bluuebunny/crossref_metadata_2025_split huggingface dataset:
Stabilization of nanoparticles under biological assembly conditions using peptoids
Authors: Robinson David B. , Buffleben George M. , Langham Mary E. , Zuckermann Ronald N. 
Published: January 2011

AbstractSequence‐specific polymers are proving to be a powerful approach to assembly and manipulation of matter on the nanometer scale. This has been most impressive in the case of DNA, and progress has been made toward templating inorganic nanoparticles using DNA nanostructures. One obstacle to this progress is that inorganic nanomaterials are often incompatible with DNA assembly conditions, which involve aqueous solutions high in either or both monovalent and divalent salt. Synthetic oligopeptide ligands have been shown by others to improve nanoparticle stability in high concentrations of monovalent salt. Ligands that are peptoids, or sequence‐specific N‐functional glycine oligomers, allow precise and flexible control over the arrangement of binding groups, steric spacers, charge, and other functionality. We have synthesized short peptoids that can prevent the aggregation of gold nanoparticles in high‐salt environments including divalent salt, and allow coadsorption of a single DNA molecule. This degree of precision and versatility is likely to prove essential in bottom‐up assembly of nanostructures and in biomedical applications of nanomaterials. © 2011 Wiley Periodicals, Inc. Biopolymers (Pept Sci) 96: 669–678, 2011.
Effect of the circumferential resection margin on survival following rectal cancer surgery
Authors: Kelly S B , Mills S J , Bradburn D M , Ratcliffe A A , Borowski D W 
Published: January 2011

AbstractBackgroundThe aim was to determine the effect of the circumferential resection margin (CRM) on overall survival following surgical excision of rectal cancer.MethodsThe effect of CRM on survival was examined by case mix-adjusted analysis of patients undergoing potentially curative excision of a rectal cancer between 1998 and 2002.ResultsOf 1896 patients, 1561 (82·3 per cent) had recorded data on the CRM. In 232 patients (14·9 per cent) tumour was found 1 mm or less from the CRM. In 370 patients (23·7 per cent) it was over 1 mm but no more than 5 mm from the CRM, and in 288 (18·4 per cent) it was over 5 mm but no more than 10 mm from the CRM. The remaining 671 patients (43·0 per cent) had a CRM exceeding 10 mm. Overall 5-year survival rates for these groups were 43·2, 51·7, 66·6 and 66·0 per cent respectively. Compared with patients with a CRM exceeding 10 mm, the adjusted risk of death was significantly increased for patients with a CRM of 1 mm or less (hazard ratio (HR) 1·61, P &lt; 0·001) and those with a margin greater than 1 mm but no larger than 5 mm (HR 1·35, P = 0·005). There was no added risk for patients with tumour more than 5 mm but 10 mm or less from the CRM (HR 1·02, P = 0·873). The adverse effect of a CRM greater than 1 mm but no larger than 5 mm was found particularly in mid-rectal cancers.ConclusionA predicted CRM of 5 mm or less on preoperative staging should be considered for neoadjuvant treatment.
Systematic review and meta-analysis of the volume–outcome relationship in pancreatic surgery
Authors: Gooiker G A , van Gijn W , Wouters M W J M , Post P N , van de Velde C J H , Tollenaar R A E M 
Published: January 2011

Abstract

Background
Many studies have shown lower mortality and higher survival rates after pancreatic surgery with high-volume providers, suggesting that centralization of pancreatic surgery can improve outcomes. The methodological quality of these studies is open to question. This study involves a systematic review of the volume–outcome relationship for pancreatic surgery with a meta-analysis of studies considered to be of good quality.

Methods
A systematic search of electronic databases up to February 2010 was performed to identify all primary studies examining the effects of hospital or surgeon volume on postoperative mortality and survival after pancreatic surgery. All articles were critically appraised with regard to methodological quality and risk of bias. After strict inclusion, meta-analysis assuming a random-effects model was done to estimate the effect of higher surgeon or hospital volume on patient outcome.

Results
Fourteen studies were included in the meta-analysis. The results showed a significant association between hospital volume and postoperative mortality (odds ratio 0·32, 95 per cent confidence interval 0·16 to 0·64), and between hospital volume and survival (hazard ratio 0·79, 0·70 to 0·89). The effect of surgeon volume on postoperative mortality was not significant (odds ratio 0·46, 0·17 to 1·26). Significant heterogeneity was seen in the analysis of hospital volume and mortality. Sensitivity analysis showed no correlation with the extent of risk adjustment or study country; after removing one outlier study, the result was homogeneous. The data did not suggest publication bias.

Conclusion
There was a consistent association between high hospital volume and lower postoperative mortality rates with improved long-term survival.
Design of a novel automated methanol feed system for pilot‐scale fermentation of Pichia pastoris
Authors: Hamaker Kent H. , Johnson Daniel C. , Bellucci Joseph J. , Apgar Kristie R. , Soslow Sherry , Gercke John C. , Menzo Darrin J. , Ton Christopher 
Published: January 2011

AbstractLarge‐scale fermentation of Pichia pastoris requires a large volume of methanol feed during the induction phase. However, a large volume of methanol feed is difficult to use in the processing suite because of the inconvenience of constant monitoring, manual manipulation steps, and fire and explosion hazards. To optimize and improve safety of the methanol feed process, a novel automated methanol feed system has been designed and implemented for industrial fermentation of P. pastoris. Details of the design of the methanol feed system are described. The main goals of the design were to automate the methanol feed process and to minimize the hazardous risks associated with storing and handling large quantities of methanol in the processing area. The methanol feed system is composed of two main components: a bulk feed (BF) system and up to three portable process feed (PF) systems. The BF system automatically delivers methanol from a central location to the portable PF system. The PF system provides precise flow control of linear, step, or exponential feed of methanol to the fermenter. Pilot‐scale fermentations with linear and exponential methanol feeds were conducted using two Mut+ (methanol utilization plus) strains, one expressing a recombinant therapeutic protein and the other a monoclonal antibody. Results show that the methanol feed system is accurate, safe, and efficient. The feed rates for both linear and exponential feed methods were within ±5% of the set points, and the total amount of methanol fed was within 1% of the targeted volume. © 2011 American Institute of Chemical Engineers Biotechnol. Prog., 2011
Chemometrics applications in biotech processes: A review
Authors: Rathore Anurag S. , Bhushan Nitish , Hadpe Sandip 
Published: January 2011

AbstractBiotech unit operations are often characterized by a large number of inputs (operational parameters) and outputs (performance parameters) along with complex correlations amongst them. A typical biotech process starts with the vial of the cell bank, ends with the final product, and has anywhere from 15 to 30 such unit operations in series. The aforementioned parameters can impact process performance and product quality and also interact amongst each other. Chemometrics presents one effective approach to gather process understanding from such complex data sets. The increasing use of chemometrics is fuelled by the gradual acceptance of quality by design and process analytical technology amongst the regulators and the biotech industry, which require enhanced process and product understanding. In this article, we review the topic of chemometrics applications in biotech processes with a special focus on recent major developments. Case studies have been used to highlight some of the significant applications. © 2011 American Institute of Chemical Engineers Biotechnol. Prog., 2011
Intracellular localization of adeno‐associated viral proteins expressed in insect cells
Authors: Gallo‐Ramírez Lilí E. , Ramírez Octavio T. , Palomares Laura A. 
Published: January 2011

AbstractProduction of vectors derived from adeno‐associated virus (AAVv) in insect cells represents a feasible option for large‐scale applications. However, transducing particles yields obtained in this system are low compared with total capsid yields, suggesting the presence of genome encapsidation bottlenecks. Three components are required for AAVv production: viral capsid proteins (VP), the recombinant AAV genome, and Rep proteins for AAV genome replication and encapsidation. Little is known about the interaction between the three components in insect cells, which have intracellular conditions different to those in mammalian cells. In this work, the localization of AAV proteins in insect cells was assessed for the first time with the purpose of finding potential limiting factors. Unassembled VP were located either in the cytoplasm or in the nucleus. Their transport into the nucleus was dependent on protein concentration. Empty capsids were located in defined subnuclear compartments. Rep proteins expressed individually were efficiently translocated into the nucleus. Their intranuclear distribution was not uniform and differed from VP distribution. While Rep52 distribution and expression levels were not affected by AAV genomes or VP, Rep78 distribution and stability changed during coexpression. Expression of all AAV components modified capsid intranuclear distribution, and assembled VP were found in vesicles located in the nuclear periphery. Such vesicles were related to baculovirus infection, highlighting its role in AAVv production in insect cells. The results obtained in this work suggest that the intracellular distribution of AAV proteins allows their interaction and does not limit vector production in insect cells. © 2011 American Institute of Chemical Engineers Biotechnol. Prog., 2011
Starvation induces physiological changes that act on the cryotolerance of Lactobacillus acidophilus RD758
Authors: Wang Yu , Delettre Jérôme , Corrieu Georges , Béal Catherine 
Published: January 2011

AbstractThe relationship between lactose starvation and cryotolerance was investigated in Lactobacillus acidophilus RD758. Cryotolerance was measured from the acidification activity of cells recovered after 18‐h lactose starvation. It was compared to that of nonstarved cells, both of them in a stationary phase and in the same medium. This measurement allowed quantifying the initial acidification activity before freezing, as well as the loss of acidification activity during freezing and the rate of loss during frozen storage. Even if initial acidification activity was similar for nonstarved and starved bacteria, the latter displayed a significantly better resistance to freezing and frozen storage at −20°C. To investigate the mechanisms that triggered these cryotolerance phenomena, the membrane fatty acid composition was determined by gas chromatography, and the proteome was established by 2‐D electrophoresis, for starved and nonstarved cells. The main outcome was that the improved cryotolerance of starved cells was ascribed to two types of physiological responses as a result of starvation. The first one corresponded to an increased synthesis of unsaturated, cyclic, and branched fatty acids, to the detriment of saturated fatty acids, thus corresponding to enhanced membrane fluidity. The second response concerned the upregulation of proteins involved in carbohydrate and energy metabolisms and in pH homeostasis, allowing the cells to be better prepared for counteracting the stress they encountered during subsequent cold stress. These two phenomena led to a cross‐protection phenomenon, which allowed better cryotolerance of Lb. acidophilus RD758, following cellular adaptation by starvation. © 2011 American Institute of Chemical Engineers Biotechnol. Prog., 2011
Effect of constitutively active ras overexpression on cell growth in recombinant chinese hamster ovary cells
Authors: Kim Yeon‐Gu , Han Young Kue , Kim Jee Yon , Lee Eun Gyo , Lee Hong Weon , Lee Gyun Min 
Published: January 2011

AbstractConstitutively active Ras (CA‐Ras) is known to enhance cell growth through the induction of various signaling cascades including the phosphoinositide 3‐kinase (PI3K)/Akt and mitogen‐activated protein kinase (MAPK)/ERK signaling pathways, although the cellular response is highly dependent on the cell type. To evaluate the effect of CA‐Ras overexpression on cell growth in recombinant Chinese hamster ovary (rCHO) cells, an erythropoietin (EPO)‐producing rCHO cell line with regulated CA‐Ras overexpression (EPO‐off‐CA‐Ras) was established using the Tet‐off system. The CA‐Ras expression level in EPO‐off‐CA‐Ras cells was tightly regulated by doxycycline addition. Although CA‐Ras overexpression slightly increased the viable cell concentration during the late exponential phase, it did not increase the maximum viable cell concentration or specific growth rate to a significant degree. Unexpectedly, CA‐Ras overexpression in rCHO cells led only to the enhancement in the activation of the MAPK/ERK signaling pathway and not the PI3K/Akt signaling pathway. Taken together, CA‐Ras overexpression in rCHO cells did not significantly affect cell growth; it also had no critical impact on viable cell concentration or EPO production, possibly due to a failure to activate the PI3K/Akt signaling pathway. © 2011 American Institute of Chemical Engineers Biotechnol. Prog., 2011
Demonstrating β‐glucan and yeast peptide clearance in biopharmaceutical downstream processes
Authors: Jiang Canping , Scherfner Sarah , Shukla Abhinav A. 
Published: January 2011

AbstractThe use of yeast‐ and plant‐derived hydrolysates in cell culture production processes has sparked concerns over the potential immunogenicity risk posed by β‐glucans and yeast peptides contained in these raw materials. This article utilizes a combination of in‐process testing from large‐scale manufacturing and scale‐down spiking studies to demonstrate the clearance of β‐glucans and yeast peptides through chromatographic steps in the downstream purification process for a monoclonal antibody. β‐Glucans were found to flow through most all three modes of chromatography (Protein A, cation and anion exchange) without binding to the resins or the product. Protein A affinity chromatography was found to provide the best clearance factor. The efficacy of the resin sanitization and storage procedures to prevent carryover from one run to the next was also demonstrated. Yeast peptides were found to be metabolized during the cell culture process and were undetectable after the Protein A purification step. The data presented here serve to allay concerns about the use of hydrolysates in cell culture production. The methodology presented here provides a template to demonstrate clearance of β‐glucans and yeast peptides through chromatographic steps in downstream processing. © 2011 American Institute of Chemical Engineers Biotechnol. Prog., 2011
A new microfluidic concept for parallel operated milliliter‐scale stirred tank bioreactors
Authors: Gebhardt Gabi , Hortsch Ralf , Kaufmann Klaus , Arnold Matthias , Weuster‐Botz Dirk 
Published: January 2011

AbstractParallel miniaturized stirred tank bioreactors are an efficient tool for “high‐throughput bioprocess design.” As most industrial bioprocesses are pH‐controlled and/or are operated in a fed‐batch mode, an exact scale‐down of these reactions with continuous dosing of fluids into the miniaturized bioreactors is highly desirable. Here, we present the development, characterization, and application of a novel concept for a highly integrated microfluidic device for a bioreaction block with 48 parallel milliliter‐scale stirred tank reactors (V = 12 mL). The device consists of an autoclavable fluidic section to dispense up to three liquids individually per reactor. The fluidic section contains 144 membrane pumps, which are magnetically driven by a clamped‐on actuator section. The micropumps are designed to dose 1.6 μL per pump lift. Each micropump enables a continuous addition of liquid with a flow rate of up to 3 mL h−1. Viscous liquids up to a viscosity of 8.2 mPa s (corresponds to a 60% v/v glycerine solution) can be pumped without changes in the flow rates. Thus, nearly all feeding solutions can be delivered, which are commonly used in bioprocesses. The functionality of the first prototype of this microfluidic device was demonstrated by double‐sided pH‐controlled cultivations of Saccharomyces cerevisiae based on signals of fluorimetric sensors embedded at the bottom of the bioreactors. Furthermore, fed‐batch cultivations with constant and exponential feeding profiles were successfully performed. Thus, the presented novel microfluidic device will be a useful tool for parallel and, thus, efficient optimization of controlled fed‐batch bioprocesses in small‐scale stirred tank bioreactors. This can help to reduce bioprocess development times drastically. © 2011 American Institute of Chemical Engineers Biotechnol. Prog., 2011.
Characterization of superporous cellulose matrix for high‐throughput adsorptive purification of lysozyme
Authors: Kale Sandeep , Lali Arvind 
Published: January 2011

AbstractProtein purification essentially requires macroporous adsorbents matrices, which can provide high efficiency in packed bed and expanded bed (EB) even at high flow rates on account of reduced pore diffusion resistance resulting from finite intraparticle flow in the superpores. Rigid spherical superporous adsorbent beads with high carboxyl group density were prepared by crosslinking of cellulose. The matrix (diameter: 100–300 μm, mean pore size: 1–3 μm, pore volume: 57–59%, and bulk density: ∼1,438 kg/m3) could be used in packed bed as well as EB for purification of various biomolecules. Attempts were made to use indigenously developed rigid, superporous crosslinked cellulose adsorbent for high‐throughput purification of lysozyme from chicken egg white's extract. A typical adsorption isotherm for lysozyme in crude was well correlated with the Langmuir isotherm model. Two maxima of binding capacity on celbeads bearing carboxymethyl (celbeads‐CM) group for lysozyme were observed at pH 4.5 and 7.5. Uptake kinetics showed that the diffusivity of lysozyme was 100 times higher than conventional matrices. Such superporous matrix can be used for high‐throughput purification of proteins from crude feedstocks and is reflected in leveling off of height equivalent to theoretical plate vs. flow curve after threshold velocity. Optimization of binding and elution conditions resulted in overall purification of lysozyme in a high yield and purity of 98.22 and 98.8%, respectively, with purification factor of 51.54 in a single step. The overall productivity (14.21 kg/m3 h) and specific activity (2.2 × 105 U/mg) were higher than that obtained with traditional particulate resins. © 2011 American Institute of Chemical Engineers Biotechnol. Prog., 2011
Acceleration of protein aggregation by amphiphilic peptides: Transformation of supramolecular structure of the aggregates
Authors: Artemova N. V. , Stein‐Margolina V. A. , Bumagina Z. M. , Gurvits B. Ya. 
Published: January 2011

AbstractProtein self‐assembly and aggregation represent a special tool in biomedicine and biotechnology to produce biological materials for a wide range of applications. The protein aggregates are very different morphologically, varying from soluble amorphous aggregates to highly ordered amyloid‐like fibrils, the latter being associated with molecular structures able to perform specific functions in living systems. Fabrication of novel biomaterials resembling natural protein assemblies has awakened interest in identification of low‐molecular‐weight biogenic agents as regulators of transformation of aggregation‐prone proteins into fibrillar structures. Short amphiphilic peptides can be considered for this role. Using dynamic light scattering, turbidimetry, fluorescence spectroscopy, and transmission electron microscopy (TEM), we have demonstrated that the Arg‐Phe dipeptide dramatically accelerates the aggregation of a model protein, α‐lactalbumin, to generate morphologically different structures. TEM revealed transformation of spherical particles observed in the control samples into branched chains of fibril‐like nanostructures in the presence of the peptide, suggesting that amphiphilic peptides can induce changes in the physicochemical properties of a protein substrate (net charge, hydrophobicity, and tendency to β‐structure formation) resulting in accumulation of peptide–protein complexes competent to self‐assembly into supramolecular structures. A number of other short amphiphilic peptides have also been shown to accelerate the aggregation process, using alternative complementary protein substrates for identification of molecular recognition modules. Peptide–protein assemblies are suggested to play the role of building blocks for formation of supramolecular structures profoundly differing from those of the individual protein substrate in type, size, and shape. © 2011 American Institute of Chemical Engineers Biotechnol. Prog., 2011
Intussusception: An anatomical perspective with review of the literature
Authors: Loukas Marios , Pellerin Megan , Kimball Zachary , de la Garza‐Jordan Julia , Tubbs R. Shane , Jordan Robert 
Published: January 2011

AbstractOriginally described over 300 years ago, the clinical scenario of intussusception remains incompletely understood. Intussusception is now one of the conditions that can be, most of the time, preoperatively diagnosed and treated with success. This article reviews the literature regarding this pathological state of the abdomen and discusses what is known regarding the presentation, diagnosis, embryology, and anatomy of intussusception. Clin. Anat. 24:552–561, 2011. © 2011 Wiley‐Liss, Inc.
Giant Metastatic Alveolar Soft Part Sarcoma in the Left Ventricle: Appearance in Echocardiography, Magnetic Resonance Imaging, and Histopathology
Authors: Strecker Thomas , Schmid Axel , Agaimy Abbas , Hugo Claudia , Weyand Michael , Zielezinski Thorsten 
Published: January 2011

AbstractAlveolar soft part sarcoma is a rare soft‐tissue neoplasm that accounts for <1% of all soft‐tissue sarcomas. Most cases arise in the extremities and head and neck region of young adults. The common sites of metastasis are lung, brain, and bone. Cardiac metastasis is extremely rare, in particular. Here we present the diagnostic evaluation and successful surgical resection of such a cardiac tumor in a patient aged 50 years with a histology‐confirmed diagnosis of metastatic alveolar soft part sarcoma. © 2011 Wiley Periodicals, Inc.The authors have no funding, financial relationships, or conflicts of interest to
disclose.
Rational Design, Synthesis and Pharmacological Evaluation of the (2R)‐ and (2S)‐Stereoisomers of 3‐(2‐Carboxypyrrolidinyl)‐2‐methyl Acetic Acid as Ligands for the Ionotropic Glutamate Receptors
Authors: Rasmussen Julie L. , Storgaard Morten , Pickering Darryl S. , Bunch Lennart 
Published: January 2011

AbstractIn this paper we describe the rational design, synthesis and pharmacological evaluation of two new stereoisomeric (S)‐glutamate (Glu) analogues. The rational design was based on hybrid structures of the natural product kainic acid, a synthetic analogue CPAA and the high‐affinity Glu analogue SYM2081. Pharmacological evaluation of the two stereoisomers revealed that one stereoisomer showed a subtype selectivity profile with low micromolar affinity for GluK1 and GluK3 and a 10‐ to 15‐fold lower affinity for GluK2. The other stereoisomer displayed full selectivity for the KA over AMPA and NMDA receptors (GluK1–3: 0.39, 0.51 and 0.099 µM, respectively).