Mean-field density functional theory of a nanoconfined classical, three-dimensional Heisenberg fluid. II. The interplay between molecular packing and orientational order

This article may be downloaded for personal use only. Any other use requires prior permission of the author and AIP Publishing. This article appeared in J. Chem. Phys. 149, 054704 (2018) and may be found at https://doi.org/10.1063/1.5040934.As in Paper I of this series of papers [S. M. Cattes et al., J. Chem. Phys. 144, 194704 (2016)], we study a Heisenberg fluid confined to a nanoscopic slit pore with smooth walls. The pore walls can either energetically discriminate specific orientations of the molecules next to them or are indifferent to molecular orientations. Unlike in Paper I, we employ a version of classical density functional theory that allows us to explicitly account for the stratification of the fluid (i.e., the formation of molecular layers) as a consequence of the symmetry-breaking presence of the pore walls. We treat this stratification within the White Bear version (Mark I) of fundamental measure theory. Thus, in this work, we focus on the interplay between local packing of the molecules and orientational features. In particular, we demonstrate why a critical end point can only exist if the pore walls are not energetically discriminating specific molecular orientations. We analyze in detail the positional and orientational order of the confined fluid and show that reorienting molecules across the pore space can be a two-dimensional process. Last but not least, we propose an algorithm based upon a series expansion of Bessel functions of the first kind with which we can solve certain types of integrals in a very efficient manner.DFG, 65143814, GRK 1524: Self-Assembled Soft-Matter Nanostructures at Interface

Different origins of hydrocephalus lead to different shunt revision rates

Introduction Hydrocephalus (HC) occurs due to multiple origins. Time course and dynamic of HC and its therapies differ between underlying pathologies. Different revision rates due to the type of HC are expected. Though hydrocephalus is known to be a life time condition, the lack of shunt malfunction years or decades after initial shunt insertion raises the hope of a superfluous shunt. Methods We conducted a retrospective survey of our OR-database during a 10 year period. All newly inserted shunt systems and subsequent shunt revisions are recorded according to quantity and time point. All patients were subdivided according their aetiology of HC. Results 260 patients were eligible with a follow-up of 4.5 years. Subgroups were: 90 patients with NPH, 76 patients with posthaemorrhagic and 16 patients had posttraumatic HC. 22 received a shunt as a consequence of a tumour, 41 were children and 15 for other causes. Overall revision rate was 39.5%. During the first 6 months 55.6%, 57.9% and 75% of patients with NPH, posthaemorrhagic and posttraumatic HC had revisions. In contrast only 38.1% of children and 20% of tumour cases required early revision. Conclusion Two different patterns of revision are evident: mainly early revisions in morphologically stable diseases such as posthaemorrhagic, posttraumatic and NPH and predominantly late revisions in changing organisms such as children and tumour patients. The conception HC may be transient because of a lack of late revisions cannot be supported by this data

Chemical Chaperones Improve Protein Secretion and Rescue Mutant Factor VIII in Mice with Hemophilia A.

nefficient intracellular protein trafficking is a critical issue in the pathogenesis of a variety of diseases and in recombinant protein production. Here we investigated the trafficking of factor VIII (FVIII), which is affected in the coagulation disorder hemophilia A. We hypothesized that chemical chaperones may be useful to enhance folding and processing of FVIII in recombinant protein production, and as a therapeutic approach in patients with impaired FVIII secretion. A tagged B-domain-deleted version of human FVIII was expressed in cultured Chinese Hamster Ovary cells to mimic the industrial production of this important protein. Of several chemical chaperones tested, the addition of betaine resulted in increased secretion of FVIII, by increasing solubility of intracellular FVIII aggregates and improving transport from endoplasmic reticulum to Golgi. Similar results were obtained in experiments monitoring recombinant full-length FVIII. Oral betaine administration also increased FVIII and factor IX (FIX) plasma levels in FVIII or FIX knockout mice following gene transfer. Moreover, in vitro and in vivo applications of betaine were also able to rescue a trafficking-defective FVIII mutant (FVIIIQ305P). We conclude that chemical chaperones such as betaine might represent a useful treatment concept for hemophilia and other diseases caused by deficient intracellular protein trafficking

Characterization of neutralizing epitopes within the major capsid protein of human papillomavirus type 33

BACKGROUND: Infections with papillomaviruses induce type-specific immune responses, mainly directed against the major capsid protein, L1. Based on the propensity of the L1 protein to self-assemble into virus-like particles (VLPs), type-specific vaccines have already been developed. In order to generate vaccines that target a broader spectrum of HPV types, extended knowledge of neutralizing epitopes is required. Despite the association of human papillomavirus type 33 (HPV33) with cervical carcinomas, fine mapping of neutralizing conformational epitopes on HPV33 has not been reported yet. By loop swapping between HPV33 and HPV16 capsid proteins, we have identified amino acid sequences critical for the binding of conformation-dependent type-specific neutralizing antibodies to surface-exposed hyper variable loops of HPV33 capsid protein L1. RESULTS: Reactivities of monoclonal antibodies (mAbs) H33.B6, H33.E12, H33.J3 and H16.56E with HPV16:33 and HPV33:16 hybrid L1 VLPs revealed the complex structures of their conformational epitopes as well as the major residues contributing to their binding sites. Whereas the epitope of mAb H33.J3 was determined by amino acids (aa) 51–58 in the BC loop of HPV33 L1, sequences of at least two hyper variable loops, DE (aa 132–140) and FGb (aa 282–291), were found to be essential for binding of H33.B6. The epitope of H33.E12 was even more complex, requiring sequences of the FGa loop (aa 260–270), in addition to loops DE and FGb. CONCLUSION: These data demonstrate that neutralizing epitopes in HPV33 L1 are mainly located on the tip of the capsomere and that several hyper variable loops contribute to form these conformational epitopes. Knowledge of the antigenic structure of HPV is crucial for designing hybrid particles as a basis for intertypic HPV vaccines

Musterwandel – Sortenwandel : aktuelle Tendenzen der diachronen Text(sorten)linguistik

The texts in this volume deal with the current transformation of text types and text patterns and thus make a significant contribution to current issues of diachronic linguistics aligned text types and different transformation processes of recent usage histor

A Comprehensive Spectral Analysis of the X-Ray Pulsar 4U 1907+09 from Two Observations with the Suzaku X-Ray Observatory

We present results from two observations of the wind-accreting X-ray pulsar 4U 1907+09 using the Suzaku observatory. The broadband time-averaged spectrum allows us to examine the continuum emission of the source and the cyclotron resonance scattering feature at ~19 keV. Additionally, using the narrow CCD response of Suzaku near 6 keV allows us to study in detail the Fe K bandpass and to quantify the Fe K beta line for this source for the first time. The source is absorbed by fully-covering material along the line of sight with a column density of NH ~2e22 /cm^2, consistent with a wind accreting geometry, and a high Fe abundance (~3-4 x solar). Time and phase-resolved analyses allow us to study variations in the source spectrum. In particular, dips found in the 2006 observation which are consistent with earlier observations occur in the hard X-ray bandpass, implying a variation of the whole continuum rather than occultation by intervening material, while a dip near the end of the 2007 observation occurs mainly in the lower energies implying an increase in NH along the line of sight, perhaps indicating clumpiness in the stellar wind.Comment: Accepted for publication in ApJ. 12 pages, 16 figure

Leveraging the ALMA Atacama Compact Array for Cometary Science: An Interferometric Survey of Comet C/2015 ER61 (PanSTARRS) and Evidence for a Distributed Source of Carbon Monosulfide

We report the first survey of molecular emission from cometary volatiles using standalone Atacama Compact Array (ACA) observations of the Atacama Large Millimeter/Submillimeter Array (ALMA) toward comet C/2015 ER61 (PanSTARRS) carried out on UT 2017 April 11 and 15, shortly after its April 4 outburst. These measurements of HCN, CS, CH$_3$OH, H$_2$CO, and HNC (along with continuum emission from dust) probed the inner coma of C/2015 ER61, revealing asymmetric outgassing and discerning parent from daughter/distributed source species. This work presents spectrally integrated flux maps, autocorrelation spectra, production rates, and parent scale lengths for each molecule, and a stringent upper limit for CO. HCN is consistent with direct nucleus release in C/2015 ER61, whereas CS, H$_2$CO, HNC, and potentially CH$_3$OH are associated with distributed sources in the coma. Adopting a Haser model, parent scale lengths determined for H$_2$CO (L$_p$ $\sim$ 2200 km) and HNC (L$_p$ $\sim$ 3300 km) are consistent with previous work in comets, whereas significant extended source production (L$_p$ $\sim$ 2000 km) is indicated for CS, suggesting production from an unknown parent in the coma. The continuum presents a point-source distribution, with a flux density implying an excessively large nucleus, inconsistent with other estimates of the nucleus size. It is best explained by the thermal emission of slowly-moving outburst ejectas, with total mass 5--8 $\times$ 10$^{10}$ kg. These results demonstrate the power of the ACA for revealing the abundances, spatial distributions, and locations of molecular production for volatiles in moderately bright comets such as C/2015 ER61

T cell-independent, TLR-induced IL-12p70 production in primary human monocytes

IL-12p70 is a key cytokine for the induction of Th1 immune responses. IL-12p70 production in myeloid cells is thought to be strictly controlled by T cell help. In this work we demonstrate that primary human monocytes can produce IL-12p70 in the absence of T cell help. We show that human monocytes express TLR4 and TLR8 but lack TLR3 and TLR7 even after preincubation with type I IFN. Simultaneous stimulation of TLR4 and TLR8 induced IL-12p70 in primary human monocytes. IL-12p70 production in peripheral blood myeloid dendritic cells required combined stimulation of TLR7/8 ligands together with TLR4 or with TLR3 ligands. In the presence of T cell-derived IL-4, but not IFN-gamma, stimulation with TLR7/8 ligands was sufficient to stimulate IL-12p70 production. In monocytes, type I IFN was required but not sufficient to costimulate IL-12p70 induction by TLR8 ligation. Furthermore, TLR8 ligation inhibited LPS-induced IL-10 in monocytes, and LPS alone gained the ability to stimulate IL-12p70 in monocytes when the IL-10 receptor was blocked. Together, these results demonstrate that monocytes are licensed to synthesize IL-12p70 through type I IFN provided via the Toll/IL-1R domain-containing adaptor inducing IFN-beta pathway and the inhibition of IL-10, both provided by combined stimulation with TLR4 and TLR8 ligands, triggering a potent Th1 response before T cell help is established

Development of a Non-invasive Methodology for the Assessment of Muscle Fibre Composition

The percentage area of fast twitch fibres of a muscle is a major determinant of muscle mechanical power and, thus, an important biomarker for the evaluation of training processes. However, the invasive character of the assessment (muscle biopsy) limits the wide application of the biomarker in the training praxis. Our purpose was to develop a non-invasive method for the assessment of fast twitch fibre content in human soleus muscle. From a theoretical point of view, the maximum muscle mechanical power depends on the fibre composition, the muscle volume and muscle specific tension. Therefore, we hypothesised that the percentage area of type II fibres would show a correlation with the maximum muscle mechanical power normalised to muscle volume and specific muscle contractile strength (i.e., plantar flexion moment divided by muscle cross-sectional area). In 20 male adults, the percentage area of type II fibres, volume and maximum cross-sectional area of the soleus muscle as well as the maximum plantar flexion moment and the maximum mechanical power were measured using muscle biopsies, magnetic resonance imaging and dynamometry. The maximum mechanical power normalised to muscle volume and specific muscle contractile strength provided a significant relationship (r = 0.654, p = 0.002) with the percentage area of type II fibres. Although the proposed assessment parameter cannot fully replace histological measurements, the predictive power of 43% can provide a relevant contribution to performance diagnostics in the training praxis