Fluctuations in pedestrian dynamics routing choices.

Routing choices of walking pedestrians in geometrically complex environments are regulated by the interplay of a multitude of factors such as local crowding, (estimated) time to destination, and (perceived) comfort. As individual choices combine, macroscopic traffic flow patterns emerge. Understanding the physical mechanisms yielding macroscopic traffic distributions in environments with complex geometries is an outstanding scientific challenge, with implications in the design and management of crowded pedestrian facilities. In this work, we analyze, by means of extensive real-life pedestrian tracking data, unidirectional flow dynamics in an asymmetric setting, as a prototype for many common complex geometries. Our environment is composed of a main walkway and a slightly longer detour. Our measurements have been collected during a dedicated high-accuracy pedestrian tracking campaign held in Eindhoven (The Netherlands). We show that the dynamics can be quantitatively modeled by introducing a collective discomfort function, and that fluctuations on the behavior of single individuals are crucial to correctly recover the global statistical behavior. Notably, the observed traffic split substantially departs from an optimal, transport-wise, partition, as the global pedestrian throughput is not maximized.

Electrochemical Reactivity and Passivation of Silicon Thin-Film Electrodes in Organic Carbonate Electrolytes.

This work focuses on the mechanisms of interfacial processes at the surface of amorphous silicon thin-film electrodes in organic carbonate electrolytes to unveil the origins of the inherent nonpassivating behavior of silicon anodes in Li-ion batteries. Attenuated total reflection Fourier-transform infrared spectroscopy, X-ray absorption spectroscopy, and infrared near-field scanning optical microscopy were used to investigate the formation, evolution, and chemical composition of the surface layer formed on Si upon cycling. We found that the chemical composition and thickness of the solid/electrolyte interphase (SEI) layer continuously change during the charging/discharging cycles. This SEI layer "breathing" effect is directly related to the formation of lithium ethylene dicarbonate (LiEDC) and LiPF6 salt decomposition products during silicon lithiation and their subsequent disappearance upon delithiation. The detected appearance and disappearance of LiEDC and LiPF6 decomposition compounds in the SEI layer are directly linked with the observed interfacial instability and poor passivating behavior of the silicon anode.

Relationship Between Evaluations of Tracheal Tube Position Using Ultrasound and Fluoroscopy in an Infant and Pediatric Population.

INTRODUCTION: A non-radiographic technique to measure the location of the tracheal tube (TT) in children is of value given the risk of inappropriate TT placement along with concerns about radiation exposure. Airway point-of-care ultrasound (POCUS) has demonstrated utility in children, but the examinations vary by age and may require non-traditional techniques or utilize less common probes. This study evaluated the performance of measuring the tracheal location of the cuffed TT using a novel, linear probe-based POCUS examination over a wide age range of children. After adjusting for the subjects' height and TT size, ultrasound measurements of the TT cuff location were compared with fluoroscopy measurements of the TT tip location. METHODS: Perioperative pediatric patients (<10 years) requiring a cuffed TT were enrolled. After routine TT placement, ultrasound and fluoroscopy images were obtained. Measurements from the TT cuff to the cricoid cartilage were obtained from the POCUS examination. Chest fluoroscopy was reviewed to measure the TT's distance from the carina. Both measurements were then compared after scaling for patient height. The duration of the ultrasound examination and image quality scores were also recorded. RESULTS: Forty-one patients were enrolled, with a median age of 3 (25th/75th percentile: 1.50/7.00) years. The POCUS examination identified the TT cuff in all cases with the highest image quality score. The median POCUS exam time was 112 (25th/75th percentile: 80.00/156.00) seconds. There was a strong correlation between the POCUS measurements and the fluoroscopy measurements, r = -0.7575, 95% CI [-0.8638, -0.5866 ], p < 0.001). CONCLUSIONS: Our results demonstrate a strong correlation between POCUS TT localization measurements and traditional measurements via fluoroscopy. This study further supports the utility of POCUS for pediatric care.

Revealing In Situ Li Metal Anode Surface Evolution upon Exposure to CO2 Using Ambient Pressure X-Ray Photoelectron Spectroscopy.

Because they deliver outstanding energy density, next-generation lithium metal batteries (LMBs) are essential to the advancement of both electric mobility and portable electronic devices. However, the high reactivity of metallic lithium surfaces leads to the low electrochemical performance of many secondary batteries. Besides, Li deposition is not uniform, which has been attributed to the low ionic conductivity of the anode surface. In particular, lithium exposure to CO2 gas is considered detrimental due to the formation of carbonate on the solid electrolyte interphase (SEI). In this work, we explored the interaction of Li metal with CO2 gas as a function of time using ambient pressure X-ray photoelectron spectroscopy to clarify the reaction pathway and main intermediates involved in the process during which oxalate formation has been detected. Furthermore, when O2 gas is part of the surrounding environment with CO2 gas, the reaction pathway is bypassed to directly promote carbonate as a single product.

Aqueous copper bioavailability linked to shipwreck-contaminated reef sediments.

Pollution from the grounding or sinking of ships can have long lasting effects on the recovery and dynamics of coastal ecosystems. Research on the impact of copper (Cu) pollution from the 2011 MV Rena shipwreck at the Astrolabe Reef (Otaiti), New Zealand, 5 years after the grounding, followed a multi-method and multi-disciplinary approach. Three independent measures of aqueous Cu using trace-element-clean-techniques substantiate the presence of high total, total dissolved (<2 µm) and elevated bioavailable Cu in the water column immediately above the aft section of the wreck where the highest sedimentary load of Cu was located. Intermittently elevated concentrations of strong Cu-binding ligands occurred in this location, and their binding strength was consistent with ligands actively produced by organisms in response to Cu induced stress. The recruitment of benthic invertebrates was modified at the high-Cu location. Taxonomic groups usually considered robust to pollution were restricted to this site (e.g. barnacles) or were the most abundant taxa present (e.g. foraminifera). Our results demonstrate that Cu-contaminated sediments can impose a persistent point source of Cu pollution in high-energy reef environments, with the potential to modify the composition and recovery of biological communities.

Historical translocations by Maori may explain the distribution and genetic structure of a threatened surf clam in Aotearoa (New Zealand).

The population genetic structure of toheroa (Paphies ventricosa), an Aotearoa (New Zealand) endemic surf clam, was assessed to determine levels of inter-population connectivity and test hypotheses regarding life history, habitat distribution and connectivity in coastal vs. estuarine taxa. Ninety-eight toheroa from populations across the length of New Zealand were sequenced for the mitochondrial cytochrome c oxidase I gene with analyses suggesting a population genetic structure unique among New Zealand marine invertebrates. Toheroa genetic diversity was high in Te Ika-a Maui (the North Island of New Zealand) but completely lacking in the south of Te Waipounamu (the South Island), an indication of recent isolation. Changes in habitat availability, long distance dispersal events or translocation of toheroa to southern New Zealand by Maori could explain the observed geographic distribution of toheroa and their genetic diversity. Given that early-Maori and their ancestors, were adept at food cultivation and relocation, the toheroa translocation hypothesis is plausible and may explain the disjointed modern distribution of this species. Translocation would also explain the limited success in restoring what may in some cases be ecologically isolated populations located outside their natural distributions and preferred niches.

Observing the Electrochemical Oxidation of Co Metal at the Solid/Liquid Interface Using Ambient Pressure X-ray Photoelectron Spectroscopy.

Recent advances of ambient pressure X-ray photoelectron spectroscopy (AP-XPS) have enabled the chemical composition and the electrical potential profile at a liquid/electrode interface under electrochemical reaction conditions to be directly probed. In this work, we apply this operando technique to study the surface chemical composition evolution on a Co metal electrode in 0.1 M KOH aqueous solution under various electrical biases. It is found that an ∼12.2 nm-thick layer of Co(OH)2 forms at a potential of about -0.4 VAg/AgCl, and upon increasing the anodic potential to about +0.4 VAg/AgCl, this layer is partially oxidized into cobalt oxyhydroxide (CoOOH). A CoOOH/Co(OH)2 mixture layer is formed on the top of the electrode surface. Finally, the oxidized surface layer can be reduced to Co0 at a cathodic potential of -1.35 VAg/Cl. These observations indicate that the ultrathin layer containing cobalt oxyhydroxide is the active phase for oxygen evolution reaction (OER) on a Co electrode in an alkaline electrolyte, consistent with previous studies.

Probing the Surface of Platinum during the Hydrogen Evolution Reaction in Alkaline Electrolyte.

Understanding the surface chemistry of electrocatalysts in operando can bring insight into the reaction mechanism, and ultimately the design of more efficient materials for sustainable energy storage and conversion. Recent progress in synchrotron based X-ray spectroscopies for in operando characterization allows us to probe the solid/liquid interface directly while applying an external potential, applied here to the model system of Pt in alkaline electrolyte for the hydrogen evolution reaction (HER). We employ ambient pressure X-ray photoelectron spectroscopy (AP-XPS) to identify the oxidation and reduction of Pt-oxides and hydroxides on the surface as a function of applied potential, and further assess the potential for hydrogen adsorption and absorption (hydride formation) during and after the HER. This new window into the surface chemistry of Pt in alkaline electrolyte brings insight into the nature of the rate limiting step, the extent of H ad/absorption, and its persistence at more anodic potentials.

Chemical states of surface oxygen during CO oxidation on Pt(1 1 0) surface revealed by ambient pressure XPS.

The study of CO oxidation on Pt(1 1 0) surface is revisited using ambient pressure x-ray photoemission spectroscopy. When the surface temperature reaches the activation temperature for CO oxidation under elevated pressure conditions, both the α-phase of PtO2 oxide and chemisorbed oxygen are formed simultaneously on the surface. Due to the exothermic nature of CO oxidation, the temperature of the Pt surface increases as CO oxidation takes place. As the CO/O2 ratio increases, the production of CO2 increases continuously and the surface temperature also increases. Interestingly, within the diffusion limited regions, the amount of surface oxide changes little while the chemisorbed oxygen is reduced.

Direct Mapping of Band Positions in Doped and Undoped Hematite during Photoelectrochemical Water Splitting.

Photoelectrochemical water splitting is a promising pathway for the direct conversion of renewable solar energy to easy to store and use chemical energy. The performance of a photoelectrochemical device is determined in large part by the heterogeneous interface between the photoanode and the electrolyte, which we here characterize directly under operating conditions using interface-specific probes. Utilizing X-ray photoelectron spectroscopy as a noncontact probe of local electrical potentials, we demonstrate direct measurements of the band alignment at the semiconductor/electrolyte interface of an operating hematite/KOH photoelectrochemical cell as a function of solar illumination, applied potential, and doping. We provide evidence for the absence of in-gap states in this system, which is contrary to previous measurements using indirect methods, and give a comprehensive description of shifts in the band positions and limiting processes during the photoelectrochemical reaction.

Long-term, high frequency in situ measurements of intertidal mussel bed temperatures using biomimetic sensors.

At a proximal level, the physiological impacts of global climate change on ectothermic organisms are manifest as changes in body temperatures. Especially for plants and animals exposed to direct solar radiation, body temperatures can be substantially different from air temperatures. We deployed biomimetic sensors that approximate the thermal characteristics of intertidal mussels at 71 sites worldwide, from 1998-present. Loggers recorded temperatures at 10-30 min intervals nearly continuously at multiple intertidal elevations. Comparisons against direct measurements of mussel tissue temperature indicated errors of ~2.0-2.5 °C, during daily fluctuations that often exceeded 15°-20 °C. Geographic patterns in thermal stress based on biomimetic logger measurements were generally far more complex than anticipated based only on 'habitat-level' measurements of air or sea surface temperature. This unique data set provides an opportunity to link physiological measurements with spatially- and temporally-explicit field observations of body temperature.

Unravelling the electrochemical double layer by direct probing of the solid/liquid interface.

The electrochemical double layer plays a critical role in electrochemical processes. Whilst there have been many theoretical models predicting structural and electrical organization of the electrochemical double layer, the experimental verification of these models has been challenging due to the limitations of available experimental techniques. The induced potential drop in the electrolyte has never been directly observed and verified experimentally, to the best of our knowledge. In this study, we report the direct probing of the potential drop as well as the potential of zero charge by means of ambient pressure X-ray photoelectron spectroscopy performed under polarization conditions. By analyzing the spectra of the solvent (water) and a spectator neutral molecule with numerical simulations of the electric field, we discern the shape of the electrochemical double layer profile. In addition, we determine how the electrochemical double layer changes as a function of both the electrolyte concentration and applied potential.

Failure mechanisms of single-crystal silicon electrodes in lithium-ion batteries.

Long-term durability is a major obstacle limiting the widespread use of lithium-ion batteries in heavy-duty applications and others demanding extended lifetime. As one of the root causes of the degradation of battery performance, the electrode failure mechanisms are still unknown. In this paper, we reveal the fundamental fracture mechanisms of single-crystal silicon electrodes over extended lithiation/delithiation cycles, using electrochemical testing, microstructure characterization, fracture mechanics and finite element analysis. Anisotropic lithium invasion causes crack initiation perpendicular to the electrode surface, followed by growth through the electrode thickness. The low fracture energy of the lithiated/unlithiated silicon interface provides a weak microstructural path for crack deflection, accounting for the crack patterns and delamination observed after repeated cycling. On the basis of this physical understanding, we demonstrate how electrolyte additives can heal electrode cracks and provide strategies to enhance the fracture resistance in future lithium-ion batteries from surface chemical, electrochemical and material science perspectives.

Physical and Chemical Stability of Antibody Drug Conjugates: Current Status.

Antibody drug conjugates (ADCs) are an emerging class of chemotherapeutic cancer treatment agents that combine the targeting specificity of antibodies with the efficient cell-killing potential of cytotoxic drugs. Unlike their protein and small-molecule therapeutic counterparts, the stability and degradation properties of ADCs are relatively unknown. Theoretically, ADC stability could be governed by properties and processes stemming from both the antibody and the linker-toxin chemistry. Recently, systematic studies of intrinsic ADC molecule stability have been presented in the primary literature. As there are burgeoning industrial and academic efforts aimed at developing optimized conjugation chemistries and antibody engineering approaches for next-generation ADCs, it is important to capture the current state of understanding of ADC stability. In this minireview, we discuss aspects of physical and chemical stability of ADCs gathered from a survey of the literature and illustrate how investigations into stability enable the development of more effective ADC molecules for the future.

In Situ Potentiodynamic Analysis of the Electrolyte/Silicon Electrodes Interface Reactions--A Sum Frequency Generation Vibrational Spectroscopy Study.

The key factor in long-term use of batteries is the formation of an electrically insulating solid layer that allows lithium ion transport but stops further electrolyte redox reactions on the electrode surface, hence solid electrolyte interphase (SEI). We have studied a common electrolyte, 1.0 M LiPF6/ethylene carbonate (EC)/diethyl carbonate (DEC), reduction products on crystalline silicon (Si) electrodes in a lithium (Li) half-cell system under reaction conditions. We employed in situ sum frequency generation vibrational spectroscopy (SFG-VS) with interface sensitivity in order to probe the molecular composition of the SEI surface species under various applied potentials where electrolyte reduction is expected. We found that, with a Si(100)-hydrogen terminated wafer, a Si-ethoxy (Si-OC2H5) surface intermediate forms due to DEC decomposition. Our results suggest that the SEI surface composition varies depending on the termination of Si surface, i.e., the acidity of the Si surface. We provide the evidence of specific chemical composition of the SEI on the anode surface under reaction conditions. This supports an electrochemical electrolyte reduction mechanism in which the reduction of the DEC molecule to an ethoxy moiety plays a key role. These findings shed new light on the formation mechanism of SEI on Si anodes in particular and on SEI formation in general.

Crystal structure of A. aeolicus LpxC with bound product suggests alternate deacetylation mechanism.

UDP-3-O-acyl-N-acetylglucosamine deacetylase (LpxC) is the first committed step to form lipid A, an essential component of the outer membrane of Gram-negative bacteria. As it is essential for the survival of many pathogens, LpxC is an attractive target for antibacterial therapeutics. Herein, we report the product-bound co-crystal structure of LpxC from the acheal Aquifex aeolicus solved to 1.6 Å resolution. We identified interactions by hydroxyl and hydroxymethyl substituents of the product glucosamine ring that may enable new insights to exploit waters in the active site for structure-based design of LpxC inhibitors with novel scaffolds. By using this product structure, we have performed quantum mechanical modeling on the substrate in the active site. Based on our results and published experimental data, we propose a new mechanism that may lead to a better understanding of LpxC catalysis and inhibition.

Translating slow-binding inhibition kinetics into cellular and in vivo effects.

Many drug candidates fail in clinical trials owing to a lack of efficacy from limited target engagement or an insufficient therapeutic index. Minimizing off-target effects while retaining the desired pharmacodynamic (PD) response can be achieved by reduced exposure for drugs that display kinetic selectivity in which the drug-target complex has a longer half-life than off-target-drug complexes. However, though slow-binding inhibition kinetics are a key feature of many marketed drugs, prospective tools that integrate drug-target residence time into predictions of drug efficacy are lacking, hindering the integration of drug-target kinetics into the drug discovery cascade. Here we describe a mechanistic PD model that includes drug-target kinetic parameters, including the on- and off-rates for the formation and breakdown of the drug-target complex. We demonstrate the utility of this model by using it to predict dose response curves for inhibitors of the LpxC enzyme from Pseudomonas aeruginosa in an animal model of infection.

A catalytic path for electrolyte reduction in lithium-ion cells revealed by in situ attenuated total reflection-Fourier transform infrared spectroscopy.

Although controlling the interfacial chemistry of electrodes in Li-ion batteries (LIBs) is crucial for maintaining the reversibility, electrolyte decomposition has not been fully understood. In this study, electrolyte decomposition on model electrode surfaces (Au and Sn) was investigated by in situ attenuated total reflection-Fourier transform infrared (ATR-FTIR) spectroscopy. Simultaneously obtained ATR-FTIR spectra and cyclic voltammetry measurements show that lithium ethylene dicarbonate and lithium propionate form on the Au electrode at 0.6 V, whereas diethyl 2,5-dioxahexane dicarboxylate and lithium propionate form on the Sn electrode surface at 1.25 V. A noncatalytic reduction path on the Au surface and a catalytic reduction path on the Sn surface are introduced to explain the surface dependence of the overpotential and product selectivity. This represents a new concept for explaining electrolyte reactions on the anode of LIBs. The present investigation shows that catalysis plays a dominant role in the electrolyte decomposition process and has important implications in electrode surface modification and electrolyte recipe selection, which are critical factors for enhancing the efficiency, durability, and reliability of LIBs.

A phase I trial of AT9283 (a selective inhibitor of aurora kinases) in children and adolescents with solid tumors: a Cancer Research UK study.

PURPOSE: A phase I trial of AT9283 (a multitargeted inhibitor of Aurora kinases A and B) was conducted in children and adolescents with solid tumors, to identify maximum-tolerated dose (MTD), safety, efficacy, pharmacokinetics, and pharmacodynamic (PD) activity. EXPERIMENTAL DESIGN: AT9283 was administered as a 72-hour continuous intravenous infusion every 3 weeks. A rolling-six design, explored six dose levels (7, 9, 11.5, 14.5, 18.5, and 23 mg/m(2)/d). Pharmacokinetic and PD assessments, included inhibition of phospho-histone 3 (pHH3) in paired skin punch biopsies. RESULTS: Thirty-three patients were evaluable for toxicity. There were six dose-limiting toxicities and the MTD was 18.5 mg/m(2)/d. Most common drug-related toxicities were hematologic (neutropenia, anemia, and thrombocytopenia in 36.4%, 18.2%, and 21.2% of patients), which were grade ≥3 in 30.3%, 6.1%, and 3% of patients. Nonhematologic toxicities included fatigue, infections, febrile neutropenia and ALT elevation. One patient with central nervous system-primitive neuroectodermal tumor (CNS-PNET) achieved a partial response after 16 cycles and 3 cases were stable for four or more cycles. Plasma concentrations were comparable with those in adults at the same dose level, clearance was similar although half-life was shorter (4.9 ± 1.5 hours, compared with 8.4 ± 3.7 hours in adults). Inhibition of Aurora kinase B was shown by reduction in pHH3 in 17 of 18 patients treated at ≥11.5 mg/m(2)/d. CONCLUSION: AT9283 was well tolerated in children and adolescents with solid tumors with manageable hematologic toxicity. Target inhibition was demonstrated. Disease stabilization was documented in intracranial and extracranial pediatric solid tumors and a phase II dose determined.

Synthesis, Structure, and SAR of Tetrahydropyran-Based LpxC Inhibitors.

In the search for novel Gram-negative agents, we performed a comprehensive search of the AstraZeneca collection and identified a tetrahydropyran-based matrix metalloprotease (MMP) inhibitor that demonstrated nanomolar inhibition of UDP-3-O-(acyl)-N-acetylglucosamine deacetylase (LpxC). Crystallographic studies in Aquifex aeolicus LpxC indicated the tetrahydropyran engaged in the same hydrogen bonds and van der Waals interactions as other known inhibitors. Systematic optimization of three locales on the scaffold provided compounds with improved Gram-negative activity. However, the optimization of LpxC activity was not accompanied by reduced inhibition of MMPs. Comparison of the crystal structure of the native product, UDP-3-O-(acyl)-glucosamine, in Aquifex aeolicus to the structure of a tetrahydropyran-based inhibitor indicates pathways for future optimization.