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Although there are, as of yet, no specific GIS applications for irrigation management, there are several products related to precision agriculture which offer tools to monitor the water use in order to improve land/crop performance and offers several GIS functionalities. These precision agriculture software packages can be used to identify strategies for improved land/crop management. Precision agriculture software provides a link between crop production records and spatial (map) data, including site-specific or land management units. Precision agriculture software is required for field data collection (spatial and non-spatial), data management and data analysis.

Satellite observation provides information of a large area with spatial resolution from under a meter up to 50 km and temporal resolution from 5 min up to a few days. Satellites measure radiances over various parts of the spectra of electromagnetic radiation. The data is subsequently processed to derive geophysical parameters for the observed area and delivered in this more informative form as satellite observation products. High resolution products are more suitable for irrigation [1], especially in cases where the land parcels are small. The satellite data of interest for the precision irrigation is mostly data relevant to the water cycle, hydrology and meteorology and provided by missions aimed at gathering such data.

Precision agriculture demands intensive field data acquisition. One of the keys to understanding productivity variability lays in frequent data acquisition and interpretation. Wireless sensor networks (WSN) are a relatively new and rapidly developing class of wireless communication networks which can provide processed real time field data from sensors distributed in the field. The sensor nodes deployed on the field measure various atmospheric and soil parameters. These measurements can help in making decision on irrigation (automating, semi automating), fertilizer and pesticide applications, intruder detection, pest detection, yield prediction, plant disease prediction, fire detection, etc. The first part of this brief is devoted to Wireless Sensor Network technology with particular focus on its application in precision agriculture.

This report describes the development of a new nanocarrier, named as polyarginine (PArg) nanocapsules, specifically designed for overcoming cellular barriers. These nanocapsules are composed of an oily core and a PArg corona. The attachment of the PArg corona was mediated by its interaction with the oily core, which was conveniently stabilized with phosphatidylcholine. Hybrid PArg/PEG nanocapsules could also be obtained by introducing PEG-stearate in the nanocapsules formation process. The nanocapsules had an average size in the range of 120–160 nm, and a positive surface charge, which varied between +56 and +28 mV for PArg and PArg/PEG nanocapsules, respectively. They could accommodate significant amounts of lipophilic drugs, i.e., docetaxel, in their core, and also polar negatively charged molecules, i.e., plasmid DNA, on their coating. As a preliminary proof-of-principle, we explored the ability of these nanocarriers to enter cancer cells and to inhibit proliferation in the non-small cell lung cancer NCI-H460 cell line, using flow cytometry and confocal microscopy analysis. The results indicated that PArg nanocapsules are rapidly and massively accumulated into the NCI-H460 cells and that the PArg shell plays a critical role in the internalization process. Moreover, the incubation with docetaxel-loaded nanocapsules with NCI-H460 cells led to an enhanced inhibition of their proliferation, as compared to the free drug. Overall, this is the first report of the potential of PArg nanocapsules as intracellular drug delivery vehicles.

La capacidad evocadora de nuestros centros históricos, ha llevado, en los últimos tiempos, a considerarlos objeto de investigación científica; superando, sino contradiciendo, la visión romántica que los puso en valor desde finales del siglo XVIII en occidente.En este sentido, y considerando tambien las actuales circunstancias socioeconómicas de la sociedad postindustrial del siglo XXI, pensamos que los estudios sitemáticos de los centros históricos, bien podrían trascender del mero territorio académico en el que un trabajo como el presente se enmarca, para perseguir con claridad una aportación científica en beneficio de un objeto artístico que seguramente puede con ellos devenir tambien en motor económico y social. Así pues, el presente trabajo se enmarca dentro de una dinámica mantenida y progresivamente consolidada dentro de las universidades europeas, que abordan, cada vez con mayor rigor científico aunque desde muy diversas perspectivas, el conocimiento de los abundantes y ricos núcleos urbanos históricos que conforman geográficamente el entorno en el que vivimos, Departamento de Urbanismo y Representación de la Arquitectura, Doctorado en Arquitectura

The aim of the present study was to obtain reference values in bulls after an intense exercise situation quantifying some biological variables in venous blood. The descriptive analysis was carried out using Statistica 8.0 program and the values obtained were pH (6.81), P CO 2 (67.81 mmHg), P O 2 (22.58 mmHg), HCO 3 - (10.82 mEq/l), BE (−23.48 mEq/l), TCO 2 (12.83 mEq/l), sO 2 (17.50%) for blood gas, and for mineral Na, iCa and K were 146.96; 1.14 and 7.49 mmol/l respectively. Finally, the mean value of Htc was 43.522%, Hb 14.80. Following exercise, and compared with values considered as physiological in cattle, some blood variables in our study were decreased (blood pH, HCO 3 - , BE, P O 2 and sO 2 ), some remained in the normal limit (Na, K, iCa, Htc) and the rest are increased ( P CO 2 , Hb, lactate) comparing with when compared to normal reference values for the bovine species.

Plasmid vectors designed to facilitate the genetic manipulation of African swine fever virus (ASFV) are described. Our results demonstrate that the beta-glucuronidase enzyme (GUS) can be used to follow gene expression in ASFV-infected cells. Infectious plaques formed by ASFV expressing GUS are visually detectable, thus providing a simple and highly sensitive method for the selection of ASFV recombinants. These and previous results have allowed us to construct two chimeric gene cassettes that constitute the basic tools for the generation of vectors to carry out the deletion of multiple target sequences from the ASFV genome. These cassettes, formed by: (a) a virus promoter; (b) the coding sequence of a reporter gene, either Lac Z or gusA; and (c) a strong signal for the 3' end formation of ASFV mRNAs, can be easily isolated by endonuclease restriction from their corresponding plasmid vectors. A general insertion/coexpression plasmid vector, pEPV2, has also been constructed. pEPV2 facilitates the insertion of foreign genes, together with the Lac Z reporter, into the thymidine kinase locus of ASFV. The functionality of pEPV2 has been tested by generating a recombinant ASFV expressing the luciferase gene. The vectors presented in this report constitute the first reported set of tools for the genetic manipulation of ASFV.

Tumor growth and metastasis entangle the alteration and recruitment of non-malignant cells to the primary tumor, among them immune cells, constituting the tumor microenvironment (TME). Communication between tumor cells and their stroma has been shown as a fundamental driving force of the tumoral process. A great deal of effort has been focused on depicting their specific interactions and crosstalk. However, most research has been carried out in 2D conventional cultures that alter cell morphology and intracellular signaling processes. Considering these premises, we have developed a 3D cell co-culture model to mimic T cell infiltration into the tumor mass and explore tumor-immune cells interactions in the TME. Expression of specific cell markers and assessment of cell proliferation were carried out to characterize the proposed 3D co-culture model. Additionally, the study and profiling of the secretome revealed a subset of particular cancer-related inflammation proteins prompted upon 3D cultivation of tumor cells in presence of lymphocytes, pointing out an intercellular communication. Altogether, these results suggest that our 3D cell co-culture model can be a useful tool to identify and study critical factors mediating the crosstalk between tumor and immune cells in the TME. Finally, the potential of this model as a drug-screening platform has been explored using docetaxel as a model antitumoral compound.

Novel markers to accurately predict the risk of malignant transformation in laryngeal epithelial precursor lesions (EPL) are needed. We tried to identify some molecular alterations occurring in laryngeal tumorigenesis. In this study, 60 paraffin-embedded EPL and 17 metachronous invasive carcinomas were immunostained for markers associated with proliferation (Ki67), cell cycle control (p53, p21, p16, p27, cyclin D1), and cell adhesion and invasion (laminin and β-catenin). Aberrant expression of p16 and p53 and positivity at cytoplasm for β-catenin and cyclin D1 were detected significantly in EPL with progression to invasive laryngeal carcinoma. All cases with basal and suprabasal reactivity of p53 showed β-catenin overexpression. We found that β-catenin protein expression increased significantly with the grade of dysplasia. This is one of the studies with the largest number of laryngeal EPL and invasive carcinoma studied sequentially. Our data confirm the role of some cell cycle regulatory proteins in the development of laryngeal carcinoma. Cytoplasmic retention of β-catenin in EPL seems to be related with more aggressive biological behavior. Combined increased p53 and cytoplasmic β-catenin protein expression could be biologically important in laryngeal tumorigenesis. Further research is required to clarify the involvement of β-catenin in the mechanism associated with malignant transformation in laryngeal tissues.

Mycobacterium aviumsubsp.paratuberculosis(Map) is the causative agent of a chronic intestinal inflammation in ruminants named Johne's disease or paratuberculosis and a possible etiopathological agent of human Crohn's disease (CD). Analysis of macrophage transcriptomes in response toMapinfection is expected to provide key missing information in the understanding of the role of this pathogen in establishing an inappropriate and persistent infection in a susceptible host and of the molecular mechanisms that might underlie the early phases of CD. In this paper we summarize transcriptomic studies of human and bovine peripheral blood mononuclear cells (PBMC), monocyte-derived macrophages (MDMs), and macrophages-like cell linesin vitroinfected withMap. Most studies included in this paper consistently reported common gene expression signatures of bovine and human macrophages in response toMapsuch as enhanced expression of the anti-inflammatory cytokines IL-10 and IL-6, which promote bacterial survival. Overexpression of IL-10 could be responsible for theMap-associated reduction in the expression of the proapoptotic TNF-αgene observed in bovine and human macrophages.

[EN] Among the internal reform processes made in the early twentieth century in Oviedo, one of the most important is the transformation undertaken in the Cathedral Square, with the demolition of the houses opposite the church. The main reason that motivates such action is none other than providing a broad perspective to the Cathedral. The arrangement of the square generated controversy, there were two points of view: the first one considered that the low value of the block justified its disappearance, the second one argued that the demolition would remove an arcaded square of great interest, being more suitable the partial perspectives of the church that offered these ensemble of streets. Despite many critics opposed to demolition, it was carried out after approval of the project in 1928., [ES] De los procesos de reforma interior acometidos a principios del pasado siglo en Oviedo, cabe destacar la transformación llevada a cabo en la plaza de la Catedral, con el derribo del caserío situado frente al templo. La finalidad principal de esta actuación consistía en dotar a la Catedral de una amplia perspectiva. La ordenación de la plaza generó una gran polémica, enfrentando dos criterios: el de los que consideraban que el escaso valor arquitectónico de la manzana, y el de los que defendían que el derribo haría desaparecer una plaza porticada de especial interés por las perspectivas parciales del templo que ofrecían las estrechas calles que conformaban el conjunto. A pesar de los muchos detractores contrarios a la demolición, ésta se llevaría a cabo en 1928, tras la aprobación del proyecto.

P. 49-56 Despite the importance of rearing wild lagomorphs in captivity for hunting and predator conservation in Spain, little is known about this production sector. Taking official data into account, in this work the number and distribution of farms in Spain and the possible number of animals produced were analysed during the period 2005-2010. In 2010, 114 wild rabbit farms were widely distributed throughout the country (especially Cataluña, Galicia, Andalucía and Castilla La Mancha regions), while 21 hare farms were registered, the majority in Extremadura, Castilla La Mancha and Andalucía. A possible production figure of 225 000-265 000 rabbits and 1 034 hares was estimated in 2010. Game farms of wild lagomorphs are established in Spain and placement would be related to a high demand for hunting and predator conservation in certain regions. Although more research is needed, the number of animals produced would be an important part of the total animals released to the wild. SI

This article reviews some of the recent patents on DNA vaccines against fish viruses, in particular against the novirhabdovirus infectious hematopoitic necrosis virus (IHNV). Although very effective in protecting fish against IHNV, only one DNA vaccine has been approved to date for use in Canada. In Europe and in US, its commercialization is restricted due to safety concerns.

Introduction and objectives The literature on the involvement of microsatellite instability in head and neck squamous cell carcinoma shows great variability, probably due to differences in the testing methods. Using a consensus detection system, we aimed to reach a reliable estimate of microsatellite instability prevalence in a subset of head and neck squamous cell carcinoma cases. Methods The microsatellite instability status of 43 patients with previously untreated primary laryngeal squamous cell carcinomas was analysed by a multiplex polymerase chain reaction assay including 5 mononucleotide repeat markers. Results Thirty-six cases showed a stable phenotype or a microsatellite stable phenotype (83.7%) and 7 cases (16.3%) showed a microsatellite instability-positive phenotype. One case showed instability in 3 of 5 markers, 1 case in 2 markers and 5 cases in 1 marker. The microsatellite instability-positive and stable cases did not differ with respect to age, tumour stage, lymph node or distant metastases. Conclusions Our data showed that a proportion of laryngeal squamous cell carcinomas are microsatellite instability positive. Knowledge of microsatellite instability patient status will allow adjusting anticancer therapy at an individual level.

Endometrial cancer is among the three most common cancers in females in industrialized countries. In the majority of cases, the tumor is confined to the uterus at the time of diagnosis and presents a good prognosis. However, after primary surgery, 15% to 20% of these tumors recur and have limited response to systemic therapy. We carried out gene expression profiling of high-risk recurrence endometrial cancers to identify new therapeutic approaches targeting the molecular pathways involved in the acquisition of an aggressive tumor phenotype. A microarray gene-expression analysis on a total of 51 human endometrial carcinomas revealed 77 genes specifically altered in high-risk recurrence tumors (P < 0.001). The bioinformatics analysis of gene–gene interactions and molecular relationships among these genes pointed to a prominent role for TGF-β1 signaling in the acquisition of an aggressive phenotype. We further showed that TGF-β1 has a principal role at the initiation of endometrial carcinoma invasion through the promotion of the epithelial to mesenchymal transition that leads to the acquisition of an invasive phenotype in HEC-1A and RL95-2 cells. Impairment of this initial step with SB-431542, a specific TGF-β1 inhibitor, precluded further persistent endometrial carcinoma invasion. In conclusion, we showed that the characterization of the molecular changes associated with the acquisition of an aggressive phenotype represents a realistic strategy for the rational identification and characterization of new potential therapeutic targets in an effort to improve the clinical management and the outcome of high-risk endometrial cancer patients. Mol Cancer Ther; 10(8); 1357–66. ©2011 AACR.

Dear Editor, The approval of intravitreal injections of ranibizumab for the management of diabetic macular edema (DME) has induced a dramatical shift in the therapeutic approach of this entity, as the major clinical trials have proven the significant benefit of this treatment for patients with center-involving DME [1–3]. As a consequence, the classification of DME needs to be updated so that a useful correlation between grading and therapeutic indication could be assumed. Nowadays, the key feature of DME is the involvement or sparing of the fovea. Whenever DME involves the fovea, a clear indication for treatment with ranibizumab seems reasonable on the basis of the results reported by the major pivotal clinical trials. However, if the fovea is spared, laser photocoagulation might be indicated. Together with this, the continuous evolution of optical coherence tomography (OCT) systems makes it possible to precisely analyze qualitatively and quantitatively cases of DME, but also to have topographical information. Given the high accuracy of the topograhical thickness maps provided by the OCT devices, one might easily recognize just by taking a quick look at them the presence or abscence of foveal involvement, therefore making the decision on whether intravitreal injections of ranibizumab would be clearly indicated (foveal involvement) or not (foveal sparing). Furthermore, the morphometric and topographical analysis of DME should be considered as dynamic information, as every treatment might induce changes in thickness but also in the topograhy of the retinal thickenning. Again, at any point through the evolution of a single case of DME, by considering the foveal involvement or sparing, further therapeutic considerations could be easily undertaken. The burden of continuous follow-up visits and treatments required by patients with DME makes necessary to simplify the analysis of the macular thickening and the treatment decision. Fluorescein angiography (FA) provides valuable information about the status of the retinal circulation, and exclusive information about retinal ischemia, highlighting areas of retinal neovascularization. However, most of the findings shown on the FA images might not change the therapeutic consideration of the majority of cases with DME. Also, a good correlation between the leakage area evidenced on FA and the retinal thickening pattern shown by the retinal thickness map provided by the OCT has previously been reported [3–6]. Finally, FA is an invasive and timeconsuming technique. Thus, the treatment decision could be established by analyzing the retinal thickness maps provided by the OCT. Previous OCT classifications have focused on qualitative parameters [7], but not considered the topographical distribution and the involvement of the fovea. Herein (see Fig.1) we propose a simplified classification and grading of DME based on the OCT topographic findings that may be of great value for the physicians in order to make the choice of the most appropriate therapy for each eye of each patient presenting with DME to the daily practice. First, the location of the macular thickening should be topographically analyzed and classified into: central (involvement of the foveal ETDRS sector by macular thickening); peripheral (involvement of juxtafoveal ETDRS sectors with sparing of the foveal sector); marginal (involvement of extrafoveal ETDRS sectors with sparing of the juxtafoveal and foveal sectors). Secondly, the extent of the macular thickening should be stratified according to the total number of areas of the ETDRS grid occupied by retinal thickening (1 if the number of sectors involved is 1 to 3; 2 if it is 4 to 6; and 3 if it is 7 to 9). Finally, the presence of vitreofoveal traction should be considered (present or absent). R. Dolz-Marco : R. Gallego-Pinazo (*) Unit of Macula, Department of Ophthalmology, University and Polytechnic Hospital La Fe, Bulevar Sur, s/n, Valencia 46026, Spain e-mail: robertogallegopinazo@gmail.com

Background Sinonasal squamous cell carcinomas (SCCs) are rare tumors with no etiologic link to tobacco and alcohol, as opposed to other SCCs of the head and neck (HNSCC). Little is known about the genetic changes in sinonasal SCC. Methods DNA copy number changes of sinonasal SCC were analyzed by multiplex ligation-dependent probe amplification (MLPA) and microarray comparative genomic hybridization (maCGH), and results were related to clinicopathologic features. Results Copy number losses most frequently included genes at 9p21, 13q14, 17p13, 17q21, and 18q11. Frequent gains were observed on 8q24, 11q13, 17q12, 19p13, and 20q11–q13. Conclusion The genomic profile of sinonasal SCC showed a number of chromosomal regions with copy number changes similar to those known in HNSCC, in spite of the differences in etiology. © 2010 Wiley Periodicals, Inc. Head Neck, 2011

Background. Second primary tumors and recur- rences are an important problem in patients with head and neck squamous cell carcinoma. The purpose of this study was to determine the genetic changes in tumor samples to improve knowledge of tumor progression. Methods. Copy number changes of 37 genes were ana- lyzed by multiplex ligation-dependent probe amplification (MLPA) in 36 primary tumors and their corresponding 21 sec- ond primary tumors and 15 recurrences. Results. CCND1 and EMS1 amplifications and gain of BCL2L1 were the most common genetic alterations in the pri- mary tumor, second primary tumor, and recurrence samples. Gains of ERBB2 and PTPN1 were associated with recurrences. Conclusion. Specific genetic profiles for each group have been found. Similarities between primary tumor and second primary tumor and dissimilarity between primary tumor and re- currence suggest that clinicopathological criteria do not always accurately differentiate these entities. Genetic profiling may aid in the diagnosis and prognosis of these difficult cases. V

Background The aim of this study was to analyze genetic alterations in the transformation-progression model of laryngeal tumors. Methods Copy number changes of 37 genes were analyzed by multiple ligation-dependent probe amplification (MLPA) in 94 tissue samples. Results In the smoker normal mucosa group TP53 loss was predominant, whereas in the precursor lesions CDKN2A loss and CDKN2D gain were most frequent. Precursor lesions with progression presented CTNNB1 loss. In the carcinoma group the most common changes were CDKN2A, MLH1, CTNNB1, and CASP6 losses and RECQL4, CCND1, and EMS1 gains. Positive lymph node primary tumors were related to TP53, IL1A, and RB1 losses and STK11 gain. The lymph node metastases differed from their corresponding primary tumor in LMNA, RECQL4, and IGF1R losses, and N33 and CDKN2D gains. Conclusions Genetic changes and new key genes were found to be associated with specific steps. We included new steps, not presented in the classic models: normal mucosa tobacco exposed, positive lymph node primary tumor, and corresponding lymph node metastases. © 2010 Wiley Periodicals, Inc. Head Neck, 2011

The objective of this study was to evaluate the efficacy of a new heat-killed Mycobacterium avium ssp. paratuberculosis (MAP) vaccine for control of premature culling in tuberculosis-free dairy cattle. Feces and gastrointestinal tissues were collected from 50 vaccinated cows and 38 nonvaccinated cows at slaughter and analyzed by bacteriological culture and histopathology. Vaccination was associated with a significant reduction of the frequency of vaccinated animals with MAP in feces and gut tissues compared with the nonvaccinated animals. In addition, the frequency of vaccinated animals with heavy bacterial load in gut tissues was 40% lower than the frequency of the nonvaccinated animals with the same MAP load. The peak age of paratuberculosis-associated culling was from 4.5 to 5 yr old (21%) in the vaccinated animals and from 3 to 4.5 yr old (60%) in the nonvaccinated animals. The vaccinated and nonvaccinated animals with suspected paratuberculosis were culled at an average age of 4.7 and 3.7 yr old, respectively. Therefore, a significant increase in the productive life of the vaccinated animals sent to slaughter with suspected paratuberculosis was observed. In addition, our analysis revealed a positive effect of the vaccine on the carcass weights of the animals with severe histopathological lesions at slaughter compared with the nonvaccinated animals. In summary, our findings suggest a therapeutic effect of the vaccine and a significant attenuation of pre-existing infection in cows naturally infected with paratuberculosis that were adults at the time of vaccination.

Mycobacterium avium subsp. paratuberculosis adapts to the environment via the regulation of genes affecting its envelope’s composition. Bacteria grown in milk (in vivo conditions) presented differences in the cell wall-associated lipids and in the expression of genes involved in lipid metabolism (FadE8, FadE6 and MAP1420) and host cell invasion (MAP1203, LprL). A different lipid profile was also observed in the envelope of intracellular bacteria after 1 h of infection. Intracellular bacteria showed up-regulation of a LuxR regulator which controls the envelope’s composition by up-regulation of FadE8, MAP1420, MAP1203 and LprL and by down-regulation of pks12, mmpL2 and MAP2594. A LuxR-overexpressing strain with a lipid-deficient envelope phenotype, infected epithelial cells more efficiently than the wild-type bacteria; however, it was not more resistant than the wild-type strain to the action of bactericidal proteins. Here we show that LuxR regulates virulence determinants and is involved in mycobacteria adaptation to the host.

There is a need for comparisons of long-term outcomes in bipolar disorder patients with predominantly manic symptoms vs. predominantly depressive symptoms, especially the course of comorbid alcohol/substance abuse.A naturalistic sample of bipolar I patients (n=120) was followed prospectively for up to 10years. At baseline, number and polarity of past episodes were used to classify patients as predominantly manic or predominantly depressive if there were more manic or more depressive episodes, respectively. 25 patients were excluded from the analyses. Outcomes including episodes, hospitalisations and suicide attempts were recorded at bimonthly visits. Mixed effects models compared the course of alcohol and other substance abuse in predominantly manic vs. depressive patients.Of the 95 patients analyzed, 44 (46.3%) had predominantly manic episodes and 51 (53.7%) had predominantly depressive episodes. At baseline, the predominantly depressive group had more history of suicide attempts (45.1% vs. 20.5%; p=0.021) and more family history of affective disorders (64.7% vs. 38.6%; p=0.020), but they had fewer previous hospitalisations than the manic group (mean 0.38 vs. 0.50; p=0.025). During the 10-year follow-up, the predominantly depressive group was associated with more episodes (p=0.001), more hospitalisations (p=0.004) and more suicide attempts (p=0.002). At baseline, there were no differences between the manic and depressive groups in the frequency of alcohol abuse (43.2% and 35.3%, p=0.565) or other substance abuse (13.6% and 9.8%, p=0.794). During the 10-year follow-up, the frequency of alcohol and other substance abuse decreased significantly in the manic group only, after controlling by age at onset and civil (marital) status.Long-term clinical outcomes differ between predominantly manic vs. depressive bipolar patients, with the predominantly depressive group having a worse prognosis and maintained alcohol and other substance abuse. These differences should be considered when designing treatment approaches for bipolar patients with comorbid alcohol/substance abuse.

Johne's disease or paratuberculosis is a chronic granulomatous inflammation of the small intestine of ruminants caused by Mycobacterium avium subsp. paratuberculosis (MAP). Recent studies suggest an association between MAP and Crohn's disease in humans. MAP can become widely distributed within the tissues of infected animals, and meat may be a possible route of exposure of MAP to humans. In this study, 47 dairy and beef cattle were examined for the occurrence of viable MAP in diaphragm muscle. At the slaughterhouse, gut tissues, diaphragm muscle, blood, and feces of the 47 animals were collected for bacteriological culture, as well as gut samples for histopathological analysis. MAP was detected by bacteriological culture and conventional and real-time IS900 polymerase chain reaction in the diaphragm muscle of six infected cattle at slaughter (13%). The six animals showing evidence of MAP in diaphragm muscle had diffuse lesions and severe granulomatous inflammation in ileocecal lymph nodes, jejunal lymph nodes, ileocecal valve, and ileum. All six had heavy bacterial load in mesenteric lymph nodes, ileocecal valve, ileum, and jejunum, and four showed clinical signs of paratuberculosis. Two animals did not show clinical signs but had viable MAP in intestinal tissues and in diaphragm muscle as well. MAP was found in blood of only one of the six animals showing evidence of MAP in diaphragm muscle and in feces of three of them. In general, there was a positive association between enteric lesion severity, clinical signs of paratuberculosis, heavy bacterial load in intestinal tissues, fecal shedding of MAP, and the presence of disseminated MAP infection in diaphragm muscle. The results of this study demonstrated that MAP can be detected and cultured from muscle of MAP-infected cattle destined for human consumption and suggest a possible risk of exposure of humans to MAP via contaminated meat.

Objective To determine the usefulness of specific and reliable serum biomarkers to predict cervical lymph node metastasis. Methods A cross-sectional study of cases and controls. Thirty-nine serum samples of head and neck squamous cell carcinoma were collected from patients during neoplasm resection. Another 10 serum samples were collected from healthy individuals as a control group. Selected serum biomarkers were E-cadherin, MMP-2, MMP-9, active MMP-13, and p53 autoantibodies. Results We found a correlation between active MMP-13 (>685 pg/mL; ROC curve analysis 95% CI for sensitivity 79.6-99.3; specificity 49.2-95.1; positive predictive value 65-100; and negative predictive value 36-100) as well as the presence of p53 autoantibodies and lymph node metastasis. Multimarker analysis using MMP-13 and p53 autoantibodies together provided better sensitivity (76%) and specificity (100%). Conclusions The combined determination of active MMP-13 and p53 autoantibodies could improve diagnosis of lymphatic metastasis in head and neck squamous cell carcinoma and aid therapeutic decision making.

Lymph nodes metastasis is a major risk factor related to poor survival in larynx and pharynx carcinomas. The aim of this study is to search for markers of lymph node involvement analyzing the genetic differences between primary larynx and pharynx squamous cell carcinomas and their corresponding lymph node metastases. Twenty-five primary tumors and their corresponding lymph node metastases were examined. DNA copy number changes of 37 genes were analyzed by multiplex ligation-dependent probe amplification (MLPA). Loss of CDKN2A (9p21) occurred in 14 out of 25 pairs (56%) of primary tumor and lymph node metastases. Loss of LMNA (1q21) was exclusively detected in 8 lymph node samples (32%). Loss of CTNNB1 (3p22) and gain of CDKN2D (19p13) were also significantly more frequent in lymph node metastases. Other aberrations related to lymph node metastases were loss of MFHAS1 (8p23), RECQL4 (8q24) and gain of N33 (8p22) and TP53 (17p13). Primary tumor and corresponding lymph node metastases showed common genetic changes. However, the lymph node metastases presented with a number of additional alterations. Acquisition of these alterations may play a role in lymphatic metastasis development.

Mycobacterium avium subsp. paratuberculosis infection of cattle takes place through the intestinal mucosa. To identify M . avium subsp. paratuberculosis genes associated with the invasion of bovine epithelial cells in vitro, we screened a library of transposon mutants. Several mutants of M . avium subsp. paratuberculosis were identified which invaded Madin-Darby bovine kidney (MDBK) epithelial cells less efficiently than wild-type (wt) M . avium subsp. paratuberculosis . The ΔOx mutant had the transposon located in the MAP3464 gene, a putative oxidoreductase gene whose expression is upregulated upon bacterial contact with MDBK cells. Complete restoration of invasion comparable to that for the wt bacterium was achieved by introducing a copy of the complete oxidoreductase operon into the ΔOx mutant. Immunoprecipitation and Western blot analysis indicated that wt M . avium subsp. paratuberculosis activates Cdc42 and RhoA pathways of internalization 15 and 60 min after infection of the host cell, respectively. The ΔOx mutant, however, failed to activate the Cdc42 pathway. To determine whether an M . avium subsp. paratuberculosis protein delivered to the host cell mediates the entry of the wt bacterium by activation of the Cdc42 pathway, affinity precipitation of active Cdc42 from MDBK-infected cells followed by mass spectrometry was carried out. We identified a 17-amino-acid bacterial peptide associated with the Cdc42 of cells infected with wt M . avium subsp. paratuberculosis but not with the ΔOx mutant. The sequence of the peptide matches MAP3985c, a hypothetical protein, possibly functioning as a putative Cdc42 effector. These findings reveal a novel signaling pathway activated during M . avium subsp. paratuberculosis entry that links the product of MAP3464 gene to activation of Cdc42 in the host cell.

New energy concepts such as Distributed Power Generation are changing the face of electric distribution and transmission. Power electronics researchers try to apply new electronic controller solutions enabling the implementation of new and more complex control algorithms. This paper presents the design, implementation and test of the Field-Programmable Gate Array (FPGA) tasks of a novel real-time controller for a NPC (Neutral Point Clamped) (three-level) multilevel converter. The controller is based on a floating-point Digital Signal Processor (DSP) and a FPGA, by operating in a cooperative way. The proposed system is instantiated to the next system: a 150 kVA back-to-back three-level NPC VSC (Voltage Source Converter) for wind turbine applications.

Solitary schwannoma is a benign, encapsulated tumour of Schwann cell origin, therefore the olfactory and optic nerves are never affected. About 25%-45% of all schwannomas occur in the head and neck but schwannoma of the external auditory canal is a rare finding, and we have found only 6 previous cases reported in the literature world-wide. Our patient was discovered by chance during a stapedectomy because the tumour was sited in the external auditory canal without distorting it.

Ultrasonic transducers have been often used to develop Local Positioning Systems (LPS) in the field of intelligent spaces. In these systems, it is necessary to design an ultrasonic beacon, which is distributed in the environment to cover a determined area where mobile robots or people can be located. This work describes the design and the implementation of an ultrasonic beacon in an FPGA-based platform. The design is flexible enough to allow the real-time configuration of the ultrasonic emission, according to parameters as efficient encoding or suitable modulation schemes. Furthermore, the beacons have available a I2C link, so they are in permanent communication for exchanging configuration parameters and synchronization, not only among them, but also with a central configuration module.

Nowadays the most used multilevel topology for variable-speed wind turbines (WTs) is the a back-to back three-level NPC (Neutral Point Clamped) VSCs (voltage source converter). One of the most critical elements in the design of this type of converters is the DC-bus capacitors. The calculus of these depends on the same factors that the same two-levels topology, and, moreover it is function of a low frequency ripple due to the current by NP point. In this work, the value of these capacitors is obtained from the analytical equations of the DC-bus voltage ripple due to the i DC (DC-bus current) and the i NP (NP current). These expressions are verified through simulation and practical results.

Structural chromosomal aberrations are common in epithelial tumors. Here, we compared the location of centromeric breaks associated with whole arm translocations in seven adenocarcinoma cell lines and nine squamous cell carcinoma cell lines using SKY, microarray-based comparative genomic hybridization (array CGH) and fluorescence in situ hybridization (FISH). Whole arm translocations were more frequent in squamous cell carcinomas (112 in nine cell lines and nine in one short-term culture) than in adenocarcinomas (13 in seven cases) and most often resulted in copy number alterations. Array CGH analysis demonstrated that in all squamous cell carcinomas and in most adenocarcinomas, the breakpoints of unbalanced whole arm translocations occurred between the two clones on the array flanking the centromeres. However, FISH with centromeric probes revealed that in squamous cell carcinomas, the marker chromosomes with whole arm translocations contained centromeres comprised of material from both participating chromosomes, while in adenocarcinomas centromeric material from only one of the chromosomes was present. These observations suggest that different mechanisms of centromeric instability underlie the formation of chromosomal aberrations in adenocarcinomas and squamous cell carcinomas.

A survey of routes for aminal cleavage of N-sulfinylimidazolidines has been carried out, and selective conditions to cleave the aminal moiety while preserving the sulfinamide group unaltered have b...

Snakehead rhabdovirus (SHRV) affects warm-water fish in Southeast Asia and belongs to the genus Novirhabdovirus by virtue of its “nonvirion” (NV) gene. To examine the function of the NV gene, we used a recently developed reverse genetic system to produce a viable recombinant SHRV carrying an NV gene deletion. The recombinant virus was produced at the same rate and same final concentrations as the wild-type virus in cultured fish cells in spite of the NV gene deletion. The role of the NV protein in fish pathogenesis was also investigated. Zebra fish ( Danio rerio ) were infected with the NV deletion mutant or with a recombinant virus containing a copy of the SHRV genome, and similar mortality rates as well as final mortalities were recorded, suggesting no apparent role for the NV protein in fish pathogenesis. Interestingly, the unsuccessful rescue of fully viable recombinants with genomes containing deletions in the G/NV gene junction suggested a role for the gene junction in virus transcription and replication. Finally, we demonstrated that the SHRV glycoprotein can be replaced by the glycoprotein of infectious hematopoietic necrosis virus (IHNV) or by a hybrid protein composed of SHRV and IHNV sequences.

The objectives of this study were to analyse whether specific chromosomal gains and losses in lymph node-negative breast cancer correlate with other features and to evaluate their prognostic value. Seventy-six lymph node-negative breast carcinomas (median follow-up 46 months; range 9-105 months) were used. Histological grade, tumour type, maximal tumour diameter, oestrogen/progesterone receptor (ER/PR), mitotic activity index (MAI), and mean nuclear area (MNA) were assessed. Whole genome DNA analysis was performed by comparative genomic hybridization (CGH). Chromosomal aberrations were compared with classical and other prognostic features. Kaplan-Meier curves and multivariate survival analysis (Cox model) were used to assess the prognostic value of the CGH and other data. Fifteen (21.4%) out of 70 patients (six cases were lost to follow-up) developed locoregional (n=3) or distant metastases (n=12). The following criteria were prognostic for (any) recurrence (in decreasing significance): 3q gain, simultaneous gain at 1q and 8q, MAIversusor =10, MNAversusor =63 microm. Loss of 1p occurred significantly more often in the large group of ductal breast carcinomas with a MAIor =10 (n=38) than in cancers with a MAI10. Moreover, 8/15 (53%) patients with recurrences had a gain at 3q, as opposed to three (5.5%) of the 55 recurrence-free patients. This association was even stronger in ductal carcinomas (hazard ratio=10.9, p0.0001). Cox regression revealed that the 3q gain was the strongest prognostic factor; other features did not have additional prognostic value. In conclusion, loss of 1p is associated with a high MAI. A gain of 3q is a stronger predictor of recurrence than grade, MAI, and other features in invasive breast cancers.

12 páginas, 3 tablas, 2 figuras., Paratuberculosis is a chronic mycobacterial infection causing granulomatous enteritis in ruminants, whose pathogenesis and epidemiology poses numerous challenges, including latency and reactivation. The most recent and complete classification of paratuberculosis immunopathological types in cattle recognized five categories. In this study, 1031 slaughtered Friesian cattle were submitted to serological, microbiological and pathological examinations with the aim of maximizing the rate of case detection. In most cases, infected animals had minimal lesions and almost no other proof of infection (38.9%), while the more characteristic types with the whole constellation of microbiological and immunological evidences accounted for a lower proportion (7.7%). As these findings in cattle suggest similarities with the epidemiology of tuberculosis in humans, we propose to re-group the original immunopathological types into two broader paratuberculosis epidemio-pathogenic forms or states: latent and patent. The former term would define infections with focal lesions and might constitute an apparent resilience status representing a difficult to detect reservoir of infection whose role could become critical if later immune-compromising factors lead to re-activation. The latter would group those cases with multifocal and diffuse inflammatory lesions with higher mycobacterial load and viability suggestive of a more immediate epidemiological risk. Interestingly, the relative frequency of presentation of each profile varied with age. The proportion of latent forms remained relatively constant between 33.8% and 54.3% through adulthood from 3 years of age, while patent forms were more frequent during the first years of age and tended to decrease among the oldest individuals., This study was funded by a grant (AGL2006-14315-CO2) from the Ministry of Economy and Competitiveness (MINECO) (Spain). Patricia Vazquez was holder of a graduate fellowship award (FPI) (BES-2007-17170) from the Spanish MINECO.

Postoperative endophthalmitis is one of the most serious potential complications of ocular lens surgery. Its incidence can be reduced by means of antibiotic prophylaxis. Although the prophylactic use of intracameral cefuroxime has been extended, other drugs, such as moxifloxacin, have arisen as alternatives. We performed a systematic literature review on the effectiveness and efficiency of intracameral cefuroxime and moxifloxacin for the prophylaxis of postoperative endophthalmitis after cataract surgery. Several bibliographic databases were searched up to October 2010 and were updated up to January 2013. Outcomes were the onset of endophthalmitis after surgery and the cost-effectiveness ratio of using both antibiotic prophylaxis alternatives. The following were included: a clinical trial reported in two papers, six observational studies, and an economic evaluation. All studies assessed cefuroxime compared with another antibiotic prophylaxis or no prophylaxis. The only randomized controlled trial performed by the European Society of Cataract and Refractive Surgery found that intracameral cefuroxime is significantly more effective than not using prophylaxis or the use of a topical antibiotic. The observational studies support these results. The economic evaluation compared different prophylaxis regimens and concluded that intracameral cefuroxime showed the best cost-effectiveness ratio. Both the observational studies and the economic evaluation have methodological limits that reduce their validity. This review confirmed that cefuroxime can prevent endophthalmitis after cataract surgery. Further randomized controlled trials, with large sample sizes, are required to compare different antibiotic prophylaxis regimens.

Squamous cell carcinomas of the head and neck generally exhibit complex karyotypes. To gain better knowledge of the changes in the subgroup of laryngeal and pharyngeal squamous cell carcinoma, chromosomal gains and losses were investigated in 42 predominantly late-stage tumours, using comparative genomic hybridization. On average, 11.2 gains and 6.8 losses were found. Gains were detected in high frequencies at 1q, 3q, 5p, 7q, 8q, 11q13, 17q, and 18p, and losses at 3p, 4p, 5q, 11qter, and 18q. Neither the number nor the type of abnormalities, nor the occurrence of specific chromosome changes, was found to be related to DNA ploidy, tumour stage, or degree of differentiation. Apart from low-level gains, many high-level amplifications were identified, in particular 3q24-qter (15 cases). Other regions recurrently involved were 11q13 (7 cases), 18p (5 cases), 18q11.2 (4 cases), and 8q23-24 and 11q14-22 (3 cases). Many of these amplified regions have not been reported before. Over half of all loci harbour genes coding for growth factors and growth factor receptors, suggesting an important role for such genes in squamous cell tumourigenesis and in the progression of late-stage tumours.

A nested assay using the reverse trascription-polymerase chain reaction (RT-PCR) was developed for the detection of infectious hematopoietic necrosis virus (IHNV) in cell cultures coinfected with infectious pancreatic necrosis virus (IPNV). Two pairs of primers were designed: one for the amplification of glycoprotein G-specific gene RNA from IHNV (or 1512 bp fragment), and the other for the amplification of an inner 753 bp fragment using the cDNA from the G gene as substrate. Direct RT-PCR was also developed for the amplification of a VP-2 gene fragment from IPNV (613 bp fragment); this method always detected the virus IPNV in the coinfected cells tested but the amplification of IHNV was not as readily achieved. IHNV, however, was detected specifically by nested PCR in coinfected cells at a multiplicity of infection that was 1000 times lower than that of IPNV. Nested PCR was therefore more sensitive than direct RT-PCR for IHNV, and may thus be more appropriate for the detection of low infective titers of IHNV in the presence of IPNV when interference occurs., This study was supported by a grant from the Comisión Interministerial de Ciencia y Tecnologı́a, projects AGF-95-0016 and AGF98-0837. We thank Mercedes Sánchez for her excellent technical assistance.

Coinfection of farm-reared salmonids involving two viruses has been described, but there is no report on the interactions between viruses. Here we examine whether infectious pancreatic necrosis virus (IPNV) strain Sp interferes with the growth of infectious hematopoietic necrosis virus (IHNV) strain S46, a coinfected isolate from rainbow trout. When BF-2 cell culture was inoculated with S46 the infective titer of the IHNV fraction decreased by 3 log10 units compared to the growth curve of IHNV in the single infection. RT-PCR assay confirmed this reduction, which after successive passages of the co-infected sample led to a decrease in IHNV mRNA and the absence of the specific PCR product for IHNV. Flow cytometry showed that only 13% of the cells inoculated with S46 strain were infected with IHNV at 48-72 h post infection, in contrast to the 50-80% of cells that were positive for IPNV. Exposure of cells to IHNV for 24 h before infection with IPNV did not affect the infective titers of either virus or the PCR results obtained in simultaneous coinfections. Moreover IHNV was not inhibited when the IPNV inoculum was reduced. So, a multiplicity of infection dependence was demonstrated for IPNV-IHNV interference; the RT-PCR assay described here was found to be a suitable technique for identifying and studying dual viral infections.

El schwannoma es un tumor benigno encapsulado que puede afectar a cualquier nervio del organismo que tenga celulas de Schwann, nunca al nervio olfatorio ni el optico. Un 25-45% aparece en cabeza y cuello, pero en el conducto auditivo externo es excepcional, y solamente se han publicado en la literatura mundial otros 6 casos previos. Presentamos un caso descubierto accidentalmente al realizar la incision en un conducto normal, no abombado, durante una estapedectomia.