Laboratory Website Research Articles

Adaptive Wavelet Neural Network Based Wind Speed Forecasting Studies

Wind has been a rapidly growing renewable power source for the last twenty years. Since wind behavior is chaotic in nature, its forecasting is not easy. At the same time, developing an accurate forecasting method is essential when wind farms are integrated into the power grid. In fact, wind speed forecasting tools can solve issues related to grid stability and reserve allocation. In this paper 30 hours ahead wind speed profile forecast is proposed using Adaptive Wavelet Neural Network (AWNN). The implemented AWNN uses a Mexican hat mother Wavelet, and Morlet Mother Wavelet for seven, eight and nine levels decompositions. For wind speed forecasting, the time series data on wind speed has been gathered from the National Renewable Energy Laboratory (NREL) website. In this work, hourly averaged 10-min wind speed data sets for the year 2004 in the Midwest ISO region (site number 7263) is taken for analysis. Data sets are normalized in the range of [-1, 1] to improve the training performance of forecasting models. Total 8760 samples were taken for this forecasting analysis. After the forecasting phase, statistical parameters are calculated to evaluate system accuracy, comparing different configurations.

Credentialing features: a platform to benchmark and optimize untargeted metabolomic methods.

The aim of untargeted metabolomics is to profile as many metabolites as possible, yet a major challenge is comparing experimental method performance on the basis of metabolome coverage. To date, most published approaches have compared experimental methods by counting the total number of features detected. Due to artifactual interference, however, this number is highly variable and therefore is a poor metric for comparing metabolomic methods. Here we introduce an alternative approach to benchmarking metabolome coverage which relies on mixed Escherichia coli extracts from cells cultured in regular and 13C-enriched media. After mass spectrometry-based metabolomic analysis of these extracts, we “credential” features arising from E. coli metabolites on the basis of isotope spacing and intensity. This credentialing platform enables us to accurately compare the number of nonartifactual features yielded by different experimental approaches. We highlight the value of our platform by reoptimizing a published untargeted metabolomic method for XCMS data processing. Compared to the published parameters, the new XCMS parameters decrease the total number of features by 15% (a reduction in noise features) while increasing the number of true metabolites detected and grouped by 20%. Our credentialing platform relies on easily generated E. coli samples and a simple software algorithm that is freely available on our laboratory Web site (http://pattilab.wustl.edu/software/credential/). We have validated the credentialing platform with reversed-phase and hydrophilic interaction liquid chromatography as well as Agilent, Thermo Scientific, AB SCIEX, and LECO mass spectrometers. Thus, the credentialing platform can readily be applied by any laboratory to optimize their untargeted metabolomic pipeline for metabolite extraction, chromatographic separation, mass spectrometric detection, and bioinformatic processing.

Using a digital story format: a contemporary approach to meeting the workforce needs of public health laboratories.

Public health laboratories are an integral partner in preparedness and emergency response. The Upper Midwest Preparedness and Emergency Response Learning Center (UMPERLC) and the State Hygienic Laboratory at the University of Iowa have a long history of working together to identify and meet the preparedness training needs of the laboratory workforce. The training, Anatomy of a Foodborne Outbreak, which uses a digital story format, provides an example of this partnership. The State Hygienic Laboratory expressed the need for training programs targeted at enhancing early detection and investigation of outbreaks. Clinical laboratory staff play a significant role in identifying patient samples that may represent the effects of foodborne illness. Given that foodborne illnesses are on the increase nationally, it is critical that laboratory staff be prepared to deal with these outbreaks. UMPERLC collaborated with State Hygienic Laboratory content experts in the design and development of a digital story, using a foodborne outbreak that focuses on testing to detect Shiga toxin-producing Escherichia coli. This narrative format was selected because seeing and hearing a story about the training content provide the learner with a deeper interaction and richer learning experience, allowing the learner to better see the bigger picture. Anatomy of a Foodborne Outbreak is available on UMPERLC's Learning Management System, Training Source (http://training-source.org). Evaluation data indicate positive learning experiences overall. The digital story format, which is a video that uses a blend of images, text, and audio narration, was an appropriate method for the content and learning outcomes of the Anatomy of a Foodborne Outbreak training. This format requires more active learning, which increases retention and transfer of knowledge. Training that is easily accessed and user-friendly is an important resource for laboratory staff. When reviewing the course completion data, the highest enrollment occurred immediately after the training program was released. To increase visibility, Anatomy of a Foodborne Outbreak is housed on both the State Hygienic Laboratory Web site and UMPERLC's Learning Management System. The course has also been added to national learning databases such as the Centers for Disease Control and Prevention TrainingFinder Real-time Affiliate Integrated Network (CDC TRAIN) and Certified in Public Health Recertification & Reporting System.

Quantitative Structure-Retention Relationships Studies of Selected Groups of Compounds Characterized by Different Pharmacological Activity Using Multiple Linear Regression Procedure

In this paper the quantitative structure-retention relationships (QSRR) studies for three different groups of drugs (cardiovascular system drugs, analgesic drugs and some compounds characterized by divergent pharmacological activity) and for chromatographic parameters (log k' or log k' w retention factors) determined with the use of the HPLC methods were performed. Molecular descriptors (over 4900 molecular modeling parameters) obtained using the HyperChem and the Dragon computer programs, and the Virtual Computational Chemistry Laboratory (VCCLAB) website were applied to derive the QSRR equations by means of multiple linear regression method with stepwise procedure. Several statistically significant QSRR equations as two-parameters for both cardiovascular and analgesic drugs, and sevenparameters for group of “other” drugs were built. Six QSRR equations with correlations R ranged from 0.9822 to 0.9957 were obtained for cardiovascular drugs, twenty-six QSRRs with R equal to 0.9120-0.9776 were derived for analgesics, and ten QSRRs with R from 0.9529 to 0.9924 were calculated for “other“ drugs. Moreover, the proposed QSRR models give important information about physico-chemical properties of analyzed drugs, and indicated that descriptors characterized topology, geometry and lipophilicity of molecular structures of analyzed compounds are crucial for prediction of their retention parameters. Additionally, derived QSRR models can be helpful to search (to prediction) HPLC retention factor for the new drug candidates.

Virtual histology laboratory with an interactive tutorial feature: transitioning into the future of histology education (725.11)

The objective of the project was to create a beta version of a virtual histology laboratory website incorporating an interactive tutorial feature that can effectively simulate an in‐class interaction with an expert. Although many virtual histology laboratories already exist and have shown their effectiveness in reducing cost and space while increasing instructional efficiency, few can be classified as a successful stand‐alone learning tool. Learning histology requires pattern recognition skills acquired through hands‐on, instructional sessions conducted by an expert identifying key structures, quizzing students and providing feedback. The interactive tutorial feature simulates this expert interaction through an overlay of annotated identification markers on characteristic histological structures and self‐assessment tool which provides instant feedback at a click of a button. This innovative add‐on feature to the virtual histology laboratory is expected to help students obtain mastery in histological pattern‐recognition on their own, and be less dependent of an expert’s presence. A beta version of the website will be available for exploration of its features and effectiveness as a stand‐alone learning tool.

X13CMS: Global Tracking of Isotopic Labels in Untargeted Metabolomics

Studies of isotopically labeled compounds have been fundamental to understanding metabolic pathways and fluxes. They have traditionally, however, been used in conjunction with targeted analyses that identify and quantify a limited number of labeled downstream metabolites. Here we describe an alternative workflow that leverages recent advances in untargeted metabolomic technologies to track the fates of isotopically labeled metabolites in a global, unbiased manner. This untargeted approach can be applied to discover novel biochemical pathways and characterize changes in the fates of labeled metabolites as a function of altered biological conditions such as disease. To facilitate the data analysis, we introduce X13CMS, an extension of the widely used mass spectrometry-based metabolomic software package XCMS. X13CMS uses the XCMS platform to detect metabolite peaks and perform retention-time alignment in liquid chromatography/mass spectrometry (LC/MS) data. With the use of the XCMS output, the program then identifies isotopologue groups that correspond to isotopically labeled compounds. The retrieval of these groups is done without any a priori knowledge besides the following input parameters: (i) the mass difference between the unlabeled and labeled isotopes, (ii) the mass accuracy of the instrument used in the analysis, and (iii) the estimated retention-time reproducibility of the chromatographic method. Despite its name, X13CMS can be used to track any isotopic label. Additionally, it detects differential labeling patterns in biological samples collected from parallel control and experimental conditions. We validated the ability of X13CMS to accurately retrieve labeled metabolites from complex biological matrices both with targeted LC/MS/MS analysis of a subset of the hits identified by the program and with labeled standards spiked into cell extracts. We demonstrate the full functionality of X13CMS with an analysis of cultured rat astrocytes treated with uniformly labeled (U-)13C-glucose during lipopolysaccharide (LPS) challenge. Our results show that out of 223 isotopologue groups enriched from U-13C-glucose, 95 have statistically significant differential labeling patterns in astrocytes challenged with LPS compared to unchallenged control cells. Only two of these groups overlap with the 32 differentially regulated peaks identified by XCMS, indicating that X13CMS uncovers different and complementary information from untargeted metabolomic studies. Like XCMS, X13CMS is implemented in R. It is available from our laboratory website at http://pattilab.wustl.edu/x13cms.php.

Wavelet based spike propagation neural network (WSPNN) for wind power forecasting

The development of wind power generation in many countries around the world in recent years has drawn the attention of research scientists to forecast wind power. The characteristics of the wind power generated are extremely variable, non-periodic and unpredictable. Therefore, wind power forecasts have gained a lot of prominence and its significance in turbine control, pre-load sharing and trading of power. Based on the literature survey, though various wind power forecasting models have been proposed, scope for developing much more efficient and accurate models is still a major challenge. This work proposes a wavelet based spike propagation neural network for wind power forecasting. First the preprocessing of historical data is carried out using wavelet technique. Then, the third generation artificial neural networks, that involve the spike response neuron model (SRNM) is trained using the gradient descent approach. The proposed model is tested on the historical wind power data obtained from Irish power grid and National Renewable Energy Laboratory (USA) website. The performance of the proposed model is validated based on the indices such as modified mean absolute percentage error (MMAPE), root mean square error (RMSE) and error variance.

Modelling the Transport and Dispersion of Atmospheric Aerosols over Warri Area of the Niger Delta Subregion of Nigeria

This study investigates the transport profile and source-sink system for atmospheric aerosols over Warri area of the Niger Delta subregion of Nigeria. The study utilized GPS information of the study locations to simulate meteorological variables over the area from the Air Resource Laboratory (ARL) website. The ARL/GFS model was used to determine the wind-field information between 1st and 8th March 2012 over sub region. In addition backward air mass trajectories were determined at various heights of 5m, 1000m and 2000m AGL for aerosol transport pattern, as well as concentration dispersion using the Hybrid Single Particle Lagrangian Integrated Trajectory (HYSPLIT) model. During the study period, aerosols were noticed to evolve from the sea of the Atlantic Ocean, hence are likely of sea salt origin. Winds over the sub region ranged between 4 and 6 m/s and predominantly in the south and south westerly directions. The maximum pollutant concentration observed was about 1.0 x 10-12 μg/m3 while the minimum was about 1.5 x 10-24 μg/m3.

An Untargeted Metabolomic Workflow to Improve Structural Characterization of Metabolites

Mass spectrometry-based metabolomics relies on MS(2) data for structural characterization of metabolites. To obtain the high-quality MS(2) data necessary to support metabolite identifications, ions of interest must be purely isolated for fragmentation. Here, we show that metabolomic MS(2) data are frequently characterized by contaminating ions that prevent structural identification. Although using narrow-isolation windows can minimize contaminating MS(2) fragments, even narrow windows are not always selective enough, and they can complicate data analysis by removing isotopic patterns from MS(2) spectra. Moreover, narrow windows can significantly reduce sensitivity. In this work, we introduce a novel, two-part approach for performing metabolomic identifications that addresses these issues. First, we collect MS(2) scans with less stringent isolation settings to obtain improved sensitivity at the expense of specificity. Then, by evaluating MS(2) fragment intensities as a function of retention time and precursor mass targeted for MS(2) analysis, we obtain deconvolved MS(2) spectra that are consistent with pure standards and can therefore be used for metabolite identification. The value of our approach is highlighted with metabolic extracts from brain, liver, astrocytes, as well as nerve tissue, and performance is evaluated by using pure metabolite standards in combination with simulations based on raw MS(2) data from the METLIN metabolite database. A R package implementing the algorithms used in our workflow is available on our laboratory website ( http://pattilab.wustl.edu/decoms2.php ).

Development of a laboratory niche Web site

This technical note presents the development of a methodological laboratory niche Web site. The "Grossing Technology in Surgical Pathology" (www.grossing-technology.com) Web site is used as an example. Although common steps in creation of most Web sites are followed, there are particular requirements for structuring the template's menu on methodological laboratory Web sites. The "nested doll principle," in which one object is placed inside another, most adequately describes the methodological approach to laboratory Web site design. Fragmentation in presenting the Web site's material highlights the discrete parts of the laboratory procedure. An optimally minimal triad of components can be recommended for the creation of a laboratory niche Web site: a main set of media, a blog, and an ancillary component (host, contact, and links). The inclusion of a blog makes the Web site a dynamic forum for professional communication. By forming links and portals, cloud computing opens opportunities for connecting a niche Web site with other Web sites and professional organizations. As an additional source of information exchange, methodological laboratory niche Web sites are destined to parallel both traditional and new forms, such as books, journals, seminars, webinars, and internal educational materials.

Visualization of the transmission of direct genomic values for paternal and maternal chromosomes for 15 traits in US Brown Swiss, Holstein, and Jersey cattle

Haplotypes are available for 220,671 Brown Swiss, Holstein, and Jersey bulls and cows that received genomic evaluations in August 2012. Differences in least squares means of direct genomic values (DGV) for paternal and maternal haplotypes of Bos taurus autosomes 1, 6, 14, and 18 for lifetime net merit were significant in all but one case. Those chromosomes were chosen to represent cases with and without known quantitative trait loci, and other chromosomes may differ as well. Paternal haplotypes had higher DGV than maternal haplotypes in most cases, and differences were larger when quantitative trait loci were present. Longer chromosomes generally accounted for more variance than shorter chromosomes, and differences among breeds were consistent with known mutations of large effect. For example, Bos taurus autosome 18 accounted for 2.5, 7, and 2.6% of the variance in lifetime net merit for Brown Swiss (BS), Holsteins, and Jerseys, respectively. Distributions of the number of positive DGV inherited from sires and dams were negatively skewed in all breeds, and modes were slightly higher for paternally than maternally derived haplotypes in Holsteins and BS (22 vs. 20 and 22 vs. 21, respectively) and slightly lower in BS (17 vs. 19). Graphical representations of DGV are available to all users through a query on the Animal Improvement Programs Laboratory (ARS, USDA, Beltsville, MD) web site. Query results were also used to illustrate several quantitative genetic principles using genotype information from real animals. For example, offspring DGV can be compared with parental DGV to demonstrate that a parent transmits the average value of its 2 chromosomes to its progeny. The frequency of DGV with positive and negative values in animals of different ages can be used to show how selection affects allele frequencies. The effect of selection for alleles with large effects versus those with small effects is demonstrated using an animal with undesirable alleles for a marker with a large effect but many desirable alleles for markers with small effects. Strategies for the use of those data in selection programs are being studied, and work is underway to add data on conformation traits to the system.

Comparison of the geographical distribution of feline immunodeficiency virus and feline leukemia virus infections in the United States of America (2000–2011)

BackgroundAlthough feline immunodeficiency virus (FIV) and feline leukemia virus (FeLV) have similar risk factors and control measures, infection rates have been speculated to vary in geographic distribution over North America. Since both infections are endemic in North America, it was assumed as a working hypothesis that their geographic distributions were similar. Hence, the purpose of this exploratory analysis was to investigate the comparative geographical distribution of both viral infections. Counts of FIV (n=17,108) and FeLV (n=30,017) positive serology results (FIV antibody and FeLV ELISA) were obtained for 48 contiguous states and District of Columbia of the United States of America (US) from the IDEXX Laboratories website. The proportional morbidity ratio of FIV to FeLV infection was estimated for each administrative region and its geographic distribution pattern was visualized by a choropleth map. Statistical evidence of an excess in the proportional morbidity ratio from unity was assessed using the spatial scan test under the normal probability model.ResultsThis study revealed distinct spatial distribution patterns in the proportional morbidity ratio suggesting the presence of one or more relevant and geographically varying risk factors. The disease map indicates that there is a higher prevalence of FIV infections in the southern and eastern US compared to FeLV. In contrast, FeLV infections were observed to be more frequent in the western US compared to FIV. The respective excess in proportional morbidity ratio was significant with respect to the spatial scan test (p < 0.05).ConclusionsThe observed variability in the geographical distribution of the proportional morbidity ratio of FIV to FeLV may be related to the presence of an additional or unique, but yet unknown, spatial risk factor. Putative factors may be geographic variations in specific virus strains and rate of vaccination. Knowledge of these factors and the geographical distributions of these infections can inform recommendations for testing, management and prevention. However, further studies are required to investigate the potential association of these factors with FIV and FeLV.

Erratum

British Journal of Clinical PharmacologyVolume 74, Issue 1 p. 224-225 Free Access Erratum This article corrects the following: Acceptability and characteristics of 124 human bioequivalence studies with active substances classified according to the Biopharmaceutic Classification System Elena Ramirez, Olga Laosa, Pedro Guerra, Blanca Duque, Beatriz Mosquera, Alberto M. Borobia, Suhua H. Lei, Antonio J. Carcas, Jesus Frias, Volume 70Issue 5British Journal of Clinical Pharmacology pages: 694-702 First Published online: July 26, 2010 First published: 11 June 2012 https://doi.org/10.1111/j.1365-2125.2012.04349.xCitations: 2AboutSectionsPDF ToolsRequest permissionExport citationAdd to favoritesTrack citation ShareShare Give accessShare full text accessShare full-text accessPlease review our Terms and Conditions of Use and check box below to share full-text version of article.I have read and accept the Wiley Online Library Terms and Conditions of UseShareable LinkUse the link below to share a full-text version of this article with your friends and colleagues. Learn more.Copy URL Share a linkShare onFacebookTwitterLinkedInRedditWechat Ramirez E, Laosa O, Guerra P, Duque B, Mosquera B, Borobia AM, Lei SH, Carcas AJ, Frias J. Br J Clin Pharmacol 2010; 70: 694–702. In [1], the article states that loratadine is a BCS Class I drug (in Table 1, column 1, line 10; Table 4, column 1, line 14; and page 698, column 1, line 4). Data were obtained from the Therapeutic System Research Laboratories website (at http://www.tsrlinc.com/services/bcs/search.cfm). The new website of Therapeutic System Research Laboratories at http://69.20.123.154/services/bcs/results.cfm yields a page displaying loratadine as Class II and the metabolite desloratadine as Class I (last accessed March 21, 2012). The corrected versions of Table 1 and 4 and the sentence on page 698 are published below. Table 1. Biopharmaceutics Classification System (BCS) of active substances (number of studies) Table 4. Results of non-BE formulations (study number of subjects, retrospective sample size calculation) classified by BCS active substances for maximum observed plasma concentration (Cmax) and area under the concentration-time curve (AUC) In one case (sildenafil) the CVIntrasubject was higher than predicted (Group A2 Table 4). REFERENCE Ramirez E, Laosa O, Guerra P, Duque B, Mosquera B, Borobia AM, Lei SH, Carcas AJ, Frias J. Acceptability and characteristics of 124 human bioequivalence studies with active substances classified according to the Biopharmaceutic Classification System. Br J Clin Pharmacol 2010; 70: 694– 702. Citing Literature Volume74, Issue1July 2012Pages 224-225 ReferencesRelatedInformation

Abstract 5267: Mouse models of cancer at The Jackson Laboratory Repository

Abstract As one of the largest collections of characterized mouse strains available, The Jackson Laboratory Repository serves the scientific community as a resource to archive and distribute mouse models. Among the hundreds of new strains acquired or developed annually are a transgenic model for prostate hyperplasia that progresses to adenoma/adenocarcinoma, a transgenic model of large B cell lymphoma similar to tumors seen in patients with SLE and Sjogren's syndrome; and a targeted mutation strain of Lats1 (large tumor suppressor) that develops soft tissue sarcomas, ovarian stromal cell tumors and increased sensitivity to carcinogens. Conditional (floxed) strains that are useful in generating tissue-specific mutants have been recently added to the Repository and include mutations of Perp (TP53 apoptosis effector), Msh2 (mutS homolog 2, E. coli), and Irf8 (interferon regulatory factor 8). A transgenic strain that expresses Cre recombinase specifically in the large intestine has applications in colon cancer research. A combination mutant strain (containing targeted mutations of Vhl, von Hippel-Lindau tumor suppressor, and Pten, phosphatase and tensin homolog, and a transgene with Cre recombinase expression driven by Cdh16, cadherin 16) is a model for benign mixed adenosquamous genital tract tumors resembling clear cell cystadenomas observed in patients with Von Hippel-Lindau syndrome. The TEL-AML1 (Etv6-RUNX1, t12;21) translocation/fusion protein associated with childhood acute lymphoblastic leukemia is conditionally expressed by a targeted mutation strain. For transplantation research, a number of “humanized” mouse strains are available. These typically are immune compromised lines and/or lines that provide continuous circulation of human growth factors supporting a platform for a humanized microenvironment. A number of new research tool strains have been added to the Repository, including a fluorescent reporter for carcinoma metastasis, the Cre reporter R26R-Confetti strain which allows individual cell labeling with nuclear-localized membrane-targeted or cytoplasmic fluorescent proteins, and transgenic strains expressing the KikGR flurorescent protein which changes color from green to red upon activation. The Repository maintains a searchable on-line resource (www.jax.org) for each strain. Researchers can submit their strains by using the on-line form available at The Jackson Laboratory website: www.jax.org/donate-a-mouse. Supported by NIH, HHMI, The Ellison Medical Foundation and several private charitable foundations. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 5267. doi:1538-7445.AM2012-5267

Resource Letter AFHEP-1: Accelerators for the Future of High-Energy Physics

This Resource Letter provides a guide to literature concerning the development of accelerators for the future of high-energy physics. Research articles, books, and Internet resources are cited for the following topics: motivation for future accelerators, present accelerators for high-energy physics, possible future machine, and laboratory and collaboration websites.

Neural mechanism of activity spread in the cat motor cortex and its relation to the intrinsic connectivity

Motor cortical points are linked by intrinsic horizontal connections having a recurrent network topology. However, it is not known whether neural activity can propagate over the area covered by these intrinsic connections and whether there are spatial anisotropies of synaptic strength, as opposed to synaptic density. Moreover, the mechanisms by which activity spreads have yet to be determined. To address these issues, an 8 × 8 microelectrode array was inserted in the forelimb area of the cat motor cortex (MCx). The centre of the array had a laser etched hole ∼500 μm in diameter. A microiontophoretic pipette, with a tip diameter of 2-3 μm, containing bicuculline methiodide (BIC) was inserted in the hole and driven to a depth of 1200-1400 μm from the cortical surface. BIC was ejected for ∼2min from the tip of the micropipette with positive direct current ranging between 20 and 40 nA in different experiments. This produced spontaneous nearly periodic bursts (0.2-1.0 Hz) of multi-unit activity in a radius of about 400 μm from the tip of the micropipette. The bursts of neural activity spread at a velocity of 0.11-0.24 ms⁻¹ (mean=0.14 mm ms⁻¹, SD=0.05)with decreasing amplitude.The area activated was on average 7.22 mm² (SD=0.91 mm²), or ∼92% of the area covered by the recording array. The mode of propagation was determined to occur by progressive recruitment of cortical territory, driven by a central locus of activity of some 400 μm in radius. Thus, activity did not propagate as a wave. Transection of the connections between the thalamus and MCx did not significantly alter the propagation velocity or the size of the recruited area, demonstrating that the bursts spread along the routes of intrinsic cortical connectivity. These experiments demonstrate that neural activity initiated within a small motor cortical locus (≤ 400 μm in radius) can recruit a relatively large neighbourhood in which a variety of muscles acting at several forelimb joints are represented. These results support the hypothesis that the MCx controls the forelimb musculature in an integrated and anticipatory manner based on a recurrent network topology

Abstract 4303: The Jackson Laboratory Repository: resource for mouse strains modeling cancer

Abstract The Jackson Laboratory Repository is an established resource for the importation, cryopreservation, development, and distribution of mouse strains vital to biomedical research. More than 500 new strains are added annually to the approximately 5,000 strains and stocks of mice currently held in the Repository collection. Newly acquired or developed strains include a model of malignant melanoma and metastasis; a xenotransplant model that provides continuous circulation of human growth factors; a targeted mutation strain for studying myeloproliferative diseases such as chronic myelomonocytic leukemia and Chronic Familial Myelocytic Leukemia-Like Syndrome; and a knock-in strain that mimics the t(9;11)(p22;q23) translocation identified in acute myeloid leukemia. Also under development are a transgenic/targeted mutation strain with increased mammary gland tumor incidence and three targeted mutation strains with increased sensitivity to carcinogens or radiation. The Repository's inducible and conditional mutation mouse strains allow researchers to generate temporal and/or tissue-specific tools for modeling human cancer. New additions to the Repository collection include strains with Cre recombinase expression specific to the colon and rectum, as well as a transgenic strain that can be used as part of a bitransgenic system utilizing the tetracycline-inducible expression of a gene of interest in blood vessel endothelial cells. For non-invasive in-vivo imaging studies, the Repository distributes a xenograft/transplant host with widespread expression of firefly luciferase and enhanced green fluorescence protein. The Repository maintains a searchable on-line resource (www.jax.org) for each strain. Researchers can submit their strains to be considered for inclusion in the Repository by using the on-line form available at The Jackson Laboratory website: http://www.jax.org/grc/index.html. The Jackson Laboratory Repository is supported by the NCRR, The Howard Hughes Medical Institute, The Ellison Medical Foundation and donations from private charitable foundations. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 4303. doi:10.1158/1538-7445.AM2011-4303

The Importance of Defining Expectations

Choosing a research mentor is the most challenging decision facing matriculating Ph.D. students in the biosciences. At the University of Wisconsin-Madison, students receive a deluge of information about research programs of potential mentors within weeks of arriving on campus. Though these programs align students with mentors who share their interests, this alone is not sufficient to predict mentoring compatibility. Here I discuss the importance of establishing and publicizing expectations for students. I strongly believe that reinforcing expectations during initial student contact and research rotations maximizes the likelihood of attracting students that will thrive in my laboratory. I will describe how my laboratory website enables students to judge my suitability as their research mentor, with particular emphasis on my “Top 10” expectations of Ph.D. students.

Modeling RNA polymerase competition: the effect of σ-subunit knockout and heat shock on gene transcription level

BackgroundModeling of a complex biological process can explain the results of experimental studies and help predict its characteristics. Among such processes is transcription in the presence of competing RNA polymerases. This process involves RNA polymerases collision followed by transcription termination.ResultsA mathematical and computer simulation model is developed to describe the competition of RNA polymerases during genes transcription on complementary DNA strands. E.g., in the barley Hordeum vulgare the polymerase competition occurs in the locus containing plastome genes psbA, rpl23, rpl2 and four bacterial type promoters. In heat shock experiments on isolated chloroplasts, a twofold decrease of psbA transcripts and even larger increase of rpl23-rpl2 transcripts were observed, which is well reproduced in the model. The model predictions are in good agreement with virtually all relevant experimental data (knockout, heat shock, chromatogram data, etc.). The model allows to hypothesize a mechanism of cell response to knockout and heat shock, as well as a mechanism of gene expression regulation in presence of RNA polymerase competition. The model is implemented for multiprocessor platforms with MPI and supported on Linux and MS Windows. The source code written in C++ is available under the GNU General Public License from the laboratory website. A user-friendly GUI version is also provided at http://lab6.iitp.ru/en/rivals.ConclusionsThe developed model is in good agreement with virtually all relevant experimental data. The model can be applied to estimate intensities of binding of the holoenzyme and phage type RNA polymerase to their promoters using data on gene transcription levels, as well as to predict characteristics of RNA polymerases and the transcription process that are difficult to measure directly, e.g., the intensity (frequency) of holoenzyme binding to the promoter in correlation to its nucleotide composition and the type of σ-subunit, the amount of transcription initiation aborts, etc. The model can be used to make functional predictions, e.g., heat shock response in isolated chloroplasts and changes of gene transcription levels under knockout of different σ-subunits or RNA polymerases or due to gene expression regulation.ReviewersThis article was reviewed by Dr. Anthony Almudevar, Dr. Aniko Szabo, Dr. Yuri Wolf (nominated by Dr. Peter Olofsson) and Prof. Marek Kimmel.

The cucurbit downy mildew pathogen Pseudoperonospora cubensis.

Kingdom Straminipila; Phylum Oomycota; Class Oomycetes; Order Peronosporales; Family Peronosporaceae; Genus Pseudoperonospora; Species Pseudoperonospora cubensis. Angular chlorotic lesions bound by leaf veins on the foliage of cucumber. Symptoms vary on different cucurbit species and varieties, specifically in terms of lesion development, shape and size. Infection of cucurbits by Ps. cubensis impacts fruit yield and overall plant health. Sporulation on the underside of leaves results in the production of sporangia that are dispersed by wind. On arrival on a susceptible host, sporangia germinate in free water on the leaf surface, producing biflagellate zoospores that swim to and encyst on stomata, where they form germ tubes. An appressorium is produced and forms a penetration hypha, which enters the leaf tissue through the stomata. Hyphae grow through the mesophyll and establish haustoria, specialized structures for the transfer of nutrients and signals between host and pathogen. Management of downy mildew in Europe requires the use of tolerant cucurbit cultivars in conjunction with fungicide applications. In the USA, an aggressive fungicide programme, with sprays every 5-7 days for cucumber and every 7-10 days for other cucurbits, has been necessary to control outbreaks and to prevent crop loss. http://www.daylab.plp.msu.edu/pseudoperonospora-cubensis/ (Day Laboratory website with research advances in downy mildew); http://veggies.msu.edu/ (Hausbeck Laboratory website with downy mildew news for growers); http://cdm.ipmpipe.org/ (Cucurbit downy mildew forecasting homepage); http://ipm.msu.edu/downymildew.htm (Downy mildew information for Michigan's vegetable growers).