A random walker on a ratchet

We analyze a model for a walker moving on a ratchet potential. This model is motivated by the properties of transport of motor proteins, like kinesin and myosin. The walker consists of two feet represented as two particles coupled nonlinearly through a bistable potential. In contrast to linear coupling, the bistable potential admits a richer dynamics where the ordering of the particles can alternate during the walking. The transitions between the two stable states on the bistable potential correspond to a walking with alternating particles. We distinguish between two main walking styles: alternating and no alternating, resembling the hand-over-hand and the inchworm walking in motor proteins, respectively. When the equilibrium distance between the two particles divided by the periodicity of the ratchet is an integer, we obtain a maximum for the current, indicating optimal transport.Comment: 10 pages, 5 figure

Improving the Cost-Effectiveness of Artificial Visual Baits for Controlling the Tsetse Fly Glossina fuscipes fuscipes

Tsetse flies, which transmit sleeping sickness to humans and nagana to cattle, are commonly controlled by stationary artificial baits consisting of traps or insecticide-treated screens known as targets. In Kenya the use of electrocuting sampling devices showed that the numbers of Glossina fuscipes fuscipes (Newstead) visiting a biconical trap were nearly double those visiting a black target of 100 cm×100 cm. However, only 40% of the males and 21% of the females entered the trap, whereas 71% and 34%, respectively, alighted on the target. The greater number visiting the trap appeared to be due to its being largely blue, rather than being three-dimensional or raised above the ground. Through a series of variations of target design we show that a blue-and-black panel of cloth (0.06 m2) flanked by a panel (0.06 m2) of fine black netting, placed at ground level, would be about ten times more cost-effective than traps or large targets in control campaigns. This finding has important implications for controlling all subspecies of G. fuscipes, which are currently responsible for more than 90% of sleeping sickness cases

Microtubules gate tau condensation to spatially regulate microtubule functions.

Tau is an abundant microtubule-associated protein in neurons. Tau aggregation into insoluble fibrils is a hallmark of Alzheimer's disease and other types of dementia1, yet the physiological state of tau molecules within cells remains unclear. Using single-molecule imaging, we directly observe that the microtubule lattice regulates reversible tau self-association, leading to localized, dynamic condensation of tau molecules on the microtubule surface. Tau condensates form selectively permissible barriers, spatially regulating the activity of microtubule-severing enzymes and the movement of molecular motors through their boundaries. We propose that reversible self-association of tau molecules, gated by the microtubule lattice, is an important mechanism of the biological functions of tau, and that oligomerization of tau is a common property shared between the physiological and disease-associated forms of the molecule

Toward Large FOV High-Resolution X-Ray Imaging Spectrometer: Microwave Multiplexed Readout of 32 TES Microcalorimeters

We performed a small-scale demonstration at GSFC of high-resolution x-ray TES microcalorimeters read out using a microwave SQUID multiplexer. This work is part of our effort to develop detector and readout technologies for future space based x-ray instruments such as the microcalorimeter spectrometer envisaged for Lynx, a large mission concept under development for the Astro 2020 Decadal Survey. In this paper we describe our experiment, including details of a recently designed, microwave-optimized low-temperature setup that is thermally anchored to the 50 mK stage of our laboratory ADR. Using a ROACH2 FPGA at room temperature, we simultaneously read out 32 pixels of a GSFC-built detector array via a NIST-built multiplexer chip with Nb coplanar waveguide resonators coupled to RF SQUIDs. The resonators are spaced 6 MHz apart (at approx. 5.9 GHz) and have quality factors of approximately 15,000. Using flux-ramp modulation frequencies of 160 kHz we have achieved spectral resolutions of 3 eV FWHM on each pixel at 6 keV. We will present the measured system-level noise and maximum slew rates, and briefly describe the implications for future detector and readout design

Metal Absorption Systems in Spectra of Pairs of QSOs

We present the first large sample of absorption systems in paired QSOs consisting of 691 absorption systems in the spectra of 310 QSOs including 170 pairings. All these absorption systems have metal lines, usually C IV or Mg II. We see 17 cases of absorption in one line-of-sight within 200 km/s (1 Mpc) of absorption in the paired line-of-sight with the probability at least approx 50% at 100kpc, declining rapidly to 23% at 100 - 200 kpc. We detect clustering on 0.5Mpc scales and see a hint of the "fingers of God" redshift-space distortion. The distribution matches absorbers arising in galaxies at z=2 with a normal correlation function and systematic infall velocities but unusually low random pair-wise velocity differences. Absorption in gas flowing out from galaxies at a mean velocity of 250 km/s would produce vastly more elongation than we see. The UV absorption from fast winds that Adelberger et al. 2005 see in spectra of LBGs is not representative of the absorption that we see. Either the winds are confined to LBGs, or they can not extend to 40 kpc with large velocities, while continuing to make UV absorption we see, implying most metals were in place in the IGM long before z=2. Separately, when we examine the absorption seen when a sight line passes a second QSO, we see 19 absorbers within 400 km/s of the partner QSO. The probability of seeing absorption is approximately constant for impact parameters 0.1 - 1.5 Mpc. Perhaps we do not see a rapid rise in the probability at small impact parameters because the UV from QSOs destroys some absorbers near to the QSOs. The 3D distribution of 64 absorbers around 313 QSOs is to first order isotropic, with just a hint of the anisotropy expected if the QSO UV emission is beamed, or alternatively QSOs might emit UV isotropically but for a surprisingly short time of only 0.3Myr.Comment: 36 pages with 25 figures and 10 Tables Submited to MNRA

Management of patients with advanced prostate cancer—metastatic and/or castration-resistant prostate cancer: report of the Advanced Prostate Cancer Consensus Conference (APCCC) 2022

Background: Innovations in imaging and molecular characterisation together with novel treatment options have improved outcomes in advanced prostate cancer. However, we still lack high-level evidence in many areas relevant to making management decisions in daily clinical practise. The 2022 Advanced Prostate Cancer Consensus Conference (APCCC 2022) addressed some questions in these areas to supplement guidelines that mostly are based on level 1 evidence. Objective: To present the voting results of the APCCC 2022. Design, setting, and participants: The experts voted on controversial questions where high- level evidence is mostly lacking: locally advanced prostate cancer; biochemical recurrence after local treatment; metastatic hormone-sensitive, non-metastatic, and metastatic castration- resistant prostate cancer; oligometastatic prostate cancer; and managing side effects of hormonal therapy. A panel of 105 international prostate cancer experts voted on the consensus questions. Outcome measurements and statistical analysis: The panel voted on 198 pre-defined questions, which were developed by 117 voting and non-voting panel members prior to the conference following a modified Delphi process. A total of 116 questions on metastatic and/or castration- resistant prostate cancer are discussed in this manuscript. In 2022, the voting was done by a web-based survey because of COVID-19 restrictions. Results and limitations: The voting reflects the expert opinion of these panellists and did not incorporate a standard literature review or formal meta-analysis. The answer options for the consensus questions received varying degrees of support from panellists, as reflected in this article and the detailed voting results are reported in the supplementary material. We report here on topics in metastatic, hormone-sensitive prostate cancer (mHSPC), non-metastatic, castration-resistant prostate cancer (nmCRPC), metastatic castration-resistant prostate cancer (mCRPC), and oligometastatic and oligoprogressive prostate cancer. Conclusions: These voting results in four specific areas from a panel of experts in advanced prostate cancer can help clinicians and patients navigate controversial areas of management for which high-level evidence is scant or conflicting and can help research funders and policy makers identify information gaps and consider what areas to explore further. However, diagnostic and treatment decisions always have to be individualised based on patient characteristics, including the extent and location of disease, prior treatment(s), co-morbidities, patient preferences, and treatment recommendations and should also incorporate current and emerging clinical evidence and logistic and economic factors. Enrolment in clinical trials is strongly encouraged. Importantly, APCCC 2022 once again identified important gaps where there is non-consensus and that merit evaluation in specifically designed trials. Patient summary: The Advanced Prostate Cancer Consensus Conference (APCCC) provides a forum to discuss and debate current diagnostic and treatment options for patients with advanced prostate cancer. The conference aims to share the knowledge of international experts in prostate cancer with healthcare providers worldwide. At each APCCC, an expert panel votes on pre-defined questions that target the most clinically relevant areas of advanced prostate cancer treatment for which there are gaps in knowledge. The results of the voting provide a practical guide to help clinicians discuss therapeutic options with patients and their relatives as part of shared and multidisciplinary decision-making. This report focuses on the advanced setting, covering metastatic hormone-sensitive prostate cancer and both non-metastatic and metastatic castration-resistant prostate cancer. Twitter summary: Report of the results of APCCC 2022 for the following topics: mHSPC, nmCRPC, mCRPC, and oligometastatic prostate cancer. Take-home message: At APCCC 2022, clinically important questions in the management of advanced prostate cancer management were identified and discussed, and experts voted on pre-defined consensus questions. The report of the results for metastatic and/or castration- resistant prostate cancer is summarised here

Brownian motors: noisy transport far from equilibrium

Transport phenomena in spatially periodic systems far from thermal equilibrium are considered. The main emphasize is put on directed transport in so-called Brownian motors (ratchets), i.e. a dissipative dynamics in the presence of thermal noise and some prototypical perturbation that drives the system out of equilibrium without introducing a priori an obvious bias into one or the other direction of motion. Symmetry conditions for the appearance (or not) of directed current, its inversion upon variation of certain parameters, and quantitative theoretical predictions for specific models are reviewed as well as a wide variety of experimental realizations and biological applications, especially the modeling of molecular motors. Extensions include quantum mechanical and collective effects, Hamiltonian ratchets, the influence of spatial disorder, and diffusive transport.Comment: Revised version (Aug. 2001), accepted for publication in Physics Report

Search for dark matter produced in association with bottom or top quarks in √s = 13 TeV pp collisions with the ATLAS detector

A search for weakly interacting massive particle dark matter produced in association with bottom or top quarks is presented. Final states containing third-generation quarks and miss- ing transverse momentum are considered. The analysis uses 36.1 fb−1 of proton–proton collision data recorded by the ATLAS experiment at √s = 13 TeV in 2015 and 2016. No significant excess of events above the estimated backgrounds is observed. The results are in- terpreted in the framework of simplified models of spin-0 dark-matter mediators. For colour- neutral spin-0 mediators produced in association with top quarks and decaying into a pair of dark-matter particles, mediator masses below 50 GeV are excluded assuming a dark-matter candidate mass of 1 GeV and unitary couplings. For scalar and pseudoscalar mediators produced in association with bottom quarks, the search sets limits on the production cross- section of 300 times the predicted rate for mediators with masses between 10 and 50 GeV and assuming a dark-matter mass of 1 GeV and unitary coupling. Constraints on colour- charged scalar simplified models are also presented. Assuming a dark-matter particle mass of 35 GeV, mediator particles with mass below 1.1 TeV are excluded for couplings yielding a dark-matter relic density consistent with measurements