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End-user input early in biomedical product development may optimize design to support high uptake and adherence. We interviewed 400 couples (800 total participants) in Uganda and Zimbabwe to assess their preferences for multipurpose prevention technologies (MPTs) for HIV and pregnancy prevention. Using a discrete choice experiment, couples made a series of choices between hypothetical MPTs, including oral tablets and vaginal rings, inserts, and films and completed an interviewer-administered questionnaire assessing sociodemographic and behavioral measures. Most couples preferred presented MPTs over male condoms. Couples' MPT choices in both countries were influenced most by the combination of product form and dosing frequency, with monthly dosing preferred over daily. Analysis highlighted differences by country as to which side effects were most important: Ugandan couples placed greater importance on effects on the vaginal environment during sex, whereas Zimbabwean couples placed more importance on changes to menstruation and other side effects (headache, cramps). Couples' preferences signaled an openness to new product forms and more frequent dosing if preferred characteristics of other attributes were achieved.

Peri-urban lakes offer many valued ecosystem services, but their vulnerability to climate change and anthropogenic disturbances increases with increasing human populations the effects and interactions of multiple stressors on lakes can lead to unexpected outcomes, affecting societal and ecological values, it is necessary to evaluate ecosystem trajectories and respective drivers in peri-urban lakes. Better management practices could thus be applied to preserve ecosystem services of peri-urban lakes. We conducted a multi-proxy paleolimnological study on Cultus Lake, British Columbia, a Canadian peri-urban lake experiencing cultural eutrophication, to reconstruct a comprehensive ecological trajectory of the lake over the past ~ 200 years. We also integrated historical data as well as historical archival information to identify the potential drivers of the changes. We identified ca. 1800–1900 CE as a reference period, reflected in muted variations across most paleo-indicators. Minor increases in sedimentary δ15N ca. 1880–1940 CE coincided with the onset of anthropogenic modifications to the Cultus Lake watershed. Signs of early eutrophication were evident by ca. 1940 CE, as indicated by increases in all sedimentary pigments. By ca. 1970–1990 CE, elevated concentrations of sedimentary cyanobacterial pigments and changes in diatom species assemblages highlighted the potential interactive effects of multiple stressors, including cultural eutrophication, climate warming and declines in the endangered Cultus Lake sockeye salmon population. Recent (ca. 1990–2008 CE) declines in sedimentary pigments and increases in cladoceran fluxes suggested an increase in top-down control of the lake food web. From the collection of changes observed in the past ~ 200 years in our study, it is clear that Cultus Lake and its associated ecosystem services would benefit from abatement of nutrient loadings from terrestrial and atmospheric sources. Our study emphasizes the complexity and interactivity of drivers in peri-urban lake ecosystems and the necessity of long-term perspectives to contextualize modern ecological conditions to inform lake and watershed management.

The attributes of an HIV microbicide may affect its acceptability, uptake and use. Quatro, a clinical study with a qualitative component, was conducted to elicit input from end-users and key informants (KIs) on four different placebo vaginal microbicide delivery forms; fast dissolving insert, ring, film and gel. In-depth interviews and focus group discussions were conducted with young women, their male partners and KIs, to explore acceptability and preferences of the four placebo products, with the intention of improving product attributes, adherence, and consequently, long term effectiveness. None of the four microbicide delivery forms stood well above others as the most preferred. Product attributes; long-action, ease of use, invisibility, female initiated and non-interference during sex were favourable in both countries. Despite preference for the long-action, on-demand products were the most liked by women. Qualitative data from the Quatro study provided rich feedback on specific attributes important to the acceptability of four HIV prevention product platforms currently in development, enabling more informed and guided product development efforts moving forward.

Cosmology now has a standard model - a remarkably simple description of the universe, its contents and its history. A symposium held last September in Cambridge, UK, gave this model a 'health check' and discussed fascinating questions that lie beyond it., Published in Nature Astronomy. Summary of the 10th Anniversary KICC Conference

The importance of transportation infrastructure to health outcomes has been increasingly recognized. However, the relationship between transportation and health is underexplored in rural areas. This study fills the gap by investigating rural health outcomes in association with two transportation infrastructures-highways and airports-in the Black Belt counties of the USA, a region characterized as predominantly rural and black and as having high poverty and unemployment. Spatial regression models are applied to analyze the 2010 data. The results suggest Black Belt counties have poorer health outcomes than their non-Black Belt counterparts, and the difference increases as the percentage of blacks increases. The results also show that the higher accessibility to an airport a county has, the better its health outcomes. Highways, however, do not have a statistically significant association with health outcomes. The poor health outcomes in the Black Belt counties are also influenced by poverty, rurality, unemployment, and low educational attainment. This research was the first to study transportation, especially airports, in the rural US South with relation to health outcomes. Our findings shed new light on removing the health disadvantages accumulated in the Black Belt.

Good Clinical Practice (GCP) is an international standard for the design, conduct, performance, monitoring, auditing, recording, analyses, and reporting of clinical trials. The goal of GCP is to ensure the protection of the rights, integrity, and confidentiality of clinical trial participants and to ensure the credibility and accuracy of data and reported results. In the United States, trial sponsors generally require investigators to complete GCP training prior to participating in each clinical trial to foster GCP and as a method to meet regulatory expectations (ie, sponsor's responsibility to select qualified investigators per 21 CFR 312.50 and 312.53(a) for drugs and biologics and 21 CFR 812.40 and 812.43(a) for medical devices). This training requirement is often extended to investigative site staff, as deemed relevant by the sponsor, institution, or investigator. Those who participate in multiple clinical trials are often required by sponsors to complete repeated GCP training, which is unnecessarily burdensome. The Clinical Trials Transformation Initiative convened a multidisciplinary project team involving partners from academia, industry, other researchers and research staff, and government to develop recommendations for streamlining current GCP training practices. Recommendations drafted by the project team, including the minimum key training elements, frequency, format, and evidence of training completion, were presented to a broad group of experts to foster discussion of the current issues and to seek consensus on proposed solutions.

Clinical trial quality is essential to bringing effective treatments to patients as quickly as possible. Clinical trials that answer important questions, yield meaningful data, and protect trial participants can provide data that support both regulatory and clinical decision making. The Food and Drug Administration's (FDA's) Center for Drug Evaluation and Research (CDER) encourages stakeholders to improve clinical trial quality and efficiency. CDER believes that a systematic approach to clinical trial quality-one that builds in quality up front and focuses on the most critical aspects of study conduct-contributes to successful trials. Beyond FDA's regulatory requirements for clinical trial quality, CDER is an active participant in multiple efforts to advance clinical trial quality, including the addendum to ICH E6 (Good Clinical Practice) and the Clinical Trials Transformation Initiative project on quality-by-design for clinical trials. These efforts aim to move clinical drug development to a desired state that centers on efficient and agile clinical development programs that reliably produce high-quality data and adhere to important ethical standards.

Deposition of distal tephra-fall deposits in lake systems with low watershed sediment fluxes can represent large geochemical anomalies in sediment elemental composition. We examine the persistence of compositional effects of fallout from the 7.63 kyr BP Mt. Mazama caldera-forming event and other tephra deposits in the micro-laminated abyssal sediments of Pettit Lake, central Idaho, which received ~50 kg m−2 of Mazama tephra-fall material. Persistent post-depositional dominance of the Mazama material is reflected in elemental composition and grain size distribution and is related to lake hypsometry and the presence of a large in-lake sediment reservoir subject to remobilization. Decoupling of recycled clastic mineral material with Mazama compositional affinity from both biogenic matter and from clastic material derived from within the watershed is shown by coherence between dated primary tephras and a radiocarbon chronology.

Spectroscopic and imaging data for low metallicity galaxies observed during the peak epoch of star formation offer detailed insights into the most distant galaxies discovered to date.

We describe the scientific motivations, the mission concept and the instrumentation of SPACE, a class-M mission proposed for concept study at the first call of the ESA Cosmic-Vision 2015-2025 planning cycle. SPACE aims to produce the largest three-dimensional evolutionary map of the Universe over the past 10 billion years by taking near-IR spectra and measuring redshifts for more than half a billion galaxies at 0, Comment: 27 pages, Experimental Astronomy, in press. The SPACE team complete list is available at http://urania.bo.astro.it/cimatti/space . The article with full resolution figures is available at http://urania.bo.astro.it/cimatti/space/publications.htm

Nitrous Oxide (N2O), an ozone depleting greenhouse gas, is an observed intermediate in aqueous nitrate/nitrite reduction mediated by both natural microbial and synthetic laboratory catalysts. Because of our interest in catalytic nitrate/nitrite remediation, we have endeavored to develop a detailed concordant experimental/theoretical picture of N2O reduction with H2 over a Pd catalyst in an aqueous environment. We use batch experiments in H2 excess and limiting conditions to examine the reduction kinetics. We use density functional theory (DFT) to model the elementary steps in N2O reduction on model Pd(100), Pd(110), Pd(111) and Pd(211) facets and including the influence of adsorbed O, H, and of H2O. Both experiments and theory agree that hydrogen is necessary for removal of adsorbed oxygen from the catalyst surface. The dissociation of N2O to N2(g) and O(ads) is facile and in the absence of H proceeds until the catalyst is O-covered. Water itself is proposed to facilitate the hydrogenation of surface O by transferring absorbed hydrogen to Pd-absorbed O and OH. We measure an apparent activation energy of 41.4 kJ/mol (0.43 eV) for N2O reduction in the presence of excess H2, a value that is within 0.1 eV of the barriers determined theoretically.

This study tested the stability, activity, and selectivity of an alumina-supported Pd–In bimetallic catalyst during repetitive sulfide fouling and oxidative regeneration conditions. Nitrate reduction with hydrogen was used as the probe reaction in a continuous-flow packed-bed reactor to assess changes in the catalyst structure as a result of the fouling and regeneration processes. Partial regeneration of a severely sulfide-fouled Pd–In catalyst was achieved with a NaOCl/NaHCO3 solution. However, the regenerated catalyst had a reduced activity for NO3 − reduction and increased selectivity towards NH3. Analysis of the catalyst bed after regeneration experiments using XPS, ICP-MS, and BET surface area revealed that bulk structural transformations of the Pd–In bimetallic catalyst occurred, as a result of preferential Pd dissolution near the column influent. The dissolved Pd showed limited mobility in the column, and was re-deposited on the catalyst, resulting in Pd enrichment on the catalyst surface and redistribution of Pd towards the end of the column. These changes along with residual sulfur content on the catalyst surface were likely responsible for the increased selectivity towards NH3. These results indicate the importance of limiting the exposure of reduced sulfur species to Pd-based catalysts, especially when treating contaminants like NO3 −, where product selectivity is a priority.

This study tested the selectivity and sustainability of an alumina-supported Pd–In bimetallic catalyst for nitrate reduction with H2 in a continuous-flow packed-bed reactor in the presence of: (i) dissolved oxygen (DO), an alternative electron acceptor to nitrate, (ii) variable NO3 −:H2 influent loadings, and (iii) the presence of a known foulant, sulfide. The sustainability of the catalyst was promising, as the catalyst was found to be stable under all conditions tested with respect to metal leaching. The presence of DO at concentrations typical of treatment conditions will increase H2 demand for NO3 − reduction, but has no negative impact on the selectivity of the catalyst. Under optimal conditions, i.e., a pH of 5.0 and a high NO3 −:H2 influent loading, low NH3 selectivity (5%) was achieved for extended periods (36 days), resulting in sustained levels of NH3 that approached the European legal limit. The biggest challenge to the sustainability of the catalyst was the addition of sulfide, that initially increased NH3 selectivity and ultimately resulted in complete deactivation of the catalyst. Further work is required to identify regeneration methods to restore sulfide-fouled catalyst activity and selectivity; however, the most effective use would be to remove sulfide prior to catalytic treatment.

The visual response of a cell in the primary visual cortex (V1) to a drifting grating stimulus at the cell's preferred orientation decreases when a second, perpendicular, grating is superimposed. This effect is called masking. To understand the nonlinear masking effect, we model the response of Macaque V1 simple cells in layer 4Calpha to input from magnocellular Lateral Geniculate Nucleus (LGN) cells. The cortical model network is a coarse-grained reduction of an integrate-and-fire network with excitation from LGN input and inhibition from other cortical neurons. The input is modeled as a sum of LGN cell responses. Each LGN cell is modeled as the convolution of a spatio-temporal filter with the visual stimulus, normalized by a retinal contrast gain control, and followed by rectification representing the LGN spike threshold. In our model, the experimentally observed masking arises at the level of LGN input to the cortex. The cortical network effectively induces a dynamic threshold that forces the test grating to have high contrast before it can overcome the masking provided by the perpendicular grating. The subcortical nonlinearities and the cortical network together account for the masking effect.

We used an isotopic mass-balance model to examine how the hydrogeologic setting of lakes influences isotopic response of evaporating lake water to idealized hydroclimatic changes. The model uses a monthly water and isotope balance approach with simplified water-column structure and groundwater exchanges. The framework for comparative simulations is provided by lakes in a region of the Northern Rocky Mountains that display high interlake geochemical variability, thought to be controlled by groundwater hydraulics. Our analysis highlights several isotopic effects of flow between aquifers and lakes, leading to possible divergence of isotopic paleorecords formed under a common climate. Amplitude of isotopic variation resulting from simulated climate forcing was greatly damped when high groundwater fluxes and/or low lake volume resulted in low lake fluid residence time. Differing precipitation and evaporation scenarios that are equivalent in annual fluid balance (P−E) resulted in different isotopic signatures, interpreted as a result of evaporation kinetics. Concentrating low-δ groundwater inflow during spring months raised springtime lake δ values, a counterintuitive result of coincidence between times of high groundwater inflow and the evaporation season. Transient effects of reduced fluid balance caused excursions opposite in sign from eventual steady-state isotopic shifts resulting from enhanced groundwater inflow dominance. Lags in response between climate forcing and isotopic signals were shortened by high groundwater fluxes and resulting short lake residence times. Groundwater-lake exchange exerts control over patterns of lake isotopic response to evaporation through effects on lake residence time, inflow composition, and seasonal timing of inflow and outflow. Sediments from groundwater-linked lakes, often used for paleoenvironmental analysis, should be expected to reflect isotopic complexities of the type shown here.

We studied golden-backed uacaris, (Cacajao melanocephalus ouakary) in the late-wet season of 1999 and in the mid-dry season of 2000 in Jau National Park (JNP), Brazil. Additional observations were taken by other scientists working in JNP. Group counts range from 2 to 30 in the wet season and from 1 to > 100 in the dry. In the wet season, we recorded uacaris only in flooded forests (igapo). During the dry season they were in igapo, campinarana, and terra firme forests. We supplemented observations via interviews with local informants on seasonal use of the forest types and of particular small patches of different habitat types that exhibit high temporal patchiness in fruit availability. We recorded a total of 13 food plant species (dry season, 4; flooded season, 9), and a further 55 were provided by interviews. We noted the physical dimensions and hardness of 26 fruit species. Despite accepted specializations of the uakaris on hard unripe fruit, we recorded incidents of insectivory and folivory. Patterns of food availability, and therefore the seasonal habitat-use patterns by golden-backed uacaris, appear to be more complex than previously realized.

The game described below appeared in conversations after a talk given by Lloyd Shapley at the Second International Workshop in Game Theory in Berkeley, Summer 1970. This was one of the problems circulating around the conference to which several participants contributed. The general problem is to study two-person zero-sum games with stochastic movement among subgames in which the subgame being played is not precisely known, but in which information about this aspect may be gathered or partially revealed by the strategy choices of the players, the actual game being played, and chance. Without stochastic movement among the subgames, such a game would be a repeated game of incomplete information defined and studied by the Mathematica Inc. group at Princeton 1966–1968; see the book of Aumann and Maschler, ‘‘Repeated Games with Incomplete Information’’, MIT Press, 1995. Granted that the problem is interesting, one searches for the simplest non-trivial example of the class and is led to the following game. Subgames. There are two basic subgames, G1 with matrix ð0 1Þ, and G2

This paper reports on the consequences of large, activity dependent, synaptic conductances for neurons in a large-scale neuronal network model of the input layer 4Cα of the Macaque primary visual cortex (Area V1). This high conductance state accounts for experimental observations about orientation selectivity, dynamics, and response magnitude (D. McLaughlin et al. (2000) Proc. Natl. Acad. Sci. USA 97: 8087-8092), and the linear dependence of Simple cells on visual stimuli (J. Wielaard et al. (2001) J. Neuroscience 21: 5203-5211). The source of large conductances in the model can be traced to inhibitory corticocortical synapses, and the model's predictions of large conductance changes are consistent with recent intracellular measurements (L. Borg-Graham et al. (1998) Nature 393: 369-373; J. Hirsch et al. (1998) J. Neuroscience 15: 9517-9528; J.S. Anderson et al. (2000) J. Neurophysiol. 84: 909-926). During visual stimulation, these conductances are large enough that their associated time-scales become the shortest in the model cortex, even below that of synaptic interactions. One consequence of this activity driven separation of time-scales is that a neuron responds very quickly to temporal changes in its synaptic drive, with its intracellular membrane potential tracking closely an effective reversal poten- tial composed of the instantaneous synaptic inputs. From the effective potential and large synaptic conductance, the spiking activity of a cell can be expressed in an interesting and simplified manner, with the result suggest- ing how accurate and smoothly graded responses are achieved in the model network. Further, since neurons in this high-conductance state respond quickly, they are also good candidates as coincidence detectors and burst transmitters.

A comprehensive review of the hydrocarbon derivative chemistry of WOs3 mixed-metal cluster compounds including synthesis, reactivity, ligand transformation, and solution dynamics is presented.

In the primate visual pathway, orientation tuning of neurons is first observed in the primary visual cortex. The LGN cells that comprise the thalamic input to V1 are not orientation tuned, but some V1 neurons are quite selective. Two main classes of theoretical models have been offered to explain orientation selectivity: feedforward models, in which inputs from spatially aligned LGN cells are summed together by one cortical neuron; and feedback models, in which an initial weak orientation bias due to convergent LGN input is sharpened and amplified by intracortical feedback. Recent data on the dynamics of orientation tuning, obtained by a cross-correlation technique, may help to distinguish between these classes of models. To test this possibility, we simulated the measurement of orientation tuning dynamics on various receptive field models, including a simple Hubel-Wiesel type feedforward model: a linear spatiotemporal filter followed by an integrate-and-fire spike generator. The computational study reveals that simple feedforward models may account for some aspects of the experimental data but fail to explain many salient features of orientation tuning dynamics in V1 cells. A simple feedback model of interacting cells is also considered. This model is successful in explaining the appearance of Mexican-hat orientation profiles, but other features of the data continue to be unexplained.

Replacing a missing gene in adult colour-blind monkeys restores normal colour vision. How the new photoreceptor cells produced by this therapy lead to colour vision is a fascinating question.

Stimulation outside the receptive field of a primary visual cortical (V1) neuron reveals intracortical neural interactions. However, previous investigators implicitly or explicitly considered the extent of cortical spatial summation and, therefore, the size of the classical receptive field to be fixed and independent of stimulus characteristics or of surrounding context. On the contrary, we found that the extent of spatial summation in macaque V1 neurons depended on contrast, and was on average 2.3-fold greater at low contrast. This adaptive increase in spatial summation at low contrast was seen in cells throughout V1 and was independent of surround inhibition.

The reaction between triplet methylene and nitric oxide, producing the formaldiminoxy (CH2NO) radical, and the subsequent decomposition and isomerization reactions of CH2NO have been studied using ab␣initio quantum chemical techniques that include the Gaussian-2 (G2), CASSCF and CASPT2 methods. Stationary points on the potential energy surfaces were located at MP2/6-31G(d) and CASSCF/cc-pVDZ levels of theory, while the electronic energies were determined using G2, G2(MP2), QCISD(T)/cc-pVTZ, RCCSD(T)/cc-pVTZ and CASPT2/cc-pVTZ approaches. G2 is believed to be reliable at equilibrium geometries, but the determination of certain transition state geometries and energies requires a MCSCF-based approach. The calculations suggest that CH2NO (2A′) forms in a barrierless reaction and could readily decompose to H+HCNO. A subsequent abstraction reaction then results in H2+CNO. No molecular elimination channel was found. An alternative pathway is the formation of CH2ON, which readily isomerizes to CH2NO.

Zeolite-NaY-supported Ir/Sn catalysts (1 wt% Ir, 0.6 wt% Sn; 1:1 molar ratio) were prepared by adsorption of the organometallic precursors Ir(CO)2(acac) and SnMe3OH or (COD)2Ir–SnMe3 {COD= 1,5-cyclooctadiene) from hexane solutions followed by activation in H2 up to 773 K. The Ir/Sn/NaY catalysts displayed high selectivity for the dehydrogenation of propane to propene at ca. 773 K and, in the presence of H2, maintained thermodynamic conversion levels for up to 24 h. After activation, the catalyst derived from the dual-source precursors ({Ir+Sn/NaY) appeared homogeneous in composition, whereas the catalyst derived from the single-source precursor (Ir–Sn/NaY) appeared heterogeneous with distinct regions of visible particles. Scanning transmission electron microscopy revealed that the nanoscale metal particles present were small and uniform in size (ca. 1 nm) in the Ir + Sn/NaY catalyst but ranged in size from 1 to 10 nm in the Ir–Sn/NaY catalyst. Energy-dispersive X-ray analysis showed that bimetallic particles were formed for both catalysts. Temperature-programmed reaction of chemiosorbed carbon monoxide indicated that the Ir/Sn/NaY catalysts were electronically modified by the presence of tin in comparison with analogously prepared Ir/NaY catalysts.

Orientation tuning of neurons is one of the chief emergent characteristics of the primary visual cortex, VI (refs 1,2). Neurons of the lateral geniculate nucleus, which comprise the thalamic input to VI, are not orientation-tuned, but the majority of VI neurons are quite selective. How orientation tuning arises within VI is still controversial1,3–17. To study this problem, we measured how the orientation tuning of neurons evolves with time18–20 using a new method: reverse correlation in the orientation domain. Orientation tuning develops after a delay of 30–45 milliseconds and persists for 40–85 ms. Neurons in layers 4Cα or 4Cβ, which receive direct input from the thalamus, show a single orientation preference which remains unchanged throughout the response period. In contrast, the preferred orientations of output layer neurons (in layers 2,3,4B, 5 or 6) usually change with time, and in many cases the orientation tuning may have more than one peak. This difference in dynamics is accompanied by a change in the sharpness of orientation tuning; cells in the input layers are more broadly tuned than cells in the output layers. Many of these observed properties of output layer neurons cannot be explained by simple feedforward models1,3–6, whereas they arise naturally in feedback networks7–17. Our results indicate that VI is more than a bank of static oriented filters; the dynamics of output layer cells appear to be shaped by intracortical feedback.

Two catalysts were prepared (ca. 1 wt% Ir), one with metal particles located on the external surface of zeolite NaY and the other with metal particles located inside the zeolite supercages. The two catalysts exhibited very different activities and selectivities for the hydrogenolysis of n- butane, with the Ir in NaY catalyst much less active and less selective (53% ethane) than the Ir on NaY catalyst (83% ethane). The differences in catalytic activity and selectivity between Ir on NaY and Ir in NaY are attributed to differences in the size of the active metal particle, an ensemble effect, and not to the location (encagement) of the particle.

The results obtained from the application of high pressure in optical absorption studies of compounds with metal-metal quadruple bonds are reviewed. The different degrees of balance between intermolecular and intramolecular effects of compression in different cases are highlighted. A consistent effect observed for [Re2Cl8]2−, [Mo2Cl8]4− , and related compounds is a continuous shift to Iower energy (red) in the δ to δ* excitation with increasing pressure. This observation is interpreted in terms of significant van der Waals interactions between the molecular chromophore and its surroundings, leading to relative stabilization of the more polarizable excited state. Changes in the intensity of the δ to δ* peak are not correlated with the changes in position. The intensity changes become consistent only at relatively high pressures, and this falloff is attributed largely to compression and deformation of the cell gasket. In certain cases, such as [Re2I8]2− and Re2(piv)4X2, piv = pivalate, X= CI, Br, rearrangement to a new species is observed upon the application of high pressure. These rearrangements are all reversible upon pressure release, but they involve different degrees of interaction between adjacent molecules.

Background Infections caused by community-associated strains of methicillin-resistant Staphylococcus aureus (CA-MRSA) are associated with a marked and prolonged host inflammatory response. In a sepsis simulation model, we tested whether the anesthetic ketamine inhibits the macrophage TNF response to antibiotic-exposed CA-MRSA bacteria via its antagonism of N-methyl-D-aspartate (NMDA) receptors. RAW264.7 cells were stimulated for 18 hrs with 105 to 107 CFU/mL inocula of either of two prototypical CA-MRSA isolates, USA300 strain LAC and USA400 strain MW2, in the presence of either vancomycin or daptomycin. One hour before bacterial stimulation, ketamine was added with or without MK-801 (dizocilpine, a chemically unrelated non-competitive NMDA receptor antagonist), APV (D-2-amino-5-phosphono-valerate, a competitive NMDA receptor antagonist), NMDA, or combinations of these agents. Supernatants were collected and assayed for TNF concentration by ELISA. Results RAW264.7 cells exposed to either LAC or MW2 in the presence of daptomycin secreted less TNF than in the presence of vancomycin. The addition of ketamine inhibited macrophage TNF secretion after stimulation with either of the CA-MRSA isolates (LAC, MW2) in the presence of either antibiotic. The NMDA inhibitors, MK-801 and APV, also suppressed macrophage TNF secretion after stimulation with either of the antibiotic-exposed CA-MRSA isolates, and the effect was not additive or synergistic with ketamine. The addition of NMDA substrate augmented TNF secretion in response to the CA-MRSA bacteria, and the addition of APV suppressed the effect of NMDA in a dose-dependent fashion. Conclusions Ketamine inhibits TNF secretion by MRSA-stimulated RAW264.7 macrophages and the mechanism likely involves NMDA receptor antagonism. These findings may have therapeutic significance in MRSA sepsis.

This study reports the results of one phase of a project, funded in part by a grant from the National Science Foundation, which was designed to make hands-on science the predominant mode of instruction in the elementary schools of a large metropolitan district. A two-part questionnaire was developed and administered as a pretest/posttest focusing on the effectiveness of mentor/colleague inservice workshops. Results indicated significant changes in teachers' beliefs about teaching science, their understanding of the nature of science, the type of instruction they used in teaching science, and their anxiety toward science teaching as a result of workshop participation.

The main result of this paper is that the set of all weighted Shapley values of a cooperative game contains the core of the game. That there is such a general relationship between core and values is somewhat surprising in light of the difference in concept behind these solutions. Indeed cooperative game theory tells us very little about the relations between core and values. Such relations are known to exist for convex games and for market games with a continuum of players. In such games the Shapley value is always in the core. Convex games have, in a sense, large cores, which 'explains' why they contain the Shapley value. In the case of market games with a continuum of players, it is the homogeneity of the games and the diagonal property of the Shapley value that guarantee this fact. More relations can be found when we consider core-like and value-like solutions. In a recent paper Owen (1990) shows that for spatial voting games the Copeland winner outcome, which is a near core solution concept, is an analogue of the Shapley value. A result concerning a relation between the core and value-like solutions for general games was noted by Weber (1988) who showed that the set of all random order values of a game contains the core. Our result generalizes Weber's since weighted values constitute a subset (dimensionally, a very small one) of random order values. Weighted Shapley values (weighted values for short) were defined by Shapley (1953 a, b) alongside the standard Shapley value and were extensively discussed in the literature (e.g., Owen (1972), Kalai, and Samet (1987), and Hart and Mas-Colell (1989)). For these values weights are assigned to the players. The value is then determined in one of two equivalent ways. In the random order approach the weights are used to determine a probability distribution over orders of the players and the value is the expected contributions of the players according to this probability distribution. In the algebraic approach the value of a unanimity game is determined first, by allocating one unit among the players of the carrying coalition according to their

We provide elementary proofs of Scarf's theorem on the non-emptiness of the core and of the K-K-M-S thoerem, based on Kakutani's fixed point theorem. We also show how these proofs can be modified to apply a coincidence theorem of Fan instead of Kakutani's fixed point theorem, for some additional simplicity.

Reductive removal by hydrogeneration using supported Pd/M (M= Cu, Pt, Ag, Co, Fe, Mo, Ni, Rh, Ir, Mn and Cr) bimetallic catalysts has emerged as a promising alternative for nitrate removal in drinking water [1]. Fundamental understanding how the atomic arrangement of Pd and a second element, such as Cu, affect the activity nitrite reduction and selectivity of dinitrogen will be accomplished by coordinated synthesis (Shapley), activity/selectivity/efficiency measurements (Werth) and nanostructure determination (Yang & Xu). In this paper, we report a systematic study of novel polyvinylpyrrolidone (PVP) stabilized nanoscale Pd-Cu colloids, with homogeneous and narrow size distribution, with Pd: Cu ratios varying from 50:50 to 90:10. Initial measurements on catalytic activity for nitrate reduction demonstrated a dependence on the relative composition. Electron microscopy studies, including Z-contrast imaging [2], energy-dispersive X-ray emission (EDX), electron diffraction and high-resolution electron microscopy (HREM), revealed a surprising change in structure at the 80:20 Pd-Cu composition, where, with less than 80% Pd,the nanoparticle forms a core-shell structure but for nanoparticles containing 80% or more Pd, it is homogeneous. We are at the pivotal point of directly correlating these nano-structures with the catalytic activity. Such an understanding is essential for the efficient development of catalysts for the purification of drinking water.

WE describe here a new view of primary visual cortex (VI) based on measurements of neural responses in V1 to patterns called ‘illusory contours’ (Fig. la, b). Detection of an object's boundary contours is a fundamental visual task. Boundary contours are defined by discontinuities not only in luminance and colour, but also in texture1–3, disparity4 and motion5–7. Two theoretical approaches can account for illusory contour perception. The cognitive approach emphasizes top-down processes8,9. An alternative emphasizes bottom-up processing. This latter view is supported by (1) stimulus constraints for illusory contour perception10–14 and (2) the discovery by von der Heydt and Peterhans15–17 of neurons in extrastriate visual area V2 (but not in V1) of macaque monkeys that respond to illusory contours. Using stimuli different from those used previously15,16, we found illusory contour responses in about half the neurons studied in V1 of macaque monkeys. Therefore, there are neurons as early as V1 with the computational power to detect illusory contours and to help distinguish figure from ground.

Human colour vision depends on three classes of cone photoreceptors, those sensitive to short (S), medium (M) or long (L) wavelengths, and on how signals from these cones are combined by neurons in the retina and brain. Macaque monkey colour vision is similar to human, and the receptive fields of macaque visual neurons have been used as an animal model of human colour processing. P retinal ganglion cells and parvocellular neurons are colour-selective neurons in macaque retina and lateral geniculate nucleus. Interactions between cone signals feeding into these neurons are still unclear. On the basis of experimental results with chromatic adaptation, excitatory and inhibitory inputs from L and M cones onto P cells (and parvocellular neurons) were thought to be quite specific (Fig. 1a). But these experiments with spatially diffuse adaptation did not rule out the 'mixed-surround' hypothesis: that there might be one cone-specific mechanism, the receptive field centre, and a surround mechanism connected to all cone types indiscriminately (Fig. 1e). Recent work has tended to support the mixed-surround hypothesis. We report here the development of new stimuli to measure spatial maps of the linear L-, M- and S-cone inputs to test the hypothesis definitively. Our measurements contradict the mixed-surround hypothesis and imply cone specificity in both centre and surround.