bluuebunny/crossref_metadata_2025_split huggingface dataset:
A continuous multicolumn countercurrent solvent gradient purification (MCSGP) process
Authors: Aumann Lars , Morbidelli Massimo 
Published: June 2007

AbstractBiomolecules are often purified via solvent gradient batch chromatography. Typically suitable smooth linear solvent gradients are applied to obtain the separation between the desired component and hundreds of impurities. The desired product is usually intermediate between weakly and strongly adsorbing impurities, and therefore a central cut is required to get the desired pure product. The stationary phases used for preparative and industrial separations have a low efficiency due to strong axial dispersion and strong mass transfer resistances. Therefore a satisfactory purification often cannot be achieved in a single chromatographic step. For large scale productions and for very valuable molecules, countercurrent operation such as the well known SMB process, is needed in order to increase separation efficiency, yield and productivity. In this work a novel multicolumn solvent gradient purification process (MCSGP‐process) is introduced, which combines two chromatographic separation techniques, which are solvent gradient batch and continuous countercurrent SMB. The process consists of several chromatographic columns, which are switched in position opposite to the flow direction. Most of the columns are equipped with a gradient pump to adjust the modifier concentration at the column inlet. Some columns are interconnected, so that non pure product streams are internally, countercurrently recycled. Other columns are short circuited and operate in batch mode. As a working example the purification of an industrial stream containing 46% of the hormone Calcitonin is considered. It is found that for the required purity the MCSGP unit achieves a yield close to 100% compared to a maximum value of a single column batch chromatography of 66%. Biotechnol. Bioeng. 2007;98: 1043–1055. © 2007 Wiley Periodicals, Inc.
Study of pellet formation of filamentous fungi Rhizopus oryzae using a multiple logistic regression model
Authors: Liu Yan , Liao Wei , Chen Shulin 
Published: June 2007

AbstractFungal pellet formation is an important topic of fermentation research. It has been reported that many factors such as agitation, medium nutrients, pH, polymer additives, and inoculum size influence the formation of fungal pellets. However, a few studies on the effects of all of these factors on fungal pellet formation have been reported. This paper conducted a comprehensive investigation using a completely randomized design (CRD) on a filamentous fungus, Rhizopus oryzae NRRL 395, in order to discover the effects of the above factors on fungal pellet formation. In addition, other factors, such as addition of biodegradable polymers and spore storage time that have not been reportedly studied were examined and their effects on pellet formation were investigated. A multiple logistic regression model was established to predict the probability of pellet formation using the above factors and their interactions as predictor variables. Model building and diagnostics were obtained using the Statistical Analysis System (SAS 9.0) program. The model developed in this study can be used to predict the pellet formation of other R. oryzae strains as well. Biotechnol. Bioeng. 2008;99: 117–128. © 2007 Wiley Periodicals, Inc.
Novel membrane bioreactor: Able to cope with fluctuating loads, poorly water soluble VOCs, and biomass accumulation
Authors: Studer Michael , Rudolf von Rohr Philipp 
Published: June 2007

AbstractBiological waste gas treatment is an attractive method for controlling air emissions of volatile organic compounds (VOCs). Microorganisms degrade the VOCs to harmless products such as carbon dioxide (CO2), biomass and water. In spite of the advantages, significant unresolved challenges remain for biological waste gas treatment. Fluctuating loads in waste gas streams, especially of VOCs with low water solubility, can often not be satisfactorily removed. Concentration peaks leave the reactor virtually untreated, while periods without VOCs in the waste gas lead to starvation of the bacteria. Furthermore, bioreactors are often subject to clogging due to biomass accumulation. In the current work, a flat sheet membrane bioreactor was developed which was able to buffer fluctuating loads of toluene, our model compound, by absorption in silicone oil prior to degradation and which continuously removed and discharged excess biomass from the reactor. The absorption and the biodegradation were both membrane based. An inverse bacterial biofilm developed on the membrane, which separated the culture medium from the absorbent. The culture medium was constantly passed along the biofilm, introducing shear stresses on the surface and thereby removing excess, inactive biomass. The toluene surface elimination capacity was virtually independent of the gas flow rate for the tested steady‐state conditions and reached a maximum of 0.6 g m−2 h−1. Experiments with fluctuating inlet mass flow rates of toluene confirmed the excellent buffering capability of the set‐up. The reactor was successfully operated for 162 days without clogging. Biotechnol. Bioeng. 2008;99: 38–48. © 2007 Wiley Periodicals, Inc.
Lipase‐catalyzed synthesis of fatty acid sugar ester using extremely supersaturated sugar solution in ionic liquids
Authors: Lee Sang Hyun , Dang Dung Thanh , Ha Sung Ho , Chang Woo‐Jin , Koo Yoon‐Mo 
Published: June 2007

AbstractThe low solubility of sugars has hampered the lipase‐catalyzed synthesis of fatty acid sugar esters in organic solvents and ionic liquids (ILs), because several solvents that are able to effectively dissolve sugars are detrimental to enzymes. In this work, in order to prepare a high concentration of sugars in ILs, we have developed a new procedure that entails mixing an aqueous sugar solution into ILs followed by removal of the water from the solution. The glucose concentrations in the supersaturated [Emim][TfO] and [Bmim][TfO] were 19 and 10 times higher, respectively, than the solubilities (6.1 and 4.8 g/L) of glucose in the ILs at 25°C. Furthermore, the supersaturated glucose solutions in ILs were maintained over a long period of time without any significant loss of glucose. In ILs that were extremely supersaturated with glucose, lipase‐catalyzed esterifications of glucose with vinyl laurate, and lauric acid were successfully carried out. The conversion increased from 8% to 96% at 1 day of reaction by using supersaturated solution in [Bmim][TfO] which had dissolved glucose concentration of 400% higher than its solubility, compared with the reaction using saturated glucose solution. By making the glucose concentration in ILs much higher than the solubility through our novel and simple method, the initial rate and conversion of the lipase‐catalyzed reaction were significantly improved. Biotechnol. Bioeng. 2008;99: 1–8. © 2007 Wiley Periodicals, Inc.
Sodium butyrate alters erythropoietin glycosylation via multiple mechanisms
Authors: Crowell Christopher K. , Qin Qiang , Grampp Gustavo E. , Radcliffe Richard A. , Rogers Gary N. , Scheinman Robert I. 
Published: June 2007

AbstractRecombinant human erythropoietin (rHuEPO) produced in a human kidney fibrosarcoma cell line, HT1080, was used as a model to study the effects of sodium butyrate (SB) on protein glycosylation. Treatment with 2 mM SB resulted in complex changes with respect to sugar nucleotide pools including an increase in UDP‐Gal and a decrease in UDP‐GlcNac. In addition, polylactosamine structures present on rHuEPO increased after SB treatment. To determine if these phenotypic changes correlated with changes in mRNA abundance, we profiled mRNA levels over a 24‐h period in the presence or absence of SB using oligonucleotide microarrays. By filtering our data through a functional glycomics gene list associated with the processes of glycan degradation, glycan synthesis, and sugar nucleotide synthesis and transport we identified 26 genes with significantly altered mRNA levels. We were able to correlate the changes in message in six of these genes with measurable phenotypic changes within our system including: neu1, b3gnt6, siat4b, b3gnt1, slc17a5, and galt. Interestingly, for the two genes: cmas and gale, our measurable phenotypic changes did not correlate with changes in mRNA expression. These data demonstrate both the utility and pit falls of coupling biochemical analysis with high throughput oligonucleotide microarrays to predict how changes in cell culture environments will impact glycoprotein oligosaccharide content. Biotechnol. Bioeng. 2008;99: 201–213. © 2007 Wiley Periodicals, Inc.
An investigation of the absolute configuration of the potent histamine H3 receptor antagonist GT‐2331 using vibrational circular dichroism
Authors: Minick Douglas J. , Copley Royston C.B. , Szewczyk Jerzy R. , Rutkowske Randy D. , Miller Luke A. 
Published: June 2007

AbstractGT‐2331 [(+)‐1] is one of the most potent members of a class of chiral drug substances used to regulate the synthesis and release of histamine by the histamine H3 receptor, and as such, is an important biomarker for pharmaceutical companies conducting research in this field. In addition to overall structural features, the bioactivity of this molecule has also been found to be highly dependent on absolute stereochemistry, making the reliable assignment of this property a necessity. X‐ray diffraction studies have provided conflicting data, leaving its three‐dimensional structure uncertain. In view of this, its absolute configuration was investigated by vibrational circular dichroism. Results from this study provided independent assignment of this important molecule as the (1S,2S)‐enantiomer. Chirality, 2007. © 2007 Wiley‐Liss, Inc.
Activity of second‐line chemotherapy in docetaxel‐refractory hormone‐refractory prostate cancer patients
Authors: Rosenberg Jonathan E. , Weinberg Vivian K. , Kelly W. Kevin , Michaelson Dror , Hussain Maha H. , Wilding George , Gross Mitchell , Hutcheon Douglass , Small Eric J. 
Published: June 2007

AbstractBACKGROUND.This randomized, noncomparative, multicenter, clinical trial evaluated ixabepilone or mitoxantrone/prednisone (MP) as second‐line chemotherapy for taxane‐refractory, hormone‐refractory, prostate cancer (HRPC).METHODS.Patients with HRPC that progressed during or within 60 days of cessation of taxane chemotherapy were randomly selected with equal probability to ixabepilone 35 mg/m2intravenously every 3 weeks, or mitoxantrone 14 mg/m2intravenously every 3 weeks and prednisone 5 mg orally twice daily. Treatment continued until progression or toxicity; crossover was allowed.RESULTS.Forty‐one patients were accrued to each arm of the study. The median number of cycles administered for each arm was 3. Median survival from protocol entry was 10.4 months with ixabepilone and 9.8 months with MP. Prostate‐specific antigen (PSA) declines of ≥50% were observed in 17% of ixabepilone (95% CI, 7‐32) and 20% of second‐line MP patients (95% CI, 9‐35). Partial responses were observed in 1 of 24 ixabepilone and in 2 of 21 MP patients with evaluable measurable disease. Median duration of second‐line ixabepilone and MP treatment was 2.2 months and 2.3 months, respectively. For third‐line crossover treatment, PSA declines of ≥50% were observed in 3 of 27 ixabepilone‐treated and 4 of 15 MP‐treated patients. Prior taxane response was associated with an increased likelihood of second‐line ixabepilone or MP response. Low baseline lactate dehydrogenase and absence of visceral metastases independently predicted improved survival. The most common grade 3/4 toxicity associated with second‐line treatment was neutropenia (54% of ixabepilone patients and 63% of MP patients).CONCLUSIONS.Ixabepilone and MP had modest activity as second‐line chemotherapy for docetaxel‐refractory HRPC. The median survival for the entire cohort treated in this study was 9.8 months. Cancer 2007. © 2007 American Cancer Society.
Survival in squamous cell carcinoma of the oral cavity
Authors: Liao Chun‐Ta , Chang Joseph Tung‐Chieh , Wang Hung‐Ming , Ng Shu‐Hang , Hsueh Chuen , Lee Li‐Yu , Lin Chih‐Hung , Chen I‐How , Huang Shiang‐Fu , Cheng Ann‐Joy , Yen Tzu‐Chen 
Published: June 2007

AbstractBACKGROUND.According to the American Joint Commission on Cancer (AJCC, 5th edition) classification system, pT4 N0 oral cavity squamous cell carcinoma (OSCC) qualifies for stage IVA status, with its implied poor prognosis. However, preliminary observations suggested that patients with pT4 N0 OSCC might have better survival than other stage IVA categories. The authors sought to identify accurate prognosticators in patients with stage III/IVA OSCC.METHODS.The authors retrospectively reviewed 513 consecutive patients with stage III/IVA OSCC who were undergoing radical surgery. Survival was plotted by Kaplan‐Meier analysis.RESULTS.One hundred seventy‐eight patients were in stage III, and 335 were in stage IVA. The 335 stage IVA patients were divided into pT4 N0 (n = 105) and pT4 N1/TAny N2 (NO pT4 N0 M0, n = 230). By univariate analysis, 5‐year neck control rates (P < .0001), distant metastases (P < .0001), disease‐free survival rates (P < .0001), and overall survival rates (P < .0001) were significantly different in pT4 N0 compared with NO pT4 N0 patients. No significant difference in survival between pT4 N0 stage IVA and pstage III could be shown. Multivariate analysis for overall survival demonstrated that the following factors were independently associated with pT4 N0: tumor depth ≥35 mm, vessel invasion, lymph invasion, and perineural invasion. In contrast, tumor depth ≥25 mm, treatment with surgery alone, poor differentiation, extracapsular spread, and pathological nodal metastases (≥8 lymph nodes) were independent predictors of overall survival in NO pT4 N0.CONCLUSIONS.In patients with stage IVA OSCC (AJCC, 1997), the survival rates for pT4 N0 are better than those for NO pT4 N0 and similar to those of patients with pstage III. Cancer 2007. © 2007 American Cancer Society.
Phase 1 trial of everolimus and gefitinib in patients with advanced nonsmall‐cell lung cancer
Authors: Milton Daniel T. , Riely Gregory J. , Azzoli Christopher G. , Gomez Jorge E. , Heelan Robert T. , Kris Mark G. , Krug Lee M. , Pao William , Pizzo Barbara , Rizvi Naiyer A. , Miller Vincent A. 
Published: June 2007

AbstractBACKGROUND.Preclinical studies have demonstrated that the inhibition of the PI3K/Akt/mTOR pathway restores gefitinib sensitivity in resistant cancer cell lines. A phase 1 study was conducted of the combination of everolimus, an mTOR inhibitor, and gefitinib to determine a daily dose of everolimus with gefitinib in patients with advanced nonsmall‐cell lung cancer (NSCLC).METHODS.Oral everolimus and gefitinib were both administered daily to patients with progressive NSCLC. Patients were enrolled in 3‐patient cohorts at everolimus dose levels of 5 and 10 mg daily. All patients received gefitinib 250 mg daily.RESULTS.Ten patients were enrolled. The maximum tolerated dose of everolimus was 5 mg when administered daily with gefitinib 250 mg. Two patients who were treated at the 10 mg dose level of everolimus experienced dose‐limiting toxicity, including grade 5 hypotension and grade 3 stomatitis. Pharmacokinetic studies demonstrated no consistent, significant interaction on the tmax, Cmax, and AUC0‐8h of either agent. Two partial radiographic responses were identified among the 8 response‐evaluable patients.CONCLUSIONS.For further study, everolimus at a dose of 5 mg daily in combination with daily gefitinib 250 mg is recommended. The 2 radiographic responses identified are encouraging. A phase 2 trial in patients with NSCLC is under way. Cancer 2007. © 2007 American Cancer Society.
Irinotecan and cisplatin with concurrent split‐course radiotherapy in locally advanced nonsmall‐cell lung cancer
Authors: Fukuda Minoru , Soda Hiroshi , Fukuda Masaaki , Kinoshita Akitoshi , Nakamura Yoichi , Nagashima Seiji , Takatani Hiroshi , Tsukamoto Kazuhiro , Kohno Shigeru , Oka Mikio 
Published: June 2007

AbstractBACKGROUND.The purpose was to determine the efficacy and toxicity of irinotecan and cisplatin with concurrent split‐course thoracic radiotherapy (TRT) in locally advanced nonsmall‐cell lung cancer.METHODS.Fifty patients fulfilling the following eligibility criteria were enrolled: chemotherapy‐naive, good performance status (PS, 0‐2), age <75, stage III, and adequate organ function. The patients received irinotecan 60 mg/m2 intravenously on Days 1, 8, and 15, and cisplatin 80 mg/m2 intravenously on Day 1 in the first group. The doses were reduced to 50 and 60 mg/m2, respectively, in the second group. Two cycles of chemotherapy were repeated every 4 weeks. Split‐course thoracic radiotherapy of 2 Gy/day commenced on Day 2 of each chemotherapy cycle, with 28 and 32 Gy administered in the first and second cycles, respectively.RESULTS.Fifty patients were eligible and 48 (16 in the first, 32 in the second group) patients were assessable for response, toxicity, and survival. The overall response was 83% (95% confidence interval [CI], 70%–93%). Grade 4 leukopenia, neutropenia, grade 3 or 4 diarrhea, pneumonitis, esophagitis, and fatigue occurred in 21%, 48%, 19%, 10%, and 19%, respectively. The median time to progression was 8.2 months. The median overall survival time and the 2‐ and 5‐year survival rates were 20.1 months, 47.1%, and 17.1%, respectively. In subgroup analysis, grade 4 neutropenia, grade 3 or 4 diarrhea, the overall response, and the median survival times of the first/second groups were 63%/41%, 19%/19%, 75%/88%, and 13.1/33.4 months, respectively.CONCLUSIONS.This combined modality of irinotecan and cisplatin with concurrent TRT is active and further investigations are warranted at the second group dose level. Cancer 2007. © 2007 American Cancer Society.
Melanoma in the young: Differences and similarities with adult melanoma
Authors: Livestro Daan P. , Kaine Emily M. , Michaelson James S. , Mihm Martin C. , Haluska Frank G. , Muzikansky Alona , Sober Arthur J. , Tanabe Kenneth K. 
Published: June 2007

AbstractBACKGROUND.Melanoma in the first 2 decades of life is rare and is less well characterized than melanoma in adults. Previously published comparisons of melanoma of the young (age ≤20 years) and in adults have been biased by the observation that primary melanomas of the young are significantly thicker on average than adult melanomas. In this study, the use of an adult control group that was matched for tumor thickness adjusted for this bias and allowed for a comparison of the biology of pediatric melanoma and adult melanoma.METHODS.The authors identified young patients with melanoma who were treated at their institution between 1971 and 2002, and matched each patient by thickness and year of diagnosis to 2 adult control patients with melanoma. The study group of 73 young patients with melanoma (aged ≤20 years) was compared with to 146 adult case‐matched control patients for clinical presentation, treatment, and clinically relevant outcome parameters, including disease‐free and cause‐specific survival. A subset of pediatric patients aged ≤13 years also was analyzed against case‐matched adult controls.RESULTS.The demographics and clinical presentation of the 2 groups were similar. Of the young patients with melanoma who underwent pathologic staging of clinically negative lymph nodes by either elective lymph node dissection or lymphatic mapping/sentinel lymph node biopsy, 11 of 25 patients (44%) had positive lymph nodes compared with 11 of 46 patients (23.9%) among the adults. The overall incidence of positive lymph nodes was 17.8% in young melanoma patients and 9.6% in thickness‐matched adult control patients. Nonetheless, 10‐year cause‐specific survival was similar between young melanoma patients and adult melanoma patients (89.4% and 79.3%, respectively). No significant differences were observed comparing young patients with melanoma aged <13 years versus age >13 years.CONCLUSIONS.Melanoma of the young had some important differences and similarities relative to adult melanoma. Lymph node metastases were more prevalent in young patients with melanoma compared with adult (thickness‐matched) control patients; however, the 5‐ and 10‐year survival rates were similar. Cancer 2007. © 2007 American Cancer Society.
National inpatient complications and outcomes after surgery for spinal metastasis from 1993–2002
Authors: Patil Chirag G. , Lad Shivanand P. , Santarelli Justin , Boakye Maxwell 
Published: June 2007

AbstractBACKGROUND.Information regarding patient outcomes, complications, and mortality after surgery for spinal metastasis has previously been derived from single‐institution series. The aim of this study was to report inpatient mortality, complications, and outcomes on a national level.METHODS.The National Inpatient Sample (NIS) was utilized to identify 26,233 admissions of surgically managed spinal metastasis in the U.S. from 1993 through 2002. Multivariate analysis was performed to analyze the effects of patient and hospital characteristics on outcomes such as mortality, complications, discharge disposition, and length of stay.RESULTS.The in‐hospital mortality rate was 5.6% and the complication rate was 21.9%. Pulmonary (6.7%) and postoperative hemorrhages or hematomas (5.9%) were the most common complications reported. A single postoperative complication increased the mean length of stay (LOS) by 7 days and the mortality rate by 11%. Multivariate analysis showed that complications were more likely in older patients and in patients with 2 or more comorbidities. With patients having no comorbidities as the reference group, 1 comorbidity increased the risk of in‐hospital death by almost 4‐fold. Mortality was significantly higher in men, in patients who had postoperative complications, and in patients who were operated in the earlier (1993–1997) year group.CONCLUSIONS.A national perspective is provided on inpatient complications and outcomes after surgery for spinal metastasis in the U.S. The significant negative effect of postoperative complications on mortality and resource utilization is demonstrated. Furthermore, preoperative comorbidity is identified as an important risk factor and its impact is defined on patient outcomes. Cancer 2007. © 2007 American Cancer Society.