The full repertoire of Drosophila gustatory receptors for detecting an aversive compound.

The ability to detect toxic compounds in foods is essential for animal survival. However, the minimal subunit composition of gustatory receptors required for sensing aversive chemicals in Drosophila is unknown. Here we report that three gustatory receptors, GR8a, GR66a and GR98b function together in the detection of L-canavanine, a plant-derived insecticide. Ectopic co-expression of Gr8a and Gr98b in Gr66a-expressing, bitter-sensing gustatory receptor neurons (GRNs) confers responsiveness to L-canavanine. Furthermore, misexpression of all three Grs enables salt- or sweet-sensing GRNs to respond to L-canavanine. Introduction of these Grs in sweet-sensing GRNs switches L-canavanine from an aversive to an attractive compound. Co-expression of GR8a, GR66a and GR98b in Drosophila S2 cells induces an L-canavanine-activated nonselective cation conductance. We conclude that three GRs collaborate to produce a functional L-canavanine receptor. Thus, our results clarify the full set of GRs underlying the detection of a toxic tastant that drives avoidance behaviour in an insect

Characterization of Swirling Fluidized Bed

This dissertation is intended to conclude and summarize the overall milestone of Final Year Project, Characterization of Swirling Fluidized Bed. In recent years, the Swirling Fluidized Bed has been regarded as one of the novel designs in fluidization technology. This new technique features an annular-blade distributor which injects the fluidizing gas through a certain inclination, is capable of fluidizing the bed and at the same time causes swirling motion of particles in a circular trajectory. In the present work, the fluidization characteristics and hydrodynamics of a swirling bed are studied using experimental approach. The behavior of gas-particle interaction in a swirling bed in terms of operation regimes, trends of pressure drop across particle bed and hysteresis effects of bed pressure drop with increasing superficial velocity of gas, are explored by varying bed configurations. Three different sizes of spherical Polyvinyl chloride particle, two sizes in irregular shape and two sizes in cylindrical form, are used as bed material by considering four bed weights from 500 g to 2000 g, with increment of 500 g in each step, three blade overlap angles of 9°, 15° and 18°, for air superficial velocities up to approximately 3.5 m/s and two blade inclination of 10° and 15°. In this report, a well-structured review of the literature is constructed to compile the critical and substantive discoveries in the past researches. Furthermore, detailed research methodology and detailed analysis of experiment results are illustrated and expounded. The findings explicitly show that the solid particle size, shape, and bed weight are the major variables that give significant impact on the fluidized bed characteristics, while the blade dimension has relatively smaller effect on the bed behavior. This project has, hopefully, revealed how everything responds in SFB and this correlated relationship could be a precious benchmark in designing a reactor bed. As a conclusion, the research is intended to demonstrate the superiority of SFB over conventional bed. Through this exploration, the author sincerely hopes that this project will become an achievable reference volume for every practitioner in this field, spanning the boundary of various disciplines especially for fluidization engineering

Reliable Multivalued Conductance States in TaOx, Memristors through Oxygen Plasma-Assisted Electrode Deposition with in Situ-Biased Conductance State Transmission Electron Microscopy Analysis

Transition metal oxide-based memristors have widely been proposed for applications toward artificial synapses. In general, memristors have two or more electrically switchable stable resistance states that device researchers see as an analogue to the ion channels found in biological synapses. The mechanism behind resistive switching in metal oxides has been divided into electrochemical metallization models and valence change models. The stability of the resistance states in the memristor vary widely depending on: oxide material, electrode material, deposition conditions, film thickness, and programming conditions. So far, it has been extremely challenging to obtain reliable memristors with more than two stable multivalued states along with endurances greater than similar to 1000 cycles for each of those states. Using an oxygen plasma-assisted sputter deposition method of noble metal electrodes, we found that the metal-oxide interface could be deposited with substantially lower interface roughness observable at the nanometer scale. This markedly improved device reliability and function, allowing for a demonstration of memristors with four completely distinct levels from similar to 6 x 10(-6) to similar to 4 x 10(-8) S that were tested up to 10(4) cycles per level. Furthermore through a unique in situ transmission electron microscopy study, we were able to verify a redox reaction-type model to be dominant in our samples, leading to the higher degree of electrical state controllability. For solid-state synapse applications, the improvements to electrical properties will lead to simple device structures, with an overall power and area reduction of at least 1000 times when compared to SRAM.11Ysciescopu

Whole-genome sequencing to understand the genetic architecture of common gene expression and biomarker phenotypes.

Initial results from sequencing studies suggest that there are relatively few low-frequency (<5%) variants associated with large effects on common phenotypes. We performed low-pass whole-genome sequencing in 680 individuals from the InCHIANTI study to test two primary hypotheses: (i) that sequencing would detect single low-frequency-large effect variants that explained similar amounts of phenotypic variance as single common variants, and (ii) that some common variant associations could be explained by low-frequency variants. We tested two sets of disease-related common phenotypes for which we had statistical power to detect large numbers of common variant-common phenotype associations-11 132 cis-gene expression traits in 450 individuals and 93 circulating biomarkers in all 680 individuals. From a total of 11 657 229 high-quality variants of which 6 129 221 and 5 528 008 were common and low frequency (<5%), respectively, low frequency-large effect associations comprised 7% of detectable cis-gene expression traits [89 of 1314 cis-eQTLs at P < 1 × 10(-06) (false discovery rate ∼5%)] and one of eight biomarker associations at P < 8 × 10(-10). Very few (30 of 1232; 2%) common variant associations were fully explained by low-frequency variants. Our data show that whole-genome sequencing can identify low-frequency variants undetected by genotyping based approaches when sample sizes are sufficiently large to detect substantial numbers of common variant associations, and that common variant associations are rarely explained by single low-frequency variants of large effect

Transient hydraulics and multiphase kick tolerance study to improve design of narrow margin well

Hydraulic and well control studies are the essential parts of well construction planning, especially for drilling of complex and challenging wells with narrow drilling margins. However, the complete applications of dynamic hydraulic analysis and multiphase kick tolerance studies in well design are scanty, which result in ineffective mud pressure management and extra cost spent on unnecessary casing strings, due to excessive emphasis on previous practices (steady-state model) with liberal sprinkling of safety factors. This research project was set out clearly to improve the well design for narrow margin field, in terms of hydraulics and well control. A deductive quantitative method constitutes major part of the research methodology, in which simulation of real case studies and interpretation were conducted. The dynamic hydraulics simulated equivalent circulating density (ECD) was compared with steadystate results in terms of accuracy and extensiveness in providing a good well design. In addition, the single bubble kick tolerance results which are commonly used by the industry in spreadsheet format were compared with the multiphase model results. Sensitivity studies were performed to understand the effect of each of the operational or well design parameters towards primary and secondary well control. As compared to steady-state hydraulics, transient model covers important parameters like pressure and temperature dependent fluid properties, thermophysical properties, detailed geometry description and operational effects, thus it is more representative to the operational ECD. Meanwhile, multiphase kick model is proven to be more effective for the evaluation of kick tolerance as it is able to provide the information of pressure development during a well control operation, from initial influx and shut-in until influx is circulated out of the well at the surface. This includes all phase transitions including dissolving of a gas kick in oil based mud and breakout of free gas when the gas contaminated mud reaches the bubble point at shallower depth in the well. The flow model is much more accurate and reliable than the over-conservative traditional single bubble theory

Analysis of 6,515 exomes reveals a recent origin of most human protein-coding variants

Establishing the age of each mutation segregating in contemporary human populations is important to fully understand our evolutionary history1,2 and will help facilitate the development of new approaches for disease gene discovery3. Large-scale surveys of human genetic variation have reported signatures of recent explosive population growth4-6, notable for an excess of rare genetic variants, qualitatively suggesting that many mutations arose recently. To more quantitatively assess the distribution of mutation ages, we resequenced 15,336 genes in 6,515 individuals of European (n=4,298) and African (n=2,217) American ancestry and inferred the age of 1,146,401 autosomal single nucleotide variants (SNVs). We estimate that ~73% of all protein-coding SNVs and ~86% of SNVs predicted to be deleterious arose in the past 5,000-10,000 years. The average age of deleterious SNVs varied significantly across molecular pathways, and disease genes contained a significantly higher proportion of recently arisen deleterious SNVs compared to other genes. Furthermore, European Americans had an excess of deleterious variants in essential and Mendelian disease genes compared to African Americans, consistent with weaker purifying selection due to the out-of-Africa dispersal. Our results better delimit the historical details of human protein-coding variation, illustrate the profound effect recent human history has had on the burden of deleterious SNVs segregating in contemporary populations, and provides important practical information that can be used to prioritize variants in disease gene discovery