Dopant Distribution in Atomic Layer Deposited ZnO:Al Films Visualized by Transmission Electron Microscopy and Atom Probe Tomography.

The maximum conductivity achievable in Al-doped ZnO thin films prepared by atomic layer deposition (ALD) is limited by the low doping efficiency of Al. To better understand the limiting factors for the doping efficiency, the three-dimensional distribution of Al atoms in the ZnO host material matrix has been examined on the atomic scale using a combination of high-resolution transmission electron microscopy (TEM) and atom probe tomography (APT). Although the Al distribution in ZnO films prepared by so-called "ALD supercycles" is often presented as atomically flat δ-doped layers, in reality a broadening of the Al-dopant layers is observed with a full-width-half-maximum of ∼2 nm. In addition, an enrichment of the Al at grain boundaries is observed. The low doping efficiency for local Al densities > ∼1 nm-3 can be ascribed to the Al solubility limit in ZnO and to the suppression of the ionization of Al dopants from adjacent Al donors.

Encapsulation method for atom probe tomography analysis of nanoparticles.

Open-space nanomaterials are a widespread class of technologically important materials that are generally incompatible with analysis by atom probe tomography (APT) due to issues with specimen preparation, field evaporation and data reconstruction. The feasibility of encapsulating such non-compact matter in a matrix to enable APT measurements is investigated using nanoparticles as an example. Simulations of field evaporation of a void, and the resulting artifacts in ion trajectory, underpin the requirement that no voids remain after encapsulation. The approach is demonstrated by encapsulating Pt nanoparticles in an ZnO:Al matrix created by atomic layer deposition, a growth technique which offers very high surface coverage and conformality. APT measurements of the Pt nanoparticles are correlated with transmission electron microscopy images and numerical simulations in order to evaluate the accuracy of the APT reconstruction.

Aplicación de un sistema in silico múltiple para la priorización en la selección de compuestos antimaláricos / Multiple in silico genetic toxicity alerting tools for antimalarial compounds prioritization

Introducción: Como parte del compromiso de GSK en la reducción del fracaso en las fases de desarrollo clínico y preclínico, se ha implementado en las fases más tempranas de desarrollo una estrategia para evitar los problemas de genotoxicidad que son los que, en mayor manera, pueden obstaculizar la progresión a fases más avanzadas. El objetivo de este trabajo es aplicar la nueva estrategia de GSK para la priorización de compuestos que permita seleccionar aquellas estructuras con menor riesgo de genotoxicidad utilizando una combinación de herramientas computacionales que predice el resultado del test de Ames. Materiales y Métodos: Compuestos de la colección de GSK, activos en el screening fenotípico frente a P. falciparum, fueron utilizados en este estudio. Tres modelos, Derek Nexus (Lhasa Limited, Leeds, UK), Leadscope y un método de mecánica cuántica desarrollado internamente se utilizaron para las predicciones in silico. Resultados: la combinación de los tres modelos de predicción tuvo un porcentaje de éxito del 75% con sólo 1 falso positivo. Conclusiones: Moléculas con 2 o más alertas de genotoxicidad generadas por este sistema múltiple deberían ser despriorizadas o ensayadas experimentalmente cuanto antes para descartar su riesgo de genotoxicidad (AU)

Introduction: As part of the commitment of GSK in reducing attrition rate in clinical and preclinical stages, it has been set up in early stages of development (H2L, Lead Op) a candidate quality strategy to avoid genotoxicity liabilities that mainly can stop the progression of compound towards advanced stages. The aim of the study is to apply the new strategy in order to triage structures with less genotoxicity risk by means an in silico multiple system that predicts the outcome of Ames test. Material & Methods: Active compounds against P. falciparum phenotypic screening from GSK collection were used. Three different models: Derek Nexus (Lhasa Limited, Leeds, UK), Leadscope and a quantum mechanics method developed internally were used for in silico predictions. Results: The use of three models have an accurately success rate, greater than 75% with only 1 false positives. Conclusions: Those molecules that fire 2 or more genotoxicity alerts should be deprioritised or tested experimentally in Ames test to confirm or discharge the genotoxicity risk (AU)

Effect of butylated hydroxytoluene, curcumin, propyl gallate and thiabendazole on cytochrome P450 forms in cultured human hepatocytes.

1. The objective of this study was to investigate the effects of four food chemicals, namely butylated hydroxytoluene (BHT), curcumin (CC), propyl gallate (PG) and thiabendazole (TB), on cytochrome P450 (CYP) forms in cultured human hepatocytes. 2. Treatment of human hepatocytes for 72 h with 2-200 microM TB produced concentration-dependent increases in CYP1A2, CYP2B6 and CYP3A4 mRNA levels, whereas treatment with BHT increased CYP2B6 and CYP3A4 mRNA levels. CYP1A2, CYP2B6 and CYP3A4 mRNA levels were induced around 48-, 21- and 9-fold, respectively, by 200 microM TB, with CYP2B6 and CYP 3A4 mRNA levels being induced around 12- and 7-fold, respectively, by 200 microM BHT. 3. In contrast, the treatment of human hepatocytes for 72 h with PG and CC had little or no effect on CYP mRNA levels. 4. The treatment of human hepatocytes with TB also induced CYP1A-dependent 7-ethoxyresorufin O-deethylase activity, whereas BHT induced CYP3A-dependent testosterone 6beta-hydroxylase activity. 5. In summary, the results demonstrate that TB is a mixed inducer of CYP forms in human hepatocytes inducing CYP1A, CYP2B and CYP3A forms, whereas BHT is an inducer of CYP2B and CYP3A forms.

Coulomb blockade anisotropic magnetoresistance effect in a (Ga,Mn)As single-electron transistor.

We observe low-field hysteretic magnetoresistance in a (Ga,Mn)As single-electron transistor which can exceed 3 orders of magnitude. The sign and size of the magnetoresistance signal are controlled by the gate voltage. Experimental data are interpreted in terms of electrochemical shifts associated with magnetization rotations. This Coulomb blockade anisotropic magnetoresistance is distinct from previously observed anisotropic magnetoresistance effects as it occurs when the anisotropy in a band structure derived parameter is comparable to an independent scale, the single-electron charging energy. Effective kinetic-exchange model calculations in (Ga,Mn)As show chemical potential anisotropies consistent with experiment and ab initio calculations in transition metal systems suggest that this generic effect persists to high temperatures in metal ferromagnets with strong spin-orbit coupling.

Identification of systems failures in successful paediatric cardiac surgery.

Patient safety will benefit from an approach to human error that examines systemic causes, rather than blames individuals. This study describes a direct observation methodology, based on a threat and error model, prospectively to identify types and sources of systems failures in paediatric cardiac surgery. Of substantive interest were the range, frequency and types of failures that could be identified and whether minor failures could accumulate to form more serious events, as has been the case in other industries. Check lists, notes and video recordings were employed to observe 24 successful operations. A total of 366 failures were recorded. Coordination and communication problems, equipment problems, a relaxed safety culture, patient-related problems and perfusion-related problems were most frequent, with a smaller number of skill, knowledge and decision-making failures. Longer and more risky operations were likely to generate a greater number of minor failures than shorter and lower risk operations, and in seven higher-risk cases frequently occurring minor failures accumulated to threaten the safety of the patient. Non-technical errors were more prevalent than technical errors and task threats were the most prevalent systemic source of error. Adverse events in surgery are likely to be associated with a number of recurring and prospectively identifiable errors. These may be co-incident and cumulative human errors predisposed by threats embedded in the system, rather than due to individual incompetence or negligence. Prospectively identifying and reducing these recurrent failures would lead to improved surgical standards and enhanced patient safety.

Large tunneling anisotropic magnetoresistance in (Ga,Mn)As nanoconstrictions.

We report a large tunneling anisotropic magnetoresistance (TAMR) in (Ga,Mn)As lateral nanoconstrictions. Unlike previously reported tunneling magnetoresistance effects in nanocontacts, the TAMR does not require noncollinear magnetization on either side of the constriction. The nature of the effect is established by a direct comparison of its phenomenology with that of normal anisotropic magnetoresistance (AMR) measured in the same lateral geometry. The direct link we establish between the TAMR and AMR indicates that TAMR may be observable in other materials showing room temperature AMR and demonstrates that the physics of nanoconstriction magnetoresistive devices can be much richer than previously thought.

Regional pancreatectomy and transverse colectomy with mesenteric vascular reconstruction for inflammatory pseudotumour of the head of pancreas and mesenteric root.

BACKGROUND: Inflammatory myofibroblastic pseudotumour is a rare pancreatic lesion. CASE OUTLINE: A 32-year-old woman with such a tumour was treated by a radical operation comprising proximal pancreatic-duodenectomy (Whipple Procedure) and transverse colectomy with resection and reconstruction of the superior mesenteric artery and vein. She remains well 6 years later. DISCUSSION: The importance of aggressive surgical clearance rather than chemotherapy is highlighted in the management of patients with these unusual tumours.

Endoleaks following conventional open abdominal aortic aneurysm repair.

OBJECTIVE: to describe the complication of <<<>>> following conventional open abdominal aortic aneurysm (AAA) repair. DESIGN: prospective case study. SETTING: two specialist vascular surgical centres. PATIENTS AND METHODS: six patients who had successful conventional open AAA repair. RESULTS: six patients presented with back or abdominal pain or hypotension between one and eighteen months later. An endoleak at the distal anastomosis was noted in five of the cases and one endoleak at the proximal anastomosis. All six cases were successfully repaired; two of these patients required Dacron graft replacement, whilst in four cases only direct resuturing was needed. There was no evidence of infection. CONCLUSIONS: an endoleak is not a phenomenon confined to stent grafts. It should be considered in all patients who present with back or abdominal pain within eighteen months of open AAA repair. The combination of computed tomography (CT) scan and digital subtraction angiography is most useful for preoperative diagnosis.

The matrix protein of HIV-1 is not sufficient for assembly and release of virus-like particles.

The matrix (MA) proteins of human immunodeficiency virus type 1 (HIV-1) and simian immunodeficiency virus (SIV) are known to be important for the targeting and assembly of lentiviral proteins. The objective of the present study was to determine whether the MA protein of HIV-1 was sufficient for particle assembly and release. Eukaryotic expression of wild-type HIV-1 Gag-Pol, HIV-1 MA alone, or SIV MA alone was analyzed with radio-immunoprecipitation, density centrifugation, and a protease protection assay. Cells that expressed HIV-1 Gag-Pol or SIV MA alone released virus-like particles (VLPs) with sucrose gradient densities of 1.15 or 1.12 g/ml, respectively. The MA and/or capsid proteins in these particles were protected from protease degradation, indicating the presence of a protective outer membrane. Expression of HIV-1 MA protein alone resulted in release of MA which pelleted through a 20% sucrose cushion but failed to enter a 20-60% sucrose gradient and was not protected from protease degradation. The MA protein of SIV was previously reported to be sufficient for production of VLPs (S. A. Gonzalez, H, K, Affrachino, H. R. Gelderblom, and A. Burney. Virology 194, 548-556, 1993; V. Liska, D. Spehner, M. Mehtali, D. Schmitt, A. Kirn, and A. M. Aubertin. J. Gen. Virol. 75, 2955-2962, 1994). Our study confirmed that result, but indicated that the MA protein of HIV-1 was not sufficient to assemble and release VLPs.

Bacterial phenotypes mediated by mviA and their relationship to the mouse virulence of Salmonella typhimurium.

The focus of this study was the phenotypic characterization of Salmonella typhimurium mutants lacking the function of the response regulator mviA. The inactivation of mviA+ (mviA::kan) is shown to induce a significant change in the growth of most virulent strains, as reflected in the size of the colonies formed on agar plates. The colony phenotype observed in these strains has been designated as the small colony morphology (Scm+) phenotype. Mutants exhibiting the Scm+ phenotype are shown to be significantly attenuated for virulence in susceptible (ItyB) mice. The Scm+ phenotype therefore provides an in vitro phenotypic marker for mviA+ activity. Further examination of Scm+ mutants has revealed that they lack expression of a 55 kDa periplasmic protein which is detected in isogenic mviA+ strains. This protein has been designated mviA+ related protein A (MrpA) and was expressed in direct correlation with virulence in all S. typhimurium strains examined.

A regional study of thyroidectomy: surgical pathology suggests scope to improve quality and reduce cost.

This study of thyroid histopathological data from hospitals in the South West Thames region was undertaken to assess current practice and the scope for improvement. Over a 6 month period, 186 thyroid operations were performed on 179 patients at eight hospitals serving almost 1.7 million people. The frequency of thyroidectomy in different hospitals varied from 13 to 35 per 100,000 per year and 6.4% of the operations were second thyroidectomies. Benign multinodular goitre was the most common histological finding (34%). A benign solitary nodule was found in 36% and malignancy in 8.4% of the specimens. Correlation of histological analysis and type of operation suggested that a variety of operations were performed for the same pathological condition and that some operations were diagnostic procedures only. Overall, 63 of the 186 operations (34%) might have been avoided by a firm preoperative diagnosis. Only 67 thyroid fine needle aspiration biopsies (FNAC) were performed at the eight hospitals during the study period. Only 15 (8%) of the patients who underwent thyroid operation had been investigated by FNAC. Reduction in thyroid surgery through more widespread use of FNAC could result in savings of 100,000 pounds per million population per year. Regional activity data show that more than 50 surgeons currently undertake a workload of less than 500 thyroidectomies each year. Increased subspecialisation may be required to reduce costs and raise standards.

Idiopathic true aneurysm of the popliteal artery in childhood.

Non-traumatic arterial aneurysms in childhood are very uncommon and are usually associated with inflammatory or degenerative conditions. A case of idiopathic true aneurysm occurring in one popliteal artery of a 14-year-old girl is described. Geniculate artery branches arose from the sac and histological examination confirmed that it was a true aneurysm. Successful treatment by the insertion of a reversed vein graft was confirmed by follow-up years after the operation.