Experimental Study into the Partitioning Behavior of Fluorine, Chlorine, Hydroxyl, and Sulfur (S2-) Between Apatite and a Synthetic Kreep Basalt Melt

The mineral apatite (Ca5 (PO4)3(F, Cl, OH)) is known for its ability to constrain the petrogenesis of the rock in which it is hosted and for its ubiquity throughout the Solar System, as it is found in lunar, martian, and terrestrial rocks alike (McCubbin et. al, 2015). The abundance of volatile elements, and for this particular study, the elevated abundance of sulfur (S2-) in high-Al basalt samples bearing apatite, could provide more insight for inquiries posed about the behavior of volatiles in lunar and martian magmatic systems (Boyce et. al, 2010). Oxygen fugacity will be an important parameter for these experiments, as the Moon, Mars, and Earth have different redox states (Herd, 2008). The objective of this experimental endeavor is to determine apatite-melt partition coefficients for the volatile elements (F-, Cl-, OH-, S2-) that make up the X-site (i.e., the typically monovalent anion site) in the mineral apatite in a lunar melt composition under lunar oxygen fugacity conditions approx.1-2 log units below the iron-wstite buffer). All experiments will be conducted at NASA, Johnson Space Center in the High Pressure Experimental Petrology Laboratory. In order to conduct apatite-melt partition experiments with oxygen fugacity as an additional parameter, we will create a synthetic mix of the lunar KREEP basalt 15386, a sample retrieved during Apollo 15 that is believed to represent an indigenous volcanic melt derived from the lunar interior (Rhodes, J.M et. al, 2006). Other geochemically significant elements including C, Co, Ni, Mo, and rare earth elements will be included in the mix at trace abundances in order to assess their partitioning behavior without effecting the overall behavior of the system. The synthetic mix will then be loaded into a piston cylinder, an apparatus used to simulate high-pressure/high-temperature conditions of planetary interiors, and exposed to 0.5 GPa of pressure, the pressure observed in the upper mantle of the Moon, and heated to the melting temperature of the materials. To make sure crystals grow large enough for the necessary analyses, the sample will be kept at the crystallization temperature for 8 hours. This extended run time should also allow the sample to achieve a steady state which is necessary to accurately assess the partitioning of these elements between apatite and melt. The results from this experimental study will allow us to determine the fate of F-, Cl-, OH-, and S2- during the magmatic evolution of the Moon

Association of Different Iowa Livestock Truck Wash Stations Service Levels with Enterobacteriaceae Counts

Data from eighteen different truck washes were used to compare the association of different service levels with Enterobacteriaceae counts. Service levels were classified into three different categories; prewash (n=78), post wash with disinfectant (n=78), and post wash without disinfectant (n=12). A total of 168 drag swabs were used for collection for the purpose of this study. Prewash services were defined as trailers before they were scraped out and washed. Post wash with or without disinfectant services were defined as after the trailers were washed and disinfectant was or was not applied. Prewash trailers tended to have higher Enterobacteriaceae counts of around 5.0 Log10CFU/m2when compared to post wash with disinfectantEnterobacteriaceae counts of around 2.2 Log10CFU/m2 and post wash without disinfectant Enterobacteriaceae counts of around 2.7 Log10CFU/m2

Adding 6 months of androgen deprivation therapy to postoperative radiotherapy for prostate cancer: a comparison of short-course versus no androgen deprivation therapy in the RADICALS-HD randomised controlled trial

Background Previous evidence indicates that adjuvant, short-course androgen deprivation therapy (ADT) improves metastasis-free survival when given with primary radiotherapy for intermediate-risk and high-risk localised prostate cancer. However, the value of ADT with postoperative radiotherapy after radical prostatectomy is unclear. Methods RADICALS-HD was an international randomised controlled trial to test the efficacy of ADT used in combination with postoperative radiotherapy for prostate cancer. Key eligibility criteria were indication for radiotherapy after radical prostatectomy for prostate cancer, prostate-specific antigen less than 5 ng/mL, absence of metastatic disease, and written consent. Participants were randomly assigned (1:1) to radiotherapy alone (no ADT) or radiotherapy with 6 months of ADT (short-course ADT), using monthly subcutaneous gonadotropin-releasing hormone analogue injections, daily oral bicalutamide monotherapy 150 mg, or monthly subcutaneous degarelix. Randomisation was done centrally through minimisation with a random element, stratified by Gleason score, positive margins, radiotherapy timing, planned radiotherapy schedule, and planned type of ADT, in a computerised system. The allocated treatment was not masked. The primary outcome measure was metastasis-free survival, defined as distant metastasis arising from prostate cancer or death from any cause. Standard survival analysis methods were used, accounting for randomisation stratification factors. The trial had 80% power with two-sided α of 5% to detect an absolute increase in 10-year metastasis-free survival from 80% to 86% (hazard ratio [HR] 0·67). Analyses followed the intention-to-treat principle. The trial is registered with the ISRCTN registry, ISRCTN40814031, and ClinicalTrials.gov, NCT00541047. Findings Between Nov 22, 2007, and June 29, 2015, 1480 patients (median age 66 years [IQR 61–69]) were randomly assigned to receive no ADT (n=737) or short-course ADT (n=743) in addition to postoperative radiotherapy at 121 centres in Canada, Denmark, Ireland, and the UK. With a median follow-up of 9·0 years (IQR 7·1–10·1), metastasis-free survival events were reported for 268 participants (142 in the no ADT group and 126 in the short-course ADT group; HR 0·886 [95% CI 0·688–1·140], p=0·35). 10-year metastasis-free survival was 79·2% (95% CI 75·4–82·5) in the no ADT group and 80·4% (76·6–83·6) in the short-course ADT group. Toxicity of grade 3 or higher was reported for 121 (17%) of 737 participants in the no ADT group and 100 (14%) of 743 in the short-course ADT group (p=0·15), with no treatment-related deaths. Interpretation Metastatic disease is uncommon following postoperative bed radiotherapy after radical prostatectomy. Adding 6 months of ADT to this radiotherapy did not improve metastasis-free survival compared with no ADT. These findings do not support the use of short-course ADT with postoperative radiotherapy in this patient population

Duration of androgen deprivation therapy with postoperative radiotherapy for prostate cancer: a comparison of long-course versus short-course androgen deprivation therapy in the RADICALS-HD randomised trial

Background Previous evidence supports androgen deprivation therapy (ADT) with primary radiotherapy as initial treatment for intermediate-risk and high-risk localised prostate cancer. However, the use and optimal duration of ADT with postoperative radiotherapy after radical prostatectomy remains uncertain. Methods RADICALS-HD was a randomised controlled trial of ADT duration within the RADICALS protocol. Here, we report on the comparison of short-course versus long-course ADT. Key eligibility criteria were indication for radiotherapy after previous radical prostatectomy for prostate cancer, prostate-specific antigen less than 5 ng/mL, absence of metastatic disease, and written consent. Participants were randomly assigned (1:1) to add 6 months of ADT (short-course ADT) or 24 months of ADT (long-course ADT) to radiotherapy, using subcutaneous gonadotrophin-releasing hormone analogue (monthly in the short-course ADT group and 3-monthly in the long-course ADT group), daily oral bicalutamide monotherapy 150 mg, or monthly subcutaneous degarelix. Randomisation was done centrally through minimisation with a random element, stratified by Gleason score, positive margins, radiotherapy timing, planned radiotherapy schedule, and planned type of ADT, in a computerised system. The allocated treatment was not masked. The primary outcome measure was metastasis-free survival, defined as metastasis arising from prostate cancer or death from any cause. The comparison had more than 80% power with two-sided α of 5% to detect an absolute increase in 10-year metastasis-free survival from 75% to 81% (hazard ratio [HR] 0·72). Standard time-to-event analyses were used. Analyses followed intention-to-treat principle. The trial is registered with the ISRCTN registry, ISRCTN40814031, and ClinicalTrials.gov , NCT00541047 . Findings Between Jan 30, 2008, and July 7, 2015, 1523 patients (median age 65 years, IQR 60–69) were randomly assigned to receive short-course ADT (n=761) or long-course ADT (n=762) in addition to postoperative radiotherapy at 138 centres in Canada, Denmark, Ireland, and the UK. With a median follow-up of 8·9 years (7·0–10·0), 313 metastasis-free survival events were reported overall (174 in the short-course ADT group and 139 in the long-course ADT group; HR 0·773 [95% CI 0·612–0·975]; p=0·029). 10-year metastasis-free survival was 71·9% (95% CI 67·6–75·7) in the short-course ADT group and 78·1% (74·2–81·5) in the long-course ADT group. Toxicity of grade 3 or higher was reported for 105 (14%) of 753 participants in the short-course ADT group and 142 (19%) of 757 participants in the long-course ADT group (p=0·025), with no treatment-related deaths. Interpretation Compared with adding 6 months of ADT, adding 24 months of ADT improved metastasis-free survival in people receiving postoperative radiotherapy. For individuals who can accept the additional duration of adverse effects, long-course ADT should be offered with postoperative radiotherapy. Funding Cancer Research UK, UK Research and Innovation (formerly Medical Research Council), and Canadian Cancer Society

A web-based Instrument to Model Social Norms: NERD Design and Results

Surveys and focus groups are well known methods for ascertaining public perceptions and opinion. The general view is that such tools provide reasonably accurate reflections of public values, and that the norms employed by people to make decisions are fixed. But what about issues where the public needs to consider novel choices where no prior experience can be drawn on? Do their preferences and beliefs change when presented with new options and new information? Recent evidence suggests they do and this paper describes an alternative way of gathering data, which takes into account the dynamic nature of social norms in response to new technologies and their applications. It also discusses the problem with traditional methods of generating information about public opinion and offers a possible solution. Our interdisciplinary research team, NERD (Norms Evolving in Response to Dilemmas), has developed a web-based survey instrument that is designed to bridge the gap between perceived and actual public opinion, which traditional surveys and focus groups are unable to capture. This paper will present some of our preliminary findings from the results of our first survey on the topic of Human Health and Genomics. We have found that there are differences in the way respondents answer which has not yet been accounted for in other participatory processes. If new technologies demand new methods for creating policies, then it is imperative to find solutions that the older, more traditional methods currently face

Development and Use of a Survey Tool to Determine the Efficacy of Livestock Truck Washes in Iowa

The transmission of disease among livestock farms could be addressed by the efficiency of truck washes to clean and disinfect trailers used for transporting animals. Collecting swab samples from trailers and cabs of identified truck wash trailers will help to determine the proper procedures and steps needed to reduce the transmission of disease. Truck washes in the state of Iowa were identified and invited to participate in a questionnaire that will provide helpful information for this research. The main goals of this study are to 1) determine the areas in the truck washing process that pose a high risk to transmit disease, and 2) to identify the location of current livestock truck washes and their capability in the event that some disease outbreak requires their involvement. This survey tool could help to provide necessary information in order to determine which service methods are best for reducing back contamination and the spread of disease among livestock herds. Determining what locations would be beneficial in collecting samples will be easier overall when the surveys are completed.</p

Regulation of the oncogenic phenotype by the nuclear body protein ZC3H8

Abstract Background The Zc3h8 gene encodes a protein with three zinc finger motifs in the C-terminal region. The protein has been identified as a component of the Little Elongation Complex, involved in transcription of small nuclear RNAs. ZC3H8 is overexpressed in a number of human and mouse breast cancer cell lines, and elevated mRNA levels are associated with a poorer prognosis for women with breast cancer. Methods We used RNA silencing to decrease levels of expression in mouse mammary tumor cells and overexpression of ZC3H8 in cells derived from the normal mouse mammary gland. We measured characteristics of cell behavior in vitro, including proliferation, migration, invasion, growth in soft agar, and spheroid growth. We assessed the ability of these cells to form tumors in syngeneic BALB/c mice. ZC3H8 protein was visualized in cells using confocal microscopy. Results Tumor cells with lower ZC3H8 expression exhibited decreased proliferation rates, slower migration, reduced ability to invade through a basement membrane, and decreased anchorage independent growth in vitro. Cells with lower ZC3H8 levels formed fewer and smaller tumors in animals. Overexpression of ZC3H8 in non-tumorigenic COMMA-D cells led to an opposite effect. ZC3H8 protein localized to both PML bodies and Cajal bodies within the nucleus. ZC3H8 has a casein kinase 2 (CK2) phosphorylation site near the N-terminus, and a CK2 inhibitor caused the numerous PML bodies and ZC3H8 to coalesce to a few larger bodies. Removal of the inhibitor restored PML bodies to their original state. A mutant ZC3H8 lacking the predicted CK2 phosphorylation site showed localization and numbers of ZC3H8/PML bodies similar to wild type. In contrast, a mutant constructed with a glutamic acid in place of the phosphorylatable threonine showed dramatically increased numbers of smaller nuclear foci. Conclusions These experiments demonstrate that Zc3h8 expression contributes to aggressive tumor cell behavior in vitro and in vivo. Our studies show that ZC3H8 integrity is key to maintenance of PML bodies. The work provides a link between the Little Elongation Complex, PML bodies, and the cancer cell phenotype

Additional file 2: of Regulation of the oncogenic phenotype by the nuclear body protein ZC3H8

Figure S2. Nuclear Protein Marker Localization in mouse and human cell lines. A) Localization of ZC3H8, PML, COILIN, CK2 and ICE2 (NARG2) in nuclear bodies in COMMA-D mouse mammary cells. B) ZC3H8, SMN, and COILIN partially co-localize in cV1A 03–31 cells. C) Localization of COILIN and DAXX in HeLa cells. D) Localization of PML in cells transfected with control or Zc3h8 shRNA vectors. (TIF 41195 kb

Additional file 1: of Regulation of the oncogenic phenotype by the nuclear body protein ZC3H8

Figure S1. Reduced expression of Zc3h8 in a second cell line and using a second targeting shRNA leads to reduced invasive behavior. A) Western blot demonstrating reduced levels of ZC3H8 protein in cV1A 03–31 cells transfected with a vector driving expression of an shRNA targeting site A. B) cV1A 03–31 cells transfected with a vector driving expression of siRNA targeting Zc3h8 at site A close a wound more slowly than cells transfected with a negative control vector in vitro. ANOVA revealed a significant difference of p < 0.05. C) A second tumor cell line, cV1A 01–51, was transfected with a vector targeting Zc3h8 at site C or negative control. Cells with reduced Zc3h8 closed a wound more slowly than negative control cells. ANOVA was used to assess significance at 12 h of p < 0.001. D) cV1A 01–51 cells with targeted Zc3h8 also formed smaller growths in syngeneic BALB/c mice than negative control cells. Student’s t-test was used to determine p < 0.001. E) cV1A 01–51 cells with reduced Zc3h8 did not form colonies in soft agar, while those transfected with a negative control formed large growths after two weeks. F) Tumor cell lines were surveyed by RT-qPCR for relative expression of Zc3h8 and Gata-3 compared to levels in virgin mammary gland, shown in a scatter plot. G) Overexpression of Zc3h8 in COMMA-D cells did not lead to a decrease in Gata-3 levels as determined by RT-qPCR. Error bars represent standard deviation. (TIF 22335 kb