bluuebunny/crossref_metadata_2025_split huggingface dataset:
Gold‐Catalyzed Synthesis of 3‐Acylimidazo[1,2‐a]pyridines via Carbene Oxidation
Authors: Zhan Haiying , Zhao Limin , Liao Jinqiang , Li Naiying , Chen Qinlin , Qiu Shuxian , Cao Hua 
Published: December 2014

AbstractA convenient gold‐catalyzed strategy for the synthesis of imidazo[1,2‐a]pyridine derivatives has been developed via gold carbene complexes. This transformation opens a new synthetic route to a variety of 3‐carbonyl‐substituted imidazo[1,2‐a]pyridines using air as oxidant affording the products in good yields.magnified image
N‐Heterocyclic Carbene‐Catalyzed Benzoin Strategy for Divergent Synthesis of Cyclitol Derivatives from Alditols
Authors: Kang Bubwoong , Sutou Toshiaki , Wang Yinli , Kuwano Satoru , Yamaoka Yousuke , Takasu Kiyosei , Yamada Ken‐ichi 
Published: December 2014

AbstractA divergent synthesis of cyclitol derivatives has been developed utilizing an N‐heterocyclic carbene‐catalyzed benzoin‐type cyclization of C2‐symmetrical dialdoses. The resulting inososes are versatile intermediates, which are readily converted into not only inositols but also amino‐, deoxy‐, O‐methyl‐ and C‐methyl‐inositols.magnified image
Mortality of older construction and craft workers employed at department of energy (DOE) nuclear sites: Follow‐up through 2011
Authors: Ringen Knut , Dement John , Welch Laura , Bingham Eula , Quinn Patricia , Chen Anna , Haas Scott 
Published: December 2014

BackgroundThe Building Trades National Medical Screening Program (BTMed) was established in 1996 to provide occupational medicine screening examinations for construction workers who have worked at US Department of Energy nuclear sites. Workers participating in BTMed between 1998 and 2011 were followed to determine their vital status and mortality experience through December 31, 2011.MethodsThe cohort includes 18,803 BTMed participants and 2,801 deaths. Cause‐specific Standardized Mortality Ratios (SMRs) were calculated based on US death rates.ResultsMortality was elevated for all causes, all cancers, cancers of the trachea, bronchus, and lung and lymphatic and hematopoietic system, mesothelioma, COPD, and asbestosis.ConclusionsConstruction workers employed at DOE sites have a significantly increased risk for occupational illnesses. Risks are associated with employment during all time periods covered including after 1980. The cancer risks closely match the cancers identified for DOE compensation from radiation exposures. Continued medical surveillance is important. Am. J. Ind. Med. 58:152–167, 2015. © 2014 Wiley Periodicals, Inc.
Terpenoid‐Biosynthese abseits bekannter Wege: unkonventionelle Cyclasen und ihre Bedeutung für die biomimetische Synthese
Authors: Baunach Martin , Franke Jakob , Hertweck Christian 
Published: December 2014

AbstractCyclisierungsreaktionen von Terpenen und Terpenoiden zählen zu den komplexesten chemischen Reaktionen in der Natur und tragen maßgeblich zur enormen Strukturvielfalt dieser größten Naturstofffamilie bei. Zahlreiche Studien auf chemischer, genetischer und biochemischer Ebene wurden durchgeführt, um mechanistische Einblicke in diese faszinierenden Reaktionen zu erlangen, die von Terpen‐ und Terpenoid‐Cyclasen katalysiert werden. Eine Vielzahl dieser Enzyme konnte seither charakterisiert werden. Nach klassischer Lehrbuchmeinung werden Terpen‐/Terpenoid‐Cyclasen gemäß ihrer Struktur und ihrem Reaktionsmechanismus in zwei große Klassen eingeteilt. Jüngste Entdeckungen neuartiger Terpenoid‐Cyclasen zeigen jedoch, dass das natürliche enzymatische Repertoire deutlich vielseitiger ist, als zunächst gedacht. Dieser Aufsatz stellt eben diese Terpenoid‐Cyclasen in den Fokus, die aus dem Rahmen fallen.
Chloroacetate‐Promoted Selective Oxidation of Heterobenzylic Methylenes under Copper Catalysis
Authors: Liu Jianming , Zhang Xin , Yi Hong , Liu Chao , Liu Ren , Zhang Heng , Zhuo Kelei , Lei Aiwen 
Published: December 2014

AbstractThe efficient selective oxidation and functionalization of CH bonds with molecular oxygen and a copper catalyst to prepare the corresponding ketones was achieved with ethyl chloroacetate as a promoter. In this transformation, various substituted N‐heterocyclic compounds were well tolerated. Preliminary mechanistic investigations indicated that organic radical species were involved in the overall process. The N‐heterocyclic compounds and ethyl chloroacetate work synergistically to activate CH bonds in the methylene group, which results in the easy generation of free radical intermediates, thus leading to the corresponding ketones in good yields.
Stabilisierung eines cysteinreichen Kegelschneckentoxins, MrIA, in Form eines 1,2,3‐Triazol‐Disulfidbrückenmimetikums
Authors: Gori Alessandro , Wang Ching‐I A. , Harvey Peta J. , Rosengren K. Johan , Bhola Rebecca F. , Gelmi Maria L. , Longhi Renato , Christie Macdonald J. , Lewis Richard J. , Alewood Paul F. , Brust Andreas 
Published: December 2014

AbstractDie Synthese von Disulfidbrückenmimetika ist eine wichtige Strategie zur Optimierung disulfidreicher Peptide beim Wirkstoff‐Design. Wir beschreiben Mimetika des Conotoxins MrIA, die durch selektiven Austausch einzelner Disulfidbindungen gegen Brücken aus einem 1,4‐disubstituierten 1,2,3‐Triazol erhalten wurden. Eine sequenzielle, Kupfer‐katalysierte Azid‐Alkin‐Klick‐Reaktion (CuAAC) mit nachfolgender Disulfidbildung führte regioselektiv zu hybriden Triazol‐Disulfid‐Analoga von MrIA. Mimetika, in denen Triazol die Cys4‐Cys13‐Disulfidbindung ersetzte, behielten ihre Tertiärstruktur sowie die volle In‐vitro‐ und In‐vivo‐Aktivität als Inhibitoren der Noradrenalin‐Wiederaufnahme bei. Diese Mimetika sind resistent gegen Reduktion mit Glutathion, was zu einer verbesserten Plasmastabilität führt und dadurch interessant für die Wirkstoff‐Entwicklung ist.
Rhodium‐Catalyzed Asymmetric Synthesis of Silicon‐Stereogenic Dibenzosiloles by Enantioselective [2+2+2] Cycloaddition
Authors: Shintani Ryo , Takagi Chihiro , Ito Tomoaki , Naito Masanobu , Nozaki Kyoko 
Published: December 2014

AbstractA rhodium‐catalyzed asymmetric synthesis of silicon‐stereogenic dibenzosiloles has been developed through a [2+2+2] cycloaddition of silicon‐containing prochiral triynes with internal alkynes. High yields and enantioselectivities have been achieved by employing an axially chiral monophosphine ligand, and the present catalysis is also applicable to the asymmetric synthesis of a germanium‐stereogenic dibenzogermole. Preliminary studies on the optical properties of these compounds are also described.
Water‐Mediated Recognition of Simple Alkyl Chains by Heart‐Type Fatty‐Acid‐Binding Protein
Authors: Matsuoka Shigeru , Sugiyama Shigeru , Matsuoka Daisuke , Hirose Mika , Lethu Sébastien , Ano Hikaru , Hara Toshiaki , Ichihara Osamu , Kimura S. Roy , Murakami Satoshi , Ishida Hanako , Mizohata Eiichi , Inoue Tsuyoshi , Murata Michio 
Published: December 2014

AbstractLong‐chain fatty acids (FAs) with low water solubility require fatty‐acid‐binding proteins (FABPs) to transport them from cytoplasm to the mitochondria for energy production. However, the precise mechanism by which these proteins recognize the various lengths of simple alkyl chains of FAs with similar high affinity remains unknown. To address this question, we employed a newly developed calorimetric method for comprehensively evaluating the affinity of FAs, sub‐Angstrom X‐ray crystallography to accurately determine their 3D structure, and energy calculations of the coexisting water molecules using the computer program WaterMap. Our results clearly showed that the heart‐type FABP (FABP3) preferentially incorporates a U‐shaped FA of C10–C18 using a lipid‐compatible water cluster, and excludes longer FAs using a chain‐length‐limiting water cluster. These mechanisms could help us gain a general understanding of how proteins recognize diverse lipids with different chain lengths.
Catalytic Asymmetric Intramolecular Homologation of Ketones with α‐Diazoesters: Synthesis of Cyclic α‐Aryl/Alkyl β‐Ketoesters
Authors: Li Wei , Tan Fei , Hao Xiaoyu , Wang Gang , Tang Yu , Liu Xiaohua , Lin Lili , Feng Xiaoming 
Published: December 2014

AbstractA catalytic asymmetric intramolecular homologation of simple ketones with α‐diazoesters was firstly accomplished with a chiral N,N′‐dioxide–Sc(OTf)3 complex. This method provides an efficient access to chiral cyclic α‐aryl/alkyl β‐ketoesters containing an all‐carbon quaternary stereocenter. Under mild conditions, a variety of aryl‐ and alkyl‐substituted ketone groups reacted with α‐diazoester groups smoothly through an intramolecular addition/rearrangement process, producing the β‐ketoesters in high yield and enantiomeric excess.
Synthesis of Annelated Phospholes through Intramolecular CH Activation by Monovalent Phosphorus
Authors: Wei Xinda , Lu Zongming , Zhao Xu , Duan Zheng , Mathey Francois 
Published: December 2014

AbstractElectrophilic terminal phosphinidene complexes [Ar‐Ar‐P‐W(CO)5] (Ar‐Ar: biaryl or an analogue thereof) undergo a spontaneous insertion of the phosphorus atom into the vicinal CH bonds to give annelated phospholes. Twelve examples are described, including biphenyl, thienyl, pyrrolyl, and benzofuryl groups as biaryl moieties. The activation energy of the insertion reaction is quite low (about 2 kcal mol−1).
Failure behavior of resorcinol–formaldehyde latex coated aramid short‐fiber‐reinforced rubber sealing under transverse tension
Authors: Zhang Bin , Gu Boqin , Yu Xiaoming 
Published: December 2014

ABSTRACTComposites composed of rubber, sepiolite fiber, and resorcinol–formaldehyde latex‐coated aramid short fibers were prepared. Mechanical and morphological characterizations were carried out. To investigate the effect of interfacial debonding on the failure behavior of short‐fiber‐reinforced rubber composites, a micromechanical representative volume element model for the composites was developed. The cohesive zone model was used to analyze the interfacial failure. We found that computational results were in good agreement with the experimental results when the interfacial fracture energy was 1 J/m2 and the interfacial strength was 10 MPa. A parametrical study on the interface and interphase of the composite was conducted. The results indicate that a good interfacial strength and a choice of interphase modulus between 40 and 50 MPa enhanced the ductile behavior and strength of the composite. The ductile properties of the composite also increased with increasing interfacial fracture energy. © 2014 Wiley Periodicals, Inc. J. Appl. Polym. Sci. 2015, 132, 41672.
Direct Patterning and Biofunctionalization of a Large‐Area Pristine Graphene Sheet
Authors: Hong Daewha , Bae KiEun , Park Duckshin , Kim Houngkyung , Hong Seok‐Pyo , Kim Mi‐Hee , Lee Bong Soo , Ko Sangwon , Jeon Seokwoo , Zheng Xu , Yun Wan Soo , Kim Yang‐Gyun , Choi Insung S. , Lee Jungkyu K. 
Published: December 2014

AbstractDirect patterning of streptavidin and NIH 3T3 fibroblast cells was successfully achieved over a large‐area pristine graphene sheet on Si/SiO2 by aryl azide‐based photografting with the conventional UV lithographic technique and surface‐initiated, atom transfer radical polymerization of oligo(ethylene glycol) methacrylate.
A new method for teaching microprocessors course using emulation
Authors: Qaralleh Esam A. , Darabkh Khalid A. 
Published: December 2014

ABSTRACTMicroprocessors course is a challenging course for both students and instructors. The challenge arises by the nature of this course which is a combination of assembly language and hardware interface. The assembly language develops the students' ability to program in a low level programming language utilizing the instruction set of the 8086 processor, understanding the addressing modes (pointer concept), and exploring the nature of different instructions along with their execution times, dependences, implicit addressing for certain instructions, as well as flow control concerning the flags. The hardware interface helps the students in connecting various system components to build up a working system. Memory and input/output communications (read/write) operations are explained using timing diagrams and handshaking signals. In this paper, the aforementioned contents are addressed through developing an interesting project that is capable of integrating both hardware and software in an attractive environment characterized by being simple and inexpensive. In this project, the PC parallel port extension is used to emulate the microprocessor bus activity in read/write operation. The results showed an impressive students' progress whereas they were so satisfied to not only their projects, but also the conceptual basics of this course. © 2014 Wiley Periodicals, Inc. Comput Appl Eng Educ 23:455–463, 2015; View this article online at wileyonlinelibrary.com/journal/cae; DOI 10.1002/cae.21616
Semisynthesis and Antifungal Activity of Novel Oxime Ester Derivatives of Carabrone Modified at C(4) against Botrytis cinerea
Authors: Wang Delong , Ren Shuangxi , Wang Hao , Yan He , Feng Juntao , Zhang Xing 
Published: December 2014

AbstractTo continuously improve the potential utility of the natural lead compound of carabrone in agrochemistry, carabrone oxime and 36 novel oxime ester derivatives of carabrone modified at C(4) were synthesized, and evaluated for their antifungal activities against Botrytis cinerea in vitro and in vivo. Of these 36 oxime ester derivatives, some compounds exhibited antifungal activities in vitro or in vivo. It was found that compounds with a pyridinyl residue can either efficiently inhibit spore germination or efficiently inhibit hyphal growth of B. cinerea, and compound 9 exhibited the highest activity in vitro and in vivo with IC50 and EC50 values of 1.17 and 12.9 μg/ml, respectively. Further, the structureactivity relationships are also discussed.
Inhibitory Effects of Constituents of an Endophytic Fungus Hypoxylon investiens on Nitric Oxide and Interleukin‐6 Production in RAW264.7 Macrophages
Authors: Chang Chun‐Wei , Chang Hsun‐Shuo , Cheng Ming‐Jen , Liu Ta‐Wei , Hsieh Sung‐Yuan , Yuan Gwo‐Fang , Chen Ih‐Sheng 
Published: December 2014

AbstractThree new compounds, hypoxyloamide (1), 8‐methoxynaphthalene‐1,7‐diol (2), and hypoxylonol (3), together with seven compounds isolated from nature for the first time, investiamide (4), hypoxypropanamide (5), hypoxylonol A (6), investienol (7), 2‐heptylfuran (8), (3S)‐5‐methyl‐8‐O‐methylmellein (9), (4R)‐O‐methylsclerone (10), along with 19 known compounds, 11–29, were isolated from the culture broth of Hypoxylon investiens BCRC 10F0115, a fungal endophyte residing in the stems of an endemic Formosan plant Litsea akoensis var. chitouchiaoensis. The structures of the new compounds were established by spectroscopic methods, including UV, IR, HR‐ESI‐MS, and extensive 1D‐ and 2D‐NMR techniques. Of these isolates, 2, 8‐methoxynaphthalen‐1‐ol (15), and 1,8‐dimethoxynaphthalene (16) showed nitric oxide (NO) inhibitory activity with IC50 values of 11.8±0.9, 17.8±1.1, and 13.3±0.5 μM, respectively, stronger than the positive control quercetin (IC50 36.8±1.3 μM). Compounds 2, 15, and 16 also showed interleukin‐6 (IL‐6) inhibitory activity with IC50 values of 9.2±1.7, 18.0±0.6, and 2.0±0.1 μM, stronger than the positive control quercetin (IC50 31.3±1.6 μM). To the best of our knowledge, this is the first report on guaiane sesquiterpene metabolites, 3, 6, and 7, from the genus Hypoxylon.
Anti‐Adipogenic Activity of the Naturally Occurring Phenanthroindolizidine Alkaloid Antofine via Direct Suppression of PPARγ Expression
Authors: Jang Eun Jung , Kim Hyo Kyeong , Jeong Hana , Lee Ye Seul , Jeong Mi Gyeong , Bae Su Jung , Kim Sanghee , Lee Sang Kook , Hwang Eun Sook 
Published: December 2014

AbstractAntofine (ANTF) is a phenanthroindolizidine alkaloid isolated from the root of Cynanchum paniculatum Kitagawa (Asclepiadaceae), which is used as an herbal remedy for pain and inflammation. ANTF also possesses antiviral and antitumorigenic activities. In this study, we investigated the role of ANTF in adipogenesis. Chronic ABTF administration suppressed adipocyte differentiation and marker expression in a dose‐dependent manner. Furthermore, acute administration of ANTF at early stages of differentiation process inhibited lipid droplet formation and adipogenic gene expression. ANTF Treatment decreased expression of PPARγ protein, a master transcription factor in the regulation of adipocyte differentiation, leading to a suppression of aP2 promoter activity. These results suggest that ANTF exerts potent anti‐adipogenic effects via direct suppression of PPARγ protein expression, with consequent downregulation of adipogenic gene expression.
Cytotoxic Compounds from the Leaves of Garcinia polyantha
Authors: Lannang Alain Meli , Tatsimo Simplice J. N. , Fouotsa Hugues , Dzoyem Jean Paul , Saxena Ajit Kumar , Sewald Norbert 
Published: December 2014

AbstractA new compound, named banganxanthone C (=12‐(1,1‐dimethylprop‐2‐en‐1‐yl)‐5,10‐dihydroxy‐9‐methoxy‐2‐methyl‐2‐(4‐methylpent‐3‐en‐1‐yl)‐2H,6H‐pyrano[3,2‐b]xanthen‐6‐one; 4), together with five known compounds, were isolated from the leaves of Garcinia polyantha. The structures of the compounds were elucidated on the basis of 1D‐ and 2D‐NMR spectroscopy. Among the known compounds, two were xanthones, one was a pentacyclic triterpene, one sterol, and one benzophenone derivative. Isoxanthochymol (2) and 4‐[(2E)‐3,7‐dimethylocta‐2,6‐dien‐1‐yl]‐1,5,8‐trihydroxy‐3‐methoxy‐9H‐xanthen‐9‐one (3) exhibited significant antiproliferative activity against the leukemia cell line TPH‐1 with IC50 inhibition values of 1.5 and 2.8 μg/ml, respectively. The cytotoxic activity was found to be related to apoptosis induction.
New Triterpenoids from the Fruiting Bodies of Ganoderma lucidum and Their Bioactivities
Authors: Liu Dong‐Ze , Zhu Yi‐Qun , Li Xiao‐Fei , Shan Wei‐Gang , Gao Peng‐Fei 
Published: December 2014

AbstractPhytochemical investigation of the AcOEt extract of G. Lucidum has led to the isolation of two new triterpenoids, 1 and 2, together with five known ones, 3–7. The structures of the new compounds were identified as 12β‐acetoxy‐3β,7β‐dihydroxy‐11,15,23‐trioxolanost‐8‐en‐26‐oic acid butyl ester (1) and 12β‐acetoxy‐3,7,11,15,23‐pentaoxolanost‐8‐en‐26‐oic acid butyl ester (2) on the basis of detailed spectroscopic analysis (mass spectrometry, and 1D‐ and 2D‐NMR experiments). The antimicrobial activities of 1 and 2 were also evaluated.
Kinetic Analysis of the Interaction of Mos1 Transposase with its Inverted Terminal Repeats Reveals New Insight into the Protein–DNA Complex Assembly
Authors: Esnault Charles , Jaillet Jérôme , Delorme Nicolas , Bouchet Nicolas , Renault Sylvaine , Douziech‐Eyrolles Laurence , Pilard Jean‐François , Augé‐Gouillou Corinne 
Published: December 2014

AbstractTransposases are specific DNA‐binding proteins that promote the mobility of discrete DNA segments. We used a combination of physicochemical approaches to describe the association of MOS1 (an eukaryotic transposase) with its specific target DNA, an event corresponding to the first steps of the transposition cycle. Because the kinetic constants of the reaction are still unknown, we aimed to determine them by using quartz crystal microbalance on two sources of recombinant MOS1: one produced in insect cells and the other produced in bacteria. The prokaryotic‐expressed MOS1 showed no cooperativity and displayed a Kd of about 300 nM. In contrast, the eukaryotic‐expressed MOS1 generated a cooperative system, with a lower Kd (∼2 nm). The origins of these differences were investigated by IR spectroscopy and AFM imaging. Both support the conclusion that prokaryotic‐ and eukaryotic‐expressed MOS1 are not similarly folded, thereby resulting in differences in the early steps of transposition.
Distribution of telomeres in the tobacco meiotic nuclei during cytomixis
Authors: Mursalimov Sergey , Sidorchuk Yuri , Baiborodin Sergey , Deineko Elena 
Published: December 2014

AbstractCytomixis is the migration of nuclei from one cell to another in higher plants, most frequently observable during microsporogenesis, which has a potential evolutionary significance. Currently, a major challenge is to label the chromatin migrating between cells to clarify its further fate. We have for the first time succeeded in visualizing the telomeric chromatin regions in the nuclei migrating between cells using fluorescent in situ hybridization. It has been shown that the telomeric signals in tobacco microsporocytes are randomly distributed in migrating nuclei without any deviations from their normal meiotic dynamics. According to our data, the chromatin migrating during cytomixis always contains telomeres and the telomeric signals are retained in the micronuclei formed after cytomixis.
Blockage of protease‐activated receptor 1 ameliorates heat‐stress induced intestinal high permeability and bacterial translocation
Authors: Xu Qiu‐lin , Guo Xiao‐hua , Liu Jing‐xian , Chen Bin , Liu Zhi‐feng , Su Lei 
Published: December 2014

AbstractAccumulated evidences indicate intestinal lesions play an important role in the pathogenesis of heatstroke. However, the underlying mechanisms by which heat stress causes intestinal barrier dysfunction and bacterial translocation remain unclear. In this study, we investigated the role of protease‐activated receptor 1 (PAR1) in heat stress‐induced intestinal hyper‐permeability and bacterial translocation. Intestinal permeability in heat stressed mouse was evaluated by determining plasma endotoxin concentration and urinal lactulose/mannitol (L/M) ratio with gastric administration of L/M solution. Venous blood, liver, spleen and mesenteric lymph node tissues were collected for bacterial load test. Real time PCR was used to determine ileum PAR1 mRNA expression. In vitro study, permeability was assessed by determining trans‐epithelial electrical resistance (TEER) in human intestinal Caco‐2 cell line. RWJ‐58259, a selective antagonist of PAR1, was used both in vivo and in vitro studies. The results showed that heat stress could increase ileum PAR1 mRNA level, urinal L/M ratio, plasma endotoxin concentration and bacterial load in the blood, spleen and mesenteric lymph nodes. Blocking PAR1 with RWJ‐58259 (10 mg/kg) pretreatment could significantly reduce heat stress‐induced above changes, but have no role to PAR1 mRNA level. In Caco‐2 cells, heat stress‐induced high permeability could also be reduced by RWJ‐58259 (5–20 µmol/L). In summary, our results demonstrated that PAR1 signaling pathway may play an important role in the heat stress‐induced elevation of intestinal permeability, bacterial translocation and the occurrence of endotoxemia.
Growth factors mediated differentiation of mesenchymal stem cells to cardiac polymicrotissue using hanging drop and bioreactor
Authors: Konstantinou Dimitrios , Lei Ming , Xia Zhidao , Kanamarlapudi Venkateswarlu 
Published: December 2014

AbstractHeart disease is the major leading cause of death worldwide and the use of stem cells promises new ways for its treatment. The relatively easy and quick acquisition of human umbilical cord matrix mesenchymal stem cells (HUMSCs) and their properties make them useful for the treatment of cardiac diseases. Therefore, the main aim of this investigation was to create cardiac polymicrotissue from HUMSCs using a combination of growth factors [sphingosine‐1‐phosphate (S1P) and suramin] and techniques (hanging drop and bioreactor). Using designated culture conditions of the growth factors (100 nM S1P and 500 µM suramin), cardiomyocyte differentiation medium (CDM), hanging drop, bioreactor and differentiation for 7 days, a potential specific cardiac polymicrotissue was derived from HUMSCs. The effectiveness of growth factors alone or in combination in differentiation of HUMSCs to cardiac polymicrotissue was analysed by assessing the presence of cardiac markers by immunocytochemistry. This analysis demonstrated the importance of those growth factors for the differentiation. This study for the first time demonstrated the formation of a cardiac polymicrotissue under specific culture conditions. The polymicrotissue thus obtained may be used in future as a ‘patch’ to cover the injured cardiac region and would thereby be useful for the treatment of heart diseases.