Clinical and Genetic Re-Evaluation of Inherited Retinal Degeneration Pedigrees following Initial Negative Findings on Panel-Based Next Generation Sequencing

Although rare, inherited retinal degenerations (IRDs) are the most common reason for blind registration in the working age population. They are highly genetically heterogeneous (>300 known genetic loci), and confirmation of a molecular diagnosis is a prerequisite for many therapeutic clinical trials and approved treatments. First-tier genetic testing of IRDs with panel-based next-generation sequencing (pNGS) has a diagnostic yield of ≈70–80%, leaving the remaining more challenging cases to be resolved by second-tier testing methods. This study describes the phenotypic reassessment of patients with a negative result from first-tier pNGS and the rationale, outcomes, and cost of second-tier genetic testing approaches. Removing non-IRD cases from consideration and utilizing case-appropriate second-tier genetic testing techniques, we genetically resolved 56% of previously unresolved pedigrees, bringing the overall resolve rate to 92% (388/423). At present, pNGS remains the most cost-effective first-tier approach for the molecular assessment of diverse IRD populations Second-tier genetic testing should be guided by clinical (i.e., reassessment, multimodal imaging, electrophysiology), and genetic (i.e., single alleles in autosomal recessive disease) indications to achieve a genetic diagnosis in the most cost-effective manner.     

Performance of supercritical carbon dioxide sprays as coolants and lubricants in representative metalworking operations

This paper investigates the cooling and lubrication properties of supercritical carbon dioxide (scCO₂) sprays as potential substitutes for aqueous emulsions and straight oils used in the metalworking industry today. Sprays of rapidly expanding scCO₂ act to cool and lubricate machining and forming processes by delivering a mixture of dry ice and lubricant deep into the cutting/forming zone. In this work, experiments with turning, milling, drilling, thread cutting, and thread forming were performed with scCO₂ and other metalworking fluids (MWFs) to evaluate their relative performance with respect to tool wear and machining torque. Observations reveal that scCO₂–MWFs are more effective in removing heat from the tool-workpiece interface than conventionally delivered (flood) aqueous MWFs as well as other gas-based MWF sprays. In addition, scCO₂–MWFs delivered in lubricant-expanded phase, where scCO₂ is used to increase volume of lubricant in the spray field, are shown to provide better lubricity than straight oils and oil-in-air minimum quantity lubrication (MQL) sprays. As a result, scCO₂–MWFs can reduce tool wear and improve machining productivity in a wide range of manufacturing operations leading to appreciable improvements in the economics of manufacturing. Also given that CO₂ is a recovered waste gas that is non-toxic, scCO₂–MWFs can improve the environmental and worker health performance of manufacturing operations.     

Dynamic modelling of CO2 absorption for post combustion capture in coal-fired power plants

Power generation from fossil fuel-fired power plants is the largest single source of CO₂ emissions. Post combustion capture via chemical absorption is viewed as the most mature CO₂ capture technique. This paper presents a study of the post combustion CO₂ capture with monoethanolamine (MEA) based on dynamic modelling of the process. The aims of the project were to compare two different approaches (the equilibrium-based approach versus the rate-based approach) in modelling the absorber dynamically and to understand the dynamic behaviour of the absorber during part load operation and with disturbances from the stripper. A powerful modelling and simulation tool gPROMS was chosen to implement the proposed work. The study indicates that the rate-based model gives a better prediction of the chemical absorption process than the equilibrium-based model. The dynamic simulation of the absorber indicates normal absorber column operation could be maintained during part load operation by maintaining the ratio of the flow rates of the lean solvent and flue gas to the absorber. Disturbances in the CO₂ loading of the lean solvent to the absorber significantly affect absorber performance. Further work will extend the dynamic modelling to the stripper for whole plant analysis.     

提高注射用头孢噻肟钠的成品率

在1.0g注射用头孢噻肟钠粉针制剂生产过程中,从影响成品率提高的各个环节入手,通过采取各个工序严格把关、对现有分装机缺陷进行改进等措施,1.0g注射用头孢噻肟钠成品率从97.15%提高到了98.51%.     

Application of one-dimensional mechanical formulations to model the sagging behavior of a polymer sheet

The deformation of a heated plastic sheet clamped on two opposite sides subject to sagging under its own weight was examined experimentally and then modeled using two separate one-dimensional approaches based upon cable (membrane) and beam formulations. The cable formulation neglects both bending and shear deformation, but includes a generalized Maxwell viscoelastic constitutive model to capture the time-dependent nature of sheet sag. The resulting equations are integrated using a Runge-Kutta technique and solved via a shooting method. The beam formulation is based upon the Timoshenko theory and thus includes shear deformation along with the flexural contributions. A finite element method is developed from application of the principle of virtual work for the beam written in curvilinear coordinates in order to include the effects of finite deformation. A generalized Maxwell model is again employed to account for the time-dependent material response. In both formulations, the method of reduced variables is used to describe the variation of material response with temperature. The effect of temperature and thermal relaxation is included. The particular case of a styrenic material is discussed in detail.     

Dynamic modelling and analysis of post-combustion CO2 chemical absorption process for coal-fired power plants

Post-combustion capture by chemical absorption using MEA solvent remains the only commercial technology for large scale CO₂ capture for coal-fired power plants. This paper presents a study of the dynamic responses of a post-combustion CO₂ capture plant by modelling and simulation. Such a plant consists mainly of the absorber (where CO₂ is chemically absorbed) and the regenerator (where the chemical solvent is regenerated). Model development and validation are described followed by dynamic analysis of the absorber and regenerator columns linked together with recycle. The gPROMS (Process Systems Enterprise Ltd.) advanced process modelling environment has been used to implement the proposed work. The study gives insights into the operation of the absorber-regenerator combination with possible disturbances arising from integrated operation with a power generation plant. It is shown that the performance of the absorber is more sensitive to the molar L/G ratio than the actual flow rates of the liquid solvent and flue gas. In addition, the importance of appropriate water balance in the absorber column is shown. A step change of the reboiler duty indicates a slow response. A case involving the combination of two fundamental CO₂ capture technologies (the partial oxyfuel mode in the furnace and the post-combustion solvent scrubbing) is studied. The flue gas composition was altered to mimic that observed with the combination. There was an initial sharp decrease in CO₂ absorption level which may not be observed in steady-state simulations.     

Reaction products of ammonium nitrate phosphate fertilizers of varying water-soluble phosphorus content in different Indian soils

Studies were undertaken on the isolation and identification of reaction products of ammonium nitrate phosphate (ANP) fertilizers containing 30, 50 and 70 per cent water-soluble phosphorus (WSP) of total phosphorus in representative soils of the vertisol, oxisol, alfisol, entisol, mollisol and aridisol groups of India. ANP fertilizers were applied in solid form to soil, and reaction products formed at and around the site of ANP fertilizer placement were identified after six weeks incubation in moist soils by X-ray diffraction technique. DCPD (dicalcium phosphate dihydrate- CaHPO₄ · 2H₂O) was the major reaction product of ANP fertilizers containing 30 and 50 per cent WSP in vertisol, entisol, aridisol, mollisol, oxisol and alfisol, and of ANP containing 70 per cent WSP in vertisol, entisol, alfisol, aridisol and mollisol. DCP (dicalcium phosphate-CaHPO₄) was detected with ANP of 30 and 50 per cent WSP in the vertisol, alfisol, entisol, mollisol and aridisol groups of soils. In addition to DCPD, FePO₄ · 2H₂O (metastrengite) and AlPO₄ · 2H₂ O-monoclinic (metavariscite) were formed in alfisol and oxisol soils with ANP of 30 and 50 per cent WSP. FePO₄ · 2H₂O and AlPO₄ · 2H₂O (metavariscite) were identified in alfisol and oxisol soils while AlPO₄ · 2H₂O-orthorhombic (variscite) was formed in alfisol soils with ANP of 70 per cent WSP.