A multi-level multi-scale approach to study essential genes in Mycobacterium tuberculosis

Background: The set of indispensable genes that are required by an organism to grow and sustain life are termed as essential genes. There is a strong interest in identification of the set of essential genes, particularly in pathogens, not only for a better understanding of the pathogen biology, but also for identifying drug targets and the minimal gene set for the organism. Essentiality is inherently a systems property and requires consideration of the system as a whole for their identification. The available experimental approaches capture some aspects but each method comes with its own limitations. Moreover, they do not explain the basis for essentiality in most cases. A powerful prediction method to recognize this gene pool including rationalization of the known essential genes in a given organism would be very useful. Here we describe a multi-level multi-scale approach to identify the essential gene pool in a deadly pathogen, Mycobacterium tuberculosis. Results: The multi-level workflow analyses the bacterial cell by studying (a) genome-wide gene expression profiles to identify the set of genes which show consistent and significant levels of expression in multiple samples of the same condition, (b) indispensability for growth by using gene expression integrated flux balance analysis of a genome-scale metabolic model, (c) importance for maintaining the integrity and flow in a protein-protein interaction network and (d) evolutionary conservation in a set of genomes of the same ecological niche. In the gene pool identified, the functional basis for essentiality has been addressed by studying residue level conservation and the sub-structure at the ligand binding pockets, from which essential amino acid residues in that pocket have also been identified. 283 genes were identified as essential genes with high-confidence. An agreement of about 73.5% is observed with that obtained from the experimental transposon mutagenesis technique. A large proportion of the identified genes belong to the class of intermediary metabolism and respiration. Conclusions: The multi-scale, multi-level approach described can be generally applied to other pathogens as well. The essential gene pool identified form a basis for designing experiments to probe their finer functional roles and also serve as a ready shortlist for identifying drug targets.

ADAPTATION OF MW LEVEL NATURAL GAS LEAN BURN ENGINE FOR PRODUCER GAS OPERATION A GRID CONNECTED POWER PLANT

Availability of producer gas engines at MW being limited necessitates to adapt engine from natural gas operation. The present work focus on the development of necessary kit for adapting a 12 cylinder lean burn turbo-charged natural gas engine rated at 900 kWe (Waukesha make VHP5904LTD) to operate on producer and set up an appropriate capacity biomass gasification system for grid linked power generation in Thailand. The overall plant configuration had fuel processing, drying, reactor, cooling and cleaning system, water treatment, engine generator and power evacuation. The overall project is designed for evacuation of 1.5 MWe power to the state grid and had 2 gasification system with the above configuration and 3 engines. Two gasification system each designed for about 1100 kg/hr of woody biomass was connected to the engine using a producer gas carburetor for the necessary Air to fuel ratio control. In the use of PG to fuel IC engines, it has been recognized that the engine response will differ as compared to the response with conventional fueled operation due to the differences in the thermo-physical properties of PG. On fuelling a conventional engine with PG, power de-rating can be expected due to the lower calorific value (LCV), lower adiabatic flame temperature (AFT) and the lower than unity product to reactant more ratio. Further the A/F ratio for producer gas is about 1/10th that of natural gas and requires a different carburetor for engine operation. The research involved in developing a carburetor for varying load conditions. The patented carburetor is based on area ratio control, consisting of a zero pressure regulator and a separate gas and air line along with a mixing zone. The 95 litre engine at 1000 rpm has an electrical efficiency of 33.5 % with a heat input of 2.62 MW. Each engine had two carburetors designed for producer gas flow each capable of handling about 1200 m3/hr in order to provide similar engine heat input at a lower conversion efficiency. Cold flow studies simulating the engine carburetion system results showed that the A/F was maintained in the range of 1.3 +/- 0.1 over the entire flow range. Initially, the gasification system was tested using woody biomass and the gas composition was found to be CO 15 +/- 1.5 % H-2 22 +/- 2% CH4 2.2 +/- 0.5 CO2 11.25 +/- 1.4 % and rest N-2, with the calorific value in the range of 5.0 MJ/kg. After initial trials on the engine to fine tune the control system and adjust various engine operating parameter a peak load of 800 kWe was achieved, while a stable operating conditions was found to be at 750 kWe which is nearly 85 % of the natural gas rating. The specific fuel consumption was found to be 0.9 kg of biomass per kWh.

Interplay of vector-like top partner multiplets in a realistic mixing set-up

The ATLAS and CMS collaborations at the LHC have performed analyses on the existing data sets, studying the case of one vector-like fermion or multiplet coupling to the standard model Yukawa sector. In the near future, with more data available, these experimental collaborations will start to investigate more realistic cases. The presence of more than one extra vector-like multiplet is indeed a common situation in many extensions of the standard model. The interplay of these vector-like multiplet between precision electroweak bounds, flavour and collider phenomenology is a important question in view of establishing bounds or for the discovery of physics beyond the standard model. In this work we study the phenomenological consequences of the presence of two vector-like multiplets. We analyse the constraints on such scenarios from tree-level data and oblique corrections for the case of mixing to each of the SM generations. In the present work, we limit to scenarios with two top-like partners and no mixing in the down-sector.

Timing Calculations for a General N-Level Dodecagonal Space Vector Structure Using Only Reference Phase Voltages

Multilevel inverters with dodecagonal (12-sided polygon) voltage space vector (SV) structures have advantages like extension of linear modulation range, elimination of fifth and seventh harmonics in phase voltages and currents for the full modulation range including extreme 12-step operation, reduced device voltage ratings, lesser dv/dt stresses on devices and motor phase windings resulting in lower EMI/EMC problems, and lower switching frequency-making it more suitable for high-power drive applications. This paper proposes a simple method to obtain pulsewidth modulation (PWM) timings for a dodecagonal voltage SV structure using only sampled reference voltages. In addition to this, a carrier-based method for obtaining the PWM timings for a general N-level dodecagonal structure is proposed in this paper for the first time. The algorithm outputs the triangle information and the PWM timing values which can be set as the compare values for any carrier-based hardware PWM module to obtain SV PWM like switching sequences. The proposed method eliminates the need for angle estimation, computation of modulation indices, and iterative search algorithms that are typical in multilevel dodecagonal SV systems. The proposed PWM scheme was implemented on a five-level dodecagonal SV structure. Exhaustive simulation and experimental results for steady-state and transient conditions are presented to validate the proposed method.

The Impact of Firm Level Contracting on Wage Levels and Inequality: Spain 1995-2002

This paper provides microeconomic evidence on the variation over time of the firm-specific wage premium in Spain from 1995 to 2002, and its impact on wage inequality. We make use of two waves of a detailed linked employer-employee data set. In addition, a new data set with financial information on firms is used for 2002 to control as flexibly as possible for differences in the performance of firms (aggregated at industry level). To our knowledge, there is no microeconomic evidence on the dynamics of the firm-specific wage premium for Spain or for any other country with a similar institutional setting. Our results suggest that there is a clear tendency towards centralization in the collective bargaining process in Spain over this seven-year period, that the firm-level contract wage premium undergoes a substantial decrease, particularly for women, and finally that the "centralization" observed in the collective bargaining process has resulted in a slight decrease in wage inequality.

The effect of firm-level contracts on the structure of wages: evidence from matched employer-employee data

Revised: 2006-11

Frame-level features conveying phonetic information for language and speaker recognition

150 p.

Increases in the relative abundance of mid-trophic level fishes concurrent with declines in apex predators in the subtropical North Pacific, 1996–2006

Catch rates for the 13 most abundant species caught in the deep-set Hawaii-based longline fishery over the past decade (1996–2006) provide evidence of a change among the top North Pacific subtropical predators. Catch rates for apex predators such as blue shark (Prionace glauca), bigeye (Thunnus obesus) and albacore (Thunnus alalunga) tunas, shortbill spearfish (Tetrapturus angustirostris), and striped marlin (Tetrapturus audax) declined by 3% to 9% per year and catch rates for four midtrophic species, mahimahi (Coryphaena hippurus), sickle pomfret (Taractichthys steindachneri), escolar (Lepidocybium flavobrunneum), and snake mackerel (Gempylus serpens), increased by 6% to 18% per year. The mean trophic level of the catch for these 13 species declined 5%, from 3.85 to 3.66. A shift in the ecosystem to an increase in midtrophic-level, fast-growing and short-lived species is indicated by the decline in apex predators in the catch (from 70% to 40%) and the increase in species with production to biomass values of 1.0 or larger in the catch (from 20% to 40%). This altered ecosystem may exhibit more temporal variation in response to climate variability.

Prioritizing county-level well-being: Moving toward assessment of Gulf Coast counties impacted by the Deepwater Horizon Industrial Disaster

To develop a portfolio of indicators and measures that could best measure changes in the social, economic, environmental and health dimensions of well-being in coastal counties we convened a group of experts March 8-9, 2011 in Charleston, SC, U.S.A. The region of interest was of the northern Gulf of Mexico, specifically, those coastal counties most impacted during the explosion and subsequent oil spill from the Macondo Prospect wellhead during the summer of 2010. Over the course of the two-day workshop participants moved through presentations and facilitated sessions to identify and prioritize potential indicators and measures deemed most valuable for capturing changes in well-being related to changes in or disruption of ecosystem services. The experts reached consensus on a list of indicators that are now being operationalized by NOAA researchers. The ultimate goal of this research project is to determine whether a meaningful set of social and economic indicators can be developed to document changes in well-being that occur as a result of changes in ecosystem services. The outcomes and outputs from the workshop that is the subject of this report helped us to identify high-quality indicators useful for measuring well-being.

Effect of salt on the level of histamine in preserved fish (Herring, Clupea harengus)

Histamine levels in batches of heavily salted (fish:salt ratio 4:1) herring (Clupea harengus) were monitored during ripening at 4°C and 25°C. The batches studied were prepared from both pre-spawning and post-spawning (spent) fish using new and used salt. Salt levels in the flesh, which reached 11 to 14% (wet weight basis) during the ripening period, were found to retard histamine formation. During normal spoilage of ice chilled fish, histamine levels had been reported to exceed 50mg/100g flesh as it approached the limit of edibility whilst, in the heavily salted fish, levels remained below 20mg/100g flesh throughout the ripening periods of 18 months for the 4°C batches and 3 months for the 25°C batches. This was the case when the samples were set up and the salt allowed penetrating the flesh at 4°C. When, however, the samples were set up and initially stored at ambient (10-15°C) temperature the histamine levels in the flesh rose above 20mg/100g before enough salt had penetrated to inhibit its generation. The gradual rise in levels which, nevertheless, occurred over the ripening periods followed significantly (5% level of significance) different trends, being greater in the batches prepared from pre-spawning than those from spent fish.

Phone-level pronunciation scoring and assessment for interactive language learning

This paper investigates a method of automatic pronunciation scoring for use in computer-assisted language learning (CALL) systems. The method utilizes a likelihood-based `Goodness of Pronunciation' (GOP) measure which is extended to include individual thresholds for each phone based on both averaged native confidence scores and on rejection statistics provided by human judges. Further improvements are obtained by incorporating models of the subject's native language and by augmenting the recognition networks to include expected pronunciation errors. The various GOP measures are assessed using a specially recorded database of non-native speakers which has been annotated to mark phone-level pronunciation errors. Since pronunciation assessment is highly subjective, a set of four performance measures has been designed, each of them measuring different aspects of how well computer-derived phone-level scores agree with human scores. These performance measures are used to cross-validate the reference annotations and to assess the basic GOP algorithm and its refinements. The experimental results suggest that a likelihood-based pronunciation scoring metric can achieve usable performance, especially after applying the various enhancements.

Automated 3D Structure Inference of Civil Infrastructure Using a Stereo Camera Set

The commercial far-range (>10m) infrastructure spatial data collection methods are not completely automated. They need significant amount of manual post-processing work and in some cases, the equipment costs are significant. This paper presents a method that is the first step of a stereo videogrammetric framework and holds the promise to address these issues. Under this method, video streams are initially collected from a calibrated set of two video cameras. For each pair of simultaneous video frames, visual feature points are detected and their spatial coordinates are then computed. The result, in the form of a sparse 3D point cloud, is the basis for the next steps in the framework (i.e., camera motion estimation and dense 3D reconstruction). A set of data, collected from an ongoing infrastructure project, is used to show the merits of the method. Comparison with existing tools is also shown, to indicate the performance differences of the proposed method in the level of automation and the accuracy of results.

Independence is elusive: set size effects on encoding precision in visual search.

Looking for a target in a visual scene becomes more difficult as the number of stimuli increases. In a signal detection theory view, this is due to the cumulative effect of noise in the encoding of the distractors, and potentially on top of that, to an increase of the noise (i.e., a decrease of precision) per stimulus with set size, reflecting divided attention. It has long been argued that human visual search behavior can be accounted for by the first factor alone. While such an account seems to be adequate for search tasks in which all distractors have the same, known feature value (i.e., are maximally predictable), we recently found a clear effect of set size on encoding precision when distractors are drawn from a uniform distribution (i.e., when they are maximally unpredictable). Here we interpolate between these two extreme cases to examine which of both conclusions holds more generally as distractor statistics are varied. In one experiment, we vary the level of distractor heterogeneity; in another we dissociate distractor homogeneity from predictability. In all conditions in both experiments, we found a strong decrease of precision with increasing set size, suggesting that precision being independent of set size is the exception rather than the rule.

Component level strategies for exploiting the lifespan of steel in products

Approximately 40% of annual demand for steel worldwide is used to replace products that have failed. With this percentage set to rise, extending the lifespan of steel in products presents a significant opportunity to reduce demand and thus decrease carbon dioxide emissions from steel production. This article presents a new, simplified framework with which to analyse product failure. When applied to the products that dominate steel use, this framework reveals that they are often replaced because a component/sub-assembly becomes degraded, inferior, unsuitable or worthless. In light of this, four products, which are representative of high steel content products in general, are analysed at the component level, determining steel mass and cost profiles over the lifespan of each product. The results show that the majority of the steel components are underexploited - still functioning when the product is discarded; in particular, the potential lifespan of the steel-rich structure is typically much greater than its actual lifespan. Twelve case studies, in which product or component life has been increased, are then presented. The resulting evidence is used to tailor life-extension strategies to each reason for product failure and to identify the economic motivations for implementing these strategies. The results suggest that a product template in which the long-lived structure accounts for a relatively high share of costs while short-lived components can be easily replaced (offering profit to the producer and enhanced utility to owners) encourages product life extension. © 2013 The Author.

Tuning the Energy Level of Organic Sensitizers for High-Performance Dye-Sensitized Solar Cells

Cost-effective organic sensitizers will play a pivotal role in the future large-scale production and application of dye-sensitized solar cells. Here we report two new organic D-pi-A dyes featuring electron-rich 3,4-ethylenedioxythiophene- and 2,2'-bis(3,4-ethylenedioxythiophene)-conjugated linkers, showing a remarkable red-shifting of photocurrent action spectra compared with their thiophene and bithiophene counterparts. On the basis of the 3-f{5'-[N,N-bis(9,9-dimethylfluorene-2-yl)phenyl]-2,2'-bis(3,4-ethylenedioxythiophene)-5-yl}2-cyanoacrylic acid dye, we have set a new efficiency record of 7.6% for solvent-free dye-sensitized solar cells based on metal-free organic sensitizers. Importantly, the cell exhibits an excellent stability, keeping over 92% of its initial efficiency after 1000 h accelerated tests under full sunlight soaking at 60 degrees C. This achievement will considerably encourage further design and exploration of metal-free organic dyes for higher performance dye-sensitized solar cells.