The existence of Wigner crystallization, one of the most significant hallmarks of strong electron correlations, has to date only been definitively observed in two-dimensional systems. In one-dimensional (1D) quantum wires Wigner crystals correspond to regularly spaced electrons; however, weakening the confinement and allowing the electrons to relax in a second dimension is predicted to lead to the formation of a new ground state constituting a zigzag chain with nontrivial spin phases and properties. Here we report the observation of such zigzag Wigner crystals by use of on-chip charge and spin detectors employing electron focusing to image the charge density distribution and probe their spin properties.
View Article and Find Full Text PDFThe folding of RNA into a wide range of structures is essential for its diverse biological functions from enzymatic catalysis to ligand binding and gene regulation. The unfolding and refolding of individual RNA molecules can be probed by single-molecule force spectroscopy (SMFS), enabling detailed characterization of the conformational dynamics of the molecule as well as the free-energy landscape underlying folding. Historically, high-precision SMFS studies of RNA have been limited to custom-built optical traps.
View Article and Find Full Text PDFResonators and the way they couple to external radiation rely on very different concepts if one considers devices belonging to the photonic and electronic worlds. The terahertz frequency range, however, provides intriguing possibilities for the development of hybrid technologies that merge ideas from both fields in novel functional designs. In this paper, we show that high-quality, subwavelength, whispering-gallery lasers can be combined to form a linear dipole antenna, which creates a very efficient, low-threshold laser emission in a collimated beam pattern.
View Article and Find Full Text PDFBusulfan (Bu) is an alkylating agent widely used in conditioning regimes prior to stem cell transplantation (SCT), most commonly in combination with cyclophosphamide (Bu-cy) or fludarabine (Bu-flu) as myeloablative conditioning prior to allograft or with high-dose melphalan (Bu-mel) prior to autologous SCT. Despite many decades of Bu use, initially orally but now intravenously (IV), a paucity of pharmacokinetic (PK) and pharmacodynamic (PD) data exists to inform evidence-based guidelines as how best to balance the efficacy and toxicity of this agent. This is a non-randomized retrospective real-world study at three hospitals investigating the role of PK guidance in dosing Bu in the setting of IV Bu-mel autologous SCT.
View Article and Find Full Text PDFObjective: Comprehensively describe the phenotypic spectrum of sporadic fatal insomnia (sFI) to facilitate diagnosis and management of this rare and peculiar prion disorder.
Methods: A survey among major prion disease reference centers in Europe identified 13 patients diagnosed with sFI in the past 20 years. We undertook a detailed analysis of clinical and histopathological features and the results of diagnostic investigations.
The production of coumarins and furanocoumarins (FCs) in higher plants is widely considered a model illustration of the adaptation of plants to their environment. In this report, we show that the multiplication of cytochrome P450 variants within the CYP71AZ subfamily has contributed to the diversification of these molecules. Multiple copies of genes encoding this enzyme family are found in Apiaceae, and their phylogenetic analysis suggests that they have different functions within these plants.
View Article and Find Full Text PDFRelapse of haematological malignancies after allogeneic haematopoietic stem cell transplant is a major cause of mortality. The immunological mechanisms that may lead to disease relapse may include immunological immaturity prior to reconstitution of the allogeneic immune system, tumour antigen downregulation or promotion of T-cell exhaustion by interactions with the tumour microenvironment. Current therapeutic strategies for post-transplant relapse are limited in their efficacy and alternative approaches are required.
View Article and Find Full Text PDFBackground: Current guideline recommendations for optimal management of nonpurulent skin and soft tissue infections (SSTIs) are based on expert consensus. There is a lack of evidence to guide emergency physicians regarding selection of patients for oral versus intravenous antibiotic therapy. The primary objective was to identify predictors associated with oral antibiotic treatment failure.
View Article and Find Full Text PDFImportance: Trastuzumab plus chemotherapy is the standard adjuvant treatment for patients with human epidermal growth factor receptor 2 (HER2)-positive early breast cancer. While the standard duration of trastuzumab treatment is 12 months, the benefits and harms of trastuzumab continued beyond the chemotherapy are unclear.
Objective: To evaluate the efficacy and safety of adjuvant trastuzumab continued beyond chemotherapy in women treated with up-front chemotherapy containing a taxane and trastuzumab.
The understanding of the correlation between structural and photoluminescence (PL) properties of self-assembled semiconductor quantum dots (QDs), particularly InGaAs QDs grown on (001) GaAs substrates, is crucial for both fundamental research and optoelectronic device applications. So far structural and PL properties have been probed from two different epitaxial layers, namely top-capped and buried layers respectively. Here, we report for the first time both structural and PL measurements from an uncapped layer of InGaAs QDs to correlate directly composition, strain and shape of QDs with the optical properties.
View Article and Find Full Text PDFObjectives: Core-binding factor acute myeloid leukaemia (CBF AML) defined by t(8;21)(q22;q22) or inv(16)(p13q22)/t(16;16)(p13;q22) has a favourable prognosis; however, 30%-40% of patients still relapse after chemotherapy. We sought to evaluate the risk factors for relapse in a de novo CBF AML cohort.
Patients/materials/methods: A retrospective review of patients from four Australian tertiary centres from 2001 to 2012, comprising 40 t(8;21) and 30 inv(16) AMLs.
Background: Infections caused by carbapenem-resistant gram-negative bacilli are an emerging public health threat. However, there is a paucity of data examining comparative incidence rates, risk factors, and outcomes in this population.
Methods: This single-center retrospective cohort study was conducted at an urban tertiary-care academic medical center.
We report spin amplification using a capacitive beam splitter in n-type GaAs where the spin polarization is monitored via a transverse electron focusing measurement. It is shown that partially spin-polarized current injected by the emitter can be precisely controlled, and the spin polarization associated with it can be amplified by the beam splitter, such that a considerably high spin polarization of around 50% can be obtained. Additionally, the spin remains coherent as shown by the observation of quantum interference.
View Article and Find Full Text PDFAims: Gastrointestinal (GI) α-synuclein (aSyn) detection as a potential biomarker of Parkinson's disease (PD) is challenged by conflicting results of recent studies. To increase sensitivity and specificity, we applied three techniques to detect different conformations of aSyn in GI biopsies obtained from a longitudinal, clinically well-characterized cohort of PD patients and healthy controls (HC).
Methods: With immunohistochemistry (IHC), we used antibodies reactive for total, phosphorylated and oligomeric aSyn; with aSyn proximity ligation assay (AS-PLA), we targeted oligomeric aSyn species specifically; and with paraffin-embedded tissue blot (AS-PET-blot) we aimed to detect fibrillary, synaptic aSyn.
Terahertz (THz) quantum cascade lasers (QCLs) have undergone rapid development since their demonstration, showing high power, broad-tunability, quantum-limited linewidth, and ultra-broadband gain. Typically, to address applications needs, continuous-wave (CW) operation, low-divergent beam profiles and fine spectral control of the emitted radiation, are required. This, however, is very difficult to achieve in practice.
View Article and Find Full Text PDFViral respiratory tract infection (vRTI) is a significant cause of morbidity and mortality in patients undergoing allogeneic hematopoietic stem cell transplantation (allo-HSCT). This study aimed to assess the epidemiologic characteristics, risk factors, and outcomes of vRTI occurring in the period from conditioning to 100 days after allo-HSCT in the era of molecular testing. This study was a retrospective record review of patients who underwent allo-HSCT at Royal Melbourne Hospital between January 2010 and December 2015.
View Article and Find Full Text PDFMucosal-associated invariant T (MAIT) cells are T cells that recognise vitamin-B derivative Ag presented by the MHC-related-protein 1 (MR1) antigen-presenting molecule. While MAIT cells are highly abundant in humans, their role in tumour immunity remains unknown. Here we have analysed the frequency and function of MAIT cells in multiple myeloma (MM) patients.
View Article and Find Full Text PDFSingle photons and entangled photon pairs are a key resource of many quantum secure communication and quantum computation protocols, and non-Poissonian sources emitting in the low-loss wavelength region around 1,550 nm are essential for the development of fibre-based quantum network infrastructure. However, reaching this wavelength window has been challenging for semiconductor-based quantum light sources. Here we show that quantum dot devices based on indium phosphide are capable of electrically injected single photon emission in this wavelength region.
View Article and Find Full Text PDFInGaAs based devices are great complements to silicon for CMOS, as they provide an increased carrier saturation velocity, lower operating voltage and reduced power dissipation (International technology roadmap for semiconductors (www.itrs2.net)).
View Article and Find Full Text PDFNatural killer (NKs) cells provide rapid responses to viral-infected and malignant cells, including acute myeloid leukemia (AML) blasts. The balance among inhibitory and activating signals, delivered by multiple interactions between ligands on target cells and NK receptors, determines the posture of the NK cell response to either one of target cell elimination or tolerance. The aim of this work was to study the influence of the differential expression of activating and inhibitory NK receptor ligands (NKRLs) by leukemic blasts on clinical outcome in newly diagnosed AML patients.
View Article and Find Full Text PDFProc Natl Acad Sci U S A
February 2018
Chimeric antigen receptor T (CAR-T) cells are effective serial killers with a faster off-rate from dying tumor cells than CAR-T cells binding target cells through their T cell receptor (TCR). Here we explored the functional consequences of CAR-mediated signaling using a dual-specific CAR-T cell, where the same cell was triggered via TCR (tcrCTL) or CAR (carCTL). The carCTL immune synapse lacked distinct LFA-1 adhesion rings and was less reliant on LFA to form stable conjugates with target cells.
View Article and Find Full Text PDFMucosal-associated invariant T (MAIT) cells represent up to 10% of circulating human T cells. They are usually defined using combinations of non-lineage-specific (surrogate) markers such as anti-TRAV1-2, CD161, IL-18Rα and CD26. The development of MR1-Ag tetramers now permits the specific identification of MAIT cells based on T-cell receptor specificity.
View Article and Find Full Text PDFBackground: Standard treatment for thyroid eye disease is with systemic corticosteroids. We aimed to establish whether orbital radiotherapy or antiproliferative immunosuppression would confer any additional benefit.
Methods: CIRTED was a multicentre, double-blind, randomised controlled trial with a 2 × 2 factorial design done at six centres in the UK.