Silica nanowires templated by amyloid-like fibrils

Many peptides self-assemble to form amyloid fibrils. We previously explored the sequence propensity to form amyloid using variants of a designed peptide with sequence KFFEAAAKKFFE. These variant peptides form highly stable amyloid fibrils with varied lateral assembly and are ideal to template further assembly of non-proteinaceous material. Herein, we show that the fibrils formed by peptide variants can be coated with a layer of silica to produce silica nanowires using tetraethyl-orthosilicate. The resulting nanowires were characterized using electron microscopy (TEM), X-ray fiber diffraction, FTIR and cross-section EM to reveal a nanostructure with peptidic core. Lysine residues play a role in templating the formation of silica on the fibril surface and, using this library of peptides, we have explored the contributions of lysine as well as arginine to silica templating, and find that sequence plays an important role in determining the physical nature and structure of the resulting nanowires

Retroperitoneal fibrosis and β-blocking agents:Is there an association?

AIM: Retroperitoneal fibrosis (RPF) is a rare chronic fibro-inflammatory disorder which may be secondary to certain drugs, including beta-blocking agents (BBAs). However, their causative role is unclear. We aimed to investigate this association. METHODS: Disproportionality analysis was carried out on cases from 1985 to October 4, 2020 in VigiBase®, the WHO pharmacovigilance database. The Bayesian-based IC025 metric and reporting odds ratio were used in order to assess the adverse event signal. We also analysed all published case reports from the literature regarding BBA-associated RPF to assess the value of suggested supportive clinical evidence. RESULTS: 1.599 individual case safety reports (ICSRs) of RPF were reported to VigiBase®, of which 132 (32%) concerned 16 different single BBA. For 12 of these agents (75%), reporting of RPF was disproportionate, indicating a potential safety signal. Line listing analysis of ICSRs showed no consistent time interval from start of BBA to RPF diagnosis (range 0,7-264 mo). Dechallenge was negative or unknown in the majority of cases (74%). In 18 published cases from the literature, time from start of BBA to RPF diagnosis varied widely (range 3-156 mo). BBA were discontinued 6 mo before (n=1) or at the time of RPF diagnosis (n=17). Most patients (84%) also received RPF specific treatment. Follow-up (FU) duration was short (median 5 mo [range 1-24 mo]) and in most cases (83%) relevant FU data were lacking. CONCLUSION: Although disproportionality analysis indicated a potential safety signal for RPF associated with BBAs, clinical evidence did not support a cause and effect relationship

Agrarische structuur, trends en beleid: ontwikkelingen in Nederland vanaf 1950

In en rond de agrarische sector in Nederland hebben zich de afgelopen decennia ingrijpende veranderingen voorgedaan. Zo is het aandeel van de agrarische sector in de nationale economie stelselmatig teruggelopen. Dit rapport brengt de structurele veranderingen in kaart en analyseert de invloed van beleidsmaatregelen. Geconcludeerd wordt dat de processen van bedrijfsbeëindiging en schaalvergroting die zich in de land/ en tuinbouw voordoen, vooral bepaald zijn door het duurder worden van arbeid, in combinatie met het beschikbaar komenvan arbeidsbesparende technische mogelijkheden.Fundamental changes have taken place in and around the Dutch agricultural sector during the past decades, and the agriculture sector¿s share in the national economy has exhibited a consistent decline. This report maps the structural changes in the sector and analyses the influence of policy measures. The report concludes that the processes resulting in the closure of farms and increases in scale are primarily determined by the increasing cost of labour incombination with the availability of labour/saving technology

Estado del arte de la quinua en el mundo en 2013

Alimento de base de las poblaciones andinas desde hace milenios, la quinua se ha convertido hoy en un producto apreciado en el mercado internacional de alimentos dietéticos, orgánicos y equitativos. Este cambio lo iniciaron los mismos productores del Altiplano Sur de Bolivia hace aproximadamente unos 40 años. En medio de un desierto de altura, ellos lograron desarrollar una floreciente producción agrícola de exportación. Aunque cuentan con lucrativos nichos de mercado, los productores de quinua no son agricultores especializados, ni residen de forma permanente en la zona de producción. Estas son algunas de las paradojas que caracterizan la producción de quinua en el Altiplano Sur de Bolivia. Después de describir el origen, la diversidad y los rasgos biológicos del ecotipo Quinua Real en el cual se basa la producción de esta zona, se plantea la importancia de la quinua en los agrosistemas locales y, más allá, en los sistemas de actividades agrícolas y no agrícolas manejados por las familias del Altiplano Sur. Movilidad geográfica y pluriactividad forman parte del modo de vida ancestral de estas poblaciones y determinan hasta hoy en día las condiciones de uso de los recursos territoriales y la organización de los productores en el contexto del auge comercial de la quinua. La producción actual de quinua en la región presenta rasgos de vulnerabilidad agroecológica y social, así como capacidades adaptativas para enfrentarlos. Se resaltan como puntos clave para la sostenibilidad de los agrosistemas locales : i) la concertación de reglas comunales e individuales para el acceso y uso de la tierra en agrosistemas socialmente equitativos y equilibrados entre cultivo y ganadería, ii) las normas internacionales para el reconocimiento de la Quinua Real en los mercados de exportación, iii) una actualización continua de las reglas y normas para mantener la adaptabilidad de los agrosistemas locales a los cambios imprevisibles del contexto socio-ecológico a varias escalas de espacio y de tiempo

Grain Boundaries in Graphene on SiC(0001ˉ\bar{1}) Substrate

Grain boundaries in epitaxial graphene on the SiC(000$\bar{1}$) substrate are studied using scanning tunneling microscopy and spectroscopy. All investigated small-angle grain boundaries show pronounced out-of-plane buckling induced by the strain fields of constituent dislocations. The ensemble of observations allows to determine the critical misorientation angle of buckling transition $\theta_c = 19 \pm~2^\circ$. Periodic structures are found among the flat large-angle grain boundaries. In particular, the observed $\theta = 33\pm2^\circ$ highly ordered grain boundary is assigned to the previously proposed lowest formation energy structural motif composed of a continuous chain of edge-sharing alternating pentagons and heptagons. This periodic grain boundary defect is predicted to exhibit strong valley filtering of charge carriers thus promising the practical realization of all-electric valleytronic devices

TUBectomy with delayed oophorectomy as an alternative to risk-reducing salpingo-oophorectomy in high-risk women to assess the safety of prevention:the TUBA-WISP II study protocol

BACKGROUND: Risk-reducing salpingectomy with delayed oophorectomy has gained interest for individuals at high risk for tubo-ovarian cancer as there is compelling evidence that especially high-grade serous carcinoma originates in the fallopian tubes. Two studies have demonstrated a positive effect of salpingectomy on menopause-related quality of life and sexual health compared with standard risk-reducing salpingo-oophorectomy.PRIMARY OBJECTIVE: To investigate whether salpingectomy with delayed oophorectomy is non-inferior to the current standard salpingo-oophorectomy for the prevention of tubo-ovarian cancer among individuals at high inherited risk.STUDY HYPOTHESIS: We hypothesize that postponement of oophorectomy after salpingectomy, to the age of 40-45 (BRCA1) or 45-50 (BRCA2) years, compared with the current standard salpingo-oophorectomy at age 35-40 (BRCA1) or 40-45 (BRCA2) years, is non-inferior in regard to tubo-ovarian cancer risk.TRIAL DESIGN: In this international prospective preference trial, participants will choose between the novel salpingectomy with delayed oophorectomy and the current standard salpingo-oophorectomy. Salpingectomy can be performed after the completion of childbearing and between the age of 25 and 40 (BRCA1), 25 and 45 (BRCA2), or 25 and 50 (BRIP1, RAD51C, and RAD51D pathogenic variant carriers) years. Subsequent oophorectomy is recommended at a maximum delay of 5 years beyond the upper limit of the current guideline age for salpingo-oophorectomy. The current National Comprehensive Cancer Network (NCCN) guideline age, which is also the recommended age for salpingo-oophorectomy within the study, is 35-40 years for BRCA1, 40-45 years for BRCA2, and 45-50 years for BRIP1, RAD51C, and RAD51D pathogenic variant carriers.MAJOR INCLUSION/EXCLUSION CRITERIA: Premenopausal individuals with a documented class IV or V germline pathogenic variant in the BRCA1, BRCA2, BRIP1, RAD51C, or RAD51D gene who have completed childbearing are eligible for participation. Participants may have a personal history of a non-ovarian malignancy.PRIMARY ENDPOINT: The primary outcome is the cumulative tubo-ovarian cancer incidence at the target age: 46 years for BRCA1 and 51 years for BRCA2 pathogenic variant carriers.SAMPLE SIZE: The sample size to ensure sufficient power to test non-inferiority of salpingectomy with delayed oophorectomy compared with salpingo-oophorectomy requires 1500 BRCA1 and 1500 BRCA2 pathogenic variant carriers.ESTIMATED DATES FOR COMPLETING ACCRUAL AND PRESENTING RESULTS: Participant recruitment is expected to be completed at the end of 2026 (total recruitment period of 5 years). The primary outcome is expected to be available in 2036 (minimal follow-up period of 10 years).TRIAL REGISTRATION NUMBER: NCT04294927.</p

Chromatic Illumination Discrimination Ability Reveals that Human Colour Constancy Is Optimised for Blue Daylight Illuminations

The phenomenon of colour constancy in human visual perception keeps surface colours constant, despite changes in their reflected light due to changing illumination. Although colour constancy has evolved under a constrained subset of illuminations, it is unknown whether its underlying mechanisms, thought to involve multiple components from retina to cortex, are optimised for particular environmental variations. Here we demonstrate a new method for investigating colour constancy using illumination matching in real scenes which, unlike previous methods using surface matching and simulated scenes, allows testing of multiple, real illuminations. We use real scenes consisting of solid familiar or unfamiliar objects against uniform or variegated backgrounds and compare discrimination performance for typical illuminations from the daylight chromaticity locus (approximately blue-yellow) and atypical spectra from an orthogonal locus (approximately red-green, at correlated colour temperature 6700 K), all produced in real time by a 10-channel LED illuminator. We find that discrimination of illumination changes is poorer along the daylight locus than the atypical locus, and is poorest particularly for bluer illumination changes, demonstrating conversely that surface colour constancy is best for blue daylight illuminations. Illumination discrimination is also enhanced, and therefore colour constancy diminished, for uniform backgrounds, irrespective of the object type. These results are not explained by statistical properties of the scene signal changes at the retinal level. We conclude that high-level mechanisms of colour constancy are biased for the blue daylight illuminations and variegated backgrounds to which the human visual system has typically been exposed