Application of defin让ive screening design to quantify the effects of process parameters on key granule characteristics and optimize operating parameters in pulsed-spray fluid-bed granulation

The pulsed-spray fluid-bed granulation (PSFBG) process was investigated and optimized using definitive scree ning design, a recently proposed new class of three-level desig n of experiment method. Such a design enabled quadratic models to be established that described the effect of six in put process parameters - inlet air temperature, inlet air humidity, binder spray rate, atomization pressure, pulse period, and pulse width - on the granule quality in a PSFBG process. Mathematical models of the mean particle size, relative size distribution width, production yield, and porosity were developed to quantify the relationships between the in flue ncing factors and critical quality attributes. On the basis of con strai nts on the desired granule properties, a design space for PSFBG was determined and ranges of the operating parameters were defined. An acceptable degree of prediction was confirmed by validation experiments, demonstrating the reliability and effectiveness of using definitive screening design to study the PSFBG process. This method can accelerate screening and optimization of this process within a large multidimensional design space.

Real-time monitoring and fault detection of pulsed-spray fluid-bed granulation using near-infrared spectroscopy and multivariate process trajectories

Pulsed spray is a useful tool forgranule size control in fluid bed granulation.To improve the quality control of pulsed-spray fluid bed granulation,a combination of in-line near-infrared(NIR)spectroscopy and p「incipal component analysis was used to develop multivariate statistical process control(MSPC)charts.Different types of MSPC charts were developed,including principal component score charts,Hotelling's T2 control charts,and distance to model X control charts,to monitor the batch evolution throughout the granulation process.Correlation optimized warping was used as an alignment method to deal with the time variation in batches caused by the granulation mechanism in MSPC modeling.The control charts developed in this study were validated on normal batches and tested on four batches that deviated from normal processing conditions to achieve real-time fault analysis.The results indicated that the NIR spectroscopy-based MSPC model included the variability in the sample set constituting the model and could withstand external variability.This research demonstrated the application of synchronized NIR spectra in conjunction w让h multivariate batch modeling as an attractive tool for process monitoring and a fault diagnosis method for effective process control in pulsed-spray fluid bed granulation.

The Nature of the Elongated Granulations and Stretched Dark Lanes in a Newly Emerging Flux Region

In this study,we explore the elongated granulations and stretched dark lanes within the emerging anti-Hale active region NOAA AR 12720.Utilizing high-resolution observations from the New Vacuum Solar Telescope,we discern a prevalence of elongated granules and stretched dark lanes associated with the emergence of new magnetic flux positioned between two primary opposing magnetic polarities.These elongated granulations and stretched dark lanes exhibit an alignment of strong transverse fields and a significant inclination angle.The endpoints of these features separate from each other,with their midpoints predominantly characterized by blueshifted signals in the photosphere.This suggests a close association between elongated granules and stretched dark lanes with the newly emerging flux.Additionally,we find that the stretched dark lanes display a more pronounced correlation with strong blueshifts and photospheric transverse magnetic fields compared to the elongated granulations.The transverse magnetic field within these stretched dark lanes reaches magnitudes of approximately 300-400 G,and the inclination angle demonstrates an“arch-like”pattern along the trajectory of the stretched dark lane.Based on these observed characteristics,we infer the presence of an emerging flux tube with an“arch-like”shape situated along the stretched dark lane.Consequently,we conclude that the stretched dark lanes likely represent manifestations of the emerging flux tube,while the elongated granulations may correspond to the gaps between the emerging flux tubes.

TMT-based quantitative proteomics reveals the potential mechanism of the FufangMuji Granules in carbon tetrachloride-induced liver injury

Background:Fufang Muji Granules is a traditional Chinese medicine of the Manchu ethnic group and is thought to treat hepatitis and liver injury by inhibiting the elevation of alpha-fetoprotein.Methods:In this investigation,tandem mass tag(TMT)-based quantitative proteomics was performed to figure out the therapeutic mechanisms of Fufang Muji Granules on liver injury caused by carbon tetrachloride(CCl_(4))in rats.Results:Biochemical analyses(alanine aminotransferase;glutamate aminotransferase;aspartate aminotransferase)and histologic analyses(hematoxylin-eosin)demonstrated that FMG was effective in ameliorating liver injury.A sum of 6,208 proteins were identified and 2,475 proteins were determined as differential abundance proteins(DAPs)in rat liver treated with Fufang Muji Granules which compared to the model group.Bioinformatics analysis indicated that the DAPs are primarily enriched in multiple pathways such as rno00280(valine,leucine,and isoleucine degradation),rno00640(Propanoate metabolism),and rno00380(Tryptophan metabolism).Western blot was employed to validate the findings from the proteomic analysis.Conclusion:This study not only provides useful information on the mechanism of Fufang Muji Granules in the treatment of liver injury but also serves as a basis for further study of Fufang Muji Granules in vivo.

基于SAT的GRANULE算法不可能差分分析

基于布尔可满足性问题(SAT)的自动化搜索方法可以直接刻画与、或、非、异或等逻辑运算,从而建立更高效的搜索模型。为更高效地评估GRANULE算法抵抗不可能差分攻击的能力,首先,基于S盒差分分布表性质优化S盒差分性质刻画的SAT模型;其次,对GRANULE算法建立基于比特的不可能差分区分器的SAT模型,通过求解模型得到多条10轮GRANULE算法的不可能差分区分器;再次,针对不可能差分区分器,给出改进的SAT自动化验证方法并验证;最后,将得到的区分器往前和往后各扩展3轮,对GRANULE-64/80算法发起16轮的不可能差分攻击,通过该攻击可以恢复80比特主密钥,时间复杂度为251.8次16轮加密,数据复杂度为241.8个选择明文。与表现次优的对GRANULE算法不可能差分分析的方法相比,所得到的区分器轮数和密钥恢复攻击轮数都提高了3轮,且时间复杂度、数据复杂度都进一步下降。

Influence of temperature on the characteristics of aerobic granulation in sequencing batch airlift reactors

Aerobic granular sludge was cultivated in sequencing batch airlift reactors （SBAR） at 25, 30, and 35℃, respectively. The effect of temperature on the granules characteristics was analyzed and the microbial community structures of the granules were probed using scanning electron microscope （SEM） and polymerase chain reaction-denaturing gradient gel electrophoresis （PCR-DGGE）. The results showed that 30℃ is optimum for matured granule cultivation, where the granules had a more compact structure, better settling ability and higher bioactivity, the oxygen utilization rate （OUR） reached 1.14 mg O2/（g MLVSS.min） with COD removal rate of 97% and TP removal rate of 75%. The removal efficiency of NH3-N increased from 68.5% to 87.5% along with the temperature increment from 25 to 35℃. The DGGE profiles revealed that the microbial community structure at 25℃ showed the least similarity with those at other temperatures. The sequencing results indicated that the majority of dominant microbes belonged to Actinobacteria and Proteobacterium. Thermomonas sp., Ottowia sp. and Curtobacteriurn ammoniigenes might play important roles at different temperatures, respectively.

Granulation of filamentous microorganisms in a sequencing batch reactor with saline wastewater

Proliferation of filamentous microorganisms frequently leads to operational failure for activate sludge systems. In this study, it was found that filamentous microorganisms could grow in compact granular structure with 5% sodium chloride in the substrate. In the early period of experiment, coccoid and rode-like bacteria predominated in the yellowish-brown granules, and later the white and the black granules were developed by filamentous microorganisms. The filamentous granules exhibited low porosity and fast settling velocity, and were more compact even than bacteria granules. It was hypothesized that the elevated pH in the later period might be a possible reason for the compact growth of filamentous granules. However, the bacteria granules showed the high bioactivity in terms of specific oxygen utilizing rate, and comprised of a wider diversity of compounds based on the thermogravimetric evaluation. The findings in this study demonstrated that filamentous microbes could form compact granular structure, which may encourage the utilization of filamentous microorganisms rather than the inhibition of their growth, as the latter is frequently used for sludge bulking control.

Effects of particle characteristics on the granulation ability of iron ores during the sintering process

The granulation behavior of iron ores is essential for subsequent parameter optimization and efficient granulation, especially under changing material conditions. In this study, the effects of surface properties and particle size were analyzed using a laboratory granulation method; an estimation of the granulation of sintering blends was subsequently conducted for the base ores. Circularity and porosity were observed to negatively affect the granulation of iron ores, whereas wettability positively affected the granulation and was the most influential factor, indicating that wetting of iron ores is desirable during granulation. When iron ores with complex size distributions were granulated, the equivalent surface area was the main influencing factor for coarse particles larger than 1 mm and the ratio of adhering fines to intermediates was the main factor for fine particles smaller than 1 mm. By combining the granulation of coarse and fine particles with their proportioning, we proposed a calculation method for estimating the granulation ability of sintering blends. Good verification was demonstrated with the designed schemes. The results suggest that the developed method is effective for predicting the granulation of iron ore mixtures.

Sludge granulation and efficiency of phase separator in UASB reactor treating combined industrial effluent

Sludge granulation and the effect of gas-liquid-solid separator （GLSS） design on the efficiency of upflow anaerobic sludge blanket （UASB） and upflow anaerobic sludge filter （UASF） reactors, operating at HRTs ranging from 3 to 12 h was investigated. VSS/TS ratio gradually increased in both the reactors with increasing sludge age （from 0.5 to more than 0.7 for UASB reactor and 0.012 to 0.043 for UASF reactor）. X-Ray diffraction analysis of the UASF sludge showed the presence of expanding clays revealing its additional absorption capability. Fuoraphyllite and albite precipitation related to excellular polymers of the microbial shell structure, showed the extended growth of microorganisms during sludge granulation. A gradual decrease （82%-69%） in COD removal with decreasing HRT was apparent in UASF reactor. In case of UASB reactor, this decrease was marginal because addition of GLSS device significantly improved （14%-20%） the overall efficiency of the UASB reactor. GLSS enhanced the efficiency of the UASB reactor by increasing the settleability of suspended particles and accelerating the coagulation of colloidal particles due to the velocity gradient.

Endoscopic management of a rare granulation polyp in a colonic diverticulum

There are many case reports on colon diverticula that cause irritable bowel syndrome,constipation,bleeding,diverticulitis,stricture due to multiple recurrences of diverticulitis,and perforation.However,few articles have examined neoplasms that arise from a diverticulum,such as adenoma and adenocarcinoma,and there have been no reports of granulation polyps that arise from a colon diverticulum after recurrent diverticulitis.We observed a rare granulation polyp that arose from a diverticulum as a result of repeated episodes of local diverticulitis.Narrow band imaging magnified colonoscopy was very useful to diagnose the polyp as a granulation polyp because of the absence of a pit pattern on the surface of the polyp.We successfully resected the polyp using endoscopic mucosal resection.We inverted the diverticulum,and the resected stalk of the polyp was used to close the diverticulum with an over-thescope clip.If a granulomatous polyp could arise from a diverticulum,differential diagnosis between a colon neoplasm and a granulomatous polyp would not only be difficult but also necessary for suitable endoscopic treatment.

DEM modeling of high shear wet granulation of a simple system

High shear wet granulation(HSWG) is one of the most poorly understood processes with known difficulties in optimization and scale up. The purpose of the current study is to develop a DEM model which can be applied under dynamic process conditions with high predictive capacity to improve process insight. The DEM model is used to predict agglomeration as a function of impeller speed and liquid addition rate in a high shear wet granulator. The DEM model tracks dynamic formation and breakage of liquid bridges between particles as liquid binder in the system is added, and corrects for the change in material properties as a function of the binder content.

Interaction between granulation and small-scale magnetic flux observed by Hinode

With the polarimetric observations obtained by the Spectro-Polarimeter on board Hinode, we study the relationship between granular development and magnetic field evolution in the quiet Sun. Six typical cases are displayed to exhibit interaction between granules and magnetic elements, and we have obtained the following results. （1） A granule develops centrosymmetrically when no magnetic flux emerges within the granular cell. （2） A granule develops and splits noncentrosymmetrically while flux emerges at an outer part of the granular cell. （3） Magnetic flux emergence in a cluster of mixed polarities is detected at the position of a granule as soon as the granule breaks up. （4） A dipole emerges accompanied by the development of a granule, and the two elements of the dipole are rooted in the adjacent intergranular lanes and face each other across the granule. Advected by the horizontal granular motion, the positive element of the dipole then cancels with the pre-existing negative flux. （5） Flux cancellation also takes place between a positive element, which is advected by granular flow, and its surrounding negative flux. （6） While magnetic flux cancellation takes place in a granular cell, the granule shrinks and then disappears. （7） Horizontal magnetic fields are enhanced at the places where dipoles emerge and where opposite polarities cancel each other, but only the horizontal fields between the dipolar elements point in an orderly way from the positive elements to the negative ones. Our results reveal that granules and small-scale magnetic fluxes influence each other. Granular flow advects magnetic flux, and magnetic flux evolution suppresses granular development. There exist extremely large Doppler blue-shifts at the site of one canceling magnetic element. This phenomenon may be caused by the upward flow produced by magnetic reconnection below the photosphere.

Promoting sludge granulation by putting xonotlite into the UASB reactors during starting-up stage

Four reactors of up-flow anaerobic sludge blanket (UASB) were concurrentlyoperated to examine the effects of the xonotlite secondary particles on promoting the sludgegranulation during the starting-up stage at room temperature. The results show that the putting ofthe xonotlite secondary particles into the UASB reactors can increase the basicity of the reactingliquid significantly. The particles can act as the media for biomass accumulation. Thus, thegranulation process of the sludge within the reactor can be largely promoted by the specialperformances of the particles both in physical and chemical aspects.

Hemozoin triggers tumor necrosis factor alpha-mediated release of lysozyme by human adherent monocytes:new evidences on leukocyte degranulation in P.falciparum malaria

Objective:Avidly phagocytosed hemozoin(malarial pigment) alters several functions of human monocytes and stimulates generation of several cytokines.Recently,we showed that phagocytosis of hemozoin by human monocytes increases expression and activity of matrix metalloproteinase-9,a proteolytic enzyme available in specific gelatinase granules,which contain several enzymes including lysozyme.Present work investigated active lysozyme release after phagocytosis of hemozoin and its dependence on production of tumor necrosis factor alpha. Methods:After phagocytosis of hemozoin,hemozoin-containing trophozoites or control meals(opsonized nonparasitized red blood cells and latex particles),monocyte supematants were monitored for 2 hours,in presence of blocking anti-human tumor necrosis factor alpha antibodies or recombinant human tumor necrosis factor alpha cytokine in selected experiments.Lysozyme release was evaluated by a specific spectrometric assay measuring lysozyme activity after coincubation of cell supematants with suspensions of Mycrococcus Lysodeikticus,while levels of soluble tumor necrosis factor alpha were analyzed by specific enzyme-linked immunodsorbent assay. Results:Levels of lysozyme activity and soluble tumor necrosis factor alpha protein were increased in hemozoin in-or trophozoites-laden monocytes supematants.Phagocytosis per se(control meals) also increased lysozyme release,but levels were significantly lower than those obtained after phagocytosis of hemozoin or trophozoites. Interestingly,all effects on lysozyme release observed after phagocytosis were abrogated by blocking anti-human tumor necrosis factor alpha antibodies,while they were mimicked by recombinant human tumor necrosis factor alpha cytokine.Conclusions:Present work shows that phagocytosis of hemozoin promotes monocyte degranulation and enhances active lysozyme release.The effect requires tumor necrosis factor alpha mediation.

TRANSFORMATION OF EFFUSION AND FORMATION OF GRANULATION TISSUE IN PATHOLOGIC PROCESS OF OTITIS MEDIA WITH EFFUSION

Objective To explore the diversity of stagnant effusions and the pathologic processes leading to granulation tissue formation in otitis media with effusion(OME). Methods Temporal bone slides from 306 ears with OME were studied histopathologically under the light microscope. Results Results of this study revealed a pathologic process in witch the type and the condition of stagnant effusion in the middle ear cleft was a variable in the dynamics of OME progression from an early stage to an advanced stage. The location of granulation tissue and retentive effusion were found to be closely related. Conclusion Early stage granulation tissue formation exhibited a pathologic process in which granulation tissue formation occurred only in areas where effusion had stagnated or was absorbed. The incidence of the retentive effusion and formation of granulation tissue was much higher and the pathologic changes most extensive in the area around the ossicular chain.

Technological Parameters for Preparation and Granulation of Ammonium Ion-Exchange Material

As a raw material,kaolin was modified to prepare a high-performance ammonium ion-exchange material.According to cation-exchange capacity (CEC) measurement,the prepared ammonium ion-exchange material has an ammonium ion-exchange capacity greater than 75mg/g and can be used to remove ammonia nitrogen in water treatment.A pharmaceutical extruder-rounder was used to study the effects of granulation process.Polyethylene glycol6000 (PEG-6000) was used as the pore-forming agent and calcining temperature of 650℃ was used as the optimal condition.NMR data indicate that 27 Al is mainly converted from hexa-coordinated Al to tetra-coordinated Al during the modification.Compared with 29 Si in the original kaolin,29 Si in the modified kaolin does not have an obvious change.A comparison of the data with Langmuir and Freundlich isotherm models shows a good correlation.The Freundlich model describes the process more accurately,and the adsorption process of ammonia nitrogen in water with the ammonium ion-exchange material closely matches the pseudo-second-order reaction.

Effects of Formulation Parameters and Process Variables on the Properties of Granules Obtained by Reactive Granulation

In this work, granulation between dodecyl-benzenesulfonic acid and sodium carbonate was investigated in a laboratory-scale high shear mixer. The effects offormulation parameters and process variables, including primary carbonate size, binder content, impeller speed, and operating temperature, were correlated to the properties ofthe product granules. Design ofexperiment and analysis ofvariance were combined to analyze the experimentaldata, and results showed that larger granule sizes with fewer fine particles can be obtained by employing higher binder contents and larger sodium carbonate sizes. The shear force ofthe impeller can extensively break oversized granules. The binder content exerted a contrasting effect on the flowability ofgranules formed with two kinds ofsodium carbonate, likely because ofdifferences in the liquid saturation ofthe solids. The dissolution rate determined by in-line size analysis showed that high binder contents were beneficialto dissolution performance, and the relationships between Hunter color and tested parameters were evaluated. The results ofthis work can be used as a reliable guidance for process controland optimization in powder detergent manufacturing.

Fluidised bed granulation of two APIs:QbD approach and development of a NIR in-line monitoring method

The study focused on the fluid-bed granulation process of a product with two active pharmaceutical ingredients,intended for coated tablets preparation and further transfer to industrial scale.The work aimed to prove that an accurate control of the critical granulation parameters can level the input material variability and offer a user-friendly process control strategy.Moreover,an in-line Near-Infrared monitoring method was developed,which offered a real time overview of the moisture level along the granulation process,thus a reliable supervision and control process analytical technology(PAT)tool.The experimental design’s results showed that the use of apparently interchangeable active pharmaceutical ingredients(APIs)and filler sorts that comply with pharmacopoeial specifications,lead to different end-product critical attributes.By adapting critical granulation parameters(i.e.binder spray rate and atomising pressure)as a function of material characteristics,led to granules with average sizes comprised in a narrow range of 280–320μm and low nongranulated fraction of under 5%.Therefore,the accurate control of process parameters according to the formulation particularities achieved the maintenance of product within the design space and removed material related variability.To complete the Quality by design(QbD)strategy,despite its limited spectral domain,the microNIR spectrometer was successfully used as a robust PAT monitoring tool that offered a real time overview of the moisture level and allowed the supervision and control of the granulation process.

On the Effect of the Rotating Chamber Reverse Speed on the Mixing of SiC Ceramic Particles in a Dry Granulation Process

In order to control the accumulation of SiC ceramic particles on the wall of the rotating chamber in the frame of a dry granulation process,the effect of the wall reverse speed on the mixing process is investigated.In particular,an Euler-Euler two-phase flow model is used to analyze the dynamics of both SiC particles and air.The numerical results show that by setting a certain reverse rotating speed of the rotating chamber,the accumulation of SiC particles on the wall can be improved,i.e.,their direction of motion in proximity to the wall can be changed and particles can be forced to re-join the granulation process.Experimental tests conducted to verify the reliability of the numerical findings,demonstrate that when the reverse rotating speed of the rotating chamber is 4 r/min,the sphericity of SiC particles in the rotating chamber is the highest and the fluidity is the best possible one.

Combination forecast for urban rail transit passenger flow based on fuzzy information granulation and CPSO-LS-SVM

In order to obtain the trend of urban rail transit traffic flow and grasp the fluctuation range of passenger flow better,this paper proposes a combined forecasting model of passenger flow fluctuation range based on fuzzy information granulation and least squares support vector machine(LS-SVM)optimized by chaos particle swarm optimization(CPSO).Due to the nonlinearity and fluctuation of the passenger flow,firstly,fuzzy information granulation is used to extract the valid data from the window according to the requirement.Secondly,CPSO that has strong global search ability is applied to optimize the parameters of the LS-SVM forecasting model.Finally,the combined model is used to forecast the fluctuation range of early peak passenger flow at Tiyu Xilu Station of Guangzhou Metro Line 3 in 2014,and the results are compared and analyzed with other models.Simulation results demonstrate that the combined forecasting model can effectively track the fluctuation of passenger flow,which provides an effective method for predicting the fluctuation range of short-term passenger flow in the future.