Field experimental evidence that grazers mediate transition between microalgal and seagrass dominance

We tested the relative effects of nutrient loading, reduced predation, and reduced grazing on eelgrass community dynamics in Chesapeake Bay and found evidence supporting the mutualistic mesograzer model in which small invertebrate grazers control accumulation of epiphytic algae, buffer eutrophication effects, and thus facilitate seagrass dominance. Experimental reduction of crustacean grazers in the field stimulated a nearly sixfold increase in epiphytic algae, and reduced seagrass biomass by 65% compared to controls with grazers. Nutrient fertilization generally had much weaker effects, but an interaction with mesograzers was key in changing the sign of fertilization effects on the system: aboveground eelgrass biomass was reduced by fertilization under reduced grazing, but increased by fertilization under ambient grazing. When protected from predators in field cages, these mesograzers limited epiphyte blooms even with nutrient enrichment, and nutrients instead enhanced grazer secondary production. Crustacean mesograzers play a key role in maintaining macrophyte (seagrass) dominance in Chesapeake Bay, in buffering eelgrass against eutrophication, and in efficiently transferring nitrogen to higher trophic levels. Yet, these crustacean grazers are also highly sensitive to predator abundance. Reducing nutrient pollution alone is unlikely to restore seagrass meadows where alterations to food webs have reduced populations of algae-feeding mesograzers. Integration of both water quality and fishery management will be more effective in restoring and maintaining healthy coastal ecosystems

Convergence towards an asymptotic shape in first-passage percolation on cone-like subgraphs of the integer lattice

In first-passage percolation on the integer lattice, the Shape Theorem provides precise conditions for convergence of the set of sites reachable within a given time from the origin, once rescaled, to a compact and convex limiting shape. Here, we address convergence towards an asymptotic shape for cone-like subgraphs of the $\Z^d$ lattice, where $d\ge2$. In particular, we identify the asymptotic shapes associated to these graphs as restrictions of the asymptotic shape of the lattice. Apart from providing necessary and sufficient conditions for $L^p$- and almost sure convergence towards this shape, we investigate also stronger notions such as complete convergence and stability with respect to a dynamically evolving environment.Comment: 23 pages. Together with arXiv:1305.6260, this version replaces the old. The main results have been strengthened and an earlier error in the statement corrected. To appear in J. Theoret. Proba

Integrating modes of policy analysis and strategic management practice : requisite elements and dilemmas

There is a need to bring methods to bear on public problems that are inclusive, analytic, and quick. This paper describes the efforts of three pairs of academics working from three different though complementary theoretical foundations and intervention backgrounds (i.e., ways of working) who set out together to meet this challenge. Each of the three pairs had conducted dozens of interventions that had been regarded as successful or very successful by the client groups in dealing with complex policy and strategic problems. One approach focused on leadership issues and stakeholders, another on negotiating competitive strategic intent with attention to stakeholder responses, and the third on analysis of feedback ramifications in developing policies. This paper describes the 10 year longitudinal research project designed to address the above challenge. The important outcomes are reported: the requisite elements of a general integrated approach and the enduring puzzles and tensions that arose from seeking to design a wide-ranging multi-method approach

Characterization of Shewanella oneidensis MtrC: a cell-surface decaheme cytochrome involved in respiratory electron transport to extracellular electron acceptors

MtrC is a decaheme c-type cytochrome associated with the outer cell membrane of Fe(III)-respiring species of the Shewanella genus. It is proposed to play a role in anaerobic respiration by mediating electron transfer to extracellular mineral oxides that can serve as terminal electron acceptors. The present work presents the first spectropotentiometric and voltammetric characterization of MtrC, using protein purified from Shewanella oneidensis MR-1. Potentiometric titrations, monitored by UV–vis absorption and electron paramagnetic resonance (EPR) spectroscopy, reveal that the hemes within MtrC titrate over a broad potential range spanning between approximately +100 and approximately -500 mV (vs. the standard hydrogen electrode). Across this potential window the UV–vis absorption spectra are characteristic of low-spin c-type hemes and the EPR spectra reveal broad, complex features that suggest the presence of magnetically spin-coupled low-spin c-hemes. Non-catalytic protein film voltammetry of MtrC demonstrates reversible electrochemistry over a potential window similar to that disclosed spectroscopically. The voltammetry also allows definition of kinetic properties of MtrC in direct electron exchange with a solid electrode surface and during reduction of a model Fe(III) substrate. Taken together, the data provide quantitative information on the potential domain in which MtrC can operate

MTN-001: Randomized Pharmacokinetic Cross-Over Study Comparing Tenofovir Vaginal Gel and Oral Tablets in Vaginal Tissue and Other Compartments

Background: Oral and vaginal preparations of tenofovir as pre-exposure prophylaxis (PrEP) for human immunodeficiency virus (HIV) infection have demonstrated variable efficacy in men and women prompting assessment of variation in drug concentration as an explanation. Knowledge of tenofovir concentration and its active form, tenofovir diphosphate, at the putative vaginal and rectal site of action and its relationship to concentrations at multiple other anatomic locations may provide key information for both interpreting PrEP study outcomes and planning future PrEP drug development. Objective: MTN-001 was designed to directly compare oral to vaginal steady-state tenofovir pharmacokinetics in blood, vaginal tissue, and vaginal and rectal fluid in a paired cross-over design. Methods and Findings: We enrolled 144 HIV-uninfected women at 4 US and 3 African clinical research sites in an open label, 3-period crossover study of three different daily tenofovir regimens, each for 6 weeks (oral 300 mg tenofovir disoproxil fumarate, vaginal 1% tenofovir gel [40 mg], or both). Serum concentrations after vaginal dosing were 56-fold lower than after oral dosing (p<0.001). Vaginal tissue tenofovir diphosphate was quantifiable in ≥90% of women with vaginal dosing and only 19% of women with oral dosing. Vaginal tissue tenofovir diphosphate was ≥130-fold higher with vaginal compared to oral dosing (p<0.001). Rectal fluid tenofovir concentrations in vaginal dosing periods were higher than concentrations measured in the oral only dosing period (p<0.03). Conclusions: Compared to oral dosing, vaginal dosing achieved much lower serum concentrations and much higher vaginal tissue concentrations. Even allowing for 100-fold concentration differences due to poor adherence or less frequent prescribed dosing, vaginal dosing of tenofovir should provide higher active site concentrations and theoretically greater PrEP efficacy than oral dosing; randomized topical dosing PrEP trials to the contrary indicates that factors beyond tenofovir's antiviral effect substantially influence PrEP efficacy. Trial Registration: ClinicalTrials.gov NCT00592124

Why alternative teenagers self-harm: exploring the link between non-suicidal self-injury, attempted suicide and adolescent identity

Background: The term ‘self-harm’ encompasses both attempted suicide and non-suicidal self-injury (NSSI). Specific adolescent subpopulations such as ethnic or sexual minorities, and more controversially, those who identify as ‘Alternative’ (Goth, Emo) have been proposed as being more likely to self-harm, while other groups such as ‘Jocks’ are linked with protective coping behaviours (for example exercise). NSSI has autonomic (it reduces negative emotions) and social (it communicates distress or facilitates group ‘bonding’) functions. This study explores the links between such aspects of self-harm, primarily NSSI, and youth subculture.&lt;p&gt;&lt;/p&gt; Methods: An anonymous survey was carried out of 452 15 year old German school students. Measures included: identification with different youth cultures, i.e. Alternative (Goth, Emo, Punk), Nerd (academic) or Jock (athletic); social background, e.g. socioeconomic status; and experience of victimisation. Self-harm (suicide and NSSI) was assessed using Self-harm Behavior Questionnaire and the Functional Assessment of Self-Mutilation (FASM).&lt;p&gt;&lt;/p&gt; Results: An “Alternative” identity was directly (r ≈ 0.3) and a “Jock” identity inversely (r ≈ -0.1) correlated with self-harm. “Alternative” teenagers self-injured more frequently (NSSI 45.5% vs. 18.8%), repeatedly self-injured, and were 4–8 times more likely to attempt suicide (even after adjusting for social background) than their non-Alternative peers. They were also more likely to self-injure for autonomic, communicative and social reasons than other adolescents.&lt;p&gt;&lt;/p&gt; Conclusions: About half of ‘Alternative’ adolescents’ self-injure, primarily to regulate emotions and communicate distress. However, a minority self-injure to reinforce their group identity, i.e. ‘To feel more a part of a group’

Durability design of reinforced concrete structures: a comparison of the use of durability indexes in the deemed-to-satisfy approach and the full-probabilistic approach

Abstract: To show the application of the chloride conductivity index test in service life prediction (SLP) using both the deemed-to-satisfy and probabilistic approaches to performance-based durability design. It is desirable to adopt a performance-based approach with respect to durability design of reinforced concrete (RC) structures. This is based on the perception that the durability of RC is achieved when the limiting value from an established test method is met. In South Africa, the durability index (DI) approach has been developed, which permits performance-based specifications for durability of RC. This approach involves the application of a test method together with a SLP model. This integrated approach links material properties directly with the expected service life of RC structures and environmental conditions. Two DIs are relevant to degradation processes in RC: the chloride conductivity index which is related to chloride ingress, and the oxygen permeability index related to carbonation. The study presented here focuses on the application of the chloride conductivity index as the main input parameter of a SLP model concerned with chloride-induced reinforcement corrosion. The methodology and output of the SLP model as applied in the deemed-to-satisfy approach are compared with those of the probabilistic approach. Both approaches are exemplified using a concrete pier cast in situ in a marine environment. The performance-based durability specifications from the deemed-to-satisfy approach are found to be more conservative compared to those of the probabilistic approach

Design of a Microsphere-Based High-Throughput Gene Expression Assay to Determine Estrogenic Potential

Recently gene expression studies have been multiplied at an accelerated rate by the use of high-density microarrays. By assaying thousands of transcripts at a time, microarrays have led to the discovery of dozens of genes involved in particular biochemical processes, for example, the response of a tissue/organ to a given chemical with therapeutic or toxic properties. The next step in these studies is to focus on the response of a subset of relevant genes to verify or refine potential therapeutic or toxic properties. We have developed a sensitive, high-throughput gene expression assay for this purpose. In this assay, based on the Luminex xMAP system, carefully selected oligonucleotides were covalently linked to fluorescently coded microspheres that are hybridized to biotinylated cRNA followed by amplification of the signal, which results in a rapid, sensitive, multiplexed assay platform. Using this system, we have developed an RNA expression profiling assay specific for 17 estrogen-responsive transcripts and three controls. This assay can evaluate up to 100 distinct analytes simultaneously in a single sample, in a 96-well plate format. This system has improved sensitivity versus existing microsphere-based assays and has sensitivity and precision comparable with or better than microarray technology. We have achieved detection levels down to 1 amol, detecting rare messages in complex cRNA samples, using as little as 2.5 μg starting cRNA. This assay offers increased throughput with decreased costs compared with existing microarray technologies, with the trade-off being in the total number of transcripts that can be analyzed

Phase 1/2 study of daratumumab, lenalidomide, and dexamethasone for relapsed multiple myeloma

Daratumumab, a human CD38 immunoglobulin G1 kappa (IgG1κ) monoclonal antibody, has activity as monotherapy in multiple myeloma (MM). This phase 1/2 study investigated daratumumab plus lenalidomide/dexamethasone in refractory and relapsed/refractory MM. Part 1 (dose escalation) evaluated 4 daratumumab doses plus lenalidomide (25 mg/day orally on days 1-21 of each cycle) and dexamethasone (40 mg/week). Part 2 (dose expansion) evaluated daratumumab at the recommended phase 2 dose (RP2D) plus lenalidomide/dexamethasone. Safety, efficacy, pharmacokinetics, immunogenicity, and accelerated daratumumab infusions were studied. In part 1 (13 patients), no dose-limiting toxicities were observed, and 16 mg/kg was selected as the R2PD. In part 2 (32 patients), median time since diagnosis was 3.2 years, with a median of 2 prior therapies (range, 1-3 prior therapies), including proteasome inhibitors (91%), alkylating agents (91%), autologous stem cell transplantation (78%), thalidomide (44%), and lenalidomide (34%); 22% of patients were refractory to the last line of therapy. Grade 3 to 4 adverse events (≥5%) included neutropenia, thrombocytopenia, and anemia. In part 2, infusion-related reactions (IRRs) occurred in 18 patients (56%); most were grade ≤2 (grade 3, 6.3%). IRRs predominantly occurred during first infusions and were more common during accelerated infusions. In part 2 (median follow-up of 15.6 months), overall response rate was 81%, with 8 stringent complete responses (25%), 3 complete responses (9%), and 9 very good partial responses (28%). Eighteen-month progression-free and overall survival rates were 72% (95% confidence interval, 51.7-85.0) and 90% (95% confidence interval, 73.1-96.8), respectively. Daratumumab plus lenalidomide/dexamethasone resulted in rapid, deep, durable responses. The combination was well tolerated and consistent with the safety profiles observed with lenalidomide/dexamethasone or daratumumab monotherapy. This trial was registered at www.clinicaltrials.gov as #NCT01615029

Lattice Boltzmann simulations in microfluidics: probing the no-slip boundary condition in hydrophobic, rough, and surface nanobubble laden microchannels

In this contribution we review recent efforts on investigations of the effect of (apparent) boundary slip by utilizing lattice Boltzmann simulations. We demonstrate the applicability of the method to treat fundamental questions in microfluidics by investigating fluid flow in hydrophobic and rough microchannels as well as over surfaces covered by nano- or microscale gas bubbles.Comment: 11 pages, 6 figure