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

University of Illinois Year of Cyberinfrastructure Final Report

The University of Illinois at Urbana-Champaign is a leader in computing and information technology (IT). Our leadership role has both produced and been produced by a culture of innovation. Many efforts have arisen over the years that have been the product of this culture. While the university’s commitment to developing digital infrastructure, resources, and support services has served campus researchers well, it has become clear that a more coherent and unified approach to assessing and addressing the IT services and support needs of campus researchers is imperative. With the support of the Vice Chancellor for Research and the Chief Information Officer, we embarked on the Year of Cyberinfrastructure (Year of CI). Through this effort, we engaged researchers across disciplines to gain an understanding of the challenges they face in order to inform how we, as a campus, should move together to address these needs. We confirmed that researchers tend to assemble needed resources and services on their own, often out of necessity. While this practice has allowed those with the ambition or, more frequently, the absolute need, to advance their fields, it has primarily benefitted only those researchers and their collaborators. Providers of resources and services have brought value to the research process, but this value has been accrued in a largely disjointed manner that has tended to favor the power users of technology. The Year of CI effort has made clear that our research support landscape is not only lacking coherence but is also very uneven across academic and research units. To support modern research practices and to be competitive and preeminent in the academic community and the world, the 21st century research university must provide a foundation of research IT infrastructure and services that are accessible by all disciplines. Our campus needs a strong vision for how IT supports research, along with the ability to realize and evolve that vision in lockstep with the changing needs of the research community and the technologies available to meet those needs. Though Illinois faces significant financial challenges, it is time to be bold and make an investment to allow the university to emerge from these challenges as the premier destination for faculty, postdocs, graduate students, undergraduate students, and research staff who seek to work in a world-class modern research environment. It is time to provide the infrastructure that will grow the campus research portfolio to new heights. The Year of CI has provided the initial assessment of the campus and indicates the steps we must take to develop the digital support ecosystem that will allow the campus to realize its vision of preeminence in research.Ope

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

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

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