Computational Investigation Identified Potential Chemical Scaffolds for Heparanase as Anticancer Therapeutics

Heparanase (Hpse) is an endo-β-D-glucuronidase capable of cleaving heparan sulfate side chains. Its upregulated expression is implicated in tumor growth, metastasis and angiogenesis, thus making it an attractive target in cancer therapeutics. Currently, a few small molecule inhibitors have been reported to inhibit Hpse, with promising oral administration and pharmacokinetic (PK) properties. In the present study, a ligand-based pharmacophore model was generated from a dataset of well-known active small molecule Hpse inhibitors which were observed to display favorable PK properties. The compounds from the InterBioScreen database of natural (69,034) and synthetic (195,469) molecules were first filtered for their drug-likeness and the pharmacophore model was used to screen the drug-like database. The compounds acquired from screening were subjected to molecular docking with Heparanase, where two molecules used in pharmacophore generation were used as reference. From the docking analysis, 33 compounds displayed higher docking scores than the reference and favorable interactions with the catalytic residues. Complex interactions were further evaluated by molecular dynamics simulations to assess their stability over a period of 50 ns. Furthermore, the binding free energies of the 33 compounds revealed 2 natural and 2 synthetic compounds, with better binding affinities than reference molecules, and were, therefore, deemed as hits. The hit compounds presented from this in silico investigation could act as potent Heparanase inhibitors and further serve as lead scaffolds to develop compounds targeting Heparanase upregulation in cancer.     

Regression analysis of surface roughness and micro-structural study in rotary ultrasonic drilling of BK7

Ceramic materials have tremendous demand in manufacturing sectors. However, poor machinability impedes their widespread applications on an industrial scale. BK-7 falls in the same category and is normally processed by ultrasonic machining. But nowadays rotary ultrasonic machining is overtaking the ultrasonic machining for processing difficult to cut materials because of its superlative material removal mechanism. Current study aims to improve the surface quality of BK7 by studying the effect of input factors on surface roughness during rotary ultrasonic machining. Response surface methodology has been used to observe the effect of input variables ― spindle speed, feed rate and ultrasonic power ― on surface roughness (SR). Thereafter, central composite design was employed to estimate the regression coefficients of quadratic model for surface roughness. Fitness of developed quadratic model was checked by ANOVA test, which also revealed that all the model terms of input factors were significant except feed and speed interaction. Feed has the maximum impact over surface roughness descended by moderate impact of power and spindle speed. The study was further reinforced on observing the surface integrity of processed surfaces using scanning electron microscopic images. Mixed flow of material was observed to occur at lower feed rate and higher levels of rpm and ultrasonic power.     

A comparative study of the tensile properties of compression molded and 3D printed PLA specimens in dry and water saturated conditions

Journal of Mechanical Science and Technology - This research work presents a comparative study of the tensile properties of polylactic acid (PLA) specimens per ASTM D638-14 fabricated by...     

Optimisation of process parameters to develop nutritionally rich spray‐dried honey powder with vitamin C content and antioxidant properties

The aim of present research was to optimise the conditions to develop nutritionally rich honey powder using honey, whey protein concentrate (WPC), aonla (Emblica officinalis. Gaertn) and basil (Ocimum sanctum) extract with the help of co‐current spray drier. Response surface methodology was applied to study the effects of inlet temperature (160–180 °C), whey protein concentrate (25–35%), feed flow rate (0.08–0.13 mL s^?1), aonla extract (6–8%) and basil extract (6–8%) on product responses, viz. bulk density, hygroscopicity, antioxidant activity (AOA), total phenolic content (TPC) and vitamin C. Statistical analysis revealed that independent variables significantly affected all the responses. The results demonstrated that increasing inlet temperature lowered the bulk density, hygroscopicity, AOA, TPC and vitamin C, whereas addition of aonla extract and basil extract increased the AOA (82.73%), TPC (63.27%) and total vitamin C content (94.89%) as these functional compounds were encapsulated by WPC. Similarly, with increase in feed flow rate and WPC, there was increase and decrease in the bulk density and hygroscopicity, respectively. The recommended optimum spray‐drying conditions were inlet air temperature (170 °C), feed rate (0.11 mL s^?1), whey protein concentrate (35%), aonla (8%) and basil extract (6%).     

Characterization and selection of suitable grades of lactose as functional fillers for capsule filling: part 1

The purpose of this work is to characterize thermal, physical and mechanical properties of different grades of lactose and better understand the relationships between these properties and capsule filling performance. Eight grades of commercially available lactose were evaluated: Pharmatose 110?M, 125?M, 150?M, 200?M, 350?M (α-lactose monohydrate), AL (anhydrous lactose containing ～80% β-AL), DCL11 (spray dried α-lactose monohydrate containing ～15% amorphous lactose) and DCL15 (granulated α-lactose monohydrate containing ～12% β-AL). In this study, different lactose grades were characterized by thermal, solid state, physical and mechanical properties and later evaluated using principal component analysis (PCA) to assess the inter-relationships among some of these properties. The lactose grades were characterized by differential scanning calorimetry (DSC), thermogravimetric analysis (TGA), X-ray diffraction (XRD), moisture sorption/desorption isotherms, particle size distribution; the flow was characterized by Carr Index (CI), critical orifice diameter (COD) and angle of friction. Plug mechanical strength was estimated from its diametric crushing strength. The first and second principal components (PC) captured 47.6% and 27.4% of variation in the physical and mechanical property data, respectively. The PCA plot grouped together 110?M, AL, DCL11 and DCL15 on the one side of plot which possessed superior properties for capsule formulation and these grades were selected for future formulation development studies (part II of this work).     

Hyperbranched poly(cyanurateamine): A new corrosion inhibitor for mild steel in hydrochloric acid medium

Hyperbranched poly(cyanurateamine) (POCYAM) was tested as a novel corrosion inhibitor for mild steel in 0.5–3 M HCl using chemical and electrochemical techniques at 25–70 °C. The results show that this compound has good corrosion inhibiting properties for mild steel in HCl at very low concentrations. Corrosion inhibition efficiency rises with POCYAM concentration. The adsorption of the POCYAM onto the mild steel surface obeys Langmuir adsorption isotherm model. The inhibition mechanism was further corroborated by the values of thermodynamic parameters obtained from the experimental data.     

材料的重要性

《材料的重要性》是《景观设计理论》的一段节选。《景观设计理论》旨在不使用专业术语或其他领域假说的前提下,结合景观设计过程向学生介绍内在理论思想。《材料的重要性》是本书的五章之一。每一章针对特定理论,解释了其基础和来源,探讨了它对设计的重要性,列举了20—21世纪与其相关的设计案例,整理了该理论的辩论(尤其是有关现代和后现代思想),最后还有相关阅读材料清单和需要学生们思考的问题。本文分为如下3个部分：第一部分,物质性,介绍“辩证唯物主义”“媒介即信息”“物质实践”和“编码”等理论及其在设计中的运用;第二部分,通过“建构表达”“地貌代理人策略”“石材的面层”“材料的暗示”“人造,但不是伪造”等理论,介绍材料的真实性及其在设计中的运用;第三部分,复写理论及应用,包括“剩余物”“复写的展示性”“未来的复写”和“虚构的复写”等内容。