Updated Aragonian biostratigraphy: Small Mammal distribution and its implications for the Miocene European Chronology

This paper contains formal definitions of the Early to Middle Aragonian (late Early–Middle Miocene) smallmammal biozones from the Aragonian type area in North Central Spain. The stratigraphical schemes of two of the best studied areas for the Lower and Middle Miocene, the Aragonian type area in Spain and the Upper Freshwater Molasse from the North Alpine Foreland Basin in Switzerland, have been compared. This comparison allows the analysis of the order of shared mammal events in the two countries, and the quantification of the resulting asynchronies based on their temporal correlations. The order of the events is very similar in Spain and Switzerland. In order to estimate the diachrony, two age-model options are used for the Swiss record. Our preferred option yields no discrepancies with SW European paleomagnetic and radiometric calibrations of the Ramblian and Early Aragonian bioevents. All Swiss first taxa occurrences precede those in the Aragonian type area by 0.74Myr on average. The asynchronies (1-2Myr) of the species arriving in the late Middle to early Late Aragonian may be higher than in the Early Aragonian (0-1Myr). The implications for the biochronological mammal Neogene system are discussed. Evidence is given confirming the unfeasibility of a formal European biozonation, since it is realised, that 1) most indicator species and many genera of rodents yielding the most detailed zonations have limited geographical ranges hampering recognition of the mammal Neogene zones; and 2) first and last taxon occurrences are diachronical. Therefore, the mammal Neogene system based on a sequence of time-ordered reference localities is preferred to the one based on selected bioevents “developed in widespread geographic areas”.Peer reviewe

Practical Applications as a Source of Credibility: A Comparison of Three Fields of Dutch Academic Chemistry

In many Western science systems, funding structures increasingly stimulate academic research to contribute to practical applications, but at the same time the rise of bibliometric performance assessments have strengthened the pressure on academics to conduct excellent basic research that can be published in scholarly literature. We analyze the interplay between these two developments in a set of three case studies of fields of chemistry in the Netherlands. First, we describe how the conditions under which academic chemists work have changed since 1975. Second, we investigate whether practical applications have become a source of credibility for individual researchers. Indeed, this turns out to be the case in catalysis, where connecting with industrial applications helps in many steps of the credibility cycle. Practical applications yield much less credibility in environmental chemistry, where application-oriented research agendas help to acquire funding, but not to publish prestigious papers or to earn peer recognition. In biochemistry practical applications hardly help in gaining credibility, as this field is still strongly oriented at fundamental questions. The differences between the fields can be explained by the presence or absence of powerful upstream end-users, who can afford to invest in academic research with promising long term benefits

Second intravenous immunoglobulin dose in patients with Guillain-Barre syndrome with poor prognosis (SID-GBS):a double-blind, randomised, placebo-controlled trial

Background Treatment with one standard dose (2 g/kg) of intravenous immunoglobulin is insufficient in a proportion of patients with severe Guillain-Barre syndrome. Worldwide, around 25% of patients severely affected with the syndrome are given a second intravenous immunoglobulin dose (SID), although it has not been proven effective. We aimed to investigate whether a SID is effective in patients with Guillain-Barre syndrome with a predicted poor outcome. Methods In this randomised, double-blind, placebo-controlled trial (SID-GBS), we included patients (>= 12 years) with Guillain-Barre syndrome admitted to one of 59 participating hospitals in the Netherlands. Patients were included on the first day of standard intravenous immunoglobulin treatment (2 g/kg over 5 days). Only patients with a poor prognosis (score of >= 6) according to the modified Erasmus Guillain-Barre syndrome Outcome Score were randomly assigned, via block randomisation stratified by centre, to SID (2 g/kg over 5 days) or to placebo, 7-9 days after inclusion. Patients, outcome adjudicators, monitors, and the steering committee were masked to treatment allocation. The primary outcome measure was the Guillain-Barre syndrome disability score 4 weeks after inclusion. All patients in whom allocated trial medication was started were included in the modified intention-to-treat analysis. Findings Between Feb 16, 2010, and June 5, 2018, 327 of 339 patients assessed for eligibility were included. 112 had a poor prognosis. Of those, 93 patients with a poor prognosis were included in the modified intention-to-treat analysis: 49 (53%) received SID and 44 (47%) received placebo. The adjusted common odds ratio for improvement on the Guillain-Barre syndrome disability score at 4 weeks was 1.4 (95% CI 0.6-3.3; p=0.45). Patients given SID had more serious adverse events (35% vs 16% in the first 30 days), including thromboembolic events, than those in the placebo group. Four patients died in the intervention group (13-24 weeks after randomisation). Interpretation Our study does not provide evidence that patients with Guillain-Barre syndrome with a poor prognosis benefit from a second intravenous immunoglobulin course; moreover, it entails a risk of serious adverse events. Therefore, a second intravenous immunoglobulin course should not be considered for treatment of Guillain-Barre syndrome because of a poor prognosis. The results indicate the need for treatment trials with other immune modulators in patients severely affected by Guillain-Barre syndrome. Funding Prinses Beatrix Spierfonds and Sanquin Plasma Products. Copyright (C) 2021 Elsevier Ltd. All rights reserved

31st Annual Meeting and Associated Programs of the Society for Immunotherapy of Cancer (SITC 2016) : part two

Background The immunological escape of tumors represents one of the main ob- stacles to the treatment of malignancies. The blockade of PD-1 or CTLA-4 receptors represented a milestone in the history of immunotherapy. However, immune checkpoint inhibitors seem to be effective in specific cohorts of patients. It has been proposed that their efficacy relies on the presence of an immunological response. Thus, we hypothesized that disruption of the PD-L1/PD-1 axis would synergize with our oncolytic vaccine platform PeptiCRAd. Methods We used murine B16OVA in vivo tumor models and flow cytometry analysis to investigate the immunological background. Results First, we found that high-burden B16OVA tumors were refractory to combination immunotherapy. However, with a more aggressive schedule, tumors with a lower burden were more susceptible to the combination of PeptiCRAd and PD-L1 blockade. The therapy signifi- cantly increased the median survival of mice (Fig. 7). Interestingly, the reduced growth of contralaterally injected B16F10 cells sug- gested the presence of a long lasting immunological memory also against non-targeted antigens. Concerning the functional state of tumor infiltrating lymphocytes (TILs), we found that all the immune therapies would enhance the percentage of activated (PD-1pos TIM- 3neg) T lymphocytes and reduce the amount of exhausted (PD-1pos TIM-3pos) cells compared to placebo. As expected, we found that PeptiCRAd monotherapy could increase the number of antigen spe- cific CD8+ T cells compared to other treatments. However, only the combination with PD-L1 blockade could significantly increase the ra- tio between activated and exhausted pentamer positive cells (p= 0.0058), suggesting that by disrupting the PD-1/PD-L1 axis we could decrease the amount of dysfunctional antigen specific T cells. We ob- served that the anatomical location deeply influenced the state of CD4+ and CD8+ T lymphocytes. In fact, TIM-3 expression was in- creased by 2 fold on TILs compared to splenic and lymphoid T cells. In the CD8+ compartment, the expression of PD-1 on the surface seemed to be restricted to the tumor micro-environment, while CD4 + T cells had a high expression of PD-1 also in lymphoid organs. Interestingly, we found that the levels of PD-1 were significantly higher on CD8+ T cells than on CD4+ T cells into the tumor micro- environment (p < 0.0001). Conclusions In conclusion, we demonstrated that the efficacy of immune check- point inhibitors might be strongly enhanced by their combination with cancer vaccines. PeptiCRAd was able to increase the number of antigen-specific T cells and PD-L1 blockade prevented their exhaus- tion, resulting in long-lasting immunological memory and increased median survival

Revision of medium-sized Cricetidae from the Miocene of the Daroca-Villafeliche area in the Calatayud-Teruel basin (Zaragoza, Spain)

Revision of Democricetodon (excluding D. sulcatus and D. cf gaillardi), Fahlbuschia, Pseudofahlbuschia and Renzimys from the Aragonian type area (Spain) results in the synonymization of the four genera, Democricetodon prevailing according to the rules of priority. Democricetodon decipiens is synonymized with D. corcolesi, D. darocensis with D. larteti, and Renzimys bilobatus with D. crusafonti. One new species of Democricetodon (D. moralesi n.sp.) is defined.Two partly contemporaneous evolutionary lineages are recognized: the Democricetodon hispanicus - D. lacombai lineage (D. hispanicus-D. moralesi n.sp.-D. jordensi-D. lacombai) and the Democricetodon franconicus - D. crusafonti lineage (D. franconicus-D. koenigswaldi-D. larteti- D. crusafonti). [RESUMEN] La revisión realizada del material de los géneros Democricetodon (excluidos D. sulcatus y D. cf gaillardi), Fahlbuschia, Pseudofahlbuschia and Renzimys del área tipo del Aragoniense (España) ha dado como resultado la sinonimia de los cuatro géneros, siendo Democricetodon el que tiene la prioridad. Democricetodon decipiens se ha sinonimizado con D. corcolesi, D. darocensis con D. larteti, y Renzimys bilobatus con D. crusafonti. Una nueva especie de Democricetodon (D. moralesi n.sp.) ha sido definidas. Dos líneas evolutivas, parcialmente contemporáneas han sido reconocidas: La línea Democricetodon hispanicus - lacombai (D. hispanicus-D. moralesi n.sp.-D. jordensi-D. lacombai) y la línea Democricetodon franconicus - D. crusafonti (D. franconicus-D. koenigswaldi-D. larteti- D. crusafonti)

Ballistic energy conversion: physical modeling and optical characterization

The growing demand for renewable energy stimulates the exploration of new materials and methods for clean energy, a process which is boosted by nanoscience and emerging nanotechnologies. Recently a high efficiency and high power density energy conversion mechanism was demonstrated through the use of jetted charged microdroplets, which fully relies on the net charges stored in the electrical double layer within a hundred nanometers of the water/gas interface, and then delivered at a metal target for converting kinetic energy to electrical energy. The method is fundamentally different from the traditional electrokinetic conversion and electrostatic generators, termed as ballistic energy conversion. It has a great potential in further applications due to the ultra-simple device design and the use of water, avoiding the challenges of new materials inventions.However, thorough theory is still lacking for both a quantitative description and an optimization of this system.Here we model and experimentally characterize the physical properties of the ballistic energy conversion system. Our model predicts the optimal working conditions of the energy harvesting including initial velocity and jet size, as well as the key performance factors including efficiency, generated target voltage, and power density. The results show that by using maximally charged droplets, an appropriate size and initial velocity of microjet, the system efficiency can be over 90%, at a generated voltage below 1 kV and a power density of at least 100 W/m2. The combination of high efficiency, huge power density, simplicity and compactness makes the ballistic energy conversion generator a promising device for green energy conversion

High-efficiency ballistic electrostatic generator using microdroplets

The strong demand for renewable energy promotes research on novel methods and technologies for energy conversion. Microfluidic systems for energy conversion by streaming current are less known to the public, and the relatively low efficiencies previously obtained seemed to limit the further applications of such systems. Here we report a microdroplet-based electrostatic generator operating by an acceleration-deceleration cycle ('ballistic' conversion), and show that this principle enables both high efficiency and compact simple design. Water is accelerated by pumping it through a micropore to form a microjet breaking up into fast-moving charged droplets. Droplet kinetic energy is converted to electrical energy when the charged droplets decelerate in the electrical field that forms between membrane and target. We demonstrate conversion efficiencies of up to 48%, a power density of 160kWm(-2) and both high- (20kV) and low- (500V) voltage operation. Besides offering striking new insights, the device potentially opens up new perspectives for low-cost and robust renewable energy conversion

Palaeontology and biostratigraphy (micromammals) of the continental Oligocene-Miocene deposits of the North-Central Ebro Basin (Huesca, Spain)

Abstract: In this paper the micromammals from three localities in the Oligocene/Miocene boundary interval and the Lower Miocene of the Ebro Basin in the Province of Huesca (northern Spain) are described. Twenty-five species are recognized, two of which are new (Quercomys daamsi de Visser and Peridyromys turbatus Alvarez Sierra et al.; Gliridae). One new subspecies belonging to the Ochotonidae (Prolagus vasconiensis fortis López Martínez & Sesé) is described. The biostratigraphy, palaeoecological implications and palaeobiogeography are discussed. Resumen: En este artículo se describen los micromamíferos de tres localidades en el intervalo del límite Oligoceno/Mioceno y el Mioceno inferior de la Cuenca del Ebro, en la provincia de Huesca (norte de España). Se han identificado veinticinco especies, dos de las cuales son nuevas (Quercomys daamsi de Visser y Peridyromys turbatus Alvarez Sierra et al;. Gliridae). Se describe una nueva subespecie perteneciente a los Ochotonidae (Prolagus vasconiensis fortis López Martínez y Sesé). Se discute la bioestratigrafía, implicaciones paleoecológicas y paleobiogeografía.Peer reviewe

Miocene small mammals from Jebel Zelten, Libya

Small mammal remains from seven localities were collected during two geological/paleontological field campaigns (1983 and 1997). The assemblages are small, but the twelve species recognized and described represent seven rodent families, one lagomorph and one bat family. The Jebel Zelten (large) mammal fauna was considered in most literature to represent one time-slice, although the interpretation of its age has been diverse. On basis of the evolutionary stage of the small mammal species, the faunal compositions and the stratigraphic sequence we conclude that the Jebel Zelten assemblages represent three periods in time and cover approximately 4... (Ver más) million years. Three assemblages can be assigned to the Middle Early Miocene (18-19 Ma), one to the Late Early Miocene (16-17) and two to the Middle Miocene (14-15Ma).Restos de micromamíferos de siete localidades han sido recogidas durante dos campañas de campo geológicas/paleontológicas (1983 y 1997). Las muestras son pequeñas pero se han reconocido y descrito doce especies que representan siete familias de roedores, una de lagomorfos y una de quirópteros. La fauna de mamíferos (macromamíferos) de Jebel Zelten ha sido considerada, en la mayoría de las publicaciones, como un único lapso temporal, aunque su interpretación temporal ha sido diversa. En base al estado evolutivo de las especies de micromamíferos, la composición faunística y la secuencia estratigráfica concluimos que las asociaciones de Jebel Zelten... (Ver más) representan tres períodos temporales differentes que cubren aproximadamente 4 millones de años. Tres asociaciones pueden asignarse al Mioceno inferior medio (18-19 Ma), una al Mioceno inferior tardío (16-17 Ma) y dos al Mioceno medio (14-15 Ma)