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

Tubularized Bladder Flap as a Continent Catheterizable Channel in Adults

OBJECTIVE: To describe a modified, less invasive, surgical technique to create a continent catheterizable channel (CCC) in adults: the tubularized bladder flap (TBF). MATERIALS AND METHODS: We retrospectively reviewed records of patients in whom a TBF CCC was constructed at adult age between 2019 and 2023. We reported on demographics, operative outcomes, and 30-day and post-30-day complications. RESULTS: A total of 11 patients (10 female) were described. The median operative time was 96 (range 90-115) minutes in patients with only TBF creation. Estimated blood loss was <100 cc in all patients. Within 30 days postoperatively, 6/11 (55%) patients developed a complication, all grade 1 Clavien Dindo. No bowel complications occurred (paralytic ileus, mechanical obstruction, or leakage/perforation). Median follow-up was 25 (range 6-56) months. In 2/11 (18%) patients surgical revision for stenosis was done; 3/11 (27%) patients underwent surgical revision for stomal leakage. CONCLUSION: TBF as a means to create a CCC avoids intraperitoneal surgery, and bowel closure (appendicovesicostomy) or anastomosis (retubularized ileum). Postoperative bowel complications were not seen in any of our patients. Surgical revision rates for a TBF CCC appear to be comparable to other CCCs. Therefore, TBF could be considered in patients with sufficient bladder capacity as TBF is less invasive than other CCC techniques and avoids potential bowel complications

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

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