bluuebunny/crossref_metadata_2025 huggingface dataset:
Model‐Based Investigation on the Mass Transfer and Adsorption Mechanisms of Mono‐Pegylated Lysozyme in Ion‐Exchange Chromatography
Authors: Morgenstern Josefine , Wang Gang , Baumann Pascal , Hubbuch Jürgen
Published: July 2017

Recent studies highlighted the potential of PEGylated proteins to improve stabilities and pharmacokinetics of protein drugs. Ion‐exchange chromatography (IEX) is among the most frequently used purification methods for PEGylated proteins. However, the underlying physical mechanisms allowing for a separation of different PEGamers (proteins with a varying number of attached PEG molecules) are not yet fully understood. In this work, mechanistic chromatography modeling is applied to gain a deeper understanding of the mass transfer and adsorption/desorption mechanisms of mono‐PEGylated proteins in IEX. Using a combination of the general rate model (GRM) and the steric mass action (SMA) isotherm, simulation results in good agreement with the experimental data are achieved. During linear gradient elution of proteins attached with PEG of different molecular weight, similar peak heights, and peak shapes at constant gradient length are observed. A superimposed effect of increased desorption rate and reduced diffusion rate as a function of the hydrodynamic radius of PEGylated proteins is identified to be the reason of this anomaly. That is why the concept of the diffusion‐desorption‐compensation effect is proposed. In addition to the altered elution orders, PEGylation results in a considerable decrease of maximum binding capacity. By using the SMA model in a kinetic formulation, the adsorption behavior of PEGylated proteins in the highly concentrated state is described mechanistically. An exponential increase in the steric hindrance effect with increasing PEG molecular weight is observed. This suggests the formation of multiple PEG layers in the interstitial space between bound proteins and an associated shielding of ligands on the adsorber surface to be the cause of the reduced maximum binding capacity. The presented in silico approach thus complements the hitherto proposed theories on the binding mechanisms of PEGylated proteins in IEX.
Transcriptome‐Based Identification of the Optimal Reference CHO Genes for Normalisation of qPCR Data
Authors: Brown Adam J. , Gibson Suzanne , Hatton Diane , James David C.
Published: July 2017

Real‐time quantitative PCR (qPCR) is the standard method for determination of relative changes in mRNA transcript abundance. Analytical accuracy, precision and reliability are critically dependent on the selection of internal control reference genes. In this study, the authors have identified optimal reference genes that can be utilised universally for qPCR analysis of CHO cell mRNAs. Initially, transcriptomic datasets were analysed to identify eight endogenous genes that exhibited high expression stability across four distinct CHO cell lines sampled in different culture phases. The relative transcript abundance of each gene in 20 diverse, commonly applied experimental conditions was then determined by qPCR analysis. Utilizing GeNorm, BestKeeper and NormFinder algorithms, the authors identified four mRNAs (Gnb1, Fkbp1a, Tmed2 and Mmadhc) that exhibited a highly stable level of expression across all conditions, validating their utility as universally applicable reference genes. Whilst any combination of only two genes can be generally used for normalisation of qPCR data, the authors show that specific combinations of reference genes are particularly suited to discrete experimental conditions. In summary, the authors report the identification of fully validated universal reference genes, optimised primer sequences robust to genomic mutations and simple reference gene pair selection guidelines that enable streamlined qPCR analyses of mRNA abundance in CHO cells with maximum accuracy and precision.
Mechanistic Modeling Based PAT Implementation for Ion‐Exchange Process Chromatography of Charge Variants of Monoclonal Antibody Products
Authors: Kumar Vijesh , Rathore Anurag S.
Published: July 2017

Process chromatography is typically used to remove product related impurities and variants that have very similar physicochemical properties to the product. Baseline separation may not be achieved in most cases due to high protein loading and thus, pooling of the elution peak can be challenging for maximizing yield and achieving consistency in product quality. Batch‐to‐batch variability in quality of the feed material also occurs in commercial manufacturing. Mechanistic modeling of process chromatography, though non‐trivial, can be an enabler for implementation of Process Analytical Technology. This paper presents one such application involving prediction of the impact of variability in feed quality and in gradient shape on separation of charge variants by cation exchange process chromatography and thereby facilitating feed forward control. Five batches having different compositions of charge variants have been used to demonstrate the proposed pooling strategy based on simulated chromatograms and the outcome has been compared to offline pooling based on fractionation. For all the conditions examined and for the desired target of main product (67%), the proposed approach resulted in remarkable consistency in product quality (67 ± 2%) while delivering a yield of greater than 90%.
Macrophages of Different Phenotypes Influence the Migration of BMSCs in PLGA Scaffolds with Different Pore Size
Authors: Dai Yuankun , Li Xuguang , Wu Ruihan , Jin Ying , Gao Changyou
Published: July 2017

Immune modulation of the scaffolds not only reduces the host immunological rejection response, but also improves the regenerative cell migration into the scaffolds. Herein a convenient immune modulation of poly(lactide‐co‐glycolide) (PLGA) scaffold is applied with macrophages of different phenotypes to evaluate its influence on the migration behavior of bone marrow mesenchymal stem cells (BMSCs). With pro‐inflammatory macrophages (M1) pre‐loading, BMSCs migrate significantly faster into the PLGA scaffold, compared with those in the control scaffold or pre‐seeded with inactivated macrophages (M0). The pore size of PLGA scaffolds is found to take a more important role, as the one with a larger pore size significantly enhance migration of BMSCs no matter the pre‐seeding of macrophages. The enhanced cell migration in the macrophage‐modulated scaffold can provide a new protocol for in situ tissue regeneration by recruiting endogenous cells.
His‐Tag Immobilization of Cutinase 1 From Thermobifida cellulosilytica for Solvent‐Free Synthesis of Polyesters
Authors: Pellis Alessandro , Vastano Marco , Quartinello Felice , Herrero Acero Enrique , Guebitz Georg M.
Published: July 2017

For many years, lipase B from Candida antarctica (CaLB) was the primary biocatalyst used for enzymatic esterification and polycondensation reactions. More recently, the need for novel biocatalysts with different selectivity has arisen in the biotechnology and biocatalysis fields. The present work describes how the catalytic potential of Thermobifida cellulosilytica cutinase 1 (Thc_Cut1) was exploited for polyester synthesis. In a first step, Thc_Cut1 was immobilized on three different carriers, namely Opal, Coral, and Amber, using a novel non‐toxic His‐tag method based on chelated Fe(III) ions (>99% protein bounded). In a second step, the biocatalyzed synthesis of an array of aliphatic polyesters was conducted. A selectivity chain study in a solvent‐free reaction environment showed how, in contrast to CaLB, Thc_Cut1 presents a certain preference for C6–C4 ester‐diol combinations reaching monomer conversions up to 78% and Mw of 878 g mol−1 when the Amber immobilized Thc_Cut1 was used. The synthetic potential of this cutinase was also tested in organic solvents, showing a marked activity decrease in polar media like that observed for CaLB. Finally, recyclability studies were performed, which showed an excellent stability of the immobilized Thc_Cut1 (retained activity >94%) over 24 h reaction cycles when a solvent‐free workup was used. Concerning a practical application of the biocatalyst's preparation, the production of oligomers with Mn values below 10 kDa is usually desired for the production of nanoparticles and for the synthesis of functional pre‐polymers for coating applications that can be crosslinked in a second reaction step.
Substrate Curvature Restricts Spreading and Induces Differentiation of Human Mesenchymal Stem Cells
Authors: Lee Sang Joo , Yang Shengyuan
Published: July 2017

While cells attach, spread, migrate, proliferate, and differentiate in three‐dimensional (3D) micromechanical environments, the mechanical factors of these environments influence the shapes, sizes, and adhesion forces of the cells. Here, the authors culture human mesenchymal stem cells (hMSCs) on a unique class of curvature‐defined substrates, micro glass ball embedded polyacrylamide gels, prepared with an improved protocol, and investigate the spreading responses of the hMSCs on the glass balls to study the effects of substrate curvature on the spreading of hMSCs. The authors find that, among the used diameters of glass balls, the minimum diameter of a glass ball on which an hMSC can attach and spread is 500 μm. In contrast to the well‐spread morphologies with randomly‐multiple lamellipodia for the hMSCs growing on the flat glass plates, the morphologies of the hMSCs growing on the glass balls are almost uniformly spindle‐shaped with two lamellipodia. The sensitivities of the attachment and spreading morphology of an hMSC to substrate curvature are very different from those of a fibroblast. The RT‐PCR analysis reveals that the substrate curvature alone can induce adipogenesis of the hMSCs. These findings imply that substrate curvature has profound effects on stem cell behaviors, and detailed and in‐depth studies on these effects and their underlying biophysical mechanisms are necessary.
Randomized clinical trial of Appendicitis Inflammatory Response score-based management of patients with suspected appendicitis
Authors: Andersson M , Kolodziej B , Andersson R E , Andersson R E , Andersson M , Eriksson T , Ramsing A , Westman L , Björkman J , Håkansson H O , Lundström T , Björkman H , Johansson P , Hjert O , Edin R , Ekström A , Wenander C , Wallon C , Andersson P , Frisk J , Arvidsson B , Lantz R , Wallin G , Wickberg Å , Stenberg E , Erixon C , Schmidt W , Räntfors J , Göthberg G , Styrud J , Elias K , Boström Le , Kretschmar G , Jonsson M , Brav C , Nilsson I , Kamran F , Hammarqvist F , Rutqvist J , Almström M , Hedberg M , Lindh V , Rosemar A , Wangberg H , Gustafsson J , Neovius G , Juhlin C , Christofferson R , Månsson C , Zittel T , Fagerström N
Published: July 2017

Background

The role of imaging in the diagnosis of appendicitis is controversial. This prospective interventional study and nested randomized trial analysed the impact of implementing a risk stratification algorithm based on the Appendicitis Inflammatory Response (AIR) score, and compared routine imaging with selective imaging after clinical reassessment.

Method

Patients presenting with suspicion of appendicitis between September 2009 and January 2012 from age 10 years were included at 21 emergency surgical centres and from age 5 years at three university paediatric centres. Registration of clinical characteristics, treatments and outcomes started during the baseline period. The AIR score-based algorithm was implemented during the intervention period. Intermediate-risk patients were randomized to routine imaging or selective imaging after clinical reassessment.

Results

The baseline period included 1152 patients, and the intervention period 2639, of whom 1068 intermediate-risk patients were randomized. In low-risk patients, use of the AIR score-based algorithm resulted in less imaging (19·2 versus 34·5 per cent; P < 0·001), fewer admissions (29·5 versus 42·8 per cent; P < 0·001), and fewer negative explorations (1·6 versus 3·2 per cent; P = 0·030) and operations for non-perforated appendicitis (6·8 versus 9·7 per cent; P = 0·034). Intermediate-risk patients randomized to the imaging and observation groups had the same proportion of negative appendicectomies (6·4 versus 6·7 per cent respectively; P = 0·884), number of admissions, number of perforations and length of hospital stay, but routine imaging was associated with an increased proportion of patients treated for appendicitis (53·4 versus 46·3 per cent; P = 0·020).

Conclusion

AIR score-based risk classification can safely reduce the use of diagnostic imaging and hospital admissions in patients with suspicion of appendicitis. Registration number: NCT00971438 (http://www.clinicaltrials.gov).
Combined LASER and femoral approach to remove a previous failure of Riata lead extraction
Authors: Dello Russo Antonio , Fassini Gaetano Michele , Conti Sergio , Vettor Giulia , Casella Michela , Tundo Fabrizio , Roberto Maurizio , Grillo Francesco , Alamanni Francesco , Tondo Claudio
Published: July 2017

Key Clinical Message

Transvenous extraction of Riata lead could be a challenging procedure due to insulation failure and conductor cables’ externalization through the eroded outer insulation. In this case, a complete lead extraction was achieved through a combined LASER and femoral approach because of the massive conductors’ externalization.
Edge‐Abundant Porous Fe3O4 Nanoparticles Docking in Nitrogen‐Rich Graphene Aerogel as Efficient and Durable Electrocatalyst for Oxygen Reduction
Authors: Liang Zibin , Xia Wei , Qu Chong , Qiu Bin , Tabassum Hassina , Gao Song , Zou Ruqiang
Published: July 2017

A novel Fe3O4 nanoparticles/nitrogen‐doped graphene aerogel (denoted as Fe3O4@NGA) hybrid material with high porosity was prepared by using iron‐based metal‐organic frameworks (MOFs), [Fe3O(H2N‐BDC)3] (H2N‐BDC=2‐aminoterephtalic acid), denoted as MIL‐88B‐NH2, as templates and nitrogen‐doped graphene aerogel (NGA) as the substrate. The obtained Fe3O4 nanoparticles demonstrate a rich edge area with abundant exposed active sites and defects, indicating great potential for oxygen adsorption and activation. When used as an electrocatalyst in alkaline solution, the Pt‐free Fe3O4@NGA exhibited excellent oxygen reduction reaction (ORR) performance and dramatically enhanced durability and tolerance towards methanol compared to commercial Pt/C catalyst, revealing its great viability and potential in practical application.
The Unusual Role of Aromatic Solvent in Single‐Site AluminumI Chemistry: Insights from Theory
Authors: Jain Shailja , Vanka Kumar
Published: July 2017

The single‐site activation of strong σ bonds (such as that of H−H, P−H, and N−H) remains a significant challenge in main‐group chemistry, with only a few cases reported to date. In this regard, recent exciting experiments performed with aluminumI complexes hold significance because they have been seen to activate a variety of strong σ bonds. Such chemistry is generally seen to occur in aromatic solvents. Current computational studies with DFT reveal the interesting reason for this: an explicit aromatic solvent molecule acts as a catalyst by converting the aluminumI complex into aluminumIII during the process. Different cases of σ‐bond activation by aluminumI complexes have been investigated and the efficiency of H−X (X=H, NHtBu, PPh2) bond activation in the presence of an explicit benzene solvent molecule is orders of magnitude higher than that in its absence. The current work therefore reveals the chemistry of aluminumI complexes to be richer and more complex than that previously realized, and shows it to be dependent on metal–solvent cooperativity; the first known example of its kind in main‐group chemistry.
Synthesis, Characterization, and Efficient Catalytic Activities of a Nickel(II) Porphyrin: Remarkable Solvent and Substrate Effects on Participation of Multiple Active Oxidants
Authors: Ahn Hye Mi , Bae Jeong Mi , Kim Min Jeong , Bok Kwon Hee , Jeong Ha Young , Lee Suk Joong , Kim Cheal
Published: July 2017

A new nickel(II) porphyrin complex, [NiII(porp)] (1), has been synthesized and characterized by 1H NMR, 13C NMR and mass spectrometry analysis. This NiII porphyrin complex 1 quantitatively catalyzed the epoxidation reaction of a wide range of olefins with meta‐chloroperoxybenzoic acid (m‐CPBA) under mild conditions. Reactivity and Hammett studies, H218O‐exchange experiments, and the use of PPAA (peroxyphenylacetic acid) as a mechanistic probe suggested that participation of multiple active oxidants NiII−OOC(O)R 2, NiIV‐Oxo 3, and NiIII‐Oxo 4 within olefin epoxidation reactions by the nickel porphyrin complex is markedly affected by solvent polarity, concentration, and type of substrate. In aprotic solvent systems, such as toluene, CH2Cl2, and CH3CN, multiple oxidants, NiII−(O)R 2, NiIV‐Oxo 3, and NiIII‐Oxo 4, operate simultaneously as the key active intermediates responsible for epoxidation reactions of easy‐to‐oxidize substrate cyclohexene, whereas NiIV‐Oxo 3 and NiIII‐Oxo 4 species become the common reactive oxidant for the difficult‐to‐oxidize substrate 1‐octene. In a protic solvent system, a mixture of CH3CN and H2O (95:5), the NiII−OOC(O)R 2 undergoes heterolytic or homolytic O−O bond cleavage to afford NiIV‐Oxo 3 and NiIII‐Oxo 4 species by general acid catalysis prior to direct interaction between 2 and olefin, regardless of the type of substrate. In this case, only NiIV‐Oxo 3 and NiIII‐Oxo 4 species were the common reactive oxidant responsible for olefin epoxidation reactions.
Over‐Stoichiometric NbO2 Nanoparticles for a High Energy and Power Density Lithium Microbattery
Authors: Asfaw Habtom D. , Tai Cheuk‐Wai , Nyholm Leif , Edström Kristina
Published: July 2017

Effective utilization of active materials in microbatteries can be enhanced by rational design of the electrodes. There is an increasing trend of using 3 D electrodes that are coated in nanosized active materials to boost both energy and power densities. This article focuses on the fabrication of 3 D electrodes based on monolithic carbon foams coated in over‐stoichiometric NbO2 nanoparticles. The electrodes exhibit remarkable energy and power densities at various current densities when tested in lithium microbatteries. An areal capacity of around 0.7 mAh cm−2 and energy density up to 45 mWh cm−3 have been achieved. More than half of the areal capacity can be accessed at a current density of about 11 mA cm−2, with the corresponding energy and power densities being 21 mWh cm−3 and 1349 mW cm−3. These values are comparable to those of microsupercapacitors containing carbon and MnO2 nanomaterials. Furthermore, the electrochemical reversibility improves progressively upon cycling along with substantial increase in the charge transfer kinetics of the electrode. Based on impedance analyses almost a fourfold decrease in the charge transfer resistance has been observed over 25 cycles. Such enhancement of the electronic properties of NbO2 can account for the high electrochemical rate performance of the 3 D electrodes.
Evaluation of primary mediastinal large B cell lymphoma by flow cytometry
Authors: Cherian Sindhu , Fromm Jonathan R.
Published: July 2017

Background

Primary mediastinal large B cell lymphoma (PMLBCL) is a B cell non‐Hodgkin lymphoma (B‐NHL) that shows morphologic, immunophenotypic, and genetic similarities to classical Hodgkin lymphoma (CHL). We evaluated the neoplastic and reactive infiltrate of PMLBCL by flow cytometry (FC).

Methods

A total of 24 cases of PMLBCL were retrospectively characterized using FC combinations for B‐NHL, T‐NHL, and CHL.

Results

The CHL assay identified the neoplastic population (NP) in all cases, while the B‐NHL assay identified the NP in 18 of 24 cases. In four cases, the neoplastic population was retrospectively identified in the B‐NHL tube, given the CHL tube‐derived immunophenotype. Neoplastic cells of PMLBCL displayed a B cell immunophenotype (CD19/CD20+), with CD40 consistently and brightly expressed. Most cases lacked immunoglobulin light chains, CD10, and CD15; CD30 was frequently expressed. All cases showed expression of CD71 and CD95. The reactive infiltrate in PMLBCL showed increases in T cells relative to reactive tissues. Lower CD4/CD8 ratios in PMLBCL relative to CHL and reactive tissues were also observed. Although not seen as commonly as with CHL, 41% of cases showed a reactive CD3/CD4/CD7bright/CD45bright+ T cell population. Reactive populations seen in PMLBCL were similar to that seen in diffuse large B cell lymphoma, not otherwise specified.

Conclusions

FC can detect the NP of PMLBCL and a FC assay for CHL performed better than a B‐NHL assay in this regard. The neoplastic cells showed a B cell immunophenotype with over‐expression of CD40. The reactive infiltrate in PMLBCL shows unique features including a prominent CD8+ T cell infiltrate. © 2017 International Clinical Cytometry Society
Secure wireless powered relaying networks: Energy harvesting policies and performance analysis
Authors: Le Quang Nhat , Do Dinh‐Thuan , An Beongku
Published: July 2017

In this paper, we investigate the problem of secure communication for a scenario, which consists of one pair of source‐destination nodes and one untrusted relay. The source communicates with the destination via the help of energy harvesting–aware untrusted relay, which acts as the helper to forward the source information to the destination; however, the relay also acts as the unintended user to eavesdrop the source information. To keep the source information confidential from untrusted relay, the destination‐assisted jamming technique is deployed. We evaluate the impact of energy harvesting protocols on such a secure communication scenario through the proposed energy transfer protocols, namely, source‐based energy harvesting protocol and maximum energy harvesting protocol. To evaluate the secrecy performance of these proposed schemes, we derive analytical expressions for two important performance metrics including intercept probability and strictly positive secrecy capacity. The numerical analysis reveals the different trade‐off between secure performance and relevant system parameters (i.e., power splitting ratio, time switching ratio, energy conversion efficiency, transmit signal‐to‐noise ratio, and relay location). Simulation results are also provided to demonstrate the accuracy of the developed analytical expression.
The challenges and rewards of leading as an interim administrator
Authors: Spirou Costas , Brown Kelli
Published: July 2017

Colleges and universities across the country are in the midst of unprecedented changes as the higher education enterprise is undergoing significant shifts and is subjected to rapid fluctuations. It is within this highly complex environment that interim administrators are often called upon to lead for various reasons. Planned or unexpected transitions of current personnel, failed searches, and internal complications brought on by politically induced circumstances require that those in interim capacities provide stability and leadership.
Reflections on academicians who have gone before us
Authors: Hodges Dawn Z.
Published: July 2017

Earlier this summer, I was checking my 6‐year‐old granddaughter out of the last day of first grade. I could tell she was reluctant to leave her teacher. When she finally let go and let herself walk down the hall with me, I said, “It's hard to leave first grade, isn't it? Our teacher, and all our friends.” She agreed and said she wished it could still be school. This is a kid who was going to the beach the following week!
Mineralogy and palaeoenvironments: the Weald Basin (Early Cretaceous), Southeast England
Authors: Akinlotan Oladapo
Published: July 2017

Determination of the mineralogy of sedimentary rocks is important in palaeoenvironmental interpretations, especially when outcrop and field data are insufficient or not accessible. The Lower Cretaceous Wealden facies, presented here as a case study, is one such example. Petrographic analysis of this suite of sediments reveals that the arenaceous facies are mainly quartz arenites, quartzose siltstones and lack significant feldspar. The clay minerals are illite, kaolinite, illite‐montmorillonite, vermiculite and illite‐smectite. The presence of quartz arenites and kaolinite suggests that the rocks were reworked from granitic and/or gneissic rocks. Directly or indirectly, the rocks may have been obtained from a stable craton. The mineral and textural maturity, together with a travel distance of ca 300 km point to matured sources. A warm and humid palaeoclimate in the source areas resulted in extensive weathering.
Episodic foresight beyond the very next event in 3‐ and 4‐year‐old children
Authors: Boden Hannah , Labuschagne Lisa G. , Hinten Ashley E. , Scarf Damian
Published: July 2017

Testing episodic foresight in children generally involves presenting them with a problem in one location (e.g., Room A) and, after a spending a delay in a different location, telling them they will be returning to Room A. Before they go, children are presented with a number of items, one of which will allow them to solve the problem in Room A. At around 3 to 4 years of age children display episodic foresight, selecting the item that will allow them to solve the problem. To date, however, no study has assessed whether 3‐ and 4‐year‐old children can plan beyond the very next event, selecting the correct item when there is a delay before returning to Room A. Here, we show that 3‐ and 4‐year‐old children can pass when a delay is imposed but that their performance is significantly worse than when they are planning for an immediate event.
Ectopic fat accumulation in the pancreas and its biomarkers: A systematic review and meta‐analysis
Authors: Singh Ruma G. , Yoon Harry D. , Poppitt Sally D. , Plank Lindsay D. , Petrov Maxim S.
Published: July 2017

Presence of fat in the pancreas increases the risk of metabolic co‐morbidities. Detection and quantification of pancreatic fat is not a routine clinical practice, at least in part because of need to use expensive imaging techniques. We aimed to systematically review common markers of pancreatic fat in blood and to investigate differences in these markers associated with fatty pancreas. The search was conducted in 3 databases (EMBASE, Scopus, and MEDLINE). Studies in humans were eligible for inclusion if they reported on biological markers and percentage of pancreatic fat or fatty pancreas prevalence. Data were pooled for correlation and effect size meta‐analysis. A total of 17 studies including 11 967 individuals were eligible for meta‐analysis. Markers of lipid metabolism, including circulating triglycerides (r = 0.38 [95% confidence interval (CI) 0.31, 0.46]) and high‐density lipoprotein cholesterol (r = −0.33 [95% CI −0.35, −0.31]), and markers of glucose metabolism, including glycated haemoglobin (r = 0.39 [95% CI 0.30, 0.48], insulin (r = 0.38 [95% CI 0.33, 0.43]), and homeostasis model assessment–insulin resistance (r = 0.37 [95% CI 0.30, 0.44], yielded the best correlations with percentage of pancreatic fat. Further, effect size analysis showed large and medium effects for the above markers of lipid and glucose metabolism. Circulating levels of triglycerides and glycated haemoglobin appear to be the best currently available markers of pancreatic fat. The approach of non‐invasive and accurate detection of pancreatic fat by blood analysis should be further explored in the future, by investigating other potential biological markers of pancreatic fat.
New onset diabetes after kidney transplantation is associated with increased mortality—A retrospective cohort study
Authors: Cooper L. , Oz N. , Fishman G. , Shohat T. , Rahamimov R. , Mor E. , Green H. , Grossman A.
Published: July 2017

Objective

Clinical outcomes in individuals with new onset diabetes after transplantation (NODAT) and the optimal treatment for this complication are poorly characterized. This study was intended to better define these issues.

Methods

Patients who underwent kidney transplantation and did not have diabetes prior to transplantation were included in the study. Clinical outcomes were compared between those who developed NODAT and those who did not. In those who developed NODAT, oral therapy was compared with insulin based therapy.

Results

A total of 266 kidney transplant recipients were included, of which 71 (27%) developed NODAT during the time of the follow‐up. Using Cox multivariate analysis adjusted for age and gender, hazard ratio for overall mortality among patients with NODAT versus those without NODAT was 2.69 (95% CI 1.04‐7.01). Among patients who developed NODAT, 29 patients (40%) were treated with an insulin‐based regimen. At the end of follow‐up, no difference was found in mean HbA1c, and therapy regimen was not associated with greater mortality.

Conclusions

New onset diabetes in kidney transplanted patients is associated with increased mortality compared with kidney transplanted patients without NODAT.
Glycaemia control and the risk of hospitalisation for infection in patients with type 2 diabetes: Hong Kong Diabetes Registry
Authors: Luk Andrea O.Y. , Lau Eric S.H. , Cheung Kitty K.T. , Kong Alice P.S. , Ma Ronald C.W. , Ozaki Risa , Chow Francis C.C. , So Wing‐Yee , Chan Juliana C.N.
Published: July 2017

Background

Infection occurs more commonly in diabetic patients compared with the general population and is an under‐recognised but important morbidity in patients with diabetes. We examined the impact of glycaemic control on hospitalisation for infection in a large prospective cohort of Chinese adults with type 2 diabetes.

Methods

Between July 1994 and June 2014, 22 846 patients with type 2 diabetes underwent detailed assessment of metabolic control and diabetes complications. Patients were followed for occurrence of infection requiring hospitalisation as identified using discharge diagnosis codes.

Results

Over a median follow‐up of 4.8 years, 20.3% of patients were hospitalised for any infection type, with respiratory tract, genitourinary tract, and skin being the most commonly affected sites. In multivariate Cox regression, time‐dependent HbA1c was associated with all‐site infection (hazard ratio [HR] 1.07 [95% confidence interval {CI}:1.05‐1.09, P < 0.001]), genitourinary tract infection (HR 1.09 [95% CI: 1.04‐1.14], P < 0.001), and skin infection (HR 1.16 [95% CI 1.12‐1.21]. P < 0.001), but not infection of respiratory tract, and was independent of age, gender, disease duration, smoking, body mass index, glomerular filtration rate, haemoglobin, history of stroke, congestive heart failure, coronary heart disease, peripheral artery disease, diabetic neuropathy and cancer, and baseline drug use. Against an arbitrary HbA1c interval of >7.0‐8.0% (53‐64 mmol/mol), patients with HbA1c ≤6.0% (42 mmol/mol) and >8.0% (64 mmol/mol) had excess risks of infection‐related hospitalisation adjusted for other factors.

Conclusions

In patients with type 2 diabetes, burden of serious infection is high. In the diabetic population, a U‐shape relationship between glycaemia and infection‐related hospitalisation was detected.
Effect of alcohol dehydrogenase‐1B and ‐7 polymorphisms on blood ethanol and acetaldehyde concentrations in healthy subjects with a history of moderate alcohol consumption
Authors: Pastorino Roberta , Iuliano Luigi , Vecchioni Alessia , Arzani Dario , Milic Mirta , Annunziata Francesca , Zerbinati Chiara , Capoluongo Ettore , Bonassi Stefano , McKay James D. , Boccia Stefania
Published: July 2017

This study aims to evaluate the effect of ADH1B and ADH7 genotypes on blood acetaldehyde and ethanol levels after alcohol ingestion, and to measure the genotoxic effect of smoking and ethanol on the buccal cells, also controlling for ADH variants. We recruited healthy Italian subjects with at least a moderate history of alcohol consumption. All subjects were given an alcoholic drink of 0.4 g ethanol /kg of body weight. Blood venous samples were collected at baseline, and 30, 60, 90, and 120 minutes after ingestion. Buccal cells were collected before ethanol ingestion. Sixty subjects were enrolled in the study. Individuals with the ADH1B GG genotype had median ethanol levels of 5.0mM (IQR 3.4–7.2), and those with the ADH1B GT/TT genotype had 4.7mM (IQR 4.2–4.8). Corresponding acetaldehyde levels were 1.5μM (IQR 0.7–2.6) for ADH1B GG genotype and 1.6μM (IQR 1.5–1.7) for ADH1B CG/GG genotype. Individuals with the ADH7 CC genotype had median ethanol levels of 5.0mM (IQR 3.3–7.2), while 5.0mM (IQR 4.7–5.6) was in those with the ADH7 CG/GG genotype. Corresponding acetaldehyde levels were 1.5 μM (IQR 0.7–2.6) for ADH7 CC genotype and 1.5 μM (IQR 1.4–1.6) for ADH7 CG/GG genotypes. A non‐significant increase in the frequency of karyolitic and pyknotic cells was found in the group of heavy drinkers and current smokers, when compared to the moderate drinkers and the non‐smokers. Our study does not support the hypothesis that ADH1B and ADH7 genotypes affect blood ethanol and acetaldehyde concentration.
Connecting the dots: Stopover strategies of an intercontinental migratory songbird in the context of the annual cycle
Authors: Paxton Kristina L. , Moore Frank R.
Published: July 2017

The phases of the annual cycle for migratory species are inextricably linked. Yet, less than five percent of ecological studies examine seasonal interactions. In this study, we utilized stable hydrogen isotopes to geographically link individual black‐and‐white warblers (Mniotilta varia)captured during spring migration with breeding destinations to understand a migrant's stopover strategy in the context of other phases of the annual cycle. We found that stopover strategy is not only a function of a bird's current energetic state, but also the distance remaining to breeding destination and a bird's time‐schedule, which has previously been linked to habitat conditions experienced in the preceding phase of the annual cycle. Birds in close proximity to their breeding destination accumulate additional energy reserves prior to arrival on the breeding grounds, as reflected by higher migratory condition upon arrival, higher refueling rates measured via blood plasma metabolites, and longer stopover durations compared to birds migrating to breeding destinations farther from the stopover site. However, late birds near their breeding destination were more likely to depart on the day of arrival (i.e., transients), and among birds that stopped over at the site, the average duration of stopover was almost half the time of early conspecifics, suggesting late birds are trying to catch‐up with the overall time‐schedule of migration for optimal arrival time on the breeding grounds. In contrast, birds with long distances remaining to breeding destinations were more likely to depart on the day of arrival and primarily used stopover to rest before quickly resuming migration, adopting similar strategies regardless of a bird's time‐schedule. Our study demonstrates that migrants adjust their en route strategies in relation to their time‐schedule and distance remaining to their breeding destination, highlighting that strategies of migration should be examined in the context of other phases of the annual cycle.
Interactive effects of leg autotomy and incline on locomotor performance and kinematics of the cellar spider, Pholcus manueli
Authors: Gerald Gary W. , Thompson Moriah M. , Levine Todd D. , Wrinn Kerri M.
Published: July 2017

Leg autotomy can be a very effective strategy for escaping a predation attempt in many animals. In spiders, autotomy can be very common (5–40% of individuals can be missing legs) and has been shown to reduce locomotor speeds, which, in turn, can reduce the ability to find food, mates, and suitable habitat. Previous work on spiders has focused mostly on the influence of limb loss on horizontal movements. However, limb loss can have differential effects on locomotion on the nonhorizontal substrates often utilized by many species of spiders. We examined the effects of leg autotomy on maximal speed and kinematics while moving on horizontal, 45° inclines, and vertical (90°) inclines in the cellar spider Pholcus manueli, a widespread species that is a denizen of both natural and anthropogenic, three‐dimensional microhabitats, which frequently exhibits autotomy in nature. Maximal speeds and kinematic variables were measured in all spiders, which were run on all three experimental inclines twice. First, all spiders were run at all inclines prior to autotomization. Second, half of the spiders had one of the front legs removed, while the other half was left intact before all individuals were run a second time on all inclines. Speeds decreased with increasing incline and following autotomy at all inclines. Autotomized spiders exhibited a larger decrease in speed when moving horizontally compared to on inclines. Stride length decreased at 90° but not after autotomy. Stride cycle time and duty factor increased after autotomy, but not when moving uphill. Results show that both incline and leg autotomy reduce speed with differential effects on kinematics with increasing incline reducing stride length, but not stride cycle time or duty factor, and vice versa for leg autotomy. The lack of a significant influence on a kinematic variable could be evidence for partial compensation to mitigate speed reduction.
Can subsets of species indicate overall patterns in biodiversity?
Authors: Klibansky Nikolai , Shertzer Kyle W. , Kellison G. Todd , Bacheler Nathan M.
Published: July 2017

Resource limitations often allow only a subset of species to be counted. But using subsets may bias inferences on spatial or temporal trends in biodiversity. Using data from a video survey on reefs in the Gulf of Mexico for which all fish species observed were counted (243 species), we investigated how the use of reduced species lists (RSLs) can impact perceived patterns in biodiversity. We estimated four common biodiversity metrics (species richness, and Margalef's, Shannon's, and Simpson's indices) at each of 2115 sampling locations, using the total species list and RSLs. For all diversity metrics, correlations between estimates using the total species list and RSLs increased with the number of species in the list. Using a bootstrap approach, we randomly generated hypothetical lists equal in length to each empirical RSL to evaluate their performance; empirical RSLs tended to perform similar to random lists of equivalent length when estimating species richness or Margalef's index, and tended to outperform most hypothetical RSLs when estimating Shannon's and Simpson's indices. To understand how to create better performing RSLs, we extended the bootstrap analysis to select RSLs of all possible lengths, using four different selection methods related to species commonness; the functional relationships between correlation and number of species in an RSL were similar among metrics but were very different among selection methods. With each hypothetical RSL, we tested common biodiversity hypotheses such as relationships with depth and latitude and compared the outcomes with the best estimate of true relationships identified using the total list. Longer lists comprised of the most common species more often identified the true relationship, but results showed complex patterns. Many short lists of the most common species yielded results opposite the true relationships, and many lists of intermediate length failed to identify any relationship while the total list showed a significant trend. Overall, these analyses show that sampling methods used for biodiversity studies should be as unselective as possible, and datasets based on more selective methods should be interpreted carefully and should not be expected to reflect true patterns in biodiversity.
Patterns and dynamics of vegetation recovery following grazing cessation in the California golden trout habitat
Authors: Nusslé Sébastien , Matthews Kathleen R. , Carlson Stephanie M.
Published: July 2017

In 1978, the Golden Trout Wilderness area was established to protect the California golden trout (Oncorhynchus mykiss aguabonita)—a vulnerable subspecies of the rainbow trout that is endemic to California—and its habitat, which is currently restricted to a few streams within high‐elevation meadows in the Sierra Nevada Mountain Range. Because of the deleterious effects of livestock grazing on riparian vegetation in the golden trout habitat (occurring since the 1800s), meadow restoration activities were initiated in 1991, including cattle exclusion. There has been renewed discussion about re‐opening these public lands to livestock grazing, and impact assessment studies are needed to inform decision makers about the potential consequences. Thus, we estimated the recovery potential of the golden trout habitat by measuring the height of riparian vegetation within areas that have been grazed vs. closed to grazing (“rested”) since 1991. We found that cattle exclusion is effective at favoring riparian vegetation growth, but that vegetation recovery from grazing could take several decades in these sensitive habitats as some “rested” areas have yet to recover to full vegetation height, even after 25 yr of rest.
Synthesis and Reactivity of Iron– and Cobalt–Dinitrogen Complexes Bearing PSiP‐Type Pincer Ligands toward Nitrogen Fixation
Authors: Imayoshi Ryuji , Nakajima Kazunari , Takaya Jun , Iwasawa Nobuharu , Nishibayashi Yoshiaki
Published: July 2017

Invited for the cover of this issue is the Nishibayashi group, University of Tokyo, collaborating with the Iwasawa group, Tokyo Institute of Technology, Japan. The cover image shows the transformation of molecular dinitrogen into silylamine as ammonia equivalent, catalyzed by Fe– and Co–dinitrogen complexes bearing PSiP‐type pincer ligands.
Atom‐Economical Synthesis of Unsymmetrical Diaryl Selenides from Arylhydrazines and Diaryl Diselenides
Authors: Taniguchi Toshihide , Murata Akinori , Takeda Motonori , Mizuno Takumi , Nomoto Akihiro , Ogawa Akiya
Published: July 2017

An atom‐economical method for the synthesis of unsymmetrical diaryl selenides from arylhydrazines and stoichiometric amounts of diselenides was developed under mild conditions. The new and facile selenide synthesis involved the use of an inexpensive base in air to form unsymmetrical diaryl selenides in good yields. This C–Se radical arylation of diaryl diselenides was performed by forming aryl radicals from arylhydrazines under oxidative conditions. The formation of a phenyl radical was supported by trapping with 2,2,6,6‐tetramethylpiperidine‐1‐oxyl (TEMPO) in air. Therefore, this synthesis might involve a homolytic aromatic substitution (HAS) mechanism. The synthesis is both low costing and environmentally friendly and, therefore, may be useful for the practical synthesis of unsymmetrical diaryl selenides.
The Value of Compressed‐Air Energy Storage for Enhancing Variable‐Renewable‐Energy Integration: The Case of Ireland
Authors: Nikolakakis Thomas , Fthenakis Vasilis
Published: July 2017

Mixed integer programming (MIP) was used to formulate a unit commitment and economic dispatch (UCED) algorithm that included two models for simulating the dynamic performance of compressed‐air energy storage (CAES) units. The first model assumes CAES operating with fixed efficiencies (FEs) on both the compression and expansion side, similar to models commonly used in industry and academia. The second model is a detailed thermoeconomic (TE) model, which uses power curves obtained by CAES manufacturers to model the effect of cavern pressure on operation limits of both the compressor and expander. The UCED and CAES models were combined to identify the contribution of CAES on minimizing the impacts of wind integration into the Irish power sector in 2020. The results of the UCED‐TE model show that the addition of a CAES unit in the North Ireland grid can reduce wind curtailment, CO2 emissions, and system costs. The cost reductions result mainly from reductions in wind curtailment and coal‐fired generation. The FE model shows much higher reductions of wind curtailment, CO2 emissions, and total system costs. However, both models show that the benefit of CAES on the system increases with variable renewable energy and CAES installed capacity. The difference in the results of the two models is reduced in scenarios of high CAES capacity. The main conclusions of the study are that existing fixed‐efficiencies CAES models overestimate reductions on wind curtailment whereas both models show the system‐wide economic benefits of CAES grow considerably as wind production grows.
Towards All‐Inorganic Transport Layers for Wide‐Band‐Gap Formamidinium Lead Bromide‐Based Planar Photovoltaics
Authors: Subbiah Anand S. , Mahuli Neha , Agarwal Sumanshu , van Hest Maikel F. A. M. , Sarkar Shaibal K.
Published: July 2017

Hybrid perovskite photovoltaic devices heavily rely on the use of organic (rather than inorganic) charge‐transport layers on top of a perovskite absorber layer because of difficulties in depositing inorganic materials on top of these fragile absorber layers. However, in comparison to the unstable and expensive organic transport materials, inorganic charge‐transport layers provide improved charge transport and stability to the device architecture. Here, we report photovoltaic devices using all‐inorganic transport layers in a planar p‐i‐n junction device configuration using formamidinium lead tribromide (FAPbBr3) as an absorber. Efficient planar devices are obtained through atomic layer deposition of nickel oxide and sputtered zinc oxide as hole‐ and electron‐transport materials, respectively. Using only inorganic charge‐transport layers resulted in planar FAPbBr3 devices with a power conversion efficiency of 6.75 % at an open‐circuit voltage of 1.23 V. The transition of planar FAPbBr3 devices making from all‐organic towards all–inorganic charge‐transport layers is studied in detail.
The influence of flow discharge variations on the morphodynamics of a diffluence–confluence unit on a large river
Authors: Hackney Christopher R. , Darby Stephen E. , Parsons Daniel R. , Leyland Julian , Aalto Rolf , Nicholas Andrew P. , Best James L.
Published: July 2017

Bifurcations are key geomorphological nodes in anabranching and braided fluvial channels, controlling local bed morphology, the routing of sediment and water, and ultimately defining the stability of their associated diffluence–confluence unit. Recently, numerical modelling of bifurcations has focused on the relationship between flow conditions and the partitioning of sediment between the bifurcate channels. Herein, we report on field observations spanning September 2013 to July 2014 of the three‐dimensional flow structure, bed morphological change and partitioning of both flow discharge and suspended sediment through a large diffluence–confluence unit on the Mekong River, Cambodia, across a range of flow stages (from 13 500 to 27 000 m3 s−1).

Analysis of discharge and sediment load throughout the diffluence–confluence unit reveals that during the highest flows (Q = 27 000 m3 s−1), the downstream island complex is a net sink of sediment (losing 2600 ± 2000 kg s−1 between the diffluence and confluence), whereas during the rising limb (Q = 19 500 m3 s−1) and falling limb flows (Q = 13 500 m3 s−1) the sediment balance is in quasi‐equilibrium. We show that the discharge asymmetry of the bifurcation varies with discharge and highlight that the influence of upstream curvature‐induced water surface slope and bed morphological change may be first‐order controls on bifurcation configuration. Comparison of our field data to existing bifurcation stability diagrams reveals that during lower (rising and falling limb) flow the bifurcation may be classified as unstable, yet transitions to a stable condition at high flows. However, over the long term (1959–2013) aerial imagery reveals the diffluence–confluence unit to be fairly stable. We propose, therefore, that the long‐term stability of the bifurcation, as well as the larger channel planform and morphology of the diffluence–confluence unit, may be controlled by the dominant sediment transport regime of the system. © 2017 The Authors. Earth Surface Processes and Landforms published by John Wiley & Sons Ltd.