Shepherding DNA ends: Rif1 protects telomeres and chromosome breaks

Cells have evolved conserved mechanisms to protect DNA ends, such as those at the termini of linear chromosomes, or those at DNA double-strand breaks (DSBs). In eukaryotes, DNA ends at chromosomal termini are packaged into proteinaceous structures called telomeres. Telomeres protect chromosome ends from erosion, inadvertent activation of the cellular DNA damage response (DDR), and telomere fusion. In contrast, cells must respond to damage-induced DNA ends at DSBs by harnessing the DDR to restore chromosome integrity, avoiding genome instability and disease. Intriguingly, Rif1 (Rap1-interacting factor 1) has been implicated in telomere homeostasis as well as DSB repair. The protein was first identified in as being part of the proteinaceous telosome. In mammals, RIF1 is not associated with intact telomeres, but was found at chromosome breaks, where RIF1 has emerged as a key mediator of pathway choice between the two evolutionary conserved DSB repair pathways of non-homologous end-joining (NHEJ) and homologous recombination (HR). While this functional dichotomy has long been a puzzle, recent findings link yeast Rif1 not only to telomeres, but also to DSB repair, and mechanistic parallels likely exist. In this review, we will provide an overview of the actions of Rif1 at DNA ends and explore how exclusion of end-processing factors might be the underlying principle allowing Rif1 to fulfill diverse biological roles at telomeres and chromosome breaks

Low resistance n-contact for UVC LEDs by a two-step plasma etching process

The impact of plasma etching on the formation of low-resistance n-contacts on the AlGaN:Si current spreading layer during the chip fabrication of ultraviolet light-emitting diodes (UV LEDs) emitting at 265 nm is investigated. A two-step plasma etching process with a first rapid etching using BCl3/Cl2 gas mixture and a second slow etching step using pure Cl2 gas has been developed. The etching sequence provides smooth mesa side-walls and an n-AlGaN surface with reduced surface damage. Ohmic n-contacts with a contact resistivity of 3.5 10-4 Ωcm2 are obtained on Si-doped Al0.65Ga0.35N layers and the operating voltages of the UVC LEDs were reduced by 2 V for a current of 20 mA. © 2020 The Author(s). Published by IOP Publishing Ltd

Multi-Layer Cyber-Physical Security and Resilience for Smart Grid

The smart grid is a large-scale complex system that integrates communication technologies with the physical layer operation of the energy systems. Security and resilience mechanisms by design are important to provide guarantee operations for the system. This chapter provides a layered perspective of the smart grid security and discusses game and decision theory as a tool to model the interactions among system components and the interaction between attackers and the system. We discuss game-theoretic applications and challenges in the design of cross-layer robust and resilient controller, secure network routing protocol at the data communication and networking layers, and the challenges of the information security at the management layer of the grid. The chapter will discuss the future directions of using game-theoretic tools in addressing multi-layer security issues in the smart grid.Comment: 16 page

Examining the role of menthol cigarettes in progression to established T smoking among youth

Background: Menthol, a flavoring compound added to cigarettes, makes cigarettes more appealing to youth and inexperienced smokers and increases cigarettes\u27 abuse liability. However, limited studies are available on menthol\u27s role in smoking progression. Methods: To assess the association between menthol in cigarettes and progression to established smoking, we used five waves of data from the Evaluation of Public Education Campaign on Teen Tobacco Cohort Study, a nationally representative longitudinal survey of U.S. youth conducted as part of “The Real Cost” evaluation. We used discrete time survival analysis to model the occurrence of two event outcomes—progression to established, current smoking and progression to established, frequent smoking—using a logit model with a menthol use indicator as the key explanatory variable. Based on this framework, we estimated the effect of prior menthol use on the odds of smoking progression. Results: In the progression to established, current smoking model, prior menthol use was significantly associated with progression [adjusted odds ratio (aOR) = 1.80, p \u3c .05, confidence interval (CI) = (1.03–3.16)]. While results were in a similar direction for the model of progression to established, frequent smoking, the association between prior menthol use and this progression model did not reach significance [aOR=1.56, CI = (0.80–3.03)]. Conclusion: The results suggest a relationship between using menthol cigarettes and progression from experi- mental to established, current smoking among youth. This study adds to a growing literature base that supports that menthol cigarettes, compared to nonmenthol cigarettes, put youth at increased risk for regular cigarette use

MGMT gene promoter methylation correlates with tolerance of temozolomide treatment in melanoma but not with clinical outcome

BACKGROUND: Despite limited clinical efficacy, treatment with dacarbazine or temozolomide (TMZ) remains the standard therapy for metastatic melanoma. In glioblastoma, promoter methylation of the counteracting DNA repair enzyme O(6)-methylguanine-DNA-methyltransferase (MGMT) correlates with survival of patients exposed to TMZ in combination with radiotherapy. For melanoma, data are limited and controversial. METHODS: Biopsy samples from 122 patients with metastatic melanoma being treated with TMZ in two multicenter studies of the Dermatologic Cooperative Oncology Group were investigated for MGMT promoter methylation. We used the COBRA (combined bisulphite restriction analysis) technique to determine aberrant methylation of CpG islands in small amounts of genomic DNA isolated from paraffin-embedded tissue sections. To detect aberrant methylation, bisulphite-treated DNA was amplified by PCR, enzyme restricted, and visualised by gel electrophoresis. RESULTS: Correlation with clinical data from 117 evaluable patients in a best-response evaluation indicated no statistically significant association between MGMT promoter methylation status and response. A methylated MGMT promoter was observed in 34.8% of responders and 23.4% of non-responders (P=0.29). In addition, no survival advantage for patients with a methylated MGMT promoter was detectable (P=0.79). Interestingly, we found a significant correlation between MGMT methylation and tolerance of therapy. Patients with a methylated MGMT promoter had more severe adverse events, requiring more TMZ dose reductions or discontinuations (P=0.007; OR 2.7 (95% CI: 1.32-5.7)). Analysis of MGMT promoter methylation comparing primaries and different metastases over the clinical course revealed no statistical difference (P=0.49). CONCLUSIONS: In advanced melanoma MGMT promoter, methylation correlates with tolerance of therapy, but not with clinical outcome

Label-free electrochemical monitoring of DNA ligase activity

This study presents a simple, label-free electrochemical technique for the monitoring of DNA ligase activity. DNA ligases are enzymes that catalyze joining of breaks in the backbone of DNA and are of significant scientific interest due to their essential nature in DNA metabolism and their importance to a range of molecular biological methodologies. The electrochemical behavior of DNA at mercury and some amalgam electrodes is strongly influenced by its backbone structure, allowing a perfect discrimination between DNA molecules containing or lacking free ends. This variation in electrochemical behavior has been utilized previously for a sensitive detection of DNA damage involving the sugar-phosphate backbone breakage. Here we show that the same principle can be utilized for monitoring of a reverse process, i.e., the repair of strand breaks by action of the DNA ligases. We demonstrate applications of the electrochemical technique for a distinction between ligatable and unligatable breaks in plasmid DNA using T4 DNA ligase, as well as for studies of the DNA backbone-joining activity in recombinant fragments of E. coli DNA ligase

Low resistance n-contact for UVC LEDs by a two-step plasma etching process

The impact of plasma etching on the formation of low-resistance n-contacts on the AlGaN:Si current spreading layer during the chip fabrication of ultraviolet light-emitting diodes (UV LEDs) emitting at 265 nm is investigated. A two-step plasma etching process with a first rapid etching using BCl3/Cl2 gas mixture and a second slow etching step using pure Cl2 gas has been developed. The etching sequence provides smooth mesa side-walls and an n-AlGaN surface with reduced surface damage. Ohmic n-contacts with a contact resistivity of 3.5 × 10−4 Ωcm2 are obtained on Si-doped Al0.65Ga0.35N layers and the operating voltages of the UVC LEDs were reduced by 2 V for a current of 20 mA.BMBF, 03ZZ0134B, Zwanzig20 - Advanced UV for Life - Verbundvorhaben: UV Power; TP2: Entwicklung von high-power UVB-LEDs um 300 nmBMBF, 03ZZ0134C, Zwanzig20 - Advanced UV for Life - Verbundvorhaben: UV Power; TP3: Epitaxieentwicklung für high-power UVC-LEDs um 260 n

Beyond solid-state lighting: Miniaturization, hybrid integration, and applications og GaN nano- and micro-LEDs

Gallium Nitride (GaN) light-emitting-diode (LED) technology has been the revolution in modern lighting. In the last decade, a huge global market of efficient, long-lasting and ubiquitous white light sources has developed around the inception of the Nobel-price-winning blue GaN LEDs. Today GaN optoelectronics is developing beyond lighting, leading to new and innovative devices, e.g. for micro-displays, being the core technology for future augmented reality and visualization, as well as point light sources for optical excitation in communications, imaging, and sensing. This explosion of applications is driven by two main directions: the ability to produce very small GaN LEDs (microLEDs and nanoLEDs) with high efficiency and across large areas, in combination with the possibility to merge optoelectronic-grade GaN microLEDs with silicon microelectronics in a fully hybrid approach. GaN LED technology today is even spreading into the realm of display technology, which has been occupied by organic LED (OLED) and liquid crystal display (LCD) for decades. In this review, the technological transition towards GaN micro- and nanodevices beyond lighting is discussed including an up-to-date overview on the state of the art

Evaluation of the long-term efficacy and safety of an imidacloprid 10%/flumethrin 4.5% polymer matrix collar (Seresto®) in dogs and cats naturally infested with fleas and/or ticks in multicentre clinical field studies in Europe

<p>Abstract</p> <p>Background</p> <p>The objective of these two GCP multicentre European clinical field studies was to evaluate the long-term efficacy and safety of a new imidacloprid/flumethrin collar (Seresto^®, Bayer AnimalHealth, Investigational Veterinary Product(IVP)) in dogs and cats naturally infested with fleas and/or ticks in comparison to a dimpylat collar ("Ungezieferband fuer Hunde/fuer Katzen", Beaphar, Control Product (CP)).</p> <p>Methods</p> <p>232 (IVP) and 81 (CP) cats and 271(IVP) and 129 (CP) dogs were treated with either product according to label claims and formed the safety population. Flea and tick counts were conducted in monthly intervals for up to 8 months in the efficacy subpopulation consisting of 118 (IVP) + 47 (CP) cats and 197 (IVP) + 94 (CP) dogs. Efficacy was calculated as reduction of infestation rate within the same treatment group and statistically compared between the two treatment groups.</p> <p>Results</p> <p>Preventive efficacy against fleas in cats/dogs varied in the IVP group between 97.4%/94.1% and 100%/100% (overall mean: 98.3%/96.7%) throughout the 8 month period and in the CP group between 57.1%/28.2% and 96.1%/67.8% (overall mean: 79.3%/57.9%). Preventive efficacy against ticks in cats/dogs varied in the IVP group between 94.0%/91.2% and 100%/100% (overall mean: 98.4%/94.7%) throughout the 8 month period and in the CP group between 90.7%/79.9% and 100%/88.0% (overall mean: 96.9%/85.6%). The IVP group was statistically non-inferior to the CP group, and on various assessment days, statistical superiority was proven for flea and tick count reduction in dogs and cats. Both treatments proved to be safe in dogs and cats with mainly minor local observations at the application site. There was moreover, no incidence of any mechanical problem with the collar in dogs and cats during the entire study period.</p> <p>Conclusions</p> <p>The imidacloprid/flumethrin collar proved to reduce tick counts by at least 90% and flea counts by at least 95% for a period of at least 7-8 months in cats and dogs under field conditions. Therefore, it can be used as sustainable long-term preventative, covering the whole flea and tick season.</p

Historical perspectives on pastoralism and land tenure transformation in Ngamiland, Botswana: What are the policy and institutional lessons?

Pastoral societies in dryland Africa continue to face changes to their pastoral systems. These systems are influenced by a range of historical factors but little use is made of this information to design policies that suit pastoralists’ landscapes. This article provides a synthesis of historical perspectives on pastoral land use and tenure transformations in Ngamiland, south of the Okavango Delta, Botswana. Little documentation of herders’ historical perspectives exists and less is known about how past experiences can be applied to sustainable pastoralism policies. In this article, current land use pressing issues are examined and analysed within the context of past experiences. We use a series of oral histories with key informants, focus group discussions, expert interviews and rangelands field observations. Ngamiland historical perspectives depict a pastoral landscape that has been shaped by a variety of factors; livestock diseases, Human-wildlife-conflicts, droughts, land tenure transformations associated with rangeland policies and the pastoral identity of the Ovaherero/Ovambanderu ethnic groups. Pastoralists have followed unique trajectories, specific to their rangeland conditions and socio-cultural context. Resilience to climate shocks and diseases has been weakened by inequitable patterns of control over rangeland resources. We recommend institutional diversity such that from experiences of the past, lessons can be drawn of the sort of processes and institutions required for pastoralism policies including targeted pastoralists’ adaptations. Using pastoralists to provide information, especially in the area of indigenous knowledge, strategies can be developed to link conservation of wildlife and rangelands with pastoral production by developing ecologically-sensitive low-volume tourism that pastoral communities can tap in to diversify their livelihoods