bluuebunny/crossref_metadata_2025 huggingface dataset:
ChemInform Abstract: THE REACTION OF ACID ANHYDRIDES, DIBASIC ACID DIESTERS, AND DIBASIC ACIDS WITH VINYLMAGNESIUM CHLORIDE
Authors: SUGA K. , WATANABE S. , FUJITA T. , TAKAHASHI Y.
Published: March 2016

Die Reaktion von Säureanhydriden wie (I), Dicarbonsäuredimethylestern wie (VII) und Dicarbonsäuren mit Vinyl‐Mg‐chlorid (II) werden untersucht und am Beispiel von Isobuttersäureanhydrid (Ia) und dem Adipinsäureester (VIIa) beschrieben.
ChemInform Abstract: AN ALKALI‐LABILE SUBSTITUTED BENZYLOXYCARBONYL AMINO‐PROTECTING GROUP
Authors: WAKSELMAN M. , GUIBE‐JAMPEL E.
Published: March 2016

Die aus (I) und (II) zugänglichen Ester (III) reagieren mit Phosgen in Toluol zu den Chlorcarbonaten (IV).
ChemInform Abstract: MALEIC ANHYDRIDE SUPPLY AND NEW PROCESSES
Authors: ‐ ‐
Published: March 2016

Nach einem neuen Verfahren der Mitsubishi Chem.
ChemInform Abstract: SYNTHESE ORGANISCHER RHODANVERBINDUNGEN UEBERSICHT 45. MITT. TEIL 1, ALIPHATISCHE RHODANVERBINDUNGEN
Authors: KNOKE D. , KOTTKE K. , POHLOUDEK‐FABINI R.
Published: March 2016

In dem ersten Teil der Übersicht werden Synthesen von aliphatischen Rhodan= Verbindungen, z.B. (III), durch Austausch von Halogen durch den Thiocyanatrest behandelt.
ChemInform Abstract: NEW COMPOUNDS, SYNTHESIS OF 3,4,5‐TRIMETHOXYBENZENESULFONAMIDES
Authors: PIFFERI G. , MONGUZZI R.
Published: March 2016

Durch Umsetzung der Trimethoxybenzoesäure (I) mit 70%iger Salpetersäure wird die Nitroverbindung (II) erhalten, die über Palladiumkohle katalytisch zum Amin (III) hydriert wird.
ChemInform Abstract: CONVERSION OF 1‐PHENYLAZO‐2‐NAPHTHOL INTO THE BENZENEDIAZONIUM ION, ANOTHER ROUTE TO PHENYL RADICALS
Authors: CADOGAN J. I. G. , MURRAY C. D. , SHARP J. T.
Published: March 2016

3 Mol p‐Chlorbenzoylnitrit (III) reagieren mit der Hydrazonform (II) von l‐Phenylazonaphthol‐(2) (I) in Benzol bei Raumtemperatur zur N‐Nitrosoverbindung (IV), die über den Diazoäther (V) in (VI) und (VII) zerfällt.
ChemInform Abstract: STUDIES OF ACENAPHTHENE DERIVATIVES PART 27, PREPARATION OF ACENAPHTHENEQUINONE MONOANIL N‐OXIDES AND THEIR REACTIONS WITH ISOCYANATES
Authors: TSUGE O. , SHINKAI I. , KOGA M.
Published: March 2016

Die aus 2‐Diazoacenaphthenon (I) mit den Nitrosoverbindungen (II) in guter Ausbeute erhältlichen Monoanil‐N‐oxide (III) reagieren mit den Isocyanaten (IV) in 66 ‐ 72%iger Ausbeute zu den Verbindungen (V), deren Salzsaure Hydrolyse die Naphthalimide (VI) ergibt.
ChemInform Abstract: VARIANTE DES SULFIDKONTRAKTIONSVERFAHRENS BEIM AUFBAU CORRINOIDER SYSTEME
Authors: GOETSCHI ERWIN , HUNKELER WALTER , WILD HANS‐JAKOB , SCHNEIDER PETER , FUHRER WALTER , GLEASON JOHN , ESCHENMOSER ALBERT
Published: March 2016

Die im Falle des 5‐Cyan‐4,4,5‐trimethyl‐Derivates des Thiopyrrolidons (II) erfolgreiche Methode der durch Dibenzoylperoxid vermittelten oxidativen Kupplung versagt Vollständig, wenn ′sie auf die Kupplung des unsubstituierten Thiopyrrolidons (II) mit? dem Pyrrolidon (Ia) angewendet wird.
ChemInform Abstract: DIE UNTERSUCHUNG DER STRUKTUR, DER EIGENSCHAFTEN UND DER CHEMISCHEN UMSETZUNGEN DES CARBAZOLS UND SEINER DERIVATE 46. MITT. DIE SYNTHESE UND DIE EIGENSCHAFTEN VON 3‐FORMYL‐9‐METHYLCARBAZOLHYDRAZONEN
Authors: POPOXA M. N. , KIRILENKO V. M. , BASOVA L. P. , SHISHKINA V. I.
Published: March 2016

Der Carbazolaldehyd (I) wird mit den Hydrazinen (II) zu Hydrazonen (III) umgesetzt.
ChemInform Abstract: PHOTOADDITION TO BENZENE OF N‐PHENYLMALEIMIDES SUBSTITUTED WITH ELECTRON‐ATTRACTING GROUPS
Authors: KARDUSH NABIL , STEVENS MALCOLM P.
Published: March 2016

Die Bestrahlung der Maleinsäureimide (Ia) in Benzol (II) in Gegenwart von Aceton und Ace‐tophenon als Sensibilisatoren führt nach 22 Std. zu den Photoaddukten (IIIa).
ChemInform Abstract: HYDRINDENE DERIVATIVES AS POTENTIAL ORAL HYPOGLYCEMIC AGENTS, N‐ALKYL 1,2,3,3A,4,8B‐HEXAHYDROINDENO(1,2‐B)PYRROLES
Authors: DE A. U. , SAHA B. P.
Published: March 2016

Die reduktive Aminierung der Keto‐indanylessigsäure (I) mit Wasserstoff und Ammoniak in absolutem Äthanol ü ber Raney‐Nickel liefert das Pyrrolidon (II), das mit Lithiumaluminiumhydrid zum Pyrrolidin (III) reduziert wird.
ChemInform Abstract: TOTAL SYNTHESIS OF DL‐METHYL ELENOLATE
Authors: KELLY ROBERT C. , SCHLETTER ILSE
Published: March 2016

Das durch Reaktion der Verbindungen (I) und (II) erhältliche Anhydrid (III) wird hydrolysiert, und die gebildete Dicarbonsäure (IV) wird zum Diol (Va) oxidiert.
ChemInform Abstract: A CONVENIENT SYNTHESIS OF ALKYLATED 4‐HYDROXY‐2‐PYRONES
Authors: SUZUKI E. , SEKIZAKI H. , INOUE S.
Published: March 2016

Die Grignard‐Verbindungen (I) setzen sich mit dem′ Säurechlorid (II) in Tetrahydrofuran bei ‐20°C zu den β‐Ketoestern (III) um.
ChemInform Abstract: A NEW SYNTHESIS OF THE COUMESTAN RING SYSTEM
Authors: KAPPE T. , SCHMIDT H.
Published: March 2016

Durch dehydrierende Cyclisierung der 4‐Hydroxy‐3‐phenylcumarine (I) mit Luftsauerstoff in siedendem Diphenyläther in Gegenwart von 10% Pd/Cwerden in 57 ‐ 80%iger Ausbeute die 6H‐Benzofuro(3,2‐c)A‐( l)‐benzopyron‐6‐one (II) erhalten, die unter UV‐Licht blau fluoreszieren.
ChemInform Abstract: 2,4,5,8‐TETRAMETHYLQUINOLINE, A CLARIFICATION
Authors: CLARET P. A. , OSBORNE A. G.
Published: March 2016

Die Synthese von 2,4,5,8‐Tetramethylchinolin (II) gelingt auf den in den Formeln wiedergegebenen und in der Literatur bisher nicht exakt beschriebenen Wegen.
ChemInform Abstract: SYNTHESIS OF SOME DERIVATIVES OF BENZ(A)ACRIDINE AND BENZ(C)ACRIDINE
Authors: MOCK J. , RITCHIE E. , TAYLOR W. C.
Published: March 2016

Die basisch katalysierte Reaktion zwischen dem Aminobenzaldehyd (I) und dem Naphthalindiol (II) führt zu den als Acetat und Tosylat und NMR‐spektroskopisch charakterisierten Benz[a]acridinol (IIIa), das mit Diazomethan methyliert den Äther (IIIb) ergibt.
ChemInform Abstract: COMPOUNDS RELATED TO ACRIDINE PART 9, COPPER CATALYZED OXIDATION OF 9‐ETHYNYLACRIDINE AND ITS REACTION WITH SECONDARY AMINES
Authors: TSUGE O. , TORII A.
Published: March 2016

Durch Oxidation von 9‐Äthinylacridin (I) mit Sauerstoff in Gegenwart von Kupferacetat in Piperidin wird das Butadiin‐Derivat (II) in 46%iger Ausbeute neben geringen Mengen des Acridinderivates (III) erhalten.
ChemInform Abstract: PHTHALAZIN UND VERWANDTE HETEROCYCLEN 11. MITT. 4‐(AMINOMETHYL)‐PHTHALAZON‐(1)‐DERIVATE
Authors: PYODYUNAS A. S. , KOST A. N. , LUBAS A. A.
Published: March 2016

Das aus Phthalsäureanhydrid (I) und Hippursäure (II) durch Erhitzen mit Acetanhydrid und Natriumacetat dargestellte Phthalylidenoxazolon (III) rea= (IV) mit verdünnter Kalilauge führt zu der Carbonsäure (V), während die Hy= Carbonsäure (V) wird.
ChemInform Abstract: THE SYNTHESIS OF 4‐BETA‐D‐RIBOFURANOSYL‐AS‐TRIAZIN‐3(4H)‐ONE 1‐OXIDE, A POTENTIAL URIDINE ANTAGONIST
Authors: SZEKERES G. L. , ROBINS R. K. , DEA P. , SCHWEIZER M. P. , LONG R. A.
Published: March 2016

166 Aufgrund der baktericiden Wirkung der Pyrazin‐N‐oxide (I) und (II) werden ähnliche Verbindungen hergestellt.
ChemInform Abstract: SYNTHESIS AND PHARMACOLOGICAL ACTIVITY OF 1‐(ARYLSULFONYL)‐3,5‐DIALKYL‐S‐TRIAZINE‐2,4,6‐(1H,3H,5H)‐TRIONES
Authors: HOLCOMB G. N. , KLEMM L. A. , SILHAVY T. J. , COUNSELL R. E.
Published: March 2016

Die Behandlung der Sulfonamide (I) mit einem Überschuß der Isocyanate (II) in Gegenwart von Triäthylamin führt zu den Triazintrionen (III).
ChemInform Abstract: DIE UNTERSUCHUNG VON LACTAMEN 23. MITT. DIE SYNTHESE VON AZEPINDERIVATEN AUF DER BASIS DES ALPHA‐OXOCAPROLACTAMS
Authors: SMIRNOVA V. G. , GLUSHKOV R. G.
Published: March 2016

Das Oxocaprolactam (I) reagiert mit Phenylmagnesiumbromid (II) zu dem Carbinol (III), das mit Lithiumaluminiumhydrid weiter zu dem Amin (IV) reduziert wird.
ChemInform Abstract: REACTION OF THE SALT OF N‐PHOSPHORYL‐N′‐METHYLIMIDAZOLE AND ITS APPLICATION TO THE SYNTHESIS OF MONOALKYL DIHYDROGEN PHOSPHATES
Authors: TAKAKU H. , SHIMADA Y. , AOSHIMA K.
Published: March 2016

Die Reaktion von phosphoriger Säure (I) und N‐Methyl‐imidazol (II) in Gegenwart von Quecksilber(II)‐chlorid bei 80°C und die anschließende Umsetzung mit den Alkoholen (IV) führt zu den Monoalkylphosphorsäureestern (V).
ChemInform Abstract: TETRAETHYLDITHIO‐OXAMIDE COMPLEXES OF TELLURIUM(IV)
Authors: CLARK E. ROY , COLLET ARNOLD J. , NAIK DINKER G.
Published: March 2016

Te‐tetrahalogenid bzw. Aryltellurtrihaloge äthyldithiooxamid in wasserfreiem Butano (Ia) bzw. (Ib).
ChemInform Abstract: METAL COMPLEXES OF AROMATIC AMINE‐N‐OXIDES
Authors: KARAYANNIS N. M. , PYTLEWSKI L. L. , MIKULSKI C. M.
Published: March 2016

Darstellung, Eigenschaften, Substituenteneffekte und Donoreigenschaften aromatischer Amin‐N‐oxide werden zusammenfassend behandelt.
ChemInform Abstract: A UV STUDY OF THE MAGNESIUM HAEMATOPORPHYRIN COMPLEX
Authors: ANAND V. D. , CARPER W. R.
Published: March 2016

Untersucht wird die Wechselwirkung zwischen Mg und dem Porphyrin in Abhängigkeit von der Konzentration, des pH‐Wertes und der Temperatur.
ChemInform Abstract: KINETICS OF MULTIDENTATE LIGAND SUBSTITUTION REACTIONS PART 15, SUBSTITUTION REACTIONS OF 1,2‐CYCLOHEXANE‐DIAMINE‐N,N,N′,N′‐TETRAACETIC ACID WITH COBALT(II) AND ZINC(II) IMINODIACETATE AND NITRILOTRIACETATE COMPLEXES
Authors: KODAMA MATSUO , HAGIYA KAORU
Published: March 2016

Polarographische Untersuchung der Kinetik der Substitutionsreaktionen sowie Diskussion der Mechanismen.
ChemInform Abstract: SPEKTROPHOTOMETRISCHE METHODE ZUR BESTIMMUNG DER STABILITAETSKONSTANTEN DER KOMPLEXVERBINDUNGEN IN LOESUNG
Authors: BORKOWSKI B. , BANCZYK K. , BORKOWSKA A.
Published: March 2016

Benutzt wird die Differenz zwischen der Extinktion der Lösung eines Indikators [2,7‐Bis‐[2‐arsono‐phenylazo ]‐l ,8‐dihydroxynaphthalindisulfonsäure‐ (3,6)] und der Extinktion einer sowohl den Indikator als auch den Komplex enthaltenden Lösung, die durch partielle Bindung des komplexbildenden Me‐ talls an den Indikator verursacht wird, (wobei die Stabilitätskonstante des Indikatorkomplexes bekannt sein muß).
ChemInform Abstract: TETRAKIS‐(N,N‐DIMETHYLDITHIOCARBAMATO)‐MOLYBDENUM(V) HALIDES
Authors: NIEUWPOORT A. , MOONEN J. H. E. , CRAS J. A.
Published: March 2016

152R Das nach bekannter Methode erhaltene Tetrakis‐[N,N‐dimethyldithiocarbamato]‐molybdän(IV) wurde in Chloroform mit berechneten Mengen von Brom und Jod umgesetzt und lieferte die Salze (I).
ChemInform Abstract: ARENE MOLYBDENUM CHEMISTRY, SOME BIS‐PI‐ALLYLIC DERIVATIVES
Authors: GREEN MALCOLM L. H. , MITCHARD LEONARD C. , SILVERTHORN WILLIAM E.
Published: March 2016

Die dimeren Verbindungen (I) reagieren mit Allylmagnesiumchlorid im Überschuß in wasserfreiem THF zu den Komplexen (IIa), die im Gegensatz zu Bis‐[n‐allyH‐nickel keine Reaktivität gegenüber Dimethylphenylphosphin oder Äthylendiamin zeigen.
ChemInform Abstract: POLAROGRAPHIC AND ESR STUDIES ON THE ELECTRODE REACTIONS OF TRIS(2,2′‐BIPYRIDINE)IRON(II) IN ACETONITRILE
Authors: TANAKA NOBUYUKI , OGATA TATEAKI , NUZUMA SHIGEYA
Published: March 2016

Untersuchung der Reduktion der Titelverbindung zu Fte(I)‐, Fe(0)‐ und Fe(‐I)‐ Komplexen durch kontrollierte Elektrolyse.
ChemInform Abstract: SYNTHESIS OF BRIDGED BICYCLOFERROCENE, PARTICIPATION OF ANHYDROUS ALUMINIUM CHLORIDE IN THE CONDENSATION REACTION
Authors: OMOTE YOSHIMORI , KOBAYASHI RYUICHIRO , NAKADA YOSHIO , SUGIYAMA NOBORU
Published: March 2016

Ein nach bekannter Methode erhaltener 1,1 ′‐Diacetylferrocen‐Aluminium‐ Chlorid‐Komplex und o‐Phenylendiamin bzw. 4‐Methyl‐1 ,2‐diaminobenzol reagieren bei Erhitzen in geschmolzenem Zustand zu den Derivaten (Ia) bzw. (Ib), deren Struktur durch IR‐, NMR; und massenspektroskopische Daten bestätigt wurde.
ChemInform Abstract: CO‐ORDINATION COMPLEXES CONTAINING MULTIDENTATE LIGANDS PART 3, THE VISIBLE SPECTRA OF SOME FIVE‐CO‐ORDINATE NICKEL(II) COMPLEXES CONTAINING TRIS(O‐DIMETHYLARSINOPHENYL)STIBINE, TRIGONAL BIPYRAMIDAL AND SQUARE PYRAMIDAL COMPLEXES
Authors: BARACCO LIVIO , HALFPENNY MICHAEL T. , MCAULIFFE CHARLES A.
Published: March 2016

(I) eine trigonal bipyramidale Struktur und (II) eine quadratisch sitzen.
ChemInform Abstract: A TRANSITION‐METAL CARBONYL COMPLEX OF PENTALENE
Authors: BROOKES A. , HOWARD J. , KNOX S. A. R. , STONE F. G. A. , WOODWARD P.
Published: March 2016

Die Verbindung (I) reagiert mit Cyclooctatetraen in siedendem Octan oder Heptan zu mehreren Komplexen, von denen einer den Pentalenkomplex (III) (12% Ausbeute) darstellt.
ChemInform Abstract: GENERATION AND REACTION OF 2,4‐DIENOLATE IONS FROM DELTA(4)‐3‐KETOSTEROIDS WITH LITHIUM HEXAMETHYLDISILAZANE
Authors: TANABE M. , CROWE D. F.
Published: March 2016

Das Testeron (I) ergibt mit Lithiumhexamethyldisilazan (II) in Tetrahydrofuran das Ion (III), das mit tert.‐Butyldimethylchlorsilan (IV) zum Silyläther (V) reagiert.
ChemInform Abstract: RHODANIN‐DERIVATE DER KETOSTEROIDE 9. MITT. UEBER FARBIGE STEROIDE
Authors: HUETTENRAUCH R. , OLTHOFF U.
Published: March 2016

Die Ketosteroide (I) und (IV) werden mit Rhodanin (II) in äthanolischer Lösung in Gegenwart von Ammoniak und Ammoniumchlorid zu den gefärbten Steroidderivaten (III) und (V) umgesetzt.
ChemInform Abstract: STEROID TOTAL SYNTHESIS PART 10, OPTICALLY ACTIVE ESTRONE PRECURSORS AND RACEMIC EQUILENIN METHYL ETHER
Authors: COHEN N. , BANNER B. L. , BLOUNT J. F. , TSAI M. , SAUCY G.
Published: March 2016

Die Synthese desÖstrons (XI) erfolgt nach den auf dem Steroid‐Sektor üblichen Verfahren und wird im Formelschema angedeutet, wobei als wesentliche Zwischenstufe das Lacton (III) hergestellt wird.
ChemInform Abstract: BUFADIENOLIDES PART 8, EPIMERIZATION OF 14ALPHA‐ AND 14BETA‐ARTEBUFOGENIN
Authors: KAMANO Y. , KUMON S. , ARAI T. , KOMATSU M.
Published: March 2016

Die Behandlung von Resibufogenin (I) liefert nach 30 Min. in 4,8 bzw. 67,5%iger Ausbeute l4ß‐Artebufogenin (III) und 14a‐Artebufogenin (II).
ChemInform Abstract: BRANCHED‐CHAIN SUGARS PART 4, SYNTHESIS OF 5,6‐DIDEOXY‐5‐C‐HYDROXYMETHYL‐1,2‐O‐ISOPROPYLIDENE‐6‐C‐NITRO‐3‐O‐SUBSTITUTED‐ALPHA‐D‐GLUCOSE DERIVATIVES
Authors: YOSHIMURA JUJI , IIDA TAKAO , WAKAI HIROO , FUNABASHI MASUO
Published: March 2016

Die Addition von Nitryljodid (in situ aus Jod und Ag‐nitrit) an die Xylofuranose‐Derivate (Ia) bzw. (Ib) gibt C‐5‐Epimerengemische der Nitroverbindungen (IIa) und (IIb), die mit Na‐boranat die L‐ido/D‐gluco‐Epimerengemische (IIIa)/ (IIIb) bzw. (IIIc)/(IIId) liefern.
ChemInform Abstract: TRITYLPYRIDINIUM‐FLUOROBORAT, EIN WIRKSAMES MITTEL ZUR TRITYLIERUNG
Authors: HANESSIAN S. , STAUB A. P. A.
Published: March 2016

Alkohole (I) werden durch Pyridiniumtrityl‐fluoroborat (II) glatt unter Eliminierung von Pyridinium‐tetrafluoroborat (IV) zu den Trityläthern (III) substituiert.
ChemInform Abstract: VERSCHIEDENE ANWENDUNGEN REAKTIVER ZWISCHENSTUFEN DER HYDRIDUEBERTRAGUNG BEI GLUCOSIDEN
Authors: HANESSIAN S. , STAUB A. P. A.
Published: March 2016

Aus den Glucosiden (Ia) und (Ib) erhält man mit Trityltetrafluoroborat in Acetonitril unter Hydridgruppenübertragung das Salz (II), aus dem die isomeren Spaltprodukte (III) und (IV) bei der Aufarbeitung gebildet werden.
ChemInform Abstract: A BIOGENETICALLY MODELED SYNTHESIS VIA AN INDOLE ACRYLIC ESTER, A TOTAL SYNTHESIS OF (+‐)‐MINOVINE
Authors: ZIEGLER FREDERICK E. , SPITZNER ERNEST B.
Published: March 2016

Durch Umsetzung der Verbindungen (I) und (II) und unmittelbar anschließende Verseifung (KOH) des gebildeten Esters (IIIa) wird die Säure (IIIb) gewonnen, deren Methylester (IIIc) mit dem Phosphoran (IV) zur Verbindung (V) umgesetzt wird.
ChemInform Abstract: AN IMPROVED SYNTHESIS OF PAVINANES
Authors: WALSH D. A. , LYLE R. E.
Published: March 2016

Bei der Herstellung der Pavine (II) aus den Dihydropapaverinen (I) können durch Behandlung mit Perchlorsäure in hoher Verdünnung die Ausbeute an (II) wesentlich verbessert und die Nebenreaktionen wie Disproportionierung etc. zurückgedrängt werden.
ChemInform Abstract: SYNTHESIS OF ′REVERSED′ NUCLEOSIDES OF SOME PURINE AND PYRIMIDINE BASES
Authors: FUKATSU SHUNZO , TAKEDA YOSHIRO , UMEZAWA SUMIO
Published: March 2016

Durch Umsetzung des Jodzuckers (III) mit dem Adenin (Ia) und nachfolgende Schutzgruppenabspaltung wird ein trennbares Gemisch der anomeren Nucleoside (IVa) und (IVb) erhalten; analog entstehen aus (III) und den Pyrimidin‐ Derivaten (II) in mäßigen Ausbeuten die Verbindungen (IVa) und (IVb) bzw. (IVc) und (IVd).
ChemInform Abstract: STUDIES ON PYROPHOSPHATES PART 2, A NEW METHOD FOR THE SYNTHESIS OF NUCLEOTIDE COENZYMES AND THEIR ANALOGS
Authors: NAKAGAWA IWAO , HATA TSUJIAKI
Published: March 2016

Die aus Alkoholen bzw. Nucleosiden mit Thiophosphonylchlorid erhaltenen Phosphordichloridate (I) werden zu den Thiophosphaten (II) hydrolysiert, deren Bistriäthylammoniumsalze mit den entsprechenden Disilbersalzen (III) die asymm. Pyrophosphate (IV) ergeben.
Improving the performance of distributed discrete event simulation by exchange of conditional look‐ahead
Authors: Fu Desheng , Becker Matthias , Szczerbicka Helena
Published: March 2016

Distributed discrete event simulation is an important approach for enabling the modeling and analysis of the behavior of large systems. This approach presents a major problem, namely, the possible low performance due to the excessive overhead in synchronizing the distributed logical processes. To counter this, our approach to distributed discrete event simulation involves conservative synchronization and its acceleration using dynamic estimation of process‐to‐process look‐ahead with a feedback mechanism. This mechanism allows for the estimation of a larger look‐ahead, which may be invalidated and recalculated during the course of the simulation, if one of the processes obtains more detailed knowledge.

In this work, we extend the dynamically estimated look‐ahead, on the basis of the local state of the logical processes, by exchanging conditional look‐aheads, in conjunction with the broadcast of invalidation announcements. A notable reduction in runtime in various cases is thus achieved, especially when the estimated look‐ahead is stochastically too conservative. Copyright © 2016 John Wiley & Sons, Ltd.
Three Cluster Organic Frameworks Constructed from Tetranuclear Cluster Units: Structure and Properties
Authors: Liu Ge , Xie Dong , Li Rui , Hou Lei , Zhang Wen‐Yan , Wang Yao‐Yu
Published: March 2016

By treating a semirigid 5‐oxyacetate isophthalic acid (H3OAIP) ligand with MnSO4/CoSO4/CdSO4 under solvothermal conditions, three isostructural cluster organic frameworks, [M2(OH)(OAIP)(DMA)]⋅H2O (M=Mn2+ (1), Co2+ (2), Cd2+ (3); DMA=N,N′‐dimethylacetamide) were constructed. The three complexes contain novel eight‐connected tetranuclear M4(OH)2(COO)6(OCH2COO)2 clusters with the unique hexagonal bipyramidal configuration, which are extended by four‐connected OAIP linkers to form an uncommon (4,8)‐connected alb‐4,8‐Cmce topology based on (3,6)‐connected kgd sublayers. Both 1 and 2 showed significant antiferromagnetic interactions between the intracluster metal ions, whereas 3 revealed strong blue photoluminescence.
Direct effects of exercise on kynurenine metabolism in people with normal glucose tolerance or type 2 diabetes
Authors: Mudry Jonathan M. , Alm Petter S. , Erhardt Sophie , Goiny Michel , Fritz Tomas , Caidahl Kenneth , Zierath Juleen R. , Krook Anna , Wallberg‐Henriksson Harriet
Published: March 2016

Background

Systemic kynurenine levels are associated with resistance to stress‐induced depression and are modulated by exercise. Tryptophan is a precursor for serotonin and kynurenine synthesis. Kynurenine is transformed into the neuroprotective catabolite kynurenic acid by kynurenine aminotransferases (KATs). PGC‐1α1 increases KAT mRNA and induces kynurenic acid synthesis. We tested the hypothesis that skeletal muscle PGC‐1α1/KAT‐kynurenine pathway is altered by exercise and type 2 diabetes.

Method

Skeletal muscle and plasma from men with normal glucose tolerance (n = 12) or type 2 diabetes (n = 12) was studied at rest, after acute exercise and during recovery. Tryptophan, Kynurenine and kynurenic acid plasma concentration were measured as well as mRNA of genes related to exercise and kynurenine metabolism.

Results

mRNA expression of KAT1, KAT2 and PPARα was modestly reduced in type 2 diabetic patients. In response to exercise, mRNA expression of KAT4 decreased and PGC‐1α1 increased in both groups. Exercise increased plasma kynurenic acid and reduced kynurenine in normal glucose tolerance and type 2 diabetic participants. Plasma tryptophan was reduced and the ratio of [kynurenic acid] * 1000/[kynurenine] increased in both groups at recovery, suggesting an improved balance between neurotoxic and neuroprotective influences. Tryptophan and kynurenine correlated with body mass index, suggesting a relationship with obesity.

Conclusions

Acute exercise directly affects circulating levels of tryptophan, kynurenine and kynurenic acid, providing a potential mechanism for the anti‐depressive effects of exercise. Furthermore, exercise‐mediated changes in kynurenine metabolism are preserved in type 2 diabetic patients. Copyright © 2016 John Wiley & Sons, Ltd.
Incongruent range dynamics between co‐occurring Asian temperate tree species facilitated by life history traits
Authors: Zhao Yun‐Peng , Yan Xiao‐Ling , Muir Graham , Dai Qiong‐Yan , Koch Marcus A. , Fu Cheng‐Xin
Published: March 2016

Postglacial expansion to former range limits varies substantially among species of temperate deciduous forests in eastern Asia. Isolation hypotheses (with or without gene flow) have been proposed to explain this variance, but they ignore detailed population dynamics spanning geological time and neglect the role of life history traits. Using population genetics to uncover these dynamics across their Asian range, we infer processes that formed the disjunct distributions of Ginkgo biloba and the co‐occurring Cercidiphyllum japonicum (published data). Phylogenetic, coalescent, and comparative data suggest that Ginkgo population structure is regional, dichotomous (to west–east refugia), and formed ˜51 kya, resulting from random genetic drift during the last glaciation. This split is far younger than the north–south population structure of Cercidiphyllum (~1.89 Mya). Significant (recent) unidirectional gene flow has not homogenized the two Ginkgo refugia, despite 2Nm > 1. Prior to this split, gene flow was potentially higher, resulting in conflicting support for a priori hypotheses that view isolation as an explanation for the variation in postglacial range limits. Isolation hypotheses (with or without gene flow) are thus not necessarily mutually exclusive due to temporal variation of gene flow and genetic drift. In comparison with Cercidiphyllum, the restricted range of Ginkgo has been facilitated by uncompetitive life history traits associated with seed ecology, highlighting the importance of both demography and lifetime reproductive success when interpreting range shifts.
Boron‐doped Diamond Electrodes Modified with Fe3O4@Au Magnetic Nanocomposites as Sensitive Platform for Detection of a Cancer Biomarker, Interleukin‐8.
Authors: Braiek Mohamed , Yang Yi , Farre Carole , Chaix Carole , Bessueille François , Baraket Abdoullatif , Errachid Abdelhamid , Zhang Aidong , Jaffrezic‐Renault Nicole
Published: March 2016

Interleukin‐8 (IL‐8), a dimeric protein composed of two identical subunits, is overexpressed in different human cancers, among them pancreatic cancers and head and neck cancers. There is a strong demand for monitoring of this biomarker protein for early cancer detection. A new concept of label‐free impedimetric immunosensors for IL‐8 detection is described in this work. A nanocomposite of gold nanoparticles (AuNPs) decorating a magnetic Fe3O4 core is synthesized using cysteamine as linker, and characterized using TEM and UV‐Vis spectrometry. After immobilization of these Fe3O4@Au magnetic nanocomposites on a boron doped diamond (BDD) electrode using a simple magnet, anti‐human IL‐8 monoclonal antibody is linked to the AuNPs, previously functionalized with thioctic acid. The functionalization of the immunosensor was characterized using two electrochemical techniques: cyclic voltammetry (CV) and electrochemical impedance spectroscopy (EIS), performed in phosphate buffer with ferro/ferricyanide as the redox probe. The EIS technique was used for affinity assays: antibody‐Antigen binding. A linear relationship between the increment in the electron transfer resistance (RCT) and the logarithmic value of IL‐8 concentration was observed between 0.1 pg/mL and 1000 pg/mL. The limit of detection (LOD) was estimated at 0.03 pg/mL.
An investigation of the impact of left-censored soil contamination data on the uncertainty of descriptive statistical parameters
Authors: Shoari Niloofar , Dubé Jean-Sébastien
Published: March 2016

Left-censored concentration data are frequently encountered because measuring instruments cannot detect concentrations below the instrument detection limit. For statistical analysis of left-censored data, the environmental literature mainly refers to the following methods: maximum likelihood estimator, regression on order statistics using log-normal and gamma assumption (rROS and GROS, respectively), and Kaplan–Meier. A number of simulation experiments examined the performance of these methods in terms of bias and/or mean square error. However, no matter which method is adopted, some uncertainty is introduced into outcomes because all that is known about a left-censored observation is that the concentration falls between 0 and the detection limit. The data used in the present study come from analysis of soil samples collected for a site characterization in Montreal, Canada. Employing nonparametric bootstrap, the authors quantify the uncertainty and bias in the mean and standard deviation estimates obtained by the maximum likelihood estimation (under log-normal, Weibull, and gamma distributions), rROS, GROS, and Kaplan–Meier methods. First, the authors demonstrate that the highest uncertainty is associated with the maximum likelihood estimator under log-normality and Weibull assumptions, whereas a gamma assumption leads to estimates with less uncertainty. Second, the authors show that although an increase in sample size improves the uncertainty, it reduces the bias only in the rROS, GROS, and Kaplan–Meier methods. Finally, comparing percentage uncertainty in the mean of contaminant data, the authors illustrate that adopting an inappropriate estimator results in large uncertainties. Environ Toxicol Chem 2016;35:2623–2631. © 2016 SETAC
Influence of bed clusters and size gradation on operational time distribution for non‐uniform bed‐load transport
Authors: Zhang Yong , Chen Dong , Garrard Rhiannon , Sun HongGuang , Lu Yuehan
Published: March 2016

The operational time distribution (OTD) defines the time for bed‐load sediment spent in motion, which is needed to characterize the random nature of sediment transport. This study explores the influence of bed clusters and size gradation on OTD for non‐uniform bed‐loads. First, both static and mobile bed armouring experiments were conducted in laboratorial flumes to monitor the transport of mixed sand/gravel sediments. Only in the mobile armouring experiment did apparent bed clusters develop, because of stable feeding and a longer transport period. Second, a generalized subordinated advection (GSA) model was applied to quantify the observed dynamics of tracer particles. Results show that for the static armour layer (without sediment feed), the best‐fit OTD assigns more weight to the large displacement of small particles, likely because of the size‐selective entrainment process. The capacity coefficient in the GSA model, which affects the width of the OTD, is space dependent only for small particles whose dynamics can be significantly affected by larger particles and whose distribution is more likely to be space dependent in a mixed sand and gravel system. However, the OTD for the mobile armour layer (with sediment recirculation) exhibited longer tails for larger particles. This is because the trailing edge of larger particles is more resistant to erosion, and their leading front may not be easily trapped by self‐organized bed clusters. The strong interaction between particle–bed may cause the capacity coefficient to be space‐dependent for bed‐load transport along mobile armour layers. Therefore, the combined laboratory experiments and stochastic model analysis show that the OTD may be affected more by particle–bed interactions (such as clusters) than by particle–particle interactions (e.g. hiding and exposing), and that the GSA model can quantify mixed‐size sand/gravel transport along river beds within either static or mobile armour layers. Copyright © 2016 John Wiley & Sons, Ltd.
Two‐dimensional‐strain echocardiography in intensive care unit patients: A prospective, observational study
Authors: Nafati Cyril , Lançon Victor , Blasco Valery , Zieleskiewicz Laurent , Harti Karim , Wiramus Sandrine , Kelway Charlotte , Reydellet Laurent , Antonini François , Albanèse Jacques , Leone Marc
Published: March 2016

Purpose

Two‐dimensional‐strain echocardiography (2D‐strain) is a promising technique for the early detection of myocardial dysfunction. Our study was aimed to assess its feasibility in the intensive care unit (ICU). Our secondary goal was to determine if 2D‐strain could predict the patient's outcome.

Methods

Conventional echocardiography and 2D‐strain were performed on 64 consecutive patients admitted to our ICU. Using 2D‐strain, the longitudinal deformation of the left ventricle was assessed. Feasibility of 2D‐strain, diagnosis performance, and 28‐day mortality prediction were determined.

Results

2D‐strain measurements could be performed in 77% of our patients. All 2D‐strain variables related to ventricular performance were significantly impaired in the patients who died compared with those who survived. Strain global medium was the only independent echocardiographic variable predictor of 28‐day mortality rate (odds ratio 0.60; 95% confidence interval 0.43–0.80, p = 0.002).

Conclusions

2D‐strain measurement is feasible in ICU patients, enabling identifying early left ventricle dysfunction. Strain global medium is an independent predictor of 28‐day mortality. © 2016 Wiley Periodicals, Inc. J Clin Ultrasound 44:368–374, 2016
Is severe progressive liver disease caused by alpha‐1‐antitrypsin deficiency more common in children or adults?
Authors: Chu Andrew S. , Chopra Kapil B. , Perlmutter David H.
Published: March 2016

The classical form of alpha‐1‐antitrypsin deficiency (A1ATD) is known to cause liver disease in children and adults, but there is relatively little information about the risk of severe, progressive liver disease and the need for liver transplantation. To better understand how newly evolving pharmacological, genetic, and cellular therapies may be targeted according to risk for progressive liver disease, we sought to determine the age distribution of A1ATD as a cause of severe liver disease, as defined by the need for liver transplantation. Using 3 US liver transplantation databases for the period 1991‐2012, we found 77.2% of 1677 liver transplants with a reported diagnosis of A1ATD were adults. The peak age range was 50‐64 years. Using 2 of the databases which included specific A1AT phenotypes, we found that many of these adults who undergo liver transplantation with A1ATD as the diagnosis are heterozygotes and have other potential causes of liver disease, most notably obesity and ethanol abuse. However, even when these cases are excluded and only ZZ and SZ phenotypes are considered, severe liver disease requiring transplantation is more than 2.5 times as likely in adults. The analysis also showed a markedly increased risk for males. In the pediatric group, almost all of the transplants are done in children less than 5 years of age. In conclusion, A1ATD causes progressive liver disease most commonly in adults with males in the highest risk category. In the pediatric group, children less than 5 years of age are highest in risk. These results suggest that A1ATD most commonly causes liver disease by mechanisms similar to age‐dependent degenerative diseases and more rarely in children by powerful modifiers. Liver Transplantation 22 886–894 2016 AASLD
Are complex DCE‐MRI models supported by clinical data?
Authors: Duan Chong , Kallehauge Jesper F. , Bretthorst G. Larry , Tanderup Kari , Ackerman Joseph J.H. , Garbow Joel R.
Published: March 2016

Purpose

To ascertain whether complex dynamic contrast enhanced (DCE) MRI tracer kinetic models are supported by data acquired in the clinic and to determine the consequences of limited contrast‐to‐noise.

Methods

Generically representative in silico and clinical (cervical cancer) DCE‐MRI data were examined. Bayesian model selection evaluated support for four compartmental DCE‐MRI models: the Tofts model (TM), Extended Tofts model, Compartmental Tissue Uptake model (CTUM), and Two‐Compartment Exchange model.

Results

Complex DCE‐MRI models were more sensitive to noise than simpler models with respect to both model selection and parameter estimation. Indeed, as contrast‐to‐noise decreased, complex DCE models became less probable and simpler models more probable. The less complex TM and CTUM were the optimal models for the DCE‐MRI data acquired in the clinic. [In cervical tumors,
,
, and
increased after radiotherapy (P = 0.004, 0.002, and 0.014, respectively)].

Conclusion

Caution is advised when considering application of complex DCE‐MRI kinetic models to data acquired in the clinic. It follows that data‐driven model selection is an important prerequisite to DCE‐MRI analysis. Model selection is particularly important when high‐order, multiparametric models are under consideration. (Parameters obtained from kinetic modeling of cervical cancer clinical DCE‐MRI data showed significant changes at an early stage of radiotherapy.) Magn Reson Med 77:1329–1339, 2017. © 2016 International Society for Magnetic Resonance in Medicine
The potential of deinking paper sludge for recycled HDPE reinforcement
Authors: Elloumi A. , Makhlouf M. , Elleuchi A. , Bradai Ch.
Published: March 2016

This article studies the potential of deinking paper sludge (DPS) and recycled high density polyethylene (RHDPE) for biocomposites (DPS/RHDPE). Different DPS loadings (0 to 20 wt%) and compatibilizer content (0 to 4 wt%) were used in (DPS/RHDPE) formulations. A commercial paper wet‐strength agent polyamideamine‐epichlorohydrin resin (PAE) was used as DPS binder. The effects of DPS composition and PAE content on RHDPE/DPS biocomposites performance were studied. First, the chemical composition, morphology and thermal behavior of DPS were characterized using X‐ray diffraction, scanning electron microscopy, fiber quality analyser, and thermogravimetric analyses. The effect of the chemical treatment was evaluated using infrared spectroscopy (FTIR). Finally, crystallization behavior and tensile properties of DPS based biocomposites were discussed. Results revealed that DPS have a nucleating effect thanks to the presence of minerals such as calcium carbonate and talc. DPS increased the stiffness and the tensile strength of RHDPE. PAE could also serve as a compatibilizer between fibers and RHDPE. POLYM. COMPOS., 39:616–623, 2018. © 2016 Society of Plastics Engineers
Analysis of endocannabinoid signaling elements and related proteins in lymphocytes of patients with Dravet syndrome
Authors: Rubio Marta , Valdeolivas Sara , Piscitelli Fabiana , Verde Roberta , Satta Valentina , Barroso Eva , Montolio Marisol , Aras Luis Miguel , Di Marzo Vincenzo , Sagredo Onintza , Fernández‐Ruiz Javier
Published: March 2016

Cannabidiol (CBD) reduces seizures in childhood epilepsy syndromes including Dravet syndrome (DS). A formulation of CBD has obtained orphan drug designation for these syndromes and clinical trials are currently underway. The mechanism responsible for CBD effects is not known, although it could involve targets sensitive to CBD in other neurological disorders. We believe of interest to investigate whether these potential targets are altered in DS, in particular whether the endocannabinoid system is dysregulated. To this end, lymphocytes from patients and controls were used for analysis of gene expression of transmitter receptors and transporters, ion channels, and enzymes associated with CBD effects, as well as endocannabinoid genes. Plasma endocannabinoid levels were also analyzed. There were no differences between DS patients and controls in most of the CBD targets analyzed, except an increase in the voltage‐dependent calcium channel α‐1h subunit. We also found that cannabinoid type‐2 (CB2) receptor gene expression was elevated in DS patients, with no changes in other endocannabinoid‐related receptors and enzymes, as well as in plasma levels of endocannabinoids. Such elevation was paralleled by an increase in CD70, a marker of lymphocyte activation, and certain trends in inflammation‐related proteins (e.g., peroxisome proliferator‐activated receptor‐γ receptors, cytokines). In conclusion, together with changes in the voltage‐dependent calcium channel α‐1h subunit, we found an upregulation of CB2 receptors, associated with an activation of lymphocytes and changes in inflammation‐related genes, in DS patients. Such changes were also reported in inflammatory disorders and may indirectly support the occurrence of a potential dysregulation of the endocannabinoid system in the brain.
UGT concentrations in human rectal tissue after multidose, oral curcumin
Authors: Asher Gary N. , Fallon John K. , Smith Philip C.
Published: March 2016

In vitro studies have demonstrated that curcumin is a substrate for uridine diphosphate glucuronosyltransferase (UGTs), with a putative ability to both induce expression and inhibit function, highlighting the potential for interaction with some drugs. Therefore, we sought to evaluate the effect of oral curcumin on intestinal UGT expression. Healthy volunteers, ages 40–80 years, who had received recent screening colonoscopy were recruited. Participants did not have any gastrointestinal or bleeding disorders, lab abnormalities, or recent antibiotic use. All participants received daily curcuminoid extract, 4 g, for 30 days. Untreated, rectal mucosal pinch biopsies were obtained at baseline and at 30 days. Microsomes were prepared from biopsy samples, using sequential centrifugation. Quantification of 14 UGT 2As and 2Bs was performed by LC‐MS/MS(MS, mass spectrometry), using quantitative‐ targeted absolute proteomics. Lowest LODs were ~0.1 pmol/mg protein. Comparisons were performed using Wilcoxon signed‐rank test. Paired baseline and 30 days biopsy samples were available for 38 participants. UGTs 1A10 and 2B17 were detected in 35 and 33 paired samples, respectively, while all other UGTs were below the limit of quantification (BLOQ). Median baseline UGT1A10 concentration was 0.60 pmol/mg (95% CI:0.32–0.92), and 0.60 pmol/mg (95% CI:0.43–1.00) after 30 days (P = 0.23). For UGT2B17, median baseline concentration was 0.83 pmol/mg (95% CI:0.32–1.62), and 1.18 pmol/mg (95% CI:0.39–1.77) after 30 days (P = 0.24). We found no differences in rectal mucosal UGT concentrations before and after 30 days of oral curcumin administration, indicating that daily curcumin use is unlikely to alter colonic UGT expression. Distal gut biopsies may not accurately reflect the proximal gut environment where UGT expression and curcumin concentrations may be higher.
A Novel Therapeutic Approach Using Mesenchymal Stem Cells to Protect Against Mycobacterium abscessus
Authors: Kim Jong-Seok , Cha Sang-Ho , Kim Woo Sik , Han Seung Jung , Cha Seung Bin , Kim Hong Min , Kwon Kee Woong , Kim So Jeong , Choi Hong-Hee , Lee Jienny , Cho Sang-Nae , Koh Won-Jung , Park Yeong-Min , Shin Sung Jae
Published: March 2016

Recent studies have demonstrated the therapeutic potential of mesenchymal stem cells (MSCs) for the treatment of acute inflammatory injury and bacterial pneumonia, but their therapeutic applications in mycobacterial infections have not been investigated. In this study, we demonstrated the use of MSCs as a novel therapeutic strategy against Mycobacterium abscessus (M. abscessus), which is the most drug-resistant and difficult-to-treat mycobacterial pathogen. The systemic intravenous injection of MSCs not only improved mouse survival but also enhanced bacterial clearance in the lungs and spleen. Additionally, MSCs enhanced IFN-γ, TNF-α, IL-6, MCP-1, nitric oxide (NO) and PGE2 production and facilitated CD4+/CD8+ T cell, CD11bhigh macrophage, and monocyte recruitment in the lungs of M. abscessus-infected mice. To precisely elucidate the functions of MSCs in M. abscessus infection, an in vitro macrophage infection system was used. MSCs caused markedly increased NO production via NF-κB activation in M. abscessus-infected macrophages cultured in the presence of IFN-γ. Inhibiting NO or NF-κB signaling using specific inhibitors reduced the antimycobacterial activity of MSCs. Furthermore, the cellular crosstalk between TNF-α released from IFN-γ-stimulated M. abscessus-infected macrophages and PGE2 produced by MSCs was necessary for the mycobacterial-killing activity of the macrophages. Finally, the importance of increased NO production in response to MSC administration was confirmed in the mouse M. abscessus infection model. Our results suggest that MSCs may offer a novel therapeutic strategy for treating this drug-resistant mycobacterial infection by enhancing the bacterial-killing power of macrophages.
Lonidamine-ethyl ester-mediated remodelling of the Sertoli cell cytoskeleton induces phosphorylation of plakoglobin and promotes its interaction with α-catenin at the blood–testis barrier
Authors: Mruk Dolores D. , Bonanomi Michele , Silvestrini Bruno
Published: March 2016

Several compounds affect male fertility by disrupting the adhesion of germ cells to Sertoli cells, which results in the release of undeveloped germ cells into the seminiferous tubule lumen that are incapable of fertilising the ovum. Indazole carboxylic acids are one class of compounds exhibiting such effects and they have been investigated as non-hormonal contraceptives for potential human use. The aims of this study were to investigate the effects of lonidamine-ethyl ester, an indazole carboxylic acid, on spermatogenesis and cell junctions, in particular, desmosomes. We found two doses of lonidamine-ethyl ester at 50 mg kg–1 to disrupt Sertoli–germ cell adhesion. By light and fluorescent microscopy, pronounced changes were observed in the distribution of actin microfilaments and intermediate filaments, as well as in the localisation of plakoglobin, a protein with structural and signalling roles at the desmosome and adherens junction at the blood–testis barrier. Furthermore, immunoblotting and immunoprecipitation experiments using testis lysates revealed a significant upregulation (P < 0.01) of plakoglobin and Tyr-phosphorylated plakoglobin. Co-immunoprecipitation experiments showed an increase in the interaction between plakoglobin and fyn proto-oncogene, an Src family non-receptor tyrosine kinase, after treatment, as well as an increase in the interaction between plakoglobin and α-catenin. Taken collectively, these data indicate that a disruption of Sertoli cell and spermatocyte–spermatid adhesion in the seminiferous epithelium by lonidamine-ethyl ester results in the phosphorylation of plakoglobin, thereby promoting its interaction with α-catenin at the blood–testis barrier.
Huygens on Inertial Structure and Relativity
Authors: Stan Marius
Published: March 2016

I explain and assess here Huygens’s concept of relative motion. I show that it allows him to ground most of the Law of Inertia and also to explain rotation. Thereby his concept obviates the need for Newton’s absolute space. Thus, his account is a powerful foundation for mechanics, although not without some tension.
Darier disease
Authors: Takagi Atsushi , Kamijo Maya , Ikeda Shigaku
Published: March 2016

Darier disease (DD) is a type of inherited keratinizing disorder that exhibits autosomal dominant inheritance. DD is caused by the mutations of ATP2A2, which encodes an endoplasmic reticulum calcium pump, sarco/endoplasmic reticulum ATPase type 2 (SERCA2). DD often develops in childhood, persists through adolescence, and causes small papules predominantly in seborrheic areas such as the face, chest and back. Further, scales and scabs may gradually develop. DD may be accompanied by non‐dermal symptoms, including psychiatric symptoms. Histologically, DD is characterized by corps ronds and grains in addition to suprabasal cleavage. There are no currently validated curative treatments available for DD, with the majority of cases treated symptomatically. Despite demonstrating efficacy in the treatment of DD, the use of oral retinoids has been limited due to the association with various adverse effects.
Serum levels of soluble programmed death‐1 and programmed death ligand‐1 in systemic sclerosis: Association with extent of skin sclerosis
Authors: Yanaba Koichi , Hayashi Mitsuha , Yoshihara Yuki , Nakagawa Hidemi
Published: March 2016

The interaction of programmed death‐1 (PD‐1) with its ligand, programmed death ligand‐1 (PD‐L1), has been considered to play a key role in the negative regulation of immune responses. Patients with diffuse cutaneous systemic sclerosis (SSc) had higher levels of soluble PD‐1 (sPD‐1) than those with limited cutaneous SSc and healthy individuals. Serum sPD‐1 levels positively correlated with the severity of skin sclerosis. In contrast, serum sPD‐L1 levels were significantly increased in patients with SSc compared with healthy individuals. Moreover, serum sPD‐L1 levels were not associated with the extent of skin sclerosis and were elevated not only in patients with diffuse cutaneous SSc, but also in those with limited cutaneous SSc. These results suggested that serum sPD‐1 levels may increase in patients with SSc and correlate with the severity of skin sclerosis. PD‐1/PD‐L1 interaction may contribute to the development of skin sclerosis in SSc.
Living on the edge: emergence of spontaneous gac mutations in Pseudomonas protegens during swarming motility
Authors: Song Chunxu , Kidarsa Teresa A. , van de Mortel Judith E. , Loper Joyce E. , Raaijmakers Jos M.
Published: March 2016

Swarming motility is a flagella‐driven multicellular behaviour that allows bacteria to colonize new niches and escape competition. Here, we investigated the evolution of specific mutations in the GacS/GacA two‐component regulatory system in swarming colonies of Pseudomonas protegens Pf‐5. Experimental evolution assays showed that repeated rounds of swarming by wildtype Pf‐5 drives the accumulation of gacS/gacA spontaneous mutants on the swarming edge. These mutants cannot swarm on their own because they lack production of the biosurfactant orfamide A, but they do co‐swarm with orfamide‐producing wildtype Pf‐5. These co‐swarming assays further demonstrated that ΔgacA mutant cells indeed predominate on the edge and that initial ΔgacA:wildtype Pf‐5 ratios of at least 2:1 lead to a collapse of the swarming colony. Subsequent whole‐genome transcriptome analyses revealed that genes associated with motility, resource acquisition, chemotaxis and efflux were significantly upregulated in ΔgacA mutant on swarming medium. Moreover, transmission electron microscopy showed that ΔgacA mutant cells were longer and more flagellated than wildtype cells, which may explain their predominance on the swarming edge. We postulate that adaptive evolution through point mutations is a common feature of range‐expanding microbial populations and that the putative fitness benefits of these mutations during dispersal of bacteria into new territories are frequency‐dependent.