Pathway choice in DNA double strand break repair: Observations of a balancing act

Proper repair of DNA double strand breaks (DSBs) is vital for the preservation of genomic integrity. There are two main pathways that repair DSBs, Homologous recombination (HR) and Non-homologous end-joining (NHEJ). HR is restricted to the S and G2 phases of the cell cycle due to the requirement for the sister chromatid as a template, while NHEJ is active throughout the cell cycle and does not rely on a template. The balance between both pathways is essential for genome stability and numerous assays have been developed to measure the efficiency of the two pathways. Several proteins are known to affect the balance between HR and NHEJ and the complexity of the break also plays a role. In this review we describe several repair assays to determine the efficiencies of both pathways. We discuss how disturbance of the balance between HR and NHEJ can lead to disease, but also how it can be exploited for cancer treatment

Finite Temperature QCD with Two Flavors of Non-perturbatively Improved Wilson Fermions

We study QCD with two flavors of non-perturbatively improved Wilson fermions at finite temperature on the $16^3 8$ lattice. We determine the transition temperature at lattice spacings as small as $a \sim 0.12$ fm, and study string breaking below the finite temperature transition. We find that the static potential can be fitted by a two-state ansatz, including a string state and a two-meson state. We investigate the role of Abelian monopoles at finite temperature.Comment: 29 pages, 22 figures, Late

Towards quantum superpositions of a mirror

We propose a scheme for creating quantum superposition states involving of order $10^{14}$ atoms via the interaction of a single photon with a tiny mirror. This mirror, mounted on a high-quality mechanical oscillator, is part of a high-finesse optical cavity which forms one arm of a Michelson interferometer. By observing the interference of the photon only, one can study the creation and decoherence of superpositions involving the mirror. All experimental requirements appear to be within reach of current technology.Comment: 5 pages, 2 figures, submitted to Phys. Rev. Let

INDIVIDUAL EDUCATIONAL PATHWAY AS THE MAIN INSTRUMENT OF EDUCATION IN INFORMATION SOCIETY

The article is devoted to "customization" of educational process at the expense of possibility of creation by the trainee of personal educational pathways if he can tell: "I know, what I don't know". Such understanding of educational process smoothly enters the concept of information society and opens new opportunities for universities in the future

Positive Organisational Psychology 2.0: Embracing The Technological Revolution

Positive Organisational Psychology (POP) has experienced significant growth in the past two decades, contributing to our understanding of work-related well-being and performance. However, the discipline is now on the cusp of a new wave of research and innovation that may reshape its discourse. This paper introduces the concept of ‘Positive Organisational Psychology 2.0’ (POP 2.0) as an evidence-based, data-driven field that utilizes technological advancements and human-centred design to understand and enhance positive characteristics of individuals, organisations, and society for optimal psychological functioning, wellbeing, and performance. The paper begins with an overview of POP’s emergence, highlighting its key characteristics and exploring the factors behind its rapid growth and declining relevance. We then conceptualize POP 2.0, outline its defining features, and advocate for a broader scope, expanded focal audience, enhanced methodologies, and transformative role shifts for practitioners. We conclude by outlining opportunities, challenges and perspectives for the next wave of innovative research

Observation of three-photon Greenberger-Horne-Zeilinger entanglement

We present the experimental observation of polarization entanglement for three spatially separated photons. Such states of more than two entangled particles, known as GHZ states, play a crucial role in fundamental tests of quantum mechanics versus local realism and in many quantum information and quantum computation schemes. Our experimental arrangement is such that we start with two pairs of entangled photons and register one photon in a way that any information as to which pair it belongs to is erased. The registered events at the detectors for the remaining three photons then exhibit the desired GHZ correlations.Comment: Revtex, 4 pages, uses floats, epsfi

Serum antimüllerian hormone levels best reflect the reproductive decline with age in normal women with proven fertility: A longitudinal study

Objective: The aim of this study was to assess which of the basal ovarian reserve markers provides the best reflection of the changes occurring in ovarian function over time (i.e., reproductive aging). Design: Prospective longitudinal study. Setting: Healthy volunteers in an academic research center. Patient(s): Eighty-one women with normal reproductive performance during the course of their lives were longitudinally assessed. In this select group of women, becoming chronologically older was considered as a proxy variable for becoming older from a reproductive point of view. Intervention(s): The women were assessed twice, with on average a 4-year interval (T 1 and T 2). The number of antral follicles on ultrasound (AFC) and blood levels of antimüllerian hormone (AMH), FSH, inhibin B, and E 2 were assessed. Main Outcome Measure(s): Longitudinal changes of the markers mentioned and the consistency of these parameters over time. Result(s): The mean ages at T 1 and T 2 were 39.6 and 43.6 years, respectively. Although AFC was strongly associated with age in a cross-sectional fashion, it did not change over time. The AMH, FSH, and inhibin B levels showed a significant change over time, in contrast to E 2 levels. The AMH and AFC were highly correlated with age both at T 1 and T 2, whereas FSH and inhibin B predominantly changed in women more than 40 years of age. To assess the consistency of these parameters over time, we investigated whether a woman's individual level above or below the mean of her age group at T 1 remained above or below the mean of her age group at T 2. Serum AMH concentrations showed the best consistency, with AFC as second best. The FSH and inhibin B showed only modest consistency, whereas E 2 showed no consistency at all. Conclusion(s): These results indicate that serum AMH represents the best endocrine marker to assess the age-related decline of reproductive capacity

Comparison of high-and low-let radiation-induced dna double-strand break processing in living cells

High-linear-energy-transfer (LET) radiation is more lethal than similar doses of low-LET radiation types, probably a result of the condensed energy deposition pattern of high-LET radiation. Here, we compare high-LET α-particle to low-LET X-ray irradiation and monitor double-strand break (DSB) processing. Live-cell microscopy was used to monitor DNA double-strand breaks (DSBs), marked by p53-binding protein 1 (53BP1). In addition, the accumulation of the endogenous 53BP1 and replication protein A (RPA) DSB processing proteins was analyzed by immunofluorescence. In contrast to α-particle-induced 53BP1 foci, X-ray-induced foci were resolved quickly and more dynamically as they showed an increase in 53BP1 protein accumulation and size. In addition, the number of individual 53BP1 and RPA foci was higher after X-ray irradiation, while focus intensity was higher after α-particle irradiation. Interestingly, 53BP1 foci induced by α-particles contained multiple RPA foci, suggesting multiple individual resection events, which was not observed after X-ray irradiation. We conclude that high-LET α-particles cause closely interspaced DSBs leading to high local concentrations of repair proteins. Our results point toward a change in DNA damage processing toward DNA end-resection and homologous recombination, possibly due to the depletion of soluble protein in the nucleoplasm. The combination of closely interspaced DSBs and perturbed DNA damage processing could be an explanation for the increased relative biological effectiveness (RBE) of high-LET α-particles compared to X-ray irradiation