A Superconducting Nanowire Binary Shift Register

We present a design for a superconducting nanowire binary shift register, which stores digital states in the form of circulating supercurrents in high-kinetic-inductance loops. Adjacent superconducting loops are connected with nanocryotrons, three terminal electrothermal switches, and fed with an alternating two-phase clock to synchronously transfer the digital state between the loops. A two-loop serial-input shift register was fabricated with thin-film NbN and achieved a bit error rate less than $10^{-4}$, operating at a maximum clock frequency of $83\,\mathrm{MHz}$ and in an out-of-plane magnetic field up to $6\,\mathrm{mT}$. A shift register based on this technology offers an integrated solution for low-power readout of superconducting nanowire single photon detector arrays, and is capable of interfacing directly with room-temperature electronics and operating unshielded in high magnetic field environments.Comment: The following article has been published in Applied Physics Letters issue 122. 10 pages, 3 figure

A Nanocryotron Memory and Logic Family

The development of superconducting electronics based on nanocryotrons has been limited so far to few-device circuits, in part due to the lack of standard and robust logic cells. Here, we introduce and experimentally demonstrate designs for a set of nanocryotron-based building blocks that can be configured and combined to implement memory and logic functions. The devices were fabricated by patterning a single superconducting layer of niobium nitride and measured in liquid helium on a wide range of operating points. The tests show $10^{-4}$ bit error rates with above $20\,\%$ margins up to $50\,$MHz and the possibility of operating under the effect of a perpendicular $36\,$mT magnetic field, with $30\,\%$ margins at $10\,$MHz. Additionally, we designed and measured an equivalent delay flip-flop made of two memory cells to show the possibility of combining multiple building blocks to make larger circuits. These blocks may constitute a solid foundation for the development of nanocryotron logic circuits and finite-state machines with potential applications in the integrated processing and control of superconducting nanowire single-photon detectors.Comment: Submitted for publication in the Applied Physics Letters special issue "Advances in Superconducting Logic", 8 pages, 5 figure

A Nanocryotron Ripple Counter Integrated with a Superconducting Nanowire Single-Photon Detector for Megapixel Arrays

Decreasing the number of cables that bring heat into the cryocooler is a critical issue for all cryoelectronic devices. Especially, arrays of superconducting nanowire single-photon detectors (SNSPDs) could require more than $10^6$ readout lines. Performing signal processing operations at low temperatures could be a solution. Nanocryotrons, superconducting nanowire three-terminal devices, are good candidates for integrating sensing and electronics on the same technological platform as SNSPDs in photon-counting applications. In this work, we demonstrated that it is possible to read out, process, encode, and store the output of SNSPDs using exclusively superconducting nanowires. In particular, we present the design and development of a nanocryotron ripple counter that detects input voltage spikes and converts the number of pulses to an $N$-digit value. The counting base can be tuned from 2 to higher values, enabling higher maximum counts without enlarging the circuit. As a proof-of-principle, we first experimentally demonstrated the building block of the counter, an integer-$N$ frequency divider with $N$ ranging from 2 to 5. Then, we demonstrated photon-counting operations at 405\,nm and 1550\,nm by coupling an SNSPD with a 2-digit nanocryotron counter partially integrated on-chip. The 2-digit counter operated in either base 2 or base 3 with a bit error rate lower than $2 \times 10^{-4}$ and a maximum count rate of $45 \times 10^6\,$s$^{-1}$. We simulated circuit architectures for integrated readout of the counter state, and we evaluated the capabilities of reading out an SNSPD megapixel array that would collect up to $10^{12}$ counts per second. The results of this work, combined with our recent publications on a nanocryotron shift register and logic gates, pave the way for the development of nanocryotron processors, from which multiple superconducting platforms may benefit

Cross-polarized photon-pair generation and bi-chromatically pumped optical parametric oscillation on a chip

Nonlinear optical processes are one of the most important tools in modern optics with a broad spectrum of applications in, for example, frequency conversion, spectroscopy, signal processing and quantum optics. For practical and ultimately widespread implementation, on-chip devices compatible with electronic integrated circuit technology offer great advantages in terms of low cost, small footprint, high performance and low energy consumption. While many on-chip key components have been realized, to date polarization has not been fully exploited as a degree of freedom for integrated nonlinear devices. In particular, frequency conversion based on orthogonally polarized beams has not yet been demonstrated on chip. Here we show frequency mixing between orthogonal polarization modes in a compact integrated microring resonator and demonstrate a bi-chromatically pumped optical parametric oscillator. Operating the device above and below threshold, we directly generate orthogonally polarized beams, as well as photon pairs, respectively, that can find applications, for example, in optical communication and quantum optics

2-Methoxyoestradiol-3,17-O,O-bis-sulphamate and 2-deoxy-D-glucose in combination: a potential treatment for breast and prostate cancer

Drug combination therapy is a key strategy to improve treatment efficacy and survival of cancer patients. In this study the effects of combining 2-methoxyoestradiol-3,17-O,O-bis-sulphamate (STX140), a microtubule disruptor, with 2-deoxy-D-glucose (2DG) were assessed in MCF-7 (breast) and LNCaP (prostate) xenograft models in vivo. In mice bearing MCF-7 xenografts, daily p.o. administration of STX140 (5 mg kg−1) resulted in a 46% (P<0.05) reduction of tumour volume. However, the combination of STX140 (5 mg kg−1 p.o.) and 2DG (2 g kg−1 i.p.) reduced tumour volume by 76% (P<0.001). 2-Methoxyoestradiol-3,17-O,O-bis-sulphamate also reduced tumour vessel density. 2-Deoxy-D-glucose alone had no significant effect on tumour volume or vessel density. A similar benefit of the combination treatment was observed in the LNCaP prostate xenograft model. In vitro the degree of inhibition of cell proliferation by STX140 was unaffected by oxygen concentrations. In contrast, the inhibition of proliferation by 2DG was enhanced under hypoxia by 20 and 25% in MCF-7 and LNCaP cells, respectively. The combination of STX140 and 2DG in LNCaP cells under normoxia or hypoxia inhibited proliferation to a greater extent than either compound alone. These results suggest that the antiangiogenic and microtubule disruption activities of STX140 may make tumours more susceptible to inhibition of glycolysis by 2DG. This is the first study to show the benefit of combining a microtubule disruptor with 2DG in the two most common solid tumours

A pulsation analysis of K2 observations of the subdwarf B star PG 1142-037 during Campaign 1 : A subsynchronously rotating ellipsoidal variable

We report a new subdwarf B pulsator, PG 1142-037, discovered during the first full-length campaign of K2, the two-gyro mission of the Kepler space telescope. 14 periodicities have been detected between 0.9 and 2.5 hr with amplitudes below 0.35 parts-per-thousand. We have been able to associate all of the pulsations with low-degree, 1Peer reviewe

STX140, but not paclitaxel, inhibits mammary tumour initiation and progression in C3(1)/SV40 T/t-antigen transgenic mice.

Despite paclitxael's clinical success, treating hormone-refractory breast cancer remains challenging. Paclitaxel has a poor pharmacological profile, characterized by a low therapeutic index (TIX) caused by severe dose limiting toxicities, such as neutropenia and peripheral neuropathy. Consequently, new drugs are urgently required. STX140, a compound previously shown to have excellent efficacy against many tumors, is here compared to paclitaxel in three translational in vivo breast cancer models, a rat model of peripheral neuropathy, and through pharmacological testing. Three different in vivo mouse models of breast cancer were used; the metastatic 4T1 orthotopic model, the C3(1)/SV40 T-Ag model, and the MDA-MB-231 xenograft model. To determine TIX and pharmacological profile of STX140, a comprehensive dosing regime was performed in mice bearing MDA-MD-231 xenografts. Finally, peripheral neuropathy was examined using a rat plantar thermal hyperalgesia model. In the 4T1 metastatic model, STX140 and paclitaxel significantly inhibited primary tumor growth and lung metastases. All C3(1)/SV40 T-Ag mice in the control and paclitaxel treated groups developed palpable mammary cancer. STX140 blocked 47% of tumors developing and significantly inhibited growth of tumors that did develop. STX140 treatment caused a significant (P<0.001) survival advantage for animals in early and late intervention groups. Conversely, in C3(1)/SV40 T-Ag mice, paclitaxel failed to inhibit tumor growth and did not increase survival time. Furthermore, paclitaxel, but not STX140, induced significant peripheral neuropathy and neutropenia. These results show that STX140 has a greater anti-cancer efficacy, TIX, and reduced neurotoxicity compared to paclitaxel in C3(1)/SV40 T-Ag mice and therefore may be of significant benefit to patients with breast cancer

Behavioral Economic Measurement of Cigarette Demand: A Descriptive Review of Published Approaches to the Cigarette Purchase Task

The cigarette purchase task (CPT) is a behavioral economic method for assessing demand for cigarettes. Growing interest in behavioral correlates of tobacco use in clinical and general populations as well as empirical efforts to inform policy has seen an increase in published articles employing the CPT. Accordingly, an examination of the published methods and procedures for obtaining these behavioral economic metrics is timely. The purpose of this investigation was to provide a review of published approaches to using the CPT. We searched specific Boolean operators ([“behavioral economic” AND “purchase task”] OR [“demand” AND “cigarette”]) and identified 49 empirical articles published through the year 2018 that reported administering a CPT. Articles were coded for participant characteristics (e.g., sample size, population type, age), CPT task structure (e.g., price framing, number and sequence of prices; vignettes, contextual factors), and data analytic approach (e.g., method of generating indices of cigarette demand). Results of this review indicate no standard approach to administering the CPT and underscore the need for replicability of these behavioral economic measures for the purpose of guiding clinical and policy decisions

Critical research gaps and translational priorities for the successful prevention and treatment of breast cancer

INTRODUCTION Breast cancer remains a significant scientific, clinical and societal challenge. This gap analysis has reviewed and critically assessed enduring issues and new challenges emerging from recent research, and proposes strategies for translating solutions into practice. METHODS More than 100 internationally recognised specialist breast cancer scientists, clinicians and healthcare professionals collaborated to address nine thematic areas: genetics, epigenetics and epidemiology; molecular pathology and cell biology; hormonal influences and endocrine therapy; imaging, detection and screening; current/novel therapies and biomarkers; drug resistance; metastasis, angiogenesis, circulating tumour cells, cancer 'stem' cells; risk and prevention; living with and managing breast cancer and its treatment. The groups developed summary papers through an iterative process which, following further appraisal from experts and patients, were melded into this summary account. RESULTS The 10 major gaps identified were: (1) understanding the functions and contextual interactions of genetic and epigenetic changes in normal breast development and during malignant transformation; (2) how to implement sustainable lifestyle changes (diet, exercise and weight) and chemopreventive strategies; (3) the need for tailored screening approaches including clinically actionable tests; (4) enhancing knowledge of molecular drivers behind breast cancer subtypes, progression and metastasis; (5) understanding the molecular mechanisms of tumour heterogeneity, dormancy, de novo or acquired resistance and how to target key nodes in these dynamic processes; (6) developing validated markers for chemosensitivity and radiosensitivity; (7) understanding the optimal duration, sequencing and rational combinations of treatment for improved personalised therapy; (8) validating multimodality imaging biomarkers for minimally invasive diagnosis and monitoring of responses in primary and metastatic disease; (9) developing interventions and support to improve the survivorship experience; (10) a continuing need for clinical material for translational research derived from normal breast, blood, primary, relapsed, metastatic and drug-resistant cancers with expert bioinformatics support to maximise its utility. The proposed infrastructural enablers include enhanced resources to support clinically relevant in vitro and in vivo tumour models; improved access to appropriate, fully annotated clinical samples; extended biomarker discovery, validation and standardisation; and facilitated cross-discipline working. CONCLUSIONS With resources to conduct further high-quality targeted research focusing on the gaps identified, increased knowledge translating into improved clinical care should be achievable within five years

The in vivo properties of STX243: a potent angiogenesis inhibitor in breast cancer

The steroidal-based drug 2-ethyloestradiol-3,17-O,O-bis-sulphamate (STX243) has been developed as a potent antiangiogenic and antitumour compound. The objective of this study was to ascertain whether STX243 is more active in vivo than the clinically relevant drug 2-methoxyoestradiol (2-MeOE2) and the structurally similar compound 2-MeOE2-3,17-O,O-bis-sulphamate (STX140). The tumour growth inhibition efficacy, antiangiogenic potential and pharmacokinetics of STX243 were examined using four in vivo models. Both STX243 and STX140 were capable of retarding the growth of MDA-MB-231 xenograft tumours (72 and 63%, respectively), whereas no inhibition was observed for animals treated with 2-MeOE2. Further tumour inhibition studies showed that STX243 was also active against MCF-7 paclitaxel-resistant tumours. Using a Matrigel plug-based model, in vivo angiogenesis was restricted with STX243 and STX140 (50 and 72%, respectively, using a 10 mg kg−1 oral dose), thereby showing the antiangiogenic activity of both compounds. The pharmacokinetics of STX243 were examined at two different doses using adult female rats. The compound was orally bioavailable (31% after a single 10 mg kg−1 dose) and resistant to metabolism. These results show that STX243 is a potent in vivo drug and could be clinically effective at treating a number of oncological conditions