bluuebunny/crossref_metadata_2025 huggingface dataset:
Boosted structured additive regression forEscherichia colifed‐batch fermentation modeling
Authors: Melcher Michael , Scharl Theresa , Luchner Markus , Striedner Gerald , Leisch Friedrich
Published: August 2016

The quality of biopharmaceuticals and patients' safety are of highest priority and there are tremendous efforts to replace empirical production process designs by knowledge‐based approaches. Main challenge in this context is that real‐time access to process variables related to product quality and quantity is severely limited. To date comprehensive on‐ and offline monitoring platforms are used to generate process data sets that allow for development of mechanistic and/or data driven models for real‐time prediction of these important quantities. Ultimate goal is to implement model based feed‐back control loops that facilitate online control of product quality. In this contribution, we explore structured additive regression (STAR) models in combination with boosting as a variable selection tool for modeling the cell dry mass, product concentration, and optical density on the basis of online available process variables and two‐dimensional fluorescence spectroscopic data. STAR models are powerful extensions of linear models allowing for inclusion of smooth effects or interactions between predictors. Boosting constructs the final model in a stepwise manner and provides a variable importance measure via predictor selection frequencies. Our results show that the cell dry mass can be modeled with a relative error of about ±3%, the optical density with ±6%, the soluble protein with ±16%, and the insoluble product with an accuracy of ±12%. Biotechnol. Bioeng. 2017;114: 321–334. © 2016 Wiley Periodicals, Inc.
Development of a Rhodobacter capsulatus self‐reporting model system for optimizing light‐dependent, [FeFe]‐hydrogenase‐driven H2 production
Authors: Wecker Matt S.A. , Beaton Stephen E. , Chado Robert A. , Ghirardi Maria L.
Published: August 2016

The photosynthetic bacterium Rhodobacter capsulatus normally photoproduces H2 as a by‐product of its nitrogenase‐catalyzed nitrogen‐fixing activity. Such H2 production, however, is expensive from a metabolic perspective, requiring nearly four times as many photons as the equivalent algal hydrogenase‐based system (Ghirardi et al., 2009 Photobiological hydrogen‐producing systems. Chem Soc Rev 38(1):52–61). Here, we report the insertion of a Clostridium acetobutylicum [FeFe]‐hydrogenase and its three attendant hydrogenase assembly proteins into an R. capsulatus strain lacking its native uptake hydrogenase. Further, this strain is modified to fluoresce upon sensing H2. The resulting strain photoproduces H2 and self‐reports its own H2 production through fluorescence. This model system represents a unique method of developing hydrogenase‐based H2 production in R. capsulatus, may serve as a powerful system for in vivo directed evolution of hydrogenases and hydrogenase‐associated genes, and provides a means of screening for increased metabolic production of H2. Biotechnol. Bioeng. 2017;114: 291–297. © 2016 Wiley Periodicals, Inc.
Überlebenskünstler im Tal des Todes
Authors: Tetsch Larissa
Published: August 2016

Der Teufelskärpfling ist eine der seltensten Wirbeltierarten der Welt und lebt nur an einem einzigen Ort: dem Teufelsloch, einem von einer Warmwasserquelle gespeisten Kalksteinbecken inmitten des Death Valley in der Mojavewüste (USA). Hatte man bislang angenommen, dass die Fische die Quelle zu einem Zeitpunkt besiedelt haben, als das heutige Wüstental noch überflutet war, offenbaren genetische Analysen jetzt ein deutlich jüngeres Alter für die Art. Anscheinend gelang es dem Teufelskärpfling, eine der trockensten Wüsten der Welt zu durchqueren, um ins Teufelsloch zu gelangen.
Für Wipfelstürmer: Baumwipfelpfad in Bad Harzburg
Authors: Högermann Christiane
Published: August 2016

Für alle, die gerne hoch hinauf möchten, bietet sich im Harz dazu eine einmalige Gelegenheit: eine innovative Waldexkursion bis in die Baumwipfel.
Risk factors for reintervention after surgery for perforated gastroduodenal ulcer
Authors: Hasselager R B , Lohse N , Duch P , Møller M H
Published: August 2016

Background

Perforated gastroduodenal ulcer carries a high mortality rate. Need for reintervention after surgical repair is associated with worse outcome, but knowledge on risk factors for reintervention is limited. The aim was to identify prognostic risk factors for reintervention after perforated gastroduodenal ulcer in a nationwide cohort.

Methods

All patients treated surgically for perforated gastroduodenal ulcer in Denmark between 2003 and 2014 were included using data from the Danish Clinical Register of Emergency Surgery. Potential risk factors for reintervention were assessed, and their crude and adjusted associations calculated by the competing risks subdistribution hazards approach.

Results

A total of 4086 patients underwent surgery for perforated gastroduodenal ulcer during the study interval. Median age was 71·1 (i.q.r. 59·6–81·0) years and the overall 90-day mortality rate was 30·8 per cent (1258 of 4086). Independent risk factors for reintervention were: male sex (adjusted hazard ratio (HR) 1·46, 95 per cent c.i. 1·20 to 1·78), in-hospital perforation (adjusted HR 1·36, 1·11 to 1·68), high BMI (adjusted HR 1·49, 1·10 to 2·01), high ASA physical status grade (adjusted HR 1·54, 1·23 to 1·94), shock on admission (adjusted HR 1·40, 1·13 to 1·74), surgical delay (adjusted HR 1·07, 1·02 to 1·14) and other co-morbidity (adjusted HR 1·24, 1·02 to 1·51). Preadmission use of steroids (adjusted HR 0·59, 0·41 to 0·84) and age above 70 years (adjusted HR 0·72, 0·59 to 0·89) were associated with a reduced risk of reoperation.

Conclusion

Obese men with coexisting diseases and high disease severity who have surgery for gastroduodenal perforation are at increased risk of reoperation.
Procalcitonin in cerebrospinal fluid in meningitis: a prospective diagnostic study
Authors: Alons Imanda M. E. , Verheul Rolf J. , Kuipers Irma , Jellema Korné , Wermer Marieke J. H. , Algra Ale , Ponjee Gabriëlle
Published: August 2016

Objectives

Bacterial meningitis is a severe but treatable condition. Clinical symptoms may be ambiguous and current diagnostics lack sensitivity and specificity, complicating diagnosis. Procalcitonin (PCT) is a protein that is elevated in serum in bacterial infection. We aimed to assess the value of PCT in cerebrospinal fluid (CSF) in the diagnosis of bacterial meningitis.

Methods

We included patients with bacterial meningitis, both community acquired and post neurosurgery. We included two comparison groups: patients with viral meningitis and patients who underwent lumbar punctures for noninfectious indications. We calculated mean differences and 95% confidence intervals of procalcitonin in CSF and plasma in patients with and without bacterial meningitis.

Results

Average PCT concentrations in CSF were 0.60 ng mL−1 (95% CI: 0.29–0.92) in the bacterial meningitis group (n = 26), 0.81 (95% CI: 0.33–1.28) in community‐acquired meningitis (n = 16) and 0.28 (95% CI: 0.10–0.45) in postneurosurgical meningitis (n = 10), 0.10 ng mL−1 (95% CI: 0.08–0.12) in the viral meningitis group (n = 14) and 0.08 ng mL−1 (95% CI: 0.06–0.09) in the noninfectious group (n = 14). Mean difference of PCT‐CSF between patients with community‐acquired bacterial meningitis and with viral meningitis was 0.71 ng mL−1 (95% CI: 0.17–1.25) and 0.73 ng mL−1 (95% CI: 0.19–1.27) for community‐acquired bacterial meningitis versus the noninfectious group. The median PCT CSF: plasma ratio was 5.18 in postneurosurgical and 0.18 in community‐acquired meningitis (IQR 4.69 vs. 0.28).

Conclusion

Procalcitonin in CSF was significantly higher in patients with bacterial meningitis when compared with patients with viral or no meningitis. PCT in CSF may be a valuable marker in diagnosing bacterial meningitis, and could become especially useful in patients after neurosurgery.
Chlorophyll Catabolites in Senescent Leaves of the Plum Tree (Prunus domestica)
Authors: Erhart Theresia , Mittelberger Cecilia , Vergeiner Clemens , Scherzer Gerhard , Holzner Barbara , Robatscher Peter , Oberhuber Michael , Kräutler Bernhard
Published: August 2016

In cold extracts of senescent leaves of the plum tree (Prunus domestica ssp. domestica), six colorless non‐fluorescent chlorophyll catabolites (NCCs) were characterized, named Pd‐NCCs. In addition, several minor NCC fractions were tentatively classified. The structure of the most polar one of the NCCs, named Pd‐NCC‐32, featured an unprecedented twofold glycosidation pattern. Three of the NCCs are also functionalized at their 32‐position by a glucopyranosyl group. In addition, two of these glycosidated NCCs carry a dihydroxyethyl group at their 18‐position. In the polar Pd‐NCC‐32, the latter group is further glycosidated at the terminal 182‐position. Four other major Pd‐NCCs and one minor Pd‐NCC were identified with five NCCs from higher plants known to belong to the ‘epi’‐series. In addition, tentative structures were derived for two minor fractions, classified as yellow chlorophyll catabolites, which represented (formal) oxidation products of two of the observed Pd‐NCCs. The chlorophyll catabolites in leaves of plum feature the same basic structural pattern as those found in leaves of apple and pear trees.
Quantum Dot‐Based Nanotools for Bioimaging, Diagnostics, and Drug Delivery
Authors: Bilan Regina , Nabiev Igor , Sukhanova Alyona
Published: August 2016

Quantum dots (QDs) are highly fluorescent nanocrystals with advanced photophysical and spectral properties: high brightness and stability against photobleaching accompanied by broad excitation and narrow emission spectra. Water‐soluble QDs functionalized with biomolecules, such as proteins, peptides, antibodies, and drugs, are used for biomedical applications. The advantages of QD‐based approaches to immuno‐histochemical analysis, single‐molecule tracking, and in vivo imaging (over traditional methods with organic dyes and fluorescent proteins) are explained. The unique spectral properties of QDs offer opportunities for designing systems for multiplexed analysis by multicolor imaging for the simultaneous detection of multiple targets. Conjugation of drug molecules with QDs or their incorporation into QD‐based drug‐delivery particles makes it possible to monitor real‐time drug tracking and carry out image‐guided therapy. Because of the tunability of their photophysical properties, QDs emitting in the near‐infrared have become an attractive tool for deep‐tissue mono‐ and multiphoton in vivo imaging. We review recent achievements in QD applications for bioimaging, targeting, and drug delivery, as well as challenges related to their toxicity and non‐biodegradability. Key and perspectives for further development of advanced QD‐based nanotools are addressed.
Long‐term outcomes of SMART stent implantation in patients with femoro‐popliteal disease
Authors: Matsumi Junya , Tobita Kazuki , Shishido Koki , Mizuno Shingo , Yamanaka Futoshi , Murakami Masato , Tanaka Yutaka , Takahashi Saeko , Akasaka Takeshi , Saito Shigeru
Published: August 2016

Objectives

This study aimed to determine the long‐term outcomes of SMART stent implantation for femoro‐popliteal (FP) lesions.

Background

The long‐term results of SMART stent implantation for FP lesions remained unknown.

Methods

We studied 319 limbs in 269 patients (mean age: 73.2 ± 7.7 years) who underwent SMART stent implantation for FP lesions (mean treated‐lesion length: 118.5 ± 81.0 mm) from 2004 to 2014, retrospectively. These patients were followed‐up for a mean of 52.8 ± 33.8 months (median: 51.0 months). Kaplan–Meier and log‐rank analyses were used to determine time to event. Hazard ratios (HRs) with 95% confidence interval (CI) were calculated through univariate and multivariate Cox proportional hazard analyses to estimate predictors of primary patency loss.

Results

Overall, 37.3% of lesions were TransAtlantic Inter‐Society Consensus (TASC) IIC/D lesions, and 41.1% exhibited chronic total occlusion. Post‐procedural primary patency rates were 87.7%, 79.4%, 68.1%, 53.7%, and 50.3%, at 1, 3, 5, 7, and 10 years, respectively; the corresponding secondary patency rates were 96.5%, 91.7%, 85.0%, 73.8%, and 67.7%, respectively. TASC IIA/B lesions had considerably better primary patency rates than C/D lesions at all time points. Multivariate analysis indicated that lesion length (with >200 mm vs. <100 mm) significantly promoted primary patency loss (HR, 2.555; 95% CI, 1.429–4.568; P = 0.002), as well as hemodialysis (HR, 1.881; 95% CI, 1.208–2.928; P = 0.005).

Conclusions

Although SMART stent implantation produced favorable long‐term results, TASC IIC/D FP lesions had poor outcomes. © 2016 Wiley Periodicals, Inc.
Probing Polyoxometalate–Protein Interactions Using Molecular Dynamics Simulations
Authors: Solé‐Daura Albert , Goovaerts Vincent , Stroobants Karen , Absillis Gregory , Jiménez‐Lozano Pablo , Poblet Josep M. , Hirst Jonathan D. , Parac‐Vogt Tatjana N. , Carbó Jorge J.
Published: August 2016

The molecular interactions between the CeIV‐substituted Keggin anion [PW11O39Ce(OH2)4]3− (CeK) and hen egg‐white lysozyme (HEWL) were investigated by molecular dynamics simulations. The analysis of CeK was compared with the CeIV‐substituted Keggin dimer [(PW11O39)2Ce]10− (CeK2) and the ZrIV‐substituted Lindqvist anion [W5O18Zr(OH2)(OH)]3− (ZrL) to understand how POM features such as shape, size, charge, or type of incorporated metal ion influence the POM⋅⋅⋅protein interactions. Simulations revealed two regions of the protein in which the CeK anion interacts strongly: cationic sites formed by Arg21 and by Arg45 and Arg68. The POMs chiefly interact with the side chains of the positively charged (arginines, lysines) and the polar uncharged residues (tyrosines, serines, aspargines) via electrostatic attraction and hydrogen bonding with the oxygen atoms of the POM framework. The CeK anion shows higher protein affinity than the CeK2 and ZrL anions, because it is less hydrophilic and it has the right size and shape for establishing interactions with several residues simultaneously. The larger, more negatively charged CeK2 anion has a high solvent‐accessible surface, which is sub‐optimal for the interaction, while the smaller ZrL anion is highly hydrophilic and cannot efficiently interact with several residues simultaneously.
Efficient Generation of Viral and Integration‐Free Human Induced Pluripotent Stem Cell‐Derived Oligodendrocytes
Authors: Espinosa‐Jeffrey Araceli , Blanchi Bruno , Biancotti Juan Carlos , Kumar Shalini , Hirose Megumi , Mandefro Berhan , Talavera‐Adame Dodanim , Benvenisty Nissim , de Vellis Jean
Published: August 2016

Here we document three highly reproducible protocols: (1) a culture system for the derivation of human oligodendrocytes (OLs) from human induced pluripotent stem cells (hiPS) and their further maturation—our protocol generates viral‐ and integration‐free OLs that efficiently commit and move forward in the OL lineage, recapitulating all the steps known to occur during in vivo development; (2) a method for the isolation, propagation and maintenance of neural stem cells (NSCs); and (3) a protocol for the production, isolation, and maintenance of OLs from perinatal rodent and human brain‐derived NSCs. Our unique culture systems rely on a series of chemically defined media, specifically designed and carefully characterized for each developmental stage of OL as they advance from OL progenitors to mature, myelinating cells. We are confident that these protocols bring our field a step closer to efficient autologous cell replacement therapies and disease modeling. © 2016 by John Wiley & Sons, Inc.
Towards Direct Synthesis of Alane: A Predicted Defect‐Mediated Pathway Confirmed Experimentally
Authors: Wang Lin‐Lin , Herwadkar Aditi , Reich Jason M. , Johnson Duane D. , House Stephen D. , Peña‐Martin Pamela , Rockett Angus A. , Robertson Ian M. , Gupta Shalabh , Pecharsky Vitalij K.
Published: August 2016

Alane (AlH3) is a unique energetic material that has not found a broad practical use for over 70 years because it is difficult to synthesize directly from its elements. Using density functional theory, we examine the defect‐mediated formation of alane monomers on Al(111) in a two‐step process: (1) dissociative adsorption of H2 and (2) alane formation, which are both endothermic on a clean surface. Only with Ti dopant to facilitate H2 dissociation and vacancies to provide Al adatoms, both processes become exothermic. In agreement, in situ scanning tunneling microscopy showed that during H2 exposure, alane monomers and clusters form primarily in the vicinity of Al vacancies and Ti atoms. Moreover, ball milling of the Al samples with Ti (providing necessary defects) showed a 10 % conversion of Al into AlH3 or closely related species at 344 bar H2, indicating that the predicted pathway may lead to the direct synthesis of alane from elements at pressures much lower than the 104 bar expected from bulk thermodynamics.
Alkali‐Doped Lithium Orthosilicate Sorbents for Carbon Dioxide Capture
Authors: Yang Xinwei , Liu Wenqiang , Sun Jian , Hu Yingchao , Wang Wenyu , Chen Hongqiang , Zhang Yang , Li Xian , Xu Minghou
Published: August 2016

New alkali‐doped (Na2CO3 and K2CO3) Li4SiO4 sorbents with excellent performance at low CO2 concentrations were synthesized. We speculate that alkali doping breaks the orderly arrangement of the Li4SiO4 crystals, hence increasing its specific surface area and the number of pores. It was shown that 10 wt % Na2CO3 and 5 wt % K2CO3 are the optimal additive ratios for doped sorbents to attain the highest conversions. Moreover, under 15 vol % CO2, the doped sorbents present clearly faster absorption rates and exhibit stable cyclic durability with impressive conversions of about 90 %, at least 20 % higher than that of non‐doped Li4SiO4. The attained conversions are also 10 % higher than the reported highest conversion of 80 % on doped Li4SiO4. The performance of Li4SiO4 is believed to be enhanced by the eutectic melt, and it is the first time that the existence of eutectic Li/Na or Li/K carbonate on doped sorbents when absorbing CO2 at high temperature is confirmed; this was done using systematical analysis combining differential scanning calorimetry with in situ powder X‐ray diffraction.
OMIP‐035: Functional analysis of natural killer cell subsets in macaques
Authors: Weisgrau Kim L. , Ries Moritz , Pomplun Nicholas , Evans David T. , Rakasz Eva G.
Published: August 2016

This panel was developed to measure the functional capability of natural killer (NK) cell subsets in rhesus macaques (Macaca mulatta). It includes markers to determine the frequency of cytokine secreting and cytotoxic NK cell subpopulations in peripheral blood mononuclear cell (PBMC) samples stimulated in vitro with human 721.221 cells. NK cell subsets were defined by the expression of killer cell immunoglobulin‐like receptors (KIRs) Mamu‐KIR3DL01 and Mamu‐KIR3DL05, and differentiation antigens CD16 and CD56. The panel can be used to assess the functional capability of NK cells in a range of normal and pathologic conditions of captive bred rhesus macaques of Indian origin. © 2016 International Society for Advancement of Cytometry
Habitat associations in a recolonizing, low‐density black bear population
Authors: Sollmann Rahel , Gardner Beth , Belant Jerrold L. , Wilton Clay M. , Beringer Jeff
Published: August 2016

American black bears are closely associated with forest habitat. They were nearly extirpated from the Central Interior Highlands, United States, in the early twentieth century, but have recolonized this part of the range since the 1960s. Due to lower population densities (as a result of recent recolonization), we hypothesized that bears in this region would show strong associations with forest habitat at both the home range and landscape scale. To test this, we analyzed hair snare and GPS telemetry data from five sampling grids with a combined spatial capture–recapture and resource selection function model to investigate individual space use within home ranges and landscape scale variation in density of black bears in the southern Missouri part of the Interior Highlands. We performed a linear discriminant analysis to identify habitat correlates of black bear density. We found that at the home range level, bears selected for more forested habitat and steeper slopes. Black bear density varied among sampling grids from 0.842 to 10.248 individuals/100 km2 which is at the low end of the spectrum of reported black bear densities. There were no clear habitat correlates for among‐grid variation in density, but in the three higher‐density grids, density declined with increasing forest cover and increasing distance from human settlements. This suggests that the bear populations benefited from more heterogeneous habitat and that rural settlements may represent food resources. Exploiting these anthropogenic resources could be facilitated by the fact that bears in our study were not hunted and were viewed as a novelty rather than a nuisance, which may lead to low perceived risk from anthropogenic sources. Our results highlight the need to interpret habitat associations of American black bears not only at local scales but also in the landscape context.
Large reptiles and cold temperatures: Do extreme cold spells set distributional limits for tropical reptiles in Florida?
Authors: Mazzotti Frank J. , Cherkiss Michael S. , Parry Mark , Beauchamp Jeff , Rochford Mike , Smith Brian , Hart Kristen , Brandt Laura A.
Published: August 2016

Distributional limits of many tropical species in Florida are ultimately determined by tolerance to low temperature. An unprecedented cold spell during 2–11 January 2010, in South Florida provided an opportunity to compare the responses of tropical American crocodiles with warm‐temperate American alligators and to compare the responses of nonnative Burmese pythons with native warm‐temperate snakes exposed to prolonged cold temperatures. After the January 2010 cold spell, a record number of American crocodiles (n = 151) and Burmese pythons (n = 36) were found dead. In contrast, no American alligators and no native snakes were found dead. American alligators and American crocodiles behaved differently during the cold spell. American alligators stopped basking and retreated to warmer water. American crocodiles apparently continued to bask during extreme cold temperatures resulting in lethal body temperatures. The mortality of Burmese pythons compared to the absence of mortality for native snakes suggests that the current population of Burmese pythons in the Everglades is less tolerant of cold temperatures than native snakes. Burmese pythons introduced from other parts of their native range may be more tolerant of cold temperatures. We documented the direct effects of cold temperatures on crocodiles and pythons; however, evidence of long‐term effects of cold temperature on their populations within their established ranges remains lacking. Mortality of crocodiles and pythons outside of their current established range may be more important in setting distributional limits.
River Management and Stakeholders' Participation: The case of the Rhone River, a fragmented institutional setting
Authors: Bréthaut Christian
Published: August 2016

There have been many authors who have examined the question of participation and the extent of its influence in water management. The empowerment of stakeholders in decision‐making processes has been a major issue in this field. The involvement of different types of public actor can be enacted in different manners and depends strongly on how the decision‐making process works in reality, on the extent to which actors are truly able to be active in this new participatory process and on who holds the responsibility for its implementation. These variables underline the various obstacles that face the implementation of a true intersectoral participation, one that successfully involves all water users. This article uses the case study of the Rhone River to explore the issues of public participation within a transboundary river where no international basin organization has been able to successfully regroup the different initiatives. I consider this example to be particularly interesting, as it allows for a comparison between different arenas that are not linked, yet are active within the same river basin. In acknowledgement of the increasing number of participatory initiatives, the article highlights and considers the difficulties associated with the implementation of participation within and between fragmented participation arenas. This article proposes an analysis of the different participation arenas of the river through the lens of three analytical variables:social efficiency,substantial efficiencyandprocedural efficiency. The focus turns to the impact of such a participation structure and questions the increased number of arenas in which stakeholders participate regarding watershed management. Copyright © 2016 John Wiley & Sons, Ltd and ERP Environment
Two Novelties in Ion‐pair Formation‐based Potentiometric Titrations of Anionic Surfactants
Authors: Mikysek Tomáš , Stočes Matěj , Vytřas Karel
Published: August 2016

Two novel approaches in ion‐pair formation‐based potentiometric titrations of anionic surfactants are presented. First, a new type of the low ohmic coated‐wire ion‐selective electrode is introduced; the polymeric membrane containing a plasticizer mixed with carbon powder. Second, didecyldimethylammonium chloride as the cationic titrant is for the first time proposed and applied, providing the titration curves with the highest potential jump.
A Two‐step Strategy for the Selective and Sensitive Detection of Dopamine with Glassy Carbon Electrodes
Authors: Wang Jianan , Wang Jichang
Published: August 2016

A new strategy is developed for using cyclic voltammetry technique to achieve sensitive and selective detection of dopamine on glassy carbon electrodes. The proposed method involves two steps, in which the cyclic voltammetric measurement is preceded by a brief period of potentiostatic treatment of the analyte solution. With this two‐step strategy redox peaks could be seen at dopamine concentration as low as 5 μM. In the co‐presence of ascorbic acid and uric acid, there are three well‐resolved anodic peaks with the peak separation between ascorbic acid and dopamine larger than 230 mV. The fact that no pre‐modification of the glassy carbon electrode is needed and the glassy carbon electrodes can be readily recovered after each measurement makes this new method attractive for the sensitive detection of dopamine.
Activity determination of FAD‐dependent glucose dehydrogenase immobilized in PEDOT: PSS‐PVA composite films for biosensor applications
Authors: Riegel Anna‐Lena , Borzenkova Natalia , Haas Verena , Scharfer Philip , Schabel Wilhelm
Published: August 2016

In this study, we propose an entirely new combination of materials as a novel formulation devoted for future generation of glucose biosensor. We combined poly(3,4‐ethylenedioxythiophene:polystyrene sulfonate) and poly(vinyl alcohol) as conducting matrix and immobilized the highly active and pioneering enzyme flavin adenine dinucleotide‐dependent glucose dehydrogenase (FAD‐GDH) into it. In this context, a good processability of the materials and the preservation of the enzymatic activity are critical steps to provide full device function later on. Thus, we thoroughly characterized the proposed pairing of materials: the influence of the composition on the film‐forming properties was investigated by scanning electron microscopy, optical microscopy, and photography; for the assessment of the enzymatic activity, we developed a spectrophotometric method. A great dependence is observed between activity and composition, ranging from inactive (1.6% retained activity) to highly active (91.5%). A high share of enzyme led to a higher enzymatic activity as long as the necessary condition of a pH higher than 6 was met. These first and fundamental findings can now be used as guidelines to tailor mediator‐free biosensors with enhanced selectivity and to enable the design of devices with improved performance.
ST8SIA2 promotes oligodendrocyte differentiation and the integrity of myelin and axons
Authors: Szewczyk Lukasz Mateusz , Brozko Nikola , Nagalski Andrzej , Röckle Iris , Werneburg Sebastian , Hildebrandt Herbert , Wisniewska Marta Barbara , Kuznicki Jacek
Published: August 2016

ST8SIA2 is a polysialyltransferase that attaches polysialic acid to the glycoproteins NCAM1 and CADM1. Polysialylation is involved in brain development and plasticity. ST8SIA2 is a schizophrenia candidate gene, and St8sia2−/− mice exhibit schizophrenia‐like behavior. We sought to identify new pathological consequences of ST8SIA2 deficiency. Our proteomic analysis suggested myelin impairment in St8sia2−/− mice. Histological and immune staining together with Western blot revealed that the onset of myelination was not delayed in St8sia2−/− mice, but the content of myelin was lower. Ultrastructure analysis of the corpus callosum showed thinner myelin sheaths, smaller and irregularly shaped axons, and white matter lesions in adult St8sia2−/− mice. Then we evaluated oligodendrocyte differentiation in vivo and in vitro. Fewer OLIG2+ cells in the cortex and corpus callosum, together with the higher percentage of undifferentiated oligodenroglia in St8sia2−/− mice suggested an impairment in oligodendrocyte generation. Experiment on primary cultures of oligodendrocyte precursor cells (OPCs) confirmed a cell‐autonomous effect of ST8SIA2 in oligodendroglia, and demonstrated that OPC to oligodendrocyte transition is inhibited in St8sia2−/− mice. Concluding, ST8SIA2‐mediated polysialylation influences on oligodendrocyte differentiation, and oligodendrocyte deficits in St8sia2 mice are a possible cause of the demyelination and degeneration of axons, resembling nerve fiber alterations in schizophrenia. GLIA 2016;65:34–49
Building and Leveraging Dynamic Capabilities: Insights from Accelerated Innovation in China
Authors: Williamson Peter J.
Published: August 2016

Plain language summary

This article explores what we can learn from a set of Chinese companies who have successfully pursued a strategy of accelerated innovation about building and leveraging dynamic capabilities. We conclude that creating flexible organizational structures and processes is key. The resulting dynamic capabilities can help achieve sustainable competitive advantage by spawning a series of innovations that enable a company to ‘run faster’ than competitors. These capabilities depend, in part, on the perceptions and behaviors of the firm's staff. Almost without exception, however, they have their roots in characteristics of the local environment. Such dynamic capabilities will be difficult to transfer and deploy overseas. A firm's ability to sustain competitive advantage abroad, therefore, depends on choosing foreign markets that share similarities with the firm's home base.

Technical summary

The dynamic capabilities framework was developed in the context of markets characterized by rapid technological change. Globalization means that firms in many industries now need similar capabilities to achieve and sustain competitive advantage. But the nature of these capabilities, their antecedents, and how they can underpin sustainable competitive advantage are incompletely understood. This article draws on a set of case studies of successful Chinese innovators to examine these questions. The dynamic capabilities we observe are underpinned by a set of processes that are themselves dynamic and flexible, rather than fixed, repeatable routines. Their antecedents mostly lie in qualities of the local environment. Hence, they tend to be context dependent, with consequent limitations in their transferability and applicability to sustaining competitive advantage in foreign markets. Copyright © 2016 Strategic Management Society.
Massive rearrangements of cellular MicroRNA signatures are key drivers of hepatocyte dedifferentiation
Authors: Lauschke Volker M. , Vorrink Sabine U. , Moro Sabrina M.L. , Rezayee Fatemah , Nordling Åsa , Hendriks Delilah F.G. , Bell Catherine C. , Sison‐Young Rowena , Park B. Kevin , Goldring Christopher E. , Ellis Ewa , Johansson Inger , Mkrtchian Souren , Andersson Tommy B. , Ingelman‐Sundberg Magnus
Published: August 2016

Hepatocytes are dynamic cells that, upon injury, can alternate between nondividing differentiated and dedifferentiated proliferating states in vivo. However, in two‐dimensional cultures, primary human hepatocytes (PHHs) rapidly dedifferentiate, resulting in loss of hepatic functions that significantly limits their usefulness as an in vitro model of liver biology, liver diseases, as well as drug metabolism and toxicity. Thus, understanding the underlying mechanisms and stalling of the dedifferentiation process would be highly beneficial to establish more‐accurate and relevant long‐term in vitro hepatocyte models. Here, we present comprehensive analyses of whole proteome and transcriptome dynamics during the initiation of dedifferentiation during the first 24 hours of culture. We report that early major rearrangements of the noncoding transcriptome, hallmarked by increased expression of small nucleolar RNAs, long noncoding RNAs, microRNAs (miRNAs), and ribosomal genes, precede most changes in coding genes during dedifferentiation of PHHs, and we speculated that these modulations could drive the hepatic dedifferentiation process. To functionally test this hypothesis, we globally inhibited the miRNA machinery using two established chemically distinct compounds, acriflavine and poly‐l‐lysine. These inhibition experiments resulted in a significantly impaired miRNA response and, most important, in a pronounced reduction in the down‐regulation of hepatic genes with importance for liver function. Thus, we provide strong evidence for the importance of noncoding RNAs, in particular, miRNAs, in hepatic dedifferentiation, which can aid the development of more‐efficient differentiation protocols for stem‐cell‐derived hepatocytes and broaden our understanding of the dynamic properties of hepatocytes with respect to liver regeneration. Conclusion: miRNAs are important drivers of hepatic dedifferentiation, and our results provide valuable information regarding the mechanisms behind liver regeneration and possibilities to inhibit dedifferentiation in vitro. (Hepatology 2016;64:1743‐1756)
Human papillomavirus testing versus cytology in primary cervical cancer screening: End‐of‐study and extended follow‐up results from the Canadian cervical cancer screening trial
Authors: Isidean Sandra D. , Mayrand Marie‐Hélène , Ramanakumar Agnihotram V. , Gilbert Laura , Reid Stephanie L. , Rodrigues Isabel , Ferenczy Alex , Ratnam Sam , Coutlée François , Franco Eduardo L. ,   CCCaST Study Group
Published: August 2016

The Canadian Cervical Cancer Screening Trial was a randomized controlled trial comparing the performance of human papillomavirus (HPV) testing and Papanicolaou cytology to detect cervical intraepithelial neoplasia of grades 2 or worse (CIN2+) among women aged 30–69 years attending routine cervical cancer screening in Montreal and St. John's, Canada (n = 10,154). We examined screening and prognostic values of enrollment cytologic and HPV testing results. Extended follow‐up data were available for St. John's participants (n = 5,754; 501,682.6 person‐months). HPV testing detected more CIN2+ than cytology during protocol‐defined (82.9 vs. 44.4%) and extended (54.2 vs. 19.3%) follow‐up periods, respectively. Three‐year risks ranged from 0.87% (95% CI: 0.37–2.05) for HPV‐/Pap‐ women to 35.77% (95% CI: 25.88–48.04) for HPV+/Pap+ women. Genotype‐specific risks ranged from 0.90% (95% CI: 0.40–2.01) to 43.84% (95% CI: 32.42–57.24) among HPV− and HPV16+ women, respectively, exceeding those associated with Pap+ or HPV+ results taken individually or jointly. Ten‐year risks ranged from 1.15% (95% CI: 0.60–2.19) for HPV−/Pap− women to 26.05% (95% CI: 15.34–42.13) for HPV+/Pap+ women and genotype‐specific risks ranged from 1.13% (95% CI: 0.59–2.14) to 32.78% (95% CI: 21.15–48.51) among women testing HPV− and HPV16+, respectively. Abnormal cytology stratified risks most meaningfully for HPV+ women. Primary HPV testing every 3 years provided a similar or greater level of reassurance against disease risks as currently recommended screening strategies. HPV‐based cervical screening may allow for greater disease detection than cytology‐based screening and permit safe extensions of screening intervals; genotype‐specific testing could provide further improvement in the positive predictive value of such screening.
Sex‐specific characterization and evaluation of the Alzheimer's disease genetic risk factor sorl1 in zebrafish during aging and in the adult brain following a 100 ppb embryonic lead exposure
Authors: Lee Jinyoung , Peterson Samuel M. , Freeman Jennifer L.
Published: August 2016

Developmental lead (Pb) exposure is suggested in laboratory studies to be a trigger for neurodegenerative diseases such as Alzheimer's disease (AD). Sortilin‐related receptor, L (DLR class) A repeats‐containing (SORL1) is a recently identified AD genetic risk factor. SORL1 has limited characterization in vertebrate models in comparison to other AD genetic risk factors. To characterize SORL1 further, protein sequence homology between humans, mice and zebrafish was analyzed and showed conservation of functional repeats and domain orientation. Next, spatial expression of sorl1 in zebrafish larvae was completed and diffuse expression in neural tissue that was not restricted to the brain was observed. Influences of sex and age on quantitative expression of sorl1 in the brain of adult zebrafish were then assessed. Sex‐specific alteration of sorl1 expression transpired during the aging process in females. The zebrafish was then utilized to investigate the impacts of a 100 ppb embryonic Pb exposure on sorl1 expression and other known AD genetic risk factors. Sex‐specific quantitative gene expression analysis was completed with adult zebrafish brain to compare those developmentally exposed to Pb or a control treatment, but no significant difference in sorl1 expression or other AD genetic risk factors was observed. Overall, this study provided characterization of sorl1 with changes in brain expression during aging being female‐specific. This finding is in agreement with females being more prone to the onset of AD, but analysis of additional AD genetic risk factors is needed to facilitate our understanding of the impact of a 100 ppb embryonic Pb exposure. Copyright © 2016 John Wiley & Sons, Ltd.
“Black cloud” vs. “white cloud” physicians – Myth or reality in apheresis medicine?
Authors: Pham Huy P. , Raju Dheeraj , Jiang Ning , Williams Lance A.
Published: August 2016

Background

Many practitioners believe in the phenomenon of either being labeled a “black cloud” or “white cloud” while on‐call. A “white‐cloud” physician is one who usually gets fewer cases. A “black‐cloud” is one who often has more cases. It is unclear if the designation is only superstitious or if there is some merit. Our aim is to objectively assess this phenomenon in apheresis medicine at our center.

Methods

A one‐year prospective study from 12/2014 to 11/2015 was designed to evaluate the number of times apheresis physicians and nurses were involved with emergent apheresis procedures between the hours from 10 PM and 7 AM. Other parameters collected include the names of the physician, apheresis nurse, type of emergent apheresis procedure, day of the week, and season of the year.

Results

During the study period, 32 emergent procedures (or “black‐cloud” events) occurred. The median time between two consecutive events was 8 days (range: 1–34 days). We found no statistically significant association between the “black‐cloud” events and attending physicians, nurses, day of the week, or season of the year by Chi‐square and Fisher's analyses. However, exploratory analysis using association rule demonstrated that “black‐cloud” events were more likely to happen on Thursday (2.19 times), with attending physician 2 (1.18 times), and during winter (1.15 times).

Conclusion

The results of this pilot study may support the common perception that some physicians or nurses are either “black cloud” or “white cloud”. A larger, multi‐center study population is needed to validate the results of this pilot study.
A Facile Preparation of Highly Thermally Stable Silver Nanoparticles Using PS‐b‐P4VP‐b‐PS Triblock Copolymer as Multidentate Ligand
Authors: Chen Fuqiang , Li Aixiang , Xu Guoyuan , Li Qiuhong , LYu Zijian
Published: August 2016

Silver nanoparticles (Ag NPs) of improved thermal stability against long‐term aggregation were prepared using the polystyrene‐b‐poly(4‐vinylpyridine)‐b‐polystyrene (PS‐b‐P4VP‐b‐PS) triblock copolymer as a multidentate ligand. First, PS‐b‐P4VP‐b‐PS was synthesized by sequential reversible addition–fragmentation transfer (RAFT) polymerization of styrene and 4‐vinylpydine using a trithiocarbonate chain transfer agent (CTA). Then Ag NPs were obtained by in situ reduction of silver nitrate using PS‐b‐P4VP‐b‐PS as a multidentate ligand. The obtained Ag NPs were stable in solution for at least 24 h while being heated at 110°C. The effect of the molar ratio of N atoms of the P4VP chain segment and AgNO3 on the stability of Ag NPs was studied, and the results suggested that Ag NPs were very stable even if the molar ratio of N atoms of the P4VP chain segment and AgNO3 was very low. This method is promising to scale up the preparation of metal NPs with good dispersibility and thermal stability, which still remains challenging. To further improve its thermal stability, 1,4‐dibromobutane was used to chemically crosslink the P4VP chain segment in solution. However, the results proved that the crosslink method is infeasible to further improve the thermal stability of Ag NPs in this system.
Community Norms and Human Rights: Supervising Haitian Colleagues on Interpersonal Psychotherapy (IPT) With a Depressed and Abused Pregnant Woman
Authors: Verdeli Helen , Therosme Tatiana , Eustache Eddy , Hilaire Olissaint St , Joseph Benissois , Sönmez Cemile Ceren , Raviola Giuseppe
Published: August 2016

After the 2010 Haiti earthquake, Zanmi Lasante, a local health care organization, implemented a collaborative stepped‐care model to address depression in community and primary care settings in rural Haiti. Specialized community health workers, the ajans santé, collaborate with local psychologists and primary care doctors to offer home‐based evaluation, support, and follow‐up. The services include brief interpersonal psychotherapy (IPT) and/or medication to persons who met locally defined criteria for depression. A cross‐national (Haiti–United States) expert mental health team has been overseeing the program. The present IPT supervision case of a severely depressed, physically abused, and pregnant young woman illustrates the U.S.‐based supervisor's internal struggle to reconcile awareness of and respect for local norms while maintaining a human rights‐based framework. It also highlights the critical role of community health workers in addressing the mental health treatment gap in regions plagued by extreme poverty and adversity.
Elastic properties of hydrogels and decellularized tissue sections used in mechanobiology studies probed by atomic force microscopy
Authors: Giménez Alícia , Uriarte Juan José , Vieyra Joan , Navajas Daniel , Alcaraz Jordi
Published: August 2016

The increasing recognition that tissue elasticity is an important regulator of cell behavior in normal and pathologic conditions such as fibrosis and cancer has driven the development of cell culture substrata with tunable elasticity. Such development has urged the need to quantify the elastic properties of these cell culture substrata particularly at the nanometer scale, since this is the relevant length scale involved in cell‐extracellular matrix (ECM) mechanical interactions. To address this need, we have exploited the versatility of atomic force microscopy to quantify the elastic properties of a variety of cell culture substrata used in mechanobiology studies, including floating collagen gels, ECM‐coated polyacrylamide gels, and decellularized tissue sections. In this review we summarize major findings in this field from our group within the context of the state‐of‐the‐art in the field, and provide a critical discussion on the applicability and complementarity of currently available cell culture assays with tunable elasticity. In addition, we briefly describe how the limitations of these assays provide opportunities for future research, which is expected to continue expanding our understanding of the mechanobiological aspects that support both normal and diseased conditions. Microsc. Res. Tech. 80:85–96, 2017. © 2016 Wiley Periodicals, Inc.
Optimization and evaluation of reference region variable flip angle (RR‐VFA) and T1 Mapping in the Prostate at 3T
Authors: Rangwala Novena A. , Dregely Isabel , Wu Holden H. , Sung Kyunghyun
Published: August 2016

Purpose

To optimize and evaluate the reference region variable flip angle (RR‐VFA) technique for simultaneous
and T1 mapping of the prostate at 3 Tesla (T).

Materials and Methods

The fat region surrounding the prostate was first identified using a fractional fat segmentation constant (tF) and a signal fat‐fraction threshold (rF), and the relative flip angle (FA) was characterized using an effective fat T1 (T1f) within the fat region. Optimal values of tF, rF, and T1f were chosen by comparing relative FA maps using RR‐VFA (ARR‐VFA) with a reference relative FA maps (AREF) in the surrounding fat and evaluating interpolation errors within the prostate. The optimized RR‐VFA was evaluated in volunteers at 3T on a single scanner (n = 10) and across three scanners (n = 4).

Results

tF, rF and T1f were optimized as 0.5, 90%, and 320 ms, respectively. Prostate ARR‐VFA showed differences of 30% among volunteers on one scanner, with no significant differences between ARR‐VFA and AREF (P = 0.41). Prostate T1 after
correction was 1998 ± 113 ms with significantly (P = 0.004) lower standard deviation than T1 before
correction. The average coefficient of variation of prostate T1 across multiple scanners decreased from 15% to 5% after
correction.

Conclusion

The optimized RR‐VFA can simultaneously measure
and T1 in the prostate without the need for an additional scan and improve T1 consistency within and across MRI scanners at 3T.

Level of Evidence: 3

J. Magn. Reson. Imaging 2017;45:751–760.
Thermal Decomposition Kinetics of Ginkgo biloba Leaves Polyprenol in Nitrogen Atmosphere
Authors: Zhang Chang‐Wei , Wang Cheng‐Zhang , Tao Ran
Published: August 2016

The nonisothermal decomposition kinetics of Ginkgo biloba leaves polyprenol (GBP) and cleaved situation of its chemical bond during thermal decomposition process were first investigated using thermogravimetric (TG) and TG‐FTIR technology. The results of thermal decomposition kinetics revealed that the nonisothermal decomposition mechanism of GBP corresponds to first‐order chemical reaction with n = 1, integral form g(a) = –ln(1 – a) and differential form f(a) = 1 – a. TG‐FTIR results demonstrated that absorbance of –CH3, unsaturated C–H bond, =CH2, accumulated C=C, –OH, and so on constantly increased with thermal decomposition reaction went on. In addition, storage life of GBP was also evaluated. These data could provide theoretical guidance for purification under high temperature and other thermal application of GBP.