3,802 research outputs found
The early development of the normative mind
Normativity is pervasive in everyday human social interactions and perhaps even constitutive of human forms of group and societal living. During the past decade, there has been increased interest in the ontogeny of normativity and the role that norms play in early social reasoning and behavior. Given the ubiquity of normativity, it is vital to investigate the development of children’s normative understanding and behavior in a variety of different contexts, ranging from prosocial behavior to rational action or from linguistic competencies to cultural norms and values. Hence, in this special issue on the early development of the normative mind, researchers from different theoretical traditions have employed a number of different methods (e.g., third-party norm enforcement, judgment and reasoning, social behavior) to address different, yet related, research questions about the ontogeny of normativity. Here, we introduce the reader to the current debate and point to important research questions for the field
Streaking temporal double slit interference by an orthogonal two-color laser field
We investigate electron momentum distributions from single ionization of Ar
by two orthogonally polarized laser pulses of different color. The two-color
scheme is used to experimentally control the interference between electron wave
packets released at different times within one laser cycle. This intracycle
interference pattern is typically hard to resolve in an experiment. With the
two-color control scheme these features become the dominant contribution to the
electron momentum distribution. Furthermore the second color can be used for
streaking of the otherwise interfering wave packets establishing a which-way
marker. Our investigation shows that the visibility of the interference fringes
depends on the degree of the which-way information determined by the
controllable phase between the two pulses.Comment: submitted to PR
Sleep-Wake Cycling and Energy Conservation: Role of Hypocretin and the Lateral Hypothalamus in Dynamic State-Dependent Resource Optimization
The hypocretin (Hcrt) system has been implicated in a wide range of physiological functions from sleep-wake regulation to cardiovascular, behavioral, metabolic, and thermoregulagtory control. These wide-ranging physiological effects have challenged the identification of a parsimonious function for Hcrt. A compelling hypothesis suggests that Hcrt plays a role in the integration of sleep-wake neurophysiology with energy metabolism. For example, Hcrt neurons promote waking and feeding, but are also sensors of energy balance. Loss of Hcrt function leads to an increase in REM sleep propensity, but a potential role for Hcrt linking energy balance with REM sleep expression has not been addressed. Here we examine a potential role for Hcrt and the lateral hypothalamus (LH) in state-dependent resource allocation as a means of optimizing resource utilization and, as a result, energy conservation. We review the energy allocation hypothesis of sleep and how state-dependent metabolic partitioning may contribute toward energy conservation, but with additional examination of how the loss of thermoregulatory function during REM sleep may impact resource optimization. Optimization of energy expenditures at the whole organism level necessitates a top-down network responsible for coordinating metabolic operations in a state-dependent manner across organ systems. In this context, we then specifically examine the potential role of the LH in regulating this output control, including the contribution from both Hcrt and melanin concentrating hormone (MCH) neurons among a diverse LH cell population. We propose that this hypothalamic integration system is responsible for global shifts in state-dependent resource allocations, ultimately promoting resource optimization and an energy conservation function of sleep-wake cycling
Emergence of geometrical optical nonlinearities in photonic crystal fiber nanowires
We demonstrate analytically and numerically that a subwavelength-core
dielectric photonic nanowire embedded in a properly designed photonic crystal
fiber cladding shows evidence of a previously unknown kind of nonlinearity (the
magnitude of which is strongly dependent on the waveguide parameters) which
acts on solitons so as to considerably reduce their Raman self-frequency shift.
An explanation of the phenomenon in terms of indirect pulse negative chirping
and broadening is given by using the moment method. Our conclusions are
supported by detailed numerical simulations.Comment: 5 pages, 3 figure
Studies on the in vitro and in vivo metabolism of the synthetic opioids U-51754, U-47931E, and methoxyacetylfentanyl using hyphenated high-resolution mass spectrometry
New Synthetic Opioids (NSOs) are one class of New Psychoactive Substances (NPS) enjoying increasing popularity in Europe. Data on their toxicological or metabolic properties have not yet been published for most of them. In this context, the metabolic fate of three NSOs, namely, trans-3,4-dichloro-N-[2-(dimethylamino)cyclohexyl]-N-methyl-benzenacetamide (U-51754), trans-4-bromo-N-[2-(dimethylamino)cyclohexyl]-N-methyl-benzamide (U-47931E), and 2-methoxy-N-phenyl-N-[1-(2-phenylethyl)piperidin-4-yl] acetamide (methoxyacetylfentanyl), was elucidated by liquid chromatography high-resolution mass spectrometry after pooled human S9 fraction (phS9) incubations and in rat urine after oral administration. The following major reactions were observed: demethylation of the amine moiety for U-51754 and U-47931E, N-hydroxylation of the hexyl ring, and combinations thereof. N-dealkylation, O-demethylation, and hydroxylation at the alkyl part for methoxyacetylfentanyl. Except for U-47931E, parent compounds could only be found in trace amounts in rat urine. Therefore, urinary markers should preferably be metabolites, namely, the N-demethyl-hydroxy and the hydroxy metabolite for U-51754, the N-demethylated metabolite for U-47931E, and the N-dealkylated metabolite as well as the O-demethylated one for methoxyacetylfentanyl. In general, metabolite formation was comparable in vitro and in vivo, but fewer metabolites, particularly those after multiple reaction steps and phase II conjugates, were found in phS9. These results were consistent with those of comparable compounds obtained from human liver microsomes, human hepatocytes, and/or human case studies
Observation of the Efimov state of the helium trimer
Quantum theory dictates that upon weakening the two-body interaction in a
three-body system, an infinite number of three-body bound states of a huge
spatial extent emerge just before these three-body states become unbound. Three
helium atoms have been predicted to form a molecular system that manifests this
peculiarity under natural conditions without artificial tuning of the
attraction between particles by an external field. Here we report experimental
observation of this long predicted but experimentally elusive Efimov state of
He by means of Coulomb explosion imaging. We show spatial images of
an Efimov state, confirming the predicted size and a typical structure where
two atoms are close to each other while the third is far away
Are the N-demethylated metabolites of U-47700 more active than their parent compound? In vitro μ-opioid receptor activation of N-desmethyl-U-47700 and N,N-bisdesmethyl-U-47700
Studies on the tissue distribution of the new synthetic opioid U-47700 and its main
metabolite N-desmethyl-U-47700 revealed about sixfold higher metabolite concentrations in pig brain as compared with the parent compound. To better assess the
toxic potential of this drug, the aim of this study was to assess the in vitro μ-opioid
receptor (MOR) activation potential of the main metabolites of U-47700, Ndesmethyl-U-47700, and N,N-bisdesmethyl-U-47700, using a live cell-based reporter
assay based on NanoLuc Binary Technology®. Cells stably expressing human MOR
and β-arrestin 2 (βarr2), each fused via a flexible linker to two complementary inactive
subunits of the nanoluciferase, were seeded on poly-D-lysine-coated 96-well plates
and treated with N-desmethyl-U-47700, N,N-bisdesmethyl-U-47700, U-47700, or
hydromorphone as reference standard. MOR activation results in functional complementation of the nanoluciferase, which can be assessed via luminescence monitoring.
The potency of the metabolites is lower than that of U-47700 (EC50 of 186 nM for
U-47700, 3770 nM for N-desmethyl-U-47700, and >5 μM for N,N-bisdesmethylU-47700). The maximal efficacy (Emax) observed (relative to hydromorphone, set
arbitrarily at 100%) decreased from 183% to 127% and 39.2% for U-47700,
N-desmethyl-U-47700, and N,N-bisdesmethyl-U-47700, respectively. Thus, the loss
of one or two methyl groups reduced the MOR activation potential, which was more
pronounced if both methyl groups were removed. It is thus anticipated that the
impact on MOR exerted by the higher metabolite concentration in brain has only
little—if any relevance for the strong toxic effects of U-47700
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