Timing molecular motion and production with a synthetic transcriptional clock

The realization of artificial biochemical reaction networks with unique functionality is one of the main challenges for the development of synthetic biology. Due to the reduced number of components, biochemical circuits constructed in vitro promise to be more amenable to systematic design and quantitative assessment than circuits embedded within living organisms. To make good on that promise, effective methods for composing subsystems into larger systems are needed. Here we used an artificial biochemical oscillator based on in vitro transcription and RNA degradation reactions to drive a variety of “load” processes such as the operation of a DNA-based nanomechanical device (“DNA tweezers”) or the production of a functional RNA molecule (an aptamer for malachite green). We implemented several mechanisms for coupling the load processes to the oscillator circuit and compared them based on how much the load affected the frequency and amplitude of the core oscillator, and how much of the load was effectively driven. Based on heuristic insights and computational modeling, an “insulator circuit” was developed, which strongly reduced the detrimental influence of the load on the oscillator circuit. Understanding how to design effective insulation between biochemical subsystems will be critical for the synthesis of larger and more complex systems

Ultra-strong Adhesion of Graphene Membranes

As mechanical structures enter the nanoscale regime, the influence of van der Waals forces increases. Graphene is attractive for nanomechanical systems because its Young's modulus and strength are both intrinsically high, but the mechanical behavior of graphene is also strongly influenced by the van der Waals force. For example, this force clamps graphene samples to substrates, and also holds together the individual graphene sheets in multilayer samples. Here we use a pressurized blister test to directly measure the adhesion energy of graphene sheets with a silicon oxide substrate. We find an adhesion energy of 0.45 \pm 0.02 J/m2 for monolayer graphene and 0.31 \pm 0.03 J/m2 for samples containing 2-5 graphene sheets. These values are larger than the adhesion energies measured in typical micromechanical structures and are comparable to solid/liquid adhesion energies. We attribute this to the extreme flexibility of graphene, which allows it to conform to the topography of even the smoothest substrates, thus making its interaction with the substrate more liquid-like than solid-like.Comment: to appear in Nature Nanotechnolog

Publisher Correction: Graphene overcoats for ultra-high storage density magnetic media.

Publisher Correction: Graphene overcoats for ultra-high storage density magnetic media

Comparative health technology assessment of robotic-assisted, direct manual laparoscopic and open surgery:a prospective study

Background: Despite many publications reporting on the increased hospital cost of robotic-assisted surgery (RAS) compared to direct manual laparoscopic surgery (DMLS) and open surgery (OS), the reported health economic studies lack details on clinical outcome, precluding valid health technology assessment (HTA). Methods: The present prospective study reports total cost analysis on 699 patients undergoing general surgical, gynecological and thoracic operations between 2011 and 2014 in the Italian Public Health Service, during which period eight major teaching hospitals treated the patients. The study compared total healthcare costs of RAS, DMLS and OS based on prospectively collected data on patient outcome in addition to healthcare costs incurred by the three approaches. Results: The cost of RAS operations was significantly higher than that of OS and DMLS for both gynecological and thoracic operations (p < 0.001). The study showed no significant difference in total costs between OS and DMLS. Total costs of general surgery RAS were significantly higher than those of OS (p < 0.001), but not against DMLS general surgery. Indirect costs were significantly lower in RAS compared to both DMLS general surgery and OS gynecological surgery due to the shorter length of hospital stay of RAS approach (p < 0.001). Additionally, in all specialties compared to OS, patients treated by RAS experienced a quicker recovery and significantly less pain during the hospitalization and after discharge. Conclusions: The present HTA while confirming higher total healthcare costs for RAS operations identified significant clinical benefits which may justify the increased expenditure incurred by this approach

Materiais didáticos no ensino e aprendizagem da matemática

O relatório final de estágio apresenta-se no âmbito do Mestrado em Educação Pré-Escolar e Ensino do 1.º Ciclo do Ensino Básico. Este inclui uma reflexão crítica relativamente às unidades curriculares de Prática de Ensino Supervisionada (II e III), em contexto de estágio, no 1.º Ciclo do Ensino Básico e na Educação Pré-Escolar. O relatório contempla ainda uma investigação cuja temática se centra na área da Matemática. Para a realização da primeira parte do relatório, foram utilizados diversos materiais construídos e implementados ao longo das PES II e III, bem como autores de referência, de forma a fundamentar o texto. Relativamente à segunda parte do relatório final de estágio foi realizada uma investigação de caráter qualitativo, que teve como principal objetivo perceber de que forma a utilização de materiais didáticos, em aulas do 1.º Ciclo do Ensino Básico, influencia a aprendizagem da Matemática, num tópico muito particular: números racionais. Desta forma, foi realizado um teste diagnóstico de forma a perceber o conteúdo em que os alunos sentiam mais dificuldades. Posteriormente, foram desenvolvidas três tarefas diferentes, utilizando materiais didáticos distintos e, foi ainda realizada uma entrevista semiestruturada aos três participantes do estudo. A análise dos dados recolhidos permitiu concluir, com alguma segurança, que a utilização de materiais didáticos, em conteúdos matemáticos, é benéfica para os alunos, pois revelam maior envolvimento nas tarefas propostas e uma melhor compreensão dos conteúdos abordados.The final apprenticeship report is related to the scope of the Masters Degree of Pre-schooling and Teaching the 1st Cycle of Basic School. It includes a critical reflection in relation to the curricular units of Supervised Teaching Practice (II and III), in the context of apprenticeship, in the 1st Cycle of Basic School and in Pre-school Education. The report also contemplates research whose theme concentrates on the fields of mathematics. For the first part of the report several different materials were used, which had been built and implemented along STP II and III, as well as authors of reference, so as to support the text. In relation to the second part of the apprenticeship final report, a qualitative research was carried out, which main purpose was to understand to which extent the use of didactic materials in the 1st cycle of Basic School classes influences the learning of mathematics, in a very particular topic: rational numbers. This way, a diagnosis was performed for a better understanding of the contents in which learners feel the most difficulties. Later on three tasks were developed, by using different didactic materials, and a semi-structured interview was held to the three participants in the study. The analysis of the collected data allowed to conclude, with some certainty, that the use of didactic materials in mathematical contents is beneficial for learners, because they reveal a greater involvement in the proposed tasks and a better understanding of the addressed contents

The Red Sea, Coastal Landscapes, and Hominin Dispersals

This chapter provides a critical assessment of environment, landscape and resources in the Red Sea region over the past five million years in relation to archaeological evidence of hominin settlement, and of current hypotheses about the role of the region as a pathway or obstacle to population dispersals between Africa and Asia and the possible significance of coastal colonization. The discussion assesses the impact of factors such as topography and the distribution of resources on land and on the seacoast, taking account of geographical variation and changes in geology, sea levels and palaeoclimate. The merits of northern and southern routes of movement at either end of the Red Sea are compared. All the evidence indicates that there has been no land connection at the southern end since the beginning of the Pliocene period, but that short sea crossings would have been possible at lowest sea-level stands with little or no technical aids. More important than the possibilities of crossing the southern channel is the nature of the resources available in the adjacent coastal zones. There were many climatic episodes wetter than today, and during these periods water draining from the Arabian escarpment provided productive conditions for large mammals and human populations in coastal regions and eastwards into the desert. During drier episodes the coastal region would have provided important refugia both in upland areas and on the emerged shelves exposed by lowered sea level, especially in the southern sector and on both sides of the Red Sea. Marine resources may have offered an added advantage in coastal areas, but evidence for their exploitation is very limited, and their role has been over-exaggerated in hypotheses of coastal colonization

Serological profile of first SARS-CoV-2 reinfection cases detected within the SIREN study.

OBJECTIVES: To describe the serological profile of first two SARS-CoV-2 confirmed reinfections in the national healthcare worker cohort study SARS-CoV-2 Immunity and Reinfection Evaluation (SIREN) and potentially identify correlates of protection against reinfection. METHODS: In addition to routine testing within the SIREN study, viral culture, sequencing and phylogenetic analysis were performed. Total antibody testing (Anti-SARS-CoV-2 nucleocapsid and Anti-SARS-CoV-2 spike) were complemented by receptor binding domain indirect ELISA and neutralising antibody assays. RESULTS: The first two SARS-CoV-2 confirmed reinfections had mild symptomatic illness episodes from which infectious virus was recovered at the time of reinfection. The recovered viruses and their sequences were closely related to viruses circulating locally during the time of reinfection and serology was consistent with reinfection. Prior to reinfection, both cases had ELISA and immunoblot detectable anti-N antibodies, but lacked live virus neutralising antibody. Within days following reinfection, neutralising antibodies became detectable and anti-N and anti-S binding antibodies were boosted. CONCLUSIONS: We hypothesise that titres of neutralising antibody can be used as a correlate of protection against reinfection. Further analysis using a case-control design is essential in order to confirm this hypothesis

Vitamin D supplementation and breast cancer prevention : a systematic review and meta-analysis of randomized clinical trials

In recent years, the scientific evidence linking vitamin D status or supplementation to breast cancer has grown notably. To investigate the role of vitamin D supplementation on breast cancer incidence, we conducted a systematic review and meta-analysis of randomized controlled trials comparing vitamin D with placebo or no treatment. We used OVID to search MEDLINE (R), EMBASE and CENTRAL until April 2012. We screened the reference lists of included studies and used the “Related Article” feature in PubMed to identify additional articles. No language restrictions were applied. Two reviewers independently extracted data on methodological quality, participants, intervention, comparison and outcomes. Risk Ratios and 95% Confident Intervals for breast cancer were pooled using a random-effects model. Heterogeneity was assessed using the I2 test. In sensitivity analysis, we assessed the impact of vitamin D dosage and mode of administration on treatment effects. Only two randomized controlled trials fulfilled the pre-set inclusion criteria. The pooled analysis included 5372 postmenopausal women. Overall, Risk Ratios and 95% Confident Intervals were 1.11 and 0.74–1.68. We found no evidence of heterogeneity. Neither vitamin D dosage nor mode of administration significantly affected breast cancer risk. However, treatment efficacy was somewhat greater when vitamin D was administered at the highest dosage and in combination with calcium (Risk Ratio 0.58, 95% Confident Interval 0.23–1.47 and Risk Ratio 0.93, 95% Confident Interval 0.54–1.60, respectively). In conclusions, vitamin D use seems not to be associated with a reduced risk of breast cancer development in postmenopausal women. However, the available evidence is still limited and inadequate to draw firm conclusions. Study protocol code: FARM8L2B5L