Sharp estimates on the first eigenvalue of the p-Laplacian with negative Ricci lower bound

We complete the picture of sharp eigenvalue estimates for the p-Laplacian on a compact manifold by providing sharp estimates on the first nonzero eigenvalue of the nonlinear operator $\Delta_p$ when the Ricci curvature is bounded from below by a negative constant. We assume that the boundary of the manifold is convex, and put Neumann boundary conditions on it. The proof is based on a refined gradient comparison technique and a careful analysis of the underlying model spaces.Comment: Sign mistake fixed in the proof of the gradient comparison theorem (theorem 5.1 pag 10), and some minor improvements aroun

Synapsins contribute to the dynamic spatial organization of synaptic vesicles in an activity-dependent manner.

The precise subcellular organization of synaptic vesicles (SVs) at presynaptic sites allows for rapid and spatially restricted exocytotic release of neurotransmitter. The synapsins (Syns) are a family of presynaptic proteins that control the availability of SVs for exocytosis by reversibly tethering them to each other and to the actin cytoskeleton in a phosphorylation-dependent manner. Syn ablation leads to reduction in the density of SV proteins in nerve terminals and increased synaptic fatigue under high-frequency stimulation, accompanied by the development of an epileptic phenotype. We analyzed cultured neurons from wild-type and Syn I,II,III(-/-) triple knock-out (TKO) mice and found that SVs were severely dispersed in the absence of Syns. Vesicle dispersion did not affect the readily releasable pool of SVs, whereas the total number of SVs was considerably reduced at synapses of TKO mice. Interestingly, dispersion apparently involved exocytosis-competent SVs as well; it was not affected by stimulation but was reversed by chronic neuronal activity blockade. Altogether, these findings indicate that Syns are essential to maintain the dynamic structural organization of synapses and the size of the reserve pool of SVs during intense SV recycling, whereas an additional Syn-independent mechanism, whose molecular substrate remains to be clarified, targets SVs to synaptic boutons at rest and might be outpaced by activity

Distribución de las precipitaciones en Rafaela y Esperanza, Santa Fe

p.85-89Para determinar el modelo estadístico que provea el mejor ajuste para la distribución de precipitaciones en las localidades de Rafaela y Esperanza (Santa Fe), se utilizaron los registros de precipitaciones mensuales de Esperanza (1929 - 1975) y Rafaela (1937 - 1998). Las distribuciones empíricas se compararon con las teóricas Normal y Logaritmica (LN), Normal Raíz Cúbica (NR) y Gamma Incompleta (GI). Según la prueba de Lilliefors, NR y GI presentaron el mejor ajuste para todos los meses (p menor 0,01). LN presentó buen ajuste (p menor 0,05) para todas las estaciones del año, excepto el invierno

Nuevos enfoques para calcular la evaporación y la transpiración

En este trabajo se presenta un modelo matemático desarrollado por F. I. Morton, en Canadá, para calcular la evaporación en grandes áreas, obviando las conocidas dificultades que se encuentran en este tipo de cálculos. El modelo se basa en algunas suposiciones simplificativas con respecto a la disponibilidad de agua en el suelo, así cano soslaya para ciertas condiciones del entorno, las complejas interrelaciones entre el suelo, la vegetación y la atmósfera. La técnica utilizada permite la aplicación de un modelo simple para calcular la evapotranspiración real cano función de la temperatura del aire y la humedad, tal coro se miden en un abrigo meteorológico. Se presenta, también, un ensayo de aplicación de este modelo a diferentes regiones climáticas de la Argentina.This paper present a mathematical model developed by F. I. Marton, in Canada, to calculate the evaporation on large areas obviating the known difficulties found in this type of conputations. The model is based on sane simplifying assumptions regarding the soil water availability as well as on the bypassing, under certain environmental conditions, of the complex interrel at ions between the ground, the vegetation cover and the atmosphere. The technique used enables the application of a simple model to compute the real evapotranspiration as a function of the air temperature and humidity as measured in a normal meteorological shelter. An essay of the application of this model to various different climatic regions of Argentina is also presented.Asociación Argentina de Geofísicos y Geodesta

Validation of an Engineered Cell Model for In Vitro and In Vivo HIF-1 alpha Evaluation by Different Imaging Modalities

n/

[18F](2S,4R)-4-Fluoroglutamine as a New Positron Emission Tomography Tracer in Myeloma

The high glycolytic activity of multiple myeloma (MM) cells is the rationale for use of Positron Emission Tomography (PET) with 18F-fluorodeoxyglucose ([18F]FDG) to detect both bone marrow (BM) and extramedullary disease. However, new tracers are actively searched because [18F]FDG-PET has some limitations and there is a portion of MM patients who are negative. Glutamine (Gln) addiction has been recently described as a typical metabolic feature of MM cells. Yet, the possible exploitation of Gln as a PET tracer in MM has never been assessed so far and is investigated in this study in preclinical models. Firstly, we have synthesized enantiopure (2S,4R)-4-fluoroglutamine (4-FGln) and validated it as a Gln transport analogue in human MM cell lines, comparing its uptake with that of 3H-labelled Gln. We then radiosynthesized [18F]4-FGln, tested its uptake in two different in vivo murine MM models, and checked the effect of Bortezomib, a proteasome inhibitor currently used in the treatment of MM. Both [18F]4-FGln and [18F]FDG clearly identified the spleen as site of MM cell colonization in C57BL/6 mice, challenged with syngeneic Vk12598 cells and assessed by PET. NOD.SCID mice, subcutaneously injected with human MM JJN3 cells, showed high values of both [18F]4-FGln and [18F]FDG uptake. Bortezomib significantly reduced the uptake of both radiopharmaceuticals in comparison with vehicle at post treatment PET. However, a reduction of glutaminolytic, but not of glycolytic, tumor volume was evident in mice showing the highest response to Bortezomib. Our data indicate that [18F](2S,4R)-4-FGln is a new PET tracer in preclinical MM models, yielding a rationale to design studies in MM patients

Alexithymia and psychopathology in patients suffering from inflammatory bowel disease : arising differences and correlations to tailoring therapeutic strategies

Comorbidity with anxiety or depression is common in patients with Inflammatory Bowel Disease (IBD) as Crohn Disease (CD) and Ulcerative Colitis (UC). Data suggest that the cognitive construct of alexithymia has high prevalence in people suffering from anxiety and mood disorders and even in people with IBD. Most studies have investigated mainly anxiety and depression, considering IBD population as a homogeneous group of patients. Little evidence shows the impact of alexithymia on the course of IBD. We evaluated a broad spectrum of psychopathological symptoms and alexithymia levels in a group of outpatients affected by IBD in clinical remission, comparing CD and UC and investigating the relationship with clinical and socio-demographic variables. One hundred and seventy IBD outpatients were screened by using the Hospital Anxiety Depression Scale (HADS), the Self-report Symptom Inventory-90-Revised (SCL-90-R) and the Toronto Alexithymia Scale (TAS-20). A high prevalence of anxious and depressive symptoms (42.35 and 25.8% respectively) together with alexithymia (31.76%) was confirmed. CD patients experienced high levels of depression (HADS Depression 35.2% p = 0.034; SCL-90-R mean 1.39 p < 0.001), somatisation (SCL-90-R mean 1.04 p < 0.001), obsessive-compulsive symptoms (SCL-90-R mean 1.2 p < 0.001), and global severity (SCL-90-R mean 1.15 p < 0.001). There is no statistical difference in the prevalence of alexithymia in both subpopulations. The levels of alexithymia are correlated to the levels of anxiety (HADS Anxiety rs = 0.516 p < 0.001), depression (HADS Depression rs = 0.556 p < 0.001; SCL-90-R rs = 0.274 p = 0.001), somatisation (SCL-90-R rs = 0.229 p = 0.005), obsessive-compulsive symptoms (SCL-90-R rs = 0.362 p < 0.001), and global severity (SCL-90-R rs = 0.265 p = 0.001). Furthermore, alexithymia is associated with a delay of diagnosis of IBD, poly-therapies and greater IBD extension. Older age, female gender, greater IBD extension, surgery, and delay of diagnosis seem to be related to a high prevalence of psychopathological symptoms such as anxiety, depression, somatisation, and obsessive-compulsive symptoms. Psychopathological symptoms and high levels of alexithymia are frequent in IBD patients and seem to be related to a high risk of poor clinical outcome. CD patients could be considered at higher risk of mental comorbidity. A more comprehensive psychiatric assessment, including alexithymia, and an integrated treatment of underlying conditions, must be taken into account in order to improve the global prognosis of the disease

Improved efficacy response attributed to diagnostic selection – Interim results of the phase 1 experience from ALKA-372-001

n/