Quantum Simulation of the Tricritical Ising Model in Tunable Josephson Junction Ladders.

Modern hybrid superconductor-semiconductor Josephson junction arrays are a promising platform for analog quantum simulations. Their controllable and nonsinusoidal energy-phase relation opens the path to implement nontrivial interactions and study the emergence of exotic quantum phase transitions. Here, we propose the analysis of an array of hybrid Josephson junctions defining a two-leg ladder geometry for the quantum simulation of the tricritical Ising phase transition. This transition provides the paradigmatic example of minimal conformal models beyond Ising criticality and its excitations are intimately related to Fibonacci non-Abelian anyons and topological order in two dimensions. We study this superconducting system and its thermodynamic phases based on bosonization and matrix-product-state techniques. Its effective continuous description in terms of a three-frequency sine-Gordon quantum field theory suggests the presence of the targeted tricritical point and the numerical simulations confirm this picture. Our results indicate which experimental observables can be adopted in realistic devices to probe the physics and the phase transitions of the model. Additionally, our proposal provides a useful one-dimensional building block to design exotic topological order in two-dimensional scalable Josephson junction arrays.

Cold atoms meet lattice gauge theory.

The central idea of this review is to consider quantum field theory models relevant for particle physics and replace the fermionic matter in these models by a bosonic one. This is mostly motivated by the fact that bosons are more 'accessible' and easier to manipulate for experimentalists, but this 'substitution' also leads to new physics and novel phenomena. It allows us to gain new information about among other things confinement and the dynamics of the deconfinement transition. We will thus consider bosons in dynamical lattices corresponding to the bosonic Schwinger or [Formula: see text] Bose-Hubbard models. Another central idea of this review concerns atomic simulators of paradigmatic models of particle physics theory such as the Creutz-Hubbard ladder, or Gross-Neveu-Wilson and Wilson-Hubbard models. This article is not a general review of the rapidly growing field-it reviews activities related to quantum simulations for lattice field theories performed by the Quantum Optics Theory group at ICFO and their collaborators from 19 institutions all over the world. Finally, we will briefly describe our efforts to design experimentally friendly simulators of these and other models relevant for particle physics. This article is part of the theme issue 'Quantum technologies in particle physics'.

Late neuroprogenitors contribute to normal retinal vascular development in a Hif2a-dependent manner.

In the adult central nervous system, endothelial and neuronal cells engage in tight cross-talk as key components of the so-called neurovascular unit. Impairment of this important relationship adversely affects tissue homeostasis, as observed in neurodegenerative conditions including Alzheimer's and Parkinson's disease. In development, the influence of neuroprogenitor cells on angiogenesis is poorly understood. Here, we show in mouse that these cells interact intimately with the growing retinal vascular network, and we identify a novel regulatory mechanism of vasculature development mediated by hypoxia-inducible factor 2a (Hif2a). By Cre-lox gene excision, we show that Hif2a in retinal neuroprogenitor cells upregulates the expression of the pro-angiogenic mediators vascular endothelial growth factor and erythropoietin, whereas it locally downregulates the angiogenesis inhibitor endostatin. Importantly, absence of Hif2a in retinal neuroprogenitor cells causes a marked reduction of proliferating endothelial cells at the angiogenic front. This results in delayed retinal vascular development, fewer major retinal vessels and reduced density of the peripheral deep retinal vascular plexus. Our findings demonstrate that retinal neuroprogenitor cells are a crucial component of the developing neurovascular unit.

Prevention of Photoreceptor Cell Loss in a Cln6nclf Mouse Model of Batten Disease Requires CLN6 Gene Transfer to Bipolar Cells.

The neuronal ceroid lipofuscinoses (NCLs) are inherited lysosomal storage disorders characterized by general neurodegeneration and premature death. Sight loss is also a major symptom in NCLs, severely affecting the quality of life of patients, but it is not targeted effectively by brain-directed therapies. Here we set out to explore the therapeutic potential of an ocular gene therapy to treat sight loss in NCL due to a deficiency in the transmembrane protein CLN6. We found that, although Cln6nclf mice presented mainly with photoreceptor degeneration, supplementation of CLN6 in photoreceptors was not beneficial. Because the level of CLN6 is low in photoreceptors but high in bipolar cells (retinal interneurons that are only lost in Cln6-deficient mice at late disease stages), we explored the therapeutic effects of delivering CLN6 to bipolar cells using adeno-associated virus (AAV) serotype 7m8. Bipolar cell-specific expression of CLN6 slowed significantly the loss of photoreceptor function and photoreceptor cells. This study shows that the deficiency of a gene normally expressed in bipolar cells can cause the loss of photoreceptors and that this can be prevented by bipolar cell-directed treatment.

Optimal persistent currents for interacting bosons on a ring with a gauge field.

We study persistent currents for interacting one-dimensional bosons on a tight ring trap, subjected to a rotating barrier potential, which induces an artificial U(1) gauge field. We show that, at intermediate interactions, the persistent current response is maximal, due to a subtle interplay of effects due to the barrier, the interaction, and quantum fluctuations. These results are relevant for ongoing experiments with ultracold atomic gases on mesoscopic rings.

QM107, a novel CD148 (RTP Type J) activating peptide therapy for treating neovascular age-related macular degeneration.

BACKGROUND AND PURPOSE: Angiogenesis is a pathological component of neovascular age-related macular degeneration. Current therapies, although successful, are prone to high levels of patient non-response and a loss of efficacy over time, indicating the need to explore other therapeutic avenues. We have shown that an interaction between syndecan-2 and the tyrosine phosphatase receptor CD148 (RTP Type J) results in the ablation of angiogenesis. Here we exploit this pathway to develop a peptide activator of CD148 as a therapy for neovascular age-related macular degeneration. EXPERIMENTAL APPROACH: We tested a peptide (QM107) derived from syndecan-2 in a variety of angiogenesis models and a pre-clinical model of neovascular age-related macular degeneration. We assessed the toxicological and inflammatory profiles of QM107 and its stability in vitreous humour. KEY RESULTS: QM107 inhibits angiogenesis in ex vivo sprouting assays and disrupts endothelial microcapillary formation via inhibition of cell migration. QM107 acts through CD148, leading to changes in GSK3A phosphorylation and ß1 integrin activation. QM107 elicits a negligible inflammatory response and exhibits limited toxicity in cultured cells, and is stable in vitreous humour. Finally, we show proof of concept that QM107 blocks angiogenesis in vivo using a model of neovascular age-related macular degeneration. CONCLUSION AND IMPLICATIONS: We have developed a CD148 activating peptide which shows promise in inhibiting angiogenesis in models of neovascular age-related macular degeneration. This treatment could either represent an alternative or augment existing therapies, and owing to its distinct mode of action be used in patients who do not respond to existing treatments.

Reduced basis surrogates for quantum spin systems based on tensor networks.

Within the reduced basis methods approach, an effective low-dimensional subspace of a quantum many-body Hilbert space is constructed in order to investigate, e.g., the ground-state phase diagram. The basis of this subspace is built from solutions of snapshots, i.e., ground states corresponding to particular and well-chosen parameter values. Here, we show how a greedy strategy to assemble the reduced basis and thus to select the parameter points can be implemented based on matrix-product-state calculations. Once the reduced basis has been obtained, observables required for the computation of phase diagrams can be computed with a computational complexity independent of the underlying Hilbert space for any parameter value. We illustrate the efficiency and accuracy of this approach for different one-dimensional quantum spin-1 models, including anisotropic as well as biquadratic exchange interactions, leading to rich quantum phase diagrams.

Egg Removal via Cloacoscopy in Three Dystocic Leopard Geckos (Eublepharis macularius).

Dystocia is a multifactorial, life-threatening condition commonly affecting pet reptiles. Treatment for dystocia can be either medical or surgical. Medical treatment usually involves the administration of oxytocin, but in some species or, in some cases, this treatment does not work as expected. Surgical treatments such as ovariectomy or ovariosalpingectomy are resolutive, but invasive in small-sized reptiles. In this paper, we describe three cases of post ovulatory egg retention in three leopard geckos (Eublepharis macularius) successfully treated through a cloacoscopic removal of the retained eggs, after a non resolutive medical treatment. The intervention was fast, non-invasive, and no procedure-related adverse effects were noted. The problem relapsed six months later in one animal, and a successful bilateral ovariosalpingectomy was performed. Cloacoscopy should be considered a valuable, non-invasive tool for egg removal in dystocic leopard geckos when the egg is accessible to manipulation. Recrudescence or complications such as adhesions, oviductal rupture, or the presence of ectopic eggs should recommend surgical intervention.

Surrogate models for quantum spin systems based on reduced-order modeling.

We present a methodology to investigate phase diagrams of quantum models based on the principle of the reduced basis method (RBM). The RBM is built from a few ground-state snapshots, i.e., lowest eigenvectors of the full system Hamiltonian computed at well-chosen points in the parameter space of interest. We put forward a greedy strategy to assemble such a small-dimensional basis, i.e., to select where to spend the numerical effort needed for the snapshots. Once the RBM is assembled, physical observables required for mapping out the phase diagram (e.g., structure factors) can be computed for any parameter value with a modest computational complexity, considerably lower than the one associated to the underlying Hilbert space dimension. We benchmark the method in two test cases, a chain of excited Rydberg atoms and a geometrically frustrated antiferromagnetic two-dimensional lattice model, and illustrate the accuracy of the approach. In particular, we find that the ground-state manifold can be approximated to sufficient accuracy with a moderate number of basis functions, which increases very mildly when the number of microscopic constituents grows-in stark contrast to the exponential growth of the Hilbert space needed to describe each of the few snapshots. A combination of the presented RBM approach with other numerical techniques circumventing even the latter big cost, e.g., tensor network methods, is a tantalizing outlook of this work.

Sex Determination in Immature Sierra Nevada Lizard (Timon nevadensis).

Sex determination has a fundamental role in a captive breeding context, both for commercial reasons and in relation to animal welfare itself. However, this can be particularly difficult, especially in reptiles with little or no sexual dimorphism. Twenty-three clinically healthy young Sierra Nevada lizards (Timon nevadensis) were included in this study for sex determination. The first attempt at sexing was carried out by cloacal probing. A small, buttoned probe was inserted very gently into the hemipenal pouches, and the length of the inserted part was evaluated and measured. Subsequently, for each animal, a contrast medium was administered into the cloaca, and radiography was performed within 5 min. Through probing, 11 males and 8 females were recognized. The test was, however, equivocal in four subjects. In contrast radiography, 14 males and 9 females were identified. All the animals were rechecked after 8 months through an ultrasound examination, confirming 15 of the 14 previously male sexed animals based on contrast radiography. All the animals identified as female (n = 9) by contrast radiography were confirmed. From these results, it seems that contrast radiography may have major sensitivity in sex determination compared to probing. This technique could represent a valid and less invasive aid for sexing young lizards.

Evaluation of Biochemical Composition of Amniotic and Allantoic Fluids at Different Stages of Pregnancy in Queens.

Fetal fluid contents have functions in protecting fetuses and are essential for fetal development and maturation. However, little is known about the exact physiological functions of fetal fluids in fetal development, as well as the changing composition throughout the gestational period in cats. In this study, the biochemical composition of amniotic (AMN) and allantoic (ALL) fluids was investigated, as well as in the maternal serum of pregnant queens. Eighteen queens were included in this study and assigned to six different groups, D20, D25, D30, D40, D45 and D60, according to the gestational stage of fetal development. A total of 44 amniotic and 37 allantoic samples were collected. Fetal fluids contained lesser concentrations of alanine aminotransferase, albumin, cholesterol, triglycerides, creatine kinase, amylase, total protein and globulin than maternal serum. Other variables, such as aspartate aminotransferase, gamma-glutamyl transferase, bilirubin and alkaline phosphatase, were in different concentrations at specific stages of gestation when compared to maternal serum. There were no differences between fetal fluids and maternal serum for lactate dehydrogenase, urea, lipase or glucose concentrations. There were greater concentrations of creatinine in amniotic fluid than in allantoic fluid or maternal serum. Based on the results of this study, fetal fluids do not accumulate as a result of the simple filtration of maternal blood, but rather, the fetus produces many of these components as a consequence of organ development and maturation.

Metaplastic Ossification of a Giant Paraprostatic Cyst in a Dog: A Case Report.

A 7-year-old male Caucasian shepherd presented with a 3 month history of intermittent hematuria, penile discharge, and abdominal pain and distension. The dog had a history of prostatic hyperplasia with multiple cysts, diagnosed by the referring clinician two years prior to the case presentation. Two oral courses of antibiotics and antiandrogens were administered by the treating veterinarian without resolution. At the case presentation visit, massive swelling was present in the mid- and caudal parts of the abdomen. Abdominal ultrasound and exploratory laparotomy revealed a paraprostatic cyst (size: 25 × 20 × 18 cm) in the caudal part of the abdomen. The cyst had a bony ridge along the wall with multiple cauliflower-like lesions extending inside. Histopathologic examination revealed an intermittently epithelial-lined inner wall of the cyst, which was partially degenerated and flattened due to the pressure of the intraluminal fluid. The luminal surface of the cyst appeared markedly irregular with multiple structures made of dense, fibrous connective tissue protruding inside with metaplastic ossification foci, consistent with severe osseous metaplasia. The epithelium showed focal secretory activity. Numerous subepithelial multifocal neutrophil and mononuclear cellular infiltrates were found. The lumen of the cyst contained a reddish-brown (blood and protein-rich) fluid. Complete surgical excision of the cyst and omentalization of the capsular remnant resulted in successful resolution of the clinical signs.

Monitoring of the Reproductive Cycle in Captive-Bred Female Boa constrictor: Preliminary Ultrasound Observations.

The Boa constrictor is one of the most common reptiles bred in captivity. To achieve a successful breeding season, thorough knowledge of the females' reproductive activity is necessary. In this regard, information on the Boa constrictor is still rather scarce. The aim of the present study was to monitor the ovarian activity and the embryonic development of boas by ultrasound. We performed brief scans on thirty non-anaesthetized snakes using a portable ultrasound system and a 7.5-10 MHz linear array transducer (Esaote MyLab™ Classic). Ultrasound features, dimensions, and echogenicity of the preovulatory and postovulatory follicles were determined. As gestation progresses, the postovulatory follicle size increases, and the embryonic silhouette becomes increasingly recognizable. During the second month after ovulation, by using color Doppler, early embryos' heart activity could be evaluated. It is possible to highlight vascular connections between the mother and the membrane covering the embryonic structures. Ultrasound also allows one to identify follicular regression or slugs (nonfertilized eggs) early. The present study suggests that ultrasound could be an excellent noninvasive technique to evaluate the reproductive activity of Boa constrictor, allowing us to precisely identify the correct time for mating, monitor embryo development and viability, and allow the early diagnosis of follicular regression.

Restoration of visual function in advanced disease after transplantation of purified human pluripotent stem cell-derived cone photoreceptors.

Age-related macular degeneration and other macular diseases result in the loss of light-sensing cone photoreceptors, causing irreversible sight impairment. Photoreceptor replacement may restore vision by transplanting healthy cells, which must form new synaptic connections with the recipient retina. Despite recent advances, convincing evidence of functional connectivity arising from transplanted human cone photoreceptors in advanced retinal degeneration is lacking. Here, we show restoration of visual function after transplantation of purified human pluripotent stem cell-derived cones into a mouse model of advanced degeneration. Transplanted human cones elaborate nascent outer segments and make putative synapses with recipient murine bipolar cells (BCs), which themselves undergo significant remodeling. Electrophysiological and behavioral assessments demonstrate restoration of surprisingly complex light-evoked retinal ganglion cell responses and improved light-evoked behaviors in treated animals. Stringent controls exclude alternative explanations, including material transfer and neuroprotection. These data provide crucial validation for photoreceptor replacement therapy and for the potential to rescue cone-mediated vision.

The potential of different countermeasures to prevent injuries with high risk of health loss among bicyclists in Sweden.

Objective: As bicyclists account for the largest share of serious injuries in Sweden, focus to improve safety for bicyclists is needed. While knowledge about fatal bicycle crashes is rather extensive, the number of studies that have investigated non-fatal injuries is still rather limited. The aim of this study was to estimate the potential of different countermeasures to reduce crashes resulting in injuries with high risk of health-loss among cyclists in Sweden. A further aim was to describe the residual-that is, crashes that were not considered to be addressed by the analyzed countermeasures.Methods: A sample of individuals with specific injury diagnoses was drawn from the Swedish national crash database Strada. A survey form was used to collect additional information about the crash and the health-related outcomes. The potential of countermeasures currently included in the Swedish Safety Performance Indicators, as well as of countermeasures that could be described as "existing but not fully implemented" was assessed. The overall potential of all countermeasures assessed was calculated, giving a grand total without double counting. Cases that were considered not to be addressed by any of the countermeasures included (i.e., the residual crashes) were described in more detail.Results: The current Swedish Safety Performance Indicators that relate to safe cycling addressed 22% of crashes. Improved maintenance by deicing and removal of snow from bicycle infrastructure was found to have the highest potential (8%), followed by improved crashworthiness of passenger cars (5%) and safer bicycle crossings (4%). The potential for existing but not fully implemented safety improvements was 56%. The greatest potential was found for Autonomous Emergency Braking with cyclist detection for passenger cars (12%), followed by studded winter tyres for bicycles (12%), and improved maintenance on non-bicycle infrastructure (11%). In total, taking double counting into consideration, all safety improvements could address 64% of all crashes. Among the residual crashes, the majority (69%) were single bicycle crashes of which most were related to wheel locking during braking and losing balance at low speed or stationary.Conclusions: Compared with fatal crashes that involve a majority of bicycle-car crashes, the crashes leading to health-loss are mostly single bicycle crashes. Therefore, innovation and development of additional countermeasures to improve safety for bicyclists should focus on single bicycle crashes.

Active safety systems for powered two-wheelers: A systematic review.

Objective: Active safety systems, of which antilock braking is a prominent example, are going to play an important role to improve powered two-wheeler (PTW) safety. This paper presents a systematic review of the scientific literature on active safety for PTWs. The aim was to list all systems under development, identify knowledge gaps and recognize promising research areas that require further efforts.Methods: A broad search using "safety" as the main keyword was performed on Scopus, Web of Science and Google Scholar, followed by manual screening to identify eligible papers that underwent a full-text review. Finally, the selected papers were grouped by general technology type and analyzed via structured form to identify the following: specific active safety system, study type, outcome type, population/sample where applicable, and overall findings.Results: Of the 8,000 papers identified with the initial search, 85 were selected for full-text review and 62 were finally included in the study, of which 34 were journal papers. The general technology types identified included antilock braking system, autonomous emergency braking, collision avoidance, intersection support, intelligent transportation systems, curve warning, human machine interface systems, stability control, traction control, and vision assistance. Approximately one third of the studies considered the design and early stage testing of safety systems (n. 22); almost one fourth (n.15) included evaluations of system effectiveness.Conclusions: Our systematic review shows that a multiplicity of active safety systems for PTWs were examined in the scientific literature, but the levels of development are diverse. A few systems are currently available in the series production, whereas other systems are still at the level of early-stage prototypes. Safety benefit assessments were conducted for single systems, however, organized comparisons between systems that may inform the prioritization of future research are lacking. Another area of future analysis is on the combined effects of different safety systems, that may be capitalized for better performance and to maximize the safety impact of new technologies.

Arousal Modulates Retinal Output.

At various stages of the visual system, visual responses are modulated by arousal. Here, we find that in mice this modulation operates as early as in the first synapse from the retina and even in retinal axons. To measure retinal activity in the awake, intact brain, we imaged the synaptic boutons of retinal axons in the superior colliculus. Their activity depended not only on vision but also on running speed and pupil size, regardless of retinal illumination. Arousal typically reduced their visual responses and selectivity for direction and orientation. Recordings from retinal axons in the optic tract revealed that arousal modulates the firing of some retinal ganglion cells. Arousal had similar effects postsynaptically in colliculus neurons, independent of activity in the other main source of visual inputs to the colliculus, the primary visual cortex. These results indicate that arousal modulates activity at every stage of the mouse visual system.

Motorcyclist injury risk as a function of real-life crash speed and other contributing factors.

The Vision Zero approach advocates for a road transport system designed with human injury tolerance and human fallibility as its basis. While biomechanical limits and the relationship between speed and injury outcome has been extensively investigated for car occupants and pedestrians, research analyzing this relationship for motorcyclists remains limited. The aim of this study was to address this issue by developing multivariate injury risk models for motorcyclists that estimate the relationship between speed and injury severity. For that purpose, motorcycle injury crashes from the German In-Depth Accident Study (GIDAS) database for the period 1999-2017 (n = 1037) were extracted. Different models were tested using logistic regression and backwards elimination of non-significant variables. The best fitting model in the current study included relative speed, type of crash opponent, impact location on the motorcycle and impact mechanism of the rider during the crash. A strong and significant relationship between relative speed and injury severity in motorcycle crashes was demonstrated. At 70 km/h, the risk for at least serious injuries in collisions with wide objects, crash barriers and narrow objects was 20%, 51%, and 64%, respectively. Further, it was found that head-on collisions between motorcycles and passenger cars, with both vehicles traveling at 60 km/h (a relative speed at 120 km/h), present 55% risk of at least serious injury to the motorcycle rider. More research is needed to fully understand the boundary conditions needed to design a safe road transport system for motorcyclists. However, this study provides important insights into the relationship between speed and injury severity for riders in various crash situations. The results may be useful in the discussion of appropriate speed limits and in determining the benefits of countermeasures which aim to reduce crash speed.

The potential of vehicle and road infrastructure interventions in fatal bicyclist accidents on Swedish roads-What can in-depth studies tell us?

Objective: The objective of this article is to describe the characteristics of fatal crashes with bicyclists on Swedish roads in rural and urban areas and to investigate the potential of bicycle helmets and different vehicle and road infrastructure interventions to prevent them. The study has a comprehensive approach to provide road authorities and vehicle manufacturers with recommendations for future priorities. Methods: The Swedish Transport Administration's (STA) in-depth database of fatal crashes was used for case-by-case analysis of fatal cycling accidents (2006-2016) on rural (n = 82) and urban (n = 102) roads. The database consists of information from the police, medical journals, autopsy reports, accident analyses performed by STA, and witness statements. The potential of helmet use and various vehicle and road infrastructure safety interventions was determined retrospectively for each case by analyzing the chain of events leading to the fatality. The potential of vehicle safety countermeasures was analyzed based on prognoses on their implementation rates in the Swedish vehicle fleet. Results: The most common accident scenario on rural roads was that the bicyclist was struck while cycling along the side of the road. On urban roads, the majority of accidents occurred in intersections. Most accidents involved a passenger car, but heavy trucks were also common, especially in urban areas. Most accidents occurred in daylight conditions (73%). Almost half (46%) of nonhelmeted bicyclists would have survived with a helmet. It was assessed that nearly 60% of the fatal accidents could be addressed by advanced vehicle safety technologies, especially autonomous emergency braking with the ability to detect bicyclists. With regard to interventions in the road infrastructure, separated paths for bicyclists and bicycle crossings with speed calming measures were found to have the greatest safety potential. Results indicated that 91% of fatally injured bicyclists could potentially be saved with known techniques. However, it will take a long time for such technologies to be widespread. Conclusions: The majority of fatally injured bicyclists studied could potentially be saved with known techniques. A speedy implementation of important vehicle safety systems is recommended. A fast introduction of effective interventions in the road infrastructure is also necessary, preferably with a plan for prioritization.