Simultaneous alignment and folding of protein sequences

Accurate comparative analysis tools for low-homology proteins remains a difficult challenge in computational biology, especially sequence alignment and consensus folding problems. We presentpartiFold-Align, the first algorithm for simultaneous alignment and consensus folding of unaligned protein sequences; the algorithm’s complexity is polynomial in time and space. Algorithmically,partiFold-Align exploits sparsity in the set of super-secondary structure pairings and alignment candidates to achieve an effectively cubic running time for simultaneous pairwise alignment and folding. We demonstrate the efficacy of these techniques on transmembrane β-barrel proteins, an important yet difficult class of proteins with few known three-dimensional structures. Testing against structurally derived sequence alignments,partiFold-Align significantly outperforms state-of-the-art pairwise sequence alignment tools in the most difficult low sequence homology case and improves secondary structure prediction where current approaches fail. Importantly, partiFold-Align requires no prior training. These general techniques are widely applicable to many more protein families. partiFold-Align is available at http://partiFold.csail.mit.edu

Microstructure and thermal stability of Fe, Ti and Ag implanted Yttria-stabilized zirconia

Yttria-stabilized zirconia (YSZ) was implanted with 15 keV Fe or Ti ions up to a dose of 8×1016 at cm−2. The resulting “dopant” concentrations exceeded the concentrations corresponding to the equilibrium solid solubility of Fe2O3 or TiO2 in YSZ. During oxidation in air at 400° C, the Fe and Ti concentration in the outermost surface layer increased even further until a surface layer was formed of mainly Fe2O3 and TiO2, as shown by XPS and ISS measurements. From the time dependence of the Fe and Ti depth profiles during anneal treatments, diffusion coefficients were calculated. From those values it was estimated that the maximum temperature at which the Fe- and Ti-implanted layers can be operated without changes in the dopant concentration profiles was 700 and 800° C, respectively. The high-dose implanted layer was completely amorphous even after annealing up to 1100° C, as shown by scanning transmission electron microscopy. Preliminary measurements on 50 keV Ag implanted YSZ indicate that in this case the amorphous layer recrystallizes into fine grained cubic YSZ at a temperature of about 1000° C. The average grain diameter was estimated at 20 nm, whereas the original grain size of YSZ before implantation was 400 nm. This result implies that the grain size in the surface of a ceramic material can be decreased by ion beam amorphisation and subsequent recrystallisation at elevated temperatures

Interdiffusion at Sb/Ge interfaces induced in thin multilayer films by nanosecond laser irradiation

Thin films consisting of 3 or 4 Sb and Ge alternating layers are irradiated with single nanosecond laser pulses (12 ns, 193 nm). Real time reflectivity (RTR) measurements are performed during irradiation, and Rutherford backscattering spectrometry (RBS) is used to obtain the concentration depth profiles before and after irradiation. Interdiffusion of the elements takes place at the layer interfaces within the liquid phase. The reflectivity transients allow to determine the laser energy thresholds both to induce and to saturate the process being both thresholds dependent on the multilayer configuration. It is found that the energy threshold to initiate the process is lower when Sb is at the surface while the saturation is reached at lower energy densities in those configurations with thinner layers

Size Doesn't Matter: Towards a More Inclusive Philosophy of Biology

notes: As the primary author, O’Malley drafted the paper, and gathered and analysed data (scientific papers and talks). Conceptual analysis was conducted by both authors.publication-status: Publishedtypes: ArticlePhilosophers of biology, along with everyone else, generally perceive life to fall into two broad categories, the microbes and macrobes, and then pay most of their attention to the latter. ‘Macrobe’ is the word we propose for larger life forms, and we use it as part of an argument for microbial equality. We suggest that taking more notice of microbes – the dominant life form on the planet, both now and throughout evolutionary history – will transform some of the philosophy of biology’s standard ideas on ontology, evolution, taxonomy and biodiversity. We set out a number of recent developments in microbiology – including biofilm formation, chemotaxis, quorum sensing and gene transfer – that highlight microbial capacities for cooperation and communication and break down conventional thinking that microbes are solely or primarily single-celled organisms. These insights also bring new perspectives to the levels of selection debate, as well as to discussions of the evolution and nature of multicellularity, and to neo-Darwinian understandings of evolutionary mechanisms. We show how these revisions lead to further complications for microbial classification and the philosophies of systematics and biodiversity. Incorporating microbial insights into the philosophy of biology will challenge many of its assumptions, but also give greater scope and depth to its investigations

Strategies for waveguide coupling for SRF cavities

Despite widespread use of coaxial couplers in SRF cavities, a single, simple waveguide coupling can be used both to transmit generator power to a cavity, and to remove a large class of Higher Order Modes (HOMs, produced by the beam). There are balances and tradeoffs to be made, such as the coupling strength of the various frequencies, the transverse component of the coupler fields on the beam axis, and the magnitude of the surface fields and currents. This paper describes those design constraints, categories of solutions, and examples from the CEBAF Energy Upgrade studies

A fiber optic synchronization system for LUX

The LUX femtosecond light source concept would support pump-probe experiments that need to synchronize laser light pulses with electron-beam-generated X-ray pulses to less than 50 fs at the experimenter endstations. To synchronize multiple endstation lasers with the X-ray pulse, we are developing a fiber-distributed optical timing network. A high frequency clock signal is distributed via fiber to RF cavities (controlling X-ray probe pulse timing) and mode-locked lasers at endstations (controlling pump pulse timing). The superconducting cavities are actively locked to the optical clock phase. Most of the RF timing error is contained within a 10 kHz bandwidth, so these errors and any others affecting X-ray pulse timing (such asRF gun phase) can be detected and transmitted digitally to correct laser timing at the endstations. Time delay through the fibers will be stabilized by comparing a retro-reflected pulse from the experimenter endstation end with a reference pulse from the sending end, and actively controlling the fiber length

A fiber optic synchronization system for LUX

The LUX femtosecond light source concept would support pump-probe experiments that need to synchronize laser light pulses with electron-beam-generated X-ray pulses to less than 50 fs at the experimenter endstations. To synchronize multiple endstation lasers with the X-ray pulse, we are developing a fiber-distributed optical timing network. A high frequency clock signal is distributed via fiber to RF cavities (controlling X-ray probe pulse timing) and mode-locked lasers at endstations (controlling pump pulse timing). The superconducting cavities are actively locked to the optical clock phase. Most of the RF timing error is contained within a 10 kHz bandwidth, so these errors and any others affecting X-ray pulse timing (such asRF gun phase) can be detected and transmitted digitally to correct laser timing at the endstations. Time delay through the fibers will be stabilized by comparing a retro-reflected pulse from the experimenter endstation end with a reference pulse from the sending end, and actively controlling the fiber length

A low-cost, Nist-traceable, high performance dielectric resonator Master Oscillator

The current CEBAF Master Oscillator (MO) uses a quartz-based 10 MHz reference to synthesize 70 MHz and 499 MHz, which are then distributed to each of the klystron galleries on site. Due to the specialized nature of CEBAF's MO requirements, it has been determined that an in-house design and fabrication would provide a cost-effective alternative to purchasing or modifying vendor equipment. A Global Positioning System (GPS) disciplined, Direct Digital Synthesis (DDS) based MO is proposed which incorporates low-cost consumer RF components, designed for cellular communications. A 499 MHz Dielectric Resonant Oscillator (DRO) Voltage Controlled Oscillator (VCO) is phase-locked to a GPS-disciplined 10 MHz reference, and micro-tuned via a DDS, in an effort to achieve the lowest phase noise possible

Superconducting Cavity Development for the CEBAF Upgrade

Long-term plans for CEBAF at Jefferson Lab call for achieving 12 GeV in the middle of the next decade and 24 GeV after 2010. In support of these plans, an Upgrade Cryomodule, capable of providing more than twice the operating voltage of the existing CEBAF modules within the same length, is being developed. In particular, this requires the development of superconducting cavities capable of consistently operating at gradients above 12 MV/m and Q {approximately} 10{sup 10}. We have engaged in a complete review of all the processes and procedures involved in the fabrication and assembly of cavities, and are modifying our chemical processing, cleaning, and assembly facilities. While we have retained the cell shape of existing CEBAF cavities, the new superconducting structure will be substantially different in several respects, such as the higher-order-modes damping and the fundamental power coupling systems. Design features and experimental results will be presented