bluuebunny/crossref_metadata_2025 huggingface dataset:
Sustainable Urban Development and Land Use Management: Wa Municipality in Perspective, Ghana
Authors: Dambeebo Daniel , Jalloh Chernor A.
Published: September 2018

Land use planning is one of the effective ways of achieving overall sustainable physical development especially, in urban areas. Various stakeholders in Ghana such as government agencies are therefore, responsible for the development and enforcement of national and local plans that specifies land areas for residential, industrial, transport and recreational facilities towards achieving sustainable development. Empirical literature within the Wa Municipality is not clear on weather enforcement and/or compliance pose as a challenge to sustainable urban development. The main objective of this study was therefore, to assess the physical development and land use planning guidelines in the Wa Municipality and analyse people compliance for sustainable land management. Both primary and secondary data were used in this study. A questionnaire was used to collect primary data from 173 households in the Wa Municipality. Besides, heads of three institutions responsible for enforcing planning guidelines were interviewed. The results maintained that physical development planning guidelines are there to guide urban development in the Wa Municipality, but enforcement and effective compliance has been weak. Also, demographic and economic variables of the respondents as well as the lack of institutional capacity are the factors responsible for low levels of compliance. The non-compliance with planning guidelines contributes to haphazard physical development. This implies that the existence of clear planning guidelines is a necessary but not sufficient condition for sustainable urban land management. It is therefore, recommended that appropriate intervention through effective education for the general public as well as resource allocation to the enforcement institutions. This will facilitate the achievement of sustainable urban land management in the Wa Municipality.
Indoor Environmental Quality Assessment of Historic Buildings in the State Park: A Case Study in Michigan
Authors: Kim Suk-Kyung
Published: September 2018

Michigan State University and the Michigan Department of Natural Resources established a partnership for sustainable park planning in October 2011. The purpose of the partnership was to enable students in the design fields to work on real-world projects and provide practical solutions. One of the notable projects was to assess old historic buildings in one state park and propose renovation plan to improve its indoor environmental quality and energy efficiency. The buildings in the park functioned as the traveler’s destination in the 1920s and still preserve original interior and exterior features.

The team of undergraduates and faculty in interior design visited the park and assessed the interior and exterior conditions of two of its buildings. They used an assessment tool which was designed on a basis of the elements in the indoor environmental quality category (IEQ) of the US Green Building Council’s LEED. Results revealed that the indoor environmental conditions of the buildings should be improved. The energy efficiency of the buildings was low. Based on this assessment, this study offered practical suggestions for improving the building’s indoor environmental quality. This study also proposed an assessment tool for the historic buildings in the state parks in Michigan to assess current indoor environmental quality of those buildings.
Reviewer Acknowledgements for Journal of Sustainable Development, Vol. 11, No. 5
Authors: Sun Sherry
Published: September 2018

Reviewer Acknowledgements for Journal of Sustainable Development, Vol. 11, No. 5, 2018
Evaluation of the TRANSIA® PLATE Staphylococcal Enterotoxins Kit for the Detection of Staphylococcal Enterotoxins in Selected Foods
Authors: Kerr David E , Bergfalk Cory , Feldsine Philip T , John Lisa , Tallent Sandra , Hammack Thomas , Brodsky Michael
Published: September 2018

The TRANSIA® PLATE Staphylococcal Enterotoxins enzyme immunoassay (EIA) was validated according to AOAC INTERNATIONAL guidelines forvalidating qualitative binary chemistry and microbiological methods. Five food matrixes were analyzed to determine the probability of detection (POD) forstaphylococcal enterotoxins (SE), including SEA, SEB, SEC1, SEC2, SEC3, SED, and SEE, by the TRANSIA PLATE Staphylococcal Enterotoxins EIA. The food matrixes tested were food types implicated in staphylococcal enterotoxin outbreaks and included raw milk cheese,liquid infant formula, eclairs, ready-to-eat ham, and canned mushrooms. Cheese and infant formula weretested with and without dialysis/concentration. Theinfant formula was also tested by an independent laboratory. Each food matrix was inoculated with specific toxins at low levels to yield fractional recoveries (0.015–0.20 ng/g of food) for POD analysis. One hundred percent recovery was achieved at concentrations ranging from <0.10 ng/g to 0.25 ng/g of toxin in the various food matrixes. At the same time, 50 Staphylococcus aureusstrains known to produce toxins and 30 non–toxin producing bacteria (including 22 Staphylococcus strains) were grown and tested. All the SE toxin–producing strains yielded positive results and all of the exclusivity strains were negative. Robustness studies showed that changes in sample volume, sample pH, and EIA assay temperature had no significant effect on performance. Stability studies showed that kits stored for 12+ months performed as well as newly made kits. This assay has been approved as a Performance TestedMethodSM.
Environmental Deficit and Contemporary Nigeria
Authors: Badru Ronald Olufemi ,   International Association for Environmental Philosophy
Published: September 2018

Three groups of claims frame this article. First, the Nigerian State is largely enmeshed in environmental deficit, given the substantial oil pollution in the Niger-delta area, the problem of erosion in the Southeast, the filthy status of the Southwest, and the incessantly worrying perturbation of the ecological stability in the Northern part of Nigeria. Second, the political leadership in Nigeria for years has not really given genuine policy priority to, and, on this model, developed a credible framework that the citizenry could buy into to sustainably address the causes and the consequences of the environmental deficit. Third, given the foregoing, this work suggests a re-thinking/re-discussion of approach to the environmental deficit. Drawing on and integrating some relevant ideas, values, and virtues in African metaphysics, epistemology, and ethics, the article develops a framework, prescribing how the democratic leadership and the citizenry ought to act in sustainably addressing the environmental deficit. Beyond the philosophic foundations, the framework is also teleologically political: (i) it emphasizes that the moral legitimacy of democratic leadership in Nigeria partly derives from its commitment to the good of the built and the natural environment, and (ii) it also stresses that the citizenry could only be good moral agents, as eco-citizens, if they develop the virtues of environmental responsibility and responsiveness, by theoretically and practically supporting the good of the built and the natural environment. The research methods of critical analysis of empirical data and reflective argumentation are adopted to pursue the goals of the work.
Fatty acid profile of Cystoseira C. Agardh (Phaeophyceae, Fucales) species from the Tunisian coast: Taxonomic and nutritional assessments
Authors: Bouafif Cyrine , Messaoud Chokri , Boussaid Mohamed , Langar Habib
Published: September 2018

A screening of the total lipids and fatty acids (FAs) of 11 brown algae species of the genus Cystoseira (Phaeophyceae, Fucales) from the Tunisian coast is presented and discussed. Cystoseira species showed low total lipid content, ranging from 19.8 to 68.2 mg·g–1 dry weight. Fourteen major FAs were detected in the lipid extract of Cystoseira. The FA profile of lipid extracts was characterized by high amounts of saturated FAs (SFAs) ranging from 40.51% to 57.91% of total FAs, with predominance of the lipid fraction of palmitic acid (>30% of total FAs). The arachidonic acid (C20:4n-6) levels were found to be significantly high, ranging from 8% to 16% of total FAs. Multivariate analyses of FA composition showed low geographic differentiation, providing further evidence of intraspecific diversity. Cystoseira crinita, Cystoseira schiffneri, Cystoseira amentacea var. stricta, and Cystoseira sedoides stood out for their low polyunsaturated fatty acid (PUFA)/SFA ratios, low n-6/n-3 PUFA ratios, high unsaturation, and low atherogenicity and thrombogenicity indices, suggesting high nutritional value.
The carbonate system in coastal waters off the northern region of the Baja California Peninsula under La Niña conditions
Authors: Oliva-Méndez Norma , Delgadillo-Hinojosa Francisco , Pérez-Brunius Paula , Valencia-Gasti Augusto , Huerta-Diaz Miguel A , Palacios-Coria Eduardo , Hernández-Ayón J Martín
Published: September 2018

In the North Pacific, variations in isopycnal depth influence the biogeochemical characteristics of the water column and the aragonite saturation horizon (ZΩa) during interannual events. The objective of this study was to assess the effect of the 2011 La Niña conditions on ZΩa in Todos Santos Bay (Baja California, Mexico) and surrounding waters. The results showed that ZΩa variability was modulated by the intensity of interannual conditions and by the water masses that were present in the region. Subarctic Water predominated in the upper 200 m with anomalous characteristics, such as low temperature and low salinity. Also, isopycnals shoaled toward the coast and ZΩa was thus ~30 m in the nearshore area, in contrast with the oceanic region, where ZΩa was ~150 m. Prior to this study, there were no records of ZΩa in Todos Santos Bay, nor were there any records of its shallowness.
Label‐Free Quantification Proteomics for the Identification of Mesenchymal Stromal Cell Matrisome Inside 3D Poly(Ethylene Glycol) Hydrogels
Authors: Devaud Yannick R. , Avilla‐Royo Eva , Trachsel Christian , Grossmann Jonas , Martin Ivan , Lutolf Matthias P. , Ehrbar Martin
Published: September 2018

Cells modulate the functional properties of their environment by depositing extracellular matrix (ECM) proteins during biological processes in vivo and in vitro. Despite the ECMs central role in tissue formation, its quantification in hydrogels like Matrigel, which have a complex materials‐inherent biopolymer composition is exceptionally challenging. Here, the use of protein‐free, synthetic poly(ethylene glycol) hydrogels enables the analysis of deposited human bone marrow mesenchymal stromal cells ECM directly harvested from fresh 3D cell cultures by a tandem mass spectrometry (LC‐MS/MS) method. In this study, it is proved that a label‐free LC‐MS/MS quantification method can selectively identify proteins deposited in 3D synthetic hydrogels following different growth factor (GF) treatments. Furthermore, it is shown that the sequence in which GFs are administered and the choice of stimuli significantly influences the number and abundance of ECM proteins. Therefore, this provides a versatile method to optimize GF treatments in synthetic hydrogel‐based regenerative medicine and tissue engineering approaches.
Localized Self‐Growth of Reconfigurable Architectures Induced by a Femtosecond Laser on a Shape‐Memory Polymer
Authors: Zhang Yachao , Li Ying , Hu Yanlei , Zhu Xuelin , Huang Yaowei , Zhang Zhen , Rao Shenglong , Hu Zhijiang , Qiu Weixin , Wang Yulong , Li Guoqiang , Yang Liang , Li Jiawen , Wu Dong , Huang Wenhao , Qiu Chengwei , Chu Jiaru
Published: September 2018

Architectures of natural organisms especially plants largely determine their response to varying external conditions. Nature‐inspired shape transformation of artificial materials has motivated academic research for decades due to wide applications in smart textiles, actuators, soft robotics, and drug delivery. A “self‐growth” method of controlling femtosecond laser scanning on the surface of a prestretched shape‐memory polymer to realize microscale localized reconfigurable architectures transformation is introduced. It is discovered that microstructures can grow out of the original surface by intentional control of localized laser heating and ablation, and resultant structures can be further tuned by adopting an asymmetric laser scanning strategy. A distinguished paradigm of reconfigurable architectures is demonstrated by combining the flexible and programmable laser technique with a smart shape‐memory polymer. Proof‐of‐concept experiments are performed respectively in information encryption/decryption, and microtarget capturing/release. The findings reveal new capacities of architectures with smart surfaces in various interdisciplinary fields including anti‐counterfeiting, microstructure printing, and ultrasensitive detection.
Sequential Gold‐Catalyzed Carbene Transfer/Ring Closure: Oxidative Cyclization of β‐(2‐Alkynylphenyl)‐α,β‐ynones to Indenofuranones
Authors: Rode Navnath , Marinelli Fabio , Arcadi Antonio , Adak Tapas , Rudolph Matthias , Rominger Frank , Hashmi A. Stephen K.
Published: September 2018

β‐(2‐Alkynylphenyl)‐α,β‐ynones undergo a gold‐catalyzed oxidative two‐fold cyclization in the presence of N‐oxides to give 1,3‐disubstituted‐8H‐indeno[1,2‐c]furan‐8‐ones in good yields. This cascade process is triggered by a selective oxygen transfer from an N‐oxide onto the gold‐activated alkynone to generate a α‐dioxocarbene intermediate which, via carbene transfer across the remaining alkyne moiety and subsequent cyclization through nucleophilic attack by a carbonyl oxygen, achieves the construction of 1,3‐disubstituted fused polycyclic furans.

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One‐Step Method for Instant Generation of Advanced Allogeneic NK Cells
Authors: Lee Daniel Y. , Lim Kwang Suk , Valencia Gabriel M. , Jung Minjin , Bull David A. , Won Young‐Wook
Published: September 2018

Conventional combinatorial anticancer therapy has shown promising outcomes; still, a significant interest in developing new methods to reinforce and possibly merge chemotherapy and immunotherapy persists. Here, a new one‐step method that immediately modifies immune cells into a targeted form of chemoimmunotherapy through spontaneous and rapid incorporation of hydrophobized antibody–drug conjugates (ADCs) on the surface of immune cells is presented. Therapeutic objectives of this approach include targeted delivery of a potent chemotherapeutic agent to avoid adverse effects, enhancing the mobilization of infused immune cells toward tumor sites, and preserving the intense cytotoxic activities of immune cells against tumor cells. The embedding of hydrophobized ADCs on the immune cell membrane using the strategy in this study provides noninvasive, nontoxic, and homogenous modifications that transiently arm immune cells with highly potent cytotoxic drugs targeted toward cancer cells. The resulting surface‐engineered immune cells with ADCs significantly suppress the tumor growth and drive the eradication of target cancer cells through combinatorial anticancer effects. This novel strategy allows convenient and timely preparation of advanced chemoimmunotherapy on a single immune cell to treat various types of cancer.
Reversible Mechanochromic Delayed Fluorescence in 2D Metal–Organic Micro/Nanosheets: Switching Singlet–Triplet States through Transformation between Exciplex and Excimer
Authors: Yang Yongsheng , Yang Xiaogang , Fang Xiaoyu , Wang Ke‐Zhi , Yan Dongpeng
Published: September 2018

Mechanochromic luminescent materials have attracted much attention and present a variety of applications in information security, data recording, and storage devices. However, most of these smart luminescent systems are based on typical fluorescence and/or phosphorescence mechanisms; the mechanochromic delayed fluorescence (MCDF) materials involving switching singlet and triplet states are rarely studied to date. Herein, new 2D layered metal–organic micro/nanosheets, [Cd(9‐AC)2(BIM)2] (named as MCDF‐1; 9‐AC = anthracene‐9‐carboxylate and BIM = benzimidazole) and its solvate form containing interlayer CH3CN (named as MCDF‐2), which exhibit reversible mechanochromic delayed fluorescence characteristics, are presented. With applying the mechanical force, the luminescent center of MCDF‐1 can be converted from 9‐AC/BIM exciplex to 9‐AC/9‐AC excimer, resulting in alternations of delayed fluorescence. Such luminescent change can be further recovered by CH3CN fumigation, accompanied by the structural transformation from MCDF‐1 to MCDF‐2. Furthermore, the force‐responsive process also refers to the energy redistribution between singlet and triplet states as inferred by both temperature‐dependent photophysics and theoretical calculations. Therefore, this work not only develops new 2D micro/nanosheets as MCDF materials, but also supplies a singlet–triplet energy switching mechanism on their reversible mechanochromic process.
Redox‐Active Organic Sodium Anthraquinone‐2‐Sulfonate (AQS) Anchored on Reduced Graphene Oxide for High‐Performance Supercapacitors
Authors: Shi Ruiying , Han Cuiping , Duan Huan , Xu Lei , Zhou Dong , Li Hongfei , Li Junqin , Kang Feiyu , Li Baohua , Wang Guoxiu
Published: September 2018

Redox active organic quinones are potentially low cost, sustainable, and high‐energy pseudocapacitive materials due to their fast and reversible redox reactivity. However, their electrically insulating nature prevents any practical application. Herein, for the first time, sodium anthraquinone‐2‐sulfonate (AQS) is examined as an organic redox‐active compound and highly conductive graphene nanosheets are incorporated to enhance the electronic conductivity. The SO3− functional group of AQS offers excellent hydrophilicity, which promotes the molecular level binding of AQS with reduced graphene oxide (rGO) and leads to a 3D interconnected xerogel (AQS@rGO). The composite exhibits a high specific capacitance of 567.1 F g−1 at 1 A g−1 with a stable capacity retention of 89.1% over 10 000 cycles at 10 A g−1. More importantly, the optimized composite maintains a high capacitance of 315.1 F g−1 even at 30 A g−1 due to the high pseudocapacitance of AQS and the capacitive contribution of rGO. First‐principles calculations further elucidate that AQS offers strong adhesion to rGO sheets with the formation of a space‐charge layer, which is favorable for the pseudocapacitance of AQS. This work opens a new avenue for developing high‐performance supercapacitors though rational combination of redox organic molecules with highly conductive graphene.
Genetic history of Chad
Authors: Shriner Daniel , Rotimi Charles N.
Published: September 2018

Objectives

The Sahel is a semi‐arid zone stretching from the Atlantic Ocean in the west to the Red Sea in the east and from the Sahara in the north to the Sudanian Savanna in the south. Here, we investigated the genetic history of the spread of Northern African ancestry common among Berbers, the Y DNA haplogroup R1b‐V88, and Chadic languages throughout the Sahel, with a focus on Chad.

Materials and methods

We integrated and analyzed genotype data from 751 individuals from Chad, Burkina Faso, Mali, South Sudan, and Sudan in the context of a global reference panel of 5,966 individuals.

Results

We found that genetic diversity in Chad was broadly divided by a north–south axis. The core ancestry of Southern Chadians was Central African, most closely related to Pygmies. Southern Chadians then experienced four waves of gene flow over the last 3,000 years from West‐Central Africans, Eastern Africans, West‐Central Africans again, and then Arabians. In contrast, Northern Chadians did not share Central African ancestry and were not influenced by the first wave of West‐Central Africans but were influenced by Northern African ancestry.

Discussion

We found that Y DNA haplogroup R1b entered the Chadian gene pool during Baggarization. Baggara Arabs spoke Arabic, not Chadic, implying that people carrying R1b‐V88 were not responsible for the spread of Chadic languages, which may have spread approximately 3,700 years ago. We found no evidence for migration of Near Eastern farmers or any ancient episodes involving Eurasian backflow.
Two‐Terminal Molecular Memory through Reversible Switching of Quantum Interference Features in Tunneling Junctions
Authors: Carlotti Marco , Soni Saurabh , Kumar Sumit , Ai Yong , Sauter Eric , Zharnikov Michael , Chiechi Ryan C.
Published: September 2018

Large‐area molecular tunneling junctions comprising self‐assembled monolayers of redox‐active molecules are described that exhibit two‐terminal bias switching. The as‐prepared monolayers undergo partial charge transfer to the underlying metal substrate (Au, Pt, or Ag), which converts their cores from a quinoid to a hydroquinoid form. The resulting rearomatization converts the bond topology from a cross‐conjugated to a linearly conjugated π system. The cross‐conjugated form correlates to the appearance of an interference feature in the transmission spectrum that vanishes for the linearly conjugated form. Owing to the presence of electron‐withdrawing nitrile groups, the reduction potential and the interference feature lie close to the work function and Fermi level of the metallic substrate. We exploited the relationship between conjugation patterns and quantum interference to create nonvolatile memory in proto‐devices using eutectic Ga–In as the top contact.
Ein N‐heterocyclischer Carbenkomplex des Silbers für die plasmaunterstützte räumlich getrennte Atomlagenabscheidung dünner Silberschichten bei Atmosphärendruck
Authors: Boysen Nils , Hasselmann Tim , Karle Sarah , Rogalla Detlef , Theirich Detlef , Winter Manuela , Riedl Thomas , Devi Anjana
Published: September 2018

Ein Silberamidkomplex eines N‐heterocyclischen Carbens, (1,3‐Di‐tert‐butyl‐imidazolin‐2‐yliden)silber(I)‐1,1,1‐trimethyl‐N‐(trimethylsilyl)silanamid [(NHC)Ag(hmds)], wurde synthetisiert, mittels Einkristall‐Röntgenstrukturanalyse, 1H‐ und 13C‐NMR‐Spektroskopie und EI‐Massenspektrometrie analysiert, sowie bezüglich seiner thermischen Eigenschaften untersucht. Diese neue halogen‐ und phosphorfreie Vorstufe für die Atomlagenabscheidung (ALD) wurde in einem plasmaunterstützten räumlich getrennten (APP‐)ALD‐Prozess unter Atmosphärendruck für die Abscheidung dünner Silberschichten genutzt. Besonders reine und elektrisch leitende dünne Silberschichten mit einem geringen Flächenwiderstand von 0.9 Ω/sq (10−5 Ωcm) wurden bei 100 °C abgeschieden und mittels Röntgenphotoelektronenspektroskopie, Rasterelektronenmikroskopie, optischer Transmissionsspektroskopie und Rutherford‐Rückstreuspektrometrie untersucht. Die Carben‐basierte ALD‐Vorstufe und der zugehörige APP‐ALD‐Prozess ermöglichen zukünftige Anwendungen solcher Silberschichten.
Improvement in mechanical properties of polyurethane‐urea nanocomposites by using modified SiO2 nanoparticles
Authors: Yarmohammadi Masoud , Khalaf Adeli Alireza , Zamani Pedram Mona , Shahidzadeh Mansour , Pirouzfar Vahid
Published: September 2018

Poly(propylene glycol) (PPG)‐based nanocomposites have been prepared one shot using various contents of functionalized SiO2 nanoparticle as filler‐crosslinker agent. Triethoxy silyl propane‐1‐amine has been used as coupling agent for functionalization of SiO2 nanoparticle to improve its reactivity. The results revealed that the mechanical properties of the samples have been improved due to the functionalized SiO2‐nanoparticle effect on chemical and three‐dimensional physical crosslinking of the polyurethane–urea nanocomposites. Addition of the functionalized nanoparticle increased strength from 0.75 to 1.58 MPa in comparison to polyurethane sample. Moreover, storage moduli of PPG‐based polyurethane sample reduced in higher than room temperatures. While, using functionalized nanoparticle improves elasticity from 0.88 MPa in polyurethane sample to 2.84 MPa in polyurethane–urea nanocomposites. © 2018 Wiley Periodicals, Inc. J. Appl. Polym. Sci. 2018, 135, 46707.
Odds are the sign is right
Authors: Knaeble Brian , Chan Julian
Published: September 2018

This article introduces a new condition based on odds ratios for sensitivity analysis. The analysis involves the average effect of a treatment or exposure on a response or outcome with estimates adjusted for and conditional on a single, unmeasured, dichotomous covariate. Results of statistical simulations are displayed to show that the odds ratio condition is as reliable as other commonly used conditions for sensitivity analysis. Other conditions utilize quantities reflective of a mediating covariate. The odds ratio condition can be applied when the covariate is a confounding variable. As an example application we use the odds ratio condition to analyze and interpret a positive association observed between Zika virus infection and birth defects.
Spatial learning and long‐term memory impairments in RasGrf1 KO, Pttg1 KO, and double KO mice
Authors: Manyes Lara , Holst Sarah , Lozano Manuel , Santos Eugenio , Fernandez‐Medarde Alberto
Published: September 2018

Background

RasGrf1 is a guanine‐nucleotide releasing factor that enhances Ras activity. Human PTTG1 is an oncoprotein found in pituitary tumors and later identified as securin, a protein isolated from yeast with a reported role in chromosome separation. It has been suggested that RasGrf1 is an important upstream component of signal transduction pathways regulating Pttg1 expression and controlling beta cell development and their physiological response. At memory formation level, there are contradictory data regarding the role of RasGrf1, while Pttg1 has not been previously studied. Both proteins are expressed in the mammalian hippocampus, which is one of the key brain areas for spatial learning and memory.

Objective

The aim of this work was to study a potential link between RasGrf1 and Pttg1 in memory formation.

Method

Spatial learning and memory test in the Pttg1 KO, RasGrf1 KO, and Pttg1‐RasGrf1 double KO and their correspondent WT mice using a Barnes maze.

Results

In comparison with the WT control mice, Pttg1 KO mice learned how to solve the task in a less efficient way, suggesting problems in memory consolidation. RasGrf1 KO mice performance was similar to controls, and they learned to use the best searching strategy. Double KO mice reached a better spatial learning level than WT.

Conclusion

A role for Pttg1 in memory consolidation/formation is suggested, while our RasGrf1 KO mice do not show hippocampus associated memory defects.
Quantitative assessment of environmental impact of biologics manufacturing using process mass intensity analysis
Authors: Madabhushi Sri R. , Gavin John , Xu Sen , Cutler Collette , Chmielowski Rebecca , Rayfield William , Tugcu Nihal , Chen Hao
Published: September 2018

Process mass intensity (PMI) is a benchmarking metric to evaluate the efficiency of a manufacturing process, which is indicative of the environmental impact of the process. Although this metric is commonly applied for small molecule manufacturing processes, it is less commonly applied to biologics. In this study, an Excel based tool developed by the ACS GCI Pharmaceutical Roundtable was used to calculate PMI of different manufacturing processes for a monoclonal antibody (mAb). For the upstream process, three different versions were compared: fed‐batch, fed‐batch with N‐1 perfusion, and perfusion in the N‐stage bioreactor. For each upstream process version, an appropriate downstream operational mode was evaluated from the following: a column chromatography process utilizing Protein A and anion exchange (AEX) resin, a Protein A column and an AEX membrane, and a three‐column periodic counter‐current (3C PCC) chromatography process for Protein A and an AEX membrane. The impact of these different process variations on PMI was evaluated. Of all the process inputs, water contributes about 92–94% of the overall PMI. Additionally, the upstream processes and the chromatography steps account for 32–47 and 34–54% of the overall PMI, respectively. Sensitivity analysis was performed to identify opportunities for further reducing PMI. These data indicate that a semicontinuous manufacturing process (perfusion, 3C PCC, and AEX membrane) is the most efficient process, resulting in a 23% reduction of PMI when compared with the fed batch and two‐column chromatography process. Together, PMI can be used to guide the development of efficient and environmentally sustainable mAb manufacturing processes. © 2018 American Institute of Chemical Engineers Biotechnol. Prog., 34:1566–1573, 2018
Circulating microRNA biomarkers for lung cancer detection in Western populations
Authors: Yu Haixin , Guan Zhong , Cuk Katarina , Brenner Hermann , Zhang Yan
Published: September 2018

Lung cancer (LC) is a leading cause of cancer‐related death in the Western world. Patients with LC usually have poor prognosis due to the difficulties in detecting tumors at early stages. Multiple studies have shown that circulating miRNAs might be promising biomarkers for early detection of LC. We aimed to provide an overview of published studies on circulating miRNA markers for early detection of LC and to summarize their diagnostic performance in Western populations. A systematic literature search was performed in PubMed and ISI Web of Knowledge to find relevant studies published up to 11 August 2017. Information on study design, population characteristics, miRNA markers, and diagnostic accuracy (including sensitivity, specificity, and AUC) were independently extracted by two reviewers. Overall, 17 studies evaluating 35 circulating miRNA markers and 19 miRNA panels in serum or plasma were included. The median sensitivity (range) and specificity (range) were, respectively, 78.4% (51.7%‐100%) and 78.7% (42.9%‐93.5%) for individual miRNAs, and 83.0% (64.0%‐100%) and 84.9% (71.0%‐100%) for miRNA panels. Most studies incorporated individual miRNA markers as panels (with 2‐34 markers), with multiple miRNA‐based panels generally outperforming individual markers. Two promising miRNA panels were discovered and verified in prospective cohorts. Of note, both studies exclusively applied miRNA ratios when building up panels. In conclusion, circulating miRNAs may bear potential for noninvasive LC screening, but large studies conducted in screening or longitudinal settings are needed to validate the promising results and optimize the marker panels.
A novel inflammation‐based nomogram system to predict survival of patients with hepatocellular carcinoma
Authors: Chen Jinbin , Fang Aiping , Chen Minshan , Tuoheti Yiminjiang , Zhou Zhongguo , Xu Li , Chen Jiancong , Pan Yangxun , Wang Juncheng , Zhu Huilian , Zhang Yaojun
Published: September 2018

Background and Aim

The existed staging systems were limited in the accuracy of prediction for overall survival (OS) of hepatocellular carcinoma (HCC) patients. The aim of this study is to establish a novel inflammation‐based prognostic system with nomogram for HCC patients.

Methods

A prospective cohort of patients was recruited and assigned to the training cohort (n = 659) and validation cohort (n = 320) randomly. Different inflammation‐based score systems were evaluated to select the best one predicting overall survival (OS). The inflammation‐based score system with the highest predicting value and the parameters best reflecting tumor burden identified by multivariate analysis were selected to construct a novel predicting nomogram system. The predictive accuracy and discriminative ability of the nomogram were evaluated by concordance index (C‐index) and calibration curve and compared with conventional staging systems.

Results

With a highest C‐index and areas under the receiver operating characteristic curve (AUC), C‐reactive protein/albumin ratio (CAR) was selected to construct the novel system, along with tumor number, tumor size, macrovascular invasion and extra‐hepatic metastases. The C‐index of the nomogram was 0.813 (95% CI, 0.789‐0.837) in the training cohort and 0.794 (95% CI, 0.756‐0.832) in the validation cohort. The calibration curve for predicting probability of survival showed that the nomogram had a high consistency with follow‐up data. The C‐index of the novel system was higher than other conventional staging systems (P < 0.001).

Conclusions

The novel inflammation‐based nomogram, developed from prospectively collected data in the present study, predicted the OS of HCC patients.
Expression of sushi domain containing two reflects the malignant potential of gastric cancer
Authors: Umeda Shinichi , Kanda Mitsuro , Miwa Takashi , Tanaka Haruyoshi , Tanaka Chie , Kobayashi Daisuke , Suenaga Masaya , Hattori Norifumi , Hayashi Masamichi , Yamada Suguru , Nakayama Goro , Fujiwara Michitaka , Kodera Yasuhiro
Published: September 2018

Hepatic recurrence of gastric cancer (GC) is uncontrollable. Discovery of causative oncogenes and the development of sensitive biomarkers to predict hepatic recurrence are required to improve patients’ outcomes. In this study, recurrence pattern‐specific transcriptome analysis of 57 749 genes was conducted to identify mRNAs specifically associated with hepatic metastasis of patients with stage III GC who underwent curative resection. GC cell lines were subjected to mRNA expression analysis, PCR array analysis, and siRNA‐mediated knockdown. The expression levels of primary cancer tissues from 154 patients with resectable GC were determined and correlated with clinicopathological variables. Among 21 genes significantly overexpressed specifically in patients with hepatic recurrence, Sushi domain containing 2 (SUSD2) was selected as a promising target. PCR array analysis revealed that SUSD2 mRNA levels positively correlated with those of FZD7, CDH2, TGFB1, SPARC, ITGA5, and ZEB1. Functional analysis revealed that knockdown of SUSD2 significantly reduced the proliferation, migration, and invasiveness GC cell lines. Patients with high SUSD2 expression were more likely to experience shorter disease‐free and overall survival. Analysis of the relation between disease recurrence pattern and SUSD2 levels revealed that significantly more patients with hepatic metastases expressed higher levels of SUSD2 mRNA. The cumulative incidence of hepatic recurrence was greater in patients with high SUSD2 expression. In conclusion, SUSD2 likely contributes to the malignant potential of GC and may serve as a novel biomarker that predicts hepatic recurrence after curative resection.
Polypyrrole‐Assisted Co3O4 Anchored Carbon Fiber as a Binder‐Free Electrode for Seawater Batteries
Authors: Kim Changmin , Kim Seona , Kwon Ohhun , Kim Jeongwon , Kim Guntae
Published: September 2018

An efficient, durable and cost‐effective air electrode is essential to achieve a practicable metal‐air battery. The conventional preparation of electrode uses polymer binders to ensure good physical contacts between catalysts and the electrode scaffold. However, the use of polymer binders introduces inevitable loss of the electrochemically active surface area and restricts access of the reactants, owing to the electrically insulating properties and hydrophobic properties of polymer binders. In this work, a binder‐free air electrode is structured by using Co oxide anchored on carbon fiber tissues with the assistance of polypyrrole‐doped carbon (PPy/C) through a simple infiltration technique. The fabricated binder‐free electrode exhibits excellent bifunctional stability for seawater batteries, presenting a comparable performance to the binder‐included Pt/C+IrO2 electrode.
Image super‐resolution reconstruction based on adaptive sparse representation
Authors: Xu Mengxi , Yang Yun , Sun Quansen , Wu Xiaobin
Published: September 2018

There are two problems in global over‐complete dictionary: lack of adaptability to image local structure and low computational efficiency. Based on the study of the adaptive sparse representation reconstruction, this paper obtained a series of corresponding sub‐dictionaries by image block subset, then the optimal sub‐dictionary for each reconstruction image block is adaptively selected, which can be more accurately sparse represented modeled to improve the effect and efficiency of the algorithm. In order to promote the ability of sparse representation model, nonlocal self‐similarity prior item is introduced. Meanwhile, the nonlocal self‐similarity model is improved by using the idea of the bilateral filter, and the space distance restraint between pixels is introduced to better keep the image edge information. Moreover, the nonlocal self‐similar distance measure is improved to reduce the amount of calculation. Experimental results show that the proposed algorithm can effectively suppress noise effects and can maintain the image edge details, at the same time, there are certain advantages at both the peak signal to noise ratio (PSNR) and visual effects.
Intensive treatment program (ITP): A case series service evaluation of the effectiveness of day patient treatment for adolescents with a restrictive eating disorder
Authors: Simic Mima , Stewart Catherine S. , Eisler Ivan , Baudinet Julian , Hunt Katrina , O'Brien Jayne , McDermott Beth
Published: September 2018

Objective

Family Therapy for Anorexia Nervosa (FT‐AN) is the first line treatment for adolescents with anorexia nervosa in the UK. However, research suggests between 10 and 40% of young people have a poor outcome. For those for whom FT‐AN alone is not effective there is a clear need to develop additional treatments. This paper describes the effectiveness of an additional treatment for adolescents who had not responded to FT‐AN, the Intensive Day Treatment Program (ITP) embedded within a comprehensive outpatient service at the Maudsley Hospital.

Method

Data from a retrospective chart review of patient files were analyzed for 105 young people aged 11–18 with restrictive eating disorders referred to the program in the first four and a half years of its operation.

Results

Young people attended ITP for only on average 28.41 days. Over this time they made significant improvements in a range of domains, including weight gain, eating disorder symptomatology, motivation to recover, quality of life and comorbid symptomatology. Young people continued to make improvements post ITP in outpatient treatment provided by the same service and 73.2% had a good or an intermediate outcome at the point of discharge from the service.

Discussion

This uncontrolled case series indicates that ITP can contribute to positive outcomes for young people who require intensification of treatment. ITP outcomes are discussed in comparison to the published literature concerning day programs for adolescents with a diagnosis of an eating disorder.
Long‐lasting effects of logging on beetles in hollow oaks
Authors: Pilskog Hanne E. , Sverdrup‐Thygeson Anne , Evju Marianne , Framstad Erik , Birkemoe Tone
Published: September 2018

There is growing evidence that biodiversity is important for ecosystem functions. Thus, identification of habitat requirements essential for current species richness and abundance to persist is crucial. Hollow oaks (Quercus spp.) are biodiversity hot spots for deadwood‐dependent insect species, and the main objective of this paper was to test the effect of habitat history and current habitat distribution at various spatial scales on the associated beetle community. We used a gradient spanning 40 km from the coast to inland areas reflecting historical logging intensity (later and lower intensities inland) through 500 years in Southern Norway, to investigate whether the historical variation in oak density is influencing the structure of beetle communities in hollow oaks today. We trapped beetles in 32 hollow oaks along this gradient in forested and seminatural landscapes over two summers. We found higher species richness and total abundance inland consistent with our expectation based on historic logging intensity. Scale‐specific environmental variables also affected the response; beetle abundances were controlled by local conditions, whereas beetle species richness responded to habitat on the landscape scale. This indicates that long time continuity as well as large areas of favorable habitat is necessary to maintain beetle species richness through time in these highly long‐lasting structures.
Evolutionary history of the endemic water shrew Neomys anomalus: Recurrent phylogeographic patterns in semi‐aquatic mammals of the Iberian Peninsula
Authors: Querejeta Marina , Castresana Jose
Published: September 2018

The Cabrera's water shrew (Neomys anomalus) is a small semi‐aquatic mammal whose taxonomic status was recently elevated from subspecies to species; as a consequence of this change, this species is now endemic to the Iberian Peninsula. In this study, we looked at its evolutionary history by combining phylogeography, the spatial distribution of genetic diversity, and species distribution modeling. To perform these analyses, we used noninvasive samples collected across the species distribution range and sequenced partial mitochondrial cytochrome b and D‐loop genes. Maximum‐likelihood and Bayesian phylogenetic trees derived from these sequences indicated that N. anomalus is divided into two main phylogroups that correlate strongly with geography, with two contact zones between the groups that showed limited spatial mixing between them. River basins were responsible for only a small percentage of the structure of the genetic diversity of this species despite its riparian habitat. The nucleotide diversity variation map showed the highest genetic diversity to be in the north of the Iberian Peninsula. Finally, species distribution modeling allowed the inference of an optimal area during the Last Interglacial in the north of the Iberian Peninsula, and multiple glacial refugia during the Last Glacial Maximum. The phylogeographic pattern of N. anomalus is strikingly similar to that of another semi‐aquatic Iberian mammal, the Pyrenean desman (Galemys pyrenaicus), revealing how Pleistocene glaciations could have had equivalent effects on species of similar ecology and distribution. This phylogeographic structure is consistent with N. anomalus having been isolated for long periods in multiple glacial refugia within the Iberian Peninsula, in agreement with the “refugia‐within‐refugia” hypothesis, and further supporting its status as a distinct species.
Immunogenic cell death of dendritic cells following modified vaccinia virus Ankara infection enhances CD8+ T cell proliferation
Authors: Tappe Kim A. , Budida Ramachandramouli , Stankov Metodi V. , Frenz Theresa , R. Shah Harshit , Volz Asisa , Sutter Gerd , Kalinke Ulrich , Behrens Georg M. N.
Published: September 2018

“Immunogenic cell death” (ICD) is associated with the emission of so‐called damage‐associated molecular patterns (DAMPs) which trigger the immune response against dead‐cell associated antigens. The secretion of the DAMP, adenosine triphosphate (ATP) has been shown to be autophagy‐dependent. Here, we demonstrate that Modified Vaccinia virus Ankara (MVA), a highly attenuated strain of vaccinia virus, induces both cell death and autophagy in murine bone marrow‐derived dendritic cells (BMDCs), which in turn confer the (cross‐)priming of OVA‐specific cytotoxic T cells (OT‐I cells). Additionally, we show that MVA infection leads to increased extracellular ATP (eATP) as well as intracellular ATP (iATP) levels, with the latter being influenced by the autophagy. Furthermore, we show that the increased eATP supports the proliferation of OT‐I cells and inhibition of the P2RX7 receptors results in an abrogation of the proliferation. These data reveal novel mechanisms on how MVA enhances adaptive immunity in vaccine strategies.
Biological Evaluation of the NIR‐Emissive Ruby Analogue [Cr(ddpd)2][BF4]3 as a Photodynamic Therapy Photosensitizer
Authors: Basu Uttara , Otto Sven , Heinze Katja , Gasser Gilles
Published: September 2018

Photodynamic therapy relies on the bioavailability of photosensitizers with suitable photophysical, chemical, and biochemical properties. Although the photophysical properties, stability, and high water solubility of the chromium(III) complex [Cr(ddpd)2][BF4]3 (ddpd = N,N′‐dimethyl‐N,N′‐dipyridin‐2‐ylpyridine‐2,6‐diamine) are very favorable, its photocytotoxicity against cancerous and non‐cancerous cell lines has not yet been elucidated. We now report the cytotoxicity and photocytotoxicity of the complex [Cr(ddpd)2][BF4]3 against human cervical cancer cells, human primary glioblastoma cells, human glioblastoma astrocytoma cells, and non‐cancerous retinal pigment epithelium cells.
Transition‐Metal‐Free Approach for the Direct Arylation of Thiophene: Experimental and Theoretical Investigations towards the (Het)‐Aryne Route
Authors: Demangeat Catherine , Saied Tarak , Ramozzi Romain , Ingrosso Francesca , Ruiz‐Lopez Manuel , Panossian Armen , Leroux Frédéric R. , Fort Yves , Comoy Corinne
Published: September 2018

This paper presents the results of our investigations on the arylation of thiophene using the transition‐metal‐free “aryne coupling” methodology. The reaction was studied by both experiment and computation (density functional theory) and comparison with phenyllithium was established. In parallel, the effects of the ligand and the salt on the coupling reaction were examined. The results underline the remarkable effect of such additives on the coupling reaction and the potency of the method to construct hetaryl–aryl backbones which open up promising access to a wide range of heterobiaryl structures using the novel “Het‐Aryne” route.
Tofacitinib Synthesis – An Asymmetric Challenge
Authors: Carvalho Luísa C. R. , Lourenço Ana , Ferreira Luísa Maria , Branco Paula Sério
Published: September 2018

Tofacitinib is a Janus activated kinase (JAK) inhibitor approved for the treatment of rheumatoid arthritis and active psoriatic arthritis. Its synthesis normally involves long synthetic sequences due to the chirality associated to the piperidine ring. This review is a comprehensive analysis of the different synthetic methods used to prepare this active pharmaceutical ingredient (API), covering the related journal and patent literature.
Optically Active 2,7,10,15‐Tetrahydroxytetraphenylene: Clathrates with Both Enantiomers of 1‐Phenylethylamine and Their Stability
Authors: Kaku Hiroto , Mitarai Akinobu , Okamoto Natsuko , Tanaka Kenta , Ichikawa Sayaka , Yamamoto Takahiro , Inai Makoto , Nishii Takeshi , Horikawa Mitsuyo , Tsunoda Tetsuto
Published: September 2018

2,7,10,15‐Tetrahydroxytetraphenylene (THTP) was synthesized in two steps by the homo‐coupling reaction of 2,2′‐dibromo‐5,5′‐dimethoxybiphenyl. Optical resolution of racemic THTP was achieved by complexation with (S)‐1‐phenylethylamine in toluene to afford (S,S)‐THTP in good yield. (R,R)‐THTP was also obtained using (R)‐1‐phenylethylamine. In the course of these studies, (S,S)‐THTP constituted an inclusion compound even with (R)‐1‐phenylethylamine. Both complexes were characterized by X‐ray structural analyses and the thermal analyses (DSC and TGA). The hydrogen bonding networks of the complex with (R)‐1‐phenylethylamine are more complicated than those of the complex with (S)‐1‐phenylethylamine. The thermal analysis suggests that the complex with (S)‐1‐phenylethylamine is a less stable clathrate than the complex with (R)‐1‐phenylethylamine.
Ag/ZnO Catalysts with Different ZnO Nanostructures for Non‐enzymatic Detection of Urea
Authors: Yoon Jaesik , Lee Doohee , Lee Eunji , Yoon Young Soo , Kim Dong‐Joo
Published: September 2018

Silver coated ZnO nanorods and nanoflakes with different crystallographic orientations were synthesized by a combination of sputter deposition and solution growth process. Catalytic properties of morphology‐dependent Ag/ZnO nanostructures were then investigated for urea sensors without enzyme. Ag/ZnO nanorods on carbon electrodes exhibit a higher catalytic activity and an improved efficiency than Ag/ZnO nanoflakes on carbon electrodes. Ag/ZnO nanorod catalysts with more electrochemically surface area (169 cm2 mg−1) on carbon electrode facilitate urea electrooxidation due to easier electron transfer, which further promotes the urea electrolysis. The Ag/ZnO nanorod catalysts also show a significant reduction in the onset voltage (0.410 V vs. Ag/AgCl) and an increase in the current density (12.0 mA cm−2 mg−1) at 0.55 V vs Ag/AgCl. The results on urea electrooxidation show that Ag/ZnO nanostructures can be a potential catalyst for non‐enzymatic biosensors and fuel cells.