429 research outputs found
An investigation into the impacts of peer discourse on students\u27 comprehension proficiency with a specific focus on English Language Learners and Students with Disabilities: A meta-analysis
This paper investigated the findings of a previously conducted meta-analysis involving the impacts of peer discussion on student’s comprehension. This paper also examined, synthesized, and analyzed the previous quantitative studies that have been conducted regarding the effectiveness of engaging students in classroom discussion after reading, in order to enhance their comprehension of what they read. The present research serves the purpose of adding to and extending the current knowledge of the roles that teachers and students play in peer discourse, the ways in which classroom interactions can impact the comprehension of culturally and linguistically diverse students, make connections between the types of discourse used and teacher methods for facilitating effective communication among students, and the types of students that seem most receptive to the benefits of interactive discussion. The findings suggest that the quality of teacher prompts and questions throughout classroom discussion seem to play a significant role in student performance in regards to comprehension. The results also suggest that open-ended questions and higher order thinking skills should be integrated into conversations surrounding complex text so that students can think more deeply about the meaning of the text and share ideas with one another that will help build their understanding
A Significant Sudden Ionospheric Disturbance associated with Gamma-Ray Burst GRB 221009A
We report the detection of a significant ionospheric disturbance in the
D-region of Earth's ionosphere which was associated with the massive gamma-ray
burst GRB 221009A that occurred on October 9 2022. We identified the
disturbance over northern Europe - a result of the increased ionisation by X-
and gamma-ray emission from the GRB - using very low frequency (VLF) radio
waves as a probe of the D-region. These observations demonstrate that an
extra-galactic GRB can have a significant impact on the terrestrial ionosphere
and illustrates that the Earth's ionosphere can be used as a giant X- and
gamma-ray detector. Indeed, these observations may provide insights into the
impacts of GRBs on the ionospheres of planets in our solar system and beyond.Comment: 3 pages, 1 figur
Quasi-Periodic Pulsations during the Impulsive and Decay phases of an X-class Flare
Quasi-periodic pulsations (QPP) are often observed in X-ray emission from
solar flares. To date, it is unclear what their physical origins are. Here, we
present a multi-instrument investigation of the nature of QPP during the
impulsive and decay phases of the X1.0 flare of 28 October 2013. We focus on
the character of the fine structure pulsations evident in the soft X-ray time
derivatives and compare this variability with structure across multiple
wavelengths including hard X-ray and microwave emission. We find that during
the impulsive phase of the flare, high correlations between pulsations in the
thermal and non-thermal emissions are seen. A characteristic timescale of ~20s
is observed in all channels and a second timescale of ~55s is observed in the
non-thermal emissions. Soft X-ray pulsations are seen to persist into the decay
phase of this flare, up to 20 minutes after the non-thermal emission has
ceased. We find that these decay phase thermal pulsations have very small
amplitude and show an increase in characteristic timescale from ~40s up to
~70s. We interpret the bursty nature of the co-existing multi-wavelength QPP
during the impulsive phase in terms of episodic particle acceleration and
plasma heating. The persistent thermal decay phase QPP are most likely
connected with compressive MHD processes in the post-flare loops such as the
fast sausage mode or the vertical kink mode.Comment: 7 pages, 4 figures, 1 tabl
Detection and Interpretation Of Long-Lived X-Ray Quasi-Periodic Pulsations in the X-Class Solar Flare On 2013 May 14
Quasi-periodic pulsations (QPP) seen in the time derivative of the GOES soft
X-ray light curves are analyzed for the near-limb X3.2 event on 14 May 2013.
The pulsations are apparent for a total of at least two hours from the
impulsive phase to well into the decay phase, with a total of 163 distinct
pulses evident to the naked eye. A wavelet analysis shows that the
characteristic time scale of these pulsations increases systematically from
25 s at 01:10 UT, the time of the GOES peak, to 100 s at 02:00 UT.
A second ridge in the wavelet power spectrum, most likely associated with
flaring emission from a different active region, shows an increase from
40 s at 01:40 UT to 100 s at 03:10 UT. We assume that the QPP that
produced the first ridge result from vertical kink-mode oscillations of the
newly formed loops following magnetic reconnection in the coronal current
sheet. This allows us to estimate the magnetic field strength as a function of
altitude given the density, loop length, and QPP time scale as functions of
time determined from the GOES light curves and RHESSI images. The calculated
magnetic field strength of the newly formed loops ranges from about 500 G
at an altitude of 24 Mm to a low value of 10 G at 60 Mm, in general
agreement with the expected values at these altitudes. Fast sausage mode
oscillations are also discussed and cannot be ruled out as an alternate
mechanism for producing the QPP
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In Vivo Cell Tracking Using PET: Opportunities and Challenges for Clinical Translation in Oncology.
Cell therapy is a rapidly evolving field involving a wide spectrum of therapeutic cells for personalised medicine in cancer. In vivo imaging and tracking of cells can provide useful information for improving the accuracy, efficacy, and safety of cell therapies. This review focuses on radiopharmaceuticals for the non-invasive detection and tracking of therapeutic cells using positron emission tomography (PET). A range of approaches for imaging therapeutic cells is discussed: Direct ex vivo labelling of cells, in vivo indirect labelling of cells by utilising gene reporters, and detection of specific antigens expressed on the target cells using antibody-based radiopharmaceuticals (immuno-PET). This review examines the evaluation of PET imaging methods for therapeutic cell tracking in preclinical cancer models, their role in the translation into patients, first-in-human studies, as well as the translational challenges involved and how they can be overcome
Loss-cone instability modulation due to a magnetohydrodynamic sausage mode oscillation in the solar corona
Solar flares often involve the acceleration of particles to relativistic energies and the generation of high-intensity bursts of radio emission. In some cases, the radio bursts can show periodic or quasiperiodic intensity pulsations. However, precisely how these pulsations are generated is still subject to debate. Prominent theories employ mechanisms such as periodic magnetic reconnection, magnetohydrodynamic (MHD) oscillations, or some combination of both. Here we report on high-cadence (0.25 s) radio imaging of a 228 MHz radio source pulsating with a period of 2.3 s during a solar flare on 2014-April-18. The pulsating source is due to an MHD sausage mode oscillation periodically triggering electron acceleration in the corona. The periodic electron acceleration results in the modulation of a loss-cone instability, ultimately resulting in pulsating plasma emission. The results show that a complex combination of MHD oscillations and plasma instability modulation can lead to pulsating radio emission in astrophysical environments.Peer reviewe
Lysosomotropism depends on glucose : a chloroquine resistance mechanism
There has been long-standing interest in targeting pro-survival autophagy as a combinational cancer therapeutic strategy. Clinical trials are in progress testing Chloroquine (CQ) or its derivatives in combination with chemo- or radio-therapy for solid and haematological cancers. While CQ has shown efficacy in pre-clinical models, its mechanism of action remains equivocal. Here, we tested how effectively CQ sensitises metastatic breast cancer cells to further stress conditions such as ionising irradiation, doxorubicin, PI3K-Akt inhibition and serum withdrawal. Contrary to the conventional model, the cytotoxic effects of CQ were found to be autophagy-independent, since genetic targeting of ATG7 or the ULK1/2 complex could not sensitise cells, like CQ, to serum depletion. Interestingly, while CQ combined with serum starvation was robustly cytotoxic, further glucose starvation under these conditions led to a full rescue of cell viability. Inhibition of hexokinase using 2-deoxyglucose (2DG) similarly led to CQ resistance. As this form of cell death did not resemble classical caspase-dependent apoptosis, we hypothesised that CQ-mediated cytotoxicity was primarily via a lysosome-dependent mechanism. Indeed, CQ treatment led to marked lysosomal swelling and recruitment of Galectin3 to sites of membrane damage. Strikingly, glucose starvation or 2DG prevented CQ from inducing lysosomal damage and subsequent cell death. Importantly, we found that the related compound, amodiaquine, was more potent than CQ for cell killing and not susceptible to interference from glucose starvation. Taken together, our data indicate that CQ effectively targets the lysosome to sensitise towards cell death but is prone to a glucose-dependent resistance mechanism, thus providing rationale for the related compound amodiaquine (currently used in humans) as a better therapeutic option for cancer
Intravital Imaging of Adoptive T-Cell Morphology, Mobility and Trafficking Following Immune Checkpoint Inhibition in a Mouse Melanoma Model
Efficient T-cell targeting, infiltration and activation within tumors is crucial for successful adoptive T-cell therapy. Intravital microscopy is a powerful tool for the visualization of T-cell behavior within tumors, as well as spatial and temporal heterogeneity in response to immunotherapy. Here we describe an experimental approach for intravital imaging of adoptive T-cell morphology, mobility and trafficking in a skin-flap tumor model, following immune modulation with immune checkpoint inhibitors (ICIs) targeting PD-L1 and CTLA-4. A syngeneic model of ovalbumin and mCherry-expressing amelanotic mouse melanoma was used in conjunction with adoptively transferred OT-1+ cytotoxic T-cells expressing GFP to image antigen-specific live T-cell behavior within the tumor microenvironment. Dynamic image analysis of T-cell motility showed distinct CD8+ T-cell migration patterns and morpho-dynamics within different tumor compartments in response to ICIs: this approach was used to cluster T-cell behavior into four groups based on velocity and meandering index. The results showed that most T-cells within the tumor periphery demonstrated Lévy-like trajectories, consistent with tumor cell searching strategies. T-cells adjacent to tumor cells had reduced velocity and appeared to probe the local environment, consistent with cell-cell interactions. An increased number of T-cells were detected following treatment, traveling at lower mean velocities than controls, and demonstrating reduced displacement consistent with target engagement. Histogram-based analysis of immunofluorescent images from harvested tumors showed that in the ICI-treated mice there was a higher density of CD31+ vessels compared to untreated controls and a greater infiltration of T-cells towards the tumor core, consistent with increased cellular trafficking post-treatment
Reduction in BACE1 decreases body weight, protects against diet-induced obesity and enhances insulin sensitivity in mice
Insulin resistance and impaired glucose homoeostasis are important indicators of Type 2 diabetes and are early risk factors of AD (Alzheimer's disease). An essential feature of AD pathology is the presence of BACE1 (β-site amyloid precursor protein-cleaving enzyme 1), which regulates production of toxic amyloid peptides. However, whether BACE1 also plays a role in glucose homoeostasis is presently unknown. We have used transgenic mice to analyse the effects of loss of BACE1 on body weight, and lipid and glucose homoeostasis. BACE1−/− mice are lean, with decreased adiposity, higher energy expenditure, and improved glucose disposal and peripheral insulin sensitivity than wild-type littermates. BACE1−/− mice are also protected from diet-induced obesity. BACE1-deficient skeletal muscle and liver exhibit improved insulin sensitivity. In a skeletal muscle cell line, BACE1 inhibition increased glucose uptake and enhanced insulin sensitivity. The loss of BACE1 is associated with increased levels of UCP1 (uncoupling protein 1) in BAT (brown adipose tissue) and UCP2 and UCP3 mRNA in skeletal muscle, indicative of increased uncoupled respiration and metabolic inefficiency. Thus BACE1 levels may play a critical role in glucose and lipid homoeostasis in conditions of chronic nutrient excess. Therefore strategies that ameliorate BACE1 activity may be important novel approaches for the treatment of diabetes
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