Context. Methanol is a common component of interstellar and circumstellar ice mantles and is often used as an evolution indicator in star-forming regions. The observations of gas-phase methanol in ...the interiors of dense molecular clouds at temperatures as low as 10 K suggest that non-thermal ice desorption must be active. Ice photodesorption has been proposed to explain the abundances of gas-phase molecules toward the coldest regions. Aims. Laboratory experiments were performed to investigate the potential photodesorption of methanol toward the coldest regions. Methods. Solid methanol was deposited at 8 K and UV-irradiated at various temperatures starting from 8 K. The irradiation of the ice was monitored by means of infrared spectroscopy and the molecules in the gas phase were detected using quadrupole mass spectroscopy. Fully deuterated methanol was used for confirmation of the results. Results. The photodesorption of methanol to the gas phase was not observed in the mass spectra at different irradiation temperatures. We estimate an upper limit of 3 × 10-5 molecules per incident photon. On the other hand, photon-induced desorption of the main photoproducts was clearly observed. Conclusions. The negligible photodesorption of methanol could be explained by the ability of UV-photons in the 114−180 nm (10.87−6.88 eV) range to dissociate this molecule efficiently. Therefore, the presence of gas-phase methanol in the absence of thermal desorption remains unexplained. On the other hand, we find CH4 to desorb from irradiated methanol ice, which was not found to desorb in the pure CH4 ice irradiation experiments.
More than 2% of adults harbor a pancreatic cyst, a subset of which progresses to invasive lesions with lethal consequences. To assess the genomic landscapes of neoplastic cysts of the pancreas, we ...determined the exomic sequences of DNA from the neoplastic epithelium of eight surgically resected cysts of each of the major neoplastic cyst types: serous cystadenomas (SCAs), intraductal papillary mucinous neoplasms (IPMNs), mucinous cystic neoplasms (MCNs), and solid pseudopapillary neoplasms (SPNs). SPNs are low-grade malignancies, and IPMNs and MCNs, but not SCAs, have the capacity to progress to cancer. We found that SCAs, IPMNs, MCNs, and SPNs contained 10 ± 4.6, 27 ± 12, 16 ± 7.6, and 2.9 ± 2.1 somatic mutations per tumor, respectively. Among the mutations identified, E3 ubiquitin ligase components were of particular note. Four of the eight SCAs contained mutations of the von Hippel–Lindau gene (VHL), a key component of the VHL ubiquitin ligase complex that has previously been associated with renal cell carcinomas, SCAs, and other neoplasms. Six of the eight IPMNs and three of the eight MCNs harbored mutations of RNF43, a gene coding for a protein with intrinsic E3 ubiquitin ligase activity that has not previously been found to be genetically altered in any human cancer. The preponderance of inactivating mutations in RNF43 unequivocally establish it as a suppressor of both IPMNs and MCNs. SPNs contained remarkably few genetic alterations but always contained mutations of CTNNB1, previously demonstrated to inhibit degradation of the encoded protein (β-catenin) by E3 ubiquitin ligases. These results highlight the essential role of ubiquitin ligases in these neoplasms and have important implications for the diagnosis and treatment of patients with cystic tumors.
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.
•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.
Diabet. Med. 29, 50–55 (2012)
Aims To evaluate the association between vitamin D insufficiency and peripheral neuropathy in a nationally representative sample of adults with diagnosed diabetes.
...Methods Vitamin D concentrations, medical examination variables and questionnaire results from the 2001–2004 National Health and Nutrition Examination Survey were analysed for adults ≥ 40 years old with diagnosed diabetes (unweighted n = 591, weighted n = 8.82 million). Neuropathy was defined as self report of peripheral neuropathy symptoms of painful sensation, tingling, numbness or loss of feeling in hands or feet. Additionally, Semmes–Weinstein monofilament test results were used as an indicator of neuropathy. Insufficient vitamin D was characterized as < 30 ng/ml.
Results In the weighted population, 81% of adults with diabetes had vitamin D insufficiency. Vitamin D insufficiency was more common among Hispanics (92%) and non‐Hispanic black people (98%) than among non‐Hispanic white people (76%). Within the 3 months preceding the questionnaire, 50% reported experiencing pain or numbness (paresthesia) in their hands or feet; 37% reported pain or tingling in hands or feet; and 38% reported numbness or loss of feeling in hands or feet. Eight per cent had 4–6 insensate areas on their feet as determined by the Semmes–Weinstein monofilament test. Logistic regressions demonstrate vitamin D insufficiency is associated with the adjusted composite paresthesia measure (odds ratio 2.12; 95% CI 1.17–3.85) and the adjusted numbness measure (odds ratio 2.04; 95% CI 1.18–3.52).
Conclusions Vitamin D insufficiency is associated with self‐reported peripheral neuropathy symptoms even after adjusting for demographic factors, obesity, co‐morbidities, use of medications for neuropathy and diabetes duration and control.
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
A nearby multiplanet system
Exoplanets can interact gravitationally with other objects orbiting the same star, affecting their evolution and stability. Studying these effects requires locating ...systems with multiple planets. Monitoring the nearby red dwarf star GJ 887, Jeffers
et al.
detected periodic radial velocity signals, indicating the presence of two planets on orbits with periods of about 9 and 22 days and a further candidate planet (see the Perspective by Davies). The inclinations of the orbits are unknown, so only minimum masses could be determined, but those were consistent with both planets being super-Earths—more massive than Earth but less than Neptune. This system is only 3.3 parsecs from the Sun, which should facilitate follow-up with other techniques.
Science
, this issue p.
1477
; see also p.
1432
Two super-Earth exoplanets orbit GJ 887, a red dwarf star located only 3.3 parsecs from the Sun.
The closet exoplanets to the Sun provide opportunities for detailed characterization of planets outside the Solar System. We report the discovery, using radial velocity measurements, of a compact multiplanet system of super-Earth exoplanets orbiting the nearby red dwarf star GJ 887. The two planets have orbital periods of 9.3 and 21.8 days. Assuming an Earth-like albedo, the equilibrium temperature of the 21.8-day planet is ~350 kelvin. The planets are interior to, but close to the inner edge of, the liquid-water habitable zone. We also detect an unconfirmed signal with a period of ~50 days, which could correspond to a third super-Earth in a more temperate orbit. Our observations show that GJ 887 has photometric variability below 500 parts per million, which is unusually quiet for a red dwarf.
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°.
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.
Display omitted
•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.
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