bluuebunny/crossref_metadata_2025_split huggingface dataset:
Evaluation of a new mist‐chamber bioreactor for biotechnological applications
Authors: Tscheschke Bernd , Dreimann Janis , von der Ruhr Jürgen W. , Schmidt Timo , Stahl Frank , Just Lothar , Scheper Thomas 
Published: December 2014

ABSTRACTIn this article we describe the development, the characterization and the evaluation of a novel bioreactor type for the cultivation of different pro‐ and eukaryotic cell‐systems: the mist‐chamber bioreactor. This innovative bioreactor meets the demand of cultivation systems for shear stress sensitive cells with high requirements for gas supply. Within the mist‐chamber bioreactor the cells are cultivated inside an aerosol of vaporized medium generated by ultrasonic vaporization. In contrast to many established bioreactor systems the mist‐chamber bioreactor offers an environment with an excellent gas supply without any impeller or gas bubble induced shear stress. A mist‐chamber bioreactor prototype has been manufactured and characterized during this work. In the technical and chemical characterization we evaluated the vaporization process, resulting in a vaporization performance of 32 mL/h at working conditions. On this basis we calculated a biomass of 1.4 g (S. cerevisiae, qs = 3.45 × 10–3 mol/g/h) and 3.4 g (Aspergillus niger, qs = 1.33 × 10–3 mol/g/h) where the growth rate becomes limited by transport processes. Additionally, we determined a homogenous cultivation area to a height of 3 cm giving a total volume of 0.45 L for the cultivation. Medium components were examined according to their stability during vaporization with the result that all components are stable for at least 5 days. After the technical characterization we demonstrated the feasibility to cultivate S. cerevisiae and F. velupites in the mist‐chamber bioreactor. The results demonstrated that the mist‐chamber bioreactor is able to transport a sufficient amount of nutrients consistently to the cell samples and offers an excellent oxygen supply without any shear stress inducing aeration. Furthermore we successfully cultivated F. velupites in a solid state cultivation in a long term experiment. The data indicate that the new bioreactor concept can contribute to improve various fermentations and cell culture processes depending on the cultured cell types. Biotechnol. Bioeng. 2015;112: 1155–1164. © 2014 Wiley Periodicals, Inc.
How does mild hypothermia affect monoclonal antibody glycosylation?
Authors: Sou Si Nga , Sellick Christopher , Lee Ken , Mason Alison , Kyriakopoulos Sarantos , Polizzi Karen M. , Kontoravdi Cleo 
Published: December 2014

ABSTRACTThe application of mild hypothermic conditions to cell culture is a routine industrial practice used to improve recombinant protein production. However, a thorough understanding of the regulation of dynamic cellular processes at lower temperatures is necessary to enhance bioprocess design and optimization. In this study, we investigated the impact of mild hypothermia on protein glycosylation. Chinese hamster ovary (CHO) cells expressing a monoclonal antibody (mAb) were cultured at 36.5°C and with a temperature shift to 32°C during late exponential/early stationary phase. Experimental results showed higher cell viability with decreased metabolic rates. The specific antibody productivity increased by 25% at 32°C and was accompanied by a reduction in intracellular nucleotide sugar donor (NSD) concentrations and a decreased proportion of the more processed glycan structures on the mAb constant region. To better understand CHO cell metabolism at 32°C, flux balance analysis (FBA) was carried out and constrained with exometabolite data from stationary phase of cultures with or without a temperature shift. Estimated fluxomes suggested reduced fluxes of carbon species towards nucleotide and NSD synthesis and more energy was used for product formation. Expression of the glycosyltransferases that are responsible for N‐linked glycan branching and elongation were significantly lower at 32°C. As a result of mild hypothermia, mAb glycosylation was shown to be affected by both NSD availability and glycosyltransferase expression. The combined experimental/FBA approach generated insight as to how product glycosylation can be impacted by changes in culture temperature. Better feeding strategies can be developed based on the understanding of the metabolic flux distribution. Biotechnol. Bioeng. 2015;112: 1165–1176. © 2014 Wiley Periodicals, Inc.
Kinetic parameter estimation in N. europaea biofilms using a 2‐D reactive transport model
Authors: Lauchnor Ellen G. , Semprini Lewis , Wood Brian D. 
Published: December 2014

ABSTRACTBiofilms of the ammonia oxidizing bacterium Nitrosomonas europaea were cultivated to study microbial processes associated with ammonia oxidation in pure culture. We explored the hypothesis that the kinetic parameters of ammonia oxidation in N. europaea biofilms were in the range of those determined with batch suspended cells. Oxygen and pH microelectrodes were used to measure dissolved oxygen (DO) concentrations and pH above and inside biofilms and reactive transport modeling was performed to simulate the measured DO and pH profiles. A two dimensional (2‐D) model was used to simulate advection parallel to the biofilm surface and diffusion through the overlying fluid while reaction and diffusion were simulated in the biofilm. Three experimental studies of microsensor measurements were performed with biofilms: i) NH3 concentrations near the Ksn value of 40 μM determined in suspended cell tests ii) Limited buffering capacity which resulted in a pH gradient within the biofilms and iii) NH3 concentrations well below the Ksn value. Very good fits to the DO concentration profiles both in the fluid above and in the biofilms were achieved using the 2‐D model. The modeling study revealed that the half‐saturation coefficient for NH3 in N. europaea biofilms was close to the value measured in suspended cells. However, the third study of biofilms with low availability of NH3 deviated from the model prediction. The model also predicted shifts in the DO profiles and the gradient in pH that resulted for the case of limited buffering capacity. The results illustrate the importance of incorporating both key transport and chemical processes in a biofilm reactive transport model. Biotechnol. Bioeng. 2015;112: 1122–1131. © 2014 Wiley Periodicals, Inc.
Molecular polygamy: The promiscuity of l‐phenylalanyl‐tRNA‐synthetase triggers misincorporation ofmeta‐ andortho‐tyrosine in monoclonal antibodies expressed by Chinese hamster ovary cells
Authors: Popp Oliver , Larraillet Vincent , Kettenberger Hubert , Gorr Ingo H. , Hilger Maximiliane , Lipsmeier Florian , Zeck Anne , Beaucamp Nicola 
Published: December 2014

ABSTRACTIn‐depth analytical characterization of biotherapeutics originating from different production batches is mandatory to ensure product safety and consistent molecule efficacy. Previously, we have shown unintended incorporation of tyrosine (Tyr) and leucine/isoleucine (Leu/Ile) at phenylalanine (Phe) positions in a recombinant produced monoclonal antibody (mAb) using an orthogonal MASCOT/SIEVE based approach for mass spectrometry data analysis. The misincorporation could be avoided by sufficient supply of phenylalanine throughout the process. Several non‐annotated signals in the primarily chromatographic peptide separation step for apparently single Phe→Tyr sequence variants (SVs) suggest a role for isobar tyrosine isoforms.Meta‐andortho‐Tyr are spontaneously generated during aerobic fed‐batch production processes usingChinese hamster ovary(CHO) cell lines. Process inducedmeta‐ andortho‐Tyr but not proteinogenicpara‐Tyr are incorporated at Phe locations in Phe‐starved CHO cultures expressing a recombinant mAb. Furthermore,meta‐ andortho‐Tyr are preferably misincorporated over Leu. Structural modeling of the l‐phenylalanyl‐tRNA‐synthetase (PheRS) substrate activation site indicates a possible fit of non‐cognateortho‐Tyr andmeta‐Tyr substrates. Dose‐dependent misincorporations of Tyr isoforms support the hypothesis thatmeta‐ andortho‐Tyr are competing, alternative substrates for PheRS in CHO processes. Finally, easily accessibleat‐linesurrogate markers for Phe→Tyr SV formation in biotherapeutic production were defined by the calculation of critical ratios formeta‐Tyr/Phe andortho‐Tyr/Phe to support early prediction of SV probability, and finally, to allow for immediate process controlled Phe→Tyr SV prevention. Biotechnol. Bioeng. 2015;112: 1187–1199. © 2014 Wiley Periodicals, Inc.
Maternal Borderline Personality Disorder and Risk of Child Maltreatment
Authors: Laulik Sarah , Allam Jayne , Browne Kevin 
Published: December 2014

A community‐based cross‐sectional study was conducted to explore the relationship between parental personality disorder and child maltreatment. This article reports on the findings of a study focusing on a subsample of 46 maltreating mothers who had all been referred for psychological assessment in the context of care proceedings. Of the 46 mothers, 13 met the full diagnostic criteria for borderline personality disorder (BPD). Of the remaining 33 mothers, 18 presented with strong features of BPD but did not meet the full criteria and 18 presented with no significant features of BPD. Results indicated that maltreating mothers with diagnosed BPD were more likely than those with BPD features and those with no significant features to have engaged in the perpetration of physical and multiple (physical abuse and neglect) types of child maltreatment. No association was found between BPD and child neglect alone. Compared to the two other groups, mothers with BPD were identified as a particularly traumatised subgroup. The tentative conclusion that may be drawn from these findings is that maltreating mothers with BPD may represent a particularly high‐risk subgroup. The results are discussed with reference to existing empirical research. Implications for clinical practice and future research are then considered. Copyright © 2014 John Wiley & Sons, Ltd.‘46 maltreating mothers… referred for psychological assessment in the context of care proceedings’‘Maltreating mothers with BPD may represent a particularly high‐risk subgroup’Key Practitioner Messages

BPD is a risk factor for interpersonal violence.
Results of this study suggest that BPD may also be a risk factor for the perpetration of physical child abuse and multiple maltreatment (physical abuse and neglect) amongst mothers involved in care proceedings.
Maltreating mothers with BPD may represent a particularly high‐risk subgroup.
The Challenge of Linear (E)‐Enones in the Rh‐Catalyzed, Asymmetric 1,4‐Addition Reaction of Phenylboronic Acid: A DFT Computational Analysis
Authors: Qin Hua‐Li , Chen Xiao‐Qing , Shang Zhen‐Peng , Kantchev Eric Assen B. 
Published: December 2014

AbstractWhy are linear (E)‐enones such challenging substrates in the Rh‐catalyzed asymmetric arylation with boronic acids, which is one of the most important asymmetric catalysis methods? DFT computations show that these substrates adopt a specific conformation in which the largest substituent is antiperiplanar to RhI π‐complexed with the CC bond within the enantioselectivity‐determining carborhodation transition state. Additionally, for such structures, there is a strong, but not exclusive, preference for s‐cis enone conformation. This folding minimizes steric interactions between the substrate and the ligand, and hence reduces the enantioselectivity. This idea is further confirmed by investigating three computation‐only substrate “probes”, one of which is capable of double asymmetric induction, and a recent computationally designed 1,5‐diene ligand. On average, excellent agreement between predicted and experimental enantioselectivity was attained by a three‐pronged approach: 1) thorough conformational search within ligand and substrate subunits to locate the most preferred carborhodation transition state; 2) including dispersion interaction and long‐range corrections by SMD/ωB97xD/DGDZVP level of theory; and 3) full substrate and ligand modeling. Based on the results, a theory‐enhanced enantioselectivity model that is applicable to both chiral diene and diphosphane ligands is proposed.
Insight into the Mechanism of Hydrogenation of Amino Acids to Amino Alcohols Catalyzed by a Heterogeneous MoOx‐Modified Rh Catalyst
Authors: Tamura Masazumi , Tamura Riku , Takeda Yasuyuki , Nakagawa Yoshinao , Tomishige Keiichi 
Published: December 2014

AbstractHydrogenation of amino acids to amino alcohols is a promising utilization of natural amino acids. We found that MoOx‐modified Rh/SiO2 (Rh–MoOx/SiO2) is an efficient heterogeneous catalyst for the reaction at low temperature (323 K) and the addition of a small amount of MoOx drastically increases the activity and selectivity. Here, we report the catalytic potential of Rh–MoOx/SiO2 and the results of kinetic and spectroscopic studies to elucidate the reaction mechanism of Rh–MoOx/SiO2 catalyzed hydrogenation of amino acids to amino alcohols. Rh–MoOx/SiO2 is superior to previously reported catalysts in terms of activity and substrate scope. This reaction proceeds by direct formation of an aldehyde intermediate from the carboxylic acid moiety, which is different from the reported reaction mechanism. This mechanism can be attributed to the reactive hydride species and substrate adsorption caused by MoOx modification of Rh metal, which results in high activity, selectivity, and enantioselectivity.
Cytologic diagnostic approach to poorly differentiated thyroid carcinoma: A single‐institution study
Authors: Kane Shubhada V. , Sharma Tanvi Paliwal 
Published: December 2014

BACKGROUNDFine‐needle aspiration cytology (FNAC) is a well‐established technique for the preoperative evaluation of thyroid nodules because it is minimally invasive, cost‐effective, quick, efficient, and safe. Various articles have discussed differences in the cytomorphology of different types of thyroid cancer. However, review articles on the cytologic diagnosis of poorly differentiated thyroid carcinoma (PDTC) are scarce as PDTC are rare tumors. Although the histologic diagnostic criteria are well standardized, the cytologic diagnostic criteria are not yet standardized. This prompted us to study the cytomorphological features of PDTC and assess features of distinction from differentiated thyroid carcinoma (DTC) and medullary thyroid carcinoma (MTC).METHODSThis was a retrospective study of thyroid FNAC smears from 44 PDTC cases retrieved from the database of a single tertiary cancer institute (2009‐2013). Papanicolaou and Giemsa smears were evaluated for 21 cytomorphologic features. Immunocytochemistry was available for 6 cases only.RESULTSThe frequencies of cytomorphologic features in the 44 cases were as follows: hypercellularity, 84.1%; insular pattern, 79.5%; small cell size, 93.2%; high nuclear‐cytoplasmic ratio, 93.2%; granular chromatin pattern, 95.45%; nuclear overlapping, 88.64%; mild pleomorphism, 86.36%; grooves/inclusions, 22.7%; binucleation/multinucleation, 9.1%; abrupt nucleomegaly, 34.1%; apoptosis, 45%; mitosis, 25%; necrosis, 34.1%; and colloid, 22.7%.CONCLUSIONA high index of suspicion is necessary for an upfront diagnosis of PDTC on FNAC. Although PDTC, DTC, and MTC have overlapping features, there are distinguishing features also. The cytologic diagnostic criteria for PDTC need to be standardized by collaborative efforts among tertiary cancer centers. A prompt diagnosis is the key feature for planning multimodality treatment. Cancer (Cancer Cytopathol) 2015;123:82–91. © 2014 American Cancer Society.
Cytomorphological features of ALK‐positive lung adenocarcinomas: Psammoma bodies and signet ring cells
Authors: Pareja Fresia , Crapanzano John P. , Mansukhani Mahesh M. , Bulman William A. , Saqi Anjali 
Published: December 2014

BACKGROUNDCorrelation between histology and genotype has been described in lung adenocarcinomas. For example, studies have demonstrated that adenocarcinomas with an anaplastic lymphoma kinase (ALK) gene rearrangement may have mucinous features. The objective of the current study was to determine whether a similar association can be identified in cytological specimens.METHODSA retrospective search for ALK‐rearranged cytopathology (CP) and surgical pathology (SP) lung carcinomas was conducted. Additional ALK‐negative (‐) lung adenocarcinomas served as controls. For CP and SP cases, the clinical data (i.e., age, sex, and smoking history), architecture, nuclear features, presence of mucin‐containing cells (including signet ring cells), and any additional salient characteristics were evaluated.RESULTSThe search yielded 20 ALK‐positive (+) adenocarcinomas. Compared with patients with ALK(‐) lung adenocarcinomas (33 patients; 12 with epidermal growth factor receptor [EGFR]‐mutation, 11 with Kristen rat sarcoma [KRAS]‐mutation, and 10 wild‐type adenocarcinomas), patients with ALK(+) adenocarcinoma presented at a younger age; and there was no correlation noted with sex or smoking status. The most common histological pattern in SP was papillary/micropapillary. Mucinous features were associated with ALK rearrangement in SP specimens. Signet ring cells and psammoma bodies were evident in and significantly associated with ALK(+) SP and CP specimens. However, psammoma bodies were observed in rare adenocarcinomas with an EGFR mutation. Both the ALK(+) and ALK(−) groups had mostly high nuclear grade.CONCLUSIONSSalient features, including signet ring cells and psammoma bodies, were found to be significantly associated with ALK(+) lung adenocarcinomas and are identifiable on CP specimens. Recognizing these may be especially helpful in the molecular triage of scant CP samples. Cancer (Cancer Cytopathol) 2014. © 2014 American Cancer Society. Cancer (Cancer Cytopathol) 2015;123:162–170. © 2014 American Cancer Society.
Combination of p16INK4a/Ki67 immunocytology and hpv polymerase chain reaction for the noninvasive analysis of HPV involvement in head and neck cancer
Authors: Linxweiler Maximilian , Bochen Florian , Wemmert Silke , Lerner Cornelia , Hasenfus Andrea , Bohle Rainer Maria , Al‐Kadah Basel , Takacs Zoltan Ferenc , Smola Sigrun , Schick Bernhard 
Published: December 2014

BACKGROUNDHigh‐risk human papillomavirus (HPV) infection has been identified as a relevant risk for the development of head and neck squamous cell carcinomas (HNSCCs). As HPV status has also gained a role as a prognostic and predictive biomarker for this entity, there is a growing demand for valid HPV testing in HNSCC patientsMETHODSLiquid‐based cytological smears from 45 HNSCC and 20 control patients were collected and used for simultaneous immunocytochemical p16INK4a/Ki67 staining using a CINtec PLUS kit after the presence of tumor cells was verified in a Papanicolaou‐stained slide. The same cytological suspension was used for the detection of HPV DNA by specific polymerase chain reaction (PCR).RESULTSTumor cells were detected in the swab material of 44 HNSCC patients corresponding to a sensitivity of 98% (44 of 45). PCR analysis revealed the presence of HPV DNA in the cytological suspension of 13 patients (13 of 65, 20%) with simultaneous p16INK4a/Ki67 expression by the tumor cells in 11 of these HPV DNA–positive samples (11 of 13, 85%) — a staining pattern that is strongly associated with a carcinogenic HPV infection.CONCLUSIONSA simultaneous immunocytochemical detection of p16INK4aand Ki67 can reliably be performed on liquid‐based cytological smears from HNSCC patients using a CINtec PLUS kit. In addition, the same cytological material can be used for the detection of HPV DNA by specific PCR. The combined results of both techniques enable better discrimination between latent and carcinogenic HPV infections as well as HPV‐negative cases and thus can provide information on the prognosis of HNSCC patients and facilitate therapeutic decisions.Cancer (Cancer Cytopathol)2015;123:219–229.©2014 American Cancer Society.
The AdaBoost Flow
Authors: Lykov Alexandr , Muzychka Stepan , Vaninsky Kirill 
Published: December 2014

We introduce a dynamical system that we call the AdaBoost flow. The flow is defined by a system of ODEs with control. We show that three algorithms of the AdaBoost family, (i) the AdaBoost algorithm of Schapire and Freund, (ii) the arc‐gv algorithm of Breiman, and (iii) the confidence rated prediction of Schapire and Singer, can be embedded in the AdaBoost flow.The nontrivial part of the AdaBoost flow equations coincides with the equations of dynamics of the nonperiodic Toda system written in terms of spectral variables. We provide a novel invariant geometrical description of the AdaBoost algorithm as a gradient flow on a foliation defined by level sets of the potential function.We propose a new approach for constructing boosting algorithms as a continuous‐time gradient flow on measures defined by various metrics and potential functions. Finally, we explain the similarity of the AdaBoost algorithm with the Perelman's construction for the Ricci flow.© 2015 Wiley Periodicals, Inc.
Using Cavity Microelectrodes for Electrochemical Noise Studies of Oxygen‐Evolving Catalysts
Authors: Rincón Rosalba A. , Battistel Alberto , Ventosa Edgar , Chen Xingxing , Nebel Michaela , Schuhmann Wolfgang 
Published: December 2014

AbstractCavity microelectrodes were used as a binder‐free platform to evaluate oxygen evolution reaction (OER) electrocatalysts with respect to gas bubble formation and departure. Electrochemical noise measurements were performed by using RuO2 as a benchmark catalyst and the perovskite La0.58Sr0.4Fe0.8Co0.2O3 as a non‐noble metal OER catalyst with lower intrinsic conductivity. Changes in the current during the OER originate from variations in electrolyte resistance during the formation of the gas phase and partial coverage of the active area. Fluctuations observed in current and conductance transients were used to establish the contribution from the ohmic overpotential and to determine the characteristic frequency of oxygen evolution. The proposed quantitative determination of gas bubble growth and departure opens up the route for a rational interface design by considering gas bubble growth and departure as a main contributing factor to the overall electrocatalytic activity at high current densities.