134 research outputs found

    Observation of the 4π\pi-periodic Josephson effect in indium arsenide nanowires

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    Quantum computation by non-Abelian Majorana zero modes (MZMs) offers an approach to achieve fault tolerance by encoding quantum information in the non-local charge parity states of semiconductor nanowire networks in the topological superconductor regime. Thus far, experimental studies of MZMs chiefly relied on single electron tunneling measurements which leads to decoherence of the quantum information stored in the MZM. As a next step towards topological quantum computation, charge parity conserving experiments based on the Josephson effect are required, which can also help exclude suggested non-topological origins of the zero bias conductance anomaly. Here we report the direct measurement of the Josephson radiation frequency in InAs nanowires with epitaxial aluminium shells. For the first time, we observe the 4π4\pi-periodic Josephson effect above a magnetic field of 200\approx 200\,mT, consistent with the estimated and measured topological phase transition of similar devices.Comment: Published version. Supplementary Information is available as ancillary file, raw data and calculations can be downloaded from http://dx.doi.org/10.4121/uuid:1f936840-5bc2-40ca-8c32-1797c12cacb

    Model selection for prognostic time-to-event gene signature discovery with applications in early breast cancer data

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    Model selection between competing models is a key consideration in the discovery of prognostic multigene signatures. The use of appropriate statistical performance measures as well as verification of biological significance of the signatures is imperative to maximise the chance of external validation of the generated signatures. Current approaches in time-to-event studies often use only a single measure of performance in model selection, such as logrank test p-values, or dichotomise the follow-up times at some phase of the study to facilitate signature discovery. In this study we improve the prognostic signature discovery process through the application of the multivariate partial Cox model combined with the concordance index, hazard ratio of predictions, independence from available clinical covariates and biological enrichment as measures of signature performance. The proposed framework was applied to discover prognostic multigene signatures from early breast cancer data. The partial Cox model combined with the multiple performance measures were used in both guiding the selection of the optimal panel of prognostic genes and prediction of risk within cross validation without dichotomising the follow-up times at any stage. The signatures were successfully externally cross validated in independent breast cancer datasets, yielding a hazard ratio of 2.55 [1.44, 4.51] for the top ranking signature.</p

    Broadband microwave spectroscopy of semiconductor nanowire-based Cooper-pair transistors

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    The Cooper-pair transistor (CPT), a small superconducting island enclosed between two Josephson weak links, is the atomic building block of various superconducting quantum circuits. Utilizing gate-tunable semiconductor channels as weak links, the energy scale associated with the Josephson tunneling can be changed with respect to the charging energy of the island, tuning the extent of its charge fluctuations. Here, we directly demonstrate this control by mapping the energy level structure of a CPT made of an indium arsenide nanowire (NW) with a superconducting aluminum shell. We extract the device parameters based on the exhaustive modeling of the quantum dynamics of the phase-biased nanowire CPT and directly measure the even-odd parity occupation ratio as a function of the device temperature, relevant for superconducting and prospective topological qubits.Comment: Published version. Supplementary Information is available as ancillary file, raw data and calculations can be downloaded from http://doi.org/10.4121/uuid:5d54f11b-6774-4ae4-96cf-25e6a91927e

    Observation of 2e-periodic Supercurrents in Nanowire Single-Cooper-Pair Transistors

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    Parity control of superconducting islands hosting Majorana zero modes (MZMs) is required to operate topological qubits made from proximitized semiconductor nanowires. We, therefore, study parity effects in hybrid InAs-Al single-Cooper-pair transistors (SCPTs) as a first step. In particular, we investigate the gate-charge supercurrent modulation and observe a consistent 2ee-periodic pattern indicating a general lack of low-energy subgap states in these nanowires at zero magnetic field. In a parallel magnetic field, an even-odd pattern develops with a gate-charge spacing that oscillates as a function of field demonstrating that the modulation pattern is sensitive to the presence of a single subgap state. In addition, we find that the parity lifetime of the SCPT decreases exponentially with magnetic field as the subgap state approaches zero energy. Our work highlights the important role that intentional quasiparticle traps and superconducting gap engineering would play in topological qubits that require quenching of the island charge dispersion.Comment: 8 pages, 4 figures, supplemental material included as ancillary fil

    Novel Dengue Virus Type 1 from Travelers to Yap State, Micronesia

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    Dengue virus type 1 (DENV-1), which was responsible for the dengue fever outbreak in Yap State, Micronesia, in 2004, was isolated from serum samples of 4 dengue patients in Japan. Genome sequencing demonstrated that this virus belonged to genotype IV and had a 29-nucleotide deletion in the 3´ noncoding region

    Genetic Design of Drugs Without Side-Effects

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    Closest string with outliers

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    Background: Given n strings s1, …, sn each of length ℓ and a nonnegative integer d, the CLOSEST STRING problem asks to find a center string s such that none of the input strings has Hamming distance greater than d from s. Finding a common pattern in many – but not necessarily all – input strings is an important task that plays a role in many applications in bioinformatics. Results: Although the closest string model is robust to the oversampling of strings in the input, it is severely affected by the existence of outliers. We propose a refined model, the CLOSEST STRING WITH OUTLIERS (CSWO) problem, to overcome this limitation. This new model asks for a center string s that is within Hamming distance d to at least n – k of the n input strings, where k is a parameter describing the maximum number of outliers. A CSWO solution not only provides the center string as a representative for the set of strings but also reveals the outliers of the set. We provide fixed parameter algorithms for CSWO when d and k are parameters, for both bounded and unbounded alphabets. We also show that when the alphabet is unbounded the problem is W[1]-hard with respect to n – k, ℓ, and d. Conclusions: Our refined model abstractly models finding common patterns in several but not all input strings

    Morphological Effects on Expression of Growth Differentiation Factor 15 (GDF15), a Marker of Metastasis

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    Cancer cells typically demonstrate altered morphology during the various stages of disease progression as well as metastasis. While much is known about how altered cell morphology in cancer is a result of genetic regulation, less is known about how changes in cell morphology affect cell function by influencing gene expression. In this study, we altered cell morphology in different types of cancer cells by disrupting the actin cytoskeleton or by modulating attachment and observed a rapid up‐regulation of growth differentiation factor 15 (GDF15), a member of the transforming growth factor‐beta (TGF‐β) super‐family. Strikingly, this up‐regulation was sustained as long as the cell morphology remained altered but was reversed upon allowing cell morphology to return to its typical configuration. The potential significance of these findings was examined in vivo using a mouse model: a small number of cancer cells grown in diffusion chambers that altered morphology increased mouse serum GDF15. Taken together, we propose that during the process of metastasis, cancer cells experience changes in cell morphology, resulting in the increased production and secretion of GDF15 into the surrounding environment. This indicates a possible relationship between serum GDF15 levels and circulating tumor cells may exist. Further investigation into the exact nature of this relationship is warranted. J. Cell. Physiol. 229: 362–373, 2014. © 2013 Wiley Periodicals, Inc.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/101833/1/jcp24458.pd

    The Colorectal cancer disease-specific transcriptome may facilitate the discovery of more biologically and clinically relevant information

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    <p>Abstract</p> <p>Background</p> <p>To date, there are no clinically reliable predictive markers of response to the current treatment regimens for advanced colorectal cancer. The aim of the current study was to compare and assess the power of transcriptional profiling using a generic microarray and a disease-specific transcriptome-based microarray. We also examined the biological and clinical relevance of the disease-specific transcriptome.</p> <p>Methods</p> <p>DNA microarray profiling was carried out on isogenic sensitive and 5-FU-resistant HCT116 colorectal cancer cell lines using the Affymetrix HG-U133 Plus2.0 array and the Almac Diagnostics Colorectal cancer disease specific Research tool. In addition, DNA microarray profiling was also carried out on pre-treatment metastatic colorectal cancer biopsies using the colorectal cancer disease specific Research tool. The two microarray platforms were compared based on detection of probesets and biological information.</p> <p>Results</p> <p>The results demonstrated that the disease-specific transcriptome-based microarray was able to out-perform the generic genomic-based microarray on a number of levels including detection of transcripts and pathway analysis. In addition, the disease-specific microarray contains a high percentage of antisense transcripts and further analysis demonstrated that a number of these exist in sense:antisense pairs. Comparison between cell line models and metastatic CRC patient biopsies further demonstrated that a number of the identified sense:antisense pairs were also detected in CRC patient biopsies, suggesting potential clinical relevance.</p> <p>Conclusions</p> <p>Analysis from our <it>in vitro </it>and clinical experiments has demonstrated that many transcripts exist in sense:antisense pairs including <it>IGF2BP2</it>, which may have a direct regulatory function in the context of colorectal cancer. While the functional relevance of the antisense transcripts has been established by many studies, their functional role is currently unclear; however, the numbers that have been detected by the disease-specific microarray would suggest that they may be important regulatory transcripts. This study has demonstrated the power of a disease-specific transcriptome-based approach and highlighted the potential novel biologically and clinically relevant information that is gained when using such a methodology.</p

    The relationships between West Nile and Kunjin viruses.

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    Until recently, West Nile (WN) and Kunjin (KUN) viruses were classified as distinct types in the Flavivirus genus. However, genetic and antigenic studies on isolates of these two viruses indicate that the relationship between them is more complex. To better define this relationship, we performed sequence analyses on 32 isolates of KUN virus and 28 isolates of WN virus from different geographic areas, including a WN isolate from the recent outbreak in New York. Sequence comparisons showed that the KUN virus isolates from Australia were tightly grouped but that the WN virus isolates exhibited substantial divergence and could be differentiated into four distinct groups. KUN virus isolates from Australia were antigenically homologous and distinct from the WN isolates and a Malaysian KUN virus. Our results suggest that KUN and WN viruses comprise a group of closely related viruses that can be differentiated into subgroups on the basis of genetic and antigenic analyses
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