Virtual Routers as a Service: The Routeflow Approach Leveraging Software-Defined Networks

ABSTRACT The networking equipment market is being transformed by the need for greater openness and flexibility, not only for research purposes but also for in-house innovation by the equipment owners. In contrast to networking gear following the model of computer mainframes, where closed software runs on proprietary hardware, the software-defined networking approach effectively decouples the data from the control plane via an open API (i.e., OpenFlow protocol) that allows the (remote) control of packet forwarding engines. Motivated by this scenario, we propose RouteFlow, a commodity routing architecture that combines the line-rate performance of commercial hardware with the flexibility of open-source routing stacks (remotely) running on general purpose computers. The outcome is a novel point in the design space of commodity routing solutions with far-reaching implications towards virtual routers and IP networks as a service. This paper documents the progress achieved in the design and prototype implementation of our work and outlines our research agenda that calls for a community-driven approach

Ethylene and phloem signals are involved in the regulation of responses to Fe and P deficiencies in roots of strategy I plants

Iron (Fe) and phosphorus (P) are two essential mineral nutrients whose acquisition by plants presents important environmental and economic implications. Both elements are abundant in most soils but scarcely available to plants. To prevent Fe or P deficiency dicot plants initiate morphological and physiological responses in their roots aimed to specifically acquire these elements. The existence of common signals in Fe and P deficiency pathways suggests the signaling factors must act in conjunction with distinct nutrient-specific signals in order to confer tolerance to each deficiency. Previous works have shown the existence of cross talk between responses to Fe and P deficiency, but details of the associated signaling pathways remain unclear. Herein, the impact of foliar application of either P or Fe on P and Fe responses was studied in P- or Fe-deficient plants of Arabidopsis thaliana, including mutants exhibiting altered Fe or P homeostasis. Ferric reductase and acid phosphatase activities in roots were determined as well as the expression of genes related to P and Fe acquisition. The results obtained showed that Fe deficiency induces the expression of P acquisition genes and phosphatase activity, whereas P deficiency induces the expression of Fe acquisition genes and ferric reductase activity, although only transitorily. Importantly, these responses were reversed upon foliar application of either Fe or P on nutrient-starved plants. Taken together, the results reveal interactions between P- and Fe-related phloem signals originating in the shoots that likely interact with hormones in the roots to initiate adaptive mechanisms to tolerate deficiency of each nutrient

Intratumoral injection of dendritic cells engineered to secrete interleukin-12 by recombinant adenovirus in patients with metastatic gastrointestinal carcinomas.

PURPOSE: To evaluate the feasibility and safety of intratumoral injection of autologous dendritic cells (DCs) transfected with an adenovirus encoding interleukin-12 genes (AFIL-12) for patients with metastatic gastrointestinal carcinomas. Secondarily, we have evaluated biologic effects and antitumoral activity. PATIENTS AND METHODS: Seventeen patients with metastatic pancreatic (n = 3), colorectal (n = 5), or primary liver (n = 9) malignancies entered the study. DCs were generated from CD14+ monocytes from leukapheresis, cultured and transfected with AFIL-12 before administration. Doses from 10 x 10(6) to 50 x 10(6) cells were escalated in three cohorts of patients. Patients received up to three doses at 21-day intervals. RESULTS: Fifteen (88%) and 11 of 17 (65%) patients were assessable for toxicity and response, respectively. Intratumoral DC injections were mainly guided by ultrasound. Treatment was well tolerated. The most common side effects were lymphopenia, fever, and malaise. Interferon gamma and interleukin-6 serum concentrations were increased in 15 patients after each treatment, as well as peripheral blood natural killer activity in five patients. DC transfected with AFIL-12 stimulated a potent antibody response against adenoviral capsides. DC treatment induced a marked increase of infiltrating CD8+ T lymphocytes in three of 11 tumor biopsies analyzed. A partial response was observed in one patient with pancreatic carcinoma. Stable disease was observed in two patients and progression in eight patients, with two of the cases fast-progressing during treatment. CONCLUSION: Intratumoral injection of DC transfected with an adenovirus encoding interleukin-12 to patients with metastatic gastrointestinal malignancies is feasible and well tolerated. Further studies are necessary to define and increase clinical efficacy

Isolation and functional characterization of proinflammatory acidic phospholipase A2 from Bothrops leucurus snake venom

AbstractIn the present study, an acidic PLA2, designated Bl-PLA2, was isolated from Bothrops leucurus snake venom through two chromatographic steps: ion-exchange on CM-Sepharose and hydrophobic chromatography on Phenyl-Sepharose. Bl-PLA2 was homogeneous on SDS-PAGE and when submitted to 2D electrophoresis the molecular mass was 15,000Da and pI was 5.4. Its N-terminal sequence revealed a high homology with other Asp49 acidic PLA2s from snake venoms. Its specific activity was 159.9U/mg and the indirect hemolytic activity was also higher than that of the crude venom. Bl-PLA2 induced low myotoxic and edema activities as compared to those of the crude venom. Moreover, the enzyme was able to induce increments in IL-12p40, TNF-α, IL-1β and IL-6 levels and no variation of IL-8 and IL-10 in human PBMC stimulated in vitro, suggesting that Bl-PLA2 induces proinflammatory cytokine production by human mononuclear cells. Bothrops leucurus venom is still not extensively explored and knowledge of its components will contribute for a better understanding of its action mechanism

Prevalence of dementia subtypes in a developing country: a clinicopathological study

OBJECTIVES: To assess the distribution of dementia subtypes in Brazil using a population-based clinicopathological study. METHOD: Brains from deceased individuals aged ≥50 years old were collected after the next of kin signed an informed consent form and provided information through standardized questionnaires. Post-mortem clinical diagnoses were established in consensus meetings, and only cases with moderate or severe dementia or without cognitive impairment were included in the analysis. Immunohistochemical neuropathological examinations were performed following the universally accepted guidelines. A diagnosis of Alzheimer's disease was made when there were at least both a moderate density of neuritic plaques (Consortium to Establish a Register for Alzheimer's disease B or C) and Braak stage III for neurofibrillary tangle distribution. For the diagnosis of vascular dementia, at least three zones or strategic areas had to be affected by infarcts, lacunae, or microinfarcts. RESULTS: From 1,291 subjects, 113 cases were classified as having moderate or severe dementia, and 972 cases were free of cognitive impairment. The neuropathological diagnoses of the dementia sub-group were Alzheimer's disease (35.4%), vascular dementia (21.2%), Alzheimer's disease plus vascular dementia (13.3%), and other causes of dementia (30.1%). Small-vessel disease, which alone was not considered sufficient for a vascular dementia diagnosis, was present in 38.9% of all of the dementia cases and in 16.8% of the group without cognitive impairment (odds ratio = 2.91; 95% confidence interval, 1.53-5.51), adjusted for age, sex, and education. CONCLUSIONS: The relatively high frequencies of vascular dementia and small-vessel disease in the dementia sub-group constitute relevant findings for public health initiatives because control of vascular risk factors could decrease the prevalence of dementia in developing countries

Peces de la cuenca del río Orinoco. Parte I: Lista de especies y distribución por subcuencas

Para efectos del presente trabajo y en función de los datos disponibles hasta la fecha, se consideran las siguientes subcuencas y/o regiones para la cuenca del Orinoco, desde su nacimiento hasta su desembocadura en el océano Atlántico: Alto Orinoco, Casiquiare, Ventuari, Atabapo, Inírida, Guaviare, Vichada, Sipapo, Tomo, Cataniapo, Bita, Meta, Parguaza, Cinaruco, Suapure, Capanaparo, Arauca, Apure, Cuchivero, Manapiare, Zuata, Caura, Pao, Aro, Caris, Caroní, Morichal Largo, Delta y Orinoco (Mapa)

Paracetamol in therapeutic dosages and acute liver injury: causality assessment in a prospective case series

Background: Acute liver injury (ALI) induced by paracetamol overdose is a well known cause of emergency hospital admission and death. However, there is debate regarding the risk of ALI after therapeutic dosages of the drug. The aim is to describe the characteristics of patients admitted to hospital with jaundice who had previous exposure to therapeutic doses of paracetamol. An assessment of the causality role of paracetamol was performed in each case. Methods: Based on the evaluation of prospectively gathered cases of ALI with detailed clinical information, thirty-two cases of ALI in non-alcoholic patients exposed to therapeutic doses of paracetamol were identified. Two authors assessed all drug exposures by using the CIOMS/RUCAM scale. Each case was classified into one of five categories based on the causality score for paracetamol. Results: In four cases the role of paracetamol was judged to be unrelated, in two unlikely, and these were excluded from evaluation. In seven of the remaining 26 cases, the RUCAM score associated with paracetamol was higher than that associated with other concomitant medications. The estimated incidence of ALI related to the use of paracetamol in therapeutic dosages was 0.4 per million inhabitants older than 15 years of age and per year (99%CI, 0.2-0.8) and of 10 per million paracetamol users-year (95% CI 4.3-19.4). Conclusions:Our results indicate that paracetamol in therapeutic dosages may be considered in the causality assessment in non-alcoholic patients with liver injury, even if the estimated incidence of ALI related to paracetamol appears to be low

A shoot Fe signaling pathway requiring the OPT3 transporter controls GSNO reductase and ethylene in arabidopsis thaliana roots

Ethylene, nitric oxide (NO) and glutathione (GSH) increase in Fe-deficient roots of Strategy I species where they participate in the up-regulation of Fe acquisition genes. However, S-nitrosoglutathione (GSNO), derived from NO and GSH, decreases in Fe-deficient roots. GSNO content is regulated by the GSNO-degrading enzyme S-nitrosoglutathione reductase (GSNOR). On the other hand, there are several results showing that the regulation of Fe acquisition genes does not solely depend on hormones and signaling molecules (such as ethylene or NO), which would act as activators, but also on the internal Fe content of plants, which would act as a repressor. Moreover, different results suggest that total Fe in roots is not the repressor of Fe acquisition genes, but rather the repressor is a Fe signal that moves from shoots to roots through the phloem [hereafter named LOng Distance Iron Signal (LODIS)]. To look further in the possible interactions between LODIS, ethylene and GSNOR, we compared Arabidopsis WT Columbia and LODIS-deficient mutant opt3-2 plants subjected to different Fe treatments that alter LODIS content. The opt3-2 mutant is impaired in the loading of shoot Fe into the phloem and presents constitutive expression of Fe acquisition genes. In roots of both Columbia and opt3-2 plants we determined 1-aminocyclopropane1-carboxylic acid (ACC, ethylene precursor), expression of ethylene synthesis and signaling genes, and GSNOR expression and activity. The results obtained showed that both 'ethylene' (ACC and the expression of ethylene synthesis and signaling genes) and 'GSNOR' (expression and activity) increased in Fe-deficient WT Columbia roots. Additionally, Fe-sufficient opt3-2 roots had higher 'ethylene' and 'GSNOR' than Fe-sufficient WT Columbia roots. The increase of both 'ethylene' and 'GSNOR' was not related to the total root Fe content but to the absence of a Fe shoot signal (LODIS), and was associated with the up-regulation of Fe acquisition genes. The possible relationship between GSNOR(GSNO) and ethylene is discussed