On generating functions in additive number theory, II: lower-order terms and applications to PDEs

We obtain asymptotics for sums of the formSigma(p)(n=1) e(alpha(k) n(k) + alpha(1)n),involving lower order main terms. As an application, we show that for almost all alpha(2) is an element of [0, 1) one hassup(alpha 1 is an element of[0,1)) | Sigma(1 \u3c= n \u3c= P) e(alpha(1)(n(3) + n) + alpha(2)n(3))| \u3c\u3c P3/4+epsilon,and that in a suitable sense this is best possible. This allows us to improve bounds for the fractal dimension of solutions to the Schrodinger and Airy equations

On generating functions in additive number theory, II: Lower-order terms and applications to PDEs

We obtain asymptotics for sums of the form $$\sum_{n=1}^P e(\alpha_kn^k + \alpha_1n),$$ involving lower order main terms. As an application, we show that for almost all $\alpha_2 \in [0,1)$ one has $$\sup_{\alpha_1 \in [0,1)} \Big| \sum_{1 \le n \le P} e(\alpha_1(n^3+n) + \alpha_2 n^3) \Big| \ll P^{3/4 + \varepsilon},$$ and that in a suitable sense this is best possible. This allows us to improve bounds for the fractal dimension of solutions to the Schr\"odinger and Airy equations

Impact of translational error-induced and error-free misfolding on the rate of protein evolution

Theoretical calculations suggest that, in addition to translational error-induced protein misfolding, a non-negligible fraction of misfolded proteins are error free.We propose that the anticorrelation between the expression level of a protein and its rate of sequence evolution be explained by an overarching protein-misfolding-avoidance hypothesis that includes selection against both error-induced and error-free protein misfolding, and verify this model by a molecular-level evolutionary simulation.We provide strong empirical evidence for the protein-misfolding-avoidance hypothesis, including a positive correlation between protein expression level and stability, enrichment of misfolding-minimizing codons and amino acids in highly expressed genes, and stronger evolutionary conservation of residues in which nonsynonymous changes are more likely to increase protein misfolding

Are female students in general and nursing students more ready for teamwork and interprofessional collaboration in healthcare?

<p>Abstract</p> <p>Background</p> <p>Interprofessional Education (IPE) is now spreading worldwide and many universities are now including IPE in their curricula. The aim of this study was to investigate whether or not such student characteristics as gender, previous working experience in healthcare, educational progress and features of the learning environment, such as educational programmes and curriculum design, have an impact on their open-mindedness about co-operation with other professions.</p> <p>Methods</p> <p>Medical and nursing students at two Swedish universities were invited to fill in the Readiness for Interprofessional Learning Scale (RIPLS). Totally, 955 students were invited and 70.2% (n = 670) participated in the study. A factor analysis of the RIPLS revealed four item groupings (factors) for our empirical data, but only one had sufficient internal consistency. This factor was labelled "Team Player".</p> <p>Results</p> <p>Regardless of the educational programme, female students were more positive to teamwork than male students. Nursing students in general displayed more positive beliefs about teamwork and collaboration than medical students. Exposure to different interprofessional curricula and previous exposure to interprofessional education were only to a minor extent associated with a positive attitude towards teamwork. Educational progress did not seem to influence these beliefs.</p> <p>Conclusions</p> <p>The establishment of interprofessional teamwork is a major challenge for modern healthcare. This study indicates some directions for more successful interprofessional education. Efforts should be directed at informing particularly male medical students about the need for teamwork in modern healthcare systems. The results also imply that study of other factors, such as the student's personality, is needed for fully understanding readiness for teamwork and interprofessional collaboration in healthcare. We also believe that the RIPL Scale still can be further adjusted.</p

Never Let a Crisis Go to Waste: Opportunities to Reduce Social Disadvantage from COVID-19

This paper identifies and examines a range of policy reform opportunities in Australia arising from COVID-19. The authors demonstrate how COVID-19 presents unique opportunities for rethinking and redesigning long-standing rules and regulations covering how people live and work in Australia, with some opportunities arising coincidentally and others requiring purposeful policy and institutional redesign. They present a broad range of ideas to address entrenched disadvantage in health, labour markets, the tax and transfer system, gender equality, education, housing and criminal justice in Australia, in order to leverage the COVID-19 crisis to build a better society

Systematic inclusion of mandatory interprofessional education in health professions curricula at Gunma University: a report of student self-assessment in a nine-year implementation

<p>Abstract</p> <p>Background</p> <p>The mandatory interprofessional education programme at Gunma University was initiated in 1999. This paper is a statistical evaluation of the programme from 1999 to 2007.</p> <p>Methods</p> <p>A questionnaire of 10 items to assess the achievement levels of the programme, which was developed independently of other assessment systems published previously, was distributed, as well as two or three open-ended questions to be answered at the end of each annual module. A multivariate analysis of variance model was used, and the factor analysis of the responses was performed with varimax rotation.</p> <p>Results</p> <p>Over all, 1418 respondents of a possible 1629 students completed the survey, for a total response rate of 87.1%. Cronbach's alpha of 10 items was 0.793, revealing high internal consistency. Our original questionnaire was categorized into four subscales as follows: "Role and responsibilities", "Teamwork and collaboration", "Structure and function of training facilities", and "Professional identity". Students in the Department of Occupational Therapy reached a relatively lower level of achievement. In the replies to the open-ended questions, requests for the participation of the medical students were repeated throughout the evaluation period.</p> <p>Conclusion</p> <p>The present four subscales measure "understanding", and may take into account the development of interprofessional education programmes with clinical training in various facilities. The content and quality of clinical training subjects may be remarkably dependent on training facilities, suggesting the importance of full consultation mechanisms in the local network with the relevant educational institutes for medicine, health care and welfare.</p

Protein Folding Activity of the Ribosome is involved in Yeast Prion Propagation.

6AP and GA are potent inhibitors of yeast and mammalian prions and also specific inhibitors of PFAR, the protein-folding activity borne by domain V of the large rRNA of the large subunit of the ribosome. We therefore explored the link between PFAR and yeast prion [PSI(+)] using both PFAR-enriched mutants and site-directed methylation. We demonstrate that PFAR is involved in propagation and de novo formation of [PSI(+)]. PFAR and the yeast heat-shock protein Hsp104 partially compensate each other for [PSI(+)] propagation. Our data also provide insight into new functions for the ribosome in basal thermotolerance and heat-shocked protein refolding. PFAR is thus an evolutionarily conserved cell component implicated in the prion life cycle, and we propose that it could be a potential therapeutic target for human protein misfolding diseases

Screening for Toxic Amyloid in Yeast Exemplifies the Role of Alternative Pathway Responsible for Cytotoxicity

The relationship between amyloid and toxic species is a central problem since the discovery of amyloid structures in different diseases. Despite intensive efforts in the field, the deleterious species remains unknown at the molecular level. This may reflect the lack of any structure-toxicity study based on a genetic approach. Here we show that a structure-toxicity study without any biochemical prerequisite can be successfully achieved in yeast. A PCR mutagenesis of the amyloid domain of HET-s leads to the identification of a mutant that might impair cellular viability. Cellular and biochemical analyses demonstrate that this toxic mutant forms GFP-amyloid aggregates that differ from the wild-type aggregates in their shape, size and molecular organization. The chaperone Hsp104 that helps to disassemble protein aggregates is strictly required for the cellular toxicity. Our structure-toxicity study suggests that the smallest aggregates are the most toxic, and opens a new way to analyze the relationship between structure and toxicity of amyloid species

Inefficient Quality Control of Thermosensitive Proteins on the Plasma Membrane

BACKGROUND: Misfolded proteins are generally recognised by cellular quality control machinery, which typically results in their ubiquitination and degradation. For soluble cytoplasmic proteins, degradation is mediated by the proteasome. Membrane proteins that fail to fold correctly are subject to ER associated degradation (ERAD), which involves their extraction from the membrane and subsequent proteasome-dependent destruction. Proteins with abnormal transmembrane domains can also be recognised in the Golgi or endosomal system and targeted for destruction in the vacuole/lysosome. It is much less clear what happens to membrane proteins that reach their destination, such as the cell surface, and then suffer damage. METHODOLOGY/PRINCIPAL FINDINGS: We have tested the ability of yeast cells to degrade membrane proteins to which temperature-sensitive cytoplasmic alleles of the Ura3 protein or of phage lambda repressor have been fused. In soluble form, these proteins are rapidly degraded upon temperature shift, in part due to the action of the Doa10 and San1 ubiquitin ligases and the proteasome. When tethered to the ER protein Use1, they are also degraded. However, when tethered to a plasma membrane protein such as Sso1 they escape degradation, either in the vacuole or by the proteasome. CONCLUSIONS/SIGNIFICANCE: Membrane proteins with a misfolded cytoplasmic domain appear not to be efficiently recognised and degraded once they have escaped the ER, even though their defective domains are exposed to the cytoplasm and potentially to cytoplasmic quality controls. Membrane tethering may provide a way to reduce degradation of unstable proteins