Versatile liquid helium scintillation counter of large volume design

Design and performance of large liquid helium scintillation counter for meson experiment

Far-field electric potentials provide access to the output from the spinal cord from wrist-mounted sensors

OBJECTIVE: Neural interfaces need to become more unobtrusive and socially acceptable to appeal to general consumers outside rehabilitation settings. APPROACH: We developed a non-invasive neural interface that provides access to spinal motor neuron activities from the wrist, which is the preferred location for a wearable. The interface decodes far-field potentials present at the tendon endings of the forearm muscles using blind source separation. First, we evaluated the reliability of the interface to detect motor neuron firings based on far-field potentials, and thereafter we used the decoded motor neuron activity for the prediction of finger contractions in offline and real-time conditions. MAIN RESULTS: The results showed that motor neuron activity decoded from the far-field potentials at the wrist accurately predicted individual and combined finger commands and therefore allowed for highly accurate real-time task classification. SIGNIFICANCE: These findings demonstrate the feasibility of a non-invasive, neural interface at the wrist for precise real-time control based on the output of the spinal cord

DNA base sequence effects on bulky lesion-induced conformational heterogeneity during DNA replication

4-Aminobiphenyl (ABP) and its structure analog 2-aminofluorene (AF) are well-known carcinogens. In the present work, an unusual sequence effect in the 5′-CTTCTG1G2TCCTCATTC-3′ DNA duplex is reported for ABP- and AF-modified G. Specifically, the ABP modification at G1 resulted in a mixture of 67% major groove B-type (B) and 33% stacked (S) conformers, while at the ABP modification at G2 exclusively resulted in the B-conformer. The AF modification at G1 and G2 lead to 25%:75% and 83%:17% B:S population ratios, respectively. These differences in preferred conformation are due to an interplay between stabilizing (hydrogen bonding and stacking that is enhanced by lesion planarity) and destabilizing (solvent exposure) forces at the lesion site. Furthermore, while the B-conformer is a thermodynamic stabilizer and the S-conformer is a destabilizer in duplex settings, the situation is reversed at the single strands/double strands (ss/ds) junction. Specifically, the twisted biphenyl is a better stacker at the ss/ds junction than the coplanar AF. Therefore, the ABP modification leads to a stronger strand binding affinity of the ss/ds junction than the AF modification. Overall, the current work provides conformational insights into the role of sequence and lesion effects in modulating DNA replication

Sulfur chemistry in a borosilicate melt Part 3. Iron-sulfur interactions and the amber chromophore

The mutual interactions of iron and sulfur in a borosilicate melt were defined as a function of the iron content, sulfur concentration, melt temperature, and oxygen fugacity. Over the range of conditions for which ions of SO4 2- - Fe3+ - Fe2+ or S2- - Fe2+ - Fe0 existed in the melt, sulfur and iron behaved as two independent redox systems. Mutual interaction occurred only for the conditions when S2- ions were in equilibrium with Fe3+ ions in the melt (for example, an oxygen fugacity of 10^-9 to 10^-11 bar at 1150 °C). The Fe3+ ion oxidized the S2- ion to the supersulfide ion, S2 -, which was identified as the amber chromophore. When the iron content of the melt was 1 wt% or less, the supersulfide ion was produced only in low concentrations; and consequently, the redox reaction producing it did not measurably affect sulfur solubility in the melt. In melts containing 10 wt% total iron, the mutual interaction of Fe3+ and S2- ions was sufficient to enhance the sulfur solubility through the formation of polysulfide species in the melt

Adenine versus guanine DNA adducts of aristolochic acids: role of the carcinogen-purine linkage in the differential global genomic repair propensity

Sherpa Romeo green journal: open accessComputational modeling is employed to provide a plausible structural explanation for the experimentally-observed differential global genome repair (GGR) propensity of the ALII-N2-dG and ALIIN6- dA DNA adducts of aristolochic acid II. Our modeling studies suggest that an intrinsic twist at the carcinogen–purine linkage of ALII-N2-dG induces lesion site structural perturbations and conformational heterogeneity of damaged DNA. These structural characteristics correlate with the relative repair propensities of AA-adducts, where GGR recognition occurs for ALII-N2-dG, but is evaded for intrinsically planar ALII-N6-dA that minimally distorts DNA and restricts the conformational flexibility of the damaged duplex. The present analysis on the ALII adduct model systems will inspire future experimental studies on these adducts, and thereby may extend the list of structural factors that directly correlate with the propensity for GGR recognition.Ye

Impact of a modified data capture period on Liu comorbidity index scores in Medicare enrollees initiating chronic dialysis

A grant from the One-University Open Access Fund at the University of Kansas was used to defray the author’s publication fees in this Open Access journal. The Open Access Fund, administered by librarians from the KU, KU Law, and KUMC libraries, is made possible by contributions from the offices of KU Provost, KU Vice Chancellor for Research & Graduate Studies, and KUMC Vice Chancellor for Research. For more information about the Open Access Fund, please see http://library.kumc.edu/authors-fund.xml.Background: The Liu Comorbidity Index uses the United States Renal Data System (USRDS) to quantify comorbidity in chronic dialysis patients, capturing baseline comorbidities from days 91 through 270 after dialysis initiation. The 270 day survival requirement results in sample size reductions and potential survivor bias. An earlier and shorter time-frame for data capture could be beneficial, if sufficiently similar comorbidity information could be ascertained. Methods: USRDS data were used in a retrospective observational study of 70,114 Medicare- and Medicaid-eligible persons who initiated chronic dialysis during the years 2000–2005. The Liu index was modified by changing the baseline comorbidity capture period to days 1–90 after dialysis initiation for persons continuously enrolled in Medicare. The scores resulting from the original and the modified comorbidity indices were compared, and the impact on sample size was calculated. Results: The original Liu comorbidity index could be calculated for 75% of the sample, but the remaining 25% did not survive to 270 days. Among 52,937 individuals for whom both scores could be calculated, the mean scores for the original and the modified index were 7.4 ± 4.0 and 6.4 ± 3.6 points, respectively, on a 24-point scale. The most commonly calculated difference between scores was zero, occurring in 44% of patients. Greater comorbidity was found in those who died before 270 days. Conclusions: A modified version of the Liu comorbidity index captures the majority of comorbidity in persons who are Medicare-enrolled at the time of chronic dialysis initiation. This modification reduces sample size losses and facilitates inclusion of a sicker portion of the population in whom early mortality is common. Keywords: Comorbidity, Kidney failure, Chronic, Renal dialysis, Epidemiologic research desig

Structural and energetic characterization of the major DNA adduct formed from the food mutagen ochratoxin A in the NarI hotspot sequence: influence of adduct ionization on the conformational preferences and implications for the NER propensity

Sherpa Romeo green journal, open accessThe nephrotoxic food mutagen ochratoxin A (OTA) produces DNA adducts in rat kidneys, the major lesion being the C8-linked-2 -deoxyguanosine adduct (OTB-dG). Although research on other adducts stresses the importance of understanding the structure of the associated adducted DNA, site-specific incorporation of OTB-dG into DNA has yet to be attempted. The present work uses a robust computational approach to determine the conformational preferences of OTB-dG in three ionization states at three guanine positions in the NarI recognition sequence opposite cytosine. Representative adducted DNA helices were derived from over 2160 ns of simulation and ranked via free energies. For the first time, a close energetic separation between three distinct conformations is highlighted, which indicates OTA-adducted DNA likely adopts a mixture of conformations regardless of the sequence context. Nevertheless, the preferred conformation depends on the flanking bases and ionization state due to deviations in discrete local interactions at the lesion site. The structural characteristics of the lesion thus discerned have profound implications regarding its repair propensity andmutagenic outcomes, and support recent experiments suggesting the induction of double-strand breaks and deletion mutations upon OTA exposure. This combined structural and energetic characterization of the OTB-dG lesion in DNA will encourage future biochemical experiments on this potentially genotoxic lesion.Ye

Computational evaluation of nucleotide insertion opposite expanded and widened DNA by the translesion synthesis polymerase Dpo4

Open accessExpanded (x) and widened (y) deoxyribose nucleic acids (DNA) have an extra benzene ring incorporated either horizontally (xDNA) or vertically (yDNA) between a natural pyrimidine base and the deoxyribose, or between the 5- and 6-membered rings of a natural purine. Far-reaching applications for (x,y)DNA include nucleic acid probes and extending the natural genetic code. Since modified nucleobases must encode information that can be passed to the next generation in order to be a useful extension of the genetic code, the ability of translesion (bypass) polymerases to replicate modified bases is an active area of research. The common model bypass polymerase DNA polymerase IV (Dpo4) has been previously shown to successfully replicate and extend past a single modified nucleobase on a template DNA strand. In the current study, molecular dynamics (MD) simulations are used to evaluate the accommodation of expanded/widened nucleobases in the Dpo4 active site, providing the first structural information on the replication of (x,y)DNA. Our results indicate that the Dpo4 catalytic (palm) domain is not significantly impacted by the (x,y)DNA bases. Instead, the template strand is displaced to accommodate the increased C1’–C1’ base-pair distance. The structural insights unveiled in the present work not only increase our fundamental understanding of Dpo4 replication, but also reveal the process by which Dpo4 replicates (x,y)DNA, and thereby will contribute to the optimization of high fidelity and efficient polymerases for the replication of modified nucleobases.Ye