OBJECTIVE: Following previous clinical trials, an antiaging product (Restorative Skin complex [RSC]; Alastin Skin Care Carlsbad, a Galderma company), was investigated for its effects on Klotho gene regulation, telomere length, and histological biopsy changes to provide a comprehensive picture of the mechanism and efficacy of its anti-aging effect. METHODS: Neonatal human fibroblasts were used for telomere length studies to examine the effect of the full RSC formulation and the amino acid components Tripeptide-1 and Hexapeptide-12 (TriHex™) on these cellular aging mechanisms. In addition, RNA sequencing was conducted using human keratinocytes specifically investigating Klotho and related genes. This was supplemented by a clinical study using biopsy samples. RESULTS: TriHex™ significantly upregulated the Klotho gene and related FGF23, FGFR1 and FOXO3B anti-aging genes. Significant telomere shortening reduction over control was demonstrated with the RSC formulation at four weeks and with TriHex™ at six weeks for all percentiles tested. Previous clinical studies demonstrated that the use of the antiaging regimen for 12 weeks produced a statistically significant improvement in scores for all evaluated parameters. Restaining of previous biopsy blocks from the clinical trial revealed positive ECM changes, stimulation of collagen, fibrillin, CD44 and elastin. LIMITATIONS: The study was limited by a relatively small numbers of patients in the clinical trial and the non-competitive nature of the trial. CONCLUSION: RSC anti-aging formulation and its TriHex™ components demonstrated significant reduction in telomere shortening, upregulation of Klotho and FOXO3 genes and biopsy validation of antiaging efficacy. This new science supplements previous trials that demonstrated clinical efficacy of the formulation

Light-induced states in He atoms were characterized using attosecond transient absorption spectroscopy. A 400 as pulse covering the 20-24 eV spectral range serves as the probe pulse, and the effect of a few-cycle near infrared pulse (12 fs, 780 nm) on the absorption spectrum is measured as a function of time delay and near-infrared intensities varying from (5.0 ± 2) × 1010 to (1 ± 0.4) × 1013 W/cm2. Light-induced states resulting from near-infrared coupling of 1s2p to 1s2s, 1s3d, and 1s3s states are observed. Absorption features that likely result from coupling of 1s3p to 1s4s, 1s4d, 1s5s, and 1s5d states are also observed. The light-induced states with the smallest detunings (1s3d and 1s3s) from the dressing frequency may shift to higher frequencies as the dressing intensity is increased. © 2013, Taylor & Francis.

The development of attosecond technology is one of the most significant recent achievements in the field of ultrafast optics; it opens up new frontiers in atomic and molecular spectroscopy and dynamics. A unique attosecond pumpprobe apparatus using a compact Mach-Zehnder interferometer is developed. The interferometer system is compact (∼290 cm²) and completely located outside of the vacuum chamber. The location reduces the mechanical vibration from vacuum components such as turbopumps and roughing pumps. The stability of the interferometer is ∼50 as RMS over 24 hours, stabilized with an active feedback loop. The pump and probe fields can be easily altered to incorporate multiple colors. In the interferometer, double optical gating optics are arranged to generate isolated attosecond pulses with a supercontinuum spectrum. The frequencies of the attosecond pulses can be selected to be in the extreme ultraviolet (XUV) region (25–55 eV, 140 as) or the vacuum ultraviolet (VUV) region (15–24 eV, ∼400 as) by metal filters. Furthermore, the near infrared probe field (1.65 eV) can be upconverted to the ultraviolet (3.1 eV). The frequency tunability in the XUV and VUV is critical for selecting excited states of target atoms and molecules.

Recording the transmitted spectrum of a weak attosecond pulse through a medium, while a strong femtosecond pulse copropagates at variable delay, probes the strong-field dynamics of atoms, molecules, and solids. Usually, the interpretation of these measurements is based on the assumption of a thin medium. Here, the propagation through a macroscopic medium of helium atoms in the region of fully allowed resonances is investigated both theoretically and experimentally. The propagation has dramatic effects on the transient spectrum even at relatively low pressures (50 mbar) and short propagation lengths (1 mm). The absorption does not evolve monotonically with the product of propagation distance and pressure, but regions with characteristics of Lorentz line shapes and characteristics of Fano line shapes alternate. Criteria are deduced to estimate whether macroscopic effects can be neglected or not in a transient absorption experiment. Furthermore, the theory in the limit of single-atom response yields a general equation for Lorentz- and Fano-type line shapes at variable pulse delay. © 2013 American Physical Society.

The decay of highly excited states of xenon after absorption of extreme ultraviolet light is directly tracked via attosecond transient absorption spectroscopy using a time-delayed near-infrared perturbing pulse. The lifetimes of the autoionizing 5s5p66p and 5s5p67p channels are determined to be (21.9 ± 1.3) fs and (48.4 ± 5.0) fs, respectively. The observed values support lifetime estimates obtained by traditional linewidth measurements. The experiment additionally obtains the temporal evolution of the decay as a function of energy detuning from the resonance center, and a quantum mechanical formalism is introduced that correctly accounts for the observed energy dependence. © 2014 American Physical Society.

Introduction

MicroRNAs (miRNAs) are small noncoding RNA molecules that exert post-transcriptional effects on gene expression by binding with cis-regulatory regions in target messenger RNA (mRNA). Polymorphisms in genes encoding miRNAs or in miRNA-mRNA binding sites confer deleterious epigenetic effects on cancer risk. miR-146a has a role in inflammation and may have a role as a tumour suppressor. The polymorphism rs2910164 in the MIR146A gene encoding pre-miR-146a has been implicated in several inflammatory pathologies, including cancers of the breast and thyroid, although evidence for the associations has been conflicting in different populations. We aimed to further investigate the association of this variant with these two cancers in an Irish cohort.

Methods

The study group comprised patients with breast cancer (BC), patients with differentiated thyroid cancer (DTC) and unaffected controls. Germline DNA was extracted from blood or from saliva collected using the DNA Genotek Oragene 575 collection kit, using crystallisation precipitation, and genotyped using TaqMan-based PCR. Data were analysed using SPSS, v22.

Results

The total study group included 1516 participants. This comprised 1386 Irish participants; 724 unaffected individuals (controls), 523 patients with breast cancer (BC), 136 patients with differentiated thyroid cancer (DTC) and three patients with dual primary breast and thyroid cancer. An additional cohort of 130 patients with DTC from the South of France was also genotyped for the variant. The variant was detected with a minor allele frequency (MAF) of 0.19 in controls, 0.22 in BC and 0.27 and 0.26 in DTC cases from Ireland and France, respectively. The variant was not significantly associated with BC (per allele odds ratio = 1.20 (0.98-1.46), P  = 0.07), but was associated with DTC in Irish patients (per allele OR = 1.59 (1.18-2.14), P = 0.002).

Conclusion

The rs2910164 variant in MIR146A is significantly associated with DTC, but is not significantly associated with BC in this cohort.

Attosecond transient absorption spectra near the energies of autoionizing states are analyzed in terms of the photon coupling mechanisms to other states. In a recent experiment, the autoionization lifetimes of highly excited states of xenon were determined and compared to a simple expression based on a model of how quantum coherence determines the decay of a metastable state in the transient absorption spectrum. Here it is shown that this procedure for extracting lifetimes is more general and can be used in cases involving either resonant or nonresonant coupling of the attosecond-probed autoionizing state to either continua or discrete states by a time-delayed near infrared (NIR) pulse. The fits of theoretically simulated absorption signals for the 6p resonance in xenon (lifetime = 21.1 fs) to this expression yield the correct decay constant for all the coupling mechanisms considered, properly recovering the time signature of twice the autoionization lifetime due to the coherent nature of the transient absorption experiment. To distinguish between these two coupling cases, the characteristic dependencies of the transient absorption signals on both the photon energy and time delay are investigated. Additional oscillations versus delay-time in the measured spectrum are shown and quantum beat analysis is used to pinpoint the major photon-coupling mechanism induced by the NIR pulse in the current xenon experiment: the NIR pulse resonantly couples the attosecond-probed state, 6p, to an intermediate 8s (at 22.563 eV), and this 8s state is also coupled to a neighboring state (at 20.808 eV).

This Report summarizes the proceedings of the 2015 Les Houches workshop on Physics at TeV Colliders. Session 1 dealt with (I) new developments relevant for high precision Standard Model calculations, (II) the new PDF4LHC parton distributions, (III) issues in the theoretical description of the production of Standard Model Higgs bosons and how to relate experimental measurements, (IV) a host of phenomenological studies essential for comparing LHC data from Run I with theoretical predictions and projections for future measurements in Run II, and (V) new developments in Monte Carlo event generators.

A review of TFTR plasma transport studies is presented. Parallel transport and the confinement of suprathermal ions are found to be relatively well described by theory. Cross-field transport of the thermal plasma, however, is anomalous with the momentum diffusivity being comparable to the ion thermal diffusivity and larger than the electron thermal diffusivity in neutral beam heated discharges. Perturbative experiments have studied nonlinear dependencies in the transport coefficients and examined the role of possible nonlocal phenomena. The underlying turbulence has been studied using microwave scattering, beam emission spectroscopy and microwave reflectometry over a much broader range in k perpendicular to than previously possible. Results indicate the existence of large-wavelength fluctuations correlated with enhanced transport.