Variability in Volume Metering Devices

The inherent variability of seed and fertilizer application from volumetric metering devices is not readily recognized. The Canadian Prairie Agricultural Machinery Institute (P AMI) suggests a maximum coefficient of variation (CV) of 15% among outlets for seeding grain or applying fertilizer. P AMI does not report down-the-row variability of individual outlets. Parameters that influence variability of volumetric measuring external fluted wheels such as rotational speed of the metering wheel, product delivery rate, seed size, and cell collection lengths were examined. In the first study, external fluted wheel meters on four grain drills were tested for seed delivery variability for wheat and soybeans, both among the metering outlets and down-the-row for individual meters. Tests on two additional drills, one an air drill and the other with external fluted metering, used two sizes of soybean seeds and two travel speeds. For wheat, down-the-row CV ranged from 12.5 to 22.5% and the CV among metering units ranged from 12.5 to 21 %. For soybeans, the CV ranged from 15.5 to 41.5% with the air drill having the lower CV. A faster travel speed gave a lower CV for both drills metering soybeans. In a second study, when metering wheat, the seeding rate variability due to cell size and seeding rate were evaluated. Each meter was evaluated with cells 0.48 or 0.96 m in length and seeding rates of 60, 80,90, and 100 kg/ha. The down-the-row CV ranged from 10 to 28% with 0.48 m length cells, and from 4 to 22% with 0.96 m length cells. Some of these CVs may be too high for a metering mechanism such as the fluted wheel to be used in SSCM

Generation of orthotopic patient-derived xenografts from gastrointestinal stromal tumor.

BackgroundGastrointestinal stromal tumor (GIST) is the most common sarcoma and its treatment with imatinib has served as the paradigm for developing targeted anti-cancer therapies. Despite this success, imatinib-resistance has emerged as a major problem and therefore, the clinical efficacy of other drugs has been investigated. Unfortunately, most clinical trials have failed to identify efficacious drugs despite promising in vitro data and pathological responses in subcutaneous xenografts. We hypothesized that it was feasible to develop orthotopic patient-derived xenografts (PDXs) from resected GIST that could recapitulate the genetic heterogeneity and biology of the human disease.MethodsFresh tumor tissue from three patients with pathologically confirmed GISTs was obtained immediately following tumor resection. Tumor fragments (4.2-mm3) were surgically xenografted into the liver, gastric wall, renal capsule, and pancreas of immunodeficient mice. Tumor growth was serially assessed with ultrasonography (US) every 3-4 weeks. Tumors were also evaluated with positron emission tomography (PET). Animals were sacrificed when they became moribund or their tumors reached a threshold size of 2500-mm3. Tumors were subsequently passaged, as well as immunohistochemically and histologically analyzed.ResultsHerein, we describe the first model for generating orthotopic GIST PDXs. We have successfully xenografted three unique KIT-mutated tumors into a total of 25 mice with an overall success rate of 84% (21/25). We serially followed tumor growth with US to describe the natural history of PDX growth. Successful PDXs resulted in 12 primary xenografts in NOD-scid gamma or NOD-scid mice while subsequent successful passages resulted in 9 tumors. At a median of 7.9 weeks (range 2.9-33.1 weeks), tumor size averaged 473 ± 695-mm³ (median 199-mm3, range 12.6-2682.5-mm³) by US. Furthermore, tumor size on US within 14 days of death correlated with gross tumor size on necropsy. We also demonstrated that these tumors are FDG-avid on PET imaging, while immunohistochemically and histologically the PDXs resembled the primary tumors.ConclusionsWe report the first orthotopic model of human GIST using patient-derived tumor tissue. This novel, reproducible in vivo model of human GIST may enhance the study of GIST biology, biomarkers, personalized cancer treatments, and provide a preclinical platform to evaluate new therapeutic agents for GIST

Neuronal activation for semantically reversible sentences

Semantically reversible sentences are prone to misinterpretation and take longer for typically developing children and adults to comprehend; they are also particularly problematic for those with language difficulties such as aphasia or Specific Language Impairment. In our study, we used fMRI to compare the processing of semantically reversible and nonreversible sentences in 41 healthy participants to identify how semantic reversibility influences neuronal activation. By including several linguistic and nonlinguistic conditions within our paradigm, we were also able to test whether the processing of semantically reversible sentences places additional load on sentence-specific processing, such as syntactic processing and syntactic-semantic integration, or on phonological working memory. Our results identified increased activation for reversible sentences in a region on the left temporal–parietal boundary, which was also activated when the same group of participants carried out an articulation task which involved saying “one, three” repeatedly. We conclude that the processing of semantically reversible sentences places additional demands on the subarticulation component of phonological working memory

Hedgehog pathway dysregulation contributes to the pathogenesis of human gastrointestinal stromal tumors via GLI-mediated activation of KIT expression.

Gastrointestinal stromal tumors (GIST) arise within the interstitial cell of Cajal (ICC) lineage due to activating KIT/PDGFRA mutations. Both ICC and GIST possess primary cilia (PC), which coordinate PDGFRA and Hedgehog signaling, regulators of gastrointestinal mesenchymal development. Therefore, we hypothesized that Hedgehog signaling may be altered in human GIST and controls KIT expression. Quantitative RT-PCR, microarrays, and next generation sequencing were used to describe Hedgehog/PC-related genes in purified human ICC and GIST. Genetic and pharmacologic approaches were employed to investigate the effects of GLI manipulation on KIT expression and GIST cell viability. We report that Hedgehog pathway and PC components are expressed in ICC and GIST and subject to dysregulation during GIST oncogenesis, irrespective of KIT/PDGFRA mutation status. Using genomic profiling, 10.2% of 186 GIST studied had potentially deleterious genomic alterations in 5 Hedgehog-related genes analyzed, including in the PTCH1 tumor suppressor (1.6%). Expression of the predominantly repressive GLI isoform, GLI3, was inversely correlated with KIT mRNA levels in GIST cells and non-KIT/non-PDGFRA mutant GIST. Overexpression of the 83-kDa repressive form of GLI3 or small interfering RNA-mediated knockdown of the activating isoforms GLI1/2 reduced KIT mRNA. Treatment with GLI1/2 inhibitors, including arsenic trioxide, significantly increased GLI3 binding to the KIT promoter, decreased KIT expression, and reduced viability in imatinib-sensitive and imatinib-resistant GIST cells. These data offer new evidence that genes necessary for Hedgehog signaling and PC function in ICC are dysregulated in GIST. Hedgehog signaling activates KIT expression irrespective of mutation status, offering a novel approach to treat imatinib-resistant GIST

Success in Managing Waste With No Identified Path to Disposal at the INEEL

The Idaho National Engineering and Environmental Laboratory (INEEL) is aggressively managing waste with no identified path to disposal (WNPD), which was previously termed special case waste (SCW). As a result of several years of this aggressive management, the INEEL has reduced its WNPD volume from approximately 38,000 m3 in 1993 to approximately 6.33 m3 in 1999. This paper discusses how the INEEL reduced its WNPD volume. It specifically discusses the beryllium reflector waste produced from the Advanced Test Reactor (ATR) as an example of the INEEL's success in managing its WNPD. The INEEL's success in reducing its WNPD volume is the result of establishing long-range strategic objectives and consistently allocating an annual budget to implement specific work tasks that are consistent with these objectives. In addition, specific short- and long-range work tasks were developed and documented in work control documents. The work tasks are evaluated annually for consistency with the strategic objectives. Since the INEEL has successfully reduced its WNPD volume, it is now focusing on disposing of the remaining volume and preventing future generation of WNPD. As a result of this focused effort, a life-cycle disposal plan was developed for the Advanced Test Reactor (ATR) beryllium waste. This plan covers beryllium reflectors currently stored in the ATR canal and beryllium reflectors generated through 2050. This plan includes a pollution prevention (P2) opportunity, which applies to the DOE complex reactor beryllium reflector waste stream. The P2 opportunity also contributes to planning for the international nuclear industry to extend the life and reduce the radionuclide activation of nonfuel material in existing and newly developed test reactor nuclear power systems. In Fiscal Year 2000, the INEEL is focusing on further reducing its WNPD volume. To completely dispose of the INEEL WNPD, it will need a national plan for disposing of some WNPD categories. Therefore, the INEEL WNPD Program is participating in the DOE complex integrated planning process for legacy and future generated WNPD waste

Understanding and Estimating Effective Population Size for Practical Application in Marine Species Management

Effective population size (Ne) determines the strength of genetic drift in a population and has long been recognized as an important parameter for evaluating conservation status and threats to genetic health of populations. Specifically, an estimate of Ne is crucial to management because it integrates genetic effects with the life history of the species, allowing for predictions of a population’s current and future viability. Nevertheless, compared with ecological and demographic parameters, Ne has had limited influence on species management, beyond its application in very small populations. Recent developments have substantially improved Ne estimation; however, some obstacles remain for the practical application of Ne estimates. For example, the need to define the spatial and temporal scale of measurement makes the concept complex and sometimes difficult to interpret. We reviewed approaches to estimation of Ne over both long-term and contemporary time frames, clarifying their interpretations with respect to local populations and the global metapopulation. We describe multiple experimental factors affecting robustness of contemporary Ne estimates and suggest that different sampling designs can be combined to compare largely independent measures of Ne for improved confidence in the result. Large populations with moderate gene flow pose the greatest challenges to robust estimation of contemporary Ne and require careful consideration of sampling and analysis to minimize estimator bias. We emphasize the practical utility of estimating Ne by highlighting its relevance to the adaptive potential of a population and describing applications in management of marine populations, where the focus is not always on critically endangered populations. Two cases discussed include the mechanisms generating Ne estimates many orders of magnitude lower than census N in harvested marine fishes and the predicted reduction in Ne from hatchery-based population supplementation

Understanding and Estimating Effective Population Size for Practical Application in Marine Species Management

Effective population size (Ne) determines the strength of genetic drift in a population and has long been recognized as an important parameter for evaluating conservation status and threats to genetic health of populations. Specifically, an estimate of Ne is crucial to management because it integrates genetic effects with the life history of the species, allowing for predictions of a population’s current and future viability. Nevertheless, compared with ecological and demographic parameters, Ne has had limited influence on species management, beyond its application in very small populations. Recent developments have substantially improved Ne estimation; however, some obstacles remain for the practical application of Ne estimates. For example, the need to define the spatial and temporal scale of measurement makes the concept complex and sometimes difficult to interpret. We reviewed approaches to estimation of Ne over both long-term and contemporary time frames, clarifying their interpretations with respect to local populations and the global metapopulation. We describe multiple experimental factors affecting robustness of contemporary Ne estimates and suggest that different sampling designs can be combined to compare largely independent measures of Ne for improved confidence in the result. Large populations with moderate gene flow pose the greatest challenges to robust estimation of contemporary Ne and require careful consideration of sampling and analysis to minimize estimator bias. We emphasize the practical utility of estimating Ne by highlighting its relevance to the adaptive potential of a population and describing applications in management of marine populations, where the focus is not always on critically endangered populations. Two cases discussed include the mechanisms generating Ne estimates many orders of magnitude lower than census N in harvested marine fishes and the predicted reduction in Ne from hatchery-based population supplementation

Human Galectin-9 Is a Potent Mediator of HIV Transcription and Reactivation.

Identifying host immune determinants governing HIV transcription, latency and infectivity in vivo is critical to developing an HIV cure. Based on our recent finding that the host factor p21 regulates HIV transcription during antiretroviral therapy (ART), and published data demonstrating that the human carbohydrate-binding immunomodulatory protein galectin-9 regulates p21, we hypothesized that galectin-9 modulates HIV transcription. We report that the administration of a recombinant, stable form of galectin-9 (rGal-9) potently reverses HIV latency in vitro in the J-Lat HIV latency model. Furthermore, rGal-9 reverses HIV latency ex vivo in primary CD4+ T cells from HIV-infected, ART-suppressed individuals (p = 0.002), more potently than vorinostat (p = 0.02). rGal-9 co-administration with the latency reversal agent "JQ1", a bromodomain inhibitor, exhibits synergistic activity (p<0.05). rGal-9 signals through N-linked oligosaccharides and O-linked hexasaccharides on the T cell surface, modulating the gene expression levels of key transcription initiation, promoter proximal-pausing, and chromatin remodeling factors that regulate HIV latency. Beyond latent viral reactivation, rGal-9 induces robust expression of the host antiviral deaminase APOBEC3G in vitro and ex vivo (FDR<0.006) and significantly reduces infectivity of progeny virus, decreasing the probability that the HIV reservoir will be replenished when latency is reversed therapeutically. Lastly, endogenous levels of soluble galectin-9 in the plasma of 72 HIV-infected ART-suppressed individuals were associated with levels of HIV RNA in CD4+ T cells (p<0.02) and with the quantity and binding avidity of circulating anti-HIV antibodies (p<0.009), suggesting a role of galectin-9 in regulating HIV transcription and viral production in vivo during therapy. Our data suggest that galectin-9 and the host glycosylation machinery should be explored as foundations for novel HIV cure strategies

A genetic record of population isolation in pocket gophers during Holocene climatic change.

ABSTRACT A long-standing question in Quaternary paleontology is whether climate-induced, population-level phenotypic change is a result of large-scale migration or evolution in isolation. To directly measure genetic variation through time, ancient DNA and morphologic variation was measured over 2,400 years in a Holocene sequence of pocket gophers (Thomomys talpoides) from Lamar Cave, Yellowstone National Park, Wyoming. Ancient specimens and modern samples collected near Lamar Cave share mitochondrial cytochrome b sequences that are absent from adjacent localities, suggesting that the population was isolated for the entire period. In contrast, diastemal length, a morphologic character correlated with body size and nutritional level, changed predictably in response to climatic change. Our results demonstrate that small mammal populations can experience the long-term isolation assumed by many theoretical models of microevolutionary change