Strain Gradients in Epitaxial Ferroelectrics

X-ray analysis of ferroelectric thin layers of Ba1/2Sr1/2TiO3 with different thickness reveals the presence of internal strain gradients across the film thickness and allows us to propose a functional form for the internal strain profile. We use this to calculate the direct influence of strain gradient, through flexoelectric coupling, on the degradation of the ferroelectric properties of thin films with decreasing thickness, in excellent agreement with the observed behaviour. This work highlights the link between strain relaxation and strain gradients in epitaxial films, and shows the pressing need to avoid strain gradients in order to obtain thin ferroelectrics with bulk-like properties.Comment: 4 pages, 3 embedded figures (1 color), revTex

Dispersive estimates for Schr\"odinger operators with point interactions in R3\mathbb{R}^3

The study of dispersive properties of Schr\"odinger operators with point interactions is a fundamental tool for understanding the behavior of many body quantum systems interacting with very short range potential, whose dynamics can be approximated by non linear Schr\"odinger equations with singular interactions. In this work we proved that, in the case of one point interaction in $\mathbb{R}^3$, the perturbed Laplacian satisfies the same $L^p-L^q$ estimates of the free Laplacian in the smaller regime $q\in[2,3)$. These estimates are implied by a recent result concerning the $L^p$ boundedness of the wave operators for the perturbed Laplacian. Our approach, however, is more direct and relatively simple, and could potentially be useful to prove optimal weighted estimates also in the regime $q\geq 3$.Comment: To appear on: "Advances in Quantum Mechanics: Contemporary Trends and Open Problems", G. Dell'Antonio and A. Michelangeli eds., Springer-INdAM series 201

Self-consistent solution of Kohn-Sham equations for infinitely extended systems with inhomogeneous electron gas

The density functional approach in the Kohn-Sham approximation is widely used to study properties of many-electron systems. Due to the nonlinearity of the Kohn-Sham equations, the general self-consistence searching method involves iterations with alternate solving of the Poisson and Schr\"{o}dinger equations. One of problems of such an approach is that the charge distribution renewed by means of the Schr\"{o}dinger equation solution does not conform to boundary conditions of Poisson equation for Coulomb potential. The resulting instability or even divergence of iterations manifests itself most appreciably in the case of infinitely extended systems. The published attempts to deal with this problem are reduced in fact to abandoning the original iterative method and replacing it with some approximate calculation scheme, which is usually semi-empirical and does not permit to evaluate the extent of deviation from the exact solution. In this work, we realize the iterative scheme of solving the Kohn-Sham equations for extended systems with inhomogeneous electron gas, which is based on eliminating the long-range character of Coulomb interaction as the cause of tight coupling between charge distribution and boundary conditions. The suggested algorithm is employed to calculate energy spectrum, self-consistent potential, and electrostatic capacitance of the semi-infinite degenerate electron gas bounded by infinitely high barrier, as well as the work function and surface energy of simple metals in the jellium model. The difference between self-consistent Hartree solutions and those taking into account the exchange-correlation interaction is analyzed. The case study of the metal-semiconductor tunnel contact shows this method being applied to an infinitely extended system where the steady-state current can flow.Comment: 38 pages, 9 figures, to be published in ZhETF (J. Exp. Theor. Phys.

Development of a Colon Cancer GEMM-Derived Orthotopic Transplant Model for Drug Discovery and Validation

Purpose: Effective therapies for KRAS-mutant colorectal cancer (CRC) are a critical unmet clinical need. Previously, we described genetically engineered mouse models (GEMM) for sporadic Kras-mutant and non-mutant CRC suitable for preclinical evaluation of experimental therapeutics. To accelerate drug discovery and validation, we sought to derive low-passage cell lines from GEMM Kras-mutant and wild-type tumors for in vitro screening and transplantation into the native colonic environment of immunocompetent mice for in vivo validation. Experimental Design: Cell lines were derived from Kras-mutant and non-mutant GEMM tumors under defined media conditions. Growth kinetics, phosphoproteomes, transcriptomes, drug sensitivity, and metabolism were examined. Cell lines were implanted in mice and monitored for in vivo tumor analysis. Results: Kras-mutant cell lines displayed increased proliferation, mitogen-activated protein kinase signaling, and phosphoinositide-3 kinase signaling. Microarray analysis identified significant overlap with human CRC-related gene signatures, including KRAS-mutant and metastatic CRC. Further analyses revealed enrichment for numerous disease-relevant biologic pathways, including glucose metabolism. Functional assessment in vitro and in vivo validated this finding and highlighted the dependence of Kras-mutant CRC on oncogenic signaling and on aerobic glycolysis. Conclusions: We have successfully characterized a novel GEMM-derived orthotopic transplant model of human KRAS-mutant CRC. This approach combines in vitro screening capability using low-passage cell lines that recapitulate human CRC and potential for rapid in vivo validation using cell line-derived tumors that develop in the colonic microenvironment of immunocompetent animals. Taken together, this platform is a clear advancement in preclinical CRC models for comprehensive drug discovery and validation efforts

Smyd3 regulates cancer cell phenotypes and catalyzes histone H4 lysine 5 methylation

Smyd3 is a lysine methyltransferase implicated in chromatin and cancer regulation. Here we show that Smyd3 catalyzes histone H4 methylation at lysine 5 (H4K5me). This novel histone methylation mark is detected in diverse cell types and its formation is attenuated by depletion of Smyd3 protein. Further, Smyd3-driven cancer cell phenotypes require its enzymatic activity. Thus, Smyd3, via H4K5 methylation, provides a potential new link between chromatin dynamics and neoplastic disease

Depth resolved lattice-charge coupling in epitaxial BiFeO3 thin film

For epitaxial films, a critical thickness (t(c)) can create a phenomenological interface between a strained bottom layer and a relaxed top layer. Here, we present an experimental report of how the t(c) in BiFeO3 thin films acts as a boundary to determine the crystalline phase, ferroelectricity, and piezoelectricity in 60 nm thick BiFeO3/SrRuO3/SrTiO3 substrate. We found larger Fe cation displacement of the relaxed layer than that of strained layer. In the time-resolved X-ray microdiffraction analyses, the piezoelectric response of the BiFeO3 film was resolved into a strained layer with an extremely low piezoelectric coefficient of 2.4 pm/V and a relaxed layer with a piezoelectric coefficient of 32 pm/V. The difference in the Fe displacements between the strained and relaxed layers is in good agreement with the differences in the piezoelectric coefficient due to the electromechanical couplingope

Risk factors of post renal transplant anaemia among Sudanese patients, a study in three renal transplant centres

<p>Abstract</p> <p>Background</p> <p>There is a relative lack of recent information about late post kidney transplantation anaemia (PTA), especially in the developing countries; data are scarce about the prevalence and risk factors of PTA. Sudan was a leading country in Africa and Arab world in kidney transplantation. The first kidney transplantation in Sudan was in 1973.</p> <p>Methods</p> <p>This is a cross-sectional hospital analytic study enrolling all kidney transplanted recipients following in the transplant referral clinics at Ahmed Gassim, Selma and Ibn Sina Hospitals, Khartoum/Sudan, in the period from 1/8/2010 to 1/9/2010, clinical and laboratory data were obtained from 114 patients, anaemia was defined as Hb levels of < 13 g/dl for male patients and < 12 g/dl for female patients, exclusion criteria were pregnancy, below 18 years old patients, multiple organ transplantation, and patients with less than one year from the transplantation.</p> <p>Results</p> <p>The study showed that 39.5% of the patients were anaemic. Univariate analysis showed that late PTA is significantly associated with not using Erythropoietin (EPO) in the pre-transplant period (p = < 0.001), history of rejection (p = 0.003), longer time from transplantation (p = 0.015), and eGFR (p < 0.0001). Multivariate analysis showed that eGFR (p = < 0.001) and not use of EPO in the pre transplant period (p < 0.001) are strong predictors of PTA. The use of Angiotensin converting enzyme inhibitors/Angiotensin receptors blockers (ACEI/ARB), immunosuppressive treatments, presence or absence of co-morbidities, donor type and donor age are not significantly associated with late PTA.</p> <p>Conclusion</p> <p>The study concluded that late PTA is common and under recognized. Risk factors for late PTA include renal dysfunction, history of rejection, longer duration of transplantation and not using EPO in the pre-transplant period. Renal dysfunction and not using EPO in the pre-transplant period are major predictors of late PTA.</p

A Novel Neural Substrate for the Transformation of Olfactory Inputs into Motor Output

Anatomical and physiological experiments in the lamprey reveal the neural circuit involved in transforming olfactory inputs into motor outputs, which was previously unknown in a vertebrate

Genome-wide Association Study of Borderline Personality Disorder Reveals Genetic Overlap with Bipolar Disorder, Major Depression and Schizophrenia

Borderline personality disorder (BOR) is determined by environmental and genetic factors, and characterized by affective instability and impulsivity, diagnostic symptoms also observed in manic phases of bipolar disorder (BIP). Up to 20% of BIP patients show comorbidity with BOR. This report describes the first case–control genome-wide association study (GWAS) of BOR, performed in one of the largest BOR patient samples worldwide. The focus of our analysis was (i) to detect genes and gene sets involved in BOR and (ii) to investigate the genetic overlap with BIP. As there is considerable genetic overlap between BIP, major depression (MDD) and schizophrenia (SCZ) and a high comorbidity of BOR and MDD, we also analyzed the genetic overlap of BOR with SCZ and MDD. GWAS, gene-based tests and gene-set analyses were performed in 998 BOR patients and 1545 controls. Linkage disequilibrium score regression was used to detect the genetic overlap between BOR and these disorders. Single marker analysis revealed no significant association after correction for multiple testing. Gene-based analysis yielded two significant genes: DPYD (P=4.42 × 10−7) and PKP4 (P=8.67 × 10−7); and gene-set analysis yielded a significant finding for exocytosis (GO:0006887, PFDR=0.019; FDR, false discovery rate). Prior studies have implicated DPYD, PKP4 and exocytosis in BIP and SCZ. The most notable finding of the present study was the genetic overlap of BOR with BIP (rg=0.28 [P=2.99 × 10−3]), SCZ (rg=0.34 [P=4.37 × 10−5]) and MDD (rg=0.57 [P=1.04 × 10−3]). We believe our study is the first to demonstrate that BOR overlaps with BIP, MDD and SCZ on the genetic level. Whether this is confined to transdiagnostic clinical symptoms should be examined in future studies

Collaborative meta-analysis finds no evidence of a strong interaction between stress and 5-HTTLPR genotype contributing to the development of depression

The hypothesis that the S allele of the 5-HTTLPR serotonin transporter promoter region is associated with increased risk of depression, but only in individuals exposed to stressful situations, has generated much interest, research, and controversy since first proposed in 2003. Multiple meta-analyses combining results from heterogeneous analyses have not settled the issue. To determine the magnitude of the interaction and the conditions under which it might be observed, we performed new analyses on 31 datasets containing 38 802 European-ancestry subjects genotyped for 5-HTTLPR and assessed for depression and childhood maltreatment or other stressful life events, and meta-analyzed the results. Analyses targeted two stressors (narrow, broad) and two depression outcomes (current, lifetime). All groups that published on this topic prior to the initiation of our study and met the assessment and sample size criteria were invited to participate. Additional groups, identified by consortium members or self-identified in response to our protocol (published prior to the start of analysis1) with qualifying unpublished data were also invited to participate. A uniform data analysis script implementing the protocol was executed by each of the consortium members. Our findings do not support the interaction hypothesis. We found no subgroups or variable definitions for which an interaction between stress and 5-HTTLPR genotype was statistically significant. In contrast, our findings for the main effects of life stressors (strong risk factor) and 5-HTTLPR genotype (no impact on risk) are strikingly consistent across our contributing studies, the original study reporting the interaction, and subsequent meta-analyses. Our conclusion is that if an interaction exists in which the S allele of 5-HTTLPR increases risk of depression only in stressed individuals, then it is not broadly generalizable, but must be of modest effect size and only observable in limited situations