The Environmental Remediation of Clark Island − A Former AlliedSignal Inc. Site

Clark Island is a 63 ha island located in Lake St-Francis, part of the St-Lawrence River, Québec, Canada. Since the early 40s the island has been used for the production of mineral acids by its fanner owner, Allied Chemicals Limited. Acidic wastes were placed over large portions of the island. The presence of these waste materials together with contaminated soils was identified as a potential threat to the nearby river water quality as well as to the underlying bedrock groundwater quality. A major remedial investigation and feasibility study was initiated in 1987. The approved scope of the remediation project included the construction of one 60,000 m3 single lined cell for the placement of contaminated soils, and one 130,000 m3 double lined cell for the placement of acidic wastes. The remediation project was implemented during the 1991-1993 period. In order to assess the efficiency of the remediation, a detailed environmental monitoring program was implemented during the works and in the following years. The general conclusion of this major project is that confining acidic wastes in lined cells provide a safe and economical way to avoid detrimental consequences to the environment

第647回千葉医学会例会・第5回千葉大学小児外科教室例会 6.

<p>(A) A schematic describing the experimental process used to test the four cell separation techniques. A single tumor from each PDX line was processed using a gentleMACS^™ Octo Dissociator to obtain a single cell suspension comprising a heterogeneous mixture of human cells (blue) and mouse cells (orange). The suspension was divided in five samples. The pre-sort sample received no further processing. The remaining 4 tubes were processed using each method to obtain separate human and mouse cell populations. Each resulting human fraction and the pre-sort sample were analyzed using ssPAL. (B) ssPAL analysis results for primer pair 5 and 43 were averaged together to obtain the human DNA percentage for each separation method. After performing ssPAL analysis, results indicate that on average, MCD yields the highest sample purity over FACS, EpCAM-M and EpCAM-SC. The starting amount of murine stromal contamination also influences the effectiveness of the kit used, with EpCAM-M and EpCAM-SC performing poorly with higher initial murine content. Error bars represent standard error.</p

Large expert-curated database for benchmarking document similarity detection in biomedical literature search

Document recommendation systems for locating relevant literature have mostly relied on methods developed a decade ago. This is largely due to the lack of a large offline gold-standard benchmark of relevant documents that cover a variety of research fields such that newly developed literature search techniques can be compared, improved and translated into practice. To overcome this bottleneck, we have established the RElevant LIterature SearcH consortium consisting of more than 1500 scientists from 84 countries, who have collectively annotated the relevance of over 180 000 PubMed-listed articles with regard to their respective seed (input) article/s. The majority of annotations were contributed by highly experienced, original authors of the seed articles. The collected data cover 76% of all unique PubMed Medical Subject Headings descriptors. No systematic biases were observed across different experience levels, research fields or time spent on annotations. More importantly, annotations of the same document pairs contributed by different scientists were highly concordant. We further show that the three representative baseline methods used to generate recommended articles for evaluation (Okapi Best Matching 25, Term Frequency-Inverse Document Frequency and PubMed Related Articles) had similar overall performances. Additionally, we found that these methods each tend to produce distinct collections of recommended articles, suggesting that a hybrid method may be required to completely capture all relevant articles. The established database server located at https://relishdb.ict.griffith.edu.au is freely available for the downloading of annotation data and the blind testing of new methods. We expect that this benchmark will be useful for stimulating the development of new powerful techniques for title and title/abstract-based search engines for relevant articles in biomedical research.Peer reviewe

Quantitation of Murine Stroma and Selective Purification of the Human Tumor Component of Patient-Derived Xenografts for Genomic Analysis.

Patient-derived xenograft (PDX) mouse models are increasingly used for preclinical therapeutic testing of human cancer. A limitation in molecular and genetic characterization of PDX tumors is the presence of integral murine stroma. This is particularly problematic for genomic sequencing of PDX models. Rapid and dependable approaches for quantitating stromal content and purifying the malignant human component of these tumors are needed. We used a recently developed technique exploiting species-specific polymerase chain reaction (PCR) amplicon length (ssPAL) differences to define the fractional composition of murine and human DNA, which was proportional to the fractional composition of cells in a series of lung cancer PDX lines. We compared four methods of human cancer cell isolation: fluorescence-activated cell sorting (FACS), an immunomagnetic mouse cell depletion (MCD) approach, and two distinct EpCAM-based immunomagnetic positive selection methods. We further analyzed DNA extracted from the resulting enriched human cancer cells by targeted sequencing using a clinically validated multi-gene panel. Stromal content varied widely among tumors of similar histology, but appeared stable over multiple serial tumor passages of an individual model. FACS and MCD were superior to either positive selection approach, especially in cases of high stromal content, and consistently allowed high quality human-specific genomic profiling. ssPAL is a dependable approach to quantitation of murine stromal content, and MCD is a simple, efficient, and high yield approach to human cancer cell isolation for genomic analysis of PDX tumors

PDX mouse model tumor transplantation schema and passage over time.

<p>(A) This schematic summarizes our protocol for PDX generation, implantation, and passaging. Tumor tissue is collected from the patient and prepped into a single cell suspension using the gentleMACS^™ Octo Dissociator. Cells are mixed 1:1 with matrigel and implanted single flank in immunosuppressed mice. Once tumor reaches end volume and is ready for passage; it is collected, processed into a single cell suspension, then cells are re-implanted in the next set of mice. (B) ssPAL analysis reveals that PDX tumors do not show significant variation in murine stromal content over successive passages. MSK-LX242 and MSK-LX29 are lung adenocarcinoma PDX lines, MSK-LX95 is a SCLC PDX line, and MSK-LX96 is a mesothelioma PDX line. Error bars represent standard error. P0 = Passage 0, P1 = Passage 1, P2 = Passage 2, etc.</p

ssPAL analysis detects spontaneous murine tumor formation.

<p>ssPAL analysis detects spontaneous murine tumor formation.</p

ssPAL analysis yields precise measurements with accuracy comparable to FACS.

<p>(A) After performing capillary electrophoresis, the presence of each PCR product (human and murine) for both primer pairs is evaluated. The peak at 206 bp corresponds to the murine fraction (orange), the peak at 211 bp correspond to the human fraction (blue). The resulting peak areas are proportional to the murine and human DNA content in a given sample. (B) ssPAL analysis is performed using two primer pairs (5 and 43) that amplify homologous regions of the mouse and human genome. This technique can accurately detect the percentages of murine DNA in pre-set mixtures of NIH 3T3 and Jurkat cells DNA within a range of 1% to 99%. Sensitivity is lost when analyzing values outside of this range. (C) FACS is the gold standard to separate human and murine cells and quantify the percentage of each population. In this representative plot, a PDX tumor from line MSK-LX29 is sorted using EpCAM and H-2K^d. (D) Murine DNA content determined by ssPAL is proportional to murine cell content measured by FACS.</p

ssPAL analysis highlights significant murine stromal content variation across multiple lung PDX lines.

<p>(A) The ssPAL analysis results for primer pairs 5 and 43 were averaged. Murine stromal contamination exhibits a wide range between PDX lines. (B) While stromal contamination is variable between PDX lines, it is consistent between tumors of the same cancer subtype. Stromal content in SCLC PDX was significantly lower than in LUAD (two-tailed Student’s <i>t</i>-test). LUAD = lung adenocarcinoma, SCLC = small cell lung cancer, PLMESO = pleural mesothelioma, LUSC = lung squamous carcinoma.</p