bluuebunny/crossref_metadata_2025 huggingface dataset:
Electromechanical Nanogenerator–Cell Interaction Modulates Cell Activity
Authors: Murillo Gonzalo , Blanquer Andreu , Vargas‐Estevez Carolina , Barrios Lleonard , Ibáñez Elena , Nogués Carme , Esteve Jaume
Published: April 2017

Noninvasive methods for in situ electrical stimulation of human cells open new frontiers to future bioelectronic therapies, where controlled electrical impulses could replace the use of chemical drugs for disease treatment. Here, this study demonstrates that the interaction of living cells with piezoelectric nanogenerators (NGs) induces a local electric field that self‐stimulates and modulates their cell activity, without applying an additional chemical or physical external stimulation. When cells are cultured on top of the NGs, based on 2D ZnO nanosheets, the electromechanical NG–cell interactions stimulate the motility of macrophages and trigger the opening of ion channels present in the plasma membrane of osteoblast‐like cells (Saos‐2) inducing intracellular calcium transients. In addition, excellent cell viability, proliferation, and differentiation are validated. This in situ cell‐scale electrical stimulation of osteoblast‐like cells can be extrapolated to other excitable cells such as neurons or muscle cells, paving the way for future bioelectronic medicines based on cell‐targeted electrical impulses.
Cyclodextrin Films with Fast Solvent Transport and Shape‐Selective Permeability
Authors: Villalobos Luis Francisco , Huang Tiefan , Peinemann Klaus‐Viktor
Published: April 2017

This study describes the molecular‐level design of a new type of filtration membrane made of crosslinked cyclodextrins—inexpensive macrocycles of glucose, shaped like hollow truncated cones. The channel‐like cavities of cyclodextrins spawn numerous paths of defined aperture in the separation layer that can effectively discriminate between molecules. The transport of molecules through these membranes is highly shape‐sensitive. In addition, the presence of hydrophobic (cavity) and hydrophilic (ester‐crosslinked outer part) domains in these films results in high permeances for both polar and nonpolar solvents.
Low‐Cost Manufacturing of Bioresorbable Conductors by Evaporation–Condensation‐Mediated Laser Printing and Sintering of Zn Nanoparticles
Authors: Shou Wan , Mahajan Bikram K. , Ludwig Brandon , Yu Xiaowei , Staggs Joshua , Huang Xian , Pan Heng
Published: April 2017

Currently, bioresorbable electronic devices are predominantly fabricated by complex and expensive vacuum‐based integrated circuit (IC) processes. Here, a low‐cost manufacturing approach for bioresorbable conductors on bioresorbable polymer substrates by evaporation–condensation‐mediated laser printing and sintering of Zn nanoparticle is reported. Laser sintering of Zn nanoparticles has been technically difficult due to the surface oxide on nanoparticles. To circumvent the surface oxide, a novel approach is discovered to print and sinter Zn nanoparticle facilitated by evaporation–condensation in confined domains. The printing process can be performed on low‐temperature substrates in ambient environment allowing easy integration on a roll‐to‐roll platform for economical manufacturing of bioresorbable electronics. The fabricated Zn conductors show excellent electrical conductivity (≈1.124 × 106 S m−1), mechanical durability, and water dissolvability. Successful demonstration of strain gauges confirms the potential application in various environmentally friendly sensors and circuits.
Designing an All‐Solid‐State Tungsten Oxide Based Electrochromic Switch with a Superior Cycling Efficiency
Authors: Ganesh Gayathri Prabhu T. , Deb Biswapriya
Published: April 2017

There are ongoing efforts to integrate electrochromic device (ECD) technology with other electrochemical systems. ECDs made with safer “solid” polymer electrolytes (SPEs) are prone to performance degradations due to their high relaxation period that is detrimental to highly dynamic switching operations. Here, the fabrication of partially crystalline WO3 based all‐solid‐state mono‐electrochrome switches is reported that shows outstanding optical and electrical stability under prolonged charge–discharge cycles. A free‐standing SPE is specially designed by dispersing LiClO4 into polyvinyl alcohol followed by thermochemical cross‐linking of the host. Continuous switching of the device shows two primary sources of performance degradations. One is associated with the polarization affecting both working and counter electrode interfaces (SPE‐WE and SPE‐CE), and the other is due to the irreversible redox reaction caused by total charge flow in the system that exceeds the double layer charge storage capacity of the CE. The conductivity and flexibility of the electrolyte are improved by adding glycerol as the plasticizer. In the CE, a nanocrystalline porous TiO2 buffer is used to avert the interface modifications. The performance of the switches is presented and compared using the spectro‐electrochemical and cyclic voltammetry data.
Hot‐Electron‐Mediated Photochemical Reactions: Principles, Recent Advances, and Challenges
Authors: Kim Minho , Lin Mouhong , Son Jiwoong , Xu Hongxing , Nam Jwa‐Min
Published: April 2017

Hot electron chemistry has drawn tremendous attention from applications related to materials, energy, sensing, and catalysis. The plasmon‐induced generation of hot electrons and their transfer behavior are very important for understanding plasmonic‐enhanced applications and for achieving practically useful efficiency. From a plasmonic perspective, well‐designed plasmonic structures that can manipulate surface plasmons are able to enhance the efficiencies of hot electron‐based processes. This progress report summarizes the recent experimental and theoretical advances on the hot electron effect, emphasizing the crucial role of surface plasmons that are highly designable by using metal nanostructures. In particular, recent breakthroughs in the emerging fields of heterogeneous catalysis based on the hot electron effect are highlighted. Important design principles, mechanisms, and concepts, as well as challenges and perspectives, are illustrated and discussed.
UV‐Blocking Photoluminescent Silicon Nanocrystal/Polydimethylsiloxane Composites
Authors: Chen Dongzhi , Sun Wei , Qian Chenxi , Wong Annabelle P. Y. , Reyes Laura M. , Ozin Geoffrey A.
Published: April 2017

It is a challenge to synthesize transparent polydimethylsiloxane (PDMS) materials that can completely absorb the light energy of ultraviolet (UV) A, B, and C regions. Herein, near‐infrared (NIR) photoluminescent PDMS composites with hydrogen‐terminated silicon nanocrystals (ncSi:H) or decyl‐terminated silicon nanocrystals (ncSi‐decyl) fabricated by combination of hydrosilylation and polymer encapsulation are reported. Their morphologies, optical and mechanical properties, and thermal stabilities are investigated. It is interesting to find that these PDMS composites filled with even a very small amount of ncSi:H or ncSi‐decyl have unprecedented UV‐blocking properties and superior thermal stabilities as compared to the PDMS reference. In particular, the ncSi‐decyl/PDMS composite possesses impressive photoluminescence. Furthermore, ncSi‐decyl are favorable for reinforcing the mechanical properties of the PDMS composites as compared to the PDMS reference and the ncSi:H/PDMS composite. The enhancement in the mechanical properties and thermal stabilities of these novel PL PDMS composites depends upon the creation of crosslinkable sites and entanglement interactions between the PDMS chains and the ncSi. These results suggest that potential applications for NIR photoluminescent ncSi/PDMS composites will likely be found in the fields of advanced UV‐blocking textiles, cosmetics, photofluids, stretchable electronic devices, anticounterfeiting materials, biological imaging, and diagnostics.
Electrospun NaVPO4F/C Nanofibers as Self‐Standing Cathode Material for Ultralong Cycle Life Na‐Ion Batteries
Authors: Jin Ting , Liu Yongchang , Li Yang , Cao Kangzhe , Wang Xiaojun , Jiao Lifang
Published: April 2017

NaVPO4F has received a great deal of attention as cathode material for Na‐ion batteries due to its high theoretical capacity (143 mA h g−1), high voltage platform, and structural stability. Novel NaVPO4F/C nanofibers are successfully prepared via a feasible electrospinning method and subsequent heat treatment as self‐standing cathode for Na‐ion batteries. Based on the morphological and microstructural characterization, it can be seen that the NaVPO4F/C nanofibers are smooth and continuous with NaVPO4F nanoparticles (≈6 nm) embedded in porous carbon matrix. For Na‐storage, this electrode exhibits extraordinary electrochemical performance: a high capacity (126.3 mA h g−1 at 1 C), a superior rate capability (61.2 mA h g−1 at 50 C), and ultralong cyclability (96.5% capacity retention after 1000 cycles at 2 C). 1D NaVPO4F/C nanofibers that interlink into 3D conductive network improve the conductivity of NaVPO4F, and effectively restrain the aggregation of NaVPO4F particles during charge/discharge process, leading to the high performance.
Early mortality and overall survival of acute myeloid leukemia based on facility type
Authors: Bhatt Vijaya R. , Shostrom Valerie , Giri Smith , Gundabolu Krishna , Monirul Islam K. M. , Appelbaum Frederick R. , Maness Lori J.
Published: April 2017

Cancer health disparities may exist based on the facility type. We aimed to determine the association between the academic status of centers and outcomes of patients with acute myeloid leukemia (AML). Using the National Cancer Data Base, we compared 1‐month mortality and long‐term overall survival (OS) of 60 738 patients with AML, who received first course treatment between 2003 and 2011 at academic or nonacademic centers (community cancer program, comprehensive community cancer program, and others). Multivariate analysis was done using logistic regression for one‐month mortality and Cox regression with backward elimination approach for OS. Patients treated at academic centers differed from those at nonacademic centers in that they were younger with a median age of 62 versus 70 years (P < .0001), more often an ethnic minority (P < .0001), had lower education level (P = .005), lower co‐morbidity score (P < .0001), a different income (P < .0001), and insurance profile (P < .0001), and more often received chemotherapy (P < .0001) and transplant (P < .0001). Receipt of care at nonacademic centers was associated with worse 1‐month mortality (29% vs. 16%, P < .0001) and 5‐year OS (15% vs. 25%; P < .0001). After adjusting for prognostic covariates, the 1‐month mortality (odds ratio, 1.52; 95% confidence interval, CI 1.46‐1.59; P < .0001) and OS were significantly worse in nonacademic centers, compared to academic centers. Our large database study suggests that the receipt of initial therapy at academic centers is associated with lower 1‐month mortality and higher long‐term OS. Investigation of the underlying reasons may allow reducing this disparity.
Compound heterozygous mutations in COL1A1 associated with an atypical form of type I osteogenesis imperfecta
Authors: Ackermann Amanda M. , Levine Michael A.
Published: April 2017

Heterozygous mutations in the genes encoding the proα1(I) or proα2(I) chains of type I procollagen (COL1A1 and COL1A2, respectively) account for most cases of osteogenesis imperfecta (OI), a disorder characterized by reduced bone strength and increased fracture risk. COL1A1 mutations can also cause rare cases of Ehlers–Danlos syndrome (EDS), a disorder that primarily affects connective tissue and often includes reduced bone mass. Here we present a kindred of three young siblings ages 1–4 years old whose mother has a history of mild type I OI. All three children are compound heterozygotes for COL1A1 mutations, with a novel frameshift mutation (c.2522delC; p.Pro841Leufs*266) from their mother and a known missense mutation (c.3196C>T; p.R1066C) from their clinically unaffected father, which has previously been described as causing a combined type I OI/EDS phenotype. The three children exhibit features of both COL1A1 mutations: early and frequent long bone fractures, joint hyperextensibility, and blue sclerae. We describe three siblings who are the first reported surviving subjects with biallelic pathogenic COL1A1 mutations. They have a more severe form of type I OI with features of EDS that represents their compound heterozygosity for two deleterious COL1A1 mutations. Their long‐term outcomes are yet to be determined.
Natural history of aortic root dilation through young adulthood in a hypermobile Ehlers–Danlos syndrome cohort
Authors: Ritter Alyssa , Atzinger Carrie , Hays Brandon , James Jeanne , Shikany Amy , Neilson Derek , Martin Lisa , Weaver Kathryn Nicole
Published: April 2017

Hypermobile Ehlers–Danlos syndrome (hEDS) is a common inherited connective tissue disorder characterized by joint hypermobility. The natural history of aortic root dilation (AoD), a potential complication of EDS, has not been well characterized in this population. We describe the natural history of aortic root size in a large cohort of patients with hEDS. A cohort of 325 patients with HEDS was identified at Cincinnati Children's Hospital Medical Center (CCHMC), including 163 patients from a previous study. Medical records were reviewed and each participant's height, weight, and aortic dimensions from up to four echocardiograms were documented. Aortic root z‐scores were calculated using two established formulas based on age (Boston or Devereux). Overall prevalence of AoD and prevalence by age were calculated and longitudinal regression was performed. The prevalence of AoD with a z‐score ≥ 2.0 was 14.2% (46/325) and with a z‐score of ≥3.0 was 5.5% (18/325). No significant increases in z‐score were seen over time for patients with multiple echocardiograms. Participants under the age of 15 years had an average decline of 0.1 standard deviations (SDs)/year. No significant change was found after 15 of age. Between the ages of 15 and 21 years, Boston z‐scores were 0.96 higher than Devereux z‐scores. The nearly 1 z‐score unit difference between formulas indicates caution prior to diagnosing AoD in patients with hEDS. In light of the low prevalence and lack of progression of AoD, routine echocardiograms may not be warranted for pediatric patients with hEDS.
Whole genome sequence association and ancestry‐informed polygenic profile of EEG alpha in a Native American population
Authors: Peng Qian , Schork Nicholas J. , Wilhelmsen Kirk C. , Ehlers Cindy L.
Published: April 2017

EEG alpha activity is the dominant oscillation in most adult humans, is highly heritable, and has been associated with a number of cognitive functions. Two EEG phenotypes, low‐ and high‐voltage alpha (LVA & HVA), have been demonstrated to have high heritabilities. They have different prevalence depending on a population's ancestral origins. In the present study we assessed the influence of ancestry admixture on EEG alpha power, and conducted a whole genome sequencing association analysis and an ancestry‐informed polygenic study on those phenotypes in a Native American (NA) population that has a high prevalence of LVA. Seven common variants, in LD with each other upstream from gene ASIC2, reached genome‐wide significance (p = 2 × 10−8) having a positive association with alpha voltage. They had lower minor allele frequencies in the NAs than in a global population sample. Overall correlations between lower degrees of NA (higher degree European) ancestry and HVA, and higher degrees of NA and LVA were also found. Additionally a rare‐variant gene‐based study identified gene TIA1 being negatively associated with LVA. Approximately 3% of SNPs exhibited a 15‐fold enrichment that explained nearly half of the total SNP‐heritability for EEG alpha. These regions showed the most significant anti‐correlations between NA ancestry and alpha voltage, and were enriched for genes and pathways mediating cognitive functions. Our findings suggested that these regions likely harbor causal variants for HVA, and lacking of such variants could explain the high prevalence of LVA in this NA population, possibly illuminating the ancestral origin and genetic basis for EEG alpha.
Genetic and environmental contributions to the association between ADHD and affective problems in early childhood—A Swedish population‐based twin study
Authors: Rydell Mina , Taylor Mark J. , Larsson Henrik
Published: April 2017

Few twin studies have explored the relative contribution of genetic and environmental factors to the association between attention deficit hyperactivity disorder (ADHD) and affective problems, and no study has focused on preschool children. We used the classical twin design to explore the genetic and environmental overlap between ADHD symptoms and affective problems in preschool children, based on 879 five‐year‐old twin pairs born in Sweden 2004–2005. Questionnaire‐based parent‐ratings were used to measure ADHD symptoms and affective problems. A bivariate twin design was used to decompose variance in ADHD and affective problems into genetic and environmental components, and to test the degree to which these components overlapped across the two traits. Our results showed that there was a significant correlation of 0.34 (95% Confidence Interval [CI] 0.29–0.38) between ADHD and affective problems. This correlation was mostly explained by additive genetic factors (64%, 95%CI 37–93%), and to a lesser extent by shared environmental factors (35%, 95%CI 10–59%). Nonshared environmental factors did not contribute to the correlation between ADHD and affective problems (0%, 95%CI −9 to 10%). These findings show that there is a significant association between ADHD and affective problems in preschool children that is mostly explained by genetic influences. This adds important knowledge about the etiology of both ADHD and affective problems by indicating that these phenotypes are linked from as early as preschool years. This also needs to be taken into consideration when diagnosing young children and clinicians should consider assessing both affective problems and ADHD if one is present.
A common genetic variant in FOXP2 is associated with language‐based learning (dis)abilities: Evidence from two Italian independent samples
Authors: Mozzi Alessandra , Riva Valentina , Forni Diego , Sironi Manuela , Marino Cecilia , Molteni Massimo , Riva Stefania , Guerini Franca R. , Clerici Mario , Cagliani Rachele , Mascheretti Sara
Published: April 2017

Language‐based Learning Disabilities (LLDs) encompass a group of complex, comorbid, and developmentally associated deficits in communication. Language impairment and developmental dyslexia (DD) represent the most recognized forms of LLDs. Substantial genetic correlations exist between language and reading (dis)abilities. Common variants in the FOXP2 gene were consistently associated with language‐ and reading‐related neuropsychological and neuroanatomical phenotypes. We tested the effect of a FOXP2 common variant, that is, rs6980093 (A/G), on quantitative measures of language and reading in two independent Italian samples: a population‐based cohort of 699 subjects (3–11 years old) and a sample of 572 children with DD (6–18 years old). rs6980093 modulates expressive language in the general population sample, with an effect on fluency scores. In the DD sample, the variant showed an association with the accuracy in the single word reading task. rs6980093 shows distinct genetic models of association in the two cohorts, with a dominant effect of the G allele in the general population sample and heterozygote advantage in the DD cohort. We provide preliminary evidence that rs6980093 associates with language and reading (dis)abilities in two independent Italian cohorts. rs6980093 is an intronic SNP, suggesting that it (or a linked variant) modulates phenotypic association via regulation of FOXP2 expression. Because FOXP2 brain expression is finely regulated, both temporally and spatially, it is possible that the two alleles at rs6980093 differentially modulate expression levels in a developmental stage‐ or brain area‐specific manner. This might help explaining the heterozygote advantage effect and the different genetic models in the two cohorts.
Multiple sclerosis broke my heart
Authors: Androdias Géraldine , Bernard Emilien , Biotti Damien , Collongues Nicolas , Durand‐Dubief Françoise , Pique Julie , Sanchez Ingrid , Delmas Clément , Ninet Jacques , Marignier Romain , Vukusic Sandra
Published: April 2017

We report 5 cases of acute heart failure (AHF) related to multiple sclerosis (MS) relapses. AHF was inaugural in 3 patients, always preceded or accompanied by signs of brainstem dysfunction; it was severe, requiring intensive care management. Echocardiography showed left ventricular hypokinesis. No other cause of AHF has been found. All patients showed a new medullary lesion on brain magnetic resonance imaging. All had rapid and complete recovery of ventricular function after intravenous corticosteroids. We concluded that the cases represent a takotsubo phenomenon. Physicians should be aware of rare cases of takotsubo cardiomyopathy in MS relapses. Ann Neurol 2017;81:754–758
Glykananalyse mittels Ionenmobilitäts‐Massenspektrometrie
Authors: Hofmann Johanna , Pagel Kevin
Published: April 2017

Kohlenhydrate bilden eine der Hauptklassen von biologischen Makromolekülen und spielen eine essentielle Rolle in lebenden Organismen. Um ihre Eigenschaften und Funktionen gezielt untersuchen zu können, ist ein fundiertes Wissen über ihre zugrundeliegende Struktur unerlässlich. Die inhärente strukturelle Komplexität von Glykanen stellt jedoch eine große Herausforderung dar, da aufgrund ihrer komplizierten Regio‐ und Stereochemie eine Vielzahl von möglichen Isomeren existieren kann, die mit etablierten analytischen Methoden schwer zu unterscheiden sind. Im letzten Jahrzehnt hat sich besonders die Ionenmobilitäts‐Massenspektrometrie zur Strukturaufklärung von Glykanen hervorgetan. Diese trennt Ionen auf der Grundlage ihrer Masse, Ladung, Größe und Form, und ist damit eine leistungsstarke Methode zur Unterscheidung von Isomeren. Dieser Kurzaufsatz hebt die jüngsten Fortschritte der Analyse von komplexen Kohlenhydraten mittels Ionenmobilitäts‐Massenspektrometrie hervor und diskutiert zukünftige Anwendungsgebiete.
Dinitrogen Splitting Coupled to Protonation
Authors: Silantyev Gleb A. , Förster Moritz , Schluschaß Bastian , Abbenseth Josh , Würtele Christian , Volkmann Christian , Holthausen Max C. , Schneider Sven
Published: April 2017

The coupling of electron‐ and proton‐transfer steps provides a general concept to control the driving force of redox reactions. N2 splitting of a molybdenum dinitrogen complex into nitrides coupled to a reaction with Brønsted acid is reported. Remarkably, our spectroscopic, kinetic, and computational mechanistic analysis attributes N−N bond cleavage to protonation in the periphery of an amide pincer ligands rather than the {Mo−N2−Mo} core. The strong effect on electronic structure and ultimately the thermochemistry and kinetic barrier of N−N bond cleavage is an unusual case of a proton‐coupled metal‐to‐ligand charge transfer process, highlighting the use of proton‐responsive ligands for nitrogen fixation.
Selective Aerobic Oxidation of Methylarenes to Benzaldehydes Catalyzed by N‐Hydroxyphthalimide and Cobalt(II) Acetate in Hexafluoropropan‐2‐ol
Authors: Gaster Eden , Kozuch Sebastian , Pappo Doron
Published: April 2017

Efficient and highly selective catalytic conditions for the aerobic autoxidation of methylarenes to benzaldehydes, based on N‐hydroxyphthalimide (NHPI) and cobalt(II) acetate in 1,1,1,3,3,3‐hexafluoropropan‐2‐ol (HFIP), were developed. The sustainable conditions enable a multigram scale preparation of benzaldehyde derivatives in high efficiency and with excellent chemoselectivity (up to 99 % conversion and 98 % selectivity).
Trihydroborates and Dihydroboranes Bearing a Pentacoordinated Phosphorus Atom: Double Ring Expansion To Balance the Coordination States
Authors: Kano Naokazu , O'Brien Nathan J. , Uematsu Ryohei , Ramozzi Romain , Morokuma Keiji
Published: April 2017

The first trihydroborate bearing a pentacoordinated phosphorus atom was synthesized as a new P−B bonded compound. Hydride abstraction of the trihydroborate gave an intermediary dihydroborane, which showed hydroboration reactivity and was trapped with pyridine whilst maintaining the P−B bond. The dihydroborane underwent a rearrangement, which involved a double ring expansion to compensate for the unbalanced coordination states of the phosphorus and boron atoms, to give a new fused bicyclic phosphine‐boronate.
Microstructure Variations in the Soft‐Hard Tissue Junction of the Human Anterior Cruciate Ligament
Authors: Zhao Lei , Lee Peter V.S. , Ackland David C. , Broom Neil D. , Thambyah Ashvin
Published: April 2017

The role of the sub‐bundles in the anterior cruciate ligament (ACL) has been defined, such that the anterior‐medial bundle directly resists anterior tibial translation while the posterior lateral bundle is involved in rotational stability. With regards to this biomechanical function, much of the previous work on bundle‐specific morphology has been carried out on the macroscale, with much less attention given to the micro‐to‐ultrastructural scalar levels. This is especially true of the enthesis and its microstructure, a biomechanically significant region that has been largely neglected in the published literature dealing with ACL sub‐bundle anatomy. In this study, the human ACL tibial enthesis was investigated at multiple scalar levels using differential interference contrast and scanning electron microscopies with the aim of determining whether the sub‐bundle ligament structure, and its known macroscale function, is consistent with its micro‐architecture at the ligament–bone junction. The investigation found that different ligament insertion morphologies exist between the two bundles, where the AM bundle has more intense interdigitation with the bone matrix than that of the PL bundle. The results suggest that such structure–function relationships, especially across scalar‐levels, provide new insight into the significance of the sub‐bundle anatomy of the ACL. Anat Rec, 300:1547–1559, 2017. © 2017 Wiley Periodicals, Inc.
Clustering multiply imputed multivariate high‐dimensional longitudinal profiles
Authors: Bruckers Liesbeth , Molenberghs Geert , Dendale Paul
Published: April 2017

In this paper, we propose a method to cluster multivariate functional data with missing observations. Analysis of functional data often encompasses dimension reduction techniques such as principal component analysis (PCA). These techniques require complete data matrices. In this paper, the data are completed by means of multiple imputation, and subsequently each imputed data set is submitted to a cluster procedure. The final partition of the data, summarizing the partitions obtained for the imputed data sets, is obtained by means of ensemble clustering. The uncertainty in cluster membership, due to missing data, is characterized by means of the agreement between the members of the ensemble and fuzziness of the consensus clustering. The potential of the method was brought out on the heart failure (HF) data. Daily measurement for four biomarkers (heart rate, diastolic, and systolic blood pressure, weight) were used to cluster the patients. To normalize the distributions of the longitudinal outcomes, the data were transformed with a natural logarithm function. A cubic spline base with 69 basis functions was employed to smooth the profiles. The proposed algorithm indicates the existence of a latent structure and divides the HF patients into two clusters, showing a different evolution in blood pressure values and weight. In general, cluster results are sensitive to choices made. Likewise for the proposed approach, alternative choices for the distance measure, procedure to optimize the objective function, choice of the scree‐test threshold, or the number of principal components, to be used in the approximation of the surrogate density, could all influence the final partition. For the HF data set, the final partition depends on the number of principal components used in the procedure.
Propensity scores based methods for estimating average treatment effect and average treatment effect among treated: A comparative study
Authors: Abdia Younathan , Kulasekera K. B. , Datta Somnath , Boakye Maxwell , Kong Maiying
Published: April 2017

Propensity score based statistical methods, such as matching, regression, stratification, inverse probability weighting (IPW), and doubly robust (DR) estimating equations, have become popular in estimating average treatment effect (ATE) and average treatment effect among treated (ATT) in observational studies. Propensity score is the conditional probability receiving a treatment assignment with given covariates, and propensity score is usually estimated by logistic regression. However, a misspecification of the propensity score model may result in biased estimates for ATT and ATE. As an alternative, the generalized boosting method (GBM) has been proposed to estimate the propensity score. GBM uses regression trees as weak predictors and captures nonlinear and interactive effects of the covariate. For GBM‐based propensity score, only IPW methods have been investigated in the literature. In this article, we provide a comparative study of the commonly used propensity score based methods for estimating ATT and ATE, and examine their performances when propensity score is estimated by logistic regression and GBM, respectively. Extensive simulation results indicate that the estimators for ATE and ATT may vary greatly due to different methods. We concluded that (i) regression may not be suitable for estimating ATE and ATT regardless of the estimation method of propensity score; (ii) IPW and stratification usually provide reliable estimates of ATT when propensity score model is correctly specified; (iii) the estimators of ATE based on stratification, IPW, and DR are close to the underlying true value of ATE when propensity score is correctly specified by logistic regression or estimated using GBM.
Using predictions from a joint model for longitudinal and survival data to inform the optimal time of intervention in an abdominal aortic aneurysm screening programme
Authors: Sweeting Michael J.
Published: April 2017

Joint models of longitudinal and survival data can be used to predict the risk of a future event occurring based on the evolution of an endogenous biomarker measured repeatedly over time. This has led naturally to the use of dynamic predictions that update each time a new longitudinal measurement is provided. In this paper, we show how such predictions can be utilised within a fuller decision modelling framework, in particular to allow planning of future interventions for patients under a ‘watchful waiting’ care pathway. Through the objective of maximising expected life‐years, the predicted risks associated with not intervening (e.g. the occurrence of severe sequelae) are balanced against risks associated with the intervention (e.g. operative risks). Our example involves patients under surveillance in an abdominal aortic aneurysm screening programme where a joint longitudinal and survival model is used to associate longitudinal measurements of aortic diameter with the risk of aneurysm rupture. We illustrate how the decision to intervene, which is currently based on a diameter measurement greater than a certain threshold, could be made more personalised and dynamic through the application of a decision modelling approach.
Overexpression of the regulatory subunit of glutamate‐cysteine ligase enhances monoclonal antibody production in CHO cells
Authors: Orellana Camila A. , Marcellin Esteban , Gray Peter P. , Nielsen Lars K.
Published: April 2017

For decades, Chinese hamster ovary (CHO) cells have been the preferred host for therapeutic monoclonal antibody (mAb) production; however, increasing mAb titer by rational engineering remains a challenge. Our previous proteomic analysis in CHO cells suggested that a higher content of glutathione (GSH) might be related to higher productivity. GSH is an important antioxidant, cell detoxifier, and is required to ensure the formation of native disulfide bonds in proteins. To investigate the involvement of GSH in mAb production, we generated stable CHO cell lines overexpressing genes involved in the first step of GSH synthesis; namely the glutamate‐cysteine ligase catalytic subunit (Gclc) and the glutamate‐cysteine ligase modifier subunit (Gclm). The two genes were reconstructed from our RNA‐Seq de novo assembly and then were functionally annotated. Once the sequences of the genes were confirmed using proteogenomics, a transiently expressed mAb was introduced into cell lines overexpressing either Gclc or Gclm. The new cell lines were compared for mAb production to the parental cell line and changes at the proteome level were measured using SWATH. As per our previous proteomics observations, overexpressing Gclm improved productivity, titer, and the frequency of high producer clones by 70%. In contrast, overexpressing Gclc, which produced a higher amount of GSH, did not increase mAb production. We show that GSH cannot be linked to higher productivity and that Gclm may be controlling other cellular processes involved in mAb production yet to be elucidated. Biotechnol. Bioeng. 2017;114: 1825–1836. © 2017 Wiley Periodicals, Inc.
Engineering of an H2O2 auto‐scavenging in vivo cascade for pinoresinol production
Authors: Lv Yongkun , Cheng Xiaozhong , Du Guocheng , Zhou Jingwen , Chen Jian
Published: April 2017

Pinoresinol is a natural lignan with a high market value that has potential pharmacological and food supplement applications. Pinoresinol is currently isolated from plants, which suffers from low efficiency and yield. To produce pinoresinol from inexpensive and industrially available eugenol, an in vivo enzymatic cascade composed of vanillyl alcohol oxidase and peroxidase was designed, which scavenges H2O2 automatically and eliminates protein purification and cofactor addition. Two peroxidases were screened and identified from Escherichia coli BL21 (DE3), and tested in the enzymatic cascade. To balance the flux, different genetic architectures were constructed by using ePathBrick and fusion gene approaches. Scavenging H2O2 alleviated by‐product toxicity and enzyme inhibition, and led to efficient pinoresinol production. Optimization of the reaction conditions achieved a titer of 11.29 g/L pinoresinol. The molar yield and productivity were 52.77% and 1.03 g/(L × h), respectively. The elegant strategy developed herein utilizes the harmful by‐product to drive the biosynthetic reaction forward and simultaneously detoxify cells, thereby preventing enzyme inhibition. Biotechnol. Bioeng. 2017;114: 2066–2074. © 2017 Wiley Periodicals, Inc.
Fast and reliable strain characterization ofStreptomyces lividansthrough micro‐scale cultivation
Authors: Koepff Joachim , Keller Matthias , Tsolis Konstantinos C. , Busche Tobias , Rückert Christian , Hamed Mohamed B. , Anné Jozef , Kalinowski Joern , Wiechert Wolfgang , Economou Anastassios , Oldiges Marco
Published: April 2017

Filamentous organisms of the genusStreptomycesplay an important role in industrial production processes, due to their extensive secondary metabolism variability, as well as their ability to secrete efficiently large amounts of (heterologous) proteins. While genetic engineering tools are available to rapidly build up large strain libraries, the subsequent strain screening and bioprocess development still constitutes a bottleneck. This is due to the lack of reliable parallelized and accelerated cultivation techniques for morphologically challenging organisms. To address this challenge, we developed an integrated cultivation workflow forStreptomyces lividansbased on a parallelized shaken 48‐well microtiter‐plate (MTP) cultivation device. In a first step, a feasible pre‐culture method was identified and validated, revealing high comparability in subsequent main cultivations (coefficient of variation of 1.1% for in‐plate replicates and 3.2% between different pre‐cultures). When validating the growth performance in 1 mL MTP cultivation against an established 1,000 mL lab‐scale cultivation system, highly comparable cultivation patterns were found for online (pH, dissolved oxygen), as well as for offline derived parameters (glucose uptake, cell‐dry‐weight, and pellet size). Additionally, the two cultivation regimes were compared with respect to transcriptional and protein secretion activity ofStreptomyces, showing overall good comparability with minor, but well explainable discrepancies, most probably caused by different energy dissipation (shaking vs. stirring) and adaption effects due to different illumination conditions. Embedded within the presented cultivation workflow, the 1 mL MTP‐based parallelized cultivation system seems to be a suitable screening tool for filamentous and industrial relevant organisms likeStreptomyces. This can contribute to widen the field of application for these organisms and facilitate screening and early‐stage bioprocess development. Biotechnol. Bioeng. 2017;114: 2011–2022. © 2017 Wiley Periodicals, Inc.
Axel Brennicke
Authors:   Alle Mitarbeiter
Published: April 2017

Am 26. Februar 2017 verstarb der Ulmer Pflanzen‐Molekularbiologe, Autor und langjährige BIUZ‐Kurator Axel Brennicke. An dieser Stelle erinnern seine Kollegen vom Institut für Molekulare Botanik der Universität Ulm sowie Mitglieder des BIUZ‐Kuratoriums an ihn.
Durchblick dank verschränkter Sinne
Authors: Tetsch Larissa
Published: April 2017

Zur Orientierung im dämmrig‐trüben Wasser nutzt der Elefantenrüsselfisch das Prinzip der Elektroortung. Mit Hilfe eines Organs im Schwanzstiel erzeugt er ein elektrisches Feld, das durch nahe Objekte verzerrt und durch Sensoren in der Fischhaut wahrgenommen wird. Um seine Umgebung möglichst naturgetreu abzubilden, verknüpft der Elefantenrüsselfisch Informationen des elektrischen und des visuellen Sinns und gewichtet sie nach ihrer Verlässlichkeit unter den gegebenen Bedingungen. Diese kognitive Meisterleistung war bislang nur von einigen hochentwickelten Säugetieren bekannt.
Tipps und Tricks zur in vitro‐Transkription
Authors: Bruch Alexander , Haag Sara
Published: April 2017

Mit Hilfe der in vitro‐Transkription werden RNAs beliebiger Sequenz in größeren Mengen hergestellt und können für unterschiedliche Fragestellungen eingesetzt werden. Die „Arbeiter” im Reagenzglas sind dabei spezielle RNA‐Polymerasen, die DNA in RNA umschreiben können. Doch was ist dabei zu beachten? Woher „weiß” die Polymerase, welche Sequenz sie transkribieren soll? Und vor allen: Wofür ist das gut?
Wie sage ich es dem Chef?
Authors: Hauk Andrea
Published: April 2017

Nachwuchs! Die ersehnte Nachricht ist da. Und wie geht es jetzt weiter? Es wird viel diskutiert über die Vereinbarkeit von Familie und Beruf. Andrea Hauk – BIUZ‐Lesern bekannt als Autorin der Laborseite – berichtet im zweiten Teil unserer neuen Reihe von ihren Erfahrungen.
Surgical and medical treatment of ocular disease in a dog with Ehlers–Danlos syndrome
Authors: Rasch Søren N.
Published: April 2017

Key Clinical Message

Correctional surgery was performed on a 3‐year‐old intact male shih tzu presenting with Ehlers–Danlos syndrome, ocular disease, and skin fold dermatitis. A one‐year follow‐up showed that no further clinical corrections were needed. Therefore, surgery could be considered in some canine patients with Ehlers–Danlos syndrome.
Diffuse hepatic hemangioma with single cutaneous hemangioma: an alerting occurrence
Authors: Al Tasseh Faten , El‐Khansa Merna , Abd Omran , Abdel Khalek Anoir , El‐Rifai Nahida
Published: April 2017

Key Clinical Message

Screening of infants with five or more cutaneous infantile hemangiomas with abdominal ultrasound is often recommended. However, diffuse hepatic hemangioma can develop even in patients with single cutaneous hemangioma. This highlights the importance of physical examination and screening ultrasound in these patients.
Obinutuzumab‐induced serum sickness following salvage therapy for chronic lymphocytic leukemia
Authors: Saba Julie , Logan Aaron C.
Published: April 2017

Key Clinical Message

The incidence of serum sickness following treatment of CLL with obinutuzumab has not been fully characterized, but is likely rare. Consideration should be given to this diagnosis in appropriate circumstances so that effective corticosteroid therapy can be initiated to alleviate inflammatory symptoms and organ dysfunction in a timely manner.
Successful bailout stenting strategy against lethal coronary dissection involving left main bifurcation
Authors: Kubota Hiroshi , Nomura Tetsuya , Hori Yusuke , Yoshioka Kenichi , Miyawaki Daisuke , Urata Ryota , Sugimoto Takeshi , Kikai Masakazu , Keira Natsuya , Tatsumi Tetsuya
Published: April 2017

Key Clinical Message

Catheter‐induced coronary dissection involving left main bifurcation is a rare complication during cardiac catheterization but can become lethal unless it is treated appropriately. Interventional cardiologists always have to pay attention to the risk of complications related to cardiac catheterization and prepare for determining the best bailout strategy for the situation.
Concomitant imatinib and ibrutinib in a patient with chronic myelogenous leukemia and chronic lymphocytic leukemia
Authors: Shea Lauren K. , Mikhail Fady M. , Forero‐Torres Andres , Davis Randall S.
Published: April 2017

Key Clinical Message

The availability of kinase and other small‐molecule inhibitors to treat hematologic malignancies is increasing. Accordingly, novel regimens that employ these therapeutics are rapidly evolving. Herein we report the safe and effective administration of two targeted kinase inhibitors in a patient with concomitant chronic myelogenous leukemia and chronic lymphocytic leukemia.
Semirational Engineering Accelerates the Laboratory Evolution of Nitrilase Catalytic Efficiency for Nicotinic Acid Biosynthesis
Authors: Gong Jin‐Song , Dong Ting‐Ting , Gu Bing‐Chen , Li Heng , Dou Wen‐Fang , Lu Zhen‐Ming , Zhou Zhe‐Min , Shi Jin‐Song , Xu Zheng‐Hong
Published: April 2017

The nitrilase‐mediated green synthesis of nicotinic acid, an important reaction in synthetic organic chemistry, has attracted considerable attention in recent years. However, the application potential of nitrilase is hindered by several limitations, such as low catalytic efficiency and byproduct formation. In this study, the site‐saturation mutagenesis of asparagine 40, phenylalanine 50, and glutamine 207 in recombinant nitrilase from Pseudomonas putida CGMCC3830 was conducted to improve the specificity of nitrilase for nicotinic acid. The resulting mutants, which contain the mutations N40G (asparagine→glycine), F50W (phenylalanine→tryptophan), and Q207E (glutamine→glutamic acid), produced higher nicotinic acid yields than the wild type. Furthermore, double and triple mutations were introduced, and four mutants that contained N40G/F50W, N40G/Q207E, F50W/Q207E, and N40G/F50W/Q207E were obtained and evaluated for their capacity to produce nicotinic acid. The double mutant F50W/Q207E and the triple mutant N40G/F50W/Q207E displayed the highest activity, which was nearly twofold higher than that of the wild type. The kinetics analysis of nicotinic acid synthesis with the mutant nitrilase revealed the higher catalytic capability of all the mutants than the wild type. These results provide new insights into the catalytic performance of P. putida nitrilase toward 3‐cyanopyridine to promote nicotinic acid production.
2D Layered α‐Fe2O3/rGO Flexible Electrode Prepared through Colloidal Electrostatic Self‐Assembly
Authors: Zhang Huifang , Lu Chunxiang , Chen Chengmeng , Xie Lijing , Zhou Pucha , Kong Qingqiang
Published: April 2017

Through the simple hydrolysis of FeCl3 in boiling water, Fe(OH)3 colloidal nanoparticles (NPs) can be achieved that exhibit a highly positively charge. Graphene oxide (GO) nanosheets are negatively charged when dispersed in water. Inspired by these fascinating characteristics, a 2D layered α‐Fe2O3/rGO hybrid film (FGHF) was fabricated through colloidal electrostatic self‐assembly with subsequent vacuum filtration and hydrothermal reduction. In this hybrid film, cubical α‐Fe2O3 NPs are well‐distributed on rGO sheets, which can provide sufficient active interfacial sites and effectively alleviate the volume variation of α‐Fe2O3 NPs during electrochemical reactions. The as‐obtained FGHF exhibits a high specific capacitance of 714 F g−1 and an outstanding rate capability of 42.6 % retention at 30 A g−1. Moreover, a flexible supercapacitor was fabricated, which can achieve a high volumetric capacitance of 16.45 F cm−3, leading to an energy density of 1.46 mWh cm−3 and a power density of 199.8 mW cm−3. The flexible nature of the FGHF allows the as‐fabricated supercapacitor to remain undamaged with almost no change in capacitive performance when bending up to 180°.
10‐Silacorroles Exhibiting Near‐Infrared Absorption and Emission
Authors: Omori Hiroto , Hiroto Satoru , Shinokubo Hiroshi
Published: April 2017

10‐Silacorroles were obtained from the Pd‐catalyzed silylative cyclization of a bis(α,α′‐dibromodipyrrin) NiII precursor with dihydrosilanes. These 10‐silacorroles show substantially red‐shifted absorption bands relative to those of normal porphyrins and isocorroles. Notably, the corresponding free base and ZnII 10‐silacorroles exhibit emissions in the NIR region. Theoretical calculations on these 10‐silacorroles revealed the presence of σ*–π* conjugation between the silyl group and the tetrapyrrole π system, which significantly lowers their LUMO energy levels.
Chiral Fidelity in the Diastereoselective and Enantiospecific Synthesis of Indenes from Axially Chiral Benzylidene Cyclanes
Authors: Mouysset Dominique , Tessonnier Cyril , Tintaru Aura , Dumur Frédéric , Jean Marion , Vanthuyne Nicolas , Bertrand Michèle P. , Siri Didier , Nechab Malek
Published: April 2017

Enantioenriched indenes were reached through a chirality conversion strategy using original axially chiral benzylidene cyclanes. Good to high remote diastereocontrol and excellent enantiocontrol were observed in this cascade involving copper‐catalyzed homologation of terminal alkynes, in situ allenoate formation and Alder‐ene cyclization.
Luminescent Ni0 Diisocyanide Chelates as Analogues of CuI Diimine Complexes
Authors: Büldt Laura A. , Larsen Christopher B. , Wenger Oliver S.
Published: April 2017

Invited for the cover of this issue is the group of Oliver S. Wenger at the University Basel. The image depicts a homoleptic Ni0 diisocyanide complex that displays photoluminescence at low temperatures. Read the full text of the article at 10.1002/chem.201700103.
„Ist das jetzt der optimale Prozess?” fragte der Kaufmann. „Vermutlich nicht” antwortete der Ingenieur.
Authors: Fricke Armin
Published: April 2017

No abstract.