Direct instrumental identification of catalytically active surface sites.

The activity of heterogeneous catalysts-which are involved in some 80 per cent of processes in the chemical and energy industries-is determined by the electronic structure of specific surface sites that offer optimal binding of reaction intermediates. Directly identifying and monitoring these sites during a reaction should therefore provide insight that might aid the targeted development of heterogeneous catalysts and electrocatalysts (those that participate in electrochemical reactions) for practical applications. The invention of the scanning tunnelling microscope (STM) and the electrochemical STM promised to deliver such imaging capabilities, and both have indeed contributed greatly to our atomistic understanding of heterogeneous catalysis. But although the STM has been used to probe and initiate surface reactions, and has even enabled local measurements of reactivity in some systems, it is not generally thought to be suited to the direct identification of catalytically active surface sites under reaction conditions. Here we demonstrate, however, that common STMs can readily map the catalytic activity of surfaces with high spatial resolution: we show that by monitoring relative changes in the tunnelling current noise, active sites can be distinguished in an almost quantitative fashion according to their ability to catalyse the hydrogen-evolution reaction or the oxygen-reduction reaction. These data allow us to evaluate directly the importance and relative contribution to overall catalyst activity of different defects and sites at the boundaries between two materials. With its ability to deliver such information and its ready applicability to different systems, we anticipate that our method will aid the rational design of heterogeneous catalysts.

In Situ Monitoring of the Surface Evolution of a Silver Electrode from Polycrystalline to Well-Defined Structures.

Capturing the surface-structural dynamics of metal electrocatalysts under certain electrochemical environments is intriguingly desired for understanding the behavior of various metal-based electrocatalysts. However, in situ monitoring of the evolution of a polycrystalline metal surface at the interface of electrode-electrolyte solutions at negative/positive potentials with high-resolution scanning tunneling microscopy (STM) is seldom. Here, we use electrochemical STM (EC-STM) for in situ monitoring of the surface evolution process of a silver electrode in both an aqueous sodium hydroxide solution and an ionic liquid of 1-methyl-1-octylpyrrolidinium bis(trifluoromethylsulfonyl) amide driven by negative potentials. We found silver underwent a surface change from a polycrystalline structure to a well-defined surface arrangement in both electrolytes. In NaOH aqueous solution, the silver surface transferred in several minutes at a turning-point potential where hydrogen adsorbed and formed mainly (111) and (100) pits. Controversially, the surface evolution in the ionic liquid was much slower than that in the aqueous solution, and cation adsorption was observed in a wide potential range. The surface evolution of silver is proposed to be linked to the surface adsorbates as well as the formation of their complexes with undercoordinated silver atoms. The results also show that cathodic annealing of polycrystalline silver is a cheap, easy, and reliable way to obtain quasi-ordered crystal surfaces.

Probability of Success and Timelines for the Development of Vaccines for Emerging and Reemerged Viral Infectious Diseases.

BACKGROUND: Anticipated success rates and timelines for COVID-19 vaccine development vary. Recent experience with developing and testing viral vaccine candidates can inform expectations regarding the development of safe and effective vaccines. OBJECTIVE: To estimate timelines and probabilities of success for recent vaccine candidates. DESIGN: ClinicalTrials.gov was searched to identify trials testing viral vaccines that had not advanced to phase 2 before 2005, and the progress of each vaccine from phase 1 through to U.S. Food and Drug Administration (FDA) licensure was tracked. Trial characteristics were double-coded. (Registration: Open Science Framework [https://osf.io/dmuzx/]). SETTING: Trials launched between January 2005 and March 2020. PARTICIPANTS: Preventive viral vaccine candidates for 23 emerging or reemerged viral infectious diseases. MEASUREMENTS: The primary end point was the probability of vaccines advancing from launch of phase 2 to FDA licensure within 10 years. RESULTS: In total, 606 clinical trials forming 220 distinct development trajectories (267 343 enrolled participants) were identified. The probability of vaccines progressing from phase 2 to licensure within 10 years was 10.0% (95% CI, 2.6% to 16.9%), with most approvals representing H1N1 or H5N1 vaccines. The average timeline from phase 2 to approval was 4.4 years (range, 6.4 weeks to 13.9 years). The probabilities of advancing from phase 1 to 2, phase 2 to 3, and phase 3 to licensure within the total available follow-up time were 38.2% (CI, 30.7% to 45.0%), 38.3% (CI, 23.1% to 50.5%), and 61.1% (CI, 3.7% to 84.3%), respectively. LIMITATIONS: The study did not account for preclinical development and relied primarily on ClinicalTrials.gov and FDA resources. Success probabilities do not capture the varied reasons why vaccines fail to advance to regulatory approval. CONCLUSION: Success probabilities and timelines varied widely across different vaccine types and diseases. If a SARS-CoV-2 vaccine is licensed within 18 months of the start of the pandemic, it will mark an unprecedented achievement for noninfluenza viral vaccine development. PRIMARY FUNDING SOURCE: McGill Interdisciplinary Initiative in Infection and Immunity (MI4) Emergency COVID-19 Research Funding program.

Long-term Cerec 3D chairside bridges milled from IPS e.max CAD LT blocks.

The experienced Cerec user can manufacture high-quality, esthetic anterior and posterior bridges from IPS e.max CAD in a manageable 3-hour chairside session. On the basis of over 8 years of experience, it can be said that these restorations are clinically very well proven, provided they are used within the range of recommended indications. Experimental retainer bridges with extensions can be seen as highly interesting alternatives, although more clinical data are required for further confirmation.

Oligonucleotide microarray chip for the quantification of MS2, ΦX174, and adenoviruses on the multiplex analysis platform MCR 3.

Pathogenic viruses are emerging contaminants in water which should be analyzed for water safety to preserve public health. A strategy was developed to quantify RNA and DNA viruses in parallel on chemiluminescence flow-through oligonucleotide microarrays. In order to show the proof of principle, bacteriophage MS2, ΦX174, and the human pathogenic adenovirus type 2 (hAdV2) were analyzed in spiked tap water samples on the analysis platform MCR 3. The chemiluminescence microarray imaging unit was equipped with a Peltier heater for a controlled heating of the flow cell. The efficiency and selectivity of DNA hybridization could be increased resulting in higher signal intensities and lower cross-reactivities of polymerase chain reaction (PCR) products from other viruses. The total analysis time for DNA/RNA extraction, cDNA synthesis for RNA viruses, polymerase chain reaction, single-strand separation, and oligonucleotide microarray analysis was performed in 4-4.5 h. The parallel quantification was possible in a concentration range of 9.6 × 10(5)-1.4 × 10(10) genomic units (GU)/mL for bacteriophage MS2, 1.4 × 10(5)-3.7 × 10(8) GU/mL for bacteriophage ΦX174, and 6.5 × 10(3)-1.2 × 10(5) for hAdV2, respectively, by using a measuring temperature of 40 °C. Detection limits could be calculated to 6.6 × 10(5) GU/mL for MS2, 5.3 × 10(3) GU/mL for ΦX174, and 1.5 × 10(2) GU/mL for hAdV2, respectively. Real samples of surface water and treated wastewater were tested. Generally, found concentrations of hAdV2, bacteriophage MS2, and ΦX174 were at the detection limit. Nevertheless, bacteriophages could be identified with similar results by means of quantitative PCR and oligonucleotide microarray analysis on the MCR 3.

Three-unit CAD/CAM-generated lithium disilicate FDPs after a mean observation time of 46 months.

OBJECTIVES: Lithium disilicate can easily be machined by CAM techniques in its metasilicate status. Due to slightly inferior material properties, the material is not yet recommended for three-unit fixed dental prosthesis (FDP) as it is the case for the press material up to the second bicuspid. Therefore, the aim of this clinical study was to evaluate the performance of CAD/CAM-fabricated lithium disilicate FDPs. MATERIALS AND METHODS: A total of 32 anterior and posterior FDPs were provided for 32 patients. Twelve FDPs were fabricated chair-side. The first recall took place 6 months after insertion and then annually. The FDPs were rated according to biological and technical complications. As failure, those events were defined, which led to the removal of a FDP. The failure-free (survival) rate and the complication-free rate were calculated according to Kaplan-Meier. RESULTS: After a mean observation time of 46 months (SD ± 8.4 months), three endodontic complications in two FDPs, two minor chippings, and one catastrophic fracture occurred. One FDP had to be removed due to persisting undefined complaints. Thus, the failure-free rate and the complication-free rate were revealed as 93 and 83 %, respectively. CONCLUSIONS: Despite the limited observation period, the results are promising, especially due to the fact that the fractured FDP did not fulfill the recommended connector dimensions. CLINICAL RELEVANCE: Inserted as a full-contour three-unit FDP within its indications, the CAD/CAM lithium disilicate ceramic offers an appropriate alternative to layered restorations.

Incidence and risk factors for recurrent Clostridioides difficile infection in pediatric at-risk groups in selected Pediatric Investigators Collaborative Network on Infections in Canada (PICNIC) hospitals.

OBJECTIVES: Incidence and risk factors for recurrent Clostridioides difficile infection (rCDI) are well established in adults, though data are lacking in pediatrics. We aimed to determine incidence of and risk factors for rCDI in pediatrics. METHODS: This retrospective cohort study of pediatric patients was conducted at 3 tertiary-care hospitals in Canada with laboratory-confirmed CDI between April 1, 2012, and March 31, 2017. rCDI was defined as an episode of CDI occurring 8 weeks or less from diagnostic test date of the primary episode. We used logistic regression to determine and quantify risk factors significantly associated with rCDI. RESULTS: In total, 286 patients were included in this study. The incidence proportion for rCDI was 12.9%. Among hospitalized patients, the incidence rate was estimated at 2.6 cases of rCDI per 1,000 hospital days at risk (95% confidence interval [CI], 1.7-3.9). Immunocompromised patients had higher incidence of rCDI (17.5%; P = .03) and higher odds of developing rCDI independently of antibiotic treatment given for the primary episode (odds ratio [OR], 2.31; 95% CI, 1.12-5.09). Treatment with vancomycin monotherapy did not show statistically significant protection from rCDI, independently of immunocompromised status (OR, 0.33; 95% CI, 0.05-1.15]). CONCLUSIONS: The identification of increased risk of rCDI in immunocompromised pediatric patients warrants further research into alternative therapies, prophylaxis, and prevention strategies to prevent recurrent disease burden within these groups. Treatment of the initial episode with vancomycin did not show statistically significant protection from rCDI.

RecHap: An Interactive Recommender System For Navigating a Large Number of Mid-Air Haptic Designs.

Designing haptics is a difficult task especially when the user attempts to design a sensation from scratch. In the fields of visual and audio design, designers often use a large library of examples for inspiration, supported by intelligent systems like recommender systems. In this work, we contribute a corpus of 10,000 mid-air haptic designs (500 hand-designed sensations augmented 20x to create 10,000), and we use it to investigate a novel method for both novice and experienced hapticians to use these examples in mid-air haptic design. The RecHap design tool uses a neural-network based recommendation system that suggests pre-existing examples by sampling various regions of an encoded latent space. The tool also provides a graphical user interface for designers to visualize the sensation in 3D view, select previous designs, and bookmark favourites, all while feeling designs in real-time. We conducted a user study with 12 participants suggesting that the tool enables people to quickly explore design ideas and experience them immediately. The design suggestions encouraged collaboration, expression, exploration, and enjoyment, which improved creativity support.

Dorsal stream contributions to perceptual asymmetries.

Neurologically normal individuals show a bias toward the left side of space, referred to as pseudoneglect due to its similarity to clinical hemispatial neglect. The left bias appears to be stronger in the lower visual field during free-viewing, which could result from preferential dorsal stream processing. The current experiments used modified greyscales tasks, incorporating motion and isoluminant color, to explore whether targeting dorsal or ventral stream processing influenced the strength of the left bias. It was expected that the left bias would be stronger on the motion task than on a task incorporating isoluminant color. In Study 1, similar left biases were observed during prolonged viewing for luminance, motion and red, but not green color. The unexpected finding of a leftward bias for red under prolonged viewing was replicated in Study 2. A leftward bias for motion was also evident during 150 ms viewing in Study 2. In Study 3, the left bias was not apparent when using a blue/yellow condition, suggesting the left bias for red under prolonged viewing was likely unique to red. Furthermore, the leftward bias for red disappeared under brief viewing conditions. It is suggested that dorsal stream processing likely underlies visual field differences in pseudoneglect.

Fusing spheroids to aligned µ-tissues in a heart-on-chip featuring oxygen sensing and electrical pacing capabilities.

Over the last decade, Organ-on-Chip (OoC) emerged as a promising technology for advanced in vitro models, recapitulating key physiological cues. OoC approaches tailored for cardiac tissue engineering resulted in a variety of platforms, some of which integrate stimulation or probing capabilities. Due to manual handling processes, however, a large-scale standardized and robust tissue generation, applicable in an industrial setting, is still out of reach. Here, we present a novel cell injection and tissue generation concept relying on spheroids, which can be produced in large quantities and uniform size from induced pluripotent stem cell-derived human cardiomyocytes. Hydrostatic flow transports and accumulates spheroids in dogbone-shaped tissue chambers, which subsequently fuse and form aligned, contracting cardiac muscle fibers. Furthermore, we demonstrate electrical stimulation capabilities by utilizing fluidic media connectors as electrodes and provide the blueprint of a low-cost, open-source, scriptable pulse generator. We report on a novel integration strategy of optical O2 sensor spots into resin-based microfluidic systems, enabling in situ determination of O2 partial pressures. Finally, a proof-of-concept demonstrating electrical stimulation combined with in situ monitoring of metabolic activity in cardiac tissues is provided. The developed system thus opens the door for advanced OoCs integrating biophysical stimulation as well as probing capabilities and serves as a blueprint for the facile and robust generation of high density microtissues in microfluidic modules amenable to scaling-up and automation.

Fourier Transform Infrared Spectroscopy for Assessing Structural and Enzymatic Reactivity Changes Induced during Feather Hydrolysis.

Chicken feathers are major byproducts of the livestock processing industry with high potential in the feed sector. In this study, we present a new approach using Fourier transform infrared (FTIR) spectroscopy to detect the structural changes of feather keratin and its availability for enzymatic hydrolysis (AEH) induced by the thermal pressure hydrolysis (TPH) process. Compared to time-consuming in vitro measurement techniques, the proposed method provides rapid information about the structural changes during TPH which enables quick adaptation of TPH conditions as the quality of the incoming feather changes. By analyzing the FTIR spectra of raw and processed feathers, it was found that AEH negatively relates to the ß-sheet content (represented by two IR peaks centered at 1635 and 1689 cm-1), while it positively relates to a new series of peaks centered around 1700 cm-1 appearing after the TPH process. The proposed FTIR technique provides a reliable and rapid approach to determine the digestibility indicated by AEH of the processed feather and may be used in process control and optimization.

Revealing the Nature of Active Sites on Pt-Gd and Pt-Pr Alloys during the Oxygen Reduction Reaction.

For large-scale applications of hydrogen fuel cells, the sluggish kinetics of the oxygen reduction reaction (ORR) have to be overcome. So far, only platinum (Pt)-group catalysts have shown adequate performance and stability. A well-known approach to increase the efficiency and decrease the Pt loading is to alloy Pt with other metals. Still, for catalyst optimization, the nature of the active sites is crucial. In this work, electrochemical scanning tunneling microscopy (EC-STM) is used to probe the ORR active areas on Pt5Gd and Pt5Pr in acidic media under reaction conditions. The technique detects localized fluctuations in the EC-STM signal, which indicates differences in the local activity. The in situ experiments, supported by coordination-activity plots based on density functional theory calculations, show that the compressed Pt-lanthanide (111) terraces contribute the most to the overall activity. Sites with higher coordination, as found at the bottom of step edges or concavities, remain relatively inactive. Sites of lower coordination, as found near the top of step edges, show higher activity, presumably due to an interplay of strain and steric hindrance effects. These findings should be vital in designing nanostructured Pt-lanthanide electrocatalysts.

Size-dependent electrocatalytic activity of gold nanoparticles on HOPG and highly boron-doped diamond surfaces.

Gold nanoparticles were prepared by electrochemical deposition on highly oriented pyrolytic graphite (HOPG) and boron-doped, epitaxial 100-oriented diamond layers. Using a potentiostatic double pulse technique, the average particle size was varied in the range from 5 nm to 30 nm in the case of HOPG as a support and between < 1 nm and 15 nm on diamond surfaces, while keeping the particle density constant. The distribution of particle sizes was very narrow, with standard deviations of around 20% on HOPG and around 30% on diamond. The electrocatalytic activity towards hydrogen evolution and oxygen reduction of these carbon supported gold nanoparticles in dependence of the particle sizes was investigated using cyclic voltammetry. For oxygen reduction the current density normalized to the gold surface (specific current density) increased for decreasing particle size. In contrast, the specific current density of hydrogen evolution showed no dependence on particle size. For both reactions, no effect of the different carbon supports on electrocatalytic activity was observed.

Facile Patterning of Thermoplastic Elastomers and Robust Bonding to Glass and Thermoplastics for Microfluidic Cell Culture and Organ-on-Chip.

The emergence and spread of microfluidics over the last decades relied almost exclusively on the elastomer polydimethylsiloxane (PDMS). The main reason for the success of PDMS in the field of microfluidic research is its suitability for rapid prototyping and simple bonding methods. PDMS allows for precise microstructuring by replica molding and bonding to different substrates through various established strategies. However, large-scale production and commercialization efforts are hindered by the low scalability of PDMS-based chip fabrication and high material costs. Furthermore, fundamental limitations of PDMS, such as small molecule absorption and high water evaporation, have resulted in a shift toward PDMS-free systems. Thermoplastic elastomers (TPE) are a promising alternative, combining properties from both thermoplastic materials and elastomers. Here, we present a rapid and scalable fabrication method for microfluidic systems based on a polycarbonate (PC) and TPE hybrid material. Microstructured PC/TPE-hybrid modules are generated by hot embossing precise features into the TPE while simultaneously fusing the flexible TPE to a rigid thermoplastic layer through thermal fusion bonding. Compared to TPE alone, the resulting, more rigid composite material improves device handling while maintaining the key advantages of TPE. In a fast and simple process, the PC/TPE-hybrid can be bonded to several types of thermoplastics as well as glass substrates. The resulting bond strength withstands at least 7.5 bar of applied pressure, even after seven days of exposure to a high-temperature and humid environment, which makes the PC/TPE-hybrid suitable for most microfluidic applications. Furthermore, we demonstrate that the PC/TPE-hybrid features low absorption of small molecules while being biocompatible, making it a suitable material for microfluidic biotechnological applications.

Organ-on-a-disc: A platform technology for the centrifugal generation and culture of microphysiological 3D cell constructs amenable for automation and parallelization.

Organ-on-a-chip (OoC) systems have evolved to a promising alternative to animal testing and traditional cell assays in drug development and enable personalization for precision medicine. So far, most OoCs do not fully exploit the potential of microfluidic systems regarding parallelization and automation. To date, many OoCs still consist of individual units, integrating only one single tissue per chip, and rely on manual, error-prone handling. However, with limited parallelization and automation, OoCs remain a low-throughput technology, preventing their widespread application in industry. To advance the concept of microphysiological systems and to overcome the limitations of current OoCs, we developed the Organ-on-a-disc (Organ-Disc) technology. Driven only by rotation, Organ-Discs enable the parallelized generation and culture of multiple 3D cell constructs per disc. We fabricated polydimethylsiloxane-free Organ-Discs using thermoplastic materials and scalable fabrication techniques. Utilizing precisely controllable centrifugal forces, cells were loaded simultaneously into 20 tissue chambers, where they formed uniform cell pellets. Subsequently, the cells compacted into dense 3D cell constructs and were cultured under vasculature-like perfusion through pump- and tubing-free, centrifugal pumping, solely requiring a low-speed rotation (<1 g) of the Organ-Disc. Here, we provide a proof-of-concept of the Organ-Disc technology, showing the parallelized generation of tissue-like cell constructs and demonstrating the controlled centrifugal perfusion. Furthermore, Organ-Discs enable versatile tissue engineering, generating cell constructs with a customizable shape and a layered multi-cell type structure. Overall, the Organ-Disc provides a user-friendly platform technology for the parallelization and automation of microphysiological systems, bringing this technology one-step closer to high-throughput applications in industry.

How Do Novice Hapticians Design? A Case Study in Creating Haptic Learning Environments.

Access to haptic technology is on the rise, in smartphones, virtual reality gear, and open-source education kits. However, engineers and interaction designers are often inexperienced in designing with haptics, and rarely have tools and guidelines for creating multisensory experiences. To examine the impact of this deficit, we supplied a haptic design kit, custom software, and technical support to nine teams (25 students) for an innovation challenge at a major haptics conference. Teams (predominantly undergraduate engineers with little haptics, interaction design, or education training) designed and built haptic environments to support learning of science topics. Qualitative analysis of surveys, interviews, team blogs, and expert assessments of teams' final demonstrations exposed three themes in these design efforts. 1) Novice teams tended to ignore many of ten design choices that experts navigate, such as explicitly choosing whether haptic and graphic feedback should reinforce versus complement one other. 2) Their design activities differed in timing and inclusion from the ten activities observed in expert process. 3) We identified three success strategies in how teams devised useful and engaging interactions and interpretable multimodal experiences, and communicated about their designs. We compare novice and expert design needs and highlight where future haptic design tools and theory need to support novice practice and training.

Redox active donor-substituted punicin derivatives.

The redox active plant material punicin from Punica granatum, 2-hydroxy-1-(pyridinium-1-yl)-5-olate, and some derivatives were modified by substitution with 2-oxochromen-4-olate moieties to give donor-substituted molecules which form distinct types of atropisomeric mesomeric betaines and tetrapolar substances. Oxidation to new negatively-charged solvatochromic quinones was achieved on treatment of these betaines with CAN, taking advantage of the stabilizing properties of the electron-donating 2-oxochromen-4-olate partial structure. The quinones can be employed in model redox reactions. Cyclovoltametric studies have been performed.

User-Friendly and Parallelized Generation of Human Induced Pluripotent Stem Cell-Derived Microtissues in a Centrifugal Heart-on-a-Chip.

IMPACT STATEMENT: With the ultimate goal in tissue engineering of approaching in vivo functionality as closely as possible, organ-on-a-chip (OoC) systems provide unprecedented game-changing opportunities by enabling creation of perfused three-dimensional tissues. Most of the recently developed OoC systems, however, require complex handling steps. Hence, a large gap still exists between technology development and collection of valuable biological data in a standardized medium- or high-throughput manner. The system presented here bridges this gap by providing a user-friendly framework for the parallelized creation of multiple physiologically relevant tissues, which could be applicable in every laboratory without additional equipment.

Revealing the nature of active sites in electrocatalysis.

Heterogeneous electrocatalysis plays a central role in the development of sustainable, carbon-neutral pathways for energy provision and the production of various chemicals. It determines the overall efficiency of electrochemical devices that involve catalysis at the electrode/electrolyte interface. In this perspective, we discuss key aspects for the identification of active centers at the surface of electrocatalysts and important factors that influence them. The role of the surface structure, nanoparticle shape/size and the electrolyte composition in the resulting catalytic performance is of particular interest in this work. We highlight challenges that from our point of view need to be tackled, and provide guidelines for the design of "real life" electrocatalysts for renewable energy provision systems as well as for the production of industrially important compounds.

Revealing Active Sites for Hydrogen Evolution at Pt and Pd Atomic Layers on Au Surfaces.

Identification of the most active surface sites is one of the key tasks in the development of new electrocatalytic materials. This is in many cases both time and resource consuming due to methodological difficulties of in situ detection of centers of this kind. In this work, we use the recently developed approach based on the analysis of the tunneling current noise recorded by electrochemical scanning tunneling microscopy (n-ECSTM) to compare the nature of the most active hydrogen evolution catalytic sites in a system consisting of sub-monolayers of platinum on a Au substrate to the one of palladium on Au. Our n-ECSTM measurements performed under reaction conditions show that in striking contrast to Pd islands on gold, where the most active centers are located close to the boundary between Au and palladium atoms, all Pt ad-atoms contribute to the overall activity rather equally at pH 1. Methodological aspects related to the use of n-ECSTM in electrocatalytic research are also discussed.