Populus alba L., an Autochthonous Species of Spain: A Source for Cellulose Nanofibers by Chemical Pretreatment

In order to identify new sustainable sources for producing cellulose nanofibers (CNFs), fast-growing poplar (Populus alba L.) wood was evaluated herein. For that purpose, bleached poplar kraft pulp was produced and submitted to TEMPO (2,2,6,6-tetramethylpiperidine-1-oxyl radical) mediated oxidation (TEMPO-ox) chemical pretreatment followed by microfluidization. The resulting CNFs were thoroughly characterized, including a rheological study at different pH values. Poplar CNFs showed properties comparable to eucalypt CNFs (reference material for CNFs production), showing high carboxylate content (1048 ± 128 µmol g−1), fibrillation yield (87.3% ± 8.1%), optical transmittance (83% at 700 nm) and thermal stability (up to more than 200 °C). Regarding the rheological study, whereas pH from 4 to 10 did not produce significant changes in rheological behavior, a reduction of pH down to 1 led to an order-of-magnitude increase on the viscoelastic functions. Therefore, poplar CNF shows potential in the pH-sensitive hydrogels application field. Finally, the possible ecotoxicity of poplar CNF was assessed. The decrease in cell viability was very low so that only concentrations causing a 10% cytotoxicity could be calculated for the assay detecting alterations in cell metabolism (10 µg mL−1) and plasma membrane integrity (60 µg mL−1).

MANUFACTURING ASPECTS OF OFFSHORE FABRICATION AND INSTALLATION

The research presented in this paper aim at identifying research commonalities between shipbuilding, offshore fabrication practices and manufacturing. As part of an exploratory effort a literature review and a case study of two offshore structures projects were performed. Research concerning shipbuilding and offshore fabrication, together with literature from other industries in construction, larger engineering projects and traditional manufacturing was reviewed. The two offshore structures projects were analyzed by means of interviews and complemented by direct observations and document reviews. The study concludes that there are gaps in the research concerned with holistic perspectives on the fabrication and installation phases of shipbuilding and offshore projects. The number of actors involved in any project of this magnitude increase barriers and communication interfaces. The dynamic nature of these types of projects was also observed and the changeability should always be a accounted factor when dealing with projects of this sort. The interviews held as part of the verification of observed phenomena in literature was limited to two projects and a single company and actors perceptions. However the collected data served well in being complementary to the literature review. It could be the task of academia to patch the gaps for overall project success, in the cases where single industry actors simply cannot see the benefit or do not have the recourses to fill them themselves. This study combines findings from traditional manufacturing industries, shipbuilding, offshore structures fabrication and large engineering projects in general.

Improved Electrophile Design for Exquisite Covalent Molecule Selectivity

Covalent inhibitors continue to show therapeutic promise. However, off-target reactivity challenges the field. Extensive efforts have been exerted to solve this issue by varying the reactivity attributes of electrophilic warheads, with features such as reversibility or metabolic vulnerability. Here we report the development of a new approach to increase the selectivity of covalent probes and small molecule inhibitors that is independent of warhead reactivity features and can be used in concert with already-existing methods. Using the Bruton’s Tyrosine Kinase (BTK) inhibitor Ibrutinib scaffold for our proof-of-concept, we reasoned that increasing the steric bulk of fumarate-based electrophiles on Ibrutinib should improve selectivity via the steric exclusion of off-targets but ideally retain rates of cysteine reactivity comparable to that of an acrylamide. Using chemical proteomic techniques, we demonstrate that elaboration of the electrophile to a tert-Butyl (t-Bu) fumarate ester significantly decreases time-dependent off-target reactivity and abolishes time-independent off-target reactivity but retains BTK target engagement. While an alkyne-bearing probe analog of Ibrutinib has 247 protein targets, our t-Bu fumarate Ibrutinib probe analog has only 7 protein targets. Of these 7 targets, BTK is the only time-independent target. This 2-order-of-magnitude increase in selectivity is also conferred to the t-Bu inhibitor itself. By shotgun proteomics, we investigated the consequences of treatment with Ibrutinib and our t-Bu analog and discovered that only 8 proteins are downregulated in response to treatment with the t-Bu analog compared to 107 with Ibrutinib. Of these 8 proteins, 7 are also downregulated by Ibrutinib and a majority of these targets are associated with BTK biology. Taken together, these findings reveal a previously-unappreciated opportunity to increase cysteine-reactive covalent inhibitor selectivity through electrophilic structure optimization.

Improved Electrophile Design for Exquisite Covalent Molecule Selectivity

Covalent inhibitors continue to show therapeutic promise. However, off-target reactivity challenges the field. Extensive efforts have been exerted to solve this issue by varying the reactivity attributes of electrophilic warheads, with features such as reversibility or metabolic vulnerability. Here we report the development of a new approach to increase the selectivity of covalent probes and small molecule inhibitors that is independent of warhead reactivity features and can be used in concert with already-existing methods. Using the Bruton’s Tyrosine Kinase (BTK) inhibitor Ibrutinib scaffold for our proof-of-concept, we reasoned that increasing the steric bulk of fumarate-based electrophiles on Ibrutinib should improve selectivity via the steric exclusion of off-targets but ideally retain rates of cysteine reactivity comparable to that of an acrylamide. Using chemical proteomic techniques, we demonstrate that elaboration of the electrophile to a tert-Butyl (t-Bu) fumarate ester significantly decreases time-dependent off-target reactivity and abolishes time-independent off-target reactivity but retains BTK target engagement. While an alkyne-bearing probe analog of Ibrutinib has 247 protein targets, our t-Bu fumarate Ibrutinib probe analog has only 7 protein targets. Of these 7 targets, BTK is the only time-independent target. This 2-order-of-magnitude increase in selectivity is also conferred to the t-Bu inhibitor itself. By shotgun proteomics, we investigated the consequences of treatment with Ibrutinib and our t-Bu analog and discovered that only 8 proteins are downregulated in response to treatment with the t-Bu analog compared to 107 with Ibrutinib. Of these 8 proteins, 7 are also downregulated by Ibrutinib and a majority of these targets are associated with BTK biology. Taken together, these findings reveal a previously-unappreciated opportunity to increase cysteine-reactive covalent inhibitor selectivity through electrophilic structure optimization.

Regime Shift of Genome Size Crossing the Chasm of Eukaryogenesis

The origin of the nucleus remains a great mystery in life science, although nearly two centuries have passed since the discovery of nuclei. To date, studies of eukaryogenesis have focused largely on micro-evolutionary explanations. Here, we examined macro-patterns of C-values (the total amount of DNA within the haploid chromosome set of an organism) for over 110,000 species and the chromosome numbers for over 11,000 species and their potential links with the state of atmospheric oxidation over geological time. Eukaryogenesis was in sync with an over 2.5 order-of-magnitude increase in genome size from prokaryote to eukaryote, and also with a rapid rise of atmospheric oxidation, suggesting that eukaryogenesis would have resulted from a regime shift of genomes driven by the oxidation-driven complexification and structuralization (e.g. chromatin packing).

A biased MC for muon production for beam-dump experiments

The search for feebly-interacting new-physics particles in the MeV-GeV mass range often involves high-intensity beams dumped into thick heavy targets. The challenge of evaluating the expected backgrounds for these searches from first principles is limited by the CPU time needed to generate the shower induced by the primary beam. We present a Monte Carlo biasing method allowing a three orders of magnitude increase in the efficiency for the simulation of the muon production in a 400 GeV/c proton beam-dump setup. At the same time, this biasing method is maintaining nearly every feature of a simulation from first principles.

Precession-driven climate cycles and time scale prior to the Hirnantian glacial maximum

Paleozoic astrochronologies are limited by uncertainties in past astronomical configurations and the availability of complete stratigraphic sections with precise, independent age control. We show it is possible to reconstruct a robust Paleozoic ~104-yr-resolution astrochronology in the well-preserved and thick Upper Ordovician reference record of Anticosti Island (Canada). The clear imprint of astronomical cycles, including ~18 k.y. precession, potential obliquity, and short and long eccentricity, constrains the entire Vauréal Formation (~1 km thick) to only ~3 m.y. in total, representing ~10 times higher accumulation rates than previously suggested. This ~104 yr resolution represents an order of magnitude increase in the current standard temporal resolution for the Katian and even allows for the detection of sub-Milankovitch climate-scale variability. The loss of a clear precession signal in the uppermost Vauréal Formation might be related to contemporaneous global cooling prior to the Hirnantian glacial maximum as indicated by the δ18O record. Complementary to the study of cyclostratigraphy of longer and often simplified records, it is important to recognize stratigraphic hiatuses and complexities on the ~104 yr scale to achieve robust sub-eccentricity-scale Paleozoic astrochronologies.

Hydraulic transmissivity inferred from ice-sheet relaxation following Greenland supraglacial lake drainages

Surface meltwater reaching the base of the Greenland Ice Sheet transits through drainage networks, modulating the flow of the ice sheet. Dye and gas-tracing studies conducted in the western margin sector of the ice sheet have directly observed drainage efficiency to evolve seasonally along the drainage pathway. However, the local evolution of drainage systems further inland, where ice thicknesses exceed 1000 m, remains largely unknown. Here, we infer drainage system transmissivity based on surface uplift relaxation following rapid lake drainage events. Combining field observations of five lake drainage events with a mathematical model and laboratory experiments, we show that the surface uplift decreases exponentially with time, as the water in the blister formed beneath the drained lake permeates through the subglacial drainage system. This deflation obeys a universal relaxation law with a timescale that reveals hydraulic transmissivity and indicates a two-order-of-magnitude increase in subglacial transmissivity (from 0.8 ± 0.3 $${\rm{m}}{{\rm{m}}}^{3}$$ m m 3 to 215 ± 90.2 $${\rm{m}}{{\rm{m}}}^{3}$$ m m 3 ) as the melt season progresses, suggesting significant changes in basal hydrology beneath the lakes driven by seasonal meltwater input.

Approaching the motional ground state of a 10-kg object

The motion of a mechanical object, even a human-sized object, should be governed by the rules of quantum mechanics. Coaxing them into a quantum state is, however, difficult because the thermal environment masks any quantum signature of the object’s motion. The thermal environment also masks the effects of proposed modifications of quantum mechanics at large mass scales. We prepared the center-of-mass motion of a 10-kilogram mechanical oscillator in a state with an average phonon occupation of 10.8. The reduction in temperature, from room temperature to 77 nanokelvin, is commensurate with an 11 orders-of-magnitude suppression of quantum back-action by feedback and a 13 orders-of-magnitude increase in the mass of an object prepared close to its motional ground state. Our approach will enable the possibility of probing gravity on massive quantum systems.

Chlorodifluoromethane Hydrodechlorination on Carbon-Supported Pd-Pt Catalysts. Beneficial Effect of Catalyst Oxidation

Previously tested 2 wt % palladium-platinum catalysts supported on Norit activated carbon preheated to 1600 °C have been reinvestigated in CHFCl2 hydrodechlorination. An additionally adopted catalyst oxidation at 350–400 °C produced nearly an order of magnitude increase in the turnover frequency of Pd/C, from 4.1 × 10−4 to 2.63 × 10−3 s−1. This increase is not caused by changes in metal dispersion or possible decontamination of the Pd surface from superficial carbon, but rather by unlocking the active surface, originally inaccessible in metal particles tightly packed in the pores of carbon. Burning carbon from the pore walls attached to the metal changes the pore structure, providing easier access for the reactants to the entire palladium surface. Calcination of Pt/C and Pd-Pt/C catalysts results in much smaller evolution of catalytic activity than that observed for Pd/C. This shapes the relationship between turnover frequency (TOF) and alloy composition, which now does not confirm the Pd-Pt synergy invoked in the previous work. The absence of this synergy is confirmed by gradual regular changes in product selectivity, from 70 to 80% towards CH2F2 for Pd/C to almost 60% towards CH4 for Pt/C. The use of even higher-preheated carbon (1800 °C), completely free of micropores, results in a Pd/C catalyst that does not need to be oxidized to achieve high activity and excellent selectivity to CH2F2 (>90%).