Combination of carbon isotope ratio with hydrogen isotope ratio determinations in sports drug testing.

Carbon isotope ratio (CIR) analysis has been routinely and successfully applied to doping control analysis for many years to uncover the misuse of endogenous steroids such as testosterone. Over the years, several challenges and limitations of this approach became apparent, e.g., the influence of inadequate chromatographic separation on CIR values or the emergence of steroid preparations comprising identical CIRs as endogenous steroids. While the latter has been addressed recently by the implementation of hydrogen isotope ratios (HIR), an improved sample preparation for CIR avoiding co-eluting compounds is presented herein together with newly established reference values of those endogenous steroids being relevant for doping controls. From the fraction of glucuronidated steroids 5β-pregnane-3α,20α-diol, 5α-androst-16-en-3α-ol, 3α-Hydroxy-5β-androstane-11,17-dione, 3α-hydroxy-5α-androstan-17-one (ANDRO), 3α-hydroxy-5β-androstan-17-one (ETIO), 3β-hydroxy-androst-5-en-17-one (DHEA), 5α- and 5β-androstane-3α,17β-diol (5aDIOL and 5bDIOL), 17β-hydroxy-androst-4-en-3-one and 17α-hydroxy-androst-4-en-3-one were included. In addition, sulfate conjugates of ANDRO, ETIO, DHEA, 3β-hydroxy-5α-androstan-17-one plus 17α- and androst-5-ene-3β,17β-diol were considered and analyzed after acidic solvolysis. The results obtained for the reference population encompassing n = 67 males and females confirmed earlier findings regarding factors influencing endogenous CIR. Variations in sample preparation influenced CIR measurements especially for 5aDIOL and 5bDIOL, the most valuable steroidal analytes for the detection of testosterone misuse. Earlier investigations on the HIR of the same reference population enabled the evaluation of combined measurements of CIR and HIR and its usefulness regarding both steroid metabolism studies and doping control analysis. The combination of both stable isotopes would allow for lower reference limits providing the same statistical power and certainty to distinguish between the endo- or exogenous origin of a urinary steroid.

Audit report of the Schedule of Debt Service and Coverage for Iowa State University of Science and Technology for the Dormitory Revenue Refunding Bonds for the year ended June 30, 2012

Audit report of the Schedule of Debt Service and Coverage for Iowa State University of Science and Technology for the Dormitory Revenue Refunding Bonds for the year ended June 30, 2012

Molecular hydrogen diffusion in nanostructured amorphous silicon thin films

We study hydrogen stability and its evolution during thermal annealing in nanostructured amorphous silicon thin films. From the simultaneous measurement of heat and hydrogen desorption, we obtain the experimental evidence of molecular diffusion in these materials. In addition, we introduce a simple diffusion model which shows good agreement with the experimental data

Production of nanometric particles in radio frequency glow discharges in mixtures of silane and methane

The formation of silicon particles in rf glow discharges has attracted attention due to their effect as a contaminant during film deposition or etching. However, silicon and silicon alloy powders produced by plasma¿enhanced chemical vapor deposition (PECVD) are promising new materials for sintering ceramics, for making nanoscale filters, or for supporting catalytic surfaces. Common characteristics of these powders are their high purity and the easy control of their stoichiometry through the composition of the precursor gas mixture. Plasma parameters also influence their structure. Nanometric powders of silicon¿carbon alloys exhibiting microstructural properties such as large hydrogen content and high surface/volume ratio have been produced in a PECVD reactor using mixtures of silane and methane at low pressure (-1 Torr) and low frequency square¿wave modulated rf power (13.56 MHz). The a¿Si1¿xCx:H powders were obtained from different precursor gas mixtures, from R=0.05 to R=9, where R=[SiH4]/([SiH4]+[CH4]). The structure of the a¿Si1¿xCx:H powder was analyzed by several techniques. The particles appeared agglomerated, with a wide size distribution between 5 and 100 nm. The silane/methane gas mixture determined the vibrational features of these powders in the infrared. Silicon-hydrogen groups were present for every gas composition, whereas carbon¿hydrogen and silicon¿carbon bonds appeared in methane¿rich mixtures (R-0.6). The thermal desorption of hydrogen revealed two main evolutions at about 375 and 660¿°C that were ascribed to hydrogen bonded to silicon and carbon, respectively. The estimated hydrogen atom concentration in the sample was about 50%.

Contribution of S6K1/MAPK signaling pathways in the response to oxidative stress: activation of RSK and MSK by hydrogen peroxide

Cells respond to different kind of stress through the coordinated activation of signaling pathways such as MAPK or p53. To find which molecular mechanisms are involved, we need to understand their cell adaptation. The ribosomal protein, S6 kinase 1 (S6K1), is a common downstream target of signaling by hormonal or nutritional stress. Here, we investigated the initial contribution of S6K1/MAPK signaling pathways in the cell response to oxidative stress produced by hydrogen peroxide (H2O2). To analyze S6K1 activation, we used the commercial anti-phospho-Thr389-S6K1 antibody most frequently mentioned in the bibliography. We found that this antibody detected an 80-90 kDa protein that was rapidly phosphorylated in response to H2O2 in several human cells. Unexpectedly, this phosphorylation was insensitive to both mTOR and PI3K inhibitors, and knock-down experiments showed that this protein was not S6K1. RSK and MSK proteins were candidate targets of this phosphorylation. We demonstrated that H2O2 stimulated phosphorylation of RSK and MSK kinases at residues that are homologous to Thr389 in S6K1. This phosphorylation required the activity of either p38 or ERK MAP kinases. Kinase assays showed activation of RSK and MSK by H2O2. Experiments with mouse embryonic fibroblasts from p38 animals" knockout confirmed these observations. Altogether, these findings show that the S6K1 signaling pathway is not activated under these conditions, clarify previous observations probably misinterpreted by non-specific detection of proteins RSK and MSK by the anti-phospho-Thr389-S6K1 antibody, and demonstrate the specific activation of MAPK signaling pathways through ERK/p38/RSK/MSK by H2O2.

Sodium/hydrogen exchanger NHA2 is critical for insulin secretion in β-cells.

NHA2 is a sodium/hydrogen exchanger with unknown physiological function. Here we show that NHA2 is present in rodent and human β-cells, as well as β-cell lines. In vivo, two different strains of NHA2-deficient mice displayed a pathological glucose tolerance with impaired insulin secretion but normal peripheral insulin sensitivity. In vitro, islets of NHA2-deficient and heterozygous mice, NHA2-depleted Min6 cells, or islets treated with an NHA2 inhibitor exhibited reduced sulfonylurea- and secretagogue-induced insulin secretion. The secretory deficit could be rescued by overexpression of a wild-type, but not a functionally dead, NHA2 transporter. NHA2 deficiency did not affect insulin synthesis or maturation and had no impact on basal or glucose-induced intracellular Ca(2+) homeostasis in islets. Subcellular fractionation and imaging studies demonstrated that NHA2 resides in transferrin-positive endosomes and synaptic-like microvesicles but not in insulin-containing large dense core vesicles in β-cells. Loss of NHA2 inhibited clathrin-dependent, but not clathrin-independent, endocytosis in Min6 and primary β-cells, suggesting defective endo-exocytosis coupling as the underlying mechanism for the secretory deficit. Collectively, our in vitro and in vivo studies reveal the sodium/proton exchanger NHA2 as a critical player for insulin secretion in the β-cell. In addition, our study sheds light on the biological function of a member of this recently cloned family of transporters.

Mixing of Rhône River water in Lake Geneva (Switzerland-France) inferred from stable hydrogen and oxygen isotope profiles

Depth profiles were sampled at different locations throughout Lake Geneva on a monthly and seasonal basis over the course of 2 years and analysed for their stable hydrogen and oxygen isotope compositions. The isotopic compositions indicate an isotopic stratification in the metalimnion during summer and fall. This is related to mixing of Rhône River water, which in summer is dominated by snow and glacier melt waters, and lake water, with the latter having a homogenous isotopic composition. The observed interflow layer is 7-15 m thick and can be traced by the distinct stable isotope composition of the water for about 55 km throughout the lake as well as into shallow bay regions. Depth of the interflow layer close to the Rhône River mouth is similar to those previously described based on echo-soundings and turbidity profiles of sediment dispersion. In contrast to previous descriptions of the interflow within Lake Geneva, the stable isotope compositions allow for direct, natural tracing of the Rhône River water even in cases where the turbidity and conductivity measurements do not indicate such an interflow. In addition, the method allows for a quantification of the Rhône River and lake water in the interflow with the fraction of Rhône River water within the interflow estimated to be up to 37% in summer. The isotopic composition further indicates different vertical mixing processes within the two lake basins of Lake Geneva, related to the density gradients and local stability within the water column. The method may be applicable to other lakes in catchments with large differences in the topography as water that originates from high altitudes or glaciers has a distinct oxygen and hydrogen isotope composition compared to other sources of water originating at lower altitudes and/or from direct precipitation over the lake. Stable isotope measurements thus improve the understanding of the circulation of water within the lake, which is fundamental for an evaluation of the water residence times, dissolved pollutant and nutrient transport as well as oxygenation.

Percolation and three-dimensional structure of supercritical water

It is well established that at ambient and supercooled conditions water can be described as a percolating network of H bonds. This work is aimed at identifying, by neutron diffraction experiments combined with computer simulations, a percolation line in supercritical water, where the extension of the H-bond network is in question. It is found that in real supercritical water liquidlike states are observed at or above the percolation threshold, while below this threshold gaslike water forms small, sheetlike configurations. Inspection of the three-dimensional arrangement of water molecules suggests that crossing of this percolation line is accompa- nied by a change of symmetry in the first neighboring shell of molecules from trigonal below the line to tetrahedral above.

2011 Annual Report for Appropriations from the Rebuild Iowa Infrastructure Fund and Revenue Bonds Capitals II Fund to the Watershed Improvement Fund

The Watershed Improvement Fund and the Watershed Improvement Review Board (WIRB) were created in 2005. This statute is now codified in Iowa Code Chapter 466A. The pmpose of the Watershed Improvement Fund is to enhance the water quality and flood prevention efforts in the state through a variety of impairment-based, locally­ directed watershed improvement projects. These projects are awarded grants through a competitive application process directed by the WIRB. Appropriations to the Fund do not revert. Interest earned on the moneys on the Fund are also retained in the Fund and are used to fund projects or pay per diem and expenses of the WIRB members. In state fiscal years 2009 (SFY2009) and 2010 (SFY2010), the Watershed Improvement Fund was appropriated $5,000,000 from the Rebuild Iowa Infrastructure Fund (RIIF). In SFY2011, the Watershed Improvement Fund was appropriated $2,000,000 from the Revenue Bonds Capitals II Fund (RBC2).

2012 Annual Report for Appropriations from the Rebuild Iowa Infrastructure Fund and Revenue Bonds Capitals II Fund to the Watershed Improvement Fund

The Watershed Improvement Fund and the Watershed Improvement Review Board (WIRB) were created in 2005. This statute is now codified in Iowa Code Chapter 466A. The purpose of the Watershed Improvement Fund is to enlmnce the water quality and flood prevention efforts in the state through a variety of impairment-based, locally­ directed watershed improvement projects. These projects are awarded grants through a competitive application process directed by the WIRB. Appropriations to the Fund do not revert except for the Capital Revenue Bonds II (RCB2) appropriation. Interest eamed on the moneys on the Fund are also retained in the Fund and are used to fund projects or pay per diem and expenses of the WIRB members. Starting July 1, 2012, the Fund is also receiving Animal Agriculture Compliance Fund Penalties. In state fiscal years 2009 (SFY2009) and 2010 (SFY2010), the Watershed Improvement Fund was appropriated $5,000,000 from the Rebuild Iowa Infrastructure Fund (RIIF). In SFY2011, the Watershed Improvement Fund was appropriated $2,000,000 from the Revenue Bonds Capitals II Fund (RBC2). No appropriation was received in fiscal year 2012. In SFY 2013, the Watershed Improvement Fund was appropriated $1,000,000 from the RIIF.

2013 Annual Report for Appropriations from the Rebuild Iowa Infrastructure Fund and Revenue Bonds Capitals II Fund to the Watershed Improvement Fund

The Watershed Improvement Fund and the Watershed Improvement Review Board (WIRB) were created in 2005. This statute is now codified in Iowa Code Chapter 466A. The purpose of the Watershed Improvement Fund is to enhance the water quality in the state through a variety of impairment-based, locally-directed watershed improvement projects. These projects are awarded grants through a competitive application process directed by the WIRB. Appropriations to the Fund do not revert except for the Capital Revenue Bonds II (RCB2) appropriation. Interest earned on the moneys on the Fund are also retained in the Fund and are used to fund projects or pay per diem and expenses of the WIRB members. Starting July 1, 2012, the Fund is also receiving Animal Agriculture Compliance Fund Penalties. In state fiscal years 2009 (SFY2009) and 2010 (SFY2010), the Watershed Improvement Fund was appropriated $5,000,000 from the Rebuild Iowa Infrastructure Fund (RIIF). In SFY2011, the Watershed Improvement Fund was appropriated $2,000,000 from the Revenue Bonds Capitals II Fund (RBC2). No appropriation was received in fiscal year 2012. In SFY 2013, the Watershed Improvement Fund was appropriated $1,000,000 from the RIIF.

2014 Annual Report for Appropriations from the Rebuild Iowa Infrastructure Fund and Revenue Bonds Capitals II Fund to the Watershed Improvement Fund

The Watershed Improvement Fund and the Watershed Improvement Review Board (WIRB) were created in 2005. This statute is now codified in Iowa Code Chapter 466A. The purpose of the Watershed Improvement Fund is to enhance the water quality in the state through a variety of impairment-based, locally-directed watershed improvement projects. These projects are awarded grants through a competitive application process directed by the WIRB. Appropriations to the Fund do not revert except for the Capital Revenue Bonds II (RCB2) appropriation. Interest earned on the moneys on the Fund are also retained in the Fund and are used to fund projects or pay per diem and expenses of the WIRB members. Starting July 1, 2012, the Fund is also receiving Animal Agriculture Compliance Fund Penalties. In state fiscal years 2009 (SFY2009) and 2010 (SFY2010), the Watershed Improvement Fund was appropriated $5,000,000 from the Rebuild Iowa Infrastructure Fund (RIIF). In SFY2011, the Watershed Improvement Fund was appropriated $2,000,000 from the Revenue Bonds Capitals II Fund (RBC2). No appropriation was received in fiscal year 2012. In SFY 2013, the Watershed Improvement Fund was appropriated $1,000,000 from the RIIF.

2015 Annual Report for Appropriations from the Rebuild Iowa Infrastructure Fund and Revenue Bonds Capitals II Fund to the Watershed Improvement Review Fund

This is the annual appropriations report submitted on behalf of the Watershed Improvement Review Board (WIRB).

Nucleophile-Catalyzed Additions to Activated Triple Bonds. Protection of Lactams, Imides, and Nucleosides with MocVinyl and Related Groups

Additions of lactams, imides, (S)-4-benzyl-1,3-oxazolidin-2-one, 2-pyridone, pyrimidine-2,4-diones (AZT derivatives), or inosines to the electron-deficient triple bonds of methyl propynoate, tert-butyl propynoate, 3-butyn-2-one, N-propynoylmorpholine, or N-methoxy-N-methylpropynamide in the presence of many potential catalysts were examined. DABCO and, second, DMAP appeared to be the best (highest reaction rates and E/Z ratios), while RuCl3, RuClCp*(PPh3)2, AuCl, AuCl(PPh3), CuI, and Cu2(OTf)2 were incapable of catalyzing such additions. The groups incorporated (for example, the 2-(methoxycarbonyl)ethenyl group that we name MocVinyl) serve as protecting groups for the above-mentioned heterocyclic CONH or CONHCO moieties. Deprotections were accomplished via exchange with good nucleophiles: the 1-dodecanethiolate anion turned out to be the most general and efficient reagent, but in some particular cases other nucleophiles also worked (e.g., MocVinyl-inosines can be cleaved with succinimide anion). Some structural and mechanistic details have been accounted for with the help of DFT and MP2 calculations.