Ion pairing of nucleotides with surfactants for enhanced sensitivity in liquid matrix assisted secondary ion mass spectrometry

In particle induced desorption-ionization mass spectrometry the strength of an analyte's signal under a given set of bombardment conditions is usually considered to be representative of the analytes relative surface activity. This rationale is generally used to explain differences in the technique's sensitivity between and within various classes of compound. In liquid matrix assisted secondary ion mass spectrometry (SIMS) sensitivity enhancement of ionic analytes by pairing with surface active counterions has been demonstrated by several groups. This technique has been utilized in this work to achieve a 10,000 fold enhancement in the signal for ATP on a double focusing magnetic sector instrument and to detect femtomole quantities of nucleoside monophosphates on a time-of-flight instrument. The analyte's signal, however, is dependent on both the analyte bulk concentration and that of the surfactant. Additionally, the surfactant concentration that produces the maximum analyte signal changes with the analyte concentration. In this study, this phenomenon has been modeled in terms of conventional solution equilibria and surface chemical principles. It is assumed that the initial surface composition and the bulk concentration are the boundary conditions of a steady state established by the competing processes of surface sputtering and surface replenishment from the bulk during analysis. Calculated surface excesses correlate well with observed relative ion intensities, suggesting that equilibrium conditions are approached in the sample matrices despite the outwardly dynamic nature of the sputtering processes

National Athletic Trainers\u27 Association Position Statement: Anabolic-Androgenic Steroids

Objective: This manuscript summarizes the best available scholarly evidence related to anabolic-androgenic steroids (AAS) as a reference for health care professionals, including athletic trainers, educators, and interested others. Background: Health care professionals associated with sports or exercise should understand and be prepared to educate others about AAS. These synthetic, testosteronebased derivatives are widely abused by athletes and nonathletes to gain athletic performance advantages, develop their physiques, and improve their body image. Although AAS can be ergogenic, their abuse may lead to numerous negative health effects. Recommendations: Abusers of AAS often rely on questionable information sources. Sports medicine professionals can therefore serve an important role by providing accurate, reliable information. The recommendations provide health care professionals with a current and accurate synopsis of the AAS-related research

Magnetic Resonance Imaging-Guided Transurethral Ultrasound Ablation of Prostate Cancer

Purpose: Magnetic resonance imaging-guided transurethral ultrasound ablation uses directional thermal ultrasound under magnetic resonance imaging thermometry feedback control for prostatic ablation. We report 12-month outcomes from a prospective multicenter trial (TACT). Materials and methods: A total of 115 men with favorable to intermediate risk prostate cancer across 13 centers were treated with whole gland ablation sparing the urethra and apical sphincter. The co-primary 12-month endpoints were safety and efficacy. Results: In all, 72 (63%) had grade group 2 and 77 (67%) had NCCN® intermediate risk disease. Median treatment delivery time was 51 minutes with 98% (IQR 95-99) thermal coverage of target volume and spatial ablation precision of ±1.4 mm on magnetic resonance imaging thermometry. Grade 3 adverse events occurred in 9 (8%) men. The primary endpoint (U.S. Food and Drug Administration mandated) of prostate specific antigen reduction ≥75% was achieved in 110 of 115 (96%) with median prostate specific antigen reduction of 95% and nadir of 0.34 ng/ml. Median prostate volume decreased from 37 to 3 cc. Among 68 men with pretreatment grade group 2 disease, 52 (79%) were free of grade group 2 disease on 12-month biopsy. Of 111 men with 12-month biopsy data, 72 (65%) had no evidence of cancer. Erections (International Index of Erectile Function question 2 score 2 or greater) were maintained/regained in 69 of 92 (75%). Multivariate predictors of persistent grade group 2 at 12 months included intraprostatic calcifications at screening, suboptimal magnetic resonance imaging thermal coverage of target volume and a PI-RADS™ 3 or greater lesion at 12-month magnetic resonance imaging (p <0.05). Conclusions: The TACT study of magnetic resonance imaging-guided transurethral ultrasound whole gland ablation in men with localized prostate cancer demonstrated effective tissue ablation and prostate specific antigen reduction with low rates of toxicity and residual disease

First observations of separated atmospheric nu_mu and bar{nu-mu} events in the MINOS detector

The complete 5.4 kton MINOS far detector has been taking data since the beginning of August 2003 at a depth of 2070 meters water-equivalent in the Soudan mine, Minnesota. This paper presents the first MINOS observations of nuµ and [overline nu ]µ charged-current atmospheric neutrino interactions based on an exposure of 418 days. The ratio of upward- to downward-going events in the data is compared to the Monte Carlo expectation in the absence of neutrino oscillations, giving Rup/downdata/Rup/downMC=0.62-0.14+0.19(stat.)±0.02(sys.). An extended maximum likelihood analysis of the observed L/E distributions excludes the null hypothesis of no neutrino oscillations at the 98% confidence level. Using the curvature of the observed muons in the 1.3 T MINOS magnetic field nuµ and [overline nu ]µ interactions are separated. The ratio of [overline nu ]µ to nuµ events in the data is compared to the Monte Carlo expectation assuming neutrinos and antineutrinos oscillate in the same manner, giving R[overline nu ][sub mu]/nu[sub mu]data/R[overline nu ][sub mu]/nu[sub mu]MC=0.96-0.27+0.38(stat.)±0.15(sys.), where the errors are the statistical and systematic uncertainties. Although the statistics are limited, this is the first direct observation of atmospheric neutrino interactions separately for nuµ and [overline nu ]µ

Role of genetic testing for inherited prostate cancer risk: Philadelphia prostate cancer consensus conference 2017

Purpose: Guidelines are limited for genetic testing for prostate cancer (PCA). The goal of this conference was to develop an expert consensus-dri

Isolation of the Heterofullerene C59N as Its Dimer (C59N)2

The heterofullerene ion C59N+ is formed efficiently in the gas phase during fast atom bombardment mass spectroscopy of a cluster-opened N-MEM (N-methoxyethoxy methyl) ketolactam. This transformation is shown to occur also in solution in the presence of strong acid, affording biazafullerenyl (C59N)2 in good yield. It is proposed that the azafullerene dimer is formed upon in situ reduction of the highly reactive azafulleronium ion. The isolation and characterization of biazafullerenyl opens a viable route for the preparation of other heterofullerenes in solution.

Increasing Tumor Accessibility with Conjugatable Disulfide-Bridged Tumor-Penetrating Peptides for Cancer Diagnosis and Treatment

Tumor-homing peptides with tissue-penetrating properties increase the efficacy of targeted cancer therapy by delivering an anticancer agent to the tumor interior. LyP-1 (CGNKRTRGC) and iRGD (CRGDKGPDC) are founding members of this class of peptides. The presence of the cysteines forming the cyclizing disulfide bond complicates conjugation of these peptides with other molecules, such as drugs. Here, we report the synthesis of conjugatable disulfide-bridged peptides and their conjugation to biologically important molecules. We have synthesized the LyP-1, iRGD, and CRGDC (GACRGDCLGA) peptides with a cysteine or maleimidohexanoic acid added externally at N-terminus of the sequences. Subsequent conjugation to payloads yielded stable compounds in which the tumor-homing properties of the peptide and the biological activity of the payload were retained

Silver (I) as DNA glue: Ag(+)-mediated guanine pairing revealed by removing Watson-Crick constraints.

Metal ion interactions with DNA have far-reaching implications in biochemistry and DNA nanotechnology. Ag(+) is uniquely interesting because it binds exclusively to the bases rather than the backbone of DNA, without the toxicity of Hg(2+). In contrast to prior studies of Ag(+) incorporation into double-stranded DNA, we remove the constraints of Watson-Crick pairing by focusing on homo-base DNA oligomers of the canonical bases. High resolution electro-spray ionization mass spectrometry reveals an unanticipated Ag(+)-mediated pairing of guanine homo-base strands, with higher stability than canonical guanine-cytosine pairing. By exploring unrestricted binding geometries, quantum chemical calculations find that Ag(+) bridges between non-canonical sites on guanine bases. Circular dichroism spectroscopy shows that the Ag(+)-mediated structuring of guanine homobase strands persists to at least 90 °C under conditions for which canonical guanine-cytosine duplexes melt below 20 °C. These findings are promising for DNA nanotechnology and metal-ion based biomedical science

Isolation of Halobacterium salinarum Retrieved Directly from Halite Brine Inclusions

Halite crystals were selected from a 186 m subsurface core taken from the Badwater salt pan, Death Valley, California to ascertain if halophilic Archaea and their associated 16S rDNA can survive over several tens of thousands of years. Using a combined microscope microdrill/micropipette system, fluids from brine inclusions were aseptically extracted from primary, hopper texture, halite crystals from 8 and 85 metres below the surface (mbls). U-Th disequilibrium dating indicates that these halite layers were deposited at 9600 and 97 000 years before present (ybp) respectively. Extracted inclusions were used for polymerase chain reaction (PCR) analysis with haloarchaea-specific 16S rDNA primers or placed into haloarchaea culture medium. Enrichment cultures were obtained from 97 kyr halite crystal inclusion fluid and haloarchaea-containing prepared crystals (positive controls), whereas inclusions from crystals of 9.6 kyr halite and the haloarchaea-free halite crystals (negative controls) resulted in no growth. Phylogenetic analysis (16S rDNA) of the 97 kyr isolate, designated BBH 001, revealed a homology of 100% with Halobacterium salinarum. DNA-DNA hybridization experiments confirmed that BBH 001 was closely related to H. salinarum (81-75% hybridization) and its ascription to this haloarchaea species. The described method of retrieving particle-containing brine from fluid inclusions offers a robust approach for assessing the antiquity of microorganisms associated with evaporites