bluuebunny/crossref_metadata_2025_split huggingface dataset:
New biotechnological perspectives of a NADH oxidase variant from Thermus thermophilus HB27 as NAD+-recycling enzyme
Authors: Rocha-Martín Javier , Vega Daniel , Bolivar Juan M , Godoy Cesar A , Hidalgo Aurelio , Berenguer José , Guisán José M , López-Gallego Fernando 
Published: November 2011

Abstract

Background
The number of biotransformations that use nicotinamide recycling systems is exponentially growing. For this reason one of the current challenges in biocatalysis is to develop and optimize more simple and efficient cofactor recycling systems. One promising approach to regenerate NAD+ pools is the use of NADH-oxidases that reduce oxygen to hydrogen peroxide while oxidizing NADH to NAD+. This class of enzymes may be applied to asymmetric reduction of prochiral substrates in order to obtain enantiopure compounds.

Results
The NADH-oxidase (NOX) presented here is a flavoenzyme which needs exogenous FAD or FMN to reach its maximum velocity. Interestingly, this enzyme is 6-fold hyperactivated by incubation at high temperatures (80°C) under limiting concentrations of flavin cofactor, a change that remains stable even at low temperatures (37°C). The hyperactivated form presented a high specific activity (37.5 U/mg) at low temperatures despite isolation from a thermophile source. Immobilization of NOX onto agarose activated with glyoxyl groups yielded the most stable enzyme preparation (6-fold more stable than the hyperactivated soluble enzyme). The immobilized derivative was able to be reactivated under physiological conditions after inactivation by high solvent concentrations. The inactivation/reactivation cycle could be repeated at least three times, recovering full NOX activity in all cases after the reactivation step. This immobilized catalyst is presented as a recycling partner for a thermophile alcohol dehydrogenase in order to perform the kinetic resolution secondary alcohols.

Conclusion
We have designed, developed and characterized a heterogeneous and robust biocatalyst which has been used as recycling partner in the kinetic resolution of rac-1-phenylethanol. The high stability along with its capability to be reactivated makes this biocatalyst highly re-useable for cofactor recycling in redox biotransformations.
Protein trafficking, ergosterol biosynthesis and membrane physics impact recombinant protein secretion in Pichia pastoris
Authors: Baumann Kristin , Adelantado Núria , Lang Christine , Mattanovich Diethard , Ferrer Pau 
Published: November 2011

Abstract

Background
The increasing availability of 'omics' databases provide important platforms for yeast engineering strategies since they offer a lot of information on the physiology of the cells under diverse growth conditions, including environmental stresses. Notably, only a few of these approaches have considered a performance under recombinant protein production conditions. Recently, we have identified a beneficial effect of low oxygen availability on the expression of a human Fab fragment in Pichia pastoris. Transcriptional analysis and data mining allowed for the selection of potential targets for strain improvement. A first selection of these candidates has been evaluated as recombinant protein secretion enhancers.

Results
Based on previous transcriptomics analyses, we selected 8 genes for co-expression in the P. pastoris strain already secreting a recombinant Fab fragment. Notably, WSC4 (which is involved in trafficking through the ER) has been identified as a novel potential target gene for strain improvement, with up to a 1.2-fold increase of product yield in shake flask cultures. A further transcriptomics-based strategy to modify the yeast secretion system was focused on the ergosterol pathway, an aerobic process strongly affected by oxygen depletion. By specifically partially inhibiting ergosterol synthesis with the antifungal agent fluconazole (inhibiting Erg11p), we tried to mimic the hypoxic conditions, in which the cellular ergosterol content was significantly decreased. This strategy led to an improved Fab yield (2-fold) without impairing cellular growth. Since ergosterol shortage provokes alterations in the plasma membrane composition, an important role of this cellular structure in protein secretion is suggested. This hypothesis was additionally supported by the fact that the addition of non-ionic surfactants also enhanced Fab secretion.

Conclusions
The current study presents a systems biotechnology-based strategy for the engineering of the industrially important yeast P. pastoris combining the use of host specific DNA microarray technologies and physiological studies under well defined environmental conditions. Such studies allowed for the identification of novel targets related with protein trafficking and ergosterol biosynthesis for improved recombinant protein production. Nevertheless, further studies will be required to elucidate the precise mechanisms whereby membrane biogenesis and composition impact on protein secretion in P. pastoris.
Mesenchymal stem cells as carriers and amplifiers in CRAd delivery to tumors
Authors: Xia Xi , Ji Teng , Chen Pingbo , Li Xiao , Fang Yong , Gao Qinglei , Liao Shujie , You Lanying , Xu Hongbin , Ma Quanfu , Wu Peng , Hu Wencheng , Wu Mingfu , Cao Li , Li Kezhen , Weng Yanjie , Han Zhiqiang , Wei Junchen , Liu Ronghua , Wang Shixuan , Xu Gang , Wang Daowen , Zhou Jianfeng , Ma Ding 
Published: November 2011

Abstract

Background
Mesenchymal stem cells (MSCs) have been considered to be the attractive vehicles for delivering therapeutic agents toward various tumor diseases. This study was to explore the distribution pattern, kinetic delivery of adenovirus, and therapeutic efficacy of the MSC loading of E1A mutant conditionally replicative adenovirus Adv-Stat3(-) which selectively replicated and expressed high levels of anti-sense Stat3 complementary DNA in breast cancer and melanoma cells.

Methods
We assessed the release ability of conditionally replicative adenovirus (CRAd) from MSC using crystal violet staining, TCID50 assay, and quantitative PCR. In vitro killing competence of MSCs carrying Adv-Stat3(-) toward breast cancer and melanoma was performed using co-culture system of transwell plates. We examined tumor tropism of MSC by Prussian blue staining and immunofluorescence. In vivo killing competence of MSCs carrying Adv-Stat3(-) toward breast tumor was analyzed by comparison of tumor volumes and survival periods.

Results
Adv-Stat3(-) amplified in MSCs and were released 4 days after infection. MSCs carrying Adv-Stat3(-) caused viral amplification, depletion of Stat3 and its downstream proteins, and led to significant apoptosis in breast cancer and melanoma cell lines. In vivo experiments confirmed the preferential localization of MSCs in the tumor periphery 24 hours after tail vein injection, and this localization was mainly detected in the tumor parenchyma after 72 hours. Intravenous injection of MSCs carrying Adv-Stat3(-) suppressed the Stat3 pathway, down-regulated Ki67 expression, and recruited CD11b-positive cells in the local tumor, inhibiting tumor growth and increasing the survival of tumor-bearing mice.

Conclusions
These results indicate that MSCs migrate to the tumor site in a time-dependent manner and could be an effective platform for the targeted delivery of CRAd and the amplification of tumor killing effects.
Banach operator pairs and common fixed points in modular function spaces
Authors: Hussain N , Khamsi MA , Latif A 
Published: November 2011

AbstractIn this article, we introduce the concept of a Banach operator pair in the setting of modular function spaces. We prove some common fixed point results for such type of operators satisfying a more general condition of nonexpansiveness. We also establish a version of the well-known De Marr's theorem for an arbitrary family of symmetric Banach operator pairs in modular function spaces without Δ2-condition.
MSC(2000)
primary 06F30; 47H09; secondary 46B20; 47E10; 47H10.
Effects of 28 days of resistance exercise while consuming commercially available pre- and post-workout supplements, NO-Shotgun® and NO-Synthesize® on body composition, muscle strength and mass, markers of protein synthesis, and clinical safety markers in males
Authors: Spillane Mike , Schwarz Neil , Leddy Sarah , Correa Tracie , Minter Melodie , Longoria Victoria , Willoughby Darryn S 
Published: November 2011

Abstract

Purpose
The effects of 28 days of heavy resistance training while ingesting the pre- and post-workout supplements, NO-Shotgun® and NO-Synthesize® were determined on body composition, muscle strength and mass, markers of protein synthesis, and clinical safety markers.

Methods
Nineteen non-resistance-trained males participated in a resistance training program 4 times/week for 28 days while either ingesting 27 g/day of carbohydrate (CARB) or NO-Shotgun® 30 min pre-exercise and 27 g/day of carbohydrate or NO- Synthesize® 30 min post-exercise (NOSS). Data were analyzed with separate 2 × 2 ANOVA (p < 0.05).

Results
Total body mass was increased in both groups (p = 0.001), but not different between groups. Fat mass was unchanged with CARB, but NOSS decreased fat mass (p = 0.026). Both groups increased fat-free mass (p = 0.001); however, the increases were greater with NOSS (p = 0.023). NOSS underwent greater increases in upper-body (p = 0.023) and lower-body (p = 0.035) strength than CARB. Myofibrillar protein significantly increased in both groups (p = 0.041), with NOSS being greater than CARB (p = 0.049). All of the MHC isoforms were significantly increased in both groups; however, NOSS was greater than CARB for MHC 1 (p = 0.013) and MHC 2A (p = 0.046). All of the myogenic regulatory factors were significantly increased in both groups; however, NOSS was greater than CARB for Myo-D (p = 0.038) and MRF-4 (p = 0.001). For the whole blood and serum clinical chemistry markers, all variables remained within normal clinical ranges.

Conclusions
Heavy resistance training for 28 days, with NO-Shotgun® and NO-Synthesize® ingested before and after exercise, respectively, significantly improved body composition and increased muscle mass and performance without abnormally impacting any of the clinical chemistry markers.
Strong nuclear EGFR expression in colorectal carcinomas is associated with cyclin-D1 but not with gene EGFR amplification
Authors: Dekanić Andrea , Dobrila Dintinjan Renata , Budisavljević Ivana , Pećanić Sanja , Žuvić Butorac Marta , Jonjić Nives 
Published: November 2011

AbstractBackgroundPrognostic and predictive significance of epidermal growth factor receptor (EGFR) in colorectal carcinomas (CRCs) is still controversial. The aim of the present study was to explore and correlate membrane and nuclear EGFR and cyclin-D1 protein expression with EGFR gene status of tumor cells.MethodsImmunohistochemical and FISH analysis was performed on 135 archival formalin fixed and paraffin embedded CRCs.ResultsStrong membrane and strong nuclear EGFR staining was detected in 16% and 57% of cases, respectively, and strong cyclin-D1 expression in 57% samples. Gene EGFR amplification was identified in 5.9% and polysomy in 7.4% of cases, while 87% showed no EGFR gene changes. A statistically significant difference was only found between tumor grade and expression of membrane EGFR, while nuclear EGFR and cyclin-D1 expression was not associated with the clinicopathologic characteristics analyzed. Tumor cells displaying gene amplification and strong protein membrane EGFR expression overlapped, while EGFR gene status showed no correlation with nuclear EGFR and cyclin-D1. There was no association between membrane EGFR and cyclin-D1, whereas nuclear EGFR expression was strongly related to cyclin-D1 expression.ConclusionsStudy results revealed heterogeneity among CRCs, which could have a predictive value by identifying biologically and probably clinically different subsets of tumors with the possibly diverse response to anti-EGFR therapies.
Planning analysis for locally advanced lung cancer: dosimetric and efficiency comparisons between intensity-modulated radiotherapy (IMRT), single-arc/partial-arc volumetric modulated arc therapy (SA/PA-VMAT)
Authors: Jiang Xiaoqin , Li Tao , Liu Yongmei , Zhou Lin , Xu Yong , Zhou Xiaojuan , Gong Youling 
Published: November 2011

Abstract

Purpose
To analyze the differences between the intensity-modulated radiotherapy (IMRT), single/partial-arc volumetric modulated arc therapy (SA/PA-VMAT) techniques in treatment planning for locally advanced lung cancer.

Materials and methods
12 patients were retrospectively studied. In each patient's case, several parameters were analyzed based on the dose-volume histograms (DVH) of the IMRT, SA/PA-VMAT plans respectively. Also, each plan was delivered to a phantom for time comparison.

Results
The SA-VMAT plans showed the superior target dose coverage, although the minimum/mean/maximum doses to the target were similar. For the total and contralateral lungs, the higher V5/10, lower V20/30 and mean lung dose (MLD) were observed in the SA/PA-VMAT plans (p < 0.05, respectively). The PA-VMAT technique improves the dose sparing (V20, V30 and MLD) of the controlateral lung more notably, comparing to those parameters of the IMRT and SA-VMAT plans respectively. The delivered monitor units (MUs) and treatment times were reduced significantly with VMAT plans, especially PA-VMAT plans (for MUs: mean 458.3 vs. 439.2 vs. 435.7 MUs, p < 0.05 and for treatment time: mean 13.7 vs. 10.6 vs. 6.4 minutes, p < 0.01).

Conclusions
The SA-VMAT technique achieves highly conformal dose distribution to the target. Comparing to the IMRT plans, the higher V5/10, lower V20/30 and MLD were observed in the total and contralateral lungs in the VMAT plans, especially in the PA-VMAT plans. The SA/PA-VMAT plans also reduced treatment time with more efficient dose delivering. But the clinical benefit of the VMAT technique for locally advanced lung cancer needs further investigations.
The plasticity of TGF-βsignaling
Authors: Cellière Geraldine , Fengos Georgios , Hervé Marianne , Iber Dagmar 
Published: November 2011

AbstractBackgroundThe family of TGF-βligands is large and its members are involved in many different signaling processes. These signaling processes strongly differ in type with TGF-βligands eliciting both sustained or transient responses. Members of the TGF-βfamily can also act as morphogen and cellular responses would then be expected to provide a direct read-out of the extracellular ligand concentration. A number of different models have been proposed to reconcile these different behaviours. We were interested to define the set of minimal modifications that are required to change the type of signal processing in the TGF-βsignaling network.ResultsTo define the key aspects for signaling plasticity we focused on the core of the TGF-βsignaling network. With the help of a parameter screen we identified ranges of kinetic parameters and protein concentrations that give rise to transient, sustained, or oscillatory responses to constant stimuli, as well as those parameter ranges that enable a proportional response to time-varying ligand concentrations (as expected in the read-out of morphogens). A combination of a strong negative feedback and fast shuttling to the nucleus biases signaling to a transient rather than a sustained response, while oscillations were obtained if ligand binding to the receptor is weak and the turn-over of the I-Smad is fast. A proportional read-out required inefficient receptor activation in addition to a low affinity of receptor-ligand binding. We find that targeted modification of single parameters suffices to alter the response type. The intensity of a constant signal (i.e. the ligand concentration), on the other hand, affected only the strength but not the type of the response.ConclusionsThe architecture of the TGF-βpathway enables the observed signaling plasticity. The observed range of signaling outputs to TGF-βligand in different cell types and under different conditions can be explained with differences in cellular protein concentrations and with changes in effective rate constants due to cross-talk with other signaling pathways. It will be interesting to uncover the exact cellular differences as well as the details of the cross-talks in future work.
Symmetry-Itemized Enumeration of Cubane Derivatives as Three-Dimensional Entities by the Fixed-Point Matrix Method of the USCI Approach
Authors: Fujita Shinsaku 
Published: November 2011

Abstract
Cubane derivatives with chiral and achiral proligands are counted as three-dimensional (3D) structural isomers by the fixed-point matrix method of the unit-subduced-cycle-index (USCI) approach (S. Fujita, “Symmetry and Combinatorial Enumeration in Chemistry,” Springer-Verlag, 1991). The numbers of such 3D structural isomers are itemized with respect to their point-group symmetries, which are subgroups of the point group Oh for a cubane skeleton. For this purpose, the full list of unit subduced cycle indices with chirality fittingness (USCI-CFs) of Oh is constructed in a tabular form. Fixed-point vectors or fixed-point matrices, which are calculated by starting from USCI-CFs, are used to count 3D structural isomers in the form of isomer-counting matrices. A Maple program source for counting cubane derivatives as 3D structural isomers is given as an example of practical calculation.
Nonhematopoietically Derived DNA Is Shorter than Hematopoietically Derived DNA in Plasma: A Transplantation Model
Authors: Zheng Yama W L , Chan K C Allen , Sun Hao , Jiang Peiyong , Su Xiaoxi , Chen Eric Z , Lun Fiona M F , Hung Emily C W , Lee Vincent , Wong John , Lai Paul B S , Li Chi-Kong , Chiu Rossa W K , Lo Y M Dennis 
Published: November 2011

Abstract

BACKGROUND
Plasma DNA is predominantly hematopoietic in origin. The size difference between maternal- and fetal-derived DNA in maternal plasma prompted us to investigate whether there was any discrepancy in molecular size between hematopoietically and nonhematopoietically derived DNA in plasma.

METHODS
Plasma DNA samples from 6 hematopoietic stem cell transplant recipients and 1 liver transplant recipient were analyzed by massively parallel paired-end sequencing. The size of each fragment was deduced from the alignment positions of the paired reads. In sex-mismatched transplant recipients, the reads from chromosome Y were used as markers for the male donor/recipient. For other transplant recipients, the reads of the donor- and recipient-specific alleles were identified from the single-nucleotide polymorphism genotypes.

RESULTS
In male patients receiving female hematopoietic stem cells, more chromosome Y–derived DNA molecules (nonhematopoietically derived) were ≤150 bp than the autosome-derived ones (mainly hematopoietically derived) (median difference, 9.9%). In other hematopoietic stem cell transplant recipients, more recipient-specific DNA molecules (nonhematopoietically derived) were ≤150 bp than the donor-specific ones (hematopoietically derived) (median difference, 14.8%). In the liver transplant recipient, more donor-derived DNA molecules (liver derived) were ≤150 bp than the recipient-derived ones (mainly hematopoietically derived) (difference, 13.4%). The nonhematopoietically derived DNA exhibited a reduction in a 166-bp peak compared with the hematopoietically derived DNA. A 10-bp periodicity in size distribution below approximately 143 bp was observed in both DNA populations.

CONCLUSIONS
Massively parallel sequencing is a powerful tool for studying posttransplantation chimerism. Plasma DNA molecules exhibit a distinct fragmentation pattern, with the nonhematopoietically derived molecules being shorter than the hematopoietically derived ones.
Synthesis of glucose esters from cellulose in ionic liquids
Authors: Ignatyev Igor A. , Doorslaer Charlie Van , Mertens Pascal G.N. , Binnemans Koen , Vos Dirk E. de 
Published: November 2011

Abstract
The transformation of cellulose into glucose ester α-d-glucose pentaacetate (GPAc) was carried out in ionic liquid 1-butyl-3-methylimidazolium chloride under mild reaction conditions. The reaction comprises two steps: the first involves a hydrolysis reaction, yielding α-d-glucose and glucose oligomers; and then only after some time, the acetylating reagent acetic anhydride is added. Under optimized conditions and with the acidic resin Amberlyst 15DRY as a hydrolysis catalyst, a 70% yield of GPAc was obtained. This product could be quantitatively isolated by simple liquid-liquid extraction, which allowed easy recycling of the ionic liquid and catalyst.
Prädiktive Bedeutung von Autoantikörpern/Predictive relevance of autoantibodies
Authors: Conrad Karsten 
Published: November 2011

Zusammenfassung
Autoantikörper (AAK) mit hoher Krankheitsspezifität sind bedeutsame Marker für die Diagnostik und Differentialdiagnostik von Autoimmunerkrankungen (AIE). Bei Negativität bestimmter AAK bzw. AAK-Kombinationen kann in vielen Fällen mit relativer Sicherheit die entsprechende AIE ausgeschlossen werden. Bei Vorliegen typischer klinischer Symptome kann mittels AAK-Bestimmung die Diagnose häufig bestätigt werden, auch wenn noch nicht das Vollbild der Erkrankung entsprechend den Klassifikations- oder Diagnosekriterien vorliegt. Da für eine optimale Kontrolle der Krankheitsentwicklung eine frühzeitige adäquate Therapie erforderlich ist, sollte die Diagnose in einem möglichst frühen Stadium der Erkrankung gesichert werden. Hierfür kommt der Bestimmung von AAK, welche eine hohe Krankheitsspezifität und eine hohe prädiktive Wertigkeit aufweisen, eine wachsende Bedeutung zu.
Multiparameteranalytik in Diagnostik und Monitoring von Autoimmunerkrankungen: Stand und Perspektiven/Multiparametric analyses in diagnostics and monitoring of autoimmune diseases: current state and perspectives
Authors: Conrad Karsten , Sack Ulrich 
Published: November 2011

Zusammenfassung
Das meist lange präklinische Stadium, die große Variabilität in den klinischen Manifestationen sowie der Notwendigkeit einer frühzeitigen adäquaten Therapie von Autoimmunerkrankungen erfordern die Suche und Evaluierung geeigneter Biomarker, welche den Erkrankungsprozess zuverlässig reflektieren und eine sichere Frühdiagnostik sowie therapeutisch relevante Aussagen (Organmanifestationen, Aktivität, Erkrankungsentwicklung, Ansprechen auf bestimmte Therapieformen) zulassen. Bisher werden vorwiegend Autoantikörper für die serologische Diagnostik, Prognostik und teilweise auch für das Monitoring von Autoimmunerkrankungen herangezogen. Sie sind in Abhängigkeit von den diagnostischen Variablen wertvolle diagnostische Marker, jedoch in Bezug auf Prognostik, Aktivität und Therapieansprechbarkeit nicht oder nur eingeschränkt nutzbar. Ziel künftiger Entwicklungen sollte es daher sein, geeignete Kombinationen von krankheitsrelevanten Autoantikörpern oder Autoantikörper-Profilen und anderen Biomarkern zu finden, welche im Rahmen einer multiparametrischen Analytik eine verlässliche Frühdiagnostik, Prognostik und Theranostik garantieren und damit über eine optimierte personalisierte Therapie wesentlich zur Verbesserung der medizinischen Betreuung von Patienten mit Autoimmunerkrankungen beitragen.
Clinical Results of a Total Knee Prosthesis with Floating Platform at 5.5 Years
Authors: Miehlke Rolf , Geyer Robert , Clemens Ulrich , Thiel Birger 
Published: November 2011

Abstract
In this study, 117 patients who had received the e.motion FP prosthesis between 2001 and 2003 were followed up for 5.5 years to assess the clinical and radiological outcomes and survival of this mobile platform prosthesis. As this design is intended to improve the mobility of the replaced knee, particular emphasis was placed on the clinical and functional results. The hypothesis was that they would be comparable to the excellent results reported in the literature of state-of-the-art total knee arthroplasty. After 66months, the average Knee Society clinical and functional scores were 93.8 points (KSS-C) and 90.5 (KSS-F) points, respectively. The clinical and radiographical results were excellent, with a low rate of anterior knee pain of 2.3 %.