Benzene-1,4-diol–5-(1H-imidazol-1-yl)pyrimidine (1/1)

The asymmetric unit of title compound, C7H6N4·C6H6O2, contains one 5-(1H-imidazol-1-yl)pyrimidine mol­ecule and two half benzene-1,4-diol mol­ecules; the benzene-1,4-diol mol­ecules are located on individual inversion centers. In the pyrimidine mol­ecule, the imidazole ring is twisted with respect to the pyrimidine ring at a dihedral angle of 25.73 (7)°. In the crystal, O—H⋯N hydrogen bonds link the mol­ecules to form supra­molecular chains. π–π stacking is also observed in the crystal, the centroid–centroid distance between parallel imdazole rings being 3.5543 (16) Å

Effect on survey response rate of hand written versus printed signature on a covering letter: randomised controlled trial [ISRCTN67566265]

BACKGROUND: It is important that response rates to postal surveys are as high as possible to ensure that the results are representative and to maximise statistical power. Previous research has suggested that any personalisation of approach helps to improve the response rate. This experiment tested whether personalising questionnaires by hand signing the covering letter improved the response rate compared with a non-personalised group where the investigator's signature on the covering letter was scanned into the document and printed. METHODS: Randomised controlled trial. Questionnaires about surgical techniques of caesarean section were mailed to 3,799 Members and Fellows of the Royal College of Obstetricians and Gynaecologists resident in the UK. Individuals were randomly allocated to receive a covering letter with either a computer printed signature or a hand written signature. Two reminders were sent to non-respondents. The outcome measures were the proportion of questionnaires returned and their time to return. RESULTS: The response rate was 79.1% (1506/1905) in the hand-signed group and 78.4% (1484/1894) in the scanned and printed signature group. There was no detectable difference between the groups in response rate or time taken to respond. CONCLUSION: No advantage was detected to hand signing the covering letter accompanying a postal questionnaire to health professionals

Neutrophil depletion reduces edema formation and tissue loss following traumatic brain injury in mice

Background: Brain edema as a result of secondary injury following traumatic brain injury (TBI) is a major clinical concern. Neutrophils are known to cause increased vascular permeability leading to edema formation in peripheral tissue, but their role in the pathology following TBI remains unclear. Methods: In this study we used controlled cortical impact (CCI) as a model for TBI and investigated the role of neutrophils in the response to injury. The outcome of mice that were depleted of neutrophils using an anti-Gr-1 antibody was compared to that in mice with intact neutrophil count. The effect of neutrophil depletion on blood-brain barrier function was assessed by Evan's blue dye extravasation, and analysis of brain water content was used as a measurement of brain edema formation (24 and 48 hours after CCI). Lesion volume was measured 7 and 14 days after CCI. Immunohistochemistry was used to assess cell death, using a marker for cleaved caspase-3 at 24 hours after injury, and microglial/macrophage activation 7 days after CCI. Data were analyzed using Mann-Whitney test for non-parametric data. Results: Neutrophil depletion did not significantly affect Evan's blue extravasation at any time-point after CCI. However, neutrophil-depleted mice exhibited a decreased water content both at 24 and 48 hours after CCI indicating reduced edema formation. Furthermore, brain tissue loss was attenuated in neutropenic mice at 7 and 14 days after injury. Additionally, these mice had a significantly reduced number of activated microglia/macrophages 7 days after CCI, and of cleaved caspase-3 positive cells 24 h after injury. Conclusion: Our results suggest that neutrophils are involved in the edema formation, but not the extravasation of large proteins, as well as contributing to cell death and tissue loss following TBI in mice

Mesoscopic models for DNA stretching under force: new results and comparison to experiments

Single molecule experiments on B-DNA stretching have revealed one or two structural transitions, when increasing the external force. They are characterized by a sudden increase of DNA contour length and a decrease of the bending rigidity. It has been proposed that the first transition, at forces of 60--80 pN, is a transition from B to S-DNA, viewed as a stretched duplex DNA, while the second one, at stronger forces, is a strand peeling resulting in single stranded DNAs (ssDNA), similar to thermal denaturation. But due to experimental conditions these two transitions can overlap, for instance for poly(dA-dT). We derive analytical formula using a coupled discrete worm like chain-Ising model. Our model takes into account bending rigidity, discreteness of the chain, linear and non-linear (for ssDNA) bond stretching. In the limit of zero force, this model simplifies into a coupled model already developed by us for studying thermal DNA melting, establishing a connexion with previous fitting parameter values for denaturation profiles. We find that: (i) ssDNA is fitted, using an analytical formula, over a nanoNewton range with only three free parameters, the contour length, the bending modulus and the monomer size; (ii) a surprisingly good fit on this force range is possible only by choosing a monomer size of 0.2 nm, almost 4 times smaller than the ssDNA nucleobase length; (iii) mesoscopic models are not able to fit B to ssDNA (or S to ss) transitions; (iv) an analytical formula for fitting B to S transitions is derived in the strong force approximation and for long DNAs, which is in excellent agreement with exact transfer matrix calculations; (v) this formula fits perfectly well poly(dG-dC) and $\lambda$-DNA force-extension curves with consistent parameter values; (vi) a coherent picture, where S to ssDNA transitions are much more sensitive to base-pair sequence than the B to S one, emerges.Comment: 14 pages, 9 figure

Narrowband Biphotons: Generation, Manipulation, and Applications

In this chapter, we review recent advances in generating narrowband biphotons with long coherence time using spontaneous parametric interaction in monolithic cavity with cluster effect as well as in cold atoms with electromagnetically induced transparency. Engineering and manipulating the temporal waveforms of these long biphotons provide efficient means for controlling light-matter quantum interaction at the single-photon level. We also review recent experiments using temporally long biphotons and single photons.Comment: to appear as a book chapter in a compilation "Engineering the Atom-Photon Interaction" published by Springer in 2015, edited by A. Predojevic and M. W. Mitchel

Deterministic processes structure bacterial genetic communities across an urban landscape

Land-use change is predicted to act as a driver of zoonotic disease emergence through human exposure to novel microbial diversity, but evidence for the effects of environmental change on microbial communities in vertebrates is lacking. We sample wild birds at 99 wildlife-livestock-human interfaces across Nairobi, Kenya, and use whole genome sequencing to characterise bacterial genes known to be carried on mobile genetic elements (MGEs) within avian-borne Escherichia coli (n=241). By modelling the diversity of bacterial genes encoding virulence and antimicrobial resistance (AMR) against ecological and anthropogenic forms of urban environmental change, we demonstrate that communities of avian-borne bacterial genes are shaped by the assemblage of co-existing avian, livestock and human communities, and the habitat within which they exist. In showing that non-random processes structure bacterial genetic communities in urban wildlife, these findings suggest that it should be possible to forecast the effects of urban land-use change on microbial diversity

Elastic properties and secondary structure formation of single-stranded DNA at monovalent and divalent salt conditions

Single-stranded DNA (ssDNA) plays a major role in several biological processes. It is therefore of fundamental interest to understand how the elastic response and the formation of secondary structures are modulated by the interplay between base pairing and electrostatic interactions. Here we measure force-extension curves (FECs) of ssDNA molecules in optical tweezers set up over two orders of magnitude of monovalent and divalent salt conditions, and obtain its elastic parameters by fitting the FECs to semiflexible models of polymers. For both monovalent and divalent salts, we find that the electrostatic contribution to the persistence length is proportional to the Debye screening length, varying as the inverse of the square root of cation concentration. The intrinsic persistence length is equal to 0.7 nm for both types of salts, and the effectivity of divalent cations in screening electrostatic interactions appears to be 100-fold as compared with monovalent salt, in line with what has been recently reported for single-stranded RNA. Finally, we propose an analysis of the FECs using a model that accounts for the effective thickness of the filament at low salt condition and a simple phenomenological description that quantifies the formation of non-specific secondary structure at low forces

Linking a dermal permeation and an inhalation model to a simple pharmacokinetic model to study airborne exposure to di(n-butyl) phthalate

Six males clad only in shorts were exposed to high levels of airborne di(n-butyl) phthalate (DnBP) and diethyl phthalate (DEP) in chamber experiments conducted in 2014. In two 6 h sessions, the subjects were exposed only dermally while breathing clean air from a hood, and both dermally and via inhalation when exposed without a hood. Full urine samples were taken before, during, and for 48 h after leaving the chamber and measured for key DnBP and DEP metabolites. The data clearly demonstrated high levels of DnBP and DEP metabolite excretions while in the chamber and during the first 24 h once leaving the chamber under both conditions. The data for DnBP were used in a modeling exercise linking dose models for inhalation and transdermal permeation with a simple pharmacokinetic model that predicted timing and mass of metabolite excretions. These models were developed and calibrated independent of these experiments. Tests included modeling of the “hood-on” (transdermal penetration only), “hood-off” (both inhalation and transdermal) scenarios, and a derived “inhalation-only” scenario. Results showed that the linked model tended to duplicate the pattern of excretion with regard to timing of peaks, decline of concentrations over time, and the ratio of DnBP metabolites. However, the transdermal model tended to overpredict penetration of DnBP such that predictions of metabolite excretions were between 1.1 and 4.5 times higher than the cumulative excretion of DnBP metabolites over the 54 h of the simulation. A similar overprediction was not seen for the “inhalation-only” simulations. Possible explanations and model refinements for these overpredictions are discussed. In a demonstration of the linked model designed to characterize general population exposures to typical airborne indoor concentrations of DnBP in the United States, it was estimated that up to one-quarter of total exposures could be due to inhalation and dermal uptake

Identification of an N-terminal 27 kDa fragment of Mycoplasma pneumoniae P116 protein as specific immunogen in M. pneumoniae infections

<p>Abstract</p> <p>Background</p> <p><it>Mycoplasma pneumoniae </it>is an important cause of respiratory tract infection and is increasingly being associated with other diseases such as asthma and extra-pulmonary complications. Considerable cross-reactivity is known to exist between the whole cell antigens used in the commercial serological testing assays. Identification of specific antigens is important to eliminate the risk of cross-reactions among different related organisms. Adherence of <it>M. pneumoniae </it>to human epithelial cells is mediated through a well defined apical organelle to which a number of proteins such as P1, P30, P116 and HMW1-3 have been localized, and are being investigated for adhesion, gliding and immunodiagnostic purposes.</p> <p>Methods</p> <p>A 609 bp fragment P116_(N-27),corresponding to the N-terminal region of <it>M. pneumoniae </it>P116 gene was cloned and expressed. A C-terminal fragment P1_(C-40),of P1 protein of <it>M. pneumoniae </it>was also expressed. Three IgM ELISA assays based on P116_(N-27),P1_(C-40)and (P116 _(N-27)+ P1_(C-40)) proteins were optimized and a detailed analysis comparing the reactivity of these proteins with a commercial kit was carried out. Comparative statistical analysis of these assays was performed with the SPSS version 15.0.</p> <p>Results</p> <p>The expressed P116_(N-27)protein was well recognized by the patient sera and was immunogenic in rabbit. P1_(C-40)of <it>M. pneumoniae </it>was also immunogenic in rabbit. In comparison to the reference kit, which is reported to be 100% sensitive and 75% specific, ELISA assay based on purified P116_(N-27),P1_(C-40)and (P116_(N-27)+ P1_(C-40)) proteins showed 90.3%, 87.1% and 96.8% sensitivity and 87.0%, 87.1% and 90.3% specificity respectively. The p value for all the three assays was found to be < 0.001, and there was a good correlation and association between them.</p> <p>Conclusion</p> <p>This study shows that an N-terminal fragment of P116 protein holds a promise for serodiagnosis of <it>M. pneumoniae </it>infection. The IgM ELISA assays based on the recombinant proteins seem to be suitable for the use in serodiagnosis of acute <it>M. pneumoniae </it>infections. The use of short recombinant fragments of P116 and P1 proteins as specific antigens may eliminate the risk of cross-reactions and help to develop a specific and sensitive immunodiagnostic assay for <it>M. pneumoniae </it>detection.</p