Miracle-dz/UniFAR-FTUs huggingface dataset:
Cauchy Six-Dimensional Formalism for Lamb Waves in Multilayered Plates

Propagation of Lamb waves in multilayered elastic anisotropic plates is studied in the framework of combination of the six-dimensional Cauchy formalism and the transfer matrix method. The closed form secular equations for dispersion curves of Lamb waves propagating in multilayered plates with arbitrary elastic anisotropy are obtained.
Poly(2‐ethyloxazoline) as matrix for highly active electrospun enzymes in organic solvents

Nanofibers are advantageous carriers for biocatalysts, because they show lower diffusion limitations due to their high surface/volume ratio. Only a few samples are known where enzymes are directly spun into nanofibers, mostly because there are not many suited polymer carriers. In this study, poly(2‐ethyloxazoline) (PEtOx) was explored regarding its usefulness to activate various enzymes in organic solvents by directly electrospinning them from aqueous solutions containing the polymer. It was found that the concentration of PEtOx in the spinning solution and also the swellability of the fibers play a great role in the activity of the enzymes in organic solvents. Using electrospun lipase B from Candida antarctica (CaLB) under optimized conditions revealed a higher carrier activity than the commercial Novozyme 435 with 10 times less immobilized protein. The electrospinning of PEtOx/CaLB fibers onto a stirrer is used to realize a biocatalytic stirrer for organic solvents. Biotechnol. Bioeng. 2017;114: 39–45. © 2016 Wiley Periodicals, Inc.
A PHYSICAL SYSTEM FOR BINOCULAR VISION THROUGH SACCADE GENERATION AND VERGENCE CONTROL

The human naturally possesses a robust and effective visual system that utilizes saccade and vergence eye movements to explore the visual environment. This article presents a system that provides the functional biological equivalent which consists of a pair of cameras that provide for saccade and vergence eye movements. Included in this article is a detailed description of a simplified equivalent of the saccade generation module (typically from the superior colliculus (SC)) based on a FLANN image segmentation method and a visual cortex (VC) equivalent model based on a hierarchical disparity estimation model for vergence control. These two models cooperate to provide the systematic means for the autonomous exploration of the scene. Combining saccade and vergence movements, we are able to selectively reconstruct the 3D relative positions of objects in the scene and segment the image of the object under vergence.
FX knockout CHO hosts can express desired ratios of fucosylated or afucosylated antibodies with high titers and comparable product quality

During antibody dependent cell cytotoxicity (ADCC) the target cells are killed by monocytes and natural killer cells. ADCC is enhanced when the antibody heavy chain's core N‐linked glycan lacks the fucose molecule(s). Several strategies have been utilized to generate fully afucosylated antibodies. A commonly used and efficient approach has been knocking out the FUT8 gene of the Chinese hamster ovary (CHO) host cells, which results in expression of antibody molecules with fully afucosylated glycans. However, a major drawback of the FUT8‐KO host is the requirement for undertaking two separate cell line development (CLD) efforts in order to obtain both primarily fucosylated and fully afucosylated antibody species for comparative studies in vitro and in vivo. Even more challenging is obtaining primarily fucosylated and FUT8‐KO clones with similar enough product quality attributes to ensure that any observed ADCC advantage(s) can be strictly attributed to afucosylation. Here, we report generation and use of a FX knockout (FXKO) CHO host cell line that is capable of expressing antibody molecules with either primarily fucosylated or fully afucosylated glycan profiles with otherwise similar product quality attributes, depending on addition of fucose to the cell culture media. Hence, the FXKO host not only obviates the requirement for undertaking two separate CLD efforts, but it also averts the need for screening many colonies to identify clones with comparable product qualities. Finally, FXKO clones can express antibodies with the desired ratio of primarily fucosylated to afucosylated glycans when fucose is titrated into the production media, to allow achieving intended levels of FcγRIII‐binding and ADCC for an antibody. Biotechnol. Bioeng. 2017;114: 632–644. © 2016 Wiley Periodicals, Inc.
Establishing very long‐chain fatty alcohol and wax ester biosynthesis in Saccharomyces cerevisiae

Wax esters (WEs) are neutral lipids and can be used for a broad range of commercial applications, including personal care products, lubricants, or coatings. They are synthesized by enzymatic reactions catalyzed by a fatty acyl reductase (FAR) and a wax ester synthase (WS). At present, commercially used WEs are mainly isolated from Simmondsia chinensis (jojoba), but the high extraction costs and limited harvest areas constrain their use. The use of FARs in combination with different WSs to achieve a synthesis of jojoba‐like WEs in bacteria and yeast has been reported previously, but the products were restricted to C28–C36 WEs. These rather short WEs make up only a very small percentage of the total WEs in natural jojoba oil. The synthesis of longer chain WEs (up to C44) in Saccharomyces cerevisiae has so far only been achieved after substrate feeding. Here we identified new routes for producing very long‐chain fatty alcohols (VLCFOHs) up to a chain length of C22 by heterologous expression of a FAR derived from Apis mellifera (AmFAR1) or Marinobacter aquaeolei VT8 (Maqu_2220) in S. cerevisiae and achieved maximum yields of 3.22 ± 0.36 mg/g cell dry weight (CDW) and 7.84 ± 3.09 mg/g CDW, respectively, after 48 h. Moreover, we enabled the synthesis of jojoba‐like WEs up to a chain length of C42, catalyzed by a combination of Maqu_2220 together with the WS from S. chinensis (SciWS) and the S. cerevisiae elongase Elo2p, with a maximum yield of 12.24 ± 3.35 mg/g CDW after 48 h. Biotechnol. Bioeng. 2017;114: 1025–1035. © 2016 Wiley Periodicals, Inc.
HIGH-SPEED PCA ENCRYPTION ALGORITHM USING RECONFIGURABLE COMPUTING

In this work, an originally bio-inspired cryptosystem is developed. It is based on the use of cellular automata (CAs) as pseudorandom bit generators and programmable cellular automata (PCA) to construct the block ciphering functions of the proposed enciphering scheme. The cryptosystem is featured by resistance on different types of attacks and high speed due to the cellular automata's parallel information processing property. The proposed architecture could be efficiently implemented in reconfigurable hardware like field programmable gate arrays (FPGAs) and could be applied in high-speed data communication. The project was implemented in two experimental hardware platforms based on Spartan 3 XC3S400fg456-4 and XILINX Spartan 3E XC3S500E.
QSAR models for prediction of chromatographic behavior of homologous Fab variants

While quantitative structure activity relationship (QSAR) models have been employed successfully for the prediction of small model protein chromatographic behavior, there have been few reports to date on the use of this methodology for larger, more complex proteins. Recently our group generated focused libraries of antibody Fab fragment variants with different combinations of surface hydrophobicities and electrostatic potentials, and demonstrated that the unique selectivities of multimodal resins can be exploited to separate these Fab variants. In this work, results from linear salt gradient experiments with these Fabs were employed to develop QSAR models for six chromatographic systems, including multimodal (Capto MMC, Nuvia cPrime, and two novel ligand prototypes), hydrophobic interaction chromatography (HIC; Capto Phenyl), and cation exchange (CEX; CM Sepharose FF) resins. The models utilized newly developed “local descriptors” to quantify changes around point mutations in the Fab libraries as well as novel cluster descriptors recently introduced by our group. Subsequent rounds of feature selection and linearized machine learning algorithms were used to generate robust, well‐validated models with high training set correlations (R2 > 0.70) that were well suited for predicting elution salt concentrations in the various systems. The developed models then were used to predict the retention of a deamidated Fab and isotype variants, with varying success. The results represent the first successful utilization of QSAR for the prediction of chromatographic behavior of complex proteins such as Fab fragments in multimodal chromatographic systems. The framework presented here can be employed to facilitate process development for the purification of biological products from product‐related impurities by in silico screening of resin alternatives. Biotechnol. Bioeng. 2017;114: 1231–1240. © 2016 Wiley Periodicals, Inc.
TPRANK: CONTEND WITH WEB SPAM USING TRUST PROPAGATION

The quantity and quality of seed sets are key factors for the success of propagation-based anti-web spam techniques. This kind of approach is simple yet effective, but the manual evaluation of seed sets is time-consuming. Therefore, a manual evaluation process is vital. In this article, we propose Trust Propagation Rank (TPRank), which automatically propagates trust to demote web spam based on a small number of reputable and spam seeds. Moreover, the proposed algorithm is extended to trust propagation (TP) spam mass in detection of web spam. Experiments were performed on two public available data sets—WEBSPAM-UK2006 and WEBSPAM-UK2007—and the results showed that both TPRank and TP spam mass outperform the state-of-the-art TrustRank in demotion up to 10.623% and spam mass algorithm in detection up to 43.216%.
Understanding of decreased sialylation of Fc‐fusion protein in hyperosmotic recombinant Chinese hamster ovary cell culture: N‐glycosylation gene expression and N‐linked glycan antennary profile

To understand the effects of hyperosmolality on protein glycosylation, recombinant Chinese hamster ovary (rCHO) cells producing the Fc‐fusion protein were cultivated in hyperosmolar medium resulting from adding NaCl (415 mOsm/kg). The hyperosmotic culture showed increased specific Fc‐fusion protein productivity (qFc) but a decreased proportion of acidic isoforms and sialic acid content of the Fc‐fusion protein. The intracellular and extracellular sialidase activities in the hyperosmotic cultures were similar to those in the control culture (314 mOsm/kg), indicating that reduced sialylation of Fc‐fusion protein at hyperosmolality was not due to elevated sialidase activity. Expression of 52 N‐glycosylation‐related genes was assessed by the NanoString nCounter system, which provides a direct digital readout using custom‐designed color‐coded probes. After 3 days of hyperosmotic culture, nine genes (ugp, slc35a3, slc35d2, gcs1, manea, mgat2, mgat5b, b4galt3, and b4galt4) were differentially expressed over 1.5‐fold of the control, and all these genes were down‐regulated. N‐linked glycan analysis by anion exchange and hydrophilic interaction HPLC showed that the proportion of highly sialylated (di‐, tri‐, tetra‐) and tetra‐antennary N‐linked glycans was significantly decreased upon hyperosmotic culture. Addition of betaine, an osmoprotectant, to the hyperosmotic culture significantly increased the proportion of highly sialylated and tetra‐antennary N‐linked glycans (P ≤ 0.05), while it increased the expression of the N‐glycan branching/antennary genes (mgat2 and mgat4b). Thus, decreased expression of the genes with roles in the N‐glycan biosynthesis pathway correlated with reduced sialic acid content of Fc‐fusion protein caused by hyperosmolar conditions. Taken together, the results obtained in this study provide a better understanding of the detrimental effects of hyperosmolality on N‐glycosylation, especially sialylation, in rCHO cells. Biotechnol. Bioeng. 2017;114: 1721–1732. © 2017 Wiley Periodicals, Inc.
Uplift Random Forests

Conventional supervised statistical learning models aim to achieve high accuracy in predicting the value of an outcome measure based on a number of input measures. However, in many applications, some type of action is randomized on the observational units. This is the case, for example, in treatment/control settings, such as those usually encountered in marketing and clinical trial applications. In these situations, we may not necessarily be interested in predicting the outcome itself, but in estimating the expected change in the outcome as a result of the action. This is precisely the idea behind uplift models, which, despite their many practical applications, have received little attention in the literature. In this article, we extend the state-of-the-art research in this area by proposing a new approach based on Random Forests. We perform carefully designed experiments using simple simulation models to illustrate some of the properties of the proposed method. In addition, we present evidence on a dataset pertaining to a large Canadian insurer on a customer retention case. The results confirm the effectiveness of the proposed method and show favorable performance relative to other existing uplift modeling approaches.
Impact of fluidic agitation on human pluripotent stem cells in stirred suspension culture

The success of human pluripotent stem cells (hPSCs) as a source of future cell therapies hinges, in part, on the availability of a robust and scalable culture system that can readily produce a clinically relevant number of cells and their derivatives. Stirred suspension culture has been identified as one such promising platform due to its ease of use, scalability, and widespread use in the pharmaceutical industry (e.g., CHO cell‐based production of therapeutic proteins) among others. However, culture of undifferentiated hPSCs in stirred suspension is a relatively new development within the past several years, and little is known beyond empirically optimized culture parameters. In particular, detailed characterizations of different agitation rates and their influence on the propagation of hPSCs are often not reported in the literature. In the current study, we systematically investigated various agitation rates to characterize their impact on cell yield, viability, and the maintenance of pluripotency. Additionally, we closely examined the distribution of cell aggregates and how the observed culture outcomes are attributed to their size distribution. Overall, our results showed that moderate agitation maximized the propagation of hPSCs to approximately 38‐fold over 7 days by keeping the cell aggregates below the critical size, beyond which the cells are impacted by the diffusion limit, while limiting cell death caused by excessive fluidic forces. Furthermore, we observed that fluidic agitation could regulate not only cell aggregation, but also expression of some key signaling proteins in hPSCs. This indicates a new possibility to guide stem cell fate determination by fluidic agitation in stirred suspension cultures. Biotechnol. Bioeng. 2017;114: 2109–2120. © 2017 Wiley Periodicals, Inc.
Responsiveness and Minimal Important Changes of the Scoliosis Research Society-22 Patient Questionnaire in Subjects With Mild Adolescent and Moderate Adult Idiopathic Scoliosis Undergoing Multidisciplinary Rehabilitation

Study Design. Single-center, prospective study. Objective. Evaluating the responsiveness and minimal important changes (MICs) for the Scoliosis Research Society-22 Patient Questionnaire (SRS-22) in adolescent idiopathic scoliosis (AIS) and adult idiopathic scoliosis (AS). Summary of Background Data. Despite the SRS-22 properties have been investigated in various different languages, there is still a lack of information concerning responsiveness and MIC, limiting the use of SRS-22 for clinical and research purposes. Methods. At the beginning and end of multidisciplinary rehabilitation programs, 149 subjects with mild AIS (Cobb angle <25°) and 140 subjects with moderate AS (Cobb angle <35°) completed the SRS-22. Upon completing the programs, subjects also performed the global perceived effect (GPE) scales test, which was divided to produce a dichotomous outcome (improved vs. stable). Responsiveness was calculated for all SRS-22 domains but satisfaction with management by distribution (effect size; standardized response mean) and anchor-based methods (receiver operating characteristic [ROC] curves; correlations between change scores of the SRS-22 and GPE). ROC curves were also used to compute the MICs. Results. The effect size ranged from 1.23 to 1.50 in AIS and from 1.02 to 1.37 in AS. The standardized response mean ranged from 0.95 to 1.27 in AIS and from 0.66 to 0.90 in AS. The ROC analyses revealed the following MIC values (area under the curve; sensitivity; specificity): function, 0.70 (0.739;66;70) for AIS and 0.60 (0.842;84;76) for AS; pain, 0.70 (0.731;71;70) for AIS and 0.40 (0.817;81;70) for AS; mental health, 0.50 (0.708;83;58) for AIS and 0.55 (0.750;69;78) for AS; self-perceived image, 0.40 (0.609;79;42) for AIS and 0.60 (0.751;61;82) for AS. Correlations between change scores of the SRS-22 domains and GPE were low to moderate, ranging from −0.347 to −0.667. Conclusion. The SRS-22 was sensitive in detecting clinical changes in subjects with adolescent and adult scoliosis. We recommend taking the MICs provided into account when assessing patients’ improvement or planning studies in these clinical contexts. Level of Evidence: 3
A dynamic metabolic flux analysis of ABE (acetone‐butanol‐ethanol) fermentation by Clostridium acetobutylicum ATCC 824, with riboflavin as a by‐product

The present study reveals that supplementing sodium acetate (NaAc) strongly stimulates riboflavin production in acetone‐butanol‐ethanol (ABE) fermentation by Clostridium acetobutylicum ATCC 824 with xylose as carbon source. Riboflavin production increased from undetectable concentrations to ∼0.2 g L−1 (0.53 mM) when supplementing 60 mM NaAc. Of interest, solvents production and biomass yield were also promoted with fivefold acetone, 2.6‐fold butanol, and 2.4‐fold biomass adding NaAc. A kinetic metabolic model, developed to simulate ABE biosystem, with riboflavin production, revealed from a dynamic metabolic flux analysis (dMFA) simultaneous increase of riboflavin (ribA) and GTP (precursor of riboflavin) (PurM) synthesis flux rates under NaAc supplementation. The model includes 23 fluxes, 24 metabolites, and 72 kinetic parameters. It also suggested that NaAc condition has first stimulated the accumulation of intracellular metabolite intermediates during the acidogenic phase, which have then fed the solventogenic phase leading to increased ABE production. In addition, NaAc resulted in higher intracellular levels of NADH during the whole culture. Moreover, lower GTP‐to‐adenosine phosphates (ATP, ADP, AMP) ratio under NaAc supplemented condition suggests that GTP may have a minor role in the cell energetic metabolism compared to its contribution to riboflavin synthesis.
Proinsulin level as a predictor of metabolic syndrome in the romanian population

Abstract Background and Aims: The aim of the present study was to determine discriminating values of proinsulin (FPP), proinsulin to insulin ratio (PIR), proinsulin to C-peptide ratio (PCPR) and Homeostasis model of assessment of insulin resistance (HOMA-IR) for the metabolic syndrome (MetS) as well as discovering sex-specific cutoff points of these parameters in the Romanian population. Material and Methods: We analyzed data from 224 patients. Circulating levels of fasting plasma glucose (FPG), fasting plasma insulin (FPI), FPP, fasting plasma C-peptide, HbA1c, and lipid profile were measured. Results: Among the 224 patients (87 males) MetS was diagnosed in 97 patients (43.3%) according to International Diabetes Federation (IDF) criteria. After stratification by gender, 43 men (49.4%) and 54 women (39.4%) had MetS. There were statistically significant differences between sexes for body mass index (BMI), % body fat, FPG, FPP, PIR, PCPR (all p<0.05). On multivariate logistic regression analysis, only age, BMI, FPP, and HOMA-IR were the independent factors associated with the presence of MetS. Conclusions: The present study showed that FPP and HOMA-IR were the best predictors for MetS in this sample of the Romanian population. Our results suggest that, regardless of gender, HOMA-IR and FPP could be the preferred parameters for predicting MetS.
Characterization of a membrane‐separated and a membrane‐less electrobioreactor for bioelectrochemical syntheses

Bioelectrochemical systems (BESs) have the potential to contribute to the energy revolution driven by the new bio‐economy. Until recently, simple reactor designs with minimal process analytics have been used. In recent years, assemblies to host electrodes in bioreactors have been developed resulting in so‐called “electrobioreactors. ” Bioreactors are scalable, well‐mixed, controlled, and therefore widely used in biotechnology and adding an electrode extends the possibilities to investigate bioelectrochemical production processes in a standard system. In this work, two assemblies enabling a separated and non‐separated electrochemical operation, respectively, are designed and extensively characterized. Electrochemical losses over the electrolyte and the membrane were comparable to H‐cells, the bioelectrochemical standard reaction system. An effect of the electrochemical measurements on pH measurements was observed if the potential is outside the range of −1,000 to +600 mV versus Ag/AgCl. Electrobiotechnological characterization of the two assemblies was done using Shewanella oneidensis as an electroactive model organism. Current production over time was improved by a separation of anodic and cathodic chamber by a Nafion® membrane. The developed electrobioreactor was used for a scale‐up of the anaerobic bioelectrochemical production of organic acids and lysine from glucose using an engineered Corynebacterium glutamicum. Comparison to a small‐scale custom‐made electrobioreactor indicates that anodic electro‐fermentation of lysine and organic acids might not be limited by the BES setup but by the biocatalysis of the cells.
Alka(e)ne synthesis in Cupriavidus necator boosted by the expression of endogenous and heterologous ferredoxin–ferredoxin reductase systems

To boost aldehyde deformylating oxygenase (ADO) activity in a Cupriavidus necator strain expressing a synthetic alkane pathway, the expression of two ferredoxin–ferredoxin reductase systems was tested. The genes of a native fd/FNR‐like system were identified in C. necator and expressed in a previously engineered alka(e)ne producing strain. The improved production of alka(e)nes in this Re2061‐pMAB1 strain confirmed the activity of the native Fd/FNR system in C. necator. Concomitantly, the expression of the heterologous system from Synechococcus elongatus was investigated identically, leading to a second strain, Re2061‐pMAB2. In the bioreactor, the aldehyde production was strongly reduced compared with the original alka(e)ne producer, leading to alka(e)nes production up to 0.37 and 1.48 g/L (22 and 82 mg/gCDW), respectively. The alka(e)ne production yield of Re2061‐pMAB2 accounted for 15% of the theoretical yield. We report here the highest level and yield of alka(e)nes production by an engineered bacterium to date.
Randomized clinical trial of 940‐ versus 1470‐nm endovenous laser ablation for great saphenous vein incompetence

The independent effect of wavelength used for endovenous laser ablation (EVLA) on patient‐reported outcomes, health‐related quality of life (HRQoL), treatment success and complications has not yet been established in a randomized clinical trial. The aim was to compare two different wavelengths, with identical energy level and laser fibres, in patients undergoing EVLA.