342 research outputs found

    Exploring 1st- and 2nd-year chiropractic students' willingness and attitudes toward peer physical examination

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    Objective This study aimed to explore chiropractic students' perceptions and attitudes about the appropriateness of peer physical examination as a teaching tool and their willingness and comfort with it. Methods A modified version of a validated questionnaire was used. First- and 2nd-year chiropractic students at Murdoch University were approached during their practical sessions. The responses were analyzed using descriptive statistics reporting frequencies and percentages. Comparison between classes, age, and sex was evaluated by cross-tabulation. Results A total of 184 questionnaires were completed with a response rate of 76.6%. Our results demonstrated that most students were comfortable with and willing to participate in peer physical examination as well as trusted it as an appropriate part of their training and a valuable learning experience. Nevertheless, a small percentage were uncomfortable with peer physical examination and regarded it as an unprofessional activity. In addition, it was revealed that younger females (≤20 years) reported feeling unnecessarily exposed and therefore significantly less comfortable with peer physical examination. They were also less comfortable when examined in the inguinal area by a student of the opposite sex. Conclusion Although peer physical examination appears to be a very popular training tool, it still has a few areas of concern that need to be investigated and addressed to improve students' attitude, perception, and comfort with this teaching technique. Further studies could investigate how other factors such as religious beliefs contribute toward students' perception and attitudes regarding peer physical examination

    Field-Aligned Current Structures during the Terrestrial Magnetosphere's Transformation into Alfven Wings and Recovery

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    On April 24th, 2023, a CME event caused the solar wind to become sub-Alfvenic, leading to the development of an Alfven Wing configuration in the Earth's Magnetosphere. Alfven Wings have previously been observed as cavities of low flow in Jupiter's magnetosphere, but the observing satellites did not have the ability to directly measure the Alfven Wings' current structures. Through in situ measurements made by the Magnetospheric Multiscale (MMS) spacecraft, the April 24th event provides us with the first direct measurements of current structures during an Alfven Wing configuration. We have found two distinct types of current structures associated with the Alfven Wing transformation as well as the magnetosphere recovery. These structures are observed to be significantly more anti-field-aligned and electron-driven than typical magnetopause currents, indicating the disruptions caused to the magnetosphere current system by the Alfven Wing formation

    The Influence Organics on Supercritical CO2 Migration in Organic-Rich Shales

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    This work describes a series of laboratory-based tests to evaluate the efficacy of CO2 for EOR and to better understand the controlling mechanisms of CO2 permeation in Bakken rock samples.https://commons.und.edu/eerc-publications/1010/thumbnail.jp

    Downregulation of Mcl-1 has anti-inflammatory pro-resolution effects and enhances bacterial clearance from the lung

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    Phagocytes not only coordinate acute inflammation and host defense at mucosal sites, but also contribute to tissue damage. Respiratory infection causes a globally significant disease burden and frequently progresses to acute respiratory distress syndrome, a devastating inflammatory condition characterized by neutrophil recruitment and accumulation of protein-rich edema fluid causing impaired lung function. We hypothesized that targeting the intracellular protein myeloid cell leukemia 1 (Mcl-1) by a cyclin-dependent kinase inhibitor (AT7519) or a flavone (wogonin) would accelerate neutrophil apoptosis and resolution of established inflammation, but without detriment to bacterial clearance. Mcl-1 loss induced human neutrophil apoptosis, but did not induce macrophage apoptosis nor impair phagocytosis of apoptotic neutrophils. Neutrophil-dominant inflammation was modelled in mice by either endotoxin or bacteria (Escherichia coli). Downregulating inflammatory cell Mcl-1 had anti-inflammatory, pro-resolution effects, shortening the resolution interval (R(i)) from 19 to 7 h and improved organ dysfunction with enhanced alveolar–capillary barrier integrity. Conversely, attenuating drug-induced Mcl-1 downregulation inhibited neutrophil apoptosis and delayed resolution of endotoxin-mediated lung inflammation. Importantly, manipulating lung inflammatory cell Mcl-1 also accelerated resolution of bacterial infection (R(i); 50 to 16 h) concurrent with enhanced bacterial clearance. Therefore, manipulating inflammatory cell Mcl-1 accelerates inflammation resolution without detriment to host defense against bacteria, and represents a target for treating infection-associated inflammation

    Characterizing genomic alterations in cancer by complementary functional associations.

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    Systematic efforts to sequence the cancer genome have identified large numbers of mutations and copy number alterations in human cancers. However, elucidating the functional consequences of these variants, and their interactions to drive or maintain oncogenic states, remains a challenge in cancer research. We developed REVEALER, a computational method that identifies combinations of mutually exclusive genomic alterations correlated with functional phenotypes, such as the activation or gene dependency of oncogenic pathways or sensitivity to a drug treatment. We used REVEALER to uncover complementary genomic alterations associated with the transcriptional activation of β-catenin and NRF2, MEK-inhibitor sensitivity, and KRAS dependency. REVEALER successfully identified both known and new associations, demonstrating the power of combining functional profiles with extensive characterization of genomic alterations in cancer genomes

    Hydrothermal dolomitization of basinal deposits controlled by a synsedimentary fault system in Triassic extensional setting, Hungary

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    Dolomitization of relatively thick carbonate successions occurs via an effective fluid circulation mechanism, since the replacement process requires a large amount of Mg-rich fluid interacting with the CaCO3 precursor. In the western end of the Neotethys, fault-controlled extensional basins developed during the Late Triassic spreading stage. In the Buda Hills and Danube-East blocks, distinct parts of silica and organic matter-rich slope and basinal deposits are dolomitized. Petrographic, geochemical, and fluid inclusion data distinguished two dolomite types: (1) finely to medium crystalline and (2) medium to coarsely crystalline. They commonly co-occur and show a gradual transition. Both exhibit breccia fabric under microscope. Dolomite texture reveals that the breccia fabric is not inherited from the precursor carbonates but was formed during the dolomitization process and under the influence of repeated seismic shocks. Dolomitization within the slope and basinal succession as well as within the breccia zones of the underlying basement block is interpreted as being related to fluid originated from the detachment zone and channelled along synsedimentary normal faults. The proposed conceptual model of dolomitization suggests that pervasive dolomitization occurred not only within and near the fault zones. Permeable beds have channelled the fluid towards the basin centre where the fluid was capable of partial dolomitization. The fluid inclusion data, compared with vitrinite reflectance and maturation data of organic matter, suggest that the ascending fluid was likely hydrothermal which cooled down via mixing with marine-derived pore fluid. Thermal gradient is considered as a potential driving force for fluid flow

    Epigenomic Profiling of Human CD4+ T Cells Supports a Linear Differentiation Model and Highlights Molecular Regulators of Memory Development

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    SummaryThe impact of epigenetics on the differentiation of memory T (Tmem) cells is poorly defined. We generated deep epigenomes comprising genome-wide profiles of DNA methylation, histone modifications, DNA accessibility, and coding and non-coding RNA expression in naive, central-, effector-, and terminally differentiated CD45RA+ CD4+ Tmem cells from blood and CD69+ Tmem cells from bone marrow (BM-Tmem). We observed a progressive and proliferation-associated global loss of DNA methylation in heterochromatic parts of the genome during Tmem cell differentiation. Furthermore, distinct gradually changing signatures in the epigenome and the transcriptome supported a linear model of memory development in circulating T cells, while tissue-resident BM-Tmem branched off with a unique epigenetic profile. Integrative analyses identified candidate master regulators of Tmem cell differentiation, including the transcription factor FOXP1. This study highlights the importance of epigenomic changes for Tmem cell biology and demonstrates the value of epigenetic data for the identification of lineage regulators

    Molecular pathway profiling of T lymphocyte signal transduction pathways; Th1 and Th2 genomic fingerprints are defined by TCR and CD28-mediated signaling

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    Contains fulltext : 108719.pdf (publisher's version ) (Open Access)BACKGROUND: T lymphocytes are orchestrators of adaptive immunity. Naive T cells may differentiate into Th1, Th2, Th17 or iTreg phenotypes, depending on environmental co-stimulatory signals. To identify genes and pathways involved in differentiation of Jurkat T cells towards Th1 and Th2 subtypes we performed comprehensive transcriptome analyses of Jurkat T cells stimulated with various stimuli and pathway inhibitors. Results from these experiments were validated in a human experimental setting using whole blood and purified CD4+ Tcells. RESULTS: Calcium-dependent activation of T cells using CD3/CD28 and PMA/CD3 stimulation induced a Th1 expression profile reflected by increased expression of T-bet, RUNX3, IL-2, and IFNgamma, whereas calcium-independent activation via PMA/CD28 induced a Th2 expression profile which included GATA3, RXRA, CCL1 and Itk. Knock down with siRNA and gene expression profiling in the presence of selective kinase inhibitors showed that proximal kinases Lck and PKCtheta are crucial signaling hubs during T helper cell activation, revealing a clear role for Lck in Th1 development and for PKCtheta in both Th1 and Th2 development. Medial signaling via MAPkinases appeared to be less important in these pathways, since specific inhibitors of these kinases displayed a minor effect on gene expression. Translation towards a primary, whole blood setting and purified human CD4+ T cells revealed that PMA/CD3 stimulation induced a more pronounced Th1 specific, Lck and PKCtheta dependent IFNgamma production, whereas PMA/CD28 induced Th2 specific IL-5 and IL-13 production, independent of Lck activation. PMA/CD3-mediated skewing towards a Th1 phenotype was also reflected in mRNA expression of the master transcription factor Tbet, whereas PMA/CD28-mediated stimulation enhanced GATA3 mRNA expression in primary human CD4+ Tcells. CONCLUSIONS: This study identifies stimulatory pathways and gene expression profiles for in vitro skewing of T helper cell activation. PMA/CD3 stimulation enhances a Th1-like response in an Lck and PKCtheta dependent fashion, whereas PMA/CD28 stimulation results in a Th2-like phenotype independent of the proximal TCR-tyrosine kinase Lck. This approach offers a robust and fast translational in vitro system for skewed T helper cell responses in Jurkat T cells, primary human CD4+ Tcells and in a more complex matrix such as human whole blood
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