Behavioral Profile of the Novel Cannabinoid Agonist AM4054

Although cannabinoid drugs have been used for thousands of years both recreationally and therapeutically, little has been known about their mechanisms of action until recently. Since the discovery of the endogenous cannabinoid CB1 receptor in 1988, the behavioral profile of cannabinoid receptor ligands has been much more thoroughly defined. Cannabinoid CB1 agonists have been shown to produce a variety of behavioral effects including suppression of locomotion, catalepsy, hypothermia, and analgesia. Research has also demonstrated that these behavioral effects can be inhibited by CB1 receptor antagonists including SR 141716 and AM 251. Although behavioral indicators of anxiety including thigmotaxis have been observed in several different paradigms, there is inconclusive and often times contradictory evidence to define the role of anxiety in CB1 receptor activation. The present study addressed the behavioral profile of AM 4054, a novel full agonist at the CB1 receptor, as well as the ability of the CB1 antagonist AM 251 to reverse these effects. To further identify and expand research on the suppression of locomotion and induction of thigmotaxis with the administration of a CB1 agonist, experiment 1 was conducted in the open field. In this experiment, each rat (n=40) was randomly assigned one of the five treatments: vehicle, 0.16, 0.32, 0.64, or 1.25 mg/kg AM 4054. After a 30 minute pre-treatment, each subject was tested in the open field for 18 minutes. Results indicated that AM 4054 produced a dose-related suppression of locomotion as well as the subtle presence of thigmotaxis in two out of four doses. In experiment 2, subjects (n=40) received either vehicle or 2.0 or 4.0 mg/kg AM 251 60 minutes prior to testing. After 30 minutes, the subjects were given either a 0.3 mg/kg dose of AM 4054 or vehicle. After a total pretreatment duration of 60 minutes, the animals were tested on a battery of tasks including an 18 minute session in locomotor boxes. Experiment 2 was a continuation of a previous study conducted in the same lab, which confirmed the effects of AM 4054 on this tetrad of tasks as being consistent with other cannabinoid agonists. In this experiment the effects of AM 4054 were reversed by the administration of the CB1 antagonist AM 251. Past studies have shown that AM 4054 is a highly potent drug with behavioral actions similar to other cannabinoid CB1 agonists. Furthermore, AM 4054 can be a useful drug in future studies, and has potential therapeutic value for the treatment of various conditions.

Retrospective study of prevalence of Community Associated Methicillin Resistant Staphylococcus Aureus (CA-MRSA) seen in Texas MedClinics, San Antonio, TX from April 2006-August 2009

Purpose. To evaluate the presence of Community Associated–Methicillin Resistant Staphylococcus Aureus, CA-MRSA, in abscesses and skin and soft tissue infections presenting at 9 urgent care clinics in San Antonio, TX. ^ Methods. During the 40-month retrospective study (April 2006 to August 2009), wound cultures collected in 9 urgent care centers were evaluated for MRSA growth, antibiotics prescribed, follow up wound care, and antibiotic prescribing habits by physicians for all patients presenting with abscesses and skin/soft tissue infections. ^ Results. Across 9 urgent care centers in San Antonio, TX, 36,797 abscesses and cases of skin and soft tissue infections were treated during 40 months. Of the 36,797 cases, 9290 patients had wound cultures sent with 5,630 cultures sent to Texas MedClinic’s primary lab. Of the 5630 cultures sent to their primary lab, this reflected a prevalence of 4727 (84 %) cultures were positive for MRSA. Of the 9290 patients who had a wound culture sent (April 10th, 2006 to August 31st, 2009), a total of 4,307 antibiotics were prescribed. The top five antibiotics prescribed for CA-MRSA were Bactrim (55.5%), Clindamycin (18.4%), Bactroban (5%), Amoxicillin (3.5%), and Doxycycline (3%) representing 85.4% of the antibiotics prescribed. 8809/9290 (94.8%) of patients required no more than 3 follow up visits. Of the 33 physicians working full time during the entire study period, 29/33 (87.8%) of the physicians were family medicine physicians and represented varied prescribing rates of antibiotics between 11-76% with 26/33 (78.8%) of physicians prescribing antibiotics greater than 40% of the time.^ Conclusions. Abscesses and soft tissue infections are a common presenting complaint to urgent care centers. This study reveals that antibiotic-prescribing practices can be improved with physician education since this high prevalence was not known previously. Also, treating abscesses with limited packing has been shown to be a viable option in this particular circumstance and would be open field for additional clinical research. Due to the high prevalence of CA-MRSA skin and soft tissue infections among patients presenting to urgent care centers presumptive treatment for MRSA is indicated. Increasing levels of resistance to penicillin antibiotics is concerning and warrants alternative antibiotic management strategies.^

In vivo longitudinal studies of spinal cord injury and vascular endothelial growth factor treatment

Approximately 12,000 new cases of spinal cord injury (SCI) are added each year to the estimated 259,000 Americans living with SCI. The majority of these patients return to society, their lives forever changed by permanent loss of sensory and motor function. While there are no FDA approved drugs for the treatment of SCI or a universally accepted standard therapy, the current though controversial treatment includes the delivery of high dosages of the corticosteroid methyliprednisolone sodium succinate, surgical interventions to stabilize the spinal column, and physical rehabilitation. It is therefore critically important to fully understand the pathology of injury and determine novel courses and rationally-based therapies for SCI. ^ Vascular endothelial growth factor (VEGF) is an attractive target for treating central nervous system (CNS) injury and disease because it has been shown to influence angiogenesis and neuroprotection. Preliminary studies have indicated that increased vasculature may be associated with functional recovery; therefore exogenous delivery of a pro-angiogenic growth factor such as VEGF may improve neurobehavioral outcome. In addition, VEGF may provide protection from secondary injury and result in increased survival and axonal sprouting. ^ In these studies, SCI rats received acute intraspinal injections of VEGF, the antibody to VEGF, or vehicle control. The effect of these various agents was investigated using longitudinalmulti-modal magnetic resonance imaging (MRI), neuro- and sensory behavioral assays, and end point immunohistochemistry. We found that rats that received VEGF after SCI had increased tissue sparing and improved white matter integrity at the earlier time points as shown by advanced magnetic resonance imaging (MRI) techniques. However, these favorable effects of VEGF were not maintained, suggesting that additional treatments with VEGF at multiple time points may be more beneficial, Histological examinations revealed that VEGF treatment may result in increased oligodendrogenesis and therefore may eventually lead to remyelination and improved functional outcome. ^ On the neurobehavioral studies, treatments with VEGF and Anti-VEGF did not significantly affect performance on tests of open-field locomotion, grid walk, inclined plane, or rearing. However, VEGF treatment resulted in significantly increased incidence of chronic neuropathic pain. This phenomenon could possibly be attributed to the fact that VEGF treatment may promote axonal sprouting and also results in tissue sparing, thereby providing a substrate for the growth of new axons. New connections made by these sprouting axons may involve components of pathways involved in the transmission of pain and therefore result in increased pain in those animals. ^

Estudio socio-territorial de la actividad hortícola en el partido de La Plata 1998-2002

El presente trabajo se propone identificar y caracterizar las unidades de análisis espacio-territorial (fracciones censales) de la actividad primaria intensiva, específicamente hortícola, y examinar el peso relativo de la actividad del Partido de La Plata en el contexto provincial y nacional. Se analizan las variables sobre mano de obra, superficie total, superficie cultivada a campo y bajo cubierta, régimen de tenencia de la tierra y componentes tecnológicos. Se examinan y comparan los censos hortícola de la Provincia de Buenos Aires 1998 y Nacional Agropecuario 2002 (CNA02). Los resultados son presentados en tablas, gráficos y mapas temáticos procesados en SIG ArcView.

Estudio socio-territorial de la actividad hortícola en el partido de La Plata 1998-2002

El presente trabajo se propone identificar y caracterizar las unidades de análisis espacio-territorial (fracciones censales) de la actividad primaria intensiva, específicamente hortícola, y examinar el peso relativo de la actividad del Partido de La Plata en el contexto provincial y nacional. Se analizan las variables sobre mano de obra, superficie total, superficie cultivada a campo y bajo cubierta, régimen de tenencia de la tierra y componentes tecnológicos. Se examinan y comparan los censos hortícola de la Provincia de Buenos Aires 1998 y Nacional Agropecuario 2002 (CNA02). Los resultados son presentados en tablas, gráficos y mapas temáticos procesados en SIG ArcView.

Estudio socio-territorial de la actividad hortícola en el partido de La Plata 1998-2002

El presente trabajo se propone identificar y caracterizar las unidades de análisis espacio-territorial (fracciones censales) de la actividad primaria intensiva, específicamente hortícola, y examinar el peso relativo de la actividad del Partido de La Plata en el contexto provincial y nacional. Se analizan las variables sobre mano de obra, superficie total, superficie cultivada a campo y bajo cubierta, régimen de tenencia de la tierra y componentes tecnológicos. Se examinan y comparan los censos hortícola de la Provincia de Buenos Aires 1998 y Nacional Agropecuario 2002 (CNA02). Los resultados son presentados en tablas, gráficos y mapas temáticos procesados en SIG ArcView.

Water harvesting for young trees using Peltier plates powered by photovoltaic solar energy

Young trees transplanted from nursery into open field require a minimum amount of soil moisture to successfully root in their new location, especially in dry-climate areas. One possibility is to obtain the required water from air moisture. This can be achieved by reducing the temperature of a surface below the air dew point temperature, inducing water vapor condensation on the surface. The temperature of a surface can be reduced by applying the thermoelectric effect, with Peltier modules powered by electricity. Here, we present a system that generates electricity with a solar photovoltaic module, stores it in a battery, and finally, it uses the electricity at the moment in which air humidity and temperature are optima to maximize water condensation while minimizing energy consumption. Also, a method to reduce the evaporation of the condensed water is proposed. The objective of the system, rather than irrigating young plants in such a degree as to boost their growth, is to maintain them alive in the dryer periods.

Water harvesting for young trees using Peltier modules powered by photovoltaic solar energy

Young trees transplanted from nursery into open field require a minimum amount of soil moisture to successfully root in their new location, especially in dry-climate areas. One possibility is to obtain the required water from air moisture. This can be achieved by reducing the temperature of a surface below the air dew point temperature, inducing water vapor condensation on the surface. The temperature of a surface can be reduced by applying the thermoelectric effect, with Peltier modules powered by electricity. Here, we present a system that generates electricity with a solar photovoltaic module, stores it in a battery, and finally, uses the electricity at the moment in which air humidity and temperature are optimal to maximize water condensation while minimizing energy consumption. Also, a method to reduce the evaporation of the condensed water is proposed. The objective of the system is to sustain young plants in drier periods, rather than exclusively irrigating young plants to boost their growth.

Diseño e implementación de un módulo para la anotación de imágenes médicas

Se comenzó el trabajo recabando información sobre los distintos enfoques que se le había dado a la anotación a lo largo del tiempo, desde anotación de imágenes a mano, pasando por anotación de imágenes utilizando características de bajo nivel, como color y textura, hasta la anotación automática. Tras entrar en materia, se procedió a estudiar artículos relativos a los diferentes algoritmos utilizados para la anotación automática de imágenes. Dado que la anotación automática es un campo bastante abierto, hay un gran numero de enfoques. Teniendo las características de las imágenes en particular en las que se iba a centrar el proyecto, se fueron descartando los poco idoneos, bien por un coste computacional elevado, o porque estaba centrado en un tipo diferente de imágenes, entre otras cosas. Finalmente, se encontró un algoritmo basado en formas (Active Shape Model) que se consideró que podría funcionar adecuadamente. Básicamente, los diferentes objetos de la imagen son identicados a partir de un contorno base generado a partir de imágenes de muestra, siendo modicado automáticamente para cubrir la zona deseada. Dado que las imágenes usadas son todas muy similares en composición, se cree que puede funcionar bien. Se partió de una implementación del algoritmo programada en MATLAB. Para empezar, se obtuvieron una serie de radiografías del tórax ya anotadas. Las imágenes contenían datos de contorno para ambos pulmones, las dos clavículas y el corazón. El primer paso fue la creación de una serie de scripts en MATLAB que permitieran: - Leer y transformar las imágenes recibidas en RAW, para adaptarlas al tamaño y la posición de los contornos anotados - Leer los archivos de texto con los datos de los puntos del contorno y transformarlos en variables de MATLAB - Unir la imagen transformada con los puntos y guardarla en un formato que la implementación del algoritmo entendiera. Tras conseguir los ficheros necesarios, se procedió a crear un modelo para cada órgano utilizando para el entrenamiento una pequeña parte de las imágenes. El modelo obtenido se probó con varias imágenes de las restantes. Sin embargo, se encontro bastante variación dependiendo de la imagen utilizada y el órgano detectado. ---ABSTRACT---The project was started by procuring information about the diferent approaches to image annotation over time, from manual image anotation to automatic annotation. The next step was to study several articles about the diferent algorithms used for automatic image annotation. Given that automatic annotation is an open field, there is a great number of approaches. Taking into account the features of the images that would be used, the less suitable algorithms were rejected. Eventually, a shape-based algorithm (Active Shape Model) was found. Basically, the diferent objects in the image are identified from a base contour, which is generated from training images. Then this contour is automatically modified to cover the desired area. Given that all the images that would be used are similar in object placement, the algorithm would probably work nicely. The work started from a MATLAB implementation of the algorithm. To begin with, a set of chest radiographs already annotated were obtained. These images came with contour data for both lungs, both clavicles and the heart. The first step was the creation of a series of MATLAB scripts to join the RAW images with the annotation data and transform them into a format that the algorithm could read. After obtaining the necessary files, a model for each organ was created using part of the images for training. The trained model was tested on several of the reimaining images. However, there was much variation in the results from one image to another. Generally, lungs were detected pretty accurately, whereas clavicles and the heart gave more problems. To improve the method, a new model was trained using half of the available images. With this model, a significant inprovement of the results can be seen.

Aeroacoustic noise prediction in high speed trains due to attached and detached flow

This paper aims to set out the influence of the flow field around high speed trains in open field. To achieve this parametric analysis of the sound pressure inside the train was performed. Three vibroacoustic models of a characteristic train section are used to predict the noise inside the train in open field by using finite element method FEM, boundary element method (BEM) and statistical energy analysis (SEA) depending on the frequency range of analysis. The turbulent boundary layer excitation is implemented as the only airborne noise source, in order to focus on the study of the attached and detached flow in the surface of the train. The power spectral densities of the pressure fluctuation in the train surface proposed by [Cockburn and Roberson 1974, Rennison et al. 2009] are applied on the exterior surface of the structural subsystems in the vibroacoustic models. An increase in the sound pressure level up to10 dB can be appreciated due to the detachment of the flow around the train. These results highlight the importance to determine the detached regions prediction, making critical the airborne noise due to turbulent boundary layer.

Vibroacoustic Problems in High Speed Trains

Passengers comfort in terms of acoustic noise levels is a key train design parameter, especially relevant in high speed trains, where the aerodynamic noise is dominant. The aim of the work, described in this paper, is to make progress in the understanding of the flow field around high speed trains in an open field, which is a subject of interest for many researchers with direct industrial applications, but also the critical configuration of the train inside a tunnel is studied in order to evaluate the external loads arising from noise sources of the train. The airborne noise coming from the wheels (wheelrail interaction), which is the dominant source at a certain range of frequencies, is also investigated from the numerical and experimental points of view. The numerical prediction of the noise in the interior of the train is a very complex problem, involving many different parameters: complex geometries and materials, different noise sources, complex interactions among those sources, broad range of frequencies where the phenomenon is important, etc. During recent years a research plan is being developed at IDR/UPM (Instituto de Microgravedad Ignacio Da Riva, Universidad Politécnica de Madrid) involving both numerical simulations, wind tunnel and full-scale tests to address this problem. Comparison of numerical simulations with experimental data is a key factor in this process.

Global variation in the genetic and biochemical basis of diamondback moth resistance to Bacillus thuringiensis

Insecticidal proteins from the soil bacterium Bacillus thuringiensis (Bt) are becoming a cornerstone of ecologically sound pest management. However, if pests quickly adapt, the benefits of environmentally benign Bt toxins in sprays and genetically engineered crops will be short-lived. The diamondback moth (Plutella xylostella) is the first insect to evolve resistance to Bt in open-field populations. Here we report that populations from Hawaii and Pennsylvania share a genetic locus at which a recessive mutation associated with reduced toxin binding confers extremely high resistance to four Bt toxins. In contrast, resistance in a population from the Philippines shows multilocus control, a narrower spectrum, and for some Bt toxins, inheritance that is not recessive and not associated with reduced binding. The observed variation in the genetic and biochemical basis of resistance to Bt, which is unlike patterns documented for some synthetic insecticides, profoundly affects the choice of strategies for combating resistance.

Mouse model of Sanfilippo syndrome type B produced by targeted disruption of the gene encoding α-N-acetylglucosaminidase

The Sanfilippo syndrome type B is an autosomal recessive disorder caused by mutation in the gene (NAGLU) encoding α-N-acetylglucosaminidase, a lysosomal enzyme required for the stepwise degradation of heparan sulfate. The most serious manifestations are profound mental retardation, intractable behavior problems, and death in the second decade. To generate a model for studies of pathophysiology and of potential therapy, we disrupted exon 6 of Naglu, the homologous mouse gene. Naglu−/− mice were healthy and fertile while young and could survive for 8–12 mo. They were totally deficient in α-N-acetylglucosaminidase and had massive accumulation of heparan sulfate in liver and kidney as well as secondary changes in activity of several other lysosomal enzymes in liver and brain and elevation of gangliosides GM2 and GM3 in brain. Vacuolation was seen in many cells, including macrophages, epithelial cells, and neurons, and became more prominent with age. Although most vacuoles contained finely granular material characteristic of glycosaminoglycan accumulation, large pleiomorphic inclusions were seen in some neurons and pericytes in the brain. Abnormal hypoactive behavior was manifested by 4.5-mo-old Naglu−/− mice in an open field test; the hyperactivity that is characteristic of affected children was not observed even in younger mice. In a Pavlovian fear conditioning test, the 4.5-mo-old mutant mice showed normal response to context, indicating intact hippocampal-dependent learning, but reduced response to a conditioning tone, perhaps attributable to hearing impairment. The phenotype of the α-N-acetylglucosaminidase-deficient mice is sufficiently similar to that of patients with the Sanfilippo syndrome type B to make these mice a good model for study of pathophysiology and for development of therapy.

Elevated anxiety and antidepressant-like responses in serotonin 5-HT1A receptor mutant mice

The brain serotonin (5-hydroxytryptamine; 5-HT) system is a powerful modulator of emotional processes and a target of medications used in the treatment of psychiatric disorders. To evaluate the contribution of serotonin 5-HT1A receptors to the regulation of these processes, we have used gene-targeting technology to generate 5-HT1A receptor-mutant mice. These animals lack functional 5-HT1A receptors as indicated by receptor autoradiography and by resistance to the hypothermic effects of the 5-HT1A receptor agonist 8-hydroxy-2-(di-n-propylamino)tetralin (8-OH-DPAT). Homozygous mutants display a consistent pattern of responses indicative of elevated anxiety levels in open-field, elevated-zero maze, and novel-object assays. Moreover, they exhibit antidepressant-like responses in a tail-suspension assay. These results indicate that the targeted disruption of the 5-HT1A receptor gene leads to heritable perturbations in the serotonergic regulation of emotional state. 5-HT1A receptor-null mutant mice have potential as a model for investigating mechanisms through which serotonergic systems modulate affective state and mediate the actions of psychiatric drugs.

Female preproenkephalin-knockout mice display altered emotional responses

The endogenous opioid system has been implicated in sexual behavior, palatable intake, fear, and anxiety. The present study examined whether ovariectomized female transgenic preproenkephalin-knockout (PPEKO) mice and their wild-type and heterozygous controls displayed alterations in fear and anxiety paradigms, sucrose intake, and lordotic behavior. To examine stability of responding, three squads of the genotypes were tested across seasons over a 20-month period. In a fear-conditioning paradigm, PPEKO mice significantly increased freezing to both fear and fear + shock stimuli relative to controls. In the open field, PPEKO mice spent significantly less time and traversed significantly less distance in the center of an open field than wild-type controls. Further, PPEKO mice spent significantly less time and tended to be less active on the light side of a dark–light chamber than controls, indicating that deletion of the enkephalin gene resulted in exaggerated responses to fear or anxiety-provoking environments. These selective deficits were observed consistently across testing squads spanning 20 months and different seasons. In contrast, PPEKO mice failed to differ from corresponding controls in sucrose, chow, or water intake across a range (0.0001–20%) of sucrose concentrations and failed to differ in either lordotic or female approach to male behaviors when primed with estradiol and progesterone, thereby arguing strongly for the selectivity of a fear and anxiety deficit which was not caused by generalized and nonspecific debilitation. These transgenic data strongly suggest that opioids, and particularly enkephalin gene products, are acting naturally to inhibit fear and anxiety.