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1,4-Dihydropyridines (DHPs) represent the blockbuster class of L-type calcium channel blockers that have tremendous therapeutic value against cardiovascular conditions. Due to their abilities to additionally target other subtypes of calcium channels, DHPs are also considered promising molecules for the treatment of neurological and psychiatric disorders. Having been in the market for more than forty years, DHP is one of the most modified scaffolds for the development of novel molecules acting on calcium channels. Taking the chemical structures of approved DHPs into account, it is noteworthy that C-4 position is the least modified part of the ring system. Therefore, in the present study, we focused on this location and carried out various molecular modifications to obtain twelve potential calcium channel blockers with a DHP-based hexahydroquinoline scaffold (DA1-DA12). The whole-cell patch clamp technique applied to analyze the blocking ability of the synthesized compounds on both L- (Ca

Increasing land developments, unreasonable utilization of land, earthquakes, typhoons, and torrential rain often cause hillside disasters. Soil depth is a crucial parameter influencing the scale of shallow landslides and sustainable land use in hillside areas. This paper presents a statistical model, integrated with environmental factors, for estimating soil depth in a catchment area with complex topography. The study area selected was upstream of the Houlong River in Taiwan. The model was developed using multinomial logistic regression and environmental factors such as hill slope, hill aspect, elevation, topographical curvature, and the normalized difference vegetation index. The results were then compared with those obtained from previous models applying Ordinary Kriging, Regression Kriging, and topographical wetness index methods. A classification error matrix and the Kappa index were then employed to assess the various models. The results showed that, for the data set used for model establishment, the overall accuracy and Kappa index were 76.6% and 0.65, respectively, whereas for the data set used for verification, they were 70.5% and 0.57, respectively. By contrast, the Ordinary Kriging method yielded an overall accuracy and a Kappa index of 45.7% and 0.15, respectively; the Regression Kriging method yielded results of 46.7% and 0.16, respectively; and the topographical wetness index method yielded results of 30.5% and −0.05, respectively. The proposed model was therefore determined to be superior to the others in terms of soil depth estimation accuracy. The proposed model can predict soil depth on a regional scale and serve as a reliable tool that provides reference data for future research on land use and shallow landslides.

1. Four experiments were conducted to determine the 4th limiting amino acid (AA) in maize-soybean meal-based diets. 2. Deletion assay methodology was used to quantify performance and carcase trait responses to potential deficiencies in essential and conditionally essential AA caused by reductions in dietary crude protein of maize-soybean meal-based diets from 202.9 to 186.5 g/kg. 3. The deletion of Val, Phe and Gly + Pro resulted in negative effects on live performance and carcase traits for male broilers, whereas AA deletion only affected wing weights for females with no response on live performance. 4. Further experimentation could not duplicate a response to Phe or Pro in male broilers. 5. Valine was identified as the potential 4th limiting AA in maize-soybean meal-based diets and was not found to be co-limiting with Ile.

This paper presents the design and implementation of a controller for stair ascent and descent in a primarily-passive stance-controlled swing-assist (SCSA) prosthesis. The prosthesis and controller enable users to perform both step-over and step-to stair ascent and descent. The efficacy of the controller and SCSA prosthesis prototype in providing improved stair ambulation was tested on a unilateral transfemoral amputee in experiments that employed motion capture apparatus to compare joint kinematics with the SCSA prosthesis, relative to performing the same activity with a microprocessor-controlled daily-use passive prosthesis. Results suggest that the SCSA knee significantly decreases compensatory motion during stair activity when compared to the passive prosthesis.

SUMMARY Continuous genetic improvement of high yielding broiler strains necessitates reevaluation of amino acid requirements. The objective of this study was to evaluate the dIle requirement of Ross 708 x Ross YP male broilers from d 0 to 18. Experimental diets were created from a common deficient corn and soybean meal-based diet providing a dIle:dLys of 52%; after manufacturing, half was retained for the creation of the summit diet (82% dIle:dLys). The remaining 5 experimental diets ranged from 57 to 77% dIle:dLys and were blended proportions of deficient and summit dIle diets. A practical control diet (PRAC-CON; 67% dIle:dLys) was manufactured separately for verification of the blended control diet (50 deficient:50 summit blend; BLEND-CON; 67% dIle:dLys); all diets were subsequently pelleted/crumbled. On d of hatch, 2,400 male chicks were equally allocated to 96 pens (12 replications/treatment). All dIle:dLys ratios were estimated using quadratic regression (QR; 95% of the asymptote), as well as linear and quadratic broken line models (LBL; QBL). Performance data demonstrated that feeding higher than starter breed nutrient specifications, for broilers, at the time of this study (67% dIle:dLys) improved broiler performance from 0 to 18 d. After considering the estimated requirements produced by the multiple regression models for all measured variables (BW, BW gain, FCR, and CV of ending BW), these data suggest that the optimum starter dIle:dLys ratio for male Ross 708 × Ross YP broilers from 0 to 18 d, ranged from 63 to 74% dIle:dLys. Further research should evaluate dIle:dLys requirements of male Ross 708 × Ross YP broilers during the remaining grow-out phases.

Developing soft robots is an important research area for biomedical applications due to the advantages of soft robots over conventional hard or rigid-bodied robots, such as compliance, biocompatibility, and biomimicry. This project aims to design and prototype biomimetic soft origami robots that can navigate in transluminal applications. Starting from a single-bellows robot conceptualization, we characterized variations in actuation among prototypes made with materials of different thickness folded into a simple octagonal bellows design. The quad-bellows prototype utilized four-bellows units with the inclusion of a scope. This prototype achieved successful navigation of an 8 mm borescope placed between 9 mm bellows units through a lumen model. The soft robot was able to interact with the environment safely and adaptable for maneuvering through a compliant and torturous environment. These traits will allow the soft robot to be applicable in the field of colonoscopy, in which critical areas of improvement include minimizing patient discomfort and achieving skilled navigation of the colonoscope. The prototype could also be suitable for future applications that require in-pipe navigations around luminal environments.

Published literature elucidating dietary valine (Val) requirements for female broilers is limited and lacks data for the finisher phase. Three experiments (Exp) were conducted to determine the Val requirement for Cobb MX × 500 females during the grower (Exp 1; 14–28 days), finisher (Exp 2; 28–42 days), and withdraw periods (Exp 3; 42–56 days). Two additional Exp were conducted to determine the Val requirement for Cobb MV × 500 male (Exp 4) and female (Exp 5) broilers from 14–35 days. Corn-soybean meal diets were fed in the experimental period of all Exp to create Val dose response titration diets. Dietary titration levels of digestible Val to digestible Lys (Val/Lys) ratios were: 64–82 in Exp 1; 65–83 in Exp 2 and 3; and 57–92 in Exp 4 and 5. Body weight (BW) gain, feed intake, and feed conversion ratio were determined for each experimental period. At the conclusion of Exp 2 through 5, broilers were processed to determine carcass traits. Requirements were determined using regression analysis, considering the requirement to be 95 % of the quadratic response. No significant linear or quadratic responses were determined for Exp 1 through 3. In Exp 4 and 5, significant responses were observed for feed conversion ratio, but not processing yields. The lack of responsiveness in Exp 1 through 3 are likely due to an inadequate reduction in dietary Val to observe female quadratic responses. Valine requirements were determined to be 78 and 77 Val/Lys for males and females, respectively, based on feed conversion responses.

An experiment was conducted to evaluate the digestible tryptophan (Trp) requirement of laying hens from 22 to 34 wk of age. A total of 252 Hy-line W-36 laying hens were selected at 16 wk of age and allocated by weight (P = 0.90) to 7 dietary treatments resulting in 12 replicate cages of 3 birds for each treatment. A Trp-deficient basal diet was formulated using corn, corn gluten meal, and soybean meal for each of the 3 dietary phases and supplemented with synthetic L-Trp to provide 105, 119, 133, 147, 162, 176, and 190 mg digestible Trp on a daily basis over the experimental period. To adapt the hens to experimental diets, pullets were fed complete diets that contained increasing amounts of corn gluten meal. Hens received a controlled amount of feed daily based on feed intake expected under commercial conditions. Linear and quadratic brokenline, and quadratic polynomial models were used to estimate digestible Trp requirements based on hen-housed egg production (HHEP), egg mass (EM), and feed efficiency (FE). FE was calculated using EM and feed intake. Digestible Trp requirements were estimated to be 137, 183, and 192 mg/d for HHEP; 133, 180, and 183 for EM and 133, 177, and 173 for FE using linear brokenline, quadratic broken-line, and quadratic polynomial analysis, respectively. The quadratic broken line model in this experiment resulted in the best fit (R-2) for all parameters measured. Linear broken line estimates resulted in lower estimates that the other models, and HHEP resulted in higher estimated digestible Trp requirement than EM and FE. CJ America Inc, USA This experiment was financially supported by CJ America Inc, USA. Mention of a trade name, proprietary product, or specific equipment does not constitute a guarantee or warranty by Virginia Tech, and does not imply approval to the exclusion of other products that may be suitable. Special thanks to Hy-Line international for providing the chicks, Elanco for SE vaccine, CJ for amino acids (lysine, methionine, tryptophan, isoleucine, and threonine) . The authors gratefully acknowledge the assistance of Dale Shumate, Kolby Foltz, Alicia Arne-son, Becky Tran, Alyssa Lyons, Siobhan Boothe (Virginia Tech, Blacksburg VA) for animal care and feed mixing assistance.

Data pertaining to the branched-chain amino acids (BCAA) are of particular importance due to the positioning of valine (Val) and isoleucine (Ile) as limiting amino acids (AA) in conventional diets. Similarly, current research evaluating their potential interaction is sparse. Therefore, two experiments were conducted using Box-Behnken design (BBD) to determine performance and carcass responses to BCAA and glycine (Gly) supplementation in male broilers from 15–34 days (Experiment 1) and 15–35 days (Experiment 2). In Experiment 1, 13 experimental diets were formulated to contain various levels of digestible BCAA supplementation based on BBD. Inclusion levels for the BCAA were based on ratios to digestible lysine (Lys) and included: 65, 75, and 85 for digestible Val; 58, 66, and 74 for digestible Ile; and 110, 130, and 150 for digestible leucine (Leu). Diets for Experiment 2 were formulated in a similar manner and design, but total glycine + serine (Gly + Ser) inclusions were substituted for Leu. Inclusion levels were the same for Val and Ile as in Experiment 1 and ratios to digestible Lys of 131, 151, and 171 for total Gly + Ser. Fifteen-hundred and sixty male broilers were distributed across 78 pens and randomly assigned to 13 experimental diets in each Experiment. Body weight (BW) gain, feed intake, and feed conversion ratio (FCR) were determined for the experimental grower period in both Experiments. On day 35 (Experiment 1) or 36 (Experiment 2), six birds per pen were processed for the evaluation of carcass traits. Data were analyzed for linear, quadratic, and interactive effects. In Experiment 1, increased Leu inclusion linearly increased (P

Compression ignition of hydrogen engines with a homogeneous pre-mixture is a promising method to enhance the thermal efficiency as well as to reduce unique NO x exhausted from the engine due to spatial reaction of the mixture. However, hydrogen gas has a relatively high self-ignition temperature. Therefore, compression ignition for a neat hydrogen-air pre-mixture is considered impossible to achieve without additives. Research on this has not yet been attempted for this reason. In order to initiate the development of a compression ignition engine operated under a neat hydrogen-air pre-mixture and room temperature conditions, this paper evaluates the feasibility of compression ignition by using a high compression ratio and analyzes the characteristics such as abnormal combustion and operation region. It is found that the neat hydrogen-air pre-mixture is self-ignited at a high compression ratio without any assisting method in room temperature, thus refuting the preconception that compression ignition of hydrogen engine is impossible. A compression ratio of at least around e = 32 is required to self-ignite the engine under cold start and decreases to e = 26 with an increased equivalence ratio under firing conditions. The minimum equivalence ratio for compression ignition is in the region of ϕ = 0.11–0.22 of an ultra lean mixture for all operating conditions. The operation region at each compression ratio is extremely narrow (around ϕ = 0.04–0.06) due to knocking and backfire resulting from the high compression ratio.

In order to grasp the possibility of achieving backfire control, high performance, and low emission in a hydrogen-fueled engine using external mixture injection, the effects of increasing the boosting pressure were analyzed in terms of backfire occurrence, combustion characteristics, and performance enhancement. As the results, it was found that backfire could be successfully controlled if the IVO time was retarded to or beyond TDC regardless of the amount of supplied energy. Also, these results show that the achievement of high power (equal to that of a gasoline engine), high efficiency (around 36.7%) and low emission (NOx of less than 16 ppm) without backfire in a hydrogen-fueled engine is possible with a boosting pressure of 1.5 bar at an equivalence ratio of Φ = 0.35 or lower.

Nocturnal cold air pools, which frequently form in complex terrain under anticyclonic systems, are a hazard to flowering buds of temperate fruit trees, but the spatial resolution to anticipate them exceeds the current weather forecast scale. To supplement the insufficient spatial resolution of official minimum temperature forecasts, a spatial interpolation scheme was developed by incorporating local geographic potential for cold air accumulation. Air temperature was measured at 10-min intervals at eight locations within a 2.1 km × 2.1 km hilly orchard area in South Korea from September 2002 to August 2003. Minimum temperature data for suspected radiative cooling nights were collected, and deviations from estimations by a conventional spatial interpolation were calculated. A digital elevation model with a 10 m cell size was used to calculate the cold air accumulation at eight locations. Zonal averages of the cold air accumulation were computed for each location by increasing the cell radius from 1 to 10. Temperature deviations were regressed to a common logarithm of the smoothed averages of cold air accumulation to derive a linear relationship between the local temperature deviation and the site topography. The highest coefficient of determination was found at a cell radius of 5, which corresponds to an approximately 1 ha boundary surrounding the point of interest. Nocturnal temperature profiles were observed and the inversion cap height was determined using a tethered balloon system. Empirical equations describing the potential effects of cold air accumulation and of the inversion profile on minimum temperature were combined with a conventional lapse rate-corrected inverse distance weighting interpolation scheme. This new interpolation scheme was successfully validated with an independent data set, showing a strong feasibility for development of a site-specific frost warning system for mountainous areas.

Loci associated with noncoding RNAs have important roles in X-chromosome inactivation (XCI), the dosage compensation mechanism by which one of two X chromosomes in female cells becomes transcriptionally silenced. The Xs start out as epigenetically equivalent chromosomes, but XCI requires a cell to treat two identical X chromosomes in completely different ways: One X chromosome must remain transcriptionally active while the other becomes repressed. In the embryo of eutherian mammals, the choice to inactivate the maternal or paternal X chromosome is random. The fact that the Xs always adopt opposite fates hints at the existence of a trans-sensing mechanism to ensure the mutually exclusive silencing of one of the two Xs. This paper highlights recent evidence supporting a model for mutually exclusive choice that involves homologous chromosome pairing and the placement of asymmetric chromatin marks on the two Xs.

Summary The stone curlew (Burhinus oedicnemus) is one of the rarest breeding birds in the UK with an estimated breeding population of under 300 pairs. In the UK a marked decrease in the numbers has occurred, mainly due to habitat change or loss, resulting in the bird no longer breeding on many of its traditional nesting grounds. Using a Geographic Information System we define potential breeding areas in a landscape known to historically support a stone curlew breeding population. With an understanding of the birds’ abiotic nesting requirements, we model optimal locations for potential breeding sites for the bird, using known historical breeding data to verify the selection process. In total, we identify 424 parcels of land (2866 hectares) providing the critical habitat requirements for the stone curlew in the overall study area, 323 (1958 hectares) of which correspond with the known historic breeding distribution of the bird. We conclude that the modelling approach outlined is valuable in the identification of potential breeding sites for the stone curlew and that the model could be operated in tandem with agri-environment payments such as those offered within the Countryside Stewardship Scheme, in an attempt to focus these payments upon areas which will deliver maximum nature conservation potential. In addition we suggest that, subject to appropriate data availability, the approach outlined be applied to other species of high-conservation concern, particularly those which are currently under consideration for introduction or re-introduction programmes.

The regulation of epigenetic phenomena by elements encoding antisense RNA’s is one of the most rapidly emerging themes in mammalian gene expression. Such regulation is epitomized by X chromosome inactivation (XCI) and autosomal imprinting. In XCI, Tsix serves as an antisense regulator of Xist, the silencer element for XCI which itself makes a non-coding transcript. Numerous antisense transcripts have also been discovered in autosomally imprinted loci, including the Igf2r/Air locus, the Prader-Willi/Angelman Syndrome (PWS/AS) locus, and the Beckwith-Wiedemann Syndrome (BWS) locus. How these antisense elements regulate XCI and imprinting remains unsolved. However, various structural and functional similarities among them imply the possibility of shared mechanism. Among the most interesting are the antagonistic relationship between sense and antisense loci and the initiation of antisense transcripts within imprinting centers. This article reviews the latest developments in antisense regulation in XCI and autosomal imprinting and speculates on molecular means by which antisense genes can regulate silencing in mammals.

The Witsenhausens counterexample (1968) is a difficult nonconvex functional optimization problem which has been outstanding for more than 30 years. Considerable amount of literature has been accumulated, but optimal solutions remain elusive. In this paper, we develop a framework that allows one to gain additional new insights to the properties of a better solution for a benchmark instance. Through our approach, we are able to zero in on a solution that is 13% better than the previously known best solution, and more than 54% better than previous results obtained by other authors. More importantly, we demonstrate that our approach, called hierarchical search, can be useful in general optimization problems.

This paper describes the SOA-based system architecture and human-in-the-loop evaluation of the Tower Information Display System (TIDS). TIDS is a cornerstone of the Staffed NextGen Tower (SNT) concept, which is an important element in the Joint Planning and Development Officepsilas (JPDOpsilas) Next Generation Air Transportation System (NextGen) Concept of Operations.

This paper describes the system architecture of the Tower Information Display System (TIDS). TIDS is the cornerstone of the Staffed NextGen Tower (SNT) concept, which addresses the important equivalent-visual-operations capability (without building a costly physical tower) identified by the NextGen roadmap. TIDS was used for a feasibility analysis at the Airport Facilities Terminal Integration Laboratory (AFTIL) facility at the FAA Technical Center, Atlantic City, NJ, in August 2007. TIDS was designed and built to provide a large screen display of current terminal traffic and a touch-screen display that implements an electronic flight strip operation. The system integrates the information from all data sources, including the AFTIL facility's High Level Architecture (HLA) based simulator, provides real-time value-added processing and gives air traffic controllers the information necessary for safe and efficient airport operations. All data sources are processed and displayed in real-time. The system also allows for multiple real-time displays whose views are individually configurable to the appropriate controller functions needed. This paper also explores the designs of future versions of TIDS that are in development following the feasibility study. These TIDS systems integrate new data sources, such as Airport Surface Detection Equipment, Model X (ASDE-X) CAT11, which provides aircraft track data derived from multi- lateration and primary radar. They also provide Air Traffic Control Towers with a NextGen extensible design for data distribution for the myriad of data sources of terminal information. The real-time processing capability will also allow for implementation and display of decision-support algorithms.

This paper describes a human-in-the-loop simulation and evaluation of the Tower Information Display System (TIDS) that was conducted in August 2007. The goal was to determine whether radar-like traffic surveillance displays could be used to control airport traffic. TIDS workstations were developed for ground and local controller positions and were integrated in a tower cab simulator. Retired controllers with prior TRACON and Airport Surface Detection Equipment Model X (ASDE-X) were recruited for participation in the simulation. The simulated airport facility was patterned after Tampa International Airport (TPA). Test scenarios were developed to allow for comparison of the performance of TIDS against the out-the-window (OTW) viewing environment, two based on visual flight rules (VFR) and two based on instrument flight rules (IFR). The results showed comparable operational efficiency between the TIDS and OTW conditions in VFR Day scenarios. Efficiency was reduced for the OTW night condition. Efficiency for the OTW condition during IFR operations was reduced, in comparison to TIDS, when visibility was most restrictive. Workload estimates showed a consistent comfortable workload across operational conditions for the TIDS. Similar estimates varied, by position (i.e., ground or local controller) in the OTW conditions depending on operational condition. Analysis of pilot-controller communication provides support for the efficiency and workload results. Ratings by controllers showed a strong preference for the use of TIDS after the completion of all scenarios. A discussion of the results is provided along with consideration of the limitations of the study and possible future development.

Background. Nebulized amphotericin B deoxycholate (AmBd) has been used to prevent invasive pulmonary aspergillosis after lung transplantation. Methods. In this retrospective study we compared the safety and tolerability of nebulized AmBd and nebulized liposomal amphotericin B (L-AmB) in 38 consecutive lung transplant recipients. Progress notes, medication administration records, microbiology, and pulmonary function reports were reviewed. Histologic sections from lung tissue were examined. Plasma amphotericin B levels were measured. Results. A total of 1206 doses of AmBd and 1149 doses of L-AmB were administered. Eighteen patients received AmBd only, 11 received L-AmB only, and 9 received the medications sequentially. The total number of complaints vs. the number of doses administered was 1.0% for AmBd-treated patients and 1.2% for L-AmB-treated patients. No differences were observed between the treatment groups on lung biopsy specimens. Plasma amphotericin B levels were

With today's highly coupled flight schedules, any disturbance to the schedule of a flight could have unforeseen impact on the downstream connecting flights. Thus, it is crucial to be able to minimize the effects of the various potential disturbances. Deicing is one such disturbance. During the winter months, deicing procedures associated with snowstorms can cause unexpected delays in the flight schedules. Due to the nonlinear nature of the total time associated with the deicing process (which we call the 'total system time', and includes time of waiting and deicing), it is difficult to predict accurately when an aircraft will complete the deicing process. It is difficult, therefore, to predict how the deicing process will influence the subsequent chain of events. In this paper, a queuing model for the deicing process was developed to assist dispatchers to have a more accurate prediction of the completion time for deicing. Moreover, the two major deicing pads at Detroit Metropolitan Wayne County Airport (DTW) were modeled. Through Monte Carlo simulation, estimates of the total system time for the two deicing pads were derived, along with the corresponding 95% confidence intervals. The simulation results were compared to the historical data in the dynamic runway occupancy measurement system (DROMS), which contains DTW surface surveillance and other aviation related data since October 2002. A decision support tool (DST) was developed, displaying the time estimates. With this deicing DST, airline dispatchers or air traffic controllers can send the next outbound flight to the deicing pad with the least amount of total system time, and, therefore, reduce potential disturbances associated with deicing.

This chapter discusses chiral bioanalysis and the developments in the field, focusing mainly on the techniques used in high-performance liquid chromatography (HPLC) and providing a brief introduction to bioanalytic applications in gas chromatography (GC), capillary electrophoresis (CE), and supercritical fluid chromatography (SFC). It includes a review of the principle types of chiral stationary phases (CSPs), their mechanism of action, typical mobile phase choices, and applicability. A method of choice must be sufficiently robust to withstand large numbers of biologic samples. It must be capable of method transfer to other research laboratories such as a contract laboratory facility, as the drug development process progresses. New chemical entity submissions to the FDA and other organizations around the world also need to incorporate validated data using freely available methods. Direct HPLC methods (rather than the use of achiral stationary phases with chiral additives or derivatization of the solute with chiral reagents) are generally preferred in pharmaceutical research. It is mainly for these reasons that HPLC (and in particular HPLC–mass spectrometry, MS–MS) is a main focus of this chapter. It is also for these reasons that the chapter only presents commercially available and proven technologies.

Some of the important characteristics required for field-oriented AC drives are a fast run-stop capability and good speed regulation regardless of sudden load change. The properties of a PDF (pseudo derivative feedback) controller are analyzed, and some key features are described compared with the PI (proportional plus integral) controller. In order to get robust speed control performance against variation of load inertia, a load disturbance observer is also applied to the PDF controller, and experimental results are presented. Nominal load inertia is measured by using a digital-signal-processor-based inverter self-tuning function, and parameters needed for the controller can be calculated to get good speed control performance. >

Finding a function that minimizes a functional is common problem, e.g., determining the feedback control law for a system. However, it remains to be a challenge due to the large and structureless search space. In this paper, we present a search algorithm, granular optimization, to deal with this type of problems under some mild constraints. The algorithm is tested on two different problems. One of them is the well-known Witsenhausen counterexample (1968). On the counterexample, the result from our automated algorithm comes close to the currently known best solution, which involves much human intervention. This shows the potential usefulness of the algorithm in more general problems.