4,975 research outputs found

    The Use of Children\u27s Literature and Reflective Writing as a Means to Help Primary Elementary Students Cope with Natural Disaster

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    Natural disasters such as hurricanes, tornadoes, floods, tsunamis, and earthquakes frequently happen across the world. Many of these natural disasters bring destruction to homes, loss of loved ones, and emotional or physical trauma. For children who are still developing coping skills, these natural disasters can bring them emotional distress because they are unable to processes their experiences in a healthy way. In a review of literature on the topic of bibliotherapy and reflective writing to help children learn coping skills, I discovered a need for these processes to be introduced in normal settings, such as school and home, to help children who have experienced natural disasters develop coping skills. My goal in conducting this research was to create a resource that includes a variety of children\u27s literature on the topic of a natural disaster and that demonstrates a coping skill for that trauma. Guiding questions and reflective writing prompts were also added to this resource for the users to guide children in identifying and learning the demonstrated, healthy coping skills. I selected twenty-one quality and award-winning books that address natural disaster for review. Nineteen of them demonstrated a healthy coping skill within the book. Using the information from the book, I created guiding questions and reflective writing prompts to help guide the children in connecting with and learning how to use the coping skill demonstrated. Future developments from my research may include a website with the resource information or a hard copy that can be sent to areas of high-need or high-risk for natural disaster. My goal is that my resource will foster healthy coping skills for children in the school setting, home, or alongside professional help

    On the Influence of a Five-Hole-Probe on the Vibration Characteristics of a Low Pressure Turbine Rotor while Performing Aerodynamic Measurements

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    For many reasons it is essential to know and assess the flow field and its characteristics up- and downstream of a turbine stage. For these purpose measurements are conducted in test rigs such as the STTF-AAAI (subsonic test turbine facility for aerodynamic, acoustic, and aeroelastic investigations) at the Institute for Thermal Turbomachinery and Machine Dynamics at Graz University of Technology. A low pressure turbine is operated in engine relevant operating conditions. The turbine is experienced high mechanical loads and is excited to vibrate (forced response). In the rotor design process forced response predictions and structural assessments are performed. However, it is not common to include instrumentation (e.g. total pressure and temperature rakes, five-hole-probes, fast response aerodynamic pressure probes) in these forced response predictions. But, these measurement devices are essential and therefore this paper investigates the influence of such an instrumentation onto the vibrational behaviour of a low pressure turbine rotor of the STTF-AAAI. Several vibration measurements at distinct circumferential and radial positions of the five-hole-probe in the flow channel are conducted. These measurement results are compared to measurements performed without a five-hole-probe in the flow channel. A clear influence of the five-hole-probe on the vibration level is shown

    Elucidation of tonic and activated B-cell receptor signaling in Burkitt's lymphoma provides insights into regulation of cell survival.

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    Burkitt's lymphoma (BL) is a highly proliferative B-cell neoplasm and is treated with intensive chemotherapy that, because of its toxicity, is often not suitable for the elderly or for patients with endemic BL in developing countries. BL cell survival relies on signals transduced by B-cell antigen receptors (BCRs). However, tonic as well as activated BCR signaling networks and their relevance for targeted therapies in BL remain elusive. We have systematically characterized and compared tonic and activated BCR signaling in BL by quantitative phosphoproteomics to identify novel BCR effectors and potential drug targets. We identified and quantified ∟16,000 phospho-sites in BL cells. Among these sites, 909 were related to tonic BCR signaling, whereas 984 phospho-sites were regulated upon BCR engagement. The majority of the identified BCR signaling effectors have not been described in the context of B cells or lymphomas yet. Most of these newly identified BCR effectors are predicted to be involved in the regulation of kinases, transcription, and cytoskeleton dynamics. Although tonic and activated BCR signaling shared a considerable number of effector proteins, we identified distinct phosphorylation events in tonic BCR signaling. We investigated the functional relevance of some newly identified BCR effectors and show that ACTN4 and ARFGEF2, which have been described as regulators of membrane-trafficking and cytoskeleton-related processes, respectively, are crucial for BL cell survival. Thus, this study provides a comprehensive dataset for tonic and activated BCR signaling and identifies effector proteins that may be relevant for BL cell survival and thus may help to develop new BL treatments

    An ultra-deep sequencing strategy to detect sub-clonal TP53 mutations in presentation chronic lymphocytic leukemia cases using multiple polymerases

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    Chronic lymphocytic leukaemia (CLL) is the most common clonal B-cell disorder characterized by clonal diversity, a relapsing and remitting course, and in its aggressive forms remains largely incurable. Current front-line regimes include agents such as fludarabine, which act primarily via the DNA damage response pathway. Key to this is the transcription factor p53. Mutations in the TP53 gene, altering p53 functionality, are associated with genetic instability, and are present in aggressive CLL. Furthermore, the emergence of clonal TP53 mutations in relapsed CLL, refractory to DNA-damaging therapy, suggests that accurate detection of sub-clonal TP53 mutations prior to and during treatment may be indicative of early relapse. In this study, we describe a novel deep sequencing workflow using multiple polymerases to generate sequencing libraries (MuPol-Seq), facilitating accurate detection of TP53 mutations at a frequency as low as 0.3%, in presentation CLL cases tested. As these mutations were mostly clustered within the regions of TP53 encoding DNA-binding domains, essential for DNA contact and structural architecture, they are likely to be of prognostic relevance in disease progression. The workflow described here has the potential to be implemented routinely to identify rare mutations across a range of diseases

    Truncated and Helix-Constrained Peptides with High Affinity and Specificity for the cFos Coiled-Coil of AP-1

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    Protein-based therapeutics feature large interacting surfaces. Protein folding endows structural stability to localised surface epitopes, imparting high affinity and target specificity upon interactions with binding partners. However, short synthetic peptides with sequences corresponding to such protein epitopes are unstructured in water and promiscuously bind to proteins with low affinity and specificity. Here we combine structural stability and target specificity of proteins, with low cost and rapid synthesis of small molecules, towards meeting the significant challenge of binding coiled coil proteins in transcriptional regulation. By iteratively truncating a Jun-based peptide from 37 to 22 residues, strategically incorporating i-->i+4 helix-inducing constraints, and positioning unnatural amino acids, we have produced short, water-stable, alpha-helical peptides that bind cFos. A three-dimensional NMR-derived structure for one peptide (24) confirmed a highly stable alpha-helix which was resistant to proteolytic degradation in serum. These short structured peptides are entropically pre-organized for binding with high affinity and specificity to cFos, a key component of the oncogenic transcriptional regulator Activator Protein-1 (AP-1). They competitively antagonized the cJun–cFos coiled-coil interaction. Truncating a Jun-based peptide from 37 to 22 residues decreased the binding enthalpy for cJun by ~9 kcal/mol, but this was compensated by increased conformational entropy (TDS ≤ 7.5 kcal/mol). This study demonstrates that rational design of short peptides constrained by alpha-helical cyclic pentapeptide modules is able to retain parental high helicity, as well as high affinity and specificity for cFos. These are important steps towards small antagonists of the cJun-cFos interaction that mediates gene transcription in cancer and inflammatory diseases

    Shrinking a large dataset to identify variables associated with increased risk of Plasmodium falciparum infection in Western Kenya

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    Large datasets are often not amenable to analysis using traditional single-step approaches. Here, our general objective was to apply imputation techniques, principal component analysis (PCA), elastic net and generalized linear models to a large dataset in a systematic approach to extract the most meaningful predictors for a health outcome. We extracted predictors for Plasmodium falciparum infection, from a large covariate dataset while facing limited numbers of observations, using data from the People, Animals, and their Zoonoses (PAZ) project to demonstrate these techniques: data collected from 415 homesteads in western Kenya, contained over 1500 variables that describe the health, environment, and social factors of the humans, livestock, and the homesteads in which they reside. The wide, sparse dataset was simplified to 42 predictors of P. falciparum malaria infection and wealth rankings were produced for all homesteads. The 42 predictors make biological sense and are supported by previous studies. This systematic data-mining approach we used would make many large datasets more manageable and informative for decision-making processes and health policy prioritization

    Study of CP violation in Dalitz-plot analyses of B0 --> K+K-KS, B+ --> K+K-K+, and B+ --> KSKSK+

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    We perform amplitude analyses of the decays B0→K+K−KS0B^0 \to K^+K^-K^0_S, B+→K+K−K+B^+ \rightarrow K^+K^-K^+, and B+→KS0KS0K+B^+ \to K^0_S K^0_S K^+, and measure CP-violating parameters and partial branching fractions. The results are based on a data sample of approximately 470×106470\times 10^6 BBˉB\bar{B} decays, collected with the BABAR detector at the PEP-II asymmetric-energy BB factory at the SLAC National Accelerator Laboratory. For B+→K+K−K+B^+ \to K^+K^-K^+, we find a direct CP asymmetry in B+→ϕ(1020)K+B^+ \to \phi(1020)K^+ of ACP=(12.8±4.4±1.3)A_{CP}= (12.8\pm 4.4 \pm 1.3)%, which differs from zero by 2.8σ2.8 \sigma. For B0→K+K−KS0B^0 \to K^+K^-K^0_S, we measure the CP-violating phase βeff(ϕ(1020)KS0)=(21±6±2)∘\beta_{\rm eff} (\phi(1020)K^0_S) = (21\pm 6 \pm 2)^\circ. For B+→KS0KS0K+B^+ \to K^0_S K^0_S K^+, we measure an overall direct CP asymmetry of ACP=(4−5+4±2)A_{CP} = (4 ^{+4}_{-5} \pm 2)%. We also perform an angular-moment analysis of the three channels, and determine that the fX(1500)f_X(1500) state can be described well by the sum of the resonances f0(1500)f_0(1500), f2′(1525)f_2^{\prime}(1525), and f0(1710)f_0(1710).Comment: 35 pages, 68 postscript figures. v3 - minor modifications to agree with published versio

    Single hadron response measurement and calorimeter jet energy scale uncertainty with the ATLAS detector at the LHC

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    The uncertainty on the calorimeter energy response to jets of particles is derived for the ATLAS experiment at the Large Hadron Collider (LHC). First, the calorimeter response to single isolated charged hadrons is measured and compared to the Monte Carlo simulation using proton-proton collisions at centre-of-mass energies of sqrt(s) = 900 GeV and 7 TeV collected during 2009 and 2010. Then, using the decay of K_s and Lambda particles, the calorimeter response to specific types of particles (positively and negatively charged pions, protons, and anti-protons) is measured and compared to the Monte Carlo predictions. Finally, the jet energy scale uncertainty is determined by propagating the response uncertainty for single charged and neutral particles to jets. The response uncertainty is 2-5% for central isolated hadrons and 1-3% for the final calorimeter jet energy scale.Comment: 24 pages plus author list (36 pages total), 23 figures, 1 table, submitted to European Physical Journal

    Viral transduction of primary human lymphoma B cells reveals mechanisms of NOTCH-mediated immune escape

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    Hotspot mutations in the PEST-domain of NOTCH1 and NOTCH2 are recurrently identified in B cell malignancies. To address how NOTCH-mutations contribute to a dismal prognosis, we have generated isogenic primary human tumor cells from patients with Chronic Lymphocytic Leukemia (CLL) and Mantle Cell Lymphoma (MCL), differing only in their expression of the intracellular domain (ICD) of NOTCH1 or NOTCH2. Our data demonstrate that both NOTCH-paralogs facilitate immune-escape of malignant B cells by up-regulating PD-L1, partly dependent on autocrine interferon-? signaling. In addition, NOTCH-activation causes silencing of the entire HLA-class II locus via epigenetic regulation of the transcriptional co-activator CIITA. Notably, while NOTCH1 and NOTCH2 govern similar transcriptional programs, disease-specific differences in their expression levels can favor paralog-specific selection. Importantly, NOTCH-ICD also strongly down-regulates the expression of CD19, possibly limiting the effectiveness of immune-therapies. These NOTCH-mediated immune escape mechanisms are associated with the expansion of exhausted CD8+ T cells in vivo.Š 2022. The Author(s)

    Standalone vertex nding in the ATLAS muon spectrometer

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    A dedicated reconstruction algorithm to find decay vertices in the ATLAS muon spectrometer is presented. The algorithm searches the region just upstream of or inside the muon spectrometer volume for multi-particle vertices that originate from the decay of particles with long decay paths. The performance of the algorithm is evaluated using both a sample of simulated Higgs boson events, in which the Higgs boson decays to long-lived neutral particles that in turn decay to bbar b final states, and pp collision data at √s = 7 TeV collected with the ATLAS detector at the LHC during 2011
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