Quantum beat photoelectron imaging spectroscopy of Xe in the VUV

Time resolved pump probe measurements of Xe, pumped at 133 nm and probed at 266 nm, are presented. The pump pulse prepared a long lived hyperfine wave packet in the Xe 5p5 2P amp; 8728;1 2 6s2[1 2] amp; 8728;1 manifold E 77185cm amp; 8722;1 9.57eV . The wave packet was monitored via single photon ionization and velocity map photoelectron images were measured. The images provide angle and time resolved data which, when obtained over a large time window 900 ps , constitute a precision quantum beat spectroscopy measurement of the hyperfine state splittings. Additionally, analysis of the full photoelectron image stack provides a quantum beat imaging modality, in which the Fourier components of the photoelectron images correlated with specific beat components can be obtained. This may also permit the extraction of isotope resolved photoelectron images in the frequency domain, in cases where nuclear spins hence beat components can be uniquely assigned to specific isotopes as herein , and also provides phase information relating to the ionization dynamics. The information content of both raw and inverted image stacks is investigated, suggesting the utility of the Fourier analysis methodology in cases where images cannot be inverte

Thirty Years After Michael E. Porter: What Do We Know About Business Exit?

Although a business exit is an important corporate change initiative, the buyer’s side seems to be more appealing to management researchers than the seller’s because acquisitions imply growth, i.e., success. Yet from an optimistic viewpoint, business exit can effectively create value for the selling company. In this paper we attempt to bring the relevance of the seller’s side back into our consciousness by asking: What do we know about business exit? We start our exploration with Porter (1976), focusing on literature that investigates the antecedents of, barriers to, and outcomes of business exit. We also include studies from related fields such as finance and economics.1 Through this research we determine three clusters of findings: factors promoting business exit, exit barriers, and exit outcomes. Overall, it is the intention of this paper to highlight the importance of business exit for research and practice. Knowing what we know about business exits and their high financial value we should bear in mind that exit need not mean failure but a new beginning for a corporation

Four “Lessons Learned” While Implementing a Multi-Site Caries Prevention Trial

As the number of dental-related randomized clinical trials (RCTs) increases, there is a need for literature to help investigators inexperienced in conducting RCTs design and implement studies. This commentary describes four “lessons learned,” or considerations important in the planning and initial implementation of RCTs in dentistry that to our knowledge have not been discussed in the general dental literature describing trial techniques. These considerations are 1) preparing or securing a thorough systematic review, 2) developing a comprehensive set of study documents, 3) designing and testing multiple recruitment strategies, and 4) employing a run-in period prior to enrollment. Attention to these considerations in the planning phases of a dental RCT can help ensure that the trial is clinically relevant while also maximizing the likelihood that its implementation will be successful

PREP1 tumor suppressor protects the late-replicating DNA by controlling its replication timing and symmetry

The synthesis of middle-to-late-replicating DNA can be affected independently of the rest of the genome by down-regulating the tumor suppressor PREP1 (PKNOX1). Indeed, DNA combing shows that PREP1 down-regulation affects DNA replication rate, increases the number of simultaneously firing origins and the asymmetry of DNA replication, leading to DNA damage. Genome-wide analysis of replication timing by Repli-seq shows that, upon PREP1 down-regulation, 25% of the genome is replicated earlier in the S-phase. The targeted DNA sequences correspond to Lamin-Associated Domains (LADs), and include late-replicating (LRRs) and temporal transition regions (TTRs). Notably, the distribution of PREP1 DNA binding sites and of its target genes indicates that DNA replication defects are independent of the overall PREP1 transcriptional activity. Finally, PREP1 down-regulation causes a substantial decrease in Lamin B1 levels. This suggests that DNA is released from the nuclear lamina earlier than in the control cells and is available for replication, thus explaining timing defects and DNA damage.This is the first evidence that the replication timing of a specific fraction of the human genome is affected by PREP1 tumor suppressor. This previously unknown function might significantly contribute to the genomic instability observed in human tumors

Results from the Xylitol for Adult Caries Trial (X-ACT)

Although caries is prevalent in adults, few preventive therapies have been tested in adult populations. This randomized clinical trial evaluated the effectiveness of xylitol lozenges in preventing caries in elevated caries-risk adults

PI3K inhibition results in enhanced HER signaling and acquired ERK dependency in HER2-overexpressing breast cancer

There is a strong rationale to therapeutically target the phosphatidylinositol 3-kinase/protein kinase B/mammalian target of rapamycin (PI3K/AKT/mTOR) pathway in breast cancer since it is highly deregulated in this disease and it also mediates resistance to anti-HER2 therapies. However, initial studies with rapalogs, allosteric inhibitors of mTORC1, have resulted in limited clinical efficacy probably due to the release of a negative regulatory feedback loop that triggers AKT and ERK signaling. Since activation of AKT occurs via PI3K, we decided to explore whether PI3K inhibitors prevent the activation of these compensatory pathways. Using HER2-overexpressing breast cancer cells as a model, we observed that PI3K inhibitors abolished AKT activation. However, PI3K inhibition resulted in a compensatory activation of the ERK signaling pathway. This enhanced ERK signaling occurred as a result of activation of HER family receptors as evidenced by induction of HER receptors dimerization and phosphorylation, increased expression of HER3 and binding of adaptor molecules to HER2 and HER3. The activation of ERK was prevented with either MEK inhibitors or anti-HER2 monoclonal antibodies and tyrosine kinase inhibitors. Combined administration of PI3K inhibitors with either HER2 or MEK inhibitors resulted in decreased proliferation, enhanced cell death and superior anti-tumor activity compared with single agent PI3K inhibitors. Our findings indicate that PI3K inhibition in HER2-overexpressing breast cancer activates a new compensatory pathway that results in ERK dependency. Combined anti-MEK or anti-HER2 therapy with PI3K inhibitors may be required in order to achieve optimal efficacy in HER2-overexpressing breast cancer. This approach warrants clinical evaluation