Adhesive and degradative properties of human placental cytotrophoblast cells in vitro.

Human fetal development depends on the embryo rapidly gaining access to the maternal circulation. The trophoblast cells that form the fetal portion of the human placenta have solved this problem by transiently exhibiting certain tumor-like properties. Thus, during early pregnancy fetal cytotrophoblast cells invade the uterus and its arterial network. This process peaks during the twelfth week of pregnancy and declines rapidly thereafter, suggesting that the highly specialized, invasive behavior of the cytotrophoblast cells is closely regulated. Since little is known about the actual mechanisms involved, we developed an isolation procedure for cytotrophoblasts from placentas of different gestational ages to study their adhesive and invasive properties in vitro. Cytotrophoblasts isolated from first, second, and third trimester human placentas were plated on the basement membrane-like extracellular matrix produced by the PF HR9 teratocarcinoma cell line. Cells from all trimesters expressed the calcium-dependent cell adhesion molecule cell-CAM 120/80 (E-cadherin) which, in the placenta, is specific for cytotrophoblasts. However, only the first trimester cytotrophoblast cells degraded the matrices on which they were cultured, leaving large gaps in the basement membrane substrates and releasing low molecular mass 3H-labeled matrix components into the medium. No similar degradative activity was observed when second or third trimester cytotrophoblast cells, first trimester human placental fibroblasts, or the human choriocarcinoma cell lines BeWo and JAR were cultured on radiolabeled matrices. To begin to understand the biochemical basis of this degradative behavior, the substrate gel technique was used to analyze the cell-associated and secreted proteinase activities expressed by early, mid, and late gestation cytotrophoblasts. Several gelatin-degrading proteinases were uniquely expressed by early gestation, invasive cytotrophoblasts, and all these activities could be abolished by inhibitors of metalloproteinases. By early second trimester, the time when cytotrophoblast invasion rapidly diminishes in vivo, the proteinase pattern of the cytotrophoblasts was identical to that of term, noninvasive cells. These results are the first evidence suggesting that specialized, temporally regulated metalloproteinases are involved in trophoblast invasion of the uterus. Since the cytotrophoblasts from first trimester and later gestation placentas maintain for several days the temporally regulated degradative behavior displayed in vivo, the short-term cytotrophoblast outgrowth culture system described here should be useful in studying some of the early events in human place

Rain Gardens in Worcester

Poster Presentation, Judge\u27s Winner (2015)https://digitalcommons.wpi.edu/gps-posters/1366/thumbnail.jp

A randomized, phase II study of afatinib versus cetuximab in metastatic or recurrent squamous cell carcinoma of the head and neck.

BackgroundAfatinib is an oral, irreversible ErbB family blocker that has shown activity in epidermal growth factor receptor (EGFR)-mutated lung cancer. We hypothesized that the agent would have greater antitumor activity compared with cetuximab in recurrent or metastatic (R/M) head and neck squamous cell carcinoma (HNSCC) patients, whose disease has progressed after platinum-containing therapy.Patients and methodsAn open-label, randomized, phase II trial was conducted in 43 centers; 124 patients were randomized (1 : 1) to either afatinib (50 mg/day) or cetuximab (250 mg/m(2)/week) until disease progression or intolerable adverse events (AEs) (stage I), with optional crossover (stage II). The primary end point was tumor shrinkage before crossover assessed by investigator (IR) and independent central review (ICR).ResultsA total of 121 patients were treated (61 afatinib, 60 cetuximab) and 68 crossed over to stage II (32 and 36 respectively). In stage I, mean tumor shrinkage by IR/ICR was 10.4%/16.6% with afatinib and 5.4%/10.1% with cetuximab (P = 0.46/0.30). Objective response rate was 16.1%/8.1% with afatinib and 6.5%/9.7% with cetuximab (IR/ICR). Comparable disease control rates were observed with afatinib (50%) and cetuximab (56.5%) by IR; similar results were seen by ICR. Most common grade ≥3 drug-related AEs (DRAEs) were rash/acne (18% versus 8.3%), diarrhea (14.8% versus 0%), and stomatitis/mucositis (11.5% versus 0%) with afatinib and cetuximab, respectively. Patients with DRAEs leading to treatment discontinuation were 23% with afatinib and 5% with cetuximab. In stage II, disease control rate (IR/ICR) was 38.9%/33.3% with afatinib and 18.8%/18.8% with cetuximab.ConclusionAfatinib showed antitumor activity comparable to cetuximab in R/M HNSCC in this exploratory phase II trial, although more patients on afatinib discontinued treatment due to AEs. Sequential EGFR/ErbB treatment with afatinib and cetuximab provided sustained clinical benefit in patients after crossover, suggesting a lack of cross-resistance

A model-based approach to recovering the structure of a plant from images

We present a method for recovering the structure of a plant directly from a small set of widely-spaced images. Structure recovery is more complex than shape estimation, but the resulting structure estimate is more closely related to phenotype than is a 3D geometric model. The method we propose is applicable to a wide variety of plants, but is demonstrated on wheat. Wheat is made up of thin elements with few identifiable features, making it difficult to analyse using standard feature matching techniques. Our method instead analyses the structure of plants using only their silhouettes. We employ a generate-and-test method, using a database of manually modelled leaves and a model for their composition to synthesise plausible plant structures which are evaluated against the images. The method is capable of efficiently recovering accurate estimates of plant structure in a wide variety of imaging scenarios, with no manual intervention

A novel self-assembled oligopeptide amphiphile for biomimetic mineralization of enamel

Background Researchers are looking for biomimetic mineralization of ena/mel to manage dental erosion. This study evaluated biomimetic mineralization of demineralized enamel induced by a synthetic and self-assembled oligopeptide amphiphile (OPA). Results The results showed that the OPA self-assembled into nano-fibres in the presence of calcium ions and in neutral acidity. The OPA was alternately immersed in calcium chloride and sodium hypophosphate solutions to evaluate its property of mineralization. Transmission electron microscopy (TEM) and scanning electron microscopy (SEM) showed nucleation and growth of amorphous calcium phosphate along the self-assembled OPA nano-fibres when it was repetitively exposed to solutions with calcium and phosphate ions. Energy dispersive spectrometry (EDS) confirmed that these nano-particles contained calcium and phosphate. Furthermore, electron diffraction pattern suggested that the nano-particles precipitated on OPA nano-fibres were comparable to amorphous calcium phosphate. Acid-etched human enamel slices were incubated at 37°C in metastable calcium phosphate solution with the OPA for biomimetic mineralization. SEM and X-ray diffraction indicated that the OPA induced the formation of hydroxyapatite crystals in organized bundles on etched enamel. TEM micrographs revealed there were 20–30 nm nano-amorphous calcium phosphate precipitates in the biomimetic mineralizing solution. The particles were found separately bound to the oligopeptide fibres. Biomimetic mineralization with or without the oligopeptide increased demineralized enamel microhardness. Conclusions A novel OPA was successfully fabricated, which fostered the biomimetic mineralization of demineralized enamel. It is one of the primary steps towards the design and construction of novel biomaterial for future clinical therapy of dental erosion.published_or_final_versio

Automated functional testing of online search services

Search services are the main interface through which people discover information on the Internet. A fundamental challenge in testing search services is the lack of oracles. The sheer volume of data on the Internet prohibits testers from verifying the results. Furthermore, it is difficult to objectively assess the ranking quality because different assessors can have very different opinions on the relevance of a Web page to a query. This paper presents a novel method for automatically testing search services without the need of a human oracle. The experimental findings reveal that some commonly used search engines, including Google, Yahoo!, and Live Search, are not as reliable as what most users would expect. For example, they may fail to find pages that exist in their own repositories, or rank pages in a way that is logically inconsistent. Suggestions are made for search service providers to improve their service quality. Copyright © 2010 John Wiley & Sons, Ltd. A novel method for automatically testing search services without the need of a human oracle is presented. The experimental findings reveal that some commonly used search engines, including Google, Yahoo!, and Live Search, are not as reliable as what most users would expect. For example, they may fail to find pages that exist in their own repositories, or rank pages in a way that is logically inconsistent. Suggestions are made for search service providers to improve their service quality. Copyright © 2010 John Wiley & Sons, Ltd.link_to_subscribed_fulltex

Mental Health in the UK Biobank: A Roadmap to Self-Report Measures and Neuroimaging Correlates

The UK Biobank (UKB) is a highly promising dataset for brain biomarker research into population mental health due to its unprecedented sample size and extensive phenotypic, imaging, and biological measurements. In this study, we aimed to provide a shared foundation for UKB neuroimaging research into mental health with a focus on anxiety and depression. We compared UKB self-report measures and revealed important timing effects between scan acquisition and separate online acquisition of some mental health measures. To overcome these timing effects, we introduced and validated the Recent Depressive Symptoms (RDS-4) score which we recommend for state-dependent and longitudinal research in the UKB. We furthermore tested univariate and multivariate associations between brain imaging-derived phenotypes (IDPs) and mental health. Our results showed a significant multivariate relationship between IDPs and mental health, which was replicable. Conversely, effect sizes for individual IDPs were small. Test–retest reliability of IDPs was stronger for measures of brain structure than for measures of brain function. Taken together, these results provide benchmarks and guidelines for future UKB research into brain biomarkers of mental health

Similarity regularized sparse group lasso for cup to disc ratio computation

© 2017 Optical Society of America. Automatic cup to disc ratio (CDR) computation from color fundus images has shown to be promising for glaucoma detection. Over the past decade, many algorithms have been proposed. In this paper, we first review the recent work in the area and then present a novel similarity-regularized sparse group lasso method for automated CDR estimation. The proposed method reconstructs the testing disc image based on a set of reference disc images by integrating the similarity between testing and the reference disc images with the sparse group lasso constraints. The reconstruction coefficients are then used to estimate the CDR of the testing image. The proposed method has been validated using 650 images with manually annotated CDRs. Experimental results show an average CDR error of 0.0616 and a correlation coefficient of 0.7, outperforming other methods. The areas under curve in the diagnostic test reach 0.843 and 0.837 when manual and automatically segmented discs are used respectively, better than other methods as well

Surface modification of HVOF thermal sprayed WC–CoCr coatings by laser treatment

In this work the affects of laser characteristics on microstructure and microhardness of high velocity oxygen fuel sprayed (HVOF) WC–CoCr coatings were investigated. The coating was deposited with a Sulzer Metco WokaJet™-400 kerosene fuel and the laser surface treatments were applied using CO2 laser with 10.6 μm wavelength. Large variations in surface properties were produced from variation in the laser processing parameters. In total, four levels of peak power (100, 200, 300 and 350 W), four levels of spot diameter (0.2, 0.4, 0.6 and 1 mm) and three levels of pulse repetition frequency (PRF) were investigated. An initial set of tests were followed by a more detailed 33 factorial design of experiments. Pulse repetition frequency and duty cycle were set in order to maintain the same overlap in the x and y directions for the raster scanned sample spot impact dimensions. Overlaps of 30% were used in the initial tests and 10% in the more detailed trials. The results have shown that care must be taken to keep the irradiance at a relatively low level compared to uncoated surfaces. High irradiance can in this case result in rough and porous surfaces. Lower levels of irradiance are shown to provide more uniform microstructures, reduced porosity and increased microhardness