Interference effects in the Coulomb blockade regime: current blocking and spin preparation in symmetric nanojunctions

We consider nanojunctions in the single-electron tunnelling regime which, due to a high degree of spatial symmetry, have a degenerate many body spectrum. As a consequence, interference phenomena which cause a current blocking can occur at specific values of the bias and gate voltage. We present here a general formalism to give necessary and sufficient conditions for interference blockade also in the presence of spin polarized leads. As an example we analyze a triple quantum dot single electron transistor (SET). For a set-up with parallel polarized leads, we show how to selectively prepare the system in each of the three states of an excited spin triplet without application of any external magnetic field.Comment: 10 pages, 9 figures. Corrected typos and updated reference

Quantum interference phenomena in transport through molecules and multiple quantum dots

In this thesis, we investigate electronic transport through molecular quantum dots weakly coupled to source and drain leads. To describe the electronic spectrum of the molecule that forms the quantum dot, the Pariser-Parr-Pople Hamiltonian for conjugated molecules is introduced and adapted to the case of a benzene molecule. The generalized master equation (GME), which is the equation of motion for the reduced density matrix (RDM), is used to calculate the current and the conductance through the system. Transport through a benzene molecule is investigated in two configurations, para- and meta configuration, which are defined by the lead molecule coupling. Interference between degenerate states leads to a suppression of the linear conductance when changing from the para to the meta configuration and to current blocking in the meta configuration for certain bias voltages. In presence of parallel polarized ferromagnetic leads, this effect can be used to obtain control over the molecules net spin by all-electrical means. In the last chapter, cotunneling processes are described by means of an effective Kondo Hamiltonian, and the results are compared to a theory which is exact to fourth order in the tunneling Hamiltonian

Inelastic cotunneling in quantum dots and molecules with weakly broken degeneracies

We calculate the nonlinear cotunneling conductance through interacting quantum dot systems in the deep Coulomb blockade regime using a rate equation approach based on the T-matrix formalism, which shows in the concerned regions very good agreement with a generalized master equation approach. Our focus is on inelastic cotunneling in systems with weakly broken degeneracies, such as complex quantum dots or molecules. We find for these systems a characteristic gate dependence of the non-equilibrium cotunneling conductance. While on one side of a Coulomb diamond the conductance decreases after the inelastic cotunneling threshold towards its saturation value, on the other side it increases monotonously even after the threshold. We show that this behavior originates from an asymmetric gate voltage dependence of the effective cotunneling amplitudes.Comment: 12 pages, 12 figures; revised published versio

Genetic landscape of congenital insensitivity to pain and hereditary sensory and autonomic neuropathies

Congenital insensitivity to pain (CIP) and hereditary sensory and autonomic neuropathies (HSAN) are clinically and genetically heterogeneous disorders exclusively or predominantly affecting the sensory and autonomic neurons. Due to the rarity of the diseases and findings based mainly on single case reports or small case series, knowledge about these disorders is limited. Here, we describe the molecular workup of a large international cohort of CIP/HSAN patients including patients from normally under-represented countries. We identify 80 previously unreported pathogenic or likely pathogenic variants in a total of 73 families in the >20 known CIP/HSAN-associated genes. The data expand the spectrum of disease-relevant alterations in CIP/HSAN, including novel variants in previously rarely recognized entities such as ATL3-, FLVCR1- and NGF-associated neuropathies and previously under-recognized mutation types such as larger deletions. In silico predictions, heterologous expression studies, segregation analyses and metabolic tests helped to overcome limitations of current variant classification schemes that often fail to categorize a variant as disease-related or benign. The study sheds light on the genetic causes and disease-relevant changes within individual genes in CIP/HSAN. This is becoming increasingly important with emerging clinical trials investigating subtype or gene-specific treatment strategies

A myelin gene causative of a catatonia-depression syndrome upon aging

Severe mental illnesses have been linked to white matter abnormalities, documented by postmortem studies. However, cause and effect have remained difficult to distinguish. CNP (20,30-cyclic nucleotide 30-phosphodiesterase) is among the oligodendrocyte/myelin-associated genes most robustly reduced on mRNA and protein level in brains of schizophrenic, bipolar or major depressive patients. This suggests that CNP reduction might be critical for a more general disease process and not restricted to a single diagnostic category. We show here that reduced expression of CNP is the primary cause of a distinct behavioural phenotype, seen only upon aging as an additional ‘pro-inflammatory hit’. This phenotype is strikingly similar in Cnp heterozygous mice and patients with mental disease carrying the AA genotype at CNP SNP rs2070106. The characteristic features in both species with their partial CNP ‘loss-of-function’ genotype are best described as ‘catatoniadepression’ syndrome. As a consequence of perturbed CNP expression, mice show secondary low-grade inflammation/neurodegeneration. Analogously, in man, diffusion tensor imaging points to axonal loss in the frontal corpus callosum. To conclude, subtle white matter abnormalities inducing neurodegenerative changes can cause/amplify psychiatric diseases.peerReviewe

Accumulated common variants in the broader fragile X gene family modulate autistic phenotypes.

Fragile X syndrome (FXS) is mostly caused by a CGG triplet expansion in the fragile X mental retardation 1 gene (FMR1). Up to 60% of affected males fulfill criteria for autism spectrum disorder (ASD), making FXS the most frequent monogenetic cause of syndromic ASD. It is unknown, however, whether normal variants (independent of mutations) in the fragile X gene family (FMR1, FXR1, FXR2) and in FMR2 modulate autistic features. Here, we report an accumulation model of 8 SNPs in these genes, associated with autistic traits in a discovery sample of male patients with schizophrenia (N = 692) and three independent replicate samples: patients with schizophrenia (N = 626), patients with other psychiatric diagnoses (N = 111) and a general population sample (N = 2005). For first mechanistic insight, we contrasted microRNA expression in peripheral blood mononuclear cells of selected extreme group subjects with high- versus low-risk constellation regarding the accumulation model. Thereby, the brain-expressed miR-181 species emerged as potential "umbrella regulator", with several seed matches across the fragile X gene family and FMR2. To conclude, normal variation in these genes contributes to the continuum of autistic phenotypes.peerReviewe