bluuebunny/crossref_metadata_2025 huggingface dataset:
Optimal design of batch‐storage network considering ownership
Authors: Yi Gyeongbeom , Reklaitis Gintaras V.
Published: January 2018

This article develops a model of multi‐national supply chain activities, which incorporates currency storage units to manage currency flows associated with activities such as raw material procurement, processing, inventory control, transportation, and finished product sales. The core contribution of this model is that it facilitates the quantitative investigation of the influence of macroscopic economic factors such as ownership on supply chain operational decisions. The supply chain system is modeled as a batch‐storage network with recycle streams. The supply chain optimization problem is posed with the objective of minimizing the opportunity costs of annualized capital investments and currency/material inventories, while taking into account the benefit to stockholders in the numeraire currency. The major constraints on the optimization are that the material and currency storage units must not be depleted. A production and inventory analysis formulation (the periodic square wave model) provides useful expressions for the upper and lower bounds and for the average levels of the currency and material inventory holdings. The expressions for the Kuhn‐Tucker conditions of the optimization problem are reduced to a subproblem that allows development of analytical lot‐sizing equations. The lot sizes of procurement, production, transportation, and financial transactions can be determined in closed form once the average flow rates are known. The key result we obtain is that optimal value of the economic order quantity changes substantially with variation in ownership, thus showing quantitatively that ownership structure does impact plant operation. © 2018 American Institute of Chemical Engineers AIChE J, 64: 2418–2425, 2018
Gamma‐glutamyl transferase predicts future stroke: A Korean nationwide study
Authors: Yang Wookjin , Kim Chi Kyung , Kim Do Yeon , Jeong Han‐Gil , Lee Seung‐Hoon
Published: January 2018

Objective

Although gamma‐glutamyl transferase (GGT) is generally regarded as an alternative biomarker for alcohol consumption, its independent role in vascular diseases emerged recently. However, its role in stroke remains unknown. The aim of this study is to clarify the impact of GGT on stroke in a large‐sized, national, standardized population cohort in Korea.

Methods

In Korea, the National Health Insurance Service (NHIS) provides full‐coverage health insurance service for all citizens. Using data from the NHIS, the NHIS–National Sample Cohort was designed by randomly selecting 2% of Koreans, carefully considering demographic characteristics. We analyzed eligible individuals from this standardized cohort. The Cox proportional hazards model was used for the study investigating the relationship between GGT and stroke.

Results

Among the 456,100 eligible participants, 7,459 patients (1.64%) developed stroke as follows: 5,789 ischemic strokes, 1,046 intracerebral hemorrhages (ICHs), and 624 subarachnoid hemorrhages. GGT was independently correlated with increased risk of stroke after adjustment for alcohol consumption and stroke risk factors (hazard ratio [HR] = 1.39, 95% confidence interval [CI] = 1.29–1.51). The risks of both ischemic stroke (HR = 1.45, 95% CI = 1.32–1.58) and ICH (HR = 1.46, 95% CI = 1.18–1.80) were significantly elevated with increasing GGT. Despite some effect modifications by sex, age, and alcohol, the risk of total stroke and ischemic stroke in association with GGT remained significant in all subgroups.

Interpretation

In a standard Korean population, GGT was a novel biomarker predicting stroke risk, independently from alcohol consumption and other risk factors. Ann Neurol 2018;83:375–386
Neutrophil hyperactivation correlates with Alzheimer's disease progression
Authors: Dong Yuan , Lagarde Julien , Xicota Laura , Corne Hélène , Chantran Yannick , Chaigneau Thomas , Crestani Bruno , Bottlaender Michel , Potier Marie‐Claude , Aucouturier Pierre , Dorothée Guillaume , Sarazin Marie , Elbim Carole
Published: January 2018

Objective

Recent studies have underlined the effect of systemic inflammation on the pathophysiology of Alzheimer's disease (AD). Neutrophils are key components of early innate immunity and contribute to uncontrolled systemic inflammation if not tightly regulated. The aim of our study was to fully characterize human circulating neutrophils at different disease stages in AD.

Methods

We analyzed neutrophil phenotypes and functions in 42 patients with AD (16 with mild cognitive impairment and 26 with dementia), and compared them to 22 age‐matched healthy subjects. This study was performed directly in whole blood to avoid issues with data interpretation related to cell isolation procedures.

Results

Blood samples from AD patients with dementia revealed neutrophil hyperactivation associated with increased reactive oxygen species production and increased levels of intravascular neutrophil extravascular traps. The homeostasis of circulating neutrophils in these patients also changed: The ratio between the harmful hyperreactive CXCR4high/CD62Llow senescent and the CD16bright/CD62Ldim immunosuppressive neutrophil subsets rose in the later stage of the disease. These abnormalities were greater in fast‐decliner than in slow‐decliner patients.

Interpretation

Our results indicate that the inflammatory properties of circulating neutrophils shift as the percentage of aged neutrophils expands in patients with AD—changes that may play an instrumental role in establishing systemic chronic inflammation. Most important, our data strongly suggest that the neutrophil phenotype may be associated with the rate of cognitive decline and may thus constitute an innovative and prognostic blood biomarker in patients with AD. Ann Neurol 2018;83:387–405
Epoxides as Alkylating Reagents for the Catellani Reaction
Authors: Cheng Hong‐Gang , Wu Chenggui , Chen Han , Chen Ruiming , Qian Guangyin , Geng Zhi , Wei Qiang , Xia Yuanyuan , Zhang Jingyang , Zhang Yuming , Zhou Qianghui
Published: January 2018

We report a cooperative catalytic system comprising a PdII complex, XPhos, and the potassium salt of 5‐norbornene‐2‐carboxylic acid that enables the use of epoxides as alkylating reagents in the Catellani reaction, thereby expanding the existing paradigm of this powerful transformation. The potassium salt of inexpensive 5‐norbornene‐2‐carboxylic acid acts as both mediator and base in the process. This mild, chemoselective, scalable, and atom‐economical protocol is compatible with a wide variety of readily available functionalized aryl iodides and epoxides, as well as terminating olefins. The resulting products undergo facile oxa‐Michael addition to furnish ubiquitous isochroman scaffolds.
Solution behavior of water‐soluble poly(acrylamide‐co‐sulfobetaine) with intensive antisalt performance as an enhanced oil‐recovery chemical
Authors: Zhang Qin , Gou Shaohua , Zhao Lei , Fei Yumei , Zhou Lihua , Li Shiwei , Wu Yuanpeng , Guo Qipeng
Published: January 2018

In the process of oilfield development, salt tolerance is an important property for enhanced oil‐recovery (EOR) chemicals. In this study, we synthesized two acrylamide‐based sulfobetaine copolymers containing 2‐hydroxy‐3‐[(3‐methacrylamidopropyl)dimethylammonio]propane sulfonate (SHPP) or 3‐(4‐acry‐loyl‐1‐methyl‐piperazinio)‐2‐hydroxypropane sulfonate (SHMP). The interactions between these two copolymers and inorganic salts were compared, and the apparent viscosity (ηapp) behaviors of copolymer–salt solutions at different shear rates and temperatures were investigated. We found that the ηapp of PAPP and PAMP showed intensive antisalt performance, exhibiting an excellent antipolyelectrolyte effect. The ηapp retention value of 30,000 mg/L PAMP in brine was 86.47 mPa s at 510 s−1, and when the temperature was increased to 90 °C, it was 99.73 mPa s; this was better than that of PAPP under the same conditions. Therefore, PAMP was more applicable as an EOR chemical that have outstanding salt tolerance and temperature resistance. © 2018 Wiley Periodicals, Inc. J. Appl. Polym. Sci. 2018, 135, 46235
Nutzung von BIM in der Angebotsbearbeitung
Authors: Schwerdtner Patrick
Published: January 2018

Die derzeitigen Diskussionen zur Methodik des Building Information Modeling (BIM) sind geprägt von sehr visionären und idealistischen Ansätzen. Immer wieder wird hervorgehoben, dass sich durch die BIM‐Methode Daten und Informationen eines Bauprojekts über alle Phasen des Lebenszyklus modellbasiert dokumentieren, austauschen und nutzen lassen. Diese Vision ist einerseits zu begrüßen, da nur durch das Aufzeigen der vielfältigen Möglichkeiten und zukünftiger Vorteile alternativer und kollaborativer Arbeitsweisen die dringend notwendigen Veränderungsprozesse in der Bauwirtschaft angestoßen werden. Andererseits hinterlassen diese großen Bilder zukünftiger Projektrealisierungen gerade bei vielen ausführenden Unternehmen den Eindruck, dass die Ansätze mit der aktuellen Praxis nur schwer in Einklang zu bringen sind.

Dennoch nutzen insbesondere Generalunternehmer seit geraumer Zeit die neuen digitalen Möglichkeiten und erstellen – unabhängig von existierenden Datenstrukturen – bereits in der Angebotsbearbeitung eigene 3‐D‐Modelle. Im Folgenden werden wesentliche Aspekte dieser modellbasierten Angebotsbearbeitung erläutert, um die besondere Perspektive der ausführenden Unternehmen und einhergehende Vorteile zu beschreiben. Abschließend werden zwei Wege zur Entwicklung einer konsistenten digitalen Prozesskette skizziert.
Alterations in local stability and dynamics of A4V SOD1 in the presence of trifluoroethanol
Authors: Kumar Vijay , Prakash Amresh , Lynn Andrew M.
Published: January 2018

Alterations in the local dynamics of Cu/Zn Superoxide dismutase (SOD1) due to mutations affect the protein folding, stability, and function leading to misfolding and aggregation seen in amyotrophic lateral sclerosis (ALS). Here, we study the structure and dynamics of the most devastating ALS mutation, A4V SOD1 in aqueous trifluoroethanol (TFE) through experiments and simulation. Far‐UV circular dichroism (CD) studies shows that TFE at intermediate concentrations (∼15% ‐ 30%) induce partially unfolded β‐sheet‐rich extended conformations in A4V SOD1 which subsequently aggregates. Molecular dynamics (MD) simulation results shows that A4V SOD1 increases local dynamics in the active site loops that leads to the destabilization of the β‐barrel and loss of hydrophobic contacts, thus stipulating a basis for aggregation. Free energy landscape (FEL) and essential dynamics (ED) analysis demonstrates the conformational heterogeneity in A4V SOD1. Our results thus shed light on the role of local unfolding and conformational dynamics in aggregation of SOD1.
Targeted metabolomic analysis of 33 amino acids and biogenic amines in human urine by ion‐pairing HPLC‐MS/MS: Biomarkers for tacrolimus nephrotoxicity after renal transplantation
Authors: Xia Tianyi , Fu Shangxi , Wang Qinghua , Wen Yan , Chan Shen‐an , Zhu Sang , Gao Shouhong , Tao Xia , Zhang Feng , Chen Wansheng
Published: January 2018

Calcineurin inhibitor nephrotoxicity, especially for the widely used tacrolimus, has become a major concern in post‐transplant immunosuppression. Multiparametric amino acid metabolomics is useful for biomarker identification of tacrolimus nephrotoxicity, for which specific quantitative methods are highlighted as a premise. This article presents a targeted metabolomic assay to quantify 33 amino acids and biogenic amines in human urine by high‐performance liquid chromatography coupled with tandem mass spectrometry. Chromatographic separation was carried out on an Agilent Zorbax SB‐C18 column (3.0 × 150 mm, 5 μm) with addition of an ion‐pairing agent in the mobile phase, and MS/MS detection was achieved in both the positive and negative multiple reaction monitoring modes. Good correlation coefficients (r2 > 0.98) were obtained for most analytes. Intra‐ and inter‐day precision, stability, carryover and incurred sample reanalysis met with the acceptance criteria of the guidance of the US Food and Drug Administration. Analysis on urine from healthy volunteers and renal transplantation patients with tacrolimus nephrotoxicity confirmed symmetric dimethylarginine and serine as biomarkers for kidney injury, with AUC values of 0.95 and 0.81 in receiver operating characteristic analysis, respectively. Additionally, symmetric dimethylarginine exhibited a tight correlation with serum creatinine, and was therefore indicative of renal function. The targeted metabolomic assay was time and cost prohibitive for amino acid analysis in human urine, facilitating the biomarker identification of tacrolimus nephrotoxicity.
Empower employees to step away, with the greater goal of enhancing leadership
Authors: Skipworth Stan
Published: January 2018

With current technology, content and functions including, news, sports scores, sending and receiving documents, accessibility by phone — even music, television, and movies — is instantly available. The descriptions of the very devices we choose to access these various information sources and systems highlight their speed: A computer with significantly greater memory and an enhanced processor and faster internet service create the expectation we are capable of handling greater amounts of data, will have a more enjoyable online experience, and will be more effective at work.
Honestly evaluate staff goals to build professional development pathways
Authors: Sutton Halley
Published: January 2018

PHOENIX — How engaged are the workers in your office? That was the question Joellen Shendy, associate vice provost and university registrar at the University of Maryland University College; and Insiya Bream, assistant vice provost for registrar strategic operations at UMUC, sought to answer when they took a survey to determine professional engagement and goals.
People with disabilities face greater risk of arrest by age 30
Authors: Sutton Halley
Published: January 2018

Those with a cognitive, physical, emotional, or sensory disability are more likely to be arrested by the time they reach their late 20s than their peers without a disability. That finding comes from data published in the American Journal of Public Health, which analyzed data on 9,000 Americans who were born between 1980 and 1984. Those with a disability of some kind faced a 43 percent probability of having been arrested by the time they reached their late 20s, versus those without a disability who faced a 30 percent probability by that same age.
Pentachloropseudilin Inhibits Transforming Growth Factor‐β (TGF‐β) Activity by Accelerating Cell‐Surface Type II TGF‐β Receptor Turnover in Target Cells
Authors: Chung Chih‐Ling , Wang Shih‐Wei , Martin René , Knölker Hans‐Joachim , Kao Yu‐Chen , Lin Ming‐Hong , Chen Jih‐Jung , Huang Yaw‐Bin , Wu Deng‐Chyang , Chen Chun‐Lin
Published: January 2018

Pentachloropseudilin (PClP) is a chlorinated phenylpyrrole compound that was first isolated from Actinoplanes (ATCC33002), and its structure has been confirmed by chemical synthesis. PClP shows broad antimicrobial activity against Gram‐negative and Gram‐positive bacteria, protozoa, fungi, and yeast. In mammalian cells, PClP is known to act as a reversible and allosteric inhibitor of myosin 1c (Myo1c). Herein, we report that PCIP is a potent inhibitor of transforming growth factor‐β (TGF‐β)‐stimulated signaling. PCIP inhibits TGF‐β‐stimulated Smad2/3 phosphorylation and plasminogen activator inhibitor‐1 (PAI‐1) promoter activation with an IC50 of 0.1 μm in target cells (A549, HepG2, and Mv1Lu cells). In addition, PCIP attenuates TGF‐β‐stimulated expression of vimentin, N‐cadherin, and fibronectin and, thus, blocks TGF‐β‐induced epithelial to mesenchymal transition (EMT) in these cells. Furthermore, cell‐surface labeling and immunoblot analysis indicates that PCIP suppresses TGF‐β‐stimulated cellular responses by attenuating cell‐surface expression of the type II TGF‐β receptor through accelerating caveolae‐mediated internalization followed by primarily lysosome‐dependent degradation of the receptor, as demonstrated by sucrose density gradient analysis and immune fluorescence staining.
Cabazitaxel inhibits proliferation and potentiates the radiation response of U87MG glioblastoma cells
Authors: Neshasteh‐Riz Ali , Zeinizade Elham , Safa Majid , Mousavizadeh Kazem
Published: January 2018

Cabazitaxel is a second‐generation semisynthetic taxane. The recognized anti‐neoplastic effect of Cabazitaxel is cell cycle perturbation by inducing arrest at G2/M. Since glioblastoma tumors have a relatively high expression of P‐gp, it is encouraging to find a treatment that is effective against these tumors. This study was conducted to examine the radiosensitizing potential of Cabazitaxel against U87MG cells. In order to evaluate the effect of Cabazitaxel, cells were treated with different concentrations of the drug at different time intervals and then cytotoxicity and cell cycle were assessed using MTT and flow cytometry assays, respectively. Annexin/PI and real‐time polymerase chain reaction (PCR) assays were used to evaluate the extent of apoptosis. Cabazitaxel exerted a consistent G2/M arrest and resulted in a concentration‐ and time‐dependent toxicity. Cabazitaxel enhanced the cytotoxicity response of U87MG cells to radiation. Apoptosis increased following Cabazitaxel‐IR administration. At the same time, these results were further supported by apoptotic genes regulation. This study provides the first preclinical evidence supporting that Cabazitaxel can render U87MG cells more susceptible to the cytotoxicity of radiation and could potentially be administered in combination modalities as a promising cell cycle‐specific radiosensitizer for the future steps of in vivo evaluation.
Sphingomyelin in microdomains of the plasma membrane regulates amino acid‐stimulated mTOR signal activation
Authors: Zama Kota , Mitsutake Susumu , Okazaki Toshiro , Igarashi Yasuyuki
Published: January 2018

Sphingomyelin (SM) is required for cells to proliferate, but the reason is not fully understood. In order to asses this question, we employed a cell line, ZS, which lacks both SMS1 and SMS2, isolated from mouse embryonic fibroblasts in SMS1 and 2 double knockout mouse, and SMS1 or SMS2 re‐expressing cells, ZS/SMS1 or ZS/SMS2, respectively. We investigated regulation of SM in activating the mammalian target of rapamycin (mTOR) signal induced by essential amino acids (EAA), using these cells. EAA‐stimulated mTOR signal was more activated in ZS/SMS1 and ZS/SMS2 cells than in controls. Treatment with methyl‐b‐cyclodextrin dramatically inhibited the activation. Interestingly, we found that the expression of CD98, LAT‐1 and ASCT‐2, amino acid transporters concerned with mTOR activation, was down‐regulated in ZS cells. Transporters localized in microdomains and formed a functional complex. Our results indicate that SM affect proliferation through the transport of amino acids via SM‐enriched microdomains.
A novel homozygous mutation in the mannose phosphate isomerase gene causing congenital disorder of glycation and hyperinsulinemic hypoglycemia in an infant
Authors: Deeb Asma , Al Amoodi Abdulla
Published: January 2018

Key Clinical Message

We report a 4 years girl with congenital disorders of glycosylation (CDG) type Ib due to a novel homozygous mutation in MPI gene. She presented with diazoxide‐responsive hyperinsulinemic hypoglycemia. CDG should be considered in unexplained hypoglycemia particularly in consanguineous families. Diagnosis enables monitoring/prevention of disease comorbidities and early effective treatment.
Synergistic Hematite‐Fullerene Electron‐Extracting Layers for Improved Efficiency and Stability in Perovskite Solar Cells
Authors: Hou Qinzhi , Ren Jing , Chen Haijun , Yang Pan , Shao Qian , Zhao Min , Zhao Xiaochong , He Hongcai , Wang Ning , Luo Qiang , Guo Zhanhu
Published: January 2018

Hematite, α‐Fe2O3, is arising as a promising electron‐extraction material in perovskite solar cells, yet present α‐Fe2O3‐based perovskite solar cells still show unsatisfactory efficiencies owing to large charge recombination. In this contribution, phenyl‐C61‐butyric acid methyl ester (PCBM) and α‐Fe2O3 synergistically worked together as the electron transport layer (ETL) in planar heterojunction perovskite solar cells. The introduction of fullerene at the top of the α‐Fe2O3 ETL improved the crystallinity of CH3NH3PbI3 perovskite and facilitated electron extraction. As a consequence, a substantially retarded charge recombination largely boosted the short‐circuit current density and power conversion efficiency of perovskite solar cells. The optimized perovskite solar cells with α‐Fe2O3/PCBM ETL showed a competitive power conversion efficiency of 14.2 %, which is 20 % higher than that of pristine α‐Fe2O3‐based solar cells. Moreover, α‐Fe2O3/PCBM‐based perovskite solar cells exhibited improved stability compared to the pristine α‐Fe2O3‐based devices, retaining over 95 % of their initial values after 45 days storage in dark in humid air.
Nonparametric algorithm for identification of outliers in environmental data
Authors: Čampulová Martina , Michálek Jaroslav , Mikuška Pavel , Bokal Drago
Published: January 2018

Outliers that can significantly affect data analysis are frequently present in environmental data sets. Most methods suggested for the detection of outliers impose restrictions on the distribution of analysed variables. However, in many environmental areas, the observed variable is influenced by a lot of different factors and its distribution is often difficult to find or cannot be estimated. Therefore, an approach for the identification of outliers in environmental time series based on nonparametric statistical techniques is presented. The core principle of the algorithm is to smoothen the data using nonparametric regression with variable bandwidth and subsequently analyse the residuals by nonparametric statistical methods. In the case that the distribution of the analysed variable is normal an efficient statistical method based on normality assumptions is presented as well. The proposed procedure is applied for the identification of outliers in hourly concentrations of particulate matter and verified by simulations.
Chemoinformatic design of amphiphilic molecules for methane hydrate inhibition
Authors: Di Profio Pietro , Canale Valentino , Marvulli Francesca , Zappacosta Romina , Fontana Antonella , Siani Gabriella , Germani Raimondo
Published: January 2018

Cationic surfactants and other low molecular weight compounds are known to inhibit nucleation and agglomeration of methane hydrates. In particular, tetralkylammonium salts are kinetic hydrate inhibitors; ie, they reduce the rate of hydrate formation. This work relates to the in‐silico determination of structural features of molecules modulating methane hydrate formation, as found experimentally, and the prediction of novel structures to be tested as candidate inhibitors. Experimental data for each molecule are the amount of absorbed methane. By inserting these numerical values into a chemoinformatic model, it was possible to find a mutual correlation between structural features and inhibition properties. A maximum amount of information is extracted from the structural features and experimental variables, and a model is generated to explain the relationship therebetween. Chemometric analysis was performed by using the software package Volsurf+ with the aim of finding a primary correlation between surfactant structures and their properties. Experimental parameters (pressure, temperature, and concentration) were further processed through an optimization procedure.

A careful study of the chemometric analysis responses and the numerical descriptors of tested surfactants allowed to define the features of a good inhibitor, as far as the amount of absorbed gas is concerned. An external prediction is finally made to project external compounds, whose structures and critical micellar concentration are known, in a statistical model, to predict the inhibition properties of a particular molecule in advance of synthesis and testing. This method allowed to find novel amphiphilic molecules for testing as candidate inhibitors in flow‐assurance.
Exploring the Effect of Polypyridyl Ligands on the Anticancer Activity of Phosphorescent Iridium(III) Complexes: From Proteosynthesis Inhibitors to Photodynamic Therapy Agents
Authors: Pracharova Jitka , Vigueras Gloria , Novohradsky Vojtech , Cutillas Natalia , Janiak Christoph , Kostrhunova Hana , Kasparkova Jana , Ruiz José , Brabec Viktor
Published: January 2018

A series of five kinetically inert bis‐cyclometalated IrIII complexes of general formula [Ir(C^N)2(N^N)][PF6] [C^N=2‐phenyl‐1‐[4‐(trifluoromethyl)benzyl]‐1H‐benzo[d]imidazol‐κN,C; N^N=1,10‐phenanthroline (phen, 1), dipyrido[3,2‐d:2′,3′‐f]quinoxaline (dpq, 2), dipyrido[3,2‐a:2′,3′‐c]phenazine (dppz, 3), benzo[i]dipyrido[3,2‐a:2′,3′‐c]phenazine (dppn, 4), and dipyrido[3,2‐a:2′,3′‐c]phenazine‐10,11‐imidazolone (dppz‐izdo, 5)] were designed and synthesized to explore the effect of the degree of π conjugation of the polypyridyl ligand on their toxicity in cancer cells. We show that less‐lipophilic complexes 1 and 2 exhibit the highest toxicity [sub‐micromolar inhibitory concentration (IC50) values] in A2780, HeLa, and MCF‐7 cancer cells, and they are markedly more efficient than clinically used platinum drugs. It is noteworthy that the investigated Ir agents display the capability to overcome acquired and inherent resistance to conventional cisplatin (in A2780cisR and MCF‐7 cells, respectively). We demonstrate that the Ir complexes, unlike clinically used platinum antitumor drugs, do not kill cells through DNA‐damage response. Rather, they kill cells by inhibiting protein translation by targeting preferentially the endoplasmic reticulum. Our findings also reveal that the toxic effect of the Ir complexes can be significantly potentiated by irradiation with visible light (by more than two orders of magnitude). The photopotentiation of the investigated Ir complexes can be attributed to a marked increase (≈10–30‐fold) in intracellular reactive oxygen species. Collectively, these data highlight the functional diversity of antitumor metal‐based drugs and the usefulness of a mechanism‐based rationale for selecting candidate agents that are effective against chemoresistant tumors for further preclinical testing.
Prebiotic Chemistry of HCN Tetramerization by Automated Reaction Search
Authors: Nandi Surajit , Bhattacharyya Debankur , Anoop Anakuthil
Published: January 2018

HCN oligomerization is considered to be one of the important pathways in chemical evolution. Nucleobases, aminoacids, and many other complex organic molecules can evolve through this pathway. We report an explorative study based on an automated reaction search method that avoids the cognitive bias present when searching chemical reaction space. We discuss the chemical space of the HCN dimer in detail, and the important trimers and tetramers are discussed briefly. A component‐wise molecular‐fingerprint‐based methodology is proposed to identify molecular similarity. We present four different thermal routes to cis/trans‐2,3‐diaminomaleonitrile and 4‐amino‐1H‐imidazole‐5‐carbonitrile, which are important intermediates in prebiotic chemistry.
Synthesis and Properties of Triaminocyclopropenium Cation Based Ionic Liquids as Hypergolic Fluids
Authors: Jin Yunhe , Wang Binshen , Zhang Wenquan , Huang Shi , Wang Kangcai , Qi Xiujuan , Zhang Qinghua
Published: January 2018

A novel family of hydrophobic triaminocyclopropenium cation based ionic liquids have been synthesized, and their structures and physicochemical properties characterized by NMR and IR spectroscopy, elemental analysis, differential scanning calorimetry, and hypergolic tests. The experimental results showed that all of these ionic liquids exhibited the expected hypergolic reactivity with the oxidizer white fuming nitric acid. Among them, the hypergolic ionic liquid based on the cyanoimidazolylborohydride anion showed excellent integrated properties, including high decomposition temperature (194 °C), high density (0.95 g cm−3), moderate viscosity (44 MPa s), ultrafast ignition delay time (6 ms), and high specific impulse (301.9 s); this demonstrates its potential as an environmentally friendly alternative to toxic hydrazine derivatives.
Direct Dimethyl Ether Synthesis: Modelling of the Kinetics from Isothermal, Experimental Data
Authors: Henrich Till , Abeln Johannes , Betz Mathias
Published: January 2018

Die einstufige Synthese von Dimethylether (DME) stellt eine Prozessintensivierung dar. Aufgrund der hohen Exothermie der Reaktion ist die genaue Kenntnis der kinetischen Parameter notwendig. Als Katalysator wurde eine Mischung zweier kommerziell erhältlicher Katalysatoren eingesetzt. Die Experimente wurden bei 50 bar und von 220 bis 280 °C durchgeführt. Das isotherme Verhalten wurde durch Messung axialer Temperaturprofile verifiziert. Aus den experimentellen Daten konnten die kinetischen Parameter, unter Berücksichtigung von Thermodynamik und Realgasverhalten, berechnet werden.
Continuous Countercurrent Extractive Biocatalysis in Aqueous Surfactant Two‐Phase Systems
Authors: Ritter Eric , Smirnova Irina
Published: January 2018

To evaluate the possibility of performing extractive biocatalysis in continuous mode, the hydrolysis of penicillin G in a micellar solution containing the nonionic surfactant Tergitol NP‐7 was chosen as model system. While the product phenylacetic acid distributes into the micellar phase, 6‐aminopenicillanic acid moves preferably into the aqueous phase. The yield in the continuous multi‐step process was higher in comparison to equivalent batch systems. Overall, the results demonstrate the suitability of aqueous surfactant two‐phase systems for continuous biocatalytic reactive extraction processes.
Survival by Hispanic ethnicity among patients with cancer participating in SWOG clinical trials
Authors: Chavez‐MacGregor Mariana , Unger Joseph M. , Moseley Anna , Ramsey Scott D. , Hershman Dawn L.
Published: January 2018

BACKGROUND

Racial disparities in cancer outcomes have been described. To the authors' knowledge, it remains unclear whether patients of Hispanic ethnicity have better or worse survival outcomes. In the current study, the authors evaluated whether Hispanic participants in SWOG clinical trials had different survival outcomes compared with non‐Hispanics.

METHODS

Adult patients registered in SWOG phase 2/3 clinical trials between 1986 and 2012 were analyzed. Studies of similar histology and stage of disease were combined. Within each analysis, Kaplan‐Meier survival curves were generated to examine differences in outcome by ethnicity. Multivariate Cox regression was used to estimate the association between ethnicity and survival outcomes, controlling for major disease‐specific prognostic factors and demographic variables plus area‐level income and education to account for socioeconomic status.

RESULTS

A total of 29,338 patients registered to 38 trials were included; 5% of these patients were Hispanic. Hispanic patients were more likely to be younger and from areas of lower income and education (all P<.05). No differences in survival were observed across tumor types except in the patients with advanced stage prostate cancer, in whom the authors observed an association between Hispanic ethnicity and worse overall survival (hazard ratio [HR], 1.40; P = .006), progression‐free survival (HR, 1.36; P = .007), and cancer‐specific survival (HR, 1.42; P = .013). After adjusting for multiple comparisons, no differences in outcomes were noted.

CONCLUSIONS

Hispanic patients participating in SWOG trials who received uniform treatment and follow‐up were found to have similar survival outcomes compared with non‐Hispanic patients, with the single exception of those patients with advanced stage prostate cancer. The results of the current study demonstrate that Hispanic patients receiving uniform treatment and follow‐up have similar outcomes compared with non‐Hispanics. Cancer 2018;124:1760‐9. © 2018 American Cancer Society
Temporal trends in the risk of second primary cancers among survivors of adult‐onset cancers, 1980 through 2013: An Australian population‐based study
Authors: Ye Yuanzi , Otahal Petr , Wills Karen E. , Neil Amanda L. , Venn Alison J.
Published: January 2018

BACKGROUND

The authors' systematic review indicated an increasing trend in the risk of second primary cancers (SPCs) from the 1980s to 2000 when considering studies from the United States and Australia. It is uncertain whether this trend has continued to increase since 2000.

METHODS

The current study was a population‐based study of 51,802 individuals with adult‐onset cancers identified in the Tasmanian Cancer Registry. Patients with a first cancer diagnosis made between 1980 and 2009 were followed up to December 2013. SPC risks were quantified using standardized incidence ratios (SIRs) and absolute excess risks (AERs). Trends in SPC risk were assessed using multivariable Poisson models.

RESULTS

With a median follow‐up of 4.8 years (mean, 6.9 years), a total of 5339 SPCs were observed. The SIRs for any SPC increased from 0.98 (95% confidence interval, 0.90‐1.07) after a first cancer diagnosis in 1980 through 1984 to 1.12 (95% confidence interval, 1.05‐1.20) in 2005 through 2009. In multivariable Poisson models accounting for patient sex, age at the time of the first cancer diagnosis, follow‐up interval, and first cancer type, the trend in SIRs increased significantly from 1980 through 2009 for all SPCs (P for trend <.001) and for specific SPCs of the head and neck, lung, digestive tract, and prostate (all P for trend <.05). From 2000 onward, the AER for specific SPCs after specific first cancers was highest for prostate cancer after first cancers of the urinary tract (AER, 54.3 per 10,000 person‐years).

CONCLUSIONS

In Tasmania, the risk of SPCs among survivors of adult‐onset cancers has increased with periods of first cancer diagnosis from 1980 through 2009. Increased cancer screening and improved medical imaging may have contributed to the greater risk in recent years. Cancer 2018;124:1808‐18. © 2018 American Cancer Society
Large‐Scale Behavior of Three‐Dimensional Continuous Phase Coexistence Models
Authors: Hairer Martin , Xu Weijun
Published: January 2018

We study a class of three‐dimensional continuous phase coexistence models, and show that, under different symmetry assumptions on the potential, the large‐scale behavior of such models near a bifurcation point is described by the dynamical models for p ∊ {2,3,4}. This result is specific to space dimension 3 and does not hold in dimension 2. © 2018 Wiley Periodicals, Inc.
A general framework for big data knowledge discovery and integration
Authors: Wang Xinyang , Qi Deyu , Lin Weiwei , Yu MinCong , Zheng Zhishuo , Zhou Naqin , Chen Pengguang
Published: January 2018

Data structure description, conceptual modeling, and logic reasoning for knowledge discovery are three critical factors for the integration of information with heterogeneity. In particular, technologies of NoSQL databases and Internet of Things raise an urgent requirement for a uniform expression of heterogeneous data, and little attention has been paid to researches on the integration of NoSQL databases with traditional data models, as well as the semantic description of big data. To tackle these problems, in this paper, a concept‐and‐relation‐oriented grid data model called GODM model is first proposed based on the definitions of Monad, Compounder, Relation, etc. Then, the GODM model is utilized to uniformly describe traditional data models and NoSQL data models, which eliminates structure differences of heterogeneous data. Next, based on the GODM relation mechanism, an extendable semantic system is built up by choosing SHOIQ(D) description logic as the example to establish the correspondence with GODM grammar subset, providing a fundamental support for semantic integration and knowledge discovery of heterogeneous data. After that, comprehensive comparisons with GODM and other models are made, especially the distinctions between GODM and OWL on the aspects of relation mechanism, hybrid schema, description logic, grammatical constructors, etc. Besides, experimental evaluations and analyses on time and space efficiencies of some primary common data models are conducted after the proposal of a general evaluation model, with the results showing that the GODM model has great advantage on properties of expressiveness, flexibility, etc, particularly time and space efficiency. In summary, the GODM model describes heterogeneous data from both aspects of data structure and semantic relationship and realizes a hybrid schema reconciling the schemaful and schemaless data models, making it especially suitable for dynamic data integration and knowledge discovery from big data models.
Functional trade‐offs and the phylogenetic dispersion of seed traits in a biodiversity hotspot of the Mountains of Southwest China
Authors: Chen Kai , Burgess Kevin S. , Yang Xiang‐Yun , Luo Ya‐Huang , Gao Lian‐Ming , Li De‐Zhu
Published: January 2018

The diversity of traits associated with plant regeneration is often shaped by functional trade‐offs where plants typically do not excel at every function because resources allocated to one function cannot be allocated to another. By analyzing correlations among seed traits, empirical studies have shown that there is a trade‐off between seedling development and the occupation of new habitats, although only a small range of taxa have been tested; whether such trade‐off exists in a biodiverse and complex landscape remains unclear. Here, we amassed seed trait data of 1,119 species from a biodiversity hotspot of the Mountains of Southwest China and analyzed the relationship between seed mass and the number of seeds and between seed mass and time to germination. Our results showed that seed mass was negatively correlated with seed number but positively correlated with time to germination. The same trend was found regardless of variation in life‐form and phylogenetic conservatism. Furthermore, the relation between seed mass and other seed traits was randomly dispersed across the phylogeny at both the order and family levels. Collectively, results suggest that there is a functional trade‐off between seedling development and new habitat occupation for seed plants in this region. Larger seeds tend to produce fewer seedlings but with greater fitness compared to those produced by smaller seeds, whereas smaller seeds tend to have a larger number of seeds that germinate faster compared to large‐seeded species. Apart from genetic constraints, species that produce large seeds will succeed in sites where resource availability is low, whereas species with high colonization ability (those that produce a high number of seeds per fruit) will succeed in new niches. This study provides a mechanistic explanation for the relatively high levels of plant diversity currently found in a heterogeneous region of the Mountains of Southwest China.
Differences among six woody perennials native to Northern Europe in their level of genetic differentiation and adaptive potential at fine local scale
Authors: Lobo Albin , Hansen Jon Kehlet , Hansen Lars Nørgaard , Dahl Kjær Erik
Published: January 2018

The ability of perennial species to adapt their phenology to present and future temperature conditions is important for their ability to retain high fitness compared to other competing plant species, pests, and pathogens. Many transplanting studies with forest tree species have previously reported substantial genetic differentiation among populations within their native range. However, the question of “how local is local” is still highly debated in conservation biology because studies on genetic patterns of variation within and among populations at the local scale are limited and scattered. In this study, we compare the level of genetic differentiation among populations of six different perennial plant species based on their variation in spring flushing. We assess the level of additive genetic variation present within the local population. For all six species, we find significant differentiation among populations from sites with mean annual temperature ranging between 7.4°C and 8.4°C. The observed variation can only be partly explained by the climate at the site of origin. Most clear relationship between early flushing and higher average spring temperature is observed for the three wind‐pollinated species in the study, while the relations are much less clear for the three insect‐pollinated species. This supports that pollination system can influence the balance between genetic drift and natural selection and thereby influence the level of local adaptation in long‐lived species. On the positive side, we find that the native populations of woody plant species have maintained high levels of additive genetic variation in spring phenology, although this also differs substantially among the six studied species.
Wrong, but useful: regional species distribution models may not be improved by range‐wide data under biased sampling
Authors: El‐Gabbas Ahmed , Dormann Carsten F.
Published: January 2018

Species distribution modeling (SDM) is an essential method in ecology and conservation. SDMs are often calibrated within one country's borders, typically along a limited environmental gradient with biased and incomplete data, making the quality of these models questionable. In this study, we evaluated how adequate are national presence‐only data for calibrating regional SDMs. We trained SDMs for Egyptian bat species at two different scales: only within Egypt and at a species‐specific global extent. We used two modeling algorithms: Maxent and elastic net, both under the point‐process modeling framework. For each modeling algorithm, we measured the congruence of the predictions of global and regional models for Egypt, assuming that the lower the congruence, the lower the appropriateness of the Egyptian dataset to describe the species' niche. We inspected the effect of incorporating predictions from global models as additional predictor (“prior”) to regional models, and quantified the improvement in terms of AUC and the congruence between regional models run with and without priors. Moreover, we analyzed predictive performance improvements after correction for sampling bias at both scales. On average, predictions from global and regional models in Egypt only weakly concur. Collectively, the use of priors did not lead to much improvement: similar AUC and high congruence between regional models calibrated with and without priors. Correction for sampling bias led to higher model performance, whatever prior used, making the use of priors less pronounced. Under biased and incomplete sampling, the use of global bats data did not improve regional model performance. Without enough bias‐free regional data, we cannot objectively identify the actual improvement of regional models after incorporating information from the global niche. However, we still believe in great potential for global model predictions to guide future surveys and improve regional sampling in data‐poor regions.
Single‐nucleotide polymorphism discovery and panel characterization in the African forest elephant
Authors: Bourgeois Stéphanie , Senn Helen , Kaden Jenny , Taggart John B. , Ogden Rob , Jeffery Kathryn J. , Bunnefeld Nils , Abernethy Katharine , McEwing Ross
Published: January 2018

The continuing decline in forest elephant (Loxodonta cyclotis) numbers due to poaching and habitat reduction is driving the search for new tools to inform management and conservation. For dense rainforest species, basic ecological data on populations and threats can be challenging and expensive to collect, impeding conservation action in the field. As such, genetic monitoring is being increasingly implemented to complement or replace more burdensome field techniques. Single‐nucleotide polymorphisms (SNPs) are particularly cost‐effective and informative markers that can be used for a range of practical applications, including population census, assessment of human impact on social and genetic structure, and investigation of the illegal wildlife trade. SNP resources for elephants are scarce, but next‐generation sequencing provides the opportunity for rapid, inexpensive generation of SNP markers in nonmodel species. Here, we sourced forest elephant DNA from 23 samples collected from 10 locations within Gabon, Central Africa, and applied double‐digest restriction‐site‐associated DNA (ddRAD) sequencing to discover 31,851 tags containing SNPs that were reduced to a set of 1,365 high‐quality candidate SNP markers. A subset of 115 candidate SNPs was then selected for assay design and validation using 56 additional samples. Genotyping resulted in a high conversion rate (93%) and a low per allele error rate (0.07%). This study provides the first panel of 107 validated SNP markers for forest elephants. This resource presents great potential for new genetic tools to produce reliable data and underpin a step‐change in conservation policies for this elusive species.
Evaluation of an individualized dose titration regimen of patiromer to prevent hyperkalaemia in patients with heart failure and chronic kidney disease
Authors: Pitt Bertram , Bushinsky David A. , Kitzman Dalane W. , Ruschitzka Frank , Metra Marco , Filippatos Gerasimos , Rossignol Patrick , Du Mond Charles , Garza Dahlia , Berman Lance , Lainscak Mitja ,   on behalf of the Patiromer‐204 Investigators
Published: January 2018

Aims

Hyperkalaemia risk precludes optimal renin–angiotensin–aldosterone system inhibitor use in patients with heart failure (HF), particularly those with chronic kidney disease (CKD). Patiromer is a sodium‐free, non‐absorbed potassium (K+)‐binding polymer approved for the treatment of hyperkalaemia. In PEARL‐HF, patiromer 25.2 g (fixed dose) prevented hyperkalaemia in HF patients with or without CKD initiating spironolactone. The current study evaluated the effectiveness of a lower starting dose of patiromer (16.4 g/day) followed by individualized titration in preventing hyperkalaemia and hypokalaemia when initiating spironolactone.

Methods and results

This open‐label 8‐week study enrolled 63 patients with CKD, serum K+ 4.3–5.1 mEq/L, and chronic HF, who, based on investigator opinion, should receive spironolactone. Eligible patients started spironolactone 25 mg/day and patiromer 16.8 g/day (divided into two doses), with patiromer titrated to maintain serum K+ 4.0–5.1 mEq/L. Mean (standard deviation) serum K+ was 4.78 (0.51) mEq/L at baseline; weekly values were 4.48–4.70 mEq/L during treatment. Serum K+ of 3.5–5.5 mEq/L at the end of study treatment (primary endpoint) was achieved by 57 (90.5%) patients; 53 (84.1%) had serum K+ 4.0–5.1 mEq/L. One patient (1.6%) developed hypokalaemia, and two patients (3.2%) developed hypomagnesaemia. Spironolactone was increased to 50 mg/day in all patients; 43 (68%) patients required one or more patiromer dose titration. Adverse events (AEs) occurred in 36 (57.1%) patients, with a low rate of discontinuations [four (6.3%) patients]. The most common AE was mild to moderate abdominal discomfort [four (6.3%) patients].

Conclusions

In this open‐label study, patiromer 16.8 g/day followed by individualized titration maintained serum K+ within the target range in the majority of patients with HF and CKD, all of whom were uptitrated to spironolactone 50 mg/day, patiromer was well tolerated, with a low incidence of hyperkalaemia, hypokalaemia, and hypomagnesaemia.