Concept drift over geological times : predictive modeling baselines for analyzing the mammalian fossil record

Fossils are the remains organisms from earlier geological periods preserved in sedimentary rock. The global fossil record documents and characterizes the evidence about organisms that existed at different times and places during the Earth's history. One of the major directions in computational analysis of such data is to reconstruct environmental conditions and track climate changes over millions of years. Distribution of fossil animals in space and time make informative features for such modeling, yet concept drift presents one of the main computational challenges. As species continuously go extinct and new species originate, animal communities today are different from the communities of the past, and the communities at different times in the past are different from each other. The fossil record is continuously increasing as new fossils and localities are being discovered, but it is not possible to observe or measure their environmental contexts directly, because the time is gone. Labeled data linking organisms to climate is available only for the present day, where climatic conditions can be measured. The approach is to train models on the present day and use them to predict climatic conditions over the past. But since species representation is continuously changing, transfer learning approaches are needed to make models applicable and climate estimates to be comparable across geological times. Here we discuss predictive modeling settings for such paleoclimate reconstruction from the fossil record. We compare and experimentally analyze three baseline approaches for predictive paleoclimate reconstruction: (1) averaging over habitats of species, (2) using presence-absence of species as features, and (3) using functional characteristics of species communities as features. Our experiments on the present day African data and a case study on the fossil data from the Turkana Basin over the last 7 million of years suggest that presence-absence approaches are the most accurate over short time horizons, while species community approaches, also known as ecometrics, are the most informative over longer time horizons when, due to ongoing evolution, taxonomic relations between the present day and fossil species become more and more uncertain.Peer reviewe

Reconstruction of the Paleocene climates of Central Europe using fossil leaves

International audienc

Xenobiotic metabolizing enzyme activities in isolated and cryopreserved human liver parenchymal cells

Liver parenchymal cells (hepatocytes) of human organ donors were isolated using a two-step collagenase perfusion technique. The average viability of the freshly isolated liver parenchymal cells, as judged by trypan blue exclusion, was 82% (SD = 7%; n = 6). The inter-individual differences in the determined enzyme activities were less than a factor of 7.5, despite the different sexes and ages of the donors. Freshly isolated parenchymal cells (PC) were cryopreserved using a computer-controlled freezing protocol. After thawing, cryopreserved cells had a mean viability of 57% (SD = 18%; n = 6). The activities of xenobiotic metabolizing enzymes in freshly isolated and cryopreserved cells were compared using PC from two donors. The enzyme activities of phenol sulfotransferase, 1-naphthol UDP-glucuronosyltransferase and microsomal epoxide hydrolase were well maintained after thawing (87-117% of activities in freshly isolated cells), whereas the activities of glutathione S-transferase, monitored with the broad spectrum substrate 1-chloro-2,4-dinitrobenzene, and the major broad spectrum cytosolic epoxide hydrolase were moderately but markedly reduced after cryopreservation (34-64% and 45-89% of levels in fresh cells, respectively). The decrease of both activities was dependent on the viability after thawing. When cryopreserved cells were purified by a Percoll centrifugation after thawing, the viability was increased from 62 to 92% for cells from one of the donors and from 88 to 98% for PC for the other donor. Subsequently the activity of glutathione S-transferase in Percoll-purified PC from the two donors was increased to 71 and 96% of levels in freshly isolated cells. It is concluded that the use of cryopreserved liver parenchymal cells of humans and other species represents a valuable tool in predicting which animal species best represents humans in hepatic metabolism and therefore should be the preferred species for investigations of metabolism and metabolism-dependent toxicities

Phase I and pharmacological study of daily oral administration of perifosine (D-21266) in patients with advanced solid tumours

Alkylphosphocholines are a novel class of antitumour agents structurally related to ether lipids that interact with the cell membrane and influence intracellular growth signal transduction pathways. We performed a phase I trial with an analogue of miltefosine, perifosine (D-21266), which was expected to induce less gastrointestinal toxicity. Objectives of the trial were: to determine the maximum-tolerated dose (MTD) for daily administration, to identify the dose-limiting toxicity (DLT) of this schedule, to assess drug accumulation and to determine the relevant pharmacokinetic parameters. 22 patients with advanced solid tumours were treated at doses ranging from 50 to 350 mg/day for 3 weeks, followed by 1 week of rest. Toxicity consisted mainly of gastrointestinal side-effects: nausea was reported by 11 patients (52%, 10 patients Common Toxicity Criteria (CTC) grades 1-2 and 1 patient CTC grade 3), vomiting by 8 (38%, all CTC grades 1-2), and diarrhoea by 9 (43%, 8 patients CTC grades 1-2 and 1 patient CTC grade 3). The severity of these side effects appeared to increase with increasing doses. Another common side-effect was fatigue, occurring in 9 patients (43%). No haematology toxicity was observed. Dose-limiting toxicity (DLT) was not reached, but gastrointestinal complaints led to an early treatment discontinuation in an increasing number of patients at the higher dose levels. Therefore, MTD was established at 200 mg/day. The pharmacokinetic studies suggested dose proportionality

‘CLAMP Online’: a new web-based palaeoclimate tool and its application to the terrestrial Paleogene and Neogene of North America

CLAMP Online is a new form-driven web facility enabling Climate Leaf Analysis Multivariate Program (CLAMP) palaeoclimate determinations to be conducted in their entirety without the need for additional software. This facility is demonstrated using physiognomic data from 82 Eocene to Pliocene fossil sites in North America, the Physg3brc CLAMP calibration file, and both locally derived climate data (Met3br) and 0.5° × 0.5° gridded climate data (GRIDMet3br). All the fossil sites fall within the physiog- nomic space defined by the Physg3brc dataset showing the versatility of this calibration for Paleogene to Present sites in North America. The fossil sites also plot in the mesic part of physiognomic space confirming that the source of the fossil material was vegetation growing under conditions where water was not growth-limiting to any significant degree. Regression equations are derived relating the local to the gridded climate predictions showing the relative predictive capabilities of each dataset, as well as offering ways to convert previously published data between the two calibrations. Palaeoclimate data (mean annual, warm month mean and cold month mean temperatures, growing season length, growing season and mean monthly growing season precipitation, precipitation during the three consecutive wettest and three consecutive driest months, and annual averages for relative and specific humidities and enthalpy) are given for all 82 sites