Effect of Phenolic Matrix Microcracking on the Structural Response of a 3-D Woven Thermal Protection System

The effect of microcracking in the phenolic matrix of a three-dimensional woven thermal protection system (TPS) and the resulting material stiffness reduction was studied via a comparison of finite element analysis results from a linear analysis and an iterative linear analysis. A TPS is necessary to protect space vehicles from the aerodynamic heating of planetary entry. The Heatshield for Extreme Entry Environment Technology (HEEET) project has developed a TPS for use in high heat-flux and pressure missions. The material is a dual-layer continuous dry weave, which is then infiltrated with a low-density phenolic resin matrix to form a rigid ablator. The phenolic resin matrix does not have structural load transfer requirements, and testing has shown that the phenolic resin can fully satisfy thermal requirements when the matrix contains microcracks. Due to high stresses in the through-the-thickness direction of the material, phenolic microcracks may form in the matrix material, which would result in a reduction of stiffness. An exploratory study was conducted to determine if reduction in material stiffness would change the load paths and/or decrease the structural margins. A comparison was performed between a linear finite element analysis that did not take into account phenolic microcracking and an iterative linear finite element analysis that accounted for propagation of phenolic microcracking. Four subcases using varying assumptions were analyzed and the results indicate that the assumed strength at which the phenolic microcracking propagates was the critical parameter for determining the extent of microcracking in the phenolic matrix. Phenolic microcracking does not have an adverse effect on the structural response of the test article and is not a critical failure

Common binding by redundant group B Sox proteins is evolutionarily conserved in Drosophila.

BACKGROUND: Group B Sox proteins are a highly conserved group of transcription factors that act extensively to coordinate nervous system development in higher metazoans while showing both co-expression and functional redundancy across a broad group of taxa. In Drosophila melanogaster, the two group B Sox proteins Dichaete and SoxNeuro show widespread common binding across the genome. While some instances of functional compensation have been observed in Drosophila, the function of common binding and the extent of its evolutionary conservation is not known. RESULTS: We used DamID-seq to examine the genome-wide binding patterns of Dichaete and SoxNeuro in four species of Drosophila. Through a quantitative comparison of Dichaete binding, we evaluated the rate of binding site turnover across the genome as well as at specific functional sites. We also examined the presence of Sox motifs within binding intervals and the correlation between sequence conservation and binding conservation. To determine whether common binding between Dichaete and SoxNeuro is conserved, we performed a detailed analysis of the binding patterns of both factors in two species. CONCLUSION: We find that, while the regulatory networks driven by Dichaete and SoxNeuro are largely conserved across the drosophilids studied, binding site turnover is widespread and correlated with phylogenetic distance. Nonetheless, binding is preferentially conserved at known cis-regulatory modules and core, independently verified binding sites. We observed the strongest binding conservation at sites that are commonly bound by Dichaete and SoxNeuro, suggesting that these sites are functionally important. Our analysis provides insights into the evolution of group B Sox function, highlighting the specific conservation of shared binding sites and suggesting alternative sources of neofunctionalisation between paralogous family members.This work was supported by a Wellcome Trust 4-year Ph.D. studentship and a Cambridge Overseas Trust studentship to S.C. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. We thank Tony Southall for providing the pUAST-Dam vector and Enrico Ferrero for providing the pUAST-SoxNDam vector. We also thank Ernst Wimmer for providing the pSLfa1180fa vector, the pBac3xP3-EGFP vector and the piggyBac transposase helper plasmid. We are indebted to Sang Chan for performing microinjections and to Bettina Fischer for support in the lab and insightful discussions about data analysis

Temperature-dependent preferences for advertisement-call frequency in females of Hyla versicolor

Abstract only availableMale treefrogs produce loud and persistent acoustic signals called advertisement calls to attract mates. Ectothermic animals like frogs face an interesting challenge, in that temperature can significantly impact characteristics of the species-specific advertisement call. The mate-choice preferences of female gray treefrogs (H. versicolor) have been extensively studied (reviewed by Gerhardt & Huber 2002). It has been found that females prefer calls with standard frequency peaks of 1.1 kHz + 2.2 kHz over calls with higher and lower frequencies at 20º C. However, it is not known how this preference is affected by temperature. To determine whether acoustic preferences based on frequency are temperature-dependent, I collected female frogs during their breeding season and tested them in a temperature-controlled anechoic testing chamber. I generated ten different computer-synthesized advertisement calls that ranged in frequency between 0.55 + 1.1 kHz to 1.5 + 3.0 kHz. In two-speaker choice tests conducted at three different temperatures (15º C, 20º C and 25º C), females "chose" (moved within 10 cm of a speaker) between a call with standard frequency peaks of 1.1 + 2.2 kHz and one of the nine alternative calls. Preliminary results indicate the preferred frequencies appeared to remain 1.1 + 2.2 kHz at lower temperatures. However, at higher temperatures, female frogs were more likely to approach high-frequency calls. These results will be discussed in the context of known temperature-dependent physiological processes in the inner ear of frogs.NIH grant to H.C. Gerhard

Effects of polyploidy on female call preference in gray treefrogs, Hyla chrysoscelis

Abstract only availableThe gray treefrog complex consists of two cryptic species; Hyla versicolor is a tetraploid (N=48) species that arose from the polyploidization of its diploid counter-part, H. chrysoscelis (N=24) and two other extinct treefrog species. Speciation via polyploidy is almost instantaneous because polyploid species are isolated reproductively from their non-polyploid ancestors. However, the establishment of newly arisen polyploid lineages requires assortative mating between polyploids. Genome duplication has been shown to affect the quality of the male's species-specific mate-attraction signal, thus polyploids could be reproductively isolated from their diploid ancestors through the action of female mating preferences. Autopolyploid individuals I generated last summer (polyploidy was verified by initial karyotyping) are currently reaching sexual maturity. Once sexually mature, the acoustic mate-choice preferences of female polyploids will be tested using playback experiments. The experimental tests will compare preferences for call traits that vary between the two species, including frequency, pulse shape, and pulse rate. We hypothesize that these changes in the communication system result from ploidy-induced changes in tissue and cellular dimensions. Thus, as a related experiment, we will also look for effects of larval density on blood cell size, male calls and female preferences. We expect to find that polyploidy affects the advertisement-call preferences of female H. chrysoscelis treefrogs, independent of other factors. Preliminary results indicate that autopolyploid individuals are able to reach sexual maturity and that there is an effect of polyploidy on blood cell size.Life Sciences Undergraduate Research Opportunity Progra

Male phonotactic responses in gray treefrogs (Hyla versicolor) [abstract]

Abstract only availableFaculty Mentor: Dr. Sarah Humfeld, Biological SciencesMany anuran amphibians, better known as frogs and toads, use acoustic signals as a means of communication. Female frogs choose mates by moving towards males making a particular call (phonotaxis). Non-calling males, which have been termed satellites, may also associate with these calling males as a result of male-male competition for mates.  My project addressed the question of whether male frogs have phonotactic preferences similar to those of females.  Most Hyla versicolor females prefer calls with a faster-than-average call rate, longer-than-average call duration and low frequency.  My main goal was to verify whether H. versicolor males demonstrate phonotactic behavior, and if so, to determine whether they have preferences similar to females.  I also wanted to learn if non-calling males were inferior to calling males.  I used two methods to answer these questions. During field observations, H. versicolor males (calling and non-calling) were weighed, their calls recorded and body temperature taken. We found no evidence to indicate that non-calling males are smaller or produce less attractive calls than callers. In laboratory phonotaxis experiments, synthetic signals from two speakers were played and the successive movements of individual males were observed. The results indicated that H. versicolor males express phonotactic responses and also have acoustic preferences, which are similar to female preferences. Fourteen of 22 males moved within 20cm of a speaker, and most of these (13) chose the call with characteristics favored by females. Based on these results we speculate that the ability of males to recognize attractive calls may maximize the reproductive success of satellite males

Four-month moxifloxacin-based regimens for drug-sensitive tuberculosis

Supported by the Global Alliance for TB Drug Development with support from the Bill and Melinda Gates Foundation, the European and Developing Countries Clinical Trials Partnership, U.S. Agency for International Development, U.K. Department for International Development, Directorate General for International Cooperation of the Netherlands, Irish Aid, Australia Department of Foreign Affairs and Trade, and National Institutes of Health, AIDS Clinical Trials Group and by grants from the National Institute of Allergy and Infectious Diseases (NIAID) (UM1AI068634, UM1 AI068636, and UM1AI106701) and by NIAID grants to the University of KwaZulu Natal, South Africa, AIDS Clinical Trials Group (ACTG) site 31422 (1U01AI069469); to the Perinatal HIV Research Unit, Chris Hani Baragwanath Hospital, South Africa, ACTG site 12301 (1U01AI069453); and to the Durban International Clinical Trials Unit, South Africa, ACTG site 11201 (1U01AI069426); Bayer Healthcare for the donation of moxifloxacin; and Sanofi for the donation of rifampin.Background: Early-phase and preclinical studies suggest that moxifloxacin-containing regimens could allow for effective 4-month treatment of uncomplicated, smear-positive pulmonary tuberculosis. Methods: We conducted a randomized, double-blind, placebo-controlled, phase 3 trial to test the noninferiority of two moxifloxacin-containing regimens as compared with a control regimen. One group of patients received isoniazid, rifampin, pyrazinamide, and ethambutol for 8 weeks, followed by 18 weeks of isoniazid and rifampin (control group). In the second group, we replaced ethambutol with moxifloxacin for 17 weeks, followed by 9 weeks of placebo (isoniazid group), and in the third group, we replaced isoniazid with moxifloxacin for 17 weeks, followed by 9 weeks of placebo (ethambutol group). The primary end point was treatment failure or relapse within 18 months after randomization. Results: Of the 1931 patients who underwent randomization, in the per-protocol analysis, a favorable outcome was reported in fewer patients in the isoniazid group (85%) and the ethambutol group (80%) than in the control group (92%), for a difference favoring the control group of 6.1 percentage points (97.5% confidence interval [CI], 1.7 to 10.5) versus the isoniazid group and 11.4 percentage points (97.5% CI, 6.7 to 16.1) versus the ethambutol group. Results were consistent in the modified intention-to-treat analysis and all sensitivity analyses. The hazard ratios for the time to culture negativity in both solid and liquid mediums for the isoniazid and ethambutol groups, as compared with the control group, ranged from 1.17 to 1.25, indicating a shorter duration, with the lower bounds of the 95% confidence intervals exceeding 1.00 in all cases. There was no significant difference in the incidence of grade 3 or 4 adverse events, with events reported in 127 patients (19%) in the isoniazid group, 111 (17%) in the ethambutol group, and 123 (19%) in the control group. Conclusions: The two moxifloxacin-containing regimens produced a more rapid initial decline in bacterial load, as compared with the control group. However, noninferiority for these regimens was not shown, which indicates that shortening treatment to 4 months was not effective in this setting. (Funded by the Global Alliance for TB Drug Development and others; REMoxTB ClinicalTrials.gov number, NCT00864383.)Publisher PDFPeer reviewe

Elevated stearoyl-CoA desaturase in brains of patients with Alzheimer\u27s disease

The molecular bases of Alzheimer\u27s disease (AD) remain unclear. We used a lipidomic approach to identify lipid abnormalities in the brains of subjects with AD (N = 37) compared to age-matched controls (N = 17). The analyses revealed statistically detectable elevations in levels of non-esterified monounsaturated fatty acids (MUFAs) and mead acid (20:3n-9) in mid-frontal cortex, temporal cortex and hippocampus of AD patients. Further studies showed that brain mRNAs encoding for isoforms of the rate-limiting enzyme in MUFAs biosynthesis, stearoyl-CoA desaturase (SCD-1, SCD-5a and SCD-5b), were elevated in subjects with AD. The monounsaturated/saturated fatty acid ratio (\u27desaturation index\u27)--displayed a strong negative correlation with measures of cognition: the Mini Mental State Examination test (r = -0.80; P = 0.0001) and the Boston Naming test (r = -0.57; P = 0.0071). Our results reveal a previously unrecognized role for the lipogenic enzyme SCD in AD

Lymphovascular and perineural invasion as selection criteria for adjuvant therapy in intrahepatic cholangiocarcinoma: a multi-institution analysis

AbstractObjectivesCriteria for the selection of patients for adjuvant chemotherapy in intrahepatic cholangiocarcinoma (IHCC) are lacking. Some authors advocate treating patients with lymph node (LN) involvement; however, nodal assessment is often inadequate or not performed. This study aimed to identify surrogate criteria based on characteristics of the primary tumour.MethodsA total of 58 patients who underwent resection for IHCC between January 2000 and January 2010 at any of three institutions were identified. Primary outcome was overall survival (OS).ResultsMedian OS was 23.0months. Median tumour size was 6.5cm and the median number of lesions was one. Overall, 16% of patients had positive margins, 38% had perineural invasion (PNI), 40% had lymphovascular invasion (LVI) and 22% had LN involvement. A median of two LNs were removed and a median of zero were positive. Lymph nodes were not sampled in 34% of patients. Lymphovascular and perineural invasion were associated with reduced OS [9.6months vs. 32.7months (P= 0.020) and 10.7months vs. 32.7months (P= 0.008), respectively]. Lymph node involvement indicated a trend towards reduced OS (10.7months vs. 30.0months; P= 0.063). The presence of either LVI or PNI in node-negative patients was associated with a reduction in OS similar to that in node-positive patients (12.1months vs. 10.7months; P= 0.541). After accounting for adverse tumour factors, only LVI and PNI remained associated with decreased OS on multivariate analysis (hazard ratio4.07, 95% confidence interval 1.60–10.40; P= 0.003).ConclusionsLymphovascular and perineural invasion are separately associated with a reduction in OS similar to that in patients with LN-positive disease. As nodal dissection is often not performed and the number of nodes retrieved is frequently inadequate, these tumour-specific factors should be considered as criteria for selection for adjuvant chemotherapy