bluuebunny/crossref_metadata_2025_split huggingface dataset:
Gene regulatory networks in embryonic stem cells and brain development
Authors: Ghosh Dhimankrishna , Yan Xiaowei , Tian Qiang 
Published: June 2009

AbstractEmbryonic stem cells (ESCs) are endowed with the ability to generate multiple cell lineages and carry great therapeutic potentials in regenerative medicine. Future application of ESCs in human health and diseases will embark on the delineation of molecular mechanisms that define the biology of ESCs. Here, we discuss how the finite ESC components mediate the intriguing task of brain development and exhibit biomedical potentials to cure diverse neurological disorders. Birth Defects Research (Part C) 87:182–191, 2009. © 2009 Wiley‐Liss, Inc.
Dynamical approaches to modeling developmental gene regulatory networks
Authors: Geard Nicholas , Willadsen Kai 
Published: June 2009

AbstractThe network of interacting regulatory signals within a cell comprises one of the most complex and powerful computational systems in biology. Gene regulatory networks (GRNs) play a key role in transforming the information encoded in a genome into morphological form. To achieve this feat, GRNs must respond to and integrate environmental signals with their internal dynamics in a robust and coordinated fashion. The highly dynamic nature of this process lends itself to interpretation and analysis in the language of dynamical models. Modeling provides a means of systematically untangling the complicated structure of GRNs, a framework within which to simulate the behavior of reconstructed systems and, in some cases, suites of analytic tools for exploring that behavior and its implications. This review provides a general background to the idea of treating a regulatory network as a dynamical system, and describes a variety of different approaches that have been taken to the dynamical modeling of GRNs. Birth Defects Research (Part C) 87:131–142, 2009. © 2009 Wiley‐Liss, Inc.
A review on data mining and continuous optimization applications in computational biology and medicine
Authors: Weber Gerhard‐Wilhelm , Özöğür‐Akyüz Süreyya , Kropat Erik 
Published: June 2009

AbstractAn emerging research area in computational biology and biotechnology is devoted to mathematical modeling and prediction of gene‐expression patterns; it nowadays requests mathematics to deeply understand its foundations. This article surveys data mining and machine learning methods for an analysis of complex systems in computational biology. It mathematically deepens recent advances in modeling and prediction by rigorously introducing the environment and aspects of errors and uncertainty into the genetic context within the framework of matrix and interval arithmetics. Given the data from DNA microarray experiments and environmental measurements, we extract nonlinear ordinary differential equations which contain parameters that are to be determined. This is done by a generalized Chebychev approximation and generalized semi‐infinite optimization. Then, time‐discretized dynamical systems are studied. By a combinatorial algorithm which constructs and follows polyhedra sequences, the region of parametric stability is detected. In addition, we analyze the topological landscape of gene‐environment networks in terms of structural stability. As a second strategy, we will review recent model selection and kernel learning methods for binary classification which can be used to classify microarray data for cancerous cells or for discrimination of other kind of diseases. This review is practically motivated and theoretically elaborated; it is devoted to a contribution to better health care, progress in medicine, a better education, and more healthy living conditions. Birth Defects Research (Part C) 87:165–181, 2009. © 2009 Wiley‐Liss, Inc.
An electron‐flow model can predict complex redox reactions in mixed‐culture fermentative BioH2: Microbial ecology evidence
Authors: Lee Hyung‐Sool , Krajmalinik‐Brown Rosa , Zhang Husen , Rittmann Bruce E. 
Published: June 2009

AbstractWe developed the first model for predicting community structure in mixed‐culture fermentative biohydrogen production using electron flows and NADH2 balances. A key assumption of the model is that H2 is produced only via the pyruvate decarboxylation‐ferredoxin‐hydrogenase pathway, which is commonly the case for fermentation by Clostridium and Ethanoligenens species. We experimentally tested the model using clone libraries to gauge community structures with mixed cultures in which we did not pre‐select for specific bacterial groups, such as spore‐formers. For experiments having final pHs 3.5 and 4.0, where H2 yield and soluble end‐product distribution were distinctly different, we established stoichiometric reactions for each condition by using experimentally determined electron equivalent balances. The error in electron balancing was only 3% at final pH 3.5, in which butyrate and acetate were dominant organic products and the H2 yield was 2.1 mol H2/mol glucose. Clone‐library analysis showed that clones affiliated with Clostridium sp. BL‐22 and Clostridium sp. HPB‐16 were dominant at final pH 3.5. For final pH 4.0, the H2 yield was 0.9 mol H2/mol glucose, ethanol, and acetate were the dominant organic products, and the electron balance error was 13%. The significant error indicates that a second pathway for H2 generation was active. The most abundant clones were affiliated with Klebsiella pneumoniae, which uses the formate‐cleavage pathway for H2 production. Thus, the clone‐library analyses confirmed that the model predictions for when the pyruvate decarboxylation‐ferredoxin‐hydrogenase pathway was (final pH 3.5) or was not (final pH 4.0) dominant. With the electron‐flow model, we can easily assess the main mechanisms for H2 formation and the dominant H2‐producing bacteria in mixed‐culture fermentative bioH2. Biotechnol. Bioeng. 2009; 104: 687–697 © 2009 Wiley Periodicals, Inc.
A comprehensive model of simultaneous denitrification and methanogenic fermentation processes
Authors: Tugtas A. Evren , Tezel U. , Pavlostathis Spyros G. 
Published: June 2009

AbstractThe denitrification process was incorporated into the IWA Anaerobic Digestion Model No. 1 (ADM1) in order to account for the effect of denitrification on the methanogenic fermentation process. The model was calibrated and optimized using previously published experimental data and kinetic parameter values obtained with a mixed, mesophilic (35°C) methanogenic culture. Model simulations were used to predict the effect of nitrate reduction on the methanogenic fermentation process in batch, semi‐continuous, and continuous flow reactors experiencing operational changes and/or system disturbances. The extended model clearly revealed the importance of substrate competition between denitrifiers and non‐denitrifiers as well as the impact of N‐oxide inhibition on process interactions between fermentation, methanogenesis, and denitrification. Biotechnol. Bioeng. 2010;105: 98–108. © 2009 Wiley Periodicals, Inc.
Manipulation of microparticles for construction of array patterns by negative dielectrophoresis using multilayered array and grid electrodes
Authors: Ino Kosuke , Shiku Hitoshi , Ozawa Fumisato , Yasukawa Tomoyuki , Matsue Tomokazu 
Published: June 2009

AbstractIn this study, a useful method was developed to fabricate array patterns of microparticles not on electrode surfaces, but on arbitrary surfaces, using negative‐dielectrophoresis (n‐DEP). First, electrodes were designed and electric field simulations were performed to manipulate microparticles toward target areas. Based on the simulation results, multilayered array and grid (MLAG) electrodes, consisting of array electrodes surrounded by insulated regions and a grid electrode, were fabricated for the formation of localized, non‐uniform electric fields. The MLAG electrode was mounted to a target substrate in a face‐to‐face configuration with a spacer. When an AC voltage (4.60 Vrmsand 1 MHz) was applied to the MLAG electrode, array patterns of 6 and 20 µm diameter microparticles were rapidly fabricated on the target substrate with ease. The results suggest that MLAG electrodes can be widely applied for the fabrication of biochips including cell arrays. Biotechnol. Bioeng. 2009; 104: 709–718 © 2009 Wiley Periodicals, Inc.
The chromatography‐free release, isolation and purification of recombinant peptide for fibril self‐assembly
Authors: Hartmann B.M. , Kaar W. , Yoo I.K. , Lua L.H.L. , Falconer R.J. , Middelberg A.P.J. 
Published: June 2009

AbstractOne of the major expenses associated with recombinant peptide production is the use of chromatography in the isolation and purification stages of a bioprocess. Here we report a chromatography‐free isolation and purification process for recombinant peptide expressed in Escherichia coli (E. coli). Initial peptide release is by homogenization and then by enzymatic cleavage of the peptide‐containing fusion protein, directly in the E. coli homogenate. Release is followed by selective solvent precipitation (SSP) to isolate and purify the peptide away from larger cell contaminants. Specifically, we expressed in E. coli the self‐assembling β‐sheet forming peptide P11‐2 in fusion to thioredoxin. Homogenate was heat treated (55°C, 15 min) and then incubated with tobacco etch virus protease (TEVp) to release P11‐2 having a native N‐terminus. SSP with ethanol at room temperature then removed contaminating proteins in an integrated isolation‐purification step; it proved necessary to add 250 mM NaCl to homogenate to prevent P11‐2 from partitioning to the precipitate. This process structure gave recombinant P11‐2 peptide at 97% polypeptide purity and 40% overall yield, without a single chromatography step. Following buffer‐exchange of the 97% pure product by bind‐elute chromatography into defined chemical conditions, the resulting peptide was shown to be functionally active and able to form self‐assembled fibrils. To the best of our knowledge, this manuscript reports the first published process for chromatography‐free recombinant peptide release, isolation and purification. The process proved able to deliver functional recombinant peptide at high purity and potentially low cost, opening cost‐sensitive materials applications for peptide‐based materials. Biotechnol. Bioeng. 2009; 104: 973–985. © 2009 Wiley Periodicals, Inc.
Rapid optimization of protein freeze‐drying formulations using ultra scale‐down and factorial design of experiment in microplates
Authors: Grant Yitzchak , Matejtschuk Paul , Dalby Paul A. 
Published: June 2009

AbstractRetaining biopharmaceutical proteins in a stable form is critical to their safety and efficacy, and is a major factor for optimizing the final product. Freeze‐dried formulations offer one route for improved stability. Currently the optimization of formulations for freeze‐drying is an empirical process that requires many time‐consuming experiments and also uses large quantities of product material. Here we describe a generic framework for the rapid identification and optimization of formulation excipients to prevent loss of protein activity during a lyophilization process. Using factorial design of experiment (DOE) methods combined with lyophilization in microplates a range of optimum formulations were rapidly identified that stabilized lactose dehydrogenase (derived from Lactobacillus leichmanii) during freeze‐drying. The procedure outlined herein involves two rounds of factorially designed experiments—an initial screen to identify key excipients and potential interactions followed by a central composite face designed optimization experiment. Polyethylene glycol (PEG) and lactose were shown to have significant effects on maintaining protein stability at the screening stage and optimization resulted in an accurate model that was used to plot a window of operation. The variation of freezing temperatures and rates of sublimation that occur across a microplate during freeze‐drying have been characterized also. The optimum formulation was then freeze‐dried in stoppered vials to verify that the microscale data was relevant to the effects observed at larger pilot scales. This work provides a generic approach to biopharmaceutical formulation screening where possible excipients can be screened for single and interactive effects thereby increasing throughput while reducing costs in terms of time and materials. Biotechnol. Bioeng. 2009; 104: 957–964. © 2009 Wiley Periodicals, Inc.
Generation and validation of a revised classification for oesophageal and junctional adenocarcinoma
Authors: Peters C J , Hardwick R H , Vowler S L , Fitzgerald R C 
Published: June 2009

Abstract

Background
Oesophageal adenocarcinoma is the commonest oesophageal malignancy in the West, but is staged using a system designed for squamous cell carcinoma. The aim was to develop and validate a staging system for oesophageal and junctional adenocarcinoma.

Methods
Patients with oesophageal adenocarcinoma (Siewert types I and II) undergoing oesophagectomy with curative intent were randomly assigned to generation (313 patients) and validation (131) data sets. Outcome in the generation data set was associated with histopathological features; a revised node (N) classification was derived using recursive partitioning and tested on the validation data set.

Results
A revised N classification based on number of involved lymph nodes (N0, none; N1, one to five; N2, six or more) was prognostically significant (P &lt; 0·001). Patients with involved nodes on both sides of the diaphragm, regardless of number, had the same outcome as the N2 group. When applied to the validation data set, the revised classification (including nodal number and location) provided greater discrimination between node-positive patients than the existing system (P &lt; 0·001).

Conclusion
A revised N classification based on number and location of involved lymph nodes provides improved prognostic power and incorporates features that may be useful before surgery in clinical management decisions.
Influence of nephron mass and a phosphorylated 38 mitogen-activated protein kinase inhibitor on the development of early and long-term injury after renal warm ischaemia
Authors: Jayle C , Faure J P , Thuillier R , Goujon J M , Richer J P , Hauet T 
Published: June 2009

AbstractBackgroundRenal ischaemia is accompanied by acute and chronic complications. Tumour necrosis factor (TNF) α production via p38 mitogen-activated protein kinase (MAPK) is one of the pivotal mechanisms linking ischaemia to inflammation and could be a therapeutic target. FR167653 (FR), an inhibitor of p38 MAPK and TNF-α production, may ameliorate renal damage through its effects on TNF-α.MethodsWarm ischaemia (WI) was induced in male pigs by bilateral clamping of the renal pedicle for 60 min or unilateral renal clamping after contralateral nephrectomy. FR was administered before and during WI, and continuously for 3 h during reperfusion in pigs exposed to the same WI conditions. Experimental groups were compared with sham-operated pigs and those subjected to unilateral nephrectomy without renal ischaemia. Renal function, fibrosis and inflammation were evaluated, and expression of monocyte chemoattractant protein 1, transforming growth factor β and TNF-α was determined after 12 weeks.ResultsFR significantly reduced renal failure in groups subjected to unilateral nephrectomy and bilateral renal ischaemia. Proteinuria was significantly reduced, and inflammation and expression of proinjury proteins were diminished, accompanied by a reduction in renal fibrosis.ConclusionControl of TNF-α production and activity prevents renal damage after prolonged WI.
Relationship between 31P metabolites and oncolytic viral therapy sensitivity in human colorectal cancer xenografts
Authors: Silberhumer G R , Zakian K , Malhotra S , Brader P , Gönen M , Koutcher J , Fong Y 
Published: June 2009

Abstract

Background
Studies using phosphorus magnetic resonance spectroscopy (MRS) have pointed to the significance of phospholipid metabolite alterations as biochemical markers for tumour progression or therapy response.

Methods
Spectroscopic imaging was performed in colorectal flank tumours in nude mice. In vivo tumour doubling times for each cell line were measured. In vivo sensitivity of each tumour line to treatment with G207 and NV1020 oncolytic viruses was assessed. Correlations between viral sensitivity and tumour doubling time and phosphorus MRS were estimated.

Results
For G207 virus, in vitro cytotoxicity tests showed cell viability at multiplicities of infection (ratio of viral particles per tumour cell) of 0·1 on day 6 as follows: C85, less than 1 per cent; HCT8, 1 per cent; LS174T, 9 per cent; HT29, 18 per cent; and C18, 92 per cent. Respective values for NV1020 were 1, 18, 4, 18 and 86 per cent. The phosphoethanolamine to phosphocholine ratio was significantly lower in virus-sensitive than -insensitive cells, and was dependent on tumour doubling time.

Conclusion
Alterations in membrane phospholipid metabolites that relate to proliferation of cancer cells affect the efficacy of oncolytic viral therapy. MRS proved a highly sensitive non-invasive tool for predicting the efficacy of viruses.
Liberal selection criteria for liver transplantation for hepatocellular carcinoma
Authors: Muscari F , Foppa B , Kamar N , Peron J M , Selves J , Suc B 
Published: June 2009

Abstract

Background
To help increase the number of transplants available for hepatocellular carcinoma in cirrhotic livers, this single-centre retrospective study compared the safety and feasibility of new, more liberal, selection criteria—no more than five tumours, with the largest tumour no greater than 5 cm (5/5 criteria)—with classical criteria.

Methods
Data from operations performed in 1990–2005 were extracted from preoperative radiological findings and postoperative specimen analyses, and four groups were constructed: Paul Brousse, Milan, University of California, San Francisco (UCSF) and 5/5 criteria. A fifth group comprised patients whose tumour load exceeded the 5/5 criteria. Survival and recurrence rates were compared.

Results
For the 110 patients in the study, survival rates (overall and disease-free) were 72·8 and 66·8 per cent at 5 and 10 years respectively, with a 5·5 per cent recurrence rate. The 5-year survival rate was 65, 77, 68 and 77 per cent for Paul Brousse, Milan, UCSF and 5/5 preoperative radiological criteria, with recurrence rates of 4, 4, 3 and 3 per cent, respectively. On multivariable analysis, the only factor that influenced survival was tumour load in excess of the 5/5 criteria.

Conclusion
Use of the more liberal 5/5 criteria for selecting patients for liver transplantation results in similar disease-free and overall survival rates to classical criteria.
Prognostic significance of peritoneal tumour cells identified at surgery for colorectal cancer
Authors: Katoh H , Yamashita K , Sato T , Ozawa H , Nakamura T , Watanabe M 
Published: June 2009

AbstractBackgroundThe prognostic significance of intraperitoneal tumour cells (IPCs) in colorectal cancer is not clear. This study aimed to determine whether detection of IPCs could be used a prognostic marker for selecting patients at high risk of recurrence.MethodsThe study included 226 patients with colorectal cancer who underwent elective resection. Clinical variables, including the presence of IPCs, were analysed for their prognostic significance.ResultsThirty-three patients (14·6 per cent) were positive for IPCs. Univariable analysis indicated that the presence of IPCs was a significant prognostic factor in patients with stage III colorectal cancer; the 5-year disease-specific survival rate was 14 per cent in IPC-positive patients versus 79 per cent in those without IPCs (P &lt; 0·001). Multivariable analysis showed that IPC positivity was the most robust prognostic factor in stage III disease (hazard ratio 2·2; P = 0·003), whereas nodal category (N1 or N2) showed no significant association with prognosis. In addition, IPCs were associated with haematogenous recurrence (P = 0·004) rather than peritoneal or local recurrence (P = 0·077) in patients with stage III disease.ConclusionThe presence of IPCs is a significant prognostic factor in patients with stage III colorectal cancer.
MicroRNAs are novel biomarkers of colorectal cancer
Authors: Aslam M I , Taylor K , Pringle J H , Jameson J S 
Published: June 2009

Abstract

Background
Recent studies have identified unique small ribonucleic acids called microRNAs (miRNAs) in colonic tumour tissue and blood that may accurately diagnose the presence of colorectal cancer and help predict disease recurrence. This review explores the potential role of these biomarkers.

Methods
A literature search identified studies describing miRNAs in colorectal cancers. The outcomes of interest included diagnosis, progression and recurrence of disease, and future therapy.

Results
Overexpression and silencing of specific miRNAs are associated with the development and progression of colorectal cancer. Such a role in oncogenesis suggest that miRNAs may be important targets for gene therapies. Differential expression of specific miRNAs in tissues and blood offers the prospect of their use in early detection and screening for colorectal cancer. MiRNAs are implicated in metastasis and cytotoxic drug resistance. Their manipulation has potential in both prevention of recurrence and palliation.

Conclusion
The miRNAs expression profile in tissue and blood has potential for their use in the detection, screening and surveillance of colorectal cancer. Furthermore, miRNAs may be targeted by gene therapy to treat colorectal cancer.
Conservative management of symptomatic spontaneous isolated dissection of the superior mesenteric artery
Authors: Cho Y P , Ko G Y , Kim H K , Moon K M , Kwon T W 
Published: June 2009

Abstract

Background
Spontaneous isolated dissection of the superior mesenteric artery (SMA) is uncommon. Because of its rarity, the risk factors, aetiology and natural history are unclear, and there is no consensus on the optimal treatment strategy.

Methods
Seven consecutive patients with symptomatic spontaneous isolated SMA dissection who received conservative treatment between March 2003 and February 2008 were included in this study. Their clinical characteristics, treatment methods and outcomes were analysed retrospectively.

Results
Acute abdominal pain was the most common clinical manifestation. Initial contrast-enhanced dynamic computed tomography (CT) showed isolated SMA dissection with partial thrombosis in all seven patients. Full anticoagulation was carried out immediately after the diagnosis. Clinical symptoms disappeared within 14 days and follow-up CT showed complete resolution of the dissection in four patients. After a mean follow-up of 23 months, there was no mortality or morbidity related to the dissection.

Conclusion
In patients with symptomatic spontaneous isolated dissection of the SMA, conservative management is feasible if there is no evidence of bowel infarction or bleeding.