578 research outputs found
Les sphingolipides : vecteurs d’agents pathogènes et cause de maladies génétiques
Les sphingolipides (SPL) sont des molécules ubiquitaires indispensables au maintien et au développement des organismes vivants. Ils ne sont pas répartis uniformément le long de la membrane mais regroupés sous forme de microdomaines lipidiques appelés rafts. On a longtemps pensé que les SPL avaient uniquement un rôle structural. On sait maintenant qu’ils jouent aussi un rôle de récepteur et de seconds messagers (intervenant dans des fonctions majeures de la vie cellulaire) et que de nombreuses maladies génétiques (sphingolipidoses) s’expliquent par un dysfonctionnement de leur métabolisme. Après un rappel des propriétés structurales des sphingolipides, cet article fait le point sur les relations entre leur rôle de récepteur et l’entrée d’agents pathogènes dans la cellule ainsi que sur les mécanismes pathologiques des sphingolipidoses.Sphingolipids are present in all eukaryotic cells and share a sphingoid base : sphingosine. They were first discovered in 1884 and for a long time they were thought to participate to membrane structure only. Recently it has been established that they are mainly located in particular areas of the membrane called rafts which are signalling platforms. It has also been demonstrated that sphingolipids are receptors and second messengers. They play a crucial role in cellular functioning and are necessary to maintenance and developing of living organisms. However due to their receptor properties, they are also gateway for penetration of pathogenic agents such as virus (Ebola, HIV) or toxins (botulinium, tetanus). These agents first bind to glycosphingolipids or proteins mainly located in rafts. The complex so formed is required for the crossing of the membrane by the pathogenic agent. Sphingolipids metabolism is regulated by numerous enzymes. A failure in the activity of one of them induces an accumulation of sphingolipids known as sphingolipidoses. These are genetic diseases having severe consequences for the survival of the organism. The precise mechanisms of the sphingolipidoses are still mainly unknown which explains why few therapeutic strategies are available. These particular properties of lipids rafts and sphingolipids explain why a growing number of studies in the medical and scientific fields are devoted to them
Propuesta de un modelo de gestión de inventario para optimizar los costos de inventario de productos terminados y mejorar su rentabilidad económica en la curtiembre Industrias Herpami E.I.R.L.
La Curtiembre INDUSTRIAS HERPAMI E.I.R.L es una planta industrial que se
dedica al procesamiento y a la comercialización de pieles tales como: tostado, satinado,
graso, espumado, flotter, crazy, crust, nobuck, gamuza, punto aguja, badanna, napa,
carnaza y charol. La clasificación del diagrama de Pareto, se realizó en base a los
ingresos anuales del año 2016 de cada uno de los productos terminados, obteniendo
como resultado 5 tipos de cuero los cuales son: tostado, satinado, graso, espumado y
flotter que representan el 80.56% del ingreso anual de la empresa. Según el historial
de la demanda de los años 2015-2016, la tendencia de los 5 tipos de cuero, es
suavización exponencial con tendencia y estacionalidad, por lo que se elaboró el
pronóstico de la demanda de cada uno de estos 5 tipos de cuero para el año 2017.
Se propuso a la empresa trabajar con el modelo del lote económico a producir (EOQ),
con el fin de optimizar los costos de inventario de producto terminado y aumentar la
rentabilidad económica. El modelo lote económico a producir consiste en determinar
la cantidad necesaria a producir para optimizar los costos de inventario, para su cálculo
fue necesario recopilar la información de los costos de mantener inventario, costos de
orden de producción, tasa de producción diaria y la tasa de demanda diaria.
Para una orden de producción en el tiempo adecuado es necesario apoyarse en el
método del punto de reorden (ROP) y el modelo de lote económico a producir.
Se determinó el stock de seguridad para los 5 tipos de cuero en forma probabilística
mediante la raíz cuadrada del tiempo de entrega promedio por la desviación estándar
de la demanda diaria sumado con la demanda diaria promedio por la desviación
estándar del tiempo de entrega en días, este resultado multiplicado por el nivel de
satisfacción del 90% estadísticamente tomando como referencia z= 1.28.
Por último, se hizo un análisis de costos de los inventarios y de rentabilidad económica
con el modelo propuesto. "The tannery INDUSTRIAS HERPAMI EIRL is an industrial plant that is dedicated to
processing and commercialization of skins as: tostado, satinado, graso, espumado,
flotter, crazy, crust, nobuck, gamuza, punto aguja, badanna, napa, carnaza and charol.
The Pareto chart classification was made based on the annual revenues of 2016 of each
one of the finished products, resulting in 5 types of leather which are: tostado, satinado,
graso, espumado and flotter, representing 80.56 % Of the company's annual income.
According to the demand history of the years 2015-2016, the trend of the 5 types of
leather, is exponential smoothing with trend and seasonality, so that the forecast of the
demand of each of these 5 types of leather for The year 2017.
It was proposed to the company to work with the model of the economic lot to be
produced (EOQ), in order to optimize the costs of finished product inventory and
increase economic profitability.
The economic lot model to be produced consists of determining the quantity needed
to produce to optimize the inventory costs, for its calculation it was necessary to collect
the information of the costs of maintaining inventory, costs of production order, daily
production rate and the daily demand rate.
For a production order in the appropriate time it is necessary to rely on the point
method (ROP) and the economic batch model to be produced.
The safety stock was determined for the 5 types of leather in a probabilistic manner by
means of the square root of the average delivery time by the standard deviation of the
daily demand plus the average daily demand for the standard deviation of the delivery
time in days, this result multiplied by the level of satisfaction of 90% statistically
taking as reference z = 1.28.
By last, it is made an analysis of the costs of inventories and economic profitability
with the proposed model.Tesi
Large genomic rearrangements in the CFTR gene contribute to CBAVD
<p>Abstract</p> <p>Background</p> <p>By performing extensive scanning of whole coding and flanking sequences of the <it>CFTR (Cystic Fibrosis Transmembrane Conductance Regulator</it>) gene, we had previously identified point mutations in 167 out of 182 (91.7%) males with isolated congenital bilateral absence of the vas deferens (CBAVD). Conventional PCR-based methods of mutation analysis do not detect gross DNA lesions. In this study, we looked for large rearrangements within the whole <it>CFTR </it>locus in the 32 CBAVD patients with only one or no mutation.</p> <p>Methods</p> <p>We developed a semi-quantitative fluorescent PCR assay (SQF-PCR), which relies on the comparison of the fluorescent profiles of multiplex PCR fragments obtained from different DNA samples. We confirmed the gross alterations by junction fragment amplification and identified their breakpoints by direct sequencing.</p> <p>Results</p> <p>We detected two large genomic heterozygous deletions, one encompassing exon 2 (c.54-5811_c.164+2186del8108ins182) [or <it>CFTRdele2</it>], the other removing exons 22 to 24 (c.3964-3890_c.4443+3143del9454ins5) [or <it>CFTRdele 22_24</it>], in two males carrying a typical CBAVD mutation on the other parental <it>CFTR </it>allele. We present the first bioinformatic tool for exon phasing of the <it>CFTR </it>gene, which can help to rename the exons and the nomenclature of small mutations according to international recommendations and to predict the consequence of large rearrangements on the open reading frame.</p> <p>Conclusion</p> <p>Identification of large rearrangements further expands the <it>CFTR </it>mutational spectrum in CBAVD and should now be systematically investigated. We have designed a simple test to specifically detect the presence or absence of the two rearrangements identified in this study.</p
Neuronal Conduction of Excitation without Action Potentials Based on Ceramide Production
International audienceBACKGROUND: Action potentials are the classic mechanism by which neurons convey a state of excitation throughout their length, leading, after synaptic transmission, to the activation of other neurons and consequently to network functioning. Using an in vitro integrated model, we found previously that peripheral networks in the autonomic nervous system can organise an unconventional regulatory reflex of the digestive tract motility without action potentials. METHODOLOGY/PRINCIPAL FINDINGS: In this report, we used combined neuropharmacological and biochemical approaches to elucidate some steps of the mechanism that conveys excitation along the nerves fibres without action potentials. This mechanism requires the production of ceramide in membrane lipid rafts, which triggers in the cytoplasm an increase in intracellular calcium concentration, followed by activation of a neuronal nitric oxide synthase leading to local production of nitric oxide, and then to guanosine cyclic monophosphate. This sequence of second messengers is activated in cascade from rafts to rafts to ensure conduction of the excitation along the nerve fibres. CONCLUSIONS/SIGNIFICANCE: Our results indicate that second messengers are involved in neuronal conduction of excitation without action potentials. This mechanism represents the first evidence-to our knowledge-that excitation is carried along nerves independently of electrical signals. This unexpected ceramide-based conduction of excitation without action potentials along the autonomic nerve fibres opens up new prospects in our understanding of neuronal functioning
Measurement of the ratios of branching fractions and
The ratios of branching fractions
and are measured, assuming isospin symmetry, using a
sample of proton-proton collision data corresponding to 3.0 fb of
integrated luminosity recorded by the LHCb experiment during 2011 and 2012. The
tau lepton is identified in the decay mode
. The measured values are
and
, where the first uncertainty is
statistical and the second is systematic. The correlation between these
measurements is . Results are consistent with the current average
of these quantities and are at a combined 1.9 standard deviations from the
predictions based on lepton flavor universality in the Standard Model.Comment: All figures and tables, along with any supplementary material and
additional information, are available at
https://cern.ch/lhcbproject/Publications/p/LHCb-PAPER-2022-039.html (LHCb
public pages
Multidifferential study of identified charged hadron distributions in -tagged jets in proton-proton collisions at 13 TeV
Jet fragmentation functions are measured for the first time in proton-proton
collisions for charged pions, kaons, and protons within jets recoiling against
a boson. The charged-hadron distributions are studied longitudinally and
transversely to the jet direction for jets with transverse momentum 20 GeV and in the pseudorapidity range . The
data sample was collected with the LHCb experiment at a center-of-mass energy
of 13 TeV, corresponding to an integrated luminosity of 1.64 fb. Triple
differential distributions as a function of the hadron longitudinal momentum
fraction, hadron transverse momentum, and jet transverse momentum are also
measured for the first time. This helps constrain transverse-momentum-dependent
fragmentation functions. Differences in the shapes and magnitudes of the
measured distributions for the different hadron species provide insights into
the hadronization process for jets predominantly initiated by light quarks.Comment: All figures and tables, along with machine-readable versions and any
supplementary material and additional information, are available at
https://cern.ch/lhcbproject/Publications/p/LHCb-PAPER-2022-013.html (LHCb
public pages
Study of the decay
The decay is studied
in proton-proton collisions at a center-of-mass energy of TeV
using data corresponding to an integrated luminosity of 5
collected by the LHCb experiment. In the system, the
state observed at the BaBar and Belle experiments is
resolved into two narrower states, and ,
whose masses and widths are measured to be where the first uncertainties are statistical and the second
systematic. The results are consistent with a previous LHCb measurement using a
prompt sample. Evidence of a new
state is found with a local significance of , whose mass and width
are measured to be and , respectively. In addition, evidence of a new decay mode
is found with a significance of
. The relative branching fraction of with respect to the
decay is measured to be , where the first
uncertainty is statistical, the second systematic and the third originates from
the branching fractions of charm hadron decays.Comment: All figures and tables, along with any supplementary material and
additional information, are available at
https://cern.ch/lhcbproject/Publications/p/LHCb-PAPER-2022-028.html (LHCb
public pages
- …