The Stokes Number Approach to Support Scale-Up and Technology Transfer of a Mixing Process

Transferring processes between different scales and types of mixers is a common operation in industry. Challenges within this operation include the existence of considerable differences in blending conditions between mixer scales and types. Obtaining the correct blending conditions is crucial for the ability to break up agglomerates in order to achieve the desired blend uniformity. Agglomerate break up is often an abrasion process. In this study, the abrasion rate potential of agglomerates is described by the Stokes abrasion (St(Abr)) number of the system. The St(Abr) number equals the ratio between the kinetic energy density of the moving powder bed and the work of fracture of the agglomerate. In this study, the St(Abr) approach demonstrates to be a useful tool to predict the abrasion of agglomerates during blending when technology is transferred between mixer scales/types. Applying the St(Abr) approach revealed a transition point between parameters that determined agglomerate abrasion. This study gave evidence that (1) below this transition point, agglomerate abrasion is determined by a combination of impeller effects and by the kinetic energy density of the powder blend, whereas (2) above this transition point, agglomerate abrasion is mainly determined by the kinetic energy density of the powder blend.     

Characterization of Cold-Shock Protein A of Antarctic <Emphasis Type="Italic">Streptomyces</Emphasis> sp. AA8321

Abstact Polar organisms should have mechanisms to survive the extremely cold environment. Four genes encoding cold-shock proteins, which are small, cold-induced bacterial proteins, have been cloned from the Antarctic bacterium Streptomyces sp. AA8321. Since the specific functions of any polar bacterial or Streptomyces cold-shock proteins have not yet been determined, we examined the role of cold-shock protein A from Streptomyces sp. AA8321 (CspA_St). Gel filtration chromatography showed that purified CspA_St exists as a homodimer under physiological conditions, and gel shift assays showed that it binds to single-stranded, but not double-stranded, DNA. Overexpression of CspA_St in Escherichia coli severely impaired the ability of the host cells to form colonies, and the cells developed an elongated morphology. Incorporation of a deoxynucleoside analogue, 5-bromo-2′-deoxyuridine, into newly synthesized DNA was also drastically diminished in CspA_St-overexpressing cells. These results suggest that CspA_St play a role in inhibition of DNA replication during cold-adaptation.     

Establishment of an In Vitro System Representing the Chicken Gut-Associated Lymphoid Tissue

The bursa of Fabricius is critical for B cell development and differentiation in chick embryos. This study describes the production in vitro, from dissociated cell suspensions, of cellular agglomerates with functional similarities to the chicken bursa. Co-cultivation of epithelial and lymphoid cells obtained from embryos at the appropriate developmental stage regularly led to agglomerate formation within 48 hours. These agglomerates resembled bursal tissue in having lymphoid clusters overlaid by well organized epithelium. Whereas lymphocytes within agglomerates were predominantly Bu-1a⁺, a majority of those emigrating onto the supporting membrane were Bu-1a⁻ and IgM⁺. Both agglomerates and emigrant cells expressed activation-induced deaminase with levels increasing after 24 hours. Emigrating cells were actively proliferating at a rate in excess of both the starting cell population and the population of cells remaining in agglomerates. The potential usefulness of this system for investigating the response of bursal tissue to avian Newcastle disease virus (strain AF2240) was examined.     

Self-organization and dynamics of an open futile cycle

The dynamic behaviour of an open futile cycle composed of two enzymes has been investigated in the vicinity of a steady-state. A necessary condition required for damped or sustained oscillations of the system is that enzyme E₂, which controls recycling of the substrate S₂, be inhibited by an excess of this substrate. In order for the system to be neutrally stable and therefore to exhibit sustained oscillations, it is not necessary for antagonist enzyme E₁ to be activated by its product S₂. If it is enzyme E₁ which is inhibited by an excess of its substrate S₁, the system has a saddle point. Other conditions for stability or instability of the system have been determined. If the enzyme E₁, which is not inhibited by the substrate, exhibits a slow conformational transition of the mnemonical type, this transition dramatically alters the stability behavior of the system. If the mnemonical enzyme E₁ were exhibiting a positive kinetic co-operativity, decreasing the rate of the conformational transition of the mnemonical enzyme will increase the stability of the whole system and will tend to damp the oscillations in the vicinity of the steady-state. If conversely the mnemonical enzyme E₁ were exhibiting a negative kinetic co-operativity, decreasing the rate of the enzyme conformational transition will decrease the stability of the system and will tend to create or amplify oscillations of the system taken as a whole. If these results may be extended to more complex metabolic cycles, involving more than two enzymes, it may be tentatively considered that positive co-operativity associated with slow transition has emerged in the course of evolution in order to limit temporal instabilities of metabolic cycles. Alternatively one may speculate that the “biological function” of negative co-operativity is to create or amplify these temporal instabilities.     

Effect of Surface Coating with Magnesium Stearate via Mechanical Dry Powder Coating Approach on the Aerosol Performance of Micronized Drug Powders from Dry Powder Inhalers

The objective of this study was to investigate the effect of particle surface coating with magnesium stearate on the aerosolization of dry powder inhaler formulations. Micronized salbutamol sulphate as a model drug was dry coated with magnesium stearate using a mechanofusion technique. The coating quality was characterized by X-ray photoelectron spectroscopy. Powder bulk and flow properties were assessed by bulk densities and shear cell measurements. The aerosol performance was studied by laser diffraction and supported by a twin-stage impinger. High degrees of coating coverage were achieved after mechanofusion, as measured by X-ray photoelectron spectroscopy. Concomitant significant increases occurred in powder bulk densities and in aerosol performance after coating. The apparent optimum performance corresponded with using 2% w/w magnesium stearate. In contrast, traditional blending resulted in no significant changes in either bulk or aerosolization behaviour compared to the untreated sample. It is believed that conventional low-shear blending provides insufficient energy levels to expose host micronized particle surfaces from agglomerates and to distribute guest coating material effectively for coating. A simple ultra-high-shear mechanical dry powder coating step was shown as highly effective in producing ultra-thin coatings on micronized powders and to substantially improve the powder aerosolization efficiency.     

Trace metals in large agglomerates (marine snow)

Marine agglomerates were collected by SCUBA from surface watersof Monterey Bay, California and one coastal site 100 km offPoint Sur, California using trace metal clean techniques. Concentrationsof Al, Fe, Mn, Cu, Ni, Zn, Cd and Pb were measured for bothweak acid soluble and refractory metals and compared to suspendmaterial collected in water bottles at the same locations. Gravimetricanalysis of agglomerate and surrounding suspended particulatematter indicated that although agglomerates represented <0.1%of total water sample volume (determined photographically),they contained up to 50% of the total particulate dry weight;trace metal concentrations in the agglomerate fraction werealso disproportionately high. Agglomerates collected withinMonterey Bay contained large quantitites of inorganic material(>40% dry weight), with most of the associated metals containedprimarily within the refractory fraction. In contrast, the offshorestation agglomerates contained <0.3% inorganic material withmetals primarily associated with the weak acid soluble fraction.Both the metal concentrations and leach characteristics of theoffshore station suggest that these agglomerates were comprisedof an active phytoplankton assemblage highly enriched in Cd.Metal concentrations in the offshore samples in conjunctionwith agglomerate abundance indicate that agglomerates may bea major transporter of trace metals out of the euphotic zone.     

Cooperative binding ensures the obligatory melibiose/Na+ cotransport in MelB

MelB catalyzes the obligatory cotransport of melibiose with Na⁺, Li⁺, or H⁺. Crystal structure determination of the Salmonella typhimurium MelB (MelB_St) has revealed a typical major facilitator superfamily (MFS) fold at a periplasmic open conformation. Cooperative binding of Na⁺ and melibiose has been previously established. To determine why cotranslocation of sugar solute and cation is obligatory, we analyzed each binding in the thermodynamic cycle using three independent methods, including the determination of melting temperature by circular dichroism spectroscopy, heat capacity change (ΔC_p), and regulatory phosphotransferase EIIA^Glc binding with isothermal titration calorimetry (ITC). We found that MelB_St thermostability is increased by either substrate (Na⁺ or melibiose) and observed a cooperative effect of both substrates. ITC measurements showed that either binary formation yields a positive sign in the ΔC_p, suggesting MelB_St hydration and a likely widening of the periplasmic cavity. Conversely, formation of a ternary complex yields negative values in ΔCp, suggesting MelB_St dehydration and cavity closure. Lastly, we observed that EIIA^Glc, which has been suggested to trap MelB_St at an outward-open state, readily binds to the MelB_St apo state at an affinity similar to MelB_St/Na⁺. However, it has a suboptimal binding to the ternary state, implying that MelB_St in the ternary complex may be conformationally distant from the EIIA^Glc-preferred outward-facing conformation. Our results consistently support the notion that binding of one substrate (Na⁺ or melibiose) favors MelB_St at open states, whereas the cooperative binding of both substrates triggers the alternating-access process, thus suggesting this conformational regulation could ensure the obligatory cotransport.     

Agglomerates Containing Pantoprazole Microparticles: Modulating the Drug Release

Pantoprazole-loaded microparticles were prepared using a blend of Eudragit® S100 and Methocel® F4M. The accelerated stability was carried out during 6 months at 40°C and 75% relative humidity. In order to improve technological characteristics of the pantoprazole-loaded microparticles, soft agglomerates were prepared viewing an oral delayed release and gastro-resistant solid dosage form. The agglomeration was performed by mixing the pantoprazole microparticles with spray-dried mannitol/lecithin powders. The effects of factors such as the amount of lecithin in the spray-dried mannitol/lecithin powders and the ratio between pantoprazole microparticles and spray-dried mannitol/lecithin powders were evaluated. The pantoprazole-loaded microparticles present no significant degradation in 6 months. The agglomerates presented spherical shape, with smooth surface and very small quantity of non-agglomerated particles. The agglomerates presented different yields (35.5–79.0%), drug loading (58–101%), and mechanical properties (tensile strength varied from 44 to 69 mN mm⁻²), when the spray-dried mannitol/lecithin powders with different lecithin amounts were used. The biopharmaceutical characteristics of pantoprazole microparticles, i.e., their delayed-release properties, were not affected by the agglomeration process. The gastro-resistance of the agglomerates was affected by the amount of spray-dried mannitol/lecithin powders. The ratio of lecithin in the spray-dried mannitol/lecithin powders was the key factor in the agglomerate formation and in the drug release profiles. The agglomerates presenting better mechanical and biopharmaceutical characteristics were prepared with 1:2 (w/w) ratio of pantoprazole-loaded microparticles and mannitol/lecithin (80:20) powder.Key words: agglomerates, delayed release, gastro-resistance, microparticles     

Plasticity of repetitive DNA in response to metal stress in Bryophytes

Abstract

The relationship between environmental stresses and the genome was investigated by examining the behaviour of repetitive DNA in response to lead or cadmium in two Bryophytes, differing from a physiological and an ecological point of view, namely the aquatic moss L. riparium and the terricolous moss F. hygrometrica. Using different experimental approaches, a direct relationship was shown to exist in these two mosses between the metal-induced stress and repetitive DNA. In fact, in both organisms, metal treatment was accompanied by a selective amplification of some GC-rich repetitive DNA sequences forming peculiar agglomerates inside the nucleus; this amplification is quantitatively proportional to the time of exposure of the plants to the metals and stops upon removal of the metal from the culture medium. Results show that ribosomal DNA sequences are involved in this metal-induced repetitive DNA agglomerate formation, although they are not the only repetitive sequences present within the heterochromatic DNA agglomerates. The plasticity of the genome of the Bryophytes in response to external stimuli, and the fact that repetitive DNA is involved in this plasticity are discussed.     

Transformed roots of Artemisia annua exhibit an unusual pattern of border cell release

Summary Border cells from Artemisia annua were examined from hairy roots grown in shake flasks, culture plates, a bubble column reactor, and a nutrient mist (aeroponic) reactor. When well-hydrated roots were subjected to shear, border cells were first released as an agglomerate and did not disperse for several hours. Staining with neutral red and fluorescein diacetate (FDA) showed that both agglomerates and dispersed cells were alive. It was determined that FDA is cleaved by pectin methylesterase (PME) and that PME may not be particularly active in the released agglomerates until the border cells disperse. Untransformed roots isolated from A. annua plants showed no border cell agglomerate formation and border cells readily dispersed. These results suggest that our hairy root clone is deficient in border cell release perhaps resulting from the transformation process.     

喀斯特生态脆弱区典型小生境土壤团聚体稳定性比较研究

为探究喀斯特小生境类型对土壤团聚体稳定性影响,揭示小生境土壤团聚体主要失稳机制,选取研究区内石缝、石沟、石槽、石土面和土面5种典型小生境为研究对象,采用干筛法、Elliott湿筛法和Le Bissonnais法测定土壤团聚体稳定性。结果表明：湿筛后,团聚体分布以水稳性团聚体（WR_>0.25）为主,含量在81.26%以上,团聚体破坏率（PAD）介于8.93%-17.39%之间,平均重量直径（MWD）在1.94-2.85 mm间,均小于干筛,团聚体稳定性表现为石槽最好,土面最差,石土面次之。LB法处理后,MWD值变化趋势为慢速湿润（SW） > 预湿润后扰动（WS） > 快速湿润（FW）,即小生境土壤团聚体最大破坏机制为大雨或暴雨时快速湿润FW产生的消散作用,团聚体稳定性同样以石槽最好,土面最差,石土面次之。相关性分析显示,LB法测定的MWD均与湿筛法的WR_>0.25呈显著正相关,与PAD呈显著负相关,即LB法和湿筛法具有良好的相关性,LB法用于测定喀斯特地区土壤团聚体稳定性是可行的（P<0.05）。LB法FW处理的MWD值与有机质呈显著正相关,即有机质对团聚体稳定性有重要影响;全氮、全磷、全钾与WR_>0.25、SW处理的MWD值呈显著正相关,与PAD呈显著负相关,即稳定的团粒结构对养分蓄积有正向效应（P<0.05）。综合不同测定方法的结果表明,土面、石土面易造成土壤流失,应加强雨季对喀斯特生态脆弱区土面、石土面小生境的防护。     

Water Content�CWater Activity�CGlass Transition Temperature Relationships of Spray-Dried Boroj�� as Related to Changes in Color and Mechanical Properties

The water content–water activity–glass transition temperature relationships of commercial spray-dried borojó powder, with and without maltodextrin, have been studied as related to changes in color and mechanical properties. The GAB and Gordon and Taylor models were well fitted to the sorption and glass transition data, respectively. The Boltzman equation adequately described the evolution of the mechanical parameter characterized in the samples with the difference between the experimental temperature and the glass transition temperature (T _g) of the sample. The color of the samples showed a sigmoid change with water activity. The changes in the mechanical properties of borojó powder related to collapse development started when the sample moved to the rubbery state and began to be significant at about 10 °C above T _g. The increase in the molecular mobility from this point on also favors browning reactions. Maltodextrin presence slows the caking kinetics but induces color changes to spray-dried borojó powder.     

Insights into the Inhibitory Mechanisms of the Regulatory Protein IIAGlc on Melibiose Permease Activity

The phosphotransfer protein IIA^Glc of the bacterial phosphoenolpyruvate:carbohydrate phosphotransferase system plays a key role in the regulation of carbohydrate metabolism. Melibiose permease (MelB) is one among several permeases subject to IIA^Glc regulation. The regulatory mechanisms are poorly understood; in addition, thermodynamic features of IIA^Glc binding to other proteins are also unknown. Applying isothermal titration calorimetry and amine-specific cross-linking, we show that IIA^Glc directly binds to MelB of Salmonella typhimurium (MelB_St) and Escherichia coli MelB (MelB_Ec) at a stoichiometry of unity in the absence or presence of melibiose. The dissociation constant values are 3–10 μm for MelB_St and 25 μm for MelB_Ec. All of the binding is solely driven by favorable enthalpy forces. IIA^Glc binding to MelB_St in the absence or presence of melibiose yields a large negative heat capacity change; in addition, the conformational entropy is constrained upon the binding. We further found that the IIA^Glc-bound MelB_St exhibits a decreased binding affinity for melibiose or nitrophenyl-α-galactoside. It is believed that sugar binding to the permease is involved in an induced fit mechanism, and the transport process requires conformational cycling between different states. Thus, the thermodynamic data are consistent with the interpretation that IIA^Glc inhibits the induced fit process and restricts the conformational dynamics of MelB_St.     

A metal‐chelate affinity reverse micellar system for protein extraction

A new nonionic reverse micellar system is developed by blending two nonionic surfactants, Triton X‐45 and Span 80. At total surfactant concentrations lower than 60 mmol/L and molar fractions of Triton X‐45 less than 0.6, thermodynamically stable reverse micelles of water content (W₀) up to 30 are formed. Di(2‐ethylhexyl) phosphoric acid (HDEHP; 1–2 mmol/L) is introduced into the system for chelating transition metal ions that have binding affinity for histidine‐rich proteins. HDEHP exists in a dimeric form in organic solvents and a dimer associated with one transition metal ion, including copper, zinc, and nickel. The copper‐chelate reverse micelles (Cu‐RM) are characterized for their W₀, hydrodynamic radius (R_h), and aggregation number (N_ag). Similar with reverse micelles of bis‐2‐ethylhexyl sodium sulfosuccinate (AOT), R_h of the Cu‐RM is also linearly related to W₀. However, N_ag is determined to be 30–90 at W₀ of 5–30, only quarter to half of the AOT reverse micelles. Then, selective metal‐chelate extraction of histidine‐rich protein (myoglobin) by the Cu‐RM is successfully performed with pure and mixed protein systems (myoglobin and lysozyme). The solubilized protein can be recovered by stripping with imidazole or ethylinediaminetetraacetic acid (EDTA) solution. Because various transition metal ions can be chelated to the reverse micelles, it is convinced that the system would be useful for application in protein purification as well as simultaneous isolation and refolding of recombinant histidine‐tagged proteins expressed as inclusion bodies. © 2009 American Institute of Chemical Engineers Biotechnol. Prog., 2010     

A Single Residue Determines the Cooperative Binding Property of a Primosomal DNA Replication Protein,PriB, to Single-Stranded DNA

PriB is a primosomal protein required for re-initiation of replication in bacteria. We characterized and compared the DNA-binding properties of PriB from Salmonella enterica serovar Typhimurium LT2 (StPriB) and Escherichia coli (EcPriB). Only one residue of EcPriB, V6, was different in StPriB (replaced by A6). Previous structural information revealed that this residue is located on the putative dimer-dimer interface of PriB and is not involved in single-stranded DNA (ssDNA) binding. The cooperative binding mechanism of StPriB to DNA is, however, very different from that of EcPriB. Unlike EcPriB, which forms a single complex with ssDNAs of various lengths, StPriB forms two or more distinct complexes. Based on these results, as well as information on structure, binding modes for forming a stable complex of PriB with ssDNA of 25 nucleotides (nt), (EcPriB)₂₅, and (StPriB)₂₅ are proposed.     

Austausch-Ungleichgewicht zwischen unabhängigen Inversionen in natürlichen Populationen von Drosophila subobscura

Zusammenfassung Natürliche Populationen von Drosophila subobscura zeigen häufig einen hochgradigen Inversionspolymorphismus. Unabhängige Inversionen eines Chromosoms, zwischen denen ein Austausch angenommen werden kann, sind nicht selten. Eine theoretische Überlegung zeigt, daß für diese Fälle ein Austauschgleichgewicht zu erwarten ist, bei dem die relative Häufigkeit der möglichen chromosomalen Transtypen A _StB und A B _St und die Cis-Typen AB und A _StB_St in einer bestimmten Proportion auftreten sollten. Diese Gleichgewichtsbedingung kann für jede gegebene relative Häufigkeit der koexistierenden, unabhängigen Inversionen leicht ermittelt und mit den gefundenen Werten verglichen werden. Unter Benützung aller bisher publizierten Angaben konnte für 13 verschiedene lokale Populationen von Drosophila subobscura ein solcher Vergleich durchgeführt werden. Das Ergebnis zeigt, daß die theoretischen Gleichgewichtswerte nur sehr selten erreicht werden. Vielmehr zeigen von 14 untersuchten, unabhängigen Inversionspaaren 12 ein vollständiges Austausch-Ungleichgewicht. Die Abweichungen sind in vielen Populationen statistisch hochgradig signifikant. Sehr oft fehlt einer der erwarteten Cis-oder Transtypen ganz. Die Ursache dafür könnten selektive Kräfte sein, die gegen den einen oder anderen Rekombinationstyp wirken. Für die Fälle, bei denen eine der Inversions-Kombinationen überhaupt nicht beobachtet werden kann, müßte dann sogar ein dominanter Letal-oder Semiletaleffekt angenommen werden, der durch die Kombination zustande kommt. Eine andere Denkmöglichkeit ist, daß Rekombination zwisehen den unabhängigen Inversionen überhaupt nicht auftritt, obwohl im Riesenchromosom zwischen ihnen längere euchromatische Abschnitte liegen. Das beobachtete Austausch-Ungleichgewicht wäre dann das Ergebnis einer absoluten Koppelung.

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Recombination disequilibrium of independent inversions in natural populations of Drosophila subobscura

Summary Coexistence of linked independent inversions is not infrequent in natural populations of Drosophila subobscura. Assuming that recombination between independent inversions does occur at a certain rate an equilibrium stage can be expected at which the frequencies of the two possible trans-types A _StB and AB _St and the two possible cis-types AB and A _StB_St are in balance. The theoretical equilibrium conditions for any given frequency of independent inversions can easily be calculated and compared to the observed frequency distribution of the four combination types of any local population. Using all available data of 13 different populations of D. subobscura it could be found that linkage equilibrium is very rarely established in nature. Out of 14 independent inversion pairs 12 showed complete or nearly complete linkage disequilibrium. In many populations the deviation from the equilibrium condition is highly significant. This may be due to selective forces acting against one or both recombination types of an association-dissociation group. In the many cases where the linkage disequilibrium is complete one of the recombination types does not occur in nature at all. It probably, then, has a dominant lethal or semilethal effect on its carriers. Another possible explanation is that recombination between independent inversions does not occur at all and that di equilibrium is the result of complete linkage.

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Herrn Prof. Mainx möchten wir für die Durchsicht des Manuskripts und für sein Interesse herzlich danken.     

Agglomerated Oral Dosage Forms of Artemisinin/β-Cyclodextrin Spray-Dried Primary Microparticles Showing Increased Dissolution Rate and Bioavailability

Artemisinin, a poorly water-soluble antimalarial drug, presents a low and erratic bioavailability upon oral administration. The aim of this work was to study an agglomerated powder dosage form for oral administration of artemisinin based on the artemisinin/β-cyclodextrin primary microparticles. These primary microparticles were prepared by spray-drying a water–methanol solution of artemisinin/β-cyclodextrin. β-Cyclodextrin in spray-dried microparticles increased artemisinin water apparent solubility approximately sixfold. The thermal analysis evidenced a reduction in the enthalpy value associated with drug melting, due to the decrease in drug crystallinity. The latter was also evidenced by powder X-ray diffraction analysis, while ¹³C-NMR analysis indicated the partial complexation with β-cyclodextrin. Agglomerates obtained by sieve vibration of spray-dried artemisinin/β-cyclodextrin primary microparticles exhibited free flowing and close packing properties compared with the non-flowing microparticulate powder. The in vitro dissolution rate determination of artemisinin from the agglomerates showed that in 10 min about 70% of drug was released from the agglomerates, whereas less than 10% of artemisinin was dissolved from raw material powder. Oral administration of agglomerates in rats yielded higher artemisinin plasma levels compared to those of pure drug. In the case of the agglomerated powder, a 3.2-fold increase in drug fraction absorbed was obtained.     

典型喀斯特森林土壤的抗蚀性

喀斯特地区生态脆弱,极易发生土壤侵蚀。受地表要素空间异质性的影响,目前相关研究仍无法完全反映出喀斯特地区不同植被类型土壤抗蚀性的特征。通过野外调查,了解样地植被群落类型及其组成等基本情况,并以"S形布点法"实地采样;通过酒精烘烤法、环刀法等方法,获取土壤含水量、土壤容重、土壤有机质、土壤团聚体、土壤微团聚体及土壤机械组成、土壤抗蚀指数等土壤抗蚀指标值。结果表明,除有机质外的其他抗蚀指标表现出0—10cm土层内与10—20cm土层内的变化规律均和抗蚀指数一致。在土壤深度0—10cm范围内,土壤抗蚀指数表征的土壤抗蚀能力强弱为:阔叶林灌丛针叶林;在10—20cm土层范围为:灌丛针叶林阔叶林。0—10cm土层内各指标表征土壤抗蚀能力的显著程度为:有机质含量、水稳性团聚体、结构破坏率、团聚状况和团聚度较显著,10—20cm土层内为有机质含量、干筛团聚体、团聚度较为显著,水稳性团聚体次之。通过综合两个土层的情况,可认为有机质含量、水稳性团聚体、团聚度能较好地表征喀斯特林地土壤抗蚀性强弱。在喀斯特地区如果以防治土壤侵蚀为目的,应考虑种植阔叶树种,避免针叶树种。     

Analytical solution for a hybrid Logistic-Monod cell growth model in batch and continuous stirred tank reactor culture

Monod and Logistic growth models have been widely used as basic equations to describe cell growth in bioprocess engineering. In the case of the Monod equation, the specific growth rate is governed by a limiting nutrient, with the mathematical form similar to the Michaelis–Menten equation. In the case of the Logistic equation, the specific growth rate is determined by the carrying capacity of the system, which could be growth-inhibiting factors (i.e., toxic chemical accumulation) other than the nutrient level. Both equations have been found valuable to guide us build unstructured kinetic models to analyze the fermentation process and understand cell physiology. In this work, we present a hybrid Logistic-Monod growth model, which accounts for multiple growth-dependent factors including both the limiting nutrient and the carrying capacity of the system. Coupled with substrate consumption and yield coefficient, we present the analytical solutions for this hybrid Logistic-Monod model in both batch and continuous stirred tank reactor (CSTR) culture. Under high biomass yield (Y_x/s) conditions, the analytical solution for this hybrid model is approaching to the Logistic equation; under low biomass yield condition, the analytical solution for this hybrid model converges to the Monod equation. This hybrid Logistic-Monod equation represents the cell growth transition from substrate-limiting condition to growth-inhibiting condition, which could be adopted to accurately describe the multi-phases of cell growth and may facilitate kinetic model construction, bioprocess optimization, and scale-up in industrial biotechnology.