177 research outputs found
Quantum transport and momentum conserving dephasing
We study numerically the influence of momentum-conserving dephasing on the
transport in a disordered chain of scatterers. Loss of phase memory is caused
by coupling the transport channels to dephasing reservoirs. In contrast to
previously used models, the dephasing reservoirs are linked to the transport
channels between the scatterers, and momentum conserving dephasing can be
investigated. Our setup provides a model for nanosystems exhibiting conductance
quantization at higher temperatures in spite of the presence of phononic
interaction. We are able to confirm numerically some theoretical predictions.Comment: 7 pages, 4 figure
Real space finite difference method for conductance calculations
We present a general method for calculating coherent electronic transport in
quantum wires and tunnel junctions. It is based upon a real space high order
finite difference representation of the single particle Hamiltonian and wave
functions. Landauer's formula is used to express the conductance as a
scattering problem. Dividing space into a scattering region and left and right
ideal electrode regions, this problem is solved by wave function matching (WFM)
in the boundary zones connecting these regions. The method is tested on a model
tunnel junction and applied to sodium atomic wires. In particular, we show that
using a high order finite difference approximation of the kinetic energy
operator leads to a high accuracy at moderate computational costs.Comment: 13 pages, 10 figure
Investigation of quantum transport by means of O(N) real-space methods
Quantum transport for different systems is investigated by developing the
Kubo formula on a basis of orthogonal polynomials. Results on quantum Hall
systems are presented with particular attention to metal insulator transitions
and new universalities. Other potential applications of the present method for
RKKY mesoscopic interaction and insight for large scale computational problems,
are given.Comment: 7 pages, 8 figure
Imaging tumour hypoxia with positron emission tomography.
Hypoxia, a hallmark of most solid tumours, is a negative prognostic factor due to its association with an aggressive tumour phenotype and therapeutic resistance. Given its prominent role in oncology, accurate detection of hypoxia is important, as it impacts on prognosis and could influence treatment planning. A variety of approaches have been explored over the years for detecting and monitoring changes in hypoxia in tumours, including biological markers and noninvasive imaging techniques. Positron emission tomography (PET) is the preferred method for imaging tumour hypoxia due to its high specificity and sensitivity to probe physiological processes in vivo, as well as the ability to provide information about intracellular oxygenation levels. This review provides an overview of imaging hypoxia with PET, with an emphasis on the advantages and limitations of the currently available hypoxia radiotracers.Cancer Research UK (CRUK) funded the National Cancer Research Institute (NCRI) PET Research Working party to organise a meeting to discuss imaging cancer with hypoxia tracers and Positron Emission Tomography. IF was funded by CRUK and is also supported by the Chief Scientific Office. ALH is supported by CRUK and the Breast Cancer Research Foundation. RM is funded by NIHR Cambridge Biomedical Research Centre.This is the accepted manuscript. The final version is available from Nature Publishing at http://www.nature.com/bjc/journal/vaop/ncurrent/full/bjc2014610a.html
The EIF4EBP3 translational repressor is a marker of CDC73 tumor suppressor haploinsufficiency in a parathyroid cancer syndrome
Germline mutation of the tumor suppressor gene CDC73 confers susceptibility to the hyperparathyroidism-jaw tumor syndrome associated with a high risk of parathyroid malignancy. Inactivating CDC73 mutations have also been implicated in sporadic parathyroid cancer, but are rare in sporadic benign parathyroid tumors. The molecular pathways that distinguish malignant from benign parathyroid transformation remain elusive. We previously showed that a hypomorphic allele of hyrax (hyx), the Drosophila homolog of CDC73, rescues the loss-of-ventral-eye phenotype of lobe, encoding the fly homolog of Akt1s1/ PRAS40. We report now an interaction between hyx and Tor, a central regulator of cell growth and autophagy, and show that eukaryotic translation initiation factor 4E-binding protein (EIF4EBP), a translational repressor and effector of mammalian target of rapamycin (mTOR), is a conserved target of hyx/CDC73. Flies heterozygous for Tor and hyx, but not Mnn1, the homolog of the multiple endocrine neoplasia type 1 (MEN1) tumor suppressor associated with benign parathyroid tumors, are starvation resistant with reduced basal levels of Thor/4E-BP. Human peripheral blood cell levels of EIF4EBP3 were reduced in patients with CDC73, but not MEN1, heterozygosity. Chromatin immunoprecipitation demonstrated occupancy of EIF4EBP3 by endogenous parafibromin. These results show that EIF4EBP3 is a peripheral marker of CDC73 function distinct from MEN1-regulated pathways, and suggest a model whereby starvation resistance and/or translational de-repression contributes to parathyroid malignant transformation
Technological literacy reconsidered: a model for enactment
The final publication is available at: http://link.springer.com/article/10.1007%2Fs10798-009-9108-6.This paper presents a model to describe technological literacy as enacted by individuals in the course of shaping their lives and the world around them. The model has two interrelated facets – the potential for and enactment of technological literacy – where enactment and potential mutually constitute each other. This potential is made up of knowledge of a particular situation, personal engagement with a situation, and social engagement in the world. Enactment requires a particular set of competencies in action, which together helps shape the situation: recognizing needs; articulating problems; contributing towards the technological process; and analysing consequences. The implications of this model for technological literacy in the context of the individual and society, and the role of technology education in developing technological literacy, are discussed
An instrument to determine the technological literacy levels of upper secondary school students
In this article, an instrument for assessing upper secondary school students’
levels of technological literacy is presented. The items making up the instrument emerged
from a previous study that employed a phenomenographic research approach to explore
students’ conceptions of technology in terms of their understanding of the nature of
technology and their interaction with technological artefacts. The instrument was validated
through administration to 1,245 students on completion of their 12 years of formal
schooling. A factor analysis was conducted on the data and Cronbach alpha reliability coefficients
determined. The results show that a five-dimension factor structure (namely,
artefact, process, direction/instruction, tinkering, and engagement) strongly supported the
dimensions as developed during the original phenomenographic study. The Cronbach
alpha reliability co-efficient of each dimension was satisfactory. Based on these findings,
the instrument has been shown to be valid and reliable and can be used with confidence
Somatic VHL gene alterations in MEN2-associated medullary thyroid carcinoma
BACKGROUND: Germline mutations in RET are responsible for multiple endocrine neoplasia type 2 (MEN2), an autosomal dominantly inherited cancer syndrome that is characterized by medullary thyroid carcinoma (MTC), pheochromocytoma, and parathyroid hyperplasia/adenoma. Recent studies suggest a "second hit" mechanism resulting in amplification of mutant RET. Somatic VHL gene alterations are implicated in the pathogenesis of MEN2 pheochromocytomas. We hypothesized that somatic VHL gene alterations are also important in the pathogenesis of MEN2-associated MTC. METHODS: We analyzed 6 MTCs and 1 C-cell hyperplasia (CCH) specimen from 7 patients with MEN2A and RET germline mutations in codons 609, 618, 620, or 634, using microdissection, microsatellite analysis, phosphorimage densitometry, and VHL mutation analysis. RESULTS: First, we searched for allelic imbalance between mutant and wild-type RET by using the polymorphic markers D10S677, D10S1239, and RET on thyroid tissue from these patients. Evidence for RET amplification by this technique could be demonstrated in 3 of 6 MTCs. We then performed LOH analysis using D3S1038 and D3S1110 which map to the VHL gene locus at 3p25/26. VHL gene deletion was present in 3 MTCs. These 3 MTCs also had an allelic imbalance between mutant and wild-type RET. Mutation analysis of the VHL gene showed a somatic frameshift mutation in 1 MTC that also demonstrated LOH at 3p25/26. In the 2 other MTCs with allelic imbalance of RET and somatic VHL gene deletion, no somatic VHL mutation could be detected. The CCH specimen did neither reveal RET imbalance nor somatic VHL gene alterations. CONCLUSION: These data suggest that a RET germline mutation is necessary for development of CCH, that allelic imbalance between mutant and wild-type RET may set off tumorigenesis, and that somatic VHL gene alterations may not play a major role in tumorigenesis of MEN2A-associated MTC
Molecular imaging of hypoxia with radiolabelled agents
Tissue hypoxia results from an inadequate supply of oxygen (O2) that compromises biological functions. Structural and functional abnormalities of the tumour vasculature together with altered diffusion conditions inside the tumour seem to be the main causes of tumour hypoxia. Evidence from experimental and clinical studies points to a role for tumour hypoxia in tumour propagation, resistance to therapy and malignant progression. This has led to the development of assays for the detection of hypoxia in patients in order to predict outcome and identify patients with a worse prognosis and/or patients that would benefit from appropriate treatments. A variety of invasive and non-invasive approaches have been developed to measure tumour oxygenation including oxygen-sensitive electrodes and hypoxia marker techniques using various labels that can be detected by different methods such as positron emission tomography (PET), single photon emission computed tomography (SPECT), magnetic resonance imaging (MRI), autoradiography and immunohistochemistry. This review aims to give a detailed overview of non-invasive molecular imaging modalities with radiolabelled PET and SPECT tracers that are available to measure tumour hypoxia
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