Spin-polarized transport through weakly coupled double quantum dots in the Coulomb-blockade regime

We analyze cotunneling transport through two quantum dots in series weakly coupled to external ferromagnetic leads. In the Coulomb blockade regime the electric current flows due to third-order tunneling, while the second-order single-barrier processes have indirect impact on the current by changing the occupation probabilities of the double dot system. We predict a zero-bias maximum in the differential conductance, whose magnitude is conditioned by the value of the inter-dot Coulomb interaction. This maximum is present in both magnetic configurations of the system and results from asymmetry in cotunneling through different virtual states. Furthermore, we show that tunnel magnetoresistance exhibits a distinctively different behavior depending on temperature, being rather independent of the value of inter-dot correlation. Moreover, we find negative TMR in some range of the bias voltage.Comment: 9 pages, 7 figures, accepted in Phys. Rev.

Molecular states in carbon nanotube double quantum dots

We report electrical transport measurements through a semiconducting single-walled carbon nanotube (SWNT) with three additional top-gates. At low temperatures the system acts as a double quantum dot with large inter-dot tunnel coupling allowing for the observation of tunnel-coupled molecular states extending over the whole double-dot system. We precisely extract the tunnel coupling and identify the molecular states by the sequential-tunneling line shape of the resonances in differential conductance.Comment: 5 pages, 4 figure

Defining and controlling double quantum dots in single-walled carbon nanotubes

We report the experimental realization of double quantum dots in single-walled carbon nanotubes. The device consists of a nanotube with source and drain contact, and three additional top-gate electrodes in between. We show that, by energizing these top-gates, it is possible to locally gate a nanotube, to create a barrier, or to tune the chemical potential of a part of the nanotube. At low temperatures we find (for three different devices) that in certain ranges of top-gate voltages our device acts as a double quantum dot, evidenced by the typical honeycomb charge stability pattern.Comment: 9 pages, 3 figure

Validity and worth in the science curriculum: learning school science outside the laboratory

It is widely acknowledged that there are problems with school science in many developed countries of the world. Such problems manifest themselves in a progressive decline in pupil enthusiasm for school science across the secondary age range and the fact that fewer students are choosing to study the physical sciences at higher levels and as careers. Responses to these developments have included proposals to reform the curriculum, pedagogy and the nature of pupil discussion in science lessons. We support such changes but argue from a consideration of the aims of science education that secondary school science is too rooted in the science laboratory; substantially greater use needs to be made of out-of-school sites for the teaching of science. Such usage should result in a school science education that is more valid and more motivating and is better at fulfilling defensible aims of school science education. Our contention is that laboratory-based school science teaching needs to be complemented by out-of-school science learning that draws on the actual world (e.g. through fieldtrips), the presented world (e.g. in science centres, botanic gardens, zoos and science museums) and the virtual worlds that are increasingly available through information and communications technologies (ICT)

Electric Field Control of Spin Transport

Spintronics is an approach to electronics in which the spin of the electrons is exploited to control the electric resistance R of devices. One basic building block is the spin-valve, which is formed if two ferromagnetic electrodes are separated by a thin tunneling barrier. In such devices, R depends on the orientation of the magnetisation of the electrodes. It is usually larger in the antiparallel than in the parallel configuration. The relative difference of R, the so-called magneto-resistance (MR), is then positive. Common devices, such as the giant magneto-resistance sensor used in reading heads of hard disks, are based on this phenomenon. The MR may become anomalous (negative), if the transmission probability of electrons through the device is spin or energy dependent. This offers a route to the realisation of gate-tunable MR devices, because transmission probabilities can readily be tuned in many devices with an electrical gate signal. Such devices have, however, been elusive so far. We report here on a pronounced gate-field controlled MR in devices made from carbon nanotubes with ferromagnetic contacts. Both the amplitude and the sign of the MR are tunable with the gate voltage in a predictable manner. We emphasise that this spin-field effect is not restricted to carbon nanotubes but constitutes a generic effect which can in principle be exploited in all resonant tunneling devices.Comment: 22 pages, 5 figure

Double quantum dot with integrated charge sensor based on Ge/Si heterostructure nanowires

Coupled electron spins in semiconductor double quantum dots hold promise as the basis for solid-state qubits. To date, most experiments have used III-V materials, in which coherence is limited by hyperfine interactions. Ge/Si heterostructure nanowires seem ideally suited to overcome this limitation: the predominance of spin-zero nuclei suppresses the hyperfine interaction and chemical synthesis creates a clean and defect-free system with highly controllable properties. Here we present a top gate-defined double quantum dot based on Ge/Si heterostructure nanowires with fully tunable coupling between the dots and to the leads. We also demonstrate a novel approach to charge sensing in a one-dimensional nanostructure by capacitively coupling the double dot to a single dot on an adjacent nanowire. The double quantum dot and integrated charge sensor serve as an essential building block required to form a solid-state spin qubit free of nuclear spin.Comment: Related work at http://marcuslab.harvard.edu and http://cmliris.harvard.ed

Serendipitous alkylation of a Plk1 ligand uncovers a new binding channel

We obtained unanticipated synthetic byproducts from alkylation of the δ[superscript 1] nitrogen (N3) of the histidine imidazole ring of the polo-like kinase-1 (Plk1) polo-box domain (PBD)-binding peptide PLHSpT. For the highest-affinity byproduct, bearing a C[subscript 6]H[subscript 5](CH[subscript 2])[subscript 8]– group, a Plk1 PBD cocrystal structure revealed a new binding channel that had previously been occluded. An N-terminal PEGylated version of this peptide containing a hydrolytically stable phosphothreonyl residue (pT) bound the Plk1 PBD with affinity equal to that of the non-PEGylated parent but showed markedly less interaction with the PBDs of the two closely related proteins Plk2 and Plk3. Treatment of cultured cells with this PEGylated peptide resulted in delocalization of Plk1 from centrosomes and kinetochores and in chromosome misalignment that effectively induced mitotic block and apoptotic cell death. This work provides insights that might advance efforts to develop Plk1 PBD-binding inhibitors as potential Plk1-specific anticancer agents.National Institutes of Health (U.S.) (Grant GM60594)National Institutes of Health (U.S.) (Grant GM68762)National Institutes of Health (U.S.) (Grant CA112967

Idebenone and Resveratrol Extend Lifespan and Improve Motor Function of HtrA2 Knockout Mice

Heterozygous loss-of-function mutation of the human gene for the mitochondrial protease HtrA2 has been associated with increased risk to develop mitochondrial dysfunction, a process known to contribute to neurodegenerative disorders such as Huntington's disease (HD) and Parkinson's disease (PD). Knockout of HtrA2 in mice also leads to mitochondrial dysfunction and to phenotypes that resemble those found in neurodegenerative disorders and, ultimately, lead to death of animals around postnatal day 30. Here, we show that Idebenone, a synthetic antioxidant of the coenzyme Q family, and Resveratrol, a bioactive compound extracted from grapes, are both able to ameliorate this phenotype. Feeding HtrA2 knockout mice with either compound extends lifespan and delays worsening of the motor phenotype. Experiments conducted in cell culture and on brain tissue of mice revealed that each compound has a different mechanism of action. While Idebenone acts by downregulating the integrated stress response, Resveratrol acts by attenuating apoptosis at the level of Bax. These activities can account for the delay in neuronal degeneration in the striata of these mice and illustrate the potential of these compounds as effective therapeutic approaches against neurodegenerative disorders such as HD or PD

Soluble TREM2 in CSF and its association with other biomarkers and cognition in autosomal-dominant Alzheimer's disease: a longitudinal observational study

BACKGROUND: Therapeutic modulation of TREM2-dependent microglial function might provide an additional strategy to slow the progression of Alzheimer's disease. Although studies in animal models suggest that TREM2 is protective against Alzheimer's pathology, its effect on tau pathology and its potential beneficial role in people with Alzheimer's disease is still unclear. Our aim was to study associations between the dynamics of soluble TREM2, as a biomarker of TREM2 signalling, and amyloid β (Aβ) deposition, tau-related pathology, neuroimaging markers, and cognitive decline, during the progression of autosomal dominant Alzheimer's disease. METHODS: We did a longitudinal analysis of data from the Dominantly Inherited Alzheimer Network (DIAN) observational study, which includes families with a history of autosomal dominant Alzheimer's disease. Participants aged over 18 years who were enrolled in DIAN between Jan 1, 2009, and July 31, 2019, were categorised as either carriers of pathogenic variants in PSEN1, PSEN2, and APP genes (n=155) or non-carriers (n=93). We measured amounts of cleaved soluble TREM2 using a novel immunoassay in CSF samples obtained every 2 years from participants who were asymptomatic (Clinical Dementia Rating [CDR]=0) and annually for those who were symptomatic (CDR>0). CSF concentrations of Aβ40, Aβ42, total tau (t-tau), and tau phosphorylated on threonine 181 (p-tau) were measured by validated immunoassays. Predefined neuroimaging measurements were total cortical uptake of Pittsburgh compound B PET (PiB-PET), cortical thickness in the precuneus ascertained by MRI, and hippocampal volume determined by MRI. Cognition was measured using a validated cognitive composite (including DIAN word list test, logical memory delayed recall, digit symbol coding test [total score], and minimental status examination). We based our statistical analysis on univariate and bivariate linear mixed effects models. FINDINGS: In carriers of pathogenic variants, a high amyloid burden at baseline, represented by low CSF Aβ42 (β=–4·28 × 10^{–2} [SE 0·013], p=0·0012), but not high cortical uptake in PiB-PET (β=–5·51 × 10^{–3} [0·011], p=0·63), was the only predictor of an augmented annual rate of subsequent increase in soluble TREM2. Augmented annual rates of increase in soluble TREM2 were associated with a diminished rate of decrease in amyloid deposition, as measured by Aβ42 in CSF (r=0·56 [0·22], p=0·011), in presymptomatic carriers of pathogenic variants, and with diminished annual rate of increase in PiB-PET (r=–0·67 [0·25], p=0·0060) in symptomatic carriers of pathogenic variants. Presymptomatic carriers of pathogenic variants with annual rates of increase in soluble TREM2 lower than the median showed a correlation between enhanced annual rates of increase in p-tau in CSF and augmented annual rates of increase in PiB-PET signal (r=0·45 [0·21], p=0·035), that was not observed in those with rates of increase in soluble TREM2 higher than the median. Furthermore, presymptomatic carriers of pathogenic variants with rates of increase in soluble TREM2 above or below the median had opposite associations between Aβ42 in CSF and PiB-PET uptake when assessed longitudinally. Augmented annual rates of increase in soluble TREM2 in presymptomatic carriers of pathogenic variants correlated with decreased cortical shrinkage in the precuneus (r=0·46 [0·22]), p=0·040) and diminished cognitive decline (r=0·67 [0·22], p=0·0020). INTERPRETATION: Our findings in autosomal dominant Alzheimer's disease position the TREM2 response within the amyloid cascade immediately after the first pathological changes in Aβ aggregation and further support the role of TREM2 on Aβ plaque deposition and compaction. Furthermore, these findings underpin a beneficial effect of TREM2 on Aβ deposition, Aβ-dependent tau pathology, cortical shrinkage, and cognitive decline. Soluble TREM2 could, therefore, be a key marker for clinical trial design and interpretation. Efforts to develop TREM2-boosting therapies are ongoing