bluuebunny/crossref_metadata_2025_split huggingface dataset:
Prozess Analytische Technologie in der Biotechnologie
Authors: Herwig C. 
Published: March 2010

AbstractBiotechnologische Prozesse sind durch eine enorme Komplexität von intrazellulären Wechselwirkungen charakterisiert. Prozess Analytische Technologie (PAT) soll nach Vorgabe von den Regulationsbehörden eingesetzt werden, um diese Prozesse wissenschaftlich basiert und robust zu entwickeln. Der Beitrag zeigt die Entwicklungen von PAT‐Sensoren für die Echtzeitmessung und die Notwendigkeit der Integration von PAT‐gerechten Daten in Quality by Design (QbD) durch Datenauswertung auf. PAT ist quantitativ und sollte als ein Werkzeug innerhalb von QbD verstanden werden, was außer der Echtzeitmessung auch den Weg mittels Datenauswertung zu kritischen Prozessparametern erlaubt. PAT ist daher nicht zwingend mit dem Kauf teurer Online‐Analytik gleichzusetzen. Die Kombination von Sensoren und Auswertemethoden sichert die Durchgängigkeit von der Prozessentwicklung in die industrielle Herstellung und wird die Wissenschaftlichkeit als essentiellen Bestandteil in der Bioprozessentwicklung verankern.
Ultraschallbasierte Informationsgewinnung in der Verfahrenstechnik
Authors: Hempel U. , Wöckel S. , Auge J. 
Published: March 2010

AbstractDie genaue Kenntnis von Prozesszuständen zu jeder Zeit an jedem Ort ist eine Vision, der die Realität mitunter nur in unzureichendem Maße gerecht wird. Die Gründe hierfür sind vielgestaltig, technisch und ökonomisch motiviert. Sensoren für die Informationsgewinnung im Prozess sollen einfach zu installieren und wartungsfrei, robust, langzeitstabil, schnell und hoch genau messend sowie preiswert sein. Diese Forderungen sind durch die unterschiedlichen messtechnischen Prinzipien in sehr unterschiedlichem Maße erfüllbar. Welche Rolle hierbei ultraschallbasierte Sensorsysteme gegenwärtig spielen und zukünftig spielen könnten ist Gegenstand des Beitrages, der die Grundlagen des Ultraschalls kurz umreißt, Fragen des Wandlerdesigns und der Signalanalyse andiskutiert sowie einen Überblick zu den zahlreichen Applikationsmöglichkeiten von Ultraschallsensorsystemen in der Prozessindustrie gibt.
Integration der Prozessanalysentechnik in die Prozessführung: Beispiele aus der industriellen Praxis bei BASF
Authors: Schocker A. , Kleinert T. 
Published: March 2010

AbstractNeue und anspruchsvolle Strategien in der Prozessführung chemischer Produktionsanlagen erfordern, dass neben klassischen Prozessparametern (Druck, Temperatur, Durchfluss) auch stoffspezifische Informationen online im Prozess gemessen werden. Die moderne Prozessanalysentechnik (PAT) eröffnet hier vielfältige Möglichkeiten mit spezifischen und unspezifischen Methoden. Die direkte Einbindung der PAT in eine Qualitätsregelung ist der konsequente Schritt hin zu einer weiter optimierten Prozessführung. Dieser Beitrag gibt einen Überblick über die PAT aus der Perspektive der Integration in die Prozessführung. Verschiedene analytische Methoden werden anhand ihrer Analysenzeiten und Taktzyklen sowie der Signalqualität und ‐verfügbarkeit für die Verwendung in der Prozessführung klassifiziert. Des Weiteren wird dargestellt, wie eine Integration in die Prozessregelung in Form von Qualitätsregelungen projektiert werden kann. Verschiedene Praxisbeispiele demonstrieren, wie sowohl kontinuierliche Messungen als auch Messsysteme mit langen Analysenzeiten für die automatisierte Steuerung der Produktionsprozesse eingesetzt werden. Mit dem Fokus auf aktuelle Entwicklungen und Trends bei der PAT werden die Potenziale für die Prozessführung aufgezeigt.
Multivariate Curve Resolution – Integration von Wissen in Chemometrische Modelle
Authors: Kessler W. , Kessler R. 
Published: March 2010

AbstractIn der Prozessdatenanalyse haben sich sowohl die Hauptkomponentenanalyse (PCA) als auch die Partial Least Square Regression (PLSR) als chemometrische Werkzeuge etabliert. Der wesentliche Nachteil von PCA und PLSR ist, dass die Hauptkomponenten abstrakte, sogenannte latente Variable darstellen und häufig den physikalisch chemischen Hintergrund nur ungenau widerspiegeln. Es ist deshalb wünschenswert, neue Methoden für die komplexe Datenanalyse zu entwickeln, die es ermöglichen, Basiswissen über den Prozess in die chemometrische Beschreibung zu integrieren. Die Methoden der multivariaten Kurvenauflösung (Multivariate Curve Resolution, MCR) erlauben das Einbringen von vorhandenem Wissen in die chemometrische Auswertung in Form von Nebenbedingungen. Hier werden an Hand von drei praktischen Beispielen aus der Prozessanalytik diese Möglichkeiten der MCR‐Methode aufgezeigt.
Degradation of polycyclic aromatic hydrocarbons: Model simulation for bioavailability and biodegradation
Authors: Owabor C. N. , Ogbeide S. E. , Susu A. A. 
Published: March 2010

AbstractA mathematical model for a one‐dimensional convective‐dispersive solute transport in a soil matrix is presented. The interplay of linear equilibrium sorption and first order degradation were incorporated into the formulation of the model. The model took into consideration the overall effects of the solid and liquid phase mass transfer resistances. Data from experiments were analysed using the temporal moments method (MOM) and CXTFIT curve‐fitting technique. The functional parameters; dispersion coefficient, first order degradation rate constant and the retardation factor were estimated using both first and second normalised moments. The solution to the model equations was achieved by the use of the backward finite difference scheme. Results obtained showed that naphthalene was more selectively degraded than pyrene and anthracene with a residual concentration of naphthalene 1.12E − 5 mg/L, 1.48 mg/L; pyrene 3.11E − 4 mg/L, 1.58 mg/L; and anthracene 7.67E − 4 mg/L, 1.61 mg/L in the axial and radial directions, respectively. Concisely, the modeling results showed the occlusion of these compounds within the fissures and cavities of the soil particles, which renders them not readily bioavailable and thus inaccessible to microbial degradation.
Synthesis of N‐Hydroxycinnamides Capped with a Naturally Occurring Moiety as Inhibitors of Histone Deacetylase
Authors: Huang Wei‐Jan , Chen Ching‐Chow , Chao Shi‐Wei , Lee Shoei‐Sheng , Hsu Fen‐Lin , Lu Yeh‐Lin , Hung Ming‐Fang , Chang Chung‐I 
Published: March 2010

AbstractHistone deacetylase (HDAC) inhibitors are regarded as promising therapeutics for the treatment of cancer. All reported HDAC inhibitors contain three pharmacophoric features: a zinc‐chelating group, a hydrophobic linker, and a hydrophobic cap for surface recognition. In this study we investigated the effectiveness of osthole, a hydrophobic Chinese herbal compound, as the surface recognition cap in hydroxamate‐based compounds as inhibitors of HDAC. Nine novel osthole‐based N‐hydroxycinnamides were synthesized and screened for enzyme inhibition activity. Compounds 9 d, 9 e, 9 g exhibited inhibitory activities (IC50=24.5, 20.0, 19.6 nM) against nuclear HDACs in HeLa cells comparable to that of suberoylanilide hydroxamic acid (SAHA; IC50=24.5 nM), a potent inhibitor clinically used for the treatment of cutaneous T‐cell lymphoma (CTCL). While compounds 9 d and 9 e showed SAHA‐like activity towards HDAC1 and HDAC6, compound 9 g was more selective for HDAC1. Compound 9 d exhibited the best cellular effect, which was comparable to that of SAHA, of enhancing acetylation of either α‐tubulin or histone H3. Molecular docking analysis showed that the osthole moiety of compound 9 d may interact with the same hydrophobic surface pocket exploited by SAHA and it may be modified to provide class‐specific selectivity. These results suggest that osthole is an effective hydrophobic cap when incorporated into N‐hydroxycinnamide‐derived HDAC inhibitors.
An in vitro Assay to Measure Targeted Drug Delivery to Bone Mineral
Authors: Jahnke Wolfgang , Henry Chrystèle 
Published: March 2010

AbstractTargeted delivery of drugs to their site of action is a promising strategy to decrease adverse effects and enhance efficacy, but successful applications of this strategy have been scarce. Human bone is a tissue with unique properties due to its high hydroxyapatite mineral content. However, with the exception of bisphosphonates, bone mineral has not been targeted in a successful clinical application of drugs that act on bone, such as anti‐resorptive or bone anabolic agents. Herein we present an NMR‐based in vitro assay to measure binding affinities of small molecules to hydroxyapatite (HAP) or bone powder. Binding was shown to be specific and competitive, and the assay can be carried out in a direct binding format or in competition mode. A selection of clinically relevant bisphosphonates was ranked by their binding affinity for HAP. The binding affinity decreases in the order: pamidronate > alendronate > zoledronate > risedronate > ibandronate. The differences in binding affinities span a factor of 2.1 between pamidronate and ibandronate, consistent with previous studies. The rank order is very similar with bone powder, although the binding capacity of bone powder is smaller and binding kinetics are slower. A zoledronate derivative that lacks the central hydroxy group binds to HAP with 2.3‐fold weaker affinity than zoledronate itself. Any small molecule can be analyzed for its binding to HAP or bone powder, and the binding of common bone‐staining agents such as alizarin and its derivatives was confirmed in the new assay. This assay supports a strategy for targeted delivery of drugs to bone by attaching a bone‐affinity tag to the active drug substance.
Synthesis of 9,9‐Dialkyl‐4,5‐diazafluorene Derivatives and Their Structure–Activity Relationships Toward Human Carcinoma Cell Lines
Authors: Wang Qiwei , Yuen Marcus Chun‐Wah , Lu Guo‐Liang , Ho Cheuk‐Lam , Zhou Gui‐Jiang , Keung Oi‐Mei , Lam Kim‐Hung , Gambari Roberto , Tao Xiao‐Ming , Wong Raymond Siu‐Ming , Tong See‐Wai , Chan Kit‐Wah , Lau Fung‐Yi , Cheung Filly , Cheng Gregory Yin‐Ming , Chui Chung‐Hin , Wong Wai‐Yeung 
Published: March 2010

AbstractA homologous set of 9,9‐dialkyl‐4,5‐diazafluorene compounds were prepared by alkylation of 4,5‐diazafluorene with the appropriate alkyl bromide and under basic conditions. The structures of these simple organic compounds were confirmed by spectroscopic techniques (FTIR, NMR, and FABMS). Their biological effects toward a panel of human carcinoma cells, including Hep3B hepatocellular carcinoma, MDAMB‐231 breast carcinoma, and SKHep‐1 hepatoma cells, were investigated; a structure–activity correlation was established with respect to the length of the alkyl chain and the fluorene ring structure. The relationship between the mean potency [log(1/IC50)] and alkyl chain length was systematically studied. The results show that compounds with butyl, hexyl, and octyl chains exhibit good growth inhibitory effects toward these three human carcinoma cell lines, and the 9,9‐dihexyl‐4,5‐diazafluorene further exhibits antitumor activity in athymic nude mice Hep3B xenograft models. For the structurally related dialkylfluorenes that lack the diaza functionality, in vitro cytotoxicity was not observed at clinically relevant concentrations.
Characteristics of pericardial effusions in patients with leukemia
Authors: Sampat Keeran , Rossi Adriana , Garcia‐Gutierrez Valentin , Cortes Jorge , Pierce Sherry , Kantarjian Hagop , Garcia‐Manero Guillermo 
Published: March 2010

AbstractBACKGROUND:Little information exists regarding the prevalence and natural history of pericardial disease in patients with leukemia. Recently, it has been reported that the use of histone deacetylase inhibitors is associated with an increased incidence of pericardial effusions (PEs). To study the characteristics and treatment relationships of PEs in patients with leukemia, the authors retrospectively analyzed a cohort of patients with leukemia evaluated at a single center.METHODS:The authors reviewed 2592 patients with acute myeloid leukemia (AML, n = 1282, 49%), acute lymphocytic leukemia (ALL, n = 336, 13%), or myelodysplastic syndrome (MDS, n = 974, 38%), who were evaluated from August 2003 to July 2008. Electronic medical records were reviewed to select patients who had undergone at least 1 echocardiographic evaluation. Data regarding diagnosis, timing, effusion size, survival, and prior therapy were collected for the patients who had echocardiographic evidence of PEs.RESULTS:PEs were detected in 325 (20%) of the patients who had echocardiograms: 21% in AML, 23% in ALL, and 18% in MDS patients. Only a small portion of PEs were detected before the initiation of therapy: 26% in AML, 25% ALL, and 15% in MDS patients. Most PEs were of minimal size (70%) overall. No significant differences in effusion characteristics, including severity, were observed among different types of therapies. The presence of PEs had no impact on the survival of the patients evaluated.CONCLUSIONS:PEs are relatively common in patients with leukemia and do not appear to be related to specific types of therapy or to survival. Cancer 2010. © 2010 American Cancer Society.
Phase 2 trial of pemetrexed disodium and carboplatin in previously untreated extensive‐stage small cell lung cancer, N0423
Authors: Chee Cheng E. , Jett James R. , Bernath Albert M. , Foster Nathan R. , Nelson Garth D. , Molina Julian , Nikcevich Daniel A. , Steen Preston D. , Flynn Patrick J. , Rowland Kendrith M. 
Published: March 2010

AbstractBACKGROUND:In extensive‐stage small cell lung cancer (SCLC), the combination of pemetrexed plus carboplatin has shown activity and appeared to be well‐tolerated. We conducted a trial to confirm the efficacy and to assess the tolerability of this chemotherapy combination.METHODS:Patients with untreated extensive‐stage SCLC were enrolled in this phase 2 open‐labeled study. They receive pemetrexed 500 mg/m2 and carboplatin (area under the curve of 5) every 21 days for a maximum 6 cycles. The primary endpoint for this trial was the confirmed response rate and the accrual goal was 70 patients.RESULTS:Forty‐six eligible patients (29 aged <70 years, 17 aged ≥70 years) were accrued to this study. The efficacy outcomes were similar between the 2 age groups. Overall, the confirmed response rate was 35% (16 of 46; 95% confidence interval [CI], 21%‐50%), where all 16 were partial responses. On the basis of these results, we had strong evidence that the study would not meet the preset efficacy criteria and was, therefore, closed before full accrual. The median duration of response was 4.4 months (95% CI, 2.9‐5.2). Median overall survival for patients aged <70 years and aged ≥70 years was 9.2 months (95% CI, 5.4‐11.6) and 10.8 months (95% CI, 2.2‐14.3), respectively. Grade 3 or higher toxicity rates were similar between the younger and older patients. Grade 3/4 and grade 4 hematological toxicities were observed in 46% and 26% of patients, respectively.CONCLUSIONS:Although well‐tolerated, the combination of pemetrexed and carboplatin is not as effective as standard therapy in patients with untreated extensive‐stage SCLC. Cancer 2010. © 2010 American Cancer Society.
Radiosurgical decompression of metastatic epidural compression
Authors: Ryu Samuel , Rock Jack , Jain Rajan , Lu Mei , Anderson Joseph , Jin Jian‐Yue , Rosenblum Mark , Movsas Benjamin , Kim Jae Ho 
Published: March 2010

AbstractBACKGROUND:Surgical decompression of metastatic epidural compression (MEC) improved ambulatory function. Spine radiosurgery can accurately target the epidural tumor and deliver high radiation doses for tumor control. Therefore, a clinical trial was performed to quantitatively determine the degree of epidural decompression by radiosurgery of metastatic epidural compression.METHODS:Sixty‐two patients with a total of 85 lesions of metastatic epidural compression were treated. Epidural compression was diagnosed by magnetic resonance imaging (MRI) scans. Main criteria of inclusion were neurological status with muscle power 4 of 5 or better. Radiosurgery was performed to the involved spine segment, including the epidural mass with median dose of 16 Gy (range 12‐20 Gy) in a single session. All patients had prospective clinical follow‐up, ranging from 1‐48 months (median 11.5 months), and 36 patients had pretreatment and post‐treatment imaging, ranging from 2‐33 months (median 9.3 months). Primary endpoints were epidural tumor control and thecal sac decompression.RESULTS:The mean epidural tumor volume reduction was 65 ± 14% at 2 months after radiosurgery. The epidural tumor area at the level of the most severe spinal cord compression was 0.82 ± 0.08 cm2 before radiosurgery and 0.41 ± 0.06 cm2 after radiosurgery (P < .001). Thecal sac patency improved from 55 ± 4% to 76 ± 3% (P < .001). Overall, neurological function improved in 81%.CONCLUSIONS:This study demonstrated a radiosurgical decompression of epidural tumor. Although neurosurgical decompression and radiotherapy is the standard treatment in patients with good performance, radiosurgical decompression can be a viable noninvasive treatment option for malignant epidural compression. Cancer 2010. © 2010 American Cancer Society.
Oxaliplatin and capecitabine in the treatment of patients with recurrent or refractory carcinoma of unknown primary site
Authors: Hainsworth John D. , Spigel David R. , Burris Howard A. , Shipley Dianna , Farley Cindy , Macias‐Perez Ines M. , Barton John , Greco F. Anthony 
Published: March 2010

AbstractBACKGROUND:Despite the widespread use of oxaliplatin‐based regimens for colorectal and other gastrointestinal cancers, there is surprisingly little information regarding their empiric use for the treatment of carcinoma of unknown primary site (CUP). In the current study, the combination of oxaliplatin and capecitabine in patients with recurrent and refractory CUP was examined.METHODS:Patients with CUP who had received at least 1 previous chemotherapy regimen were treated with oxaliplatin (130 mg/m2 intravenously on Day 1) and capecitabine (1000 mg/m2 orally twice daily on Days 1‐14). Treatment cycles were repeated every 21 days. Patients with objective response or stable disease after 2 cycles continued treatment for 6 cycles or until disease progression.RESULTS:Nine of 48 patients (19%) had objective responses to treatment; an additional 22 patients had stable disease at the time of first re‒evaluation. After a median follow‐up of 17 months, the median progression‐free and overall survivals were 3.7 months and 9.7 months, respectively. This regimen was reasonably well tolerated by most patients.CONCLUSIONS:The combination of oxaliplatin and capecitabine was found to have activity as a salvage treatment for patients with CUP. This regimen should be considered in patients with clinical and pathologic features suggesting a primary site in the gastrointestinal tract. Further development of the regimen as a first‐line therapy, or with bevacizumab added, is indicated. Cancer 2010. © 2010 American Cancer Society.
Histology‐specific nomogram for primary retroperitoneal soft tissue sarcoma
Authors: Ardoino Ilaria , Miceli Rosalba , Berselli Mattia , Mariani Luigi , Biganzoli Elia , Fiore Marco , Collini Paola , Stacchiotti Silvia , Casali Paolo Giovanni , Gronchi Alessandro 
Published: March 2010

AbstractBACKGROUND:This study was conducted to develop a histology‐specific nomogram to predict postoperative overall survival (OS) at 5 and 10 years in primary retroperitoneal soft tissue sarcoma (STS).METHODS:Data registered at a single institution (National Cancer Institute, Milan, Italy) prospective sarcoma database were used. In the present analysis, patients with primary localized retroperitoneal STS resected with curative intent between 1985 and 2007 were included. A parametric piecewise exponential survival multivariate model was used for nomogram development, and internal validation was performed with standard methodologies. Known prognostic variables, such as age, tumor burden, histologic variant (as reviewed by a sarcoma pathologist), grade, and surgical margins were considered as putative predictors.RESULTS:Among the 192 patients analyzed, within 10 years from surgery, 114 patients were alive, with a median follow‐up time of 55 months (interquartile range, 25‐104 months). Among the investigated factors, only histologic subtype did not reach significance at the 10% level. The relative hazard increased while increasing tumor size up to about 25 cm, and decreased thereafter.CONCLUSIONS:A histology‐specific nomogram for retroperitoneal STS is now available. It can be used for better assessing the risk of the single patient and then making individualized decisions within the specific subset of retroperitoneal sarcomas. Cross‐check external validation should be performed. Cancer 2010. © 2010 American Cancer Society.
BD focalpoint slide profiler performance with atypical glandular cells on SurePath Papanicolaou smears
Authors: Chute Deborah J. , Lim Harumi , Kong Christina S. 
Published: March 2010

AbstractBACKGROUND:The FocalPoint Slide Profiler is an automated cervical cytology screening system that is approved for primary screening. It identifies up to 25% of slides as requiring No Further Review. However, few studies have evaluated FocalPoint performance with glandular abnormalities.METHODS:Sixty‐six SurePath Papanicolaou (Pap) tests with a diagnosis of atypical glandular cells were identified. A total of 172 Pap tests with a diagnosis of “endometrial cells present” were included as controls. Follow‐up histology was abnormal if diagnosed as high‐grade squamous intraepithelial lesions, adenocarcinoma in situ, carcinoma, or complex endometrial hyperplasia. The FocalPoint software ranked each case into 1 of 7 categories: quintiles 1 (high risk) through 5 (low risk), No Further Review, and Process Review.RESULTS:A total of 215 slides were qualified for review; 38 (57.6%) atypical glandular cells cases were abnormal on follow‐up biopsy, and 27 (71.1%) atypical glandular cells with abnormal follow‐up qualified for review; no cases were classified No Further Review, and 9 (33%) were ranked in quintile 1. Twenty‐three (82.1%) atypical glandular cells with benign follow‐up were qualified for review; 3 (11%) cases were classified No Further Review, and 4 (17%) were ranked in quintile 1. There was a statistically significant difference between the ranking of benign atypical glandular cells cases, abnormal atypical glandular cells cases, and control cases (P = .03). However, when collapsed into No Further Review versus all other quintiles, the differences were not significant (P = .20).CONCLUSIONS:The FocalPoint Slide Profiler did not classify glandular lesions with abnormal follow‐up in the No Further Review category. However, these cases were not preferentially ranked in quintile 1. FocalPoint‐screened slides need to be carefully reviewed for glandular abnormalities, regardless of the quintile ranking. Cancer (Cancer Cytopathol) 2010. © 2010 American Cancer Society.