Herkimer, County of and Herkimer Highway Department Unit, United Public Service Employees Union

In the matter of the fact-finding between the County of Herkimer, employer, and the UPSEU (Herkimer Highway Department), union. PERB case no. M2009-305. Before: Robert Flynt, fact finder

A survey of popular R packages for cluster analysis

Cluster analysis is a set of statistical methods for discovering new group/class structure when exploring datasets. This article reviews the following popular libraries/commands in the R software language for applying different types of cluster analysis: from the stats library, the kmeans and hclust functions; the mclust library; the poLCA library; and the clustMD library. The packages/functions cover a variety of cluster analysis methods for continuous data, categorical data or a collection of the two. The contrasting methods in the different packages are briefly introduced and basic usage of the functions is discussed. The use of the different methods is compared and contrasted and then illustrated on example data. In the discussion, links to information on other available libraries for different clustering methods and extensions beyond basic clustering methods are given. The code for the worked examples in Section 2 is available at http://www.stats.gla.ac.uk/~nd29c/Software/ClusterReviewCode.

Charlotte Valley Central School District and Charlotte Valley Teachers Association

In the matter of the fact-finding between the Charlotte Valley Central School District, employer, and the Charlotte Valley Teachers Association, union. PERB case no. M2011-066. Before: Robert E. Flynt, fact finder

Creation of mutant corticosteroid binding globulin: One step closer to a diagnostic device

Abstract only availableMuch is known about how traditional and alternative medicines interact separately. However, there is very little knowledge of how the usage of alternative medicine affects the metabolism of traditional medicines when they are used together. This is especially important because of the amount of people who take alternative medicine in addition to antiretroviral drugs. The practice of using traditional and alternative medicines may induce cytochrome p450 enzymes, which metabolize traditional medicines used to treat HIV and AIDS. Cortisol is a steroid hormone produced by the body at a fairly constant rate. It is metabolized to 6OH-cortisol through the P450 enzyme pathway. As such, the ratio of hydroxycortisol to cortisol is an indirect indicator of the P450 enzyme activity. The ultimate goal of this project is to create a simple diagnostic device that will aid in assessing whether the usage of traditional medicine in combination with alternative medicine induces CYP3A4, to dangerous levels. The diagnostic device will detect the levels of 6OH-cortisol with a mutant version of the protein corticosteroid binding globulin (CBG), that preferentially binds to the 6OH-cortisol complex. The first step in this process was to create the mutant version of CBG. The mutation was found to have the closest binding pocket with a change in the asparagine 17 site to a valine, modeled by several computer programs. PCR was then performed with primers that contained the mutation and the wild type CBG, thus creating the CBG containing the mutation. A fluorescence assay is to be performed to determine how well the mutant CBG actually binds to the 6OH-cortisol. The results of the assay are in progress.Missouri Academy at Northwest Missouri State Universit

The impact of age, biogenesis, and genomic clustering on Drosophila microRNA evolution

The molecular evolutionary signatures of miRNAs inform our understanding of their emergence, biogenesis, and function. The known signatures of miRNA evolution have derived mostly from the analysis of deeply conserved, canonical loci. In this study, we examine the impact of age, biogenesis pathway, and genomic arrangement on the evolutionary properties of Drosophila miRNAs. Crucial to the accuracy of our results was our curation of high-quality miRNA alignments, which included nearly 150 corrections to ortholog calls and nucleotide sequences of the global 12-way Drosophilid alignments currently available. Using these data, we studied primary sequence conservation, normalized free-energy values, and types of structure-preserving substitutions. We expand upon common miRNA evolutionary patterns that reflect fundamental features of miRNAs that are under functional selection. We observe that melanogaster-subgroup-specific miRNAs, although recently emerged and rapidly evolving, nonetheless exhibit evolutionary signatures that are similar to well-conserved miRNAs and distinct from other structured noncoding RNAs and bulk conserved non-miRNA hairpins. This provides evidence that even young miRNAs may be selected for regulatory activities. More strikingly, we observe that mirtrons and clustered miRNAs both exhibit distinct evolutionary properties relative to solo, well-conserved miRNAs, even after controlling for sequence depth. These studies highlight the previously unappreciated impact of biogenesis strategy and genomic location on the evolutionary dynamics of miRNAs, and affirm that miRNAs do not evolve as a unitary class

Prognostic and predictive value of circulating tumor cells and CXCR4 expression as biomarkers for a CXCR4 peptide antagonist in combination with carboplatin-etoposide in small cell lung cancer: exploratory analysis of a phase II study.

Background Circulating tumor cells (CTCs) and chemokine (C-X-C motif) receptor 4 (CXCR4) expression in CTCs and tumor tissue were evaluated as prognostic or predictive markers of CXCR4 peptide antagonist LY2510924 plus carboplatin-etoposide (CE) versus CE in extensive-stage disease small cell lung cancer (ED-SCLC). Methods This exploratory analysis of a phase II study evaluated CXCR4 expression in baseline tumor tissue and peripheral blood CTCs and in post-treatment CTCs. Optimum cutoff values were determined for CTC counts and CXCR4 expression in tumors and CTCs as predictors of survival outcome. Kaplan-Meier estimates and hazard ratios were used to determine biomarker prognostic and predictive values. Results There was weak positive correlation at baseline between CXCR4 expression in tumor tissue and CTCs. Optimum cutoff values were H-score ≥ 210 for CXCR4+ tumor, ≥7% CTCs with CXCR4 expression (CXCR4+ CTCs), and ≥6 CTCs/7.5 mL blood. Baseline H-score for CXCR4+ tumor was not prognostic of progression-free survival (PFS) or overall survival (OS). Baseline CXCR4+ CTCs ≥7% was prognostic of shorter PFS. CTCs ≥6 at baseline and cycle 2, day 1 were prognostic of shorter PFS and OS. None of the biomarkers at their respective optimum cutoffs was predictive of treatment response of LY2510924 plus CE versus CE. Conclusions In patients with ED-SCLC, baseline CXCR4 expression in tumor tissue was not prognostic of survival or predictive of LY2510924 treatment response. Baseline CXCR4+ CTCs ≥7% was prognostic of shorter PFS. CTC count ≥6 at baseline and after 1 cycle of treatment were prognostic of shorter PFS and OS

Adaptive evolution of testis-specific, recently evolved, clustered miRNAs in Drosophila

The propensity of animal miRNAs to regulate targets bearing modest complementarity, most notably via pairing with miRNA positions approximately 2-8 (the "seed"), is believed to drive major aspects of miRNA evolution. First, minimal targeting requirements have allowed most conserved miRNAs to acquire large target cohorts, thus imposing strong selection on miRNAs to maintain their seed sequences. Second, the modest pairing needed for repression suggests that evolutionarily nascent miRNAs may generally induce net detrimental, rather than beneficial, regulatory effects. Hence, levels and activities of newly emerged miRNAs are expected to be limited to preserve the status quo of gene expression. In this study, we unexpectedly show that Drosophila testes specifically express a substantial miRNA population that contravenes these tenets. We find that multiple genomic clusters of testis-restricted miRNAs harbor recently evolved miRNAs, whose experimentally verified orthologs exhibit divergent sequences, even within seed regions. Moreover, this class of miRNAs exhibits higher expression and greater phenotypic capacities in transgenic misexpression assays than do non-testis-restricted miRNAs of similar evolutionary age. These observations suggest that these testis-restricted miRNAs may be evolving adaptively, and several methods of evolutionary analysis provide strong support for this notion. Consistent with this, proof-of-principle tests show that orthologous miRNAs with divergent seeds can distinguish target sensors in a species-cognate manner. Finally, we observe that testis-restricted miRNA clusters exhibit extraordinary dynamics of miRNA gene flux in other Drosophila species. Altogether, our findings reveal a surprising tissue-directed influence of miRNA evolution, involving a distinct mode of miRNA function connected to adaptive gene regulation in the testis

Florida\u27s 1926 Senatorial Primary

If historical speculation were profitable, few Florida elections would offer more possibilities than the Democratic Senatorial primary of 1926. An election which ended as a routine skirmish between an entrenched incumbent, Duncan U. Fletcher, and a relatively obscure politico, Jerry W. Carter, could have been a struggle for political survival. To fully comprehend the possibilities of 1926, it is necessary to review some historical antecedents

An evaluation of the storm prediction center day one probabilistic convective outlook using diagnostic parameters

The Storm Prediction Center issues daily probabilistic convective outlooks forecasting the intensity and probability of severe weather hazards (tornadoes, hail, and wind). There is limited literature on wind and hailstorm environments, and the probabilistic convective outlooks environmental characteristics. To address these gaps, this research paper verifies the Storm Prediction Centers Day One 1200 UTC probabilistic outlook from March 26, 2008, through the year 2019. Bias and the Heidke skill score were used to evaluate the forecasts that had at least 10 observed reports to create three categories: overforecast, good skill, and poor skill. The archived surface object analysis from the Storm Prediction Center was used to collect parameter data of the max value within an 11.1 by 11.1 km box centered on the first report of day for each hazard’s category to nearest hour to create a climatological dataset. Analyzing verification statistics in the nearly 12-year period found there was a change in forecast ideology when marginal and enhanced risk were introduced in late 2014. The number of skillful forecasts for both wind and hail nearly doubled from 2014–2019, and in the same period there was a drastic drop in forecasts with an overforecast bias for both hail and wind. The mixedlayer lifting condensation level was the only tornado parameter skillful in differentiating the mean between tornado overforecast and good skill. Skillful tornado forecasts were associated with higher heights accompanied by low mixed-layer convective inhibition and high effective significant tornado parameter values. Skillful hail forecasts were characterized by drier environments (low precipitable water amounts), moderate convective available potential energy, strong deep-layer shear, and moderate significant severe parameter values. Skillful wind forecasts environments were portrayed by high derecho composite parameter values, high probability of a mesoscale complex system parameter values, and strong wind shear between 0-1 km.Thesis (M.S.

Sidney J. Catts: The Road to Power

The South produced a bumper crop of political demagogues between 1890 and 1920. This unparalleled but dubious array of luminaries included James E. Ferguson of Texas, Huey Long of Louisiana, James K. Vardaman and Theodore Bilbo of Mississippi, Tom Heflin of Alabama, Tom Watson of Georgia, Cole Blease, “Cotton” Ed Smith, and Ben Tillman of South Carolina, as well as many others. These politicos broke the back of conservative Bourbonism with their emotional appeals to the religious and racial intolerance of the newly powerful masses of voters. Once in office they frequently championed social and economic reform such as the abolition of the convict lease system, restriction of child labor, ameliorative labor legislation, woman suffrage, shifting tax burdens to corporations, railroad regulation, expanded educational opportunities, and many other creative measures