Supplemental Material - Effects of Gamification on Motivations of Elementary School Students: An Action Research Field Experiment

Supplemental Material for Effects of Gamification on Motivations of Elementary School Students: An Action Research Field Experiment by Mohammed Mohammed, Amal Fatemah, and Lobna Hassan in Simulation & Gaming</p

Case study of a nearly zero energy building in Italian climatic conditions

The building sector is an important stakeholder in the energy and environmental scenario of any country. It continues to grow across the world due to factors such as population growth, and economic and infrastructure development. Within the European Union, buildings account for 40% of the total energy requirements and 30% of carbon dioxide emissions. The building sector is keen to improve its sustainability standards and also to help achieve the 20-20-20 targets set by the European Union. The present work aims to design a nearly zero energy sports gymnasium building in Calolziocorte, Italy. Various sustainability techniques are applied in an integrated design project approach using ECOTECT software to undertake the energy modelling exercise. Firstly, the base-case is modelled with conventional building materials and the total energy demand is calculated. Duly considering the local climatic conditions, sustainable materials are chosen for walls, the floor, the roof, and windows and a 38% reduction is noted in the total energy demand of the building compared to the base-case. The impact of louvers as a passive design technique has also been examined on the total energy demand of the building. The monthly load/discomfort analysis is undertaken for various individual functions inside the building to identify the critical areas that consume more energy. The monthly load/discomfort analysis is performed with the proposed materials and the air infiltration rate is improved through the building envelope and 63% reduction is noted in the total energy demand of the building compared to the base-case. A solar access analysis is conducted to understand the on-site energy production and then the building net energy demand is calculated, which is reduced to 90% compared to the base-case

Self-Running Liquid Metal Drops that Delaminate Metal Films at Record Velocities

This paper describes a new method to spontaneously accelerate droplets of liquid metal (eutectic gallium indium, EGaIn) to extremely fast velocities through a liquid medium and along predefined metallic paths. The droplet wets a thin metal trace (a film ∼100 nm thick, ∼ 1 mm wide) and generates a force that simultaneously delaminates the trace from the substrate (enhanced by spontaneous electrochemical reactions) while accelerating the droplet along the trace. The formation of a surface oxide on EGaIn prevents it from moving, but the use of an acidic medium or application of a reducing bias to the trace continuously removes the oxide skin to enable motion. The trace ultimately provides a sacrificial pathway for the metal and provides a mm-scale mimic to the templates used to guide molecular motors found in biology (e.g., actin filaments). The liquid metal can accelerate along linear, curved and U-shaped traces as well as uphill on surfaces inclined by 30 degrees. The droplets can accelerate through a viscous medium up to 180 mm/sec which is almost double the highest reported speed for self-running liquid metal droplets. The actuation of microscale objects found in nature (e.g., cells, microorganisms) inspires new mechanisms, such as these, to manipulate small objects. Droplets that are metallic may find additional applications in reconfigurable circuits, optics, heat transfer elements, and transient electronic circuits; the paper demonstrates the latter

Self-Running Liquid Metal Drops that Delaminate Metal Films at Record Velocities

This paper describes a new method to spontaneously accelerate droplets of liquid metal (eutectic gallium indium, EGaIn) to extremely fast velocities through a liquid medium and along predefined metallic paths. The droplet wets a thin metal trace (a film ∼100 nm thick, ∼ 1 mm wide) and generates a force that simultaneously delaminates the trace from the substrate (enhanced by spontaneous electrochemical reactions) while accelerating the droplet along the trace. The formation of a surface oxide on EGaIn prevents it from moving, but the use of an acidic medium or application of a reducing bias to the trace continuously removes the oxide skin to enable motion. The trace ultimately provides a sacrificial pathway for the metal and provides a mm-scale mimic to the templates used to guide molecular motors found in biology (e.g., actin filaments). The liquid metal can accelerate along linear, curved and U-shaped traces as well as uphill on surfaces inclined by 30 degrees. The droplets can accelerate through a viscous medium up to 180 mm/sec which is almost double the highest reported speed for self-running liquid metal droplets. The actuation of microscale objects found in nature (e.g., cells, microorganisms) inspires new mechanisms, such as these, to manipulate small objects. Droplets that are metallic may find additional applications in reconfigurable circuits, optics, heat transfer elements, and transient electronic circuits; the paper demonstrates the latter

Self-Running Liquid Metal Drops that Delaminate Metal Films at Record Velocities

This paper describes a new method to spontaneously accelerate droplets of liquid metal (eutectic gallium indium, EGaIn) to extremely fast velocities through a liquid medium and along predefined metallic paths. The droplet wets a thin metal trace (a film ∼100 nm thick, ∼ 1 mm wide) and generates a force that simultaneously delaminates the trace from the substrate (enhanced by spontaneous electrochemical reactions) while accelerating the droplet along the trace. The formation of a surface oxide on EGaIn prevents it from moving, but the use of an acidic medium or application of a reducing bias to the trace continuously removes the oxide skin to enable motion. The trace ultimately provides a sacrificial pathway for the metal and provides a mm-scale mimic to the templates used to guide molecular motors found in biology (e.g., actin filaments). The liquid metal can accelerate along linear, curved and U-shaped traces as well as uphill on surfaces inclined by 30 degrees. The droplets can accelerate through a viscous medium up to 180 mm/sec which is almost double the highest reported speed for self-running liquid metal droplets. The actuation of microscale objects found in nature (e.g., cells, microorganisms) inspires new mechanisms, such as these, to manipulate small objects. Droplets that are metallic may find additional applications in reconfigurable circuits, optics, heat transfer elements, and transient electronic circuits; the paper demonstrates the latter

Nanoparticle Formulation Derived from Carboxymethyl Cellulose, Polyethylene Glycol, and Cabazitaxel for Chemotherapy Delivery to the Brain

Nanoparticles provide a unique opportunity to explore the benefits of selective distribution and release of cancer therapeutics at sites of disease through varying particle sizes and compositions that exploit the enhanced permeability of tumor-associated blood vessels. Though delivery of larger as opposed to smaller and/or actively transported molecules to the brain is <i>prima facie</i> a challenging endeavor, we wondered whether nanoparticles could improve the therapeutic index of existing drugs for use in treating brain tumors via these vascular effects. We therefore selected a family of nanoparticles composed of cabazitaxel–carboxymethyl cellulose amphiphilic polymers to investigate the potential for delivering a brain-penetrant taxane to intracranial brain tumors in mice. Among a small set of nanoparticle formulations, we found evidence for nanoparticle accumulation in the brain, and one such formulation demonstrated activity in an orthotopic model of glioma, suggesting that such nanoparticles could be useful for the treatment of glioma and brain metastases of other tumor types

Additional file 1: of Measurement of blood pressure for the diagnosis and management of hypertension in different ethnic groups: one size fits all

Diagnostic output of raw data at different BP thresholds. (DOCX 19 kb

Discovery of Nanomolar DCAF1 Small Molecule Ligands

DCAF1 is a substrate receptor of two distinct E3 ligases (CRL4DCAF1 and EDVP), plays a critical physiological role in protein degradation, and is considered a drug target for various cancers. Antagonists of DCAF1 could be used toward the development of therapeutics for cancers and viral treatments. We used the WDR domain of DCAF1 to screen a 114-billion-compound DNA encoded library (DEL) and identified candidate compounds using similarity search and machine learning. This led to the discovery of a compound (Z1391232269) with an SPR KD of 11 μM. Structure-guided hit optimization led to the discovery of OICR-8268 (26e) with an SPR KD of 38 nM and cellular target engagement with EC50 of 10 μM as measured by cellular thermal shift assay (CETSA). OICR-8268 is an excellent tool compound to enable the development of next-generation DCAF1 ligands toward cancer therapeutics, further investigation of DCAF1 functions in cells, and the development of DCAF1-based PROTACs

Discovery of OICR12694: A Novel, Potent, Selective, and Orally Bioavailable BCL6 BTB Inhibitor

B cell lymphoma 6 (BCL6), a highly regulated transcriptional repressor, is deregulated in several forms of non-Hodgkin lymphoma (NHL), most notably in diffuse large B-cell lymphoma (DLBCL). The activities of BCL6 are dependent on protein–protein interactions with transcriptional co-repressors. To find new therapeutic interventions addressing the needs of patients with DLBCL, we initiated a program to identify BCL6 inhibitors that interfere with co-repressor binding. A virtual screen hit with binding activity in the high micromolar range was optimized by structure-guided methods, resulting in a novel and highly potent inhibitor series. Further optimization resulted in the lead candidate 58 (OICR12694/​JNJ-65234637), a BCL6 inhibitor with low nanomolar DLBCL cell growth inhibition and an excellent oral pharmacokinetic profile. Based on its overall favorable preclinical profile, OICR12694 is a highly potent, orally bioavailable candidate for testing BCL6 inhibition in DLBCL and other neoplasms, particularly in combination with other therapies

Discovery of Nanomolar DCAF1 Small Molecule Ligands

DCAF1 is a substrate receptor of two distinct E3 ligases (CRL4DCAF1 and EDVP), plays a critical physiological role in protein degradation, and is considered a drug target for various cancers. Antagonists of DCAF1 could be used toward the development of therapeutics for cancers and viral treatments. We used the WDR domain of DCAF1 to screen a 114-billion-compound DNA encoded library (DEL) and identified candidate compounds using similarity search and machine learning. This led to the discovery of a compound (Z1391232269) with an SPR KD of 11 μM. Structure-guided hit optimization led to the discovery of OICR-8268 (26e) with an SPR KD of 38 nM and cellular target engagement with EC50 of 10 μM as measured by cellular thermal shift assay (CETSA). OICR-8268 is an excellent tool compound to enable the development of next-generation DCAF1 ligands toward cancer therapeutics, further investigation of DCAF1 functions in cells, and the development of DCAF1-based PROTACs