A conserved spider silk domain acts as a molecular switch that controls fibre assembly

A huge variety of proteins are able to form fibrillar structures(1), especially at high protein concentrations. Hence, it is surprising that spider silk proteins can be stored in a soluble form at high concentrations and transformed into extremely stable fibres on demand(2,3). Silk proteins are reminiscent of amphiphilic block copolymers containing stretches of polyalanine and glycine-rich polar elements forming a repetitive core flanked by highly conserved non-repetitive amino-terminal(4,5) and carboxy-terminal(6) domains. The N-terminal domain comprises a secretion signal, but further functions remain unassigned. The C-terminal domain was implicated in the control of solubility and fibre formation(7) initiated by changes in ionic composition(8,9) and mechanical stimuli known to align the repetitive sequence elements and promote beta-sheet formation(10-14). However, despite recent structural data(15), little is known about this remarkable behaviour in molecular detail. Here we present the solution structure of the C-terminal domain of a spider dragline silk protein and provide evidence that the structural state of this domain is essential for controlled switching between the storage and assembly forms of silk proteins. In addition, the C-terminal domain also has a role in the alignment of secondary structural features formed by the repetitive elements in the backbone of spider silk proteins, which is known to be important for the mechanical properties of the fibre.

What is the learning in games-based learning?

This chapter explores the nature of “learning” in games-based learning and the cognitive and motivational processes that might underpin that learning by drawing on psychological theories and perspectives. Firstly, changing conceptions of learning over the last few decades are reviewed. This is described in relation to the changes in formal learning theories and connections made between learning theory and GBL. Secondly, the chapter reviews empirical research on the learning outcomes that have been identified for GBL, with specific focus on cognitive benefits, school attainment, collaborative working, and the motivational and engaging appeal of games. Finally, an overview of the dominant theoretical perspectives/findings mostly associated with GBL is presented in an attempt to broaden understanding of the potential for GBL in the classroom.

A simple method to determine the water activity of ethanol-containing samples

The water activity (a(w)) of microbial substrates, biological samples, and foods and drinks is usually determined by direct measurement of the equilibrium relative humidity above a sample. However, these materials can contain ethanol, which disrupts the operation of humidity sensors. Previously, an indirect and problematic technique based on freezing-point depression measurements was needed to calculate the a(w) when ethanol was present. We now describe a rapid and accurate method to determine the a(w) of ethanol-containing samples at ambient temperatures. Disruption of sensor measurements was minimized by using a newly developed, alcohol-resistant humidity sensor fitted with an alcohol filter. Linear equations were derived from a(w) measurements of standard ethanol-water mixtures, and from Norrish's equation, to correct sensor measurements. To our knowledge, this is the first time that electronic sensors have been used to determine the a(w) of ethanol- containing samples.

Bricks vs. clicks: Which is better for marketing remanufactured products?

The economical and environmental benefits are the central issues for remanufacturing. Whereas extant remanufacturing research focuses primarily on such issues in remanufacturing technologies, production planning, inventory control and competitive strategies, we provide an alternative yet somewhat complementary approach to consider both issues related to different channels structures for marketing remanufactured products. Specifically, based on observations from current practice, we consider a manufacturer sells new units through an independent retailer but with two options for marketing remanufactured products: (1) marketing through its own e-channel (Model M) or (2) subcontracting the marketing activity to a third party (Model 3P). A central result we obtain is that although Model M is always greener than Model 3P, firms have less incentive to adopt it because both the manufacturer and retailer may be worse off when the manufacturer sells remanufactured products through its own e-channel rather than subcontracting to a third party. Extending both models to cases in which the manufacturer interacts with multiple retailers further reveals that the more retailers in the market, the greener Model M relative to Model 3P.

Biomass-derived Oxymethylene Ethers as Diesel Additives: A Thermodynamic Analysis

Conversion of biomass for production of liquid fuels can help in reducing the greenhouse gas (GHG) emissions which are predominantly generated by combustion of fossil fuels. Adding oxymethylene ethers (OMEs) in conventional diesel fuel has the potential to reduce soot formation during the combustion in a diesel engine. OMEs are downstream products of syngas, which can be generated by the gasification of biomass. In this research, a thermodynamic analysis has been conducted through development of data intensive process models of all the unit operations involved in production of OMEs from biomass. Based on the developed model, the key process parameters affecting the OMEs production including equivalence ratio, H2/CO ratio, and extra water flow rate were identified. This was followed by development of an optimal process design for high OMEs production. It was found that for a fluidized bed gasifier with heat capacity of 28 MW, the conditions for highest OMEs production are at an air amount of 317 tonne/day, at H2/CO ratio of 2.1, and without extra water injection. At this level, the total OMEs production is 55 tonne/day (13 tonne/day OME3 and 9 tonne/day OME4). This model would further be used in a techno-economic assessment study of the whole biomass conversion chain to determine the most attractive pathways.

The Prognostic Significance of Combining VEGFA, FLT1 and KDR mRNA Expressions in Brain Tumors

Tumor cells require angiogenesis to deliver nutrients and oxygen to support their fast growth and metabolism. The vascular endothelial growth factor (VEGF) pathway plays an important role in promoting angiogenesis, including tumor-induced angiogenesis. Recent clinical trials have demonstrated the benefit of targeting VEGF in the treatment of glioblastoma. However, the prognostic significance of the expression of VEGFA and its receptors VEGFR1 (FLT1) and VEGFR2 (KDR) are still largely elusive. In the present study, we aimed to investigate the prognostic significance of these three factors, alone or in combination, in glioma patients. Gene mRNA expression was extracted from three independent brain tumor cohorts totaling 242 patients and the association between gene expression and survival was tested. We found that when VEGFA, FLT1 and KDR expressions were considered alone, only VEGFA demonstrated a significant association with patient survival. Patients with high expression of both VEGFA and either receptor had significantly worse survival than patients expressing both factors at a low level. Importantly, we found that those patients whose tumors overexpressed all three genes had a significantly shorter survival compared to those patients with a low level expression of these genes. Our results suggest that a high level expression of VEGFA and its receptors, both FLT1 and KDR, may be required for brain tumor progression, and that these three factors should be considered together as a prognostic indicator for brain tumor patients.

EphA2 Expression Is a Key Driver of Migration and Invasion and a Poor Prognostic Marker in Colorectal Cancer

PURPOSE: EphA2, a member of the Eph receptor tyrosine kinases family, is an important regulator of tumor initiation, neovascularization, and metastasis in a wide range of epithelial and mesenchymal cancers; however, its role in colorectal cancer recurrence and progression is unclear.

EXPERIMENTAL DESIGN: EphA2 expression was determined by immunohistochemistry in stage II/III colorectal tumors (N = 338), and findings correlated with clinical outcome. The correlation between EphA2 expression and stem cell markers CD44 and Lgr5 was examined. The role of EphA2 in migration/invasion was assessed using a panel of KRAS wild-type (WT) and mutant (MT) parental and invasive colorectal cancer cell line models.

RESULTS: Colorectal tumors displayed significantly higher expression levels of EphA2 compared with matched normal tissue, which positively correlated with high CD44 and Lgr5 expression levels. Moreover, high EphA2 mRNA and protein expression were found to be associated with poor overall survival in stage II/III colorectal cancer tissues, in both univariate and multivariate analyses. Preclinically, we found that EphA2 was highly expressed in KRASMT colorectal cancer cells and that EphA2 levels are regulated by the KRAS-driven MAPK and RalGDS-RalA pathways. Moreover, EphA2 levels were elevated in several invasive daughter cell lines, and downregulation of EphA2 using RNAi or recombinant EFNA1 suppressed migration and invasion of KRASMT colorectal cancer cells.

CONCLUSIONS: These data show that EpHA2 is a poor prognostic marker in stage II/III colorectal cancer, which may be due to its ability to promote cell migration and invasion, providing support for the further investigation of EphA2 as a novel prognostic biomarker and therapeutic target. Clin Cancer Res; 22(1); 230-42. ©2015 AACR.

Perceived difficulty of various steps of manual small incision cataract surgery among trainees in rural China

Background: The perceived difficulty of steps of manual small incision cataract surgery among trainees in rural China was assessed. Design: Cohort study. Participants: Fifty-two trainees at the end of a manual small incision cataract surgery training programme. Methods: Participants rated the difficulty of 14 surgical steps using a 5-point scale, 1 (very easy) to 5 (very difficult). Demographic and professional information was recorded for trainees. Main Outcome Measure: Mean ratings for surgical steps. Results: Questionnaires were completed by 49 trainees (94.2%, median age 38 years, 8 [16.3%] women). Twenty six (53.1%) had performed ≤50 independent cataract surgeries prior to training. Trainees rated cortical aspiration (mean score±standard deviation=3.10±1.14) the most difficult step, followed by wound construction (2.76±1.08), nuclear prolapse into the anterior chamber (2.74±1.23) and lens delivery (2.51±1.08). Draping the surgical field (1.06±0.242), anaesthetic block administration (1.14±0.354) and thermal coagulation (1.18±0.441) were rated easiest. In regression models, the score for cortical aspiration was significantly inversely associated with performing >50 independent manual small incision cataract surgery surgeries during training (P=0.01), but not with age, gender, years of experience in an eye department or total number of cataract surgeries performed prior to training. Conclusions: Cortical aspiration, wound construction and nuclear prolapse pose the greatest challenge for trainees learning manual small incision cataract surgery, and should receive emphasis during training. Number of cases performed is the strongest predictor of perceived difficulty of key steps. © 2013 Royal Australian and New Zealand College of Ophthalmologists.

Visual outcomes and astigmatism after sutureless, manual cataract extraction in rural China: study of cataract outcomes and up-take of services (SCOUTS) in the caring is hip project, report 1.

OBJECTIVE: To study the visual acuity and astigmatism of persons undergoing cataract extraction by local surgeons in rural China. METHODS: Visual acuity, keratometry, and refraction were measured 10 to 14 months postoperatively for all cataract cases during 4 months in Sanrao, China. RESULTS: Among 313 eligible subjects, 242 (77%) could be contacted, of whom 176 (73%) were examined. Of those who were examined, mean +/- SD age was 69.3 +/- 10.5 years, 66.5% were female, 35 had been operated on bilaterally at Sanrao, and 85.2% had a preoperative presenting visual acuity of 6/60 or worse. Presenting and best-corrected postoperative acuity in the eye that was operated on were 6/18 or better in 83.4% and 95.7%, respectively. Among 27 fellow eyes operated on elsewhere, 40.7% had a presenting acuity of 6/18 or better and 40.7% were blind (P < .001). Mean +/- SD postoperative astigmatism did not differ between 211 eyes that were operated on (-1.13 +/- 0.84 diopters) and 109 eyes that were not (-1.13 +/- 1.17 diopters; P = .27). Presence of operative complications (8.5%) and older age were associated with worse vision; bilateral surgery was associated with better vision. CONCLUSIONS: These results confirm the effectiveness of skill transfer in this setting, with superior outcomes to most studies in rural Asia and to eyes in this cohort operated on at other facilities.

Visual function and postoperative care after cataract surgery in rural China: study of cataract outcomes and up-take of services (SCOUTS) in the caring is hip project, report 2.

OBJECTIVE:

To study the postoperative visual function and uptake of refraction and second-eye surgery among persons undergoing cataract surgery in rural China.

METHODS:

Self-reported visual function was measured 10 to 14 months after surgery. Subjects with improvement of 2 or more lines with refraction were offered glasses, and those with significant cataract were offered second-eye surgery.

RESULTS:

Among 313 eligible subjects, 242 (77%) could be contacted; 176 (73%) of those contacted were examined. Interviewed subjects had a mean +/- SD age of 69.9 +/- 10.2 years, and 63.6% were female. The mean +/- SD visual function score was 88.4 +/- 12.3, higher than previously reported for cataract programs in rural China and significantly (P = .03) correlated with presenting vision. Forty-two percent of subjects had spectacles, more than half being reading glasses. Though 87% of subjects' vision improved with refraction, only 35% accepted prescriptions, the most common reason for refusal being lack of perceived need. Second-eye surgery was accepted by a total of 48% (85 of 176) of patients, cost being the biggest reason for refusal.

CONCLUSIONS:

Visual function was high in this cohort. Potential benefit of refraction and second-eye surgery was substantial, but uptake of services was modest. Programs to improve service uptake should focus on reading glasses and cost-reduction strategies such as tiered pricing.

Ocular comorbidities among cataract-operated patients in rural China: the caring is hip Study of Cataract Outcomes and Uptake of Services (SCOUTS), report No. 3.

PURPOSE: To determine the prevalence and impact on vision and visual function of ocular comorbidities in a rural Chinese cataract surgical program, and to devise strategies to reduce their associated burden. DESIGN: Cross-sectional cohort study. PARTICIPANTS: Persons undergoing cataract surgery by one of two recently trained local surgeons at a government-run village-level hospital in rural Guangdong between August 8 and December 31, 2005. INTERVENTIONS: Eligible subjects were invited to return for a comprehensive ocular examination and visual function interview 10 to 14 months after surgery. Prevalent ocular comorbid conditions were identified. MAIN OUTCOME MEASURES: Presenting and best-corrected vision, visual function, and treatability of the comorbidity. RESULTS: Of 313 persons operated within the study window, 242 (77%) could be contacted by telephone; study examinations and interviews were performed on 176 (74%). Examined subjects had a mean age of 69.4+/-10.5 years, 116 (66%) were female, and 149 (85%) had been blind (presenting vision < or = 6/60) in the operative eye before surgery. Among unoperated eyes, 89 of 109 (81.7%) had > or =1 ocular comorbidities, whereas for operated eyes the corresponding proportion was 72 of 211 (34.1%). The leading comorbidity among operated eyes was refractive error (43/72 [59.7%]), followed by glaucoma/glaucoma suspect (14/72 [19.4%]), whereas for unoperated eyes, it was cataract (80/92 [87.0%]), followed by refractive error (12/92 [13.0%]). Among operated eyes with comorbidities, 90.3% (65/72) had > or =1 comorbidities that were treatable. In separate models adjusting for age and gender, persons with > or =1 comorbidities in the operated eye had significantly worse presenting vision (P<0.001) than those without such findings, but visual function (P = 0.197) and satisfaction with surgery (P = 0.796) were unassociated with comorbidities. CONCLUSIONS: Ocular comorbidities are highly prevalent among persons undergoing cataract surgery in this rural Asian setting, and their presence is significantly associated with poorer visual outcomes. The fact that the great majority of comorbidities encountered in this program are treatable suggests that strategies to reduce their impact can be successful.

Distribution and visual impact of postoperative refractive error after cataract surgery in rural China: study of cataract outcomes and up-take of services report 4.

PURPOSE: To model the possible impact of using average-power intraocular lenses (IOLs) and evaluate the postoperative refractive error in patients having cataract surgery in rural China.SETTING: Rural Guangdong, China.METHODS: Patients having cataract surgery by local surgeons were examined and visual function was assessed 10 to 14 months after surgery. Subjective refraction at near and distance was performed bilaterally by an ophthalmologist. Patients had a target refraction of -0.50 diopter (D) based on ocular biometry.RESULTS: Of the 313 eligible patients, 242 (77%) could be contacted and 176 (74% of contacted patients, 56% overall) were examined. Examined patients had a mean age of 69.4 +/- 10.5 years. Of the 211 operated eyes, 73.2% were within +/-1.0 D of the target refraction after surgery. The best presenting distance vision was in patients within +/-1.0 D of plano and the best presenting near vision, in those with mild myopia (<-1.0 D to > or =2.0 D) (P= .005). However, patients with hyperopia (>+1.0 D) reported significantly better adjusted visual function than those with emmetropia or myopia (<-1.0 D). When the predicted use of an average-power IOL (median +21.5 D) was modeled, predicted visual acuity was significantly reduced (P= .001); however, predicted visual function was not significantly altered (P>.3).CONCLUSIONS: Accurate selection of postoperative refractive error was achieved by local surgeons in this rural area. Based on visual function results, aiming for mild postoperative myopia may not be suitable in this setting. Implanting average-power IOLs significantly reduced postoperative presenting vision, but not visual function.