bluuebunny/crossref_metadata_2025 huggingface dataset:
Total Synthesis of Isodaphlongamine H: A Possible Biogenetic Conundrum
Authors: Chattopadhyay Amit Kumar , Ly Vu Linh , Jakkepally Shashidhar , Berger Gilles , Hanessian Stephen
Published: January 2016

Herein we describe the first synthetic efforts toward the total synthesis of isodaphlongamine H, a calyciphylline B‐type alkaloid. The strategy employs a chemoenzymatic process for the preparation of a functionalized cyclopentanol with a quaternary center. This molecule is elaborated to form an enantiopure 1‐aza‐perhydrocyclopentalene core, representing rings A and E of all calyciphylline B‐type alkaloids. Further transformations involve the formation of a cyclic enaminone, 1,4‐conjugate addition with a cyclopentenyl subunit, and intramolecular aldol cyclization to achieve a pentacyclic intermediate, ultimately forming isodaphlongamine H in a total of 24 steps from the commercially available compound 2‐carbethoxycyclopentanone. Isodaphlongamine H exhibits promising inhibitory activity against a panel of human cancer cell lines.
Nitrogen‐Doped Graphene for Photocatalytic Hydrogen Generation
Authors: Chang Dong Wook , Baek Jong‐Beom
Published: January 2016

Photocatalytic hydrogen (H2) generation in a water splitting process has recently attracted tremendous interest because it allows the direct conversion of clean and unlimited solar energy into the ideal energy resource of H2. For efficient photocatalytic H2 generation, the role of the photocatalyst is critical. With increasing demand for more efficient, sustainable, and cost‐effective photocatalysts, various types of semiconductor photocatalysts have been intensively developed. In particular, on the basis of its superior catalytic and tunable electronic properties, nitrogen‐doped graphene is a potential candidate for a high‐performance photocatalyst. Nitrogen‐doped graphene also offers additional advantages originating from its unique two‐dimensional sp2‐hybridized carbon network including a large specific surface area and exceptional charge transport properties. It has been reported that nitrogen‐doped graphene can play diverse but positive functions including photo‐induced charge acceptor/meditator, light absorber from UV to visible light, n‐type semiconductor, and giant molecular photocatalyst. Herein, we summarize the recent progress and general aspects of nitrogen‐doped graphene as a photocatalyst for photocatalytic H2 generation. In addition, challenges and future perspectives in this field are also discussed.
MapMaker and PathTracer for tracking carbon in genome‐scale metabolic models
Authors: Tervo Christopher J. , Reed Jennifer L.
Published: January 2016

Constraint‐based reconstruction and analysis (COBRA) modeling results can be difficult to interpret given the large numbers of reactions in genome‐scale models. While paths in metabolic networks can be found, existing methods are not easily combined with constraint‐based approaches. To address this limitation, two tools (MapMaker and PathTracer) were developed to find paths (including cycles) between metabolites, where each step transfers carbon from reactant to product. MapMaker predicts carbon transfer maps (CTMs) between metabolites using only information on molecular formulae and reaction stoichiometry, effectively determining which reactants and products share carbon atoms. MapMaker correctly assigned CTMs for over 97% of the 2,251 reactions in an Escherichia coli metabolic model (iJO1366). Using CTMs as inputs, PathTracer finds paths between two metabolites. PathTracer was applied to iJO1366 to investigate the importance of using CTMs and COBRA constraints when enumerating paths, to find active and high flux paths in flux balance analysis (FBA) solutions, to identify paths for putrescine utilization, and to elucidate a potential CO2 fixation pathway in E. coli. These results illustrate how MapMaker and PathTracer can be used in combination with constraint‐based models to identify feasible, active, and high flux paths between metabolites.
Exploring mild enzymatic sustainable routes for the synthesis of bio‐degradable aromatic‐aliphatic oligoesters
Authors: Pellis Alessandro , Guarneri Alice , Brandauer Martin , Acero Enrique Herrero , Peerlings Henricus , Gardossi Lucia , Guebitz Georg M.
Published: January 2016

The application of Candida antarctica lipase B in enzyme‐catalyzed synthesis of aromatic‐aliphatic oligoesters is here reported. The aim of the present study is to systematically investigate the most favorable conditions for the enzyme catalyzed synthesis of aromatic‐aliphatic oligomers using commercially available monomers. Reaction conditions and enzyme selectivity for polymerization of various commercially available monomers were considered using different inactivated/activated aromatic monomers combined with linear polyols ranging from C2 to C12. The effect of various reaction solvents in enzymatic polymerization was assessed and toluene allowed to achieve the highest conversions for the reaction of dimethyl isophthalate with 1,4‐butanediol and with 1,10‐decanediol (88 and 87% monomer conversion respectively). Mw as high as 1512 Da was obtained from the reaction of dimethyl isophthalate with 1,10‐decanediol. The obtained oligomers have potential applications as raw materials in personal and home care formulations, for the production of aliphatic‐aromatic block co‐polymers or can be further functionalized with various moieties for a subsequent photo‐ or radical polymerization.
Contribution of domain 30 of tropoelastin to elastic fiber formation and material elasticity
Authors: Muiznieks Lisa D. , Miao Ming , Sitarz Eva E. , Keeley Fred W.
Published: January 2016

Elastin is a fibrous structural protein of the extracellular matrix that provides reversible elastic recoil to vertebrate tissues such as arterial vessels, lung, and skin. The elastin monomer, tropoelastin, contains a large proportion of intrinsically disordered and flexible hydrophobic sequences that collectively are responsible for the initial phase separation of monomers during assembly, and are essential for driving elastic recoil. While structural disorder of hydrophobic sequences is controlled by a high proline and glycine residue composition, hydrophobic domain 30 of human tropoelastin is atypically proline‐poor, and forms β‐sheet amyloid‐like fibrils as an individual peptide. We explored the contribution of confined regions of secondary structure at the location of domain 30 in human tropoelastin to fiber assembly and mechanical properties using a set of mutations designed to inhibit or enhance the propensity of β‐sheet formation at this location. Our data support a dual role for confined β‐sheet secondary structure in domain 30 of tropoelastin in guiding the formation of fibers, and as a determinant of stiffness and viscoelastic properties of cross‐linked materials. Together, these results suggest a mechanism for specificity in fiber assembly, and elucidate structure‐function relationships for the rational design of elastomeric biomaterials with defined mechanical properties. © 2016 Wiley Periodicals, Inc. Biopolymers 105: 267–275, 2016.
The use of an imagery mnemonic to teach the Krebs cycle
Authors: Morisaki Ryoma , Bon Charles , Levitt Jacob O.
Published: January 2016

The Krebs Cycle is a highly taught biochemical pathway that is traditionally difficult to learn. Twenty‐seven undergraduate students were randomized to a rote memorization arm or to a mnemonic arm. They were given a pre‐test, then shown a lecture corresponding to their assigned method, and then given an immediate Week 0 post‐test and a Week 4 post‐test. Groups scored comparably low on the pre‐test (p = 0.7113). Students in the mnemonic arm performed better on the Week 0 post‐test than those using rote (p = 0.0055). By Week 4, there was evidence of knowledge decay, with both arms' having comparably low scores (mnemonic vs. rote, p = 0.3739). The mnemonic assists in rapid acquisition of knowledge but probably has to be reviewed iteratively over time to demonstrate its full potential over rote memorization. A limited number of students from only one school was used. © 2016 by The International Union of Biochemistry and Molecular Biology, 44:224–229, 2016.
Prospective evaluation of radiation‐induced skin toxicity in a race/ethnically diverse breast cancer population
Authors: Wright Jean L. , Takita Cristiane , Reis Isildinha M. , Zhao Wei , Lee Eunkyung , Nelson Omar L. , Hu Jennifer J.
Published: January 2016

We evaluated predictors of radiation‐induced skin toxicity in a prospective study of a tri‐racial/ethnic breast cancer population. We evaluated patient demographics, tumor characteristics, and treatment variables in the first 392 patients in a prospective study assessing radiation‐induced skin toxicity. Logistic regression analyses were conducted to evaluate potential predictors of skin toxicity. The study consists of 59 non‐Hispanic whites (NHW; 15%), 241 Hispanic Whites (HW; 62%), 79 black or African Americans (AA; 20%), and 13 others (3%). Overall, 48% developed grade 0–1 skin toxicity, 49.8% grade 2, and 2.2% grade 3 by the National Cancer Institute's Common Toxicity Criteria for Adverse Events (CTCAE) scale. Twenty‐one percent developed moist desquamation. In multivariate analysis, higher body mass index (BMI; OR = 2.09; 95%CI = 1.15, 3.82), higher disease stage (OR = 1.82; 95%CI = 1.06, 3.11), ER‐positive/PR‐negative status (OR = 2.74; 95%CI = 1.26, 5.98), and conventionally fractionated regimens (OR = 3.25; 95%CI = 1.76, 6.01) were significantly associated with higher skin toxicity grade after adjustment for age, race, ethnicity, ER status, and breast volume. BMI specifically predicted for moist desquamation, but not degree of erythema. In this racially and ethnically diverse cohort of breast cancer patients receiving radiation to the intact breast, risk factors including BMI, disease stage, and conventionally fractionated radiation predicted for higher skin toxicity grade, whereas age, race, ethnicity, and breast volume did not. BMI specifically predicted for moist desquamation, suggesting that preventive measures to address this particular outcome should be investigated.
Marine Pyridoacridine Alkaloids: Biosynthesis and Biological Activities
Authors: Ibrahim Sabrin R. M. , Mohamed Gamal A.
Published: January 2016

Pyridoacridines are a class of strictly marine‐derived alkaloids that constitute one of the largest chemical families of marine alkaloids. During the last few years, both natural pyridoacridines and their analogues have constituted excellent targets for synthetic works. They have been the subject of intense study due to their significant biological activities; cytotoxic, antibacterial, antifungal, antiviral, insecticidal, anti‐HIV, and anti‐parasitic activities. In the present review, 95 pyridoacridine alkaloids isolated from marine organisms are discussed in term of their occurrence, biosynthesis, biological activities, and structural assignment.
The safety and effectiveness of bivalirudin in female patients with acute myocardial infarction undergoing primary angioplasty: A subgroup analysis of the BRIGHT trial
Authors: Liang Zhenyang , Li Yi , Wang Jingping , Wang Dongmei , Wang Shouli , Ma Likun , Liu Huiliang , Yang Lixia , Stone Gregg W. , Han Yaling
Published: January 2016

Background

Being female is an independent predictor of adverse events during percutaneous coronary interventions (PCI).

Objective

To evaluate the safety and efficiency of bivalirudin during emergency PCI in female patients with acute myocardial infarction (AMI).

Methods

The present study was a subgroup analysis of the randomized Bivalirudin in Acute Myocardial Infarction vs. Heparin and GPI plus Heparin (BRIGHT) trial. A total of 392 female patients enrolled in the BRIGHT trial were assigned to receive bivalirudin with post‐procedure dose infusion (n = 127) or heparin with or without tirofiban (n = 265). The primary efficiency endpoint was 30‐day net adverse clinical events (NACEs). The secondary efficiency endpoints were 30‐day major cardiac and cerebral events (MACCEs) and bleeding events defined according to Bleeding Academic Research Consortium (BARC) definitions.

Results

For female patients, bivalirudin treatment was associated with significantly lower incidences of 30‐day NACEs (6.3% vs. 21.5%, P < 0.001), any bleeding (2.4% vs. 12.8%, P = 0.001) and BARC 2–5 type bleeding (1.6% vs. 7.2%, P = 0.021) compared with the control regimen. The incidence of MACCEs (3.4% vs. 9.4%, P = 0.055) and stent thrombosis (0% vs. 1.1%, P = 0.229) were comparable between the two groups. Multivariate analysis showed that bivalirudin (OR: 0.245, 95% CI: 0.113–0.532, P < 0.001), transradial access (OR: 0.119, 95% CI: 0.067–0.211, P < 0.001), and statin (OR: 0.254, 95% CI: 0.08–0.807, P = 0.02) were independent protective factors for 30‐day NACEs in female patients.

Conclusions

The use of bivalirudin during emergency PCI for AMI in female patients significantly reduced the bleeding risk with anticoagulation effects compared with heparin with or without tirofiban. © 2016 Wiley Periodicals, Inc.
Enhanced Ene‐Reductase Activity through Alteration of Artificial Nicotinamide Cofactor Substituents
Authors: Löw Sebastian A. , Löw Isabell M. , Weissenborn Martin J. , Hauer Bernhard
Published: January 2016

The reduction of activated C=C double bonds is an important reaction in synthetic chemistry owing to the potential formation of up to two new stereogenic centers. Artificial nicotinamide cofactors were recently presented as alternative suppliers of hydride equivalents needed for alkene reduction. To study the effect of cofactors on the reduction of activated alkenes, a set of N‐substituted synthetic nicotinamide cofactors with differing oxidation potentials were synthesized and their electrochemical and kinetic behavior was studied. The effects of the synthetic cofactors on enzyme activity of four ene reductases are outlined in this study, where the cofactor mimic with an N‐substituted 4‐hydroxy‐phenyl residue led to a sixfold higher vmax relative to the natural cofactor NADH.
Uniform Two‐Dimensional Co3O4 Porous Sheets: Facile Synthesis and Enhanced Photocatalytic Performance
Authors: Liu Jiangyong , Wang Dan , Wang Min , Kong Dejia , Zhang Yi , Chen Jian‐Feng , Dai Liming
Published: January 2016

The preparation of high‐quality two‐dimensional materials with highly interesting properties and applications, such as graphene and graphene analogues, is a rapidly expanding research area. Herein, two‐dimensional porous Co3O4 sheets with high uniformity were synthesized via a facile hydrothermal route. Various characterizations were performed to investigate this sheet‐like structure. Owing to the desired promotion effects and multiple functionalities derived from this unique structure, the porous Co3O4 sheets present an enhanced photocatalytic performance in comparison with the bulk Co3O4 powder.
Transition‐Metal‐Mediated Cleavage of Fluoro‐Silanes under Mild Conditions
Authors: Kameo Hajime , Kawamoto Tatsuya , Sakaki Shigeyoshi , Bourissou Didier , Nakazawa Hiroshi
Published: January 2016

Si−F bond cleavage of fluoro‐silanes was achieved by transition‐metal complexes under mild and neutral conditions. The Iridium‐hydride complex [Ir(H)(CO)(PPh3)3] was found to readily break the Si−F bond of the diphosphine‐ difluorosilane {(o‐Ph2P)C6H4}2Si(F)2 to afford a silyl complex [{[o‐(iPh2P)C6H4]2(F)Si}Ir(CO)(PPh3)] and HF. Density functional theory calculations disclose a reaction mechanism in which a hypervalent silicon species with a dative Ir→Si interaction plays a crucial role. The Ir→Si interaction changes the character of the H on the Ir from hydridic to protic, and makes the F on Si more anionic, leading to the formation of Hδ+⋅⋅⋅Fδ− interaction. Then the Si−F and Ir−H bonds are readily broken to afford the silyl complex and HF through σ‐bond metathesis. Furthermore, the analogous rhodium complex [Rh(H)(CO)(PPh3)3] was found to promote the cleavage of the Si−F bond of the triphosphine‐monofluorosilane {(o‐Ph2P)C6H4}3Si(F) even at ambient temperature.
Fine Substituent Effects in Sandwich Complexes: A Threshold Ionization Study of Monosubstituted Chromium Bisarene Compounds
Authors: Ketkov Sergey Yu. , Markin Gennady V. , Tzeng Sheng Y. , Tzeng Wen B.
Published: January 2016

Mass‐analyzed threshold ionization spectra of jet‐cooled [(η6‐PhMe)(η6‐PhH)Cr] and [(η6‐Ph2)(η6‐PhH)Cr] reveal with unprecedented accuracy the effects of methyl and phenyl groups on the electronic structure of bis(η6‐benzene)chromium. These “pure” substituent effects allow quantitative experimental determination of the ionization energy changes caused by the mutual substituent influence in bisarene systems. Two types of such influence have been revealed for the first time in bis(η6‐toluene)chromium.
ChemInform Abstract: [TM13@Bi20]‐ Clusters in Three‐Shell Icosahedral Matryoshka Structure: Being as Superatoms.
Authors: Kou C. Y. , Zhuang L. , Wang G. Q. , Cui H. , Yuan H. K. , Tian C. L. , Wang J. Z. , Chen H.
Published: January 2016

Using the DFT method the 33‐atom intermetalloid [M13@Bi20]‐ clusters (M: 3d, 4d transition metals) which are composed of Bi20 pentagonal dodecahedra surrounded by M12 icosahedra with a single M atom at the center are systematically examined to explore the possibility of the clusters being superatoms.
ChemInform Abstract: Structural and Crystal Chemical Properties of Alkali Rare‐Earth Double Phosphates.
Authors: Farmer J. Matt , Boatner L. A. , Chakoumakos Bryan C. , Rawn Claudia J. , Richardson Jim
Published: January 2016

Crystals of K3Ln(PO4)2 (Ln: Lu, Yb, Er, Ho, Dy, Gd, Nd, Ce, Y, Sc) and M3Lu(PO4)2 (M: Rb, Cs) are prepared from a M4P2O7/Ln2O3 flux (Pt crucible, 1235 °C, 4 h) and their crystal structures are determined by single crystal XRD and powder neutron diffraction.
ChemInform Abstract: Crystal Structures of Cristobalite‐Type and Coesite‐Type PON Redetermined on the Basis of Single‐Crystal X‐Ray Diffraction Data.
Authors: Bykov Maxim , Bykova Elena , Dyadkin Vadim , Baumann Dominik , Schnick Wolfgang , Dubrovinsky Leonid , Dubrovinskaia Natalia
Published: January 2016

Single crystals of cristobalite‐type PON (cri‐PON) are prepared by a two‐step condensation process starting with the reaction of POCl3 and liq.
ChemInform Abstract: A High‐Performance Electrocatalyst for Oxygen Evolution Reaction: LiCo0.8Fe0.2O2.
Authors: Zhu Yinlong , Zhou Wei , Chen Yubo , Yu Jie , Liu Meilin , Shao Zongping
Published: January 2016

Layered LiCo1‐xFexO2 (x = 0—1) is prepared by sol‐gel processing applying stoichiometric amounts of metal nitrates and EDTA and citric acid in molar ratios of 1:1:2 at pH≈6.
ChemInform Abstract: Enantio‐ & Chemo‐Selective Preparation of Enantiomerically Enriched Aliphatic Nitro Alcohols Using Candida parapsilosis ATCC 7330.
Authors: Venkataraman Sowmyalakshmi , Chadha Anju
Published: January 2016

The title biocatalyst mediates the asymmetric, chemoselective reduction of nitroketones wherein the keto group is preferred with respect to the nitro group.
ChemInform Abstract: Copper‐Catalyzed Asymmetric Conjugate Addition of Dimethylzinc to Acyl‐N‐methylimidazole Michael Acceptors: A Powerful Synthetic Platform.
Authors: Drissi‐Amraoui Sammy , Morin Marie S. T. , Crevisy Christophe , Basle Olivier , Marcia de Figueiredo Renata , Mauduit Marc , Campagne Jean‐Marc
Published: January 2016

The enantioselective addition of dimethylzinc to α,β‐unsaturated ketones of type (I) in the presence of Cu(OTf)2 and the chiral NHC (IMD) as catalysts affords the corresponding 1,4‐adducts (III) in high regio‐ and enantioselectivities.
ChemInform Abstract: One‐Pot Synthesis of New Triazole—Imidazo[2,1‐b][1,3,4]thiadiazole Hybrids via Click Chemistry and Evaluation of Their Antitubercular Activity.
Authors: Ramprasad Jurupula , Nayak Nagabhushana , Dalimba Udayakumar , Yogeeswari Perumal , Sriram Dharmarajan
Published: January 2016

Title compounds (III) are synthesized via one‐pot click chemistry protocol.
ChemInform Abstract: Single‐Flask Multicomponent Palladium‐Catalyzed α,γ‐Coupling of Ketone Enolates: Facile Preparation of Complex Carbon Scaffolds.
Authors: Grigalunas Michael , Norrby Per‐Ola , Wiest Olaf , Helquist Paul
Published: January 2016

A novel Pd‐catalyzed reaction sequence consisting of α‐alkenylation of a ketone with an alkenyl bromide and direct one‐pot coupling with an alkyl or alkenyl bromide is described providing access to structurally diverse α,β‐unsaturated ketones.
ChemInform Abstract: Reusable Biomacromolecule‐Pd Complex Catalyzed C—C Cross‐Coupling Reactions via C—S Cleavage of Disulfides.
Authors: Yang Quanlu , Wu Shang , Quan Zhengjun , Du Baoxin , Wang Mingming , Li Peidong , Zhang Yinpan , Lei Ziqiang , Wang Xicun
Published: January 2016

Natural wool supported Pd(OAc)2‐complex is found to be an effective catalyst for the C—S bonds cleavage and C—C bonds formation from various disulfides with arylboronic acids or terminal alkynes, giving the desired coupling products in high yields.
ChemInform Abstract: Direct Synthesis of Hemiaminal Ethers via a Three‐Component Reaction of Aldehydes, Amines and Alcohols.
Authors: Beltran Alvaro , Alvarez Eleuterio , Diaz‐Requejo M. Mar , Perez Pedro J.
Published: January 2016

in the presence of molecular sieves as a solid acid and dehydrating agent
ChemInform Abstract: Diastereoselective Fluorocyclopropanation of Chiral Allylic Alcohols Using an α‐Fluoroiodomethylzinc Carbenoid.
Authors: Navuluri Chandrasekhar , Charette Andre B.
Published: January 2016

A highly diastereoselective fluorocyclopropanation of allylic alcohols (I), (IV), and (VI) and glyceraldehyde derived allylic ethers (VIII) and (X) is developed using fluorocarbenoid (II) as methylene source.
ChemInform Abstract: Ring Opening of Bicyclo[3.1.0]hexan‐2‐ones: A Versatile Synthetic Platform for the Construction of Substituted Benzoates.
Authors: Feierfeil Johannes , Grossmann Adriana , Magauer Thomas
Published: January 2016

A convenient method is described for the thermolytic conversion of a range of structurally diverse bicyclo[3.1.0]hexan‐2‐ones having an ester and a chloro substituent on the three‐membered ring.
ChemInform Abstract: Ni(II)‐Catalyzed Sulfonylation of ortho C—H Bonds in Aromatic Amides Utilizing an N,N‐Bidentate Directing Group.
Authors: Yokota Ayana , Chatani Naoto
Published: January 2016

The Ni(II)‐catalyzed sulfonylation of ortho C—H bonds in aromatic amides of type (I) or (IV) is described.
ChemInform Abstract: Transition Metal‐Free Aroylation of NH‐Sulfoximines with Methyl Arenes.
Authors: Zou Ya , Xiao Jing , Peng Zhihong , Dong Wanrong , An Delie
Published: January 2016

A simple procedure is elaborated for the synthesis of N‐aroyl sulfoximines (III) and (V) by an aroylation reaction of NH‐sulfoximines with methylarenes.
ChemInform Abstract: Water‐Soluble Salen—Pd Complex as an Efficient Catalyst for Suzuki—Miyaura Reaction of Sterically Hindered Substrates in Pure Water.
Authors: Liu Ya‐shuai , Gu Ning‐ning , Liu Ping , Ma Xiao‐wei , Liu Yan , Xie Jian‐wei , Dai Bin
Published: January 2016

A wide range of biaryl compounds are obtained with high functional group tolerance.
ChemInform Abstract: On the Reactivity of Pyrido[3′,2′:4,5]furo(thieno)[3,2‐d]pyrimidin‐7(8)‐ones with Some Alkyl Mono‐ and Di‐halides: Synthesis of New Heterocyclic Systems Containing Thiazolo[3,2‐a]pyrimidine and Pyrimido[2,1‐b]thiazine Moiety.
Authors: Sirakanyan Samvel N. , Spinelli Domenico , Geronikaki Athina , Hovakimyan Anush A.
Published: January 2016

The reaction of the title compounds with methyl iodide gives S‐methylated compounds [e.g. (III)].
ChemInform Abstract: Synthesis of Novel Spiro[indol‐2,2′‐pyrroles] Using Isocyanide‐Based Multicomponent Reaction.
Authors: Jalli Venkataprasad , Krishnamurthy Suvratha , Kawasaki Hiroyoshi , Moriguchi Tetsuji , Tsuge Akihiko
Published: January 2016

An efficient and facile method for the synthesis of novel spiro[indole‐2,2′‐pyrroles] (IV) from N‐methyl‐3‐isatin imines, alkyl isocyanide, and dialkyl acetylenedicarboxylate is achieved by [3 + 2] cycloaddition reaction.
ChemInform Abstract: Regio‐ and Stereoselective Synthesis of Spiropyrrolizidines and Piperazines Through Azomethine Ylide Cycloaddition Reaction.
Authors: Haddad Saoussen , Boudriga Sarra , Porzio Francois , Soldera Armand , Askri Moheddine , Knorr Michael , Rousselin Yoann , Kubicki Marek M. , Golz Christopher , Strohmann Carsten
Published: January 2016

A new family of spirooxindolepyrrolizidines is obtained by an unprecedented isomerization of some spiroadducts obtained by one‐pot three‐component [3+2] cycloaddition reaction of pyrrolidinediones, L‐proline, and cyclic ketones.
ChemInform Abstract: Gold‐Catalyzed Cycloisomerization of [3]‐Cumulenols.
Authors: Ferrand Laura , Das Neves Nicolas , Malacria Max , Mouries‐Mansuy Virginie , Ollivier Cyril , Fensterbank Louis
Published: January 2016

The two‐step, one‐pot protocol for the coupling of 1,3‐butadiynes with aldehydes by subsequent gold(I)‐catalyzed cycloisomerization furnishes furan derivatives via tetrafunctionalized [3]‐cumulenol intermediates.
ChemInform Abstract: Successive Cu/Pd Transmetalation Relay Catalysis in Stereoselective Synthesis of Tetraarylethenes.
Authors: Song Chuanling , Sun Yihua , Wang Jianwu , Chen Hui , Yao Jiannian , Tung Chen‐Ho , Xu Zhenghu
Published: January 2016

Tetrasubstituted olefins are prepared as a single stereoisomers by a Cu/Pd‐catalyzed isomerization/insertion/oxidative coupling cascade reaction of cyclopropenes with internal alkynes.
ChemInform Abstract: Aqueous Titanium Trichloride Promoted Reductive Cyclization of o‐Nitrostyrenes to Indoles: Development and Application to the Synthesis of Rizatriptan and Aspidospermidine.
Authors: Tong Shuo , Xu Zhengren , Mamboury Mathias , Wang Qian , Zhu Jieping
Published: January 2016

The title reaction offers a straightforward synthesis of functionalized indoles from structurally diverse o‐nitrostyrenes.
ChemInform Abstract: One‐Pot Three‐Component Reactions of Methyl Ketones, Phenols and a Nucleophile: An Expedient Way to Synthesize Densely Substituted Benzofurans.
Authors: Cheng Cheng , Liu Changhui , Gu Yanlong
Published: January 2016

Other nucleophiles, such as 1,2,4‐trimethoxybenzene and thiophenol, can also be utilized instead of the indole component.
ChemInform Abstract: (Z)‐Stereoselective Synthesis of Mono‐ and Bis‐heterocyclic Benzimidazol‐2‐ones via Cascade Processes Coupled with the Ugi Multicomponent Reaction.
Authors: Xu Zhigang , Martinez‐Ariza Guillermo , Cappelli Alexandra P. , Roberts Sue A. , Hulme Christopher
Published: January 2016

The acid treatment of various Ugi adducts afford 1,5‐benzodiazepines which subsequently undergo a rearrangement affording benzimidazolones.
ChemInform Abstract: Synthesis of 3‐Substituted 2‐Aminochromones via Sn(IV)‐Promoted Annulation of Ynamides with 2‐Methoxyaroyl Chlorides.
Authors: Liu Hongxu , Yang Yanyan , Wang Shen , Wu Jie , Wang Xiao‐Na , Chang Junbiao
Published: January 2016

This tandem Friedel—Crafts acylation/oxo‐Michael addition/elimination strategy provides a general access to 2‐aminochromones under mild conditions and tolerates a wide range of functional groups.
ChemInform Abstract: Facile Construction of Novel Heterocyclic Compounds: Three‐Component, One‐Pot Synthesis of 2‐Hydroxybenzoyl‐1,2‐dihydropyridine‐3‐carboxylates, Ketones, Pyridone‐3‐carboxylates and Benzopyrido‐1,3‐oxazole‐4‐carboxylates.
Authors: Rajkumar Kommera , Suman Pathi , Raju Bhimapaka China
Published: January 2016

This facile and catalyst‐free method furnishes various biologically interesting heterocyclic compounds by a three‐component, one‐pot approach.
ChemInform Abstract: Regioselective, Molecular Iodine‐Mediated C3 Iodination of Quinolines.
Authors: Sun Kai , Lv Yunhe , Wang Junjie , Sun Jingjing , Liu Lulu , Jia Mingyang , Liu Xin , Li Zhenduo , Wang Xin
Published: January 2016

This method allows the regioselective C3 iodination of quinolines on gram scale with good yields.
ChemInform Abstract: Access to Highly Substituted 7‐Azaindoles from 2‐Fluoropyridines via 7‐Azaindoline Intermediates.
Authors: Nuhant Philippe , Allais Christophe , Chen Ming Z. , Coe Jotham W. , Dermenci Alpay , Fadeyi Olugbeminiyi O. , Flick Andrew C. , Mousseau James J.
Published: January 2016

A sequence for the synthesis of 2‐fluoro‐3‐(2‐nitroethyl)pyridines and their reaction to 7‐azaindolines is presented.
ChemInform Abstract: Tandem 1,2‐Sulfur Migration and (Aza)‐Diels—Alder Reaction of β‐Thio‐α‐diazoimines: Rhodium Catalyzed Synthesis of (Fused)‐Polyhydropyridines, and Cyclohexenes.
Authors: Yadagiri Dongari , Anbarasan Pazhamalai
Published: January 2016

The title reaction proceeds via 1‐azadiene (II) intermediate, which undergoes self aza‐Diels—Alder reaction and subsequent 1,2‐sulfur migration to give tetrahydropyridines [e.g. (III)].
ChemInform Abstract: Synthesis of Indolizine Derivatives by Pd‐Catalyzed Oxidative Carbonylation.
Authors: Xu Tongyu , Alper Howard
Published: January 2016

Pd‐catalyzed three component reactions of propargylic pyridines, alcohols, and carbon monoxide afford a wide variety of highly functionalized indolizine derivatives.
ChemInform Abstract: Rhodium(III)‐Catalyzed Annulation of 2‐Arylimidazo[1,2‐a]pyridines and Alkynes via Direct Double C—H Activation.
Authors: Wang Wei , Niu Jun‐Long , Liu Wen‐Bo , Shi Tan‐Hao , Hao Xin‐Qi , Song Mao‐Ping
Published: January 2016

A series of naphthoimidazo[1,2‐a]pyridines is smoothly synthesized by rhodium‐catalyzed reaction of 2‐arylimidazo[1,2‐a]pyridines with symmetrical and unsymmetrical alkynes.
ChemInform Abstract: Stereoselective Synthesis of Hernandulcin, Peroxylippidulcine A, Lippidulcines A, B and C and Taste Evaluation.
Authors: Rigamonti Marco Giulio , Gatti Francesco Gilberto
Published: January 2016

The first stereoselective synthesis of peroxylippidulcine A (IIa) and lippidulcines A (IIb), B (III), and C (IV) is described.
ChemInform Abstract: Diterpenes from the Roots of Oryza sativa L. and Their Inhibition Activity on NO Production in LPS‐Stimulated RAW264.7 Macrophages.
Authors: Baek Nam‐In , et al.
Published: January 2016

isolation, structure elucidation and bioactivity of two new pimarane diterpenoids, momilactone D (I) and E (II), along with three known diterpenoids
ChemInform Abstract: Directing Remote Meta‐C‐H Functionalization with Cleavable Auxiliaries
Authors: Frost Christopher G. , Paterson Andrew J.
Published: January 2016

Review: 10 refs.
ChemInform Abstract: So Called “Dual Emission” for 3MLCT Luminescence in Ruthenium Complex Ions: What Is Really Happening?
Authors: Magde Douglas , Magde, Michael D. Jr. , Glazer Edith C.
Published: January 2016

Review: 55 refs.
ChemInform Abstract: Chemical Synthesis of Crystalline Proteins
Authors: Huang Yichao , Liu Lei
Published: January 2016

Review: 27 refs.
ChemInform Abstract: Bulk and Surface Analysis of Carbonaceous Materials
Authors: Shuttleworth Peter S. , Baccile Niki , White Robin J. , Nectoux Eric , Budarin Vitaliy L.
Published: January 2016

Review: 125 refs.
Impaired mitochondrial function is abrogated by dexrazoxane in doxorubicin‐treated childhood acute lymphoblastic leukemia survivors
Authors: Lipshultz Steven E. , Anderson Lynn M. , Miller Tracie L. , Gerschenson Mariana , Stevenson Kristen E. , Neuberg Donna S. , Franco Vivian I. , LiButti Daniel E. , Silverman Lewis B. , Vrooman Lynda M. , Sallan Stephen E. ,   for the Dana‐Farber Cancer Institute Acute Lymphoblastic Leukemia Consortium
Published: January 2016

BACKGROUND

Impaired cardiac function in doxorubicin‐treated childhood cancer survivors is partly mediated by the disruption of mitochondrial energy production. Doxorubicin intercalates into mitochondrial DNA (mtDNA) and disrupts genes encoding for polypeptides that make adenosine triphosphate.

METHODS

This cross‐sectional study examined mtDNA copy numbers per cell and oxidative phosphorylation (OXPHOS) in peripheral blood mononuclear cells (PBMCs) in 64 childhood survivors of high‐risk acute lymphoblastic leukemia (ALL) who had been treated on Dana‐Farber Cancer Institute childhood ALL protocols and had received doxorubicin alone (42%) or doxorubicin with the cardioprotectant dexrazoxane (58%). The number of mtDNA copies per cell and the OXPHOS enzyme activity of nicotinamide adenine dinucleotide dehydrogenase (complex I [CI]) and cytochrome c oxidase (complex IV [CIV]) were measured with quantitative real‐time polymerase chain reaction immunoassays and thin‐layer chromatography, respectively.

RESULTS

At a median follow‐up of 7.8 years after treatment, the median number of mtDNA copies per cell for patients treated with doxorubicin alone (1106.3) was significantly higher than the median number for those who had also received dexrazoxane (310.5; P = .001). No significant differences were detected between the groups for CI or CIV activity.

CONCLUSIONS

Doxorubicin‐treated survivors had an increased number of PBMC mtDNA copies per cell, and concomitant use of dexrazoxane was associated with a lower number of mtDNA copies per cell. Because of a possible compensatory increase in mtDNA copies per cell to maintain mitochondrial function in the setting of mitochondrial dysfunction, overall OXPHOS activity was not different between the groups. The long‐term sustainability of this compensatory response in these survivors at risk for cardiac dysfunction over their lifespan is concerning. Cancer 2016;122:946–53. © 2016 American Cancer Society.
Organization of projection neurons and local neurons of the primary auditory center in the fruit flyDrosophila melanogaster
Authors: Matsuo Eriko , Seki Haruyoshi , Asai Tomonori , Morimoto Takako , Miyakawa Hiroyoshi , Ito Kei , Kamikouchi Azusa
Published: January 2016

Acoustic communication between insects serves as an excellent model system for analyzing the neuronal mechanisms underlying auditory information processing. The detailed organization of auditory neural circuits in the brain has not yet been described. To understand the central auditory pathways, we used the brain of the fruit flyDrosophila melanogasteras a model and performed a large‐scale analysis of the interneurons associated with the primary auditory center. By screening expression driver strains and performing single‐cell labeling of these strains, we identified 44 types of interneurons innervating the primary auditory center. Five types were local interneurons whereas the other 39 types were projection interneurons connecting the primary auditory center with other brain regions. The projection neurons comprised three frequency‐selective pathways and two frequency‐embracive pathways. Mapping of their connection targets revealed that five neuropils in the brain—the wedge (WED), anterior ventrolateral protocerebrum, posterior ventrolateral protocerebrum (PVLP), saddle (SAD), and gnathal ganglia (GNG)—were intensively connected with the primary auditory center. In addition, several other neuropils, including visual and olfactory centers in the brain, were directly connected to the primary auditory center. The distribution patterns of the spines and boutons of the identified neurons suggest that auditory information is sent mainly from the primary auditory center to the PVLP, WED, SAD, GNG, and thoracico‐abdominal ganglia. Based on these findings, we established the first comprehensive map of secondary auditory interneurons, which indicates the downstream information flow to parallel ascending pathways, multimodal pathways, and descending pathways. J. Comp. Neurol. 524:1099–1164, 2016. © 2016 Wiley Periodicals, Inc.
High‐Pressure Raman and Calorimetry Studies of Vanadium(III) Alkyl Hydrides for Kubas‐Type Hydrogen Storage
Authors: Morris Leah , Trudeau Michel L. , Reed Daniel , Book David , Antonelli David M.
Published: January 2016

Reversible hydrogen storage under ambient conditions has been identified as a major bottleneck in enabling a future hydrogen economy. Herein, we report an amorphous vanadium(III) alkyl hydride gel that binds hydrogen through the Kubas interaction. The material possesses a gravimetric adsorption capacity of 5.42 wt % H2 at 120 bar and 298 K reversibly at saturation with no loss of capacity after ten cycles. This corresponds to a volumetric capacity of 75.4 kgH2 m−3. Raman experiments at 100 bar confirm that Kubas binding is involved in the adsorption mechanism. The material possesses an enthalpy of H2 adsorption of +0.52 kJ mol−1 H2, as measured directly by calorimetry, and this is practical for use in a vehicles without a complex heat management system.
Diffusion of Oligonucleotides from within Iron‐Cross‐Linked, Polyelectrolyte‐Modified Alginate Beads: A Model System for Drug Release
Authors: Privman Vladimir , Domanskyi Sergii , Luz Roberto A. S. , Guz Nataliia , Glasser M. Lawrence , Katz Evgeny
Published: January 2016

An analytical model to describe diffusion of oligonucleotides from stable hydrogel beads is developed and experimentally verified. The synthesized alginate beads are Fe3+‐cross‐linked and polyelectrolyte‐doped for uniformity and stability at physiological pH. Data on diffusion of oligonucleotides from inside the beads provide physical insights into the volume nature of the immobilization of a fraction of oligonucleotides due to polyelectrolyte cross‐linking, that is, the absence of a surface‐layer barrier in this case. Furthermore, the results suggest a new simple approach to measuring the diffusion coefficient of mobile oligonucleotide molecules inside hydrogels. The considered alginate beads provide a model for a well‐defined component in drug‐release systems and for the oligonucleotide‐release transduction steps in drug‐delivering and biocomputing applications. This is illustrated by destabilizing the beads with citrate, which induces full oligonucleotide release with nondiffusional kinetics.
Visible‐Light‐Driven Water Oxidation on a Photoanode by Supramolecular Assembly of Photosensitizer and Catalyst
Authors: Li Hua , Li Fei , Wang Yong , Bai Lichen , Yu Fengshou , Sun Licheng
Published: January 2016

A ruthenium water oxidation catalyst (WOC) bearing hydrophobic ligands was incorporated on the surface of a dye‐sensitized nanostructured TiO2 film by formation of a host–guest adduct with the dye. This provides a new strategy for constructing photocatalytically active electrodes for water oxidation. The resultant photoanode exhibits a photocurrent of 800 μA cm−2 under visible‐light illumination (λ>400 nm, 300 mW cm−2) and 240 μA cm−2 under simulated sunlight illumination (AM 1.5G, 100 mW cm−2) with an applied bias of 0.2 V vs. NHE in neutral phosphate buffer.
Ammonia Decomposition with Manganese Nitride–Calcium Imide Composites as Efficient Catalysts
Authors: Yu Pei , Guo Jianping , Liu Lin , Wang Peikun , Wu Guotao , Chang Fei , Chen Ping
Published: January 2016

Ammonia has high gravimetric and volumetric hydrogen densities and is, therefore, considered a promising carrier for the production of COx‐free molecular H2 for forthcoming energy systems. Alkaline earth metals are generally regarded as structural promoters of catalysts and employed in numerous catalytic processes. Here, we report that calcium imide (CaNH) has a strong synergistic effect on Mn6N5 in catalyzing the decomposition of NH3, leading to a ca. 40 % drop in apparent activation energy. At 773 K, the H2 formation rate over a Mn6N5‐11CaNH composite catalyst is about an order of magnitude higher than that of Mn6N5 and comparable to the highly active Ni/SBA‐15 and Ru/Al2O3 catalysts. Analysis by means of temperature‐programmed decomposition (TPD), X‐ray diffraction (XRD), and X‐ray absorption near edge spectroscopy (XANES) reveal that CaNH participates in the catalysis via forming a [Ca6MnN5]‐like intermediate, thus altering the reaction pathway and energetics. A two‐step catalytic cycle, accounting for the synergy between CaNH and Mn6N5, is proposed.
Antihyperalgesic Activity ofRhodiolaroseain a Diabetic Rat Model
Authors: Déciga‐Campos Myrna , González‐Trujano Maria Eva , Ventura‐Martínez Rosa , Montiel‐Ruiz Rosa Mariana , Ángeles‐López Guadalupe Esther , Brindis Fernando
Published: January 2016

Preclinical Research

Rhodiola rosea L. (Crassulaceae) is used for enhancing physical and mental performance. Recent studies demonstrated thatR. roseahad anti‐inflammatory activity in animal models, for example, carrageenan‐ and nystatin‐induced edema in rats, possibly by inhibiting phospholipase A2and cyclooxygenases‐1 and ‐2. In addition,R. roseahad antinociceptive activity in thermal and chemical pain tests as well as mechanical hyperalgesia. The purpose of the present study was to assess the antihyperalgesic effect of an ethanol extract ofRhodiola rosea(R. rosea) in a diabetic rat model. Rats were administered a single dose ofstreptozotocin (STZ; 50 mg/kg, i.p.) and hyperalgesia was evaluated four weeks later. Formalin‐evoked (0.5%) flinching was increased in diabetic rats compared with nondiabetic controls Systemic (1–100 mg/kg, i.p.) and local (0.1–10 mg/paw into the dorsal surface of the right hind paw) administration ofR. roseaethanol extract dose‐dependently reduced formalin‐induced hyperalgesia in diabetic rats. The antihyperalgesic effect ofR. roseawas compared with gabapentin. These results suggest thatR. roseaethanol extract may have potential as a treatment for diabetic hyperalgesia. Drug Dev Res 77 : 29–36, 2016. © 2016 Wiley Periodicals, Inc.
Synthesis of p‐O‐Alkyl Salicylanilide Derivatives as Novel EGFR Inhibitors
Authors: Zhang Li , Hou Lin , Sun Wenyan , Yu Zidong , Wang Jibo , Gao Hua , Yang Guiming
Published: January 2016

Preclinical Research

Epidermal growth factor receptor (EGFR), a validated target for anticancer drugs, plays a critical role in tumorigenesis and tumor development. A series of p‐O‐alkyl salicylanilide derivatives were designed and synthesized as novel EGFR inhibitors using a salicylic acid scaffold. A simulated six‐membered ring strategy formed through intramolecular hydrogen bonds was employed to mimic the planar quinazoline of the EGFR antagonist, gefitinib. The derived compounds with hydroxyl at the ortho position were more potent than ones with methoxyl group. In particular, compounds 5d and 5b displayed significant EGFR inhibitory (IC50 values = 0.30 and 0.45 μM, respectively) activity as well as potent antiproliferative activity in A431 and HCT‐116 tumor cells. These salicylanilides could be considered as promising lead compounds for developing novel EGFR inhibitors. Drug Dev Res 77 : 37–42, 2016. © 2016 Wiley Periodicals, Inc.
Significance of myocardial tenascin‐C expression in left ventricular remodelling and long‐term outcome in patients with dilated cardiomyopathy
Authors: Yokokawa Tetsuro , Sugano Yasuo , Nakayama Takafumi , Nagai Toshiyuki , Matsuyama Taka‐aki , Ohta‐Ogo Keiko , Ikeda Yoshihiko , Ishibashi‐Ueda Hatsue , Nakatani Takeshi , Yasuda Satoshi , Takeishi Yasuchika , Ogawa Hisao , Anzai Toshihisa
Published: January 2016

Aim

Dilated cardiomyopathy (DCM) has a variety of causes, and no useful approach to predict left ventricular (LV) remodelling and long‐term outcome has yet been established. Myocardial tenascin‐C (TNC) is known to appear under pathological conditions, possibly to regulate cardiac remodelling. The aim of this study was to clarify the significance of myocardial TNC expression in LV remodelling and the long‐term outcome in DCM.

Methods and results

One hundred and twenty‐three consecutive DCM patients who underwent endomyocardial biopsy for initial diagnosis were studied. Expression of TNC in biopsy sections was analysed immunohistochemically to quantify the ratio of the TNC‐positive area to the whole myocardial tissue area (TNC area). Clinical parameters associated with TNC area were investigated. The patients were divided into two groups based on receiver operating characteristic analysis of TNC area to predict death: high TNC group with TNC area ≥2.3% (22 patients) and low TNC group with TNC area <2.3% (101 patients). High TNC was associated with diabetes mellitus. Comparing echocardiographic findings between before and 9 months after endomyocardial biopsy, the low TNC group was associated with decreased LV end‐diastolic diameter and increased LV ejection fraction, whereas the high TNC group was not. Survival analysis revealed a worse outcome in the high TNC group than in the low TNC group (P < 0.001). Multivariable Cox regression analysis revealed that TNC area was independently associated with poor outcome (HR = 1.347, P = 0.032).

Conclusions

Increased myocardial TNC expression was associated with worse LV remodeling and long‐term outcome in DCM.
Transcriptional regulation of early T‐cell development in the thymus
Authors: Seo Wooseok , Taniuchi Ichiro
Published: January 2016

T‐cell development occurs in multipotent progenitors arriving in the thymus, which provides a highly specialized microenvironment. Specification and sequential commitment processes to T cells begin in early thymic progenitors upon receiving thymus‐specific environmental cues, resulting in the activation of the genetically programmed transcriptional cascade that includes turning on and off numerous transcription factors in a precise manner. Thus, early thymocyte differentiation has been an excellent model system to study cell differentiation processes. This review summarizes recent advances in our knowledge on thymic T‐cell development from newly arrived multipotent T‐cell progenitors to fully committed T‐cell precursors, from the transcriptional regulation perspective.
Entrapment of 5‐aminolevulinic acid under edible composite film of konjac glucomannan and chitosan
Authors: Tripetch Phattanit , Borompichaichartkul Chaleeda , Duangmal Kiattisak , Srzednicki George
Published: January 2016

5‐Aminolevulinic acid (5‐ALA) is a known plant regulator and growth promoter. It is a very sensitive and highly unstable compound that is easy to deteriorate. Here we propose a novel approach to stabilize 5‐ALA into a film. Films from konjac glucomannan (KGM), KGM treated with alkali solution (KGOH), chitosan (CHI) as well as blends between KGOH and CHI were fabricated for 5‐ALA entrapment. It was found that the efficiency of KGM film, KGOH film and CHI film for 5‐ALA entrapment was 55.7 ± 0.73%, 58.3 ± 0.36% and 60.3 ± 0.18 %, respectively. A 25:75 (%w/w) blended film (KGOH/CHI) showed the highest entrapment efficiency of 5‐ALA (65.9 ± 0.37%) versus other films. The possible mechanism for entrapment of 5‐ALA in blended film was postulated under two mechanisms. A secondary amide that leads to the interaction between the amino group of CHI and carboxyl group of 5‐ALA is proposed as the first mechanism. The fact that the 5‐ALA molecule was entrapped within the complexity of KGOH structure is proposed as the second mechanism. Therefore, stabilizing 5‐ALA in a film may be an alternative way to use and preserve 5‐ALA for further applications.
Sustainability assessment of photobiological hydrogen production using anaerobic bacteria (Rhodospirillum rubrum) via exergy concept: Effect of substrate concentrations
Authors: Dadak Ali , Aghbashlo Mortaza , Tabatabaei Meisam , Najafpour Ghasem , Younesi Habibollah
Published: January 2016

The detailed exergy analysis of photobiological hydrogen production from syngas through water–gas shift (WGS) reaction via anaerobic bacteria Rhodospirillum rubrum was presented. Several exergetic parameters for the fermentation process were computed based on both the conventional exergy and eco‐exergy concepts. The microorganisms were supported using acetate as carbon source at various concentrations (0.5–3 g/L) in a CO‐enriched media in a batch culture and produced hydrogen by utilizing the harmful carbon monoxide. The results manifested that the cumulative rational exergetic efficiency based on the conventional exergy was lower than that obtained using the eco‐exergy concept. However, the cumulative exergy destruction based on the conventional exergy concept was higher than of the eco‐exergy theory. Therefore, it seems that the eco‐exergy concept was much more suitable as decision‐making tool to assess the sustainability of renewable energy projects containing living microorganisms. The highest cumulative process exergetic efficiency values were achieved at the acetate concentration of 1 g/L via the exergy and eco‐exergy concepts, at 0.5156% and 0.5139%, respectively. This revealed the suitability of this dosage for large‐scale biohydrogen production. Principally, the findings of this study can provide a theoretical framework for decision making on sustainability and renewability of the biological hydrogen production. © 2016 American Institute of Chemical Engineers Environ Prog, 35: 1166–1176, 2016