A Multivariate Statistical Analysis of Spiral Galaxy Luminosities. II. Morphology-Dependent Multiwavelength Emission Properties

This is the second of two papers based on a systematic multi-wavelength (X, B, H, 12$\mu$m, FIR, 6cm) statistical analysis of the {\it Einstein Observatory Galaxy Catalog} sample of 234 `normal' S0/a-Irr galaxies. This sample is representative of spiral galaxies (Paper I), and its wide wavelength coverage provides a unique opportunity for a systematic exploration of the relations among different emission bands, that can give novel insight on the different emission processes and their relation to galaxian components, as a function of galaxy morphology.Comment: text, 7 figs, 2 tables, submitted to Ap.

Light-year Scale Radio Cores in Four LINER Galaxies

The LINER galaxies NGC 2911, NGC 3079, NGC 3998, and NGC 6500 were observed at 5 GHz with the European VLBI Network at a resolution of 5 milliarcsecond and found to possess flat-spectrum, variable, high-brightness temperature ($T_{\rm B} > 10^8$ K) radio cores. These radio characteristics reinforce the view that these LINERs host central engines associated with active galactic nuclei.Comment: 6 page

New H2O masers in Seyfert and FIR bright galaxies

Extragalactic water vapor masers with 50, 1000, 1, and 230 solar (isotropic) luminosities were detected toward Mrk1066 (UGC2456), Mrk34, NGC3556 and Arp299, respectively. The interacting system Arp299 appears to show two maser hotspots separated by 20 arcsec. A statistical analysis of 53 extragalactic H2O sources indicates (1) that the correlation between IRAS Point Source and H2O luminosities, established for individual star forming regions in the galactic disk, also holds for AGN dominated megamaser galaxies, (2) that maser luminosities are not correlated with 60/100 micron color temperatures and (3) that only a small fraction of the luminous megamasers detectable with 100-m sized telescopes have so far been identified. The slope of the H2O luminosity function, -1.5, indicates that the number of detectable masers is almost independent of their luminosity. If the LF is not steepening at very high maser luminosities, H2O megamasers at significant redshifts should be detectable with present day state-of-the-art facilities.Comment: 16 pages, 10 postscript figures; style file: aa.cls. Accepted for publication in the Main Journal of Astronomy & Astrophysic

Generation of \u3b2 cell-specific human cytotoxic T cells by lentiviral transduction and their survival in immunodeficient human leucocyte antigen-transgenic mice

Several \u3b2 cell antigens recognized by T cells in the non-obese diabetic (NOD) mouse model of type 1 diabetes (T1D) are also T cell targets in the human disease. While numerous antigen-specific therapies prevent diabetes in NOD mice, successful translation of rodent findings to patients has been difficult. A human leucocyte antigen (HLA)-transgenic mouse model incorporating human \u3b2 cell-specific T cells might provide a better platform for evaluating antigen-specific therapies. The ability to study such T cells is limited by their low frequency in peripheral blood and the difficulty in obtaining islet-infiltrating T cells from patients. We have worked to overcome this limitation by using lentiviral transduction to 'reprogram' primary human CD8 T cells to express three T cell receptors (TCRs) specific for a peptide derived from the \u3b2 cell antigen islet-specific glucose-6-phosphatase catalytic subunit-related protein (IGRP265-273 ) and recognized in the context of the human class I major histocompatibility complex (MHC) molecule HLA-A2. The TCRs bound peptide/MHC multimers with a range of avidities, but all bound with at least 10-fold lower avidity than the anti-viral TCR used for comparison. One exhibited antigenic recognition promiscuity. The \u3b2 cell-specific human CD8 T cells generated by lentiviral transduction with one of the TCRs released interferon (IFN)-\u3b3 in response to antigen and exhibited cytotoxic activity against peptide-pulsed target cells. The cells engrafted in HLA-A2-transgenic NOD-scid IL2r\u3b3(null) mice and could be detected in the blood, spleen and pancreas up to 5\u2009weeks post-transfer, suggesting the utility of this approach for the evaluation of T cell-modulatory therapies for T1D and other T cell-mediated autoimmune diseases

Microplasma-synthesized ultra-small NiO nanocrystals, a ubiquitous hole transport material

We report on a one-step hybrid atmospheric pressure plasma-liquid synthesis of ultra-small NiO nanocrystals (2 nm mean diameter), which exhibit strong quantum confinement. We show the versatility of the synthesis process and present the superior material characteristics of the nanocrystals (NCs). The band diagram of the NiO NCs, obtained experimentally, highlights ideal features for their implementation as a hole transport layer in a wide range of photovoltaic (PV) device architectures. As a proof of concept, we demonstrate the NiO NCs as a hole transport layer for three different PV device test architectures, which incorporate silicon quantum dots (Si-QDs), nitrogen-doped carbon quantum dots (N-CQDs) and perovskite as absorber layers. Our results clearly show ideal band alignment which could lead to improved carrier extraction into the metal contacts for all three solar cells. In addition, in the case of perovskite solar cells, the NiO NC hole transport layer acted as a protective layer preventing the degradation of halide perovskites from ambient moisture with a stable performance for >70 days. Our results also show unique characteristics that are highly suitable for future developments in all-inorganic 3(rd) generation solar cells (e.g. based on quantum dots) where quantum confinement can be used effectively to tune the band diagram to fit the energy level alignment requirements of different solar cell architectures

A De Novo Protein Binding Pair By Computational Design and Directed Evolution

The de novo design of protein-protein interfaces is a stringent test of our understanding of the principles underlying protein-protein interactions and would enable unique approaches to biological and medical challenges. Here we describe a motif-based method to computationally design protein-protein complexes with native-like interface composition and interaction density. Using this method we designed a pair of proteins, Prb and Pdar, that heterodimerize with a Kd of 130 nM, 1000-fold tighter than any previously designed de novo protein-protein complex. Directed evolution identified two point mutations that improve affinity to 180 pM. Crystal structures of an affinity- matured complex reveal binding is entirely through the designed interface residues. Surprisingly, in the in vitro evolved complex one of the partners is rotated 180 relative to the original design model, yet still maintains the central computationally designed hotspot interaction and preserves the character of many peripheral interactions. This work demon- strates that high-affinity protein interfaces can be created by designing complementary interaction surfaces on two noninteracting partners and under- scores remaining challenges.Chemistry and Chemical Biolog

The effects of an extensive exercise programme on the progression of Mild Cognitive Impairment (MCI): study protocol for a randomised controlled trial

Background Exercise interventions to prevent dementia and delay cognitive decline have gained considerable attention in recent years. Human and animal studies have demonstrated that regular physical activity targets brain function by increasing cognitive reserve. There is also evidence of structural changes caused by exercise in preventing or delaying the genesis of neurodegeneration. Although initial studies indicate enhanced cognitive performance in patients with mild cognitive impairment (MCI) following an exercise intervention, little is known about the effect of an extensive, controlled and regular exercise regimen on the neuropathology of patients with MCI. This study aims to determine the effects of an extensive exercise programme on the progression of MCI. Methods/design This randomised controlled clinical intervention study will take place across three European sites. Seventy-five previously sedentary patients with a clinical diagnosis of MCI will be recruited at each site. Participants will be randomised to one of three groups. One group will receive a standardised 1-year extensive aerobic exercise intervention (3 units of 45 min/week). The second group will complete stretching and toning (non-aerobic) exercise (3 units of 45 min/week) and the third group will act as the control group. Change in all outcomes will be measured at baseline (T0), after six months (T1) and after 12 months (T2). The primary outcome, cognitive performance, will be determined by a neuropsychological test battery (CogState battery, Trail Making Test and Verbal fluency). Secondary outcomes include Montreal Cognitive Assessment (MoCA), cardiovascular fitness, physical activity, structural changes of the brain, quality of life measures and measures of frailty. Furthermore, outcome variables will be related to genetic variations on genes related to neurogenesis and epigenetic changes in these genes caused by the exercise intervention programme. Discussion The results will add new insights into the prevailing notion that exercise may slow the rate of cognitive decline in MCI

Expanding the clinical spectrum of hereditary fibrosing poikiloderma with tendon contractures, myopathy and pulmonary fibrosis due to <i>FAM111B </i>mutations

BACKGROUND: Hereditary Fibrosing Poikiloderma (HFP) with tendon contractures, myopathy and pulmonary fibrosis (POIKTMP [MIM 615704]) is a very recently described entity of syndromic inherited poikiloderma. Previously by using whole exome sequencing in five families, we identified the causative gene, FAM111B (NM_198947.3), the function of which is still unknown. Our objective in this study was to better define the specific features of POIKTMP through a larger series of patients. METHODS: Clinical and molecular data of two families and eight independent sporadic cases, including six new cases, were collected. RESULTS: Key features consist of: (i) early-onset poikiloderma, hypotrichosis and hypohidrosis; (ii) multiple contractures, in particular triceps surae muscle contractures; (iii) diffuse progressive muscular weakness; (iv) pulmonary fibrosis in adulthood and (v) other features including exocrine pancreatic insufficiency, liver impairment and growth retardation. Muscle magnetic resonance imaging was informative and showed muscle atrophy and fatty infiltration. Histological examination of skeletal muscle revealed extensive fibroadipose tissue infiltration. Microscopy of the skin showed a scleroderma-like aspect with fibrosis and alterations of the elastic network. FAM111B gene analysis identified five different missense variants (two recurrent mutations were found respectively in three and four independent families). All the mutations were predicted to localize in the trypsin-like cysteine/serine peptidase domain of the protein. We suggest gain-of-function or dominant-negative mutations resulting in FAM111B enzymatic activity changes. CONCLUSIONS: HFP with tendon contractures, myopathy and pulmonary fibrosis, is a multisystemic disorder due to autosomal dominant FAM111B mutations. Future functional studies will help in understanding the specific pathological process of this fibrosing disorder

Parkinson’s disease mouse models in translational research

Animal models with high predictive power are a prerequisite for translational research. The closer the similarity of a model to Parkinson’s disease (PD), the higher is the predictive value for clinical trials. An ideal PD model should present behavioral signs and pathology that resemble the human disease. The increasing understanding of PD stratification and etiology, however, complicates the choice of adequate animal models for preclinical studies. An ultimate mouse model, relevant to address all PD-related questions, is yet to be developed. However, many of the existing models are useful in answering specific questions. An appropriate model should be chosen after considering both the context of the research and the model properties. This review addresses the validity, strengths, and limitations of current PD mouse models for translational research