The experiences induced by psychedelics share a wide variety of subjective features, related to the complex changes in perception and cognition induced by this class of drugs. A remarkable increase ...in introspection is at the core of these altered states of consciousness. Self-oriented mental activity has been consistently linked to the Default Mode Network (DMN), a set of brain regions more active during rest than during the execution of a goal-directed task. Here we used fMRI technique to inspect the DMN during the psychedelic state induced by Ayahuasca in ten experienced subjects. Ayahuasca is a potion traditionally used by Amazonian Amerindians composed by a mixture of compounds that increase monoaminergic transmission. In particular, we examined whether Ayahuasca changes the activity and connectivity of the DMN and the connection between the DMN and the task-positive network (TPN). Ayahuasca caused a significant decrease in activity through most parts of the DMN, including its most consistent hubs: the Posterior Cingulate Cortex (PCC)/Precuneus and the medial Prefrontal Cortex (mPFC). Functional connectivity within the PCC/Precuneus decreased after Ayahuasca intake. No significant change was observed in the DMN-TPN orthogonality. Altogether, our results support the notion that the altered state of consciousness induced by Ayahuasca, like those induced by psilocybin (another serotonergic psychedelic), meditation and sleep, is linked to the modulation of the activity and the connectivity of the DMN.
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DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Diffusion and movement of subcutaneously injected biologics and high‐concentration immunoglobulin G (IgG) therapeutics away from the injection site and through the subcutaneous (SC) tissue may be ...concentration dependent. This possibility was confirmed by in situ measurement of diffusion coefficients of unlabeled bovine IgG in phosphate‐buffered saline within an in vitro hyaluronic acid matrix that represents the SC electrostatic environment. Diffusion decreased from 2.67 to 0.05 × 10−7 cm2/s when IgG concentration increased from 25 to 73 mg/mL. The results demonstrated that in situ detection of unlabeled proteins within an in vitro SC environment provides another useful tool for the preclinical characterization of injectable biologics.
Representative diffusion experiment (n = 3 injections, 20 μL) for bovine serum albumin at 60 min.
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BFBNIB, FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SBCE, SBMB, UL, UM, UPUK
There are currently more than 560 therapeutic monoclonal antibodies (mAbs) at various stages of research and clinical testing, including candidates for administration by subcutaneous (SC) injection. ...Preclinical studies based on in vitro measurements of high molecular weight proteins within simulated SC matrices are assisting laboratory studies of interactions of injectable biotherapeutic proteins within the SC environment in relation to bioavailability. We report a new method for directly measuring diffusion of unlabeled, high molecular weight proteins injected into an in vitro matrix that simulates the negatively charged environment of the SC. The matrix consists of 10 mg/ml HA in a repurposed cell culture chamber. The measurement consists of pipetting triplicate 20 μl protein samples into the matrix, placing the chamber in a laboratory scanner, activating tryptophan residues in the protein at 280 nm, and imaging the resulting protein fluorescence at 384 nm over a 0.5–4 h time period thus tracking protein movement. This facile approach enables mapping of protein concentration as a function of time and distance within the matrix, and determination of diffusion coefficients, D, within ±10%. Bovine IgG and BSA gave D = 2.3 ± 0.2*10−7 and 4.6 ± 0.2*10−7 cm2/s at 24°C, respectively, for initial protein concentrations of 21 mg/mL.
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BFBNIB, FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SBCE, SBMB, UL, UM, UPUK
Current study is an attempt to look into the various theoretical concepts/ theories that help to understand what motivates individuals, especially young people, to travel and which are the practical ...implications of the analysed theories. In particular, we chose Maslow's Theory of Needs to analyse youth travel motivations. The study draws its base from two streams of literature, one being associated with motivations and the other dealing with the question of how motivations can influence travelling patterns of an individual. The literature review was done extensively and articles published in the domain of tourist motivations and related areas were traced and reviewed. Our analysis of youth tourism centred on Maslow's hierarchy of needs and confirmed its validity as an explanation of the most important youth travellers' motivations. The results also indicate that, due to recent technological developments affecting societies and young tourists' behaviours - especially those of Millennials - new needs have emerged, which are discussed in detail. The research has been carried out in light of the available literature and it fails to address empirical evidence. Also, the analysis of youth tourism needs to be extended to other motivation theories as those which are presented in this work.
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CEKLJ, NUK, ODKLJ, UL, UM, UPUK
The measurement of yield stress and shear thinning flow behavior of slurries formed from unpretreated corn stover at solids loadings of 100–300 g/L provides a key metric for the ability to move, ...pump, and mix this lignocellulosic slurry, particularly since corn stover slurries represent a major potential feedstock for biorefineries. This study compared static yield stress values and flow hysteresis of corn stover slurries of 100, 150, 200, 250, and 300 g/L, after these slurries were formed by adding pellets to a cellulase enzyme solution (Celluclast 1.5 L) in a fed‐batch manner. A rotational rheometer was used to quantitate relative yield stress and its dependence on processing history at insoluble solids concentrations of 4%–21% (wt/vol). Key findings confirmed previous observations that yield stress increases with solids loadings and reaches ~3000 Pa at 25% (wt/vol) solids concentration compared to ~200 Pa after enzyme liquefaction. While optimization of slurry forming (i.e., liquefaction) conditions remains to be done, metrics for quantifying liquefaction extent are needed. The method for obtaining comparative metrics is demonstrated here and shows that the yield stress, shear thinning and shear thickening flow behaviors of enzyme liquefied corn stover slurries can be analyzed using a wide‐gap rheometry setup with relative measuring geometries to mimic the conditions that may exist in a mixing vessel of a bioreactor while applying controlled and precise levels of strain.
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BFBNIB, FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SBCE, SBMB, UL, UM, UPUK
We report on single- and double-charge photofragment formation by synchrotron radiation, following C 1s core excitation and ionization and Cl 2p inner excitation and ionization of chlorobenzene, C
6
...H
5
Cl. From a comparison of experimental near-edge X-ray absorption fine structure spectra and theoretical
ab initio
calculations, the nature of various core and inner shell transitions of the molecule and pure atomic features were identified. To shed light on the normal Auger processes following excitation or ionization of the molecule at the Cl 2p or C 1s sites, we addressed the induced ionic species formation. With energy resolved electron spectra and ion time-of-flight spectra coincidence measurements, the ionic species were correlated with binding energy regions and initial states of vacancies. We explored the formation of the molecular dication C
6
H
5
Cl
2+
, the analogue benzene dication C
6
H
4
2+
, and the singly charged species produced by single loss of a carbon atom, C
5
H
n
Cl
+
. The appearance and intensities of the spectral features associated with these ionic species are shown to be strongly site selective and dependent on the energy ranges of the Auger electron emission. Unexpected intensities for the analogue double charged benzene C
6
H
4
2+
ion were observed with fast Auger electrons. The transitions leading to C
6
H
5
Cl
2+
were identified from the binding energy representation of high resolution electron energy spectra. Most C
6
H
5
Cl
2+
ions decay into two singly charged moieties, but intermediate channels are opened leading to other heavy dicationic species, C
6
H
4
2+
and C
6
H
4
Cl
2+
, the channel leading to the first of these being much more favored than the other.
Dications formation following excitation and ionization of chlorobenzene.
Purpose
Little is known about how tourists’ eating habits change between everyday life and holidays. This study aims to identify market segments based on changes in food consumption and experiences ...of a sun-and-sea destination’s local food. The authors evaluate to what extent tourists consume local food and assess the contribution of local food experiences to the tourists’ overall experience.
Design/methodology/approach
The target population was all tourists visiting the Algarve in the Summer 2018 and included both domestic and international sun-and-sea tourists. A sample of 378 valid questionnaires was collected. Data analysis included descriptive analysis, statistical tests and cluster analysis.
Findings
Cluster analysis identified three segments: non-foodies, selective foodies and local gastronomy foodies. Results indicate that tourists change their eating habits during holidays, eating significantly more seafood and fish and less legumes, meat, fast food and cereals and their derivatives. International and domestic sun-and-sea tourists reported that eating local food contributes significantly to their overall tourism experience.
Practical implications
Sun-and-sea destinations should promote the offer of local dishes, especially those that include locally produced fish and seafood, to improve the tourist experience, differentiate the destination and increase sustainability.
Originality/value
The authors address three identified research gaps: a posteriori segmentation based on tourists’ food consumption behaviour; measurement of changes in eating practices between home and in a sun-and-sea destination; and assessment of the role of food experiences to overall tourism experience of tourists visiting a sun-and-sea destination.
The World Health Organization considers the Zika virus (ZIKV) outbreak in the Americas a global public health emergency. The neurologic complications due to ZIKV infection comprise microcephaly, ...meningoencephalitis, and Guillain-Barré syndrome. We describe a fatal case of an adult patient receiving an immunosuppressive regimen following heart transplant. The patient was admitted with acute neurologic impairment and experienced progressive hemodynamic instability and mental deterioration that finally culminated in death. At autopsy, a pseudotumoral form of ZIKV meningoencephalitis was confirmed. Zika virus infection was documented by reverse trancriptase-polymerase chain reaction, immunohistochemistry, and immunofluorescence and electron microscopy of the brain parenchyma and cerebral spinal fluid. The sequencing of the viral genome in this patient confirmed a Brazilian ZIKV strain. In this case, central nervous system involvement and ZIKV propagation to other organs in a disseminated pattern is quite similar to that observed in other fatal Flaviviridae viral infections.
Transmission of Paracoccidioides spp. fungi to humans is usually related to manipulation of soil. Rural workers are the most affected group. We report an outbreak of paracoccidioidomycosis after ...deforestation and massive earth removal during construction of a highway in Rio de Janeiro, Brazil. Extensive environmental disturbances might be involved in fungal transmission.
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DOBA, IZUM, KILJ, NUK, ODKLJ, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Patient-specific cardiomyocytes obtained from induced pluripotent stem cells (CM-iPSC) offer unprecedented mechanistic insights in the study of inherited cardiac diseases. The objective of this work ...was to study a type 2 long QT syndrome (LQTS2)-associated mutation (c.1600C > T in KCNH2, p.R534C in hERG) in CM-iPSC. Peripheral blood mononuclear cells were isolated from two patients with the R534C mutation and iPSCs were generated. In addition, the same mutation was inserted in a control iPSC line by genome editing using CRISPR/Cas9. Cells expressed pluripotency markers and showed spontaneous differentiation into the three embryonic germ layers. Electrophysiology demonstrated that action potential duration (APD) of LQTS2 CM-iPSC was significantly longer than that of the control line, as well as the triangulation of the action potentials (AP), implying a longer duration of phase 3. Treatment with the I
inhibitor E4031 only caused APD prolongation in the control line. Patch clamp showed a reduction of I
on LQTS2 CM-iPSC compared to control, but channel activation was not significantly affected. Immunofluorescence for hERG demonstrated perinuclear staining in LQTS2 CM-iPSC. In conclusion, CM-iPSC recapitulated the LQTS2 phenotype and our findings suggest that the R534C mutation in KCNH2 leads to a channel trafficking defect to the plasma membrane.
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IZUM, KILJ, NUK, PILJ, PNG, SAZU, UL, UM, UPUK
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