly fission or to convert U-238 to fissile Pu-239. Doing so improves fuel economy by a factor that might approach 140. With fast neutrons, a fuel resource expected to last for a century with thermal reactors could conceivably last 14,000 years. One of the primary technological rainbows that might lead to this pot of gold is to use reactors that are cooled by liquid metal, with the common choices being limited to sodium, lead, or a eutectic mixture of sodium and potassium called NaK. Using liquid metals and fast neutron spectra requires materials and fuels whose characteristics are considerably different from those in conventional reactors. Doing this safely – and within the bounds of regulations – requires adequately testing and computer model validation. In the mid 1960s, the U.S. Atomic Energy Commission shifted most of its nuclear technology investment expenditures away from projects that would improve on light water reactors. The general consensus was that those reactors had been commercialized to the point where private industry would invest the resources required for improvements. In 1965, the Joint Committee on Atomic Energy (JCAE), the President and the AEC determined that the time was right to apply available resources to serious research and development of liquid metal cooled fast breeder reactors. That effort included the recognized need for a large-capacity, highly capable testing reactor. A group of scientists, technologists, economic boosters and elected officials in the state of Washington joined forces and put together a proposal for a fast neutron test facility. Similar people associated with the Idaho National Reactor Testing station and the closely aligned Argonne National Laboratory in Illinois assumed that their site was the logical location for such a facility. After all, they had already hosted so many experimental, test and demonstration reactors. Their site was the National Reactor Testing Station before it was renamed as the Idaho National Laboratory. Those loosely aligned individuals and corporate entities did not take into account the well-organized group in Washington. They did not understand the national government's desire to soften the economic blow that had been dealt to eastern Washington with the winding down of the plutonium production reactors. They also failed to recognize the importance of Milton Shaw's personal animosity towards Albert Crewe, then serving as the director of Argonne National Laboratory. Shaw was then serving as the director of AEC-Headquarters’ Division of Reactor Development and Technology; his opinion carried a great deal of weight in the AEC decision process. The reactor that the Atomic Energy Commission designed, sited, built and operated at the Hanford Site in Eastern Washington to provide the proper environment for testing fast reactor fuels and materials operated from 1982-1992. That shutdown happened about 15 years after Presidents Ford and Carter had determined that the US would not pursue liquid metal breeder reactors. The AEC took from 1967-1982 to move from conception to an operating test facility. Some of the delay was caused by the annual budget battles that questioned the need for the facility after the cancellation of the fast breeder reactor program. The design was reviewed and approved by the Nuclear Regulatory Commission (NRC), though regulation of the facilities construction and operation was retained by DOE. That facility – the 400 MWth Fast Flux Test Facility (FFTF) – remains the highest capacity, most modern and least used test reactor in the U.S. DOE's possession. It is still intact with its internals filled with an inert argon gas purge. Though final environmental impact assessments have been conducted and a decision has been made to entomb the facility, budgets and preparation of detailed engineering plans move slowly at DOE; no destruction has begun yet. There is a pervasive myth floating around the DOE that actions taken during the George W. Bush administration to more completely remove the sodium coolant from the system has made it impossible for the system to be restored. According to a 2007 detailed study funded by DOE as part of the Global Nuclear Energy Partnership (GNEP) the action taken was to drill a 3/4" carefully engineered hole in a non pressure barrier. The study determined that adequate recovery from that action would add a little less than $1 M to the $500 M facility restoration cost estimate. (See pages 56-57 of the linked PDF) What Kind Of Reputation Did The FFTF Earn? During the 15 years following the 1976-77 turn away from developing fast breeder reactors as a national priority, the FFTF was completed, put through an extensive start-up testing program and used operationally for the next 10 years. Because FFTF's primary mission of supporting an expansive breeder reactor program had been cancelled before the facility ever started up, its supporters were put into the position of existence justification before they even opened for business. The facility was used for materials testing, medical isotope production, and was proposed for use as a plutonium burner, a source for Pu-238 for space missions and as a prototype liquid metal power reactor. One of the test series conducted at the FFTF validated the system's passive safety claims. The unvalidated nature of those claims was a major objection raised by the project's more vocal opponents, including Arthur Tamplin and Thomas Cochrane, both of the Natural Resources Defense Council (NRDC). During its operational life, the FFTF demonstrated the value of having been built with a view towards longevity and reliable operation. At times, it could run for many months without reducing power. That is valuable when operating to "burn up" fuel or highly irradiate materials with neutrons. In 1990, President George H. W. Bush and his Secretary of Energy, James Watkins determined that the FFTF was no longer needed and could be sacrificed in the name of budget cutting. They justified the decision by claiming that the US was no longer pursuing fast reactor technology. Apparently, the staff people who supplied this budget cutting recommendation and justification ignored the Integral Fast Reactor (IFR) project in Idaho, which was then in its 18th year and still going strong. In 1992, the FFTF was ordered to be placed in standby by President Clinton and Hazel O'Leary, his first Secretary of Energy. On Jan 19, 2001, the last day of the Clinton Administration, Bill Richardson, then serving as the Secretary of Energy, signed the Record of Decision (ROD) on the Final Environmental Impact Statement for closing and decommissioning the facility. In December 2001, President George W. Bush and his Secretary of Energy, Spencer Abraham ordered that the facility be permanently shutdown by completing the sodium removal. In 2007, as part of the Global Nuclear Energy Partnership, the Department of Energy funded a study to determine if the facility could be economically restored on a usefully short schedule. With a 20% contingency and conservative schedule assumptions, that study indicated that restoration would take about 5-6 years and cost $500 million. The study ended up in a room known to insiders as the abandoned room, a place where all of the GNEP Environmental Impact Statement paperwork accumulated with no consideration given to reviewing the documents and making a final decision. At the end of the Obama Administration, DOE began identifying the mission need and requirements for a new fast reactor testing facility. Though the documents produced as part of that effort only mention the FFTF in passing, it now appears that the process for meeting user demands for fast neutron testing capability will include evaluating the option of restoring the FFTF. With a more diverse and less politically vulnerable user base compared to the 1970s vintage fast breeder reactor program, the FFTF should finally get the chance to perform its primary mission for a lengthy period of time. As the US DOE has found with the Advanced Test Reactor (ATR), a 50 year-old facility initially built to serve a single customer, there is a wide range of potential customers and a sustainable demand for a well run neutron irradiation user facility that might last for numerous decades. It's time to move from repeated bipartisan efforts to permanently kill the FFTF to a broad-based effort to recognize value and restore the facility that our parents built and carefully put away in case we might need it.
News Article | February 17, 2017
Softline Solutions, a leader in Search Engine Marketing solutions with more than 15 years of experience, is excited to announce that they are now providing marketing services to Island Air, an airline company that has served the islands of Hawaii for more than 35 years. “We are excited about adding this amazing client to our Travel & Hospitality division,” Rony Mirzaians, Head of Marketing for Softline Solutions said. “With Island Air’s fabulous reputation and commitment to its customers, and Softline’s award-winning marketing approach, we believe that this is an unbeatable match. We will work tirelessly to provide Island Air with a marketing campaign that not only caters to its customers, but upholds the brand’s legacy for excellence.” Softline Solutions will become Island Air’s new Paid Search marketing partner immediately. About Softline Solutions Softline Solutions has over a decade of experience creating, managing, and growing profitable marketing campaigns for a variety of companies over a gamut of industries. They offer a plethora of services including Google Adwords, Bing Ads, CRO, eCommerce marketing, Facebook ads, consulting, programmatic search, SEO, and much more.. For more information, please visit http://www.softlinesolutions.com. About Island Air Island Air has more than three decades of service throughout the islands of Hawaii. With a fleet consisting of ATR 72 and Q400 aircraft, they are dedicated to providing the best flying experiences and services to each and every one of their customers. For more information, please visit http://www.islandair.com.
News Article | February 27, 2017
Pakistan International Airlines was considered a global leader until the 1970s but plagued by controversies over recent years and saddled with billions of dollars of debt (AFP Photo/RIZWAN TABASSUM) Pakistan's national carrier said Sunday it would investigate allegations that a plane flew from Karachi to Saudi Arabia carrying seven extra passengers, but denied they stood in the aisles for the three-hour journey. The probe was ordered after a report in the English-language daily Dawn. The paper said the January 20 flight to Medina carried 416 passengers, seven more than its capacity of 409 including jump seats, in a serious breach of air safety regulations. The newspaper quoted sources as saying that in case of an emergency, passengers without seats would not have access to oxygen masks and could block any emergency evacuation. Pakistan International Airlines' spokesman Danyal Gilani said media reports that some passengers travelled standing "are exaggerated and baseless. It is not possible for anyone to travel like that in an aircraft, regardless of the duration of the flight." But he said: "The matter pertaining to the travel of more passengers than the booked load...is under investigation," and the airline had ordered a "thorough probe into it, and all concerned are being questioned". "PIA is committed to ensure the safety of the passengers and cannot allow any incident to happen which compromises safety," he added. It was the latest embarrassing incident for the airline, considered a global leader until the 1970s but plagued by controversies over recent years and saddled with billions of dollars of debt. A PIA turboprop built by European manufacturer ATR plummeted into a mountain in a northern region on December 7, bursting into flames and killing all 47 people on board. The airline was later mocked after its staff were photographed sacrificing a goat on a runway to ward off bad luck. Domestic flights are often delayed for VIPs while flight employees have been caught smuggling goods ranging from iPhones to narcotics. In 2013 one of its pilots was jailed for nine months in Britain for being drunk before he was due to fly from Leeds to Islamabad with 156 people on board.
News Article | March 1, 2017
Coloring hair has become a common practice, particularly for people who want to hide their graying locks. But an ingredient in many of today's commercial hair dyes has been linked to allergic reactions and skin irritation. Now scientists have developed a potentially safer alternative by mimicking the hair's natural color molecule: melanin. Their report appears in the journal ACS Biomaterials Science & Engineering. The permanent hair dye ingredient p-phenylenediamine (PPD) has been associated, although rarely, with allergic reactions including facial swelling and rashes. Coloring hair with natural melanin would be an intuitive alternative to PPD. But previous research has found that the pigment molecules clump together, forming rods and spheres too large to penetrate into the hair shaft to create lasting color. Jong-Rok Jeon and colleagues wanted to build on the idea of using melanin but with a molecule that mimics the real thing. The researchers turned to polydopamine, a black substance that is structurally similar to melanin and has been explored for use in a variety of biomedical applications. Polydopamine with iron ions transformed gray hairs into black and lasted through three wash cycles. Lighter shades could also be achieved with polydopamine by pairing it with copper and aluminum ions. And toxicity tests showed that mice treated with the colorant didn't have noticeable side effects, while those that received a PPD-based dye developed bald spots. Explore further: Hair dyeing poised for first major transformation in 150 years More information: Kyung Min Im et al. Metal-Chelation-Assisted Deposition of Polydopamine on Human Hair: A Ready-to-Use Eumelanin-Based Hair Dyeing Methodology, ACS Biomaterials Science & Engineering (2017). DOI: 10.1021/acsbiomaterials.7b00031 Abstract Permanent dyeing of gray hair has become an increasingly active area in the cosmetics industry because of the increasingly aging population in developed countries. So far, p-phenylenediamine (PPD) and related diamine-based monomeric compounds have been widely used for the dyeing processes, but toxicological studies have revealed such compounds to be carcinogenic and allergenic. Here, we for the first time demonstrated that polydopamine, a mimic of human eumelanin, gives rise within a commercially acceptable period of time (i.e., 1 h) to deep black colors (i.e., natural Asian hair colors) in human keratin hairs in the presence of ferrous ions. The dyed hairs showed excellent resistance to conventional detergents, and the detailed color was readily varied by changing the kind of metal ion used. SEM images and FT-IR-ATR spectra suggested that the extent of polydopamine aggregation was crucial for the dyeing efficiency. High-resolution (15 T) FT-ICR mass spectrometry performed on the products detached from hairs with either 0.1 N HCl or NaOH indicated that similar polydopamine products were recruited into the hair matrices whether in the presence or absence of metal-based chelating. Polydopamine chains were determined using EPR and ICP-OES to use chelation of ferrous ions to self-assemble as well as to bind keratin surfaces in the dyeing conditions. Also, mice subjected to skin toxicity tests showed much greater viability and much less hair loss with our dyeing agents than with PPD. In conclusion, this study showed that a safe eumelanin mimic may be used to permanently dye gray hair, and showed three kinds of deposition mechanisms (i.e., innate binding ability of polydopamine, metal-assisted self-assembly of polydopamine, and metal-related bridging between keratin surface and polydopamine) to be involved.
News Article | February 17, 2017
AeroVision International has announced it will open a new forward stocking location to service customers in Europe, the Middle East and Africa in collaboration with B&H Worldwide, a leading aerospace logistics provider. “Our newly initiated warehouse will be adjacent to London’s Heathrow Airport, allowing customers outside of North America greatly improved access to AeroVision’s inventory of regional aircraft parts” said Pete Gibson, AeroVision’s Vice President of Aircraft Services. “Utilizing the 24/7/365 support of B&H Worldwide will cut lead times for normal shipments and greatly reduce the response time for EMEA customer’s AOG situations.” Rick Cramblet, Executive Vice President of AeroVision said, “The relationship with B&H Worldwide, utilizing their LHR warehouse location, is the first step in building out a global support network for our customers. Additional forward stocking locations will be added as quickly as possible, enabling our customers to reduce their investment in inventory while increasing their dispatch reliability.” "We are delighted to have been chosen to provide these specialist logistics services to a leading global provider like AeroVision International. Our highly trained team at Heathrow will be focused on providing a first class service, which will enable AeroVision to maintain the highest integrity of its forward stocking supply chain," stated B&H Worldwide’s V.P. Americas, Reg Echeumuna. About AeroVision International LLC: Founded in 2003, AeroVision International has become a trusted business partner to business and regional aircraft MR&O shops worldwide. AeroVision supplies business and regional commuter engines and engine parts (PT6 / PW100 / JT15D / PW300 / PW500 / TFE-731 / AE3007) in support of operators and MRO facilities around the world. With a strong focus on Embraer ERJ-135/145 and ATR 42 aircraft, AeroVision offers sales & leasing of aircraft, engines, auxiliary power units, avionics and landing gear as well as outright or exchange sales of all major internal and external spare parts. Information on AeroVision’s support for the ERJ aircraft can be found at http://www.aerovi.com. About B&H Worldwide: Established in 1988 in the UK, B&H Worldwide is a market leader in the highly specialist aerospace parts industry. Over the last quarter of a century is has expanded globally and today operates from ten strategically located aerospace hubs around the world and has a customer base which includes airlines, spare part stockists, MROs and repair vendors. Its innovative, in-house designed IT solutions are highly tailored to suit customer operating models and its OnTrack software sets the benchmark for the aerospace logistics industry.
News Article | March 2, 2017
Research and Markets has announced the addition of the "Global Market for Regional Aircrafts - 2017-2025 - Market Dynamics, Competitive Landscape, OEM Strategies & Plans, Trends & Growth Opportunities, Market Outlook through 2025" report to their offering. The global market for regional aircrafts is in a flux with stagnation of market demand for new aircrafts in 2016 after a marked demand boom phase and increasing competitive intensity with the entry of new players making a market foray with new, scratch up aircraft programs which is set to alter & transform market dynamics. The regional aircraft market continues to be dominated by Bombardier & Embraer respectively in the jets segment with new, underdevelopment aircraft programs from incumbents getting delayed & still far from entry into service while ATR continues to play second fiddle with its traditional turboprop offerings, the demand for which have been impacted as of-late with the softening of oil prices putting significant pressure on order intake in 2016. The demand for regional aircrafts, however, may have an impact going forward from the emerging aviation trend making a departure from the traditional hub and spoke model relying significantly on regional aircrafts with the opening of new point to point routes by airlines enabled by the introduction of new longer range narrow body and medium wide body aircrafts by the OEMs which has already spelled an uncertain future for large capacity wide body aircrafts operating from the hubs, especially, Airbus A380 & the Boeing 747. However, the opening of new regional routes over medium to long term is likely to be the key & most significant driver of regional aircraft segment by catalyzing fleet growth across carriers globally led by the Asia-Pacific region. The long term outlook for regional aircrafts, thus, is bullish with strong projected passenger traffic growth and focus on air connectivity as a priority for regional development. Section 4: Financial Performance Snapshot Charts & Analysis for each OEM Section 5: Strategic Positioning & SWOT Analysis For Each of the 3 Key Regional Aircraft Manufacturers Section 6: Key Strategies & Plans For Each of the Top 3 Regional Aircraft OEMs For more information about this report visit http://www.researchandmarkets.com/research/nbhjx4/global_market_for