Build-up Approach Research Articles

An Overview of Three-Dimensional Printing in Pharmaceutical Technology

Three-dimensional printing (3DP) in pharmaceutical technology is a new technique that can build the desired objects directly from CAD models using a layer-by-layer material build-up approach. This article presents an overview of the 3DP technique with a brief look into the history of the 3DP process and various methods like stereolithography, fused deposition method, hot melt extrusion, polyjet, etc., their merits and demerits, and applications of 3DP in pharmaceutical technology. The challenges 3DP has surmounted in the areas of pharmaceutical and biomedical research related to additive manufacturing are outlined in this review.. The use of 3DP has increased recently. Personalized medicine may now have access to a whole new range of options due to 3DP. The concept of specialists and researchers is to create customized oral pills using 3DP. Since technology is still developing, any regulations on security, safety, and privacy have yet to exist. Thus, these issues will be of more significant concern shortly. The applications of 3DP technologies in modern drug delivery are highlighted in this article, which expounds on using these technologies for forward-thinking advancements in pharmacy practice.

Computational design of serine hydrolases.

Enzymes that proceed through multistep reaction mechanisms often utilize complex, polar active sites positioned with sub-angstrom precision to mediate distinct chemical steps, which makes their de novo construction extremely challenging. We sought to overcome this challenge using the classic catalytic triad and oxyanion hole of serine hydrolases as a model system. We used RFdiffusion1 to generate proteins housing catalytic sites of increasing complexity and varying geometry, and a newly developed ensemble generation method called ChemNet to assess active site geometry and preorganization at each step of the reaction. Experimental characterization revealed novel serine hydrolases that catalyze ester hydrolysis with catalytic efficiencies (k cat /K m ) up to 3.8 x 103 M-1 s-1, closely match the design models (Cα RMSDs < 1 Å), and have folds distinct from natural serine hydrolases. In silico selection of designs based on active site preorganization across the reaction coordinate considerably increased success rates, enabling identification of new catalysts in screens of as few as 20 designs. Our de novo buildup approach provides insight into the geometric determinants of catalysis that complements what can be obtained from structural and mutational studies of native enzymes (in which catalytic group geometry and active site makeup cannot be so systematically varied), and provides a roadmap for the design of industrially relevant serine hydrolases and, more generally, for designing complex enzymes that catalyze multi-step transformations.

Aerodatabase Development and Integration and Mission Analysis of a Mach 2 Supersonic Civil Aircraft

The request for faster and greener civil aviation is urging the worldwide scientific community and aerospace industry to develop a new generation of supersonic aircraft, which are expected to be environmentally sustainable and to guarantee a high-level protection of citizens. A key aspect to monitor the potential environmental impact of new configurations is the aerodynamic efficiency and its impact onto the real mission. To pursue this goal, this paper discloses increasing-fidelity aerodynamic modeling approaches to improve the conceptual design of high-speed vehicles. The disclosed methodology foresees the development of aerodynamic aerodatabases by means of incremental steps starting from simplified methods (panels methods and/or low-fidelity CFD simulations) up to very reliable data based on high-fidelity CFD simulations and experimental measurements with associated confidence levels. This multifidelity approach enables the possibility of supporting the aircraft design process at different stages of its design cycle, from the estimation of preliminary aerodynamic coefficients at the beginning of the conceptual design, up to the development of tailored aerodatabases at advanced design phases. For each design stage, a build-up approach is adopted, starting from the investigation of the clean external configuration up to the complete one, including control surfaces’ effects and, if any, the effects of the integration of the propulsive effects. In addition, the applicability of the approach is guaranteed for a wide range of supersonic and hypersonic aircraft, and the developed methodology is here applied to the characterization of Mach 2 aircraft configuration, a relevant case study of the H2020 MORE&amp;LESS project.

Aerodynamic Appraisal of the VEGA-C Launcher

In the framework of the VEGA Consolidation and Evolution Preparation Program, carried out by the European Space Agency to develop the VEGA-C launcher, several aerodynamic design activities have been performed with the help of both numerical and experimental campaigns. The results of those design efforts contributed to the definition of the launcher aerodynamic database, necessary to feed flight mechanics and vehicle performance characterizations. Launcher aerodynamic database is obtained by means of a buildup approach that exploits several contributions ranging from engineering judgments, flowfield numerical analyses, and wind tunnel tests. The final aerodynamic database has been also provided with suitable uncertainty models to assure reliable estimations of the launcher aerodynamic coefficients in the ranges of Mach, altitude, and attitude, expected for the vehicle along with the ascent flight. In this paper, the final aerodatabase and the whole building process are presented and discussed in detail. Finally, comparisons between wind tunnel data and results of flowfield simulations are also shown, together with extrapolation to flight judgments to accommodate for the Reynolds number effects. Result comparisons highlight that numerical and experimental data compare rather well, thus confirming the reliability of the present design efforts.

Fatigue of short carbon fiber reinforced PEEK under compression: Influence of the load ratio and predictions from heat buildup measurements

AbstractFew works investigate the fatigue of short fiber reinforced thermoplastics under cyclic compression. Furthermore, the heat buildup approach to quickly predict the fatigue lifetime of these materials has not yet been investigated for compression–compression loadings. This paper first describes an experimental protocol to perform well‐controlled cyclic compression tests without anti‐buckling device that may induced bias. The uniaxiality of the global loading is checked during the test based on kinematic and thermoelastic coupling field measurements. Then, the paper compares the results from fatigue and heat buildup tests performed on polyetheretherketone reinforced with 30 wt% of short carbon fibers for several load ratios. It is shown that the fatigue lifetime is higher in compression than in tension and depends on the compression load ratio. The heat buildup approach appears to be relevant to quickly predict the fatigue lifetime of the material for the different loading ratios studied, including compression–compression.

The build-up approach. Could it be an alternative to the CAPM?

Background: The paper contains the economic background for implementing the build-up approach as an alternative method to the Capital Assets Pricing Model (CAPM).&#x0D; Research purpose: This study aims to consider company-specific risk premium that makes cost estimation unique, subjective, and different within the economic factors that may be considered and used for entity cost of equity estimation, valuation, or other economic metrics.&#x0D; Methods: The author analyzes the most recent literature on companies’ cost of equity and estimating specific risk premiums. Each component of the cost of capital in the build-up approach was analyzed and interpreted. The petroleum industry was analyzed between 2011 and 2021. The Mercer model for specific risk was used.&#x0D; Conclusions: The build-up approach seems the best choice to calculate equity costs in a turbulent economic environment. However, due to its mathematical structure, it could be criticized for the huge subjectivity in the assessment risk premium rate. The key to using this method is to make it less subjective. This paper suggests an approach that minimizes the subjectivity in the build-up model. So far, there is no comprehensive analysis of the Polish market that has been prepared from the perspective of the petroleum industry’s specific risk premium. This research creates possibilities for further comprehensive analysis related to models to calculate company risk premiums and the factors that affect them.

Https://www.ijeast.com/papers/251-257,%20Tesma0701,IJEAST.pdf

3D Printing or Additive manufacturing is a novel method of manufacturing parts directly from a digital model using a layer-by-layer material build-up approach. This tool- less manufacturing method can produce fully dense metallic parts in a short time, with high precision. Features of additive manufacturing like freedom of part design, part complexity, and lightweighting. The frame is an important part of a TwoWheeler and it carries the load acting on the vehicle. So, it must be strong enough to resist the shock, twist, vibration, and other stresses. Stainless Steel material is used for printing chassis. The Modeling of the 2-wheeler chassis for the bike is done using CATIA V5 software and Metal 3D printing of the chassisis performed using EBAM (Electronic beam addition manufacturing) method.

Aerodynamic Characterization of Hypersonic Transportation Systems and Its Impact on Mission Analysis

This paper aims to provide technical insights on the aerodynamic characterization activities performed in the field of the H2020 STRATOFLY project, for the Mach 8 waverider reference configuration. Considering the complexity of the configuration to be analyzed at conceptual/preliminary design stage, a build-up approach has been adopted. The complexity of the aerodynamic model increases incrementally, from the clean external configuration up to the complete configuration, including propulsion systems elements and flight control surfaces. At each step, the aerodynamic analysis is complemented with detailed mission analysis, in which the different versions of the aerodynamic databases are used as input for the trajectory simulation. eventually, once the contribution to the aerodynamic characterization of flight control surfaces is evaluated, stability and trim analysis is carried out. The comparison of the results obtained through the different mission analysis campaigns clearly shows that the accuracy of aerodynamic characterization may determine the feasibility or unfeasibility of a mission concept.

The Treachery of Images: How Realism Influences Brain and Behavior.

Although the cognitive sciences aim to ultimately understand behavior and brain function in the real world, for historical and practical reasons, the field has relied heavily on artificial stimuli, typically pictures. We review a growing body of evidence that both behavior and brain function differ between image proxies and real, tangible objects. We also propose a new framework for immersive neuroscience to combine two approaches: (i) the traditional build-up approach of gradually combining simplified stimuli, tasks, and processes; and (ii) a newer tear-down approach that begins with reality and compelling simulations such as virtual reality to determine which elements critically affect behavior and brain processing.

Effects of Thermal Cycling on Wire and Arc Additive Manufacturing of Al-5356 Components

Wire and arc additive manufacturing (WAAM) provides a promising alternative to conventional machining for the production of large structures with complex geometry, as well as individualized low quantity components, using cost-efficient production resources. Due to the layer-by-layer build-up approach, process conditions, such as energy input, deposition patterns and heat conduction during the additive manufacturing process result in a unique thermal history of the structure, affecting the build-up properties. This experimental study aims to describe the effects of thermal cycling on the geometrical and material properties of wire arc additive manufactured Al-5356 aluminum alloy. Under consideration, that Al-5356 is a non-heat treatable alloy, a significant effect on geometrical formation is expected. Linear wall samples were manufactured using pulsed cold metal transfer (CMT-P) under variation of wire-feed rate, travel speed and interpass temperatures. The samples were analyzed in terms of geometry; microstructural composition; hardness and residual stress. Furthermore, the mechanical properties were determined in different building directions.

Effective Protocol for Daily High-quality Direct Posterior Composite Restorations: Layering and Finishing.

Currently, there is a trend towards simplification of materials and clinical procedures. Simplification and quality can go together if the dentist works with materials and techniques that are well proven in vitro and in vivo. The placement of a high-quality class-1/2 direct posterior composite restoration can be time efficient following a standardized layering protocol and using composite materials that adapt well to the tooth surface and are able to mimic the natural tooth. When these materials are applied in a controlled way, finishing and polishing can also be shortened. In this article, an effective layering and finishing/polishing protocol for medium-sized class-1/2 direct posterior composite restorations is presented. Following the histo-anatomic buildup of natural teeth, dentin must be concave, as opposed to convex enamel. An isochromatic, medium-opaque, highly filled flowable composite is used to replace dentin. Enamel is replaced with a medium-translucent small-particle hybrid composite. Enamel is modelled in an anatomical way, following a successive cusp-by-cusp buildup approach. Clinical experience shows that the combination of both materials used according to this so-called bi-laminar histo-anatomical layering approach results in restorations that blend in very well within the surrounding tooth structure. Following a simplified finishing and polishing protocol, the composite restorations will have a correct contour, seamless margins, and a smooth, glossy surface.

Effect of control surfaces on the aerodynamic database of the Stratofly hypersonic vehicle

This paper aims at studying the control surfaces of the STRATOFLY project reference aircraft, funded by the European Commission, under the framework of Horizon 2020 plan. The values of aerodynamic coefficients in a wide range of flow free-stream conditions are stored in the aircraft aerodynamic database. The research goal is to update a pre-existent database that was developed with fixed control surfaces using the six control surfaces deflection as input. Different Mach numbers determine different flow regimes: subsonic, transonic, supersonic, and hypersonic. In subsonic, transonic and low supersonic regimes a vortex-lattice solver is used to obtain the global coefficients assuming an unviscous flow on a simplified model. In hypersonic flow a build-up approach is applied: the control surfaces deflection contribution is developed by assuming a two-dimensional flow on the airfoil and by applying shock-expansion theory on the geometry. Then the paper analyses results showing stability and L/D results. The final paragraph focuses on trimmability at cruise Mach. No trimmed solution is obtainable to optimize the propulsive system. The solution proposed to solve this issue is to extend the four elevons: larger elevons are found to be able to trim the vehicle at the desired angle of attack.

3D metal printing technology: the need to re-invent design practice

3D printing or additive manufacturing is a novel method of manufacturing parts directly from digital model using layer-by-layer material build-up approach. This tool-less manufacturing method can produce fully dense metallic parts in short time, with high precision. Features of additive manufacturing like freedom of part design, part complexity, light weighting, part consolidation, and design for function are garnering particular interests in metal additive manufacturing for aerospace, oil and gas, marine, and automobile applications. Powder bed fusion, in which each powder bed layer is selectively fused using energy source like laser, is the most promising additive manufacturing technology that can be used for manufacturing small, low-volume, complex metallic parts. This review presents overview of 3D Printing technologies, materials, applications, advantages, disadvantages, challenges, economics, and applications of 3D metal printing technology, the DMLS process in detail, and also 3D metal printing perspectives in developing countries.

Asymmetric Synthesis of (-)-6'-β-Fluoro-aristeromycin via Stereoselective Electrophilic Fluorination.

(-)-6'-β-Fluoro-aristeromycin (2), a potent inhibitor of S-adenosylhomocysteine (AdoHcy) hydrolase, has been synthesized via stereoselective electrophilic fluorination followed by a purine base build-up approach. Interestingly, purine base condensation using a cyclic sulfate resulted in a synthesis of (+)-5'-β-fluoro-isoaristeromycin (2a). Computational analysis indicates that the fluorine atom controlled the regioselectivity of the purine base substitution.

Computational-Fluid-Dynamics Best Practices for Aircraft Wing-Tip Vortex Roll-Up

Best practices for simulating aircraft wing-tip vortex roll-up with Reynolds-averaged Navier–Stokes computational fluid dynamics were developed using a build-up approach with the NASA OVERFLOW flow solver. Methods were tested for accuracy and computational expense beginning with a simple case, then building up step by step in complexity toward a realistic aircraft geometry. The cases tested started two-dimensionally with an inviscid vortex, then a viscous vortex, then three-dimensionally with a basic rectangular finite wing, a semispan wing that included validating wind-tunnel test data, and finally to a realistic wing/body aircraft configuration that also included wind-tunnel data. Comparisons were also made with algebraic vortex models used to initialize large-eddy simulations of wake decay.

Forecasting linear aliphatic copolyester degradation through modular block design

The development of efficient methods to predict the degradation of renewable polymeric materials is continuously sought in the field of polymer science. Herein, we present a modular build-up approach to create polyester-based materials with forecasted degradation rates based on the hydrolysis of the constituent polymer blocks. This involved the strategic combination of critical factors affecting polyester hydrolysis, i.e. hydrophobicity and degree of crystallinity. The starting point of this method was a toolbox of polymers with different hydrophobicities and degrees of crystallinity, as well as an understanding of their inherent differences in hydrolysis rate. Knowledge of the hydrolysis of each polymer block module enabled the prediction of the overall degradation behavior of the constructed copolymers. Taking advantage of the primary factors that affect polymer degradation, block copolymers could be independently designed to incorporate soft or rigid and faster or slower degradation properties. This approach generated a shift for how molecular design can be used to predict the degradation behavior of intended materials for different applications.

3D Metal Printing Technology

Abstract: 3D Printing or Additive manufacturing is a novel method of manufacturing parts directly from digital model by using layer by layer material build-up approach. This tool-less manufacturing method can produce fully dense metallic parts in short time, with high precision. Features of additive manufacturing like freedom of part design, part complexity, light weighting, part consolidation and design for function are garnering particular interests in metal additive manufacturing for aerospace, oil & gas, marine and automobile applications. Powder bed fusion, in which each powder bed layer is selectively fused by using energy source like laser, is the most promising additive manufacturing technology that can be used for manufacturing small, low volume, complex metallic parts. This review presents overview of 3D Printing technologies, materials, applications, advantages, disadvantages, challenges, economics and applications of 3D metal printing technology.

Synthesis of a high specific activity methyl sulfone tritium isotopologue of fevipiprant (NVP-QAW039).

The synthesis of a triple tritiated isotopologue of the CRTh2 antagonist NVP-QAW039 (fevipiprant) with a specific activity >3 TBq/mmol is described. Key to the high specific activity is the methylation of a bench-stable dimeric disulfide precursor that is in situ reduced to the corresponding thiol monomer and methylated with [(3)H3]MeONos having per se a high specific activity. The high specific activity of the tritiated active pharmaceutical ingredient obtained by a build-up approach is discussed in the light of the specific activity usually to be expected if hydrogen tritium exchange methods were applied.

Modeling and Incremental Nonlinear Dynamic Inversion Control of a Novel Unmanned Tiltrotor

A novel, tiltrotor, unmanned aerial vehicle configuration has been designed, and a preliminary dynamic model has been created for control design purposes based on a component buildup approach. This method has been preferred over a conventional stability derivative approach because it models the nonlinear aircraft dynamics in the entire flight envelope, ranging from hover to forward-flight conditions at any airflow angles. The flight control system has then been synthesized based on an incremental nonlinear dynamic inversion technique. The incremental strategy was adopted to solve the problem of the nonlinear dynamic model not being control affine due to effector redundancy, dramatic nonlinearities, and cross-coupling effects introduced by the use of thrust vectoring during hover and transition phases. Local control derivatives were calculated online from the dynamic model. Effector redundancy was managed, developing a control allocation module for distributing the control effort according to a daisy-chaining logic and according to the actuator availability and effectiveness. The timescale separation principle was applied, dividing control laws into two loops: an outer loop controlling slower dynamics, and outputting virtual controls for an inner loop controlling faster dynamics. Different piloting logics were identified for hover and forward-flight conditions, although the largest possible degree of commonality was sought. A command blending strategy was devised to control the aircraft during transition phases. Simulations confirmed the effectiveness of the proposed solutions, showing satisfactory tracking of reference inputs with moderate control effort.

Three-Dimensional Temperature Gradient Mechanism in Selective Laser Melting of Ti-6Al-4V

Selective laser melting (SLM) is widely used in making three-dimensional functional parts layer by layer. Temperature magnitude and history during SLM directly determine the molten pool dimensions and surface integrity. However, due to the transient nature and small size of the molten pool, the temperature gradient and the molten pool size are challenging to measure and control. A three-dimensional finite element (FE) simulation model has been developed to simulate multilayer deposition of Ti-6Al-4 V in SLM. A physics-based layer buildup approach coupled with a surface moving heat flux was incorporated into the modeling process. The melting pool shape and dimensions were predicted and experimentally validated. Temperature gradient and thermal history in the multilayer buildup process was also obtained. Furthermore, the influences of process parameters and materials on the melting process were evaluated.