Simulation of TSV Protrusion in 3DIC Integration by Directly Loading on Coarse-Grained Phase-Field Crystal Model

As thermal management in 3DIC integration becomes increasingly important in advanced semiconductor node processes, novel experimental and modeling approaches are in great demand to reveal the critical material issues involving multiscale microstructures that govern the behavior of through-silicon-via (TSV) protrusion. Here, a coarse-grained phase-field crystal model properly coupled with mechanics through the atomic density field is used to simulate the formation of polycrystalline structures and protrusion of nano-TSVs from the atomic scale. TSVs with different grain structures are directly loaded, and protrusion/intrusion profiles are obtained along with displacement, stress, and strain fields. Thermodynamic driving forces from external loadings and the mismatch of Young’s modulus between adjoining grains as well as detailed displacement and strain distributions are ascribed to control the complex deformation in TSVs. TSVs with sizes up to around 30 nm and an aspect ratio of 4 are successfully investigated, and a further increase in the size and aspect ratio to cover the micrometer range is feasible, which lays down a solid basis toward a multiscale material database for simulation inputs to the design of TSV-based 3DIC integration and relevant electronic design automation (EDA) tools.

DEVELOPMENT, OPTIMIZATION AND EVALUATION OF PULSATILE DRUG DELIVERY CAPSULES LOADED WITH CARVEDILOL BY APPLYING QUALITY BY DESIGN

Objective: The purpose of this research is to find the best way for designing carvedilol pulsatile drug delivery system capsules. Methods: The research paves the way to improve the method of preparing carvedilol pulsatile drug delivery by adjusting critical material attributes (CMA) such as coating polymer concentration, critical process parameters (CPP) such as inlet temperature and atomizing air pressure, and their impact on critical quality attributes (CQA) like particle size (PS in nm), entrapment efficiency in percentage (% EE) and amount of drug delivered in percent (%ADR) at 12 h in the carvedilol pulsatile pellets filled capsules by applying the Box-Behnken design. By varying the polymer concentration and process parameters, nearly 15 formulations were created. Results: Based on the influence of CMA, CPP on CQA, the formulation CP13 was determined to be the most optimized formulation among the 15 formulations. The optimized levels of CMA were found to be-1 level of coating polymer concentration and CPP was found to be-1 level of inlet temperature, 0 level of atomizing air pressure and it optimized CQA like PS was found to be 1017.5±8.4 nm, % EE was found to be 96.8±2.8 %, % ADR at 12 h was found to be 88.4±3.4 %. Carvedilol Pulsatile drug delivery system was designed by using optimized fluidized bed coater in order to decrease the usage of attributes, decrease the productivity cost and enhance the usage of specific attributes at fixed concentration for further manufacturing scale. Conclusion: By the current results it was concluded that the optimized CMA and CPP that shown in the results are the suitable attributes for the best formulation of carvedilol pulsatile drug delivery system capsules.

Direct RNA Nanopore Sequencing of SARS-CoV-2 Extracted from Critical Material from Swabs

In consideration of the increasing prevalence of COVID-19 cases in several countries and the resulting demand for unbiased sequencing approaches, we performed a direct RNA sequencing (direct RNA seq.) experiment using critical oropharyngeal swab samples collected from Italian patients infected with SARS-CoV-2 from the Palermo region in Sicily. Here, we identified the sequences SARS-CoV-2 directly in RNA extracted from critical samples using the Oxford Nanopore MinION technology without prior cDNA retrotranscription. Using an appropriate bioinformatics pipeline, we could identify mutations in the nucleocapsid (N) gene, which have been reported previously in studies conducted in other countries. In conclusion, to the best of our knowledge, the technique used in this study has not been used for SARS-CoV-2 detection previously owing to the difficulties in the extraction of RNA of sufficient quantity and quality from routine oropharyngeal swabs. Despite these limitations, this approach provides the advantages of true native RNA sequencing and does not include amplification steps that could introduce systematic errors. This study can provide novel information relevant to the current strategies adopted in SARS-CoV-2 next-generation sequencing.

A LITERARY READING IN THE LINGUISTIC EFFORTS OF IBN QUTAYBA IN HIS BOOK ADAB ‎AL-KĀTIB “THE WRITER'S LITERATURE”‎

Ibn Qutayba (d. 276 AH / 889 AD) was attentive in both the Arabic linguistics‏ ‏and its literature, ‎whereas he hath assorted numerous workbooks which testify his care about, and those who came ‎after, have been benefited from his critical material on the fields of language and literature, this ‎incipit of the research is concerned with reading Ibn Qutayba's linguistic views through the ‎subject of his book Adab al-Kātib “The Writer's Literature” particularly those related to ‎orthography and solecism in the Arabs’ language, and the importance of the research lies in ‎shedding light on the Arab linguistic legacy in the third century AH\ ninth century AD, and ‎displaying the impact of Ibn Qutayba in it, and the objective of the research is to analyze what ‎was mentioned in two important linguistic topics from the book of Adab al-Kātib “The Writer’s ‎Literature” which are: the topic of rectification of the hand and the topic of rectification of the ‎tongue, which they are both linguistic topics that show the prevailing linguistics status in the era ‎of Ibn Qutayba, thence, they are also considered a door to understanding the linguistic opinions ‎that the writer gleaned from his wells and sheikhs.‎ The research deals with linguistic problems related to the orthography and the Arab solecism and ‎phonetics among the populace in the era of Ibn Qutayba, relying on a research framework that ‎begins with a preamble considering both the writer and the book, and then deals with the ‎linguistics status in the third century AH through what was mentioned in the book’s sermon, then ‎he presents some of what was mentioned in his book Adab al-Kātib ”The Writer’s Literature” in ‎the two chapters; rectification of the hand and rectification of the tongue, then epitomized the ‎disputations between Ibn Qutayba and the commentators of his book regarding the two ‎mentioned sections, and the research is concluded with a brief epilogue that presents his most ‎prominent conclusions.‎

PRELIMINARY STUDY OF INSULIN DRY POWDER FORMULATION: CRITICAL PROCESS PARAMETERS ON SPRAY-FREEZE-DRYING AND CRITICAL MATERIAL ATTRIBUTE OF TREHALOSE AND INULIN AS STABILIZER

Objective: The aim of this study was to obtain recommendations about critical process parameters (CPP) and optimal ratio of trehalose and inulin as critical material attribute (CMA) on insulin dry powder formulation with spray-freeze-drying (SFD) method. Methods: Inulin dry powder was formulated with the SFD method, which consisted of an atomization process and freeze-drying (FD). SFD processes were optimized in order to obtain dry powder and CPP was analyzed. All seven variations of formulas proceeded with physicochemical characterization to obtain the optimal formula. Results: In the early optimization, there was a slight time lag between the atomization process and FD; as a result, some of the powder coagulated and crystallized. Another critical parameter was that the FD process should not be interrupted for at least 50 h of FD. Dry powder proceeded with physicochemical characterization, a formula without inulin showed semicrystalline properties, while six formulas had amorphous properties due to its combination. All formulas had a spherulite shape and rough surface. Five formulas with the combination of trehalose and inulin obtained dry powders with a diameter range of 30-43 μm, moisture content below 3.5% and high encapsulation efficiency (EE). Formula with the ratio of 1:1 (F4) showed optimal properties with moisture content and EE of 2.62% and 99.68%, respectively. Conclusion: This study concluded that there were two critical process parameters in the SFD method. There should be no time lag in SFD process and FD time which should not be interrupted. The optimal ratio for trehalose and inulin was shown by F4 with ratio of 1:1.

High Photoresponse Black Phosphorus TFTs Capping with Transparent Hexagonal Boron Nitride

Black phosphorus (BP), a single elemental two-dimensional (2D) material with a sizable band gap, meets several critical material requirements in the development of future nanoelectronic applications. This work reports the ambipolar characteristics of few-layer BP, induced using 2D transparent hexagonal boron nitride (h-BN) capping. The 2D h-BN capping have several advantages over conventional Al2O3 capping in flexible and transparent 2D device applications. The h-BN capping technique was used to achieve an electron mobility in the BP devices of 73 cm2V−1s−1, thereby demonstrating n-type behavior. The ambipolar BP devices exhibited ultrafast photodetector behavior with a very high photoresponsivity of 1980 mA/W over the ultraviolet (UV), visible, and infrared (IR) spectral ranges. The h-BN capping process offers a feasible approach to fabricating n-type behavior BP semiconductors and high photoresponse BP photodetectors.

A Customized Knee Antibiotic-Loaded PMMA Spacer: A Pre-Liminary Design Analysis

A preliminary design of customized antibiotic-loaded poly-methyl-methacrylate (ALPMMA) spacer characterized by an appropriate footprint according to the specific patient’s anatomy and a reliable mechanical response to severe functional loads (i.e., level walking and 45° bent knee) is reported. The targeted virtual prototyping process takes origin from a novel patented 3D geometrical conceptualization characterized by added customization features and it is validated by a preliminary FEM-based analysis. Mechanical and thermomechanical properties of the antibiotic-doped orthopedic PMMA cement, which will be used for the future prototype manufacturing, were measured experimentally by testing samples taken during a real day-running orthopedic surgery and manufactured according to the surgeon protocol. FEM analysis results indicate that small area is subjected to intensive stresses, validating the proposed geometry from the mechanical point of view, under the two loading scenarios, moreover the value of safety margins results positive, and this is representative of the lower stress magnitude compared to the critical material limits. The experimental data confirm that the presence of antibiotic will last during the surgeon period moreover, the temperature dependent modulus of the bone cement is slightly affected by the body range temperature whereas it will drastically drop for higher temperature out the range of interest. A complete customization, according to a patient anatomy, and the corresponding real prototype spacer will be manufactured by 3D printing techniques, and it will be validated by destructive testing during the second stage of this activity before commercialization.

Integrating Elastic Tensor and PC-SAFT Modeling with Systems-Based Pharma 4.0 Simulation, to Predict Process Operations and Product Specifications of Ternary Nanocrystalline Suspensions

Comminution of BCS II APIs below the 1 μm threshold followed by solidification of the obtained nanosuspensions improves their dissolution properties. The breakage process reveals new crystal faces, thus creating altered crystal habits of improved wettability, facilitated by the adsorption of stabilizing polymers. However, process-induced transformations remain unpredictable, mirroring the current limitations of our atomistic level of understanding. Moreover, conventional equations of estimating dissolution, such as Noyes–Whitney and Nernst–Brunner, are not suitable to quantify the solubility enhancement due to the nanoparticle formation; hence, neither the complex stabilizer contribution nor the adsorption influence on the interfacial tension occurring between the water and APIs is accounted for. For such ternary mixtures, no numeric method exists to correlate the mechanical properties with the interfacial energy, capable of informing the key process parameters and the thermodynamic stability assessment of nanosuspensions. In this work, an elastic tensor analysis was performed to quantify the API stability during process implementation. Moreover, a novel thermodynamic model, described by the stabilizer-coated nanoparticle Gibbs energy anisotropic minimization, was structured to predict the material’s system solubility quantified by the application of PC-SAFT modeling. Comprehensively merging elastic tensor and PC-SAFT analysis into the systems-based Pharma 4.0 algorithm provided a validated, multi-level, built-in method capable of predicting the critical material quality attributes and corresponding key process parameters.