Influence of shape-memory stent grafts on local aortic compliance

The effect of repair techniques on the biomechanics of the aorta is poorly understood, resulting in significant levels of postoperative complications for patients worldwide. This study presents a computational analysis of the influence of Nitinol-based devices on the biomechanical performance of a healthy patient-specific human aorta. Simulations reveal that Nitinol stent-grafts stretch the artery wall so that collagen is stretched to a straightened high-stiffness configuration. The high-compliance regime (HCR) associated with low diastolic lumen pressure is eliminated, and the artery operates in a low-compliance regime (LCR) throughout the entire cardiac cycle. The slope of the lumen pressure–area curve for the LCR post-implantation is almost identical to that of the native vessel during systole. This negligible change from the native LCR slope occurs because the stent-graft increases its diameter from the crimped configuration during deployment so that it reaches a low-stiffness unloading plateau. The effective radial stiffness of the implant along this unloading plateau is negligible compared to the stiffness of the artery wall. Provided the Nitinol device unloads sufficiently during deployment to the unloading plateau, the degree of oversizing has a negligible effect on the pressure–area response of the vessel, as each device exerts approximately the same radial force, the slope of which is negligible compared to the LCR slope of the native artery. We show that 10% oversizing based on the observed diastolic diameter in the mid descending thoracic aorta results in a complete loss of contact between the device and the wall during systole, which could lead to an endoleak and stent migration. 20% oversizing reaches the Dacron enforced area limit (DEAL) during the pulse pressure and results in an effective zero-compliance in the later portion of systole.

     

The Wavelet-Based Cluster Analysis for Temporal Gene Expression Data

A variety of high-throughput methods have made it possible to generate detailed temporal expression data for a single gene or large numbers of genes. Common methods for analysis of these large data sets can be problematic. One challenge is the comparison of temporal expression data obtained from different growth conditions where the patterns of expression may be shifted in time. We propose the use of wavelet analysis to transform the data obtained under different growth conditions to permit comparison of expression patterns from experiments that have time shifts or delays. We demonstrate this approach using detailed temporal data for a single bacterial gene obtained under 72 different growth conditions. This general strategy can be applied in the analysis of data sets of thousands of genes under different conditions.[1,2,3,4,5,6,7,8,9,10,11,12,13,14,15,16,17,18,19,20,21,22,23,24,25,26,27,28,29]     

Validity of Antibodies in Lymphocyte Supernatant in Diagnosing Tuberculosis in Severely Malnourished Children Presenting with Pneumonia

BackgroundThe diagnosis of tuberculosis (TB) in young children can be challenging, especially in severely malnourished children. There is a critical need for improved diagnostics for children. Thus, we sought to evaluate the performance of a technique that measures antibodies in lymphocyte supernatant (ALS) for the diagnosis of TB in severely malnourished children presenting with suspected pneumonia.MethodsChildren less than 5 years with severe acute malnutrition and radiological features of pneumonia admitted to the Dhaka Hospital of International Centre for Diarrhoeal Disease Research, Bangladesh, were enrolled consecutively following informed written consent. In addition to clinical and radiological assessment, samples taken for TB diagnosis included gastric lavage fluid and induced sputum for microbiological confirmation. ALS was measured from venous blood, and results were evaluated in children classified as “confirmed”, “non-confirmed TB” or “not TB”.ResultsAmong 224 children who had ALS analysis, 12 (5.4%) children had microbiologically “confirmed TB”, a further 41 (18%) had clinically diagnosed “non-confirmed TB” and the remaining 168 (75%) were considered not to have TB. ALS was positive in 89 (40%) and negative in 85 (39%) of children, with a large number (47 or 21%) reported as “borderline”. These proportions were similar between the three diagnostic groups. The sensitivity and specificity of ALS when comparing “Confirmed TB” to “Not TB” was only 67% (95% CI: 31–91%) and 51% (95% CI: 42–60%), respectively.

Conclusions and Significance

Our data suggest that ALS is not sufficiently accurate to improve the diagnosis of TB in children with severe malnutrition.     

ArchAlign: coordinate-free chromatin alignment reveals novel architectures

To facilitate identification and characterization of genomic functional elements, we have developed a chromatin architecture alignment algorithm (ArchAlign). ArchAlign identifies shared chromatin structural patterns from high-resolution chromatin structural datasets derived from next-generation sequencing or tiled microarray approaches for user defined regions of interest. We validated ArchAlign using well characterized functional elements, and used it to explore the chromatin structural architecture at CTCF binding sites in the human genome. ArchAlign is freely available at http://www.acsu.buffalo.edu/~mjbuck/ArchAlign.html.     

Morning Sleep Inertia in Alertness and Performance: Effect of Cognitive Domain and White Light Conditions

The transition from sleep to wakefulness entails a temporary period of reduced alertness and impaired performance known as sleep inertia. The extent to which its severity varies with task and cognitive processes remains unclear. We examined sleep inertia in alertness, attention, working memory and cognitive throughput with the Karolinska Sleepiness Scale (KSS), the Psychomotor Vigilance Task (PVT), n-back and add tasks, respectively. The tasks were administered 2 hours before bedtime and at regular intervals for four hours, starting immediately after awakening in the morning, in eleven participants, in a four-way cross-over laboratory design. We also investigated whether exposure to Blue-Enhanced or Bright Blue-Enhanced white light would reduce sleep inertia. Alertness and all cognitive processes were impaired immediately upon awakening (p<0.01). However, alertness and sustained attention were more affected than cognitive throughput and working memory. Moreover, speed was more affected than accuracy of responses. The light conditions had no differential effect on performance except in the 3-back task (p<0.01), where response times (RT) at the end of four hours in the two Blue-Enhanced white light conditions were faster (200 ms) than at wake time. We conclude that the effect of sleep inertia varies with cognitive domain and that it’s spectral/intensity response to light is different from that of sleepiness. That is, just increasing blue-wavelength in light may not be sufficient to reduce sleep inertia. These findings have implications for critical professions like medicine, law-enforcement etc., in which, personnel routinely wake up from night-time sleep to respond to emergency situations.     

Over-expression of an FT-homologous gene of apple induces early flowering in annual and perennial plants

The protein encoded by the FLOWERING LOCUS T (FT) gene from Arabidopsis thaliana seems to be the long-searched florigen, and over-expression of FT orthologues resulted in accelerated flower development in annual and perennial plants. In the present study, we isolated two allelic mRNA sequences of an FT-homologous gene from apple, which was designated as MdFT1. Using a SSR motif this gene was mapped on LG 12 of apple. Over-expression of MdFT1 in Arabidopsis and the commercially important tree species poplar and apple itself using the CaMV 35S or the Arabidopsis Suc2 promoter resulted in significant accelerated flowering compared with wild-type plants. Transgenic T₀ plants of Arabidopsis flowered 4–6 days on average earlier than wild-type Arabidopsis under LD conditions. Under short-day conditions Suc2::MdFT1 plants of the T₁-generation flowered after 66 ± 18 days, while wild-type plants flowered about 22 days later. All transgenic Arabidopsis plants showed a normal habit except for the early flowering phenotype. Early flowering was detected 6–10 months after transformation in transgenic polar clones containing MdFT1 driven by the CaMV 35S, whereas plants of the transgenic apple clone T780 set up its first flowers during in vitro cultivation. Based on our results we conclude that MdFT1 is responsible for inducing flowering and that the function of the apple FT1 gene is conserved in annual herbaceous species as well as perennial woody species. Furthermore, we discuss the role of MdFT1 in flower development with regard to the findings of genetic studies on apple.     

BLUE LIGHT Exposure Reduces Objective Measures of Sleepiness during Prolonged Nighttime Performance Testing

This study examined the effects of nocturnal exposure to dim, narrowband blue light (460 nm, ～1 lux, 2 µW/cm²), compared to dim broad spectrum (white) ambient light (～0.2 lux, 0.5 µW/cm²), on subjective and objective indices of sleepiness during prolonged nighttime performance testing. Participants were also exposed to a red light (640 nm, ～1 lux, 0.7µW/cm²) placebo condition. Outcome measures were driving simulator and psychomotor vigilance task (PVT) performance, subjective sleepiness, salivary melatonin, and electroencephalographic (EEG) activity. The study had a repeated-measures design, with three counterbalanced light conditions and a four-week washout period between each condition. Participants (n?=?8) maintained a regular sleep-wake schedule for 14 days prior to the ～14 h laboratory study, which consisted of habituation to light conditions followed by neurobehavioral performance testing from 21:00 to 08:30 h under modified constant-routine conditions. A neurobehavioral test battery (2.5 h) was presented four times between 21:00 and 08:30 h, with a 30 min break between each. From 23:30 to 05:30 h, participants were exposed to blue or red light, or remained in ambient conditions. Compared to ambient light exposure, blue light exposure suppressed EEG slow wave delta (1.0–4.5 Hz) and theta (4.5–8 Hz) activity and reduced the incidence of slow eye movements. PVT reaction times were significantly faster in the blue light condition, but driving simulator measures, subjective sleepiness, and salivary melatonin levels were not significantly affected by blue light. Red light exposure, as compared to ambient light exposure, reduced the incidence of slow eye movements. The results demonstrate that low-intensity, blue light exposure can promote alertness, as measured by some of the objective indices used in this study, during prolonged nighttime performance testing. Low intensity, blue light exposure has the potential to be applied to situations where it is desirable to increase alertness but not practical or appropriate to use bright light, such as certain occupational settings.     

Transcriptome of Extracellular Vesicles Released by Hepatocytes

The discovery that the cells communicate through emission of vesicles has opened new opportunities for better understanding of physiological and pathological mechanisms. This discovery also provides a novel source for non-invasive disease biomarker research. Our group has previously reported that hepatocytes release extracellular vesicles with protein content reflecting the cell-type of origin. Here, we show that the extracellular vesicles released by hepatocytes also carry RNA. We report the messenger RNA composition of extracellular vesicles released in two non-tumoral hepatic models: primary culture of rat hepatocytes and a progenitor cell line obtained from a mouse foetal liver. We describe different subpopulations of extracellular vesicles with different densities and protein and RNA content. We also show that the RNA cargo of extracellular vesicles released by primary hepatocytes can be transferred to rat liver stellate-like cells and promote their activation. Finally, we provide in vitro and in vivo evidence that liver-damaging drugs galactosamine, acetaminophen, and diclofenac modify the RNA content of these vesicles. To summarize, we show that the extracellular vesicles secreted by hepatocytes contain various RNAs. These vesicles, likely to be involved in the activation of stellate cells, might become a new source for non-invasive identification of the liver toxicity markers.