Inkjet-Printed Nanocavities on a Photonic Crystal Template

The last decade has witnessed the rapid development of inkjet printing as an attractive bottom-up microfabrication technology due to its simplicity and potentially low cost. The wealth of printable materials has been key to its widespread adoption in organic optoelectronics and biotechnology. However, its implementation in nanophotonics has so far been limited by the coarse resolution of conventional inkjet-printing methods. In addition, the low refractive index of organic materials prevents the use of “soft-photonics” in applications where strong light confinement is required. This study introduces a hybrid approach for creating and fine tuning high-Q nanocavities, involving the local deposition of an organic ink on the surface of an inorganic 2D photonic crystal template using a commercially available high-resolution inkjet printer. The controllability of this approach is demonstrated by tuning the resonance of the printed nanocavities by the number of printer passes and by the fabrication of photonic crystal molecules with controllable splitting. The versatility of this method is evidenced by the realization of nanocavities obtained by surface deposition on a blank photonic crystal. A new method for a free-form, high-density, material-independent, and high-throughput fabrication technique is thus established with a manifold of opportunities in photonic applications.Part of this work was performed using the Darwin Supercomputer of the University of Cambridge High Performance Computing Service (http://www.hpc.cam.ac.uk/), provided by Dell Inc. using Strategic Research Infrastructure Funding from the Higher Education Funding Council for England and funding from the Science and Technology Facilities Council. V.P. gratefully acknowledges financial support from the United Kingdom Engineering and Physical Sciences Research Council (EPSRC) through the Centre for Innovative Manufacturing in Large Area Electronics (CIMLAE, program grant EP/K03099X/1) and the project Integration of Printed Electronics with Silicon for Smart sensor systems (iPESS). V.P. also acknowledges financial support from the Priority Academic Program Development of Jiangsu Higher Education Institutions (PAPD) and the Collaborative Innovation Center of Suzhou Nano Science and Technology

Gastric stimulation: influence of electrical parameters on gastric emptying in control and diabetic rats

BACKGROUND: The aim of this study was to test the effect of different pulse frequencies and amplitudes during gastric stimulation (GS) on gastric emptying in the rat. METHODS: GS was performed in 2 groups of laparotomized rats: healthy control animals, and rats with acute diabetes. The effects of four pulse frequencies (0.5, 1, 10, 20 Hz) and three pulse amplitudes (5, 20, 40 mA) were tested. The volumes emptied from the stomach after the oro-gastric instillation of a nutrient solution were compared to those obtained in animals without GS. Intragastric pH values were assessed under basal conditions and after GS. RESULTS: In both groups, GS increased emptied volumes compared to conditions without stimulation (p < 0.05) for pulse frequencies above 0.5 Hz. Increases in pulse frequencies accelerated gastric emptying (p < 0.01) with a plateau at around 10 Hz. The increase in pulse amplitudes resulted in larger emptied volumes only when the pulse frequency was 1 Hz (p < 0.04) while the opposite effect was observed at 20 Hz (p < 0.04). The most effective combinations to enhance gastric emptying compared to baseline conditions were 10 Hz with 5 or 20 mA. The overall effect of GS on gastric emptying compared to baseline conditions without stimulation, was greater in diabetic than in controls rats (p < 0.05). During stimulation, intragastric pH values were not different from basal conditions during fasting or after a meal in control and diabetic rats. CONCLUSIONS: Although both pulse frequency and amplitude should be considered during GS, frequency appears to be the most critical point. The possibility of increasing gastric emptying by electrical stimulation in diabetic rats suggests potential clinical applications for this method

Additive growth inhibitory effects of ibandronate and antiestrogens in estrogen receptor-positive breast cancer cell lines

INTRODUCTION: Bisphosphonates are inhibitors of osteoclast-mediated tumor-stimulated osteolysis, and they have become standard therapy for the management of bone metastases from breast cancer. These drugs can also directly induce growth inhibition and apoptosis of osteotropic cancer cells, including estrogen receptor-positive (ER+) breast cancer cells. METHODS: We examined the anti-proliferative properties of ibandronate on two ER+ breast cancer cell lines (MCF-7 and IBEP-2), and on one ER negative (ER-) cell line (MDA-MB-231). Experiments were performed in steroid-free medium to assess ER regulation and the effect of ibandronate in combination with estrogen or antiestrogens. RESULTS: Ibandronate inhibited cancer cell growth in a dose- and time-dependent manner (approximate IC(50): 10(-4 )M for MCF-7 and IBEP-2 cells; 3 × 10(-4 )M for MDA-MB-231 cells), partly through apoptosis induction. It completely abolished the mitogenic effect induced by 17β-estradiol in ER+ breast cancer cells, but affected neither ER regulation nor estrogen-induced progesterone receptor expression, as documented in MCF-7 cells. Moreover, ibandronate enhanced the growth inhibitory action of partial (4-hydroxytamoxifen) and pure (ICI 182,780, now called fluvestrant or Faslodex™) antiestrogens in estrogen-sensitive breast cancer cells. Combination analysis identified additive interactions between ibandronate and ER antagonists. CONCLUSION: These data constitute the first in vitro evidence for additive effects between ibandronate and antiestrogens, supporting their combined use for the treatment of bone metastases from breast cancer

The Antidiabetic Drug Ciglitazone Induces High Grade Bladder Cancer Cells Apoptosis through the Up-Regulation of TRAIL

International audienceBACKGROUND: Ciglitazone belongs to the thiazolidinediones class of antidiabetic drug family and is a high-affinity ligand for the Peroxisome Proliferator-Activated Receptor γ (PPARγ). Apart from its antidiabetic activity, this molecule shows antineoplastic effectiveness in numerous cancer cell lines. METHODOLOGY/PRINCIPAL FINDINGS: Using RT4 (derived from a well differentiated grade I papillary tumor) and T24 (derived from an undifferentiated grade III carcinoma) bladder cancer cells, we investigated the potential of ciglitazone to induce apoptotic cell death and characterized the molecular mechanisms involved. In RT4 cells, the drug induced G2/M cell cycle arrest characterized by an overexpression of p53, p21(waf1/CIP1) and p27(Kip1) in concomitance with a decrease of cyclin B1. On the contrary, in T24 cells, it triggered apoptosis via extrinsic and intrinsic pathways. Cell cycle arrest and induction of apoptosis occurred at high concentrations through PPARγ activation-independent pathways. We show that in vivo treatment of nude mice by ciglitazone inhibits high grade bladder cancer xenograft development. We identified a novel mechanism by which ciglitazone kills cancer cells. Ciglitazone up-regulated soluble and membrane-bound TRAIL and let TRAIL-resistant T24 cells to respond to TRAIL through caspase activation, death receptor signalling pathway and Bid cleavage. We provided evidence that TRAIL-induced apoptosis is partially driven by ciglitazone-mediated down-regulation of c-FLIP and survivin protein levels through a proteasome-dependent degradation mechanism. CONCLUSIONS/SIGNIFICANCE: Therefore, ciglitazone could be clinically relevant as chemopreventive or therapeutic agent for the treatment of TRAIL-refractory high grade urothelial cancers

The CXCL12γ Chemokine Displays Unprecedented Structural and Functional Properties that Make It a Paradigm of Chemoattractant Proteins

The CXCL12γ chemokine arises by alternative splicing from Cxcl12, an essential gene during development. This protein binds CXCR4 and displays an exceptional degree of conservation (99%) in mammals. CXCL12γ is formed by a protein core shared by all CXCL12 isoforms, extended by a highly cationic carboxy-terminal (C-ter) domain that encompass four overlapped BBXB heparan sulfate (HS)-binding motifs. We hypothesize that this unusual domain could critically determine the biological properties of CXCL12γ through its interaction to, and regulation by extracellular glycosaminoglycans (GAG) and HS in particular. By both RT-PCR and immunohistochemistry, we mapped the localization of CXCL12γ both in mouse and human tissues, where it showed discrete differential expression. As an unprecedented feature among chemokines, the secreted CXCL12γ strongly interacted with cell membrane GAG, thus remaining mostly adsorbed on the plasmatic membrane upon secretion. Affinity chromatography and surface plasmon resonance allowed us to determine for CXCL12γ one of the higher affinity for HS (Kd = 0.9 nM) ever reported for a protein. This property relies in the presence of four canonical HS-binding sites located at the C-ter domain but requires the collaboration of a HS-binding site located in the core of the protein. Interestingly, and despite reduced agonist potency on CXCR4, the sustained binding of CXCL12γ to HS enabled it to promote in vivo intraperitoneal leukocyte accumulation and angiogenesis in matrigel plugs with much higher efficiency than CXCL12α. In good agreement, mutant CXCL12γ chemokines selectively devoid of HS-binding capacity failed to promote in vivo significant cell recruitment. We conclude that CXCL12γ features unique structural and functional properties among chemokines which rely on the presence of a distinctive C-ter domain. The unsurpassed capacity to bind to HS on the extracellular matrix would make CXCL12γ the paradigm of haptotactic proteins, which regulate essential homeostatic functions by promoting directional migration and selective tissue homing of cells

Human and Non-Human Primate Genomes Share Hotspots of Positive Selection

Among primates, genome-wide analysis of recent positive selection is currently limited to the human species because it requires extensive sampling of genotypic data from many individuals. The extent to which genes positively selected in human also present adaptive changes in other primates therefore remains unknown. This question is important because a gene that has been positively selected independently in the human and in other primate lineages may be less likely to be involved in human specific phenotypic changes such as dietary habits or cognitive abilities. To answer this question, we analysed heterozygous Single Nucleotide Polymorphisms (SNPs) in the genomes of single human, chimpanzee, orangutan, and macaque individuals using a new method aiming to identify selective sweeps genome-wide. We found an unexpectedly high number of orthologous genes exhibiting signatures of a selective sweep simultaneously in several primate species, suggesting the presence of hotspots of positive selection. A similar significant excess is evident when comparing genes positively selected during recent human evolution with genes subjected to positive selection in their coding sequence in other primate lineages and identified using a different test. These findings are further supported by comparing several published human genome scans for positive selection with our findings in non-human primate genomes. We thus provide extensive evidence that the co-occurrence of positive selection in humans and in other primates at the same genetic loci can be measured with only four species, an indication that it may be a widespread phenomenon. The identification of positive selection in humans alongside other primates is a powerful tool to outline those genes that were selected uniquely during recent human evolution

A emergência das doenças emergentes e as doenças infecciosas emergentes e reemergentes no Brasil The emergence of emerging diseases and emerging and reemerging infectious diseases in Brazil

O artigo discute a emergência do conceito de doenças infecciosas emergentes e reemergentes. Postula-se que o conceito surge frente às limitações da teoria da transição epidemiológica em explicar as tendências recentes da morbidade e mortalidade. São discutidas as bases da teoria da transição epidemiológica e as razões de sua superação. Em seguida, são apresentados o conceito de doenças emergentes e reemergentes, os fatores relacionados à emergência das doenças infecciosas e as principais ocorrências no Brasil. Por fim, são abordados os desafios colocados pela emergência e reemergência das doenças infecciosas, e propostas para o seu enfrentamento.<br>This article discusses the emergence of the concept of emerging and reemerging infectious diseases. It argues that the concept surfaces due to the limits of the epidemiologic transition theory in explaining the current trends in morbidity and mortality. The bases of the epidemiologic transition theory are discussed, as well as the reasons for its limits. Then, the concept of emerging and reemerging infectious diseases, the factors related to them, and the major episodes of emergence and reemergence of diseases in Brazil are presented. Finally, the article discusses the challenges brought by the emergence and reemergence of infectious diseases, and the proposals to face them

Ammattiosaamisen näytöt yrityksen ja ammattiopiston yhteistyössä

Opinnäytetyön aiheena oli selvittää, miten ammattiosaamisen näytöt toimivat paikallisen osuuskaupan ja ammattiopiston yhteistyössä koskien ravintolan salipuolen tarjoilijoita. Ammattiosaamisen näytöt ovat olleet käytössä työssäoppijoiden arvioinnissa viisi vuotta. Tavoitteena oli saada tietoa näyttöjen hyödyistä työantajanäkökulmasta katsottuna sekä löytää mahdollisia kehittämiskohteita. Opinnäytetyön teoreettisessa osassa selvennettiin työssäoppimisen ja ammattiosaamisen näytön käsitteitä, mikä on niiden merkitys ammattikoulutuksessa ja toisaalta niiden merkitys työelämälle. Lisäksi selvitettiin yritysten rekrytointikäytäntöjä ja sitä, mitä on työelämän ja oppilaitosten yhteistyö. Tutkimuksen empiirisessä osassa käytettiin puolistrukturoitua teemahaastattelua. Haastateltavat olivat paikallisen osuuskaupan ravintoloiden esimiehiä, ja haastattelut tehtiin kuudelle henkilölle. Haastattelut nauhoitettiin ja litteroitiin sanasta sanaan tietokoneelle jatkoanalyysia varten. Tutkimuksen tuloksena vahvistui se, että ammattiosaamisen näytöt ovat kaikille selkeä asia ja niistä on hyötyä sekä työnantajalle että opiskelijalle. Yhteistyö osuuskaupan ja ammattiopiton kanssa toimii hyvin, eivätkä näyttötilanteet ole aiheuttaneet suurempia ongelmia. Ainoastaan työssäoppijan osaamisen arviointi koetaan hankalana nykyisellä asteikolla. Alan ammattiopistotasoista koulutusta tarvitaan edelleen Joensuun alueella, ja tutkimuksen mukaan sitä pitäisi jopa lisätä. Koulutetun työvoiman puute ei vielä ole maakunnassa suuri ongelma verrattuna pääkaupunkiseutuun, mutta uhkakuvia on jo nyt havaittavissa. Tähän tulisi yhteistyökumppaneiden kiinnittää huomiota, jotta jatkossa Joensuun alueella koulutetaan riittävästi työvoimaa alalle.The purpose of the thesis was to find out how the collaboration between a company and vocational college works concerning vocational skills demonstrations of restaurant waiters. In addition, the task was to examine if there is any benefit of skills demonstrations for the company, and how to develop co-operation. Partners for the study are a local hotel and restaurant company and a local vocational college. The information was gathered from literature, journals, the Internet and by interviewing. In the theoretical part of the study the main issue was to explain what on-the-job learning is and what vocational skills demonstrations are, and what their consequence is for vocational education and for work life. Also how companies carry out their recruitment was clarified. Data for this study were collected by interviewing six supervisors in partner restaurants. The results of the study show that vocational skills demonstrations are perceived well without any complexities. Rather the results indicate more utilities for students, for the company and for the vocational school. The final result of this thesis was that it is important to keep on vocational education in Joensuu and even to enhance it. Now the lack of trained waiters is a fact in southern Finland. A vision is that it will be a threat also in eastern Finland in the future. To ensure professional labour for hotel and restaurant business, companies support for vocational education is essential