Automatic Summarization of Changes in Biological Image Sequences Using Algorithmic Information Theory

An algorithmic information-theoretic method is presented for object-level summarization of meaningful changes in image sequences. Object extraction and tracking data are represented as an attributed tracking graph (ATG). Time courses of object states are compared using an adaptive information distance measure, aided by a closed-form multidimensional quantization. The notion of meaningful summarization is captured by using the gap statistic to estimate the randomness deficiency from algorithmic statistics. The summary is the clustering result and feature subset that maximize the gap statistic. This approach was validated on four bioimaging applications: 1) It was applied to a synthetic data set containing two populations of cells differing in the rate of growth, for which it correctly identified the two populations and the single feature out of 23 that separated them; 2) it was applied to 59 movies of three types of neuroprosthetic devices being inserted in the brain tissue at three speeds each, for which it correctly identified insertion speed as the primary factor affecting tissue strain; 3) when applied to movies of cultured neural progenitor cells, it correctly distinguished neurons from progenitors without requiring the use of a fixative stain; and 4) when analyzing intracellular molecular transport in cultured neurons undergoing axon specification, it automatically confirmed the role of kinesins in axon specification.     

Polyphosphazene membranes. I. Solid-state photocrosslinking of poly[(4-ethylphenoxy)-(phenoxy)phosphazene]

Dense films of poly[(4-ethylphenoxy)(phenoxy)phosphazene] (PEPP), a potentially attractive ion-exchange membrane material, were crosslinked to varying degrees using UV light and a photoinitiator. This polymer contained two kinds of substituents: phenoxy groups to be used for possible functionalization (e.g., sulfonation) and ethylphenoxy side-chains for photocrosslinking, where hydrogens at the benzylic carbons could be abstracted by a photoinitiator-leaving macroradicals that after recombination formed covalent bonds. The polyphosphazene polymer was synthesized, mixed with a photoinitiator, shaped into a thin film by solvent casting, and irradiated with UV light for a specified period of time. Benzophenone (BP), was selected as the photoinitiator because it was miscible with poly-phosphazene, had the highest rate of hydrogen abstraction, and absorbed UV light of 365 nm wavelength. The half-life of benzophenone in 50 μm-thick irradiated films was determined to be 20 min. When the BP–PEPP molar ratio was increased from 0 to 0.5, the glass transition temperature increased after irradiation from −8.8 to 53.5°C. At the same time, the equilibrium swelling in dimethylacetamide, at 25°C, decreased from infinity to 0.31. Tensile strength tests of the crosslinked films revealed a nonlinear dependence on BP–PEPP molar ratio. © 1996 John Wiley & Sons, Inc.     

Food hygiene and hazard analysis critical control point in the United Kingdom food industry: practices, perceptions, and attitudes.

A mail survey was designed and distributed to 1,650 managers of food businesses across the manufacturing, retail, and catering sectors of the United Kingdom food industry. Respondents were asked about the food hygiene practices of their business, their use of systems such as hazard analysis critical control point (HACCP), and their attitudes toward a range of food hygiene-related issues. Complete responses were received from 254 businesses, a response rate of 15.3%. The results showed that 69% of manufacturers were using HACCP systems, significantly more than the 13% and 15% in the retail and catering sectors, respectively (P < 0.05); 53% of manufacturing, 59% of retail, and 48% of catering managers thought that their business represented a low risk to food safety. Among businesses using HACCP, specific training in the system was significantly related to the likelihood that businesses had adopted all seven of the HACCP principles (P < 0.05). Business size was a significant factor in the use of HACCP in both the manufacturing and retail sectors. Higher levels of food hygiene qualifications among business managers, business status, and higher perceptions among managers of the risk to food safety of the business were also significantly related to HACCP use in all sectors (P < 0.05). The results from this survey have implications for the future development of HACCP, particularly within the UK retail and catering sectors. Risk communication and training are highlighted as areas of concern for marketing HACCP within these industry sectors.     

Design and synthesis of conformationally constrained cyclophilin inhibitors showing a cyclosporin-A phenotype in C. elegans

Cyclophilin A (CypA) is a member of the immunophilin family of proteins and receptor for the immunosuppressant drug cyclosporin A (CsA). Here we describe the design and synthesis of a new class of small-molecule inhibitors for CypA that are based upon a dimedone template. Electrospray mass spectrometry is utilised as an initial screen to quantify the protein affinity of the ligands. Active inhibitors and fluorescently labelled derivatives are then used as chemical probes for investigating the biological role of cyclophilins in the nematode Caenorhabditis elegans.     

Dual Inhibition of MEK and PI3K Pathway in KRAS and BRAF Mutated Colorectal Cancers

Colorectal cancer (CRC) is a heterogeneous disease with multiple underlying causative genetic mutations. Genetic mutations in the phosphatidylinositol-3 kinase (PI3K) and the mitogen activated protein kinase (MAPK) pathways are frequently implicated in CRC. Targeting the downstream substrate MEK in these mutated tumors stands out as a potential target in CRC. Several selective inhibitors of MEK have entered clinical trial evaluation; however, clinical activity with single MEK inhibitors has been rarely observed and acquired resistance seems to be inevitable. Amplification of the driving oncogene KRAS(13D), which increases signaling through the ERK1/2 pathway, upregulation of the noncanonical wingless/calcium signaling pathway (Wnt), and coexisting PIK3CA mutations have all been implicated with resistance against MEK inhibitor therapy in KRAS mutated CRC. The Wnt pathway and amplification of the oncogene have also been associated with resistance to MEK inhibitors in CRCs harboring BRAF mutations. Thus, dual targeted inhibition of MEK and PI3K pathway effectors (mTOR, PI3K, AKT, IGF-1R or PI3K/mTOR inhibitors) presents a potential strategy to overcome resistance to MEK inhibitor therapy. Many clinical trials are underway to evaluate multiple combinations of these pathway inhibitors in solid tumors.     

Metabolomic Profiling of Plasma from Melioidosis Patients Using UHPLC-QTOF MS Reveals Novel Biomarkers for Diagnosis

To identify potential biomarkers for improving diagnosis of melioidosis, we compared plasma metabolome profiles of melioidosis patients compared to patients with other bacteremia and controls without active infection, using ultra-high-performance liquid chromatography-electrospray ionization-quadruple time-of-flight mass spectrometry. Principal component analysis (PCA) showed that the metabolomic profiles of melioidosis patients are distinguishable from bacteremia patients and controls. Using multivariate and univariate analysis, 12 significant metabolites from four lipid classes, acylcarnitine (n = 6), lysophosphatidylethanolamine (LysoPE) (n = 3), sphingomyelins (SM) (n = 2) and phosphatidylcholine (PC) (n = 1), with significantly higher levels in melioidosis patients than bacteremia patients and controls, were identified. Ten of the 12 metabolites showed area-under-receiver operating characteristic curve (AUC) >0.80 when compared both between melioidosis and bacteremia patients, and between melioidosis patients and controls. SM(d18:2/16:0) possessed the largest AUC when compared, both between melioidosis and bacteremia patients (AUC 0.998, sensitivity 100% and specificity 91.7%), and between melioidosis patients and controls (AUC 1.000, sensitivity 96.7% and specificity 100%). Our results indicate that metabolome profiling might serve as a promising approach for diagnosis of melioidosis using patient plasma, with SM(d18:2/16:0) representing a potential biomarker. Since the 12 metabolites were related to various pathways for energy and lipid metabolism, further studies may reveal their possible role in the pathogenesis and host response in melioidosis.     

Tripalmitin–Sodium Dodecyl Sulfate Emulsion Droplet Liquid vs. Solid State Impacts in vitro Digestive Lipolysis

Questions remain as to the impact of lipid structure, including crystallinity, on digestibility and metabolic response. This study was undertaken to determine the impact of triacylglycerol crystallinity on digestibility using undercooled (liquid emulsion, LE) and crystalline (solid emulsion, SE) particles exposed to an in vitro model simulating upper gastrointestinal tract (GIT) digestive conditions. By hot microfluidization, 10 wt% tripalmitin oil‐in‐water emulsions (D_3,2 ~ 0.115 nm) with 0.9 wt% sodium dodecyl sulfate (SDS) were prepared. SE demonstrated complex melting behavior, was predominantly in the beta polymorph, and consisted of a heterogeneous mixture of anisometric particles. In vitro duodenal lipolysis was more extensive for the spherically shaped LE droplets vs. SE (P < 0.05), despite the fact that exposure to simulated gastric conditions (at pH 2, but not at pH 7) induced partial crystallization. Therefore, lipid droplet physical state impacted and was impacted by exposure to gastrointestinal conditions, with differences observed in fatty acid digestive release and implications for lipid absorption.     

Preliminary Evidence on the Diagnostic and Molecular Role of Circulating Soluble EGFR in Non-Small Cell Lung Cancer

Assessment of biological diagnostic factors providing clinically-relevant information to guide physician decision-making are still needed for diseases with poor outcomes, such as non-small cell lung cancer (NSCLC). Epidermal growth factor receptor (EGFR) is a promising molecule in the clinical management of NSCLC. While the EGFR transmembrane form has been extensively investigated in large clinical trials, the soluble, circulating EGFR isoform (sEGFR), which may have a potential clinical use, has rarely been considered. This study investigates the use of sEGFR as a potential diagnostic biomarker for NSCLC and also characterizes the biological function of sEGFR to clarify the molecular mechanisms involved in the course of action of this protein. Plasma sEGFR levels from a heterogeneous cohort of 37 non-advanced NSCLC patients and 54 healthy subjects were analyzed by using an enzyme-linked immunosorbent assay. The biological function of sEGFR was analyzed in vitro using NSCLC cell lines, investigating effects on cell proliferation and migration. We found that plasma sEGFR was significantly decreased in the NSCLC patient group as compared to the control group (median value: 48.6 vs. 55.6 ng/mL respectively; p = 0.0002). Moreover, we demonstrated that sEGFR inhibits growth and migration of NSCLC cells in vitro through molecular mechanisms that included perturbation of EGF/EGFR cell signaling and holoreceptor internalization. These data show that sEGFR is a potential circulating biomarker with a physiological protective role, providing a first approach to the functional role of the soluble isoform of EGFR. However, the impact of these data on daily clinical practice needs to be further investigated in larger prospective studies.     

In Situ X-ray Diffraction and Young's Modulus Measurement during Heat Treatment of High-Alumina Cement Castables

In situ Young's modulus measurements and synchrotron radiation-energy dispersive diffraction have been used to study changes in high-alumina castables subjected to heat treatment from room temperature to 1600°C. Particular attention was paid to the hydrate conversion process and the effects of high temperature.     

Vitamin D and Death by Sunshine

Exposure to sunlight is the major cause of skin cancer. Ultraviolet radiation (UV) from the sun causes damage to DNA by direct absorption and can cause skin cell death. UV also causes production of reactive oxygen species that may interact with DNA to indirectly cause oxidative DNA damage. UV increases accumulation of p53 in skin cells, which upregulates repair genes but promotes death of irreparably damaged cells. A benefit of sunlight is vitamin D, which is formed following exposure of 7-dehydrocholesterol in skin cells to UV. The relatively inert vitamin D is metabolized to various biologically active compounds, including 1,25-dihydroxyvitamin D3. Therapeutic use of vitamin D compounds has proven beneficial in several cancer types, but more recently these compounds have been shown to prevent UV-induced cell death and DNA damage in human skin cells. Here, we discuss the effects of vitamin D compounds in skin cells that have been exposed to UV. Specifically, we examine the various signaling pathways involved in the vitamin D-induced protection of skin cells from UV.