Human placental cytotrophoblasts produce the immunosuppressive cytokine interleukin 10.

The mechanism by which the mammalian mother accepts the implanting fetus as an allograft remains unexplained, but is likely to be the result of a combination of factors. Mononuclear cytotrophoblasts, the specialized fetal cells of the placenta that invade the uterus, play an important role. These cells express HLA-G, an unusual major histocompatibility complex class I-B molecule, and secrete cytokines and pregnancy-specific proteins that can regulate immune function. We investigated whether cytotrophoblasts secrete interleukin 10 (IL-10), a cytokine that potently inhibits alloresponses in mixed lymphocyte reactions. Cytotrophoblasts from all stages of pregnancy produced IL-10 in vitro, but neither placental fibroblasts nor choriocarcinoma (malignant trophoblast) cell lines did so. Spontaneous IL-10 production averaged 650, 853, and 992 pg/10(6) cells in the first, second, and third trimesters of pregnancy, respectively. IL-10 secretion dropped approximately 10-fold after the first 24 h of culture, and was paralleled by a decrease in messenger RNA. IL-10 messenger RNA was detected in biopsies of the placenta and the portion of the uterus that contains invasive cytotrophoblasts, suggesting that this cytokine is also produced in vivo. IL-10 secreted by cytotrophoblasts in vitro is bioactive, as determined by its ability to suppress interferon gamma production in an allogeneic mixed lymphocyte reaction. We conclude that human cytotrophoblast IL-10 may be an important factor that contributes to maternal tolerance of the allogeneic fetus

Risk-Averse Matchings over Uncertain Graph Databases

A large number of applications such as querying sensor networks, and analyzing protein-protein interaction (PPI) networks, rely on mining uncertain graph and hypergraph databases. In this work we study the following problem: given an uncertain, weighted (hyper)graph, how can we efficiently find a (hyper)matching with high expected reward, and low risk? This problem naturally arises in the context of several important applications, such as online dating, kidney exchanges, and team formation. We introduce a novel formulation for finding matchings with maximum expected reward and bounded risk under a general model of uncertain weighted (hyper)graphs that we introduce in this work. Our model generalizes probabilistic models used in prior work, and captures both continuous and discrete probability distributions, thus allowing to handle privacy related applications that inject appropriately distributed noise to (hyper)edge weights. Given that our optimization problem is NP-hard, we turn our attention to designing efficient approximation algorithms. For the case of uncertain weighted graphs, we provide a $\frac{1}{3}$-approximation algorithm, and a $\frac{1}{5}$-approximation algorithm with near optimal run time. For the case of uncertain weighted hypergraphs, we provide a $\Omega(\frac{1}{k})$-approximation algorithm, where $k$ is the rank of the hypergraph (i.e., any hyperedge includes at most $k$ nodes), that runs in almost (modulo log factors) linear time. We complement our theoretical results by testing our approximation algorithms on a wide variety of synthetic experiments, where we observe in a controlled setting interesting findings on the trade-off between reward, and risk. We also provide an application of our formulation for providing recommendations of teams that are likely to collaborate, and have high impact.Comment: 25 page

Hydrostatic pressure does not cause detectable changes to survival of human retinal ganglion

Purpose: Elevated intraocular pressure (IOP) is a major risk factor for glaucoma. One consequence of raised IOP is that ocular tissues are subjected to increased hydrostatic pressure (HP). The effect of raised HP on stress pathway signaling and retinal ganglion cell (RGC) survival in the human retina was investigated. Methods: A chamber was designed to expose cells to increased HP (constant and fluctuating). Accurate pressure control (10-100mmHg) was achieved using mass flow controllers. Human organotypic retinal cultures (HORCs) from donor eyes (<24h post mortem) were cultured in serum-free DMEM/HamF12. Increased HP was compared to simulated ischemia (oxygen glucose deprivation, OGD). Cell death and apoptosis were measured by LDH and TUNEL assays, RGC marker expression by qRT-PCR (THY-1) and RGC number by immunohistochemistry (NeuN). Activated p38 and JNK were detected by Western blot. Results: Exposure of HORCs to constant (60mmHg) or fluctuating (10-100mmHg; 1 cycle/min) pressure for 24 or 48h caused no loss of structural integrity, LDH release, decrease in RGC marker expression (THY-1) or loss of RGCs compared with controls. In addition, there was no increase in TUNEL-positive NeuN-labelled cells at either time-point indicating no increase in apoptosis of RGCs. OGD increased apoptosis, reduced RGC marker expression and RGC number and caused elevated LDH release at 24h. p38 and JNK phosphorylation remained unchanged in HORCs exposed to fluctuating pressure (10-100mmHg; 1 cycle/min) for 15, 30, 60 and 90min durations, whereas OGD (3h) increased activation of p38 and JNK, remaining elevated for 90min post-OGD. Conclusions: Directly applied HP had no detectable impact on RGC survival and stress-signalling in HORCs. Simulated ischemia, however, activated stress pathways and caused RGC death. These results show that direct HP does not cause degeneration of RGCs in the ex vivo human retina

Design and fabrication of plasmonic cavities for magneto-optical sensing (article)

This is the author accepted manuscript. The final version is available from AIP Publishing via the DOI in this record.The dataset associated with this article is located in ORE at: http://hdl.handle.net/10871/32604The design and fabrication of a novel plasmonic cavity, intended to allow far-field recovery of signals arising from near field magneto-optical interactions, is presented. Finite element modeling is used to describe the interaction between a gold film, containing cross-shaped cavities, with a nearby magnetic under-layer. The modeling revealed strong electric field confinement near the center of the cross structure for certain optical wavelengths, which may be tuned by varying the length of the cross through a range that is compatible with available fabrication techniques. Furthermore, the magneto optical Kerr effect (MOKE) response of the composite structure can be enhanced with respect to that of the bare magnetic film. To confirm these findings, cavities were milled within gold films deposited upon a soluble film, allowing relocation to a ferromagnetic film using a float transfer technique. Cross cavity arrays were fabricated and characterized by optical transmission spectroscopy prior to floating, revealing resonances at optical wavelengths in good agreement with the finite element modeling. Following transfer to the magnetic film, circular test apertures within the gold film yielded clear magneto-optical signals even for diameters within the sub-wavelength regime. However, no magneto-optical signal was observed for the cross cavity arrays, since the FIB milling process was found to produce nanotube structures within the soluble under-layer that adhered to the gold. Further optimization of the fabrication process should allow recovery of magneto-optical signal from cross cavity structures.Financial support from the UK Engineering and Physical Science Research Council (EPSRC) grants EP/1038470/I and EP/1038411/1 is gratefully acknowledged. We also acknowledge the support of Seagate Technology (Ireland) under SOW 00077300.0. RMB contribution to project was supported by the Royal Academy of Engineering under the Research Chairs and Senior Research Fellowships Scheme

Management and efficacy of intensified insulin therapy starting in outpatients

Diabetic patients under multiple injection insulin therapy (i.e., intensified insulin therapy, IIT) usually start this treatment during hospitalization. We report here on the logistics, efficacy, and safety of IIT, started in outpatients. Over 8 months, 52 type I and type II diabetics were followed up whose insulin regimens consecutively had been changed from conventional therapy to IIT. Two different IIT strategies were compared: free mixtures of regular and intermediate (12 hrs)-acting insulin versus the basal and prandial insulin treatment with preprandial injections of regular insulin, and ultralente (24 hrs-acting) or intermediate insulin for the basal demand. After 8 months HbA1 levels had decreased from 10.6%±2.4% to 8.0%±1.3% (means±SD). There was no difference between the two regimens with respect to metabolic control; but type II patients maintained the lowered HbA1 levels better than type I patients. Only two patients were hospitalized during the follow-up time because of severe hypoglycemia. An increase of body weight due to the diet liberalization during IIT became a problem in one-third of the patients. Our results suggest that outpatient initiation of IIT is safe and efficacious with respect to near-normoglycemic control. Weight control may become a problem in IIT patients

Probabilistic Clustering of Time-Evolving Distance Data

We present a novel probabilistic clustering model for objects that are represented via pairwise distances and observed at different time points. The proposed method utilizes the information given by adjacent time points to find the underlying cluster structure and obtain a smooth cluster evolution. This approach allows the number of objects and clusters to differ at every time point, and no identification on the identities of the objects is needed. Further, the model does not require the number of clusters being specified in advance -- they are instead determined automatically using a Dirichlet process prior. We validate our model on synthetic data showing that the proposed method is more accurate than state-of-the-art clustering methods. Finally, we use our dynamic clustering model to analyze and illustrate the evolution of brain cancer patients over time

Electro-optically tunable microring resonators in lithium niobate

Optical microresonators have recently attracted a growing attention in the photonics community. Their applications range from quantum electro-dynamics to sensors and filtering devices for optical telecommunication systems, where they are likely to become an essential building block. The integration of nonlinear and electro-optical properties in the resonators represents a very stimulating challenge, as it would incorporate new and more advanced functionality. Lithium niobate is an excellent candidate material, being an established choice for electro-optic and nonlinear optical applications. Here we report on the first realization of optical microring resonators in submicrometric thin films of lithium niobate. The high index contrast films are produced by an improved crystal ion slicing and bonding technique using benzocyclobutene. The rings have radius R=100 um and their transmission spectrum has been tuned using the electro-optic effect. These results open new perspectives for the use of lithium niobate in chip-scale integrated optical devices and nonlinear optical microcavities.Comment: 15 pages, 8 figure

The SNAPSHOT study protocol : SNAcking, Physical activity, Self-regulation, and Heart rate Over Time

Peer reviewedPublisher PD

Experimental infection of dogs with a feline endogenous retrovirus RD-114

<p>Abstract</p> <p>Background</p> <p>The feline endogenous retrovirus RD114 is contained in the genome of cats. The virus may contaminate live canine vaccines based on cultured feline cells. The <it>in vivo </it>infectivity, acute and subacute pathogenicity, and viral proliferation of the RD114 virus were evaluated by experimental infection of dogs.</p> <p>Methods</p> <p>Nine specific pathogen free dogs were divided into three groups, with each group consisting of one female and two male dogs. Dogs were subcutaneously inoculated in the neck with either 1 ml RD114 stock virus (group A), inactivated RD114 virus suspension (group B), or cell culture medium (group C) as a negative control. To assess blood cell counts and biochemical properties, blood samples from each group were collected 5 days before inoculation, just prior to inoculation, and 1, 3, 7 and 10 days post-inoculation.</p> <p>Result</p> <p>During the experimental period of 51 days, none of the dogs inoculated with RD114 virus showed any clinical signs, significant increases in rectal temperature or abnormal blood biochemical characteristics including C-reactive protein when compared with the negative controls. We were not able to re-isolate the RD114 virus from buffy coat cells of group A dogs. Additionally, we could not detect RD114 provirus in the genomic DNA isolated from peripheral blood leukocytes, lymph node, spleen and sternal bone marrow cells.</p> <p>Conclusions</p> <p>Signs of RD114 virus proliferation were not found after subcutaneous infection of dogs. Although the potential risk caused by infection with RD114 virus in dogs could not be assessed in this study, we suspect that RD114 virus has little or no virulence in dogs.</p