bluuebunny/crossref_metadata_2025 huggingface dataset:
De Novo Design of Skin‐Penetrating Peptides for Enhanced Transdermal Delivery of Peptide Drugs
Authors: Menegatti Stefano , Zakrewsky Michael , Kumar Sunny , De Oliveira Joshua Sanchez , Muraski John A. , Mitragotri Samir
Published: January 2016

Skin‐penetrating peptides (SPPs) are attracting increasing attention as a non‐invasive strategy for transdermal delivery of therapeutics. The identification of SPP sequences, however, currently performed by experimental screening of peptide libraries, is very laborious. Recent studies have shown that, to be effective enhancers, SPPs must possess affinity for both skin keratin and the drug of interest. We therefore developed a computational process for generating and screening virtual libraries of disulfide‐cyclic peptides against keratin and cyclosporine A (CsA) to identify SPPs capable of enhancing transdermal CsA delivery. The selected sequences were experimentally tested and found to bind both CsA and keratin, as determined by mass spectrometry and affinity chromatography, and enhance transdermal permeation of CsA. Four heptameric sequences that emerged as leading candidates (ACSATLQHSCG, ACSLTVNWNCG, ACTSTGRNACG, and ACSASTNHNCG) were tested and yielded CsA permeation on par with previously identified SPP SPACE TM. An octameric peptide (ACNAHQARSTCG) yielded significantly higher delivery of CsA compared to heptameric SPPs. The safety profile of the selected sequences was also validated by incubation with skin keratinocytes. This method thus represents an effective procedure for the de novo design of skin‐penetrating peptides for the delivery of desired therapeutic or cosmetic agents.
Synthesis of Thin‐Layered Molybdenum Disulfide‐Based Polyaniline Nanointerfaces for Enhanced Direct Electrochemical DNA Detection
Authors: Yang Tao , Meng Le , Chen Huaiyin , Luo Shizhong , Li Weihua , Jiao Kui
Published: January 2016

The low electronic conductivity limits the application of molybdenum disulfide (MoS2) in electrochemical sensing field, let alone the label‐free and self‐signal amplification DNA sensing. Aiming at this problem, a novel polyaniline‐molybdenum disulfide (PANI‐MoS2) nanocomposite through a facile oxidation polymerization aniline monomer on the thin‐layer MoS2 matrix is prepared, which is preobtained via a simple ultrasonic exfoliation method. It is generally appreciated that conducting polymers, e.g., polyaniline (PANI), can work as a direct transducer based on themselves‐signal without any label or indicator. Moreover, MoS2 not only serves as an excellent conductive skeleton provided a high electrolytic accessible surface area for redox‐active PANI, but also supports a direct path for electron transfer. Therefore, the hybrid of PANI and MoS2 exhibits superior electrochemical performance to pure PANI and MoS2, and can be considered as a superior candidate for direct and label‐free electrochemical DNA sensing. A series of experiments are performed to investigate the effect of synthetic conditions (component, dosage of MoS2, and reaction time) on probe DNA (pDNA) immobilization and hybridization adopting the PANI self‐signal as the measure signal. The results show that the dosage of MoS2 has a more influence on pDNA immobilization and hybridization.
Electrochemical Stability of Li10GeP2S12 and Li7La3Zr2O12 Solid Electrolytes
Authors: Han Fudong , Zhu Yizhou , He Xingfeng , Mo Yifei , Wang Chunsheng
Published: January 2016

The electrochemical stability window of solid electrolyte is overestimated by the conventional experimental method using a Li/electrolyte/inert metal semiblocking electrode because of the limited contact area between solid electrolyte and inert metal. Since the battery is cycled in the overestimated stability window, the decomposition of the solid electrolyte at the interfaces occurs but has been ignored as a cause for high interfacial resistances in previous studies, limiting the performance improvement of the bulk‐type solid‐state battery despite the decades of research efforts. Thus, there is an urgent need to identify the intrinsic stability window of the solid electrolyte. The thermodynamic electrochemical stability window of solid electrolytes is calculated using first principles computation methods, and an experimental method is developed to measure the intrinsic electrochemical stability window of solid electrolytes using a Li/electrolyte/electrolyte‐carbon cell. The most promising solid electrolytes, Li10GeP2S12 and cubic Li‐garnet Li7La3Zr2O12, are chosen as the model materials for sulfide and oxide solid electrolytes, respectively. The results provide valuable insights to address the most challenging problems of the interfacial stability and resistance in high‐performance solid‐state batteries.
Goltz syndrome and PORCN: A view from Europe
Authors: Happle Rudolf
Published: January 2016

Goltz syndrome (focal dermal hypoplasia) is an X‐linked dominant, multisystem birth defect with lethality for male embryos. The hypoplastic skin lesions follow Blaschko's lines and often show herniation of subcutaneous fatty tissue. Extracutaneous defects mainly involve the brain, the bones, the teeth, and the eyes. All of these anomalies show a segmental arrangement reflecting functional X‐chromosome mosaicism. The present contribution tells the story how the molecular cause of Goltz syndrome was investigated and found by the group of the geneticist Karl–Heinz Grzeschik from Marburg, Germany. © 2016 Wiley Periodicals, Inc.
Ein durch eine synthetische Glycopeptid‐Vakzine induzierter monoklonaler Antiköper unterscheidet normale von malignen Brustzellen und ermöglicht die Diagnose von humanen Pankreaskarzinomen
Authors: Palitzsch Björn , Gaidzik Nikola , Stergiou Natascha , Stahn Sonja , Hartmann Sebastian , Gerlitzki Bastian , Teusch Nicole , Flemming Peer , Schmitt Edgar , Kunz Horst
Published: January 2016

In Studien zur Entwicklung einer Tumorimmuntherapie diente die chemische Synthese definierter tumorassoziierter Glycopeptidantigene als Schlüssel zur Gewinnung eines hochselektiven biologischen Reagenzes, eines monoklonalen Antikörpers, der vollständig zwischen malignen und normalen Epithelzellen unterscheidet und Tumorzellen in Pankreastumoren spezifisch markiert. Das Mucin MUC1, das in vielen häufigen Tumoren überexprimiert ist, bildet das Ziel dieser Strategie. Tumorassoziiertes MUC1 unterscheidet sich signifikant von jenem, das auf Normalzellen exprimiert wird, insbesondere durch veränderte Glycosylierung. Strukturell definiertes tumorassoziiertes MUC1 kann aus Tumorzellen nicht isoliert werden. Durch Synthese von MUC1‐Glycopeptid‐Vakzinen und deren Struktur‐Aktivitäts‐Analyse in Immunisierungen haben wir einen monoklonalen Antikörper gewonnen, der spezifisch zwischen normalen und malignen menschlichen Epithelzellen unterscheidet.
Enantioselective C−H Olefination of α‐Hydroxy and α‐Amino Phenylacetic Acids by Kinetic Resolution
Authors: Xiao Kai‐Jiong , Chu Ling , Yu Jin‐Quan
Published: January 2016

Significant progress has been made in the past decade regarding the development of enantioselective C−H activation reactions by desymmetrization. However, the requirement for the presence of two chemically identical prochiral C−H bonds represents an inherent limitation in scope. Reported is the first example of kinetic resolution by a palladium(II)‐catalyzed enantioselective C−H activation and C−C bond formation, thus significantly expanding the scope of enantioselective C−H activation reactions.
Chemoproteomics‐Enabled Discovery of a Potent and Selective Inhibitor of the DNA Repair Protein MGMT
Authors: Wang Chao , Abegg Daniel , Hoch Dominic G. , Adibekian Alexander
Published: January 2016

We present a novel chemical scaffold for cysteine‐reactive covalent inhibitors. Chloromethyl triazoles (CMTs) are readily accessed in only two chemical steps, thus enabling the rapid optimization of the pharmacological properties of these inhibitors. We demonstrate the tunability of the CMTs towards a specific biological target by synthesizing AA‐CW236 as the first potent non‐pseudosubstrate inhibitor of the O6‐alkylguanine DNA methyltransferase (MGMT), a protein of major clinical significance for the treatment of several severe cancer forms. Using quantitative proteomics profiling techniques, we show that AA‐CW236 exhibits a high degree of selectivity towards MGMT. Finally, we validate the effectiveness of our MGMT inhibitor in combination with the DNA alkylating drug temozolomide in breast and colon cancer cells by fluorescence imaging and a cell‐viability assay. Our results may open a new avenue towards the development of a clinically approved MGMT inhibitor.
Studies on the antioxidant properties of some phytoestrogens
Authors: Kładna Aleksandra , Berczyński Paweł , Kruk Irena , Piechowska Teresa , Aboul‐Enein Hassan Y.
Published: January 2016

Isoflavones genistein and daidzein are nonsteroidal phytoestrogens occurring mainly in soybean foods. These phytoestrogens possess estrogenic properties and show a variety of health benefits as anti‐inflammatory agents. However, the mechanism of their action has not been identified in detail. The aim of this study is to characterize the antioxidant powers of genistein, daidzein and daidzein metabolite–equol through their activities to scavenge superoxide anion radical (O•2−), hydroxyl radical (HO•), 2,2–diphenyl–1‐picrylhydrazyl radical (DPPH•) and hydrogen peroxide (H2O2) using chemiluminescence and spectrophotometry techniques. Potassium superoxide in dimethyl sulphoxide (DMSO) and 18‐crown‐6 ether were used as a source of O•2−. Hydroxyl radicals were produced using the Fenton reaction. In free radical assays, genistein had the IC50 values (an amount of antioxidant concentration required to decrease the initial radical concentration by 50%) 0.391 ± 0.012 mM for O•2−, 0.621 ± 0.028 mM for HO• and 1.89 ± 0.16 mM for DPPH•. The IC50 values for daidzein for these free radicals were 1.924 ± 0.011 mM, 0.702 ± 0.012 mM and 2.81 ± 0.03 mM, respectively. Equol was the most active the free radical scavenger with IC50 = 0.451 ± 0.018 mM for HO• and IC50 = 1.36 ± 0.11 mM for DPPH•. All tested compounds exerted a significant effect on the H2O2: IC50 = 18.1 ± 1.1 μM for genistein, IC50 = 2.1 ± 0.5 μM for daidzein, and IC50 = 1.06 ± 0.2 μM for equol. These findings show that genistein, daidzein and equol are effective free radical scavengers and possess high antioxidant power in vitro. Copyright © 2016 John Wiley & Sons, Ltd.
Involvement of autophagy in the procedure of endoplasmic reticulum stress introduced apoptosis in bone marrow mesenchymal stem cells from nonobese diabetic mice
Authors: Meng Yan , Ji Juan , Tan Wei , Guo Genkai , Xia Yunfei , Cheng Chun , Gu Zhifeng , Wang Zhiwei
Published: January 2016

Recent studies showed that bone marrow mesenchymal stem cells (BM‐MSCs) from nonobese diabetic (NOD) mice exhibited the phenomenon of apoptosis. However, the mechanisms of apoptosis remained largely unknown. In this study, endoplasmic reticulum (ER) stress and autophagy were evidenced in BM‐MSCs from NOD mice for the first time. We found the ER stress‐mediated apoptosis was supported by the up‐regulation of ER stress markers including augmented phosphorylation of phosphorylated protein kinase RNA‐like ER kinase and eukaryotic translation initiator factor 2α as well as cleavage of caspase‐3. Evidence of autophagy included the formation of the acidic vesicular organelles and increase of LC3 accumulation. Intriguingly, blockage of ER stress could reduce the apoptosis of BM‐MSCs from NOD mice and alleviated accumulation of LC3, which indicated that ER stress induced apoptosis and autophagy. Furthermore, our results showed that the mechanism of ER stress‐induced autophagy was associated with the decrease of p‐S6 (a marker of mTOR activity). Here, we demonstrated that ER stress‐induced cell death was mediated by autophagy that was partly attributed to the inactivation of the mammalian target of rapamycin.

Significance Paragraph

We report for the first time that endoplasmic reticulum (ER) stress mediated apoptosis of bone marrow mesenchymal stem cells (BM‐MSCs) from nonobese diabetic (NOD) mice. The evidence of autophagy was also found in BM‐MSCs from NOD mice, included the formation of the acidic vesicular organelles and increase of LC3 accumulation. Furthermore, we demonstrated that ER stress‐induced cell death was mediated by autophagy that was partly attributed to the inactivation of the mammalian target of rapamycin. Deciphering the mechanisms of ER stress signalling involved in the apoptosis of BM‐MSCs from NOD mice will help improve transplantation efficacy of BM‐MSCs in type 1 diabetes patients. Copyright © 2016 John Wiley & Sons, Ltd.
A case of pituitary apoplexy masquerading as subarachnoid hemorrhage
Authors: Choudhury Maitrayee , Eligar Vinay , DeLloyd Anna , Davies John Stephen
Published: January 2016

Key Clinical Message

Pituitary apoplexy may cause xanthochromia and mimic the clinical presentation of subarachnoid hemorrhage.
Urinary retention secondary to acute vasculitic penile swelling in a pediatric patient
Authors: Farkas Nicholas , Black John , Gupta Ashish
Published: January 2016

Key Clinical Message

Acute urinary retention secondary to vasculitic penile swelling in children is extremely rare. Henoch–Schönlein purpura is a self‐limiting IgA‐mediated cutaneous vasculitis, which can cause soft tissue edema. Acute urinary retention requires urgent intervention to prevent obstructive uropathy. Suprapubic catheterization provides an effective management strategy in the emergency setting.
ChemInform Abstract: Blue‐Emitting Sr3Si8‐xAlxO7+xN8‐x :Eu2+ Discovered by a Single‐Particle‐Diagnosis Approach: Crystal Structure, Luminescence, Scale‐Up Synthesis, and Its Abnormal Thermal Quenching Behavior.
Authors: Wang Xiao‐Jun , Wang Le , Takeda Takashi , Funahashi Shiro , Suehiro Takayuki , Hirosaki Naoto , Xie Rong‐Jun
Published: January 2016

Sr3Si8‐xAlxO7+xN8‐x :Eu2+ (x = 1.5—3.5) phosphor powders are prepared by firing appropriate amounts of SrCO3, Si3N4, SiO2, AlN, and Eu2O3 (1 MPa N2, 1500 °C, 2 h).
ChemInform Abstract: Phase Behavior in the LiBH4—LiBr System and Structure of the Anion‐Stabilized Fast Ionic, High Temperature Phase.
Authors: Cascallana‐Matias Irene , Keen David A. , Cussen Edmund J. , Gregory Duncan H.
Published: January 2016

Polycrystalline samples of Li(BH4)1‐xBrx are prepared from appropriate mixtures of LiBH4 and LiBr by both intermittent ball milling (24 h, 2 min breaks) alone and ball milling (4 h) followed by annealing (573 K, 5‐24 h).
ChemInform Abstract: Sm3S3BO3: The First Sulfide Borate Without S—O and B—S Bonds.
Authors: Guo Sheng‐Ping , Chi Yang , Xue Huai‐Guo
Published: January 2016

Sm3S3BO3 is obtained via solid‐state reaction of a 3:1:3 molar mixture of Sm2O3, B, and S (evacuated quartz tubes, staged heating at 300—950 °C, 5 h/stage, 10 d; cooling to 300 °C within 5 d).
ChemInform Abstract: A Terbium Rich Orthoborate LiSrTb2(BO3)3 and its Analogues.
Authors: Chen Pengyun , Xia Mingjun , Li R. K.
Published: January 2016

Single crystals of LiSrTb2(BO3)3 are grown by heating a 1:12:12:6 molar mixture of Tb4O7, SrCO3, H3BO3, and Li2CO3 (Pt crucible, 950 °C, 1 d; cooling to 500 °C at a rate of 1.5 °C/h).
ChemInform Abstract: Enantioselective ortho‐C—H Cross‐Coupling of Diarylmethylamines with Organoborons.
Authors: Laforteza Brian N. , Chan Kelvin S. L. , Yu Jin‐Quan
Published: January 2016

This method exploits the synthetically practical and easily deprotected para‐nitrobenzenesulfonamide as a directing group and a chiral mono‐N‐protected amino acid ligand (FLE) is used as promoter.
ChemInform Abstract: Rhodium(I)‐Catalyzed [2 + 2 + 2] Cycloaddition Between Allene, Alkyne, and Imine via a Strained Azarhodacycle Intermediate.
Authors: Oonishi Yoshihiro , Hato Yoshio , Sato Yoshihiro
Published: January 2016

The new cyclization reaction proceeds via a strained azarhodacycle, giving a 5,7‐fused cyclic amide or a tricyclic product containing an 8‐azabicyclo[3.2.1]octane skeleton in high yield.
ChemInform Abstract: Platinum(IV)‐Catalyzed Synthesis of Unsymmetrical Polysubstituted Benzenes via Intramolecular Cycloaromatization Reaction.
Authors: Zheng Shuyan , Zhang Jinghua , Shen Zhengwu
Published: January 2016

The Pt‐catalyzed intramolecular cycloaromatization of enynes (I) and (III) proceeds via a tandem skeletal rearrangement, dehydration, and double bond isomerization to afford polysubstituted benzenes (II) and (IV).
ChemInform Abstract: [2 + 2] Photocycloaddition of Cinnamates in Flow and Development of a Thiourea Catalyst.
Authors: Telmesani Reem , Park Sung H. , Lynch‐Colameta Tessa , Beeler Aaron B.
Published: January 2016

The bis(thiourea)‐catalyzed dimerization of cinnamates (I) in a flow photoreactor gives rise to diaryl‐cyclobutanedicarboxylates as a mixture of diastereomers (II) and (III).
ChemInform Abstract: Palladium(II)‐Catalyzed Allylic C—H Oxidation of Hindered Substrates Featuring Tunable Selectivity over Extent of Oxidation.
Authors: Xing Xiangyou , O'Connor Nicholas R. , Stoltz Brian M.
Published: January 2016

Depending on the presence or absence of water a two‐electron oxidation to the allylic acetates or a four‐electron oxidation to the corresponding enals takes place.
ChemInform Abstract: Visible‐Light‐Induced Photocatalytic Trifluoromethylation/1,2‐Carbon Migration Sequences for the Synthesis of CF3‐Substituted Cyclic Ketones.
Authors: Woo Saet Byeol , Kim Dae Young
Published: January 2016

CF3‐Substituted ketones [(III), (V), (VII), (IX), and (XI)] are conveniently synthesized via title reaction sequence induced by blue light irradiation under mild reaction conditions.
ChemInform Abstract: Cu‐Catalyzed Cyanation of Arylboronic Acids with Acetonitrile: A Dual Role of TEMPO.
Authors: Zhu Yamin , Li Linyi , Shen Zengming
Published: January 2016

Mechanistic studies indicate that a TEMPO‐CH2CN species, generated in situ, is the active, highly reactive cyanating agent.
ChemInform Abstract: Copper‐Mediated One‐Pot Synthesis of Trifluorostyrene Derivatives from Tetrafluoroethylene and Arylboronate.
Authors: Kikushima Kotaro , Sakaguchi Hironobu , Saijo Hiroki , Ohashi Masato , Ogoshi Sensuke
Published: January 2016

A copper‐mediated synthesis of trifluorostyrene derivatives is developed.
ChemInform Abstract: A Mild and General One‐Pot Synthesis of Densely Functionalized Diaryliodonium Salts.
Authors: Qin Linlin , Hu Bao , Neumann Kiel D. , Linstad Ethan J. , McCauley Katelyenn , Veness Jordan , Kempinger Jayson J. , DiMagno Stephen G.
Published: January 2016

A scalable synthesis is presented which gives access to a wide range of very densely functionalized diaryliodonium salts from aryl iodides under mild conditions.
ChemInform Abstract: Hypervalent Iodine(III) in Direct Oxidative Amination of Arenes with Heteroaromatic Amines.
Authors: Manna Srimanta , Serebrennikova Polina O. , Utepova Irina A. , Antonchick Andrey P. , Chupakhin Oleg N.
Published: January 2016

The title reaction amination applies to electron‐rich arenes and amino derivatives of electron‐deficient heterocycles.
ChemInform Abstract: A Highly Efficient Heterogeneous Aerobic Alcohol Oxidation Catalyzed by Immobilization of Bipyridine Copper(I) Complex in MCM‐41.
Authors: Zhao Hong , Chen Qiurong , Wei Li , Jiang Yuanyuan , Cai Mingzhong
Published: January 2016

A novel MCM‐41‐immobilized bipyridine copper(I) complex is synthesized and used for the aerobic oxidation of primary benzylic and allylic alcohols to aldehydes.The catalyst is reusable for at least 10 consecutive runs without significant loss of activity.
ChemInform Abstract: Synthesis of α‐Alkylated Ketones via Tandem Acceptorless Dehydrogenation/α‐Alkylation from Secondary and Primary Alcohols Catalyzed by Metal—Ligand Bifunctional Iridium Complex [Cp*Ir(2,2′‐bpyO)(H2O)].
Authors: Wang Rongzhou , Ma Juan , Li Feng
Published: January 2016

Compared to previous methods, the new strategy leads completely selectively to α‐alkylated ketones under more environmentally benign conditions.
ChemInform Abstract: ortho‐C—H Benzylation of Aryl Imines with Benzyl Phosphates under Cobalt—Pyphos Catalysis.
Authors: Xu Wengang , Paira Rupankar , Yoshikai Naohiko
Published: January 2016

Aryl and hetaryl imines as well as imines derived from 4‐chromanone and 1‐tetralone are ortho‐benzylated in a scalable manner with variously substituted benzylic phosphonates and diphosphonates.
ChemInform Abstract: Copper‐Catalyzed Diazo Cross‐/Homo‐Coupling Toward Tetrasubstituted Olefins and Applications on the Synthesis of Maleimide Derivatives.
Authors: Zhu Chenghao , Xu Guangyang , Ding Dong , Qiu Lin , Sun Jiangtao
Published: January 2016

The method allows for the preparation of symmetric and unsymmetric diaryl as well as arylalkyl substituted biscarboxylated olefins which are obtained with high to excellent Z‐selectivity.
ChemInform Abstract: Highly Diastereoselective Synthesis of Spirocyclopropane‐Oxindoles Using InCl3 as a Catalyst in Water.
Authors: Muthusamy Sengodagounder , Ramkumar Rajagopal
Published: January 2016

1‐Alkyl‐3‐diazoindol‐2‐ones react with chalcones, dimethyl fumarate, or methyl acrylate providing the title compounds in good yields with remarkable diastereoselectivities and regioselectivities in the case of unsymmetrically substituted chalcones.
ChemInform Abstract: Chemical Fixation of CO2 into Cyclic Carbonates by Azo‐Containing Schiff Base Metal Complexes.
Authors: Ikiz Mesut , Ispir Esin , Aytar Emine , Ulusoy Mahmut , Karabuga Semistan , Aslantas Mehmet , Celik Oemer
Published: January 2016

Two new ligands containing a ‐N=N‐ group and their metal complexes are synthesized and examined as catalysts for the synthesis of cyclic carbonates starting from epoxides with CO2.
ChemInform Abstract: Y(OTf)3‐Catalyzed Cascade Propargylic Substitution/Aza‐Meyer—Schuster Rearrangement: Stereoselective Synthesis of α,β‐Unsaturated Hydrazones and Their Conversion into Pyrazoles.
Authors: Liu Wenfei , Wang Han , Zhao Haiying , Li Baoguo , Chen Shufeng
Published: January 2016

Title reaction may also be embedded in a 3‐step sequence to the respective pyrroles starting from aceto‐ or benzophenone and phenylacetylene.
ChemInform Abstract: Green Synthesis of Tri/Tetrasubstituted 1H‐Imidazoles and 2,3‐Dihydroquinazolin‐4(1H)‐ones Using Nano Aluminum Nitride as Solid Source of Ammonia.
Authors: Hajjami Maryam , Ghorbani‐Choghamarani Arash , Yousofvand Zakieh , Norouzi Masoomeh
Published: January 2016

A simple, green, and cost‐effective protocol is achieved for the synthesis of tri‐ and tetrasubstituted imidazoles and pyrimidine derivatives using nano aluminium nitride as a solid source of ammonia.
ChemInform Abstract: Base‐Mediated Syntheses of Di‐ and Trisubstituted Imidazoles from Amidine Hydrochlorides and Bromoacetylenes.
Authors: Chen Xiao Yun , Englert Ulli , Bolm Carsten
Published: January 2016

A new transition metal‐free method for the preparation of title compounds (III), (V) and (VII) is reported.
ChemInform Abstract: Imidazoles from Nitroallylic Acetates and α‐Bromonitroalkenes with Amidines: Synthesis and Trypanocidal Activity Studies.
Authors: Gopi Elumalai , Kumar Tarun , Menna‐Barreto Rubem F. S. , Valenca Wagner O. , da Silva Eufranio N. Jr. , Namboothiri Irishi N. N.
Published: January 2016

Cascade reactions of amidines (II) with title compounds (I) and (IV) afford 2,4,5‐trisubstituted and 2,4‐disubstituted imidazoles (III), (V), and (VI), respectively.
ChemInform Abstract: Novel Synthesis and Cytotoxic Activity of 1,4‐Disubstituted 3‐Methylidene‐3,4‐dihydroquinolin‐2(1H)‐ones.
Authors: Pieta Marlena , Kedzia Jacek , Janecka Anna , Pomorska Dorota K. , Rozalski Marek , Krajewska Urszula , Janecki Tomasz
Published: January 2016

The title compounds are prepared in a 3‐step sequence starting from (I) via N‐alkylation, Grignard addition and Horner‐Wadsworth‐Emmons reaction with formaldehyde.
ChemInform Abstract: Base‐Promoted Synthesis of Dibenzoxazepinamines and Quinazolinimines under Metal‐Free Conditions.
Authors: Feng Jian‐Bo , Wu Xiao‐Feng
Published: January 2016

Dibenzoxazepinamines and quinazolinimines are synthesized in good to excellent yields from commercially available starting materials using a practical and efficient methodology.
ChemInform Abstract: Synthesis of Silaphenalenes by Ruthenium‐Catalyzed Annulation Between 1‐Naphthylsilanes and Internal Alkynes through C—H Bond Cleavage.
Authors: Tokoro Yuichiro , Sugita Kengo , Fukuzawa Shin‐ichi
Published: January 2016

The use of asymmetric alkynes affords mixtures of regioisomers.
ChemInform Abstract: Secondary Metabolites from Aspergillus fumigatus, an Endophytic Fungus from the Liverwort Heteroscyphus tener (Steph.) Schiffn.
Authors: Xie Fei , Li Xiao‐Bin , Zhou Jin‐Chuan , Xu Qing‐Qing , Wang Xiao‐Ning , Yuan Hui‐Qing , Lou Hong‐Xiang
Published: January 2016

isolation, structure determination and cytotoxicity of three new metabolites, asperfumigatin (I), isochaetominine (II), and 8‐O‐methylasterric acid (III) along with nineteen known metabolites
ChemInform Abstract: New Rare Earth Langbeinite Phosphosilicates KBaREEZrP2SiO12 (REE: La, Nd, Sm, Eu, Gd, Dy) for Lanthanide Comprising Nuclear Waste Storage.
Authors: Kumar Sathasivam Pratheep , Gopal Buvaneswari
Published: January 2016

KBaYMP2SiO12 (M: Zr, Sn), KBaLnZrP2SiO12 (Ln: La, Nd, Sm, Eu, Gd, Dy), and the spent nuclear fuel waste variant KBaY0.6La0.1Nd0.1Sm0.1 Eu0.1ZrP2SiO12 are prepared from stoichiometric aqueous solutions containing KCl, ZrOCl2, and SnCl4 to which Ba(NO3)2 and Y(NO3)3 solutions are added prior to precipitation with H3PO4 and Si(OEt)4 dissolved in a 1:1 mixture of HNO3 and EtOH.
ChemInform Abstract: The Diarylprolinol Silyl Ethers: Ten Years After
Authors: Donslund Bjarke S. , Johansen Tore Kiilerich , Poulsen Pernille H. , Halskov Kim Soeholm , Joergensen Karl Anker
Published: January 2016

Review: [perspectives of different activation modes made available by the title aminocatalysis system; 85 refs.
ChemInform Abstract: Boron‐Selective Reactions as Powerful Tools for Modular Synthesis of Diverse Complex Molecules
Authors: Xu Liang , Zhang Shuai , Li Pengfei
Published: January 2016

Review: 50 refs.
ChemInform Abstract: Liquid Phase Oxidation Chemistry in Continuous‐Flow Microreactors
Authors: Gemoets Hannes P. L. , Su Yuanhai , Shang Minjing , Hessel Volker , Luque Rafael , Noel Timothy
Published: January 2016

Review: 347 refs.
ChemInform Abstract: Neutron Methods for the Direct Determination of the Magnetic Induction in Thick Films
Authors: Kozhevnikov S. V. , Ott F. , Radu F.
Published: January 2016

Review: 37 refs.
ChemInform Abstract: Natural Supramolecular Protein Assemblies
Authors: Pieters Bas J. G. E. , van Eldijk Mark B. , Nolte Roeland J. M. , Mecinovic Jasmin
Published: January 2016

Review: structural and functional studies on a diverse set of natural supramolecular protein assemblies; 51 refs.
A Potent and Selective P‐gp Modulator for Altering Multidrug Resistance Due to Pump Overexpression
Authors: Guglielmo Stefano , Contino Marialessandra , Lazzarato Loretta , Perrone Maria Grazia , Blangetti Marco , Fruttero Roberta , Colabufo Nicola Antonio
Published: January 2016

P‐glycoprotein (P‐gp) is a membrane protein responsible for the active transport of several endogenous and exogenous substances. It constitutes a defense mechanism and, at the same time, it severely compromises the success rate of antitumor chemotherapy. In this study a small library of alkyl/oxyalkyl derivatives of MC70 [4′‐(6,7‐dimethoxy‐3,4‐dihydro‐1H‐isoquinolin‐2‐ylmethyl)biphenyl‐4‐ol], a well‐known P‐gp inhibitor, was synthesized through straightforward functionalization of the phenolic group present in the structure of MC70. All compounds were characterized for their effect on P‐gp, proving capable of blocking P‐gp‐mediated calcein‐AM efflux with micromolar potency, following their ability to act as high‐affinity substrates of this transporter. Excitingly, compound 4 [6,7‐dimethoxy‐2‐((4′‐butoxybiphen‐4‐yl)methyl)‐1,2,3,4‐tetrahydroisoquinoline] exhibited low nanomolar potency (5.2 nm) and had a peculiar activity profile, acting both as a positive allosteric modulator and as a substrate of the transporter. A new and more efficient synthesis of MC70 is also described.
Evaluation and management of intrahepatic and extrahepatic cholangiocarcinoma
Authors: Esnaola Nestor F. , Meyer Joshua E. , Karachristos Andreas , Maranki Jennifer L. , Camp E. Ramsay , Denlinger Crystal S.
Published: January 2016

Cholangiocarcinomas are rare biliary tract tumors that are often challenging to diagnose and treat. Cholangiocarcinomas are generally categorized as intrahepatic or extrahepatic depending on their anatomic location. The majority of patients with cholangiocarcinoma do not have any of the known or suspected risk factors and present with advanced disease. The optimal evaluation and management of patients with cholangiocarcinoma requires thoughtful integration of clinical information, imaging studies, cytology and/or histology, as well as prompt multidisciplinary evaluation. The current review focuses on recent advances in the diagnosis and treatment of patients with cholangiocarcinoma and, in particular, on the role of endoscopy, surgery, transplantation, radiotherapy, systemic therapy, and liver‐directed therapies in the curative or palliative treatment of these individuals. Cancer 2016;122:1349–1369. © 2016 American Cancer Society.
Stabilization of active fault‐tolerant control systems by uncertain nonhomogeneous markovian jump models
Authors: Faraji‐Niri Mona , Jahed‐Motlagh Mohammad Reza , Barkhordari‐Yazdi Mojtaba
Published: January 2016

This article investigates the stabilization and control problems for a general active fault‐tolerant control system (AFTCS) in a stochastic framework. The novelty of the research lies in utilizing uncertain nonhomogeneous Markovian structures to take account for the imperfect fault detection and diagnosis (FDD) algorithms of the AFTCS. The underlying AFTCS is supposed to be modeled by two random processes of Markov type; one characterizing the system fault process and the other describing the FDD process. It is assumed that the FDD algorithm is imperfect and provides inaccurate Markovian parameters for the FDD process. Specifically, it provides uncertain transition rates (TRs); the TRs that lie in an interval without any particular structures. This framework is more consistent with real‐world applications to accommodate different types of faults. It is more general than the previously developed AFTCSs because of eliminating the need for an accurate estimation of the fault process. To solve the stabilizability and the controller design problems of this AFTCS, the whole system is viewed as an uncertain nonhomogeneous Markovian jump linear system (NHMJLS) with time‐varying and uncertain specifications. Based on the multiple and stochastic Lyapunov function for the NHMJLS, first a sufficient condition is obtained to analyze the system stabilizability and then, the controller gains are synthesized. Unlike the previous fault‐tolerant controllers, the proposed robust controller only needs to access the FDD process, besides it is easily obtainable through the existing optimization techniques. It is successfully tested on a practical inverted pendulum controlled by a fault‐prone DC motor. © 2016 Wiley Periodicals, Inc. Complexity 21: 318–329, 2016
Small, abnormal B lymphoid blast populations in chronic myelogenous leukemia at diagnosis: Does this finding indicate an accelerated course?
Authors: Soma Lori , Oehler Vivian G. , Ding Cheng , Cherian Sindhu
Published: January 2016

Background

The 2008 WHO is not specific regarding subclassification of chronic myelogenous leukemia (CML) with less than 20% abnormal B lymphoid blasts (ABLB), and suggests patients with ABLB often show rapid progression (Swerdlow, 2008). Recent studies have shown variable outcomes when small abnormal B cell populations are seen by flow cytometry (El Rassi et al., Cancer 2015; 121:872–875; Vrotsos et al., Cytometry B Clin Cytom 2015).

Methods

The hematopathology database was searched (7.4‐year period), and patients identified through routine clinical study, who were BCR‐ABL1 positive CML and had an ABLB of less than 20%. Flow cytometric (FC) and histologic data was evaluated to determine immunophenotypic abnormalities, immunohistochemical patterns, and percentage of ABLB, hematogones, and mature B cells.

Results

Seven patients with CML and ABLB identified by FC studies were found, five of which also had available histologic material to review. ABLB by FC ranged from 0.006% to 3.4%, typically demonstrated an immunophenotype with increased CD10, increased CD19, and decreased CD38, without myeloid antigens, abnormalities similar to that reported previously (Vrotsos et al., Cytometry B Clin Cytom 2015). The ABLB population was found only in diagnostic samples and always with more numerous hematogones. By immunohistochemistry, three of five patients showed ≥10% TdT positive cells. All patients showed a response to tyrosine kinase inhibitor therapy, and no patients progressed to clinical lymphoid blast phase.

Conclusions

Immature B cells, occasionally including a small subset with an abnormal phenotype can be observed in chronic phase CML at diagnosis. We believe an approach incorporating clinical data, cytogenetic/molecular findings, and morphologic evaluation may be helpful when determining the best management of CML patients at diagnosis if small ABLB populations are identified by FC. © 2016 Clinical Cytometry Society
Utility of TTF‐1 and Napsin‐A in the work‐up of malignant effusions
Authors: El Hag Mohamed , Schmidt Lindsay , Roh Michael , Michael Claire W.
Published: January 2016

Background

Similar to TTF‐1, Napsin‐A is recently used increasingly to differentiate between pulmonary adenocarcinoma (P‐ADC) and extra‐pulmonary adenocarcinoma (EP‐ADC). The aim of this study was to compare the performance of TTF‐1 and Napsin‐A in determining the primary origin of adenocarcinoma in malignant serous effusion.

Methods

Following IRB approval, cellblocks from 139 cases of malignant serous effusions of histologically or clinically determined origin including: 26 P‐ADC, 108 EP‐ADC, 2 pulmonary squamous cell carcinoma (P‐SQC), and 3 pulmonary small cell carcinoma (P‐SCC) were retrieved. Each case was stained with Napsin‐A and TTF‐1 and evaluated for positivity and intensity of staining.

Results

Napsin‐A and TTF‐1 stained positive in 17/26 (65%) and 14/26 (54%) of P‐ADC and in 2/108 (1.8%) and 0/108 (0%) of EP‐ADC with a PPV of 89 and 100%, respectively. In combination, they positively stained 18/26 (70%) of P‐ADC with a PPV of 90%. Out of 9 poorly differentiated P‐ADC, 7 (78%) stained positive for Napsin‐A, while 4 (45%) were reactive for TTF‐1. Both Napsin‐A and TTF‐1 were negative in P‐SQC, while P‐SCC reacted positively for TTF‐1 in 2/3 (66%) of cases and none for Napsin‐A.

Conclusion

Napsin‐A and TTF‐1 are both useful markers in distinguishing P‐ADC from EP‐ADC. However, Napsin‐A performed better in poorly differentiated P‐ADC and its mimickers. The nuclear staining of TTF‐1 is crispier and much easier to interpret than Napsin‐A cytoplasmic stain. An antibody panel including TTF‐1 and Napsin‐A or a dual stain will be very helpful in determining the origin of metastatic adenocarcinoma in serous effusion. Diagn. Cytopathol. 2016;44:299–304. © 2016 Wiley Periodicals, Inc.
Genomic population structure of freshwater‐resident and anadromous ide (Leuciscus idus) in north‐western Europe
Authors: Skovrind Mikkel , Olsen Morten Tange , Vieira Filipe Garrett , Pacheco George , Carl Henrik , Gilbert M. Thomas P. , Møller Peter Rask
Published: January 2016

Climate change experts largely agree that future climate change and associated rises in oceanic water levels over the upcoming decades, will affect marine salinity levels. The subsequent effects on fish communities in estuarine ecosystems however, are less clear. One species that is likely to become increasingly affected by changes in salinity is the ide (Leuciscus idus). The ide is a stenohaline freshwater fish that primarily inhabits rivers, with frequent anadromous behavior when sea salinity does not exceed 15%. Unlike most other anadromous Baltic Sea fish species, the ide has yet to be subjected to large‐scale stocking programs, and thus provides an excellent opportunity for studying the natural population structure across the current salinity gradient in the Danish Belts. To explore this, we used Genotyping‐by‐Sequencing to determine genomic population structure of both freshwater resident and anadromous ide populations in the western Baltic Sea region, and relate the results to the current salinity gradient and the demographic history of ide in the region. The sample sites separate into four clusters, with all anadromous populations in one cluster and the freshwater resident populations in the remaining three. Results demonstrate high level of differentiation between sites hosting freshwater resident populations, but little differentiation among anadromous populations. Thus ide exhibit the genomic population structure of both a typical freshwater species, and a typical anadromous species. In addition to providing a first insight into the population structure of north‐western European ide, our data also (1) provide indications of a single illegal introduction by man; (2) suggest limited genetic effects of heavy pollution in the past; and (3) indicate possible historical anadromous behavior in a now isolated freshwater population.
The influence of iron deficiency on the functioning of skeletal muscles: experimental evidence and clinical implications
Authors: Stugiewicz Magdalena , Tkaczyszyn Michał , Kasztura Monika , Banasiak Waldemar , Ponikowski Piotr , Jankowska Ewa A.
Published: January 2016

Skeletal and respiratory myopathy not only constitutes an important pathophysiological feature of heart failure and chronic obstructive pulmonary disease, but also contributes to debilitating symptomatology and predicts worse outcomes in these patients. Accumulated evidence from laboratory experiments, animal models, and interventional studies in sports medicine suggests that undisturbed systemic iron homeostasis significantly contributes to the effective functioning of skeletal muscles. In this review, we discuss the role of iron status for the functioning of skeletal muscle tissue, and highlight iron deficiency as an emerging therapeutic target in chronic diseases accompanied by a marked muscle dysfunction.
Enantiopure Chiral Concave 1,10‐Phenanthrolines
Authors: Reck Lisa M. , Haberhauer Gebhard , Lüning Ulrich
Published: January 2016

Chiral information has been introduced into concave 1,10‐phenanthrolines of different ring sizes by using a 2,7‐disubstituted naphthalene bridgehead, which causes axial chirality. A tetraphenolic 2‐(dihydroxynaphthyl)‐9‐(dihydroxyphenyl)‐1,10‐phenanthroline was synthesized as a key intermediate. Two strategies were followed to obtain the bimacrocyclic chiral concave 1,10‐phenanthrolines: quadruple Williamson ether synthesis or alkenylation of the OH groups and subsequent ring‐closing metathesis followed by hydrogenation. The overall yields of bimacrocyles 19 were 10 to 17 % starting from the respective Suzuki coupling of the substituted arenes 11 and 13 to 2,9‐dichloro‐1,10‐phenanthroline (5). Racemic mixtures of the three concave 1,10‐phenanthrolines 19 were separated by using chiral high‐performance liquid chromatography (HPLC) techniques, and their absolute stereochemistry was assigned by comparison of simulated and experimental circular dichroism (CD) spectra. The enantiopure concave 1,10‐phenanthrolines were used as ligands in a copper‐catalysed cyclopropanation, and their selectivity was determined by chiral gas chromatography (GC).
Validation of CE modeling with a contactless conductivity array detector
Authors: Caslavska Jitka , Koenka Israel Joel , Hauser Peter C. , Thormann Wolfgang
Published: January 2016

Dynamic computer simulation data are compared for the first time with CE data obtained with a laboratory made system comprising an array of 8 contactless conductivity detectors (C4Ds). The experimental setup featured a 50 μm id linear polyacrylamide (LPA) coated fused‐silica capillary of 70 cm length and a purpose built sequential injection analysis manifold for fluid handling of continuous or discontinuous buffer configurations and sample injection. The LPA coated capillary exhibits a low EOF and the manifold allows the placement of the first detector at about 2.7 cm from the sample inlet. Agreement of simulated electropherograms with experimental data was obtained for the migration and separation of cationic and anionic analyte and system zones in CZE configurations in which EOF and other column properties are constant. For configurations with discontinuous buffer systems, including ITP, experimental data obtained with the array detector revealed that the EOF is not constant. Comparison of simulation and experimental data of ITP systems provided the insight that the EOF can be estimated with an ionic strength dependent model similar to that previously used to describe EOF in fused‐silica capillaries dynamically double coated with Polybrene and poly(vinylsulfonate). For the LPA coated capillaries, the electroosmotic mobility was determined to be 17‐fold smaller compared to the case with the charged double coating. Simulation and array detection provide means for quickly investigating electrophoretic transport and separation properties. Without realistic input parameters, modeling alone is not providing data that match CE results.
Electromembrane extraction of gonadotropin‐releasing hormone agonists from plasma and wastewater samples
Authors: Nojavan Saeed , Bidarmanesh Tina , Mohammadi Ali , Yaripour Saeid
Published: January 2016

In the present study, for the first time electromembrane extraction followed by high performance liquid chromatography coupled with ultraviolet detection was optimized and validated for quantification of four gonadotropin‐releasing hormone agonist anticancer peptides (alarelin, leuprolide, buserelin and triptorelin) in biological and aqueous samples. The parameters influencing electromigration were investigated and optimized. The membrane consists 95% of 1‐octanol and 5% di‐(2‐ethylhexyl)‐phosphate immobilized in the pores of a hollow fiber. A 20 V electrical field was applied to make the analytes migrate from sample solution with pH 7.0, through the supported liquid membrane into an acidic acceptor solution with pH 1.0 which was located inside the lumen of hollow fiber. Extraction recoveries in the range of 49 and 71% within 15 min extraction time were obtained in different biological matrices which resulted in preconcentration factors in the range of 82–118 and satisfactory repeatability (7.1 < RSD% < 19.8). The method offers good linearity (2.0–1000 ng/mL) with estimation of regression coefficient higher than 0.998. The procedure allows very low detection and quantitation limits of 0.2 and 0.6 ng/mL, respectively. Finally, it was applied to determination and quantification of peptides in human plasma and wastewater samples and satisfactory results were yielded.
OSL dating of past lake levels for a large dammed lake in southern Tibet and determination of possible controls on lake evolution
Authors: Chen Yiwei , Aitchison Jonathan C. , Zong Yongqiang , Li Sheng‐Hua
Published: January 2016

Fluvio‐lacustrine terraces along Phung Chu (river) on the central southern Tibetan Plateau indicate that a large palaeo‐dammed‐lake formerly existed in this area. Based on landscape survey, optically stimulated luminescence (OSL) dating and sedimentary analyses, this research shows that the Phung Chu was blocked and a dammed‐lake over 2500 km2in size formed before 30 ka ago. OSL dating analysis suggests the fluvio‐lacustrine sediments were well bleached and yield accurate age estimates for two lake drainage events. The first drainage event took place after 30 ka, resulted in river incision and formed a high terrace at 50 m height from the present river level. The second drainage happened after 3.7 ka, resulted in further river incision and formed the second terrace at 25 m height from the present river level. According to the distribution of the fluvio‐lacustrine sediments, active normal faults (particularly the Kharta Fault) in this region and the high gradient slopes after Phung Chu enters the Yö Ri gorge, seismically‐induced landsliding is regarded as highly likely to have been the cause of river blockage and associated formation of a dammed‐lake, although glacial damming is also a possible cause. The volume of drainages from this dammed‐lake may have led to catastrophic flooding and analogous modern lakes represent significant geo‐hazard risks to down‐river human settlements. As dammed‐lakes are special phases in fluvial evolution, often involving river blockage, breakthrough and drastic catchment change, these processes can reveal how tectonic or climatic events modify landforms. However, such tectonic‐derived landform changes can also impact palaeo‐climate of the region. Thus this study has added new evidence regarding the evolutionary history of a dammed lake including its formation, duration, extent and final drainage, which is crucial for understanding its general landscape process mechanisms and for better assessing geo‐hazard risks. Copyright © 2016 John Wiley & Sons, Ltd.
The acheulean handaxe: More like a bird's song than a beatles' tune?
Authors: Corbey Raymond , Jagich Adam , Vaesen Krist , Collard Mark
Published: January 2016

The goal of this paper is to provoke debate about the nature of an iconic artifact—the Acheulean handaxe. Specifically, we want to initiate a conversation about whether or not they are cultural objects. The vast majority of archeologists assume that the behaviors involved in the production of handaxes were acquired by social learning and that handaxes are therefore cultural. We will argue that this assumption is not warranted on the basis of the available evidence and that an alternative hypothesis should be given serious consideration. This alternative hypothesis is that the form of Acheulean handaxes was at least partly under genetic control.
Multiple Hypothesis Testing of Market Risk Forecasting Models
Authors: Esposito Francesco P. , Cummins Mark
Published: January 2016

Extending previous risk model backtesting literature, we construct multiple hypothesis testing (MHT) with the stationary bootstrap. We conduct multiple tests which control for the generalized confidence level and employ the bootstrap MHT to design multiple comparison testing. We consider absolute and relative predictive ability to test a range of competing risk models, focusing on value‐at‐risk and expected shortfall (ExS). In devising the test for the absolute predictive ability, we take the route of recent literature and construct balanced simultaneous confidence sets that control for the generalized family‐wise error rate, which is the joint probability of rejecting true hypotheses. We implement a step‐down method which increases the power of the MHT in isolating false discoveries. In testing for the ExS model predictive ability, we design a new simple test to draw inference about recursive model forecasting capability. In the second suite of statistical testing, we develop a novel device for measuring the relative predictive ability in the bootstrap MHT framework. The device, which we coin multiple comparison mapping, provides a statistically robust instrument designed to answer the question: ‘Which model is the best model?’ Copyright © 2016 John Wiley & Sons, Ltd.