Engineered mosaic protein polymers; a simple route to multifunctional biomaterials

Abstract: Background: Engineered living materials (ELMs) are an exciting new frontier, where living organisms create highly functional materials. In particular, protein ELMs have the advantage that their properties can be manipulated via simple molecular biology. Caf1 is a protein ELM that is especially attractive as a biomaterial on account of its unique combination of properties: bacterial cells export it as a massive, modular, non-covalent polymer which is resistant to thermal and chemical degradation and free from animal material. Moreover, it is biologically inert, allowing the bioactivity of each 15 kDa monomeric Caf1 subunit to be specifically engineered by mutagenesis and co-expressed in the same Escherichia coli cell to produce a mixture of bioactive Caf1 subunits. Results: Here, we show by gel electrophoresis and transmission electron microscopy that the bacterial cells combine these subunits into true mosaic heteropolymers. By combining two separate bioactive motifs in a single mosaic polymer we demonstrate its utility by stimulating the early stages of bone formation by primary human bone marrow stromal cells. Finally, using a synthetic biology approach, we engineer a mosaic of three components, demonstrating that Caf1 complexity depends solely upon the variety of monomers available. Conclusions: These results demonstrate the utility of engineered Caf1 mosaic polymers as a simple route towards the production of multifunctional biomaterials that will be useful in biomedical applications such as 3D tissue culture and wound healing. Additionally, in situ Caf1 producing cells could create complex bacterial communities for biotechnology. Graphical abstract

Graphic Warning Labels Elicit Affective and Thoughtful Responses from Smokers: Results of a Randomized Clinical Trial

Objective Observational research suggests that placing graphic images on cigarette warning labels can reduce smoking rates, but field studies lack experimental control. Our primary objective was to determine the psychological processes set in motion by naturalistic exposure to graphic vs. text-only warnings in a randomized clinical trial involving exposure to modified cigarette packs over a 4-week period. Theories of graphic-warning impact were tested by examining affect toward smoking, credibility of warning information, risk perceptions, quit intentions, warning label memory, and smoking risk knowledge. Methods Adults who smoked between 5 and 40 cigarettes daily (N = 293; mean age = 33.7), did not have a contra-indicated medical condition, and did not intend to quit were recruited from Philadelphia, PA and Columbus, OH. Smokers were randomly assigned to receive their own brand of cigarettes for four weeks in one of three warning conditions: text only, graphic images plus text, or graphic images with elaborated text. Results Data from 244 participants who completed the trial were analyzed in structural-equation models. The presence of graphic images (compared to text-only) caused more negative affect toward smoking, a process that indirectly influenced risk perceptions and quit intentions (e.g., image-\u3enegative affect-\u3erisk perception-\u3equit intention). Negative affect from graphic images also enhanced warning credibility including through increased scrutiny of the warnings, a process that also indirectly affected risk perceptions and quit intentions (e.g., image-\u3enegative affect-\u3erisk scrutiny-\u3ewarning credibility-\u3erisk perception-\u3equit intention). Unexpectedly, elaborated text reduced warning credibility. Finally, graphic warnings increased warning-information recall and indirectly increased smoking-risk knowledge at the end of the trial and one month later. Conclusions In the first naturalistic clinical trial conducted, graphic warning labels are more effective than text-only warnings in encouraging smokers to consider quitting and in educating them about smoking’s risks. Negative affective reactions to smoking, thinking about risks, and perceptions of credibility are mediators of their impact

A Versatile Approach to Ullmann C−N Couplings at Room Temperature: New Families of Nucleophiles and Electrophiles for Photoinduced, Copper-Catalyzed Processes

The use of light to facilitate copper-catalyzed cross-couplings of nitrogen nucleophiles can enable C−N bond formation to occur under unusually mild conditions. In this study, we substantially expand the scope of such processes, establishing that this approach is not limited to reactions of carbazoles with iodobenzene and alkyl halides. Specifically, we demonstrate for the first time that other nitrogen nucleophiles (e.g., common pharmacophores such as indoles, benzimidazoles, and imidazoles) as well as other electrophiles (e.g., hindered/deactivated/heterocyclic aryl iodides, an aryl bromide, an activated aryl chloride, alkenyl halides, and an alkynyl bromide) serve as suitable partners. Photoinduced C−N bond formation can be achieved at room temperature using a common procedure with an inexpensive catalyst (CuI) that does not require a ligand coadditive and is tolerant of moisture and a variety of functional groups

Agri-Environmental Policy at the Crossroads: Guideposts on a Changing Landscape

Agri-environmental policy is at a crossroads. Over the past 20 years, a wide range of policies addressing the environmental implications of agricultural production have been implemented at the Federal level. Those policies have played an important role in reducing soil erosion, protecting and restoring wetlands, and creating wildlife habitat. However, emerging agri-environmental issues, evolution of farm income support policies, and limits imposed by trade agreements may point toward a rethinking of agri-environmental policy. This report identifies the types of policy tools available and the design features that have improved the effectiveness of current programs. It provides an indepth analysis of one policy tool that may be an important component of a future policy package-agri-environmental payments. The analysis focuses on issues and tradeoffs that policymakers would face in designing a program of agri-environmental payments.conservation programs, environmental policy, agricultural policy, policy instruments, agricultural program design, soil erosion, nitrogen runoff, Environmental Economics and Policy,

Properties and Detection of Spin Nematic Order in Strongly Correlated Electron Systems

A spin nematic is a state which breaks spin SU(2) symmetry while preserving translational and time reversal symmetries. Spin nematic order can arise naturally from charge fluctuations of a spin stripe state. Focusing on the possible existence of such a state in strongly correlated electron systems, we build a nematic wave function starting from a t-J type model. The nematic is a spin-two operator, and therefore does not couple directly to neutrons. However, we show that neutron scattering and Knight shift experiments can detect the spin anisotropy of electrons moving in a nematic background. We find the mean field phase diagram for the nematic taking into account spin-orbit effects.Comment: 13 pages, 11 figures. (v2) References adde

Effect of inhaled tacrolimus on ischemia reperfusion injury in rat lung transplant model

ObjectiveSystemic tacrolimus therapy has been shown to protect against lung ischemia-reperfusion injury in animal models. We sought to investigate on a functional and cellular level if inhaled nanoparticle tacrolimus administered to the donor lung before procurement could similarly attenuate ischemia-reperfusion injury after lung transplant.MethodsAn isogenic orthotopic rat model of single left lung transplant was used. Donor animals were pretreated with inhaled tacrolimus (treatment group) or inhaled lactose (controls) before lung procurement. Lung grafts were subjected to 3 hours of cold ischemia followed by 4 hours of reperfusion after graft implantation. Recipient animal arterial blood gas measurement and isograft wet to dry weight ratios were obtained. Macrophage, neutrophil, and T-cell accumulation and activation in lung isografts, including γδ T-cell, T-helper, and cytotoxic T-cell subtypes were analyzed by flow cytometry. Tacrolimus levels were measured in the lung isograft using liquid chromatography/mass spectrometry. Isograft cytokine levels were measured with commercial enzyme-linked immunosorbent assay and microbead array kits.ResultsOxygenation in treatment group animals was significantly higher than in controls. The presence of macrophages, neutrophils, and all T-cell subtypes in the isografts as well as isograft levels of inflammatory cytokines were all less in the treatment group versus controls, although no single variable achieved statistical significance.ConclusionsInhaled nanoparticle tacrolimus treatment of lung donors is associated with an attenuation of ischemia-reperfusion injury on a functional and cellular level in lung transplant

Approximating the inspiral of test bodies into Kerr black holes

We present a new approximate method for constructing gravitational radiation driven inspirals of test-bodies orbiting Kerr black holes. Such orbits can be fully described by a semi-latus rectum $p$, an eccentricity $e$, and an inclination angle $\iota$; or, by an energy $E$, an angular momentum component $L_z$, and a third constant $Q$. Our scheme uses expressions that are exact (within an adiabatic approximation) for the rates of change ($\dot{p}$, $\dot{e}$, $\dot{\iota}$) as linear combinations of the fluxes ($\dot{E}$, $\dot{L_z}$, $\dot{Q}$), but uses quadrupole-order formulae for these fluxes. This scheme thus encodes the exact orbital dynamics, augmenting it with approximate radiation reaction. Comparing inspiral trajectories, we find that this approximation agrees well with numerical results for the special cases of eccentric equatorial and circular inclined orbits, far more accurate than corresponding weak-field formulae for ($\dot{p}$, $\dot{e}$, $\dot{\iota}$). We use this technique to study the inspiral of a test-body in inclined, eccentric Kerr orbits. Our results should be useful tools for constructing approximate waveforms that can be used to study data analysis problems for the future LISA gravitational-wave observatory, in lieu of waveforms from more rigorous techniques that are currently under development.Comment: 15 pages, 5 figures, submitted to PR

The Sloan Digital Sky Survey Reverberation Mapping Project: Technical Overview

The Sloan Digital Sky Survey Reverberation Mapping project (SDSS-RM) is a dedicated multi-object RM experiment that has spectroscopically monitored a sample of 849 broad-line quasars in a single 7 deg$^2$ field with the SDSS-III BOSS spectrograph. The RM quasar sample is flux-limited to i_psf=21.7 mag, and covers a redshift range of 0.1<z<4.5. Optical spectroscopy was performed during 2014 Jan-Jul dark/grey time, with an average cadence of ~4 days, totaling more than 30 epochs. Supporting photometric monitoring in the g and i bands was conducted at multiple facilities including the CFHT and the Steward Observatory Bok telescopes in 2014, with a cadence of ~2 days and covering all lunar phases. The RM field (RA, DEC=14:14:49.00, +53:05:00.0) lies within the CFHT-LS W3 field, and coincides with the Pan-STARRS 1 (PS1) Medium Deep Field MD07, with three prior years of multi-band PS1 light curves. The SDSS-RM 6-month baseline program aims to detect time lags between the quasar continuum and broad line region (BLR) variability on timescales of up to several months (in the observed frame) for ~10% of the sample, and to anchor the time baseline for continued monitoring in the future to detect lags on longer timescales and at higher redshift. SDSS-RM is the first major program to systematically explore the potential of RM for broad-line quasars at z>0.3, and will investigate the prospects of RM with all major broad lines covered in optical spectroscopy. SDSS-RM will provide guidance on future multi-object RM campaigns on larger scales, and is aiming to deliver more than tens of BLR lag detections for a homogeneous sample of quasars. We describe the motivation, design and implementation of this program, and outline the science impact expected from the resulting data for RM and general quasar science.Comment: 25 pages, submitted to ApJS; project website at http://www.sdssrm.or

Support for children identified with acute flaccid paralysis under the global polio eradication programme in Uttar Pradesh, India: a qualitative study

Background Cases of polio in India declined after the implementation of the polio eradication programme especially in these recent years. The programme includes surveillance of acute flaccid paralysis (AFP) to detect and diagnose cases of polio at early stage. Under this surveillance, over 40,000 cases of AFP are reported annually since 2007 regardless of the number of actual polio cases. Yet, not much is known about these children. We conducted a qualitative research to explore care and support for children with AFP after their diagnosis. Methods The research was conducted in a district of western Uttar Pradesh classified as high-risk area for polio. In-depth interviews with parents of children with polio (17), with non-polio AFP (9), healthcare providers (40), and key informants from community including international and government officers, religious leaders, community leaders, journalists, and academics (21) were performed. Results Minimal medicine and attention were provided at government hospitals. Therefore, most parents preferred private-practice doctors for their children with AFP. Many were visited at homes to have stool samples collected by authorities. Some were visited repetitively following the sample collection, but had difficulty in understanding the reasons for these visits that pertained no treatment. Financial burden was a common concern among all families. Many parents expressed resentment for their children's disease, notably have been affected despite receiving multiple doses of polio vaccine. Both parents and healthcare providers lacked information and knowledge, furthermore poverty minimised the access to available healthcare services. Medicines, education, and transportation means were identified as foremost needs for children with AFP and residual paralysis. Conclusions Despite the high number of children diagnosed with AFP as part of the global polio eradication programme, we found they were not provided with sufficient medical support following their diagnosis. Improvement in the quality and sufficiency of the healthcare system together with integration of AFP surveillance with other services in these underprivileged areas may serve as a key solution