Network alterations underlying neurodegenerative diseases often precede symptoms and functional deficits. Thus, their early identification is central for improved prognosis. In Huntington's disease ...(HD), the cortico-striatal networks, involved in motor function processing, are the most compromised neural substrate. However, whether the network alterations are intrinsic of the striatum or the cortex is not fully understood.
In order to identify early HD neural deficits, we characterized neuronal ensemble calcium activity and network topology of HD striatal and cortical cultures. We used large-scale calcium imaging combined with activity-based network inference analysis. We extracted collective activity events and inferred the topology of the neuronal network in cortical and striatal primary cultures from wild-type and R6/1 mouse model of HD. Striatal, but not cortical, HD networks displayed lower activity and a lessened ability to integrate information. GABA
receptor blockade in healthy and HD striatal cultures generated similar coordinated ensemble activity and network topology, highlighting that the excitatory component of striatal system is spared in HD. Conversely, NMDA receptor activation increased individual neuronal activity while coordinated activity became highly variable and undefined. Interestingly, by boosting NMDA activity, we rectified striatal HD network alterations.
Overall, our integrative approach highlights striatal defective network integration capacity as a major contributor of basal ganglia dysfunction in HD and suggests that increased excitatory drive may serve as a potential intervention. In addition, our work provides a valuable tool to evaluate in vitro network recovery after treatment intervention in basal ganglia disorders.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
•Nine real-world problems that concerns the planning of bus services are solved.•The problem is modeled as a variant of the Open Vehicle Routing Problem.•The objective is to minimize the makespan ...instead of the total cost.•A competitive multi-start algorithm is proposed.•A specific local search for the considered problem is proposed.
The aim of this paper is to solve a real-world problem proposed by an international company operating in Spain and modeled as a variant of the Open Vehicle Routing Problem in which the makespan, i.e., the maximum time spent on the vehicle by one person, must be minimized. A competitive multi-start algorithm, able to obtain high quality solutions within reasonable computing time is proposed. The effectiveness of the algorithm is analyzed through computational testing on a set of 19 school-bus routing benchmark problems from the literature, and on 9 hard real-world problem instances.
Knowledge of the neutrino flux produced by the Neutrinos at the Main Injector (NuMI) beamline is essential to the neutrino oscillation and neutrino interaction measurements of the MINERvA, MINOS+, ...NOvA and MicroBooNE experiments at Fermi National Accelerator Laboratory. We have produced a flux prediction which uses all available and relevant hadron production data, incorporating measurements of particle production off of thin targets as well as measurements of particle yields from a spare NuMI target exposed to a 120 GeV proton beam. The result is the most precise flux prediction achieved for a neutrino beam in the one to tens of GeV energy region. We have also compared the prediction to in situ measurements of the neutrino flux and find good agreement.
Flavonoids are recognized to regulate animals' food digestion processes trough interaction with digestive enzymes. The binding capacity of hesperetin (HES), luteolin (LUT), quercetin (QUE), catechin ...(CAT) and rutin (RUT) with pancreatic α-amylase were evaluated, using UV–Vis spectroscopy, fluorescence and molecular docking. Using p-nitrophenyl-α-d-maltopentoside (pNPG5) as substrate analog, LUT showed the best inhibitory capacity, even better than that of the positive control, acarbose (ACA). A mixed-type inhibition was observed for HES, LUT and QUE, a competitive-type for ACA, while no inhibition was observed with CAT and RUT. In agreement with kinetic results, α-amylase presented a higher affinity for LUT, when analyzed by fluorescence quenching. The binding of flavonoids to amylase followed a static mechanism, where the binding of one flavonoid per enzyme molecule was observed. Docking analysis showed that flavonoids bound near to enzyme active site, while ACA bound in another site behind the catalytic triad. Extrinsic fluorescence analysis, together with docking analysis pointed out that hydrophobic interactions regulated the flavonoid-α-amylase interactions. The present study provides evidence to understand the relationship of flavonoids structure with their inhibition mechanism.
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•The inhibitory capacities of 5 flavonoids against α-amylase activity were analyzed.•The flavonoid luteolin was better inhibitor than acarbose.•Static quenching, hydrophobic binding and one cavity for enzyme-flavonoids are proposed.•Enzyme-flavonoids interactions can be explained by SAR.
Context.
It has so far proven impossible to reproduce all aspects of the solar plage chromosphere in quasi-realistic numerical models. The magnetic field configuration in the lower atmosphere is one ...of the few free parameters in such simulations. The literature only offers proxy-based estimates of the field strength, as it is difficult to obtain observational constraints in this region. Sufficiently sensitive spectro-polarimetric measurements require a high signal-to-noise ratio, spectral resolution, and cadence, which are at the limit of current capabilities.
Aims.
We use critically sampled spectro-polarimetric observations of the Ca
II
8542 Å line obtained with the CRISP instrument of the Swedish 1-m Solar Telescope to study the strength and inclination of the chromospheric magnetic field of a plage region. This will provide direct physics-based estimates of these values, which could aid modelers to put constraints on plage models.
Methods.
We increased the signal-to-noise ratio of the data by applying several methods including deep learning and PCA. We estimated the noise level to be 1 × 10
−3
I
c
. We then used STiC, a non-local thermodynamic equilibrium inversion code to infer the atmospheric structure and magnetic field pixel by pixel.
Results.
We are able to infer the magnetic field strength and inclination for a plage region and for fibrils in the surrounding canopy. In the plage we report an absolute field strength of |
B
| = 440 ± 90 G, with an inclination of 10° ±16° with respect to the local vertical. This value for |
B
| is roughly double of what was reported previously, while the inclination matches previous studies done in the photosphere. In the fibrillar region we found |
B
| = 300 ± 50 G, with an inclination of 50° ±13°.
Elastic neutrino scattering on electrons is a precisely known purely leptonic process that provides a standard candle for measuring neutrino flux in conventional neutrino beams. Using a total sample ...of 810 neutrino-electron scatters after background subtraction, the measurement reduces the normalization uncertainty on the ν μ NuMI beam flux between 2 and 20 GeV from 7.6 to 3.9%. This is the most precise measurement of neutrino-electron scattering to date, will reduce uncertainties on MINER ν A's absolute cross section measurements, and demonstrates a technique that can be used in future neutrino beams such as long baseline neutrino facility.
ABSTRACT
Many catalogues of isolated compact groups of galaxies (CGs) have been extracted using Hickson’s criteria to identify isolated, dense systems of galaxies, with at least three or four ...galaxies concordant in magnitude and redshift. But is not clear to what extent the catalogues of CGs are complete and reliable, relative to 3D truly isolated, dense groups. Using five different semi-analytical models of galaxy formation (SAMs), we identify isolated dense groups in 3D real space, containing at least three galaxies. We then build mock redshift space galaxy catalogues and run a Hickson-like CG finder. We find that the Hickson-like algorithm in redshift space is poor at recovering 3D CGs of at least three galaxies, with a purity of $\sim 10{{\ \rm per \, cent}}$ and a completeness of $\sim 22{{\ \rm per \, cent}}$. Among the $\sim 90{{\ \rm per \, cent}}$ of spurious systems, typically $60{{\ \rm per\ cent}}$ are dense structures that failed the 3D isolation criteria, while the remaining $40{{\ \rm per \, cent}}$ are chance alignments of galaxies along the line of sight, nearly all of which are within regular groups, with some variation with the SAM used for the analysis. In other words, while only 10 per cent of CGs are isolated dense groups, as intended, half are dense structures embedded within larger groups, and one-third are chance alignments within larger groups. The low completeness of the extracted CG sample is mainly due to the flux limits of the selection criteria. Our results suggest that a new observational algorithm to identify compact groups in redshift space is required to obtain dense isolated galaxy systems.
Final-state kinematic imbalances are measured in mesonless production of νμ+A→μ-+p+X in the MINERvA tracker. Initial- and final-state nuclear effects are probed using the direction of the μ- - p ...transverse momentum imbalance and the initial-state momentum of the struck neutron. Differential cross sections are compared to predictions based on current approaches to medium modeling. These models underpredict the cross section at intermediate intranuclear momentum transfers that generally exceed the Fermi momenta. As neutrino interaction models need to correctly incorporate the effect of the nucleus in order to predict neutrino energy resolution in oscillation experiments, this result points to a region of phase space where additional cross section strength is needed in current models, and demonstrates a new technique that would be suitable for use in fine-grained liquid argon detectors where the effect of the nucleus may be even larger.
Neutron production in antineutrino interactions can lead to bias in energy reconstruction in neutrino oscillation experiments, but these interactions have rarely been studied. MINERvA previously ...studied neutron production at an average antineutrino energy of ~3 GeV in 2016 and found deficiencies in leading models. In this paper, the MINERvA 6 GeV average antineutrino energy dataset is shown to have similar disagreements. A measurement of the cross section for an antineutrino to produce two or more neutrons and have low visible energy is presented as an experiment-independent way to explore neutron production modeling. This cross section disagrees with several leading models’ predictions. Neutron modeling techniques from nuclear physics are used to quantify neutron detection uncertainties on this result.
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