Structure of Cross-Bridges in Vertebrate Skeletal Muscle Activated by Photolysis of Caged Ca2+

In order to understand the contraction mechanism in vertebrate skeletal muscle, one must correlate the structural and mechanical details of the cross-bridge cycle on the millisecond time scale. Using electron microscopy, I investigated the structure of cross-bridges in fibers activated by photolysis of caged ca2+ and then ultra­rapidly frozen and freeze substituted with tannic acid and OsO4. Sections from relaxed fibers show helical tracks, presumed to be rnyosin heads, on the thick filament surface. Optical diffraction patterns show strong meridional spots and layer lines up to the 6th order of the 429 Å repeat, indicating preservation and resolution of periodic structures smaller than 100 Å . Following photo-release of ca2+, the myosin 1/429 Å-1 layer line becomes less intense, and higher orders disappear, both with a time course which precedes the rise in tension. Å 1/360 Å-1 layer line appears early in contraction ( 12-15 ms) and becomes stronger at later times. The intensity of the 1/143 Å_-1 meridional spot decreases initially and then increases to greater than its value in relaxed fibers, while it broadens six-fold laterally. The 1/430 Å-1 meridional spot is present during contraction but markedly weakened. The 1/215 Å-1 meridional spot is weak or absent. These results are consistent with time resolved X-ray diffraction data on the periodic structures within the fiber. The intensification of the 1/360 Å-1 layer line, with a concomitant decrease in the intensity of the 1/429 Å-1 layer line, supports the view that at least some cross­bridges decorate the thin filament during contraction with an act in based set of periodicities, but not to the same degree as is seen in rigor. The lateral spread of the 1/ 143 Å-1 meridional spot indicates a disorder of axial coherence among thick filaments during tension development. In sections along the (1,1) plane of activated fibers, the individual cross-bridges have a wide range of shapes and angles, perpendicular to the fiber axis or pointing toward or away from the Z-line. Fibers frozen at 12-15 ms, 30-35 ms, and 210-220 ms after photolysis all show surprisingly similar cross-bridges. Thus, a highly variable distribution of cross-bridge shapes and angles is established early in contraction

Architectures for Dynamic Data Scaling in 2/4/8K Pipeline FFT Cores

This paper presents architectures for supporting dynamic data scaling in pipeline fast Fourier transforms (FFTs), suitable when implementing large size FFTs in applications such as digital video broadcasting and digital holographic imaging. In a pipeline FFT, data is continuously streaming and must, hence, be scaled without stalling the dataflow. We propose a hybrid floating-point scheme with tailored exponent datapath, and a co-optimized architecture between hybrid floating point and block floating point (BFP) to reduce memory requirements for 2-D signal processing. The presented co-optimization generates a higher signal-to-quantization-noise ratio and requires less memory than for instance convergent BFP. A 2048-point pipeline FFT has been fabricated in a standard-CMOS process from AMI Semiconductor (Lenart and Öwall, 2003), and a field-programmable gate array prototype integrating a 2-D FFT core in a larger design shows that the architecture is suitable for image reconstruction in digital holographic imaging

A hybrid interconnect network-on-chip and a transaction level modeling approach for reconfigurable computing

This paper presents a hybrid interconnect network consisting of a local network with dedicated wires and a global hierarchical network. A distributed memory approach enables the possibility to use generic memory banks as routing buffers, simplifies the implementation and reduces the area requirements of routers. A SystemC simulation environment (SCENIC) has been developed to simulate and instrument models, and to setup different topologies and scenarios. Modules are designed as transaction level models to improve design time and simulation speed

Modeling and exploration of a reconfigurable architecture for digital holographic imaging

The use of coarse-grain reconfigurable architectures (CGRA) is a suitable alternative for hardware acceleration in many application areas, including digital holographic imaging. In this paper, we propose a CGRA-based system with an array of processing and memory cells, which communicate using a local and a global communication network, and a stream memory controller to manage data transfers to external memory. We present our SystemC-based exploration environment (SCENIC) and methodology used to construct and evaluate systems containing reconfigurable architectures. A case study illustrates the advantages with rapid system level exploration to find and solve bottlenecks in complex designs prior to RTL description

Asymmetric function theory

The classical theory of symmetric functions has a central position in algebraic combinatorics, bridging aspects of representation theory, combinatorics, and enumerative geometry. More recently, this theory has been fruitfully extended to the larger ring of quasisymmetric functions, with corresponding applications. Here, we survey recent work extending this theory further to general asymmetric polynomials.Comment: 36 pages, 8 figures, 1 table. Written for the proceedings of the Schubert calculus conference in Guangzhou, Nov. 201

Littlewood-Richardson coefficients for reflection groups

In this paper we explicitly compute all Littlewood-Richardson coefficients for semisimple or Kac-Moody groups G, that is, the structure coefficients of the cohomology algebra H^*(G/P), where P is a parabolic subgroup of G. These coefficients are of importance in enumerative geometry, algebraic combinatorics and representation theory. Our formula for the Littlewood-Richardson coefficients is given in terms of the Cartan matrix and the Weyl group of G. However, if some off-diagonal entries of the Cartan matrix are 0 or -1, the formula may contain negative summands. On the other hand, if the Cartan matrix satisfies $a_{ij}a_{ji}\ge 4$ for all $i,j$, then each summand in our formula is nonnegative that implies nonnegativity of all Littlewood-Richardson coefficients. We extend this and other results to the structure coefficients of the T-equivariant cohomology of flag varieties G/P and Bott-Samelson varieties Gamma_\ii(G).Comment: 51 pages, AMSLaTeX, typos correcte

A Federated Database for Obesity Research:An IMI-SOPHIA Study

Obesity is considered by many as a lifestyle choice rather than a chronic progressive disease. The Innovative Medicines Initiative (IMI) SOPHIA (Stratification of Obesity Phenotypes to Optimize Future Obesity Therapy) project is part of a momentum shift aiming to provide better tools for the stratification of people with obesity according to disease risk and treatment response. One of the challenges to achieving these goals is that many clinical cohorts are siloed, limiting the potential of combined data for biomarker discovery. In SOPHIA, we have addressed this challenge by setting up a federated database building on open-source DataSHIELD technology. The database currently federates 16 cohorts that are accessible via a central gateway. The database is multi-modal, including research studies, clinical trials, and routine health data, and is accessed using the R statistical programming environment where statistical and machine learning analyses can be performed at a distance without any disclosure of patient-level data. We demonstrate the use of the database by providing a proof-of-concept analysis, performing a federated linear model of BMI and systolic blood pressure, pooling all data from 16 studies virtually without any analyst seeing individual patient-level data. This analysis provided similar point estimates compared to a meta-analysis of the 16 individual studies. Our approach provides a benchmark for reproducible, safe federated analyses across multiple study types provided by multiple stakeholders.</p

A Federated Database for Obesity Research:An IMI-SOPHIA Study

Obesity is considered by many as a lifestyle choice rather than a chronic progressive disease. The Innovative Medicines Initiative (IMI) SOPHIA (Stratification of Obesity Phenotypes to Optimize Future Obesity Therapy) project is part of a momentum shift aiming to provide better tools for the stratification of people with obesity according to disease risk and treatment response. One of the challenges to achieving these goals is that many clinical cohorts are siloed, limiting the potential of combined data for biomarker discovery. In SOPHIA, we have addressed this challenge by setting up a federated database building on open-source DataSHIELD technology. The database currently federates 16 cohorts that are accessible via a central gateway. The database is multi-modal, including research studies, clinical trials, and routine health data, and is accessed using the R statistical programming environment where statistical and machine learning analyses can be performed at a distance without any disclosure of patient-level data. We demonstrate the use of the database by providing a proof-of-concept analysis, performing a federated linear model of BMI and systolic blood pressure, pooling all data from 16 studies virtually without any analyst seeing individual patient-level data. This analysis provided similar point estimates compared to a meta-analysis of the 16 individual studies. Our approach provides a benchmark for reproducible, safe federated analyses across multiple study types provided by multiple stakeholders

A Federated Database for Obesity Research:An IMI-SOPHIA Study

Obesity is considered by many as a lifestyle choice rather than a chronic progressive disease. The Innovative Medicines Initiative (IMI) SOPHIA (Stratification of Obesity Phenotypes to Optimize Future Obesity Therapy) project is part of a momentum shift aiming to provide better tools for the stratification of people with obesity according to disease risk and treatment response. One of the challenges to achieving these goals is that many clinical cohorts are siloed, limiting the potential of combined data for biomarker discovery. In SOPHIA, we have addressed this challenge by setting up a federated database building on open-source DataSHIELD technology. The database currently federates 16 cohorts that are accessible via a central gateway. The database is multi-modal, including research studies, clinical trials, and routine health data, and is accessed using the R statistical programming environment where statistical and machine learning analyses can be performed at a distance without any disclosure of patient-level data. We demonstrate the use of the database by providing a proof-of-concept analysis, performing a federated linear model of BMI and systolic blood pressure, pooling all data from 16 studies virtually without any analyst seeing individual patient-level data. This analysis provided similar point estimates compared to a meta-analysis of the 16 individual studies. Our approach provides a benchmark for reproducible, safe federated analyses across multiple study types provided by multiple stakeholders.</p