Structural constraints in the packaging of bluetongue virus genomic segments.

The mechanism used by bluetongue virus (BTV) to ensure the sorting and packaging of its 10 genomic segments is still poorly understood. In this study, we investigated the packaging constraints for two BTV genomic segments from two different serotypes. Segment 4 (S4) of BTV serotype 9 was mutated sequentially and packaging of mutant ssRNAs was investigated by two newly developed RNA packaging assay systems, one in vivo and the other in vitro. Modelling of the mutated ssRNA followed by biochemical data analysis suggested that a conformational motif formed by interaction of the 5' and 3' ends of the molecule was necessary and sufficient for packaging. A similar structural signal was also identified in S8 of BTV serotype 1. Furthermore, the same conformational analysis of secondary structures for positive-sense ssRNAs was used to generate a chimeric segment that maintained the putative packaging motif but contained unrelated internal sequences. This chimeric segment was packaged successfully, confirming that the motif identified directs the correct packaging of the segment

Development of Catalytic Strategies and Microreactor Technology for the Synthesis of Bio-based Furanics from Lignocellulosederived Carbohydrates

In this research project, efforts have been given to developing efficient catalytic strategies and microreactor technology for the synthesis of HMF or furfural from the lignocellulose-derived C6 or C5 sugars, by exploring (i) the insights into the kinetics and reaction network of the homogeneous acid-catalyzed sugar dehydration to HMF and furfural, (ii) the structure-acidity-performance relation of the heterogeneous bi-functional acid catalyst for the glucose dehydration to HMF, and (iii) utilization of microreactors as a platform for reaction and kinetic studies and as a tool for process intensification and up-scaling

Distributed analyses of disease risk and association across networks of de-identified medical systems

Health information networks continue to expand under the Affordable Care Act yet little research has been done to query and analyze multiple patient populations in parallel. Differences between hospitals relating to patient demographics, treatment approaches, disease prevalences, and medical coding practices all pose significant challenges for multi-site analysis and interpretation. Furthermore, numerous methodological issues arise when attempting to analyze disease association in heterogeneous health care settings. These issues will only continue to increase as greater numbers of hospitals are linked. To address these challenges, I developed the Shared Health Research Informatics Network (SHRINE), a distributed query and analysis system used by more than 60 health institutions for a wide range of disease studies. SHRINE was used to conduct one of the largest comorbidity studies in Autism Spectrum Disorders. SHRINE has enabled population scale studies in diabetes, rheumatology, public health, and pathology. Using Natural Language Processing, we de-identify physician notes and query pathology reports to locate human tissues for high-throughput biological validation. Samples and evidence obtained using these methods supported novel discoveries in human metabolism and paripartum cardiomyopathy, respectively. Each hospital in the SHRINE network hosts a local peer database that cannot be overridden by any federal agency. SHRINE can search both coded clinical concepts and de-identified physician notes to obtain very large cohort sizes for analysis. SHRINE intelligently clusters phenotypic concepts to minimize differences in health care settings. I then analyzed a statewide sample of all Massachusetts acute care hospitals and found diagnoses codes useful for predicting Acute Myocardial Infarction (AMI). The AMI association methods selected 96 clinical concepts. Manual review of PubMed citations supported the automated associations. AMI associations were most often discovered in the circulatory system and were most strongly linked to background diabetic retinopathy, diabetes with renal manifestations, and hypertension with complications. AMI risks were strongly associated with chronic kidney failure, liver diseases, chronic airway obstruction, hemodialysis procedures, and medical device complications. Learning the AMI associated risk factors improved disease predictions for patients in Massachusetts acute care hospitals

Statistical PT-symmetric lasing in an optical fiber network

PT-symmetry in optics is a condition whereby the real and imaginary parts of the refractive index across a photonic structure are deliberately balanced. This balance can lead to a host of novel optical phenomena, such as unidirectional invisibility, loss-induced lasing, single-mode lasing from multimode resonators, and non-reciprocal effects in conjunction with nonlinearities. Because PT-symmetry has been thought of as fragile, experimental realizations to date have been usually restricted to on-chip micro-devices. Here, we demonstrate that certain features of PT-symmetry are sufficiently robust to survive the statistical fluctuations associated with a macroscopic optical cavity. We construct optical-fiber-based coupled-cavities in excess of a kilometer in length (the free spectral range is less than 0.8 fm) with balanced gain and loss in two sub-cavities and examine the lasing dynamics. In such a macroscopic system, fluctuations can lead to a cavity-detuning exceeding the free spectral range. Nevertheless, by varying the gain-loss contrast, we observe that both the lasing threshold and the growth of the laser power follow the predicted behavior of a stable PT-symmetric structure. Furthermore, a statistical symmetry-breaking point is observed upon varying the cavity loss. These findings indicate that PT-symmetry is a more robust optical phenomenon than previously expected, and points to potential applications in optical fiber networks and fiber lasers.Comment: Submitted to Nature Communications, Pages 1-19: Main manuscript; Pages 20-38: Supplementary material

Studi Tinjauan Perencanaan Sistem Plumbing Air Bersih (Studi Kasus: Gedung Sekolah Tinggi Ilmu Bahasa Arab)

carefully considered to ensure that the water demand of the students and staff can be met effectively and efficiently. Calculations show that a water demand of 0.35 m3/min is required, and various existing pipe diameters are used, ranging from 65mm for the main pipes, 60mm and 50mm for the header pipes, to 40mm, 32mm, 30mm, 25mm, 20mm, and 15mm for the shaft pipes. However, after controlling for velocity values using Epanet software, it was found that some pipes had values below 1.8m/s and above 2.4m/s, which could compromise system efficiency. Therefore, the effective pipe diameter for the header pipes was found to be 125mm and 90mm, and for the shaft pipes, it ranged from 90mm to 15mm. The results of this study highlight that the clean water piping system in the STIBA building must be carefully designed and evaluated to meet the clean water demands of the students and staff effectively and efficiently. This can be achieved by selecting effective pipe diameters based on the Epanet calculations and ensuring that the velocity values remain within the specified limits

Appearance of the universal value e2/he^{2}/h of the zero-bias conductance in a Weyl semimetal-superconductor junction

We study the differential conductance of a time-reversal symmetric Weyl semimetal-superconductor (N-S) junction with an s-wave superconducting state. We find that there exists an extended regime where the zero-bias differential conductance acquires the universal value $e^{2}/h$ per unit channel, independent of the pairing and chemical potentials on each side of the junction, due to a perfect cancellation of Andreev and normal reflection contributions. This universal conductance can be attributed to the interplay of the unique spin/orbital-momentum locking and s-wave pairing that couples Weyl nodes of the same chirality. We expect that the universal conductance can serve as a robust and distinct signature for time-reversal symmetric Weyl fermions, and be observed in the recently discovered time-reversal symmetric Weyl semimetals.Comment: 12 pages, 4 figure

Nanoscale Membrane Domain Formation Driven by Cholesterol

Biological membranes generate specific functions through compartmentalized regions such as cholesterol-enriched membrane nanodomains that host selected proteins. Despite the biological significance of nanodomains, details on their structure remain elusive. They cannot be observed via microscopic experimental techniques due to their small size, yet there is also a lack of atomistic simulation models able to describe spontaneous nanodomain formation in sufficiently simple but biologically relevant complex membranes. Here we use atomistic simulations to consider a binary mixture of saturated dipalmitoylphosphatidylcholine and cholesterol - the "minimal standard" for nanodomain formation. The simulations reveal how cholesterol drives the formation of fluid cholesterol-rich nanodomains hosting hexagonally packed cholesterol-poor lipid nanoclusters, both of which show registration between the membrane leaflets. The complex nanodomain substructure forms when cholesterol positions itself in the domain boundary region. Here cholesterol can also readily flip-flop across the membrane. Most importantly, replacing cholesterol with a sterol characterized by a less asymmetric ring region impairs the emergence of nanodomains. The model considered explains a plethora of controversial experimental results and provides an excellent basis for further computational studies on nanodomains. Furthermore, the results highlight the role of cholesterol as a key player in the modulation of nanodomains for membrane protein function.Peer reviewe