3,498 research outputs found

    Individual differences and course attendance: Why do students skip class?

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    Individual differences are theorised as being key predictors of students’ lecture attendance. Understanding students’ (lack of) motivation for studying is an essential first step in supporting these individual differences and potentially increasing class/lecture attendance. The current study explored the role of students’ deficits in motivations (ability/effort/task value) for studying and their predictive relationship with course attendance, while controlling for prior competence and academic self-concept. Second-year students (n = 219; Female = 40) undertaking three semester-long courses in English as a foreign language participated in the year-long study. The structural model tested included prior achievement and self-concept (Time-1; 15 weeks prior), the motivational deficits for studying in the course (Time-2; ability, effort and task value), and class attendance across the two semesters of study. Self-concept negatively predicted all motivational deficits (moderate-large effects), and positively predicted attendance. Two of the motivational deficits (ability and effort) also had strongly contrasting effects (positive and negative respectively) on attendance. The implications and practical suggestions for intervention are discussed

    The dune effect on sand-transporting winds on Mars

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    Wind on Mars is a significant agent of contemporary surface change, yet the absence of in situ meteorological data hampers the understanding of surface–atmospheric interactions. Airflow models at length scales relevant to landform size now enable examination of conditions that might activate even small-scale bedforms (ripples) under certain contemporary wind regimes. Ripples have the potential to be used as modern ‘wind vanes’ on Mars. Here we use 3D airflow modelling to demonstrate that local dune topography exerts a strong influence on wind speed and direction and that ripple movement likely reflects steered wind direction for certain dune ridge shapes. The poor correlation of dune orientation with effective sand-transporting winds suggests that large dunes may not be mobile under modelled wind scenarios. This work highlights the need to first model winds at high resolution before inferring regional wind patterns from ripple movement or dune orientations on the surface of Mars today

    HLA-DM Mediates Epitope Selection by a “Compare-Exchange” Mechanism when a Potential Peptide Pool Is Available

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    BACKGROUND: HLA-DM (DM) mediates exchange of peptides bound to MHC class II (MHCII) during the epitope selection process. Although DM has been shown to have two activities, peptide release and MHC class II refolding, a clear characterization of the mechanism by which DM facilitates peptide exchange has remained elusive. METHODOLOGY/PRINCIPAL FINDINGS: We have previously demonstrated that peptide binding to and dissociation from MHCII in the absence of DM are cooperative processes, likely related to conformational changes in the peptide-MHCII complex. Here we show that DM promotes peptide release by a non-cooperative process, whereas it enhances cooperative folding of the exchange peptide. Through electron paramagnetic resonance (EPR) and fluorescence polarization (FP) we show that DM releases prebound peptide very poorly in the absence of a candidate peptide for the exchange process. The affinity and concentration of the candidate peptide are also important for the release of the prebound peptide. Increased fluorescence energy transfer between the prebound and exchange peptides in the presence of DM is evidence for a tetramolecular complex which resolves in favor of the peptide that has superior folding properties. CONCLUSION/SIGNIFICANCE: This study shows that both the peptide releasing activity on loaded MHCII and the facilitating of MHCII binding by a candidate exchange peptide are integral to DM mediated epitope selection. The exchange process is initiated only in the presence of candidate peptides, avoiding possible release of a prebound peptide and loss of a potential epitope. In a tetramolecular transitional complex, the candidate peptides are checked for their ability to replace the pre-bound peptide with a geometry that allows the rebinding of the original peptide. Thus, DM promotes a "compare-exchange" sorting algorithm on an available peptide pool. Such a "third party"-mediated mechanism may be generally applicable for diverse ligand recognition in other biological systems

    Safety and feasibility of ultrasound-triggered targeted drug delivery of doxorubicin from thermosensitive liposomes in liver tumours (TARDOX): a single-centre, open-label, phase 1 trial

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    BACKGROUND: Previous preclinical research has shown that extracorporeal devices can be used to enhance the delivery and distribution of systemically administered anticancer drugs, resulting in increased intratumoural concentrations. We aimed to assess the safety and feasibility of targeted release and enhanced delivery of doxorubicin to solid tumours from thermosensitive liposomes triggered by mild hyperthermia, induced non-invasively by focused ultrasound. METHODS: We did an open-label, single-centre, phase 1 trial in a single UK hospital. Adult patients (aged ≥18 years) with unresectable and non-ablatable primary or secondary liver tumours of any histological subtype were considered for the study. Patients received a single intravenous infusion (50 mg/m2) of lyso-thermosensitive liposomal doxorubicin (LTLD), followed by extracorporeal focused ultrasound exposure of a single target liver tumour. The trial had two parts: in part I, patients had a real-time thermometry device implanted intratumourally, whereas patients in part II proceeded without thermometry and we used a patient-specific model to predict optimal exposure parameters. We assessed tumour biopsies obtained before and after focused ultrasound exposure for doxorubicin concentration and distribution. The primary endpoint was at least a doubling of total intratumoural doxorubicin concentration in at least half of the patients treated, on an intention-to-treat basis. This study is registered with ClinicalTrials.gov, number NCT02181075, and is now closed to recruitment. FINDINGS: Between March 13, 2015, and March 27, 2017, ten patients were enrolled in the study (six patients in part I and four in part II), and received a dose of LTLD followed by focused ultrasound exposure. The treatment resulted in an average increase of 3·7 times in intratumoural biopsy doxorubicin concentrations, from an estimate of 2·34 μg/g (SD 0·93) immediately after drug infusion to 8·56 μg/g (5·69) after focused ultrasound. Increases of two to ten times were observed in seven (70%) of ten patients, satisfying the primary endpoint. Serious adverse events registered were expected grade 4 transient neutropenia in five patients and prolonged hospital stay due to unexpected grade 1 confusion in one patient. Grade 3-4 adverse events recorded were neutropenia (grade 3 in one patient and grade 4 in five patients), and grade 3 anaemia in one patient. No treatment-related deaths occurred. INTERPRETATION: The combined treatment of LTLD and non-invasive focused ultrasound hyperthermia in this study seemed to be clinically feasible, safe, and able to enhance intratumoural drug delivery, providing targeted chemo-ablative response in human liver tumours that were refractory to standard chemotherapy. FUNDING: Oxford Biomedical Research Centre, National Institute for Health Research

    Quantifying The Causes of Differences in Tropospheric OH within Global Models

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    The hydroxyl radical (OH) is the primary daytime oxidant in the troposphere and provides the main loss mechanism for many pollutants and greenhouse gases, including methane (CH4). Global mean tropospheric OH differs by as much as 80% among various global models, for reasons that are not well understood. We use neural networks (NNs), trained using archived output from eight chemical transport models (CTMs) that participated in the POLARCAT Model Intercomparison Project (POLMIP), to quantify the factors responsible for differences in tropospheric OH and resulting CH4 lifetime (τCH4) between these models. Annual average τCH4, for loss by OH only, ranges from 8.0–11.6 years for the eight POLMIP CTMs. The factors driving these differences were quantified by inputting 3-D chemical fields from one CTM into the trained NN of another CTM. Across all CTMs, the largest mean differences in τCH4 (ΔτCH4) result from variations in chemical mechanisms (ΔτCH4 = 0.46 years), the photolysis frequency (J) of O3→O(1D) (0.31 years), local O3 (0.30 years), and CO (0.23 years). The ΔτCH4 due to CTM differences in NOx (NO + NO2) is relatively low (0.17 years), though large regional variation in OH between the CTMs is attributed to NOx. Differences in isoprene and J(NO2) have negligible overall effect on globally averaged tropospheric OH, though the extent of OH variations due to each factor depends on the model being examined. This study demonstrates that NNs can serve as a useful tool for quantifying why tropospheric OH varies between global models, provided essential chemical fields are archived

    TEX11 is mutated in infertile men with azoospermia and regulates genome-wide recombination rates in mouse

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    Genome‐wide recombination is essential for genome stability, evolution, and speciation. Mouse Tex11, an X‐linked meiosis‐specific gene, promotes meiotic recombination and chromosomal synapsis. Here, we report that TEX11 is mutated in infertile men with non‐obstructive azoospermia and that an analogous mutation in the mouse impairs meiosis. Genetic screening of a large cohort of idiopathic infertile men reveals that TEX11 mutations, including frameshift and splicing acceptor site mutations, cause infertility in 1% of azoospermic men. Functional evaluation of three analogous human TEX11 missense mutations in transgenic mouse models identified one mutation (V748A) as a potential infertility allele and found two mutations non‐causative. In the mouse model, an intronless autosomal Tex11 transgene functionally substitutes for the X‐linked Tex11 gene, providing genetic evidence for the X‐to‐autosomal retrotransposition evolution phenomenon. Furthermore, we find that TEX11 protein levels modulate genome‐wide recombination rates in both sexes. These studies indicate that TEX11 alleles affecting expression level or substituting single amino acids may contribute to variations in recombination rates between sexes and among individuals in humans.Howard Hughes Medical Institute (Award)National Institutes of Health (U.S.) (NIH/NIGMS grant R01GM076327

    Quantum simulation of the wavefunction to probe frustrated Heisenberg spin systems

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    Quantum simulators are controllable quantum systems that can reproduce the dynamics of the system of interest, which are unfeasible for classical computers. Recent developments in quantum technology enable the precise control of individual quantum particles as required for studying complex quantum systems. Particularly, quantum simulators capable of simulating frustrated Heisenberg spin systems provide platforms for understanding exotic matter such as high-temperature superconductors. Here we report the analog quantum simulation of the ground-state wavefunction to probe arbitrary Heisenberg-type interactions among four spin-1/2 particles . Depending on the interaction strength, frustration within the system emerges such that the ground state evolves from a localized to a resonating valence-bond state. This spin-1/2 tetramer is created using the polarization states of four photons. The single-particle addressability and tunable measurement-induced interactions provide us insights into entanglement dynamics among individual particles. We directly extract ground-state energies and pair-wise quantum correlations to observe the monogamy of entanglement
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