Inhibition of NK cell-mediated Cytotoxicity by Tubular Epithelial Cell Expression of Clr Proteins

Cytotoxic effector cells can target and kill parenchymal cells of the kidney which results in injury and loss of function. Endogenous regulatory systems may exist to attenuate Natural Killer (NK) and other effector cell activation and cytotoxicity in diverse conditions, including ischemia-reperfusion injury associated with kidney transplantation. Understanding these mechanisms will direct new therapeutic strategies. Kidney tubular epithelial cells (TEC), the predominant cell type in kidneys, may negatively regulate NK cell activation by surface expression of C-type lectin-related proteins (Clr). Clr-b and -f were found to be expressed by wild type (WT) TEC. Clr-b was upregulated by TNFα+IFNγ in vitro. Elimination of both Clr-b and Clr-f expression with siRNA resulted in increased NK killing of TEC compared to individual silencing of Clr-b or Clr-f TEC (p\u3c0.01), or WT control TEC (p\u3c0.001). NK cells treated in vitro with soluble Clr-b and Clr-f reduced their capacity to kill Clr-b/-f -/- TEC as compared to untreated NK cells (p\u3c0.05). NK cells therefore are regulated by proteins expressed by TEC and thus may represent an important endogenous regulatory system in the kidney to limit organ injury. As no current drugs exist to specifically target NK cells, Clr-b and Clr-f soluble proteins that bind to NK cells may represent a novel and clinically feasible strategy to protect organs from NK cell-mediated inflammation during ischemia-reperfusion and other kidney injury models

Planet Populations as a Function of Stellar Properties

Exoplanets around different types of stars provide a window into the diverse environments in which planets form. This chapter describes the observed relations between exoplanet populations and stellar properties and how they connect to planet formation in protoplanetary disks. Giant planets occur more frequently around more metal-rich and more massive stars. These findings support the core accretion theory of planet formation, in which the cores of giant planets form more rapidly in more metal-rich and more massive protoplanetary disks. Smaller planets, those with sizes roughly between Earth and Neptune, exhibit different scaling relations with stellar properties. These planets are found around stars with a wide range of metallicities and occur more frequently around lower mass stars. This indicates that planet formation takes place in a wide range of environments, yet it is not clear why planets form more efficiently around low mass stars. Going forward, exoplanet surveys targeting M dwarfs will characterize the exoplanet population around the lowest mass stars. In combination with ongoing stellar characterization, this will help us understand the formation of planets in a large range of environments.Comment: Accepted for Publication in the Handbook of Exoplanet

How Noisy Adaptation of Neurons Shapes Interspike Interval Histograms and Correlations

Channel noise is the dominant intrinsic noise source of neurons causing variability in the timing of action potentials and interspike intervals (ISI). Slow adaptation currents are observed in many cells and strongly shape response properties of neurons. These currents are mediated by finite populations of ionic channels and may thus carry a substantial noise component. Here we study the effect of such adaptation noise on the ISI statistics of an integrate-and-fire model neuron by means of analytical techniques and extensive numerical simulations. We contrast this stochastic adaptation with the commonly studied case of a fast fluctuating current noise and a deterministic adaptation current (corresponding to an infinite population of adaptation channels). We derive analytical approximations for the ISI density and ISI serial correlation coefficient for both cases. For fast fluctuations and deterministic adaptation, the ISI density is well approximated by an inverse Gaussian (IG) and the ISI correlations are negative. In marked contrast, for stochastic adaptation, the density is more peaked and has a heavier tail than an IG density and the serial correlations are positive. A numerical study of the mixed case where both fast fluctuations and adaptation channel noise are present reveals a smooth transition between the analytically tractable limiting cases. Our conclusions are furthermore supported by numerical simulations of a biophysically more realistic Hodgkin-Huxley type model. Our results could be used to infer the dominant source of noise in neurons from their ISI statistics

First metatarsophalangeal joint arthrodesis versus proximal phalanx hemiarthroplasty for hallux rigidus: feasibility study for a randomised controlled trial

BACKGROUND: Osteoarthritis of the first metatarsophalangeal joint (hallux rigidus) leads to pain and poor function and mobility. Arthrodesis is the gold standard treatment for end-stage disease. Total joint arthroplasties have been attempted, but early loosening has been attributed to dorsally directed shear forces on the metatarsal component. Metallic proximal phalangeal hemiarthroplasty theoretically avoids this. Whilst early results are promising, no comparative trials exist comparing this to arthrodesis. METHODS/DESIGN: The primary objectives are to determine the range of outcome scores between the two treatment arms (to inform a power calculation). Outcome measures will include the MOXFQ, AOFAS-Hallux and EuroQol EQ-5D-5 L. Secondary objectives are to determine the accrual rate, dropout rate and trial acceptability to both patients and surgeons. These data will allow the development of a larger trial with longer follow-up.This is a prospective randomised controlled single-centre study comparing proximal phalanx hemiarthroplasty (AnaToemic, Arthrex Ltd., Sheffield, UK) with arthrodesis (15 patients in each arm). Randomisation will be performed using a 1:1 allocation ratio in blocks of six.Patients meeting the eligibility criteria will be recruited from three foot and ankle consultant surgeon's clinics (East Lancashire Hospitals NHS Trust). If agreeable, informed consent will be obtained before patients are randomised.The outcome measure scores will be completed pre-operatively and repeated at 6 weeks, 3 months and 12 months. A radiological review will be performed at 6 weeks and 12 months to determine rates of loosening (hemiarthroplasty) and union (arthrodesis). Data on length of stay, return to work, complications and re-operation rates will also be collected.The analysis will compare the change in outcome scores between treatment groups at all follow-up time points. Scores will be compared using a Student t-test, adjusting for scores at baseline.This study will be conducted in accordance with the current revision of the Declaration of Helsinki (1996) and the ICH-GCP Guideline (International Conference on Harmonisation, Good Clinical Practice, E6(R1), 1996). This study has been approved by the sponsor, the Trust Research and Development office. Ethical approval has been received from the National Research Ethics Service (North East: 12/NE/0385 for protocol version 5.3 dated 3 June 2013). TRIAL REGISTRATION: Current Controlled Trials ISRCTN88273654

PENGARUH POTENSIAL DAN LAJU ALIR TERHADAP DEGRADASI ZAT WARNA REMAZOL YELLOW FG MENGGUNAKAN KOMPOSIT TiO2-NiO DALAM FOTO ELEKTRODEGRADASI DENGAN METODE ALIR (FLOW)

We investigate the chemo-kinematic properties of the Milky Way disc by exploring the first year of data from the Apache Point Observatory Galactic Evolution Experiment (APOGEE), and compare our results to smaller optical high-resolution samples in the literature, as well as results from lower resolution surveys such as GCS, SEGUE and RAVE. We start by selecting a high-quality sample in terms of chemistry ($\sim$ 20.000 stars) and, after computing distances and orbital parameters for this sample, we employ a number of useful subsets to formulate constraints on Galactic chemical and chemodynamical evolution processes in the Solar neighbourhood and beyond (e.g., metallicity distributions -- MDFs, [$\alpha$/Fe] vs. [Fe/H] diagrams, and abundance gradients). Our red giant sample spans distances as large as 10 kpc from the Sun. We find remarkable agreement between the recently published local (d $<$ 100 pc) high-resolution high-S/N HARPS sample and our local HQ sample (d $<$ 1 kpc). The local MDF peaks slightly below solar metallicity, and exhibits an extended tail towards [Fe/H] $= -$1, whereas a sharper cut-off is seen at larger metallicities. The APOGEE data also confirm the existence of a gap in the [$\alpha$/Fe] vs. [Fe/H] abundance diagram. When expanding our sample to cover three different Galactocentric distance bins, we find the high-[$\alpha$/Fe] stars to be rare towards the outer zones, as previously suggested in the literature. For the gradients in [Fe/H] and [$\alpha$/Fe], measured over a range of 6 $<$ R $<$ 11 kpc in Galactocentric distance, we find a good agreement with the gradients traced by the GCS and RAVE dwarf samples. For stars with 1.5 $<$ z $<$ 3 kpc, we find a positive metallicity gradient and a negative gradient in [$\alpha$/Fe]