Lattice Monte Carlo simulations as link between ab-initio calculations and macroscopic behavior of dopants and defects in silicon

In this work, we show that lattice Monte Carlo simulations can be used to span the time and distance scales between underlying atomistic processes and macroscopic diffusion behavior. We use ab- initio calculations of binding energies versus configuration to calculate hopping rates of vacancies for use in lattice Monte Carlo (LMC) simulations of diffusion and aggregation in silicon. The LMC simulations consider the biased nature of vacancy hop frequencies in the neighborhood of dopants, with interactions up to sixth-nearest- neighbor distances included. We use these simulations to investigate the expected macroscopic diffusion behavior, as well as the process by which dopant/defect aggregation occurs. Specific phenomena investigated include collective behavior leading to greatly enhanced diffusivity at high doping levels, the time dependence of effective diffusivity due to the formation of dopant/vacancy clusters, and dopant fluxes in the presence of a vacancy gradient.     

Cardiac Toxicity Associated with Immune Checkpoint Inhibitors: A Systematic Review

Immune checkpoint inhibitors (ICIs) are an important advancement in the field of cancer treatment, significantly improving the survival of patients with a series of advanced malignancies, like melanoma, non-small cell lung cancer (NSCLC), hepatocellular carcinoma (HCC), renal cell carcinoma (RCC), and Hodgkin lymphoma. ICIs act upon T lymphocytes and antigen-presenting cells, targeting programmed cell death protein 1 (PD1), programmed cell death protein ligand 1 (PD-L1), and cytotoxic T-lymphocyte antigen 4 (CTLA-4), breaking the immune tolerance of the T cells against malignant cells and enhancing the body’s own immune response. A variety of cardiac-adverse effects are associated with ICI-based treatment, including pericarditis, arrhythmias, cardiomyopathy, and acute coronary syndrome, with myocarditis being the most studied due to its often-unexpected onset and severity. Overall, Myocarditis is rare but presents an immune-related adverse event (irAE) that has a high fatality rate. Considering the rising number of oncological patients treated with ICIs and the severity of their potential adverse effects, a good understanding and continuous investigation of cardiac irAEs is of the utmost importance. This systematic review aimed to revise recent publications (between 2016–2022) on ICI-induced cardiac toxicities and highlight the therapeutical approach and evolution in the selected cases.     

Neutron poison distribution in the central reflector to reduce the DLOFC temperature of a Th-LEU fueled OTTO PBMR DPP-400 core

In a previous study using a mixture of thorium and 20 a/o% LEU at 16 gram per fuel sphere heavy metal loading and adjusting the effective fuel enrichment to produce the same amount of cumulative energy per fuel sphere as with the 10 a/o% Low Enriched Uranium (LEU), the maximum Depressurized Loss Of Forced Cooling (DLOFC) temperature was reduced from 2273 to 1925 °C and 1811 °C for a symmetric and asymmetric core, respectively using an once-through-then-out (OTTO) fuelling scheme. This article presents an additional strategy for reducing the maximum DLOFC temperature by placing an optimized distribution of neutron poisons in the central reflector. This strategy produced maximum DLOFC temperatures of 1509 and 1448 °C for the symmetric and the asymmetric cores, respectively. These results are impressive as it means that the less complicated OTTO cycle with its lower capital cost achieved the same cumulative energy produced per fuel sphere than the standard six-pass refuelling scheme and that at substantially lower maximum DLOFC temperatures. Both the addition of the neutron poisons to the central reflector and the creation of a radially asymmetric core resulted in lower burn-ups that had to be reversed by increasing the enrichment of the fuel.     

Adaptive Stochastic Gradient Descent Optimisation for Image Registration

We present a stochastic gradient descent optimisation method for image registration with adaptive step size prediction. The method is based on the theoretical work by Plakhov and Cruz (J. Math. Sci. 120(1):964–973, 2004). Our main methodological contribution is the derivation of an image-driven mechanism to select proper values for the most important free parameters of the method. The selection mechanism employs general characteristics of the cost functions that commonly occur in intensity-based image registration. Also, the theoretical convergence conditions of the optimisation method are taken into account. The proposed adaptive stochastic gradient descent (ASGD) method is compared to a standard, non-adaptive Robbins-Monro (RM) algorithm. Both ASGD and RM employ a stochastic subsampling technique to accelerate the optimisation process. Registration experiments were performed on 3D CT and MR data of the head, lungs, and prostate, using various similarity measures and transformation models. The results indicate that ASGD is robust to these variations in the registration framework and is less sensitive to the settings of the user-defined parameters than RM. The main disadvantage of RM is the need for a predetermined step size function. The ASGD method provides a solution for that issue.     

Recovering the initial state of an infinite-dimensional system using observers

Let A be the generator of a strongly continuous semigroup T on the Hilbert space X, and let C be a linear operator from D(A) to another Hilbert space Y (possibly unbounded with respect to X, not necessarily admissible). We consider the problem of estimating the initial state z₀∈D(A) (with respect to the norm of X) from the output function y(t)=CT_tz₀, given for all t in a bounded interval [0,τ]. We introduce the concepts of estimatability and backward estimatability for (A,C) (in a more general way than currently available in the literature), we introduce forward and backward observers, and we provide an iterative algorithm for estimating z₀ from y. This algorithm generalizes various algorithms proposed recently for specific classes of systems and it is an attractive alternative to methods based on inverting the Gramian. Our results lead also to a very general formulation of Russell’s principle, i.e., estimatability and backward estimatability imply exact observability. This general formulation of the principle does not require T to be invertible. We illustrate our estimation algorithms on systems described by wave and Schrödinger equations, and we provide results from numerical simulations.     

The micromilling process for high aspect ratio microstructures

High aspect ratio microstructures are currently created by several processes which include lithography (X-ray, deep ultraviolet, etc.) and mechanical machining (diamond machining, microdrilling, etc.) The lithographic processes require more extensive processing equipment such as an energy source, mask/mask holder/mask aligner, photoresist and substrate, and chemical development capacity. In addition, these processes are serial in nature and each adds to the tolerances of the finished structure. The current mechanical processes provide for the direct removal of the substrate material in a single step but are more limited in the geometric patterns which can be created. In conventional machining, the process which provides the most versatility in geometric patterns is milling. The micromilling process has two basic components. The first is the fabrication of small milling cutters with very sharp cutting edges. The second is the actual removal of the workpiece material with a very precise and repeatable machine tool. Several basic cutter designs have been fabricated using focused ion beam micromachining and are undergoing testing. The cutter diameters are nominally 100 micrometers and 22 micrometers. Results have been obtained which show that this process can be very effective for the rapid fabrication of molds and mask structures.     

Laminar compressible flow between close rotating disks: An asymptotic and numerical study

Laminar steady compressible flow between close rotating thermally conducting axisymmetric disks with inflow was investigated by means of a numerical solution of the Navier-Stokes equation and an asymptotic analysis. The approximate solution, obtained for small ?, E and H (Rossby and Ekman numbers, and height/radius, respectively) is valid for “merged”, “close” and “separate” boundary layers on the disks, corresponding to β? 1, $\text{β ? 1}$ and β? 1, respectively (where $\text{β =}\text{H}\text{2}\text{√}\text{E}\text{ρ}$, and ρ is the non-dimensional density). These three cases may appear simultaneously in different regions of the same system due to the large variation of ρ in the radial direction. The small ? (i.e. negligible convection terms) does not necessarily imply small perturbations of the pressure, and a special treatment of the pressure term was used in order to account for this feature, which sometimes culminates in inversion of the radial pressure gradient. Thenumerical solution was obtained by a finite-difference, modified Cheng-Allen method, using a non-uniform mesh. The numerical and the approximate solution are in good agreement.     

Determination of three-dimensional structures of proteins by simulated annealing with interproton distance restraints. Application to crambin, potato carboxypeptidase inhibitor and barley serine proteinase inhibitor 2

An automated method, based on the principle of simulated annealing,is presented for determining the three-dimensional structuresof proteins on the basis of short (<5 Å) interprotondistance data derived from nuclear Overhauser enhancement (NOE)measurements. The method makes use of Newton's equations ofmotion to increase temporarily the temperature of the systemin order to search for the global minimum region of a targetfunction comprising purely geometric restraints. These consistof interproton distances supplemented by bond lengths, bondangles, planes and soft van der Waals repulsion terms. The latterreplace the dihedral, van der Waals, electrostatic and hydrogen-bondingpotentials of the empirical energy function used in moleculardynamics simulations. The method presented involves the implementationof a number of innovations over our previous restrained moleculardynamics approach [Clore,G.M., Brünger,A.T., Karplus,M.and Gronenborn,A.M. (1986) J. Mol. Biol., 191, 523–551].These include the development of a new effective potential forthe interproton distance restraints whose functional form isdependent on the magnitude of the difference between calculatedand target values, and the design and implementation of robustand fully automatic protocol. The method is tested on threesystems: the model system crambin (46 residues) using X-raystructure derived interproton distance restraints, and potatocarboxypeptidase inhibitor (CPI; 39 residues) and barley serineproteinase inhibitor 2 (BSPI-2; 64 residues) using experimentallyderived interproton distance restraints. Calculations were carriedout starting from the extended strands which had atomic r.m.s.differences of 57, 38 and 33 Å with respect to the crystalstructures of BSPI-2, crambin and CPI respectively. Unbiasedsampling of the conformational space consistent with the restraintswas achieved by varying the random number seed used to assignthe initial velocities. This ensures that the different trajectoriesdiverge during the early stages of the simulations and onlyconverge later as more and more interproton distance restraintsare satisfied. The average backbone atomic r.m.s. differencebetween the converged structures is 2.2 ± 0.3 Åfor crambin (nine structures), 2.4 ± 0.3 Å forCPI (eight structures) and 2.5 ± 0.2 Å for BSPI-2(five structures). The backbone atomic r.m.s. difference betweenthe mean structures derived by averaging the coordinates ofthe converged structures and the corresponding X-ray structuresis 1.2 Å for crambin, 1.6 Å for CPI and 1.7 Åfor BSPI-2.     

Modification of (CH)x chains during thermal cis-trans isomerization

It is shown that the isomerization of cis polyacetylene at 195°C for long periods is accompanied by structural modifications. Infra-red and pyrolysis gas-chromatography data suggest that the aromatization process occurs even at this temperature.