107 research outputs found

    A gap-filling method for room temperature data based on autoencoder neural networks

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    This study explores the applicability of a deep learning-based approach for reconstructing missing room temperature data from different domains where relatively few training samples are available. For that purpose, the existing convolutional, long short-term memory (LSTM) and feed-forward autoencoders were combined with a suitable domain adaptation procedure. Eventually, the developed models were evaluated on data collected in four buildings with significant differences in thermal mass, design and location. The findings pointed out that the domain adaptation can be conducted effciently by using a small data sample from the target domain. Additionally, the results showed that the proposed model can reconstruct up to 80 % of the missing daily room temperature inputs with RMSE accuracy of 0.6 °C

    Population Pharmacokinetics of Palbociclib and Its Correlation with Clinical Efficacy and Safety in Patients with Advanced Breast Cancer.

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    Neutropenia is the most frequent dose-limiting toxicity reported in patients with metastatic breast cancer receiving palbociclib. The objective of this study was to investigate the pharmacokinetic-pharmacodynamic (PK/PD) relationships for toxicity (i.e., absolute neutrophil count, ANC) and efficacy (i.e., progression-free survival, PFS). A semi-mechanistic PK/PD model was used to predict neutrophils' time course using a population approach (NONMEM). Influence of demographic and clinical characteristics was evaluated. Cox proportional hazards models were developed to evaluate the influence of palbociclib PK on PFS. A two-compartment model with first-order absorption and a lag time adequately described the 255 palbociclib concentrations provided by 44 patients. The effect of the co-administration of proton-pump inhibitors in fasting conditions increased palbociclib clearance by 56%. None of the tested covariates affected the PD parameters. Model-based simulations confirmed the concentration-dependent and non-cumulative properties of palbociclib-induced neutropenia, reversible after treatment withdrawal. The ANC nadir occurred approximately at day 24 of each cycle. Cox analyses revealed a trend for better PFS with increasing palbociclib exposure in older patients. By characterizing palbociclib-induced neutropenia, this model offers support to clinicians to rationally optimize treatment management through patient-individualized strategies

    Differences in the food consumption between kidney stone formers and non-formers in the Swiss Kidney Stone Cohort.

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    OBJECTIVE Diet has a major influence on the formation and management of kidney stones. However, kidney stone formers' diet is difficult to capture in a large population. Our objective was to describe the dietary intake of kidney stone formers in Switzerland and to compare it to non-stone formers. METHODS We used data from the Swiss Kidney Stone Cohort (n=261), a multicentric cohort of recurrent or incident kidney stone formers with additional risk factors, and a control group of CT-scan proven non-stone formers (n=197). Dieticians conducted two consecutive 24-h dietary recalls, using structured interviews and validated software (GloboDiet). We took the mean consumption per participant of the two 24-h dietary recalls to describe the dietary intake and used two-part models to compare the two groups. RESULTS The dietary intake was overall similar between stone and non-stone formers. However, we identified that kidney stone formers had a higher probability of consuming cakes and biscuits (odds ratio, OR[95% CI] =1.56[1.03; 2.37]) and soft drinks (OR=1.66[1.08; 2.55]). Kidney stone formers had a lower probability of consuming nuts and seeds (OR =0.53[0.35; 0.82]), fresh cheese (OR=0.54[0.30; 0.96]), teas (OR=0.50[0.3; 0.84]), and alcoholic beverages (OR=0.35[0.23; 0.54]), especially wine (OR=0.42[0.27; 0.65]). Furthermore, among consumers, stone formers reported smaller quantities of vegetables (β coeff[95% CI]= - 0.23[- 0.41; - 0.06]), coffee (β coeff= - 0.21[- 0.37; - 0.05]), teas (β coeff= - 0.52[- 0.92; - 0.11]) and alcoholic beverages (β coeff= - 0.34[- 0.63; - 0.06]). CONCLUSION Stone formers reported lower intakes of vegetables, tea, coffee, and alcoholic beverages, more specifically wine, but reported drinking more frequently soft drinks than non-stone formers. For the other food groups, stone formers and non-formers reported similar dietary intakes. Further research is needed to better understand the links between diet and kidney stone formation and develop dietary recommendations adapted to the local settings and cultural habits

    Role of the ubiquitin-binding domain of Polη in Rad18-independent translesion DNA synthesis in human cell extracts

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    In eukaryotic cells, the Rad6/Rad18-dependent monoubiquitination of the proliferating cell nuclear antigen (PCNA) plays an essential role in the switching between replication and translesion DNA synthesis (TLS). The DNA polymerase Polη binds to PCNA via a consensus C-terminal PCNA-interacting protein (PIP) motif. It also specifically interacts with monoubiquitinated PCNA thanks to a recently identified ubiquitin-binding domain (UBZ). To investigate whether the TLS activity of Polη is always coupled to PCNA monoubiquitination, we monitor the ability of cell-free extracts to perform DNA synthesis across different types of lesions. We observe that a cis-syn cyclobutane thymine dimer (TT-CPD), but not a N-2-acetylaminofluorene-guanine (G-AAF) adduct, is efficiently bypassed in extracts from Rad18-deficient cells, thus demonstrating the existence of a Polη-dependent and Rad18-independent TLS pathway. In addition, by complementing Polη-deficient cells with PIP and UBZ mutants, we show that each of these domains contributes to Polη activity. The finding that the bypass of a CPD lesion in vitro does not require Ub-PCNA but nevertheless depends on the UBZ domain of Polη, reveals that this domain may play a novel role in the TLS process that is not related to the monoubiquitination status of PCNA

    Evidence for a Rad18-Independent Frameshift Mutagenesis Pathway in Human Cell-Free Extracts

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    Bypass of replication blocks by specialized DNA polymerases is crucial for cell survival but may promote mutagenesis and genome instability. To gain insight into mutagenic sub-pathways that coexist in mammalian cells, we examined N-2-acetylaminofluorene (AAF)-induced frameshift mutagenesis by means of SV40-based shuttle vectors containing a single adduct. We found that in mammalian cells, as previously observed in E. coli, modification of the third guanine of two target sequences, 5'-GGG-3' (3G) and 5'-GGCGCC-3' (NarI site), induces –1 and –2 frameshift mutations, respectively. Using an in vitro assay for translesion synthesis, we investigated the biochemical control of these events. We showed that Pol eta, but neither Pol iota nor Pol zeta, plays a major role in the frameshift bypass of the AAF adduct located in the 3G sequence. By complementing PCNA-depleted extracts with either a wild-type or a non-ubiquitinatable form of PCNA, we found that this Pol eta-mediated pathway requires Rad18 and ubiquitination of PCNA. In contrast, when the AAF adduct is located within the NarI site, TLS is only partially dependent upon Pol eta and Rad18, unravelling the existence of alternative pathways that concurrently bypass this lesion

    Bryophyte gas-exchange dynamics along varying hydration status reveal a significant carbonyl sulphide (COS) sink in the dark and COS source in the light

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    Carbonyl sulphide (COS) is a potential tracer of gross primary productivity (GPP), assuming a unidirectional COS flux into the vegetation that scales with GPP. However, carbonic anhydrase (CA), the enzyme that hydrolyses COS, is expected to be light independent, and thus plants without stomata should continue to take up COS in the dark. We measured net CO2 (A(C) ) and COS (A(S) ) uptake rates from two astomatous bryophytes at different relative water contents (RWCs), COS concentrations, temperatures and light intensities. We found large A(S) in the dark, indicating that CA activity continues without photosynthesis. More surprisingly, we found a nonzero COS compensation point in light and dark conditions, indicating a temperature-driven COS source with a Q10 (fractional change for a 10°C temperature increase) of 3.7. This resulted in greater A(S) in the dark than in the light at similar RWC. The processes underlying such COS emissions remain unknown. Our results suggest that ecosystems dominated by bryophytes might be strong atmospheric sinks of COS at night and weaker sinks or even sources of COS during daytime. Biotic COS production in bryophytes could result from symbiotic fungal and bacterial partners that could also be found on vascular plants.Funding was provided by the European Research Council (ERC) early career starting grant SOLCA (grant no. 338264) and the French Agence National de la Recherche (ANR) project ORCA. T.E.G. was funded by the IdEx post-doctoral programme of the Université de Bordeaux and by a Marie Skłodowska-Curie Intra-European fellowship (grant no. 653223). J.R. was funded by NERC grant NE/M00113X/1

    Soil macrofauna communities in Brazilian land-use systems

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    Soil animal communities include more than 40 higher-order taxa, representing over 23% of all described species. These animals have a wide range of feeding sources and contribute to several important soil functions and ecosystem services. Although many studies have assessed macroinvertebrate communities in Brazil, few of them have been published in journals and even fewer have made the data openly available for consultation and further use. As part of ongoing efforts to synthesise the global soil macrofauna communities and to increase the amount of openly-accessible data in GBIF and other repositories related to soil biodiversity, the present paper provides links to 29 soil macroinvertebrate datasets covering 42 soil fauna taxa, collected in various land-use systems in Brazil. A total of 83,085 georeferenced occurrences of these taxa are presented, based on quantitative estimates performed using a standardised sampling method commonly adopted worldwide to collect soil macrofauna populations, i.e. the TSBF (Tropical Soil Biology and Fertility Programme) protocol. This consists of digging soil monoliths of 25 x 25 cm area, with handsorting of the macroinvertebrates visible to the naked eye from the surface litter and from within the soil, typically in the upper 0-20 cm layer (but sometimes shallower, i.e. top 0-10 cm or deeper to 0-40 cm, depending on the site). The land-use systems included anthropogenic sites managed with agricultural systems (e.g. pastures, annual and perennial crops, agroforestry), as well as planted forests and native vegetation located mostly in the southern Brazilian State of Paraná (96 sites), with a few additional sites in the neighbouring states of São Paulo (21 sites) and Santa Catarina (five sites). Important metadata on soil properties, particularly soil chemical parameters (mainly pH, C, P, Ca, K, Mg, Al contents, exchangeable acidity, Cation Exchange Capacity, Base Saturation and, infrequently, total N), particle size distribution (mainly % sand, silt and clay) and, infrequently, soil moisture and bulk density, as well as on human management practices (land use and vegetation cover) are provided. These data will be particularly useful for those interested in estimating land-use change impacts on soil biodiversity and its implications for below-ground foodwebs, ecosystem functioning and ecosystem service delivery.Quantitative estimates are provided for 42 soil animal taxa, for two biodiversity hotspots: the Brazilian Atlantic Forest and Cerrado biomes. Data are provided at the individual monolith level, representing sampling events ranging from February 2001 up to September 2016 in 122 sampling sites and over 1800 samples, for a total of 83,085 ocurrences

    L’encadrement pénal de la réforme

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