Design of an Efficient Pumping Scheme for Mid-IR Dy3+:Ga5Ge20Sb10S65 PCF Fiber Laser

This letter illustrates the design of a novel medium infrared (Mid-IR) laser based on a photonic crystal fiber made of dysprosium-doped chalcogenide glass, Dy3+:Ga5Ge20Sb10S65. In order to perform a realistic investigation, the simulation is performed by taking into account the spectroscopic parameters measured on the rare earth-doped glass sample. The simulated results show that an optical beam emission close to 4400-nm wavelength can be obtained by employing two pump beams at 2850 nm (pump #1) and 4092 nm (pump #2) wavelengths. The pump beams can be provided by commercial quantum cascade lasers. As example, for the pump powers of 50 mW (pump #1) and 1 W (pump #2), the input mirror reflectivity of 99%, the output mirror reflectivity of 30%, and the optical cavity length of 50 cm, a signal power close to 350 mW at the wavelength of 4384 nm can be generated. This result indicates that the designed source configuration is feasible for high beam quality Mid-IR light generation and it is efficient enough to find applications in optical free propagation links, optical remote sensing, and medicine

Dysprosium-doped chalcogenide Master Oscillator Power Amplifier (MOPA) for Mid-IR emission

The paper describes the design of a medium infrared fiber laser based on a dysprosium-doped chalcogenide glass Dy3+: Ga5Ge20Sb10S65. To obtain a high efficiency, the fiber laser is followed by an optical amplifier. The optimized optical source exploits a master oscillator power amplifier (MOPA) configuration. The MOPA pump and signal wavelengths are 1709 and 4384 nm, respectively. Spectroscopic parameters measured on preliminary samples of chalcogenide glasses are taken into account to fulfill realistic simulations. The MOPA emission is maximized by applying a particle swarm optimization approach. For the dysprosium concentration 6, ×, 1025 ions/m3 and the input pump power of 3 W, an output power of 637 mW can be obtained for optical fiber losses close to 1 dB m-1. The optimized MOPA configuration allows a laser efficiency larger than 21%. By considering the high beam quality provided by photonic crystal fibers, it is a good candidate for medium infrared light generation whose main applications include, but are not limited to, molecular spectroscopy and environmental monitoring

In vitro and in silico characterization of an antimalarial compound with antitumor activity targeting human DNA topoisomerase IB

Human DNA topoisomerase IB controls the topological state of supercoiled DNA through a complex catalytic cycle that consists of cleavage and religation reactions, allowing the progression of fundamental DNA metabolism. The catalytic steps of human DNA topoisomerase IB were analyzed in the presence of a drug, obtained by the open-access drug bank Medicines for Malaria Venture. The experiments indicate that the compound strongly and irreversibly inhibits the cleavage step of the enzyme reaction and reduces the cell viability of three different cancer cell lines. Molecular docking and molecular dynamics simulations suggest that the drug binds to the human DNA topoisomerase IB-DNA complex sitting inside the catalytic site of the enzyme, providing a molecular explanation for the cleavage-inhibition effect. For all these reasons, the aforementioned drug could be a possible lead compound for the development of an efficient anti-tumor molecule targeting human DNA topoisomerase IB

Generation of three iPSC lines from fibroblasts of a patient with Aicardi Goutières Syndrome mutated in TREX1

Fibroblasts from a patient with Aicardi Gouti\ue8res Syndrome (AGS) carrying a compound heterozygous mutation in TREX1, were reprogrammed into induced pluripotent stem cells (iPSCs) to establish isogenic clonal stem cell lines: UNIBSi006-A, UNIBSi006-B, and UNIBSi006-C. Cells were transduced using the episomal Sendai viral vectors, containing human OCT4, SOX2, c-MYC and KLF4 transcription factors. The transgene-free iPSC lines showed normal karyotype, expressed pluripotent markers and displayed in vitro differentiation potential toward cells of the three embryonic germ layers

Real-time detection of TDP1 activity using a fluorophore-quencher coupled DNA-biosensor

Real-time detection of enzyme activities may present the easiest and most reliable way of obtaining quantitative analyses in biological samples. We present a new DNA-biosensor capable of detecting the activity of the potential anticancer drug target tyrosyl-DNA phosphodiesterase 1 (TDP1) in a very simple, high throughput, and real-time format. The biosensor is specific for Tdp1 even in complex biological samples, such as human cell extracts, and may consequently find future use in fundamental studies as well as a cancer predictive tool allowing fast analyses of diagnostic cell samples such as biopsies. TDP1 removes covalent 3'DNA adducts in DNA single-strand break repair. This enzymatic activity forms the basis of the design of the TDP1-biosensor, which consists of a short hairpin-forming oligonucleotide having a 5'fluorophore and a 3'quencher brought in close proximity by the secondary structure of the biosensor. The specific action of TDP1 removes the quencher, thereby enabling optical detection of the fluorophore. Since the enzymatic action of TDP1 is the only "signal amplification" the increase in fluorescence may easily be followed in real-time and allows quantitative analyses of TDP1 activity in pure enzyme fractions as well as in crude cell extracts. In the present study we demonstrate the specificity of the biosensor, its ability to quantitatively detect up- or down-regulated TDP1 activity, and that it may be used for measuring and for analyzing the mechanism of TDP1 inhibition

The impact of capital structure on the decision to outsource with long term contracts

This paper analyzes how capital structure affects the firms’ strategic choice between outsourcing with long term contracts and outsourcing to the spot market. When outsourcing to the spot market firms are exposed to price uncertainty, whereas a long term contract allows them to set in advance the outsourcing price. We show that, to the extent that leverage and uncertainty can lead to financial distress costs in bad states of nature, firms may use long term contracts as a risk management device to hedge input price uncertainty.N/

Optimisation of the Schizosaccharomyces pombe urg1 expression system

The ability to study protein function in vivo often relies on systems that regulate the presence and absence of the protein of interest. Two limitations for previously described transcriptional control systems that are used to regulate protein expression in fission yeast are: the time taken for inducing conditions to initiate transcription and the ability to achieve very low basal transcription in the "OFF-state". In previous work, we described a Cre recombination-mediated system that allows the rapid and efficient regulation of any gene of interest by the urg1 promoter, which has a dynamic range of approximately 75-fold and which is induced within 30-60 minutes of uracil addition. In this report we describe easy-to-use and versatile modules that can be exploited to significantly tune down P urg1 "OFF-levels" while maintaining an equivalent dynamic range. We also provide plasmids and tools for combining P urg1 transcriptional control with the auxin degron tag to help maintain a null-like phenotype. We demonstrate the utility of this system by improved regulation of HO-dependent site-specific DSB formation, by the regulation Rtf1-dependent replication fork arrest and by controlling Rhp18(Rad18)-dependent post replication repair

Developing Core Outcome Sets (COS) and Core Outcome Measures Sets (COMS) in Cosmetic Gynecological Interventions: Protocol for a Development and Usability Study.

BACKGROUND: Studies evaluating cosmetic gynecological interventions have followed variable methodology and reported a diversity of outcomes. Such variations limit the comparability of studies and the value of research-based evidence. The development of core outcome sets (COS) and core outcome measures sets (COMS) would help address these issues, ensuring a minimum of outcomes important to all stakeholders, primarily women requesting or having experienced cosmetic gynecological interventions. OBJECTIVE: This protocol describes the methods used in developing a COS and COMS for cosmetic gynecological interventions. METHODS: An international steering group within CHORUS, including health care professionals, researchers, and women with experience in cosmetic gynecological interventions from 4 continents, will guide the development of COS and COMS. Potential outcome measures and outcomes will be identified through comprehensive literature reviews. These potential COS and COMS will be entered into an international, multi-perspective web-based Delphi survey where Delphi participants judge which domains will be core. A priori thresholds for consensus will get established before each Delphi round. The Delphi survey results will be evaluated quantitatively and qualitatively in subsequent stakeholder group consensus meetings in the process of establishing "core" outcomes. RESULTS: Dissemination and implementation of the resulting COS and COMS within an international context will be promoted and reviewed. CONCLUSIONS: This protocol presents the steps in developing a COS and COMS for cosmetic gynecological interventions. Embedding the COS and COMS for cosmetic gynecological interventions within future clinical trials, systematic reviews, and practice guidelines could contribute to enhancing the value of research and improving overall patient care. TRIAL REGISTRATION: Core Outcome Measures in Effectiveness Trials (COMET) 1592; https://tinyurl.com/n8faysuh. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): PRR1-10.2196/28032

Serous cystic neoplasm of the pancreas: A multinational study of 2622 patients under the auspices of the International Association of Pancreatology and European Pancreatic Club (European Study Group on Cystic Tumors of the Pancreas)

OBJECTIVES: Serous cystic neoplasm (SCN) is a cystic neoplasm of the pancreas whose natural history is poorly known. The purpose of the study was to attempt to describe the natural history of SCN, including the specific mortality. DESIGN: Retrospective multinational study including SCN diagnosed between 1990 and 2014. RESULTS: 2622 patients were included. Seventy-four per cent were women, and median age at diagnosis was 58\u2005years (16-99). Patients presented with non-specific abdominal pain (27%), pancreaticobiliary symptoms (9%), diabetes mellitus (5%), other symptoms (4%) and/or were asymptomatic (61%). Fifty-two per cent of patients were operated on during the first year after diagnosis (median size: 40\u2005mm (2-200)), 9% had resection beyond 1\u2005year of follow-up (3\u2005years (1-20), size at diagnosis: 25\u2005mm (4-140)) and 39% had no surgery (3.6\u2005years (1-23), 25.5\u2005mm (1-200)). Surgical indications were (not exclusive) uncertain diagnosis (60%), symptoms (23%), size increase (12%), large size (6%) and adjacent organ compression (5%). In patients followed beyond 1\u2005year (n=1271), size increased in 37% (growth rate: 4\u2005mm/year), was stable in 57% and decreased in 6%. Three serous cystadenocarcinomas were recorded. Postoperative mortality was 0.6% (n=10), and SCN's related mortality was 0.1% (n=1). CONCLUSIONS: After a 3-year follow-up, clinical relevant symptoms occurred in a very small proportion of patients and size slowly increased in less than half. Surgical treatment should be proposed only for diagnosis remaining uncertain after complete workup, significant and related symptoms or exceptionally when exists concern with malignancy. This study supports an initial conservative management in the majority of patients with SCN