New Means (new + mean)

Distribution by Scientific Domains

Selected Abstracts

New Means for Political Empowerment in the Asian Pacific American Community

Steven Hill
First page of article [source]

Highly efficient gene transfer into hepatocyte-like HepaRG cells: New means for drug metabolism and toxicity studies

Veronique Laurent
Abstract HepaRG progenitor cells are capable of differentiating into hepatocyte-like cells that express a large set of liver-specific functions. These cells, however, only express small amounts of an important cytochrome P450, the CYP2E1, which limits their use for toxicological studies of drugs metabolized by this pathway. Our aim was to establish an efficient transfection protocol to increase CYP2E1 expression in HepaRG cells. Transfection protocols of the green fluorescent protein (GFP) reporter gene were evaluated using electroporation and cationic lipids belonging to the lipophosphonates, lipophosphoramidates and lipids derived from glycine betaine. Following optimization of the charge ratios, plasmid DNA and formulations with neutral co-lipids, the lipophosphoramidate compounds KLN47 and BSV10, allowed expression of the GFP in ,50% of adherent progenitor HepaRG cells, while electroporation targeted GFP expression in ,85% of both progenitor and differentiated cells in suspension. Transient enforced expression of active CYP2E1 was also achieved in progenitors and/or differentiated HepaRG cells using the electroporation and the lipophosphoramidate compound BSV10. Importantly, in electroporated cells, CYP2E1 expression level was correlated with a significant increase in CYP2E1-specific enzymatic activity, which opens new perspectives for this CYP-dependent drug metabolism and toxicity studies using HepaRG cells. [source]

Diabetes management in the new millennium using insulin pump therapy

Bruce W. Bode
Abstract Current goals of therapy of type 1 and 2 diabetes are to achieve near normal glycemia, minimize the risk of severe hypoglycemia, limit excessive weight gain, improve quality of life and delay or prevent late vascular complications. As discussed in this review, insulin pump or continuous subcutaneous insulin infusion (CSII) therapy provides a treatment option that can dramatically aid in achieving all of these goals. In comparison to multiple daily injections (MDI), CSII uses only rapid-acting insulin, provides greater flexibility in timing of meals and snacks, has programmable basal rates to optimize overnight glycemic control, can reduce the risk of exercise-induced hypoglycemia, and enhances patients' ability to control their own diabetes. Most important, in adults and adolescents with type 1 diabetes, CSII has been shown to lower HbA1c levels, reduce the frequency of severe hypoglycemia and limit excessive weight gain versus MDI without increasing the risk of diabetic ketoacidosis. Similarly positive results are being seen with CSII in adults with type 2 diabetes. The effectiveness of CSII and improvements in pump technology have fueled a dramatic increase in the use of this therapy. Practical guidelines are presented for selection of patients, initiation of treatment, patient education, follow-up assessments and troubleshooting. The recent introduction of methods for continuous glucose monitoring provides a new means to optimize the basal and bolus capabilities of CSII and offers the hope of the development of a feedback-controlled artificial pancreas. Copyright © 2002 John Wiley & Sons, Ltd. [source]

Short-term erosion rates from a 7Be inventory balance

Christopher G. Wilson
Abstract Detailed soil erosion studies bene,t from the ability to quantify the magnitude of erosion over time scales appropriate to the process. An inventory balance for 7Be was used to calculate sediment erosion in a 30·73 m2 plot during a series of runoff-producing thunderstorms occurring over three days at the Deep Loess Research Station in Treynor, Iowa, USA. The inventory balance included determination of the pre- and post-storm 7Be inventories in the soil, the atmospheric in,ux of 7Be during the event, and pro,les of the 7Be activity in the soil following the atmospheric deposition. The erosion calculated in the plot using the 7Be inventory balance was 0·058 g cm,2, which is 23 per cent of the annual average erosion determined using 137Cs inventories. The calculated erosion from the mass balance is similar to the 0·059 g cm,2 of erosion estimated from the amount of sediment collected at the outlet of the 6 ha ,eld during the study period and the delivery ratio (0·64). The inventory balance of 7Be provides a new means for evaluating soil erosion over the time period most relevant to quantifying the prediction of erosion from runoff. Copyright © 2003 John Wiley & Sons, Ltd. [source]

Is Privately-provided Electronic Money Next?

Catherine England
To survive, any new electronic money will need to provide some advantage to its users, such as lower transaction costs, increased privacy, a greater ability to avoid taxes, or a more stable value than its government-provided competitors. Any successful new money will have to overcome substantial barriers to entry, however. These barriers to entry occur primarily in the form of the costs of switching to a different means of payment and require an understanding of the role played by ,network economics.' Unless a substantial number of the individuals and businesses with whom a person trades use the same money, any new means of payment will have little value. A temptation facing government regulators will be to extend and expand regulations to apply to new means of payment and forms of money. A more productive role of governments is to attempt to protect their own money-creation franchises by minimising the advantages offered by privately-provided alternatives. Governments should enforce contracts and punish fraud while remaining vigilant with respect to inflation, keep tax rates low and protect the privacy of their citizens. [source]

Anti-adhesion therapy of bacterial diseases: prospects and problems

Itzhak Ofek
Abstract The alarming increase in drug-resistant bacteria makes a search for novel means of fighting bacterial infections imperative. An attractive approach is the use of agents that interfere with the ability of the bacteria to adhere to tissues of the host, since such adhesion is one of the initial stages of the infectious process. The validity of this approach has been unequivocally demonstrated in experiments performed in a wide variety of animals, from mice to monkeys, and recently also in humans. Here we review various approaches to anti-adhesion therapy, including the use of receptor and adhesin analogs, dietary constituents, sublethal concentrations of antibiotics and adhesin-based vaccines. Because anti-adhesive agents are not bactericidal, the propagation and spread of resistant strains is much less likely to occur than as a result of exposure to bactericidal agents, such as antibiotics. Anti-adhesive drugs, once developed, may, therefore, serve as a new means to fight infectious diseases. [source]

Calling capital: call centre strategies in New Brunswick and New Zealand

Wendy Larner
This article compares government promoted call centre initiatives in New Zealand and New Brunswick, Canada, thereby identifying differing policies and practices associated with ,globalization'. Both New Brunswick and New Zealand are small resource based economies in which policy makers aspire to attract foreign investment into call centres as a new means of economic growth and job creation. However there are significant differences between the two call centre strategies. In New Brunswick the provincial government plays a central role, most notably through the use of incentives to lure companies to the province but also through the coordination of education and training. In New Zealand an informal network made up of public and private sector actors drives the strategy, and the relevant government agency (Trade NZ) plays only a coordinating role. Despite these differences both call centre strategies aspire to link service sector activities into global flows and networks, and foster low wage and feminized forms of employment. [source]

Confinement of Thermoresponsive Hydrogels in Nanostructured Porous Silicon Dioxide Templates,

E. Segal
Abstract A thermoresponsive hydrogel, poly(N -isopropylacrylamide) (poly(NIPAM)), is synthesized in,situ within an oxidized porous Si template, and the nanocomposite material is characterized. Infiltration of the hydrogel into the interconnecting nanoscale pores of the porous SiO2 host is confirmed by scanning electron microscopy. The optical reflectivity spectrum of the nanocomposite hybrid displays Fabry,Pérot fringes characteristic of thin film interference, enabling direct, real-time observation of the volume phase transition of the confined poly(NIPAM) hydrogel. Reversible optical reflectivity changes are observed to correlate with the temperature-dependent volume phase transition of the hydrogel, providing a new means of studying nanoscale confinement of responsive hydrogels. The confined hydrogel displays a swelling and shrinking response to changes in temperature that is significantly faster than that of the bulk hydrogel. The porosity and pore size of the SiO2 template, which are precisely controlled by the electrochemical synthesis parameters, strongly influence the extent and rate of changes in the reflectivity spectrum of the nanocomposite. The observed optical response is ascribed to changes in both the mechanical and the dielectric properties of the nanocomposite. [source]

Improving M cell mediated transport across mucosal barriers: do certain bacteria hold the keys?

IMMUNOLOGY, Issue 1 2004
Angela L. Man
Summary Specialized microfold (M) cells of the follicle-associated epithelium (FAE) of the mucosal-associated lymphoid tissue (MALT) in gut and the respiratory system play an important role in the genesis of both mucosal and systemic immune responses by delivering antigenic substrate to the underlying lymphoid tissue where immune responses start. Although it has been shown that dendritic cells (DC) also have the ability to sample antigens directly from the gut lumen, M cells certainly remain the most important antigen-sampling cell to be investigated in order to devise novel methods to improve mucosal delivery of biologically active compounds. Recently, novel information on the interactions between bacteria and FAE have come to light that unveil further the complex cross-talk taking place at mucosal interfaces between bacteria, epithelial cells and the immune system and which are central to the formation and function of M cells. In particular, it has been shown that M cell mediated transport of antigen across the FAE is improved rapidly by exposure to certain bacteria, thus opening the way to identify new means to achieve a more effective mucosal delivery. Here, these novel findings and their potential in mucosal immunity are analysed and discussed, and new approaches to improve antigen delivery to the mucosal immune system are also proposed. [source]

Nanotechnologies: Tools for sustainability in a new wave of water treatment processes

Jean-Yves Bottero
Abstract In the environmental technology industry alone, nanomaterials will enable new means of reducing the production of industrial wastes, using resources more sparingly, remediating industrial contamination, providing potable water, and improving the efficiency of energy production. This paper discusses three new kinds of nanotechnology materials that should be developed in the future: Membranes, oxidants, and adsorbents. Nanoscale control of membrane architecture may yield membranes of greater selectivity and lower cost in both water treatment and water fabrication. Fullerene-based oxidant nanomaterials such as C60 have a high electron affinity and reactivity, and are capable of producing reactive oxygen species such as singlet oxygen and superoxides. Fullerenes might be used in engineered systems to photocatalytically oxidize organic contaminants, or inhibit or inactivate microbes. The ability to tailor surfaces can help to increase adsorbing capacities or recognize specific contaminants. The potential environmental risks are that nanomaterials could interact with biota and that their toxicity adversely may affect ecosystems. As nanochemistry emerges as an important force behind new environmental technologies, we are also presented with the responsibility of considering the environmental implications of an emerging technology at its inception and taking every precaution to ensure that these technologies develop as tools of sustainability rather than becoming future liabilities. [source]

January northern hemisphere circumpolar vortex variability and its relationship with hemispheric temperature and regional teleconnections

Robert V. Rohli
Abstract Variability in the hemispheric-scale atmospheric circulation can be directly linked to variations in surface environmental features, such as temperature, precipitation, salinity of water bodies, and pollutant transport. One indicator of the behavior of the hemispheric-scale circulation is the circumpolar vortex (CPV). This research utilizes a geographic information system approach to characterize variability in the Northern Hemispheric (NH) CPV. Specifically, the area, shape, and centroid of the January NHCPV are analyzed for 1959,2001 because it may provide insight about relationships between hemispheric-scale circulation and global temperature change. We also use a new means of characterizing the hemispheric-scale circulation using a ,circularity ratio' (Rc). Results suggest that the January NHCPV has exhibited no long-term trends in area or shape, and that the mean centroid is positioned at approximately 85.3°N, 178.0°W. Regional patterns emerge, which suggest that the area and circularity are associated with variability in surface temperature and moist static energy. Furthermore, the area of the January NHCPV is associated with variability in the Arctic Oscillation, while the shape is tied to variability in the Pacific-North American teleconnection pattern. These results will facilitate understanding of the relationship between hemispheric-scale circulation, regional circulation, and local temperatures. Copyright © 2005 Royal Meteorological Society. [source]

Polymerization of methyl methacrylate in the presence of a nonpolar hydrocarbon solvent.


Abstract This article presents the ternary phase diagram for methyl methacrylate (MMA), poly(methyl methacrylate) (PMMA), and n -hexane system at 70°C. It was constructed by both theoretical calculations and online laser light scattering (LLS) technique. In situ polymerization of MMA in a nonpolar nonsolvent carried out in a LLS cell provides a new means for the accurate detection of the cloud points of highly viscous polymer mixtures, with polymer weight fractions over 0.6. The ternary phase diagram measured in this study can be used to design the reaction conditions for the precipitation and/or dispersion polymerization in a nonpolar nonsolvent medium where polymerization kinetics as well as polymer particle morphologies are strongly affected by thermodynamic phase separation phenomena. © 2010 Wiley Periodicals, Inc. J Appl Polym Sci, 2010 [source]

22R -Hydroxycholesterol protects neuronal cells from ,-amyloid-induced cytotoxicity by binding to ,-amyloid peptide

Zhi-Xing Yao
Abstract 22R -hydroxycholesterol, a steroid intermediate in the pathway of pregnenolone formation from cholesterol, was found at lower levels in Alzheimer's disease (AD) hippocampus and frontal cortex tissue specimens compared to age-matched controls. ,-Amyloid (A,) peptide has been shown to be neurotoxic and its presence in brain has been linked to AD pathology. 22R -hydroxycholesterol was found to protect, in a dose-dependent manner, against A,-induced rat sympathetic nerve pheochromocytoma (PC12) and differentiated human Ntera2/D1 teratocarcinoma (NT2N) neuron cell death. Other steroids tested were either inactive or acted on rodent neurons only. The effect of 22R -hydroxycholesterol was found to be stereospecific because its enantiomer 22S -hydroxycholesterol failed to protect the neurons from A,-induced cell death. Moreover, the effect of 22R -hydroxycholesterol was specific for A,-induced cell death because it did not protect against glutamate-induced neurotoxicity. The neuroprotective effect of 22R -hydroxycholesterol was seen when using A,1,42 but not the A,25,35 peptide. To investigate the mechanism of action of 22R -hydroxycholesterol we examined the direct binding of this steroid to A, using a novel cholesterol-protein binding blot assay. Using this method the direct specific binding, under native conditions, of 22R -hydroxycholesterol to A,1,42 and A,17,40, but not A,25,35, was observed. These data suggest that 22R -hydroxycholesterol binds to A, and the formed 22R -hydroxycholesterol/A, complex is not toxic to rodent and human neurons. We propose that 22R -hydroxycholesterol offers a new means of neuroprotection against A, toxicity by inactivating the peptide. [source]

Variations in the Understanding of Interpersonal Behavior: Adherence to the Interpersonal Circle as a Moderator of the Rigidity,Psychological Well-Being Relation

Terence J. G. Tracey
ABSTRACT The idiothetic structure of interpersonal trait perceptions was examined as it moderated the interpersonal rigidity,psychological well-being relation. The focus was on the extent to which individuals' perceptions of the similarity of interpersonal behavior fits (i.e., adhered to) the normative interpersonal circle. In two samples of college students, individual differences in adherence to the interpersonal circle moderated the relation of interpersonal rigidity with various indices of psychological well-being. We found that those individuals whose perceptions of interpersonal traits were better represented by the interpersonal circle had negative relations between interpersonal rigidity and satisfaction with life, self-confidence, self-liking, and complementarity and positive relations with interpersonal problems. The results suggest that adherence to the interpersonal circle may be a new means of viewing traitedness and that cognitive interpretation of traits may have an important moderating function. [source]

Treatment of alopecia areata with the 308-nm xenon chloride excimer laser: Case report of two successful treatments with the excimer laser

Cuneyt Gundogan MD
Abstract Background and Objectives Alopecia areata is a common disease of unknown etiology; it causes significant cosmetic and psycho-social distress for most of the people it affects. We report on an innovative form of treatment in two patients with typical alopecia areata on the capillitium. Study Design/Patients and Methods We successfully treated two patients whose alopecia areata had worsened progressively for 3 and 14 weeks. The treatment involved the use of a 308 nm xenon chloride excimer laser (dosage 300,2,300 mJ/cm2 per session). Results After 11 and 12 sessions within a 9-week and 11-week period, the entire affected focus showed homogenous and thick regrowth. No relapse was observed during the follow-up period of 5 and 18 months. Conclusions The use of the excimer laser is an effective, elegant, and safe means of treatment and has good tolerability. Analogous to topical treatment of alopecia areata, the immunosuppressive mechanism of the excimer laser can be interpreted as an induction of T-cell apoptosis. This new means of treatment has yet to be discussed in medical literature. Further studies with greater numbers are needed to assess its potential more precisely and evaluate the excimer laser in treating alopecia areata. Lasers Surg. Med. 34:86,90, 2004. © 2004 Wiley-Liss, Inc. [source]

Seascape genetics along a steep cline: using genetic patterns to test predictions of marine larval dispersal

Abstract Coupled biological and physical oceanographic models are powerful tools for studying connectivity among marine populations because they simulate the movement of larvae based on ocean currents and larval characteristics. However, while the models themselves have been parameterized and verified with physical empirical data, the simulated patterns of connectivity have rarely been compared to field observations. We demonstrate a framework for testing biological-physical oceanographic models by using them to generate simulated spatial genetic patterns through a simple population genetic model, and then testing these predictions with empirical genetic data. Both agreement and mismatches between predicted and observed genetic patterns can provide insights into mechanisms influencing larval connectivity in the coastal ocean. We use a high-resolution ROMS-CoSINE biological-physical model for Monterey Bay, California specifically modified to simulate dispersal of the acorn barnacle, Balanus glandula. Predicted spatial genetic patterns generated from both seasonal and annual connectivity matrices did not match an observed genetic cline in this species at either a mitochondrial or nuclear gene. However, information from this mismatch generated hypotheses testable with our modelling framework that including natural selection, larval input from a southern direction and/or increased nearshore larval retention might provide a better fit between predicted and observed patterns. Indeed, moderate selection and a range of combined larval retention and southern input values dramatically improve the fit between simulated and observed spatial genetic patterns. Our results suggest that integrating population genetic models with coupled biological-physical oceanographic models can provide new insights and a new means of verifying model predictions. [source]

Murine in vitro whole bladder model: A method for assessing phenotypic responses to pharmacologic stimuli and hypoxia

Joel C. Hutcheson
Abstract Aims Recent advances in genetic manipulation have allowed for over expression or deletion of selective genes in mice. This offers urologic investigators new means of understanding bladder function in the context of normal development or the response to outlet obstruction. It is important to correlate any genetic manipulations in mice with specific phenotypic properties such as voiding patterns, or muscle strip physiology. We describe a simple in vivo whole bladder preparation that may be used to study the phenotypic changes in bladder function. Methods Murine bladders were mounted on a 30 gauge needle and mounted in an organ chamber containing a physiologic buffer solution. Passive bladder properties were assessed with cystometry, and active contractile responses were measured in response to electrical field stimulation and agonists. The effects of hypoxia were also studied. Results Compliance in the murine bladder is dependent upon actin myosin interactions, and increased in the presence of calcium free buffer and EGTA. The sarcoplasmic reticulum plays a smaller role in the contraction of murine bladder than in other species. Murine bladder smooth muscle demonstrated a remarkable ability to withstand hypoxia. Conclusions This simple model can be adapted to help study the murine bladder smooth muscle phenotype under highly controlled circumstances. © 2004 Wiley-Liss, Inc. [source]

Weak localization and the Mooij rule in disordered metals

Mi-Ae Park
Abstract Weak localization leads to the same correction to both the conductivity and the McMillan's electron,phonon coupling constant , (and ,tr, transport electron,phonon coupling constant). Consequently the temperature dependence of the thermal electrical resistivity is decreasing as the conductivity is decreasing due to weak localization, which results in the decrease of the temperature coefficient of resistivity (TCR) with increasing the residual resistivity. When , and ,tr are approaching zero, only the residual resistivity part remains and it gives rise to the negative TCR. Accordingly, the Mooij rule is a manifestation of weak localization correction to the conductivity and the electron,phonon interaction. This understanding provides a new means of probing the phonon-mechanism in exotic superconductors and an opportunity of fabricating new novel devices. [source]

Azimuthal anisotropy of light extraction from photonic crystal light-emitting diodes

Chun-Feng Lai
Abstract Photonic crystal (PhC) light-emitting diodes (LEDs) exhibiting anisotropic light extraction have been investigated experimentally and theoretically. It is found that the anisotropic light extraction strongly depends on the lattice constant and orientation. Optical images of the anisotropy in the azimuthal direction are obtained using annular structure with triangular lattice. 6-fold symmetric light extraction patterns with varying number of petals are observed. More petals in multiple of 6 appear in the observed image with lattice constant increasing. This anisotropic behavior suggests a new means to optimize the PhC design of GaN LED for light extraction. (© 2008 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim) [source]

Riding The Ciliate Cell Cycle,A Thirty-Five-Year Prospective,

ABSTRACT. Studies of the ciliate cell cycle have moved from early examination of its biochemistry with heat-synchronized Tetra-hymena through descriptive studies of Paramecium using small synchronous cell samples. These studies described what happens during the cell cycle and provided some initial insights into control, especially the idea that there was a point at which cells became committed to division. This early work was followed by an analytical phase in which the same small sample techniques, combined with gene mutations, were used to tease apart some major features of the regulation of cell growth kinetics, including regulation of macronuclear DNA content and regulation of cell size, the control of timing of initiation of macronuclear DNA synthesis, and the control of commitment to division in Paramecium. The availability of new molecular genetic approaches and new means of manipulating cells en masse made it possible to map out some of the basic features of the molecular biology of cell cycle regulation in ciliates. The challenge before us is to move beyond the ,me-too-ism' of validating the presence of basic molecular regulative machinery underlying the cell cycle in ciliates to a deeper analysis of the role of specific molecules in processes unique to ciliates or to analysis of the role of regulatory molecules in the control of cell process that can be uniquely well studied in ciliates. [source]

Optimizing the Response From a Passively Controlled Biventricular Assist Device

Nicholas Richard Gaddum
Abstract Recent studies into rotary biventricular support have indicated that inadequate left/right flow balancing may lead to vascular congestion and/or ventricular suckdown. The implementation of a passive controller that automatically adjusts left/right flow during total and partial cardiac support would improve physiological interaction. This has encouraged the development of a biventricular assist device (BiVAD) prototype that achieves passive control of the two rotary pumps' hydraulic output by way of a nonrotating double pressure plate configuration, the hub, suspended between the ventricular assist device (VAD) impellers. Fluctuations in either the VAD's inlet or outlet pressure will cause the hub to translate, and in doing so, affect each pump's hydraulic outputs. In order to achieve partial support, the floating assembly needed to respond to pathologic blood pressure signals while being insensitive to residual ventricular function. An incorporated mechanical spring,mass,damper assembly affects the passive response to optimize the dynamic interaction between the prototype and the supported cardiovascular system. It was found that increasing the damping from a medium to a high level was effective in filtering out the higher frequency ventricular pressure signals, reducing a modified amplitude ratio by up to 72%. A spring response was also identified as being inherent in the passive response and was characterized as being highly nonlinear at the extremes of the floating assembly's translation range. The results from this study introduce a new means of BiVAD control as well as the characterization of a fully passive mechanical physiological controller. [source]

Australian tropical forest canopy crane: New tools for new frontiers

Abstract An industrial crane was installed in the Daintree lowland rainforest in 1998 to provide a new means of accessing the canopy. Approximately 0.95 ha of forest, including 680 trees of 82 species with a diameter at breast height of greater than 10 cm, are accessible using the crane. The site was hit by a Category 3 Cyclone in 1999 and has shown a remarkable rate of recovery. The crane has been used for a very wide range of research including tree physiology and ecology, interactions with vertebrate and invertebrate biodiversity and studies of carbon and water fluxes. Results from studies on this crane and 11 other cranes around the world are changing views of the importance of the rainforest canopy. [source]

Reactivity of Intein Thioesters: Appending a Functional Group to a Protein

CHEMBIOCHEM, Issue 9 2006
Jeet Kalia
Abstract The success of genome sequencing has heightened the demand for new means to manipulate proteins. An especially desirable goal is the ability to modify a target protein at a specific site with a functional group of orthogonal reactivity. Here, we achieve that goal by exploiting the intrinsic electrophilicity of the thioester intermediate formed during intein-mediated protein splicing. Detailed kinetic analyses of the reaction of nitrogen nucleophiles with a chromogenic small-molecule thioester revealed that the ,-hydrazino acetyl group was the optimal nucleophile for attacking a thioester at neutral pH to form a stable linkage. A bifunctional reagent bearing an ,-hydrazino acetamido and azido group was synthesized in high overall yield. This reagent was used to attack the thioester linkage between a target protein and intein, and thereby append an azido group to the target protein in a single step. The azido protein retained full biological activity. Furthermore, its azido group was available for chemical modification by Huisgen 1,3-dipolar azide,alkyne cycloaddition. Thus, the mechanism of intein-mediated protein splicing provides the means to install a useful functional group at a specific site,the C terminus,of virtually any protein. [source]

Prediction of Tyrosinase Inhibition Activity Using Atom-Based Bilinear Indices

CHEMMEDCHEM, Issue 4 2007
Yovani Marrero-Ponce Prof.
Abstract A set of novel atom-based molecular fingerprints is proposed based on a bilinear map similar to that defined in linear algebra. These molecular descriptors (MDs) are proposed as a new means of molecular parametrization easily calculated from 2D molecular information. The nonstochastic and stochastic molecular indices match molecular structure provided by molecular topology by using the kth nonstochastic and stochastic graph-theoretical electronic-density matrices, Mk and Sk, respectively. Thus, the kth nonstochastic and stochastic bilinear indices are calculated using Mk and Sk as matrix operators of bilinear transformations. Chemical information is coded by using different pair combinations of atomic weightings (mass, polarizability, vdW volume, and electronegativity). The results of QSAR studies of tyrosinase inhibitors using the new MDs and linear discriminant analysis (LDA) demonstrate the ability of the bilinear indices in testing biological properties. A database of 246 structurally diverse tyrosinase inhibitors was assembled. An inactive set of 412 drugs with other clinical uses was used; both active and inactive sets were processed by hierarchical and partitional cluster analyses to design training and predicting sets. Twelve LDA-based QSAR models were obtained, the first six using the nonstochastic total and local bilinear indices and the last six with the stochastic MDs. The discriminant models were applied; globally good classifications of 99.58 and 89.96,% were observed for the best nonstochastic and stochastic bilinear indices models in the training set along with high Matthews correlation coefficients (C) of 0.99 and 0.79, respectively, in the learning set. External prediction sets used to validate the models obtained were correctly classified, with accuracies of 100 and 87.78,%, respectively, yielding C values of 1.00 and 0.73. This subset contains 180 active and inactive compounds not considered to fit the models. A simulated virtual screen demonstrated this approach in searching tyrosinase inhibitors from compounds never considered in either training or predicting series. These fitted models permitted the selection of new cycloartane compounds isolated from herbal plants as new tyrosinase inhibitors. A good correspondence between theoretical and experimental inhibitory effects on tyrosinase was observed; compound CA6 (IC50=1.32,,M) showed higher activity than the reference compounds kojic acid (IC50=16.67,,M) and L -mimosine (IC50=3.68,,M). [source]

Neighboring in Netville: How the Internet Supports Community and Social Capital in a Wired Suburb

CITY & COMMUNITY, Issue 4 2003
Keith Hampton
What is the Internet doing to local community? Analysts have debated about whether the Internet is weakening community by leading people away from meaningful in-person contact; transforming community by creating new forms of community online; or enhancing community by adding a new means of connecting with existing relationships. They have been especially concerned that the globe-spanning capabilities of the Internet can limit local involvements. Survey and ethnographic data from a "wired suburb" near Toronto show that high-speed, always-on access to the Internet, coupled with a local online discussion group, transforms and enhances neighboring. The Internet especially supports increased contact with weaker ties. In comparison to nonwired residents of the same suburb, more neighbors are known and chatted with, and they are more geographically dispersed around the suburb. Not only did the Internet support neighboring, it also facilitated discussion and mobilization around local issues. [source]