Anomalous Hall-effect measurement study on Co/Pt nanosized dot

Dot arrays made of polycrystalline Co/Pt multilayer with an average grain size of 20 nm are fabricated by using a laser interference lithography and their magnetic properties are examined by detecting anomalous Hall effect. It is revealed that the ratio of dots which have stable single domain state increases from 35% to 85% while the dot diameter decreased from 200 to 120 nm. The energy barrier height of magnetization reversal is estimated as 4.0 10-12 erg from sweep rate dependence of the coercivity. The energy corresponds to the switching volume comparable with the volume of a physical grain in the multilayer film

Exploring DCO+^+ as a tracer of thermal inversion in the disk around the Herbig Ae star HD163296

We aim to reproduce the DCO$^+$ emission in the disk around HD163296 using a simple 2D chemical model for the formation of DCO$^+$ through the cold deuteration channel and a parametric treatment of the warm deuteration channel. We use data from ALMA in band 6 to obtain a resolved spectral imaging data cube of the DCO$^+$ $J$=3--2 line in HD163296 with a synthesized beam of 0."53$\times$ 0."42. We adopt a physical structure of the disk from the literature that reproduces the spectral energy distribution. We then apply a simplified chemical network for the formation of DCO$^+$ that uses the physical structure of the disk as parameters along with a CO abundance profile, a constant HD abundance and a constant ionization rate. Finally, from the resulting DCO$^+$ abundances, we calculate the non-LTE emission using the 3D radiative transfer code LIME. The observed DCO$^+$ emission is reproduced by a model with cold deuteration producing abundances up to $1.6\times 10^{-11}$. Warm deuteration, at a constant abundance of $3.2\times 10^{-12}$, becomes fully effective below 32 K and tapers off at higher temperatures, reproducing the lack of DCO$^+$ inside 90 AU. Throughout the DCO$^+$ emitting zone a CO abundance of $2\times 10^{-7}$ is found, with $\sim$99\% of it frozen out below 19 K. At radii where both cold and warm deuteration are active, warm deuteration contributes up to 20\% of DCO$^+$, consistent with detailed chemical models. The decrease of DCO$^+$ at large radii is attributed to a temperature inversion at 250 AU, which raises temperatures above values where cold deuteration operates. Increased photodesorption may also limit the radial extent of DCO$^+$. The corresponding return of the DCO$^+$ layer to the midplane, together with a radially increasing ionization fraction, reproduces the local DCO$^+$ emission maximum at $\sim$260 AU.Comment: 9 pages, 5 figures, accepted 7th July 201

Systematic reviews as a “lens of evidence”: determinants of participation in breast cancer screening

OBJECTIVE: To assess determinants of the participation rate in breast cancer screening (BCS) programs by conducting a systematic review of reviews. METHODS: We conducted a systematic search in Pubmed via Medline, Scopus, Embase, and Cochrane identifying the literature up to April 2019. Out of 2,258 revealed unique abstracts, we included 31 reviews from which 25 were considered as systematic. We applied the Walsh & McPhee Systems Model of Clinical Preventive Care to systematise the determinants of screening participation. RESULTS: The reviews, mainly in high-income settings, reported a wide range for BCS participation rate: 16-90%. The determinants of BCS participation were simple low-cost interventions, such as invitation letters, basic information on screening, multiple reminders, fixed appointments, prompts from healthcare professionals, and healthcare organizational factors (eg. close proximity to screening facility). More complex interventions (such as face-to-face counselling or home visits), mass media or improved access to transport should not be encouraged by policy makers unless other information appears. The repeated participation in mammography screening was consistently high, above 62%. Previous positive experience with screening influenced the repeated participation in screening programs. The reviews were inconsistent in the use of terminology related to BCS participation, which may have contributed to the heterogeneity in the reported outcomes. CONCLUSIONS: This study shows that consistent findings of systematic reviews bring more certainty into the conclusions on effects of simple invitation techniques, fixed appointments and prompts, as well as healthcare organizational factors on promoting participation rate in screening mammography

Mining Disaggregase Sequence Space to Safely Counter TDP-43, FUS, and α-Synuclein Proteotoxicity.

Hsp104 is an AAA+ protein disaggregase, which can be potentiated via diverse mutations in its autoregulatory middle domain (MD) to mitigate toxic misfolding of TDP-43, FUS, and α-synuclein implicated in fatal neurodegenerative disorders. Problematically, potentiated MD variants can exhibit off-target toxicity. Here, we mine disaggregase sequence space to safely enhance Hsp104 activity via single mutations in nucleotide-binding domain 1 (NBD1) or NBD2. Like MD variants, NBD variants counter TDP-43, FUS, and α-synuclein toxicity and exhibit elevated ATPase and disaggregase activity. Unlike MD variants, non-toxic NBD1 and NBD2 variants emerge that rescue TDP-43, FUS, and α-synuclein toxicity. Potentiating substitutions alter NBD1 residues that contact ATP, ATP-binding residues, or the MD. Mutating the NBD2 protomer interface can also safely ameliorate Hsp104. Thus, we disambiguate allosteric regulation of Hsp104 by several tunable structural contacts, which can be engineered to spawn enhanced therapeutic disaggregases with minimal off-target toxicity

What determines the effects and costs of breast cancer screening?

__Background:__ Multiple reviews demonstrated high variability in effectiveness and cost-effectiveness outcomes among studies on breast cancer screening (BCS) programmes. No study to our knowledge has summarized the current evidence on determinants of effectiveness and cost-effectiveness of the most used BCS approaches or tried to explain differences in conclusions of systematic reviews on this topic. Based on published reviews, this systematic review aims to assess the degree of variability of determinants for (a) effectiveness and (b) cost-effectiveness of BCS programmes using mammography, clinical breast examination, breast self-examination, ultrasonography, or their combinations among the general population. __Methods:__ We will perform a comprehensive systematic literature search in Cochrane, Scopus, Embase, and Medline (via Pubmed). The search will be supplemented with hand searching of references of the included reviews, with hand searching in the specialized journals, and by contacting prominent experts in the field. Additional search for grey literature will be conducted on the websites of international cancer associations and networks. Two trained research assistants will screen titles and abstracts of publications independently, with at least random 10% of all abstracts being also screened by the principal researcher. The full texts of the systematic reviews will then be screened independently by two authors, and disagreements will be solved by consensus. The included reviews will be grouped by publication year, outcomes, designs of original studies, and quality. Additionally, for reviews published since 2011, transparency in reporting will be assessed using the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) checklist for the review on determinants of effectiveness and a modified PRISMA checklist for the review on determinants for cost-effectiveness. The study will apply the Assessing the Methodological Quality of Systematic Reviews checklist to assess the methodological quality of systematic reviews. We will report the data extracted from the systematic reviews in a systematic format. Meta-meta-analysis of extracted data will be conducted when feasible. __Discussion:__ This systematic review of reviews will examine the degree of variability in the effectiveness and cost-effectiveness of BCS programmes. _Systematic review registration:_ PROSPERO CRD42016050764and CRD42016050765

Gender gap in STEM: a cross-sectional study of primary school students’ self-perception and test anxiety in mathematics

Contribution: Significant gender differences are observed on primary school students’ perception of self-efficacy and test anxiety in mathematics. Girls perceive themselves to be significantly worse than boys in mathematics and report higher test anxiety toward mathematics exams. Gender differences in self-efficacy become more pronounced as students grow up, and test anxiety increases for all students. However, the present study shows that teachers’ do not perceive differences in self-efficacy in mathematics between boys and girls. Background: The low presence of women in science, technology, engineering, and mathematics (STEM) might be explained by the attitude of young students toward mathematics. Different studies show that girls are less interested in STEM areas than boys during secondary school. A study on the reasons for this fact pointed out that the early years of education can provide a relevant insight to reverse the situation. Research Questions: Is there any age-dependent gender difference in primary school students in aspects related to mathematics? Are teachers aware of students’ perceptions? Methodology: This work presents a study of over 2000 primary school students (6–12 years old) and 200 teachers in Aragón (Spain). The study consists of a survey on aspects that influence the experience of female and male students with mathematics and Spanish language for comparison purposes and teacher’s awareness of students’ perception. Findings: The present study shows that during primary school, girls are more likely to experiment a negative attitude toward mathematics than boys as they grow up, and teachers may not perceive girls’ situation. La baja presencia de mujeres en ciencia, tecnología, la ingeniería y las matemáticas (STEM) podrían explicarse por la actitud de las niños y niñas hacia las matemáticas. Diferentes estudios muestran que las niñas están menos interesadas en las áreas STEM que niños cuando cursan educación secundaria. Además, un estudio sobre los motivos para este hecho señaló que los primeros años de educación podrían proporcionar una visión relevante para revertir la situación. Por ello, este trabajo parte de las siguientes preguntas de investigación, ¿Existe alguna diferencia de género que sea dependiente de la edad en estudiantes de educación primaria en aspectos relacionados con las matemáticas? ¿Conoce el profesorado la autopercepción de sus estudiantes? Las principales contribuciones de este trabajo son que las diferencias significativas de género se observan en la percepción de autoeficacia de los estudiantes de primaria y ansiedad ante los exámenes en matemáticas. Las niñas se perciben a sí mismas significativamente peor que los niños en matemáticas e indican mayor ansiedad ante los exámenes de matemáticas. Las diferencias de género en la autoeficacia se vuelven más pronunciada a medida que los estudiantes crecen, mientras que la ansiedad ante los exámenes aumenta para todos los estudiantes. Pese a estos resultados, el presente estudio muestra que los profesores no perciben diferencias en la autoeficacia en matemáticas entre niños y niñas. Este estudio se basa en las encuestas realizadas a más de 2000 escolares (6-12 años) y 200 profesores en Aragón (España). El estudio consiste en una encuesta a los estudiantes sobre aspectos que pueden influir en la experiencia de los niños y niñas con las matemáticas, así como con la lengua española para disponer de una materia que permita establecer comparaciones y una encuesta al profesor que incluye cuestiones sobre su percepción de los estudiantes. El principal hallazgo del estudio es que, durante la escuela primaria, es más probable que las niñas experimenten una actitud negativa hacia matemáticas que los niños a medida que crecen, y que los maestros pueden no ser conscientes de la situación de las niñas

Substrato com Organosuper® para formação de mudas de pepineiro em ambientes protegidos e bandejas de poliestireno

Culture environments, trays and doses of organic compost were evaluated in the formation of cucumber seedlings (Cucumis sativus L.). Five environmental conditions were tested: (A1) a greenhouse with height of 2.5 m, covered with polyethylene film, (A2) nursery with height of 2.5 m, monofilament fabric, 50% shading, (A3) nursery with height of 2.5 m, heat-reflective screen, 50% shading, (A4) nursery with a height of 1.8 m, covered with coconut tree straw and (A5) greenhouse with height of 4.0 m, covered with polyethylene film, with zenith opening and thermo-reflective cloth under the plastic. Trays of 72 (R1) and 128 (R2) cells were filled with 93% soil and 7% organic compound (S1), 86% soil and 14% organic compound (S2) and 79% soil and 21% organic compound (S3). It was used a randomized design in split-split-plot scheme, with five replicates (environments x trays x substrates). The greenhouses provide the best environments for the formation of cucumber seedlings. A tray of 72 cells is the best container, promoting more vigorous seedlings in substrate with soil and 7 or 14% organic compound.Ambientes de cultivo, bandejas e doses de composto orgânico foram avaliados na formação de mudas de pepino (Cucumis sativus L.). Cinco ambientes de cultivo foram testados: (A1) estufa agrícola com altura de 2,5 m coberta com filme de polietileno; (A2) viveiro com altura de 2,5 m, tela de monofilamento com 50% de sombreamento; (A3) viveiro com altura de 2,5 m, tela termorrefletora, com 50% de sombreamento; (A4) viveiro com altura de 1,8 m, coberto com palha de coqueiro, e (A5) estufa agrícola com altura de 4,0 m, coberta com filme de polietileno, com abertura zenital e tela termorrefletora sob o filme. Bandejas de 72 (R1) e 128 (R2) células foram preenchidas com 93% de solo e 7% de composto orgânico (S1); 86% de solo e 14% de composto orgânico (S2), e 79% de solo e 21% de composto orgânico (S3). Utilizou-se um delineamento inteiramente casualizado, em esquema de parcelas subsubdivididas, com cinco repetições (ambientes x bandejas x substratos). As estufas agrícolas propiciam os melhores ambientes para a formação das mudas de pepino. A bandeja de 72 células é o melhor recipiente, promovendo plântulas mais vigorosas no substrato com solo e 7 ou 14 % de composto orgânico.22623

What determines the effects and costs of breast cancer screening?

__Background:__ Multiple reviews demonstrated high variability in effectiveness and cost-effectiveness outcomes among studies on breast cancer screening (BCS) programmes. No study to our knowledge has summarized the current evidence on determinants of effectiveness and cost-effectiveness of the most used BCS approaches or tried to explain differences in conclusions of systematic reviews on this topic. Based on published reviews, this systematic review aims to assess the degree of variability of determinants for (a) effectiveness and (b) cost-effectiveness of BCS programmes using mammography, clinical breast examination, breast self-examination, ultrasonography, or their combinations among the general population. __Methods:__ We will perform a comprehensive systematic literature search in Cochrane, Scopus, Embase, and Medline (via Pubmed). The search will be supplemented with hand searching of references of the included reviews, with hand searching in the specialized journals, and by contacting prominent experts in the field. Additional search for grey literature will be conducted on the websites of international cancer associations and networks. Two trained research assistants will screen titles and abstracts of publications independently, with at least random 10% of all abstracts being also screened by the principal researcher. The full texts of the systematic reviews will then be screened independently by two authors, and disagreements will be solved by consensus. The included reviews will be grouped by publication year, outcomes, designs of original studies, and quality. Additionally, for reviews published since 2011, transparency in reporting will be assessed using the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) checklist for the review on determinants of effectiveness and a modified PRISMA checklist for the review on determinants for cost-effectiveness. The study will apply the Assessing the Methodological Quality of Systematic Reviews checklist to assess the methodological quality of systematic reviews. We will report the data extracted from the systematic reviews in a systematic format. Meta-meta-analysis of extracted data will be conducted when feasible. __Discussion:__ This systematic review of reviews will examine the degree of variability in the effectiveness and cost-effectiveness of BCS programmes. _Systematic review registration:_ PROSPERO CRD42016050764and CRD42016050765

Phosphorylation of the androgen receptor is associated with reduced survival in hormonerefractory prostate cancer patients

Cell line studies demonstrate that the PI3K/Akt pathway is upregulated in hormone-refractory prostate cancer (HRPC) and can result in phosphorylation of the androgen receptor (AR). The current study therefore aims to establish if this has relevance to the development of clinical HRPC. Immunohistochemistry was employed to investigate the expression and phosphorylation status of Akt and AR in matched hormone-sensitive and -refractory prostate cancer tumours from 68 patients. In the hormone-refractory tissue, only phosphorylated AR (pAR) was associated with shorter time to death from relapse (<i>P</i>=0.003). However, when an increase in expression in the transition from hormone-sensitive to -refractory prostate cancer was investigated, an increase in expression of PI3K was associated with decreased time to biochemical relapse (<i>P</i>=0.014), and an increase in expression of pAkt<sup>473</sup> and pAR<sup>210</sup> were associated with decreased disease-specific survival (<i>P</i>=0.0019 and 0.0015, respectively). Protein expression of pAkt<sup>473</sup> and pAR<sup>210</sup> also strongly correlated (<i>P</i><0.001, c.c.=0.711) in the hormone-refractory prostate tumours. These results provide evidence using clinical specimens, that upregulation of the PI3K/Akt pathway is associated with phosphorylation of the AR during development of HRPC, suggesting that this pathway could be a potential therapeutic target

Enzyme-Powered Gated Mesoporous Silica Nanomotors for On-Command Intracellular Payload Delivery

[EN] The introduction of stimuli-responsive cargo release capabilities on self-propelled micro- and nano- motors holds enormous potential in a number of applications in the biomedical field. Herein, we report the preparation of mesoporous silica nano-particles gated with pH-responsive supramolecular nanovalves and equipped with urease enzymes which act as chemical engines to power the nanomotors. The nanoparticles are loaded with different cargo molecules ([Ru(bpy)(3)]Cl-2 (bpy = 2,2'-bipyridine) or doxorubicin), grafted with benzimidazole groups on the outer surface, and capped by the formation of inclusion complexes between benzimidazole and cyclodextrin-modified urease. The nanomotor exhibits enhanced Brownian motion in the presence of urea. Moreover, no cargo is released at neutral pH, even in the presence of the biofuel urea, due to the blockage of the pores by the bulky benzimidazole:cyclodextrin-urease caps. Cargo delivery is only triggered on-command at acidic pH due to the protonation of benzimidazole groups, the dethreading of the supramolecular nanovalves, and the subsequent uncapping of the nanoparticles. Studies with HeLa cells indicate that the presence of biofuel urea enhances nanoparticle internalization and both [Ru(bpy)(3)]Cl-2 or doxorubicin intracellular release due to the acidity of lysosomal compartments. Gated enzyme-powered nanomotors shown here display some of the requirements for ideal drug delivery carriers such as the capacity to self-propel and the ability to "sense" the environment and deliver the payload on demand in response to predefined stimuli.A.L.-L. is grateful to La Caixa Banking Foundation for his Ph.D. grant. A.G.-F. thanks the Spanish government for her FPU fellowship. The authors are grateful to the Spanish Government (MINECO Projects MAT2015-64139-C4-1, CTQ2014-58989- PCTQ2015-71936-REDT, CTQ2015-68879-R (MICRODIA) and CTQ2015-72471-EXP (Enzwim)), the BBVA foundation (MEDIROBOTS), the CERCA Programme by the Generalitat de Catalunya, and the Generalitat Valenciana (Project PROMETEO/2018/024 and PROMETEOII/2014/061) for support. T.P. thanks MINECO for the Juan de la Cierva postdoctoral fellowship and the European Union's Horizon 2020 research and innovation program, under the Marie Sk¿odowska-Curie Individual Fellowship (H2020-MSCA-IF2018, DNA-bots). A.C.H. thanks MINECO for the Severo Ochoa fellowship. The authors would like to thank A. Miguel Lopez for the development of the python code for motion analysis.Llopis-Lorente, A.; García-Fernández, A.; Murillo-Cremaes, N.; Hortelao, A.; Patiño, T.; Villalonga, R.; Sancenón Galarza, F.... (2019). Enzyme-Powered Gated Mesoporous Silica Nanomotors for On-Command Intracellular Payload Delivery. ACS Nano. 13(10):12171-12183. https://doi.org/10.1021/acsnano.9b067061217112183131