bluuebunny/crossref_metadata_2025 huggingface dataset:
Highly Sensitive and Selective Biosensors Based on Organic Transistors Functionalized with Cucurbit[6]uril Derivatives
Authors: Jang Moonjeong , Kim Hyoeun , Lee Sunri , Kim Hyun Woo , Khedkar Jayshree K. , Rhee Young Min , Hwang Ilha , Kim Kimoon , Oh Joon Hak
Published: June 2015

Biosensors based on a field‐effect transistor platform allow continuous monitoring of biologically active species with high sensitivity due to the amplification capability of detected signals. To date, a large number of sensors for biogenic substances have used high‐cost enzyme immobilization methods. Here, highly sensitive organic field‐effect transistor (OFET)‐based sensors functionalized with synthetic receptors are reported that can selectively detect acetylcholine (ACh+), a critical ion related to the delivery of neural stimulation. A cucurbit[6]uril (CB[6]) derivative, perallyloxyCB[6] ((allyloxy)12CB[6], AOCB[6]), which is soluble in methanol but insoluble in water, has been solution‐deposited as a selective sensing layer onto a water‐stable p‐channel semiconductor, 5,5′‐bis‐(7‐dodecyl‐9H‐fluoren‐2‐yl)‐2,2′‐bithiophene layer. The OFET‐based sensors exhibit a detection limit down to 1 × 10–12
m of ACh+, which is six orders of magnitude lower than that of ion‐selective electrode‐based sensors. Moreover, these OFET‐based sensors show highly selective discrimination of ACh+ over choline (Ch+). The findings demonstrate a viable method for the fabrication of OFET‐based biosensors with high sensitivity and selectivity, and allow for practical applications of OFETs as high‐performance sensors for biogenic substances.
Highly UV‐Sensitive and Responsive Benzothiophene/Dielectric Polymer Blend‐Based Organic Thin‐Film Phototransistor
Authors: Ljubic Darko , Smithson Chad S. , Wu Yiliang , Zhu Shiping
Published: June 2015

It is reported on drain current modulation by UV light, in an organic thin‐film phototransistor, based on a small molecule semiconductor 2,7‐dipentylbenzo[b]benzo[4,5]thieno[2,3‐d]thiophene (BTBT‐C5) blended with a linear unsaturated polyester (L‐upe) to form the active channel material. The electrical properties of the phototransistor (L‐upe+BTBT‐C5) and physical properties of thin‐films are evaluated by means of two‐ and three‐terminal current–voltage characteristics (in the dark and under UV light) and structure–morphology analysis, respectively. Upon illumination with UV light, a dramatic change in the electrical properties of the L‐upe+BTBT‐C5 transistors is observed, compared to low responsive control transistors based on a blend of poly(methyl methacrylate) and BTBT‐C5. Drain current is increased by more than six orders of magnitude with maximum photosensitivity and responsivity of 4.0 × 106 and 11.1 A W−1, respectively, using a VG = 0 V. Modulated photoelectrical properties are explained by structure–morphology characteristics and efficient charge trapping at the polymer/semiconductor interface due to the presence of electron‐withdrawing groups in the polymer. Fast rise time of 1.80 s and slow relaxation time of 24.27 s, estimated using bi‐exponential fitting models, confirm a charge trapping/releasing mechanism and reveal sensing‐memory properties of the devices.
Upscaling of Perovskite Solar Cells: Fully Ambient Roll Processing of Flexible Perovskite Solar Cells with Printed Back Electrodes
Authors: Schmidt Thomas M. , Larsen‐Olsen Thue T. , Carlé Jon E. , Angmo Dechan , Krebs Frederik C.
Published: June 2015

A scaling effort on perovskite solar cells is presented where the device manufacture is progressed onto flexible substrates using scalable techniques such as slot‐die roll coating under ambient conditions. The printing of the back electrode using both carbon and silver is essential to the scaling effort. Both normal and inverted device geometries are explored and it is found that the formation of the correct morphology for the perovskite layer depends heavily on the surface upon which it is coated and this has significant implications for manufacture. The time it takes to form the desired layer morphology falls in the range of 5–45 min depending on the perovskite precursor, where the former timescale is compatible with mass production and the latter is best suited for laboratory work. A significant loss in solar cell performance of around 50% is found when progressing to using a fully scalable fabrication process, which is comparable to what is observed for other printable solar cell technologies such as polymer solar cells. The power conversion efficiency (PCE) for devices processed using spin coating on indium tin oxide (ITO)‐glass with evaporated back electrode yields a PCE of 9.4%. The same device type and active area realized using slot‐die coating on flexible ITO‐polyethyleneterphthalate (PET) with a printed back electrode gives a PCE of 4.9%.
A Phase 2 study of L‐asparaginase encapsulated in erythrocytes in elderly patients with Philadelphia chromosome negative acute lymphoblastic leukemia: The GRASPALL/GRAALL‐SA2‐2008 study
Authors: Hunault‐Berger Mathilde , Leguay Thibaut , Huguet Françoise , Leprêtre Stéphane , Deconinck Eric , Ojeda-Uribe Mario , Bonmati Caroline , Escoffre‐Barbe Martine , Bories Pierre , Himberlin Chantal , Chevallier Patrice , Rousselot Philippe , Reman Oumedaly , Boulland Marie‐Laure , Lissandre Severine , Turlure Pascal , Bouscary Didier , Sanhes Laurence , Legrand Ollivier , Lafage‐Pochitaloff Marina , Béné Marie C , Liens David , Godfrin Yann , Ifrah Norbert , Dombret Hervé ,   Group for Research on Adult Acute Lymphoblastic Leukemia (GRAALL)
Published: June 2015

Purpose: The GRASPALL/GRAALL‐SA2‐2008 Phase II trial evaluated the safety and efficacy of L‐asparaginase encapsulated within erythrocytes (GRASPA®) in patients ≥ 55 years with Philadelphia chromosome‐negative acute lymphoblastic leukemia. Findings: Thirty patients received escalating doses of GRASPA® on Day 3 and 6 of induction Phases 1 and 2. The primary efficacy endpoint was asparagine depletion < 2 µmol/L for at least 7 days. This was reached in 85 and 71% of patients with 100 and 150 IU/kg respectively but not with 50 IU/kg. Grade 3/4 infection, hypertransaminasemia, hyperbilirubinemia and deep vein thrombosis occurred in 77, 20, 7, and 7% of patients, respectively. No allergic reaction or clinical pancreatitis was observed despite 17% of Grade 3/4 lipase elevation. Anti‐asparaginase antibodies were detected in 50% of patients and related to a reduction in the duration of asparagine depletion during induction Phase 2 without decrease of encapsulated L‐asparaginase activity. Complete remission rate was 70%. With a median follow‐up of 42 months, median overall survival was 15.8 and 9.7 months, in the 100 and 150 IU/kg cohorts respectively. Conclusions: The addition of GRASPA®, especially at the 100 IU/kg dose level, is feasible in elderly patients without excessive toxicity and associated with durable asparagine depletion. (clinicaltrials.gov identifier NCT01523782). Am. J. Hematol. 90:811–818, 2015. © 2015 Wiley Periodicals, Inc.
Intestinal malrotation in Rubinstein–Taybi syndrome
Authors: Stevens Cathy A.
Published: June 2015

Rubinstein–Taybi syndrome (RSTS) is a multiple congenital anomaly syndrome which may include malformations of the central nervous system, heart, genitourinary tract, and other organs. However, intestinal malrotation has not been previously known to be associated with RSTS. This report documents six persons with RSTS who also had malrotation of the intestine requiring surgical repair. This suggests a possible increased frequency of malrotation in RSTS. Diagnostic studies for malrotation should be considered if recurrent vomiting, abdominal pain, and other symptoms of possible malrotation are present. © 2015 Wiley Periodicals, Inc.
The role of candidate‐gene CNTNAP2 in childhood apraxia of speech and specific language impairment
Authors: Centanni T. M. , Sanmann J. N. , Green J. R. , Iuzzini‐Seigel J. , Bartlett C. , Sanger W. G. , Hogan T. P.
Published: June 2015

Childhood apraxia of speech (CAS) is a debilitating pediatric speech disorder characterized by varying symptom profiles, comorbid deficits, and limited response to intervention. Specific Language Impairment (SLI) is an inherited pediatric language disorder characterized by delayed and/or disordered oral language skills including impaired semantics, syntax, and discourse. To date, the genes associated with CAS and SLI are not fully characterized. In the current study, we evaluated behavioral and genetic profiles of seven children with CAS and eight children with SLI, while ensuring all children were free of comorbid impairments. Deletions within CNTNAP2 were found in two children with CAS but not in any of the children with SLI. These children exhibited average to high performance on language and word reading assessments in spite of poor articulation scores. These findings suggest that genetic variation within CNTNAP2 may be related to speech production deficits. © 2015 Wiley Periodicals, Inc.
Epimerization of the α Stereocenter in d‐Ribose‐Derived Nitrones: Direct Access to Variant Quinolizidines with d‐Ribo and d‐Arabino Configurations
Authors: Rowicki Tomasz , Malinowski Maciej , Łapczyński Sebastian , Gryszel Maciej , Czerwińska Karolina , Madura Izabela , Sas Wojciech
Published: June 2015

The concise synthesis of two polyhydroxyquinolizidines from 2,3‐O‐isopropylidene‐d‐ribofuranose was accomplished. Epimerization of the intermediate N‐(3‐alkenyl)nitrone resulted in exceptionally straightforward access to an iminosugar with a d‐arabino configuration. A plausible mechanism of the epimerization via nitrone‐enehydroxylamine tautomerism explaining the reaction course has been proposed.
Synthesis and the Stimuli‐Responsive Characteristics of Cyclic Cholamide Nicotinamide Adenine Dinucleotide (NAD+) Derivative with Aggregation in Basic Aqueous Solution
Authors: Li Dazhi , Yang Yunxu , Hu Biwei , Yang Chao , Huo Baolong , Wang Aizhi , Yu Feifei , Xue Lingwei , Dong Yajun , Fan Weiping
Published: June 2015

A cyclic cholamide nicotinamide adenine dinucleotide (NAD+) derivative (CCN) has been synthesized with high yield. CCN is able to form nanomicelles in basic aqueous solution and emits fluorescence. The emission intensity shows a good linear relation and a good reversibility with pH value (pH 7–11). The mechanism for pH‐mediated changes in optical properties was demonstrated to be the tautomeric equilibriums of CCN/CCN‐OH.
Iodine‐Catalyzed Facile Synthesis of Pyrrolo‐ and Indolo[1,2‐a]quinoxalines
Authors: Wang Chao , Li Yun , Guo Rui , Tian Jingjing , Tao Cheng , Cheng Bin , Wang Hongyu , Zhang Jun , Zhai Hongbin
Published: June 2015

A practical and green approach to pyrrolo‐ and indolo[1,2‐a]quinoxalines has been developed based upon an oxidative reaction of 1‐(2‐aminophenyl)pyrroles or 2‐(3‐methyl‐1H‐1‐indolyl)aniline with benzylamines in the presence of O2 as the environmentally friendly oxidant and iodine as an economical and effective catalyst.
Cumyl Hydroperoxide‐Promoted Oxidative Amidation of 2‐Oxoaldehydes with Amines under Metal‐Free Conditions for the Synthesis of Unsymmetrical Oxamides
Authors: Zheng Yang , Zhan Zhen , Cheng Xu , Ma Xiaojun , Li Jie , Hai Li , Wu Yong
Published: June 2015

An efficient cumyl hydroperoxide‐promoted oxidative coupling of 2‐oxoaldehydes and amines to give unsymmetrical oxamides has been developed. The reactions proceeded smoothly at room temperature under metal‐free conditions and generated the corresponding products in good yields. The mild method can tolerate a variety of functional groups, and is operationally simple.
Theoretical Studies on the Mechanism of the Michael Addition Reaction Catalyzed by a Thiourea‐Cinchona‐Amine: Triple Activation
Authors: Zhou Mei‐Juan , Li Yun , Dang Li
Published: June 2015

This paper attempts to illuminate the mechanism of the catalytic Michael addition of 2,4‐pentanedione with acrylaldehyde mediated by a thiourea‐cinchona‐amine catalyst via density functional theory calculations. The calculated results show that the C−C coupling easily occurs once the electronegative and electropositive sites of the reactants are generated by the catalyst. However, the previously proposed mechanism with the formation of an imine from the carbonyl group of reactants and the amine group of catalyst fails due to high reaction barriers for both the formation of the imine and the hydrolysis of the imine with water in order to regenerate the catalyst. Instead, the reaction pathways going through the protonation of the amine in the catalyst and formation of hydrogen bonds between the reactants and catalyst have smaller barriers. Our study will be helpful in designing new catalysts or extending the substrate scope of the reaction.
Modulation of Creutzfeldt‐Jakob disease prion propagation by the A224V mutation
Authors: Watts Joel C. , Giles Kurt , Serban Ana , Patel Smita , Oehler Abby , Bhardwaj Sumita , Guan Shenheng , Greicius Michael D. , Miller Bruce L. , DeArmond Stephen J. , Geschwind Michael D. , Prusiner Stanley B.
Published: June 2015

Objective

Mutations in the gene encoding the prion protein (PrP) are responsible for approximately 10 to 15% of cases of prion disease in humans, including Creutzfeldt‐Jakob disease (CJD). Here, we report on the discovery of a previously unreported C‐terminal PrP mutation (A224V) in a CJD patient exhibiting a disease similar to the rare VV1 subtype of sporadic (s) CJD and investigate the role of this mutation in prion replication and transmission.

Methods

We generated transgenic (Tg) mice expressing human PrP with the V129 polymorphism and A224V mutation, denoted Tg(HuPrP,V129,A224V) mice, and inoculated them with different subtypes of sCJD prions.

Results

Transmission of sCJD VV2 or MV2 prions was accelerated in Tg(HuPrP,V129,A224V) mice, compared to Tg(HuPrP,V129) mice, with incubation periods of ∼110 and ∼210 days, respectively. In contrast, sCJD MM1 prions resulted in longer incubation periods in Tg(HuPrP,V129,A224V) mice, compared to Tg(HuPrP,V129) mice (∼320 vs. ∼210 days). Prion strain fidelity was maintained in Tg(HuPrP,V129,A224V) mice inoculated with sCJD VV2 or MM1 prions, despite the altered replication kinetics.

Interpretation

Our results suggest that A224V is a risk factor for prion disease and modulates the transmission behavior of CJD prions in a strain‐specific manner, arguing that residues near the C‐terminus of PrP are important for controlling the kinetics of prion replication. Ann Neurol 2015;78:540–553
The Higgs boson, supersymmetry and dark matter: Relations and Perspectives
Authors: Arbey Alexandre , Battaglia Marco , Mahmoudi Farvah
Published: June 2015

The discovery of a light Higgs boson at the LHC opens a broad program of studies and measurements to understand the role of this particle in connection with New Physics and Cosmology. Supersymmetry is the best motivated and most thoroughly formulated and investigated model of New Physics which predicts a light Higgs boson and can explain dark matter. This paper discusses how the study of the Higgs boson connects with the search for supersymmetry and for dark matter at the LHC and at a future collider and with dedicated underground dark matter experiments.

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Faltungszustand des Proteins Tau bei Bindung an Mikrotubuli
Authors: Kadavath Harindranath , Jaremko Mariusz , Jaremko Łukasz , Biernat Jacek , Mandelkow Eckhard , Zweckstetter Markus
Published: June 2015

Mikrotubuli werden durch so genannte Mikrotubuli‐assoziierte Proteine reguliert. Wenig ist jedoch über die Struktur dieser Proteine im Komplex mit Mikrotubuli bekannt. Hier zeigen wir, dass das Mikrotubuli‐assoziierte Protein Tau, das in Lösung intrinsisch ungeordnet ist, bei Bindung an Mikrotubuli lokal in eine stabile Struktur faltet. Während Tau flexibel in Lösung ist und eine β‐Faltblattstruktur in Amyloidfibrillen annimmt, falten die konservierten Hexapeptide in den Wiederholungssequenzen 2 und 3 in eine Haarnadelschleife im Komplex mit Mikrotubuli. Dies zeigt, dass die Bindung an Mikrotubuli eine spezifische Konformation im Tau‐Protein stabilisiert.
Die radiative Lebensdauer von Ytterbium‐Cryptaten mit Nahinfrarot‐Lumineszenz – Der Schlüssel zu extrem hohen Quantenausbeuten
Authors: Doffek Christine , Seitz Michael
Published: June 2015

Eine effektive Strategie zur Verbesserung der Lanthanoidenlumineszenz im Nahinfrarot‐Bereich wurde erstmals erfolgreich eingesetzt. Diese involviert die systematische Verkürzung der radiativen Lumineszenzlebensdauer τrad in molekularen Ytterbium‐Komplexen. Der zweizähnige Chelatligand 2,2′‐Bipyridin‐N,N′‐dioxid wurde als entscheidendes Strukturelement für die signifikante Senkung von τrad in makrobicyclischen Yb‐Cryptaten identifiziert. Wird dieser neue Ansatz mit herkömmlichen Strategien kombiniert, so können bisher unerreichte absolute Quantenausbeuten von bis zu 12 % erzielt werden. Diese außergewöhnliche Effizienz stellt den höchsten Wert dar, der jemals für jegliche Art von molekularen Lanthanoidspezies im nahen Infrarot‐Bereich gemessen wurde. Der hier erbrachte Beweis der prinzipiellen Durchführbarkeit dieser Strategie eröffnet neue Perspektiven für das Gebiet der Lanthanoiden‐Lumineszenz.
The Rapid Exfoliation and Subsequent Restacking of Layered Titanates Driven by an Acid–Base Reaction
Authors: Yuan Huiyu , Dubbink David , Besselink Rogier , ten Elshof Johan E.
Published: June 2015

Two‐dimensional (2D) (hydro)oxide materials, that is, nanosheets, enable the preparation of advanced 2D materials and devices. The general synthesis route of nanosheets involves exfoliating layered metal (hydro)oxide crystals. This exfoliation process is considered to be time‐consuming, hindering their industrial‐scale production. Based on in situ exfoliation studies on the protonated layered titanate H1.07Ti1.73O4⋅H2O (HTO), it is now shown that ion intercalation‐assisted exfoliation driven by chemical reaction provides a viable and fast route to isolated nanosheets. Contrary to the general expectation, data indicate that direct exfoliation of HTO occurs within seconds after mixing of the reactants, instead of proceeding via a swollen state as previously thought. These findings reveal that ion intercalation‐assisted exfoliation driven by chemical reaction is a promising exfoliation route for large‐scale synthesis.
Acid‐Triggered Degradable Reagents for Differentiation of Adaptive and Innate Immune Responses to Leishmania‐Associated Sugars
Authors: Roychoudhury Rajarshi , Martinez Pedro A. , Grinnage‐Pulley Tara , Schaut Robert G. , Petersen Christine A. , Pohl Nicola L. B.
Published: June 2015

Lipopolysaccharides (LPS) of Leishmania spp are known to alter innate immune responses. However, the ability of these sugars to specifically alter adaptive T‐cell responses is unclear. To study cap sugar–T‐cell interactions, pathogen mimics (namely glycodendrimer‐coated latex beads with acid‐labile linkers) were synthesized. Upon lysosomal acidification, linker breakdown releases glycodendrimers for possible loading on antigen presenting molecules to induce T‐cell growth. T‐cell proliferation was indeed higher after macrophage exposure to mannobioside or ‐trioside‐containing glycodendrimers than to non‐functionalized beads. Yet, blocking phagolysosomal acidification only reduced T‐cell proliferation with macrophages exposed to beads with an acid‐labile‐linker and not to covalently‐linked beads. These sugar‐modified reagents show that oligosaccharides alone can drive T‐cell proliferation by acidification‐requiring presentation, most significantly in NKT receptor (CD160)‐restricted T cells.
Eine universelle Herstellungsmethode für extrem kleine magneto‐fluoreszierende Nanohybride
Authors: Feld Artur , Merkl Jan‐Philip , Kloust Hauke , Flessau Sandra , Schmidtke Christian , Wolter Christopher , Ostermann Johannes , Kampferbeck Michael , Eggers Robin , Mews Alf , Schotten Theo , Weller Horst
Published: June 2015

Die Saat‐Emulsionspolymerisation ist eine effiziente Herstellungsmethode für nanoskalige multifunktionale Hybridmaterialien. In einem zweistufigen Prozess wurden zunächst Eisenoxidnanopartikel mit einer Hülle aus Polystyrol verkapselt. Diese wurden anschließend mit Quantenpunkten in Quantenstäben (QDQRs) belegt, sodass Nanohybride mit Eisenoxidkern und QDQR‐Satelliten resultierten. Die Synthese einer nahtlosen Polystyrolhülle ermöglicht sowohl die Fixierung des Konstruktes als auch die Steuerung seiner Zusammensetzung. Dadurch bleiben die Fluoreszenzeigenschaften der QDQRs und die magnetischen Eigenschaften des Eisenoxids unverändert, was mittels Einzelpartikeluntersuchung, Messung der Fluoreszenzabklingzeit und Relaxometrie nachgewiesen werden kann. Die Biofunktionalisierung erfolgte direkt durch Copolymerisation von entsprechenden Affinitätsmolekülen. Die Anwendbarkeit der Methode auf verschiedenartige Nanopartikel wurde demonstriert.
Copper‐Catalyzed Regioselective Hydroalkylation of 1,3‐Dienes with Alkyl Fluorides and Grignard Reagents
Authors: Iwasaki Takanori , Shimizu Ryohei , Imanishi Reiko , Kuniyasu Hitoshi , Kambe Nobuaki
Published: June 2015

Copper complexes generated in situ from CuCl2, alkyl Grignard reagents, and 1,3‐dienes play important roles as catalytic active species for the 1,2‐hydroalkylation of 1,3‐dienes by alkyl fluorides through CF bond cleavage. The alkyl group is introduced to an internal carbon atom of the 1,3‐diene regioselectively, thus giving rise to the branched terminal alkene product.
Thiophene, Selenophene, and Tellurophene‐based Three‐Dimensional Organic Frameworks
Authors: Li Peng‐Fei , Schon Tyler B. , Seferos Dwight S.
Published: June 2015

3D frameworks are important because of their potential to combine the advantageous properties of porous materials with those associated with polymers. A series of novel 3D aromatic frameworks are presented that incorporate the heterocycles thiophene, selenophene, and tellurophene. The specific surface area and pore width of frameworks depends on the element that is used to build the framework. Optoelectronic properties are element‐dependent, with heavy atoms red‐shifting the optical properties and decreasing the energy gap of the solid. The metalloid nature of tellurophene allows the properties of this material to be tuned based on its oxidation state, even as an insoluble solid. The incorporation of the optoelectronic active thiophene, selenophene, and tellurophene units and the effect that they have on properties was studied. A supercapcitor device was fabricated using these frameworks, showing that these 3D frameworks are promising for optoelectronic uses.
A Photoactivatable AIE Polymer for Light‐Controlled Gene Delivery: Concurrent Endo/Lysosomal Escape and DNA Unpacking
Authors: Yuan Youyong , Zhang Chong‐Jing , Liu Bin
Published: June 2015

Endo/lysosomal escape of gene vectors and the subsequent unpacking of nucleic acids in cytosol are two major challenges for efficient gene delivery. Herein, we report a polymeric gene delivery vector, which consists of a photosensitizer (PS) with aggregation‐induced emission (AIE) characteristics and oligoethylenimine (OEI) conjugated via an aminoacrylate (AA) linker that can be cleaved by reactive oxygen species (ROS). In aqueous media, the polymer could self‐assemble into bright red fluorescent nanoparticles (NPs), which can efficiently bind to DNA through electrostatic interaction for gene delivery. Upon visible light irradiation, the generated ROS can break the endo/lysosomal membrane and the polymer, resulting in light‐controlled endo/lysosomal escape and unpacking of DNA for efficient gene delivery. The smart polymer represents the first successful gene vector to simultaneously address both challenges with a single light excitation process.
Ruthenium‐Catalyzed Monoalkenylation of Aromatic Ketones by Cleavage of Carbon–Heteroatom Bonds with Unconventional Chemoselectivity
Authors: Kondo Hikaru , Akiba Nana , Kochi Takuya , Kakiuchi Fumitoshi
Published: June 2015

Ruthenium‐catalyzed selective monoalkenylation of ortho CO or CN bonds of aromatic ketones was achieved. The reaction allowed the direct comparison of the relative reactivities of the cleavage of different carbon‐heteroatom bonds, thus suggesting an unconventional chemoselectivity, where smaller, more‐electron‐donating groups are more easily cleaved. Selective monofunctionalization of CO bonds in the presence of ortho CH bonds was also achieved.
Cp*RhIII‐katalysierte Arylierung von C(sp3)‐H‐Bindungen
Authors: Wang Xiaoming , Yu Da‐Gang , Glorius Frank
Published: June 2015

Die erste Cp*RhIII‐katalysierte Arylierung nichtaktivierter C(sp3)‐H‐Bindungen wird vorgestellt. Nichtaktivierte primäre C(sp3)‐H‐Bindungen von 2‐Alkylpyridinen können mit RhIII aktiviert und mit Triarylboroxinen umgesetzt werden, um neue C(sp3)‐Aryl‐Bindungen zu knüpfen. Die entwickelte Methode erlaubt auch die einfache Synthese unsymmetrischer Triarylmethane durch RhIII‐katalysierte C(sp3)‐H‐Arylierung von Diarylmethanen.
Effective Formylation of Amines with Carbon Dioxide and Diphenylsilane Catalyzed by Chelating bis(tzNHC) Rhodium Complexes
Authors: Nguyen Thanh V. Q. , Yoo Woo‐Jin , Kobayashi Shū
Published: June 2015

The reductive formylation of amines using CO2 and hydrosilanes is an attractive method for incorporating CO2 into valuable organic compounds. However, previous systems required either high catalyst loadings or high temperatures to achieve high efficiency, and the substrate scope was mostly limited to simple amines. To address these problems, a series of alkyl bridged chelating bis(NHC) rhodium complexes (NHC=N‐heterocyclic carbene) have been synthesized and applied to the reductive formylation of amines using CO2 and Ph2SiH2. A rhodium‐based bis(tzNHC) complex (tz=1,2,3‐triazol‐5‐ylidene) was identified to be highly effective at a low catalyst loading and ambient temperature, and a wide substrate scope, including amines with reducible functional groups, were compatible.
Total Synthesis and Structural Revision of Antibiotic CJ‐16,264
Authors: Nicolaou K. C. , Shah Akshay A. , Korman Henry , Khan Tabrez , Shi Lei , Worawalai Wisuttaya , Theodorakis Emmanuel A.
Published: June 2015

The total synthesis and structural revision of antibiotic CJ‐16,264 is described. Starting with citronellal, the quest for the target molecule featured a novel bis‐transannular Diels–Alder reaction that casted stereoselectively the decalin system and included the synthesis of six isomers before demystification of its true structure.
Asymmetric Construction of Spirooxindoles by Organocatalytic Multicomponent Reactions Using Diazooxindoles
Authors: Wu Ming‐Yue , He Wei‐Wei , Liu Xin‐Yuan , Tan Bin
Published: June 2015

The first highly diastereo‐ and enantioselective multicomponent reaction of diazooxindoles, nitrosoarenes, and nitroalkenes using a newly developed hydrogen‐bond catalyst has been successfully developed for the efficient construction of a series of spirooxindole derivatives with excellent functional‐group tolerance. Spirooxindoles are formed in excellent yields and stereoselectivities, and the method represents an unprecedented approach for trapping the active intermediate with a nitroalkene to form biologically important compounds having three contiguous stereogenic centers with excellent asymmetric induction.
Visible‐Light‐Activated Molecular Switches
Authors: Bléger David , Hecht Stefan
Published: June 2015

The ability to influence key properties of molecular systems by using light holds much promise for the fields of materials science and life sciences. The cornerstone of such systems is molecules that are able to reversibly photoisomerize between two states, commonly referred to as photoswitches. One serious restriction to the development of functional photodynamic systems is the necessity to trigger switching in at least one direction by UV light, which is often damaging and penetrates only partially through most media. This review provides a summary of the different conceptual strategies for addressing molecular switches in the visible and near‐infrared regions of the optical spectrum. Such visible‐light‐activated molecular switches tremendously extend the scope of photoswitchable systems for future applications and technologies.
Folding of the Tau Protein on Microtubules
Authors: Kadavath Harindranath , Jaremko Mariusz , Jaremko Łukasz , Biernat Jacek , Mandelkow Eckhard , Zweckstetter Markus
Published: June 2015

Microtubules are regulated by microtubule‐associated proteins. However, little is known about the structure of microtubule‐associated proteins in complex with microtubules. Herein we show that the microtubule‐associated protein Tau, which is intrinsically disordered in solution, locally folds into a stable structure upon binding to microtubules. While Tau is highly flexible in solution and adopts a β‐sheet structure in amyloid fibrils, in complex with microtubules the conserved hexapeptides at the beginning of the Tau repeats two and three convert into a hairpin conformation. Thus, binding to microtubules stabilizes a unique conformation in Tau.
The Radiative Lifetime in Near‐IR‐Luminescent Ytterbium Cryptates: The Key to Extremely High Quantum Yields
Authors: Doffek Christine , Seitz Michael
Published: June 2015

A powerful strategy for the improvement of near‐IR lanthanoid luminescence has been successfully employed for the first time, which involves the rational and deliberate shortening of the radiative luminescence lifetimes τrad in molecular ytterbium complexes. In this context, the bidentate chelating unit 2,2′‐bipyridine‐N,N′‐dioxide has been identified as being responsible for decreasing τrad substantially in macrobicyclic Yb cryptates. This strategy, when combined with conventional approaches, yields unprecedented absolute near‐IR quantum yields of up to 12 %. This extraordinary efficiency represents the highest value measured for any molecular lanthanoid near‐IR emitter. The proof‐of‐concept for the implementation of the new strategy opens up entirely new prospects for the field of lanthanoid luminescence.
1,5‐Di(nitramino)tetrazole: High Sensitivity and Superior Explosive Performance
Authors: Fischer Dennis , Klapötke Thomas M. , Stierstorfer Jörg
Published: June 2015

Highly energetic 1,5‐di(nitramino)tetrazole and its salts were synthesized. The neutral compound is very sensitive and one of the most powerful non‐nuclear explosives to date. Selected nitrogen‐rich and metal salts were prepared. The potassium salt can be used as a sensitizer in place of tetracene. The obtained compounds were characterized by low‐temperature X‐ray diffraction, IR and Raman spectroscopy, multinuclear NMR spectroscopy, elemental analysis, and DSC. Calculated energetic performances using the EXPLO5 code based on calculated (CBS‐4M) heats of formation and X‐ray densities support the high energetic performances of the 1,5‐dinitraminotetrazolates as energetic materials. The sensitivities towards impact, friction, and electrostatic discharge were also explored.
Selective Aryl–Fluoride Reductive Elimination from a Platinum(IV) Complex
Authors: Dubinsky‐Davidchik Ina , Goldberg Israel , Vigalok Arkadi , Vedernikov Andrei N.
Published: June 2015

A difluoro(mesityl)platinum(IV) complex underwent highly selective reductive elimination of 2‐fluoromesitylene upon heating in toluene. Kinetic analysis and DFT calculations suggest that the CF coupling involves a five‐coordinate PtIV transient intermediate resulting from the rate‐limiting dissociation of the pyridine ligand.
Cp*RhIII‐Catalyzed Arylation of C(sp3)H Bonds
Authors: Wang Xiaoming , Yu Da‐Gang , Glorius Frank
Published: June 2015

The first Cp*RhIII‐catalyzed arylation of unactivated C(sp3)H bonds is presented. The unactivated primary C(sp3)H bond of 2‐alkylpyridines can be activated by RhIII and further reacts with triarylboroxines to efficiently build new C(sp3)aryl bonds. The methodology also provides a facile and efficient synthesis of unsymmetrical triarylmethanes by RhIII‐catalyzed C(sp3)H arylation of diarylmethanes.
Experimental investigation of moisture diffusion in short‐glass‐fiber‐reinforced polyamide 6,6
Authors: Zhang Shi , Huang Zhigao , Zhang Yun , Zhou Huamin
Published: June 2015

Moisture diffusion in polyamide 6,6 (PA66) and its short glass fiber‐reinforced composites has a great influence on their mechanical properties and service lives under hydrothermal environments. Hence, the moisture diffusion in neat PA66 and its composites was studied comprehensively in this study with the general Fickian model. To systematically investigate the effects of the fiber content, humidity, temperature, and humidity–temperature coupling effect on the diffusion coefficient and equilibrium concentration, gravimetric experiments for the PA66 composites were carried out under different hydrothermal conditions. The results show that the equilibrium moisture concentration depended on the relative humidity and fiber content but only depended weakly on temperature. The diffusion velocity was affected by the three aforementioned factors with different trends. The analysis of variance demonstrated that the humidity–temperature coupling effect played an important role in the diffusion process. The regression analysis gave the corresponding quadratic regression equations. © 2015 Wiley Periodicals, Inc. J. Appl. Polym. Sci. 2015, 132, 42369.
Current progress in the production of PLA–ZnO nanocomposites: Beneficial effects of chain extender addition on key properties
Authors: Murariu Marius , Paint Yoann , Murariu Oltea , Raquez Jean‐Marie , Bonnaud Leila , Dubois Philippe
Published: June 2015

Poly(lactic acid) (PLA) nanocomposites characterized by multifunctional end‐use properties are of high interest as new biosourced materials for the production of smart films, fibers, and injection‐molded components. In this work, PLA–ZnO nanocomposites designed for the extrusion of films were obtained by melt‐compounding PLA with up to 5 wt % ZnO rod‐like nanoparticles, nanofiller previously surface‐treated with a specific silane (triethoxycaprylylsilane). To improve the processing and performances of nanocomposites such as their stability at high temperature, the addition of a selected chain‐extender (CE) was considered. It was revealed that the co‐addition of nanofiller (ZnO) and epoxy functional styrene‐acrylate oligomeric CE (Joncryl® ADR 4300F) leads to a very significant enhancement of the properties (molecular, rheological, thermal, etc.) of PLA–ZnO nanocomposites. After addition of 1% CE into nanocomposites, the PLA molecular weights were found to be nearly twofold higher, while the isothermal tests (at 220 and 240°C) confirmed a significant increase in thermal stability. Because the CE plays a key role in limiting the degrading effects of ZnO, due to a gain in melt viscosity and increased molecular mass, a better ability to process nanocomposites by extrusion was found. The good nanofiller dispersion and specific end‐use characteristics owing to the presence of ZnO nanoparticles (such as UV shielding) were again confirmed on extruded films. These developments are being viewed as a promising approach that can open new perspectives in the application of PLA–ZnO nanocomposites with specific end‐use properties (UV protection, antibacterial, gas‐barrier, and self‐cleaning) at larger scale. © 2015 Wiley Periodicals, Inc. J. Appl. Polym. Sci. 2015, 132, 42480.
Investigation of the thermostability of poly(ethylene terephthalate)–hemp fiber composites: Extending natural fiber reinforcements to high‐melting thermoplastics
Authors: Talla Aimé Sylvain Fotso , Erchiqui Fouad , Kaddami Hamid , Kocaefe Duygu
Published: June 2015

The thermal stability of poly(ethylene terephthalate) reinforced with 1, 5, 10, 15, and 20% hemp fibers was investigated with the aim of extending the applications of biocomposites to high‐melting thermoplastics. The material was injection‐molded following compounding with a torque‐based Rheomix at 240, 250, and 260°C. A combination of thermogravimetric methods at 5, 10, and 20°C/min, Liu and Yu's collecting temperature method, and Friedman's kinetic method were used for testing and analysis. A significant thermostability for all formulations was observed below 300°C; this demonstrated their potential for successful melt processing. Moreover, two degradation steps were observed in the temperature ranges 313–390 and 390–490°C. The associated apparent activation energies within the temperature ranges were determined as 150–262 and 182–242 kJ/mol, respectively. We found that the thermostability was significantly affected by the heating rates; however, the effect of the temperature of the mixing chamber was negligible. These findings suggest that the successful melt processing of high‐melting thermoplastics reinforced with natural fibers is possible with limited fiber thermodegradation. © 2015 Wiley Periodicals, Inc. J. Appl. Polym. Sci. 2015, 132, 42500.
Largely toughening biodegradable poly(lactic acid)/thermoplastic polyurethane blends by adding MDI
Authors: Zhao Fei , Huang Han‐Xiong , Zhang Shui‐Dong
Published: June 2015

This work focuses on largely toughening poly(lactic acid)/thermoplastic polyurethane (PLA/TPU) blend with lower content (20 wt %) of TPU using appropriate contents of 4,4‐methylene diphenyl diisocyanate (MDI) via simple melt blending. Both scanning electron micrographs and differential scanning calorimetry curves suggest little change of the compatibility between the PLA and TPU phases by adding the MDI. Dynamic rheological test demonstrates that a reaction occurs between the TPU phase and MDI during melt blending. Combining the rheological behaviors and gel contents of the blends, it can be speculated that adding the MDI extends the TPU chains and forms branched and crosslinked structure in the TPU chains sequentially. Toughening mechanism is analyzed and different impact strengths for the blends with different MDI contents are explained based on combined effects of the decreased crystallinities for the PLA matrix and the extended, branched and crosslinked structure in the TPU chains. A 0.8 wt % MDI content is optimal in terms of the impact strength (100.6 kJ/m2) and the elongation at break (392.4%). The former is about 1.9 and 32.5 times of that for the blend without MDI and the PLA, respectively. Moreover, the MDI results in some increase in the tensile strength of the blends. © 2015 Wiley Periodicals, Inc. J. Appl. Polym. Sci. 2015, 132, 42511.
Environmental flow releases trigger spawning migrations by Australian grayling Prototroctes maraena, a threatened, diadromous fish
Authors: Amtstaetter Frank , O'connor Justin , Pickworth Andrew
Published: June 2015

Monitoring fish movement can test the effectiveness of environmental flow releases when they are used to trigger spawning behaviour. Environmental flow releases have been used to enhance Australian grayling (Prototroctes maraena) spawning in regulated rivers in south‐eastern Australia and resource managers require knowledge of the effectiveness on the conservation of this threatened species.

Australian grayling movement was monitored in the Thomson River, south‐eastern Australia using acoustic telemetry to determine whether the species undergoes a spawning migration, where they migrate and timing in relation to environmental flow releases. Drift netting was used to verify whether spawning took place.

Adult Australian grayling undertook downstream spawning migrations (up to 140 km) to the lower Thomson River, coinciding with environmental flow releases.

The findings of this study support the use of environmental flow releases to trigger spawning migrations by Australian grayling. In addition, they provide managers of other species with an example of the potential effectiveness of environmental flow releases in triggering fish migration or spawning that can assist in rationalizing this management intervention.

Copyright © 2015 John Wiley & Sons, Ltd.
Newly developed microsatellite markers for the pan‐European duck mussel, Anodonta anatina: revisiting the main mitochondrial lineages
Authors: Lopes‐Lima Manuel , Sousa Ronaldo , Teixeira Amílcar , Varandas Simone , Riccardi Nicoletta , Aldridge David C. , Froufe Elsa
Published: June 2015

Freshwater mussels of the family Unionidae are one of the most threatened groups worldwide and have suffered severe decline over recent decades. Although the freshwater duck mussel, Anodonta anatina (Linnaeus, 1758), is still widespread, this species has shown evidence of recent declines and is already protected in some European countries.

Informed conservation efforts must take into account patterns in genetic diversity and phylogeography. In the present study, 20 newly developed polymorphic loci were described and tested in seven populations of A. anatina, belonging to three previously detected divergent mtDNA lineages. The genetic diversity patterns, within and among A. anatina populations, were evaluated to test their congruence with those lineages.

A high genetic differentiation (FST) was found among all populations, with the exception of those in Central Europe (Germany) and the UK, which were not strongly structured.

The present study confirms the division of the species into three evolutionarily significant units corresponding to the three previously detected mtDNA lineages, which should be managed independently. Furthermore, owing to the high differentiation among southern European populations, the establishment of distinct management units for the Guadalquivir, Guadiana and Douro populations in the Iberian Peninsula is also proposed.

Copyright © 2015 John Wiley & Sons, Ltd.
A BAFF Receptor His159Tyr Mutation in Sjögren's Syndrome–Related Lymphoproliferation
Authors: Papageorgiou Aristea , Mavragani Clio P. , Nezos Andrianos , Zintzaras Elias , Quartuccio Luca , De Vita Salvatore , Koutsilieris Michael , Tzioufas Athanasios G. , Moutsopoulos Haralampos M. , Voulgarelis Michael
Published: June 2015

Objective

To study the prevalence, clinical associations, and functional implications of the His159Tyr mutation of the BAFF receptor (BAFF‐R) in patients with Sjögren's syndrome (SS).

Methods

The BAFF‐R His159Tyr mutation was evaluated using polymerase chain reaction (PCR)–based assays in 247 patients with SS (of whom 70 had SS complicated by lymphoma [SS‐lymphoma]), 145 with systemic lupus erythematosus (SLE), and 101 with rheumatoid arthritis (RA), as well as 180 healthy controls. Real‐time PCR and Western blotting were performed for the quantification of both NF‐κB1 and NF‐κB2 messenger RNA (mRNA) transcript and protein levels in isolated B cells from patients with SS‐lymphoma carrying the mutation (SS‐lymphoma–BAFF‐RHis159Tyr–derived B cells) compared to B cells from patients with SS‐lymphoma who were not carriers of the mutation and healthy controls.

Results

Both the SS‐lymphoma and SS‐nonlymphoma patient subgroups exhibited significantly higher frequencies of the His159Tyr BAFF‐R mutation compared to healthy controls (8.6% of SS‐lymphoma patients and 6.2% of SS‐nonlymphoma patients versus 1.7% of healthy controls; P = 0.02 and P = 0.04, respectively). The corresponding frequencies of the His159Tyr BAFF‐R mutation in SLE and RA patients were 3.5% and 3%, respectively. Of interest, 71.4% of the SS patients with mucosa‐associated lymphoid tissue (MALT) lymphoma who were between the ages of 31 and 40 years at disease onset were mutation carriers. The generalized odds ratio for the development of SS‐related MALT lymphoma in the younger age at onset (age <40 years) group in the presence of the BAFF‐R mutation was 6.1 (95% confidence interval 2.0–18.7) (P < 0.01). Expression of NF‐κB at both the mRNA and protein level was up‐regulated in SS‐lymphoma–BAFF‐RHis159Tyr–derived B cells.

Conclusion

This study identifies an increased prevalence of the BAFF‐R His159Tyr mutation in patients with SS, particularly in those with SS complicated by MALT lymphoma whose disease onset occurred at a younger age. BAFF‐RHis159Tyr–mediated activation of the alternate NF‐κB pathway might contribute to the pathogenesis of SS‐related lymphoproliferative disease.
Rational Design of Antirheumatic Prodrugs Specific for Sites of Inflammation
Authors: Onuoha Shimobi C. , Ferrari Mathieu , Sblattero Daniele , Pitzalis Costantino
Published: June 2015

Objective

Biologic drugs, such as the anti–tumor necrosis factor (anti‐TNF) antibody adalimumab, have represented a breakthrough in the treatment of rheumatoid arthritis. Yet, concerns remain over their lack of efficacy in a sizable proportion of patients and their potential for systemic side effects such as infection. Improved biologic prodrugs specifically targeted to the site of inflammation have the potential to alleviate current concerns surrounding biologic anticytokine therapies. The purpose of this study was to design, construct, and evaluate in vitro and ex vivo the targeting and antiinflammatory capacity of activatable bispecific antibodies.

Methods

Activatable dual variable domain (aDVD) antibodies were designed and constructed to target intercellular adhesion molecule 1 (ICAM‐1), which is up‐regulated at sites of inflammation, and anti‐TNF antibodies (adalimumab and infliximab). These bispecific molecules included an external arm that targets ICAM‐1 and an internal arm that comprises the therapeutic domain of an anti‐TNF antibody. Both arms were linked to matrix metalloproteinase (MMP)–cleavable linkers. The constructs were tested for their ability to bind and neutralize both in vitro and ex vivo targets.

Results

Intact aDVD constructs demonstrated significantly reduced binding and anti‐TNF activity in the prodrug formulation as compared to the parent antibodies. Human synovial fluid and physiologic concentrations of MMP enzyme were capable of cleaving the external domain of the antibody, revealing a fully active molecule. Activated antibodies retained the same binding and anti‐TNF inhibitory capacities as the parent molecules.

Conclusion

The design of a biologic prodrug with enhanced specificity for sites of inflammation (synovium) and reduced specificity for off‐target TNF is described. This construct has the potential to form a platform technology that is capable of enhancing the therapeutic index of drugs for the treatment of RA and other inflammatory diseases.
Interleukin‐21 Receptor Blockade Inhibits Secondary Humoral Responses and Halts the Progression of Preestablished Disease in the (NZB × NZW)F1 Systemic Lupus Erythematosus Model
Authors: Zhang Ming , Yu Gang , Chan Brian , Pearson Joshua T. , Rathanaswami Palaniswami , Delaney John , Ching Lim Ai , Babcook John , Hsu Hailing , Gavin Marc A.
Published: June 2015

Objective

Systemic lupus erythematosus (SLE) is a complex autoimmune disease that is driven in part by chronic B and T lymphocyte hyperresponsiveness to self antigens. A deficiency of interleukin‐21 (IL‐21) or IL‐21 receptor (IL‐21R) in mice dramatically reduces inflammation and B and T cell activation in models of autoimmunity, including SLE. However, whether IL‐21 is essential for the maintenance and amplification of preestablished inflammation has not been widely examined in various animal models. The purpose of this study was to examine the impact of novel mouse IL‐21R neutralizing antibodies on recall responses to antigen challenge and on disease progression in the (NZB × NZW)F1 (NZB/NZW) mouse model of SLE.

Methods

Humoral and cellular immune responses to immunization with sheep red blood cells (SRBCs) were measured in mice dosed with IL‐21R blocking antibodies. Progression of nephritis and markers of immune activation was monitored in NZB/NZW mice following different anti–IL‐21R treatment regimens.

Results

IL‐21R blockade specifically inhibited secondary IgG responses to SRBC immunization. In NZB/NZW mice, IL‐21R blockade completely inhibited the onset of nephritis, which was associated with dramatic reductions in splenomegaly and in B cell and T cell activation. When administered to mice with preexisting disease, anti–IL‐21R antibody halted the disease progression and mortality and reversed the nephritis in a subset of mice. Furthermore, treatment cessation was not followed by rapid reemergence of disease.

Conclusion

Our results highlight the importance of IL‐21 in promoting humoral recall responses and in sustaining autoimmune inflammation.