Geometrical jitter and bolometric regime in photon detection by straight superconducting nanowire

We present a direct observation of the geometrical jitter in single photon detection by a straight superconducting nanowire. Differential measurement technique was applied to the 180-{\mu}m long nanowire similar to those commonly used in the technology of superconducting nanowire single photon detectors (SNSPD). A non-gaussian geometrical jitter appears as a wide almost uniform probability distribution (histogram) of the delay time (latency) of the nanowire response to detected photon. White electrical noise of the readout electronics causes broadened, Gaussian shaped edges of the histogram. Subtracting noise contribution, we found for the geometrical jitter a standard deviation of 8.5 ps and the full width at half maximum (FWHM) of the distribution of 29 ps. FWHM corresponds to the propagation speed of the electrical signal along the nanowire of $6.2\times10^{6}$ m/s or 0.02 of the speed of light. Alternatively the propagation speed was estimated from the central frequency of the measured first order self-resonance of the nanowire. Both values agree well with each other and with previously reported values. As the intensity of the incident photon flux increases, the wide probability distribution collapses into a much narrower Gaussian distribution with a standard deviation dominated by the noise of electronics. We associate the collapse of the histogram with the transition from the discrete, single photon detection to the uniform bolometric regim

A heuristic solution method for node routing based solid waste collection problems

This paper considers a real world waste collection problem in which glass, metal, plastics, or paper is brought to certain waste collection points by the citizens of a certain region. The collection of this waste from the collection points is therefore a node routing problem. The waste is delivered to special sites, so called intermediate facilities (IF), that are typically not identical with the vehicle depot. Since most waste collection points need not be visited every day, a planning period of several days has to be considered. In this context three related planning problems are considered. First, the periodic vehicle routing problem with intermediate facilities (PVRP-IF) is considered and an exact problem formulation is proposed. A set of benchmark instances is developed and an efficient hybrid solution method based on variable neighborhood search and dynamic programming is presented. Second, in a real world application the PVRP-IF is modified by permitting the return of partly loaded vehicles to the depots and by considering capacity limits at the IF. An average improvement of 25% in the routing cost is obtained compared to the current solution. Finally, a different but related problem, the so called multi-depot vehicle routing problem with inter-depot routes (MDVRPI) is considered. In this problem class just a single day is considered and the depots can act as an intermediate facility only at the end of a tour. For this problem several instances and benchmark solutions are available. It is shown that the algorithm outperforms all previously published metaheuristics for this problem class and finds the best solutions for all available benchmark instances

Timing jitter in photon detection by straight superconducting nanowires: Effect of magnetic field and photon flux

We studied the effect of the external magnetic field and photon flux on timing jitter in photon detection by straight superconducting NbN nanowires. At two wavelengths 800 and 1560 nm, statistical distribution in the appearance time of the photon count exhibits Gaussian shape at small times and exponential tail at large times. The characteristic exponential time is larger for photons with smaller energy and increases with external magnetic field while variations in the Gaussian part of the distribution are less pronounced. Increasing photon flux drives the nanowire from quantum detection mode to the bolometric mode that averages out fluctuations of the total number of nonequilibrium electrons created by the photon and drastically reduces jitter. The difference between Gaussian parts of distributions for these two modes provides the measure for the electron-number fluctuations. Corresponding standard deviation increases with the photon energy. We show that the two-dimensional hot-spot detection model explains qualitatively the effect of magnetic field

Observation of enhanced chiral asymmetries in the inner-shell photoionization of uniaxially oriented methyloxirane enantiomers

Most large molecules are chiral in their structure: they exist as two enantiomers, which are mirror images of each other. Whereas the rovibronic sublevels of two enantiomers are almost identical, it turns out that the photoelectric effect is sensitive to the absolute configuration of the ionized enantiomer - an effect termed Photoelectron Circular Dichroism (PECD). Our comprehensive study demonstrates that the origin of PECD can be found in the molecular frame electron emission pattern connecting PECD to other fundamental photophysical effects as the circular dichroism in angular distributions (CDAD). Accordingly, orienting a chiral molecule in space enhances the PECD by a factor of about 10

AI/ML combined with next-generation sequencing of VHH immune repertoires enables the rapid identification of de novo humanized and sequence-optimized single domain antibodies: a prospective case study

Introduction: In this study, we demonstrate the feasibility of yeast surface display (YSD) and nextgeneration sequencing (NGS) in combination with artificial intelligence and machine learning methods (AI/ML) for the identification of de novo humanized single domain antibodies (sdAbs) with favorable early developability profiles.Methods: The display library was derived from a novel approach, in which VHH-based CDR3 regions obtained from a llama (Lama glama), immunized against NKp46, were grafted onto a humanized VHH backbone library that was diversified in CDR1 and CDR2. Following NGS analysis of sequence pools from two rounds of fluorescence-activated cell sorting we focused on four sequence clusters based on NGS frequency and enrichment analysis as well as in silico developability assessment. For each cluster, long short-term memory (LSTM) based deep generative models were trained and used for the in silico sampling of new sequences. Sequences were subjected to sequence- and structure-based in silico developability assessment to select a set of less than 10 sequences per cluster for production.Results: As demonstrated by binding kinetics and early developability assessment, this procedure represents a general strategy for the rapid and efficient design of potent and automatically humanized sdAb hits from screening selections with favorable early developability profiles

Intracellular calcium strongly potentiates agonist-activated TRPC5 channels

TRPC5 is a calcium (Ca2+)-permeable nonselective cation channel expressed in several brain regions, including the hippocampus, cerebellum, and amygdala. Although TRPC5 is activated by receptors coupled to phospholipase C, the precise signaling pathway and modulatory signals remain poorly defined. We find that during continuous agonist activation, heterologously expressed TRPC5 currents are potentiated in a voltage-dependent manner (∼5-fold at positive potentials and ∼25-fold at negative potentials). The reversal potential, doubly rectifying current–voltage relation, and permeability to large cations such as N-methyl-d-glucamine remain unchanged during this potentiation. The TRPC5 current potentiation depends on extracellular Ca2+: replacement by Ba2+ or Mg2+ abolishes it, whereas the addition of 10 mM Ca2+ accelerates it. The site of action for Ca2+ is intracellular, as simultaneous fura-2 imaging and patch clamp recordings indicate that potentiation is triggered at ∼1 µM [Ca2+]. This potentiation is prevented when intracellular Ca2+ is tightly buffered, but it is promoted when recording with internal solutions containing elevated [Ca2+]. In cell-attached and excised inside-out single-channel recordings, increases in internal [Ca2+] led to an ∼10–20-fold increase in channel open probability, whereas single-channel conductance was unchanged. Ca2+-dependent potentiation should result in TRPC5 channel activation preferentially during periods of repetitive firing or coincident neurotransmitter receptor activation