Une bibliothèque de recherche face à l'édition électronique

Le développement des collections de périodiques a toujours constitué une composante majeure des politiques d'acquisition des bibliothèques de recherche. Aujourd'hui, les voilà confrontées simultanément, et de manière aiguë, à une difficulté certes récurrente : l'augmentation ininterrompue du coût des abonnements, et à une nouveauté radicale encore très difficile à maîtriser et qui engendre plutôt des surcoûts : la mise sur le marché de documents numérisés, principalement des périodiques. Organe d'un établissement pionnier en matière d'utilisation des réseaux informatiques pour la diffusion des résultats de la recherche, la bibliothèque du CERN a depuis plusieurs années déjà intégré cette nouvelle donne dans sa politique d'acquisition

Oxaliplatin induces drug resistance more rapidly than cisplatin in H69 small cell lung cancer cells

Cisplatin produces good responses in solid tumours including small cell lung cancer (SCLC) but this is limited by the development of resistance. Oxaliplatin is reported to show activity against some cisplatin-resistant cancers but there is little known about oxaliplatin in SCLC and there are no reports of oxaliplatin resistant SCLC cell lines. Studies of drug resistance mainly focus on the cellular resistance mechanisms rather than how the cells develop resistance. This study examines the development of cisplatin and oxaliplatin resistance in H69 human SCLC cells in response to repeated treatment with clinically relevant doses of cisplatin or oxaliplatin for either 4 days or 2h. Treatments with 200ng/ml cisplatin or 400ng/ml oxaliplatin for 4 days produced sublines (H69CIS200 and H69OX400 respectively) that showed low level (approximately 2-fold) resistance after 8 treatments. Treatments with 1000ng/ml cisplatin or 2000ng/ml oxaliplatin for 2h also produced sublines, however these were not stably resistant suggesting shorter treatment pulses of drug may be more effective. Cells survived the first five treatments without any increase in resistance, by arresting their growth for a period and then regrowing. The period of growth arrest was reduced after the sixth treatment and the H69CIS200 and H69OX400 sublines showed a reduced growth arrest in response to cisplatin and oxaliplatin treatment suggesting that "regrowth resistance" initially protected against drug treatment and this was further upregulated and became part of the resistance phenotype of these sublines. Oxaliplatin dose escalation produced more surviving sublines than cisplatin dose escalation but neither set of sublines were associated with increased resistance as determined by 5-day cytotoxicity assays, also suggesting the involvement of regrowth resistance. The resistant sublines showed no change in platinum accumulation or glutathione levels even though the H69OX400 subline was more sensitive to buthionine sulfoximine treatment. The H69CIS200 cells were cross-resistant to oxaliplatin demonstrating that oxaliplatin does not have activity against low level cisplatin resistance. Relative to the H69 cells, the H69CIS200 and H69OX400 sublines were more sensitive to paclitaxel and taxotere suggests the taxanes may be useful in the treatment of platinum resistant SCLC. These novel cellular models of cisplatin and oxaliplatin resistant SCLC will be useful in developing strategies to treat platinum-resistant SCLC

Science Hybrid Orbiter and Lunar Relay (SCHOLR) Architecture and Design

Considered both a stepping-stone to deep space and a key to unlocking the mysteries of planetary formation, the Moon offers a unique opportunity for scientific study. Robotic precursor missions are being developed to improve technology and enable new approaches to exploration. Robots, lunar landers, and satellites play significant roles in advancing science and technologies, offering close range and in-situ observations. Science and exploration data gathered from these nodes and a lunar science satellite is intended to support future human expeditions and facilitate future utilization of lunar resources. To attain a global view of lunar science, the nodes will be distributed over the lunar surface, including locations on the far side of the Moon. Given that nodes on the lunar far side do not have direct line-of-sight for Earth communications, the planned presence of such nodes creates the need for a lunar communications relay satellite. Since the communications relay capability would only be required for a small portion of the satellite s orbit, it may be possible to include communication relay components on a science spacecraft. Furthermore, an integrated satellite has the potential to reduce lunar surface mission costs. A SCience Hybrid Orbiter and Lunar Relay (SCHOLR) is proposed to accomplish scientific goals while also supporting the communications needs of landers on the far side of the Moon. User needs and design drivers for the system were derived from the anticipated needs of future robotic and lander missions. Based on these drivers and user requirements, accommodations for communications payload aboard a science spacecraft were developed. A team of interns identified and compared possible SCHOLR architectures. The final SCHOLR architecture was analyzed in terms of orbiter lifetime, lunar surface coverage, size, mass, power, and communications data rates. This paper presents the driving requirements, operational concept, and architecture views for SCHOLR within a lunar surface nodal network. Orbital and bidirectional link analysis, between lunar nodes, orbiter, and Earth, as well as a conceptual design for the spacecraft are also presente

Structure and mechanism of human DNA polymerase η

The variant form of the human syndrome xeroderma pigmentosum (XPV) is caused by a deficiency in DNA polymerase eta (Pol eta), a DNA polymerase that enables replication through ultraviolet-induced pyrimidine dimers. Here we report high-resolution crystal structures of human Pol eta at four consecutive steps during DNA synthesis through cis-syn cyclobutane thymine dimers. Pol eta acts like a 'molecular splint' to stabilize damaged DNA in a normal B-form conformation. An enlarged active site accommodates the thymine dimer with excellent stereochemistry for two-metal ion catalysis. Two residues conserved among Pol eta orthologues form specific hydrogen bonds with the lesion and the incoming nucleotide to assist translesion synthesis. On the basis of the structures, eight Pol eta missense mutations causing XPV can be rationalized as undermining the molecular splint or perturbing the active-site alignment. The structures also provide an insight into the role of Pol eta in replicating through D loop and DNA fragile sites

How does culture impinge upon managers' demeanor of earnings management? Evidence from cross-country analysis

We examine the impact of national culture on earnings. Specifically, we examine managers’ likelihood of using accrual or real earnings management and the role of culture on various attributes of earnings (accruals quality, persistence, smoothing, and predictability). We measure national culture using Hofstede’s six dimensions of culture (1984, 2001, and 2010). Using data from 36 countries during 1997-2018, we find that managers are likely to use both accruals and real earnings management in high power distance countries. In long-term oriented countries, managers are more likely to use real earnings management. In uncertainty avoidance countries, in high individualist countries, and in higher indulgent versus restraint countries, managers are less likely to use either type of earnings management. In masculine countries, managers tend to use lower accruals management rather and rely on production cost real earnings management. We also find the use of accruals management and the use of real earnings management are substitutes for each other. In addition, we are able to classify countries into four earnings quality groups based on the culture impact on the earnings attributes (primarily driven by accruals quality, predictability, and smoothing). Persistence is generally not significant in classifying countries by earnings attributes. Our findings indicate that a universal set of accounting standards is a challenging goal to achieve given the cultural diversity across countries. To improve the existing corporate governance framework and to ensure high quality and uniform financial statements, the enforcement of standards should be tailored to specific cultures, or at a minimum, corporate boards need to be more culturally diversified

Clinical, radiologic, pathologic, and molecular characteristics of long-term survivors of diffuse intrinsic pontine glioma (DIPG): a collaborative report from the International and European Society for Pediatric Oncology DIPG registries

Purpose Diffuse intrinsic pontine glioma (DIPG) is a brainstem malignancy with a median survival of < 1 year. The International and European Society for Pediatric Oncology DIPG Registries collaborated to compare clinical, radiologic, and histomolecular characteristics between short-term survivors (STSs) and long-term survivors (LTSs). Materials and Methods Data abstracted from registry databases included patients from North America, Australia, Germany, Austria, Switzerland, the Netherlands, Italy, France, the United Kingdom, and Croatia. Results Among 1,130 pediatric and young adults with radiographically confirmed DIPG, 122 (11%) were excluded. Of the 1,008 remaining patients, 101 (10%) were LTSs (survival ≥ 2 years). Median survival time was 11 months (interquartile range, 7.5 to 16 months), and 1-, 2-, 3-, 4-, and 5-year survival rates were 42.3% (95% CI, 38.1% to 44.1%), 9.6% (95% CI, 7.8% to 11.3%), 4.3% (95% CI, 3.2% to 5.8%), 3.2% (95% CI, 2.4% to 4.6%), and 2.2% (95% CI, 1.4% to 3.4%), respectively. LTSs, compared with STSs, more commonly presented at age < 3 or > 10 years (11% v 3% and 33% v 23%, respectively; P < .001) and with longer symptom duration ( P < .001). STSs, compared with LTSs, more commonly presented with cranial nerve palsy (83% v 73%, respectively; P = .008), ring enhancement (38% v 23%, respectively; P = .007), necrosis (42% v 26%, respectively; P = .009), and extrapontine extension (92% v 86%, respectively; P = .04). LTSs more commonly received systemic therapy at diagnosis (88% v 75% for STSs; P = .005). Biopsies and autopsies were performed in 299 patients (30%) and 77 patients (10%), respectively; 181 tumors (48%) were molecularly characterized. LTSs were more likely to harbor a HIST1H3B mutation (odds ratio, 1.28; 95% CI, 1.1 to 1.5; P = .002). Conclusion We report clinical, radiologic, and molecular factors that correlate with survival in children and young adults with DIPG, which are important for risk stratification in future clinical trials

From evidence to action: applying gender mainstreaming to pay gaps in the Welsh public sector

Progress on reducing gender disparities remains painfully slow, despite efforts to identify the determinants of gender pay gaps and specify size and shape. Recent studies highlight the need for a more nuanced account of the way that public policy shapes organizational responses and insights into the types of organizational practices that diminish pay disparities. In response, this research reports on an action research intervention in three large Welsh public organizations, subject to a unique statutory equality duty. Data demonstrate how an evidence‐based gender mainstreaming approach facilitated the development of a ‘no blame’ strategy, which legitimized organizational proactivity through collaborative and empowering change management processes. The research contributes to the study of gender pay gaps by demonstrating that gender mainstreaming, with facilitative local conditions and supportive public policy, shapes action on gender segregation, with particular success in women's low‐paid employment. Conclusions highlight theoretical and policy implications arising from the research

Cadmium accumulation and interactions with zinc, copper, and manganese, analysed by ICP-MS in a long-term Caco-2 TC7 cell model

The influence of long-term exposure to cadmium (Cd) on essential minerals was investigated using a Caco-2 TC7 cells and a multi-analytical tool: microwave digestion and inductively coupled plasma mass spectrometry. Intracellular levels, effects on cadmium accumulation, distribution, and reference concentration ranges of the following elements were determined: Na, Mg, Ca, Cr, Fe, Mn, Co, Ni, Cu, Zn, Mo, and Cd. Results showed that Caco-2 TC7 cells incubated long-term with cadmium concentrations ranging from 0 to 10 lmol Cd/l for 5 weeks exhibited a significant increase in cadmium accumulation. Furthermore, this accumulation was more marked in cells exposed long-term to cadmium compared with controls, and that this exposure resulted in a significant accumulation of copper and zinc but not of the other elements measured. Interactions of Cd with three elements: zinc, copper, and manganese were particularly studied. Exposed to 30 lmol/l of the element, manganese showed the highest inhibition and copper the lowest on cadmium intracellular accumulation but Zn, Cu, and Mn behave differently in terms of their mutual competition with Cd. Indeed, increasing cadmium in the culture medium resulted in a gradual and significant increase in the accumulation of zinc. There was a significant decrease in manganese from 5 lmol Cd/l exposure, and no variation was observed with copper. Abbreviation: AAS – Atomic absorption spectrometry; CRM– Certified reference material; PBS – Phosphate buffered saline without calcium and magnesium; DMEM – Dubelcco’s modified Eagle’s medium

LGBTQ+ Substance Use and Sexual Health and Wellbeing: A Special Commentary

Although there has been some increased visibility in professional counseling literature pertaining to LGBTQ+ issues, gaps still exist. One such omission is how LGBTQ+ sexual wellbeing is negatively influenced by substance use. This commentary briefly reviews ways LGBTQ+ sexual wellbeing is negatively impacted by substance use. We provide commentary on how counselors may bolster sexual wellbeing when working with LGBTQ+ substance users and highlight gaps in counseling research. Lastly, recommendations for integrating this content into counselor training are provided