High-bit rate ultra-compact light routing with mode-selective on-chip nanoantennas

Optical nanoantennas provide a promising pathway toward advanced manipulation of light waves, such as directional scattering, polarization conversion, and fluorescence enhancement. Although these functionalities were mainly studied for nanoantennas in free space or on homogeneous substrates, their integration with optical waveguides offers an important “wired” connection to other functional optical components. Taking advantage of the nanoantenna’s versatility and unrivaled compactness, their imprinting onto optical waveguides would enable a marked enhancement of design freedom and integration density for optical on-chip devices. Several examples of this concept have been demonstrated recently. However, the important question of whether nanoantennas can fulfill functionalities for high-bit rate signal transmission without degradation, which is the core purpose of many integrated optical applications, has not yet been experimentally investigated. We introduce and investigate directional, polarization-selective, and mode-selective on-chip nanoantennas integrated with a silicon rib waveguide. We demonstrate that these nanoantennas can separate optical signals with different polarizations by coupling the different polarizations of light vertically to different waveguide modes propagating into opposite directions. As the central result of this work, we show the suitability of this concept for the control of optical signals with ASK (amplitude-shift keying) NRZ (nonreturn to zero) modulation [10 Gigabit/s (Gb/s)] without significant bit error rate impairments. Our results demonstrate that waveguide-integrated nanoantennas have the potential to be used as ultra-compact polarization-demultiplexing on-chip devices for high–bit rate telecommunication applications

Using effective medium theories to design tailored nanocomposite materials for optical systems

Modern optical systems are subject to very restrictive performance, size and cost requirements. Especially in portable systems size often is the most important factor, which necessitates elaborate designs to achieve the desired specifications. However, current designs already operate very close to the physical limits and further progress is difficult to achieve by changing only the complexity of the design. Another way of improving the performance is to tailor the optical properties of materials specifically to the application at hand. A class of novel, customizable materials that enables the tailoring of the optical properties, and promises to overcome many of the intrinsic disadvantages of polymers, are nanocomposites. However, despite considerable past research efforts, these types of materials are largely underutilized in optical systems. To shed light into this issue we, in this paper, discuss how nanocomposites can be modeled using effective medium theories. In the second part, we then investigate the fundamental requirements that have to be fulfilled to make nanocomposites suitable for optical applications, and show that it is indeed possible to fabricate such a material using existing methods. Furthermore, we show how nanocomposites can be used to tailor the refractive index and dispersion properties towards specific applications

The Vehicle, 1968, Vol. 10 no. 2

Vol. 10, No. 2 Table of Contents 1st Prize, ArtCorner of My MindGerry Moreheadpage 4 #1Clyde Simspage 5 Aesthetics for a VagabondByron Nelsonpage 5 1st Prize, Short StorySteam HeatCharles Whitepage 6 a drawingSally Roachpage 6 an untitled themeCatherine Waitepage 8 MoodKevin Sheapage 9 1st Prize, PoetryHome ThoughtsJane Careypage 10 an untitled poemCatherine Waitepage 11 a drawingSally Roachpage 11 GraceJames T. Jonespage 12 LonelinessSally Roachpage 14 Love, JimmyAstaire Pappaspage 14 CapturedJeff Nelsonpage 15 Winnie Davis Neely AwardUnconcernRoger Zulaufpage 17 an untitled poemDavid N. Deckerpage 17 Morality and American Foreign Policy: The Ever-widening GapBruce L. Berrypage 18 La LibertadChris Holavespage 19 1966Roger Zulaufpage 19 SinThomas W. Phippspage 20 a drawingRoger Perkinspage 20 Summer SweatJerry J. Carterpage 20 1st Prize, EssayCuriosityThomas W. Phippspage 21 A Bottle of DreamsMaurice Snivelypage 21 Chalk DustCatherine Waitepage 22 Diffused Existence or, a Meager Attempt at Helping You Over the Rough SpotsJan Gerlachpage 22 To *e.e.Paula Bresnanpage 22 A PoemThomas W. Phippspage 22 Beach PartyJerol Mikeworthpage 22 Wexford\u27s PartyRoy Lueckepage 23 The Four O\u27Clock ClubSally Roachpage 23 Chesterpage 24https://thekeep.eiu.edu/vehicle/1018/thumbnail.jp

Assessing the carcinogenic potential of low-dose exposures to chemical mixtures in the environment: the challenge ahead.

Lifestyle factors are responsible for a considerable portion of cancer incidence worldwide, but credible estimates from the World Health Organization and the International Agency for Research on Cancer (IARC) suggest that the fraction of cancers attributable to toxic environmental exposures is between 7% and 19%. To explore the hypothesis that low-dose exposures to mixtures of chemicals in the environment may be combining to contribute to environmental carcinogenesis, we reviewed 11 hallmark phenotypes of cancer, multiple priority target sites for disruption in each area and prototypical chemical disruptors for all targets, this included dose-response characterizations, evidence of low-dose effects and cross-hallmark effects for all targets and chemicals. In total, 85 examples of chemicals were reviewed for actions on key pathways/mechanisms related to carcinogenesis. Only 15% (13/85) were found to have evidence of a dose-response threshold, whereas 59% (50/85) exerted low-dose effects. No dose-response information was found for the remaining 26% (22/85). Our analysis suggests that the cumulative effects of individual (non-carcinogenic) chemicals acting on different pathways, and a variety of related systems, organs, tissues and cells could plausibly conspire to produce carcinogenic synergies. Additional basic research on carcinogenesis and research focused on low-dose effects of chemical mixtures needs to be rigorously pursued before the merits of this hypothesis can be further advanced. However, the structure of the World Health Organization International Programme on Chemical Safety 'Mode of Action' framework should be revisited as it has inherent weaknesses that are not fully aligned with our current understanding of cancer biology

Ex vivo fucosylation improves human cord blood engraftment in NOD-SCID IL-2Rγ null mice

Delayed engraftment remains a major hurdle after cord blood (CB) transplantation. It may be due, at least in part, to low fucosylation of cell surface molecules important for homing to the bone marrow microenvironment. Because fucosylation of specific cell surface ligands is required before effective interaction with selectins expressed by the bone marrow microvasculature can occur, a simple 30-minute ex vivo incubation of CB hematopoietic progenitor cells with fucosyltransferase-VI and its substrate (GDP-fucose) was performed to increase levels of fucosylation. The physiologic impact of CB hematopoietic progenitor cell hypofucosylation was investigated in vivo in NOD-SCID interleukin (IL)-2Rγ null (NSG) mice. By isolating fucosylated and nonfucosylated CD34 + cells from CB, we showed that only fucosylated CD34 + cells are responsible for engraftment in NSG mice. In addition, because the proportion of CD34 + cells that are fucosylated in CB is significantly less than in bone marrow and peripheral blood, we hypothesize that these combined observations might explain, at least in part, the delayed engraftment observed after CB transplantation. Because engraftment appears to be correlated with the fucosylation of CD34 + cells, we hypothesized that increasing the proportion of CD34 + cells that are fucosylated would improve CB engraftment. Ex vivo treatment with fucosyltransferase-VI significantly increases the levels of CD34 + fucosylation and, as hypothesized, this was associated with improved engraftment. Ex vivo fucosylation did not alter the biodistribution of engrafting cells or pattern of long-term, multilineage, multi-tissue engraftment. We propose that ex vivo fucosylation will similarly improve the rate and magnitude of engraftment for CB transplant recipients in a clinical setting

Flavopiridol Pharmacogenetics: Clinical and Functional Evidence for the Role of SLCO1B1/OATP1B1 in Flavopiridol Disposition

Flavopiridol is a cyclin-dependent kinase inhibitor in phase II clinical development for treatment of various forms of cancer. When administered with a pharmacokinetically (PK)-directed dosing schedule, flavopiridol exhibited striking activity in patients with refractory chronic lymphocytic leukemia. This study aimed to evaluate pharmacogenetic factors associated with inter-individual variability in pharmacokinetics and outcomes associated with flavopiridol therapy.Thirty-five patients who received single-agent flavopiridol via the PK-directed schedule were genotyped for 189 polymorphisms in genes encoding 56 drug metabolizing enzymes and transporters. Genotypes were evaluated in univariate and multivariate analyses as covariates in a population PK model. Transport of flavopiridol and its glucuronide metabolite was evaluated in uptake assays in HEK-293 and MDCK-II cells transiently transfected with SLCO1B1. Polymorphisms in ABCC2, ABCG2, UGT1A1, UGT1A9, and SLCO1B1 were found to significantly correlate with flavopiridol PK in univariate analysis. Transport assay results indicated both flavopiridol and flavopiridol-glucuronide are substrates of the SLCO1B1/OATP1B1 transporter. Covariates incorporated into the final population PK model included bilirubin, SLCO1B1 rs11045819 and ABCC2 rs8187710. Associations were also observed between genotype and response. To validate these findings, a second set of data with 51 patients was evaluated, and overall trends for associations between PK and PGx were found to be consistent.Polymorphisms in transport genes were found to be associated with flavopiridol disposition and outcomes. Observed clinical associations with SLCO1B1 were functionally validated indicating for the first time its relevance as a transporter of flavopiridol and its glucuronide metabolite. A second 51-patient dataset indicated similar trends between genotype in the SLCO1B1 and other candidate genes, thus providing support for these findings. Further study in larger patient populations will be necessary to fully characterize and validate the clinical impact of polymorphisms in SLCO1B1 and other transporter and metabolizing enzyme genes on outcomes from flavopiridol therapy

Biomarker analysis of cetuximab plus oxaliplatin/leucovorin/5-fluorouracil in first-line metastatic gastric and oesophago-gastric junction cancer: results from a phase II trial of the Arbeitsgemeinschaft Internistische Onkologie (AIO)

<p>Abstract</p> <p>Background</p> <p>The activity of the epidermal growth factor receptor (EGFR)-directed monoclonal antibody cetuximab combined with oxaliplatin/leucovorin/5-fluorouracil (FUFOX) was assessed in first-line metastatic gastric and oesophago-gastric junction (OGJ) cancer in a prospective phase II study showing a promising objective tumour response rate of 65% and a low mutation frequency of <it>KRAS </it>(3%). The aim of the correlative tumour tissue studies was to investigate the relationship between <it>EGFR </it>gene copy numbers, activation of the EGFR pathway, expression and mutation of E-cadherin, V600E BRAF mutation and clinical outcome of patients with gastric and OGJ cancer treated with cetuximab combined with FUFOX.</p> <p>Methods</p> <p>Patients included in this correlative study (<it>n </it>= 39) were a subset of patients from the clinical phase II study. The association between <it>EGFR </it>gene copy number, activation of the EGFR pathway, abundance and mutation of E-cadherin which plays an important role in these disorders, BRAF mutation and clinical outcome of patients was studied. <it>EGFR </it>gene copy number was assessed by FISH. Expression of the phosphorylated forms of EGFR and its downstream effectors Akt and MAPK, in addition to E-cadherin was analysed by immunohistochemistry. The frequency of mutant V600E BRAF was evaluated by allele-specific PCR and the mutation profile of the E-cadherin gene <it>CDH1 </it>was examined by DHPLC followed by direct sequence analysis. Correlations with overall survival (OS), time to progression (TTP) and overall response rate (ORR) were assessed.</p> <p>Results</p> <p>Our study showed a significant association between increased <it>EGFR </it>gene copy number (≥ 4.0) and OS in gastric and OGJ cancer, indicating the possibility that patients may be selected for treatment on a genetic basis. Furthermore, a significant correlation was shown between activated EGFR and shorter TTP and ORR, but not between activated EGFR and OS. No V600E BRAF mutations were identified. On the other hand, an interesting trend between high E-cadherin expression levels and better OS was observed and two <it>CDH1 </it>exon 9 missense mutations (A408V and D402H) were detected.</p> <p>Conclusion</p> <p>Our finding that increased <it>EGFR </it>gene copy numbers, activated EGFR and the E-cadherin status are potentially interesting biomarkers needs to be confirmed in larger randomized clinical trials.</p> <p>Trial registration</p> <p>Multicentre clinical study with the European Clinical Trials Database number 2004-004024-12.</p

Stat1 Phosphorylation Determines Ras Oncogenicity by Regulating p27Kip1

Inactivation of p27Kip1 is implicated in tumorigenesis and has both prognostic and treatment-predictive values for many types of human cancer. The transcription factor Stat1 is essential for innate immunity and tumor immunosurveillance through its ability to act downstream of interferons. Herein, we demonstrate that Stat1 functions as a suppressor of Ras transformation independently of an interferon response. Inhibition of Ras transformation and tumorigenesis requires the phosphorylation of Stat1 at tyrosine 701 but is independent of Stat1 phosphorylation at serine 727. Stat1 induces p27Kip1 expression in Ras transformed cells at the transcriptional level through mechanisms that depend on Stat1 phosphorylation at tyrosine 701 and activation of Stat3. The tumor suppressor properties of Stat1 in Ras transformation are reversed by the inactivation of p27Kip1. Our work reveals a novel functional link between Stat1 and p27Kip1, which act in coordination to suppress the oncogenic properties of activated Ras. It also supports the notion that evaluation of Stat1 phosphorylation in human tumors may prove a reliable prognostic factor for patient outcome and a predictor of treatment response to anticancer therapies aimed at activating Stat1 and its downstream effectors