183 research outputs found
Block to granular-like transition in dense bubble flows
We have experimentally investigated 2-dimensional dense bubble flows
underneath inclined planes. Velocity profiles and velocity fluctuations have
been measured. A broad second-order phase transition between two dynamical
regimes is observed as a function of the tilt angle . For low
values, a block motion is observed. For high values, the velocity
profile becomes curved and a shear velocity gradient appears in the flow.Comment: Europhys. Lett. (2003) in pres
Instability of dilute granular flow on rough slope
We study numerically the stability of granular flow on a rough slope in
collisional flow regime in the two-dimension. We examine the density dependence
of the flowing behavior in low density region, and demonstrate that the
particle collisions stabilize the flow above a certain density in the parameter
region where a single particle shows an accelerated behavior. Within this
parameter regime, however, the uniform flow is only metastable and is shown to
be unstable against clustering when the particle density is not high enough.Comment: 4 pages, 6 figures, submitted to J. Phys. Soc. Jpn.; Fig. 2 replaced;
references added; comments added; misprints correcte
Europatitan eastwoodi, a new sauropod from the lower Cretaceous of Iberia in the initial radiation of somphospondylans in Laurasia
The sauropod of El Oterillo II is a specimen that was excavated from the Castrillo de la Reina Formation (Burgos, Spain), late Barremian-early Aptian, in the 2000s but initially remained undescribed. A tooth and elements of the axial skeleton, and the scapular and pelvic girdle, represent it. It is one of the most complete titanosauriform sauropods from the Early Cretaceous of Europe and presents an opportunity to deepen our understanding of the radiation of this clade in the Early Cretaceous and study the paleobiogeographical relationships of Iberia with Gondwana and with other parts of Laurasia. The late Barremian-early Aptian is the time interval in the Cretaceous with the greatest diversity of sauropod taxa described in Iberia: two titanosauriforms, Tastavinsaurus and Europatitan; and a rebbachisaurid, Demandasaurus. The new sauropod Europatitan eastwoodi n. gen. n. sp. presents a series of autapomorphic characters in the presacral vertebrae and scapula that distinguish it from the other sauropods of the Early Cretaceous of Iberia. Our phylogenetic study locates Europatitan as the basalmost member of the Somphospondyli, clearly differentiated from other clades such as Brachiosauridae and Titanosauria, and distantly related to the contemporaneous Tastavinsaurus. Europatitan could be a representative of a Eurogondwanan fauna like Demandasaurus, the other sauropod described from the Castrillo de la Reina Formation. The presence of a sauropod fauna with marked Gondwananan affinities in the Aptian of Iberia reinforces the idea of faunal exchanges between this continental masses during the Early Cretaceous. Further specimens and more detailed analysis are needed to elucidate if this Aptian fauna is caused by the presence of previously unnoticed Aptian land bridges, or it represents a relict fauna from an earlier dispersal event
Diphasic non-local model for granular surface flows
Considering recent results revealing the existence of multi-scale rigid
clusters of grains embedded in granular surface flows, i.e. flows down an
erodible bed, we describe here the surface flows rheology through a non-local
constitutive law. The predictions of the resulting model are compared
quantitatively to experimental results: The model succeeds to account for the
counter-intuitive shape of the velocity profile observed in experiments, i.e. a
velocity profile decreasing exponentially with depth in the static phase and
remaining linear in the flowing layer with a velocity gradient independent of
both the flowing layer thickness, the angle between the flow and the
horizontal, and the coefficient of restitution of the grains. Moreover, the
scalings observed in rotating drums are recovered, at least for small rotating
speed.Comment: 7 pages, submitted to Europhys. Let
Thick surface flows of granular materials: The effect of the velocity profile on the avalanche amplitude
A few years ago, Bouchaud al. introduced a phenomenological model to describe
surface flows of granular materials [J. Phys. Fr. I, 4, 1383 (1994)]. According
to this model, one can distinguish between a static phase and a rolling phase
that are able to exchange grains through an erosion/accretion mechanism.
Boutreux et al. [Phys. Rev. E, 58, 4692 (1998)] proposed a modification of the
exchange term in order to describe thicker flows where saturation effects are
present. However, these approaches assumed that the downhill convection
velocity of the grains is constant inside the rolling phase, a hypothesis that
is not verified experimentally. In this article, we therefore modify the above
models by introducing a velocity profile in the flow, and study the physical
consequences of this modification in the simple situation of an avalanche in an
open cell. We present a complete analytical description of the avalanche in the
case of a linear velocity profile, and generalize the results for a power-law
dependency. We show, in particular, that the amplitude of the avalanche is
strongly affected by the velocity profile.Comment: 7 figures, accepted for publication in Phys. Rev.
Bioavailability of two oral fentanyl transmucosal formulations in healthy volunteers: an open-label, crossover, randomised study.
Introduction: Oral transmucosal fentanyl citrate (OTFC)
was the first product specifically designed for the treatment of
breakthrough pain. It is formulated as a sweetened lozenge on
a plastic handle (stick) and it is self-administered by the patient,
allowing the modulability or flexibility in dosing.
Objectives: To prove bioequivalence of a test (T) OTFC product compared to the reference (R) formulation.
Material and methods: Open-label, crossover, randomized,
single-dose bioequivalence study in healthy volunteers, with two
study periods and two sequences, with a washout period of at
least 10 days. On each study day, subjects received 400 ÎĽg of
fentanyl. They were instructed to rub the tablet gently against
the buccal mucosa and not to suck on or chew it, and the investigators controlled each administration to ensure that it was
consumed during 15 minutes. Given the high pharmacokinetic
variability, a two-stage design was established and bioequivalence decision was based on 94.12% confidence intervals of Cmax
and AUC0-t geometric means ratio.
Results: 36 subjects completed the study according to
the protocol. Mean Cmax were similar with both formulations
(814.78 pg/ml for T and 781.83 pg/ml for R) and were attained at the same time (40 min. for T and 50 min. for R), and their
bioavailability was also very close (AUC0-t: 3920.12 pg.h/ml
for T and 3679.39 pg.h/ml for R). Bioequivalence was confirmed for the two primary parameters, Cmax and AUC0-t. No
period or sequence effects were observed in any parameter.
As bioequivalence was proved in the first phase of the study, it
was not necessary to proceed to the second stage. The estimated intraindividual variability was 24.66% and 19.01%, respectively for T and R formulations. Both formulations were well
tolerated; 15 mild adverse events were reported.
Discussion: The test OTFC product is bioequivalent to the
reference one and therefore interchangeable when used clinically. OTFC administration provides faster fentanyl absorption
than enteral route and the rate of absorption can be modulated
by the administration technique, providing a unique flexibility
among all breakthrough pain treatments. The results showed
a fast time to maximum concentrations (tmax), in accordance
with those originally reported for the reference product, probably favoured by the strict administration technique. Proper
patient education is essential to optimize the use of OTFC, as
well-trained patients can take advantage of its flexibility to selfcontrolling pain relief
Single-institution experience in clinical trials during the COVID-19 pandemic in Spain: Not so bad after all?
The impact of the COVID-19 outbreak in Spain during
March-April 2020 has been unbalanced throughout
the different regions of the country. The alarm status
defined by the government on March 14, and still in
place at the time of this writing, has transformed the
country in different perspectives, including care of
patients with cancer.1 In many centers, clinical trial
activity was suspended, because it was not considered
a priority under the health care challenge of the
COVID-19 pandemic.2 Nevertheless, experimental
therapy is the only and/or best therapeutic option for
many patients with cancer
La Cantalera: an exceptional window onto the vertebrate biodiversity of the Hauterivian-Barremian transition in the Iberian Peninsula.
La Cantalera is an accumulation site for fossil vertebrates consisting mainly of teeth and isolated postcranial remains. It has the greatest vertebrate biodiversity of any site from the Hauterivian-Barremian transition in the Iberian Peninsula. Up to now, 31 vertebrate taxa have been recognized: an osteichthyan (Teleostei indet.), two amphibians (Albanerpetonidae indet. and Discoglossidae indet.), a chelonian (Pleurosternidae? indet.), a lizard (Paramacellodidae? indet.), four crocodylomorphs (cf. Theriosuchus sp., Bernissartiidae indet., Goniopholididae indet., cf. Lisboasaurus sp.), two pterosaurs (Istiodactylidae? indet., Ornithocheiridae? indet.), four ornithopod dinosaurs (Iguanodontoidea indet., Hadrosauroidea? indet., “Hypsilophodontidae” indet., Rhabdodontidae? indet.), a thyreophoran (Polacanthidae indet.), a sauropod (Euhelopodidae indet.), eleven theropods (Carcharodontosauridae? indet., Baryonychinae indet., aff. Paronychodon sp., Maniraptora indet. 1-3, Dromaeosaurinae indet. 1-3, Velociraptorinae indet., Avialae? indet.) and three or four multituberculate mammals (Cantalera abadi, Eobaatar sp., Plagiaulacidae or Eobaataridae gen. et sp. indet., “Plagiaulacida” indet.). Nine ootaxa have also been distinguished at the site of La Cantalera. Oofamilies assigned to dinosaurs (Elongaloolithidae, Prismatoolithidae, cf. Spheroolithidae), to crocodiles (Krokolithidae) and eggshells of two oofamilies incertidae sedis are represented. This association is consistent with the record of bone and tooth remains from the site. La Cantalera was formed in a marshy environment where there was an intermittent body of water. The great majority of the vertebrate fossil remains lack evidence of transport, so the preserved association is a good representation of the vertebrate ecosystem in or around the marshy area of La Cantalera. The vertebrate association of La Cantalera displays certain differences with respect to those from lacustrine environments of the Hauterivian-Barremian transition of the Iberian Range. These differences include, for example, the absence of Chondrichthyes, the merely token presence of the osteichthyans, the scarcity of chelonians, the presence of exclusively multituberculate mammals, the lower diversity of sauropods and the greater diversity of theropods
Outbreak of acute gastroenteritis in an air force base in Western Greece
BACKGROUND: On the 20(th )September 2005, soldiers and staff at the Air Force base in Western Greece experienced an outbreak of acute gastroenteritis. The purpose of this study was to identify the agent and the source of the outbreak in order to develop control measures and to avoid similar outbreaks in the future. METHODS: A case-control analytical approach was employed with 100 randomly selected cases and 66 controls. Patients completed standardized questionnaires, odds ratios were calculated and statistical significance was determined using χ(2 )test. In addition, to identify the source of the infection, we performed bacteriological examination of food samples (included raw beef, cooked minced meat, grated cheese and grated cheese in sealed package) collected from the cuisine of the military unit. RESULTS: More than 600 out of the 1,050 individuals who ate lunch that day, became ill. The overall attack rate, as the military doctor of the unit estimated it, was at least 60%. The overall odds ratio of gastroenteritis among those who had lunch was 370 (95% CI: 48–7700) as compared to those who didn't eat lunch. Among the symptoms the most prominent were watery diarrhoea (96%) and abdominal pain (73%). The mean incubation period was 9 h and the median duration of the symptoms was 21 h. In the bacteriological examination, Staphylococcus aureus was detected in a sample of raw beef (2,000 cfu per g) and in two samples of grated cheese; leftover cheese from lunch (7,800 cfu per g) and an unopened package purchased from the market (3,000 cfu per g). CONCLUSION: The findings of this study suggest that the aetiological agent of this outbreak was S. aureus. The food vehicle was the grated cheese, which was mixed with the beef and served for lunch in the military unit. This outbreak highlights the capacity of enterotoxin-producing bacteria to cause short term, moderately-severe illness in a young and healthy population. It underscores the need for proper food handling practices and reinforces the public health importance of timely notification of such outbreaks
Role of β-glucosidase 2 in aberrant glycosphingolipid metabolism: model of glucocerebrosidase deficiency in zebrafish
β-glucosidases (GBA1 [glucocerebrosidase], GBA2, and GBA3) are ubiquitous, essential enzymes. Lysosomal GBA1 and cytosol-facing GBA2 degrade glucosylceramide (GlcCer); GBA1 deficiency causes Gaucher disease (GD), a lysosomal storage disorder characterized by lysosomal accumulation of GlcCer, which is partly converted to glucosylsphingosine (GlcSph). GBA1 and GBA2 also may transfer glucose from GlcCer to cholesterol, yielding glucosylated cholesterol (GlcChol). Here, we aimed to clarify the role of zebrafish Gba2 in glycosphingolipid metabolism during Gba1 deficiency in zebrafish (Danio rerio), which are able to survive total Gba1 deficiency. We developed Gba1 and Gba2 zebrafish knockouts (gba1-/- and gba2-/-, respectively) using CRISPR/Cas9, modulated glucosidases genetically and pharmacologically, studied GlcCer metabolism in individual larvae, and explored the feasibility of pharmacologic or genetic interventions. Activity-based probes and quantification of relevant glycolipid metabolites confirmed enzyme deficiency. GlcSph increased in gba1-/- larvae (0.09 pmol/fish) but did not increase more in gba1-/-:gba2-/- larvae. GlcCer was comparable in gba1-/- and wild-type (WT) larvae but increased in gba2-/- and gba1-/-:gba2-/- larvae. Independent of Gba1 status, GlcChol was low in all gba2-/- larvae (0.05 vs. 0.18. pmol/fish in WT). Pharmacologic inactivation of zebrafish Gba1 comparably increased GlcSph. Inhibition of glucosylceramide synthase in Gba1-deficient larvae reduced GlcCer and GlcSph, and concomitant inhibition of glucosylceramide synthase and Gba2 with iminosugars also reduced excessive GlcChol. Finally, overexpression of human GBA1 and injection of recombinant GBA1 both decreased GlcSph. We determined that zebrafish larvae offer an attractive model to study glucosidase actions in glycosphingolipid metabolism in vivo, and we identified distinguishing characteristics of zebrafish Gba2 deficiency. Animal science
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