Further results in J and CTOD estimation procedures for SE(T) fracture specimens - Part I: Homogeneous materials

This study provides further developments of the evaluation procedure for J and CTOD in SE(T) fracture specimens based on plastic eta-factors and load separation analysis. Non-linear finite element analyses for plane-strain and 3-D models provide the relationship between plastic work and crack driving forces which define the eta-values. Further analyses based on the load separation method define alternative eta-values for the analyzed specimen configurations. Overall, the present results provide improved estimation equations for J and CTOD as a function of loading condition (pin load vs. clamp ends), crack geometry and strain hardening properties. (C) 2011 Elsevier Ltd. All rights reserved.

The Aurora A and B kinases are up-regulated in bone marrow-derived chronic lymphocytic leukemia cells and represent potential therapeutic targets

Background The malignant B cells in chronic lymphocytic leukemia receive signals from the bone marrow and lymph node microenvironments which regulate their survival and proliferation. Characterization of these signals and the pathways that propagate them to the interior of the cell is important for the identification of novel potential targets for therapeutic intervention. Design and Methods We compared the gene expression profiles of chronic lymphocytic leukemia B cells purified from bone marrow and peripheral blood to identify genes that are induced by the bone marrow microenvironment. Two of the differentially expressed genes were further studied in cell culture experiments and in an animal model to determine whether they could represent appropriate therapeutic targets in chronic lymphocytic leukemia. Results Functional classification analysis revealed that the majority of differentially expressed genes belong to gene ontology categories related to cell cycle and mitosis. Significantly up-regulated genes in bone marrow-derived tumor cells included important cell cycle regulators, such as Aurora A and B, survivin and CDK6. Down-regulation of Aurora A and B by RNA interference inhibited proliferation of chronic lymphocytic leukemia-derived cell lines and induced low levels of apoptosis. A similar effect was observed with the Aurora kinase inhibitor VX-680 in primary chronic lymphocytic leukemia cells that were induced to proliferate by CpG-oligonucleotides and interleukin-2. Moreover, VX-680 significantly blocked leukemia growth in a mouse model of chronic lymphocytic leukemia. Conclusions Aurora A and B are up-regulated in proliferating chronic lymphocytic leukemia cells and represent potential therapeutic targets in this disease.

A systematic study of transfection efficiency and cytotoxicity in HeLa cells using iron oxide nanoparticles prepared with organic and inorganic bases

Magnetic iron oxide nanoparticles (magnetite) (MNPs) were prepared using different organic and inorganic bases. Strong inorganic base (KOH) and organic bases (NH4OH and 1,4-diazabicyclo[2.2.2]octane (DABCO)) were used in the syntheses of the MNPs. The MNPs were characterized by X-ray diffraction (XRD), scanning electron microscope (SEM). Fourier transform infrared spectroscopy (FT-IR) and magnetization measurements. MNPs prepared with strong inorganic base yielded an average size of 100 nm, whereas the average size of the MNPs prepared with the organic bases was 150 nm. The main competitive phase for MNPs prepared with the strong inorganic and organic bases was maghemite; however, syntheses with KOH yielded a pure magnetite phase. The transfection study performed with the MNPs revealed that the highest transfection rate was obtained with the MNPs prepared with KOH (74%). The correlation between the magnetic parameters and the transfection ratio without transfection agents indicated that MNPs prepared with KOH were a better vector for possible applications of these MNPs in biomedicine. HeLa cells incubated with MNP-KOH at 10 mu g/mL for 24 and 48 h exhibited a decrease in population in comparison with the control cells and it was presumably related to the toxicity of the MNPs. However, the cells incubated with MNP-KOH at 50 and 100 mu g/mL presented a very small difference in the viability between the cell populations studied at 24 and 48 h. These data illustrate the viability of HeLa cells treated with MNP-KOH and suggest the potential use of these MNPs in biomedical applications. (C) 2012 Elsevier B.V. All rights reserved.

Revisiting the Security of the ALRED Design and Two of Its Variants: Marvin and LetterSoup

The ALRED construction is a lightweight strategy for constructing message authentication algorithms from an underlying iterated block cipher. Even though this construction's original analyses show that it is secure against some attacks, the absence of formal security proofs in a strong security model still brings uncertainty on its robustness. In this paper, aiming to give a better understanding of the security level provided by different authentication algorithms based on this design strategy, we formally analyze two ALRED variants-the MARVIN message authentication code and the LETTERSOUP authenticated-encryption scheme,-bounding their security as a function of the attacker's resources and of the underlying cipher's characteristics.

Geochemical constraints on blueschist- and amphibolite-facies rocks of the Central Cordillera of Colombia: the Andean Barragan region

Subduction zones are one of the most characteristic features of planet Earth. Convergent plate junctions exert enormous influence on the formation and recycling of continental crust, and they are also responsible for major mineral resources and earthquakes, which are of crucial importance for society. A subduction-related geologic unit containing high-pressure rocks occurs in the Barragan area (Valle del Cauca Department) on the western flank of the Central Cordillera of the Colombian Andes. Blueschists and amphibolites, serpentinized meta-ultramafic rocks, graphite-chlorite-muscovite-quartz schists, protocataclasites, and graphite-chlorite-andalusite-andesine-garnet-muscovite +/- titanite schists are exposed in this region. In spite of the petrotectonic importance of blueschists, the high-pressure metamorphism of the Central Cordillera of Colombia has been rarely studied. New geochemical data indicate that protoliths of the blueschist- and amphibolite-facies rocks possessed normal mid-ocean ridge basalt bulk compositions. Ar-40/Ar-39 geochronology for a metapelite rock associated with the blueschists shows a plateau age of similar to 120 million years. We suggest that high-P/T conditions were present from similar to 150 to 125 Ma, depending on the model of generation and exhumation considered.

Progression to Adrenocortical Tumorigenesis in Mice and Humans through Insulin-Like Growth Factor 2 and beta-Catenin

Dysregulation of the WNT and insulin-like growth factor 2 (IGF2) signaling pathways has been implicated in sporadic and syndromic forms of adrenocortical carcinoma (ACC). Abnormal beta-catenin staining and CTNNB1 mutations are reported to be common in both adrenocortical adenoma and ACC, whereas elevated IGF2 expression is associated primarily with ACC. To better understand the contribution of these pathways in the tumorigenesis of ACC, we examined clinicopathological and molecular data and used mouse models. Evaluation of adrenal tumors from 118 adult patients demonstrated an increase in CTNNB1 mutations and abnormal beta-catenin accumulation in both adrenocortical adenoma and ACC. In ACC, these features were adversely associated with survival. Mice with stabilized beta-catenin exhibited a temporal progression of increased adrenocortical hyperplasia, with subsequent microscopic and macroscopic adenoma formation. Elevated Igf2 expression alone did not cause hyperplasia. With the combination of stabilized beta-catenin and elevated Igf2 expression, adrenal glands were larger, displayed earlier onset of hyperplasia, and developed more frequent macroscopic adenomas (as well as one carcinoma). Our results are consistent with a model in which dysregulation of one pathway may result in adrenal hyperplasia, but accumulation of a second or multiple alterations is necessary for tumorigenesis. (Ant J Pathol 2012, 181:1017-1033; http://dx.doi.org/10.1016/j.ajpath.2012.05.026)

Drug-targeting in combined cancer chemotherapy: tumor growth inhibition in mice by association of paclitaxel and etoposide with a cholesterol-rich nanoemulsion

Lipid nanoemulsions (LDE) may be used as carriers of paclitaxel (PTX) and etoposide (ETP) to decrease toxicity and increase the therapeutic action of those drugs. The current study investigates the combined chemotherapy with PTX and ETP associated with LDE. Four groups of 10-20 B16F10 melanoma-bearing mice were treated with LDE-PTX and LDE-ETP in combination (LDE-PTX + ETP), commercial PTX and ETP in combination (PTX + ETP), single LDE-PTX, and single LDE-ETP. PTX and ETX doses were 9 mu mol/kg administered in three intraperitoneal injections on three alternate days. In two control groups mice were treated with saline solution or LDE alone. Tumor growth, metastasis presence, cell-cycle distribution, blood cell counts and histological data were analyzed. Toxicity of all treatments was evaluated in mice without tumors. Tumor growth inhibition was similarly strong in all treatment groups. However, there was a greater reduction in the number of animals bearing metastases in the LDE-PTX + ETP group (30 %) in comparison to the PTX + ETP group (82 %, p < 0.05). Reduction of cellular density, blood vessels and increase of collagen fibers in tumor tissues were observed in the LDE-PTX + ETP group but not in the PTX + ETP group, and in both groups reduced melanoma-related anemia and thrombocytosis were observed. Flow cytometric analysis suggested that LDE-PTX + ETP exhibited greater selectivity to neoplastic cells than PTX-ETP, showing arrest (65 %) in the G(2)/M phase of the cell cycle (p < 0.001). Toxicity manifested by weight loss and myelosuppression was markedly milder in the LDE-PTX + ETP than in the PTX + ETP group. LDE-PTX + ETP combined drug-targeting therapy showed markedly superior anti-cancer properties and reduced toxicity compared to PTX + ETP.

Local Injections of Adipose-Derived Mesenchymal Stem Cells Modulate Inflammation and Increase Angiogenesis Ameliorating the Dystrophic Phenotype in Dystrophin-Deficient Skeletal Muscle

The effects of adipose-derived mesenchymal stem cells (ADMSC) transplantation on degeneration, regeneration and skeletal muscle function were investigated in dystrophin-deficient mice (24-week-old). ADMSC transplantation improved muscle strength and, resistance to fatigue. An increase in fiber cross-sectional area and in the number of fibers with centralized nuclei and augment of myogenin content were observed. In ADMSC-treated muscles a decrease in muscle content of TNF-alpha, IL-6 and oxidative stress measured by Amplex(A (R)) reagent were observed. The level of TGF-beta 1 was lowered whereas that of VEGF, IL-10 and IL-4 were increased by ADMSC treatment. An increase in markers of macrophage M1 (CD11 and F4-80) and a decrease in T lymphocyte marker (CD3) and arginase-1 were also observed in ADMSCs-treated dystrophic muscle. No change was observed in iNOS expression. Increased phosphorylation of Akt, p70S6k and 4E-BP1 was found in dystrophic muscles treated with ADMSC. These results suggest that ADMSC transplantation modulates inflammation and improves muscle tissue regeneration, ameliorating the dystrophic phenotype in dystrophin-deficient mice.

Active crop sensor to detect variability of nitrogen supply and biomass on sugarcane fields

Nitrogen management has been intensively studied on several crops and recently associated with variable rate on-the-go application based on crop sensors. Such studies are scarce for sugarcane and as a biofuel crop the energy input matters, seeking high positive energy balance production and low carbon emission on the whole production system. This article presents the procedure and shows the first results obtained using a nitrogen and biomass sensor (N-Sensor (TM) ALS, Yara International ASA) to indicate the nitrogen application demands of commercial sugarcane fields. Eight commercial fields from one sugar mill in the state of Sao Paulo, Brazil, varying from 15 to 25 ha in size, were monitored. Conditions varied from sandy to heavy soils and the previous harvesting occurred in May and October 2009, including first, second, and third ratoon stages. Each field was scanned with the sensor three times during the season (at 0.2, 0.4, and 0.6 m stem height), followed by tissue sampling for biomass and nitrogen uptake at ten spots inside the area, guided by the different values shown by the sensor. The results showed a high correlation between sensor values and sugarcane biomass and nitrogen uptake, thereby supporting the potential use of this technology to develop algorithms to manage variable rate application of nitrogen for sugarcane.

Does anti-obsessional pharmacotherapy treat so-called comorbid depressive and anxiety states?

Background: Obsessive-compulsive disorder (OCD) is a chronic condition that normally presents high rates of psychiatric comorbidity. Depression, tic disorders and other anxiety disorders are among the most common comorbidities in OCD adult patients. There is evidence that the higher the number of psychiatric comorbidities, the worse the OCD treatment response. However, little is known about the impact of OCD treatment on the outcome of the psychiatric comorbidities usually present in OCD patients. The aim of this study was to investigate the impact of exclusive, conventional treatments for OCD on the outcome of additional psychiatric disorders of OCD patients, detected at baseline. Methods: Seventy-six patients with primary OCD admitted to the treatment protocols of the Obsessive-Compulsive Spectrum Disorders Program between July 2007 and December 2009 were evaluated at pre-treatment and after 12 months. Data were analyzed to verify possible associations between,OCD treatment response and the outcome of psychiatric comorbidities. Results: Results showed a significant association between OCD treatment response and improvement of major depression and dysthymia (p-value = 0.002), other anxiety disorders (generalized anxiety disorder, social phobia, specific phobia, posttraumatic stress disorder, panic disorder, agoraphobia and anxiety disorder not otherwise specified) (p-value = 0.054) and tic disorders (p-value = 0.043). Limitations: This is an open, non-blinded study, without rating scales for comorbid conditions. Further research is necessary focusing on the possible mechanisms by which OCD treatment could improve these specific disorders. Conclusions: Our results suggest that certain comorbid disorders may benefit from OCD-targeted treatment. (C) 2012 Elsevier B.V. All rights reserved.

Equid herpesvirus type-1 exhibits neurotropism and neurovirulence in a mouse model

Intranasal inoculation of equid herpesvirus type-1 (EHV-1) Brazilian strains A4/72 and A9/92 induced an acute and lethal infection in four different inbred mouse strains. Clinical and neurological signs appeared between the 2nd and 3rd day post inoculation (dpi) and included weight loss, ruffled fur, a hunched posture, crouching in corners, nasal and ocular discharges, dyspnoea, dehydration and increased salivation. These signs were followed by increased reactivity to external stimulation, seizures, recumbency and death. The virus was recovered consistently from the brain and viscera of all mice with neurological signs. Histopathological changes consisted of leptomeningitis, focal haemorrhage, ventriculitis, neuronal degeneration and necrosis, neuronophagia, non-suppurative inflammation, multifocal gliosis and perivascular infiltration of polymorphonuclear and mononuclear cells. Immunohistochemical examination demonstrated that EHV-1 strains A4/72 and A9/92 replicated in neurons of the olfactory bulb, the cortex and the hippocampus. In contrast, mice inoculated with the EHV-1 Brazilian strain A3/97 showed neither weight loss nor apparent clinical or neurological signs; however, the virus was recovered consistently from their lungs at 3 dpi. These three EHV-1 strains showed distinct degrees of virulence and tissue tropism in mice. EHV-1 strains A4/72 and A9/92 exhibited a high degree of central nervous system tropism with neuroinvasion and neurovirulence. EHV-1 strain A3/97 was not neurovirulent despite being detected in the brains of infected BALB/c nude mice. These findings indicate that several inbred mouse strains are susceptible to neuropathogenic EHV-1 strains and should be useful models for studying the pathogenesis and mechanisms contributing to EHV-induced myeloencephalopathy in horses. (C) 2011 Elsevier Ltd. All rights reserved.

RELATIONS BETWEEN SOIL SURFACE ROUGHNESS, TORTUOSITY, TILLAGE TREATMENTS, RAINFALL INTENSITY AND SOIL AND WATER LOSSES FROM A RED YELLOW LATOSOL

The soil surface roughness increases water retention and infiltration, reduces the runoff volume and speed and influences soil losses by water erosion. Similarly to other parameters, soil roughness is affected by the tillage system and rainfall volume. Based on these assumptions, the main purpose of this study was to evaluate the effect of tillage treatments on soil surface roughness (RR) and tortuosity (T) and to investigate the relationship with soil and water losses in a series of simulated rainfall events. The field study was carried out at the experimental station of EMBRAPA Southeastern Cattle Research Center in Sao Carlos (Fazenda Canchim), in Sao Paulo State, Brazil. Experimental plots of 33 m(2) were treated with two tillage practices in three replications, consisting of: untilled (no-tillage) soil (NTS) and conventionally tilled (plowing plus double disking) soil (CTS). Three successive simulated rain tests were applied in 24 h intervals. The three tests consisted of a first rain of 30 mm/h, a second of 30 mm/h and a third rain of 70 mm/h. Immediately after tilling and each rain simulation test, the surface roughness was measured, using a laser profile meter. The tillage treatments induced significant changes in soil surface roughness and tortuosity, demonstrating the importance of the tillage system for the physical surface conditions, favoring water retention and infiltration in the soil. The increase in surface roughness by the tillage treatments was considerably greater than its reduction by rain action. The surface roughness and tortuosity had more influence on the soil volume lost by surface runoff than in the conventional treatment. Possibly, other variables influenced soil and water losses from the no-tillage treatments, e. g., soil type, declivity, slope length, among others not analyzed in this study.

Impact of Land Degradation on Soil Microbial Biomass and Activity in Northeast Brazil

Land degradation causes great changes in the soil biological properties. The process of degradation may decrease soil microbial biomass and consequently decrease soil microbial activity. The study was conducted out during 2009 and 2010 at the four sites of land under native vegetation (NV), moderately degraded land (LDL), highly degraded land (HDL) and land under restoration for four years (RL) to evaluate changes in soil microbial biomass and activity in lands with different degradation levels in comparison with both land under native vegetation and land under restoration in Northeast Brazil. Soil samples were collected at 0-10 cm depth. Soil organic carbon (SOC), soil microbial biomass C (MBC) and N (MBN), soil respiration (SR), and hydrolysis of fluorescein diacetate (FDA) and dehydrogenase (DHA) activities were analyzed. After two years of evaluation, soil MBC, MBN, FDA and DHA had higher values in the NV, followed by the RL. The decreases of soil microbial biomass and enzyme activities in the degraded lands were approximately 8-10 times as large as those found in the NV. However, after land restoration, the MBC and MBN increased approximately 5-fold and 2-fold, respectively, compared with the HDL. The results showed that land degradation produced a strong decrease in soil microbial biomass. However, land restoration may promote short- and long-term increases in soil microbial biomass.

Joint loading decreased by inexpensive and minimalist footwear in elderly women with knee osteoarthritis during stair descent

Objective Previous studies indicate that flexible footwear, which mimics the biomechanics of walking barefoot, results in decreased knee loads in patients with knee osteoarthritis (OA) during walking. However, the effect of flexible footwear on other activities of daily living, such as descending stairs, remains unclear. Our objective was to evaluate the influence of inexpensive and minimalist footwear (Moleca) on knee adduction moment (KAM) during stair descent of elderly women with and without knee OA. Methods. Thirty-four elderly women were equally divided into an OA group and a control group (CG). Stair descent was evaluated in barefoot condition, while wearing the Moleca, and while wearing heeled shoes. Kinematics and ground reaction forces were measured to calculate KAM by using inverse dynamics. Results. The OA group experienced a higher KAM during midstance under the barefoot condition (233.3%; P = 0.028), the Moleca (379.2%; P = 0.004), and heeled shoes (217.6%; P = 0.007). The OA group had a similar knee load during early, mid, and late stance with the Moleca compared with the barefoot condition. Heeled shoes increased the knee loads during the early-stance (versus barefoot [16.7%; P < 0.001] and versus the Moleca [15.5%; P < 0.001]), midstance (versus barefoot [8.6%; P = 0.014] and versus the Moleca [9.5%; P = 0.010]), and late-stance phase (versus barefoot [10.6%; P = 0.003] and versus the Moleca [9.2%; P < 0.001]). In the CG, the Moleca produced a knee load similar to the barefoot condition only during the early-stance phase. Conclusion. Besides the general foot protection, the inexpensive and minimalist footwear contributes to decreasing knee loads in elderly women with OA during stair descent. The loads are similar to the barefoot condition and effectively decreased when compared with heeled shoes.

Glandular trichomes on aerial and underground organs in Chrysolaena species (Vernonieae - Asteraceae): Structure, ultrastructure and chemical composition

Although the occurrence of glandular trichomes is frequently reported for aerial vegetative organs, many questions still remain opened about the presence of such trichomes in underground systems. Here, we present, for the first time, a comparative study concerning the structure, ultrastructure and chemical aspects of both, the aerial and underground glandular trichomes of two different Chrysolaena species, C obovata and C platensis. Glandular trichomes (GTs) were examined using LM, SEM, and TEM and also analyzed by GC-MS and HPLC coupled to UV/DAD and HR-ESI-MS (HPLC-UV-MS). In both aerial (leaf and bud) and underground (rhizophore) organs, the GTs are multicellular, biseriate and formed by five pairs of cells: a pair of support cells, a pair of basal cells, and three pairs of secreting cells. These secreting cells have, at the beginning of secretory process, abundance of smooth ER. The same classes of secondary metabolites are biosynthesized and stored in both aerial and underground GTs of C platensis and C obovata. These GTs from aerial and underground organs have similar cellular and sub-cellular anatomy, however the belowground trichomes show a higher diversity of compounds when compared to those from the leaves. We also demonstrate by means of HPLC-UV-DAD that the sesquiterpene lactones are located inside the trichomes and that hirsutinolides are not artifacts. (C) 2012 Elsevier GmbH. All rights reserved.