Benchmarking of calculation schemes in Apollo2 and COBAYA3 for VVER lattices

This paper presents solutions of the NURISP VVER lattice benchmark using APOLLO2, TRIPOLI4 and COBAYA3 pin-by-pin. The main objective is to validate MOC based calculation schemes for pin-by-pin cross-section generation with APOLLO2 against TRIPOLI4 reference results. A specific objective is to test the APOLLO2 generated cross-sections and interface discontinuity factors in COBAYA3 pin-by-pin calculations with unstructured mesh. The VVER-1000 core consists of large hexagonal assemblies with 2mm inter-assembly water gaps which require the use of unstructured meshes in the pin-by-pin core simulators. The considered 2D benchmark problems include 19-pin clusters, fuel assemblies and 7-assembly clusters. APOLLO2 calculation schemes with the step characteristic method (MOC) and the higher-order Linear Surface MOC have been tested. The comparison of APOLLO2 vs.TRIPOLI4 results shows a very close agreement. The 3D lattice solver in COBAYA3 uses transport corrected multi-group diffusion approximation with interface discontinuity factors of GET or Black Box Homogenization type. The COBAYA3 pin-by-pin results in 2, 4 and 8 energy groups are close to the reference solutions when using side-dependent interface discontinuity factors.

Optimización de una energía mediante cortes de grafos. Segmentación de imágenes

La segmentación de imágenes puede plantearse como un problema de minimización de una energía discreta. Nos enfrentamos así a una doble cuestión: definir una energía cuyo mínimo proporcione la segmentación buscada y, una vez definida la energía, encontrar un mínimo absoluto de la misma. La primera parte de esta tesis aborda el segundo problema, y la segunda parte, en un contexto más aplicado, el primero. Las técnicas de minimización basadas en cortes de grafos permiten obtener el mínimo de una energía discreta en tiempo polinomial mediante algoritmos de tipo min-cut/max-flow. Sin embargo, estas técnicas solo pueden aplicarse a energías que son representabas por grafos. Un importante reto es estudiar qué energías son representabas así como encontrar un grafo que las represente, lo que equivale a encontrar una función gadget con variables adicionales. En la primera parte de este trabajo se estudian propiedades de las funciones gadgets que permiten acotar superiormente el número de variables adicionales. Además se caracterizan las energías con cuatro variables que son representabas, definiendo gadgets con dos variables adicionales. En la segunda parte, más práctica, se aborda el problema de segmentación de imágenes médicas, base en muchas ocasiones para la diagnosis y el seguimiento de terapias. La segmentación multi-atlas es una potente técnica de segmentación automática de imágenes médicas, con tres aspectos importantes a destacar: el tipo de registro entre los atlas y la imagen objetivo, la selección de atlas y el método de fusión de etiquetas. Este último punto puede formularse como un problema de minimización de una energía. A este respecto introducimos dos nuevas energías representables. La primera, de orden dos, se utiliza en la segmentación en hígado y fondo de imágenes abdominales obtenidas mediante tomografía axial computarizada. La segunda, de orden superior, se utiliza en la segmentación en hipocampos y fondo de imágenes cerebrales obtenidas mediante resonancia magnética. ABSTRACT The image segmentation can be described as the problem of minimizing a discrete energy. We face two problems: first, to define an energy whose minimum provides the desired segmentation and, second, once the energy is defined we must find its global minimum. The first part of this thesis addresses the second problem, and the second part, in a more applied context, the first problem. Minimization techniques based on graph cuts find the minimum of a discrete energy in polynomial time via min-cut/max-flow algorithms. Nevertheless, these techniques can only be applied to graph-representable energies. An important challenge is to study which energies are graph-representable and to construct graphs which represent these energies. This is the same as finding a gadget function with additional variables. In the first part there are studied the properties of gadget functions which allow the number of additional variables to be bounded from above. Moreover, the graph-representable energies with four variables are characterised and gadgets with two additional variables are defined for these. The second part addresses the application of these ideas to medical image segmentation. This is often the first step in computer-assisted diagnosis and monitoring therapy. Multiatlas segmentation is a powerful automatic segmentation technique for medical images, with three important aspects that are highlighted here: the registration between the atlas and the target image, the atlas selection, and the label fusion method. We formulate the label fusion method as a minimization problem and we introduce two new graph-representable energies. The first is a second order energy and it is used for the segmentation of the liver in computed tomography (CT) images. The second energy is a higher order energy and it is used for the segmentation of the hippocampus in magnetic resonance images (MRI).

Optical signal impairment study of cascaded optical filters in 40 Gbps DQPSK and 100 Gbps PM-DQPSK systems

Optical filters are crucial elements in optical communications. The influence of cascaded filters in the optical signal will affect the communications quality seriously. In this paper we will study and simulate the optical signal impairment caused by different kinds of filters which include Butterworth, Bessel, Fiber Bragg Grating (FBG) and Fabry-Perot (FP). Optical signal impairment is analyzed from an Eye Opening Penalty (EOP) and optical spectrum point of view. The simulation results show that when the center frequency of all filters aligns with the laser’s frequency, the Butterworth has the smallest influence to the signal while the F-P has the biggest. With a -1dB EOP, the amount of cascaded Butterworth optical filters with a bandwidth of 50 GHz is 18 in 40 Gbps NRZ-DQPSK systems and 12 in 100 Gbps PMNRZ- DQPSK systems. The value is reduced to 9 and 6 respectively for Febry-Perot optical filters. In the situation of frequency misalignment, the impairment caused by filters is more serious. Our research shows that with a frequency deviation of 5 GHz, only 12 and 9 Butterworth optical filters can be cascaded in 40 Gbps NRZ-DQPSK and 100 Gbps PM-NRZ-DQPSK systems respectively. We also study the signal impairment caused by different orders of the Butterworth filter model. Our study shows that although the higher-order has a smaller clipping effect in the transmission spectrum, it will introduce a more serious phase ripple which seriously affects the signal. Simulation result shows that the 2nd order Butterworth filter has the best performance.

Numerical issues in Lagrangian tracking and topological evolution of fluid particles in wallbounded turbulent flows

The determination of the local Lagrangian evolution of the flow topology in wall-bounded turbulence, and of the Lagrangian evolution associated with entrainment across the turbulent / non-turbulent interface into a turbulent boundary layer, require accurate tracking of a fluid particle and its local velocity gradients. This paper addresses the implementation of fluid-particle tracking in both a turbulent boundary layer direct numerical simulation and in a fully developed channel flow simulation. Determination of the sub-grid particle velocity is performed using both cubic B-spline, four-point Hermite spline and higher-order Hermite spline interpolation. Both wall-bounded flows show similar oscillations in the Lagrangian tracers of both velocity and velocity gradients, corresponding to the movement of particles across the boundaries of computational cells. While these oscillation in the particle velocity are relatively small and have negligible effect on the particle trajectories for time-steps of the order of CFL = 0.1, they appear to be the cause of significant oscillations in the evolution of the invariants of the velocity gradient tensor.

A Mea Culpa for The Felix Culpa? A Greater Goods Response to the Problems of Evil and Hell

In this paper I want to develop a particular kind of greater-good response to the problems of evil and hell, one which hence can serve as a backup plan should the free will defense not satisfy. Ultimately, this response will appear to belong to several traditions in theodicy. Like all greater-goods views, this one relies on explaining the existence of evil in terms of the greater goods that come out of it. Among these goods are the greater goods of Incarnation and Atonement, their respective goodness consisting in large part in the higher-order divine good of glorifying God through the display of divine virtue.

Designing conditions for in vitro formation of amyloid protofilaments and fibrils

We have been able to convert a small α/β protein, acylphosphatase, from its soluble and native form into insoluble amyloid fibrils of the type observed in a range of pathological conditions. This was achieved by allowing slow growth in a solution containing moderate concentrations of trifluoroethanol. When analyzed with electron microscopy, the protein aggregate present in the sample after long incubation times consisted of extended, unbranched filaments of 30–50 Å in width that assemble subsequently into higher order structures. This fibrillar material possesses extensive β-sheet structure as revealed by far-UV CD and IR spectroscopy. Furthermore, the fibrils exhibit Congo red birefringence, increased fluorescence with thioflavine T and cause a red-shift of the Congo red absorption spectrum. All of these characteristics are typical of amyloid fibrils. The results indicate that formation of amyloid occurs when the native fold of a protein is destabilized under conditions in which noncovalent interactions, and in particular hydrogen bonding, within the polypeptide chain remain favorable. We suggest that amyloid formation is not restricted to a small number of protein sequences but is a property common to many, if not all, natural polypeptide chains under appropriate conditions.

Rap1 protein regulates telomere turnover in yeast

Telomere length is maintained through a dynamic balance between addition and loss of the terminal telomeric DNA. Normal telomere length regulation requires telomerase as well as a telomeric protein–DNA complex. Previous work has provided evidence that in the budding yeasts Kluyveromyces lactis and Saccharomyces cerevisiae, the telomeric double-stranded DNA binding protein Rap1p negatively regulates telomere length, in part by nucleating, by its C-terminal tail, a higher-order DNA binding protein complex that presumably limits access of telomerase to the chromosome end. Here we show that in K. lactis, truncating the Rap1p C-terminal tail (Rap1p-ΔC mutant) accelerates telomeric repeat turnover in the distal region of the telomere. In addition, combining the rap1-ΔC mutation with a telomerase template mutation (ter1-kpn), which directs the addition of mutated telomeric DNA repeats to telomeres, synergistically caused an immediate loss of telomere length regulation. Capping of the unregulated telomeres of these double mutants with functionally wild-type repeats restored telomere length control. We propose that the rate of terminal telomere turnover is controlled by Rap1p specifically through its interactions with the most distal telomeric repeats.

The Escherichia coli SOS mutagenesis proteins UmuD and UmuD′ interact physically with the replicative DNA polymerase

The Escherichia coli umuDC operon is induced in response to replication-blocking DNA lesions as part of the SOS response. UmuD protein then undergoes an RecA-facilitated self-cleavage reaction that removes its N-terminal 24 residues to yield UmuD′. UmuD′, UmuC, RecA, and some form of the E. coli replicative DNA polymerase, DNA polymerase III holoenzyme, function in translesion synthesis, the potentially mutagenic process of replication over otherwise blocking lesions. Furthermore, it has been proposed that, before cleavage, UmuD together with UmuC acts as a DNA damage checkpoint system that regulates the rate of DNA synthesis in response to DNA damage, thereby allowing time for accurate repair to take place. Here we provide direct evidence that both uncleaved UmuD and UmuD′ interact physically with the catalytic, proofreading, and processivity subunits of the E. coli replicative polymerase. Consistent with our model proposing that uncleaved UmuD and UmuD′ promote different events, UmuD and UmuD′ interact differently with DNA polymerase III: whereas uncleaved UmuD interacts more strongly with β than it does with α, UmuD′ interacts more strongly with α than it does with β. We propose that the protein–protein interactions we have characterized are part of a higher-order regulatory system of replication fork management that controls when the umuDC gene products can gain access to the replication fork.

Measurements of attractive forces between proteins and end-grafted poly(ethylene glycol) chains

The surface force apparatus was used to measure directly the molecular forces between streptavidin and lipid bilayers displaying grafted Mr 2,000 poly(ethylene glycol) (PEG). These measurements provide direct evidence for the formation of relatively strong attractive forces between PEG and protein. At low compressive loads, the forces were repulsive, but they became attractive when the proteins were pressed into the polymer layer at higher loads. The adhesion was sufficiently robust that separation of the streptavidin and PEG uprooted anchored polymer from the supporting membrane. These interactions altered the properties of the grafted chains. After the onset of the attraction, the polymer continued to bind protein for several hours. The changes were not due to protein denaturation. These data demonstrate directly that the biological activity of PEG is not due solely to properties of simple polymers such as the excluded volume. It is also coupled to the competitive interactions between solvent and other materials such as proteins for the chain segments and to the ability of this material to adopt higher order intrachain structures.

Protein folding kinetics exhibit an Arrhenius temperature dependence when corrected for the temperature dependence of protein stability

The anomalous temperature dependence of protein folding has received considerable attention. Here we show that the temperature dependence of the folding of protein L becomes extremely simple when the effects of temperature on protein stability are corrected for; the logarithm of the folding rate is a linear function of 1/T on constant stability contours in the temperature–denaturant plane. This convincingly demonstrates that the anomalous temperature dependence of folding derives from the temperature dependence of the interactions that stabilize proteins, rather than from the super Arrhenius temperature dependence predicted for the configurational diffusion constant on a rough energy landscape. However, because of the limited temperature range accessible to experiment, the results do not rule out models with higher order temperature dependences. The significance of the slope of the stability-corrected Arrhenius plots is discussed.

Blind separation of auditory event-related brain responses into independent components

Averaged event-related potential (ERP) data recorded from the human scalp reveal electroencephalographic (EEG) activity that is reliably time-locked and phase-locked to experimental events. We report here the application of a method based on information theory that decomposes one or more ERPs recorded at multiple scalp sensors into a sum of components with fixed scalp distributions and sparsely activated, maximally independent time courses. Independent component analysis (ICA) decomposes ERP data into a number of components equal to the number of sensors. The derived components have distinct but not necessarily orthogonal scalp projections. Unlike dipole-fitting methods, the algorithm does not model the locations of their generators in the head. Unlike methods that remove second-order correlations, such as principal component analysis (PCA), ICA also minimizes higher-order dependencies. Applied to detected—and undetected—target ERPs from an auditory vigilance experiment, the algorithm derived ten components that decomposed each of the major response peaks into one or more ICA components with relatively simple scalp distributions. Three of these components were active only when the subject detected the targets, three other components only when the target went undetected, and one in both cases. Three additional components accounted for the steady-state brain response to a 39-Hz background click train. Major features of the decomposition proved robust across sessions and changes in sensor number and placement. This method of ERP analysis can be used to compare responses from multiple stimuli, task conditions, and subject states.

Position- and orientation-independent activity of the Schizosaccharomyces pombe meiotic recombination hot spot M26

The activity of the M26 meiotic recombination hot spot of Schizosaccharomyces pombe depends on the presence of the heptamer 5′-ATGACGT-3′. Transplacement of DNA fragments containing the ade6-M26 gene to other chromosomal loci has previously demonstrated that the heptamer functions in some, but not all, transplacements, suggesting that hot spot activity depends on chromosomal context. In this study, hot spot activity was tested in the absence of gross DNA changes by using site-directed mutagenesis to create the heptamer sequence at novel locations in the genome. When created by mutagenesis of 1–4 bp in the ade6 and ura4 genes, the heptamer was active as a recombination hot spot, in an orientation-independent manner, at all locations tested. Thus, the heptamer sequence can create an active hot spot in other chromosomal contexts, provided that the gross chromosomal structure is not altered; this result is consistent with the hypothesis that a specific higher-order chromatin structure is required for M26 hot spot activity.

The active oligomeric state of the minimalistic influenza virus M2 ion channel is a tetramer

The influenza A virus M2 integral membrane protein is an ion channel that permits protons to enter virus particles during uncoating of virions in endosomes and also modulates the pH of the trans-Golgi network in virus-infected cells. The M2 protein is a homo-oligomer of 97 residues, and analysis by chemical cross-linking and SDS/PAGE indicates M2 forms a tetramer. However, a higher order molecular form is sometimes observed and, thus, it is necessary to determine the active form of the molecule. This was done by studying the currents of oocytes that expressed mixtures of the wild-type M2 protein (epitope tagged) and the mutant protein M2-V27S, which is resistant to the inhibitor amantadine. The composition of mixed oligomers of the two proteins expressed at the plasma membrane of individual oocytes was quantified after antibody capture of the cell surface expressed molecules and it was found that the subunits mixed freely. When the ratio of wild-type to mutant protein subunits was 0.85:0.15, the amantadine sensitivity was reduced to 50% and for a ratio of 0.71:0.29 to 20%. These results are consistent with the amantadine-resistant mutant being dominant and the oligomeric state being a tetramer.

A Polymer Model for the Structural Organization of Chromatin Loops and Minibands in Interphase Chromosomes

A quantitative model of interphase chromosome higher-order structure is presented based on the isochore model of the genome and results obtained in the field of copolymer research. G1 chromosomes are approximated in the model as multiblock copolymers of the 30-nm chromatin fiber, which alternately contain two types of 0.5- to 1-Mbp blocks (R and G minibands) differing in GC content and DNA-bound proteins. A G1 chromosome forms a single-chain string of loop clusters (micelles), with each loop ∼1–2 Mbp in size. The number of ∼20 loops per micelle was estimated from the dependence of geometrical versus genomic distances between two points on a G1 chromosome. The greater degree of chromatin extension in R versus G minibands and a difference in the replication time for these minibands (early S phase for R versus late S phase for G) are explained in this model as a result of the location of R minibands at micelle cores and G minibands at loop apices. The estimated number of micelles per nucleus is close to the observed number of replication clusters at the onset of S phase. A relationship between chromosomal and nuclear sizes for several types of higher eukaryotic cells (insects, plants, and mammals) is well described through the micelle structure of interphase chromosomes. For yeast cells, this relationship is described by a linear coil configuration of chromosomes.

A Discrete Stage of Baculovirus GP64-mediated Membrane Fusion

Viral fusion protein trimers can play a critical role in limiting lipids in membrane fusion. Because the trimeric oligomer of many viral fusion proteins is often stabilized by hydrophobic 4-3 heptad repeats, higher-order oligomers might be stabilized by similar sequences. There is a hydrophobic 4-3 heptad repeat contiguous to a putative oligomerization domain of Autographa californica multicapsid nucleopolyhedrovirus envelope glycoprotein GP64. We performed mutagenesis and peptide inhibition studies to determine if this sequence might play a role in catalysis of membrane fusion. First, leucine-to-alanine mutants within and flanking the amino terminus of the hydrophobic 4-3 heptad repeat motif that oligomerize into trimers and traffic to insect Sf9 cell surfaces were identified. These mutants retained their wild-type conformation at neutral pH and changed conformation in acidic conditions, as judged by the reactivity of a conformationally sensitive mAb. These mutants, however, were defective for membrane fusion. Second, a peptide encoding the portion flanking the GP64 hydrophobic 4-3 heptad repeat was synthesized. Adding peptide led to inhibition of membrane fusion, which occurred only when the peptide was present during low pH application. The presence of peptide during low pH application did not prevent low pH–induced conformational changes, as determined by the loss of a conformationally sensitive epitope. In control experiments, a peptide of identical composition but different sequence, or a peptide encoding a portion of the Ebola GP heptad motif, had no effect on GP64-mediated fusion. Furthermore, when the hemagglutinin (X31 strain) fusion protein of influenza was functionally expressed in Sf9 cells, no effect on hemagglutinin-mediated fusion was observed, suggesting that the peptide does not exert nonspecific effects on other fusion proteins or cell membranes. Collectively, these studies suggest that the specific peptide sequences of GP64 that are adjacent to and include portions of the hydrophobic 4-3 heptad repeat play a dynamic role in membrane fusion at a stage that is downstream of the initiation of protein conformational changes but upstream of lipid mixing.