Very long optical path-length from a compact multi-pass cell

The multiple-pass optical cell is an important tool for laser absorption spectroscopy and its many applications. For most practical applications, such as trace-gas detection, a compact and robust design is essential. Here we report an investigation into a multi-pass cell design based on a pair of cylindrical mirrors, with a particular focus on achieving very long optical paths. We demonstrate a path-length of 50.31 m in a cell with 40 mm diameter mirrors spaced 88.9 mm apart - a 3-fold increase over the previously reported longest path-length obtained with this type of cell configuration. We characterize the mechanical stability of the cell and describe the practical conditions necessary to achieve very long path-lengths

Exploring the Law of Detrital Zircon: LA-ICP-MS and CA-TIMS Geochronology of Jurassic Forearc Strata, Cook Inlet, Alaska, USA

Uranium-lead (U-Pb) geochronology studies commonly employ the law of detrital zircon: A sedimentary rock cannot be older than its youngest zircon. This premise permits maximum depositional ages (MDAs) to be applied in chronostratigraphy, but geochronologic dates are complicated by uncertainty. We conducted laser ablation-inductively coupled plasma-mass spectrometry (LA-ICP-MS) and chemical abrasion-thermal ionization mass spectrometry (CA-TIMS) of detrital zircon in forearc strata of southern Alaska (USA) to assess the accuracy of several MDA approaches. Six samples from Middle–Upper Jurassic units are generally replete with youthful zircon and underwent three rounds of analysis: (1) LA-ICP-MS of ∼115 grains, with one date per zircon; (2) LA-ICP-MS of the ∼15 youngest grains identified in round 1, acquiring two additional dates per zircon; and (3) CA-TIMS of the ∼5 youngest grains identified by LA-ICP-MS. The youngest single-grain LA-ICP-MS dates are all younger than—and rarely overlap at 2σ uncertainty with—the CA-TIMS MDAs. The youngest kernel density estimation modes are typically several million years older than the CA-TIMS MDAs. Weighted means of round 1 dates that define the youngest statistical populations yield the best coincidence with CA-TIMS MDAs. CA-TIMS dating of the youngest zircon identified by LA-ICP-MS is indispensable for critical MDA applications, eliminating laser-induced matrix effects, mitigating and evaluating Pb loss, and resolving complexities of interpreting lower-precision, normally distributed LA-ICP-MS dates. Finally, numerous CA-TIMS MDAs in this study are younger than Bathonian(?)–Callovian and Oxfordian faunal correlations suggest, highlighting the need for additional radioisotopic constraints—including CA-TIMS MDAs—for the Middle–Late Jurassic geologic time scale

Common cancer-associated imbalances in the DNA damage response confer sensitivity to single agent ATR inhibition

ATR is an attractive target in cancer therapy because it signals replication stress and DNA lesions for repair and to S/G2 checkpoints. Cancer-specific defects in the DNA damage response (DDR) may render cancer cells vulnerable to ATR inhibition alone. We determined the cytotoxicity of the ATR inhibitor VE-821 in isogenically matched cells with DDR imbalance. Cell cycle arrest, DNA damage accumulation and repair were determined following VE-821 exposure. Defects in homologous recombination repair (HRR: ATM, BRCA2 and XRCC3) and base excision repair (BER: XRCC1) conferred sensitivity to VE-821. Surprisingly, the loss of different components of the trimeric non-homologous end-joining (NHEJ) protein DNA-PK had opposing effects. Loss of the DNA-binding component, Ku80, caused hypersensitivity to VE-821, but loss of its partner catalytic subunit, DNA-PKcs, did not. Unexpectedly, VE-821 was particularly cytotoxic to human and hamster cells expressing high levels of DNA-PKcs. High DNA-PKcs was associated with replicative stress and activation of the DDR. VE-821 suppressed HRR, determined by RAD51 focus formation, to a greater extent in cells with high DNA-PKcs. Defects in HRR and BER and high DNA-PKcs expression, that are common in cancer, confer sensitivity to ATR inhibitor monotherapy and may be developed as predictive biomarkers for personalised medicine

Exploring the quality of social information disclosed in non-financial reports of Croatian companies

By enacting the provisions of Directive 2014/95/EU and the Croatian Accounting Act on disclosing non-financial and diversity information, companies of public interest registering 500 and more employees are required to disclose non-financial information. The purpose of this research is to assess the quality of disclosed social information in non- financial/sustainability reports of Croatian companies. The assessment of the social information was grounded on the framework defined by globally accepted sustainability reporting standards by assessing the quality of social subcategories of human rights, labour practice, community/society and product, measured by attributes of relevance, clarity, verifiability, comparability and clarity. With the overall quality score of 13.16 (out of possible 36), the results prove that Croatian companies do disclose certain social information, but the reliability of this information for benchmarking and competitiveness assessment is questionable, as a consensus on the minimum of information to be disclosed as a fundamental requirement for benchmarking has not yet been reached

Phase I, Dose-Escalation, Two-Part Trial of the PARP Inhibitor Talazoparib in Patients with Advanced Germline BRCA1/2 Mutations and Selected Sporadic Cancers

Talazoparib inhibits PARP catalytic activity, trapping PARP1 on damaged DNA and causing cell death in BRCA1/2-mutated cells. We evaluated talazoparib therapy in this two-part, phase I, first-in-human trial. Antitumor activity, MTD, pharmacokinetics, and pharmacodynamics of once-daily talazoparib were determined in an open-label, multicenter, dose-escalation study (NCT01286987). The MTD was 1.0 mg/day, with an elimination half-life of 50 hours. Treatment-related adverse events included fatigue (26/71 patients; 37%) and anemia (25/71 patients; 35%). Grade 3 to 4 adverse events included anemia (17/71 patients; 24%) and thrombocytopenia (13/71 patients; 18%). Sustained PARP inhibition was observed at doses ≥0.60 mg/day. At 1.0 mg/day, confirmed responses were observed in 7 of 14 (50%) and 5 of 12 (42%) patients with BRCA mutation–associated breast and ovarian cancers, respectively, and in patients with pancreatic and small cell lung cancer. Talazoparib demonstrated single-agent antitumor activity and was well tolerated in patients at the recommended dose of 1.0 mg/day

Drivers and technology-related obstacles in moving to multichannel retailing

Today, multichannel retailing is a key strategic issue for most retailers. Yet, while there are many drivers associated with retailers going multichannel so too are there technology-related obstacles, however, few prior empirical studies explore these themes. In light of this, by using a multi-case approach to understand the key drivers and technology-related obstacles associated with retailers moving to multichannel retailing our study makes two key contributions. First, we extend prior theory by providing novel empirical insights into the main drivers underpinning retailers using a multichannel strategy. We find that meeting customer needs and increasing sales were the primary drivers behind retailers using the strategy, although there is diversity in the way retailers respond to these motives. Second, we provide empirical support for a proposed theoretical framework which summarises the key technology-related obstacles retailers encounter when going multichannel, by stage of implementation. The framework reveals that retailers face technology-related obstacles when implementing a multichannel strategy due to the need to switch/acquire resources and achieve channel integration. Furthermore, the framework highlights that these resource and channel integration issues are often interrelated with each other and with other staff engagement and cultural issues, vary by retailer and stage of implementation, and pose greater obstacles to retailers using new and multiple channels than the extant literature suggests

The Emergence of Hospital Federations: An Integration of Perspectives from Organizational Theory

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/68464/2/10.1177_107755878704400206.pd

‘Better late than never’: the interplay between green technology and age for firm growth

This paper investigates the relationship between green/non-green technologies and firm growth. By combining the literature on eco-innovations, industrial organisation and entrepreneurial studies, we examine the dependence of this relationship on the pace at which firms grow and the age of the firm. From a dataset of 5498 manufacturing firms in Italy for the period of 2000–2008, longitudinal fixed effects quantile models are estimated, in which the firm’s age is set to moderate the effects of green and non-green patents on employment growth. We find that the positive effect of green technologies on growth is greater than that of non-green technologies. However, this result does not apply to struggling and rapidly growing firms. With fast-growing (above the median) firms, age moderates the growth effect of green technologies. Inconsistent with the extant literature, this moderation effect is positive: firm experience appears important for the growth benefits of green technologies, possibly relative to the complexity of their management