bluuebunny/crossref_metadata_2025_split huggingface dataset:
Toward consistent and productive complex media for industrial fermentations: Studies on yeast extract for a recombinant yeast fermentation process
Authors: Zhang Jinyou , Reddy Jayanthi , Buckland Barry , Greasham Randolph 
Published: March 2003

AbstractYeast extract (YE) is commonly used as a key component in the complex media for industrial fermentations. However, the lot‐to‐lot variation of this raw material frequently requires extensive “use testing” of many lots to identify only the few that support desired fermentation performance. Through extensive fermentation studies and chemical analyses, we have identified adenine and two metabolizable carbon sources, trehalose and lactate, as the principle components in YE that affect the production of a recombinant protein antigen by a yeast strain. Adenine is required for culture growth and the relationship between biomass and measured adenine can be expressed by a Michaelis‐Menten model, while the slowly metabolized trehalose serves to maintain the energy supply to the continued antigen synthesis. The rapidly utilized lactate exerts an indirect positive effect by sparing some of the accumulated ethanol from being consumed for growth to being utilized in the product formation. The effects of these YE components are mutually dependent. Based on the database generated from 40 lots at laboratory scale, a relatively high level of carbon sources in YE (trehalose plus lactate, >9.5% w/w) and an intermediate level of adenine (0.14–0.24% w/w) appear to be the minimal requirement of a good lot for this recombinant yeast fermentation. Many poor lots were improved in lab fermenters by rational supplementation of trehalose, lactate, or adenine to compensate for their insufficiencies. At the large production scale, predictions based on adenine and trehalose/lactate contents in various YE lots used correlated reasonably well with culture growth and antigen yield, illustrating the feasibility of such a simple chemical/biochemical analysis as a rapid and reliable initial screening tool. Without incurring any compositional change to an established manufacturing medium, this study demonstrates an effective approach to achieve consistency in fermentations employing complex nutrients and to improve fermentation productivities supported by suboptimal lots of raw material. © 2003 Wiley Periodicals, Inc. Biotechnol Bioeng 82: 640–652, 2003.
Generally applicable fed‐batch culture concept based on the detection of metabolic state by on‐line balancing
Authors: Jobé Anna Marya , Herwig Christoph , Surzyn Martin , Walker Bernhard , Marison Ian , von Stockar Urs 
Published: March 2003

AbstractIn many microorganisms, flux limitations in oxidative metabolism lead to the formation of overflow metabolites even under fully aerobic conditions. This can be avoided if the specific growth rate is controlled at a low enough value. This is usually accomplished by controlling the substrate feeding profile in a fed‐batch process. The present work proposes a control concept which is based on the on‐line detection of metabolic state by on‐line calculation of mass and elemental balances. The advantages of this method are: 1) the check of measurement consistency based on all of the available measurements, 2) the minimum requirement of a priori knowledge of metabolism, and 3) the exclusive use of simple and established on‐line techniques which do not require direct measurement of the metabolite in question. The control concept has been linked to a simple adaptive controller and applied to fed‐batch cultures of S. cerevisiae and E. coli, organisms which express different overflow metabolites, ethanol and acetic acid, respectively. Oxidative and oxidoreductive states of S. cerevisiae and E. coli cultures were detected with high precision. As demonstrated by the formation of acetic acid in E. coli cultures, metabolic states could be correctly distinguished for systems for which traditional methods, such as respiratory quotient (RQ), are insensitive. Hence, it could be shown that the control concept allowed avoidance of overflow metabolite formation and operation at maximum oxidative biomass productivity and oxidative conversion of substrate into biomass. Based on mass and elemental balances, the proposed method additionally provides a richness of additional information, such as yield coefficients and estimation of concentrations and specific conversion rates. These data certainly help the operator to additionally evaluate the state of the process on‐line. © 2003 Wiley Periodicals, Inc. Biotechnol Bioeng 82: 627–639, 2003.
Economically pertinent continuous amide formation by direct lipase‐catalyzed amidation with ammonia
Authors: Slotema Wouter F. , Sandoval Georgina , Guieysse David , Straathof Adrie J.J. , Marty Alain 
Published: March 2003

AbstractAn economically pertinent process for the lipase‐catalyzed synthesis of amides was developed. A continuous plug flow reactor was used. The model reaction was the production of oleamide, a lubricant and anti‐slip agent, via direct Candida antarctica lipase B‐catalyzed amidation of oleic acid with ammonia. Of all solvents tested, 2‐methyl‐2‐butanol was found to respond optimally to the demands formulated in our specifications. A continuous conversion of oleic acid into oleamide of 85% was obtained. A productivity of 4.5 tons oleamide per kg of enzyme per year was calculated, indicating a contribution of enzyme to the product price of only 4%. The volumetric productivity, 100 g · L−1 · h−1, is 4 to 100 times higher than in literature procedures. A simple crystallization procedure leads to 99% purity. © 2003 Wiley Periodicals, Inc. Biotechnol Bioeng 82: 664–669, 2003.
Physiological responses of chemostat cultures of Aspergillus niger (B1‐D) to simulated and actual oxidative stress
Authors: Bai Zhonghu , Harvey Linda M. , McNeil Brian 
Published: March 2003

AbstractThe physiological responses of chemostat cultures of the filamentous fungus, Aspergillus niger (B1‐D) to simulated and actual oxidative stress, imposed respectively by addition of exogenous menadione (MD; a superoxide radical generating reagent) and gassing the culture with oxygen enriched air (25%, 50%, 75%, and 100% [v/v]), were examined. Changes in the levels of intracellular superoxide anions and defensive enzyme activities, such as catalase (CAT), superoxide dismutase (SOD), and glutathione peroxidase (GPx), were monitored, together with glutathione and respiratory activity in both the dynamic phase and when a new steady state was established. Culture response to MD addition was distinct from that upon exposure to enriched oxygen conditions, in that MD caused elevated levels of intracellular protein, whereas oxygen enrichment caused reduced protein content, especially at low dilution rates. An unexpectedly low level of superoxide radical was found in oxygen‐enriched steady‐state cultures (⩾50%) at a range of dilution rates, which was not caused by elevated SOD activity. Under these conditions, it was noted that the ratio of rotenone‐insensitive/total respiration increased, suggesting increased activity of the alternative respiratory pathway. This may have had the effect of reducing the endogenous generation of superoxide radicals under oxygen rich conditions, but also may have reduced the ATP yield due to the non–proton‐pumping nature of the alternative respiratory pathway. Thus, the negative culture effects noted in many studies at high oxygen levels may not simply be due to elevated endogenous superoxide generation, but could be in part due to the consequences of metabolic changes in the culture that seek to minimize superoxide generation. The dynamic culture response was characterized by rapid elevation of intracellular superoxide anions and associated protective enzymes, especially SOD, and was clearly distinct from the adaptive response just described. © 2003 Wiley Periodicals, Inc. Biotechnol Bioeng 82: 691–701, 2003.
Metabolic engineering of Lactobacillus fermentum for production of mannitol and pure L‐lactic acid or pyruvate
Authors: Aarnikunnas Johannes , von Weymarn Niklas , Rönnholm Kent , Leisola Matti , Palva Airi 
Published: March 2003

AbstractFor production of mannitol in combination with pure L‐lactic acid or pyruvate, the D‐ and L‐lactate dehydrogenase genes (ldhD and ldhL) of a mannitol‐producing Lactobacillus fermentum strain were cloned and stepwise inactivated. For inactivation of both ldh genes by a gene replacement technique, deletion constructs removing a 0.4‐kb fragment from the promoter and the 5′ end region of the ldh genes were used. The first inactivation mutant, designated L. fermentum GRL1030, carried the deletion in ldhD (ΔldhD). A double mutant, ΔldhD‐ΔldhL, was constructed by the inactivation of the ldhL gene of strain GRL1030, resulting in strain L. fermentum GRL1032. The correctness of the both mutants was confirmed at the DNA level by polymerase chain reaction, as shown by the absence of ldh transcripts by northern blotting and as a lack of the corresponding enzyme activity. In bioreactor cultivations, the single mutant GRL1030 produced mannitol and L‐lactic acid as expected. Mannitol and lactic acid yields and productivities were practically unaffected by deletion of the ldhD gene. The double mutant GRL1032 produced mannitol and pyruvate as expected. However, although the yield of mannitol from fructose remained high, its volumetric productivity was reduced. The double mutation negatively affected the glucose consumption rate, resulting in reduced cellular growth. In addition to pyruvate, the double mutant produced 2,3‐butanediol. More surprisingly, some lactic acid was still produced. © 2003 Wiley Periodicals, Inc. Biotechnol Bioeng 82: 653–663, 2003.
Cyclic fed‐batch culture for production of human serum albumin in Pichia pastoris
Authors: Bushell M. E. , Rowe M. , Avignone‐Rossa C. A. , Wardell J. N. 
Published: March 2003

AbstractSimple cyclic fed‐batch culture (cfbc), consisting of a constant medium feed with periodic withdrawals of culture, resulted in a product yield (13.4 mg protein per gram biomass) similar to that obtained using the complex multiphase industrial production strategy (13.7 mg protein per gram biomass). In cfbc, productivity was ultimately limited by the rate at which the cells could assimilate methanol. Glycerol was inhibitory to growth at high concentrations. However, product yield continued to increase as the glycerol concentration was increased. In chemostat culture, dissolved oxygen concentration influenced product yield independently of any detectable influence on cell growth. © 2003 Wiley Periodicals, Inc. Biotechnol Bioeng 82: 678–683, 2003.
Optimization‐based framework for inferring and testing hypothesized metabolic objective functions
Authors: Burgard Anthony P. , Maranas Costas D. 
Published: March 2003

AbstractAn optimization‐based framework is introduced for testing whether experimental flux data are consistent with different hypothesized objective functions. Specifically, we examine whether the maximization of a weighted combination of fluxes can explain a set of observed experimental data. Coefficients of importance (CoIs) are identified that quantify the fraction of the additive contribution of a given flux to a fitness (objective) function with an optimization that can explain the experimental flux data. A high CoI value implies that the experimental flux data are consistent with the hypothesis that the corresponding flux is maximized by the network, whereas a low value implies the converse. This framework (i.e., ObjFind) is applied to both an aerobic and anaerobic set of Escherichia coli flux data derived from isotopomer analysis. Results reveal that the CoIs for both growth conditions are strikingly similar, even though the flux distributions for the two cases are quite different, which is consistent with the presence of a single metabolic objective driving the flux distributions in both cases. Interestingly, the CoI associated with a biomass production flux, complete with energy and reducing power requirements, assumes a value 9 and 15 times higher than the next largest coefficient for the aerobic and anaerobic cases, respectively. © 2003 Wiley Periodicals, Inc. Biotechnol Bioeng 82: 670–677, 2003.
The influence of transport phenomena during high‐pressure processing of packed food on the uniformity of enzyme inactivation
Authors: Hartmann Chr. , Delgado A. 
Published: March 2003

AbstractHere we deal with the influence of heat‐transport effects on a high‐pressure‐induced enzyme inactivation in packed substances. Special attention is given to the influence of the geometrical scale and to the heat‐transfer characteristics of the packaging material. The investigation is based on mathematical modeling and numerical simulation. The method accounts both for compression phase and holding phase. The model includes convective and conductive heat transfer, fluid motion as well as an enzyme transport equation with a first‐order kinetic source term accounting for the inactivation. Three configurations with a total volume of 0.8 L, 6.3 L, and 50.3 L are considered. The pressure medium is water. The enzyme solution isB. subtilisα‐amylase dissolved in a TRIS‐HCl‐buffer. The packaging material is polypropylene. The heat‐transfer coefficient for conduction through the packaging material is varied to simulate both changes in the material properties as well as modifications of the packaging material thickness. It is found that the efficiency of the inactivation increases with increasing chamber volume as long as the kinetic inactivation constant is increasing with temperature. In the considered case the activity retention obtained in a 0.8 L volume is about 2.4 times larger than the one obtained for the same process carried out in a 50.3 L volume. Furthermore, it was found that the properties of the packaging material could induce a significant degree of nonuniformity (worst case = 69%). An appropriate choice of the material can lead to maximum inactivation and maximum process uniformity since advantage is taken from the slow heat exchange after the compression phase. © 2003 Wiley Periodicals, Inc. Biotechnol Bioeng 82: 725–735, 2003.
Suggested improvements to the standard filter paper assay used to measure cellulase activity
Authors: Coward‐Kelly Guillermo , Aiello‐Mazzari Cateryna , Kim Sehoon , Granda Cesar , Holtzapple Mark 
Published: March 2003

AbstractTwo suggestions can be found in the literature to improve the reproducibility of the Mandels' filter paper assay: add supplemental cellobiase and increase the boiling time for color development. Here we provide data that strongly supports adding supplemental cellobiase. Adding supplemental cellobiase increased assay response by 56%. Cellulases from different sources have different cellobiase activities, which would cause significant variation in the assay response. There is no need for additional boiling time—5 minutes is sufficient. For maximum reproducibility, it is essential that the water bath vigorously boil so that temperature excursions are minimized. © 2003 Wiley Periodicals, Inc. Biotechnol Bioeng 82: 745–749, 2003.
Influence of morphology on the near‐infrared spectra of mycelial biomass and its implications in bioprocess monitoring
Authors: Vaidyanathan Seetharaman , White Stewart , Harvey Linda M. , McNeil Brian 
Published: March 2003

AbstractBioprocesses that employ mycelial microorganisms are commercially important. The application of optical techniques for the measurement of biomass in such processes is limited by the morphological heterogeneity exhibited by the mycelial microorganism employed. We investigated the influence of morphology on the near‐infrared (NIR) spectra of the biomass of Streptomyces fradiae, a filamentous microorganism, by studying the spectra of mycelial suspensions that were manipulated to generate a range of morphological forms. Computerized image analysis was used to characterize the morphological forms. Principal component analysis was used to assess the spectral variations and study correlations to the manipulated mycelial morphology. Although morphology was found to influence the near infrared transmittance spectra of biomass, the influence was less pronounced than in the visible region, the spectral information at longer wavelengths (1600–2350 nm) showing greater stability to morphological variations. Long‐wave NIR spectral information is therefore likely to be more useful in estimating biomass in mycelial bioprocesses. Furthermore, the NIR reflectance spectra of dried biomass were found to show correlations to the morphological variations introduced, suggesting that NIR spectra may be useful in obtaining morphology related information. © 2003 Wiley Periodicals, Inc. Biotechnol Bioeng 82: 715–724, 2003.
Supernumerary humeral heads of the biceps brachii muscle revisited
Authors: Rodríguez‐Niedenführ Marc , Vázquez Teresa , Choi David , Parkin Ian , Sañudo José R. 
Published: March 2003

AbstractSupernumerary humeral heads of the biceps brachii muscle were found in 27 (15.4%) of 175 cadavers. They were bilateral in five cadavers and unilateral in 22 (8 left, 14 right), giving a total of 32 examples in 350 arms (9.1%). Depending on their origin and location, the supernumerary heads were classified as superior, infero‐medial, and infero‐lateral humeral heads. Previous studies were reviewed using this classification. The infero‐medial humeral head was observed in 31 of 350 (9%) arms and was therefore the most common variation. The superior humeral head was observed in five (1.5%). The infero‐lateral humeral head was the least common variation, observed only in one (0.3%) of 350 arms. A biceps brachii with three heads was observed in 27 of 350 (7.7%) arms and with four heads in five (1.4%) arms. Clin. Anat. 16:197–203, 2003. © 2003 Wiley‐Liss, Inc.
Force‐length characteristics of the in vivo human gastrocnemius muscle
Authors: Maganaris Constantinos N. 
Published: March 2003

AbstractIn this study, the force‐length characteristics of the in vivo medial (GM) and lateral (GL) heads of the human gastrocnemius muscle were estimated from measurements in eight healthy male subjects. This involved: 1) dynamometry‐based measurements of the moment generated during maximal isometric plantar flexion; 2) ultrasound‐based measurements of fascicular length and pennation angle; and 3) ultrasound‐based calculations of moment arm lengths. All measurements were taken over the ankle angle range from 20° of dorsiflexion to 30° of plantar flexion. Tendon forces were calculated by dividing the moments recorded by the muscle moment arm lengths, and fascicular forces were calculated by dividing the tendon forces estimated by the cosine of pennation angle. In the transition from 30° of plantar flexion to 20° of dorsiflexion, the GM muscle fascicular length and force increased linearly from 24 to 39 mm and from 222 to 931 N, respectively. Over the same ankle angle range, the GL muscle fascicular length and force increased linearly from 30 to 47 mm and from 139 to 393 N, respectively. Estimates of the sarcomeric lengths corresponding to the fascicular lengths measured indicated that the two muscles operated in the range 1.4–2.2 μm, below the optimal length region for force generation according to the cross‐bridge mechanism of contraction. These results indicate that the force–length relation of the in vivo human gastrocnemius muscle is limited to the ascending limb of the bell‐shaped force–length curve obtained from experiments on isolated material. Clin. Anat. 16:215–223, 2003. © 2003 Wiley‐Liss, Inc.
Anatomical study of the “trochanteric bursa”
Authors: Dunn Tirith , Heller C. Ann , McCarthy Stanley W. , Dos Remedios Cristobal 
Published: March 2003

AbstractTo resolve ambiguity in the literature about the anatomy of the “trochanteric bursa” or trochanteric subgluteus maximus bursa, this study examines the constancy, structure, and relationships of this bursa in a series of anatomical dissections of the hip. Sixteen embalmed hip specimens, from subjects aged 63–91 years, were examined. Subgluteus maximus bursae were demonstrated in 13 hips. In each of these a bursa, the deep bursa, was seen immediately superficial to the common attachment of the gluteus medius, minimus, and vastus lateralis muscles onto the greater trochanter. In five hips a smaller second bursa, the superficial bursa, was reflected with the gluteus maximus muscle. In two hips, four bursae were identified. The additional bursae were associated with either the deep or the superficial bursa. Examination of histological samples from the bursal walls confirmed the presence of a synovial lining in varying stages of development in seven of the eight bursae examined. Branches of the inferior gluteal nerve were seen to supply deep and superficial bursae in two dissections. The study data indicate that subgluteus maximus bursae at the level of the greater trochanter are an expected finding in the older age group and that they vary in number, position, and histological appearance. These features give rise to the hypothesis that these bursae are acquired as a consequence of excessive friction between the greater trochanter and the gluteus maximus as it inserts into the fascia lata. Clin. Anat. 16:233–240, 2003. © 2003 Wiley‐Liss, Inc.
How should we treat short hepatic veins and paracaval branches in anterior hepatectomy using the hanging maneuver without mobilization of the liver?
Authors: Hirai Ichiro , Murakami Gen , Kimura Wataru , Kanamura Tetsuhiro , Sato Iwao 
Published: March 2003

AbstractThis study investigates the relevant anatomy for applying the hanging maneuver to hepatectomy by an anterior approach, where liver mobilization is not possible. Using 176 cadaveric livers, we morphometrically investigated the distribution of venous openings within the retrohepatic portion of the inferior vena cava (IVC); next, we conducted a series of experiments to identify which course for insertion of a pair of forceps preserved the thickest of these veins. After anterior dissection of the liver, we carried out an anterior incision along a plane within an area free of venous openings in the IVC. The area free of venous openings was between the thickest caudate vein and the inferior right hepatic vein (IRHV), and averaged 16.2 mm in width. When forceps were inserted along the rightward course connecting the right inferior angle of the right lobe and the same pocket‐like space between the terminals of the middle and right hepatic veins, the caudate vein was very likely to be preserved, whereas the IRHV was not. In contrast, the leftward course connecting the gallbladder fossa and the pocket‐like space provided an almost opposite incidence of damage. The portal territory of the hilar bifurcation was most likely to be damaged during a virtual incision along an avascular plane; however, the caudate branch of left portal origin was rarely damaged. The rightward course may be the best method for forceps insertion in cases where there is no IRHV. To preserve the caudate vein and the IRHV, taping on the right side of the IRHV and retracting to the right, or changing the direction of the forceps from leftward to rightward when the tip of the forceps is anterior to the IVC is recommended. The hanging maneuver by an anterior approach without mobilization is convenient for right or left hepatectomy for large tumors or hardened liver. Clin. Anat. 16:224–232, 2003. © 2003 Wiley‐Liss, Inc.