Monte Carlo Algorithm for Mobility Calculations in Thin Body Field Effect Transistors: Role of Degeneracy and Intersubband Scattering

Abstract. We generalize the Monte Carlo algorithm originally designed for small signal analysis of the three-dimensional electron gas to quasitwo-dimensional electron systems. The method allows inclusion of arbitrary scattering mechanisms and general band structure. Contrary to standard Monte Carlo methods to simulate transport, this algorithm takes naturally into account the fermionic nature of electrons via the Pauli exclusion principle. The method is based on the solution of the linearized Boltzmann equation and is exact in the limit of negligible driving fields. The theoretically derived Monte Carlo algorithm has a clear physical interpretation. The diffusion tensor is calculated as an integral of the velocity autocorrelation function. The mobility tensor is related to the diffusion tensor via the Einstein relation for degenerate statistics. We demonstrate the importance of degeneracy effects by evaluating the low-field mobility in contemporary field-effect transistors with a thin silicon body. We show that degeneracy effects are essential for the correct interpretation of experimental mobility data for field effect transistors in single-and double-gate operation mode. In double-gate structures with (100) crystal orientation of the silicon film degeneracy effects lead to an increased occupation of the higher subbands. This opens an additional channel for elastic scattering. Increased intersubband scattering compensates the volume inversion induced effect on the mobility enhancement and leads to an overall decrease in the mobility per channel in doublegate structures

A Numerical Study of Coulomb Interaction Effects on 2D Hopping Transport

We have extended our supercomputer-enabled Monte Carlo simulations of hopping transport in completely disordered 2D conductors to the case of substantial electron-electron Coulomb interaction. Such interaction may not only suppress the average value of hopping current, but also affect its fluctuations rather substantially. In particular, the spectral density $S_I (f)$ of current fluctuations exhibits, at sufficiently low frequencies, a $1/f$-like increase which approximately follows the Hooge scaling, even at vanishing temperature. At higher $f$, there is a crossover to a broad range of frequencies in which $S_I (f)$ is nearly constant, hence allowing characterization of the current noise by the effective Fano factor F\equiv S_I(f)/2e \left. For sufficiently large conductor samples and low temperatures, the Fano factor is suppressed below the Schottky value (F=1), scaling with the length $L$ of the conductor as $F = (L_c / L)^{\alpha}$. The exponent $\alpha$ is significantly affected by the Coulomb interaction effects, changing from $\alpha = 0.76 \pm 0.08$ when such effects are negligible to virtually unity when they are substantial. The scaling parameter $L_c$, interpreted as the average percolation cluster length along the electric field direction, scales as $L_c \propto E^{-(0.98 \pm 0.08)}$ when Coulomb interaction effects are negligible and $L_c \propto E^{-(1.26 \pm 0.15)}$ when such effects are substantial, in good agreement with estimates based on the theory of directed percolation.Comment: 19 pages, 7 figures. Fixed minor typos and updated reference

Failure of Fibrotic Liver Regeneration in Mice Is Linked to a Severe Fibrogenic Response Driven by Hepatic Progenitor Cell Activation

Failure of fibrotic liver to regenerate after resection limits therapeutic options and increases demand for liver transplantation, representing a significant clinical problem. The mechanism underlying regenerative failure in fibrosis is poorly understood. Seventy percent partial hepatectomy (PHx) was performed in C57Bl/6 mice with or without carbon tetrachloride (CCl4)-induced liver fibrosis. Liver function and regeneration was monitored at 1 to 14 days thereafter by assessing liver mass, alanine aminotransferase (ALT), mRNA expression, and histology. Progenitor (oval) cell mitogen tumor necrosis factor-like weak inducer of apoptosis (TWEAK) and TWEAK-neutralizing antibody were used to manipulate progenitor cell proliferation in vivo. In fibrotic liver, hepatocytes failed to replicate efficiently after PHx. Fibrotic livers showed late (day 5) peak of serum ALT (3542 ± 355 IU/L compared to 93 ± 65 IU/L in nonfibrotic livers), which coincided with progenitor cell expansion, increase in profibrogenic gene expression and de novo collagen deposition. In fibrotic mice, inhibition of progenitor activation using TWEAK-neutralizing antibody after PHx resulted in strongly down-regulated profibrogenic mRNA, reduced serum ALT levels and improved regeneration. Failure of hepatocyte-mediated regeneration in fibrotic liver triggers activation of the progenitor (oval) cell compartment and a severe fibrogenic response. Inhibition of progenitor cell proliferation using anti-TWEAK antibody prevents fibrogenic response and augments fibrotic liver regeneration. Targeting the fibrogenic progenitor response represents a promising strategy to improve hepatectomy outcomes in patients with liver fibrosis

BRCA1 and BRCA2 mutations in a population-based study of male breast cancer

Background: The contribution of BRCA1 and BRCA2 to the incidence of male breast cancer (MBC) in the United Kingdom is not known, and the importance of these genes in the increased risk of female breast cancer associated with a family history of breast cancer in a male first-degree relative is unclear. Methods: We have carried out a population-based study of 94 MBC cases collected in the UK. We screened genomic DNA for mutations in BRCA1 and BRCA2 and used family history data from these cases to calculate the risk of breast cancer to female relatives of MBC cases. We also estimated the contribution of BRCA1 and BRCA2 to this risk. Results: Nineteen cases (20%) reported a first-degree relative with breast cancer, of whom seven also had an affected second-degree relative. The breast cancer risk in female first-degree relatives was 2.4 times (95% confidence interval [CI] = 1.4–4.0) the risk in the general population. No BRCA1 mutation carriers were identified and five cases were found to carry a mutation in BRCA2. Allowing for a mutation detection sensitivity frequency of 70%, the carrier frequency for BRCA2 mutations was 8% (95% CI = 3–19). All the mutation carriers had a family history of breast, ovarian, prostate or pancreatic cancer. However, BRCA2 accounted for only 15% of the excess familial risk of breast cancer in female first-degree relatives. Conclusion: These data suggest that other genes that confer an increased risk for both female and male breast cancer have yet to be found

Spacelike distance from discrete causal order

Any discrete approach to quantum gravity must provide some prescription as to how to deduce continuum properties from the discrete substructure. In the causal set approach it is straightforward to deduce timelike distances, but surprisingly difficult to extract spacelike distances, because of the unique combination of discreteness with local Lorentz invariance in that approach. We propose a number of methods to overcome this difficulty, one of which reproduces the spatial distance between two points in a finite region of Minkowski space. We provide numerical evidence that this definition can be used to define a `spatial nearest neighbor' relation on a causal set, and conjecture that this can be exploited to define the length of `continuous curves' in causal sets which are approximated by curved spacetime. This provides evidence in support of the ``Hauptvermutung'' of causal sets.Comment: 32 pages, 16 figures, revtex4; journal versio

Sm/Lsm Genes Provide a Glimpse into the Early Evolution of the Spliceosome

The spliceosome, a sophisticated molecular machine involved in the removal of intervening sequences from the coding sections of eukaryotic genes, appeared and subsequently evolved rapidly during the early stages of eukaryotic evolution. The last eukaryotic common ancestor (LECA) had both complex spliceosomal machinery and some spliceosomal introns, yet little is known about the early stages of evolution of the spliceosomal apparatus. The Sm/Lsm family of proteins has been suggested as one of the earliest components of the emerging spliceosome and hence provides a first in-depth glimpse into the evolving spliceosomal apparatus. An analysis of 335 Sm and Sm-like genes from 80 species across all three kingdoms of life reveals two significant observations. First, the eukaryotic Sm/Lsm family underwent two rapid waves of duplication with subsequent divergence resulting in 14 distinct genes. Each wave resulted in a more sophisticated spliceosome, reflecting a possible jump in the complexity of the evolving eukaryotic cell. Second, an unusually high degree of conservation in intron positions is observed within individual orthologous Sm/Lsm genes and between some of the Sm/Lsm paralogs. This suggests that functional spliceosomal introns existed before the emergence of the complete Sm/Lsm family of proteins; hence, spliceosomal machinery with considerably fewer components than today's spliceosome was already functional

Fibulin-3 is necessary to prevent cardiac rupture following myocardial infarction

Despite the high prevalence of heart failure in the western world, there are few effective treatments. Fibulin-3 is a protein involved in extracellular matrix (ECM) structural integrity, however its role in the heart is unknown. We have demonstrated, using single cell RNA-seq, that fibulin-3 was highly expressed in quiescent murine cardiac fibroblasts, with expression highest prior to injury and late post-infarct (from ~ day-28 to week-8). In humans, fibulin-3 was upregulated in left ventricular tissue and plasma of heart failure patients. Fibulin-3 knockout (Efemp1−/−) and wildtype mice were subjected to experimental myocardial infarction. Fibulin-3 deletion resulted in significantly higher rate of cardiac rupture days 3–6 post-infarct, indicating a weak and poorly formed scar, with severe ventricular remodelling in surviving mice at day-28 post-infarct. Fibulin-3 knockout mice demonstrated less collagen deposition at day-3 post-infarct, with abnormal collagen fibre-alignment. RNA-seq on day-3 infarct tissue revealed upregulation of ECM degradation and inflammatory genes, but downregulation of ECM assembly/structure/organisation genes in fibulin-3 knockout mice. GSEA pathway analysis showed enrichment of inflammatory pathways and a depletion of ECM organisation pathways. Fibulin-3 originates from cardiac fibroblasts, is upregulated in human heart failure, and is necessary for correct ECM organisation/structural integrity of fibrotic tissue to prevent cardiac rupture post-infarct