The binding conformation of Taxol in β-tubulin: A model based on electron crystallographic density

The chemotherapeutic drug Taxol is known to interact within a specific site on β-tubulin. Although the general location of the site has been defined by photoaffinity labeling and electron crystallography, the original data were insufficient to make an absolute determination of the bound conformation. We have now correlated the crystallographic density with analysis of Taxol conformations and have found the unique solution to be a T-shaped Taxol structure. This T-shaped or butterfly structure is optimized within the β-tubulin site and exhibits functional similarity to a portion of the B9-B10 loop in the α-tubulin subunit. The model provides structural rationalization for a sizeable body of Taxol structure–activity relationship data, including binding affinity, photoaffinity labeling, and acquired mutation in human cancer cells.

Construction of a Sustainable City Park in Ruddle, WV: A Model for Sustainable Park Design in Humid Climates

Three sustainable projects were studied under a sustainable park model for humid climates to determine where their costs lie in terms of installation, maintenance or both. These projects included the use of solar lighting to replace every configuration of conventional lighting, inclusion of a water garden/bog filter and Riparian Buffer System for the purposes of filtering sediments and nutrients out of runoff to prevent contaminated runoff from reaching the river that was adjacent to the park model location and construction of a LEED-inspired building to serve as the concession stand/restrooms building. The aggregate cost savings of instituting all three projects over ten years was $74,120 and the entire project paid itself off in approximately four years.

Building International CSR on Solid Foundations: Location and Network Aspects of Nonmarket Environments in Europe and Non-Europe Markets. ACES Working Papers, 2011

Multinational companies' (MNCs) corporate social responsibility (CSR) programs frequently comprise a portfolio of disconnected country-level programs or, alternatively, consist of blanket corporate policies that apply in the same way across the geographies where the company operates. Yet, the international nonmarket environment in which CSR programs operate is neither a completely fragmented nor a perfectly homogeneous one. Building on the concept of stakeholder-issue-networks, we develop a model that explicitly takes into consideration the role of geography in the characterization of a firm's nonmarket environment. This allows us to develop a taxonomy of nonmarket environments on the basis of their geographic spread and their degree of cross-border connectedness. We then explore the strategic and organizational implications that different ideal types of (cross-border) nonmarket environments have for the development of international CSR policies.

Age model of sediment core V20-120 (Table 2)

Time series analyses of atmospheric and oceanic variables in a late Pleistocene record from the northwest Pacific show the complex relationship of the response of various segments of the climate system to changes in the earth's orbit. Most variance spectra of time series from this subarctic record contain frequency peaks with periods corresponding to at least one of the major orbital components of eccentricity, obliquity, or precession. Although the radiolarian faunal (water mass) assemblages have prominent spectral peaks with 41,000-year periods which are coherent with obliquity at this frequency, only the Transitional faunal assemblage contains variance focused at a frequency corresponding to the 100,000-year period of eccentricity. Three of these faunal time series also show variance concentrated at a frequency with a 20,000-year period. These three time series are not coherent at a 20,000-year frequency with either of the dominant spectral peaks of precession. They are coherent, however, with variations in the second harmonic of the obliquity cycle. Changes in obliquity apparently affect siliceous faunal abundances in the northwest Pacific region of this high-latitude site more than variations in eccentricity or precession. Maxima in the time series of quartz abundance occur during low values of eccentricity and high glacial ice volume. Because atmospheric winds serve as the major source of supply of quartz to the sediments at this site, these high quartz values reflect increased aridity at the source region. Except for short periods during interglacials, the characteristics of the surface waters in this region of the subarctic Pacific during much of the last 460,000 years were similar to those which exist today in the Sea of Okhotsk. The spectrum of winter sea surface temperature estimates, derived from siliceous microfaunal abundances, contains dominant frequency peaks at periods of 100,000, 41,000, and 23,000 years which are coherent with eccentricity, obliquity, and precession, respectively. Based upon the relationship of the Subarctic Front with the dominance of specific faunal asemblages, the front was positioned south of its present-day location throughout much of the late Pleistocene.

Age model and ostracod countings from IODP Site 306-U1314

We present a detailed study of glacial/interglacial deep sea benthic ostracod assemblage variability at IODP Site U1314 (subpolar North Atlantic) in relation to the history of ice-rafting events and changes in deep ocean circulation over the past 170 ky. Our records of ostracod diversity, abundance and dissolution and sediment properties (IRD and CaCO3) show an excellent correspondence to high amplitude orbital and millennial variability observed in the climate records (d13C and d18O) from neighboring deep water sites, suggesting that the benthic meiofauna fluctuates synchronously with the prevailing oceanographic conditions (surface ocean conditions, deep ocean circulation and water temperature and food flux). Krithe (dominant), Argilloecia and Cytheropteron are the most abundant and diverse genera in association with Rockallia enigmatica. Three ostracod assemblages are recognized. The genera Pennyella, Argilloecia, Pelecocythere, Ambocythere, Pseudobosquetina, Bradleya and Nannocythere are associated with interglacials and interstadials, and possibly reflect increased flux of food to the sediments and more vigorous NADW formation. A transitional assemblage composed of species of Cytheropteron, Xestoleberis and Eucythere is restricted to climatic transitions and indicate moderate environmental conditions and seasonal productivity. A glacial/stadial assemblage is characterized by a temporal predominance of either intermediate-depth and shallow water Arctic/subarctic species (belonging to Cytheropteron, Polycope, Pedicythere, Swainocythere, Cluthia, Heterocyprideis, Elofsonella and Finmarchinella) or abyssal North Atlantic ostracods (Bythocythere, Dutoitella, Bathycythere and Bythocypris). The influx of high latitude taxa can be partially explained by ice-rafting, but may also represent a shift of the location of intermediate and deep water convection to the area south of Iceland. Therefore the combination of species characteristic of different watermasses during glacials may reflect shifts in the influence of high nutrient southern source water (e.g. AABW) vs. low nutrient GNAIW during glacials.

High velocity jet noise source location and reduction.

"February 22, 1977."

Movement trajectories in the presence of a distracting stimulus: Evidence for a response activation model of selective reaching

Consistent with action-based theories of attention, the presence of a nontarget stimulus in the environment has been shown to alter the characteristics of goal-directed movements. Specifically, it has been reported that movement trajectories veer away from (Howard & Tipper, 1997) or towards (Welsh, Elliott, & Weeks, 1999) the location of a nontarget stimulus. The purpose of the experiments reported in this paper was to test a response activation model of selective reaching conceived to account for these variable results. In agreement with the model, the trajectory changes in the movements appear to be determined by the activation levels of each competing response at the moment of response initiation. The results of the present work, as well as those of previous studies, are discussed within the framework of the model of response activation.

Functional-structural plant modelling using a combination of architectural analysis, L-systems and a canonical model of function

This paper presents a new method for producing a functional-structural plant model that simulates response to different growth conditions, yet does not require detailed knowledge of underlying physiology. The example used to present this method is the modelling of the mountain birch tree. This new functional-structural modelling approach is based on linking an L-system representation of the dynamic structure of the plant with a canonical mathematical model of plant function. Growth indicated by the canonical model is allocated to the structural model according to probabilistic growth rules, such as rules for the placement and length of new shoots, which were derived from an analysis of architectural data. The main advantage of the approach is that it is relatively simple compared to the prevalent process-based functional-structural plant models and does not require a detailed understanding of underlying physiological processes, yet it is able to capture important aspects of plant function and adaptability, unlike simple empirical models. This approach, combining canonical modelling, architectural analysis and L-systems, thus fills the important role of providing an intermediate level of abstraction between the two extremes of deeply mechanistic process-based modelling and purely empirical modelling. We also investigated the relative importance of various aspects of this integrated modelling approach by analysing the sensitivity of the standard birch model to a number of variations in its parameters, functions and algorithms. The results show that using light as the sole factor determining the structural location of new growth gives satisfactory results. Including the influence of additional regulating factors made little difference to global characteristics of the emergent architecture. Changing the form of the probability functions and using alternative methods for choosing the sites of new growth also had little effect. (c) 2004 Elsevier B.V. All rights reserved.

A scaleless data model for direct and progressive spatial query processing

A progressive spatial query retrieves spatial data based on previous queries (e.g., to fetch data in a more restricted area with higher resolution). A direct query, on the other side, is defined as an isolated window query. A multi-resolution spatial database system should support both progressive queries and traditional direct queries. It is conceptually challenging to support both types of query at the same time, as direct queries favour location-based data clustering, whereas progressive queries require fragmented data clustered by resolutions. Two new scaleless data structures are proposed in this paper. Experimental results using both synthetic and real world datasets demonstrate that the query processing time based on the new multiresolution approaches is comparable and often better than multi-representation data structures for both types of queries.

Local industrial systems and the location of FDI in Italy

This article investigates the determinants of foreign direct investment (FDI)location across Italian provinces. Specifically it examines the relationship between industry- specific local industrial systems and the location of inward FDI. This extends previous analysis beyond the mere density of activity, to illustrate the importance of the specific nature of agglomerations in attracting inward investment. The article develops a model of FDI location choice using a unique FDI database stratified by industry and province. The results also suggest that the importance of agglomeration differs between industries, and offers some explanation for this.

Optimization of facility location-allocation problem in customer-driven supply chain

This paper develops and applies an integrated multiple criteria decision making approach to optimize the facility location-allocation problem in the contemporary customer-driven supply chain. Unlike the traditional optimization techniques, the proposed approach, combining the analytic hierarchy process (AHP) and the goal programming (GP) model, considers both quantitative and qualitative factors, and also aims at maximizing the benefits of deliverer and customers. In the integrated approach, the AHP is used first to determine the relative importance weightings or priorities of alternative locations with respect to both deliverer oriented and customer oriented criteria. Then, the GP model, incorporating the constraints of system, resource, and AHP priority is formulated to select the best locations for setting up the warehouses without exceeding the limited available resources. In this paper, a real case study is used to demonstrate how the integrated approach can be applied to deal with the facility location-allocation problem, and it is proved that the integrated approach outperforms the traditional costbased approach.

A general linear model for MEG beamformer imaging

A new general linear model (GLM) beamformer method is described for processing magnetoencephalography (MEG) data. A standard nonlinear beamformer is used to determine the time course of neuronal activation for each point in a predefined source space. A Hilbert transform gives the envelope of oscillatory activity at each location in any chosen frequency band (not necessary in the case of sustained (DC) fields), enabling the general linear model to be applied and a volumetric T statistic image to be determined. The new method is illustrated by a two-source simulation (sustained field and 20 Hz) and is shown to provide accurate localization. The method is also shown to locate accurately the increasing and decreasing gamma activities to the temporal and frontal lobes, respectively, in the case of a scintillating scotoma. The new method brings the advantages of the general linear model to the analysis of MEG data and should prove useful for the localization of changing patterns of activity across all frequency ranges including DC (sustained fields). © 2004 Elsevier Inc. All rights reserved.

Damage location in structures by monitoring vibration characteristics

The aim of this work was to investigate the feasibility of detecting and locating damage in large frame structures where visual inspection would be difficult or impossible. This method is based on a vibration technique for non-destructively assessing the integrity of structures by using measurements of changes in the natural frequencies. Such measurements can be made at a single point in the structure. The method requires that initially a comprehensive theoretical vibration analysis of the structure is undertaken and from it predictions are made of changes in dynamic characteristics that will occur if each member of the structure is damaged in turn. The natural frequencies of the undamaged structure are measured, and then routinely remeasured at intervals . If a change in the natural frequencies is detected a statistical method. is used to make the best match between the measured changes in frequency and the family of theoretical predictions. This predicts the most likely damage site. The theoretical analysis was based on the finite element method. Many structures were extensively studied and a computer model was used to simulate the effect of the extent and location of the damage on natural frequencies. Only one such analysis is required for each structure to be investigated. The experimental study was conducted on small structures In the laboratory. Frequency changes were found from inertance measurements on various plane and space frames. The computational requirements of the location analysis are small and a desk-top micro computer was used. Results of this work showed that the method was successful in detecting and locating damage in the test structures.

A two-stage model of orientation integration for Battenberg-modulated micropatterns

The visual system pools information from local samples to calculate textural properties. We used a novel stimulus to investigate how signals are combined to improve estimates of global orientation. Stimuli were 29 × 29 element arrays of 4 c/deg log Gabors, spaced 1° apart. A proportion of these elements had a coherent orientation (horizontal/vertical) with the remainder assigned random orientations. The observer's task was to identify the global orientation. The spatial configuration of the signal was modulated by a checkerboard pattern of square checks containing potential signal elements. The other locations contained either randomly oriented elements (''noise check'') or were blank (''blank check''). The distribution of signal elements was manipulated by varying the size and location of the checks within a fixed-diameter stimulus. An ideal detector would only pool responses from potential signal elements. Humans did this for medium check sizes and for large check sizes when a signal was presented in the fovea. For small check sizes, however, the pooling occurred indiscriminately over relevant and irrelevant locations. For these check sizes, thresholds for the noise check and blank check conditions were similar, suggesting that the limiting noise is not induced by the response to the noise elements. The results are described by a model that filters the stimulus at the potential target orientations and then combines the signals over space in two stages. The first is a mandatory integration of local signals over a fixed area, limited by internal noise at each location. The second is a taskdependent combination of the outputs from the first stage. © 2014 ARVO.

A New Charging and Billing Model and Architecture for the Ubiquitous Consumer Wireless World

In a Ubiquitous Consumer Wireless World (UCWW) environment the provision, administration and management of the authentication, authorization and accounting (AAA) policies and business services are provided by third-party AAA service providers (3P-AAA-SPs) who are independent of the wireless access network providers (ANPs). In this environment the consumer can freely choose any suitable ANP, based on his/her own preferences. This new AAA infrastructural arrangement necessitates assessing the impact and re-thinking the design, structure and location of ‘charging and billing’ (C&B) functions and services. This paper addresses C&B issues in UCWW, proposing potential architectural solutions for C&B realization. Implementation approaches of these novel solutions together with a software testbed for validation and performance evaluation are addressed.