Nano-scale superhydrophobicity: suppression of protein adsorption and promotion of flow-induced detachment

Wall adsorption is a common problem in microfluidic devices, particularly when proteins are used. Here we show how superhydrophobic surfaces can be used to reduce protein adsorption and to promote desorption. Hydrophobic surfaces, both smooth and having high surface roughness of varying length scales (to generate superhydrophobicity), were incubated in protein solution. The samples were then exposed to flow shear in a device designed to simulate a microfluidic environment. Results show that a similar amount of protein adsorbed onto smooth and nanometer-scale rough surfaces, although a greater amount was found to adsorb onto superhydrophobic surfaces with micrometer scale roughness. Exposure to flow shear removed a considerably larger proportion of adsorbed protein from the superhydrophobic surfaces than from the smooth ones, with almost all of the protein being removed from some nanoscale surfaces. This type of surface may therefore be useful in environments, such as microfluidics, where protein sticking is a problem and fluid flow is present. Possible mechanisms that explain the behaviour are discussed, including decreased contact between protein and surface and greater shear stress due to interfacial slip between the superhydrophobic surface and the liquid

Global patterns of extinction risk and conservation needs for Rodentia and Eulipotyphla

AIM: To explore global patterns in spatial aggregations of species richness, vulnerability and data deficiency for Rodentia and Eulipotyphla. To evaluate the adequacy of existing protected area (PA) network for these areas. To provide a focus for local conservation initiatives. LOCATION: Global. METHODS: Total species, globally threatened (GT) species, and Data Deficient (DD) species richness were calculated for a 1° resolution grid. Correspondence analyses between global species richness against GT species richness were performed. To assess PA network adequacy, a correspondence analysis was conducted to identify areas of high richness and GT species richness that have poor protection. RESULTS: Six hotspots were identified for GT eulipotyphlans, encompassing 40% of GT species. Three of these contain higher numbers of GT species than would be expected based on their overall species richness. Ten priority regions were identified for GT rodents, which together contain 34% of all GT species. Six contain higher numbers of GT rodent species than would be expected based on their overall species richness. For DD species, 15% of DD eulipotyphlans were represented within three priority regions, whereas 18 were identified for rodents, capturing 53% of all DD species. Areas containing lower numbers of protected GT eulipotyphlan species than expected include Mexico; Cameroonian Highlands; Albertine Rift; Tanzania; Kenya; Ethiopia; western Asia; India; and Sri Lanka. Areas containing lower numbers of protected GT rodent species than expected are Borneo, Sumatra and Sulawesi. Five eulipotyphlans and 44 rodents have ranges which fall completely outside of PAs. MAIN CONCLUSION: Rodentia and Eulipotyphla priority regions should be considered separately to one another and to other mammals. This analysis approach allows us to pinpoint and delineate geographical areas which represent key regions at a global level for rodents and eulipotyphlans, in order to facilitate conservation, field research and capacity building at a local level

Sequencing of Androgen-Deprivation Therapy of Short Duration With Radiotherapy for Nonmetastatic Prostate Cancer (SANDSTORM): A Pooled Analysis of 12 Randomized Trials

Càncer de pròstata; Teràpia de privació d'andrògensCáncer de próstata; Terapia de privación de andrógenosProstate cancer; Androgen-deprivation therapyPURPOSE The sequencing of androgen-deprivation therapy (ADT) with radiotherapy (RT) may affect outcomes for prostate cancer in an RT-field size-dependent manner. Herein, we investigate the impact of ADT sequencing for men receiving ADT with prostate-only RT (PORT) or whole-pelvis RT (WPRT). MATERIALS AND METHODS Individual patient data from 12 randomized trials that included patients receiving neoadjuvant/concurrent or concurrent/adjuvant short-term ADT (4-6 months) with RT for localized disease were obtained from the Meta-Analysis of Randomized trials in Cancer of the Prostate consortium. Inverse probability of treatment weighting (IPTW) was performed with propensity scores derived from age, initial prostate-specific antigen, Gleason score, T stage, RT dose, and mid-trial enrollment year. Metastasis-free survival (primary end point) and overall survival (OS) were assessed by IPTW-adjusted Cox regression models, analyzed independently for men receiving PORT versus WPRT. IPTW-adjusted Fine and Gray competing risk models were built to evaluate distant metastasis (DM) and prostate cancer–specific mortality. RESULTS Overall, 7,409 patients were included (6,325 neoadjuvant/concurrent and 1,084 concurrent/adjuvant) with a median follow-up of 10.2 years (interquartile range, 7.2-14.9 years). A significant interaction between ADT sequencing and RT field size was observed for all end points (P interaction < .02 for all) except OS. With PORT (n = 4,355), compared with neoadjuvant/concurrent ADT, concurrent/adjuvant ADT was associated with improved metastasis-free survival (10-year benefit 8.0%, hazard ratio [HR], 0.65; 95% CI, 0.54 to 0.79; P < .0001), DM (subdistribution HR, 0.52; 95% CI, 0.33 to 0.82; P = .0046), prostate cancer–specific mortality (subdistribution HR, 0.30; 95% CI, 0.16 to 0.54; P < .0001), and OS (HR, 0.69; 95% CI, 0.57 to 0.83; P = .0001). However, in patients receiving WPRT (n = 3,049), no significant difference in any end point was observed in regard to ADT sequencing except for worse DM (HR, 1.57; 95% CI, 1.20 to 2.05; P = .0009) with concurrent/adjuvant ADT. CONCLUSION ADT sequencing exhibits a significant impact on clinical outcomes with a significant interaction with field size. Concurrent/adjuvant ADT should be the standard of care where short-term ADT is indicated in combination with PORT.Funding support for this study comes from the Prostate Cancer Foundation and ASTRO to AUK. AUK also thanks generous donations from the DeSilva, McCarrick, and Bershad families. A.T. acknowledges support from Cancer Research UK (C33589/A28284 and C7224/A28724) the National Institute for Health Research (NIHR) Cancer Research Network. This project represents independent research supported by the National Institute for Health research (NIHR) Biomedical Research Centre at The Royal Marsden NHS Foundation Trust and the Institute of Cancer Research, London. N.G.Z. is supported by the American Cancer Society – Tri State CEOs Against Cancer Clinician Scientist Development Grant, CSDG‐20‐013‐01‐CCE (2020)

Interaction of CO2 laser-modified nylon with osteoblast cells in relation to wettability

It has been amply demonstrated previously that CO2 lasers hold the ability to surface modify various polymers. In addition, it has been observed that these surface enhancements can augment the biomimetic nature of the laser irradiated materials. This research has employed a CO2 laser marker to produce trench and hatch topographical patterns with peak heights of around 1 μm on the surface of nylon 6,6. The patterns generated have been analysed using white light interferometery, optical microscopy and X-ray photoelectron spectroscopy was employed to determine the surface oxygen content. Contact angle measurements were used to characterize each sample in terms of wettability. Generally, it was seen that as a result of laser processing the contact angle, surface roughness and surface oxygen content increased whilst the apparent polar and total surface energies decreased. The increase in contact angle and reduction in surface energy components was found to be on account of a mixed intermediate state wetting regime owing to the change in roughness due to the induced topographical patterns. To determine the biomimetic nature of the modified and as-received control samples each one was seeded with 2×104 cells/ml normal human osteoblast cells and observed after periods of 24 hours and 4 days using optical microscopy and SEM to determine mean cell cover densities and variations in cell morphology. In addition a haeymocytometer was used to show that the cell count for the laser patterned samples had increased by up to a factor of 1.5 compared to the as-received control sample after 4 days of incubation. Significantly, it was determined that all laser-induced patterns gave rise to better cell response in comparison to the as-received control sample studied due to increased preferential cell growth on those surfaces with increased surface roughness

Addressing ethical challenges in the Genetics Substudy of the National Eye Survey of Trinidad and Tobago (GSNESTT).

BACKGROUND: The conduct of international collaborative genomics research raises distinct ethical challenges that require special consideration, especially if conducted in settings that are research-naïve or resource-limited. Although there is considerable literature on these issues, there is a dearth of literature chronicling approaches taken to address these issues in the field. Additionally no previous ethical guidelines have been developed to support similar research in Trinidad and Tobago. METHODS: A literature review was undertaken to identify strategies used to address common ethical issues relevant to human genetics and genomics research in research-naïve or resource-limited settings. Strategies identified were combined with novel approaches to develop a culturally appropriate, multifaceted strategy to address potential challenges in the Genetics Substudy of the National Eye Survey of Trinidad and Tobago (GSNESTT). RESULTS: Regarding the protection of study participants, we report a decision to exclude children as participants; the use of a Community Engagement and Sensitization Strategy to increase the genetic literacy of the target population; the involvement of local expertise to ensure cultural sensitivity and to address potential comprehension barriers in informed consent; and an audit of the informed consent process to ensure valid consent. Concerning the regulation of the research, we report on ethics approvals from relevant authorities; a Materials Transfer Agreement to guide sample ownership and export; and a Sample Governance Committee to oversee data use and data access. Finally regarding the protection of the interests of scientists from the host country, we report on capacity building efforts to ensure that local scientists have access to data collected through the project and appropriate recognition of their contributions in future publications. CONCLUSION: This paper outlines an ethical framework for the conduct of population-based genetics and genomics research in Trinidad and Tobago; highlights common issues arising in the field and strategies to address these

Audiovisual time perception is spatially specific

Our sensory systems face a daily barrage of auditory and visual signals whose arrival times form a wide range of audiovisual asynchronies. These temporal relationships constitute an important metric for the nervous system when surmising which signals originate from common external events. Internal consistency is known to be aided by sensory adaptation: repeated exposure to consistent asynchrony brings perceived arrival times closer to simultaneity. However, given the diverse nature of our audiovisual environment, functionally useful adaptation would need to be constrained to signals that were generated together. In the current study, we investigate the role of two potential constraining factors: spatial and contextual correspondence. By employing an experimental design that allows independent control of both factors, we show that observers are able to simultaneously adapt to two opposing temporal relationships, provided they are segregated in space. No such recalibration was observed when spatial segregation was replaced by contextual stimulus features (in this case, pitch and spatial frequency). These effects provide support for dedicated asynchrony mechanisms that interact with spatially selective mechanisms early in visual and auditory sensory pathways

Multisensory causal inference in the brain

At any given moment, our brain processes multiple inputs from its different sensory modalities (vision, hearing, touch, etc.). In deciphering this array of sensory information, the brain has to solve two problems: (1) which of the inputs originate from the same object and should be integrated and (2) for the sensations originating from the same object, how best to integrate them. Recent behavioural studies suggest that the human brain solves these problems using optimal probabilistic inference, known as Bayesian causal inference. However, how and where the underlying computations are carried out in the brain have remained unknown. By combining neuroimaging-based decoding techniques and computational modelling of behavioural data, a new study now sheds light on how multisensory causal inference maps onto specific brain areas. The results suggest that the complexity of neural computations increases along the visual hierarchy and link specific components of the causal inference process with specific visual and parietal regions

Recombinant Rabbit Leukemia Inhibitory Factor and Rabbit Embryonic Fibroblasts Support the Derivation and Maintenance of Rabbit Embryonic Stem Cells

Abstract The rabbit is a classical experimental animal species. A major limitation in using rabbits for biomedical research is the lack of germ-line-competent rabbit embryonic stem cells (rbESCs). We hypothesized that the use of homologous feeder cells and recombinant rabbit leukemia inhibitory factor (rbLIF) might improve the chance in deriving germ-line-competent rbES cells. In the present study, we established rabbit embryonic fibroblast (REF) feeder layers and synthesized recombinant rbLIF. We derived a total of seven putative rbESC lines, of which two lines (M5 and M23) were from culture Condition I using mouse embryonic fibroblasts (MEFs) as feeders supplemented with human LIF (hLIF) (MEF+hLIF). Another five lines (R4, R9, R15, R21, and R31) were derived from Condition II using REFs as feeder cells supplemented with rbLIF (REF+rbLIF). Similar derivation efficiency was observed between these two conditions (8.7% vs. 10.2%). In a separate experiment with 2?3 factorial design, we examined the effects of feeder cells (MEF vs. REF) and LIFs (mLIF, hLIF vs. rbLIF) on rbESC culture. Both Conditions I and II supported satisfactory rbESC culture, with similar or better population doubling time and colony-forming efficiency than other combinations of feeder cells with LIFs. Rabbit ESCs derived and maintained on both conditions displayed typical ESC characteristics, including ESC pluripotency marker expression (AP, Oct4, Sox2, Nanog, and SSEA4) and gene expression (Oct4, Sox2, Nanog, c-Myc, Klf4, and Dppa5), and the capacity to differentiate into three primary germ layers in vitro. The present work is the first attempt to establish rbESC lines using homologous feeder cells and recombinant rbLIF, by which the rbESCs were derived and maintained normally. These cell lines are unique resources and may facilitate the derivation of germ-line-competent rbESCs.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/98439/1/cell%2E2012%2E0001.pd

Anti-thrombogenicity by Layer-by-Layer

Anti-thrombogenic films with high durability were fabricated in a wet process. Anti-thrombogenicity was achieved with polyelectrolyte multilayer thin film prepared from poly(vinyl alcohol)-poly(acrylic acid)(PVA-PAA) blends, deposited in alternate layers with poly(allylamine hydrochloride) (PAH). Film durability, assessed by abrasion resistance and water resistance, was enhanced by forming crosslinks via amide bonds induced by heat treatment of the film. The film was found to be resistant to protein adsorption, as measured by the amount of fibrinogen adsorbed from an aqueous solution. Anti-thrombogenic efficacy was assessed in ex vivo experiments by the ability of stainless steel mesh, coated with the polyelectrolyte and inserted into a pig blood vessel, to inhibit thrombus formation. Mesh coated with the polyelectrolyte did not reduce blood flow over a period of 15 minutes, whereas with uncoated mesh blood flow stopped within 6 minutes because of blood vessel blockage by thrombus formation

Strobe sequence design for haplotype assembly

Abstract Background Humans are diploid, carrying two copies of each chromosome, one from each parent. Separating the paternal and maternal chromosomes is an important component of genetic analyses such as determining genetic association, inferring evolutionary scenarios, computing recombination rates, and detecting cis-regulatory events. As the pair of chromosomes are mostly identical to each other, linking together of alleles at heterozygous sites is sufficient to phase, or separate the two chromosomes. In Haplotype Assembly, the linking is done by sequenced fragments that overlap two heterozygous sites. While there has been a lot of research on correcting errors to achieve accurate haplotypes via assembly, relatively little work has been done on designing sequencing experiments to get long haplotypes. Here, we describe the different design parameters that can be adjusted with next generation and upcoming sequencing technologies, and study the impact of design choice on the length of the haplotype. Results We show that a number of parameters influence haplotype length, with the most significant one being the advance length (distance between two fragments of a clone). Given technologies like strobe sequencing that allow for large variations in advance lengths, we design and implement a simulated annealing algorithm to sample a large space of distributions over advance-lengths. Extensive simulations on individual genomic sequences suggest that a non-trivial distribution over advance lengths results a 1-2 order of magnitude improvement in median haplotype length. Conclusions Our results suggest that haplotyping of large, biologically important genomic regions is feasible with current technologies