bluuebunny/crossref_metadata_2025 huggingface dataset:
Clinical Utility of Serum Tumor Markers in the Diagnosis of Malignant Intestinal Occlusion. A Prospective Observational Study
Authors: Marrelli Daniele , Caruso Stefano , Neri Alessandro , Pedrazzani Corrado , Capuano Lucia , Mazzei Maria Antonietta , Roviello Franco
Published: January 2011

Aim

The aim of the present observational study was to evaluate the diagnostic accuracy of CEA, CA 19-9 and CA 72-4 in patients with bowel obstruction.

Methods

One-hundred three patients admitted to an emergency unit with clinical and radiological signs of intestinal occlusion of unknown origin were prospectively studied. Patients submitted to emergency surgery were excluded. All patients underwent standard diagnostic procedures and serological assay of tumor markers.

Results

Colorectal cancer was diagnosed in 22 patients (21.4%), while 81 patients (78.6%) presented a benign condition. The sensitivity of CEA, CA 19-9 and CA 72-4 for colorectal cancer was 36.4%, 31.8% and 9.1%, respectively. Marker specificity was 91.4%, 90.1% and 95.1%, respectively. The combination of CEA and CA 19–9 increased the sensitivity to 45.5% but decreased the specificity to 83.9%. The overall accuracy was 79.6%, 77.7% and 76.7%, respectively. All positive cancer cases had advanced disease. All patients with CEA levels >10 ng/mL or CA 19-9 >100 U/mL had colorectal cancer.

Conclusions

Even in a highly selected population, tumor marker sensitivity was rather low and specificity incomplete. However, elevated levels may guide the diagnostic and therapeutic course in patients with obstructing colorectal cancer.
Tissue engineering of bone and cartilage: a view through the patent literature
Authors: Wolfinbarger Lloyd
Published: January 2011

Background: Tissue engineering takes on many approaches. It is mostly followed by those in the field through scientific literature. However, there is a virtually untapped resource in patent literature.

Objective: This review focuses on patents through the United States Patent and Trademark Office (USPTO). This source is used only because the author is most familiar with this resource. This article is not intended to be instructional regarding patents, patent law, or how to apply for patents, nor is it intended to be all inclusive of the patent literature. However, the reader might see the value of following the patent literature as a source of ideas, technologies, methodologies, and knowledge with respect to tissue engineering.
Radiation dose from CT scanning: can it be reduced?
Authors: Trinavarat Panruethai , Kritsaneepaiboon Supika , Rongviriyapanich Chantima , Visrutaratna Pannee , Srinakarin Jiraporn
Published: January 2011

CT has been used to save many patients’ lives and the demand for CT is still increasing. At the same time, there has been increasing concern of the probability of cancer induction by CT radiation. It is necessary for everyone involved in CT scanning, particularly physicians who have to communicate with patients when planning a CT scan, to have a basic knowledge of the CT radiation dose and its potential adverse effects. We have undertaken a systematic review of the literatures to document the radiation dose from CT, the lifetime cancer risk from CT exposure, CT dose parameters, the internationnal CT diagnostic reference levels, and the use and limitation of the CT effective dose. In addition, we conducted a brief survey of the use of CT scan in some university hospitals in Thailand and estimated current CT doses at these hospitals. Our review and survey suggests that CT scanning provides a great benefit in medicine but it also becomes the major source of X-ray exposure. Radiation doses from a CT scan are much higher than most conventional radiographic procedures. This raises concerns about the carcinogenic potentials. We encourage every CT unit to adhere to the International Guidelines of CT dose parameter references. Our preliminary survey from some university hospitals in Thailand revealed that CT radiation doses are within acceptable standard ranges. However, the justification for utilization of CT scans should also be required and monitored. The importance of adequate communication between attending physician and consulting radiologist is stressed.
Clinical and laboratory diagnosis of spinocerebellar ataxia type 3 in a large Chinese family
Authors: Yang Sirui , Xu Weihong , Li Shibo , Liu Shicheng , Lu Honghua , Hao Xiaosheng , Jia Feiyong , Xue Guiling
Published: January 2011

Background: Hereditary ataxia is a group of hereditary diseases that are characterized by chronic progressive uncoordinated gait and are frequently associated with cerebellar atrophy.

Objectives: To investigate evidence-based diagnosis of hereditary ataxia by retrospective analysis of the diagnostic process in one Chinese family.

Methods: Clinical records of 15 ataxia patients from one Chinese family with 46 family members were retrospectively reviewed and a tentative diagnosis was made based on clinical manifestations, signs and symptoms, mode of inheritance, and progression. Since hereditary ataxia is a group of heterogeneous diseases having various subtypes and overlapping symptoms, we adopted a stepwise evaluation to achieve a tentative diagnosis. To confirm the diagnosis, we performed polymerase chain reaction (PCR) specific for the suspected causative gene of spinocerebellar ataxia (SCA) subtype 3 (SCA3).

Results: Through analysis of hereditary and clinical characteristics of family histories of the patients, we suspected that the family might suffer from SCA, especially, SCA3. The PCR assay for SCA3 showed that, five of the ten samples analyzed had a CAG trinucleotide expansion of the SCA3 gene, and four of the five members developed ataxia. The remaining one, a seven-year-old girl, showed no symptoms or signs except for uvula deviation. No clinical symptoms were found in five other members with negative PCR results. Thus, based on both clinical findings and laboratory results, we further confirmed that the family suffered from SCA3.

Conclusion: Hereditary ataxias are disorders sharing overlapping symptoms. Comprehensive analysis of medical and family records together with genetic diagnosis improves diagnostic efficiency of hereditary ataxia and aides in family counseling.
Antiviral activities of aerial subsets of Artemisia species against Herpes Simplex virus type 1 (HSV1) in vitro
Authors: Karamoddini Mehrangiz Khajeh , Emami Seyed Ahmad , Ghannad Masoud Sabouri , Sani Esmaeel Alizadeh , Sahebkar Amirhossein
Published: January 2011

Background: Drug resistance to current anti-herpetic drugs has been increasingly reported. Therefore, there is a need for finding new antiviral agents, in particular from natural sources.

Objective: In the present study, antiviral activity of subset extracts obtained from aerial parts of Artemisia including A. incana, A. chamaemelifolia, A. campesteris, A. fragrans, A. annua, A. vulgaris, and A. persica were investigated against Herpes Simplex type I (HSV1).

Methods: Different concentrations of extracts (400, 200, 100, 50, 25, 12.5, 6.25, and 3.125 μg/mL) were obtained from subset of each plant separately, and used against KOS strain of HSV1 in HeLa cells. After 24 hours incubation, tetrazolium dye (MTT), was added. The dye absorption by viable cells was measured and compared to the positive control (extract-untreated cells) and acyclovir (as anti-viral agent).

Results: The extracts obtained from A. annua had the highest antiviral activity while those of A. chamaemelifolia showed the lowest activity.

Conclusion: Subset extracts of A. annua may be an appropriate candidate for further development of anti HSV1 infection.
Archaeology as a High Court in Ancient Israelite History: A Reply to Nadav Na’aman
Authors: Finkelstein Israel
Published: January 2011

This is a rejoinder to N. Na'aman, "Does Archaeology Really Deserve the Status of A ‘High Court’ in Biblical and Historical Research?," B. Becking and L.L. Grabbe (eds.) Between Evidence and Ideology (OtSt, 59; Leiden: Brill, 165–183) that claims that although archaeological evidence can be fragmentary and may be misinterpreted, when solid data from well-excavated sites is compared to assumptions regarding the nature of biblical texts and their date of compilation, the former should prevail, at least until tested by new archaeological evidence or extra-biblical texts.
City as Political Form: Four Archetypes of Urban Transformation
Authors: Aureli Pier Vittorio
Published: January 2011

Pier Vittorio Aureli focuses on the category of archetype as an alternative to the idea of type. Four examples – the axial streets of Renaissance Rome, the 17th‐century Parisian place, the 19th‐century independent block in Berlin and the 20th‐century Viennese superblock – are explored here to describe the emergence of modern urban forms that explicitly embody power relations.
Type, Field, Culture, Praxis
Authors: Carl Peter
Published: January 2011

Here, Peter Carl substitutes the term ‘type’ for the typical, and ‘typology’ for typicality. In so doing he frees up the notion of type for contemporary design, liberating it from the strictures of its performance history and precedents that have often veered towards standardisation.
Typological Instruments: Connecting Architecture and Urbanism
Authors: Bos Caroline , van Berkel/UNStudio Ben
Published: January 2011

For Caroline Bos and Ben van Berkel of UNStudio, type in architecture ‘exists to direct, to connect or to be instrumental’ rather than to prescribe. They describe how in their projects for Arnhem Central in the Netherlands and the Raffles City development in Hangzhou, China, they have deftly developed and applied typologies in order to gain control of the design process in complex urban contexts.
The Metropolis as Integral Substance
Authors:   l'AUC Architects and Urbanists (François Decoster, Caroline Poulin, Djamel Klouche)
Published: January 2011

l'AUC Architects and Urbanists (François Decoster, Caroline Poulin and Djamel Klouche) advocate an approach to typological urbanism that they refer to as ‘urbanism of substance’. Here they describe three projects for Paris in which they have developed this strategy for maximising the intensity between local, metropolitan and global conditions.
Transcending Type: Designing for Urban Complexity
Authors: Shane David Grahame
Published: January 2011

David Grahame Shane, the author of a major new study Urban Design Since 1945: A Global Perspective, looks at type with the benefit of historical hindsight. Warning against its potential inflexibility and its use over the centuries as a reductive instrument in city creation, he is insistent that type should only be applied if deformed to respond to the informal patchwork of hybrid urban conditions.
Combined exposures to workplace psychosocial stressors: Relationships with mental health in a sample of NZ cleaners and clerical workers
Authors: Lilley R. , LaMontagne A.D. , Firth H.
Published: January 2011

Background

A combined measure of two common psychosocial stressors, called job pressure has previously been shown to be strongly associated with poor mental health in high status workers. This study tests the generalizability of this association to lower status workers.

Methods

A national random sample of cleaners and clerical workers was obtained from the New Zealand (NZ) electoral roll by occupational title (n = 596). Cross‐sectional data on job stressors, demographics, and mental health (GHQ‐12) was collected by computer‐assisted telephone interviews.

Results

Combined exposure to low job control, high job demands, and job insecurity (high job pressure) was associated with markedly elevated odds (13‐fold or higher) of poor mental health after adjustment for age, sex, occupation, and education.

Conclusion

Combined with previous findings this suggests simultaneous exposure to more than one occupational psychosocial stressor may greatly increase the risk of poor mental health among both lower and higher status workers. This report adds to the larger literature in this area, supporting the need for expanded policy and practice intervention to reduce job stressors across the working population. Am. J. Ind. Med. 54:405–409, 2011. © 2011 Wiley‐Liss, Inc.
Association of GWAS loci with PD in China
Authors: Chang Xue‐Li , Mao Xue‐Ye , Li Hui‐Hua , Zhang Jin‐Hong , Li Nan‐Nan , Burgunder Jean‐Marc , Peng Rong , Tan Eng‐King
Published: January 2011

Genome‐wide association studies (GWAS) have identified numerous single‐nucleotide polymorphisms (SNPs) at four loci (SNCA, PARK16, LRRK2, BST1) that can modulate the risk of Parkinson's disease (PD). The strength of these associations has yet to be clarified in Mainland China. Ethnic specific effect is an important consideration in GWAS analysis. Using a case–control methodology, we genotyped multiple SNPs at these four loci to investigate their association with risk of PD in Mainland China. A total of 1,146 study subjects comprising 636 patients with PD and 510 unrelated healthy controls were recruited. The minor alleles at SNPs rs894278, rs1994090, rs2046932, rs4698412, and rs7304279 were found to be significantly higher in cases than in controls, while the minor alleles were found to significantly reduce the risk of developing PD at SNPs rs823128, rs823156, rs6532194, rs1191532, and rs16856139. These associations remained after taking into considerations the effects of age and gender. We showed that multiple SNPs at LRRK2 and SNCA increase risk of PD, while PARK16 SNPs are associated with a lower risk of PD in China. Our study findings will contribute to further research using GWAS‐linked data and research on ethnic specific effect of common variants. © 2011 Wiley‐Liss, Inc.
Special features of historical papers from the viewpoint of bibliometrics
Authors: Marx Werner
Published: January 2011

This paper deals with the specific features of historical papers relevant for information retrieval and bibliometrics. The analysis is based mainly on the citation indexes accessible under the Web of Science (WoS) but also on field‐specific databases: the Chemical Abstracts Service (CAS) literature database and the INSPEC database. First, the journal coverage of the WoS (in particular of the WoS Century of Science archive), the limitations of specific search fields as well as several database errors are discussed. Then, the problem of misspelled citations and their “mutations” is demonstrated by a few typical examples. Complex author names, complicated journal names, and other sources of errors that result from prior citation practice are further issues. Finally, some basic phenomena limiting the meaning of citation counts of historical papers are presented and explained.
The importance of theories of knowledge: Browsing as an example
Authors: Hjørland Birger
Published: January 2011

The study on information science (IS) by Bates (2007) is an important contribution to the literature on browsing in IS. It is explicitly based on “behavioural science.” I use this article as the point of departure for demonstrating how more social and interpretative understandings may provide fruitful improvements for research in information seeking, browsing, and related phenomena. It is part of my ongoing publication of articles about philosophical issues in IS and it is intended to be accompanied by analyses of other examples of contributions to core issues in IS. Although it is mainly formulated as a discussion based on a specific paper, it should be seen as part of a general discussion of the philosophical foundation of IS and as support for the emerging social paradigm in this field. The article argues that human browsing should not be conceptualized primarily in biological terms and should not be understood as random exploratory processes, but rather it should be seen as a kind of orienting strategy governed by people's metatheories or “paradigms.” Information professionals should know how different metatheories are distributed in the information ecology and, thus, be able to help people developing fruitful browsing strategies.
Modifying behavioral phenotypes in Fmr1KO mice: genetic background differences reveal autistic‐like responses
Authors: Spencer Corinne M. , Alekseyenko Olga , Hamilton Shannon M. , Thomas Alexia M. , Serysheva Ekaterina , Yuva‐Paylor Lisa A. , Paylor Richard
Published: January 2011

Fragile X syndrome (FXS) is the most common inherited form of intellectual disability in humans. In addition to cognitive impairment, patients may exhibit hyperactivity, attention deficits, social difficulties and anxiety, and autistic‐like behaviors. The degree to which patients display these behaviors varies considerably and is influenced by family history, suggesting that genetic modifiers play a role in the expression of behaviors in FXS. Several studies have examined behavior in a mouse model of FXS in which the Fmr1 gene has been ablated. Most of those studies were done in Fmr1 knockout mice on a pure C57BL/6 or FVB strain background. To gain a better understanding of the effects of genetic background on behaviors resulting from the loss of Fmr1 gene expression, we generated F1 hybrid lines from female Fmr1 heterozygous mice on a pure C57BL/6J background bred with male Fmr1 wild‐type (WT) mice of various background strains (A/J, DBA/2J, FVB/NJ, 129S1/SvImJ and CD‐1). Male Fmr1 knockout and WT littermates from each line were examined in an extensive behavioral test battery. Results clearly indicate that multiple behavioral responses are dependent on genetic background, including autistic‐like traits that are present on limited genetic backgrounds. This approach has allowed us to identify improved models for different behavioral symptoms present in FXS including autistic‐like traits.
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

Sequence‐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

Background

The aim was to determine the effect of the circumferential resection margin (CRM) on overall survival following surgical excision of rectal cancer.

Methods

The 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.

Results

Of 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 < 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.

Conclusion

A 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

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

Large‐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

Biotech 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

Production 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

The 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

Constitutively 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

The 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

Parallel 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

Protein 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

Protein 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

Originally 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

Alveolar 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

In 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).
The COSY and DQF‐COSY NMR spectra of an AX system of spins I = 3/2
Authors: Kempgens P.
Published: January 2011

The 2D NMR COSY and DQF‐COSY spectra of an AX system of spins I = 3/2 have been calculated by numerical density matrix calculations. The results are presented in two extreme cases, namely in the slow relaxation regime and in the fast relaxation regime. It is concluded that in addition to the usual advantages that the DQF‐COSY NMR experiment offer compared with the conventional COSY NMR experiment (observation of only‐coupled spins, antiphase character of both diagonal and cross‐peaks and intensity of the cross peaks comparable to the intensity of the diagonal peaks), the DQF‐COSY NMR experiment appear to be more reliable for interpretation and analysis than the conventional COSY NMR experiment and this is particularly true for quadrupolar nuclei relaxing usually very quickly. © 2011 Wiley Periodicals, Inc. Concepts Magn Reson Part A 38A: 7–15, 2011.
Detecting evolving patterns of self‐organizing networks by flow hierarchy measurement
Authors: Luo Jianxi , Magee Christopher L.
Published: January 2011

Hierarchies occur widely in evolving self‐organizing ecological, biological, technological, and social networks, but detecting and comparing hierarchies is difficult. Here we present a metric and technique to quantitatively assess the extent to which self‐organizing directed networks exhibit a flow hierarchy. Flow hierarchy is a commonly observed but theoretically overlooked form of hierarchy in networks. We show that the ecological, neurobiological, economic, and information processing networks are generally more hierarchical than their comparable random networks. We further discovered that hierarchy degree has increased over the course of the evolution of Linux kernels. Taken together, our results suggest that hierarchy is a central organizing feature of real‐world evolving networks, and the measurement of hierarchy opens the way to understand the structural regimes and evolutionary patterns of self‐organizing networks. Our measurement technique makes it possible to objectively compare hierarchies of different networks and of different evolutionary stages of a single network, and compare evolving patterns of different networks. It can be applied to various complex systems, which can be represented as directed networks. © 2011 Wiley Periodicals, Inc. Complexity, 2011
El Farol revisited: A note on emergence, game theory, and society
Authors: Shubik Martin
Published: January 2011

The El Farol paper examined the evolution of behavior of visits to a potentially crowded facility, providing an insightful view of how independent agents can coordinate in a “good enough” manner in many situations. This view is extended to considering the interaction between rules and behavior. The context may be such that the importance of the outcome is sufficiently high to merit an extra layer of complexity in the guidance of the emergent behavior and that behavior may signal the need for the additional complexity. © 2011 Wiley Periodicals, Inc. Complexity, 2011
Active shunt current shaping scheme for multiple paralleled DC–DC converters
Authors: Lo Yu‐Kang , Yu Ching‐Hui , Pan Tian‐Fu , Chiu Huang‐Jen
Published: January 2011

A new shunt current shaping scheme for multiple paralleled dc–dc converters is proposed in this paper. The current command for the shunt current shaper is indirectly obtained by forcing the source current to follow the demanded sinusoidal signal. The amplitude of the demanded sinusoidal source current that is in‐phase with the source voltage can be determined from the sensed load currents of the post‐stage dc–dc converters. Neither high‐order filters nor time‐consuming computations are required. The shunt current shaper supplies all the harmonics and the out‐of‐phase fundamental of the distorted input current and the power source only supplies the in‐phase fundamental component. Experimental results on a prototype system verify the feasibility of the presented scheme. The implemented shunt current shaper demonstrates an efficiency of 92% and a nearly unity power factor at the utility side. Copyright © 2011 John Wiley & Sons, Ltd.
Pulmonary fibrosis: a possible diabetic complication
Authors: Yang Junling , Xue Qianfei , Miao Lining , Cai Lu
Published: January 2011

Diabetic complications affect many organs in diabetic patients. Emerging evidence indicates that diabetes can increase the risk of pulmonary dysfunction. Early epidemiological studies from different populations on whether diabetes was an independent risk for pulmonary dysfunction were inconclusive. Recent epidemiological studies and systematic reviews clearly indicate that diabetes is an independent risk factor for pulmonary dysfunction. Given that pulmonary fibrosis is an important predictor of mortality in people with this chronic disease, whether diabetes directly causes pulmonary fibrosis is an important unresolved clinical question. This review combines recent epidemiological data with findings from basic research to indicate that diabetes induces pulmonary fibrosis. We then discuss the possible underlying mechanisms for the histological and biochemical pathology. At the end of this review, we emphasize that diabetic pulmonary fibrosis as a potential diabetic complication warrants more attention. Copyright © 2011 John Wiley & Sons, Ltd.