Holocene settlement shifts and paleoenvironments on the Central Iranian Plateau: investigating linked systems

For thousands of years, humans have inhabited locations that are highly vulnerable to the impacts of climate change, earthquakes, and floods. In order to investigate the extent to which Holocene environmental changes may have impacted on cultural evolution, we present new geologic, geomorphic, and chronologic data from the Qazvin Plain in northwest Iran that provides a backdrop of natural environmental changes for the simultaneous cultural dynamics observed on the Central Iranian Plateau. Well-resolved archaeological data from the neighbouring settlements of Zagheh (7170—6300 yr BP), Ghabristan (6215—4950 yr BP) and Sagzabad (4050—2350 yr BP) indicate that Holocene occupation of the Hajiarab alluvial fan was interrupted by a 900 year settlement hiatus. Multiproxy climate data from nearby lakes in northwest Iran suggest a transition from arid early-Holocene conditions to more humid middle-Holocene conditions from c. 7550 to 6750 yr BP, coinciding with the settlement of Zagheh, and a peak in aridity at c. 4550 yr BP during the settlement hiatus. Palaeoseismic investigations indicate that large active fault systems in close proximity to the tell sites incurred a series of large (MW ~7.1) earthquakes with return periods of ~500—1000 years during human occupation of the tells. Mapping and optically stimulated luminescence (OSL) chronology of the alluvial sequences reveals changes in depositional style from coarse-grained unconfined sheet flow deposits to proximal channel flow and distally prograding alluvial deposits sometime after c. 8830 yr BP, possibly reflecting an increase in moisture following the early-Holocene arid phase. The coincidence of major climate changes, earthquake activity, and varying sedimentation styles with changing patterns of human occupation on the Hajiarab fan indicate links between environmental and anthropogenic systems. However, temporal coincidence does not necessitate a fundamental causative dependency.

A 96-well plate fluorescence assay for assessment of cellular permeability and active efflux in Salmonella enterica serovar Typhimurium and Escherichia coli

Multiply antibiotic-resistant (MAR) mutants of Escherichia coli and Salmonella enterica are characterized by reduced susceptibility to several unrelated antibiotics, biocides and other xenobiotics. Porin loss and/or active efflux have been identified as a key mechanisms of MAR. A single rapid test was developed for MAR. The intracellular accumulation of the fluorescent probe Hoechst (H) 33342 (bisbenzimide) by MAR mutants and those with defined disruptions in efflux pump and porin genes was determined in 96-well plate format. The accumulation of H33342 was significantly (P < 0.0001) reduced in MAR mutants of S. enterica serovar Typhimurium (n = 4) and E. coli (n = 3) by 41 +/- 8% and 17.3 +/- 7.2%, respectively, compared with their parental strains, which was reversed by the transmembrane proton gradient-collapsing agent carbonyl cyanide-m-chlorophenyl hydrazone (CCCP) and the efflux pump inhibitor phenylalanine-arginine-beta-naphthylamide (PA beta N). The accumulation of H33342 was significantly reduced in mutants of Salmonella Typhimurium with defined disruptions in genes encoding the porins OmpC, OmpF, OmpX and OmpW, but increased in those with disruptions in efflux pump components TolC, AcrB and AcrF. Reduced accumulation of H33342 in three other MAR mutants of Salmonella Typhimurium correlated with the expression of porin and efflux pump proteins. The intracellular accumulation of H33342 provided a sensitive and specific test for MAR that is cheap and relatively rapid. Differential sensitivity to CCCP and PA beta N provided a further means to phenotypically identify MAR mutants and the role of active efflux in each strain.

Passive and active hybrid approach to buildings design in Saudi Arabia

The building sector is one of the highest consumers of energy in the world. This has led to high dependency on using fossil fuel to supply energy without due consideration to its environmental impact. Saudi Arabia has been through rapid development accompanied by population growth, which in turn has increased the demand for construction. However, this fast development has been met without considering sustainable building design. General design practices rely on using international design approaches and features without considering the local climate and aspects of traditional passive design. This is by constructing buildings with a large amount of glass fully exposed to solar radiation. The aim of this paper is to investigate the development of sustainability in passive design and vernacular architecture. Furthermore, it compares them with current building in Saudi Arabia in terms of making the most of the climate. Moreover, it will explore the most sustainable renewable energy that can be used to reduce the environmental impact on modern building in Saudi Arabia. This will be carried out using case studies demonstrating the performance of vernacular design in Saudi Arabia and thus its benefits in terms of environmental, economic and social sustainability. It argues that the adoption of a hybrid approach can improve the energy efficiency as well as reduce the carbon footprint of buildings. This is by combining passive design, learning from the vernacular architecture and implementing innovative sustainable technologies.

Identification of critical residues in the active site of porcine membrane-bound aminopeptidase P

The membrane-bound form of mammalian aminopeptidase P (AP-P; EC 3.4. 11.9) is a mono-zinc-containing enzyme that lacks any of the typical metal binding motifs found in other zinc metalloproteases. To identify residues involved in metal binding and catalysis, sequence and structural information was used to align the sequence of porcine membrane-bound AP-P with other members of the peptidase clan MG, including Escherichia coli AP-P and methionyl aminopeptidases. Residues predicted to be critical for activity were mutated and the resultant proteins were expressed in COS-1 cells. Immunoelectrophoretic blot analysis was used to compare the levels of expression of the mutant proteins, and their ability to hydrolyze bradykinin and Gly-Pro-hydroxyPro was assessed. Asp449, Asp460, His523, Glu554, and Glu568 are predicted to serve as metal ion ligands in the active site, and mutagenesis of these residues resulted in fully glycosylated proteins that were catalytically inactive. Mutation of His429 and His532 also resulted in catalytically inactive proteins, and these residues, by analogy with E. coli AP-P, are likely to play a role in shuttling protons during catalysis. These studies indicate that mammalian membrane-bound AP-P has an active-site configuration similar to that of other members of the peptidase clan MG, which is compatible with either a dual metal ion model or a single metal ion in the active site. The latter model is consistent, however, with the known metal stoichiometry of both the membrane-bound and cytosolic forms of AP-P and with a recently proposed model for methionyl aminopeptidase.

Redox-active, dinuclear sandwich compounds [Cp*Fe(μ-L)FeCp*] (L = naphthalene and anthracene)

Although there has been much interest in the chemistry of bimetallic transition metal complexes, compounds with naphthalene or anthracene as bridging ligands are still rare. In this article, we describe the synthesis of the homodinuclear iron complexes [Cp*Fe(μ-η4:η4-L)FeCp*] (1: L = C10H8, 2: L = C14H10; Cp* = η5-C5Me5). The complexes were characterized by 1H and 13C{1H} NMR, UV/Vis, and 57Fe Mössbauer spectroscopy, and their molecular structures were determined by X-ray crystallography. Both complexes are diamagnetic as a result of the strong magnetic coupling of the 17e FeI centers mediated by the polyarene bridge. An analysisof the redox behavior of 1 and 2 by cyclic voltammetry andUV/Vis spectroelectrochemistry shows that the complexes can be oxidized reversibly in two well-separated one-electron steps to the monocation [Cp*Fe(μ-L)FeCp*]+ and the dication [Cp*Fe(μ-L)FeCp*]2+. The reduction to the monoanion [Cp*Fe(μ-L)FeCp*]– was also observed.

Janus PEG-based dendrimers for use in combination therapy: controlled multi-drug loading and sequential release

The increasing use of drug combinations to treat disease states, such as cancer, calls for improved delivery systems that are able to deliver multiple agents. Herein, we report a series of novel Janus dendrimers with potential for use in combination therapy. Different generations (first and second) of PEG-based dendrons containing two different “model drugs”, benzyl alcohol (BA) and 3-phenylpropionic acid (PPA), were synthesized. BA and PPA were attached via two different linkers (carbonate and ester, respectively) to promote differential drug release. The four dendrons were coupled together via (3 + 2) cycloaddition chemistries to afford four Janus dendrimers, which contained varying amounts and different ratios of BA and PPA, namely, (BA)2-G1-G1-(PPA)2, (BA)4-G2-G1-(PPA)2, (BA)2-G1-G2-(PPA)4, and (BA)4-G2-G2-(PPA)4. Release studies in plasma showed that the dendrimers provided sequential release of the two model drugs, with BA being released faster than PPA from all of the dendrons. The different dendrimers allowed delivery of increasing amounts (0.15–0.30 mM) and in exact molecular ratios (1:2; 2:1; 1:2; 2:2) of the two model drug compounds. The dendrimers were noncytotoxic (100% viability at 1 mg/mL) toward human umbilical vein endothelial cells (HUVEC) and nontoxic toward red blood cells, as confirmed by hemolysis studies. These studies demonstrate that these Janus PEG-based dendrimers offer great potential for the delivery of drugs via combination therapy.

The extratropical upper troposphere and lower stratosphere

The extratropical upper troposphere and lower stratosphere (Ex-UTLS) is a transition region between the stratosphere and the troposphere. The Ex-UTLS includes the tropopause, a strong static stability gradient and dynamic barrier to transport. The barrier is reflected in tracer profiles. This region exhibits complex dynamical, radiative, and chemical characteristics that place stringent spatial and temporal requirements on observing and modeling systems. The Ex-UTLS couples the stratosphere to the troposphere through chemical constituent transport (of, e.g., ozone), by dynamically linking the stratospheric circulation with tropospheric wave patterns, and via radiative processes tied to optically thick clouds and clear-sky gradients of radiatively active gases. A comprehensive picture of the Ex-UTLS is presented that brings together different definitions of the tropopause, focusing on observed dynamical and chemical structure and their coupling. This integral view recognizes that thermal gradients and dynamic barriers are necessarily linked, that these barriers inhibit mixing and give rise to specific trace gas distributions, and that there are radiative feedbacks that help maintain this structure. The impacts of 21st century anthropogenic changes to the atmosphere due to ozone recovery and climate change will be felt in the Ex-UTLS, and recent simulations of these effects are summarized and placed in context.

Electro-active nanofibres electrospun from blends of poly-vinyl cinnamate and a cholesteric liquid crystalline silicone polymer

Electrospinning was used to generate polymer nanofibres from blends of poly-vinyl cinnamate (PVCN) and a cholesteric silicone polymer. Only blends that contained at least 40 % of PVCN produced fibres. Both differential scanning calorimetry and electron dispersion spectroscopy data indicate that the samples are miscible over a wide temperature interval. The variation of fibre diameter with concentration is nonlinear with a well-defined minimum corresponding to an 80 % PVCN blend. The fibres are birefringent with Kerr constants similar to that of cholesteric liquid crystals. Although not significant, the Kerr constant increases with increasing silicone polymer concentration.

Optimisation of recombinant production of active human cardiac SERCA2a ATPase

Methods for recombinant production of eukaryotic membrane proteins, yielding sufficient quantity and quality of protein for structural biology, remain a challenge. We describe here, expression and purification optimisation of the human SERCA2a cardiac isoform of Ca2+ translocating ATPase, using Saccharomyces cerevisiae as the heterologous expression system of choice. Two different expression vectors were utilised, allowing expression of C-terminal fusion proteins with a biotinylation domain or a GFP- His8 tag. Solubilised membrane fractions containing the protein of interest were purified onto Streptavidin-Sepharose, Ni-NTA or Talon resin, depending on the fusion tag present. Biotinylated protein was detected using specific antibody directed against SERCA2 and, advantageously, GFP-His8 fusion protein was easily traced during the purification steps using in-gel fluorescence. Importantly, talon resin affinity purification proved more specific than Ni-NTA resin for the GFP-His8 tagged protein, providing better separation of oligomers present, during size exclusion chromatography. The optimised method for expression and purification of human cardiac SERCA2a reported herein, yields purified protein (> 90%) that displays a calcium-dependent thapsigargin-sensitive activity and is suitable for further biophysical, structural and physiological studies. This work provides support for the use of Saccharomyces cerevisiae as a suitable expression system for recombinant production of multi-domain eukaryotic membrane proteins.

Mixing apples with oranges? Partisanship and active labour market policies in Europe

There are competing theoretical expectations and conflicting empirical results concerning the impact of partisanship on spending on active labour market policies (ALMPs). This paper argues that one should distinguish between different ALMPs. Employment incentives and rehabilitation programmes incentivize the unemployed to accept jobs. Direct job creation reduces the supply of labour by creating non-commercial jobs. Training schemes raise the human capital of the unemployed. Using regression analysis this paper shows that the positions of political parties towards these three types of ALMPs are different. Party preferences also depend on the welfare regime in which parties are located. In Scandinavia, left-wing parties support neither employment incentives nor direct job creation schemes. In continental and Liberal welfare regimes, left-wing parties oppose employment incentives and rehabilitation programmes to a lesser extent and they support direct job creation. There is no impact of partisanship on training. These results reconcile the previously contradictory findings concerning the impact of the Left on ALMPs.