Recombinant expression of Streptococcus pneumoniae capsular polysaccharides in Escherichia coli.

Currently, Streptococcus pneumoniae is responsible for over 14 million cases of pneumonia worldwide annually, and over 1 million deaths, the majority of them children. The major determinant for pathogenesis is a polysaccharide capsule that is variable and is used to distinguish strains based on their serotype. The capsule forms the basis of the pneumococcal polysaccharide vaccine (PPV23) that contains purified capsular polysaccharide from 23 serotypes, and the pneumococcal conjugate vaccine (PCV13), containing 13 common serotypes conjugated to CRM197 (mutant diphtheria toxin). Purified capsule from S. pneumoniae is required for pneumococcal conjugate vaccine production, and costs can be prohibitively high, limiting accessibility of the vaccine in low-income countries. In this study, we demonstrate the recombinant expression of the capsule-encoding locus from four different serotypes of S. pneumoniae within Escherichia coli. Furthermore, we attempt to identify the minimum set of genes necessary to reliably and efficiently express these capsules heterologously. These E. coli strains could be used to produce a supply of S. pneumoniae serotype-specific capsules without the need to culture pathogenic bacteria. Additionally, these strains could be applied to synthetic glycobiological applications: recombinant vaccine production using E. coli outer membrane vesicles or coupling to proteins using protein glycan coupling technology

p-wave Holographic Superconductors and five-dimensional gauged Supergravity

We explore five-dimensional ${\cal N}=4$ $SU(2)\times U(1)$ and ${\cal N}=8$ SO(6) gauged supergravities as frameworks for condensed matter applications. These theories contain charged (dilatonic) black holes and 2-forms which have non-trivial quantum numbers with respect to U(1) subgroups of SO(6). A question of interest is whether they also contain black holes with two-form hair with the required asymptotic to give rise to holographic superconductivity. We first consider the ${\cal N}=4$ case, which contains a complex two-form potential $A_{\mu\nu}$ which has U(1) charge $\pm 1$. We find that a slight generalization, where the two-form potential has an arbitrary charge $q$, leads to a five-dimensional model that exhibits second-order superconducting transitions of p-wave type where the role of order parameter is played by $A_{\mu\nu}$, provided $q \gtrsim 5.6$. We identify the operator that condenses in the dual CFT, which is closely related to ${\cal N}=4$ Super Yang-Mills theory with chemical potentials. Similar phase transitions between R-charged black holes and black holes with 2-form hair are found in a generalized version of the ${\cal N}=8$ gauged supergravity Lagrangian where the two-forms have charge $q\gtrsim 1.8$.Comment: 35 pages, 14 figure

Low temperature properties of holographic condensates

In the current work we study various models of holographic superconductors at low temperature. Generically the zero temperature limit of those models are solitonic solution with a zero sized horizon. Here we generalized simple version of those zero temperature solutions to small but non-zero temperature T. We confine ourselves to cases where near horizon geometry is AdS^4. At a non-zero temperature a small horizon would form deep inside this AdS^4 which does not disturb the UV physics. The resulting geometry may be matched with the zero temperature solution at an intermediate length scale. We understand this matching from separation of scales by setting up a perturbative expansion in gauge potential. We have a better analytic control in abelian case and quantities may be expressed in terms of hypergeometric function. From this we calculate low temperature behavior of various quatities like entropy, charge density and specific heat etc. We also calculate various energy gaps associated with p-wave holographic superconductor to understand the underlying pairing mechanism. The result deviates significantly from the corresponding weak coupling BCS counterpart.Comment: 17 Page

The Rich Structure of Gauss-Bonnet Holographic Superconductors

We study fully backreacting, Gauss-Bonnet (GB) holographic superconductors in 5 bulk spacetime dimensions. We explore the system's dependence on the scalar mass for both positive and negative GB coupling, $\alpha$. We find that when the mass approaches the Breitenlohner-Freedman (BF) bound and $\alpha\rightarrow L^2/4$ the effect of backreaction is to increase the critical temperature, $T_c$, of the system: the opposite of its effect in the rest of parameter space. We also find that reducing $\alpha$ below zero increases $T_c$ and that the effect of backreaction is diminished. We study the zero temperature limit, proving that this system does not permit regular solutions for a non-trivial, tachyonic scalar field and constrain possible solutions for fields with positive masses. We investigate singular, zero temperature solutions in the Einstein limit but find them to be incompatible with the concept of GB gravity being a perturbative expansion of Einstein gravity. We study the conductivity of the system, finding that the inclusion of backreaction hinders the development of poles in the conductivity that are associated with quasi-normal modes approaching the real axis from elsewhere in the complex plane.Comment: 26 pages, 11 figures, V3, Added discussion of non-tachyonic scalars, alterations to figures and tex

Higher Derivative BLG: Lagrangian and Supersymmetry Transformations

Working to lowest non-trivial order in fermions, we consider the four-derivative order corrected Lagrangian and supersymmetry transformations of the Euclidean Bagger-Lambert-Gustavsson theory. By demonstrating supersymmetric invariance of the Lagrangian we determine all numerical coefficients in the system. In addition, the supersymmetry algebra is shown to close on the scalar and gauge fields. We also comment on the extension to Lorentzian and other non-Euclidean $\mathcal{N}=8$ 3-algebra theories.Comment: 23 page

Endothelin receptor B antagonists decrease glioma cell viability independently of their cognate receptor

Background: Endothelin receptor antagonists inhibit the progression of many cancers, but research into their influence on glioma has been limited. Methods: We treated glioma cell lines, LN-229 and SW1088, and melanoma cell lines, A375 and WM35, with two endothelin receptor type B (ETRB)-specific antagonists, A-192621 and BQ788, and quantified viable cells by the capacity of their intracellular esterases to convert non-fluorescent calcein AM into green-fluorescent calcein. We assessed cell proliferation by labeling cells with carboxyfluorescein diacetate succinimidyl ester and quantifying the fluorescence by FACS analysis. We also examined the cell cycle status using BrdU/propidium iodide double staining and FACS analysis. We evaluated changes in gene expression by microarray analysis following treatment with A-192621 in glioma cells. We examined the role of ETRB by reducing its expression level using small interfering RNA (siRNA). Results: We report that two ETRB-specific antagonists, A-192621 and BQ788, reduce the number of viable cells in two glioma cell lines in a dose- and time-dependent manner. We describe similar results for two melanoma cell lines. The more potent of the two antagonists, A-192621, decreases the mean number of cell divisions at least in part by inducing a G2/M arrest and apoptosis. Microarray analysis of the effects of A-192621 treatment reveals up-regulation of several DNA damage-inducible genes. These results were confirmed by real-time RT-PCR. Importantly, reducing expression of ETRB with siRNAs does not abrogate the effects of either A-192621 or BQ788 in glioma or melanoma cells. Furthermore, BQ123, an endothelin receptor type A (ETRA)-specific antagonist, has no effect on cell viability in any of these cell lines, indicating that the ETRB-independent effects on cell viability exhibited by A-192621 and BQ788 are not a result of ETRA inhibition. Conclusion: While ETRB antagonists reduce the viability of glioma cells in vitro, it appears unlikely that this effect is mediated by ETRB inhibition or cross-reaction with ETRA. Instead, we present evidence that A-192621 affects glioma and melanoma viability by activating stress/DNA damage response pathways, which leads to cell cycle arrest and apoptosis. This is the first evidence linking ETRB antagonist treatment to enhanced expression of DNA damage-inducible genes

Mathematical modeling of the metastatic process

Mathematical modeling in cancer has been growing in popularity and impact since its inception in 1932. The first theoretical mathematical modeling in cancer research was focused on understanding tumor growth laws and has grown to include the competition between healthy and normal tissue, carcinogenesis, therapy and metastasis. It is the latter topic, metastasis, on which we will focus this short review, specifically discussing various computational and mathematical models of different portions of the metastatic process, including: the emergence of the metastatic phenotype, the timing and size distribution of metastases, the factors that influence the dormancy of micrometastases and patterns of spread from a given primary tumor.Comment: 24 pages, 6 figures, Revie

Revisiting soliton contributions to perturbative amplitudes

Open Access funded by SCOAP3. CP is a Royal Society Research Fellow and partly supported by the U.S. Department of Energy under grants DOE-SC0010008, DOE-ARRA-SC0003883 and DOE-DE-SC0007897. ABR is supported by the Mitchell Family Foundation. We would like to thank the Mitchell Institute at Texas A&M and the NHETC at Rutgers University respectively for hospitality during the course of this work. We would also like to acknowledge the Aspen Center for Physics and NSF grant 1066293 for a stimulating research environment

Democratic experimentation in early childhood education

Qualifications of the early years workforce are a salient predictors of quality and therefore of children’s outcomes. International reports advise that a majority of staff is trained at Bachelor’s levels and rank countries according to this criterion. There is fewer consensus on what this professionalism should be. In a majority of countries, large numbers of professionals are untrained, unqualified and sometimes invisible in the official reports. Many of these unqualified “assistants” take up crucial “care” tasks, while the teacher’s tasks are defined as “education”. The separation between care and education occurs in split systems as well as in systems where education and care are supposed to be integrated. In addition, the growing diversity of families challenges our preconceived ideas about “the good life” for children. These observations urge us to rethink professionalism in terms of reflexivity and the capacity of co-constructing pedagogy with parents and children. A case study in Ghent shows how low qualified professionals develop research capacities. The analysis of their experience suggests that “learning” may be less a quality of the individual than a quality of the systemic relationships that are build in the teams as well as in the interaction between teams and their social contexts

Subclinical thyroid dysfunction and cognitive decline in old age

<p>Background: Subclinical thyroid dysfunction has been implicated as a risk factor for cognitive decline in old age, but results are inconsistent. We investigated the association between subclinical thyroid dysfunction and cognitive decline in the PROspective Study of Pravastatin in the Elderly at Risk (PROSPER).</p> <p>Methods: Prospective longitudinal study of men and women aged 70–82 years with pre-existing vascular disease or more than one risk factor to develop this condition (N = 5,154). Participants taking antithyroid medications, thyroid hormone supplementation and/or amiodarone were excluded. Thyroid function was measured at baseline: subclinical hyper- and hypothyroidism were defined as thyroid stimulating hormones (TSH) <0.45 mU/L or >4.50 mU/L respectively, with normal levels of free thyroxine (FT4). Cognitive performance was tested at baseline and at four subsequent time points during a mean follow-up of 3 years, using five neuropsychological performance tests.</p> <p>Results: Subclinical hyperthyroidism and hypothyroidism were found in 65 and 161 participants, respectively. We found no consistent association of subclinical hyper- or hypothyroidism with altered cognitive performance compared to euthyroid participants on the individual cognitive tests. Similarly, there was no association with rate of cognitive decline during follow-up.</p> <p>Conclusion: We found no consistent evidence that subclinical hyper- or hypothyroidism contribute to cognitive impairment or decline in old age. Although our data are not in support of treatment of subclinical thyroid dysfunction to prevent cognitive dysfunction in later life, only large randomized controlled trials can provide definitive evidence.</p&gt