bluuebunny/crossref_metadata_2025 huggingface dataset:
Loop-Mediated Isothermal Amplification for Detection of Endogenous Sad1 Gene in Cotton: An Internal Control for Rapid Onsite GMO Testing
Authors: Singh Monika , Bhoge Rajesh K , Randhawa Gurinderjit
Published: April 2018

Background: Confirming the integrity of seed samples in powdered form is important prior to conducting a genetically modified organism (GMO) test. Rapid onsite methods may provide a technological solution to check for genetically modified (GM) events at ports of entry. In India, Bt cotton is the commercialized GM crop with four approved GM events; however, 59 GM events have been approved globally. GMO screening is required to test for authorized GM events. The identity and amplifiability of test samples could be ensured first by employing endogenous genes as an internal control. Objective: A rapid onsite detection method was developed for an endogenous reference gene, stearoyl acyl carrier protein desaturase (Sad1) of cotton, employing visual and real-time loop-mediated isothermal amplification (LAMP). Methods: The assays were performed at a constant temperature of 63°C for 30 min for visual LAMP and 62ºC for 40 min for real-time LAMP. Positive amplification was visualized as a change in color from orange to green on addition of SYBR® Green or detected as real-time amplification curves. Results: Specificity of LAMP assays was confirmed using a set of 10 samples. LOD for visual LAMP was up to 0.1%, detecting 40 target copies, and for real-time LAMP up to 0.05%, detecting 20 target copies. Conclusions: The developed methods could be utilized to confirm the integrity of seed powder prior to conducting a GMO test for specific GM events of cotton. Highlights: LAMP assays for the endogenous Sad1 gene of cotton have been developed to be used as an internal control for onsite GMO testing in cotton.
Study on the Role of Video Educational Games with a Linguistic Approach in English Language Education of the 2nd Grade High School Students
Authors: Jalalian Farzad
Published: April 2018

The inability of English language learners to recall English concepts is a major challenge faced by teachers. This paper aims to determine the effectiveness of video educational games with a linguistic approach in English language education of the 2nd grade high school students. This is an applied and quasi-experimental study conducted in 2016. For the purpose of this study, we divided the participants into test and control groups and omitted the impacts of covariate (pretest scores measured before execution of any test on the learners). The statistical population consists of 90 students, divided into three groups each consisting of 30 students. Due to the long process of the research, we used availability sampling method in order to minimize the drop in the number of participants. The data was analyzed by SPSS and ANCOVA. The results of this study confirmed that a significant difference exists between English language recalling ability of 2nd grade high school students in test and control groups who are provided with video educational games with and without English language concepts respectively. We concluded that video educational games play an effective role in English language recalling ability of the students. Therefore, it is recommended that video educational games be used for enriching the leisure times of English learners.
Advances in the cellular structural biology of nucleic acids
Authors: Giassa Ilektra‐Chara , Rynes Jan , Fessl Tomas , Foldynova‐Trantirkova Silvie , Trantirek Lukas
Published: April 2018

Conventional biophysical and chemical biology approaches for delineating relationships between the structure and biological function of nucleic acids (NAs) abstract NAs from their native biological context. However, cumulative experimental observations have revealed that the structure, dynamics and interactions of NAs might be strongly influenced by a broad spectrum of specific and nonspecific physical‐chemical environmental factors. This consideration has recently sparked interest in the development of novel tools for structural characterization of NAs in the native cellular context. Here, we review the individual methods currently being employed for structural characterization of NA structure in a native cellular environment with a focus on recent advances and developments in the emerging fields of in‐cell NMR and electron paramagnetic resonance spectroscopy and in‐cell single‐molecule FRET of NAs.
Assessment of ligand binding at a site relevant to SOD1 oxidation and aggregation
Authors: Manjula Ramu , Wright Gareth S. A. , Strange Richard W. , Padmanabhan Balasundaram
Published: April 2018

Cu/Zn superoxide dismutase‐1 (SOD1) mutations are causative for a subset of amyotrophic lateral sclerosis (ALS) cases. These mutations lead to structural instability, aggregation and ultimately motor neuron death. We have determined crystal structures of SOD1 in complex with a naphthalene‐catechol‐linked compound which binds with low micro‐molar affinity to a site important for oxidative damage‐induced aggregation. SOD1 Trp32 oxidation is indeed significantly inhibited by ligand binding. Our work shows how compound linking can be applied successfully to ligand interactions on the SOD1 surface to generate relatively good binding strength. The ligand, positioned in a region important for SOD1 fibrillation, offers the possibility that it, or a similar compound, could prevent the abnormal self‐association that drives SOD1 toxicity in ALS.
The Sensitivity of Future Ocean Oxygen to Changes in Ocean Circulation
Authors: Palter Jaime B. , Trossman David S.
Published: April 2018

A decline in global ocean oxygen concentrations has been observed over the twentieth century and is predicted to continue under future climate change. We use a unique modeling framework to understand how the perturbed ocean circulation may influence the rate of ocean deoxygenation in response to a doubling of atmospheric CO2and associated global warming. These simulations suggest that much of the oxygen decline under warming is due to changes in ocean mixing and O2solubility. However, in our model, the large‐scale ocean circulation response to CO2doubling slows the pace of future oxygen loss by 20%. Oxygen concentration changes are most sensitive to circulation perturbations in the Southern Ocean. A small stabilizing effect on oxygen arises from the reduction of export productivity and associated respiration in the ocean interior. A slowdown of the Atlantic Meridional Overturning Circulation increases the residence time of the deep Atlantic Ocean but does not cause a major oxygen decline at the time of CO2doubling, because respiration is slow at these depths. The simulations show that the decrease in O2solubility associated with ocean warming is greater than the realized decrease in preformed O2, particularly at high latitudes, where circulation changes reduce the proportion of undersaturated waters sinking into the ocean interior. Finally, in the tropical Pacific oxygen minimum zone, a predicted weakening of the Walker Circulation slows the regional upwelling of nutrients and the associated export productivity and respiration, preventing the intensification of hypoxia there.
Sideband Asymmetry in Ionospheric Cross Modulation
Authors: de Boer P. T. , Vester M.
Published: April 2018

We study the phenomenon of ionospheric cross modulation between LF/MF broadcast stations using modern reception techniques, allowing us to see details that were not seen with the analog receiving techniques from the 1940s. We show experimentally that the sidebands of the transferred modulation are often asymmetric, in amplitude and/or phase. We give qualitative and quantitative explanations for this asymmetry, based on taking contributions from outside the first Fresnel zone into account. The asymmetry is found to be strongest for longer paths, lower carrier frequency, and disturbing transmitter closer to the receiver.
The Prismatic Topography of Pinctada maxima Shell Retains Stem Cell Multipotency and Plasticity In Vitro
Authors: Alakpa Enateri V. , Saeed Anwer , Chung Peter , Riehle Mathis O. , Gadegaard Nikolaj , Dalby Matthew J. , Cusack Maggie
Published: April 2018

The shell of the bivalve mollusc Pinctada maxima is composed of the calcium carbonate polymorphs calcite and aragonite (nacre). Mother‐of‐pearl, or nacre, induces vertebrate cells to undergo osteogenesis and has good osteointegrative qualities in vivo. The calcite counterpart, however, is less researched in terms of the response of vertebrate cells. This study shows that isolation of calcite surface topography from the inherent chemistry allows viable long‐term culture of bone marrow derived mesenchymal stem cells (MSCs). Self‐renewal is evident from the increased gene expression of the self‐renewal markers CD63, CD166, and CD271 indicating that cells cultured on the calcite topography maintain their stem cell phenotype. MSCs also retain their multipotency and can undergo successful differentiation into osteoblasts and adipocytes. When directed to adipogenesis, MSCs cultured on prism replicas are more amenable to differentiation than MSCs cultured on tissue culture polystyrene indicating a higher degree of plasticity in MSCs growing on calcite P. maxima prismatic topography. The study highlights the potential of the calcite topography of P. maxima as a biomimetic design for supporting expansion of MSC populations in vitro, which is of fundamental importance if it meets the demands for autologous MSCs for therapeutic use.
Sulfonimidamides: Synthesis and Applications in Preparative Organic Chemistry
Authors: Nandi Ganesh Chandra , Arvidsson Per I.
Published: April 2018

During the last one and half decades, chemists within vastly different areas of science have witnessed a rising interest in chemical matters incorporating the sulfonimidamide functional group. New synthetic routes to sulfonimidamides have been reported, and the utility of these products has been demonstrated in synthetic, medicinal, agrochemical, and material science applications. In this review, we described the synthesis of sulfonimidamide and their applications in synthetic organic chemistry.

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A new model for simulating particle transport in a low‐viscosity fluid for fluid‐driven fracturing
Authors: Hu Xiaodong , Wu Kan , Song Xianzhi , Yu Wei , Tang Jizhou , Li Gensheng , Shen Zhonghou
Published: April 2018

Fluid‐driven fracture (i.e., Hydraulic fracturing) is an important way to stimulate the well productivity in the development of unconventional reservoirs. A low‐viscosity fluid called slickwater is widely used in the unconventional fracturing. It is a big challenge to simulate the particle (or proppant) transport in the low‐viscosity fluid in a field‐scale fracture. A new model to simulate particle transport in the low‐viscosity fluid in a field‐scale fracture is developed. First, a new parameter is defined, called the rate of proppant bed wash‐out, by which we incorporated the mechanism of proppant bed wash‐out into Eulerian‐Eulerian proppant transport model. Second, we proposed a novel way to consider the effect of proppant settling on the proppant concentration in the upper layer (or suspending layer) to accurately simulate the proppant transport. Additionally, a dimension reduction strategy was used to make the model quickly solved. Our simulation results were compared with published experimental data and they were consistent. After validation, the effect of fluid viscosity, injection rate, fracture height, and proppant concentration on the proppant distribution in a fracture is investigated. This study provides a new model to simulate particle transport. Meanwhile, it gives critical insights into understanding particle transport in the field‐scale fracture. © 2018 American Institute of Chemical EngineersAIChE J, 64: 3542–3552, 2018
A study on the micromixing performance in microreactors for polymer solutions
Authors: Zha Li , Pu Xin , Shang Minjing , Li Guangxiao , Xu Wenhua , Lu Qinghua , Su Yuanhai
Published: April 2018

Microreactors are widely applied for various polymerization processes to produce polymers with controlled molecular weight and structures. In this work, the mixing of polymer solutions in capillary microreactors was investigated with the aid of the biazo‐coupling reaction system and high‐speed camera. A smaller inner diameter, a higher Dean number and a lower Torsion number could promote the micromixing performance in microreactors. Unlike the mixing of Newtonian fluids in microreactors or micromixers, the mixing of polymer solutions follows different mechanisms and it is more difficult to reach homogeneous condition. However, the good micromixing performance in capillary microreactor systems for polymer solutions still could be obtained with high shear rates and long enough capillary length at relatively high correlated Reynolds numbers (NRe > 29). Furthermore, the micromixing time in the capillary microreactors was evaluated based on a modified stretching efficiency model and its value was in the range of 0.1–8.0 ms. © 2018 American Institute of Chemical Engineers AIChE J, 64: 3479–3490, 2018
Modeling of asphaltene and water associations in petroleum reservoir fluids using cubic‐plus‐association EOS
Authors: Jia Wenlong , Okuno Ryosuke
Published: April 2018

Asphaltene is a group of complex compounds commonly present in petroleum reservoir fluids. It is conceivable that asphaltenes strongly interact with water through hydrogen bonding, affecting phase behavior of water/oil mixtures with/without forming an asphaltene‐rich phase. In this research, the cubic‐plus‐association equation of state (CPA EOS) is applied to multiphase behavior resulting from self‐ and cross‐associations of asphaltenes and water in petroleum fluids. This article also presents a new correlation for binary interaction parameters for water with n‐alkanes for the CPA EOS by using three‐phase data for water/n‐alkane binaries. A method is proposed to characterize mixtures of asphaltene‐containing oil with water using the CPA EOS. Results show that the CPA EOS can represent multiphase behavior for water/oil mixtures with up to four equilibrium phases: asphaltene‐rich, solvent‐rich, aqueous, and vapor phases. Case studies include bitumen/water mixtures, involving asphaltene‐water emulsion, water solution in bitumen, and their continuous transition with varying temperature. © 2018 American Institute of Chemical Engineers AIChE J, 64: 3429–3442, 2018
The role of diversification in community assembly of the oaks (QuercusL.) across the continental U.S.
Authors: Cavender‐Bares Jeannine , Kothari Shan , Meireles José Eduardo , Kaproth Matthew A. , Manos Paul S , Hipp Andrew L.
Published: April 2018

Premise of the Study

Evolutionary and biogeographic history, including past environmental change and diversification processes, are likely to have influenced the expansion, migration, and extinction of populations, creating evolutionary legacy effects that influence regional species pools and the composition of communities. We consider the consequences of the diversification process in shaping trait evolution and assembly of oak‐dominated communities throughout the continental United States (U.S.).

Methods

Within the U.S. oaks, we tested for phylogenetic and functional trait patterns at different spatial scales, taking advantage of a dated phylogenomic analysis of American oaks and the U.S. Forest Service (USFS) Forest Inventory and Analysis (FIA).

Key Results

We find (1) phylogenetic overdispersion at small grain sizes throughout the U.S. across all spatial extents and (2) a shift from overdispersion to clustering with increasing grain sizes. Leaf traits have evolved in a convergent manner, and these traits are clustered in communities at all spatial scales, except in the far west, where species with contrasting leaf types co‐occur.

Conclusions

Our results support the hypotheses that (1) interspecific interactions were important in parallel adaptive radiation of the genus into a range of habitats across the continent and (2) that the diversification process is a critical driver of community assembly. Functional convergence of complementary species from distinct clades adapted to the same local habitats is a likely mechanism that allows distantly related species to coexist. Our findings contribute to an explanation of the long‐term maintenance of high oak diversity and the dominance of the oak genus in North America.
A probiotic modulates the microbiome and immunity in multiple sclerosis
Authors: Tankou Stephanie K. , Regev Keren , Healy Brian C. , Tjon Emily , Laghi Luca , Cox Laura M. , Kivisäkk Pia , Pierre Isabelle V. , Hrishikesh Lokhande , Gandhi Roopali , Cook Sandra , Glanz Bonnie , Stankiewicz James , Weiner Howard L.
Published: April 2018

Objective

Effect of a probiotic on the gut microbiome and peripheral immune function in healthy controls and relapsing‐remitting multiple sclerosis (MS) patients.

Methods

MS patients (N = 9) and controls (N = 13) were orally administered a probiotic containing Lactobacillus, Bifidobacterium, and Streptococcus twice‐daily for two months. Blood and stool specimens were collected at baseline, after completion of the 2‐month treatment, and 3 months after discontinuation of therapy. Frozen peripheral blood mononuclear cells (PBMCs) were used for immune cell profiling. Stool samples were used for 16S rRNA profiling and metabolomics.

Results

Probiotic administration increased the abundance of several taxa known to be depleted in MS such as Lactobacillus. We found that probiotic use decreased the abundance of taxa previously associated with dysbiosis in MS, including Akkermansia and Blautia. Predictive metagenomic analysis revealed a decrease in the abundance of several KEGG (Kyoto Encyclopedia of Genes and Genomes) pathways associated with altered gut microbiota function in MS patients, such as methane metabolism, following probiotic supplementation. At the immune level, probiotic administration induced an anti‐inflammatory peripheral immune response characterized by decreased frequency of inflammatory monocytes, decreased mean fluorescence intensity (MFI) of CD80 on classical monocytes, as well as decreased human leukocyte antigen (HLA) D related MFI on dendritic cells. Probiotic administration was also associated with decreased expression of MS risk allele HLA‐DQA1 in controls. Probiotic‐induced increase in abundance of Lactobacillus and Bifidobacterium was associated with decreased expression of MS risk allele HLA.DPB1 in controls.

Interpretation

Our results suggest that probiotics could have a synergistic effect with current MS therapies. Ann Neurol 2018
Wood‐Derived Ultrathin Carbon Nanofiber Aerogels
Authors: Li Si‐Cheng , Hu Bi‐Cheng , Ding Yan‐Wei , Liang Hai‐Wei , Li Chao , Yu Zi‐You , Wu Zhen‐Yu , Chen Wen‐Shuai , Yu Shu‐Hong
Published: April 2018

Carbon aerogels with 3D networks of interconnected nanometer‐sized particles exhibit fascinating physical properties and show great application potential. Efficient and sustainable methods are required to produce high‐performance carbon aerogels on a large scale to boost their practical applications. An economical and sustainable method is now developed for the synthesis of ultrathin carbon nanofiber (CNF) aerogels from the wood‐based nanofibrillated cellulose (NFC) aerogels via a catalytic pyrolysis process, which guarantees high carbon residual and well maintenance of the nanofibrous morphology during thermal decomposition of the NFC aerogels. The wood‐derived CNF aerogels exhibit excellent electrical conductivity, a large surface area, and potential as a binder‐free electrode material for supercapacitors. The results suggest great promise in developing new families of carbon aerogels based on the controlled pyrolysis of economical and sustainable nanostructured precursors.
Urbanising the Rural: Reflections on India's National Rurban Mission
Authors: Singh Chandni , Rahman Andaleeb
Published: April 2018

India's development trajectory is marked by growing economic prosperity but high inequality, which often exacerbates the existing rural–urban divide. One of the current policy instruments to address this divide is the National Rurban Mission, which aims to improve infrastructure and service provision, facilitate regional development and attract investment in rural areas. Against the backdrop of growing rural unrest on one hand and emerging evidence of unsustainable development in the urban on the other, we examine the National Rural Mission and its discursive underpinnings. We find that while the mission and its stated aims are a promising step to improve regional development, its focus on ‘smart villages’ and seeing urbanisation as the only development model, undermines the strengths and challenges in rural India. We highlight ways in which the mission can avoid some past pitfalls of development interventions in India while strengthening its mandate of facilitating inclusive regional development.
Immunolocalization of G Protein‐Coupled Estrogen Receptor in the Pig Epididymis
Authors: Malivindi Rocco , Aquila Saveria , Rago Vittoria
Published: April 2018

The presence of estrogen in the genital ducts of different mammalian species has been extensively studied and the estrogen influence on the functional activity of the male genital tract has been hypothesized. Conversely, very few data have been reported on pig excurrent ducts: the localization of classical estrogen receptors (ERα and ERβ) is scarcely known, while the expression of the G protein‐coupled receptor (GPER1), a membrane estrogen receptor, is still unknown in pig. The aim of the present study was to evaluate GPER1 expression in the different regions of the mature pig epididymis, using immunohistochemistry, western blot and RT‐PCR analyses. The results showed that GPER1 is mainly expressed in the epithelial cells of the corpus epididymis compared to the caput and the cauda, while muscle cells are moderately immunostained and stromal cells are unstained. The presence of GPER1 was confirmed by Western blot and RT‐PCR analyses. In our study, we have demonstrated for the first time the GPER1 expression in male porcine epididymis, revealing a new mediator of estrogen signaling at this site. In conclusion, these new data suggest that estrogen action via GPER1 may contribute to sperm maturation in the corpus and sperm protection/storage in the cauda. Interestingly, the presence of GPER1 in the muscle layer may be indicative of a possible GPER1 involvement in the estrogen regulation of duct contractility. Anat Rec, 2018. © 2018 Wiley Periodicals, Inc.
CCL21 as a Potential Serum Biomarker for Pulmonary Arterial Hypertension in Systemic Sclerosis
Authors: Hoffmann‐Vold Anna‐Maria , Hesselstrand Roger , Fretheim Håvard , Ueland Thor , Andreassen Arne K. , Brunborg Cathrine , Palchevskiy Vyacheslav , Midtvedt Øyvind , Garen Torhild , Aukrust Pål , Belperio John A. , Molberg Øyvind
Published: April 2018

Objective

Systemic sclerosis (SSc) is a major cause of pulmonary arterial hypertension (PAH). Murine models indicate key roles for chemokines CCL19 and CCL21 and their receptor CCR7 in lung inflammation leading to PAH. The objective of this study was to assess the chemokine CCL19–CCL21 axis in patients with SSc‐related PAH.

Methods

Serum samples obtained from 2 independent prospective SSc cohorts (n = 326), patients with idiopathic PAH (n = 12), and healthy control subjects (n = 100) were analyzed for CCL19/CCL21 levels, by enzyme‐linked immunosorbent assay. The levels were defined as either high or low, using the mean + 2 SD value in controls as the cutoff value. Risk stratification at the time of PAH diagnosis and PAH‐related events were performed. Descriptive and Cox regression analyses were conducted.

Results

CCL21 levels were higher in patients with SSc compared with controls and were elevated prior to the diagnosis of PAH. PAH was more frequent in patients with high CCL21 levels (≥0.4 ng/ml) than in those with low CCL21 levels (33.3% versus 5.3% [P < 0.001]). In multivariate analyses, CCL21 was associated with PAH (hazard ratio [HR] 5.1, 95% CI 2.39–10.76 [P < 0.001]) and occurrence of PAH‐related events (HR 4.7, 95% CI 2.12–10.46, P < 0.001). Risk stratification at the time of PAH diagnosis alone did not predict PAH‐related events. However, when risk at diagnosis was combined with high or low CCL21 level, there was a significant predictive effect (HR 1.3, 95% CI 1.03–1.60 [P = 0.027]). A high CCL21 level was associated with decreased survival (P < 0.001).

Conclusion

CCL21 appears to be a promising marker for predicting the risk of SSc‐related PAH and PAH progression. CCL21 may be part of a dysregulated immune pathway linked to the development of lung vascular damage in SSc.
A dual‐label time‐resolved fluorescence immunoassay for the simultaneous determination of carcinoembryonic antigen and squamous cell carcinoma antigen
Authors: Mao Qian , Liu Xiaohong , Chen CuiCui , Ye Jingwen , Liang Huankun , Li Binxian , Sun Xinyi , Sun Lin , Sun Yuman , Mu Xiaomei , Li Laiqing
Published: April 2018

Among women worldwide, cervical cancer is the second‐most common cancer, and cervical smears and DNA detection have low sensitivity or are too expensive. The concentrations of carcinoembryonic antigen (CEA) and squamous cell carcinoma (SCC) in the serum were detected using a sandwich immunoassay. The CEA and SCC in the serum were captured by anti‐CEA and anti‐SCC antibodies. After combining other anti‐CEA‐ and anti‐SCC‐labeled antibodies with europium (III) (Eu3+) and samarium (III) (Sm3+) chelates, CEA and SCC were detected with time‐resolved fluorometry (TRF). The linear correlation coefficients (R2) of the CEA and SCC standard curves were 0.9997 and 0.9997, respectively. The minimum detection level for CEA was 1.15 ng/mL (the linear dynamic range was 3.24–543.67 ng/mL), and the average recovery was 100.83%. The sensitivity for SCC detection was 0.54 ng/mL (the linear dynamic range was 2.47–96.58 ng/mL), and the average recovery was 101.02%. High R2 between the results of commercial assays and this method were obtained (R2 = 0.9983 for CEA, R2 = 0.9878 for SCC). These findings indicated that the dual‐label TRFIA invented in this study has high sensitivity, accuracy, and specificity in clinical analysis, which indicates that this method could be used for the early diagnosis and follow‐up surveillance of cervical cancer.
Systematicity of Search Index: A new measure for exploring information search patterns
Authors: Perkovic Sonja , Bown Nicola J. , Kaptan Gulbanu
Published: April 2018

Many studies on information search in multi‐attribute decision making rely on the analysis of transitions from 1 piece of information to the next. One challenge is to categorize information search that includes an equal amount of alternative‐ and attribute‐wise transitions. We propose a measure, the Systematicity of Search Index (SSI), for exploring information search based on sequences of either alternative‐ or attribute‐wise transitions. The SSI explores information search in terms of systematicity or the proportion of nonrandom search, that is, search that is alternative‐ or attribute‐wise, corrected for chance. Our experiment confirms the validity of the SSI and shows that the SSI can shed light on processes not captured by the measures analysing single transitions, such as Payne's Search Index.
Can earthworms biosynthesize highly luminescent quantum dots?
Authors: Talaeeshoar Farzane , Delavari H. Hamid , Poursalehi Reza
Published: April 2018

Band gap tunable cadmium selenide (CdSe) quantum dots (QDs) were synthesized within earthworms that emit in the middle of the visible spectrum. We demonstrated that this luminescence emission is a combination of the earthworm's protein and QD luminescence, such that the contribution of QDs in the luminescence was negligible. Eisenia fetida earthworms were used for QD biosynthesis and were exposed to different concentrations of CdCl2 and Na2SeO3 in standard soil for an adequate exposure time. The size of the CdSe QDs based on the effective mass model was in agreement with the size measured from the transmission electron microscopy analysis, with an average diameter of 7 nm. Ultraviolet–visible and photoluminescence analyses confirmed the synthesis of CdSe QDs with unique absorption and luminescence at 430 nm and 605 nm, respectively.
Effect of annealing temperature and dopant concentration on the thermoluminescence sensitivity in LiF:Mg,Cu,Ag material
Authors: Yahyaabadi Akram , Torkzadeh Falamarz , Rezaei Ochbelagh Dariush , Hosseini Pooya Seyed Mahdi
Published: April 2018

LiF:Mg,Cu,Ag is a new dosimetry material that is similar to LiF:Mg,Cu,P in terms of dosimetric properties. The effect of the annealing temperature in the range of 200 to 350°C on the thermoluminescence (TL) sensitivity and the glow curve structure of this material at different concentrations of silver (Ag) was investigated. It has been demonstrated that the optimum values of the annealing temperature and the Ag concentration are 240°C and 0.1 mol% for better sensitivity, respectively. The TL intensity decreases at annealing temperatures lower than 240°C or higher than 240°C, reaching a minimum at 300°C and then again increases for various Ag concentrations. It was observed that the glow curve structure altered and the area under the low temperature peak as well as the area under the main dosimetric peak decreased with increasing annealing temperature. The position of the main dosimetric peak moved in the direction of higher temperatures, but at 320 and 350°C annealing temperatures, it shifted to lower temperatures. It was also observed that the TL sensitivity could partially be recovered by a combined annealing procedure.
An impurity characterization based approach for the rapid development of integrated downstream purification processes
Authors: Timmick Steven M. , Vecchiarello Nicholas , Goodwine Chaz , Crowell Laura E. , Love Kerry R. , Love J. Christopher , Cramer Steven M.
Published: April 2018

In this study, we describe a new approach for the characterization of process‐related impurities along with an in silico tool to generate orthogonal, integrated downstream purification processes for biological products. A one‐time characterization of process‐related impurities from product expression in Pichia pastoris was first carried out using linear salt and pH gradients on a library of multimodal, salt‐tolerant, and hydrophobic charge induction chromatographic resins. The Reversed‐phase ultra‐performance liquid chromatography (UPLC) analysis of the fractions from these gradients was then used to generate large data sets of impurity profiles. A retention database of the biological product was also generated using the same linear salt and pH gradients on these resins, without fraction collection. The resulting two data sets were then analyzed using an in silico tool, which incorporated integrated manufacturing constraints to generate and rank potential three‐step purification sequences based on their predicted purification performance as well as whole‐process “orthogonality” for impurity removal. Highly ranked sequences were further examined to identify templates for process development. The efficacy of this approach was successfully demonstrated for the rapid development of robust integrated processes for human growth hormone and granulocyte‐colony stimulating factor.
Quantification of metronidazole in healthy subjects' feces using an LC–MS/MS method
Authors: Vanol Pravin G. , Sanyal Mallika , Shah Priyanka A. , Shrivastav Pranav S.
Published: April 2018

A highly selective and sensitive liquid chromatography–tandem mass spectrometry (LC MS/MS) method was developed for the quantification of metronidazole (MTZ) in human feces. The analyte was recovered from feces after liquid–liquid extraction with ethyl acetate and separated on Waters Symmetry® C18 (100 × 4.6 mm, 5μm) column using 0.1% formic acid in water and acetonitrile (40:60, v/v) as the mobile phase. A stable‐deuterated internal standard metronidazole‐d4 (MTZ‐d4) was used in the study. Mass analysis was performed on a triple quadrupole mass spectrometer in the positive electrospray ionization mode. A linear response function of MTZ was established in the concentration range of 0.50–250 ng/g, based on dry mass. The mean extraction recovery of MTZ (97.28%) and MTZ‐d4 (96.76%) from spiked feces samples was consistent at higher as well as lower concentrations. Post‐column infusion analysis showed no ion‐suppression/enhancement effects and the mean IS‐normalized matrix factor ranged from 0.986 to 1.013. Spiked feces samples stored at −20 and − 70°C for long‐term stability were stable for at least 3 months, while extracted samples (dry and wet extracts) were stable up to 24 h. The method was applied to determine MTZ in feces of 12 healthy Indian subjects.
Synthesis and Characterization of Pyridine Compounds for Amperometric Measurements of Leukocyte Esterase
Authors: Hanson Douglas , Menard Travis , Blazek Teresa , McHardy Stanton , Gorski Waldemar
Published: April 2018

We introduce a new class of substrates (compounds I–III) for leukocyte esterase (LE) that react with LE yielding anodic current in direct proportion to LE activity. The kinetic constants Km and kcat for the enzymatic reactions were determined by amperometry at a glassy carbon electrode. The binding affinity of I–III for LE was two orders of magnitude better than that of existing optical LE substrates. The specificity constant kcat/Km was equal to 2.7, 3.8, and 5.8×105 m−1 s−1 for compounds containing the pyridine (I), methoxypyridine (II), and (methoxycarbonyl)pyridine (III), respectively, thus showing an increase in catalytic efficiency in this order. Compound III had the lowest octanol/water partition coefficient (log p=0.33) along with the highest topological surface area (tPSA=222 Å2) and the best aqueous solubility (4.0 mg mL−1). The average enzymatic activity of LE released from a single leukocyte was equal to 4.5 nU when measured with compound III.
Organic Polysulfides Based on −S−S−S− Structure as Additives or Cosolvents for High Performance Lithium‐Sulfur Batteries
Authors: Gu Sui , Jin Jun , Zhuo Shangjun , Qian Rong , Wen Zhaoyin
Published: April 2018

Lithium‐sulfur (Li−S) batteries are presently attracting immense research interest on the global level due to their excellent specific capacity and energy density. However, the practical development of Li−S batteries has so far been hindered by a series of obstacles. To enhance the sulfur utilization rate and facilitate capacity performance of Li−S batteries, a new organosulfide, dimethyl trisulfide (DMTS, CH3S3CH3), as electrolyte additive or cosolvent was employed. Boosted capacities were demonstrated with appropriate amount of DMTS. Li−S batteries with 5 % and 10 % DMTS delivered discharge capacities of 1207(1st)/1009(100th) and 1648(1st)/1133(100th) mAh g−1, respectively. Such high capacities are particularly attractive for Li−S batteries towards high energy density devices. The methyl‐terminated polysulfides (DMTS and reaction products of DMTS/S8) were supposed to contribute the extra capacity.
Efficient In Situ Utilization of Caustic for Sequential Recovery and Separation of Sn, Fe, and Cu in Microbial Fuel Cells
Authors: Huang Liping , Lin Zheqian , Quan Xie , Zhao Qingliang , Yang Wulin , Logan Bruce E.
Published: April 2018

A novel strategy to sequentially recover and separate Sn(II), Fe(II) and Cu(II) from a synthetic wastewater from printed circuit board (PrCB) manufacturing in a single microbial fuel cell (MFCSn)‐MFCFe‐MFCCu process was achieved, where in‐situ produced caustic was primarily utilized for Sn precipitation (MFCSn) and then secondly used for Fe deposition (MFCFe) and anaerobic Cu(II) reduction in the final MFCCu. An external resistance of 1000 Ω in the MFCSn and MFCFe, and a 10 Ω resistor in the MFCCu achieved predominant recovery of Sn (MFCSn: 80.8±0.8 %), Fe (MFCFe: 59.1±0.8 %), and Cu (MFCCu: 68.2±1.8 %) in the three MFCs, with separation factors of 32.1±1.6 for Sn (MFCSn) and 7.5±1.8 for Fe (MFCFe), and complete recovery of Cu (MFCCu, 42‐mesh cathodes). The metal concentrations in the final effluent were below national discharge limits (Sn, 2.0 mg/L; Fe, 5.0 mg/L; Cu, 0.2 mg/L). The metal recoveries ranged from 2.6 (Sn, MFCSn)–12.0 (Cu, MFCCu), and the separation factors were 8.4 (Sn, MFCSn)–∞ (Cu, MFCCu) times those of the open circuit controls. Cathodes with 120‐mesh size of stainless steel mesh produced lower metal recoveries [33.7 % (Sn, MFCSn) and 27.0 % (Fe, MFCFe) decrease] and separation factors than MFCs with 42‐mesh cathodes. This study provides a viable approach for efficiently recovering and separating Sn, Fe and Cu from stripping solutions produced in PrCB manufacturing, with simultaneous power production.
Tetrachlorinated Polycyclic Aromatic Dicarboximides: New Electron‐Poor π‐Scaffolds and NIR Emitters by Palladium‐Catalyzed Annulation Reaction
Authors: Mahl Magnus , Shoyama Kazutaka , Rühe Jessica , Grande Vincenzo , Würthner Frank
Published: April 2018

Herein we report a palladium‐catalyzed annulation reaction consisting of a Suzuki–Miyaura cross‐coupling and a C−H arylation cascade for the synthesis of tetrachlorinated polycyclic aromatic dicarboximides (PADIs). This convergent synthetic route afforded a broad series of hitherto unknown electron‐deficient PADIs under optimized reaction conditions by coupling of a dibromo‐tetrachloro‐perylene dicarboximide with different polycyclic aromatic hydrocarbon (PAH) boronic acid pinacol esters in up to 89 % yields. The new PADI compounds show broad absorption in the visible range and some of them emit in the near‐infrared (NIR) region. Cyclic and square wave voltammetric studies revealed that these tetrachlorinated PADIs are more electron‐deficient than a non‐chlorinated reference compound and they possess lower lying frontier orbitals. Thus, the newly synthesized electron‐poor PADIs are potential n‐type semiconductors. Moreover, these chlorinated PADIs are interesting building blocks for the construction of large π‐extended arrays by metal‐mediated coupling reactions.
Selective Activation of N,N′‐Diacyl Rhodamine Pro‐fluorophores Paired with Releasing Enzyme, Porcine Liver Esterase (PLE)
Authors: Abney Kristopher K. , Ramos‐Hunter Susan J. , Romaine Ian M. , Goodwin J. Shawn , Sulikowski Gary A. , Weaver C. David
Published: April 2018

This study reports the synthesis and testing of a family of rhodamine pro‐fluorophores and an enzyme capable of converting pro‐fluorophores to Rhodamine 110. We prepared a library of simple N,N′‐diacyl rhodamines and investigated porcine liver esterase (PLE) as an enzyme to activate rhodamine‐based pro‐fluorophores. A PLE‐expressing cell line generated an increase in fluorescence rapidly upon pro‐fluorophore addition demonstrating the rhodamine pro‐fluorophores are readily taken up and fluorescent upon PLE‐mediated release. Rhodamine pro‐fluorophore amides trifluoroacetamide (TFAm) and proponamide (PAm) appeared to be the best substrates using a cell‐based assay using PLE expressing HEK293. Our pro‐fluorophore series showed diffusion into live cells and resisted endogenous hydrolysis. The use of our engineered cell line containing the exogenous enzyme PLE demonstrated the rigorousness of amide masking when compared to cells not containing PLE. This simple and selective pro‐fluorophore rhodamine pair with PLE offers the potential to be used in vitro and in vivo fluorescence based assays.
The Design of Water Oxidation Electrocatalysts from Nanoscale Metal–Organic Frameworks
Authors: Shao Qi , Yang Jian , Huang Xiaoqing
Published: April 2018

Metal–organic frameworks (MOFs), as the shining stars in field of materials science, have become an important class of highly efficient catalysts for electrochemical oxygen evolution reaction (OER). Although tremendous progresses have been achieved by exploring two MOF‐based groups: the MOF‐derived electrocatalysts and the direct MOF electrocatalysts in recently years, it appears that both activity and stability of these two kinds of MOF‐based electrocatalysts have big rooms for improvement. In order to overcome these issues, a comprehensive summary of the advanced designs of catalysts is timely urgent. Here, the advanced engineering strategies including structural, carbon‐based, metal‐based and substrate‐engineered strategies of MOF‐derived catalysts have been introduced. In addition, the detailed explorations of the nanostructured direct MOF catalysts for OER are also reviewed. Finally, short comments and perspectives about the future development of the MOF‐based OER electrocatalysts are provided.
Metal‐Free Deoxygenation and Reductive Disilylation of Nitroarenes by Organosilicon Reducing Reagents
Authors: Bhattacharjee Argha , Hosoya Hiromu , Ikeda Hideaki , Nishi Kohei , Tsurugi Hayato , Mashima Kazushi
Published: April 2018

A metal‐free deoxygenation and reductive disilylation of nitroarenes was achieved using N,N′‐bis(trimethylsilyl)‐4,4′‐bipyridinylidene (1) under mild and neutral reaction conditions, and a broad functional group tolerance was possible in this reaction. Mono‐deoxygenation, giving a synthetically valuable N,O‐bis(trimethylsilyl)phenylhydroxylamine (7 a) as a readily available and safe phenylnitrene source from nitrobenzene, and double‐deoxygenation, giving N,N‐bis(trimethylsilyl)anilines 8, were easily controlled by varying the amounts of 1 and reaction temperature as well as adding dibenzothiophene (DBTP). Reaction of 2‐arylnitrobenzenes with 1 resulted in the formation of the corresponding carbazoles 14 via in situ‐generated phenylnitrene species derived by thermolysis of N,O‐bis(trimethylsilyl)phenylhydroxylamines 7, followed by their subsequent intramolecular C−H insertion. In addition, the intramolecular N−N coupling reaction proceeded in the reduction of 2,2′‐dinitrobiphenyl derivatives by 1, giving the corresponding benzo[c]cinnolines.
Designing Anticancer Peptides by Constructive Machine Learning
Authors: Grisoni Francesca , Neuhaus Claudia S. , Gabernet Gisela , Müller Alex T. , Hiss Jan A. , Schneider Gisbert
Published: April 2018

Constructive (generative) machine learning enables the automated generation of novel chemical structures without the need for explicit molecular design rules. This study presents the experimental application of such a deep machine learning model to design membranolytic anticancer peptides (ACPs) de novo. A recurrent neural network with long short‐term memory cells was trained on α‐helical cationic amphipathic peptide sequences and then fine‐tuned with 26 known ACPs by transfer learning. This optimized model was used to generate unique and novel amino acid sequences. Twelve of the peptides were synthesized and tested for their activity on MCF7 human breast adenocarcinoma cells and selectivity against human erythrocytes. Ten of these peptides were active against cancer cells. Six of the active peptides killed MCF7 cancer cells without affecting human erythrocytes with at least threefold selectivity. These results advocate constructive machine learning for the automated design of peptides with desired biological activities.
Potentially inappropriate medication use in older patients with breast and colorectal cancer
Authors: Karuturi Meghan S. , Holmes Holly M. , Lei Xiudong , Johnson Michael , Barcenas Carlos H. , Cantor Scott B. , Gallick Gary E. , Bast Robert C. , Giordano Sharon H.
Published: April 2018

BACKGROUND

The objective of this study was to determine patient characteristics associated with potentially inappropriate medication (PIM) use and its impact on outcomes for patients with breast or colorectal cancer receiving adjuvant chemotherapy.

METHODS

The Surveillance, Epidemiology, and End Results database, linked to Medicare claims, was used. The cohort included patients who were 66 years old or older and were diagnosed with stage II or III breast or colorectal cancer between July 1, 2007, and December 31, 2009. The Drugs to Avoid in the Elderly (DAE) list and the Beers criteria were used to identify PIM use. Univariate/multivariate logistic regression determined the association of baseline PIMs with covariates. Event‐free survival (EFS) was defined as the time from chemotherapy initiation to the first emergency room (ER) visit, hospitalization, death, or a composite until 3 months after chemotherapy. Cox proportional hazards modeling determined the association of PIMs with EFS.

RESULTS

The analysis included 1595 patients with breast cancer and 1528 patients with colorectal cancer. The baseline PIM frequencies were 22.2% (according to the DAE list) and 27.6% (according to the Beers criteria) in the breast cohort and 15.5% (according to the DAE list) and 24.8% (according to the Beers criteria) in the colorectal cohort. Among patients with breast cancer, 37.5% had at least 1 adverse outcome; associations included the use of ≥5 medications, an advanced stage, higher comorbidity, and prior ER visits/hospitalizations. Baseline PIM use according to the DAE list was associated with an increased risk of death in patients with breast cancer. Among patients with colorectal cancer, 45% had at least 1 adverse outcome, and associations included the use of ≥5 medications, older age, female sex, and higher comorbidity. A time‐to‐event analysis revealed no association between baseline PIM use and most outcomes.

CONCLUSIONS

These findings require further prospective confirmation, but they support a correlation between polypharmacy and adverse outcomes for cancer patients and call into question the association with PIMs. Cancer 2018;124:3000‐7. © 2018 American Cancer Society.
Long‐lived 15N Hyperpolarization and Rapid Relaxation as a Potential Basis for Repeated First Pass Perfusion Imaging – Marked Effects of Deuteration and Temperature
Authors: Harris Talia , Gamliel Ayelet , Uppala Sivaranjan , Nardi‐Schreiber Atara , Sosna Jacob , Gomori J. Moshe , Katz‐Brull Rachel
Published: April 2018

Deuteration of the exchangeable hydrogens of [15N2]urea was found to prolong the T1 of the 15N sites to more than 3 min at physiological temperatures. This significant increase in the lifetime of the hyperpolarized state of [15N2]urea, compared to [13C]urea – a pre‐clinically proven perfusion agent, makes [15N2]urea a promising perfusion agent. The molecular parameters that may lead to this profound effect were assessed by investigating small molecules with different molecular structures containing 15N sites bound to labile protons and determining the hyperpolarized 15N T1 in H2O and D2O. Dissolution in D2O led to marked prolongation for all of the selected sites. In whole human blood, the T1 of [15N2]urea was shortened. We present a general strategy for exploiting the markedly longer T1 outside the body and the quick decay in blood for performing multiple hyperpolarized perfusion measurements with a single hyperpolarized dose. Improved storage of the generated [15N2]urea polarization prior to the contact with the blood is demonstrated using higher temperatures due to further T1 prolongation.
Randomized clinical trial pilot study of prolonged exposure versus present centred affect regulation therapy for PTSD and anger problems with male military combat veterans
Authors: Ford Julian D. , Grasso Damion J. , Greene Carolyn A. , Slivinsky Michelle , DeViva Jason C.
Published: April 2018

A randomized controlled trial pilot study (www.ClinicalTrials.org; NCT01228539) with N = 31 U.S. male military recent combat veterans with PTSD and severe anger problems was conducted comparing 10‐session individual therapy versions of Trauma Affect Regulation: Guide for Education and Therapy (TARGET) versus prolonged exposure (PE). TARGET had fewer drop‐outs than PE (i.e., 29% vs. 64%). At post‐test, improvements were found for both interventions in increased emotion regulation and hope, and reduced PTSD symptoms, hostility, experiential avoidance, and mental health problems. At a four‐month follow‐up, comparable proportions (approximately 40%) of recipients in each therapy maintained clinically significant gains. Self‐rated expectancy of therapeutic outcome and working alliance was comparable for both PE and TARGET early in therapy, at mid‐treatment, and at the end of treatment. While preliminary, these results suggest that TARGET may be a viable therapeutic option for male military veterans with PTSD and anger problems.