915 research outputs found
Noise Impacts from Professional Dog Grooming Forced-Air Dryers
This study was designed to measure the sound output of four commonly used brands of forced-air dryers used by dog groomers in the United States. Many dog groomers have questions about the effect of this exposure on their hearing, as well as on the hearing of the dogs that are being groomed. Readings taken from each dryer at 1 meter (the likely distance of the dryer from the groomer and the dog) showed average levels ranging from 105.5 to 108.3 dB SPL or 94.8 to 108.0 dBA. Using the 90 dBA criterion required by the US Occupational Safety and Health Administration, dog groomers/bathers are at risk if exposure to the lowest intensity dryer (94.8 dBA) exceeds 4 hours per day. If the more stringent 85 dBA criterion and 3 dB tradeoff is applied, less than one hour of exposure is permissible in an 8 hour day. Cautions are recommended for any persons exposed to noise from forced-air dryers
IL-10 Immunomodulation of Myeloid Cells Regulates a Murine Model of Ovarian Cancer
Elevated levels of IL-10 in the microenvironment of human ovarian cancer and murine models of ovarian cancer are well established and correlate with poor clinical prognosis. However, amongst a myriad of immunosuppressive factors, the actual contribution of IL-10 to the ovarian tumor microenvironment, the mechanisms by which it acts, and its possible functional redundancy are unknown. We previously demonstrated that elimination of the myeloid-derived suppressor cell (MDSC) compartment within the ovarian tumor ascites inhibited tumor progression and, intriguingly, significantly decreased local IL-10 levels. Here we identify a novel pathway in which the tumor-infiltrating MDSC are the predominant producers of IL-10 and, importantly, require it to develop their immunosuppressive function in vivo. Importantly, we demonstrate that the role of IL-10 is critical, and not redundant with other immunosuppressive molecules, to in vivo tumor progression: blockade of the IL-10 signaling network results in alleviation of MDSC-mediated immunosuppression, altered T cell phenotype and activity, and improved survival. These studies define IL-10 as a fundamental modulator of both MDSC and T cells within the ovarian tumor microenvironment. Importantly, IL-10 signaling is shown to be necessary to the development and maintenance of a permissive tumor microenvironment and represents a viable target for anti-tumor strategies
Mechanism of recruitment of WASP to the immunological synapse and of its activation following TCR ligation
Producción CientíficaF-actin polymerization following engagement of the T cell receptor (TCR) is dependent on WASP and is critical for T cell activation. The link between TCR and WASP is not fully understood. In resting cells, WASP exists in a complex with WIP, which inhibits its activation by Cdc42. We show that the adaptor protein CrkL binds directly to WIP. Further, TCR ligation results in the formation of a ZAP-70-CrkL-WIP-WASP complex, which is recruited to lipid rafts and the immunological synapse. TCR engagement also causes PKCtheta-dependent phosphorylation of WIP, causing the disengagement of WASP from the WIP-WASP complex, thereby releasing it from WIP inhibition. These results suggest that the ZAP-70-CrkL-WIP pathway and PKCtheta link TCR to WASP activation
Local Bacteria Affect the Efficacy of Chemotherapeutic Drugs
In this study, the potential effects of bacteria on the efficacy of frequently used chemotherapies was examined. Bacteria and cancer cell lines were examined in vitro and in vivo for changes in the efficacy of cancer cell killing mediated by chemotherapeutic agents. Of 30 drugs examined in vitro, the efficacy of 10 was found to be significantly inhibited by certain bacteria, while the same bacteria improved the efficacy of six others. HPLC and mass spectrometry analyses of sample drugs (gemcitabine, fludarabine, cladribine, CB1954) demonstrated modification of drug chemical structure. The chemoresistance or increased cytotoxicity observed in vitro with sample drugs (gemcitabine and CB1954) was replicated in in vivo murine subcutaneous tumour models. These findings suggest that bacterial presence in the body due to systemic or local infection may influence tumour responses or off-target toxicity during chemotherapy
Cryovolcanic rates on Ceres revealed by topography
Cryovolcanism, defined here as the extrusion of icy material from depth, may be an important planetary phenomenon in shaping the surfaces of many worlds in the outer Solar System and revealing their thermal histories. However, the physics, chemistry and ubiquity of this geologic process remain poorly understood, especially in comparison to the better-studied silicate volcanism on the terrestrial planets. Ceres is the only plausibly cryovolcanic world to be orbited by a spacecraft up to now, making it the best opportunity to test the importance of cryovolcanism on bodies in the outer Solar System and compare its effects to silicate volcanism on terrestrial planets. Here, we analyse images from NASA’s Dawn mission and use the finite element method to show that Ceres has experienced cryovolcanism throughout its geologic history, with an average cryomagma extrusion rate of ~10^4 m^3 yr^(−1). This result shows that volcanic phenomena are important on Ceres, but orders of magnitude less so than on the terrestrial planets
AKT1 (E17K) mutation profiling in breast cancer: prevalence, concurrent oncogenic alterations, and blood-based detection.
BACKGROUND: The single hotspot mutation AKT1 [G49A:E17K] has been described in several cancers, with the highest incidence observed in breast cancer. However, its precise role in disease etiology remains unknown.
METHODS: We analyzed more than 600 breast cancer tumor samples and circulating tumor DNA for AKT1 (E17K) and alterations in other cancer-associated genes using Beads, Emulsions, Amplification, and Magnetics digital polymerase chain reaction technology and targeted exome sequencing.
RESULTS: Overall AKT1 (E17K) mutation prevalence was 6.3 % and not correlated with age or menopausal stage. AKT1 (E17K) mutation frequency tended to be lower in patients with grade 3 disease (1.9 %) compared with those with grade 1 (11.1 %) or grade 2 (6 %) disease. In two cohorts of patients with advanced metastatic disease, 98.0 % (n = 50) and 97.1 % (n = 35) concordance was obtained between tissue and blood samples for the AKT1 (E17K) mutation, and mutation capture rates of 66.7 % (2/3) and 85.7 % (6/7) in blood versus tissue samples were observed. Although AKT1-mutant tumor specimens were often found to harbor concurrent alterations in other driver genes, a subset of specimens harboring AKT1 (E17K) as the only known driver alteration was also identified. Initial follow-up survival data suggest that AKT1 (E17K) could be associated with increased mortality. These findings warrant additional long-term follow-up.
CONCLUSIONS: The data suggest that AKT1 (E17K) is the most likely disease driver in certain breast cancer patients. Blood-based mutation detection is achievable in advanced-stage disease. These findings underpin the need for a further enhanced-precision medicine paradigm in the treatment of breast cancer
Management of difficult airway in intratracheal tumor surgery
BACKGROUND: Tracheal malignancies are usual victim of delay in diagnosis by virtue of their symptoms resembling asthma. Sometimes delayed diagnosis may lead to almost total airway obstruction. For difficult airways, not leaving any possibility of manipulation into neck region or endoscopic intervention, femorofemoral cardiopulmonary bypass can be a promising approach. CASE PRESENTATION: We are presenting a case of tracheal adenoid cystic carcinoma (cylindroma) occupying about 90% of the tracheal lumen. It was successfully managed by surgical excision of mass by sternotomy and tracheotomy under femorofemoral cardiopulmonary bypass (CPB). CONCLUSION: Any patient with recurrent respiratory symptoms should be evaluated by radiological and endoscopic means earlier to avoid delay in diagnosis of such conditions. Femorofemoral cardiopulmonary bypass is a relatively safe way of managing certain airway obstructions
Integration of hormonal signaling networks and mobile microRNAs is required for vascular patterning in Arabidopsis roots
Peer reviewe
High-throughput, quantitative analyses of genetic interactions in E. coli.
Large-scale genetic interaction studies provide the basis for defining gene function and pathway architecture. Recent advances in the ability to generate double mutants en masse in Saccharomyces cerevisiae have dramatically accelerated the acquisition of genetic interaction information and the biological inferences that follow. Here we describe a method based on F factor-driven conjugation, which allows for high-throughput generation of double mutants in Escherichia coli. This method, termed genetic interaction analysis technology for E. coli (GIANT-coli), permits us to systematically generate and array double-mutant cells on solid media in high-density arrays. We show that colony size provides a robust and quantitative output of cellular fitness and that GIANT-coli can recapitulate known synthetic interactions and identify previously unidentified negative (synthetic sickness or lethality) and positive (suppressive or epistatic) relationships. Finally, we describe a complementary strategy for genome-wide suppressor-mutant identification. Together, these methods permit rapid, large-scale genetic interaction studies in E. coli
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