887 resultados para DDoS attack defense


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Objectives: In fast ball sports like beach volleyball, decision-making skills are a determining factor for excellent performance. The current investigation aimed to identify factors that influence the decisionmaking process in top-level beach volleyball defense in order to find relevant aspects for further research. For this reason, focused interviews with top players in international beach volleyball were conducted and analyzed with respect to decision-making characteristics. Design: Nineteen world-tour beach volleyball defense players, including seven Olympic or world champions, were interviewed, focusing on decision-making factors, gaze behavior, and interactions between the two. Methods: Verbal data were analyzed by inductive content analysis according to Mayring (2008). This approach allows categories to emerge from the interview material itself instead of forcing data into preset classifications and theoretical concepts. Results: The data analysis showed that, for top-level beach volleyball defense, decision making depends on opponent specifics, external context, situational context, opponent's movements, and intuition. Information on gaze patterns and visual cues revealed general tendencies indicating optimal gaze strategies that support excellent decision making. Furthermore, the analysis highlighted interactions between gaze behavior, visual information, and domain-specific knowledge. Conclusions: The present findings provide information on visual perception, domain-specific knowledge, and interactions between the two that are relevant for decision making in top-level beach volleyball defense. The results can be used to inform sports practice and to further untangle relevant mechanisms underlying decision making in complex game situations.

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The purpose of this study was to determine if storage for up to 4 h in human saliva results in a decrease of erosive tooth wear (ETW) and in an increase of surface microhardness (SMH) of enamel samples after an erosive attack with subsequent abrasion. Furthermore, we determined the impact of individual salivary parameters on ETW and SMH. Enamel samples were distributed into five groups: group 1 had neither erosion nor saliva treatment; groups 2-5 were treated with erosion, then group 2 was placed in a humid chamber and groups 3-5 were incubated in saliva for 30 min, 2 h, and 4 h, respectively. After erosion and saliva treatments, all groups were treated with abrasion. Surface microhardness and ETW were measured before and after erosion, incubation in saliva, and abrasion. Surface microhardness and ETW showed significant changes throughout the experiment: SMH decreased and ETW increased in groups 2-5, regardless of the length of incubation in saliva. The results of groups 3-5 (exposed to saliva) were not significantly different from those of group 2 (not exposed to saliva). Exposure of eroded enamel to saliva for up to 4 h was not able to increase SMH or reduce ETW. However, additional experiments with artificial saliva without proteins showed protection from erosive tooth wear. The recommendation to postpone toothbrushing of enamel after an erosive attack should be reconsidered.

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Aberrant glycosylation is a key feature of malignant transformation and reflects epigenetic and genetic anomalies among the multitude of molecules involved in glycan biosynthesis. Although glycan biosynthesis is not template bound, altered tumor glycosylation is not random, but associated with common glycosylation patterns. Evidence suggests that acquisition of distinct glycosylation patterns evolves from a ‘microevolutionary’ process conferring advantages in terms of tumor growth, tumor dissemination, and immune escape. Such glycosylation modifications also involve xeno- and hypersialylation. Xeno-autoantigens such as Neu5Gc-gangliosides provide potential targets for immunotherapy. Hypersialylation may display ‘enhanced self’ to escape immunosurveillance and involves several not mutually exclusive inhibitory pathways that all rely on protein–glycan interactions. A better understanding of tumor ‘glycan codes’ as deciphered by lectins, such as siglecs, selectins, C-type lectins and galectins, may lead to novel treatment strategies, not only in cancer, but also in autoimmune disease or transplantation.

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BACKGROUND AND PURPOSE Copeptin has been associated with recurrent cerebrovascular events after transient ischemic attack (TIA). In an independent cohort, we evaluated copeptin for the prediction of recurrent cerebrovascular events within 3 months after TIA and assessed the incremental value of copeptin compared with the ABCD2 (age, blood, clinical features of TIA, duration of symptoms, presence of diabetes mellitus) and ABCD3-I (ABCD2, dual TIA [the presence of ≥2 TIA symptoms within 7 days], imaging [the presence of abnormal findings on neuroimaging]) scores. METHODS This prospective, multicenter cohort study was conducted at 3 tertiary Stroke Centers in Switzerland and Germany. RESULTS From March 2009 through April 2011, we included 302 patients with TIA admitted within 24 hours from symptom onset. Of 28 patients with a recurrent cerebrovascular event within 3 months (stroke or TIA), 11 patients had a stroke. Although the association of copeptin with recurrent cerebrovascular events was not significant, the association with stroke alone as end point was significant. After adjusting for the ABCD2 score, a 10-fold increase in copeptin levels was associated with an odds ratio for stroke of 3.39 (95% confidence interval, 1.28-8.96; P=0.01). After addition of copeptin to the ABCD2 score, the area under the curve of the ABCD2 score improved from 0.60 (95% confidence interval, 0.46-0.74) to 0.74 (95% confidence interval, 0.60-0.88, P=0.02). In patients with MRI (n=223), the area under the curve of the ABCD3-I score increased in similar magnitude, although not significantly. Based on copeptin, 31.2% of patients were correctly reclassified across the risk categories of the ABCD2 score (net reclassification improvement; P=0.17). CONCLUSIONS Copeptin improved the prognostic value of the ABCD2 score for the prediction of stroke but not TIA, and it may help clinicians in refining risk stratification for patients with TIA. CLINICAL TRIAL REGISTRATION URL http://www.clinicaltrials.gov. Unique identifier: NCT00878813.

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BACKGROUND AND PURPOSE Visit-to-visit variability in systolic blood pressure (SBP) is associated with an increased risk of stroke and was reduced in randomized trials by calcium channel blockers and diuretics but not by renin-angiotensin system inhibitors. However, time of day effects could not be determined. Day-to-day variability on home BP readings predicts stroke risk and potentially offers a practical method of monitoring response to variability-directed treatment. METHODS SBP mean, maximum, and variability (coefficient of variation=SD/mean) were determined in 500 consecutive transient ischemic attack or minor stroke patients on 1-month home BP monitoring (3 BPs, 3× daily). Hypertension was treated to a standard protocol. Differences in SBP variability from 3 to 10 days before to 8 to 15 days after starting or increasing calcium channel blockers/diuretics versus renin-angiotensin system inhibitors versus both were compared by general linear models, adjusted for risk factors and baseline BP. RESULTS Among 288 eligible interventions, variability in SBP was reduced after increased treatment with calcium channel blockers/diuretics versus both versus renin-angiotensin system inhibitors (-4.0 versus 6.9 versus 7.8%; P=0.015), primarily because of effects on maximum SBP (-4.6 versus -1.0 versus -1.0%; P=0.001), with no differences in effect on mean SBP. Class differences were greatest for early-morning SBP variability (3.6 versus 17.0 versus 38.3; P=0.002) and maximum (-4.8 versus -2.0 versus -0.7; P=0.001), with no effect on midmorning (P=0.29), evening (P=0.65), or diurnal variability (P=0.92). CONCLUSIONS After transient ischemic attack or minor stroke, calcium channel blockers and diuretics reduced variability and maximum home SBP, primarily because of effects on morning readings. Home BP readings enable monitoring of response to SBP variability-directed treatment in patients with recent cerebrovascular events.

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by Israel Cohen

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Dysfunction of Paneth and goblet cells in the intestine contributes to inflammatory bowel disease (IBD) and colitis-associated colorectal cancer (CAC). Here, we report a role for the NAD+-dependent histone deacetylase SIRT1 in the control of anti-bacterial defense. Mice with an intestinal specific Sirt1 deficiency (Sirt1int-/-) have more Paneth and goblet cells with a consequent rearrangement of the gut microbiota. From a mechanistic point of view, the effects on mouse intestinal cell maturation are mediated by SIRT1-dependent changes in the acetylation status of SPDEF, a master regulator of Paneth and goblet cells. Our results suggest that targeting SIRT1 may be of interest in the management of IBD and CAC.

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Approximately 0.2 % of all angiosperms are classified as metal hyperaccumulators based on their extraordinarily high leaf metal contents, for example >1 % zinc, >0.1 % nickel or >0.01 % cadmium (Cd) in dry biomass. So far, metal hyperaccumulation has been considered to be a taxon-wide, constitutively expressed trait, the extent of which depends solely on available metal concentrations in the soil. Here we show that in the facultative metallophyte Arabidopsis halleri, both insect herbivory and mechanical wounding of leaves trigger an increase specifically in leaf Cd accumulation. Moreover, the Cd concentrations accumulated in leaves can serve as an elemental defense against herbivory by larvae of the Brassicaceae specialist small white (Pieris rapae), thus allowing the plant to take advantage of this non-essential trace element and toxin. Metal homeostasis genes are overrepresented in the systemic transcriptional response of roots to the wounding of leaves in A. halleri, supporting that leaf Cd accumulation is preceded by systemic signaling events. A similar, but quantitatively less pronounced transcriptional response was observed in A. thaliana, suggesting that the systemically regulated modulation of metal homeostasis in response to leaf wounding also occurs in non-hyperaccumulator plants. This is the first report of an environmental stimulus influencing metal hyperaccumulation.

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Insect-induced defenses occur in nearly all plants and are regulated by conserved signaling pathways. As the first described plant peptide signal, systemin regulates antiherbivore defenses in the Solanaceae, but in other plant families, peptides with analogous activity have remained elusive. In the current study, we demonstrate that a member of the maize (Zea mays) plant elicitor peptide (Pep) family, ZmPep3, regulates responses against herbivores. Consistent with being a signal, expression of the ZmPROPEP3 precursor gene is rapidly induced by Spodoptera exigua oral secretions. At concentrations starting at 5 pmol per leaf, ZmPep3 stimulates production of jasmonic acid, ethylene, and increased expression of genes encoding proteins associated with herbivory defense. These include proteinase inhibitors and biosynthetic enzymes for production of volatile terpenes and benzoxazinoids. In accordance with gene expression data, plants treated with ZmPep3 emit volatiles similar to those from plants subjected to herbivory. ZmPep3-treated plants also exhibit induced accumulation of the benzoxazinoid phytoalexin 2-hydroxy-4,7-dimethoxy-1,4-benzoxazin-3-one glucoside. Direct and indirect defenses induced by ZmPep3 contribute to resistance against S. exigua through significant reduction of larval growth and attraction of Cotesia marginiventris parasitoids. ZmPep3 activity is specific to Poaceous species; however, peptides derived from PROPEP orthologs identified in Solanaceous and Fabaceous plants also induce herbivory-associated volatiles in their respective species. These studies demonstrate that Peps are conserved signals across diverse plant families regulating antiherbivore defenses and are likely to be the missing functional homologs of systemin outside of the Solanaceae.

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Sterols are an essential class of lipids in eukaryotes, where they serve as structural components of membranes and play important roles as signaling molecules. Sterols are also of high pharmacological significance: cholesterol-lowering drugs are blockbusters in human health, and inhibitors of ergosterol biosynthesis are widely used as antifungals. Inhibitors of ergosterol synthesis are also being developed for Chagas's disease, caused by Trypanosoma cruzi. Here we develop an in silico pipeline to globally evaluate sterol metabolism and perform comparative genomics. We generate a library of hidden Markov model-based profiles for 42 sterol biosynthetic enzymes, which allows expressing the genomic makeup of a given species as a numerical vector. Hierarchical clustering of these vectors functionally groups eukaryote proteomes and reveals convergent evolution, in particular metabolic reduction in obligate endoparasites. We experimentally explore sterol metabolism by testing a set of sterol biosynthesis inhibitors against trypanosomatids, Plasmodium falciparum, Giardia, and mammalian cells, and by quantifying the expression levels of sterol biosynthetic genes during the different life stages of T. cruzi and Trypanosoma brucei. The phenotypic data correlate with genomic makeup for simvastatin, which showed activity against trypanosomatids. Other findings, such as the activity of terbinafine against Giardia, are not in agreement with the genotypic profile.

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Plant invertases are sucrolytic enzymes that are essential for the regulation of carbohydrate metabolism and source–sink relationships. While their activity has been well documented during abiotic and biotic stresses, the role of proteinaceous invertase inhibitors in regulating these changes is unknown. Here, we identify a putative Nicotiana attenuata cell wall invertase inhibitor (NaCWII) which is strongly up-regulated in a jasmonate (JA)-dependent manner following simulated attack by the specialist herbivore Manduca sexta. To understand the role of NaCWII in planta, we silenced its expression by RNA interference and measured changes in primary and secondary metabolism and plant growth following simulated herbivory. NaCWII-silenced plants displayed a stronger depletion of carbohydrates and a reduced capacity to increase secondary metabolite pools relative to their empty vector control counterparts. This coincided with the attenuation of herbivore-induced CWI inhibition and growth suppression characteristic of wild-type plants. Together our findings suggest that NaCWII may act as a regulatory switch located downstream of JA accumulation which fine-tunes the plant's balance between growth and defense metabolism under herbivore attack. Although carbohydrates are not typically viewed as key factors in plant growth and defense, our study shows that interfering with their catabolism strongly influences plant responses to herbivory.

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In monocotyledonous plants, 1,4-benzoxazin-3-ones, also referred to as benzoxazinoids or hydroxamic acids, are one of the most important chemical barriers against herbivores. However, knowledge about their behavior after attack, mode of action and potential detoxification by specialized insects remains limited. We chose an innovative analytical approach to understand the role of maize 1,4-benzoxazin-3-ones in plant–insect interactions. By combining unbiased metabolomics screening and simultaneous measurements of living and digested plant tissue, we created a quantitative dynamic map of 1,4-benzoxazin-3-ones at the plant–insect interface. Hypotheses derived from this map were tested by specifically developed in vitro assays using purified 1,4-benzoxazin-3-ones and active extracts from mutant plants lacking 1,4-benzoxazin-3-ones. Our data show that maize plants possess a two-step defensive system that effectively fends off both the generalist Spodoptera littoralis and the specialist Spodoptera frugiperda. In the first step, upon insect attack, large quantities of 2-β-d-glucopyranosyloxy-4,7-dimethoxy-1,4-benzoxazin-3-one (HDMBOA-Glc) are formed. In the second step, after tissue disruption by the herbivores, highly unstable 2-hydroxy-4,7-dimethoxy-1,4-benzoxazin-3-one (HDMBOA) is released by plant-derived β-glucosidases. HDMBOA acts as a strong deterrent to both S. littoralis and S. frugiperda. Although constitutively produced 1,4-benzoxazin-3-ones such as 2,4-dihydroxy-7-methoxy-1,4-benzoxazin-3-one (DIMBOA) are detoxified via glycosylation by the insects, no conjugation of HDMBOA in the insect gut was found, which may explain why even the specialist S. frugiperda has not evolved immunity against this plant defense. Taken together, our results show the benefit of using a plant–insect interface approach to elucidate plant defensive processes and unravel a potent resistance mechanism in maize.

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Ethylene responsive factors (ERFs) are a large family of plant-specific transcription factors that are involved in the regulation of plant development and stress responses. However, little to nothing is known about their role in herbivore-induced defense. We discovered a nucleus-localized ERF gene in rice (Oryza sativa), OsERF3, that was rapidly up-regulated in response to feeding by the rice striped stem borer (SSB) Chilo suppressalis. Antisense and over-expression of OsERF3 revealed that it positively affects transcript levels of two mitogen-activated protein kinases (MAPKs) and two WRKY genes as well as concentrations of jasmonate (JA), salicylate (SA) and the activity of trypsin protease inhibitors (TrypPIs). OsERF3 was also found to mediate the resistance of rice to SSB. On the other hand, OsERF3 was slightly suppressed by the rice brown planthopper (BPH) Nilaparvata lugens (Stål) and increased susceptibility to this piercing sucking insect, possibly by suppressing H2O2 biosynthesis. We propose that OsERF3 affects early components of herbivore-induced defense responses by suppressing MAPK repressors and modulating JA, SA, ethylene and H2O2 pathways as well as plant resistance. Our results also illustrate that OsERF3 acts as a central switch that gears the plant’s metabolism towards an appropriate response to chewing or piercing/sucking insects.

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Plants produce large amounts of secondary metabolites in their shoots and roots and store them in specialized secretory structures. Although secondary metabolites and their secretory structures are commonly assumed to have a defensive function, evidence that they benefit plant fitness under herbivore attack is scarce, especially below ground. Here, we tested whether latex secondary metabolites produced by the common dandelion (Taraxacum officinale agg.) decrease the performance of its major native insect root herbivore, the larvae of the common cockchafer (Melolontha melolontha), and benefit plant vegetative and reproductive fitness under M. melolontha attack. Across 17 T. officinale genotypes screened by gas and liquid chromatography, latex concentrations of the sesquiterpene lactone taraxinic acid β-D-glucopyranosyl ester (TA-G) were negatively associated with M. melolontha larval growth. Adding purified TA-G to artificial diet at ecologically relevant concentrations reduced larval feeding. Silencing the germacrene A synthase ToGAS1, an enzyme that was identified to catalyze the first committed step of TA-G biosynthesis, resulted in a 90% reduction of TA-G levels and a pronounced increase in M. melolontha feeding. Transgenic, TA-G-deficient lines were preferred by M. melolontha and suffered three times more root biomass reduction than control lines. In a common garden experiment involving over 2,000 T. officinale individuals belonging to 17 different genotypes, high TA-G concentrations were associated with the maintenance of high vegetative and reproductive fitness under M. melolontha attack. Taken together, our study demonstrates that a latex secondary metabolite benefits plants under herbivore attack, a result that provides a mechanistic framework for root herbivore driven natural selection and evolution of plant defenses below ground.

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BACKGROUND The presence of prodromal transient ischemic attacks (TIAs) has been associated with a favorable outcome in anterior circulation stroke. We aimed to determine the association between prodromal TIAs or minor stroke and outcomes at 1 month, in the Basilar Artery International Cooperation Study, a registry of patients presenting with an acute symptomatic and radiologically confirmed basilar artery occlusion. METHODS A total of 619 patients were enrolled in the registry. Information on prodromal TIAs was available for 517 patients and on prodromal stroke for 487 patients. We calculated risk ratios and corresponding 95% confidence intervals (CIs) for poor clinical outcome (modified Rankin Scale score ≥4) according to the variables of interest. RESULTS Prodromal minor stroke was associated with poor outcome (crude risk ratio [cRR], 1.26; 95% CI, 1.12-1.42), but TIAs were not (cRR, .93; 95% CI, .79-1.09). These associations remained essentially the same after adjustment for confounding variables. CONCLUSIONS Prodromal minor stroke was associated with an unfavorable outcome in patients with basilar artery occlusion, whereas prodromal TIA was not.