On the role of shake-off in single-photon double ionization

The role of shake-off for double ionization of atoms by a single photon with finite energy has become the subject of debate. In this letter, we attempt to clarify the meaning of shake-off at low photon energies by comparing different formulations appearing in the literature and by suggesting a working definition. Moreover, we elaborate on the foundation and justification of a mixed quantum-classical ansatz for the calculation of single-photon double ionization

RhoG regulates endothelial apical cup assembly downstream from ICAM1 engagement and is involved in leukocyte trans-endothelial migration

During trans-endothelial migration (TEM), leukocytes use adhesion receptors such as intercellular adhesion molecule-1 (ICAM1) to adhere to the endothelium. In response to this interaction, the endothelium throws up dynamic membrane protrusions, forming a cup that partially surrounds the adherent leukocyte. Little is known about the signaling pathways that regulate cup formation. In this study, we show that RhoG is activated downstream from ICAM1 engagement. This activation requires the intracellular domain of ICAM1. ICAM1 colocalizes with RhoG and binds to the RhoG-specific SH3-containing guanine-nucleotide exchange factor (SGEF). The SH3 domain of SGEF mediates this interaction. Depletion of endothelial RhoG by small interfering RNA does not affect leukocyte adhesion but decreases cup formation and inhibits leukocyte TEM. Silencing SGEF also results in a substantial reduction in RhoG activity, cup formation, and TEM. Together, these results identify a new signaling pathway involving RhoG and its exchange factor SGEF downstream from ICAM1 that is critical for leukocyte TEM

The DNA-damage signature in Saccharomyces cerevisiae is associated with single-strand breaks in DNA

BACKGROUND: Upon exposure to agents that damage DNA, Saccharomyces cerevisiae undergo widespread reprogramming of gene expression. Such a vast response may be due not only to damage to DNA but also damage to proteins, RNA, and lipids. Here the transcriptional response of S. cerevisiae specifically induced by DNA damage was discerned by exposing S. cerevisiae to a panel of three "radiomimetic" enediyne antibiotics (calicheamicin γ(1)(I), esperamicin A1 and neocarzinostatin) that bind specifically to DNA and generate varying proportions of single- and double-strand DNA breaks. The genome-wide responses were compared to those induced by the non-selective oxidant γ-radiation. RESULTS: Given well-controlled exposures that resulted in similar and minimal cell death (~20–25%) across all conditions, the extent of gene expression modulation was markedly different depending on treatment with the enediynes or γ-radiation. Exposure to γ-radiation resulted in more extensive transcriptional changes classified both by the number of genes modulated and the magnitude of change. Common biological responses were identified between the enediynes and γ-radiation, with the induction of DNA repair and stress response genes, and the repression of ribosomal biogenesis genes. Despite these common responses, a fraction of the response induced by gamma radiation was repressed by the enediynes and vise versa, suggesting that the enediyne response is not entirely "radiomimetic." Regression analysis identified 55 transcripts with gene expression induction associated both with double- or single-strand break formation. The S. cerevisiae "DNA damage signature" genes as defined by Gasch et al. [1] were enriched among regulated transcripts associated with single-strand breaks, while genes involved in cell cycle regulation were associated with double-strand breaks. CONCLUSION: Dissection of the transcriptional response in yeast that is specifically signaled by DNA strand breaks has identified that single-strand breaks provide the signal for activation of transcripts encoding proteins involved in the DNA damage signature in S. cerevisiae, and double-strand breaks signal changes in cell cycle regulation genes

Quantitative Magnetization Transfer in In Vivo Healthy Human Skeletal Muscle at 3 T

The value of quantitative MR methods as potential biomarkers in neuromuscular disease is being increasingly recognized. Previous studies of the magnetization transfer ratio have demonstrated sensitivity to muscle disease. The aim of this work was to investigate quantitative magnetization transfer imaging of skeletal muscle in healthy subjects at 3 T to evaluate its potential use in pathological muscle. The lower limb of 10 subjects was imaged using a 3D fast low-angle shot acquisition with variable magnetization transfer saturation pulse frequencies and amplitudes. The data were analyzed with an established quantitative two-pool model of magnetization transfer. T1 and B1 amplitude of excitation radiofrequency field maps were acquired and used as inputs to the quantitative magnetization transfer model, allowing properties of the free and restricted proton pools in muscle to be evaluated in seven different muscles in a region of interest analysis. The average restricted pool T2 relaxation time was found to be 5.9 ± 0.2μs in the soleus muscle and the restricted proton pool fraction was 8 ± 1%. Quantitative magnetization transfer imaging of muscle offers potential new biomarkers in muscle disease within a clinically feasible scan time. Magn Reson Med, 2010. © 2010 Wiley-Liss, Inc

Efficacy of electronic apex locators in comparison with intraoral radiographs in working length determination- a systematic review and meta-analysis.

BACKGROUND: Successful endodontic treatment needs accurate determination of working length (WL). Electronic apex locators (EALs) were presented as an alternative to radiographic methods; and since then, they have evolved and gained popularity in the determination of WL. However, there is insufficient evidence on the post-operative pain, adequacy, and accuracy of EALs in determining WL. OBJECTIVE: The systematic review and meta-analysis aims to gather evidence regarding the effectiveness of EALs for WL determination when compared to different imaging techniques along with postoperative pain associated with WL determination, the number of radiographs taken during the procedure, the time taken, and the adverse effects. METHODS: For the review, clinical studies with cross-over and parallel-arm randomized controlled trials (RCTs) were searched in seven electronic databases, followed by cross-referencing of the selected studies and related research synthesis. Risk of bias (RoB) assessment was carried out with Cochrane's RoB tool and a random-effects model was used. The meta-analysis was performed with the RevMan software 5.4.1. RESULTS: Eleven eligible RCTs were incorporated into the review and eight RCTs into the meta-analysis, of which five had high RoB and the remaining six had unclear RoB. Following meta-analysis, no significant difference in postoperative pain was found among the EAL and radiograph groups (SMD 0.00, CI .29 to .28, 354 participants; P value = 0.98). Radiograph group showed better WL accuracy (SMD 0.55, CI .11 to .99, 254 participants; P value = 0.02), while the EAL group had 10% better WL adequacy (RR 1.10, CI 1.03-1.18, 573 participants; P value = 0.006). CONCLUSION: We found very low-certainty evidence to support the efficacy of different types of EAL compared to radiography for the outcomes tested. We were unable to reach any conclusions about the superiority of any type of EAL. Well-planned RCTs need to be conducted by standardizing the outcomes and outcome measurement methods

Human AlkB Homolog ABH8 Is a tRNA Methyltransferase Required for Wobble Uridine Modification and DNA Damage Survival

tRNA nucleosides are extensively modified to ensure their proper function in translation. However, many of the enzymes responsible for tRNA modifications in mammals await identification. Here, we show that human AlkB homolog 8 (ABH8) catalyzes tRNA methylation to generate 5-methylcarboxymethyl uridine (mcm[superscript 5]U) at the wobble position of certain tRNAs, a critical anticodon loop modification linked to DNA damage survival. We find that ABH8 interacts specifically with tRNAs containing mcm5U and that purified ABH8 complexes methylate RNA in vitro. Significantly, ABH8 depletion in human cells reduces endogenous levels of mcm[superscript 5]U in RNA and increases cellular sensitivity to DNA-damaging agents. Moreover, DNA-damaging agents induce ABH8 expression in an ATM-dependent manner. These results expand the role of mammalian AlkB proteins beyond that of direct DNA repair and support a regulatory mechanism in the DNA damage response pathway involving modulation of tRNA modification.United States. National Institutes of Health (grant CA055042)United States. National Institutes of Health (grant ES002109)United States. National Institutes of Health (grant ES01701)National Institutes of Health (U.S.). Intramural Research ProgramWestaway Research FundNational Center for Research Resources (U.S.) (grant S10-RR023783

Bacterial etiology of sexually transmitted infections at a STI clinic in Ghana; use of multiplex real time PCR

Background: Most sexually transmitted infection (STI) management efforts focus on the syndromic approach to diagnose and treat patients. However, most women with STIs have been shown to be entirely asymptomatic, or if symptoms exist, are often missed when either clinical or conventional bacteriologic diagnostic tools are employed.Methods: We assessed the performance of a multiplex real time PCR assay to describe other potential pathogens that could be missed by conventional bacteriological techniques in 200 women attending a routine STI clinic in Kumasi, Ghana.Results: Although a total 78.00% of the women were asymptomatic, 77.1% of them tested positive for at least one bacterial STI pathogen. Mycoplasma genitalium was the most commonly detectable pathogen present in 67.5% of all women. Of those testing positive, 25.0% had single infections, while 38.0% and 19.5% had double and triple infections respectively. Altogether, 86.54% and 90.91% of the symptomatic and asymptomatic women respectively tested positive for at least one pathogen (p<0.05). There were no significant associations (p<0.05) between the clinical manifestations of the symptomatic women and the pathogens detected in their samples.Conclusions: Our study confirmed the importance of complementing the syndromic approach to STI management with pathogen detection and most importantly recognise that STIs in women are asymptomatic and regular empirical testing even for both symptomatic and asymptomatic patients is critical for complete clinical treatment.Funding: EOD (Ellis Owusu-Dabo Research working group, KCCR)Keywords: Etiology, Syndromic, Sexually Transmitted Infections, Multiplex real time PC

Feasibility of Surgeon-Delivered Audit and Feedback Incorporating Peer Surgical Coaching to Reduce Fistula Incidence following Cleft Palate Repair: A Pilot Trial

Background: Improving surgeons\u27 technical performance may reduce their frequency of postoperative complications. The authors conducted a pilot trial to evaluate the feasibility of a surgeon-delivered audit and feedback intervention incorporating peer surgical coaching on technical performance among surgeons performing cleft palate repair, in advance of a future effectiveness trial. Methods: A nonrandomized, two-arm, unblinded pilot trial enrolled surgeons performing cleft palate repair. Participants completed a baseline audit of fistula incidence. Participants with a fistula incidence above the median were allocated to an intensive feedback intervention that included selecting a peer surgical coach, observing the coach perform palate repair, reviewing operative video of their own surgical technique with the coach, and proposing and implementing changes in their technique. All others were allocated to simple feedback (receiving audit results). Outcomes assessed were proportion of surgeons completing the baseline audit, disclosing their fistula incidence to peers, and completing the feedback intervention. Results: Seven surgeons enrolled in the trial. All seven completed the baseline audit and disclosed their fistula incidence to other participants. The median baseline fistula incidence was 0.4 percent (range, 0 to 10.5 percent). Two surgeons were unable to receive the feedback intervention. Of the five remaining surgeons, two were allocated to intensive feedback and three to simple feedback. All surgeons completed their assigned feedback intervention. Among surgeons receiving intensive feedback, fistula incidence was 5.9 percent at baseline and 0.0 percent following feedback (adjusted OR, 0.98; 95 percent CI, 0.44 to 2.17). Conclusion: Surgeon-delivered audit and feedback incorporating peer coaching on technical performance was feasible for surgeons